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SciRIFF-4096-0214-v2

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[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nPropofol infusion versus intermittent meperidine and midazolam injection for conscious sedation in ERCP.\nReport Abstract 1:\nERCP generally requires longer time than standard endoscopy. Only few studies have shown benefit of intermittent propofol over conventional sedation. This study was conducted to compare satisfaction, recovery score, and recovery/safety profiles for ERCP sedation between continuous infusion of propofol and conventional sedation.\n One hundred thirty-four patients with ASA I-III underwent ERCP and were randomly assigned into two groups (n=67 each). Patients underwent propofol sedation or meperidine/midazolam sedation. Supplemental oxygen was offered only when oxygen saturation was lower than 90 %. Oxygen saturation, blood pressure, heart rate, recovery score, times for recovery and satisfaction score after procedure were recorded and analyzed.\n Average amount of meperidine, midazolam and propofol per each patient were 61.54 (+/- 27.29), 7.80 (+/- 3.73), 299.90 (+/- 146.15) mg, respectively. Time to regain full consciousness in the propofol arm was significantly shorter than in the conventional arm (17.24 +/- 5.99 versus 34.25 +/- 16.06 min, p<0.001). The rates of desaturation, bradycardia and hypotension in both arms were low and comparable. Propofol provided higher level of recovery scores at 15, 30, 45 and 60 min after the procedure (p < 0.001).\n Continuous infusion of propofol for ERCP by direction of gastroenterologist yields no difference in the completion rate and adverse profiles when compared with conventional technique but it provides a better recovery profile. The maintainance of appropriate level of sedation by well trained personnel is the key to achieve this success.\n\n\nReport Title 2:\nSedation with propofol for interventional endoscopy by trained nurses in high-risk octogenarians: a prospective, randomized, controlled study.\nReport Abstract 2:\nSedation with the short-acting anesthetic agent propofol has shown several advantages, particularly in interventional endoscopy. So far, however, there are no valid data on the safety of nurse-administered propofol sedation (NAPS) during interventional endoscopy in elderly high-risk patients.\n A total of 150 patients aged > 80 years with high comorbidity were randomized to receive midazolam plus meperidine (n = 75) or propofol alone (n = 76) for sedation during endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasound (EUS), or double-balloon endoscopy (DBE). Sedation was supervised by a trained nurse and a trained physician both of whom were not involved in the endoscopic procedure. Vital signs were continuously monitored as well as patient cooperation and tolerance. Mortality and morbidity at 30 days was analyzed.\n The overall cardiopulmonary complication rate was 16 % in the midazolam group and 23.7 % in the propofol group ( P > 0.05). The mean decline in oxygen saturation (initial vs. lowest O (2) saturation) and the mean decline of blood pressure (initial vs. lowest blood pressure) were significantly greater with propofol (7 % +/- 3 % vs. 4 % +/- 2 % [ P < 0.05] and 10 % +/- 2 % vs. 8 % +/- 2 %, respectively [ P < 0.05]). No procedure had to be interrupted due to serious adverse events. Patient cooperation was statistically significantly better in the propofol group (7 +/- 2 vs. 5 +/- 2 points). Patients sedated with propofol showed a significantly lower oxygen saturation rate during recovery time (8 % vs. 28 %; P < or = 0.01).\n NAPS during interventional endoscopy is as safe as midazolam/pethidine sedation even in high-risk patients aged > 80 years.\n\n\nReport Title 3:\nSedation with propofol for routine ERCP in high-risk octogenarians: a randomized, controlled study.\nReport Abstract 3:\nAdequate patient sedation is mandatory for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In this respect it is known that the short-acting anesthetic propofol offers certain potential advantages for sedation during ERCP, but there are no controlled studies concerning the feasibility and safety of propofol sedation in elderly, high-risk patients.\n One hundred and fifty consecutive patients aged >or=80 yr with high comorbidity (ASA score >or=III: 91 %), randomly received midazolam plus meperidine (n = 75) or propofol alone (n = 75) for sedation during ERCP. Vital signs were continuously monitored and procedure-related parameters, recovery time, and quality as well as patients' cooperation and tolerance of the procedure were assessed.\n Clinically relevant changes in vital signs were observed at comparable frequencies with a temporary oxygen desaturation (<90%) occurring in eight patients in the propofol-group and seven patients receiving midazolam/meperidine (n.s.). Hypotension was documented in two patients in the propofol group and one patient receiving midazolam/meperidine. Propofol provided a significantly better patient cooperation than midazolam/meperidine (p < 0.01), but the procedure tolerability was rated nearly the same by both groups. Mean recovery time was significantly shorter in the propofol group (22 +/- 7 min vs 31 +/- 8 min for midazolam/meperidine (p < 0.01)) while the recovery score was significantly higher under propofol (8.3 +/- 1.2 vs 6.1 +/- 1.1(p < 0.01)). During recovery a significant lower number of desaturation events (<90%) were observed in the propofol group (12%) than in the midazolam/meperidine group (26%, p < 0.01).\n Under careful monitoring the use of propofol for sedation during ERCP is superior to midazolam/meperidine even in high-risk octogenarians.", "role": "user" }, { "content": "Results from individual studies suggested that patients have a better recovery profile after propofol sedation for ERCP procedures than after midazolam and meperidine sedation. As there was no difference between the two sedation techniques as regards safety, propofol sedation is probably preferred for patients undergoing ERCP procedures. However, in all of the studies that were identified only non-anaesthesia personnel were involved in administering the sedation. It would be helpful if further research was conducted where anaesthesia personnel were involved in the administration of sedation for ERCP procedures. This would clarify the extent to which anaesthesia personnel should be involved in the administration of propofol sedation.", "role": "assistant" } ]

[ { "content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nGenetic heterogeneity at the glucose-6-phosphate dehydrogenase locus in southern Italy: a study on a population from the Matera district. Glucose-6-phosphate dehydrogenase (G6PD) has been analyzed by gel electrophoresis and by quantitative assay in an unselected sample of 1524 schoolboys from the province of Matera (Lucania) in southern Italy. We have identified 43 subjects with a G6PD variant. Of these, 31 had severe G6PD deficiency, nine had mild to moderate deficiency, and three had a non-deficient electrophoretic variant. The overall rate of G6PD deficiency was 2. 6%. The frequency of G6PD deficiency, ranging from 7. 2% on the Ionian Coast to zero on the eastern side of the Lucanian Apennines, appears to be inversely related to the distance of each town examined from the Ionian Coast, suggesting that this geographic distribution may reflect, at least in part, gene flow from Greek settlers. Biochemical characterization has shown that most of the G6PD deficiency in this population is accounted for by G6PD Mediterranean. In addition, we have found several examples of two other known polymorphic variants (G6PD Cagliari and G6PD A-); three new polymorphic variants, G6PD Metaponto (class III), G6PD Montalbano (class III), and G6PD Pisticci (class IV); and two sporadic variants, G6PD Tursi (class III) and G6PD Ferrandina (class II). These data provide further evidence for the marked genetic heterogeneity of G6PD deficiency within a relatively narrow geographic area and they prove the presence in the Italian peninsula of a gene (GdA-) regarded as characteristically African.", "role": "user" }, { "content": "{\"Disease\": [\"G6PD deficiency\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to train a model for image classification.\n\nKeywords: image classification images\n\nDataset Information:\nFGVC-Aircraft: FGVC-Aircraft contains 10,200 images of aircraft, with 100 images for each of 102 different aircraft model variants, most of which are airplanes. The (main) aircraft in each image is annotated with a tight bounding box and a hierarchical airplane model label.\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nJFT-300M: JFT-300M is an internal Google dataset used for training image classification models. Images are labeled using an algorithm that uses complex mixture of raw web signals, connections between web-pages and user feedback.\nCaltech-101: The Caltech101 dataset contains images from 101 object categories (e.g., “helicopter”, “elephant” and “chair” etc.) and a background category that contains the images not from the 101 object categories.\n\nAvailable Datasets: A: FGVC-Aircraft B: ConvAI2 C: JFT-300M D: Caltech-101", "role": "user" }, { "content": "Caltech-101", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: COVID-19: Novel Coronavirus May Lead to A Cardiac Arrest or heart attack\n\nResearch Abstract:\nPatients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19).\nAdditionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome.\nAs the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues.\nWhile the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period.\nWe provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome.\"]}", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nBackground: Limited data are available on the management of pregnant women with severe or critical forms of COVID-19, such as the optimal timing of provider-initiated delivery, and post-partum care, including antithrombotic prophylaxis. We present the clinical course, pre- and post-partum management, and outcomes of two pregnant women critically ill with COVID-19. Cases: Both women had confirmed SARS-CoV-2 pneumonia with rapid clinical decompensation that required admission to the intensive care unit, intubation, and delivery by emergency cesarean section at 32 and 29 weeks. Both patients clinically improved in the first two postoperative days, but this was followed by clinical, laboratory and radiological deterioration on the third postoperative day; however, they both improved again after full anticoagulation. This pattern suggests the possible formation of pulmonary microthrombi in the early puerperium. We discuss the challenges faced by the multiprofessional team in the management of these patients. Conclusions: There are few resources to guide health professionals caring for pregnant women with critical COVID-19. These two cases contribute to the rapidly evolving knowledge on the management and outcomes of pregnant women with COVID-19.", "role": "user" }, { "content": "[\"Case Report\"]", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nSince late December 2019, a novel, emerging coronavirus was identified as the infectious agent responsible for a generally mild but sometimes severe and even life-threatening disease, termed as \"coronavirus disease 2019\" (COVID-19). The pathogen was initially named as \"2019 novel coronavirus\" (2019-nCoV) and later renamed as \"Severe Acute Respiratory Coronavirus type 2\" (SARS-CoV-2). COVID-19 quickly spread from the first epicenter, the city of Wuhan, province of Hubei, mainland China, into neighboring countries, and became a global pandemic. As of July 15th 2020, the outbreak is still ongoing, with SARS-CoV-2 affecting 213 countries and territories. The coronavirus has caused a dramatic toll of deaths and imposed a severe burden, both from a societal and economic point of view. COVID-19 has challenged health systems, straining and overwhelming healthcare facilities and settings, including hospital and community pharmacies. On the other hand, COVID-19 has propelled several changes. During the last decades, pharmacy has shifted from being products-based and patient-facing to being services-based and patient-centered. Pharmacies have transitioned from being compounding centers devoted to the manipulation of materia medica to pharmaceutical centers, clinical pharmacies and fully integrated \"medical-pharmaceutical networks\", providing a significant range of non-prescribing services. Moreover, roles, duties and responsibilities of pharmacists have paralleled such historical changes and have known a gradual expansion, incorporating new skills and reflecting new societal demands and challenges. The COVID-19 outbreak has unearthed new opportunities for pharmacists: community and hospital pharmacists have, indeed, played a key role during the COVID-19 pandemic, suggesting that a fully integrated, inter-sectoral and inter-professional collaboration is necessary to face crises and public health emergencies. Preliminary, emerging evidence seems to suggest that, probably, a new era in the history of pharmacies (\"the post-COVID-19 post-pharmaceutical care era\") has begun, with community pharmacists acquiring more professional standing, being authentic heroes and frontline health workers.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nLearning long-term dependencies still remains difficult for recurrent neural networks (RNNs) despite their success in sequence modeling recently. In this paper, we propose a novel gated RNN structure, which contains only one gate. Hidden states in the proposed grouped distributor unit (GDU) are partitioned into groups. For each group, the proportion of memory to be overwritten in each state transition is limited to a constant and is adaptively distributed to each group member. In other word, every separate group has a fixed overall update rate, yet all units are allowed to have different paces. Information is therefore forced to be latched in a flexible way, which helps the model to capture long-term dependencies in data. Besides having a simpler structure, GDU is demonstrated experimentally to outperform LSTM and GRU on tasks including both pathological problems and natural data set.\n\nCited Works Summary:\n[1]: In this paper we compare different types of recurrent units in recurrent neural networks (RNNs). Especially, we focus on more sophisticated units that implement a gating mechanism, such as a long short-term memory (LSTM) unit and a recently proposed gated recurrent unit (GRU). We evaluate these recurrent units on the tasks of polyphonic music modeling and speech signal modeling. Our experiments revealed that these advanced recurrent units are indeed better than more traditional recurrent units such as tanh units. Also, we found GRU to be comparable to LSTM.", "role": "user" }, { "content": "Previous work has clearly indicated the advantages of the gating units over the more traditional recurrent units [1] . Both LSTM and GRU perform well in tasks that require capturing long-term dependencies. However, the choice of these two structures may depend heavily on the dataset and corresponding task.", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Public health actions, such as social distancing, can make people feel isolated and lonely and can increase stress and anxiety. However, these actions are necessary to reduce the spread of COVID-19. \n\nResearch Abstract:\nSocial distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19.\nIn this work we analyze the effect of current social distancing measures in the United States.\nWe quantify the reduction in doubling rate, by state, that is associated with social distancing.\nWe find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\nAt the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases.\nInstead, social distancing has merely stabilized the spread of the disease.\nWe provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing.\nWe also discuss the policy implications of our findings.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\"]}", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nA suspension of cerebellar granule cells was prepared from 10-15 day old ICR mice (Taconic Biotechnology, Inc., Germantown, NY) using the procedures described in previous investigations from our laboratory (Oyama et al., 1996; Carpenter et al., 1997; Boldyrev et al., 2000).", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nOsteosarcoma : the addition of muramyl tripeptide to chemotherapy improves overall survival -- a report from the Children 's Oncology Group . PURPOSE To compare three-drug chemotherapy with cisplatin , doxorubicin , and methotrexate with four-drug chemotherapy with cisplatin , doxorubicin , methotrexate , and ifosfamide for the treatment of osteosarcoma . To determine whether the addition of muramyl tripeptide ( MTP ) to chemotherapy enhances event-free survival ( EFS ) and overall survival in newly diagnosed patients with osteosarcoma . PATIENTS AND METHODS Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments . All patients received identical cumulative doses of cisplatin , doxorubicin , and methotrexate and underwent definitive surgical resection of primary tumor . Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 x 2 factorial design . The primary end points for analysis were EFS and overall survival . RESULTS In the current analysis , there was no evidence of interaction , and we were able to examine each intervention separately . The chemotherapy regimens resulted in similar EFS and overall survival . There was a trend toward better EFS with the addition of MTP ( P = .08 ) . The addition of MTP to chemotherapy improved 6-year overall survival from 70 % to 78 % ( P = .03 ) . The hazard ratio for overall survival with the addition of MTP was 0.71 ( 95 % CI , 0.52 to 0.96 ) . CONCLUSION The addition of ifosfamide to cisplatin , doxorubicin , and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma . The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS .", "role": "user" }, { "content": "{\"Intervention\": [\"receive ifosfamide and/or MTP\", \"muramyl tripeptide ( MTP )\", \"cisplatin , doxorubicin , and methotrexate\", \"four-drug chemotherapy with cisplatin , doxorubicin , methotrexate , and ifosfamide\", \"muramyl tripeptide\"], \"Outcome\": [\"EFS\", \"EFS and overall survival\", \"hazard ratio for overall survival\", \"overall survival\", \"overall survival -- a\", \"6-year overall survival\", \"event-free survival ( EFS ) and overall survival\"], \"Participant\": [\"Children \\u0027s\", \"osteosarcoma\", \"Six hundred sixty-two\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We introduce a unified framework for saliency and co-saliency detection.\n\nKeywords: co-saliency detection images\n\nDataset Information:\nHKU-IS: HKU-IS is a visual saliency prediction dataset which contains 4447 challenging images, most of which have either low contrast or multiple salient objects.\nTweetEval: TweetEval introduces an evaluation framework consisting of seven heterogeneous Twitter-specific classification tasks.\nECSSD: The Extended Complex Scene Saliency Dataset (ECSSD) is comprised of complex scenes, presenting textures and structures common to real-world images. ECSSD contains 1,000 intricate images and respective ground-truth saliency maps, created as an average of the labeling of five human participants.\nSALICON: The SALIency in CONtext (SALICON) dataset contains 10,000 training images, 5,000 validation images and 5,000 test images for saliency prediction. This dataset has been created by annotating saliency in images from MS COCO.\n\nAvailable Datasets: A: HKU-IS B: TweetEval C: ECSSD D: SALICON", "role": "user" }, { "content": "ECSSD", "role": "assistant" } ]

[ { "content": "Consider the following research inquiry and associated key terms. Review the dataset summaries provided and determine which datasets are suitable for addressing the research question. Base your decision on your understanding of machine learning datasets.\nProvide your answer as a JSON list. For example, for the inquiry \"Semi supervised image classification\", a possible response could be: [\"CIFAR-10\", \"CIFAR-100\"]. Ensure the response contains only the dataset names in JSON format.\n\nResearch Inquiry: I want to train an object detector from the ParallelEye dataset.\n\nKey Terms: object detection images\n\nDataset Summaries:\nKITTI: KITTI (Karlsruhe Institute of Technology and Toyota Technological Institute) is one of the most popular datasets for use in mobile robotics and autonomous driving. It consists of hours of traffic scenarios recorded with a variety of sensor modalities, including high-resolution RGB, grayscale stereo cameras, and a 3D laser scanner.\nMOT15: MOT2015 is a dataset for multiple object tracking. It contains 11 different indoor and outdoor scenes of public places with pedestrians as the objects of interest, where camera motion, camera angle and imaging condition vary greatly.\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\nMOT17: The Multiple Object Tracking 17 (MOT17) dataset is a dataset for multiple object tracking. Similar to its previous version MOT16, this challenge contains seven different indoor and outdoor scenes of public places with pedestrians as the objects of interest.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\n\nDataset Options: A: KITTI B: MOT15 C: SNIPS D: MOT17 E: COCO", "role": "user" }, { "content": "[\"KITTI\", \"COCO\"]", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nRandomized controlled trial : Multimodal Anxiety and Social Skill Intervention for adolescents with autism spectrum disorder . Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted .", "role": "user" }, { "content": "{\"Intervention\": [\"Social Skills Intervention ( MASSI ) program\", \"Social Skill Intervention\", \"MASSI\", \"Multimodal Anxiety and\"], \"Outcome\": [\"anxiety symptoms\", \"feasibility\", \"therapist fidelity\", \"ASD social impairment\", \"feasible\", \"preliminary outcomes\", \"subject adherence\"], \"Participant\": [\"ASD\", \"30\", \"ASD and anxiety symptoms\", \"autism spectrum disorder\", \"adolescents\"]}", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Survey on Coexistence in Heterogeneous Wireless Networks in TV White Spaces \nChapter Title: Distributed and Decentralized Approaches for SelfCoexistence of CR Networks. \n1. Abstract of Cited Paper (BIB001): Very recently, regulatory bodies worldwide have approved dynamic access of unlicensed networks to the TV white space (TVWS) spectrum. Hence, in the near future, multiple heterogeneous and independently operated unlicensed networks will coexist within the same geographical area over shared TVWS. Although heterogeneity and coexistence are not unique to TVWS scenarios, their distinctive characteristics pose new and challenging issues. In this paper, the problem of the coexistence interference among multiple heterogeneous and independently operated secondary networks (SNs) in the absence of secondary cooperation is addressed. Specifically, the optimal coexistence strategy, which adaptively and autonomously selects the channel maximizing the expected throughput in the presence of coexistence interference, is designed. More in detail, at first, an analytical framework is developed to model the channel selection process for an arbitrary SN as a decision process. Then, the problem of the optimal channel selection, i.e., the channel maximizing the expected throughput, is proved to be computationally prohibitive (NP-hard). Finally, under the reasonable assumption of identically distributed interference on the available channels, the optimal channel selection problem is proved not to be NP-hard, and a computationally efficient (polynomial-time) algorithm for finding the optimal strategy is designed. Numerical simulations validate the theoretical analysis. \n2. Abstract of Cited Paper (BIB002): IEEE This paper focuses on coexistence and self- coexistence challenges between secondary heterogeneous wireless networks/users sharing TV Whitespace spectrum. The coexistence problems arise from having several primary and secondary networks of different technologies cohabiting the same licensed spectrum simultaneously. The self- coexistence problems arise from many secondary systems /users coexisting at the same place while using identical or different technologies. In particular, fair distribution of available spectrum becomes a serious issue. In this work we use a game theoretic approach to model the self-coexistence problem as a competitive game between secondary networks. We show that our game belongs to the class of congestion-averse games which are known to posses pure Nash Equilibria. This leads us to a decentralized approach for spectrum sharing among systems with different PHY/MAC characteristics. We show that our proposal outperforms other centralized algorithms in terms of user fairness and per-user theoretical data rates.\n\nReview Chapter:", "role": "user" }, { "content": "A game theoretic approach for solving the coexistence problem between cognitive radio networks sharing the same spectrum in the uplink is proposed by Gao et. al. in BIB001 . The problem is formulated as an uplink channel allocation problem, which is further subdivided into two subproblems: the subchannel allocation problem and the transmit power allocation problem. The cognitive radio networks, which in the worst case scenario are controlled by different operators, participate in a noncooperative game in which each CR network independently selects the channels it will use in a way that will maximize their own utilities. The game is played in two levels, where players' solve the subchannel allocation game and then in the second level solve the transmission power problem. The authors note, that the second level game has a Nash equilibrium, which can be reached using algorithms such as iterative water filling. The subchannel allocation game, on the other hand, does not possess the properties which guarantee a Nash equilibrium. The authors propose a practical heuristic algorithm, which does not reach the global optimum, but is more efficient as it does not require global knowledge about all the cells operating in the same space. However, the authors address the coexistence problem only in the uplink and on a single channel basis, assuming all other channels have the same characteristics. Furthermore, they do not consider the presence of heterogeneous networks but rather assume that all secondary networks are of the same type, but belonging to different operators. Therefore, issues arising due to differences in MAC/PHY layers are not addressed. An interference avoidance strategy is proposed in BIB002 which aims to adaptively and autonomously enable the CR networks select the channels so as to maximize the throughput in presence of coexistence interference. The coexistence problem is formulated as an optimal sensing sequence and optimal stopping rule optimization problem, with the objective of maximizing the expected reward, i.e., average throughput achievable by the secondary user in a given time-slot. The algorithm is attractive because it features no cooperation overhead among the various networks, i.e., each network independently selects the TVWS channels to use. However, some of the assumptions are too simplistic, such as the hypothesis of identically and independently distributed coexistence interference levels. Furthermore, the authors compare the performance of the algorithm only to a simple sense-before-talk algorithm in terms of expected average throughput, while the complexity of the algorithm is compared to an exhaustive search solution, which is known to have excessive computational times, especially when considering higher number of available channels. In BIB003 the authors propose a decentralized algorithm to address the problem of self-coexistence in TVWS, between secondary networks of three different types, IEEE 802.22, IEEE 802.11af and IEEE.802.15. They consider the usage of independent mechanisms where there is no central manager for decision-making, no database for information queries and storage and no common physical communication channel between the networks for information exchange. The selfcoexistence and interference mitigation are ensured only based on the individual observations of the secondary users, which means that there is no need to synchronize and coordinate between networks to reach a fair solution. The SCDM algorithm is based on congestion-averse games (CAG) for self-coexistence decision-making in TVWS and addresses the challenges of self-coexistence in terms of fairness and efficiency of resource allocation. For comparative purposes to centralized solutions, the same the game is solved also in centralized manner where the authors assume the presence of a controller with global knowledge who applies the CAG algorithm on behalf of networks.", "role": "assistant" } ]

[ { "content": "Given the full text of a scientific research paper, write an abstract section for the paper. Your response should contain only the abstract without any other text.\n\nArticle text:\na correlation between cr intensity and global lcc was observed for the first time more than 10 years ago @xcite and led to a new direction in science - cosmoclimatology @xcite .\nit is based on the concept of a causal relationship between cr and cc .\nsome arguments against this causality were presented in @xcite .\nthe purpose of this study is to continue further an analysis of possible reasons for the observed correlation between cr and lcc .\nas the input cc data , we took the same observations with weather satellites ( isccp project ) that were used in @xcite .\nwe analysed sky fractions covered by clouds , averaged over observation months ( d2 series ) . in compliance with the isccp cloud height classification made according to the pressure at their upper boundary\n, clouds were separated into low ( lcc,@xmath0680 hpa ) , medium ( mcc , 440 - 680 hpa ) and high ( hcc,@xmath1440hpa ) . because of the ongoing discussion on the calibration quality of isccp radiometers after 1996 @xcite we used both the data obtained earlier , during the 22nd cycle of solar activity ( july 1986 - december 1995 ) , and the complete set of data , till 2005 . for comparison of cc and cr variations we used the data from several neutron monitors of the worldwide network ( thule , apatity , moscow , climax , huancayo )\n+ in an analysis of the latitude dependence of cr and lcc variations we split the entire latitude range ( from @xmath2 to @xmath3 ) into nine equal intervals of @xmath4 width .\nwe also analysed the dynamics of global ( i.e. globe - averaged ) cc .\nto better reveal the cc variations of nontrivial origin , we subtracted the winter - summer seasonal variations from the temporal curves , although in some cases seasonal variations were considered as well .\n, the best fit is @xmath5 ; ( d ) correlation of cr and lcc variations with respect to the average temporal evolution curve - thin smooth lines in figures 1a and 1b ( short - term correlation ) , @xmath6 .\nthe short - dash lines in all panels are the average levels over the period 1986 - 1996 , the long - dash lines in figures 1c and 1d are linear regression lines with a slope @xmath7 , the thin smooth line in fig.1c is the best power - law fit to the scatter plot , and @xmath8 is the correlation coefficient.,width=326 ] figure 1 shows the temporal evolution of ( a ) cr intensity , ( b ) global lcc and ( c ) the correlation of cr and lcc deviations from their means . to illustrate the cr intensity evolution we took as a proxy the data of the climax monitor , which is situated at a latitude of @xmath9 .\nthe cr intensity fluctuations at other latitudes show qualitatively similar temporal behavior , although with different variation amplitudes .\nthe cr and lcc deviations from their means are positively correlated .\nthe linear regression slope is [email protected] and the corresponding correlation coefficient is 0.538 , which confirms the existence of positive correlation between cr and lcc that was found in @xcite .\n+ however , an attempt to understand what is the reason and what is the consequence here failed .\nwe wanted to find a possible time shift between the cr and lcc variations by the method of least squares .\nhowever , it turned out that the sum of squared deviations has a flat broad minimum at a respective shift of the cr and lcc curves from -11 to + 6 months .\nthat is , one can not say which variation is the cause and which is the consequence .\n+ on the assumption that cr are indeed responsible for at least some part of the cc one can use the observed correlation to estimate this part .\nthis estimation depends on the model for the relationship between cr and lcc . with a linear model\n( @xmath11 , where @xmath12 ; @xmath13 and @xmath14 are the cloud coverage and cr intensity respectively ; and @xmath15 and @xmath16 are their mean values ) , the regression slope @xmath17 gives the cc fraction related to cr , to be approximately 16% .\nwithin two standard deviations this fraction should not exceed 20% .\nhowever , a least - squares estimation of the parameters @xmath18 and @xmath19 shows that the relation between cr and lcc is most likely non - linear .\nwe obtained the values @xmath20 and @xmath21 ( thin solid line in fig.1c ) .\nthis shows that the most likely cc fraction related to cr does not exceed 2% .\n+ the above conclusion is valid only if the models of relationship between cr and lcc are correct and the cr variations at the climax latitude , @xmath22 , adequately describe the global variation picture . for @xmath23 the cc fraction which positively correlates with cr\ncan be much higher .\nunfortunately , because of the relatively small magnitude of cr and lcc variations one can not reliably estimate the parameter @xmath19 and thus evaluate more precisely the positively correlated cc fraction .\nalthough the method of least squares is more adequate at @xmath24 , in the domain of available experimental data ( fig.1c ) the behavior of the curves for different values of @xmath19 is similar , as well as the corresponding sums of the squared deviations .\nfigure 1 and the analysis given in the previous section concern the total variations of cr and lcc relative to their average values . the main contribution to these variations is from the long - term variations related to the 11-year solar activity cycle . to reveal possible correlations in short - time cr and lcc variations\n, we excluded the contribution from long - term variations . for this purpose\nwe approximated the temporal evolution of cr and lcc by a fifth - order polynomial ( smooth solid lines in figures 1a and 1b ) and calculated deviations from this approximation . because we used the monthly averaged d2-series data , this analysis is related to monthly variations .\nwe did not find any statistically significant correlations between the cr intensity and global lcc .\nthe estimated regression line slope is @xmath25 and the corresponding correlation coefficient is -0.090 ( fig.1d ) .\nthis negative result is in indirect agreement with the absence of even shorter ( few days ) correlations ( forbush decreases , cr ground - level enhancements ) pointed out in @xcite . because the cr intensity depends on the latitude it is reasonable to analyse the variation of cc characteristics with latitude .\nfigure 2a shows the latitude dependence of lcc , mcc and hcc .\nit is seen that there is a small minimum for lcc in the equatorial region , which could be connected with the reduction of cr intensity , but it is not confirmed by the local maxima in mcc and hcc . in polar regions , where the cr intensity is the highest , there is an opposite decrease of lcc , which apparently is connected with the dominant influence of the atmospheric conditions , eg\n. low temperatures .\nthe highest lcc is in the southern latitude bands with the largest part of the area occupied by oceans , i.e. with a relatively large density of water vapor .\n+ the altitude dependence of cc does not correspond to the altitude dependence of the cr intensity : a further bad feature .\nin most of the latitude bands , mcc and hcc are smaller than lcc , which is opposite to cr with their intensity rising with height .\nall this shows that even if there is a causal connection between cr and lcc , its character is more complicated than a direct and positive correlation .\n+ we have already mentioned that the global lcc - cr correlation is positive : @xmath26 .\nfigure 2b shows the latitude dependence of the cc - cr correlation coefficient . here\nagain we used as a proxy of the cr temporal variations just the neutron counting rate at climax . in spite of the latitude dependence of the cr variation amplitude ,\nthe value of the lcc - cr correlation coefficient does not depend on this amplitude due to the similarity of the temporal behavior of cr variations at different latitude bands .\nit is remarkable to note that in most latitude bands , mcc and hcc have negative correlation with cr in contrast to the positive lcc - cr correlation which was the main argument for the claimed causal cr - cc connection @xcite .\nfigure 3 shows the latitude dependence of the sensitivity and correlation between mcc and lcc . the sensitivity of one variable to another , according to the definition @xcite , is the derivative of the first variable on the second in log - coordinates . in our case\nthe sensitivity is the slope of the linear regression line @xmath7 in the mcc - lcc plot .\none can notice two features : + ( i ) the sensitivity of mcc to lcc and mcc - lcc correlation coefficient are negative at all latitudes , which is another support of their global anticorrelation .\nthe negative sensitivity of mcc to lcc is difficult to explain in the framework of the causal connection between cc and cr , since the rise of the cr intensity has to change cc similarly at all altitudes ; + ( ii ) the highest negative sensitivity and the correlation between mcc and lcc is observed in tropical and subtropical regions @xmath27 as well as in southern latitude bands with the highest fraction of water : @xmath28 .\nin our opinion the analysis performed here , as well as our previous arguments @xcite , gives grounds to assert that cr are not the dominant factor leading to cc formation .\nthe negative correlation of lcc and mcc , most prominent in the tropics and subtropics and at the latitudes where one can expect excess water vapor formation , allows one to turn to the traditional picture describing the main reasons for cloud formation that are connected with solar activity .\n+ solar radiation increases together with the number of sunspots in the middle of the solar cycle .\nthis radiation is strongest in the tropics and subtropics .\nalthough the relative increase in radiation intensity is insignificant ( @xmath290.1% ) , it leads to an increase in the average ground - level temperature and enhances vertical convective flows of heated air .\nsince the cloud height in the isccp experiment is classified according to the pressure at the upper cloud boundary , the convective lift of clouds to higher altitudes leads to a redistribution of the assigned altitudes .\nthat is , it decreases lcc and increases mcc , which is reflected in the negative correlations of lcc and mcc .\nthus , an increase in convective flows leads to a significant strengthening ( @xmath292% ) of the effect of increased solar radiation . +\nalong with the periodic variations of the ground - level earth s temperature , related to the periodicity of solar cycles , a systematic temperature increase due to global warming was observed in the last century .\nthe warming was particularly strong during the last two decades .\nfigure 4a shows the average temperature growth , and figures 4b-4d demonstrate the temporal evolution of hcc , mcc and lcc , respectively .\none can see both periodic and systematic variations of mcc and lcc , which are negatively correlated .\nthe data on the graphs suggest that the tendency of lcc reduction , which appeared after 1995 @xcite is not due to malfunctioning of the weather satellite equipment but due to a global warming of the earth s climate .\n+ summing up , one can state that with an increase in the ground - level earth s temperature during solar activity maxima or general global warming , the average cc height becomes somewhat greater .\nthis effect is most prominent in the tropics , subtropics and above the surface of the ocean .\nthe simultaneous reduction of lcc and of cr intensity is not evidence for a causal relationship between these two phenomena .\nthey correlate due to the presence of a common driving force : changes in solar activity .\n+ _ acknowledgments _\n+ k.kudela wishes to acknowledge the vega grant agency , project 2/7063/27 .\na.d.erlykin acknowledges the support of the john c. taylor charitable foundation and is grateful to e.a.vashenyuk for granting access to the apatity neutron monitor data and to s.p.perov for useful discussions .\n99 svensmark h. and friis - christensen e. , 1997 , j. atm .\nsolar - terr .\nphys . , 59 , 1225 palle bago , e. and butler c.j . , 2000 , 41 , 4 svensmark h. , 2007 , news rev .\ngeophys . , 48 , 118 sloan t. and wolfendale a.w.,2008 , environ .\nlett . , 3 , 024 001(6pp ) marsh n. and svensmark h. , 2003 , space sci .\n, 107 , 317 kristjnsson et al . , 2008 , atm .\n, 8 , 7373 uchaikin v.v . and ryzhov v.v . ,\n1988 , stochastic theory of the transport of high - energy particles , novosibirsk , nauka ( in russian ) , p.144", "role": "user" }, { "content": "various aspects of the connection between cloud cover ( cc ) and cosmic rays ( cr ) are analysed . \n we argue that the anticorrelation between the temporal behaviour of low ( lcc ) and middle ( mcc ) clouds evidences against the causal connection between them and cr . \n nevertheless , if a part of low clouds ( lcc ) is connected and varies with cr , then its most likely value averaged over the globe should not exceed 20% at the two standard deviation level . \n correlation , cosmic rays , clouds", "role": "assistant" } ]

[ { "content": "Analyze the following text to identify specific entities. Focus on the categories provided: [\"Chemical\", \"Protein\"].\n\nDeliver your findings as a JSON structure: {\"Chemical\": [\"ExampleChemical\", ...], \"Protein\": [\"ExampleProtein\", ...]}. Each key represents an entity type, and the associated list contains the entities found. \n\nEnsure the response is strictly the JSON format without any extra text.\n\nSource:\n\nInborn errors in the metabolism of glutathione.\nGlutathione is a tripeptide composed of glutamate, cysteine and glycine. Glutathione is present in millimolar concentrations in most mammalian cells and it is involved in several fundamental biological functions, including free radical scavenging, detoxification of xenobiotics and carcinogens, redox reactions, biosynthesis of DNA, proteins and leukotrienes, as well as neurotransmission/neuromodulation. Glutathione is metabolised via the gamma-glutamyl cycle, which is catalyzed by six enzymes. In man, hereditary deficiencies have been found in five of the six enzymes. Glutathione synthetase deficiency is the most frequently recognized disorder and, in its severe form, it is associated with hemolytic anemia, metabolic acidosis, 5-oxoprolinuria, central nervous system (CNS) damage and recurrent bacterial infections. Gamma-glutamylcysteine synthetase deficiency is also associated with hemolytic anemia, and some patients with this disorder show defects of neuromuscular function and generalized aminoaciduria. Gamma-glutamyl transpeptidase deficiency has been found in patients with CNS involvement and glutathionuria. 5-Oxoprolinase deficiency is associated with 5-oxoprolinuria but without a clear association with other symptoms. Dipeptidase deficiency has been described in one patient. All disorders are very rare and inherited in an autosomal recessive manner. Most of the mutations are leaky so that many patients have residual enzyme activity. Diagnosis is made by measuring the concentration of different metabolites in the gamma-glutamyl cycle, enzyme activity and in glutathione synthetase and gamma-glutamylcysteine synthetase deficiency, also by mutation analysis. Prenatal diagnosis has been preformed in glutathione synthetase deficiency. The prognosis is difficult to predict, as few patients are known, but seems to vary significantly between different patients. The aims of the treatment of glutathione synthesis defects are to avoid hemolytic crises and to increase the defense against reactive oxygen species. No treatment has been recommended for gamma-glutamyl transpeptidase, 5-oxoprolinase and dipeptidase deficiency.", "role": "user" }, { "content": "{\"Chemical\": [\"oxygen\", \"cysteine\", \"Glutathione\", \"glycine\", \"Gamma-glutamyl\", \"glutamate\", \"gamma-glutamyl\", \"Gamma-glutamylcysteine\", \"leukotrienes\", \"tripeptide\", \"glutathione\", \"gamma-glutamylcysteine\"], \"Protein\": [\"5-Oxoprolinase\", \"gamma-glutamyl transpeptidase\", \"gamma-glutamylcysteine synthetase\", \"dipeptidase\", \"Dipeptidase\", \"glutathione synthetase\", \"Gamma-glutamylcysteine synthetase\", \"Gamma-glutamyl transpeptidase\", \"Glutathione synthetase\", \"5-oxoprolinase\"]}", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nliving donor kidney transplantation is the treatment of choice for patients with end - stage renal failure for several reasons .\nthe transplant is performed when the donor and the recipient are in optimum medical condition and at a time that is convenient for them and for their families .\nmoreover , recipients of living donor kidney grafts enjoy greater long - term graft survival and a better quality of life than do recipients of cadaveric kidney grafts .\nit reduces the number of patients on the wait list for a cadaveric kidney and therefore increases the likelihood that patients with no potential living donor can undergo transplantation .\nthis is particularly important because the gap between the number of cadaveric donors and the number of patients on the waiting list is increasing due to significant reduction in traffic accidents as well as the promotion of more healthy lifestyles with emphasis on exercise and improved dietary habits and the subsequent reduction in the incidence of stroke .\nan increase in the number of living donors ( including living - unrelated donors ) may ameliorate this trend .\nalmost all studies that report medical outcomes of living kidney donors more than a year from donation are retrospective .\nalthough practical for evaluation of long - term outcomes , retrospective studies are vulnerable to certain methodological pitfalls and biases that may limit their interpretability .\nmost important is the potential for selection bias , which may alter findings if there is a difference between included and nonincluded donors either as a result of non - participation or because the study investigators are unable to locate the subject . in studies that follow living kidney donors , donors in good health may be more likely to participate because of greater survival or greater ability to meet the requirements of participation .\nthe aim of this study is to evaluate the impact and safety of kidney donation on living kidney donors in a prospective fashion .\ndonors included in this study were male or female and donors were of a minimum of 21 years and a maximum of 65 years of age .\ndonor has been fully informed and has given written informed consent . while criteria for exclusions were donor has hypertension or diabetes mellitus , donor is pregnancy or breastfeeding , donor is known to be hcv , hbv , and hiv positive , donor has significant liver disease , defined as having during the past 28 days continuously elevated ast and/or alt levels 3 times greater than the upper value of the normal range of the investigational site , donor with malignancy or history of malignancy , or active systemic or localized major infection , donor is participating or has participated in another clinical trial , evidence of infiltrate , cavitation or consolidation on x ray obtained during the screening / baseline evaluation , subjects with a screening / baseline hemoglobin < 11 gm / dl , total white blood cell count 2,000/mm , and platelet count 100000/mm , fasting triglycerides 400 mg / dl , or fasting total cholesterol 300 mg / dl . in this prospective study , the outcome of 81 consecutive living kidney donors , who donated their kidneys between december 2007 and november 2008 in our center , was thoroughly evaluated .\nclinical , laboratory , and radiological assessments were carried out at pre - donation ( basal ) , 3 , 6 , 12 , and 24 months after donation qualitative data were displayed in cross tabulation and quantitative data were described in terms of arithmetic mean sd .\nthe mean age at time of donation was 37.8 9.8 years ( range : 2264 years ) and the majority were females ( 61 , 75.3% ) .\nthey were 45 parents ( 37 mothers ) , 28 siblings ( 19 sisters ) , and 8 emotionally related ( 5 wives ) .\nthere were no significant differences between the means of systolic and diastolic blood pressures while 4 donors out of the 81 donors developed mild hypertension which was easily controlled on one antihypertensive drug ( table 1 ) .\nthe mean serum creatinine levels increased significantly in the first three months after donation and afterwards it decreased significantly till the end of the observation period .\nlikewise , the mean levels of both measured and estimated creatinine clearance either by cockcroft and gault equation or by mdrd decreased significantly in the first three months after donation afterwards it increased significantly till the end of the study .\nthe urinary protein excretion estimated either by 24 hours urine collection or protein creatinine ratio increased significantly in the first three months after donation and afterwards it stabilized over the remaining period of the study ( table 2 ) . after donation , biochemical changes over the first 24 months ( table 3 )\nthere was significant increase in the levels of the serum uric acid three months after donation , which was stabilized afterwards .\nthe blood sugar , serum calcium , phosphorus , liver enzymes alt , ast , total protein , serum albumin , and bilirubin remained within normal levels throughout the observational period .\nthere were modest increases in the levels of the serum triglycerides and cholesterol after donation .\nthere was a significant increase in the means of the longitudinal diameter ( cm ) of the remaining kidney at basal , 3 , 6 , 12 , and 24 months 10.93 0.88 , 11.53 0.9 , 11.55 0.79 , 11.67 0.73 , 11.79 0.76 , respectively ( p < 0.001 ) . also , transverse diameters ( cm ) of the left kidney increased significantly over time 4.21 0.59 , 4.51 0.62 , 4.54 0.64 , 4.61 0.58 , and 4.84 0.50 , respectively ( p < 0.001 ) . out of 42 female donors , eleven have got successful post donation pregnancies .\nalthough practical for evaluation of long - term outcomes , retrospective studies are vulnerable to certain methodological pitfalls and biases that may limit their interpretability .\nthe policy in the urology and nephrology center , mansura university , egypt , is to perform kidney transplantation from related donors .\nstrict ethical policies and rules of the international community were strictly followed to ensure the protection and safety of living donors and appropriate recognition for their heroic act while combating transplant tourism , organ trafficking , and transplant commercialism . in this study , most of the donors were female ( 75.3% ) , and this in accordance with that reported previously by biller - andorno , 2002 , being approximately 65% of live kidney donors , were women and approximately 65% of recipients were men .\nthis perhaps is reflecting a psychological submission or discrimination of women in many countries , including western nations . in our study , most of the donors were mothers , sisters , and wives and this could explain the predominance of female donors .\nfurthermore , since it is reported that the incidence of end stage renal disease is more frequent among males this may partly explain why there are more wives than husbands who donate in the case of transplants between spouses .\nall our donors except four enjoyed normal blood pressure throughout the observational period and the hypertension was mild and easily controlled with single antihypertensive agent .\nthe majority of the studies that assess hypertension in living kidney donors were retrospective and did not include control groups that were assembled and followed along with donor controlled studies in which the average follow - up was at least [ 7 , 8 ] . years after donation ( range : 6 to 13 years ) , blood pressure was 5 mm hg higher in donors than in control participants .\nit is worth to mention that the age of these donors was above fifty and developed progressive increase in body weight after donation which makes them vulnerable to develop hypertension . in this study ,\nlikewise , the mean levels of measured and estimated creatinine clearance follow the same pattern of improvement . samhan and omar , 1999 , studied the early changes in kidney function following live kidney donation .\nthey reported an immediate and significant increase in effective renal plasma flow ( erpf ) of the remaining kidney .\nthe median value increased from 50.4% to 90% of the preoperative total erpf at 3 months after donation .\nthe median levels of serum creatinine concentrations increased by 30% in comparison with the prenephrectomy level likewise the median values of creatinine clearance at 3 months after the donor nephrectomy dropped down to 76% of the prenephrectomy value .\nreviewed studies which reported gfr in categories , 12% of donors developed a gfr between 30 and 59 ml / min ( range : 028% ) , and 0.2% a gfr less than 30 ml / min ( range : 02.2% ) .\nan initial decrease in gfr after donation was not accompanied by accelerated losses over that anticipated with normal aging .\nan initial decrease in gfr is not followed by accelerated losses over a subsequent 15 years .\nfuture studies will provide better estimates and identify those donors at least risk of long - term morbidity . in our study\n, there was a compensatory hypertrophy of the remaining kidney evidenced by increase in the both longitudinal and transverse diameters of the remaining kidney overtime during the observational period .\nin accordance to our results , bohlouli et al . , 2010 , reported that remnant kidney length , anterior - posterior diameter , and cortical thickness were significantly increased during postnephrectomy follow - up .\nthis compensatory hypertrophy could explain the improvement of kidney function which starts to occur at the end of the study .\nprevious reports showed that there were no significant changes . in urinary protein in the first three months after donation , these results in contrary to our results and may due to progressive and significant increase in the bmi in among our donors . it is reported that , after nephrectomy , there is a compensatory hemodynamic change ; also there has been a concern that kidney donors ( who undergo a 50% reduction in renal mass with donation ) might have compensatory glomerular hyperfiltration and hypertrophy .\n, 2006 , reviewed forty - eight studies from 27 countries followed a total of 5048 donors .\nan average of 7 years after donation ( range : 125 years ) , the average 24 hours urine protein was 154 mg / day so kidney donation results in small increases in urinary protein .\nthe donor who developed postdonation hyperglycemia was a 48-year - old mother , who showed a predonation normal glucose tolerance curve and developed postdonation progressive increase in body weight , beside her positive family history for diabetes mellitus .\nboudville and isbel , 2010 , reported that this incidence of postdonation dm ranging from 1.7 : 7.4% with a follow - up of more than 20 years in some studies .\nibrahima and associates reported that kidney donors , similar to the general population , are at risk for development of type 2 diabetes mellitus ( t2 dm ) .\nof the 2954 who responded , 154 developed t2 dm 17.7 9.0 years after donation .\nthe multivariable risk of development of t2 dm was associated with type 1 dm in the recipient , male gender , and body mass index > 30 kg / m at time of donation .\nthese preliminary and short - term data demonstrate that factors associated with t2 dm in kidney donors are similar to those in the general population and donors screened carefully at the time of donation do not appear to have an acceleration diabetic kidney disease .\nsignificant increases in the levels of serum uric acid in the first three months after donation were reported in our donors , which could be explained by the mild transient impaired renal function in the early postdonation period . in the current study ,\nthere was a significant increase in the mean levels of serum triglycerides which was stabilized afterwards .\non the other hand , there were no significant differences in the mean levels of serum total cholesterol , ldl , or hdl in the first three months , but their levels showed significant increase at 3 , 6 , 12 , and 24 months . according to tavakol et al . , 2009 ,\nthis could explain the increase of serum lipids among our donors who developed postdonation significant increase in body mass index .\nit is worth mentioning that 11 female donors have got successful postdonation pregnancies . in accordance ,\nibrahim et al . , 2009 , reported that pregnancy in kidney donors has generally been viewed to be favorable and determined fetal and maternal outcomes in a large cohort of kidney donors . in accordance to our study , ibrahim and\ntheir colleagues , 2009 , stated that a total of 2102 women have donated a kidney at their institution : 1589 donors responded to pregnancy surveys , 1085 reported pregnancies , and 504 reported none . in this large survey of previous living donors in a single center , fetal and maternal outcomes and pregnancy outcomes after kidney donation were similar to those reported in the general population .\nobese potential live kidney donors should be advised to maintained ideal body weight in order to avoid proteinuria , hypertension , and diabetes mellitus .\nproteinuria increases with marginal significance but appears to be of no clinical consequence . despite the reduction in gfr in the early post donation period ,\nalthough living kidney donation is a safe procedure which carries a minimal risk in comparison with the heroic act and the major benefits for the transplant recipients , the proper selection and the pretransplant assessment of the potential kidney donors together with postdonation meticulous and regular ( lifelong ) follow - up is strongly recommended .\nfuture controlled , prospective studies with long periods of follow - up will better delineate safety and identify donors at lowest risk for long - term morbidity .\na world registry of living donors is necessary to evaluate the real magnitude of the long - term risk to living donors .", "role": "user" }, { "content": "virtually , all studies reporting the outcomes of living kidney donation beyond the first year from donation were retrospective . in this prospective study , \n the outcome of 81 consecutive living kidney donors was thoroughly evaluated . \n clinical , laboratory , and radiological assessments were carried out at predonation ( basal ) , 3 , 6 , 12 , and 24 months after donation . \n the mean age at time of donation was 37.8 9.8 years and the majority was females ( 75.3% ) . \n the mean bmi increased significantly after donation ( p < 0.04 ) . \n the mean serum creatinine levels ( mg / dl ) were 0.75 0.14 , 1.01 0.22 , 0.99 0.21 , 0.98 0.20 , and 0.94 0.20 ( p < 0.0001 ) . \n likewise , the mean levels of measured creatinine clearance ( ml / min ) were 148.8 35.7 , 94.7 26.6 , 95.5 24.6 , 96.7 20.2 , and 101.6 26.2 ( p < 0.0001 ) . the mean \n 24 hours urinary protein excretion ( gm / dl ) were 0.09 0.03 , 0.19 0.18 , 0.16 0.09 , 0.18 0.25 , and 0.17 0.12 ( p < 0.0001 ) . \n there were significant increases in the means of the longitudinal and transverse diameters of the remaining kidney over time ( p < 0.001 ) . out of 42 female donors , eleven female donors have got successful postdonation pregnancies . there were no reported surgical complications , either intra- or postoperative . \n long - term follow - up is necessary for all living kidney donors through local institutional and world registries . \n this trial is registered with clinicaltrials.gov nct00813579 .", "role": "assistant" } ]

[ { "content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which key gene is involved in interstitial 6q25 microdeletion syndrome?\n\nPassages: Interstitial 6q25 microdeletion syndrome: ARID1B is the key gene.\nInterstitial deletions of the long arm of chromosome 6 are rare. Clinically, these deletions are considered to be part of a unique microdeletion syndrome associated with intellectual disability and speech impairment, typical dysmorphic features, structural anomalies of the brain, microcephaly, and non-specific multiple organ anomalies. The critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It has been hypothesized that haploinsufficiency of these genes impairs normal development of the brain and is responsible for the phenotype. This case report describes a girl presenting with typical features of 6q microdeletion syndrome, including global developmental delay, speech impairment, distinct dysmorphic features, dysgenesis of the corpus callosum, common limb anomalies, and hearing loss. Chromosome analysis by array-CGH revealed a small interstitial 6q deletion spanning approximately 1.1 Mb of DNA and containing only one coding gene, ARID1B. We suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations.\nWe suggest that ARID1B is the key gene behind 6q microdeletion syndrome, and we discuss its possible role in the phenotypic manifestations.\nInterstitial 6q25 microdeletion syndrome: ARID1B is the key gene\nitical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14. It ha\nThe critical region for the interstitial 6q microdeletion phenotype was mapped to 6q24-6q25, particularly the 6q25.3 region containing the genes ARID1B and ZDHHC14.", "role": "user" }, { "content": "ARID1B", "role": "assistant" } ]

[ { "content": "Analyze the provided text to identify gene-related entities. \n\nFormat your findings as a JSON object: {\"Gene\": [\"ExampleGene\", ...]}. Use the entity type as the key, and list the entities under it. If no entities are found, use an empty list.\n\nFocus solely on the JSON output.\n\nText:\n\nThe eta7/csn3-3 auxin response mutant of Arabidopsis defines a novel function for the CSN3 subunit of the COP9 signalosome. The COP9 signalosome (CSN) is an eight subunit protein complex conserved in all higher eukaryotes. In Arabidopsis thaliana, the CSN regulates auxin response by removing the ubiquitin-like protein NEDD8/RUB1 from the CUL1 subunit of the SCF(TIR1/AFB) ubiquitin-ligase (deneddylation). Previously described null mutations in any CSN subunit result in the pleiotropic cop/det/fus phenotype and cause seedling lethality, hampering the study of CSN functions in plant development. In a genetic screen to identify enhancers of the auxin response defects conferred by the tir1-1 mutation, we identified a viable csn mutant of subunit 3 (CSN3), designated eta7/csn3-3. In addition to enhancing tir1-1 mutant phenotypes, the csn3-3 mutation alone confers several phenotypes indicative of impaired auxin signaling including auxin resistant root growth and diminished auxin responsive gene expression. Unexpectedly however, csn3-3 plants are not defective in either the CSN-mediated deneddylation of CUL1 or in SCF(TIR1)-mediated degradation of Aux/IAA proteins. These findings suggest that csn3-3 is an atypical csn mutant that defines a novel CSN or CSN3-specific function. Consistent with this possibility, we observe dramatic differences in double mutant interactions between csn3-3 and other auxin signaling mutants compared to another weak csn mutant, csn1-10. Lastly, unlike other csn mutants, assembly of the CSN holocomplex is unaffected in csn3-3 plants. However, we detected a small CSN3-containing protein complex that is altered in csn3-3 plants. We hypothesize that in addition to its role in the CSN as a cullin deneddylase, CSN3 functions in a distinct protein complex that is required for proper auxin signaling.", "role": "user" }, { "content": "{\"Gene\": [\"RUB1\", \"NEDD8\", \"cullin deneddylase\", \"TIR1\", \"COP9\", \"csn1\", \"CUL1\", \"SCF(TIR1/AFB) ubiquitin-ligase\", \"csn3\", \"tir1\", \"csn\", \"CSN\", \"ubiquitin-like protein\", \"CSN3\"]}", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: Proper Vitamin D Levels May Reduce Coronavirus Complications\n\nResearch Abstract:\nThe severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation.\nA principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs).\nTreg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation.\nLow vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections.\nVitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19.\nVitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes.\nThese conditions are reported to carry a higher mortality in COVID-19.\nIf vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.", "role": "user" }, { "content": "{\"verdict\": \"SUPPORT\", \"evidence\": [\"A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs).\", \"Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation.\", \"Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections.\", \"Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19.\", \"Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes.\", \"These conditions are reported to carry a higher mortality in COVID-19.\", \"If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.\"]}", "role": "assistant" } ]

[ { "content": "Given the following biomedical passages, answer the question succinctly. Ensure your response is precise and limited to the answer only.\n\nQuestion: Which properties of the mRNA does N6-methyladenosine (m6A) affect?\n\nPassages: N(6)-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate.\nm(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts.\nRecent discoveries of reversible N(6)-methyladenosine (m(6)A) methylation on messenger RNA (mRNA) and mapping of m(6)A methylomes in mammals and yeast have revealed potential regulatory functions of this RNA modification\nMonitoring m6A levels upon WTAP depletion allowed the definition of accurate and near single-nucleotide resolution methylation maps and their classification into WTAP-dependent and -independent sites. WTAP-dependent sites are located at internal positions in transcripts, topologically static across a variety of systems we surveyed, and inversely correlated with mRNA stability, consistent with a role in establishing \"basal\" degradation rates.\nMethylations of adenosine residues (m6A) in pre-mRNA are important for formation of late simian virus 40 mRNAs\nThe data argues for a role of internal m6A moieties in modulating the processing-linked transport of mRNA from the nucleus to the cytoplasm of nontransformed cells.\nN6-Methyladenosine (m6A) residues, which are found internally in viral and cellular mRNA populations at the sequences Apm6ApC and Gpm6ApC, have been proposed to play a role in mRNA processing and transport.\nThe role of Fat Mass and Obesity-associated protein (FTO) and its substrate N6-methyladenosine (m6A) in mRNA processing and adipogenesis remains largely unknown.\nN6-methyladenosine (m6A) is a common modification of mRNA with potential roles in fine-tuning the RNA life cycle.\nThe results of that study and of experiments using inhibitors of methylation suggest that m6A might be involved in mRNA processing events.\nPrevious studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known.\nThe methylation of internal adenosine residues in eukaryotic mRNA, forming N6-methyladenosine (m6A), is catalyzed by a complex multicomponent enzyme. Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known.\nPrevious studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known. As a step toward better understanding the mechanism and function of this ubiquitous posttranscriptional modification, we have shown that HeLa mRNA (N6-adenosine)-methyltransferase requires at least two separate protein factors, MT-A and MT-B, and MT-A contains the AdoMet binding site on a 70-kDa subunit (MT-A70).\nThe methylation of internal adenosine residues in eukaryotic mRNA, forming N6-methyladenosine (m6A), is catalyzed by a complex multicomponent enzyme. Previous studies suggested that m6A affects the efficiency of mRNA processing or transport, although the mechanism by which this occurs is not known.", "role": "user" }, { "content": "mRNA stability", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nWe introduce the concept of channel aggregation in ConvNet architecture, a novel compact representation of CNN features useful for explicitly modeling the nonlinear channels encoding especially when the new unit is embedded inside of deep architectures for action recognition.\nThe channel aggregation is based on multiple-channels features of ConvNet and aims to be at the spot finding the optical convergence path at fast speed.\nWe name our proposed convolutional architecture “nonlinear channels aggregation networks (NCAN)” and its new layer “nonlinear channels aggregation layer (NCAL)”.\nWe theoretically motivate channels aggregation functions and empirically study their effect on convergence speed and classification accuracy.\nAnother contribution in this work is an efficient and effective implementation of the NCAL, speeding it up orders of magnitude.\nWe evaluate its performance on standard benchmarks UCF101 and HMDB51, and experimental results demonstrate that this formulation not only obtains a fast convergence but stronger generalization capability without sacrificing performance.\nWith modern learnable representations such as deep convolutional neural networks (CNNs) matured in many image understanding tasks BID7 , human action recognition has received a significant amount of attentions BID11 BID2 BID9 BID3 BID12 .\nDue to the fact that video itself provides an additional temporal clue and that the parameters and the calculations of CNNs grow exponentially, training CNNs with such large-scale parameters in video domain is time-consuming.\nHowever, it remains unclear how the effective convergence accelerators could be conducted for the optimal path by formulizing the handcrafted rules.\nSince videos consist of still images, training tricks and methods, such as Relu, BN, have been shown to transfer to videos directly.\nRecent theoretical and empirical works have demonstrated the importance of quickly training deep architectures successfully, and the effective convergence accelerators advanced in the 2D image, such as relu BID4 and batch normalization BID5 , have been developed for fast convergence.\nThis is in part inspired by observations of the limited GPU memory and computing power, especially when confronting the large-scale video dataset which may introduce a large majority of parameters.\nAnother pipeline of algorithms focuses on the training optimizer of CNNs, for examples, sgd, momentum, nesterov, adagrad and adadelta.\nHowever, training CNNs utilizing the large-scale video datasets is still nontrivial in video task, particularly if one seeks a compact but fast long termporal dynamic representation that can be processed efficiently.Our current work reconsiders the means of facilitating convergence of ConvNets to increase the understanding of how to embed some hand-crafted rules inside of CNNs for fast convergence in a more thorough fashion.\nIn addition to the accelerators and effective optimizers, we tend to explore a thorough method causing the value of the loss function to descend rapidly.\nIntuitively, we argue that CNNs will accelerate training process once the complex relationship across convolutional features channels is modeled, explicitly, by the hand-crafted rules.\nIn the existing units 3D convolution implements a linear partial sum of channels BID6 , 3D max-pooling takes the maximum feature by channels and 3D average-pooling make a spatial-channel average of features.\nUnfortunately, all the 3D units conduct a linear channels aggregation, implicitly and locally.\nDespite that the implicit linear aggregation has been applied to broad fields, there seems to be less works explicitly taking modeling the complex nonlinear relationship across channels into account.\nIn fact, either one-stream or two-stream algorithms ignore the channel-level encoding.\nFor video recognition task, a very tricky problem is how to train the CNN architectures for the sake of making a lower loss rapidly in the scarcity of videos.\nWe conjecture that there is complex nonlinear relationship among the channels of CNN features.\nOnce this implicit relationship is explicitly modeled, such accomplishment will facilitate converging with faster search to the optimal trajectory.In this paper, we proposed a nonlinear channels aggregation layer (NCAL), which explicitly models the complex nonlinear relationships across channels.\nSince a standard CNN provides a whole hierarchy of video representations, the first question worthy exploring is where the NACL should take place.\nFor example, we can aggregate the output of the fully-connected layers of CNN architecture pre-trained on videos.\nA drawback of such implementation is that the convolutional features channels of CNN itself are still implicitly encoded and are unaware of the lower level channels relationship.\nThe alternative is to model the nonlinear channels aggregation of some intermediate network layer.\nIn this case, the lower layers fail to extract the representative features from video sequences, but the upper layers can reason about the overall dynamics in the video.\nThe former is prone to sacrificing the recognition performance while the latter is thus thought of as the appropriate convolutional features for the compact aggregation.\nHere we build our methods on top of the successful Inception V1 architecture.\nMore specifically, three main contributions are provided in this work.\nOur first contribution is to introduce the concept of nonlinear channels aggregation for fast convergence.\nWe also show that, in this manner, it is possible to apply the concept of nonlinear channels aggregation to the intermediate layers of a CNN representation by constructing an efficient nonlinear channels aggregation layer (NCAL).Here\nwe build our methods on top of the successful Inception V1 architecture. More\nspecifically, three main contributions are provided in this work. Our\nfirst contribution is to introduce the concept of nonlinear channels aggregation for fast convergence. We\nalso show that, in this manner, it is possible to construct an efficient nonlinear channels aggregation by applying the concept of nonlinear channels aggregation to the intermediate layers of the standard CNN. More\nimportantly, it is explicitly and globally that the nonlinear channels relationship is modeled compared to the traditional local and implicit units.Our second contribution is to simplify the process of nonlinear channels aggregation layer (NCAL) and make a fast yet accurate implementation of it. Notably\n, the proposed NCAL can be embodied inside of any standard CNN architectures, and not break the rest components of structures. More broadly\n, the proposed NCAL is not limited to action recognition, that is, it can be applied to any task with CNNs. Here we introduce\nit into action recognition, and leave the explorations of it on the other domains in the future.Our third contribution is to leverage these ideas to construct a novel nonlinear channels aggregation network, perform the training process end-to-end. We show that such\nnonlinear channels encoding results in a fast decline in the value of the loss function of CNNs while obtains efficient and accurate classification of actions in videos.The rest of the paper is organized as follows: Section 2 describes the related works, and section 3 represents the principle of the nonlinear channels aggregation networks (NCAN) and the backward propagation of NCAN. This is followed\nby the experiments in section 4. Finally, we conclude\nthis paper in Section 6.\nWe present nonlinear channels aggregation, a powerful and new, yet simple concept in the context of deep learning that captures the global channels relationship.\nWe introduce a novel nonlinear channels aggregation layer (NCAL) and make a fast yet accurate implementation of NCAL, which allows us to embed the principle of complex channels encoding to the mainstream CNN architectures and back-propagate the gradients through NCALs.\nExperiments on video sequences demonstrate the effective power of nonlinear channels aggregation on facilitating training CNNs.In this paper we fit the complex channels relationships by capturing the global channels aggregation.\nStill, there seems to be some possible research directions that can be further expanded, modeling the nonlinear functions across channels.\nIn the future it is beneficial to explore multiple-scale channel-levels by pyramid coding across channels.\nIn sublimation, we can embed any hand-crafted rules, channels aggregation in the mainstream architectures, to making CNN working as we expect.", "role": "user" }, { "content": "An architecture enables CNN trained on the video sequences converging rapidly", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: I want to design an agent that can take a photo and a text query and generate\n\nKeywords: conversational image editing images text\n\nDataset Information:\nConvAI2: The ConvAI2 NeurIPS competition aimed at finding approaches to creating high-quality dialogue agents capable of meaningful open domain conversation. The ConvAI2 dataset for training models is based on the PERSONA-CHAT dataset.\nCOCO: The MS COCO (Microsoft Common Objects in Context) dataset is a large-scale object detection, segmentation, key-point detection, and captioning dataset. The dataset consists of 328K images.\nWikiSQL: WikiSQL consists of a corpus of 87,726 hand-annotated SQL query and natural language question pairs. These SQL queries are further split into training (61,297 examples), development (9,145 examples) and test sets (17,284 examples).\nSNIPS: The SNIPS Natural Language Understanding benchmark is a dataset of over 16,000 crowdsourced queries distributed among 7 user intents of various complexity: SearchCreativeWork (e.g. Find me the I, Robot television show), GetWeather (e.g.\n\nAvailable Datasets: A: ConvAI2 B: COCO C: WikiSQL D: SNIPS", "role": "user" }, { "content": "COCO", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nNo information is available on the use of remdesivir during breastfeeding. Remdesivir is given intravenously because it is poorly absorbed orally, so infants are not likely to absorb clinically important amounts of the drug from milk. In addition, a newborn infants have received intravenous remdesivir therapy for Ebola with no serious adverse drug reactions.[1,2] Given this limited information, it does not appear that mothers receiving remdesivir need to avoid nursing, but until more data are available, remdesivir should be used with careful infant monitoring during breastfeeding. The most common adverse effects reported after intravenous infusion include elevated aminotransferase and bilirubin levels and other liver enzyme elevations, diarrhea, rash, renal impairment and hypotension.", "role": "user" }, { "content": "[\"Treatment\"]", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\n…indicates that cholinergic and glutamatergic functions regulate cortical development and may contribute to postnatal critical periods (Bear and Singer, 1986; Hohmann et al., 1991; Robertson et al., 1998; for review, see Hohmann and Berger-Sweeney, 1998; Fox et al., 1999; Yuste and Sur, 1999).", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Potential for Development of an Escherichia coli—Based Biosensor for Assessing Bioavailable Methionine: A Review \nChapter Title: E. coli as a Biosensor \n1. Abstract of Cited Paper (BIB001): A plasmid-borne transcriptional fusion between the Escherichia coli nitrate reductase (narG) promoter and the Photorhabdus luminescens lux operon provides E. coli with a highly bioluminescent phenotype in the presence of nitrate. This E. coli biosensor can detect nitrate to a level of 5 x 10(-5) mol l-1 (0.3 ppm), levels relevant to those levels encountered in brewing water. Since induction of the narG promoter requires NarL, the plasmid-based sensor can also be used to interrogate enteric bacteria for the presence of functional homologues of this E. coli regulatory protein. Obesumbacterium proteus, an important bacterial brewery contaminant, failed to provide nitrate-dependent bioluminescence demonstrating divergence in this organism from E. coli in the mechanism of nitrate reductase regulation. \n2. Abstract of Cited Paper (BIB002): A bacterial biosensor for benzene, toluene, and similar compounds has been constructed, characterized, and field tested on contaminated water and soil. The biosensor is based on a plasmid incorporating the transcriptional activator xylR from the TOL plasmid of Pseudomonas putida mt-2. The XylR protein binds a subset of toluene-like compounds and activates transcription at its promoter, Pu. A reporter plasmid was constructed by placing the luc gene for firefly luciferase under the control of XylR and Pu. When Escherichia coli cells were transformed with this plasmid vector, luminescence from the cells was induced in the presence of benzene, toluene, xylenes, and similar molecules. Accurate concentration dependencies of luminescence were obtained and exhibited K1/2 values ranging from 39.0 +/- 3.8 microM for 3-xylene to 2,690 +/- 160 microM for 3-methylbenzylalcohol (means +/- standard deviations). The luminescence response was specific for only toluene-like molecules that bind to and activate XylR. The biosensor cells were field tested on deep aquifer water, for which contaminant levels were known, and were able to accurately detect toluene derivative contamination in this water. The biosensor cells were also shown to detect BETX (benzene, toluene, and xylene) contamination in soil samples. These results demonstrate the capability of such a bacterial biosensor to accurately measure environmental contaminants and suggest a potential for its inexpensive application in field-ready assays. \n3. Abstract of Cited Paper (BIB003): The increasing demand for on-line measurement of milk composition directs science and industry to search for practical solutions, and biosensors may be a possibility. The specific objective of this work was to develop an electrochemical biosensor to determine lactose concentration in fresh raw milk. The sensor is based on serial reactions of three enzymes--beta-galactosidase, glucose oxidase, and horseradish peroxidase--immobilized on a glassy carbon electrode. The sequential enzymatic reactions increase the selectivity and sensitivity of the sensor. The sensor requires dilution of the raw milk and the addition of 5-aminosalicylic acid. Lactose concentrations in raw milk measured by the sensor were in good agreement with those measured by a reference laboratory using infrared technology. The results were obtained in milk samples that varied in fat and protein composition. From the results, we conclude that an electrochemical biosensor for determination of lactose concentration in fresh raw milk can be developed, and that the biosensor presented in this study maintained the qualities required for further development into an online sensor in the milking parlor. \n4. Abstract of Cited Paper (BIB004): An automated flow-injection system with an integrated biosensor array using bacterial cells for the selective and simultaneous determination various mono- and disaccharides is described. The selectivity of the individually addressable sensors of the array was achieved by the combination of the metabolic response, measured as the O(2) consumption, of bacterial mutants of Escherichia coli K12 lacking different transport systems for individual carbohydrates. Kappa-carrageenan was used as immobilization matrix for entrapment of the bacterial cells in front of 6 individually addressable working electrodes of a screen-printed sensor array. The local consumption of molecular oxygen caused by the metabolic activity of the immobilized cells was amperometrically determined at the underlying screen-printed gold electrodes at a working potential of -600 mV vs. Ag/AgCl. Addition of mono- or disaccharides for which functional transport systems exist in the used transport mutant strains of E. coli K12 leads to an enhanced metabolic activity of the immobilized bacterial cells and to a concomitant depletion of oxygen at the electrode. Parallel determination of fructose, glucose, and sucrose was performed demonstrating the high selectivity of the proposed analytical system. \n5. Abstract of Cited Paper (BIB005): Testing for arsenic pollution is commonly performed with chemical test kits of unsatisfying accuracy. Bacterial biosensors are an interesting alternative as they are easily produced, simple, and highly accurate devices. Here, we describe the development of a set of bacterial biosensors based on a nonpathogenic laboratory strain of Escherichia coli, the natural resistance mechanism of E. coli against arsenite and arsenate, and three reporter proteins: bacterial luciferase, β-galactosidase and Green Fluorescent Protein (GFP). The biosensors were genetically optimized to reduce background expression in the absence of arsenic. In calibration experiments with the biosensors and arsenite-amended potable water, arsenite concentrations at 4 μg of As/L (0.05 μM) were routinely and accurately measured. The currently most quantitative system expressed the bacterial luciferase as reporter protein, responding proportional with a concentration range between 8 and 80 μg of As/L. Sensor cells could be stored as frozen b... \n6. Abstract of Cited Paper (BIB006): A microbial biosensor is an analytical device that couples microorganisms with a transducer to enable rapid, accurate and sensitive detection of target analytes in fields as diverse as medicine, environmental monitoring, defense, food processing and safety. The earlier microbial biosensors used the respiratory and metabolic functions of the microorganisms to detect a substance that is either a substrate or an inhibitor of these processes. Recently, genetically engineered microorganisms based on fusing of the lux, gfp or lacZ gene reporters to an inducible gene promoter have been widely applied to assay toxicity and bioavailability. This paper reviews the recent trends in the development and application of microbial biosensors. Current advances and prospective future direction in developing microbial biosensor have also been discussed. \n7. Abstract of Cited Paper (BIB007): A bacterial biosensor is reported that responds to Pb 2+ in the range of 50-400 μM by expressing green fluorescence protein (GFP). The genetic element that senses Pb 2+ includes the regulatory protein gene (PbrR) along with operator/promoter (PbrO/P) of the lead resistance operon from plasmid pMOL30. PbrO/P also controls the gfp reporter gene expression. Escherichia coli DH5α is the host organism. GFP response to induction by Pb 2+ peaked at 250 pM. Decline in fluorescence beyond 250 μM was related to drop in copy number of the biosensor plasmid in the cells. A formula that estimates available Pb 2+ concentration in test samples with 95 % accuracy was derived by multiple regression of fluorescence and cell density values at various Pb 2+ concentrations at 12 h growth. The biosensor was tested for co-inducibility by Cd 2+ , Zn 2+ and Hg 2+ . Only Zn 2+ showed mild induction at high concentrations and the highest fluorescence obtained was 8.5 times lower than that obtained with Pb 2+ . The induction method used here allows water collected from natural resources to be directly tested by using it to prepare the growth medium for the biosensor. This biosensor offers a simple and quick method for detection of available lead in the aquatic environment. \n8. Abstract of Cited Paper (BIB008): A whole-cell bacterial biosensor for measuring aqueous concentrations of aromatic aldehydes was developed. It is based on the E. coli BL21DE3(RIL) expressing the green fluorescent protein under the control of an alcohol dehydrogenase inducible promoter belonging to the archaeon Sulfolobus solfataricus (Sso2536adh promoter). Since it was previously reported that the BldR regulatory protein is the transcription factor required for aromatic aldehyde response in S. solfataricus, the gene encoding for the sensor protein BldR was co-expressed in the biosensor strain on a different compatible plasmid. Gel mobility shift assays showed that the purified recombinant protein can bind specifically to the Sso2536adh promoter. We demonstrated the ability of the archaeal promoter and the BldR transcription factor to operate in a bacterial context to drive active gene expression in a hybrid archaeal/eukaryal fusion. Furthermore, the E. coli BL21DE3(RIL) biosensor strain displayed a specific response and high sensitivity to the different aromatic aldehydes used, suggesting its potential low-cost application to environmentally relevant samples.\n\nReview Chapter:", "role": "user" }, { "content": "Among all microorganisms, E. coli is one of the most highly investigated bacteria for the purposes of biosensor fabrication. It is easy to cultivate, with simple nutritive requirements and rapid growth [34] . E. coli is a Gram negative microorganism with very well known genetics which enables the construction of a wide variety of biosensors BIB007 . The complete E. coli genome has been sequenced and the information deposited to the National Center for Biotechnology Information (NCBI) BIB001 . Thus, each DNA sequence of interest is routinely available to the public and can be used for a wide range of potential further genetic manipulations. In promoter-based E. coli biosensors, a gene promoter, inducible by the analyte of interest, is fused to a reporter that generates a signal in response to the analyte that can be easily monitored and measured. A strong SOS E. coli promoter fused to a lux gene resulted in the development of a construct which served in a dose-dependent detection of 6 genotoxic chemicals including mitomycin C, N-methyl-N-nitro-N-nitrosoguanidine, nalidixic acid, dimethylsulfate, hydrogen peroxide, and formaldehyde . An E. coli BL21 DE3 (RIL) biosensor strain displayed a specific response and high sensitivity to different aromatic aldehydes. The response was measured by monitoring the fluorescence of a reporter (green fluorescent protein) fused to an alcohol dehydrogenase inducible promoter (Sso2536adh) belonging to the archaeon Sulfolobus solfataricus BIB009 . A plasmid-borne transcriptional fusion between the E. coli nitrate reductase (narG) promoter and the Photorhabdus luminescens lux operon was used to generate a modified E. coli with a highly bioluminescent phenotype in the presence of nitrate that enabled the detection of nitrate to a level of 5 × 10 -5 mol L -1 (0.3 ppm) BIB002 . Following the same approach, biosensors for toluene, arsenite and arsenate, and lead have also been generated BIB003 BIB006 BIB008 . In addition to environmental testing and analyses, E. coli-based biosensors were found to be useful in the food industry as well. E. coli derived β-galactosidase, glucose oxidase, and horseradish peroxidase were immobilized on a glassy carbon electrode to generate a biosensor for quantification of lactose in raw milk BIB004 . Simultaneous determination of various mono-and disaccharides was performed by a sensor array comprised of bacterial mutants of E. coli K12 lacking different transport systems for individual carbohydrates BIB005 .", "role": "assistant" } ]

[ { "content": "Examine the text below and extract disease-related entities. Present your findings in a structured JSON format.\n\nYour response should be a JSON object with keys as entity types and values as lists of entities. If no entities are found, return an empty list for that type.\n\nContent:\n\nComplement deficiency and nephritis. A report of a family. A family is described in which three children had homozygous deficiency of C3 and in which both parents and two other children were heterozygous for the C3 null gene. One child with heterozygous C3 deficiency was found to have membranoproliferative glomerulonephritis; proteinuria and/or microscopical haematuria was present in all three homozygous C3-deficient children. All children with homozygous or heterozygous C3 deficiency were, to a varying degree, susceptible to infection. The only child of the family with normal complement had no increased risk of infection and no renal disease. This family study provides further support for the proposal that C3 deficiency predisposes to nephritis..", "role": "user" }, { "content": "{\"Disease\": [\"proteinuria\", \"nephritis\", \"haematuria\", \"C3-deficient\", \"glomerulonephritis\", \"Complement deficiency\", \"C3 deficiency\", \"deficiency of C3\", \"renal disease\"]}", "role": "assistant" } ]

[ { "content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nHIV Coinfection Is Associated with Low-Fitness rpoB Variants in Rifampicin-Resistant Mycobacterium tuberculosis\n\nContent Extracts:\nINTRODUCTION\n<p>Tuberculosis (TB), caused by members of the Mycobacterium tuberculosis complex, is a leading cause of death worldwide, killing more people than any other infectious disease. Among the many factors driving the global TB epidemics, two factors stand out as particularly important: antibiotic resistance and HIV coinfection (1). Although the impact of both of these factors individually is well recognized, the interaction between them is less clear and likely depends on the particular epidemiologic setting (2). HIV coinfection and drug-resistant TB often coexist in severe epidemics, which indicates spread of drug-resistant M. tuberculosis strains from immunocompromised patients (3–5). The propensity of drug-resistant M. tuberculosis strains to spread is influenced by the fitness cost associated with drug resistance determinants (6). Specifically, bacterial strains that have acquired drug resistance-conferring mutations may be less transmissible than their susceptible counterparts, although this fitness cost can be ameliorated by compensatory mutations (7–10). Moreover, the effect of different resistance-conferring mutations on fitness can be heterogeneous (11). In the clinical setting, there is a selection for high-fitness and/or compensated drug-resistant M. tuberculosis strains in TB patients (12). However, in immunocompromised hosts, such as HIV-coinfected patients, even strains with low-fitness resistance mutations might propagate efficiently (13–15), which could partially explain why drug-resistant TB has been associated with HIV coinfection (16, 17). However, to date, no evidence directly supports the notion that the immunological environment created by HIV coinfection modifies the fitness of drug-resistant M. tuberculosis (5, 18, 19).</p><p>In this study, we tested the hypothesis that resistance-conferring mutations with low fitness in M. tuberculosis are overrepresented among HIV-coinfected TB patients. We focused our analysis on isoniazid and rifampicin, the two most important first-line anti-TB drugs, for which resistance-conferring mutations have been shown to differ in their fitness effects when measured in the laboratory (11). In addition, the frequency of the resistance alleles found in a clinical setting correlates well with the in vitro fitness of strains (12, 20). To explore the association between HIV coinfection and the fitness effect of different drug resistance-conferring mutations in M. tuberculosis, we compiled a collection of drug-resistant strains using the global International Epidemiology Databases to Evaluate AIDS (IeDEA, http://www.iedea.org) consortium (21, 22) as a platform. For this study, 312 strains were collected from HIV-coinfected and HIV uninfected TB patients originating from nine countries on three continents: Peru, Thailand, South Africa, Kenya, Côte d'Ivoire, Botswana, Democratic Republic of the Congo, Nigeria, and Tanzania (Fig. 1; see also Table S1 in the supplemental material). The association between the fitness of isoniazid resistance-conferring mutations and HIV coinfection was tested in a univariate analysis (Fig. S1). Isoniazid resistance-conferring mutations were divided into three groups, as previously described (23): katG S315T mutation, katG mutations other than S315T, and inhA promoter mutations only. The S315T substitution in katG causes high-level isoniazid resistance while retaining some catalase/peroxidase functions (24). Conversely, the inhA promoter mutation does not affect KatG activity. Other substitutions/deletions in katG have been associated with a lower fitness in the laboratory and are observed only rarely among clinical isolates (23, 25, 26). In the case of rifampicin, the association between the fitness of rpoB variants and HIV coinfection was tested in both a univariate and multivariate analysis (Table 1). Resistance-conferring variants in rpoB were classified into two groups based on their fitness effects documented previously (11, 20, 27). The mutation rpoB S450L was considered high fitness, since this mutation was previously shown to confer a low fitness cost in the laboratory (11) and is generally the most common in clinical strains (28). Any other resistance-conferring variant affecting rpoB was considered low fitness (11). The multivariable logistic regression model with outcome of low-fitness rpoB variants was adjusted for host-related factors (history of TB, country of isolation, sex, and age) (29) and bacterial factors (M. tuberculosis lineage, presence of an rpoA-C compensatory mutation, clustering of the genome inferred by genetic relatedness). Seventy-six patients from Tanzania and Botswana were excluded from the model due to missing or unknown clinical data (see the supplemental methods file).</p>\n\n\n<p>(A) Frequency of M. tuberculosis lineages by HIV status for countries sampled. Countries colored in gray were sampled. The bar plots indicate the proportion of each lineage represented in this study. Magenta corresponds to M. tuberculosis lineage 1, blue corresponds to M. tuberculosis lineage 2, purple corresponds to M. tuberculosis lineage 3, and red corresponds to M. tuberculosis lineage 4. Solid color corresponds to HIV-negative patients, and hatches correspond to HIV-coinfected TB patients. The number of genomes sampled in each country is indicated on top of the bar plots. (B) Phylogenetic tree of the data set used in the study. Maximum likelihood phylogeny of 312 whole-genome sequences based on 18,531 variable positions. The scale bar indicates the number of substitutions per polymorphic site. The phylogeny was rooted on Mycobacterium canettii. M. tuberculosis strains isolated from HIV-coinfected patients are indicated by black dots. The peripheral ring depicts the country of isolation of the strains sequenced.</p><p>Results of the univariate and multivariate analysis showing host and bacterial factors associated with low fitness rpoB variants in 203 TB patientsa</p><p>Number of observations in model, 203; CI, confidence interval. The odds ratios and P values were obtained from the regression model.</p>\n\nINTRODUCTION\n<p>Out of 312 patients, 113 (36.2%) were HIV coinfected, 120 (38.5%) were women, 115 (36.9%) were newly diagnosed TB cases (therefore, treatment naive), 276 (88.5%) harbored isoniazid resistance-conferring mutations, with or without additional resistance, and 282 (90.4%) harbored rifampicin resistance-conferring mutations, with or without additional resistance. In total, 78.8% (n = 246) of the strains were classified as being at least multidrug resistant, defined as resistance to isoniazid and rifampicin with or without additional resistance to second-line drugs. Among the 113 HIV-coinfected individuals, 34 (30%) were on antiretroviral therapy (ART), 26 (23%) were not, and 53 (47%) had an unknown ART start date. Four of the eight known M. tuberculosis lineages were represented in the following proportions: 11 L1 (3.5%), 57 L2 (18.3%), 38 L3 (12.2%), and 206 L4 (66.0%). After dividing a total of 276 isoniazid-resistant strains into the three groups of isoniazid resistance-conferring mutations defined above, we found similar proportions in HIV-coinfected and HIV-uninfected patients (chi-square test, P = 0.54; Fig. S1), and, as expected, the katG S315T mutation was the most frequent mutation in both categories (overall, found in 80% of isoniazid-resistant strains). In the case of rifampicin resistance, a univariate and multivariate analysis of 203 strains with complete clinical records indicated that HIV-coinfected TB patients carried a higher proportion of low-fitness rpoB resistance variants than HIV-negative patients (72.3% versus 51.4%). The univariate analysis showed higher odds of having a low-fitness rpoB variant in HIV-coinfected patients (odds ratio, 2.46 [95% confidence interval, 1.30 to 4.66], P = 0.006) (Table 1). Our multivariable regression analysis confirmed these results and showed an association between low-fitness rpoB variants and HIV coinfection while controlling for other factors (odds ratio, 4.58 [95% confidence interval, 1.69, 12.44], P = 0.003) (Table 1). This association can be explained in at least two ways. First, HIV-coinfected patients are thought to have fewer lung cavities on average and lower sputum bacillary load (30, 31). The resulting smaller M. tuberculosis population size would lead to fewer replication events, possibly reducing the number of mutations available for selection to act upon. In other words, low-fitness variants and high-fitness variants would co-occur less often in an HIV-coinfected patient, such that competition between them would be less likely. This scenario would be relevant for de novo acquisition of low-fitness drug-resistant variants within an HIV-coinfected patient. Second, following the transmission of a drug-resistant strain with low fitness to a host with reduced immunity, weaker immune pressure acting on this strain might lead to better bacterial survival. The association between low-fitness rpoB variants and HIV coinfection remained significant even after adjusting for the different epidemiologic settings (i.e., countries) and the strain genetic background (i.e., M. tuberculosis lineages). We also observed that strains carrying the rpoB S450L resistance-conferring mutation were more likely to also carry a compensatory mutation in rpoA-C (97.4% versus 2.6%) (Table 1). Even though this phenomenon seems counterintuitive, it has been described multiple times (7, 9, 32–34) and, thus, might point to different mechanisms of compensation in strains carrying resistance mutations other than rpoB S450L. In addition, in our study, L4 strains were associated with low-fitness rpoB variants compared to L2 (odds ratio, 3.10 [95% confidence interval, 0.94, 10.21], P = 0.06) (Table 1), indicating that the strain genetic background plays a role in shaping the cost of resistance, as was previously shown for other bacterial species (35) and for other drugs (36). In the regression analysis, we had several categorical variables with only a few observations. Therefore, statistical power, especially for country of isolation, was low, and the results should be interpreted with care.</p><p>HIV-coinfected TB patients are generally thought to have a reduced potential for TB transmission (30, 37), because these patients have reduced formation of lung cavities, more extrapulmonary disease, and a shorter period of infectiousness due to earlier diagnosis or higher mortality, especially in the absence of antiretroviral treatment and if antibiotic resistance is already present (4). Based on the overrepresentation of low-fitness rpoB mutations in the context of HIV coinfection, one would expect a further reduction of the transmission potential of drug-resistant TB in this context. However, outbreaks of drug-resistant TB in HIV-coinfected patients have been reported (3). Such outbreaks might be explained by (i) a higher risk of M. tuberculosis infection and reinfection due to diminished host immunity, (ii) on-going transmission of drug-resistant M. tuberculosis from a larger pool of immunocompetent TB patients to immunocompromised patients, (iii) transmission occurring in conducive environments, such as health care settings, where both HIV-coinfected individuals and drug-resistant TB patients are more likely to coexist, and (iv) M. tuberculosis strains carrying high-fitness drug resistance mutations.</p><p>In summary, using a global sample of drug-resistant M. tuberculosis clinical strains from HIV-coinfected and HIV-negative TB patients, we showed that low-fitness rpoB variants were overrepresented in HIV-coinfected patients, and that this association was independent from other potential confounding factors. Taken together, our results provide new insights into how HIV coinfection can impact the fitness of drug-resistant M. tuberculosis.</p>\n\nData availability.\n<p>The M. tuberculosis whole-genome sequences from the patients are available on NCBI under several project identifiers. The accession number for each genome is indicated in Supplemental Table S1.</p>\n\n\n<p>Supplemental material is available online only.</p>", "role": "user" }, { "content": "We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity.", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nOntheproteinlevel,EScellsexpressonlythesmallerAnnexinA7isoformof47kDa(Fig.1B,neuro-2acellsandhearttissueareincludedforcontrol).", "role": "user" }, { "content": "[\"protein\"]", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nWe present a variation of the Autoencoder (AE) that explicitly maximizes the mutual information between the input data and the hidden representation. The proposed model, the InfoMax Autoencoder (IMAE), by construction is able to learn a robust representation and good prototypes of the data. IMAE is compared both theoretically and then computationally with the state of the art models: the Denoising and Contractive Autoencoders in the one-hidden layer setting and the Variational Autoencoder in the multi-layer case. Computational experiments are performed with the MNIST and Fashion-MNIST datasets and demonstrate particularly the strong clusterization performance of IMAE.\n\nCited Works Summary:\n[1]: Previous work has shown that the difficulties in learning deep generative or discriminative models can be overcome by an initial unsupervised learning step that maps inputs to useful intermediate representations. We introduce and motivate a new training principle for unsupervised learning of a representation based on the idea of making the learned representations robust to partial corruption of the input pattern. This approach can be used to train autoencoders, and these denoising autoencoders can be stacked to initialize deep architectures. The algorithm can be motivated from a manifold learning and information theoretic perspective or from a generative model perspective. Comparative experiments clearly show the surprising advantage of corrupting the input of autoencoders on a pattern classification benchmark suite.", "role": "user" }, { "content": "An information theoretic description of an AE was given by [1] where, with restrictive assumptions, they observed that reducing the reconstruction loss of an AE is related to maximizing the mutual information between the visible and hidden variables.", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nEvidence for this specific role of piRNAs comes from the studies in y [5-7], zebrafish [8,9] and mouse [10-13].", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nEach node joins a cluster and the cluster elects a leader in a multihop, distributed manner [15].", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Cryptic Variation between Species and the Basis of Hybrid Performance\nContent:\nAbstract:\nCrosses between closely related species give two contrasting results. One result is that species hybrids may be inferior to their parents, for example, being less fertile[1]. The other is that F1 hybrids may display superior performance( heterosis), for example with increased vigour[2]. Although various hypotheses have been proposed to account for these two aspects of hybridisation, their biological basis is still poorly understood[3]. To gain further insights into this issue, we analysed the role that variation in gene expression may play. We took a conserved trait, flower asymmetry in Antirrhinum, and determined the extent to which the underlying regulatory genes varied in expression among closely related species. We show that expression of both genes analysed, CYC and RAD, varies significantly between species because of cis-acting differences. By making a quantitative genotype-phenotype map, using a range of mutant alleles, we demonstrate that the species lie on a plateau in gene expression-morphology space, so that the variation has no detectable phenotypic effect. However, phenotypic differences can be revealed by shifting genotypes off the plateau through genetic crosses. Our results can be readily explained if genomes are free to evolve within an effectively neutral zone in gene expression space. The consequences of this drift will be negligible for individual loci, but when multiple loci across the genome are considered, we show that the variation may have significant effects on phenotype and fitness, causing a significant drift load. By considering these consequences for various gene-expression–fitness landscapes, we conclude that F1 hybrids might be expected to show increased performance with regard to conserved traits, such as basic physiology, but reduced performance with regard to others. Thus, our study provides a new way of explaining how various aspects of hybrid performance may arise through natural variation in gene activity.\nIntroduction:\nCrosses between closely related species give two contrasting results[3]. One result is that species hybrids may be inferior to their parents, with reduced fertility or viability[1]. The other is that F1 hybrids may be superior( heterosis), with increased vigour[2],[4]. Hybrid inferiority is commonly explained through incompatible interactions between loci[5]–[8]. Hybrid superiority is either explained through accumulation of different recessive deleterious mutations in each species, or by loci exhibiting heterozygote advantage( overdominance)[9]. The deleterious recessives hypothesis has received support from studies on domesticated inbred varieties[10], although it is unclear how such deleterious mutations would become fixed in natural populations with larger effective population sizes( though see[11],[12]). The hypothesis of heterozygote advantage suffers from the problem that it is unclear why overdominance should be prevalent[13]. One approach to understanding the basis of hybrid performance is to analyse interspecific variation at a few interacting loci and then extrapolate these findings. Variation between closely related species mainly involves either loci with small quantitative effects, or loci conferring no detectable phenotypic effect, known as cryptic variation[14]–[20]. Gene expression studies have revealed extensive differences between species in both cis- and tran-regulation across the genome[21]–[25]. However, the relationship between such variation in gene expression and phenotype has not been extensively explored. To address this issue, we have analysed interspecific variation in expression of two interacting developmental loci in Antirrhinum. The Antirrhinum species group of southern Europe comprises about 20 species with diverse morphologies[26],[27]. These species can be intercrossed in the laboratory to give fertile hybrids, allowing the genetic basis of the species variation to be studied. So far, these studies have largely addressed divergent traits such as flower shape and colour or leaf shape and size[28]–[32]. However, to determine whether cryptic variation may also be prevalent, we chose here to analyse a conserved trait – flower asymmetry. All the species in the group have asymmetric flowers with matching upper and lower petals. The asymmetry depends on four key dorsoventral genes, CYCLOIDEA( CYC), DICHOTOMA( DICH), RADIALIS( RAD), and DIVARICATA( DIV)[33]–[36]. CYC and DICH encode related proteins belonging to TCP family of transcription factors, whereas RAD and DIV encode members of the Myb transcription factor family. The interaction between CYC and RAD has been studied in detail[37],[38]. RAD is a likely downstream target of CYC and acts in parallel with CYC to control dorsal and lateral petal development. As their interaction had been well characterised, we chose this pair of genes for our studies on cryptic variation. We show here that species of the Antirrhinum group exhibit variation in the levels of CYC and RAD expression. This variation is cryptic as it lies within a plateau in gene expression–morphology( GEM) space. However, phenotypic effects can be revealed by creating genotypes in which the species alleles are shifted off the plateau. By considering the consequences of such patterns of variation for multiple loci and in relation to possible gene expression–fitness( GEF) spaces, we conclude that F1 hybrids might be expected to show increased performance with regard to basic physiological traits such as growth. This finding provides an explanation for hybrid vigour that avoids some of the pitfalls of previous hypotheses. Hybrid inferiority may also be expected in the longer term for nonphysiological traits such as those involved in sexual reproduction.\nDiscussion:\nSpecies from the Antirrhinum group exhibit significant cis-acting variation in levels of CYC and RAD expression. This variation is cryptic, having no obvious phenotypic consequences in a wild-type genetic background. The lack of phenotype arises because the species lies on a plateau in GEM space. However, phenotypic effects can be revealed if the species are shifted off the plateau by construction of double heterozygotes. In such backgrounds, species carrying alleles with relative high levels of gene expression exhibit near wild-type phenotypes, whereas species with lower expression tend to give notched flowers with reduced dorsalisation. Recombination analysis allows the contribution of each locus to be determined. In the case of A. charidemi, the main source of phenotypic variation is due to a difference in expression at the CYC locus. Our findings bridge those from several other studies. Comparative analysis of Caenorhabditis species has revealed changes in genes controlling the conserved trait of vulval development[18]. These changes are more substantial than those we describe, most likely because of the different timescale of these studies: divergence times are about 14–18 million y for Caenorhabditis species[46], compared to 1–5 million y for Antirrhinum[47]. Cryptic variation underlying vulval development has also been described within Caenorhabditis species[20], although the genetic basis of this variation has yet to be determined. Extensive variation in gene expression has been observed between Drosophila sibling species[21],[22] and its phenotypic consequences studied for divergent traits, such as denticle pattern[48]–[50]. Divergent ecological traits have also been shown to reflect variation in gene activity within Arabidopsis thaliana[51]–[54]. Our results suggest that variation in gene expression may also be found to underlie highly conserved traits and that this variation can have phenotypic consequences in certain genetic backgrounds, depending on the structure of the GEM spaces involved. Although cryptic variation of the kind we describe would be expected to have little effect on species hybrid performance for each locus, we show that the cumulative effect of such variation at many loci could have a major effect. The magnitude and direction of this effect depends on the population size and topography of the GEF spaces in the various species habitats. For example, if GEF spaces have a radial fitness peak that is preserved across habitats, then for 1, 000 loci and an effective population size Ne of 1, 000 the fitness benefit in species hybrids would be 0. 125, which is very substantial. This benefit arises because each species is expected to drift around its fitness peak within a radial neutral zone. For multiple loci this causes each species to lie significantly below the optimum( i. e., there is a drift load). As the species diverge, they come to represent separate samples of the neutral zone, each carrying a different combination of alleles contributing to drift load. A species hybrid will then represent an average of two samples and is therefore expected to lie nearer the peak than either sample alone, creating hybrid superiority. This hybrid benefit will be lost in the F2 as the alleles segregate, creating genotypes with fitness similar to those of the parents. GEF spaces with elongated peaks and elliptical neutral zones are also expected to show similar benefits in hybrid fitness. However, in this case the F2 genotypes are expected to have lower fitness than the parents when the elliptical zones are tilted in gene expression space. Hybrid inferiority arises for GEF spaces that have curved or L-shaped neutral zones( L-shaped zones correspond to the standard Dobzhansky-Muller incompatibility). The phenotype and fitness of species hybrids will reflect the extent to which these various GEF scenarios apply to the many thousands of genes in the genome. Radial or elliptical neutral domains, centred around a common position in GEF space, would be expected for loci that are under similar normalising selection in multiple environments. This situation likely applies to the CYC and RAD genes as all species in the Antirrhinum group have similar asymmetric closed flowers. It would also be expected for many loci controlling basic physiology and growth. F1 hybrids would therefore be expected to show higher fitness and increased performance with respect to these traits. This provides an explanation for hybrid vigour that avoids the pitfalls of previous models that require fixation of loci with major deleterious effects or that invoke special mechanisms for heterozygote advantage. A similar explanation has been proposed to account for the origin of hybrid vigour between domesticated inbred lines[10]. Hybrid vigour is usually lost in F2s or recombinant inbred lines, indicating that many of the loci involved interact to give tilted rather than untilted neutral zones. Although hybrid vigour is commonly observed for physiological traits, the overall fitness of species hybrids is often lower than that of the parents, with sterility or other dysgenic effects being observed. This observation may partly reflect adaptation to different environments and thus shifts in the shape of fitness surfaces that drive changes in genotype. However, it may also reflect loci that interact to give curved or L-shaped neutral zones[8]. Such zones will be prevalent for traits that involve more complicated epistatic interactions, perhaps accounting for the dysgenic effects observed in F1s. The negative contribution of loci with curved neutral zones is likely to increase with time, as loci drift towards the extremities of the banana-shaped neutral domains. The overall fitness of an F1 hybrid will depend on the relative contribution of superior and inferior effects across the genome. In this paper we have concentrated on variation in gene expression levels. Other forms of variation, such as in gene expression patterns, protein activities, or chromosome arrangements are also likely to play an important role in species divergence. The corresponding fitness spaces may be more difficult to visualise because variation for each gene may no longer be represented along a single axis. Nevertheless, the principles may be similar to those described above, with both hybrid inferiority and superiority reflecting effectively neutral variation at multiple loci, but differing with respect to the topography of the fitness spaces involved.", "role": "user" }, { "content": "A major conundrum in biology is why hybrids between species display two opposing features . On the one hand , hybrids are often more vigorous or productive than their parents , a phenomenon called hybrid vigor or hybrid superiority . On the other hand they often show reduced vigour and fertility , known as hybrid inferiority . Various theories have been proposed to account for these two aspects of hybrid performance , yet we still lack a coherent account of how these conflicting characteristics arise . To address this issue , we looked at the role that variation in gene expression between parental species may play . By measuring this variation and its effect on phenotype , we show that expression for specific genes may be free to vary during evolution within particular bounds . Although such variation may have little phenotypic effect when each locus is considered individually , the collective effect of variation across multiple genes may become highly significant . Using arguments from theoretical population genetics we show how these effects might lead to both hybrid superiority and inferiority , providing fresh insights into the age-old problem of hybrid performance .", "role": "assistant" } ]

[ { "content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: CHO Mouth Rinse Ameliorates Neuromuscular Response with Lower Endogenous CHO Stores.\nSummary: PURPOSE This study aim ed to investigate carbohydrate ( CHO ) mouth rinse response on neuromuscular activity , fuel oxidation rates , and cycling performance with different initial levels of endogenous CHO availability . METHODS In a double-blind , r and omized placebo-controlled design , eight males completed six experimental mouth rinse trials : CHO ( 6.4 % maltodextrin ) or placebo solution in a fed state ( FED ) , 12-h fasted state ( FAST ) , or a combined exercise-depleted muscle glycogen and 12-h fasted state ( DEP ) . Trials consisted of 30-min cycling at 90 % of gas exchange threshold , followed by a 20-km cycling time trial . Plasma lactate , plasma glucose , oxygen uptake , and EMG activity were measured , and CHO and fat oxidation rates were calculated . RESULTS CHO mouth rinse maintained higher plasma glucose levels as the constant load exercise progressed ( P = 0.023 ) . The reduced EMG activity in the DEP condition with the placebo during constant load exercise was ameliorated with CHO mouth rinse ( P < 0.01 ) . Furthermore , the power output and the EMG activity throughout the 20-km time trial were reduced in the DEP condition with placebo but were both restored with CHO mouth rinse ( P < 0.05 ) . Time trial performance was only improved with CHO in the DEP compared with the corresponding placebo ( P < 0.05 ) , and no differences between supplements were observed in the FED or FAST states . Analyses of the qualitative inference showed \" benefit very likely \" of CHO mouth rinse on exercise performance in DEP , \" possibly benefit \" in FAST , and \" negligible or trivial \" in FED . CHO mouth rinse had no effect on CHO and fat oxidation rates in either exercise mode . CONCLUSION The CHO mouth rinse influences exercise performance when endogenous CHO availability is low , and an enhanced central motor drive is potentially the main influencing mechanism\n\n\nReport 2:\nTitle: Mouth Rinsing with Maltodextrin Solutions Fails to Improve Time Trial Endurance Cycling Performance in Recreational Athletes\nSummary: The carbohydrate ( CHO ) concentration of a mouth rinsing solution might influence the CHO sensing receptors in the mouth , with consequent activation of brain regions involved in reward , motivation and regulation of motor activity . The purpose of the present study was to examine the effects of maltodextrin mouth rinsing with different concentrations ( 3 % , 6 % and 12 % ) after an overnight fast on a 20 km cycling time trial performance . Nine recreationally active , healthy males ( age : 24 ± 2 years ; V˙O2max : 47 ± 5 mL·kg−1·min−1 ) participated in this study . A double-blind , placebo-controlled r and omized study was conducted . Participants mouth-rinsed every 2.5 km for 5 s. Maltodextrin mouth rinse with concentrations of 3 % , 6 % or 12 % did not change time to complete the time trial and power output compared to placebo ( p > 0.05 ) . Time trial completion times were 40.2 ± 4.0 , 40.1 ± 3.9 , 40.1 ± 4.4 , and 39.3 ± 4.2 min and power output 205 ± 22 , 206 ± 25 , 210 ± 24 , and 205 ± 23 W for placebo , 3 % , 6 % , and 12 % maltodextrin conditions , respectively . Heart rate , lactate , glucose , and rating of perceived exertion did not differ between trials ( p > 0.05 ) . In conclusion , mouth rinsing with different maltodextrin concentrations after an overnight fast did not affect the physiological responses and performance during a 20 km cycling time trial in recreationally active males\n\n\nReport 3:\nTitle: Effect of a carbohydrate mouth rinse on simulated cycling time-trial performance commenced in a fed or fasted state.\nSummary: It is presently unclear whether the reported ergogenic effect of a carbohydrate ( CHO ) mouth rinse on cycling time-trial performance is affected by the acute nutritional status of an individual . Hence , the aim of this study was to investigate the effect of a CHO mouth rinse on a 60-min simulated cycling time-trial performance commenced in a fed or fasted state . Twelve competitive male cyclists each completed 4 experimental trials using a double-blinded Latin square design . Two trials were commenced 2 h after a meal that contained 2.5 g·kg(-1 ) body mass of CHO ( FED ) and 2 after an overnight fast ( FST ) . Prior to and after every 12.5 % of total time during a performance ride , either a 10 % maltodextrin ( CHO ) or a taste-matched placebo ( PLB ) solution was mouth rinsed for 10 s then immediately expectorated . There were significant main effects for both pre-ride nutritional status ( FED vs. FST ; p < 0.01 ) and CHO mouth rinse ( CHO vs. PLB ; p < 0.01 ) on power output with an interaction evident between the interventions ( p < 0.05 ) . The CHO mouth rinse improved mean power to a greater extent after an overnight fast ( 282 vs. 273 W , 3.4 % ; p < 0.01 ) compared with a fed state ( 286 vs. 281 W , 1.8 % ; p < 0.05 ) . We concluded that a CHO mouth rinse improved performance to a greater extent in a fasted compared with a fed state ; however , optimal performance was achieved in a fed state with the addition of a CHO mouth rinse\n\n\nReport 4:\nTitle: Mouth Rinsing With Carbohydrate Solutions at the Postprandial State Fail to Improve Performance During Simulated Cycling Time Trials\nSummary: Abstract Ispoglou , T , O'Kelly , D , Angelopoulou , A , Bargh , M , O'Hara , JP , and Duckworth , LC . Mouth rinsing with carbohydrate solutions at the postpr and ial state fail to improve performance during simulated cycling time trials . J Strength Cond Res 29(8 ) : 2316–2325 , 2015—Mouth rinsing with carbohydrate ( CHO ) solutions during cycling time trials results in performance enhancements ; however , most studies have used approximately 6 % CHO solutions . Therefore , the purpose of this study was to compare the effectiveness of mouth rinsing with 4 , 6 , and 8 % CHO solutions on 1-hour simulated cycling time trial performance . On 4 occasions , 7 trained male cyclists completed at the postpr and ial period , a set amount of work as fast as possible in a r and omized counterbalanced order . The subjects rinsed their mouth for 5 seconds , on completion of each 12.5 % of the trial , with 25 ml of a non-CHO placebo and 4 , 6 , and 8 % CHO solutions . No additional fluids were consumed during the time trial . Heart rate ( HR ) , ratings of perceived exertion ( RPE ) , thirst ( TH ) , and subjective feelings ( SF ) were recorded after each rinse . Furthermore , blood sample s were drawn every 25 % of the trial to measure blood glucose and blood lactate concentrations , whereas whole-body CHO oxidation was monitored continuously . Time to completion was not significant between conditions with the placebo , 4 , 6 , and 8 % conditions completing the trials in 62.0 ± 3.0 , 62.8 ± 4.0 , 63.4 ± 3.4 , and 63 ± 4.0 minutes , respectively . There were no significant differences between conditions in any of the variables mentioned above ; however , significant time effects were observed for HR , RPE , TH , and SF . Post hoc analysis showed that TH and SF of subjects in the CHO conditions but not in the placebo were significantly increased by completion of the time trial . In conclusion , mouth rinsing with CHO solutions did not impact 1-hour cycling performance in the postpr and ial period and in the absence of fluid intake . Our findings suggest that there is scope for further research to explore the activation regions of the brain and whether they are receptive to CHO dose , before specific recommendations for athletic population s are established . Consequently , mouth rinsing as a practical strategy for coaches and athletes is question able under specific conditions and should be carefully considered before its inclusion . Emphasis should be focused on appropriate dietary and fluid strategies during training and competition\n\n\nReport 5:\nTitle: The effect of carbohydrate mouth rinse on 1-h cycle time trial performance.\nSummary: PURPOSE AND METHOD To investigate the possible role of carbohydrate ( CHO ) receptors in the mouth in influencing exercise performance , seven male and two female endurance cyclists ( VO(2max ) 63.2 + /- 2.7 ( mean + /- SE ) mL.kg*(-1).min(-1 ) ) completed two performance trials in which they had to accomplish a set amount of work as quickly as possible ( 914 + /- 40 kJ ) . On one occasion a 6.4 % maltodextrin solution ( CHO ) was rinsed around the mouth for every 12.5 % of the trial completed . On the other occasion , water ( PLA ) was rinsed . Subjects were not allowed to swallow either the CHO solution or water , and each mouthful was spat out after a 5-s rinse . RESULTS Performance time was significantly improved with CHO compared with PLA ( 59.57 + /- 1.50 min vs 61.37 + /- 1.56 min , respectively , P = 0.011 ) . This improvement result ed in a significantly higher average power output during the CHO compared with the PLA trial ( 259 + /- 16 W and 252 + /- 16 W , respectively , P = 0.003 ) . There were no differences in heart rate or rating of perceived exertion ( RPE ) between the two trials ( P > 0.05 ) . CONCLUSION The results demonstrate that carbohydrate mouth rinse has a positive effect on 1-h time trial performance . The mechanism responsible for the improvement in high-intensity exercise performance with exogenous carbohydrate appears to involve an increase in central drive or motivation rather than having any metabolic cause . The nature and role of putative CHO receptors in the mouth warrants further investigation", "role": "user" }, { "content": "Interestingly , careful analysis of the plots by Li et al. [ 1 ] revealed that the study by Pottier et al. [ 4 ] ( using an approximately 3 h restricted alimentary state ) impacted the results as much as some overnight fasting studies [ 5 , 6 ] , thus suggesting that different pr and ial states may have only negligible influence on the ergogenic benefit of CHO mouth rinse .\nFor example , a recent study [ 17 ] showed that CHO mouth rinse had negligible effect on 20 km cycling time trial performance when the pre-exercise endogenous glycogen levels ( muscle and probably liver ) were adequate in the fed or fasted state condition .", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nUnsupervised learning of disentangled representations is an open problem in machine learning.\nThe Disentanglement-PyTorch library is developed to facilitate research, implementation, and testing of new variational algorithms.\nIn this modular library, neural architectures, dimensionality of the latent space, and the training algorithms are fully decoupled, allowing for independent and consistent experiments across variational methods.\nThe library handles the training scheduling, logging, and visualizations of reconstructions and latent space traversals.\nIt also evaluates the encodings based on various disentanglement metrics.\nThe library, so far, includes implementations of the following unsupervised algorithms VAE, Beta-VAE, Factor-VAE, DIP-I-VAE, DIP-II-VAE, Info-VAE, and Beta-TCVAE, as well as conditional approaches such as CVAE and IFCVAE.\nThe library is compatible with the Disentanglement Challenge of NeurIPS 2019, hosted on AICrowd and was used to compete in the first and second stages of the challenge, where it was ranked among the best few participants.\nThere are two overlapping avenues in representation learning.\nOne focuses on learning task-specific transformations often optimized towards specific domains and applications.\nThe other approach learns the intrinsic factors of variation, in a disentangled and taskinvariant fashion.\nThe unsupervised disentanglement of latent factors, where changes in a single factor of variation shifts the latent encoding in a single direction, is an open problem of representation learning (Bengio et al., 2013; Lake et al., 2016) .\nDisentangled representations are valuable in few-shot learning, reinforcement learning, transfer learning, as well as semisupervised learning (Bengio et al., 2013; Peters et al., 2017; .\nIn this work, we developed a library based on the functionalities of the PyTorch framework, which facilitates research, implementation, and testing of new variational algorithms focusing on representation learning and disentanglement.\nThe library branches from the Disentanglement Challenge of NeurIPS 2019, hosted on AICrowd (aicrowd.com), and was used to compete in the first and second stages of the challenge where it was highly ranked.\nThe Disentanglement-PyTorch library is released under the GNU General Public License at https://github.com/amir-abdi/disentanglement-pytorch.", "role": "user" }, { "content": "Disentanglement-PyTorch is a library for variational representation learning", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Generation of Functional Eyes from Pluripotent Cells\nContent:\nAbstract:\nPluripotent cells such as embryonic stem( ES) and induced pluripotent stem( iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision.\nIntroduction:\nEvery body organ consists of tissue groups with multiple cell types. Therefore, recovery from organ damage requires the replacement of a variety of distinct cell types. The retina is the light detecting tissue of the eye, and consists of seven major cell classes. All retinal cell classes are generated from a common multipotent retinal progenitor. The conversion of pluripotent cells to retinal progenitors would, in theory, provide a source of all the cell classes necessary for retinal repair. Pluripotent cells treated with extrinsic factors express retinal markers in vitro and in vivo[1]–[5]. When transplanted to the subretinal space of mice lacking functional photoreceptors, human embryonic stem cells directed toward a retinal lineage integrate into the outer nuclear layer, express photoreceptor markers, and restore a light response as determined by the electroretinogram( ERG)[5]. However, it is not known if any other functional retinal cell classes can be derived from pluripotent cells, or if these cells can form the complex neural network necessary for vision. Vertebrate retina formation begins in the anterior neural plate in a region called the eye field. A group of transcription factors collectively called the eye field transcription factors or EFTFs( pax6, rx1, tbx3[or ET], nr2e1[or tailless], six3, lhx2, and six6[or optx2]) and the neural patterning gene otx2 are essential for normal eye formation[6]. When overexpressed together in developing Xenopus embryos by RNA microinjection, these genes can induce eye-like structures as defined by the expression of markers for some retinal cell classes[7]. The overall aim of this study was to determine if pluripotent cells overexpressing these transcription factors could be intentionally driven toward retinal progenitors that differentiate into multiple retinal cell classes and form a functional retina. Primitive ectoderm cells isolated from the animal pole of blastula stage embryos are pluripotent. If treated with the appropriate inducer, they can form endodermal, mesodermal, or ectodermal cell types[8]. Here we provide evidence that these pluripotent cells misexpressing the EFTFs differentiate into all retinal cell classes. Using both the ERG and a vision-based behavioral assay, we found that eyes generated from EFTF-expressing pluripotent cells are molecularly and functionally similar to the normal eye. These results suggest that by using the correct combination of gene products, it may be possible to reprogram more readily available pluripotent cell types to a multipotent retinal cell lineage useful in healing damaged or diseased retinas.\nDiscussion:\nThe induced retinal cells generated here are multipotent, as they differentiate into all retinal cell classes and even express markers for some retinal cell subtypes. We observed stereotypical retinal cell morphology in eyes completely derived from EFTF-expressing pluripotent cells and in mosaic retinas. Lamba and colleagues recently demonstrated that human embryonic stem cells could be directed to differentiate into photoreceptors and respond to a light stimulus as measured by ERG in crx−/− mice( a model for Leber's congenital amaurosis)[5]. This important finding strongly suggests that in vitro generated cells can form functional retinal cells in a nonfunctioning retina. We show that pluripotent cells can generate all retinal cell classes. When transplanted to the anterior neural plate, these cells form eyes and a neural network capable of driving a vision-guided behavior. Not all donor cells were reprogrammed to a retinal lineage by the EFTFs. Why this might be is unclear. One hypothesis is that a subset of the pluripotent cells was refractory to the effects of the EFTFs. Alternatively, some cells may not have received a sufficient dose or the appropriate relative level of each EFTF. This possibility is intriguing, since subsets of the EFTFs are coordinately expressed in specific regions of the forebrain and developing olfactory placodes[7]. It will be interesting to determine if specific EFTF subsets can fate pluripotent cells to other( nonretinal) neural lineages. Eye fields and early optic vesicles form eye-like structures with lenses when transplanted ectopically or when cultured in vitro[21]–[26]. Similarly, EFTF-expressing pluripotent cells formed ectopic eye-like structures when transplanted to the embryonic flank. Although induced cells expressed retinal markers and exhibited retinal cell morphology in culture, morphologically normal eyes never formed. These results demonstrate fundamental differences between the induced retinal cells and the embryonic eye field. In isolation, EFTF-expressing pluripotent cells may be unable to recapitulate the complex inductive and morphological changes necessary for complete eye formation in culture. EFTFs may redirect pluripotent cells to a more restricted lineage than isolated eye fields, which may include additional tissues necessary for in vitro eye formation. Our transplantation experiments are consistent with this interpretation. While both eye fields and EFTF-expressing pluripotent cells generated epidermis, forebrain, and olfactory tissue when grafted to the anterior neural plate, transplanted eye fields also formed muscle and head mesenchyme( Figure 4 and unpublished data). A requirement for mesoderm is supported by the work of Asashima, showing that tissue recombinants including lateral marginal zone or the mesoderm inducer Activin A generates muscle as well as pax6 expressing eye-like structures with lens in vivo as well as in vitro[27],[28]. The presence of lens in these tissue recombinants may also be telling as EFTF-expressing pluripotent cells very infrequently formed lens. The reduced ability of the EFTFs to induce lens in the embryonic flank may be the cause of the abnormal layering we observed, since the lens and retina are dependent on each other for their normal formation. It is interesting that YFP-expressing pluripotent cells were rarely detected in the lens, yet often present in the cornea since the surface ectoderm forms both the lens and the cornea. All surgeries were performed on stage 15 embryos. At this developmental stage, the presumptive lens ectoderm lies lateral to, and outside the neural plate[29],[30]. Therefore, successful removal of part or the entire eye field would spare the host presumptive lens ectoderm in the majority of the animals. Following neurulation, the externally localized( YFP-negative) lens ectoderm comes to lie over the evaginating optic vesicle, they make contact, the lens placode forms, and together they invaginate to form the optic cup and lens vesicle( reviewed in[31]). We speculate, that once the YFP-negative lens vesicle separates from the surface ectoderm, the cornea forms from the remaining surface ectoderm( YFP-positive) and neural crest-derived mesenchyme[32]. YFP-expressing pluripotent cells did not form neural tissue( retina or brain), but were always observed in the epidermis of tadpoles. This suggests that the transplanted, control cells move from the eye field to the surface ectoderm outside the neural plate. Conversely, EFTF-expressing pluripotent cells( and transplanted eye fields) remained in the anterior neural plate. In Xenopus, expression of the EFTFs pax6, rx1, as well as otx2 redirect ventral progenitors normally destined to form epidermis into the eye field where they form retina[20]. It will be important to identify the transcriptional targets of the EFTFs and the mechanism( s) responsible for these morphological movements. Eyes generated from pluripotent cells continued to grow throughout the life of the animals and contained a population of mitotically active cells in the CMZ suggesting the presence of retinal stem cells. During early embryonic development, cells throughout the forming retina are proliferative. Progenitors of the central retina are the first to leave the cell cycle and differentiate into the six neuronal and one glial cell class of the mature retina. In some species( including Xenopus), the most peripheral cells of the retina never differentiate but form the retinal stem cells of the CMZ[33],[34]. The Wnt, Shh, BMP, Insulin/IGF, and FGF signaling pathways have all been implicated in establishing and maintaining the adult retinal stem cell niche( reviewed in[34]–[37]). Determining the effect( s) of these extrinsic factors on induced retinal cells and the formation of the CMZ in induced eyes will help define the molecular mechanisms regulating the formation and maintenance of retinal stem cells and the niche in which they reside. EFTF-expressing pluripotent cells form functional retinal cells and eyes when transplanted to the developing embryo, but can these induced retinal cells also differentiate into all the functional retinal cell classes in a mature normal or damaged retinal environment? Cultured mouse, monkey, and human pluripotent cells can be driven down a retinal lineage as determined by the expression of marker genes, including the EFTFs[2]–[4]. When transplanted to the mouse retina, human ES cells directed to a retinal lineage partially restore light-elicited ERG responses[5]. Noggin is a key component in the cocktail used to bias human ES cells to a retinal lineage, and we found it was also sufficient to direct Xenopus pluripotent cells to retinal cell classes and eventually functional eyes. The assays presented here demonstrate a rapid and simple system for testing individual and combinations of intrinsic and extrinsic factors for their ability to direct pluripotent cells to multipotent retinal cells, with the option of testing them functionally. Future studies can now address how to maintain induced retinal cell cultures in a proliferative, multipotent state and drive them to all the retinal cell classes necessary to repair a damaged or degenerating mature retina.", "role": "user" }, { "content": "The goal of regenerative medicine is to replace dead or dying cells . Successful cell replacement depends on the ability of donor cells to differentiate into all functional cell types lost in the target organ . Blindness resulting from retinal disease or damage , for example , would require the replacement of as many as seven specialized cell types found in the retina . The most celebrated characteristic of pluripotent cells is their ability to differentiate into any adult cell type . This defining feature , however , presents the challenge of identifying the conditions for their conversion to the cell types needed for tissue repair . We asked if pluripotent cells could be directed to generate all the retinal cell types necessary to form a functional eye in the frog , Xenopus laevis . If left untreated , transplanted pluripotent cells only form the epidermal layer of the skin . However , when forced to express the eye field transcription factor ( EFTF ) genes , the cells differentiate into all seven retinal cell classes and eventually organize themselves into a functioning eye that can detect light and guide tadpoles in a vision-based behavior . Our results demonstrate that pluripotent cells can be purposely altered to generate all the functional retinal cell classes necessary for sight .", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nItisnoteworthythatLysotrackerdye,whichselectivelyaccumulatesinacidiccompartments,exhibitedthemostmarkedreductioninlysosomallabeling.", "role": "user" }, { "content": "[\"dye\", \"acidic\"]", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nINTRODUCTION: Perceptions of health risks inform decisions about protective behaviors, but COVID-19 was an unfamiliar risk as it began to spread across the U.S. In the initial stage of the epidemic, authors examined perceived risks for COVID-19 infection and infection fatality and whether these risk perceptions were associated with protective behaviors. They also examined whether findings differed between later versus earlier responders. METHODS: Between March 10 and March 31, 2020, a cross-sectional online survey was conducted with a nationally representative U.S. sample (n=6,684). Half responded before March 13, 2020 (versus later). Participants assessed their risks of COVID-19 infection and infection fatality (0%-100%) which were transformed into quartiles (1-4). They reported their implementation of protective behaviors like handwashing and social distancing (yes/no). Analyses were conducted in AprilMay 2020. RESULTS: Median perceived risk was 10.00% for COVID-19 infection and 5.00% for infection fatality, but respondents showed large disagreement. An increase of 1 quartile in perceived infection risk was associated with being 1.45 times (95% CI=1.33, 1.58) more likely to report handwashing, with perceived infection fatality risk showing no significant association. When predicting social distancing behaviors such as avoiding crowds, both quartile-based risk perceptions were significant (OR=1.24, 95% CI=1.17, 1.30 for infection and OR=1.19, 95% CI=1.13, 1.26 for infection fatality). Perceived COVID-19 infection risk, protective behaviors, and their relationship increased among later (versus earlier) responders. CONCLUSIONS: Despite disagreements about the risks, people perceiving greater risks were more likely to implement protective behaviors-especially later (versus earlier) in March 2020. These findings have implications for risk communication.", "role": "user" }, { "content": "[\"Prevention\"]", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nSectionswerelightlycounterstainedandviewedwithbrightanddarkfieldmicroscopy.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Analyze the following collection of medical RCT summaries. Your goal is to craft a concise synthesis of the findings. Focus on the core insights and present them succinctly. Only include the synthesis in your response. Below are the RCT summaries:\n\n\n\nReport 1:\nTitle: The effect of health and nutrition education intervention on women's postpartum beliefs and practices: a randomized controlled trial\nSummary: Background ' Sitting month ' is the Chinese tradition for postpartum customs . Available studies indicate that some of the traditional postpartum practice s are potentially harmful for women 's health . However , no intervention study aim ing at postpartum practice s has been performed . In this paper we evaluated the effect of a health and nutrition education intervention , which focused on improving postpartum dietary quality and optimal health behaviors . Methods The study design was a r and omized controlled trial conducted in both urban and rural area of Hubei between August 2003 and June 2004 . A total of 302 women who attended the antenatal clinic during the third trimester with an uncomplicated pregnancy were recruited . Women r and omized to the education intervention group in both urban and rural area received two two-hour prenatal education sessions and four postpartum counseling visits . Control group women received usual health care during pregnancy and postpartum period . Women were followed up until 42 days postpartum . Outcome measures were nutrition and health knowledge , dietary behavior , health behavior and health problems during the postpartum period . Results Women in the intervention groups exhibited significantly greater improvement in overall dietary behaviors such as consumption of fruits , vegetables , soybean and soybean products as well as nutrition and health knowledge than those in the control groups . Significantly more women in the intervention groups give up the traditional behavior taboos . The incidence of constipation , leg cramp or joint pain and prolonged lochia rubra was significantly lower in the intervention groups as compared with the control groups . Conclusion The study shows that health and nutrition education intervention enable the women take away some of the unhealthy traditional postpartum practice s and decrease the prevalence of postpartum health problems . The intervention has potential for adaptation and development to large-scale implementation . Trial registration\n\n\nReport 2:\nTitle: Defecatory symptoms during and after the first pregnancy: prevalences and associated factors\nSummary: A prospect i ve cohort study was undertaken to evaluate the impact of pregnancy and the first delivery on the defecatory symptoms and to identify associated factors . Included were 487 nulliparous pregnant women who completed four question naires . Flatus and fecal incontinence , constipation , and painful defecation are already present in early pregnancy and are significantly predictive for reporting symptoms after delivery , except for fecal incontinence . A third or fourth degree sphincter tear was significantly associated with fecal incontinence 12 months postpartum and with de novo fecal incontinence , while other factors associated with de novo onset of symptoms were of borderline significance . Defecation symptoms already present in early pregnancy are highly predictive for reported symptoms at 12 months postpartum except for fecal incontinence that is mainly related to anal sphincter lesion . Therefore , investigating the effects of childbirth in general on the anorectal function is not justified without knowledge of this function during pregnancy\n\n\nReport 3:\nTitle: Randomized, Clinical Trial of Bowel Confinement vs. Laxative Use After Primary Repair of a Third-Degree Obstetric Anal Sphincter Tear\nSummary: PURPOSE : Third-degree tears are generally managed by primary anal sphincter repair . Postoperatively , some physicians recommend laxative use , whereas others favor bowel confinement after anorectal reconstructive surgery . This r and omized trial was design ed to compare a laxative regimen with a constipating regimen in early postoperative management after primary obstetric anal sphincter repair . METHODS : A total of 105 females were r and omized after primary repair of a third-degree tear to receive lactulose ( laxative group ) or codeine phosphate ( constipated group ) for three days postoperatively . Patients were review ed at three days and at three months postpartum . Recorded outcome measures were symptomatic and functional outcome and early postoperative morbidity . RESULTS : Forty-nine patients were r and omly assigned to the constipated group and 56 patients to the laxative group . The first postoperative bowel motion occurred at a median of four ( mean , 4.5 ( range , 1–9 ) ) days in the constipated group and at two ( mean , 2.5 ( range , 1–7 ) ) days in the laxative group ( P < 0.001 ) . Patients in the constipated group had a significantly more painful first evacuation compared with the laxative group ( P < 0.001 ) . The mean duration of hospital stay was 3.7 ( range , 2–6 ) days in the constipated group and 3.05 days in the laxative group ( range , 2–5 ; P = 0.001 ) . Nine patients in the constipated group complained of troublesome postoperative constipation compared with three in the laxative group ( P = 0.033 ) . Continence scores , anal manometry , and endoanal ultrasound findings were similar in the two groups at three months postpartum . CONCLUSIONS : Patients in the laxative group had a significantly earlier and less painful bowel motion and earlier postnatal discharge . There was no difference in the symptomatic or functional outcome of repair between the two regimens\n\n\nReport 4:\nTitle: Changes in Bowel Function: Pregnancy and the Puerperium\nSummary: Pregnancy is a time when women are susceptible to bowel habit perturbations . The purpose of this study was to provide new baseline data for a range of bowel habit parameters . Prospect i ve 7-day bowel habit diaries were completed during each of the three trimesters of pregnancy and after birth . Sensations of incomplete evacuation and time spent defecating were significantly increased during all three trimesters of pregnancy compared with after birth ( P < 0.05 ) . Symptoms of urgency were higher in nonlactating mothers ( 41 % of occasions ) compared with lactating women ( 17 % pf occasions ) ( P=0.07 ) . This study has confirmed the importance of investigating a range of bowel habit parameters during and after pregnancy — investigation of constipation per se may obscure changes in individual bowel habit parameters\n\n\nReport 5:\nTitle: Constipation in Pregnancy: Prevalence, Symptoms, and Risk Factors\nSummary: OBJECTIVE : To prospect ively estimate constipation prevalence and risk factors in pregnancy . METHODS : We enrolled healthy pregnant women in this longitudinal study during the first trimester . At each trimester and 3 months postpartum , participants completed a self-administered bowel symptom question naire , physical activity and dietary fiber intake measures , and a prospect i ve 7-day stool diary . Constipation was defined using the Rome II criteria ( presence of at least two of the following symptoms for at least one quarter of defecations : straining , lumpy or hard stools , sensation of incomplete evacuation , sensation of anorectal obstruction , manual maneuvers to facilitate defecation , and fewer than three defecations per week ) . Generalized linear logistic models explored factors associated with constipation during pregnancy . RESULTS : One hundred three women were enrolled with mean ( ±st and ard deviation ) age of 28 ( ±5 ) years ; 54 % were nulliparous and 92 % white . Constipation prevalence rates were 24 % ( 95 % confidence interval [ CI ] 16–33 % ) , 26 % ( 95 % CI 17–38 % ) , 16 % ( 95 % CI 8–26 % ) , and 24 % ( 95 % CI 13–36 % ) in the first , second , and third trimesters and 3 months postpartum , respectively . Additionally , irritable bowel syndrome ( by Rome II criteria ) prevalence rates were 19 % ( 95 % CI 12–28 % ) , 13 % ( 95 % CI 6–23 % ) , 13 % ( 95 % CI 6–23 % ) and 5 % ( 95 % CI 1–13 % ) in the first , second , and third trimesters and 3 months postpartum , respectively . In multivariable longitudinal analysis , iron supplements ( OR 3.5 , 95 % CI 1.04–12.10 ) and past constipation treatment ( OR 3.58 , 95 % CI 1.50–8.57 ) were associated with constipation during pregnancy . CONCLUSION : Constipation measured using the Rome II criteria affects up to one fourth of women throughout pregnancy and at 3 months postpartum . LEVEL OF EVIDENCE :\n\n\nReport 6:\nTitle: Constipation during pregnancy: a longitudinal survey based on self-reported symptoms and the Rome II criteria\nSummary: An increase in the prevalence of constipation during pregnancy has been suggested to occur . We design ed a prospect i ve study to evaluate the prevalence of constipation during pregnancy and puerperium , to investigate possible associations with eating habits and lifestyle , and to evaluate the frequency of laxative use . A structured question naire was developed addressing demographics , obstetric characteristics , lifestyle , eating habits , variables required for the diagnosis of constipation , and laxative use to evaluate the prevalence of constipation during pregnancy and puerperium . The question naire was administered in the obstetric clinic in the first trimester of pregnancy , and by telephone in the second and third trimesters , and in the puerperal period . The prevalence of self-reported constipation in these time periods was 45.4 , 37.1 , 39.4 , and 41.8 % , respectively . Prevalence defined by the Rome II criteria for the same time periods was 29.6 , 19 , 21.8 , and 24.7 % . These values were similar to the data previously reported for the female population . Agreement between the self-reported and Rome II results was moderate . The self-reported criterion showed high sensitivity in all time periods , using the Rome II criterion as gold-st and ard . No factor was associated with variations in the prevalence of constipation during pregnancy , though an increase was recorded in the consumption of fruit , vegetables , fiber , and water . The prevalence of constipation during pregnancy and puerperium is similar to that recorded among the female population from the same geographic area\n\n\nReport 7:\nTitle: Stool form scale as a useful guide to intestinal transit time.\nSummary: BACKGROUND Stool form scales are a simple method of assessing intestinal transit rate but are not widely used in clinical practice or research , possibly because of the lack of evidence that they are responsive to changes in transit time . We set out to assess the responsiveness of the Bristol stool form scale to change in transit time . METHODS Sixty-six volunteers had their whole-gut transit time ( WGTT ) measured with radiopaque marker pellets and their stools weighed , and they kept a diary of their stool form on a 7-point scale and of their defecatory frequency . WGTT was then altered with senna and loperamide , and the measurements were repeated . RESULTS The base-line WGTT measurements correlated with defecatory frequency ( r = 0.35 , P = 0.005 ) and with stool output ( r = -0.41 , P = 0.001 ) but best with stool form ( r = -0.54 , P < 0.001 ) . When the volunteers took senna ( n = 44 ) , the WGTT decreased , whereas defecatory frequency , stool form score , and stool output increased ( all , P < 0.001 ) . With loperamide ( n = 43 ) all measurements changed in the opposite direction . Change in WGTT from base line correlated with change in defecatory frequency ( r = 0.41 , P < 0.001 ) and with change in stool output ( n = -0.54 , P < 0.001 ) but best with change in stool form ( r = -0.65 , P < 0.001 ) . CONCLUSIONS This study has shown that a stool form scale can be used to monitor change in intestinal function . Such scales have utility in both clinical practice and research\n\n\nReport 8:\nTitle: [Use of polyethylene glycol in the treatment of puerperal constipation].\nSummary: We evaluated the efficiency of polyethylene glycol at low dosage as a treatment for constipation in the puerperium . A prospect i ve , open label and control study was performed in 225 puerpery patients . We observed a 94.7 % of study group patients and a 10.7 % of a control group patients had a evacuation in the first 48 hours , ( p < 0.01 ) . Decreased consistency of the stools was seen in the PEG group ( 74.3 % ) . According to our findings , low doses of PEG were useful and safe as a treatment for constipation in the puerperium , without side effects\n\n\nReport 9:\nTitle: Treatment of functional constipation with the Yun-chang capsule: a double-blind, randomized, placebo-controlled, dose-escalation trial.\nSummary: BACKGROUND AND AIM Functional constipation is a common functional bowel disorder for which there is no reliable medical treatment . This study was design ed to determine the therapeutic efficacy and safety of the Yun-chang capsule , a Chinese herbal formula , in the treatment of patients with functional constipation . METHODS In our multi-center , prospect i ve , double-blind , r and omized , placebo-controlled , dose-escalation trial , patients with functional constipation received 70 mg of Yun-chang capsule plus 35 mg placebo ( group A ) , 105 mg of Yun-chang capsule ( group B ) , or 105 mg placebo ( group C ) , three times daily for 2 weeks . The primary end-points were the changes in main symptom score and cumulative symptom score 2 weeks after the treatment . The secondary end-points were adverse events . RESULTS A total of 140 patients were recruited and 132 met the inclusion criteria ; 44 patients constituted each of the three treatment groups . Compared with patients in group C , patients in groups A and B had significant improvement in the main symptom score , cumulative symptom score , the change from baseline of the main symptom score , and the change from baseline of the cumulative symptom score at week 1 and week 2 . The scores showed slight superiority of group B over group A at week 1 and week 2 , although these differences were not statistically significant . There were no differences in adverse events . CONCLUSIONS The Yun-chang capsule is efficacious and safe for the treatment of patients with functional constipation . Larger and longer-term trials are required to fully assess the benefits and safety of this treatment for functional constipation", "role": "user" }, { "content": "Results were pooled in a meta- analysis only where there was no substantial statistical heterogeneity .\nFuture trials should report on the following important outcomes : pain or straining on defecation ; incidence of postpartum constipation , quality of life , time to first bowel movement after delivery , and adverse effects caused by the intervention such as : nausea or vomiting , pain and flatus", "role": "assistant" } ]

[ { "content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Jagged and Delta-like ligands control distinct events during airway progenitor cell differentiation\nContent Overview:\nAbstract:\nNotch signaling regulates cell fate selection during development in multiple organs including the lung. Previous studies on the role of Notch in the lung focused mostly on Notch pathway core components or receptor-specific functions. It is unclear, however, how Jagged or Delta-like ligands collectively or individually( Jag1, Jag2, Dll1, Dll4) influence differentiation of airway epithelial progenitors. Using mouse genetic models we show major differences in Jag and Dll in regulation and establishment of cell fate. Jag ligands had a major impact in balancing distinct cell populations in conducting airways, but had no role in the establishment of domains and cellular abundance in the neuroendocrine( NE) microenvironment. Surprisingly, Dll ligands were crucial in restricting cell fate and size of NE bodies and showed an overlapping role with Jag in differentiation of NE-associated secretory( club) cells. These mechanisms may potentially play a role in human conditions that result in aberrant NE differentiation, including NE hyperplasias and cancer.\nIntroduction:\nNotch signaling is a major regulator of progenitor cell fate and differentiation during organogenesis, repair-regeneration, and cancer. In mammals, four Notch receptors( Notch1–4) and five ligands( Delta-like: Dll1, Dll3 and Dll4 and Jagged: Jag1 and Jag2) have been described. All ligands, except Dll3, are Notch activating. Signaling is triggered by ligand-receptor binding through cell-cell interactions, which leads to sequential cleavage of the Notch receptor and binding of its intracellular domain( NICD) to a CSL/RBPJk-activator complex for activation of downstream target genes, such as HEY/HES-family members( Radtke and Raj, 2003; Bray, 2006). While different Notch receptors are known to act in a variety of biological processes, evidence from genetic studies suggest that the Notch effects are not necessarily dependent on the type of NICD but rather of NICD dosage( Liu et al., 2015). Notably, specific Notch ligand-receptor binding in mammalian cells appears to be mostly non-selective or context-dependent. Interestingly, systemic deletion of Jag1, Jag2, or Dll4 has been shown to result in distinct phenotypes, suggesting that these ligands could mediate unique functions not entirely due to the receptor they activate( D'Souza et al., 2009; Choi et al., 2009). Indeed, Notch ligands were reported to activate distinct targets even through binding to the same Notch receptor and ligand-specific effects have been observed in multiple contexts( Nandagopal et al., 2018). The Notch pathway plays a crucial role in the developing lung. When airways are still forming epithelial progenitors initiate a differentiation program that gives rise to secretory( club, goblet), multiciliated, and neuroendocrine( NE) cells. Previous studies addressing the role of Notch in the lung focused largely on central components of this pathway( Rbpjk, Pofut1, and Hes1). Disruption of Rbpjk or the o-fucosyl-transferase Pofut1 required for Notch signaling results in aberrant expansion of multiciliated and NE cells at the cost of secretory cells( Tsao et al., 2009; Tsao et al., 2011; Morimoto et al., 2010). Subsequent studies showed that club cells are more sensitive to deficiency in Notch2 while Notch 1-3 receptors contribute to control the NE population in an additive manner( Morimoto et al., 2012). However, it was unclear whether individual ligand families( Delta-like and Jagged) or specific ligands( Dll1, Dll4, Jag1, and Jag2) influence distinct aspects of differentiation of airway epithelial progenitors. Notably, these ligands have been reported in partially overlapping but also distinct domains in the lung( Post et al., 2000; Kong et al., 2004; Tsao et al., 2009; Xu et al., 2010b; Zhang et al., 2013; Mori et al., 2015). Here we explored the role of ligands using single and double conditional Jagged and Delta-like null alleles targeted to epithelial progenitors from early lung development. We show remarkably distinct roles of these ligands in the developing intra- and extrapulmonary airways and in the control of the expansion and differentiation of the NE microenvironment.\nDiscussion:\nHere we provide evidence for distinct roles of Notch ligands once epithelial progenitors initiate differentiation. We show that Jagged-driven Notch signaling differentially regulates cell type-specific programs of cell fate in a temporal and spatial fashion along the developing respiratory tract epithelium. In extrapulmonary airways( largely trachea here) we found that Jag ligands are not required to induce or maintain the fate of basal cell precursors. These precursors are known to generate luminal cells in fetal airways( Yang et al., 2018) and we now report that double Jag1 and Jag2 deletion leads to a major imbalance between the basal and luminal compartments with an expansion of basal cell precursors. By contrast, loss of both Jag ligands in intrapulmonary airways had no detectable impact on the NEB microenvironment. Unexpectedly, we found that Dll inactivation in Dll1cnull; Dll4cnull mutants resulted in marked expansion of NEBs and their associated secretory cells. Our analysis of the ontogeny of Notch ligands showed that Jag2 is expressed well before Jag1 in the epithelium and that both Dll1 and Dll4 appear only after NEBs form in intrapulmonary airways. Establishment of NE vs non-NE fate is known to be associated with induction of Ascl1 and a classic mechanism of lateral inhibition involving activation of Notch-Hes1 in neighboring cells( Borges et al., 1997; Ito et al., 2000; Collins et al., 2004). Interestingly, although Ascl1-labeled NE precursors have been reported in the embryonic lung as early as E12. 5, we found no expression of Dll( or Jag) ligands by these cells prior to E13. 5( Figure 1; Beckers et al., 1999; Post et al., 2000; Li and Linnoila, 2012; Kuo and Krasnow, 2015). This was intriguing since there is evidence that Hes1 is expressed and already active early in the developing lung epithelium in spite of no evidence of ligand expression in intrapulmonary airways to activate Notch signaling nearby NE cells( Tsao et al., 2009; Noguchi et al., 2015). This suggests that at these initial stages NE vs. non-NE cell fate selection is mediated by Hes1 in a Notch-independent fashion. Consistent with this, Hes1 deletion in lung epithelial progenitors at the onset of lung development( Shhcre/+; Hes1flox/flox) results in aberrant expansion of NEB precursors as early as E13. 5( Noguchi et al., 2015). Hes1-dependency on Notch is likely established at later developmental stages and could explain why genetic inactivation of the key Notch pathway components Pofut1 or Rbpjk using the ShhCre driver( the same used to delete Hes1, above), had no apparent effect in NE abundance at early( E14. 5) stages compared to the severe effects at later( E18. 5) stages( Tsao et al., 2009) and not shown). Our Dll1cnull; Dll4cnull mutants provided the first genetic proof that these ligands are crucially involved in regulating the size the NEBs, with no clear role in controlling other aspects such as the number of PNECs or NEBs per airway. By contrast, Jag ligands had no detectable influence in NEB size or abundance. Even at E14. 5, when NEBs are forming along the proximal-distal axis of intrapulmonary airways, Jag2 is still strongly expressed only at partially overlapping proximal domains such that nascent distal clusters of Ascl1+ cells arise in non-Jag2 or non-Jag1-expressing areas( Figure 1—figure supplement 2). Together our data suggest a model for the role of Notch ligands in lung development( Figure 7) in which early, when epithelial progenitors start to differentiate, a wave of Jag-Notch activation initiating in the trachea progresses in a proximal-distal fashion to establish the balance of secretory vs. multiciliated cell fates in intrapulmonary airways. A program of NE cell fate also emerges in intrapulmonary airways and as NEB start to express Dll ligands, Dll-Notch signaling is turned on in adjacent cells to form NEB-associated CCs. Local activation of Notch signaling in these cells shelters the NEB microenvironment from the neighboring epithelium, preventing aberrant NEB expansion. This role is restricted to Dll1 and Dll4, given that Jag1, Jag2 single or double mutants showed no detectable effect in the size of NEBs, NEB-associated CCs or local Notch activation. The NEB microenvironment is maintained by Dll ligands that induce Notch to maintain the local balance of NE and non-NE cell types. The relevance of a late Notch-dependent phase is underscored by the expansion of the NE domain when Dll ligands are unavailable to induce Notch to generate NE-associated CCs locally. Our observations are not in conflict with recent reports that describe aggregation of NEB by a mechanism of NE cell migration( slithering)( Kuo and Krasnow, 2015; Noguchi et al., 2015; Branchfield et al., 2016). Rather we envision that the cell fate specification events described above precede these migratory and cluster-forming events, or overlap at least partially with mechanisms reported here. Intriguingly, in spite of the absence of Dll ligands and having Jag1 and Jag2 as the sole ligands available, the NEB-associated CC in Dll1cnull; Dll4cnull airways exhibited robust Notch activation and maintained the unique features of CCs in this microenvironment( strong Upk3a, SSEA1, and low Cyp2f2). This suggested that the features above do not necessarily depend on the differential activation of Notch by NE-derived Dll ligands and can result from Jag-Notch activation in the cells immediately adjacent to NEBs. We speculate that a currently unidentified cell membrane-associated component of NE cells or a short-range diffusible signal( s) emanating from NEBs modulates Notch signaling or influences the cell fate program in adjacent CCs to endow these features( Figure 7). Lastly, the strength of receptor-ligand interactions is well known to depend on post-translational modifications of Notch receptors, particularly by the family of Fringe proteins, Lunatic( Lfng), Manic( Mfng) and Radical( Rfng)( Stanley and Okajima, 2010). Mass spectrometric analysis has demonstrated Lfng to promote Notch activation by Dll1 and decrease its activation by Jag1( Kakuda and Haltiwanger, 2017). Lfng is expressed in NEBs rather than in the NEB-associated CCs, which activates Notch signaling( Xu et al., 2010b; Xu et al., 2010a). This is reminiscent of the developing intestinal epithelium where Fringe is expressed in the ligand-presenting cells to promote Notch activity in the neighboring cells( Kadur Lakshminarasimha Murthy et al., 2018). There is currently no evidence that these proteins influence epithelial Notch signaling in the developing lung epithelium( van Tuyl et al., 2005; Xu et al., 2010b; Xu et al., 2010a). In summary our study provides novel insights into developmental mechanisms mediated by Jag/Dll/Notch in the lung. These observations could be of significance in studies of human conditions associated with aberrant expansion or differentiation of NEBs and their associated CCs. Indeed, analysis of human biopsies from normal donors and patients with pulmonary NE cell hyperplasias suggest that both the NE and NE-associated CC components are coordinately altered( Guha et al., 2017). Further studies examining the impact of Notch ligands and downstream signals in these diseases are likely to provide important insights into their pathogenesis.", "role": "user" }, { "content": "Cells communicate with each other by sending messages through a range of signaling pathways . One of the ways cells signal to each other is through a well-studied pathway known as Notch . In this pathway , cells display molecules on their surface , known as Notch ligands , that can activate Notch receptor proteins on the surface of neighboring cells . Once the Notch receptors bind to these ligands , they trigger various responses inside the cell . Notch ligands exist in two different families: Delta-like ( Dll ) ligands and Jagged ( Jag ) ligands . The layer of cells that lines the airways in the lungs consists of several different cell types . These include secretory cells that produce the fluid covering the airway surface , multiciliated cells , and neuroendocrine cells . Together these cells work as a barrier to protect the lung from environmental particles that may be breathed in . Additionally , the lung also has multipotent progenitor cells , which can become any of the other types . When Notch signaling is missing from the lung during embryonic development , not enough secretory cells are made , while other cell types are made in excess . This is because the multipotent progenitor cells need to communicate via Notch signaling to decide what type of cell to become and keep the right proportion of different cell types in the airways . In other organs , multipotent progenitors can become different types of cells depending on whether Notch signaling was activated by Dll or by Jag ligands , but it was unknown if this also happened in the lungs . Stupnikov et al . investigated the situation in the airways during development by looking at where and when Dll and Jag ligands first appeared , and by inactivating the genes that code for these ligands . They found that Jag ligands appeared well before Dll ligands , and that when the genes coding for Jag ligands were inactivated , more ciliated cells were produced . By contrast , loss of Dll ligands resulted in an increase in the neuroendocrine and their associated secretory cells , with little effect on the multiciliated cells . This increase resembled what is seen in some human diseases . The results suggest that the diversity of Notch effects in the airways depends on which Notch ligand is locally available . These observations may help to understand the mechanism of certain diseases involving neuroendocrine cells in the lung , such as small cell carcinoma or bronchial carcinoid tumors .", "role": "assistant" } ]

[ { "content": "Analyze the provided clinical trial criteria. Identify and extract distinct entities from the text.\n\nReturn the results as a JSON structure. Ensure the output is strictly in JSON format without any additional commentary.\n\nCriteria Text:\n\npatients affected by mono-lateral symptomatic knee articular degenerative pathology with history of chronic (for at least 4 months) pain or swelling;\nimaging findings of degenerative changes of the joint (osteoarthritis or chondropathy with Kellgren Lawrence Score from 0 to 3 at X-ray evaluation).", "role": "user" }, { "content": "{\"Condition\": [\"pain\", \"knee articular degenerative pathology\", \"degenerative changes\", \"chondropathy\", \"osteoarthritis\", \"swelling\"], \"Device\": [], \"Drug\": [], \"Measurement\": [\"Kellgren Lawrence Score\"], \"Mood\": [], \"Multiplier\": [], \"Negation\": [], \"Observation\": [], \"Person\": [], \"Procedure\": [\"X-ray\", \"imaging\"], \"Qualifier\": [\"symptomatic\", \"mono-lateral\"], \"ReferencePoint\": [], \"Scope\": [\"osteoarthritis or chondropathy with Kellgren Lawrence Score from 0 to 3 at X-ray\", \"osteoarthritis or chondropathy\", \"pain or swelling\"], \"Temporal\": [\"for at least 4 months\", \"chronic\"], \"Value\": [\"from 0 to 3\"], \"Visit\": []}", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nTetracaine ( ametop ) compared to placebo for reducing pain associated with intramuscular injection of palivizumab ( synagis ) . Infants receive many painful immunizations before they are 2 years old . The purpose of this study was to evaluate if topical tetracaine reduces the pain of intramuscular palivizumab compared to placebo . There were two study injections , one with tetracaine and one with placebo . Pain was scored by their parents and a pediatric nurse . Topical tetracaine was not associated with a significant reduction in pain score , although it did lead to faster recovery times . Additional pain-reduction strategies are required .", "role": "user" }, { "content": "{\"Intervention\": [\"Tetracaine ( ametop )\", \"topical tetracaine\", \"placebo .\", \"placebo\", \"palivizumab\", \"tetracaine\"], \"Outcome\": [\"Pain\", \"recovery\", \"pain score\"], \"Participant\": [\"Infants\", \"pain of intramuscular palivizumab\", \"pain associated with intramuscular injection of palivizumab ( synagis )\"]}", "role": "assistant" } ]

[ { "content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: Recurring patterns in bacterioplankton dynamics during coastal spring algae blooms\nContent Overview:\nAbstract:\nA process of global importance in carbon cycling is the remineralization of algae biomass by heterotrophic bacteria, most notably during massive marine algae blooms. Such blooms can trigger secondary blooms of planktonic bacteria that consist of swift successions of distinct bacterial clades, most prominently members of the Flavobacteriia, Gammaproteobacteria and the alphaproteobacterial Roseobacter clade. We investigated such successions during spring phytoplankton blooms in the southern North Sea( German Bight) for four consecutive years. Dense sampling and high-resolution taxonomic analyses allowed the detection of recurring patterns down to the genus level. Metagenome analyses also revealed recurrent patterns at the functional level, in particular with respect to algal polysaccharide degradation genes. We, therefore, hypothesize that even though there is substantial inter-annual variation between spring phytoplankton blooms, the accompanying succession of bacterial clades is largely governed by deterministic principles such as substrate-induced forcing.\nIntroduction:\nPelagic zones of the world's oceans seemingly constitute rather homogenous habitats, however, they feature enough spatial and temporal variation to support a large number of species with distinct niches. This phenomenon has been termed 'paradox of the plankton' by G. Evelyn Hutchinson( Hutchinson, 1961). Interactions within planktonic microbial communities are manifold and complex( see Amin et al.,( 2012) and Worden et al.( 2015) for reviews). Still, planktonic microbial communities are simple in comparison to benthic or terrestrial soil communities and thus particularly suitable for the study of microbial community composition dynamics. In recent years, continuous biodiversity studies at long-term sampling stations have started to reveal discernible deterministic patterns within marine microbial plankton communities( see Fuhrman et al.( 2015) for a recent review). This is particularly true for less dynamic oligotrophic oceanic regions that are dominated by the members of the alphaproteobacterial Pelagibacteriaceae( SAR11 clade) and the cyanobacterial Prochlorococcaceae( Prochlorococcus marinus). By contrast, more dynamic eutrophic coastal regions are subject to frequent system perturbations and thus seldom in a state of equilibrium. This can lead to apparently stochastic changes in bacterioplankton community composition. To capture recurrence of biodiversity patterns in such coastal areas, sampling must occur at the order of weekly to sub-weekly time scales over multiple years. Owing to the lack of such intensively sampled long-term time series data, our current understanding of the extent and predictability of recurring microbial biodiversity patterns for such marine habitats is still limited. A particularly important connection in the marine carbon cycle exists between marine microalgae as primary producers and heterotrophic bacteria that feed on algal biomass. Global photosynthetic carbon fixation is estimated to exceed 100 Gigatons yearly, of which marine algae contribute about half( Falkowski et al., 1998; Field et al., 1998; Sarmento and Gasol, 2012). Planktonic uni- to pluricellular algae such as diatoms, haptophytes, and autotrophic dinoflagellates are the most important marine primary producers. Diatoms alone are estimated to contribute 20–40% to global carbon fixation( Nelson et al., 1995; Mann, 1999; Armbrust, 2009). Primary production by planktonic microalgae differs from primary production by sessile macroalgae or land plants as it is much less constant, but culminates in blooms that are often massive, as occurs worldwide during spring blooms from temperate to polar regions. These blooms are highly dynamic phenomena that are time-limited by nutrients, predator grazing and viral infections. Bloom termination results in a short-lived massive release of algal organic matter that is consumed by dedicated clades of heterotrophic bacterioplankton. This trophic connection leads to synchronized blooms of planktonic bacteria during phytoplankton blooms, as has been described in various studies( Bell and Kuparinen, 1984; Niu et al., 2011; Tada et al., 2011; Teeling et al., 2012; Yang et al., 2015; Tan et al., 2015). The activities of these heterotrophic bacteria impact the proportion of algal biomass that is directly mineralized and released back into the atmosphere mostly as carbon dioxide, and the algae-derived biomass that sinks out to the bottom of the sea as carbonaceous particles. These are further remineralized by particle-associated bacteria while sinking and by benthic bacteria when reaching the sediment, even in the deep sea( e. g. Ruff et al., 2014). The remainder is buried for a long time as kerogen and forms the basis for future oil and gas reservoirs. The ratio between bacterial mineralization and burial of algae-derived organic matter thus has a profound influence on the atmospheric carbon dioxide concentration( Falkowski et al., 1998). However, the bulk of bacteria during phytoplankton blooms are free-living and not attached to particles or algae. These bacteria play a pivotal role in the mineralization of algae-derived non-particulate dissolved organic matter( DOM). The bacterial clades that respond most to phytoplankton blooms belong to the classes Flavobacteriia( phylum Bacteroidetes) and Gammaproteobacteria, and the Roseobacter clade within class Alphaproteobacteria( Buchan et al., 2014). This response is typically not uniform, but consists of a series of distinct clades that bloom one after another. In the year 2009, we investigated the response of bacterioplankton to a diatom-dominated spring phytoplankton bloom in the German Bight( Teeling et al., 2012). Within the free-living bacteria( 0. 2 to 3 µm) we observed a swift succession of bacterial clades that were dominated by Flavobacteriia and Gammaproteobacteria, with consecutively blooming Ulvibacter( Flavobacteriia), Formosa( Flavobacteriia), Reinekea( Gammaproteobacteria), Polaribacter( Flavobacteriia) genera and SAR92( Gammaproteobacteria) as prominent clades. Using time-series metagenome and metaproteome analyses, we demonstrated that the substrate-spectra of some of these clades were notably distinct. The succession of bacterioplankton clades hence constituted a succession of distinct gene function repertoires, which suggests that changes in substrate availability over the course of the bloom were among the forces that shaped the bacterioplankton community. Dominance of bottom-up over top-down control is assumed to be characteristic for the initial phases of spring phytoplankton blooms. After winter, inorganic nutrients are aplenty, and the overall abundance of microbes is low. When suitable temperature and sunlight conditions are met in spring, algae and subsequently bacteria can enter an almost unrestricted proliferation. In contrast, predators such as flagellates, protists and zooplankton can only start proliferating when their food sources are available in larger numbers. Hence, top-down control by predation sets in only during later bloom phases. This situation is distinct from summer and fall phytoplankton blooms. Pronounced differences between blooming clades were found in the gene frequencies and protein expression profiles of transporters and carbohydrate-active enzymes( CAZymes;[Cantarel et al., 2009; Lombard et al., 2014]), such as glycoside hydrolase( GH), polysaccharide lyase( PL), carbohydrate esterase( CE), or carbohydrate-binding module( CBM) containing genes. The latter indicates a pronounced niche partitioning with respect to algal polysaccharide degradation. Marine algae produce large quantities of distinct polysaccharides, for example storage, cell matrix and cell wall constituents, or as part of extracellular transparent exopolymer particles( TEP). It has been recently shown that in particular Flavobacteriales and Rhodobacterales respond to TEP availability( Taylor et al., 2014). The diversity of algal polysaccharides is too high for a single bacterial species to harbor all the genes required for the complete degradation of all naturally occurring variants. Thus, polysaccharide-degrading bacteria specialize on dedicated subsets of polysaccharides, which is why the decomposition of algal polysaccharides during and after algal blooms is a concerted effort among distinct bacterial clades with distinct glycan niches( e. g. Xing et al., 2015). In this study, we provide evidence that the succession of bacterioplankton clades that we reported for the 2009 North Sea spring phytoplankton bloom re-occurred during the spring blooms from 2010 to 2012. We tested whether the bacterioplankton clades and their associated CAZyme repertoires differ from year to year or exhibit recurrent patterns. We analyzed spring bacterioplankton community composition via 16S rRNA catalyzed reporter deposition fluorescence in situ hybridization( CARD-FISH) and 16S rRNA gene tag sequencing, as well as gene function repertoires by deep metagenome sequencing. Our efforts have culminated into the as of yet highest resolved dataset capturing the response of planktonic bacteria to marine spring phytoplankton blooms and have allowed identification of recurring patterns that might ultimately lead to an explanatory model for bacterioplankton succession dynamics during spring algae blooms.\nDiscussion:\nBacterioplankton communities during spring phytoplankton blooms in the coastal North Sea undergo swift and dynamic composition changes and thus are difficult to investigate. Nonetheless, we found clades that recurrently reached high abundances among Flavobacteriia( Formosa, Polaribacter, NS3a marine group, Ulvibacter, VIS6 clade Cryomorphaceae, Tenacibaculum), Gammaproteobacteria( Alteromonadaceae/Colwelliaceae, SAR92, Reinekea) and Roseobacter clade Alphaproteobacteria( DC5-80-3, NAC11-7). Recurrence was not only detectable on the taxonomic but also on the functional level with a highly predictable increase in TonB-dependent polysaccharide uptake systems and distinct CAZyme patterns. The niches of abundant bacterioplankton clades are more complex and manifold than the glycan niches that we explore in this study. CAZymes, however, have the advantage that they allow linking of gene repertoires and possible environmental functions in a way currently not feasible for other macromolecules such as proteins and lipids. Our results suggest that besides stochastic also deterministic effects influence phytoplankton-bacterioplankton coupling during blooms. They indicate that during spring phytoplankton blooms similar principles of resource partitioning and specialization are at play as within human gut microbiota that decompose fiber-rich plant material, albeit at a much larger scale. Rather the availability of substrates commonly occurring in microalgae than one-to-one interactions of particular phytoplankton and bacterioplankton species caused the succession of free-living bacterioplankton clades.", "role": "user" }, { "content": "Small algae in the world's oceans remove about as much carbon dioxide from the atmosphere as land plants . These algae do not grow continuously , but often surge in numbers during temporary blooms . Such blooms can be large enough to be seen from space by satellites . The lifespan of algae within such blooms is short , and when they die , marine bacteria feed on the remnants , which releases much of the stored carbon dioxide . Much of an algal cell consists of different types of polysaccharides . These large molecules are essentially made from sugars linked together . Polysaccharides are varied molecules and can contain many different sugars that can be linked in a number of different ways . During algae blooms bacteria proliferate that are specialized in the degradation of these polysaccharides . In 2012 , researchers reported how over the progression of an algae bloom different groups of marine bacteria bloomed in rapid succession . However , it remained unknown whether the same or different groups of bacteria respond to algae blooms at the same place from year to year , and whether or not these bacteria use the same enzymes to degrade the polysaccharides . Teeling , Fuchs et al . – who include many of the researchers from the 2012 study – now report on the analysis of a series of algae blooms that occurred in the southern North Sea between 2009 and 2012 . The analysis is based on samples collected every week during the spring seasons , and shows that certain groups of related bacteria , known as clades , became common during each bloom . Teeling , Fuchs et al . also found indications that the clades that repeatedly occurred had similar sets of genes for degrading algal polysaccharides , but that the sets were different between the clades . These data suggest that there is a specialized bacterial community that together can degrade the complex mixture of algal polysaccharides during blooms . This community reappears each year with an unexpectedly low level of variation . Since different species of algae made up the blooms in each year , this finding suggests that the major polysaccharides in these algae are similar or even identical . Future work will focus on the specific activities of bacterial enzymes that are needed to degrade polysaccharides during algae blooms . Study of these enzymes in the laboratory will help to resolve , which polysaccharides are attacked in which manner , and to ultimately help to identify the most abundant algal polysaccharides . This will improve our current understanding of the carbon cycle in the world’s oceans .", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A Review of Interoperability Standards in E-health and Imperatives for their Adoption in Africa \nChapter Title: INTRODUCTION \n1. Abstract of Cited Paper (BIB001): This most widely used textbook in the field has been thoroughly revised and updated to reflect changes in the health care industry and the renewed focus on health care information technology initiatives. Two new chapters cover Federal efforts to enhance quality of patient care through the use of health care information technology and strategy considerations. Additionally, reflecting the increased focus on global health, the book features an international perspective on health care information technology. Case studies of organizations experiencing management-related information system challenges have been updated and several new cases have been added. These reality-based cases are designed to stimulate discussion among students and enable them to apply concepts in the book to real-life scenarios. The book's companion Web site features lecture slides, a test bank, and other materials to enhance students' understanding. \n2. Abstract of Cited Paper (BIB002): Is there any evidence that e-health—using information technology to manage patient care—can have a positive impact in developing countries? Our systematic review of evaluations of e-health implementations in developing countries found that systems that improve communication between institutions, assist in ordering and managing medications, and help monitor and detect patients who might abandon care show promise. Evaluations of personal digital assistants and mobile devices convincingly demonstrate that such devices can be very effective in improving data collection time and quality. Donors and funders should require and sponsor outside evaluations to ensure that future e-health investments are well-targeted.\n\nReview Chapter:", "role": "user" }, { "content": "The healthcare domain is highly transaction-intensive and requires interactions between the multidisciplinary team of healthcare professionals, the subject of care or patient, administration personnel, medical insurers, suppliers and other stakeholders [2] BIB002 . Quality healthcare requires effective collaboration and the ability to communicate essential information between and among all the stakeholders in order to facilitate continuity of care . The adoption of information and communication technologies (ICT) to support healthcare delivery has the potential to positively impact the quality of care, improve healthcare service efficiencies, and enable scaleup of healthcare programmes especially in hard-toreach communities in developing countries BIB003 . According to World Health Organization (WHO) and International Telecommunication Union (ITU) , this is simply what e-health entails, i.e., the use of ICTs E-health offers many benefits to healthcare consumers, providers, as well as managers and policy makers. From a consumer's perspective, e-health facilitates access to quality healthcare services, especially to people in remote and under-resourced communities. Consumers can receive better and safer healthcare, since relevant health information is more readily available to care providers when required. Consumers also become active participants in ensuring their well-being through access to more reliable, accredited health information . For the provider, e-health supports informed decision making through the availability of more accurate health information, access to medical knowledge databases and best practises. Multidisciplinary teams of care providers can share health information and coordinate health interventions in an effective manner, thereby reducing unnecessary duplication of efforts. Adverse drug events can be averted through the use of e-prescription systems that flag alerts when an order is made for medications which have adverse interactions with other medications that a patient is currently on, or to which the patient is known to be allergic. Furthermore, time spent clarifying and re-writing illegible prescriptions is freed up and can be better utilized . Policy makers benefit from e-health through access to more accurate and reliable information, upon which healthcare investment decisions can be based. Thus, health service interventions can be directed to where they are most urgently needed. Managers can better monitor and evaluate health intervention programmes through access to more accurate national health data summaries . Despite the potential of e-health to positively influence the quality of care and improve healthcare service efficiencies, its widespread adoption has been very slow due to a number of factors, including the high cost of acquisition, especially at the initial stage , resistance to change on the part of healthcare professionals , security, privacy and confidentiality concern [9] BIB001 , and lack of technical skills . The inability of healthcare information systems (HISs) to interoperate on a national scale exacerbates the slow uptake of ehealth. According to the ITU , one of the barriers to reaping the full benefits of e-health is this inability to share information. Standardization is key to achieving interoperability. However, the e-health standardization arena is fraught with many challenges, which include the huge number of available standards, with many of them competing and overlapping, and some even contradicting one another . This paper provides a literature review of what interoperability entails in the healthcare domain and the special role of standardization in the achievement of interoperability. Currently, e-health interoperability and standardization, as well as their level of adoption in Africa, is under-researched, with little or no published research available. The paper primarily aims to inform the health informatics community in Africa, who may be looking for an overview of, or introduction to, the ehealth interoperability and standardization landscape. The remainder of the paper is structured as follows: in Section 2, we give an in-depth discussion of e-health interoperability, its levels, benefits and challenges, as well as the factors that enable interoperability. Section 3 provides a summary of e-health standards development landscape through a review of the prominent standards development organizations (SDOs). Section 4 takes a look at the role of standardization in achieving interoperability. In addition to providing the benefits of standardization, the section includes a classification scheme for e-health interoperability standards, together with the level(s) of interoperability that are typically addressed by such standards (using a selection of standards as examples). Section 5 gives an overview of e-health standards adoption and implementation in Africa, highlights the prevalence of non-interoperable healthcare systems on the continent and some of the challenges that prevent the widespread adoption of e-health interoperability standards. In Section 6, we discuss some of the global initiatives to overcome the barriers. We conclude the paper in Section 7.", "role": "assistant" } ]

[ { "content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nGeometric and energetic data from ab initio calculations of haloethene, haloimine, halomethylphosphine, haloiminophosphine, halodiazene, halodiphosphene and halocyclopropane Authors\n\nContent Extracts:\nValue of the Data\n<p>• Systematic and high-quality quantum chemical results in this article can be used by scientists to understand the nature of chemical bonding in these compounds and to explore special phenomena such as the cis effect [1]. • General/trivial trends and some anomalies can be observed in both geometric and energetic data of the compounds.</p><p>Experimental results are currently very limited and these trends can provide further insights into development of future experiments. • Provided source codes can be modified for uses in other classes of compounds.</p>\n\nData\n<p>In this data set, we present the theoretical results from a combinatorial investigation of substituted cyclopropane and doublebonded (a combination of C, N and P) compounds. The data in this paper were generated and optimized in vacuum by ab initio quantum chemical calculations at HF/6-311++G(d,p), B3LYP/6-311++G(d,p), MP2/6-311++G(d,p) and CCSD/6-311++G(d,p) levels of calculations.</p><p>• The geometric data include all the available bond lengths of A1=A2 and A1-a, all bond angles of a-A1-b and a-A1-A2, and dihedral angles of a-A1-A2-b, where A1/A2 and a/b refer to the central and peripheral atoms respectively. • The energetic data include electronic energy (Eelec), thermal correction to enthalpy (Hcorr), enthalpy (H), entropy (S), and</p><p>Gibbs free energy at 298.15 K (G). • The data are available in tables (.xlsx files) along with other associated Unix shell scripts (as text files) and Wolfram Mathematica notebooks (.nb files) are provided in the supplementary information. • Output files which include vibrational spectrum are also available and can be viewed in IQmol. [2] Here we include geometric and energetic data of the halogenated forms of seven classes of compounds: ethene (C=C), imine (C=N), methylphosphine (C=P), iminophosphine (N=P), diazene (N=N), diphosphene (P=P) and cyclopropane (∆) where substitutions are via halogenation (including F, Cl, Br and I) with all degrees of substitution from mono-to tetra-substitution. The total numbers of all possible compounds are as follows: 175 for C=C (Table 1), 125 for C=N (Table 2), 125 for C=P (Table 3), 50 for N=P (Table 4), 30 for N=N (Table 5), 30 for P=P (Table 6) and 315 for ∆ (Table 7). The total number of structures are summarized in Table 8. The dataset described in this paper is the most comprehensive compared to other previously published results on these compounds [3][4][5][6].</p>\n\nTable 1 List of 175 structures for haloethene (C=C) Empirical Formula\n<p>Number of Empirical Formula Isomer/Formula Total number of structures Empirical Formula Number of Empirical Formula Isomer/Formula Total number of structures * If α is H there is no R/S and the number of total isomers must be calculated separately for this case.</p>\n\nExperimental Design, Materials, and Methods\n<p>Q-Chem input files (.inp) were generated using shell scripts previously described elsewhere [7][8][9]. The ab initio calculations were performed using the Q-Chem 5.1 program package [10] to optimize the structures at HF, B3LYP, MP2 and CCSD levels of theory on 6-311++G(d,p) basis set. The rationale behind the choosing of this basis set is the availability of iodine, which was used as a part to fulfill all possible halogenation in this combinatorial investigation. Frequency calculations confirm that structures are minima on the electronic potential energy surface for all HF, B3LYP and MP2 jobs and some CCSD jobs where possible. The output files were processed using Wolfram Mathematica [11] to extract relevant geometric and energetic data of all the seven classes of compounds.</p>", "role": "user" }, { "content": "This article presents theoretical data on geometric and energetic features of halogenated compounds of cyclopropane (∆) and ethene (C=C), imine (C=N), methylphosphine (C=P), iminophosphine (N=P), diazene (N=N) and diphosphene (P=P). The data were obtained from ab initio geometric optimization and frequency calculations at HF, B3LYP, MP2 and CCSD levels of theory on 6-311++G(d,p) basis set. Input structures were generated by shell scripts and run by Q-Chem quantum chemical package. The output files were processed to extract geometric and energetic information by Wolfram Mathematica.", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nNicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD(+)) precursors, due to its numerous potential health benefits mediated via elevated NAD(+) content in the body. NAD(+) is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD(+) precursors.", "role": "user" }, { "content": "[\"Treatment\", \"Mechanism\"]", "role": "assistant" } ]

[ { "content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: NAD+ enhances ribitol and ribose rescue of α-dystroglycan functional glycosylation in human FKRP-mutant myotubes\nContent Overview:\nAbstract:\nMutations in the fukutin-related protein( FKRP) cause Walker-Warburg syndrome( WWS), a severe form of congenital muscular dystrophy. Here, we established a WWS human induced pluripotent stem cell-derived myogenic model that recapitulates hallmarks of WWS pathology. We used this model to investigate the therapeutic effect of metabolites of the pentose phosphate pathway in human WWS. We show that functional recovery of WWS myotubes is promoted not only by ribitol but also by its precursor ribose. Moreover, we found that the combination of each of these metabolites with NAD+ results in a synergistic effect, as demonstrated by rescue of α-dystroglycan glycosylation and laminin binding capacity. Mechanistically, we found that FKRP residual enzymatic capacity, characteristic of many recessive FKRP mutations, is required for rescue as supported by functional and structural mutational analyses. These findings provide the rationale for testing ribose/ribitol in combination with NAD+ to treat WWS and other diseases associated with FKRP mutations.\nIntroduction:\nMutations in the fukutin-related protein( FKRP) gene result in a broad spectrum of muscular dystrophy( MD) phenotypes, ranging from mild Limb-Girdle MD( LGMDR9) to Walker-Warburg syndrome( WWS), the most severe form of congenital MD( CMD)( Beltran-Valero de Bernabé et al., 2004; Brockington et al., 2001a; Brockington et al., 2001b). The biochemical hallmark of FKRP muscle disorders is hypoglycosylation of α-dystroglycan( α-DG), which leads to disruption in the interaction of α-DG with extracellular matrix proteins, in particular laminin-α2, which is essential for muscle fiber integrity( Ervasti and Campbell, 1993; Ibraghimov-Beskrovnaya et al., 1992). Due to its rarity and reduced life expectancy( <3 years), disease pathogenesis and treatment strategies remain elusive for WWS. To date, there is no effective treatment for FKRP-associated MDs( Ortiz-Cordero et al., 2021). FKRP is a ribitol-5-phosphate transferase, that in tandem with fukutin( FKTN), adds ribitol 5-phosphate onto the 3GalNAc-β1-3GlcNAc-β1–4( P-6) Man-1-Thr/Ser modification of α-DG( Core M3)( Manya et al., 2004; Yoshida-Moriguchi et al., 2013), using cytidine diphosphate( CDP)-ribitol, which is produced by isoprenoid synthase domain-containing protein( ISPD)( Gerin et al., 2016; Kanagawa et al., 2016; Praissman et al., 2016; Riemersma et al., 2015). The presence of ribitol-5-phosphate is essential for the subsequent addition of −3Xylα1-3GlcAβ1 and( 3Xylα1-3GlcAβ1) n- and, therefore, for allowing α-DG to bind to extracellular membrane ligands( Inamori et al., 2012; Manya et al., 2016; Praissman et al., 2014; Willer et al., 2014). The addition of the pentose phosphate pathway( PPP) metabolites ribitol or ribose, a precursor of ribitol( Gerin et al., 2016; Huck et al., 2004), to fibroblasts from patients with ISPD mutations resulted in increased CDP-ribitol levels and rescue of α-DG functional glycosylation. However, rescue varied significantly among samples with different mutations( Gerin et al., 2016; van Tol et al., 2019). Cataldi et al., 2018 documented that ribitol treatment in FKRP mutant mice modeling severe LGMDR9 partially restored α-DG functional glycosylation. More recently, Nickolls et al., 2020 showed that ribitol treatment of embryoid bodies from an LGMDR9 patient-specific induced pluripotent stem( iPS) cell line partly recovered the glycosylation defect. Taken together, these results raise several possibilities:( i) ribitol and ribose may also have a beneficial effect in WWS associated with FKRP mutations,( ii) rescue by PPP metabolites might be mutation-specific, and( iii) other metabolites may potentiate the recovery of α-DG functional glycosylation. Another metabolite of interest is β-nicotinamide adenine( NAD+). NAD forms( NAD+, NADH, NADP, and NADPH) are essential cofactors for oxidoreductases in the PPP( Singh et al., 2017). Moreover, Bailey et al., 2019 reported that NAD+ supplementation in FKRP-deficient zebrafish led to decreased muscle degeneration and improved muscle function when administered at gastrulation, before muscle development occurs. Nevertheless, to date, no human model exists to test or validate the therapeutic potential of these or any other compounds for WWS. In this study, we took advantage of the ability of iPS cells to differentiate into skeletal myotubes( Selvaraj et al., 2019b) to establish a novel WWS patient-specific in vitro model. Our results demonstrate that this system recapitulates the major skeletal muscle hallmarks of WWS. Moreover, we find that ribitol and ribose can partially rescue functional glycosylation of α-DG, and that administration of NAD+ along with each of these PPP metabolites significantly potentiates α-DG functional glycosylation rescue.\nDiscussion:\nMyoblasts harvested from patients are commonly used to model muscular dystrophies in vitro. However, in cases like WWS, the short lifespan along with the difficulty in obtaining tissue from patients represents major hurdles in establishing patient-specific myoblasts lines. The generation of patient-specific iPS cells circumvents the restricted patient tissue availability and the limited cell proliferation capacity seen in ex vivo expanded primary cells( Kondo et al., 2013; McKeithan et al., 2020; Sampaziotis et al., 2015; Young et al., 2016). To date, several experimental studies in animal models have provided evidence supporting the potential therapeutic application of gene therapy( Gicquel et al., 2017; Xu et al., 2013) and cell therapy( Azzag et al., 2020; Frattini et al., 2017) for FKRP-associated muscular dystrophies, but these studies are still at early stages, and therefore, currently there are no clinical trials underway. In this study, we show that PPP metabolites are able to increase functional glycosylation of α-DG in WWS patient-specific iPS cell-derived myotubes associated with FKRP mutations( FP4). Besides ribitol, we show that ribose is also able to provide significant increase in IIH6 immunoreactivity in FKRP mutants, which is accompanied by rescue of laminin binding. Our results indicate that both these PPP metabolites increase ribitol-5-P and CDP-ribitol levels in FP4-treated myotubes. The enhanced functional glycosylation of α-DG in FP4 mutant myotubes is hypothesized to be due to increased CDP-ribitol levels leading to increased ribitol-5-P transferase activity in the disease-causing FKRP mutant. We show for the first time that NAD+ can increase functional glycosylation of α-DG in a human WWS FKRP model, and when combined with ribitol or ribose, can significantly potentiate the rescue of the muscle pathology in vitro. Studies in dystroglycan( dag1) and FKRP zebrafish mutants have demonstrated a beneficial effect for NAD+( Bailey et al., 2019; Goody et al., 2012). Although the mechanism is not entirely elucidated, NAD+ was reported to promote increased ADP-ribosylation of integrin receptors, which in turn increase integrin and laminin binding, increase laminin-111 organization and subcellular localization of paxillin to cell adhesion complexes( Goody et al., 2012; Zolkiewska, 2005). Interestingly, overexpression of paxillin rescues muscle structure in dag1 but not in FKRP mutants, suggesting a different mechanism of action( Bailey et al., 2019). Previous studies in two Duchenne MD mouse models showed that NAD+ improved muscle function via reduced parylation, as well as increased mitochondria function and expression of structural proteins( Ryu et al., 2016). Our data on the quantification of core α-DG in FKRP-C318Y myotubes that had been treated or not with NAD+ revealed a significant increase in core α-DG upon NAD+ treatment, whereas β-DG levels remained unchanged( Figure 5—figure supplement 1), suggesting that NAD+ supplementation specifically increases α-DG. Although further studies are required to elucidate the mechanism by which NAD+ may lead to increased α-DG, a plausible hypothesis is a post-translational effect. Importantly, we show that functional FKRP mediates the rescue by ribitol, ribose, and NAD+ since FKRP KO and FKRP-C318CY myotubes do not show IIH6 rescue upon treatment with any of these compounds or combinations. Based on the recently reported FKRP crystal structure( Kuwabara et al., 2020), C318 is located in the zinc finger loop( G288 to C318) of the FKRP catalytic domain, which has been proposed to be of fundamental importance for the catalytic activity of FKRP( Kuwabara et al., 2020). Our results suggest that the ability of PPP metabolites to partially rescue α-DG functional glycosylation is mutation dependent. Although further studies are required to determine which patients could benefit from this potential treatment, our results suggest that phenotypes associated with mutations in the zinc finger loop region may not be rescued by ribitol and ribose, whereas FKRP mutations in other regions of the catalytic domain are amenable to rescue, as shown for FP4. This is in line with previous studies in ISPD fibroblasts, in which rescue of functional glycosylation of α-DG was found to be mutation dependent( Gerin et al., 2016; van Tol et al., 2019). Dietary interventions can provide a feasible and economically accessible solution for the treatment of MD associated with CDP-ribitol defects. Although ribitol/NAD+ showed promising results in our model, clinical trials to assess the safety of ribitol are still necessary. On the other hand, ribose is a commercially available supplement, and to date, with no major side effects in humans( Dodd et al., 2004; Seifert et al., 2017; Thompson et al., 2014). Furthermore, NAD+ levels can be increased by several vitamin B3 forms, such as nicotinic acid( niacin) and nicotinamide riboside, which have been investigated, showing no major side effects( Elhassan et al., 2019; Guyton and Bays, 2007; Pirinen et al., 2020). Although future research studies are necessary to determine the optimal dosage of the combined approach, the safety record of these compounds justifies using ribose/NAD+ as potential candidates to treat FKRP-associated MD. Together, our results support the use of iPS cell-derived myotubes as a reliable platform for in vitro disease modeling and drug screening. Importantly, our data provide a rationale for the potential use of ribitol/NAD+ and ribose/NAD+ as therapeutics to increase α-DG functional glycosylation in patients with FKRP mutations.", "role": "user" }, { "content": "Healthy muscles are complex machines that require a myriad of finely tuned molecules to work properly . For instance , a protein called alpha-DG sits at the surface of healthy muscle cells , where it strengthens the tissue by latching onto other proteins in the environment . To perform its role correctly , it first needs to be coated with sugar molecules , a complex process which requires over 20 proteins , including the enzyme FKRP . Faulty forms of FKRP reduce the number of sugars added to alpha-DG , causing the muscle tissue to weaken and waste away , potentially leading to severe forms of diseases known as muscular dystrophies . Drugs that can restore alpha-DG sugar molecules could help to treat these conditions . Previous studies on mice and fish have highlighted two potential candidates , known as ribitol and NAD+ , which can help to compensate for reduced FKRP activity and allow sugars to be added to alpha-DG again . Yet no model is available to test these molecules on actual human muscle cells . Here , Ortiz-Cordero et al . developed such a model in the laboratory by growing muscle cells from naïve , undifferentiated cells generated from skin given by a muscular dystrophy patient with a faulty form of FKRP . The resulting muscle fibers are in essence identical to the ones present in the individual . As such , they can help to understand the effect various drugs have on muscular dystrophies . The cells were then put in contact with either NAD+ , ribitol , or a precursor of ribitol known as ribose . Ortiz-Cordero et al . found that ribitol and ribose restored the ability of FKRP to add sugars to alpha-DG , reducing muscle damage . Combining NAD+ with ribitol or ribose had an even a bigger impact , further increasing the number of sugars on alpha-DG . The human muscle cell model developed by Ortiz-Cordero et al . could help to identify new compounds that can treat muscular conditions . In particular , the findings point towards NAD+ , ribose and ribitol as candidates for treating FKRP-related muscular dystrophies . Further safety studies are now needed to evaluate whether these compounds could be used in patients .", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nThe Boltzmann distribution is a natural model for many systems, from brains to materials and biomolecules, but is often of limited utility for fitting data because Monte Carlo algorithms are unable to simulate it in available time.\nThis gap between the expressive capabilities and sampling practicalities of energy-based models is exemplified by the protein folding problem, since energy landscapes underlie contemporary knowledge of protein biophysics but computer simulations are challenged to fold all but the smallest proteins from first principles.\nIn this work we aim to bridge the gap between the expressive capacity of energy functions and the practical capabilities of their simulators by using an unrolled Monte Carlo simulation as a model for data.\nWe compose a neural energy function with a novel and efficient simulator based on Langevin dynamics to build an end-to-end-differentiable model of atomic protein structure given amino acid sequence information.\nWe introduce techniques for stabilizing backpropagation under long roll-outs and demonstrate the model's capacity to make multimodal predictions and to, in some cases, generalize to unobserved protein fold types when trained on a large corpus of protein structures.\nMany natural systems, such as cells in a tissue or atoms in a protein, organize into complex structures from simple underlying interactions.\nExplaining and predicting how macroscopic structures such as these arise from simple interactions is a major goal of science and, increasingly, machine learning.The Boltzmann distribution is a foundational model for relating local interactions to system behavior, but can be difficult to fit to data.\nGiven an energy function U ✓ [x] , the probability of a system configuration x scales exponentially with energy as DISPLAYFORM0 where the (typically intractable) constant Z normalizes the distribution.\nImportantly, simple energy functions U ✓ [x] consisting of weak, local interactions can collectively encode complex system behaviors, such as the structures of materials and molecules or, when endowed with latent variables, the statistics of images, sound, and text BID0 BID17 .\nUnfortunately, learning model parameters✓ and generating samples x ⇠ p ✓ (x) of the Boltzmann distribution is difficult in practice, as these procedures depend on expensive Monte Carlo simulations that may struggle to mix effectively.\nThese difficulties have driven a shift towards generative models that are easier to learn and sample from, such as directed latent variable models and autoregressive models (Goodfellow et al., 2016) .The\nprotein folding problem provides a prime example of both the power of energy-based models at describing complex relationships in data as well as the challenge of generating samples from them. Decades\nof research in biochemistry and biophysics support an energy landscape theory of An unrolled simulator as a model for protein structure. NEMO combines\na neural energy function for coarse protein structure, a stochastic simulator based on Langevin dynamics with learned (amortized) initialization, and an atomic imputation network to build atomic coordinate output from sequence information. It is trained\nend-to-end by backpropagating through the unrolled folding simulation.protein folding (Dill et al., 2017) , in which the folds that natural protein sequences adopt are those that minimize free energy. Without the availability\nof external information such as coevolutionary information (Marks et al., 2012) or homologous structures (Martí-Renom et al., 2000) to constrain the energy function, however, contemporary simulations are challenged to generate globally favorable low-energy structures in available time.How can we get the representational benefits of energy-based models with the sampling efficiency of directed models? Here we explore a potential\nsolution of directly training an unrolled simulator of an energy function as a model for data. By directly training the sampling\nprocess, we eschew the question 'when has the simulator converged' and instead demand that it produce a useful answer in a fixed amount of time. Leveraging this idea, we construct\nan end-to-end differentiable model of protein structure that is trained by backpropagtion through folding ( FIG0 ). NEMO (Neural energy modeling and optimization\n) can learn at scale to generate 3D protein structures consisting of hundreds of points directly from sequence information. Our main contributions are:• Neural energy simulator\nmodel for protein structure that composes a deep energy function, unrolled Langevin dynamics, and an atomic imputation network for an end-to-end differentiable model of protein structure given sequence information• Efficient sampling algorithm that is based on a transform integrator for efficient sampling in transformed coordinate systems• Stabilization techniques for long roll-outs of simulators that can exhibit chaotic dynamics and, in turn, exploding gradients during backpropagation• Systematic analysis of combinatorial generalization with a new dataset of protein sequence and structure\nWe described a model for protein structure given sequence information that combines a coarse-grained neural energy function and an unrolled simulation into an end-to-end differentiable model.\nTo realize this idea at the scale of real proteins, we introduced an efficient simulator for Langevin dynamics in transformed coordinate systems and stabilization techniques for backpropagating through long simulator roll-outs.\nWe find that that model is able to predict the structures of protein molecules with hundreds of atoms while capturing structural uncertainty, and that the model can structurally generalize to distant fold classifications more effectively than a strong baseline.\n(MPNN, bottom left) , and outputs energy function weights l as well as simulator hyperparameters (top center).\nSecond, the simulator iteratively modifies the structure via Langevin dynamics based on the gradient of the energy landscape (Forces, bottom center).\nThird, the imputation network constructs predicted atomic coordinates X from the final simulator time step x (T ) .\nDuring training, the true atomic coordinates X (Data) , predicted atomic coordinates X, simulator trajectory x (1) , . . . , x (T ) , and secondary structure predictions SS (Model) feed into a composite loss function (Loss, bottom right), which is then optimized via backpropagation.", "role": "user" }, { "content": "We use an unrolled simulator as an end-to-end differentiable model of protein structure and show it can (sometimes) hierarchically generalize to unseen fold topologies.", "role": "assistant" } ]

[ { "content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Is recursive splicing more common in short introns?\n\nText: Recent work in human and fruitfly tissues revealed that long introns are extensively processed cotranscriptionally and in a stepwise manner, before their two flanking exons are spliced together\nCutting a Long Intron Short: Recursive Splicing and Its Implications.\nFurthermore, we uncover the potential to investigate the multi-step nature of splicing, assessing various types of recursive splicing events\nRecursive splicing is a process in which large introns are removed in multiple steps by re-splicing at ratchet points--5' splice sites recreated after splicing.\nTogether, these results indicate that recursive splicing is commonly used in Drosophila, occurs in humans, and provides insight into the mechanisms by which some large introns are removed.\nRecursive splicing in long vertebrate genes.\nMoreover, the RS-sites are found in some of the longest introns across vertebrates.\nThe peculiarities of large intron splicing in animals.\nThese \"large introns\" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites.\nUsing a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing\nSubdivision of large introns in Drosophila by recursive splicing at nonexonic elements.\nRecursive splice sites predicted with highly stringent criteria are found at much higher frequency than expected in the sense strands of introns>20 kb, but they are found only at the expected frequency on the antisense strands, and they are underrepresented within introns<10 kb.\nThese transcripts arise by use of two alternative transcription sites and complex alternative splicing mechanisms and encode proteins with long or short N-terminal domains, complete or incomplete GGL domains, 7 distinct C-terminal domains and a common internal domain where the RGS domain is found.\nThese patterns of enrichment and conservation indicate that recursive splice sites are advantageous in the context of long introns.\nMany genes with important roles in development and disease contain exceptionally long introns, but special mechanisms for their expression have not been investigated.\nHowever, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing.\nThe effect of splice site strength was context-dependent and much more significant for the 3' splice site of the longer alternative intron than for the 3' splice site of the shorter alternative intron and the common 5' splice sites; it was also more significant in the rat minigene than in the mouse minigene.\nCutting a Long Intron Short: Recursive Splicing and Its Implications.\nRecursive splicing in long vertebrate genes.", "role": "user" }, { "content": "no", "role": "assistant" } ]

[ { "content": "Evaluate the given public health statement using the provided research abstract. Your goal is to determine the relationship between the claim and the abstract content.\n\n- \"decision\": Indicate whether the abstract \"SUPPORTS\", \"CONTRADICTS\", or provides \"INSUFFICIENT\" information regarding the claim.\n- \"justification\": List sentences from the abstract that back your decision. If the decision is \"INSUFFICIENT\", leave this list empty.\n\nStatement: isolation during the pandemic may worsen or trigger mental health problems\n\nResearch Abstract:\nSocial distancing measures, with varying degrees of restriction, have been imposed around the world in order to stem the spread of COVID-19.\nIn this work we analyze the effect of current social distancing measures in the United States.\nWe quantify the reduction in doubling rate, by state, that is associated with social distancing.\nWe find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states.\nAt the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases.\nInstead, social distancing has merely stabilized the spread of the disease.\nWe provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing.\nWe also discuss the policy implications of our findings.", "role": "user" }, { "content": "{\"verdict\": \"NEI\", \"evidence\": []}", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nThat methylation of promoter sequences does not necessarily lead to silencing has been demonstrated before by Sijen et al. (2001).", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nALEPHExactL2 : Uses the limited-memory BFGS algorithm (Liu & Nocedal, 1989) implemented in ALCHEMY to learn discriminative MLN weights for the clauses in the final theory returned by ALEPH.", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "Examine the text provided from a scientific article. Identify entities and classify them.\n\nPresent your findings in a JSON format: {\"Gene\": [\"SSX\", ...]}. If no entities are found, use an empty list.\n\nText:\n\nCollagen XVIII, containing an endogenous inhibitor of angiogenesis and tumor growth, plays a critical role in the maintenance of retinal structure and in neural tube closure (Knobloch syndrome). Knobloch syndrome (KS) is an autosomal recessive disorder defined by the occurrence of high myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities and occipital encephalocele. The KS causative gene had been assigned to a 4.3 cM interval at 21q22.3 by linkage analysis of a large consanguineous Brazilian family. We reconstructed the haplotypes of this family with ten additional markers (five were novel) and narrowed the candidate interval to a region of < 245 kb, which contains 24 expressed sequence tags, the KIAA0958 gene and the 5' end of the COL18A1 gene. We identified a homozygous mutation at the AG consensus acceptor splice site of COL18A1 intron 1 exclusively among the 12 KS patients, which was not found among 140 control chromosomes. This mutation predicts the creation of a stop codon in exon 4 and therefore the truncation of the alpha1(XVIII) collagen short form, which was expressed in human adult retina. These findings provide evidence that KS is caused by mutations in COL18A1 which, therefore, has a major role in determining the retinal structure as well as in the closure of the neural tube. Therefore, we show for the first time that the absence of a collagen isoform impairs embryonic cell proliferation and/or migration as a primary or secondary effect.", "role": "user" }, { "content": "{\"Gene\": [\"COL18A1\", \"KS causative gene\", \"AG consensus acceptor splice site\", \"Collagen XVIII\", \"KIAA0958\", \"alpha1(XVIII) collagen\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We present a novel self-adapting dissimilarity data term (SDDT) for the disparity estimation problem\n\nKeywords: disparity estimation images\n\nDataset Information:\nEPIC-KITCHENS-100: This paper introduces the pipeline to scale the largest dataset in egocentric vision EPIC-KITCHENS. The effort culminates in EPIC-KITCHENS-100, a collection of 100 hours, 20M frames, 90K actions in 700 variable-length videos, capturing long-term unscripted activities in 45 environments, using head-mounted cameras.\nMPI Sintel: MPI (Max Planck Institute) Sintel is a dataset for optical flow evaluation that has 1064 synthesized stereo images and ground truth data for disparity. Sintel is derived from open-source 3D animated short film Sintel.\nMiddlebury: The Middlebury Stereo dataset consists of high-resolution stereo sequences with complex geometry and pixel-accurate ground-truth disparity data. The ground-truth disparities are acquired using a novel technique that employs structured lighting and does not require the calibration of the light projectors.\nMVSEC: The Multi Vehicle Stereo Event Camera (MVSEC) dataset is a collection of data designed for the development of novel 3D perception algorithms for event based cameras. Stereo event data is collected from car, motorbike, hexacopter and handheld data, and fused with lidar, IMU, motion capture and GPS to provide ground truth pose and depth images.\n\nAvailable Datasets: A: EPIC-KITCHENS-100 B: MPI Sintel C: Middlebury D: MVSEC", "role": "user" }, { "content": "Middlebury", "role": "assistant" } ]

[ { "content": "Review the provided collection of medical RCT summaries. Your objective is to distill the essential insights into a brief conclusion. Focus solely on the synthesis of findings without additional commentary. The RCT summaries are as follows:\n\n\n\nReport Title 1:\nUnstable articular fractures of the distal radius. Comparative techniques of ligamentotaxis.\nReport Abstract 1:\nLigamentotaxis employing either pins and plaster or external fixators, frequently in conjunction with supplemental Kirschner wire internal fixation, has proved to be a reliable means of maintaining an accurate reduction of unstable articular fractures of the distal radius. Critical preoperative evaluation and surgical restoration of articular congruity along with attention to key technical details have resulted in a reproducible successful recovery. In our experience, the advantages of the pins and plaster technique are its relatively simple methodology, its comparatively low cost, and its high level of patient acceptance. The distinctive advantages of the external fixator are its superior mechanical efficiency, its capacity for fracture adjustment during the healing period, and the fact that it ensures unimpeded access to wounds. Nonetheless, regardless of the specific method chosen, this study clearly supports the contention that precision in patient selection and pin placement are the prerequisites for successful ligamentotaxis in the management of distal radius fractures.\n\n\nReport Title 2:\nDynamic external fixation of unstable fractures of the distal part of the radius. A prospective, randomized comparison with static external fixation.\nReport Abstract 2:\nA prospective, randomized study was done to compare the results of dynamic external fixation (the Clyburn device) with those of static external fixation (the AO/ASIF device) in the treatment of fifty unstable fractures of the distal part of the radius. Mobilization of the wrist from neutral to 30 degrees of flexion was begun in the dynamic-fixator group at approximately two weeks, and full motion, allowing 30 degrees of extension, was started at approximately four weeks. The external fixation frames in both groups were kept in place for approximately ten weeks. Mobilization of the wrist in the dynamic-fixator group provided little gain in the mean motion of the wrist at the time of the removal of the fixator or at the one, six, or twelve-month evaluation. The static-fixator group had greater flexion of the wrist and radial deviation at the early and late follow-up examinations, while the dynamic-fixator group demonstrated only greater ulnar deviation one month after the fixator had been removed. Motion of the wrist in the dynamic-fixator group resulted in a statistically significant loss of radial length compared with that in the static-fixator group (four millimeters compared with one millimeter, p < 0.001). Complications were more frequent in the dynamic-fixator group. As evaluated with a modification of the scoring system of Gartland and Werley, 92 percent of the results at one year were excellent or good in the static-fixator group and 76 percent, in the dynamic-fixator group. The results of this study cannot support the concept of early mobilization with a dynamic external fixator for the treatment of unstable fractures of the distal part of the radius.\n\n\nReport Title 3:\nRedisplaced unstable fractures of the distal radius: a prospective randomised comparison of four methods of treatment.\nReport Abstract 3:\nWe performed a prospective, randomised trial on 120 patients with redisplaced fractures of the distal radius comparing four methods of treatment. The four treatment groups, each containing 30 patients, were remanipulation and plaster, open reduction and bone grafting, and closed external fixation with and without mobilisation of the wrist at three weeks. The radiological results showed improvement in angulation of the distal radius for the open reduction and bone grafting group. Functional results at six weeks, three and six months and at one year, however, showed no difference between any of the four groups. The main influence on final outcome was carpal malalignment which had a statistically significant negative effect on function.\n\n\nReport Title 4:\nImprovement of the bone-pin interface strength in osteoporotic bone with use of hydroxyapatite-coated tapered external-fixation pins. A prospective, randomized clinical study of wrist fractures.\nReport Abstract 4:\nAchieving adequate fixation strength in osteoporotic bone is a challenge. In this study, we examined the use of hydroxyapatite-coated tapered external-fixation pins for the fixation of wrist fractures in patients with osteoporosis.\n Twenty female patients with osteoporosis and a fracture of the wrist were divided into two paired groups and randomized to receive either standard tapered pins or hydroxyapatite-coated tapered pins. Two pins were inserted in the distal part of the radius, two pins were inserted in the second metacarpal, and an external fixation device was mounted. All fixation devices were removed six weeks after surgery.\n The mean pin-insertion torque (and standard deviation) was 461 +/- 254 Nmm in the group managed with standard pins and 332 +/- 176 Nmm in the group managed with hydroxyapatite-coated pins (p = 0.01). The mean pin-extraction torque was 191 +/- 155 Nmm in the group managed with standard pins and 600 +/- 214 Nmm in the group managed with hydroxyapatite-coated pins (p < 0.0001, power 95%). The mean extraction torque was lower than the corresponding insertion torque at each pin position in the group managed with standard pins (p < 0.05), whereas the mean extraction torque was higher than the corresponding insertion torque at each pin position in the group managed with hydroxyapatite-coated pins (p = 0.001). Two patients managed with standard pins and no patient managed with hydroxyapatite-coated pins had a pin-track infection. Pain during pin removal did not differ between the two groups.\n The present study showed that hydroxyapatite-coated tapered external-fixation pins provided improved fixation in the treatment of wrist fractures in patients with osteoporosis.\n\n\nReport Title 5:\nWrist-bridging versus non-bridging external fixation for displaced distal radius fractures: a randomized assessor-blind clinical trial of 38 patients followed for 1 year.\nReport Abstract 5:\nNon-bridging external fixation has been introduced to achieve better fracture fixation and functional outcomes in distal radius fractures, but has not been specifically evaluated in a randomized study in the elderly. The purpose of this trial was to compare wrist-bridging and non-bridging external fixation for displaced distal radius fractures.\n The inclusion criteria were women >/= 50 or men >/= 60 years, acute extraarticular or intraarticular fracture, and dorsal angulation of >/=20 degrees or ulnar variance >/= 5 mm. The patients completed the disabilities of the arm, shoulder and hand (DASH) questionnaire before and at 10, 26 and 52 weeks after surgery. Pain (visual analog scale), range of motion and grip strength were measured by a blinded assessor.\n 38 patients (mean age 71 years, 31 women) were randomized at surgery (19 to each group). Mean operating time was shorter for wrist-bridging fixation by 10 (95% CI 3-17) min. There was no significant difference in DASH scores between the groups. No statistically significant differences in pain score, range of motion, grip strength, or patient satisfaction were found. The non-bridging group had a significantly better radial length at 52 weeks; mean difference in change in ulnar variance from baseline was 1.4 (95% CI 0.1-2.7) mm (p = 0.04). Volar tilt and radial inclination were similar in both groups.\n For moderately or severely displaced distal radius fractures in the elderly, non-bridging external fixation had no clinically relevant advantage over wrist-bridging fixation but was more effective in maintaining radial length.\n\n\nReport Title 6:\nExternal fixation of distal radial fractures: four compared with five pins: a randomized prospective study.\nReport Abstract 6:\nThe purpose of this study of distal radial fractures was to compare the radiographic and clinical results after use of a standard four-pin external fixator with those after use of a five-pin fixator with the fifth pin stabilizing the distal radial articular fragment.\n In an open prospective trial, fifty patients with an unstable distal radial fracture were randomized for treatment with closed reduction and either a standard small Association for the Study of Internal Fixation (ASIF) four-pin fixator (twenty-five patients) or a five-pin external fixator (twenty-five patients). The fixators were removed at nine weeks, and all patients were assessed radiographically and clinically at six months.\n Follow-up radiographs demonstrated significantly less loss of alignment and length with the five-pin external fixator. Pin site infections were more prevalent with the four-pin fixator. The range of motion of the wrist and forearm, the grip strength, and the Lidstrom functional ratings at six months were all significantly better after use of the five-pin fixator.\n The use of a five-pin external fixator, with the fifth pin stabilizing the distal radial articular fragment, yields better radiographic and functional results than does a four-pin fixator.\n\n\nReport Title 7:\nPins and plaster vs external fixation in the treatment of unstable distal radial fractures. A randomized prospective study.\nReport Abstract 7:\n90 unstable fractures of the distal radius were studied in a randomized, prospective manner. Follow-up consisted of patient questionnaire, medical record review, therapist evaluation and radiography at 4 months, 1 year and 2 years post-operatively. Overall results were good or excellent in 94%. No significant differences were found between treatment groups (external fixation and pins and plaster) in final results, range of motion, intrinsic tightness, grip strength, or the presence of arthritis. The complication rate was high for both groups (45%), and half of the complications were major. External fixation maintained radial length more effectively (significantly in those patients followed for 2 years) but was associated with higher initial costs (20 times) and a greater number of minor complications.\n\n\nReport Title 8:\nRedisplaced unstable fractures of the distal radius. A randomised, prospective study of bridging versus non-bridging external fixation.\nReport Abstract 8:\nA randomised, prospective study was carried out on 60 patients with unstable fractures of the distal radius to compare bridging with non-bridging external fixation using pins placed in the distal fragment of the radius. The radiological results showed significant improvement in the non-bridging group at all stages of review. In particular, normal volar tilt and carpal alignment were regained and maintained. The functional results at six weeks, three months, six months and one year showed statistically better grip strength and flexion in the non-bridging group at all stages of review. Other ranges of movement showed an early advantage in the non-bridging group. Non-bridging external fixation is the treatment of choice for unstable fractures of the distal radius which have sufficient space for the placement of pins in the distal fragment.", "role": "user" }, { "content": "There is insufficient robust evidence to determine the relative effects of different methods of external fixation. Adequately powered studies could provide better evidence.", "role": "assistant" } ]

[ { "content": "You will be presented with the full text of a scientific research paper. Write an abstract summarizing the key points. Your response should contain only the abstract without any other text.\n\nArticle text:\nthe brackets were introduced by van der hucht et al .\n( 1981 ) to differentiate wolf - rayet central stars from massive central stars . ]\ncentral stars of planetary nebulae ( pn ) are hydrogen - deficient central stars that exhibit emission line spectra very similar to massive wolf - rayet stars . until recently it has been impossible to calculate stellar evolutionary models where the star eliminates all of its hydrogen - rich envelop at the top of the asymptotic giant branch ( agb ) .\nthis prompted the association of these objects with the born - again scenario ( iben et al .\n1983 ) , whereby a white dwarf experiences a last helium shell flash , after which it rejoins the tip of the agb for a second time and repeats its evolution , this time as a hydrogen - deficient central star .\nthe pn around [ wc ] central stars do not appear to have any characteristics which distinguish them from the pn of hydrogen - rich central stars .\na marginally higher nebular c / h ratio ( de marco & barlow 2001 ) , as well as a slightly higher pn expansion velocity ( gorny & stasinska 1995 ) , do not appear to be sufficient to characterise the sample s evolution .\nother puzzling peculiarities concern spectral appearance differences amongst members of the hydrogen - deficient central star group .\nsome hydrogen deficient central stars appear to have weaker lines than others ( called _ weak emission lines stars _\n( _ wels _ ) by tylenda , acker & stenholm ( 1993 ) ) , while in the strong - lined [ wc ] group , there appears to be a classification gap , with [ wc ] stars populating the [ wc11 - 8 ] class ( called [ wcl ] ) and [ wc5-wo1 ] ( called [ wce ] ; pottasch 1996 , crowther , de marco & barlow 1998 ) . additionally , while it is currently believed that [ wcl ] stars evolve into [ wce ] stars , the stellar abundances seem to differ in the two groups , with the more evolved group having a lower carbon abundance than the less evolved group ( see de marco & barlow ( 2001 ) for a summary of results from the literature ) , a fact that can not be easily explained .\non the other hand , infrared space observatory ( iso ) spectroscopy of pn with [ wcl ] central stars has shown that all have crystalline silicate features in their mid- to far - infrared spectra , in addition to the previously known carbon - rich pah - type features that dominate their mid - infrared spectra , betraying the simultaneous presence of both carbon - rich and oxygen - rich dust ( see barlow 1997 , waters et al .\n1998 , cohen et al . 1999 ,\ncohen 2001 ) .\nthe relatively warm temperatures deduced for the o - rich dust , together with the high nebular densities of their compact nebulae , appear to imply that the c - rich central stars evolved relatively recently from an o - rich composition .\nthis would in turn suggest that these [ wcl ] pn have been on the agb recently and so did not result from a born - again evolutionary phase , for which low - density nebulae are expected .\nthis would also imply that the carbon - rich [ wcl ] stars systematically result from oxygen - rich agb giants .\nrecent improvements in theoretical stellar evolutionary calculations have succeeded in eliminating hydrogen from the stellar atmosphere at the tip of the agb , so that the requirement that the central star undergo a born - again event in order to get rid of its hydrogen is no longer in place . according to herwig ( 2000 ) a thermal pulse\njust before the star departs from the agb can eliminate most of the hydrogen , while a well - timed post - agb pulse ( probabilistically rarer ) could account for the extreme hydrogen deficiency observed in [ wcl ] stars .\nthe combination of the iso observations and the new evolutionary calculations therefore contributes to the revision of theories about the origin of [ wcl ] central stars and for the first time we may have a viable scenario that does not require the star to go through a born - again episode .\nthe pn swst 1 around the central star hd 167362 ( we will give both star and nebula the name swst 1 ) exhibits a broad 10@xmath0 m silicate emission feature ( aitken & roche 1982 ) and has been suggested to be amongst the youngest of [ wcl ] nebulae , possibly having experienced the transition from the agb in the last century .\nthe spectrum of swst 1 was first reported by fleming ( 1895 ) , but the first complete spectroscopic analysis was carried out by swings and struve ( 1940 , 1943 ) .\nthe traditional wr c iv @xmath135806/c iii @xmath135696 line diagnostic ratio positions it within the [ wc9 ] spectral class ( crowther et al .\n1998 - see also previous classifications by cohen ( 1975 ) and by carlson and henize ( 1979 ) ) , but the weakness of its lines compared to other [ wc9 ] stars ( e.g. bd+303639 , he 2 - 99 ) or even cooler [ wc10 ] stars ( e.g. cpd56@xmath148032 , he 2 - 113 , m 4 - 18 ) prompted crowther et al .\n( 1998 ) to flag it as _ peculiar _ and has therefore essentially left it in a class of its own .\ntylenda et al . (\n1993 ) listed it amongst their _ wels _ because of the weakness of its spectral lines , but swst 1 does not resemble stars in this class either ( e.g. cn 3 - 1 , de marco 2000 ) since it has many more stellar emission features than any _ wels _ , indicative of a denser wind . in this paper we tried to determine whether the physical characteristics of the central star and the pn can shed light on the reason for these differences , i.e. whether swst 1 is at an intermediate phase between stars in the [ wcl ] class and their ancestors . in the sections that follow we present optical echelle spectra , near - infrared spectra and archival iue spectra , as well as hst images of this central star and its pn .\nusing these data we carry out a thorough analysis , to try and single out the peculiarities of this object . in section 2\nwe present our observational data , while in section 3 we derive some observational parameters .\nthe distance , luminosity and mass are discussed in section 4 .\nthe stellar analysis is tackled in section 5 , while the nebular analysis is carried out in sections 6 to 8 .\nfinally ( section 9 ) a review of the secular variability is reported and conclusions are drawn in section 10 .\nswst 1 was observed with the 3.9 m anglo - australian telescope ( aat ) on may 14 and 15 , 1993 , using the 31.6 l / mm grating of the ucl echelle spectrograph ( ucles ) , with a 1024@xmath151024 pixel tektronix ccd as detector .\nfour settings of the ccd were needed in order to obtain spectral coverage in the range 36009700 . at each wavelength setting , 5 arcsec wide - slit spectra were obtained for absolute spectro - photometry , while 1.5 arcsec narrow slit spectra ( r=50,000 ) were obtained for maximum resolution in the range 41005400 \n. the continuum signal - to - noise ratio of the averaged exposures ranges from @xmath165 in the far blue to @xmath1630 in the red .\na log of the observations is presented in table [ tab : aat93_log ] .\nthe data were reduced using the iraf ( v2.10 ) package at the ucl starlink node .\nwavelength calibration was with respect to comparison th - ar arc exposures .\nabsolute flux calibration was with respect to the b3iv star hd 60753 , whose energy distribution has been measured by oke ( 1992 ) .\ndetails of the laborious echelle data flux calibration procedure can be found in de marco , barlow & storey ( 1997 ; hereafter dbs97 ) .\nsubsequent data reduction was carried out with the starlink dipso package ( howarth et al .\nafter flux calibration , the narrow slit spectra were scaled up to the continuum level of the wide slit spectra .", "role": "user" }, { "content": "the hydrogen - deficient [ wcl ] type central star hd167362 and its planetary nebula ( pn ) swst 1 are investigated . \n the central star has a carbon - rich emission line spectrum and yet the nebula exhibits a 10-@xmath0 m emission feature from warm silicate dust , perhaps indicating a recent origin for the carbon - rich stellar spectrum . \n its stellar and nebular properties might therefore provide further understanding as to the origin of the [ wcl ] central star class . \n the central star optical and uv spectra are modelled with state of the art non - lte codes for expanding atmospheres , from which the stellar parameters are determined . using the sobolev approximation code isa - wind \n , we find t@xmath1=40000 k , log(@xmath2/m@xmath3 yr@xmath4)=6.72 , l=8900 l@xmath3 ( for a distance of 2.0 kpc ) , and @xmath5 @xmath6 900 km s@xmath4 . \n the abundance mass fractions for helium , carbon and oxygen is determined to be 37% , 51% and 12% , respectively . from this \n we derive c / o=4.3 ( by mass ) , confirming that the star suffered efficient third dredge - up . \n the nitrogen abundance is close to zero , while an upper limit of @xmath710% by mass is established for h. the model uses a composite beta velocity law which allows us to reproduce the optical line profiles . \n the overall shape of the de - reddened spectrum agrees with the v - scaled ( @xmath8=11.48 mag , e(b v)=0.46 mag ) model atmosphere , showing the nebular - derived reddening to be consistent with the reddening indicated by the stellar analysis . \n we confirm our model results by using the co - moving frame code cmfgen , although a few differences remain . \n the pn has a high electron density ( log(n@xmath9/@xmath10)=4.5 ) and a small ionized radius ( 0.65 arcsec - measured from the hst - wf / pc h@xmath11 images ) , indicating a young object . \n its nebular abundances are not peculiar . \n the nebular c / o ratio is close to solar , confirming the pn as an o - rich nebula . \n the nebular n / o ratio of 0.08 is _ not _ indicative of a type - i pn although the high stellar luminosity points to a relatively stellar mass . \n near - ir spectroscopy is presented and fitted together with iras fluxes by using two blackbody curves with temperatures 1200 k and 230 k , indicating the presence of hot dust . \n we also report the first detection of h@xmath12 in this young and compact pn . \n all of the published spectroscopy since the discovery of swst 1 in 1895 has been re - examined and it is concluded that no clear spectral variability is seen , in contrast to claims in some previously - published studies . \n if an event occurred that has turned it into a hydrogen - deficient central star , it did not happen in the last 100 years . \n = = = = = = = = # 1 # 1 # 1 # 1 @mathgroup@group @mathgroup@normal@groupeurmn @mathgroup@bold@groupeurbn @mathgroup@group @mathgroup@normal@groupmsamn @mathgroup@bold@groupmsamn = `` 019 = ' ' 016 = `` 040 = ' ' 336 = \" 33e = = = = = = = = # 1 # 1 # 1 # 1 = = = = = = = = [ firstpage ] stars : individual : hd167362 - stars : wolf - rayet - stars : abundances - stars : agb and post - agb - stars : atmospheres - stars : evolution - planetary nebulae : individual : swst 1 - planetary nebulae : general", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\n…1990; Vorontsov and Blekhman 2001; Zhao\net al. 2002; Kuznetsov and Proshchalykin 2006;\nKovář 2007; Hoàng 2007; Kuznetsov and Proshcha-\nlykin 2007; Poutsma et al. 2008; Tyumaseva and\nGuskova 2008; USDA-ROBO 2008; Sato et al. 2008;\nKrivets and Korovinskaya 2009; Tyumaseva and\nZhdanova 2009;…", "role": "user" }, { "content": "Background", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Peer-to-Peer Information Retrieval: An Overview \nChapter Title: Introduction \n1. Abstract of Cited Paper (BIB001): We present SETS , an architecture for efficient search in peer-to-peer networks, building upon ideas drawn from machine learning and social network theory. The key idea is to arrange participating sites in a topic-segmented overlay topology in which most connections are short-distance, connecting pairs of sites with similar content. Topically focused sets of sites are then joined together into a single network by long-distance links. Queries are matched and routed to only the topically closest regions. We discuss a variety of design issues and tradeoffs that an implementor of SETS would face. We show that SETS is efficient in network traffic and query processing load. \n2. Abstract of Cited Paper (BIB002): Peer-to-peer sharing systems are becoming increasingly popular and an exciting new class of innovative, internet-based data management systems. In these systems, users contribute their own resources (processing units and storage devices) and content (i.e., documents) to the P2P community. We focus on the management of content and resources in such systems. Our goal is to harness all available resources in the P2P network so that the users can access all available content efficiently. Efficiency is taken both from (i) the point of view of the system, in that we strive to ensure fair load distribution among all peer nodes, and (ii) from the point of view of the users, in that we strive to ensure low user-request response times. We propose a novel architecture for this new class of applications, which differs drastically from what is either found currently in existing products or proposed in academia. We contribute and study novel solutions that achieve our goals, while at the same time addressing the formidable challenges due to the autonomy of peers, their heterogeneous processing and storage capacities, their different content contributions, the huge system scale, and the highly dynamic system environment. \n3. Abstract of Cited Paper (BIB003): Peer-to-peer (P2P) systems are application-layer networks that let networked hosts share resources in a distributed environment. An important attribute of P2P networks is the ability to efficiently search the contents of other peers. In this article, the authors survey existing search techniques for information retrieval (IR) in P2P networks, including recent techniques that they propose. They also present a realistic experimental evaluation and comparison of these techniques, using a distributed middleware infrastructure they designed and implemented. \n4. Abstract of Cited Paper (BIB004): Peer-to-Peer (P2P) networking is aimed at exploiting the potential of widely distributed information pools and its effortless access and retrieval irrespectively of underlying networking protocols, operating systems of devices. However, prohibiting limitations have been identified and perhaps the most important one is the successful location of relevant information sources and the efficient query routing in large, highly distributed P2P networks. In this paper, a novel, cluster-based architecture for IR over P2P networks is presented and its evaluation is focused on retrieval effectiveness. We reason in favour of using clustering for P2P IR, by considering two fundamental hypotheses drawn from current P2P file-sharing systems. We also study the potential usefulness of a simplified version of Dempster-Shafer (D-S) theory of evidence combination for results fusion in the network. We simulated the IR behavior of the system by using the TREC 6 and 7 ad-hoc track. The proposed architecture bears very promising results in terms of precision and recall. \n5. Abstract of Cited Paper (BIB005): This paper proposes the live demonstration of a prototype of MINERVA, a novel P2P Web search engine. The search engine is layered on top of a DHT-based overlay network that connects an a-priori unlimited number of peers, each of which maintains a personal local database and a local search facility. Each peer posts a small amount of metadata to a physically distributed directory that is used to efficiently select promising peers from across the peer population that can best locally execute a query. The proposed demonstration serves as a proof of concept for P2P Web search by deploying the project on standard notebook PCs and also invites everybody to join the network by instantly installing a small piece of software from a USB memory stick. \n6. Abstract of Cited Paper (BIB006): Peer-to-peer (P2P) networks integrate autonomous computing resources without requiring a central coordinating authority, which makes them a potentially robust and scalable model for providing federated search capability to large-scale networks of text-based digital libraries. However, peer-to-peer networks have so far provided very limited support for full-text federated search with relevance-based document ranking. This paper provides solutions to full-text federated search of text-based digital libraries in hierarchical peer-to-peer networks. Existing approaches to full-text search are adapted and new methods are developed for the problems of resource representation, resource selection, and result merging according to the unique characteristics of hierarchical peer-to-peer networks. Experimental results demonstrate that the proposed approaches offer a better combination of accuracy and efficiency than more common alternatives for federated search of text-based digital libraries in peer-to-peer networks. \n7. Abstract of Cited Paper (BIB007): Peer-to-peer (P2P) networks integrate autonomous computing resources without requiring a central coordinating authority, which makes them a potentially robust and scalable model for providing federated search capability to large-scale networks of text digital libraries. However, P2P networks have so far mostly used simple search techniques based on document names or controlled-vocabulary terms, and provided very limited support for full-text search of document contents. \n8. Abstract of Cited Paper (BIB008): Recent progress in peer to peer (P2P) search algorithms has presented viable structured and unstructured approaches for full-text search. We posit that these existing approaches are each best suited for different types of queries. We present PHIRST, the first system to facilitate effective full-text search within P2P databases. PHIRST works by effectively leveraging between the relative strengths of these approaches. Similar to structured approaches, agents first publish terms within their stored documents. However, frequent terms are quickly identified and not exhaustively stored, resulting in a significant reduction in the system's storage requirements. During query lookup, agents use unstructured search to compensate for the lack of fully published terms. Additionally, they explicitly weigh between the costs involved in structured and unstructured approaches, allowing for a significant reduction in query costs. Finally, we address how node failures can be effectively addressed through storing multiple copies of selected data. We evaluated the effectiveness of our approach using both real-world and artificial queries. We found that in most situations our approach yields near perfect recall. We discuss the limitations of our system, as well as possible compensatory strategies. \n9. Abstract of Cited Paper (BIB009): This work describes an algorithm which aims at increasing the quantity of relevant documents retrieved from a Peer-To-Peer (P2P) network. The algorithm is based on a statistical model used for ranking documents, peers and ultra-peers, and on a \"piggybacking\" technique performed when the query is routed across the network. The algorithm \"amplifies\" the statistical information about the neighborhood stored in each ultra-peer. The preliminary experiments provided encouraging results as the quantity of relevant documents retrieved through the network almost doubles once query piggybacking is exploited.\n\nReview Chapter:", "role": "user" }, { "content": "In an information retrieval peer-to-peer network the central task is searching: given a query return some list of document references: the search results. A query can originate from any peer in the network, and has to be routed to one or more other peers that can provide search results based on an index. The peers thus supply and consume results. A search result is a compact representation of a document. A document can contain text, image, audio, video, or a mixture of these BIB004 . A search result is sometimes called a snippet and at least includes a pointer to the full document and commonly additional metadata like a title, a summary, the size of the document, etc. A concrete example: search results as displayed by modern search engines. Each displayed result links to the associated full document. The compact representation provides a first filtering opportunity for users enabling them to choose what links they want to follow. Peer-to-peer information retrieval networks can be divided into two classes based on the location of the documents pointed to: first, those with internal document references where the documents have to be downloaded from other peers within the network, for example, digital libraries BIB010 BIB007 , and second, those with external document references where obtaining the actual documents, locating and transferring, is outside of the scope of the peer-to-peer network, for example, a peerto-peer Web search engine BIB006 . In the next sections we compare peer-to-peer information retrieval networks with other applications and paradigms. Peer-to-peer information retrieval has been an active research area for about a decade. In this section we first reveal the main focus of peer-to-peer information retrieval, followed by an in-depth overview of optimization techniques developed over the years. A practical view on the goal of peer-to-peer information retrieval is minimizing the number of messages sent per query while maintaining high recall and precision BIB004 . There are several approaches to this which represent trade-offs. Let us start with the two common strategies to partition indices over multiple machines: partition-by-document and partition-by-keyword ]. In partition-by-document each peer is responsible for maintaining a local index over a specific set of documents: the postings for all terms of a particular document are located at one specific peer. In some cases the documents themselves are also stored at that peer, but they need not be. The strict and aggregated local indices architectures are commonly used in peer-to-peer networks that use this partitioning. In contrast, in partition-by-keyword each peer is responsible for storing the postings for some specific keywords in the index. A natural architecture for this is the distributed global index. An early investigation into the feasibility of a peer-to-peer Web search network was done by . They view partition-by-document as a more tractable starting point, but show that partition-by-keyword can get within range of the performance of partition-by-document by applying various optimizations to a distributed global index. In contrast BIB001 conclude that partition-by-document approaches scale poorly, because document collections do not \"naturally\" cluster in a way that allows query routing to a small fraction of peers and thus each query requires contacting nearly all peers in the system. Perhaps due to this article much of the research in peerto-peer information retrieval has focused on partition-by-keyword using a distributed global index BIB005 . Unfortunately, a distributed global index is not without drawbacks since it is intended for performing efficient lookups, not for efficient search BIB002 ]. First, a hash table provides load balancing rather naively, by resorting to the uniformity of the hash function used BIB003 ]. As term posting lists differ in size this can cause hotspots to emerge for popular terms which debalances the load. Second, the intersection of term posting lists used in distributed global indices ignores the correlations between terms which can lead to unsatisfactory search accuracy BIB008 ]. Third, the communication cost for an intersection grows proportionally with the number of query terms and the length of the inverted lists. Several optimizations have been proposed such as storing multiterm query results for a particular term locally to avoid intersections and requiring each peer to store additional information for terms strongly correlated with the terms it already stores. The choice of resource descriptions in a distributed global index is thus limited by the high communication costs of index updates: full text representations are unlikely to work well due to the massive network traffic that this requires. Fourth, skewed corpus statistics as a result of term partitioning may lead to globally incomparable ranking scores. Finally, distributed hash tables are vulnerable to a variety of network attacks that compromise the security and privacy of users . Many authors fail to see a number of benefits unique to partition-by-document local indices, such as the low costs for finding popular items, advanced query processing, inexpensive index updates, and high churn resilience. Admittedly, the primary challenge for such indices is routing the query to suitable peers. Our stance is that both approaches have their merit and complement each other. Recent research indeed confirms the effectiveness of using local indices for popular query terms and a global index for rare query terms BIB009 . conclude that Web-scale search is not possible with peer-to-peer technology. The overhead introduced by communication between peers is too large to offer reasonable query response times given the capacity of the Internet. However, much work, discussed in the next section, has been done since their paper and the nature and capacity of the Internet has changed significantly in the intervening time. compare the performance of several peer-to-peer architectures for information retrieval combined with common optimizations. They test three approaches: a distributed global index augmented with Bloom filters and caching; aggregated local indices with query flooding; and strict local indices using random walks. All of these are one-step term-document indices. Interestingly, they all consume approximately the same amount of bandwidth during query processing, although the aggregated local indices are the most efficient. However, the distributed global index offers the lowest latency of these three approaches, closely followed by aggregated local indices and strict local indices being orders of magnitude slower. For all approaches the forwarding of queries in the network introduces the most latency, while answering queries is relatively inexpensive. Even though the distributed global index is really fast its major drawback rears its ugly head at indexing and publishing time. When new documents are added to the network this uses six times as much bandwidth and nearly three times as much time compared to the aggregated local indices for updating the posting lists. Strict local indices resolve all this locally and incur no costs in terms of time or bandwidth for publishing documents. This study clearly shows that an architecture should achieve a balance between retrieval speed and update frequency.", "role": "assistant" } ]

[ { "content": "Analyze the provided text excerpt from a scientific document. Identify and extract distinct entities based on predefined categories.\n\nDeliver the results as a JSON structure where each key represents an entity category, and the associated value is a list of identified entities. If no entities are found for a category, return an empty list.\n\nText Excerpt:\n\nGlucocorticoids and interferon-alpha in the acquired immunodeficiency syndrome. Some patients with acquired immunodeficiency syndrome (AIDS) develop glucocorticoid resistance characterized by low receptor affinity (Kd) for glucocorticoids in mononuclear, cells and high values of ACTH and cortisol. As glucocorticoids regulate interferon-alpha (IFN alpha) production, we hypothesized that IFN alpha, a cytokine produced predominantly by monocytes in AIDS, should be increased in cortisol-resistant AIDS, attributing the lack of cortisol inhibition to IFN alpha production. Therefore, we examined glucocorticoid receptor characteristics on monocytes by [3H]dexamethasone binding and measured IFN alpha, cortisol, and ACTH in AIDS patients with (AIDS-GR) or without glucocorticoid resistance (AIDS-C) and controls (C). Monocytes of AIDS-GR patients had a receptor Kd of 10. 5 + /-4. 2 nmol / L that was higher than that in the AIDS-C group (2. 9 + /-0. 8 nmol / L) and normal subjects (2. 0 + /-0. 8 nmol / L; P < 0. 01). IFN alpha levels were increased in the AIDS-GR group (17 + /-6 vs. 4 + /-1 U / mL in the AIDS-C group and 2 + /-0. 5 U / mL in the C group; P < 0. 01). Correlations were found between plasma IFN alpha and receptor Kd on monocytes of AIDS-GR (r = 0. 77) and between IFN alpha and plasma cortisol in the same group (r = 0. 74). The poly (I) -poly (C) -induced IFN alpha production by monocytes was inhibited by glucocorticoids in the C and AIDS-C groups (approximately 80% inhibition in both groups); the effect was reversed by the receptor antagonist RU-38486. By contrast, glucocorticoids failed to inhibit IFNalpha production from AIDS-GR monocytes (approximately 20% inhibition). In conclusion, elevated IFN alpha levels in AIDS-GR may be due to the lack of inhibitory effect of cortisol on IFN alpha production due to cortisol resistance in monocytes", "role": "user" }, { "content": "{\"CellLine\": [], \"CellType\": [\"monocytes\", \"AIDS - GR monocytes\", \"mononuclear\"], \"DNA\": [], \"Protein\": [\"poly (I) - poly (C) - induced IFN alpha\", \"cytokine\", \"IFNalpha\", \"glucocorticoid receptor\", \"interferon - alpha\", \"IFN alpha\", \"plasma IFN alpha\"], \"RNA\": []}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: This survey studies the learning and inference capabilities in nine popular trackers.\n\nKeywords: visual tracking video\n\nDataset Information:\nViolin: Video-and-Language Inference is the task of joint multimodal understanding of video and text. Given a video clip with aligned subtitles as premise, paired with a natural language hypothesis based on the video content, a model needs to infer whether the hypothesis is entailed or contradicted by the given video clip.\nIMPPRES: An IMPlicature and PRESupposition diagnostic dataset (IMPPRES), consisting of >25k semiautomatically generated sentence pairs illustrating well-studied pragmatic inference types.\nOTB: Object Tracking Benchmark (OTB) is a visual tracking benchmark that is widely used to evaluate the performance of a visual tracking algorithm. The dataset contains a total of 100 sequences and each is annotated frame-by-frame with bounding boxes and 11 challenge attributes.\nGLUE: General Language Understanding Evaluation (GLUE) benchmark is a collection of nine natural language understanding tasks, including single-sentence tasks CoLA and SST-2, similarity and paraphrasing tasks MRPC, STS-B and QQP, and natural language inference tasks MNLI, QNLI, RTE and WNLI.\n\nAvailable Datasets: A: Violin B: IMPPRES C: OTB D: GLUE", "role": "user" }, { "content": "OTB", "role": "assistant" } ]

[ { "content": "Analyze the given paragraph from COVID-19 research. Determine the relevant topics discussed in the text. Your response should be a JSON array containing the identified topics. Ensure the output is a valid JSON array with no additional commentary.\n\nText:\n\nPURPOSE: The purpose of this study is to elucidate the chest imaging findings of suspected COVID-19 patients presenting to the emergency department and the relationship with their demographics and RT-PCR testing results. METHODS: Patients presenting to the ED between March 12 and March 28, 2020, with symptoms suspicious for COVID-19 and subsequent CXR and/or CT exam were selected. Patients imaged for other reasons with findings suspicious for COVID-19 were also included. Demographics, laboratory test results, and history were extracted from the medical record. Descriptive statistics were used to explore the relationship between imaging and these factors. RESULTS: A total of 227 patients from the emergency department were analyzed (224 CXRs and 25 CTs). Of the 192 patients with COVID-19 results, 173 (90.1%) had COVID-19 RT-PCR (+). Abnormal imaging (CXR, 85.7% and/or CT, 100%) was noted in 155 (89.6%) of COVID-19 RT-PCR (+) cases. The most common imaging findings were mixed airspace/interstitial opacities (39.8%) on CXR and peripheral GGOs on CT (92%). The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. CONCLUSION: We found a similar spectrum of thoracic imaging findings in COVID-19 patients as previous studies. The most common demographic were African Americans (76.8%). Furthermore, 97.1% of African Americans were RT-PCR (+) compared to 65.8% of Caucasians. Both CT and CXR can accurately identify COVID-19 pneumonitis in 89.6% of RT-PCR (+) cases, 89.5% of false negatives, and 72.7% of cases with no RT-PCR result.", "role": "user" }, { "content": "[\"Diagnosis\"]", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\nGroup-based HIV risk reduction intervention for adolescent girls : evidence of feasibility and efficacy . The purposes of this pilot study were ( a ) to assess the feasibility of a community-based , small group HIV risk reduction intervention with adolescent girls , and ( b ) to obtain preliminary evidence of the efficacy of this theoretically-guided intervention using a controlled design . The feasibility of the intervention was demonstrated by successfully implementing it with 33 sexually-active , single girls . Preliminary evidence of the efficacy of the intervention was obtained using a randomized trial with 62 sexually-active , single girls . Data obtained at a 3-month follow-up assessment showed that girls who received the HIV-related intervention improved their HIV-related knowledge and enhanced their motivation for risk reduction compared to girls who received a control ( health promotion ) intervention . Effect sizes suggest that the HIV intervention also reduced several risk behaviors ( e.g. , vaginal sex without a condom , giving oral sex , and alcohol and drug use before sex ) . Challenges to implementation and suggestions for intervention enhancement are discussed .", "role": "user" }, { "content": "{\"Intervention\": [\"control ( health promotion ) intervention .\", \"theoretically-guided intervention\"], \"Outcome\": [\"feasibility\", \"Effect\", \"motivation for risk reduction\", \"HIV-related knowledge\", \"giving oral sex\", \"alcohol and drug use before sex\", \"efficacy\", \"vaginal sex without a condom\", \"reduced several risk behaviors\"], \"Participant\": [\"adolescent girls\", \"adolescent girls :\"]}", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nDual-energy (DE) chest radiographs provide greater diagnostic information than standard radiographs by separating the image into bone and soft tissue, revealing suspicious lesions which may otherwise be obstructed from view. However, acquisition of DE images requires two physical scans, necessitating specialized hardware and processing, and images are prone to motion artifact. Generation of virtual DE images from standard, single-shot chest radiographs would expand the diagnostic value of standard radiographs without changing the acquisition procedure. We present a Multi-scale Conditional Adversarial Network (MCA-Net) which produces high-resolution virtual DE bone images from standard, single-shot chest radiographs. Our proposed MCA-Net is trained using the adversarial network so that it learns sharp details for the production of high-quality bone images. Then, the virtual DE soft tissue image is generated by processing the standard radiograph with the virtual bone image using a cross projection transformation. Experimental results from 210 patient DE chest radiographs demonstrated that the algorithm can produce high-quality virtual DE chest radiographs. Important structures were preserved, such as coronary calcium in bone images and lung lesions in soft tissue images. The average structure similarity index and the peak signal to noise ratio of the produced bone images in testing data were 96.4 and 41.5, which are significantly better than results from previous methods. Furthermore, our clinical evaluation results performed on the publicly available dataset indicates the clinical values of our algorithms. Thus, our algorithm can produce high-quality DE images that are potentially useful for radiologists, computer-aided diagnostics, and other diagnostic tasks.\n\nCited Works Summary:\n[1]: We investigate conditional adversarial networks as a general-purpose solution to image-to-image translation problems. These networks not only learn the mapping from input image to output image, but also learn a loss function to train this mapping. This makes it possible to apply the same generic approach to problems that traditionally would require very different loss formulations. We demonstrate that this approach is effective at synthesizing photos from label maps, reconstructing objects from edge maps, and colorizing images, among other tasks. Indeed, since the release of the pix2pix software associated with this paper, a large number of internet users (many of them artists) have posted their own experiments with our system, further demonstrating its wide applicability and ease of adoption without the need for parameter tweaking. As a community, we no longer hand-engineer our mapping functions, and this work suggests we can achieve reasonable results without hand-engineering our loss functions either.\n\n[2]: Automatic organ segmentation is an important yet challenging problem for medical image analysis. The pancreas is an abdominal organ with very high anatomical variability. This inhibits previous segmentation methods from achieving high accuracies, especially compared to other organs such as the liver, heart or kidneys. In this paper, we present a probabilistic bottom-up approach for pancreas segmentation in abdominal computed tomography (CT) scans, using multi-level deep convolutional networks (ConvNets). We propose and evaluate several variations of deep ConvNets in the context of hierarchical, coarse-to-fine classification on image patches and regions, i.e. superpixels. We first present a dense labeling of local image patches via @math and nearest neighbor fusion. Then we describe a regional ConvNet ( @math ) that samples a set of bounding boxes around each image superpixel at different scales of contexts in a \"zoom-out\" fashion. Our ConvNets learn to assign class probabilities for each superpixel region of being pancreas. Last, we study a stacked @math leveraging the joint space of CT intensities and the @math dense probability maps. Both 3D Gaussian smoothing and 2D conditional random fields are exploited as structured predictions for post-processing. We evaluate on CT images of 82 patients in 4-fold cross-validation. We achieve a Dice Similarity Coefficient of 83.6 @math 6.3 in training and 71.8 @math 10.7 in testing.\n\n[3]: Generative Adversarial Nets [8] were recently introduced as a novel way to train generative models. In this work we introduce the conditional version of generative adversarial nets, which can be constructed by simply feeding the data, y, we wish to condition on to both the generator and discriminator. We show that this model can generate MNIST digits conditioned on class labels. We also illustrate how this model could be used to learn a multi-modal model, and provide preliminary examples of an application to image tagging in which we demonstrate how this approach can generate descriptive tags which are not part of training labels.\n\n[4]: Despite the breakthroughs in accuracy and speed of single image super-resolution using faster and deeper convolutional neural networks, one central problem remains largely unsolved: how do we recover the finer texture details when we super-resolve at large upscaling factors? The behavior of optimization-based super-resolution methods is principally driven by the choice of the objective function. Recent work has largely focused on minimizing the mean squared reconstruction error. The resulting estimates have high peak signal-to-noise ratios, but they are often lacking high-frequency details and are perceptually unsatisfying in the sense that they fail to match the fidelity expected at the higher resolution. In this paper, we present SRGAN, a generative adversarial network (GAN) for image super-resolution (SR). To our knowledge, it is the first framework capable of inferring photo-realistic natural images for 4x upscaling factors. To achieve this, we propose a perceptual loss function which consists of an adversarial loss and a content loss. The adversarial loss pushes our solution to the natural image manifold using a discriminator network that is trained to differentiate between the super-resolved images and original photo-realistic images. In addition, we use a content loss motivated by perceptual similarity instead of similarity in pixel space. Our deep residual network is able to recover photo-realistic textures from heavily downsampled images on public benchmarks. An extensive mean-opinion-score (MOS) test shows hugely significant gains in perceptual quality using SRGAN. The MOS scores obtained with SRGAN are closer to those of the original high-resolution images than to those obtained with any state-of-the-art method.\n\n[5]: The chest X-ray is one of the most commonly accessible radiological examinations for screening and diagnosis of many lung diseases. A tremendous number of X-ray imaging studies accompanied by radiological reports are accumulated and stored in many modern hospitals Picture Archiving and Communication Systems (PACS). On the other side, it is still an open question how this type of hospital-size knowledge database containing invaluable imaging informatics (i.e., loosely labeled) can be used to facilitate the data-hungry deep learning paradigms in building truly large-scale high precision computer-aided diagnosis (CAD) systems. In this paper, we present a new chest X-ray database, namely ChestX-ray8, which comprises 108,948 frontal-view X-ray images of 32,717 unique patients with the text-mined eight disease image labels (where each image can have multi-labels), from the associated radiological reports using natural language processing. Importantly, we demonstrate that these commonly occurring thoracic diseases can be detected and even spatially-located via a unified weakly-supervised multi-label image classification and disease localization framework, which is validated using our proposed dataset. Although the initial quantitative results are promising as reported, deep convolutional neural network based reading chest X-rays (i.e., recognizing and locating the common disease patterns trained with only image-level labels) remains a strenuous task for fully-automated high precision CAD systems.\n\n[6]: \n\n[7]: Remarkable progress has been made in image recognition, primarily due to the availability of large-scale annotated datasets and deep convolutional neural networks (CNNs). CNNs enable learning data-driven, highly representative, hierarchical image features from sufficient training data. However, obtaining datasets as comprehensively annotated as ImageNet in the medical imaging domain remains a challenge. There are currently three major techniques that successfully employ CNNs to medical image classification: training the CNN from scratch, using off-the-shelf pre-trained CNN features, and conducting unsupervised CNN pre-training with supervised fine-tuning. Another effective method is transfer learning, i.e., fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. In this paper, we exploit three important, but previously understudied factors of employing deep convolutional neural networks to computer-aided detection problems. We first explore and evaluate different CNN architectures. The studied models contain 5 thousand to 160 million parameters, and vary in numbers of layers. We then evaluate the influence of dataset scale and spatial image context on performance. Finally, we examine when and why transfer learning from pre-trained ImageNet (via fine-tuning) can be useful. We study two specific computer-aided detection (CADe) problems, namely thoraco-abdominal lymph node (LN) detection and interstitial lung disease (ILD) classification. We achieve the state-of-the-art performance on the mediastinal LN detection, and report the first five-fold cross-validation classification results on predicting axial CT slices with ILD categories. Our extensive empirical evaluation, CNN model analysis and valuable insights can be extended to the design of high performance CAD systems for other medical imaging tasks.", "role": "user" }, { "content": "In this case, deep learning has been successfully applied in image classification, image segmentation, and image-to-image translation [6] . Deep learning also yields similar improvements in performance in the medical vision field for anatomical and pathological structures detection and segmentation tasks. [5] [7] [2] [3] The boost of hardware and algorithms for deep learning have given the possibility of training CNN with many layers on large-scale datasets. Our work is closely related to the current state-of-the-art CNN models for image synthesis [1] and image transformation [4] . [1] proposed a conditional GAN (cGAN) that can generate realistic images given the outlines of the target image as the prior condition. [4] employed a GAN structure for generating high-resolution images from nominal resolution images. Our proposed method for generation of virtual DE images benefits from these excellent works on the application of GAN. The standard radiographs were used as a strong prior condition for generating virtual DE images using structure similar to cGAN [1] . The adversarial network structure also helps generation of super-resolution DE images (normally around 2022 pixels @math 2022 pixels). In this paper, a customized GAN structure was designed for the generation of virtual DE bone images.", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nFace anti-spoofing (a.k.a presentation attack detection) has drawn growing attention due to the high-security demand in face authentication systems. Existing CNN-based approaches usually well recognize the spoofing faces when training and testing spoofing samples display similar patterns, but their performance would drop drastically on testing spoofing faces of unseen scenes. In this paper, we try to boost the generalizability and applicability of these methods by designing a CNN model with two major novelties. First, we propose a simple yet effective Total Pairwise Confusion (TPC) loss for CNN training, which enhances the generalizability of the learned Presentation Attack (PA) representations. Secondly, we incorporate a Fast Domain Adaptation (FDA) component into the CNN model to alleviate negative effects brought by domain changes. Besides, our proposed model, which is named Generalizable Face Authentication CNN (GFA-CNN), works in a multi-task manner, performing face anti-spoofing and face recognition simultaneously. Experimental results show that GFA-CNN outperforms previous face anti-spoofing approaches and also well preserves the identity information of input face images.\n\nCited Works Summary:\n[1]: In this paper, we propose a novel framework leveraging the advantages of the representational ability of deep learning and domain generalization for face spoofing detection. In particular, the generalized deep feature representation is achieved by taking both spatial and temporal information into consideration, and a 3D convolutional neural network architecture tailored for the spatial-temporal input is proposed. The network is first initialized by training with augmented facial samples based on cross-entropy loss and further enhanced with a specifically designed generalization loss, which coherently serves as the regularization term. The training samples from different domains can seamlessly work together for learning the generalized feature representation by manipulating their feature distribution distances. We evaluate the proposed framework with different experimental setups using various databases. Experimental results indicate that our method can learn more discriminative and generalized information compared with the state-of-the-art methods.\n\n[2]: Though having achieved some progresses, the hand-crafted texture features, e.g., LBP [23], LBP-TOP [11] are still unable to capture the most discriminative cues between genuine and fake faces. In this paper, instead of designing feature by ourselves, we rely on the deep convolutional neural network (CNN) to learn features of high discriminative ability in a supervised manner. Combined with some data pre-processing, the face anti-spoofing performance improves drastically. In the experiments, over 70 relative decrease of Half Total Error Rate (HTER) is achieved on two challenging datasets, CASIA [36] and REPLAY-ATTACK [7] compared with the state-of-the-art. Meanwhile, the experimental results from inter-tests between two datasets indicates CNN can obtain features with better generalization ability. Moreover, the nets trained using combined data from two datasets have less biases between two datasets.\n\n[3]: Face anti-spoofing is crucial to prevent face recognition systems from a security breach. Previous deep learning approaches formulate face anti-spoofing as a binary classification problem. Many of them struggle to grasp adequate spoofing cues and generalize poorly. In this paper, we argue the importance of auxiliary supervision to guide the learning toward discriminative and generalizable cues. A CNN-RNN model is learned to estimate the face depth with pixel-wise supervision, and to estimate rPPG signals with sequence-wise supervision. The estimated depth and rPPG are fused to distinguish live vs. spoof faces. Further, we introduce a new face anti-spoofing database that covers a large range of illumination, subject, and pose variations. Experiments show that our model achieves the state-of-the-art results on both intra- and cross-database testing.", "role": "user" }, { "content": "Recently, deep learning based methods [2] [1] have been proposed to address face anti-spoofing. They use CNNs to learn highly discriminative representations by taking face anti-spoofing as a binary classification problem. However, most of them easily suffer overfitting. Current publicly available face anti-spoofing datasets are too limited to cover various potential spoofing types. A very recent work [3] by Liu . leverages the depth map and rPPG signal as auxiliary supervision to train CNN instead of treating face anti-spoofing as a simple binary classification problem in order to avoid overfitting. Another critical issue for face anti-spoofing is domain shift. To bridge the gap between training and testing domains, [1] generalizes CNN to unknown conditions by minimizing the feature distribution dissimilarity across domains, . minimizing the Maximum Mean Discrepancy distance among representations.", "role": "assistant" } ]

[ { "content": "Examine the citation provided below. Determine the primary purpose of this citation within the context of the research paper. \n\nCitation:\n\nPubertal stage was scored by trained nurses according to Tanner (24,25) as a means of controlling for differences among children in maturational development not captured in reference growth curves for BMI (26).", "role": "user" }, { "content": "Method", "role": "assistant" } ]

[ { "content": "Examine the provided text and determine the interactions between chemical entities and genes. Focus on identifying any connections present.\n\nPresent your findings in a structured JSON format. Each relationship should be represented as an array entry. If no interactions are detected, return an empty array.\n\nText Content:\n\nAltered vasoreactivity to angiotensin II in experimental diabetic neuropathy: role of nitric oxide. We evaluated the effects of angiotensin II and an angiotensin-converting enzyme inhibitor (cilazapril) on nerve blood flow (NBF) and electrophysiology in control and diabetic rats. When applied locally to the sciatic nerve, the dose-response curve of angiotensin II was more potent in experimental diabetic neuropathy (EDN) than control rats. No difference existed in plasma angiotensin II levels between EDN and controls. The rats were given typical rat pellets or pellets treated with 10 mg/kg per day cilazapril for 4 weeks. Diabetes caused a significant reduction in NBF, nerve conduction velocity, and compound muscle action potential (CMAP) amplitudes. NBF was significantly increased in diabetic rats supplemented with cilazapril diet, and nerve conduction velocity and amplitudes of the CMAP were also improved after 4 weeks on this diet. Direct application 10 (-3) mol/L cilazapril on sciatic nerve did not increase NBF in normal and EDN rats. We topically applied the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine, on sciatic nerve and observed reduced inhibition of NBF in EDN, which was correctable with a cilazapril diet. These results suggest that diabetic neuropathy may have an increasing vasopressor action with angiotensin II and this is likely to be the mechanism of NOS inhibition. Angiotensin II-converting enzyme inhibitors may have potential in the treatment of diabetic neuropathy.", "role": "user" }, { "content": "[[\"NG-nitro-L-arginine\", \"INHIBITOR\", \"NOS\"], [\"NG-nitro-L-arginine\", \"INHIBITOR\", \"nitric oxide synthase\"], [\"cilazapril\", \"REGULATOR\", \"nitric oxide synthase\"], [\"cilazapril\", \"INHIBITOR\", \"angiotensin-converting enzyme\"], [\"cilazapril\", \"INHIBITOR\", \"angiotensin II\"]]", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: The proposed approach can be easily combined with existing deep CNNs, and it improves robustness of the deep CNNs\n\nKeywords: image classification\n\nDataset Information:\nAirport: The Airport dataset is a dataset for person re-identification which consists of 39,902 images and 9,651 identities across six cameras.\nHandNet: The HandNet dataset contains depth images of 10 participants' hands non-rigidly deforming in front of a RealSense RGB-D camera. The annotations are generated by a magnetic annotation technique.\nCIFAR-10: The CIFAR-10 dataset (Canadian Institute for Advanced Research, 10 classes) is a subset of the Tiny Images dataset and consists of 60000 32x32 color images. The images are labelled with one of 10 mutually exclusive classes: airplane, automobile (but not truck or pickup truck), bird, cat, deer, dog, frog, horse, ship, and truck (but not pickup truck).\nETH: ETH is a dataset for pedestrian detection. The testing set contains 1,804 images in three video clips.\n\nAvailable Datasets: A: Airport B: HandNet C: CIFAR-10 D: ETH", "role": "user" }, { "content": "CIFAR-10", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nAttention is a very efficient way to model the relationship between two sequences by comparing how similar two intermediate representations are. Initially demonstrated in NMT, it is a standard in all NLU tasks today when efficient interaction between sequences is considered. However, we show that attention, by virtue of its composition, works best only when it is given that there is a match somewhere between two sequences. It does not very well adapt to cases when there is no similarity between two sequences or if the relationship is contrastive. We propose an Conflict model which is very similar to how attention works but which emphasizes mostly on how well two sequences repel each other and finally empirically show how this method in conjunction with attention can boost the overall performance.\n\nCited Works Summary:\n[1]: An attentional mechanism has lately been used to improve neural machine translation (NMT) by selectively focusing on parts of the source sentence during translation. However, there has been little work exploring useful architectures for attention-based NMT. This paper examines two simple and effective classes of attentional mechanism: a global approach which always attends to all source words and a local one that only looks at a subset of source words at a time. We demonstrate the effectiveness of both approaches over the WMT translation tasks between English and German in both directions. With local attention, we achieve a significant gain of 5.0 BLEU points over non-attentional systems which already incorporate known techniques such as dropout. Our ensemble model using different attention architectures has established a new state-of-the-art result in the WMT'15 English to German translation task with 25.9 BLEU points, an improvement of 1.0 BLEU points over the existing best system backed by NMT and an n-gram reranker.\n\n[2]: The dominant sequence transduction models are based on complex recurrent or convolutional neural networks that include an encoder and a decoder. The best performing models also connect the encoder and decoder through an attention mechanism. We propose a new simple network architecture, the Transformer, based solely on attention mechanisms, dispensing with recurrence and convolutions entirely. Experiments on two machine translation tasks show these models to be superior in quality while being more parallelizable and requiring significantly less time to train. Our model achieves 28.4 BLEU on the WMT 2014 English-to-German translation task, improving over the existing best results, including ensembles, by over 2 BLEU. On the WMT 2014 English-to-French translation task, our model establishes a new single-model state-of-the-art BLEU score of 41.0 after training for 3.5 days on eight GPUs, a small fraction of the training costs of the best models from the literature.\n\n[3]: Abstract: Neural machine translation is a recently proposed approach to machine translation. Unlike the traditional statistical machine translation, the neural machine translation aims at building a single neural network that can be jointly tuned to maximize the translation performance. The models proposed recently for neural machine translation often belong to a family of encoder-decoders and consists of an encoder that encodes a source sentence into a fixed-length vector from which a decoder generates a translation. In this paper, we conjecture that the use of a fixed-length vector is a bottleneck in improving the performance of this basic encoder-decoder architecture, and propose to extend this by allowing a model to automatically (soft-)search for parts of a source sentence that are relevant to predicting a target word, without having to form these parts as a hard segment explicitly. With this new approach, we achieve a translation performance comparable to the existing state-of-the-art phrase-based system on the task of English-to-French translation. Furthermore, qualitative analysis reveals that the (soft-)alignments found by the model agree well with our intuition.", "role": "user" }, { "content": "[3] introduced attention first in neural machine translation. It used a feed-forward network over addition of encoder and decoder states to compute alignment score. Our work is very similar to this except we use element wise difference instead of addition to build our conflict function. [2] came up with a scaled dot-product attention in their Transformer model which is fast and memory-efficient. Due to the scaling factor, it didn't have the issue of gradients zeroing out. On the other hand, [1] has experimented with global and local attention based on the how many hidden states the attention function takes into account. Their experiments have revolved around three attention functions - dot, concat and general. Their findings include that dot product works best for global attention. Our work also belongs to the global attention family as we consider all the hidden states of the sequence.", "role": "assistant" } ]

[ { "content": "Examine the provided abstract from a computer science paper. Your objective is to identify and extract relationships between entities. Present these relationships in a structured JSON format.\n\nInput Text:\n\nCurrently, N-gram models are the most common and widely used models for statistical language modeling. In this paper, we investigated an alternative way to build language models, i.e., using artificial neural networks to learn the language model. Our experiment result shows that the neural network can learn a language model that has performance even better than standard statistical methods.", "role": "user" }, { "content": "[[\"N-gram models\", \"statistical language modeling\", \"USED-FOR\"], [\"artificial neural networks\", \"language models\", \"USED-FOR\"], [\"artificial neural networks\", \"statistical methods\", \"COMPARE\"]]", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Parasite-Dependent Expansion of TNF Receptor II–Positive Regulatory T Cells with Enhanced Suppressive Activity in Adults with Severe Malaria\nContent:\nAbstract:\nSevere Plasmodium falciparum malaria is a major cause of global mortality, yet the immunological factors underlying progression to severe disease remain unclear. CD4+CD25+ regulatory T cells( Treg cells) are associated with impaired T cell control of Plasmodium spp infection. We investigated the relationship between Treg cells, parasite biomass, and P. falciparum malaria disease severity in adults living in a malaria-endemic region of Indonesia. CD4+CD25+Foxp3+CD127lo Treg cells were significantly elevated in patients with uncomplicated( UM; n = 17) and severe malaria( SM; n = 16) relative to exposed asymptomatic controls( AC; n = 10). In patients with SM, Treg cell frequency correlated positively with parasitemia( r = 0. 79, p = 0. 0003) and total parasite biomass( r = 0. 87, p<0. 001), both major determinants for the development of severe and fatal malaria, and Treg cells were significantly increased in hyperparasitemia. There was a further significant correlation between Treg cell frequency and plasma concentrations of soluble tumor necrosis factor receptor II( TNFRII) in SM. A subset of TNFRII+ Treg cells with high expression of Foxp3 was increased in severe relative to uncomplicated malaria. In vitro, P. falciparum–infected red blood cells dose dependently induced TNFRII+Foxp3hi Treg cells in PBMC from malaria-unexposed donors which showed greater suppressive activity than TNFRII− Treg cells. The selective enrichment of the Treg cell compartment for a maximally suppressive TNFRII+Foxp3hi Treg subset in severe malaria provides a potential link between immune suppression, increased parasite biomass, and malaria disease severity. The findings caution against the induction of TNFRII+Foxp3hi Treg cells when developing effective malaria vaccines.\nIntroduction:\nInfection with Plasmodium falciparum causes over 1 million deaths each year and an effective malaria vaccine remains elusive. The cellular immune responses controlling parasite replication and disease severity in falciparum malaria are not fully understood. Natural Treg cells characterized by the expression of the transcription factor forkhead box P3( Foxp3)[1],[2], the IL-2 receptor α chain CD25[3] and low expression levels of the IL-7 receptor α( CD127)[4],[5], are widely accepted to be a specialized immunosuppressive subpopulation of CD4+ T cells[2]. Treg cells suppress cellular immune responses through direct contact with immune effector cells and via the production of regulatory cytokines, including IL-10[6],[7]. Whilst it is understood that effector T cell responses are important components of host anti-parasitic immunity[8],[9], the role of Treg cells as suppressors of T cell responses in malaria remains unclear. In mouse experimental malaria models, Treg cells have been associated with increased[10],[11] or delayed[12] disease progression. Importantly, in each of these studies, Treg depletion was associated with improved control of parasite growth. Pre-clinical blood stage P. falciparum infection initiated by sporozoite challenge results in an expansion of Treg cell numbers in malaria-naïve, adult volunteers associated with increased parasite replication[13]. Studies of natural infection are limited, but have shown that Treg cell numbers are increased in neonates born to mothers with placental P. falciparum malaria[14] and, in a cohort study in a malaria-endemic region of Kenya, higher baseline Treg cell numbers are associated with an increased risk of subsequent development of clinical malaria[15]. Recent studies have demonstrated a functional deficit in Treg cells in Fulani, an ethnic group with lesser parasitization and a lower risk of clinical malaria[16]. Taken together, these studies imply an important role for Treg cells in the development of clinical malaria, with suppression of T cell-mediated control of parasite replication a plausible explanation[13]. The role of Treg cells in modifying disease severity in malaria is currently unknown and their relationship to parasite biomass has not been examined. The latter has fundamental implications for clinical presentation since parasite replication and biomass are major determinants of the development of severe and fatal malaria[17]–[19]. To better understand the role of Treg cells in disease progression/severity and their relationship with parasite biomass, we examined Treg cell frequency, phenotype and function in adults with uncomplicated( UM) or severe falciparum malaria( SM) in a malaria-endemic area of Papua, Indonesia. Our findings indicate that increased Treg cell numbers are strongly associated with peripheral parasitemia and parasite biomass in severe disease, providing a plausible explanation for a key role of Treg cells in parasite replication and disease severity. Furthermore, we observed an altered Treg cell phenotype in severe disease, with the induction of a TNFRII+ population recently associated with ‘maximally suppressive’ activity in animal models[20]. The functional consequences of this finding may underlie progression to hyperparasitemia and severe disease.\nDiscussion:\nWe report increased CD4+CD25+Foxp3+CD127lo Treg cell frequency in adult patients with uncomplicated and severe P. falciparum malaria. While there was no difference in the frequency or absolute counts of Treg cells between UM and SM patients, patients with SM had significantly more TNFRII+ Treg cells with elevated Foxp3 expression. Because Foxp3 expression is directly correlated with Treg cell suppressor activity[25], our data suggest that Treg cell activity is increased in severe falciparum malaria. Indeed, PBMC from patients with SM showed poor antigen-specific proliferation relative to PBMC from patients with UM. Although the reasons for impaired immune responses in severe disease may be multi-factorial, this finding is consistent with a greater immunosuppressive capacity of TNFRII+ Treg cells in patients with SM. Our in vitro data on PBMC from malaria-unexposed donors further support that TNFRII+ Treg cells exert greater suppressive activity relative to TNFRII−, which is in accordance with recent findings in mice[20]. Increased TNFRII+ Treg cells were found after in vitro exposure of previously malaria-unexposed PBMC to high ratios of pRBC compared to low ratios, suggesting a parasitemia threshold has to be overcome for their induction. While the in vitro model may not necessarily reflect the in vivo response, the in vitro data reflect our observations of increased levels of this suppressive TNFRII+Foxp3hi Treg subset in patients with severe malaria who had significantly higher parasitemia and parasite biomass relative to patients with uncomplicated malaria. Due to the cross-sectional nature of this study, which is inherent to human studies of severe malaria, we cannot determine whether the increase in TNFRII+ Treg cells in severe malaria is a cause or consequence of progression from uncomplicated to severe disease. In vitro assays were performed using the P. falciparum lab strain 3D7 and while we cannot exclude different reactivity in malaria-exposed subjects it is unlikely that stimulation of PBMC from malaria-unexposed Australian blood bank donors resulted in antigen-specific recall of memory T cell responses to epitopes within the 3D7 strain. Although suppressor function requires Treg cell activation via their T cell receptor, their suppressive capacity is not antigen specific and can promote generalized immune suppression[26]. Furthermore, TNFRII+ Treg cells were functional following exposure to parasitized or unparasitized RBC suggesting that the appearance of TNFRII+Foxp3hi Treg cells was unlikely to have been promoted by mitogenic molecules from parasite extracts. The increase in Treg cells in UM and SM indicates that the induction of Treg cells in pre-clinical infection[13], continues into clinical disease. This finding is further supported by the fall in Treg cell frequency and activity following parasite clearance with drug treatment in patients with UM. Importantly, our findings highlight that increased Treg cell numbers are strongly associated with peripheral parasitemia and parasite biomass in severe disease, providing a plausible explanation for a key role of Treg cells in parasite replication and disease severity. While Treg cells may ameliorate potentially deleterious immune responses[11] or endothelial cell activation[27] in severe malaria, our results suggest that in severe disease this may occur at the cost of impairing effector T cell-mediated constraint of parasite growth. Because parasite replication and biomass are major determinants of severe and fatal malaria[17]–[19], Treg cells may thus exacerbate disease severity in SM. In contrast to previous studies showing impaired TGFβ in uncomplicated and severe malaria in children[28], plasma levels of TGFβ in adults were significantly higher in both uncomplicated and severe malaria. This pattern of TGFβ elevation parallels the pattern seen with elevated Treg cells in uncomplicated and severe disease and is consistent with the known effects of TGFβ in inducing Foxp3 and the Treg phenotype[29]. A limitation of our study is our inability to measure TGFβ in all subjects in whom Treg cells data were also available. Nevertheless, we speculate that differences in the pattern of TGFβ production in uncomplicated and severe disease between adults and children may be associated with differences in Treg responses between these two age groups. As such, our results in adults may not be generalizable to severe malaria in paediatric age groups in whom immune responses and disease phenotypes differ[30]. The anti-inflammatory cytokine IL-10 has been suggested to inhibit pro-inflammatory immune responses to malarial antigen[31]. As found previously[32]–[34], we observed increased plasma levels of IL-10 in adults with both UM and SM. The correlation between plasma IL-10 levels and Treg cell frequency observed in both UM and SM patients is consistent with the known association between IL-10 and Treg cell activity[6],[7]. Although this association does not infer causality, our in vitro data shows that IL-10 is detectable as early as 24 hours following PBMC culture in the presence of high concentrations of pRBC as also found by others[35]. These data lead to the speculation that IL-10 secretion may precede and contribute to the relative increase in Treg cells observed in vitro and ex vivo. Indeed, expansion of Foxp3hiTreg cells in vitro can be partially inhibited using anti-IL-10R blocking antibody( Anja Scholzen, personal communication). Another cytokine recently suggested to expand murine Treg cells in vitro is TNF[36]. In our in vitro cultures, we did not observe an increase in TNF levels until day 4 of culture. Even after day 4 TNF concentrations remained in the pg/mL range, while expansion of murine Treg cells required TNF concentrations in the ng/mL[36]. For these reasons we think it is unlikely that the relative increase in Treg cells following exposure to high pRBC ratios is TNF-mediated. Furthermore, although plasma TNF concentrations were significantly elevated in adults with severe P. falciparum malaria, these remain in the low pg/mL range as also reported by others[19],[32]. Recently, the ability of Treg cells to shed large amounts of TNFRII has been identified as a novel mechanism by which Tregs cells can inhibit the effects of TNF[22]. TNF has been associated with accelerated parasite clearance in falciparum malaria[37] and clinical use of TNF inhibitors increases the risk of hyperparasitemia following malaria infection[38]. At low concentrations, soluble TNFRs stabilize TNF and prolong its half-life[39], however at high concentrations the soluble receptors compete for TNF binding with cellular receptors, particularly membrane bound TNF[40], thereby inhibiting TNF bioactivity[41]. Although TNFRII shedding by Treg cells may represent a further counter-regulatory mechanism to suppress potentially deleterious TNF-mediated inflammatory responses induced after rupture of parasitized red blood cells[19],[42], the high concentrations of TNFRII associated with Tregs in SM may inhibit TNF bioactivity and contribute to impaired control of parasite growth and progression to severe disease. In conclusion our findings support a role for Treg cells in malaria disease progression and parasite growth during clinical malaria and furthermore indicate that P. falciparum can expand a potent TNFRII+Foxp3hi suppressor Treg cell subset that is associated with, and may contribute to severe malaria and hyperparasitemia in adults. Future studies are indicated in other human populations and age groups assessing the role of this maximally suppressive Treg subpopulation in susceptibility to severe malaria and other inflammatory diseases. Furthermore, differences among candidate malaria vaccines and human populations in the function and phenotype of vaccine-induced Tregs may influence efficacy in protecting against uncomplicated and severe malaria.", "role": "user" }, { "content": "Malaria is a major global health problem responsible for more than 1 million deaths annually . Severity of malaria disease is associated with the inability of host immune cells to efficiently eliminate malaria parasites from the blood . Little is known about immune regulatory factors controlling the onset of severe and potentially fatal malaria . Regulatory T ( Treg ) cells are a small specialized subset of immune cells that suppress the activation and expansion of effector immune cells which partake in parasite elimination . We investigated the relationship between Treg cells , parasite burden , and disease severity in adult malaria patients with either uncomplicated or severe malaria . We demonstrated that Treg cell frequency was elevated in malaria patients and associated with high parasite burden in severe malaria but not in uncomplicated malaria . Comparison of Treg cell characteristics allowed us to identify a new highly suppressive subset of Treg cells that was elevated in severe malaria patients . Our results indicate that severe malaria is accompanied by the induction of highly suppressive Treg cells that can promote parasite growth and caution against the induction of these Treg cells when developing effective malaria vaccines .", "role": "assistant" } ]

[ { "content": "Examine the provided text and determine the interactions between chemical entities and genes. Focus on identifying any connections present.\n\nPresent your findings in a structured JSON format. Each relationship should be represented as an array entry. If no interactions are detected, return an empty array.\n\nText Content:\n\nBinding site of amiloride to urokinase plasminogen activator depends on species. A novel drug candidate is checked on its potency on animal models before it can advance to human phase of the research. Usually negative results on animal phase disqualify it. Targeting specific enzymes by small chemicals raises the question about the appropriateness of this approach. As an example, the urokinase (uPA) is recognized as an important enzyme responsible for cancer metastasis and angiogenesis. It is therefore important to ask the question if a small chemical will inhibit uPA of different species with the same or different potency. Using DNA sequence and known structure of uPA we have modeled 3D structures of uPAs for several different species. By theoretical calculations we have determined most probable structure of amiloride/uPAs complexes. Catalytic triad (B57, B102, B195) and specificity pocket (B187-B197, B212-B229) are highly conserved in all cases, and are the regions responsible for proteolytic activity and recognition of the substrate. Significant differences were observed in a different region (loop B93-B101), that we identified as binding site of amiloride to the tissue plasminogen activator (tPA). Although tPA shares the same function of activating plasminogen and it is structurally similar to uPA. Amiloride is a specific inhibitor of uPA but does not inhibit tPA. Our study shows that predicted position of amiloride depends on species and in some cases was located, as expected, in the specificity pocket, but in the other cases close to the loop B93-B101. This location could weaken affinity of binding or prevent inhibition of uPA. Therefore, drug screening and elimination process based solely on animal study, without careful structural analysis, could lead to the elimination of potential drugs for humans.", "role": "user" }, { "content": "[[\"Amiloride\", \"NOT\", \"tPA\"], [\"amiloride\", \"DIRECT-REGULATOR\", \"urokinase plasminogen activator\"], [\"amiloride\", \"DIRECT-REGULATOR\", \"tissue plasminogen activator\"], [\"Amiloride\", \"INHIBITOR\", \"uPA\"], [\"amiloride\", \"DIRECT-REGULATOR\", \"tPA\"]]", "role": "assistant" } ]

[ { "content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nData-driven design of bi-selective OSDAs for intergrowth zeolites\n\nContent Extracts:\n\n<p>phase competition metrics and shape selectivity towards the frameworks, thus bypassing expensive dual-OSDA approaches typically used in the synthesis of intergrowths.</p><p>Finally, we propose potential OSDAs to obtain hypothesized disordered frameworks such as AEI/SAV. This work may accelerate zeolite discovery through data-driven synthesis optimization and design.</p><p>Zeolites are nanoporous materials with a myriad of applications in catalysis and separations. 1,2 Thanks to a broad diversity in topology and composition, their shape selectivity can be tuned along with their thermal stability and catalytic activity. 3 While the complex polymorphism observed in zeolites is key to creating tailored nanoporous materials for targeted applications, it hinders synthesis efforts due to phase competition between different metastable structures. Often, crystallizing a desired framework requires labor-intensive optimization of synthesis conditions to overcome the nucleation and growth of competing phases.</p><p>Synthesis routes selective towards one framework usually rely on organic structure-directing agents (OSDAs) which template the pore and cage structure of the targeted material. 4 However, selection of cost-effective OSDAs to crystallize the desired frameworks has historically depended on trial-and-error processes. 5 While computational approaches have been developed to design OSDAs de novo, [6][7][8][9] these methods often lead to complex OSDAs with low synthetic accessibility or low selectivity towards the targeted framework. 10 Compared to pure-phase frameworks, intergrown zeolites exhibit a structure that is disordered in at least one dimension. Typically, intergrowths are formed by periodic building units related to each other by symmetry operations such as rotations or translations, 11 and whose stacking enables them to form a defect-free interface between two topologically distinct domains. Although manually describing such structural faults is possible, 11 computational methods have enabled enumerating intergrown families such as ABC-6 12 or simulating diffraction patterns. 13 More recently, structural descriptors have been proposed to quantify whether two phases are topologically or geometrically compatible to form intergrown structures. 14 As differences in local crystallographic environments affect confinement and transport properties, intergrowth zeolites display catalytic behavior distinct from the pure end-member phases. 15,16 For example, the silicoaluminophosphate form of the CHA/AEI intergrowth is a competitive catalyst for the methanol-to-olefin (MTO) reaction compared to the commercial SAPO-34 catalyst. 17,18 However, the challenges of selective zeolite synthesis are exacerbated in the case of intergrowths. Traditional routes for synthesizing the high-silica form of CHA/AEI require the combination of two specific OSDAs for CHA and AEI, 19 which increases the synthesis complexity and cost. In addition, tuning the synthesis conditions to favor the formation of the desired intergrowth requires labor-intensive experimentation.</p><p>Nevertheless, this dual-OSDA approach has been the standard for crystallizing several intergrown zeolites, 20 despite being limited by: (i) the need to design two equally-selective OSDAs, (ii) the heuristic optimization of the synthesis conditions to avoid the collapse to a single phase, and (iii) avoiding formation of extraneous competing phases.</p><p>Recently, we have performed high-throughput simulations to quantify phase competition in zeolites. 10,21,22 The large number of simulated zeolite-OSDA pairs allowed rationalizing historical synthesis outcomes from the literature, explaining accessibility windows, and aluminum distributions in single zeolite frameworks as a function of OSDA shape and charge distribution. Furthermore, the data was used to control the synthesis of an aluminosilicate CHA/AEI intergrowth with an OSDA with dual selectivity. By designing OSDAs with shapes and binding energies competitive towards the two frameworks forming the intergrowth, we have demonstrated that this disordered structure can be crystallized in its high-silica form. 10 In this work, we extend these design principles towards several other intergrown zeolites by combining simulations and data mining. Starting from a dataset of hundreds of thousands of zeolite-OSDA pairs, we singled out potential bi-selective OSDAs for the synthesis of both known and hypothesized intergrowths. To demonstrate the applicability of the method towards small, medium, and large-pore zeolites, we designed potential bi-selective OSDAs for the CHA/AFX, MTT/TON, and BEC/ISV intergrowths. Finally, the strategy is extended to several known frameworks, and one example of a hypothesized intergrowth. This work is expected to accelerate the discovery of intergrowth zeolites through theory and simulations. This new computational strategy for designing an intergrowth zeolite is shown in Fig. 1. OSDAs known to be selective towards pure phase zeolites are used as references for the shape, such as N-ethyl-N-methyl-2,2,6,6-tetramethylpiperidinium for AEI 23 and N,N,Ntrimethyladamantammonium for CHA 24 (Fig. 1a). Then, new OSDAs for the intergrowth can be designed using phase competition and shape metrics. Binding metrics built upon binding energies were calculated for OSDAs retrieved from the literature and for chemically modified ones. 10, 25 In particular, we define the competition energy by comparing the binding energies of one OSDA towards all calculated frameworks, and adopting the second-best zeolite-OSDA pair as the energy reference. This quantifies how strong are the phase competition effects for a given OSDA, with more negative values indicating less competition. Moreover, the shape of an OSDA is quantified by first projecting nuclear coordinates of the molecule into a two-dimensional space using a principal component analysis, and later measuring the two axes describing the molecule (see Supporting Information). 10 When designing bi-selective OSDAs for intergrowth systems, we postulate that an ideal bi-selective OSDA should: (i) be an equally strong binder towards both phases forming the intergrowth, (ii) be a weak binder towards all other competing phases (Fig. 1b), and (iii) have a geometry that is in-between the reference OSDAs in the shape space, thus favoring the crystallization of both structures (Fig. 1c). 10 Beyond the previously demonstrated CHA/AEI intergrowth, we discuss the application of this method to many other intergrown zeolites of practical interest. For example, the highsilica CHA/AFX zeolite is used in applications such as MTO reaction, or selective catalytic reduction of NO x (NO x -SCR), but is typically synthesized using a mixture of OSDAs. 20 Although both zeolites are ABC-6 structures and have cages with similar diameters, the aft cage in AFX zeolite is 40% longer than the cha cage. This discrepancy in size has led AFX to be synthesized with longer OSDAs, including diquaternary ammonium molecules such Along with the binding energies, bi-selective OSDAs should also satisfy c, shape matching requirements. Often, binding energy metrics give rise to selectivity domains in the shape space.</p><p>as 1,4-bis(1-azoniabicyclo[2.2.2]octane)butyl, 26 or monocationic OSDAs such as 1,3-bis(1adamantyl)imidazolium. 27 Figure 2 shows the proposed OSDAs for a CHA/AFX intergrowth based on the biselectivity design principles. As the gme cage in the AFX framework is not occupied by an OSDA, but may be stabilized by an inorganic structure-directing agent, the binding energy per SiO 2 alone, as is traditionally normalized, does not determine the likelihood of crystallizing this framework. 10 Quantifying phase competition effects of both inorganic and organic structure-directing agents at the same could provide additional insights on these phase boundaries, but simulations with these effects are overly expensive. Instead, the proposed OSDAs can also be compared with respect to their binding energy normalized per OSDA (Table S1 in the Supporting Information), which has been proven useful to describe structure-direction in cage-based zeolites. 10 All computer-designed OSDAs in Fig. 2b exhibit intermediate binding energies both for CHA and AFX. In addition, the templates are longer than TMAda, as required to favor the formation of the AFX framework in addition to the cha cage. Interestingly, most of the proposed OSDAs may crystallize the aft cage by promoting intermolecular π − π stacking, which enables two molecules to fit in a single aft cage (Fig. S1 in the Supporting Information). On the other hand, flexible OSDAs may favor the crystallization of the cha cage by adopting a folded conformation, or the aft cage by adopting the longer conformation (Fig. S2).</p><p>The MTT and TON zeolites also form intergrowths of practical interest. Both zeolites have one-dimensional medium-sized pores and can be synthesized in the aluminosilicate form. The slight differences in pore sizes of MTT and TON could lead to membranes with high shape selectivity, as has been observed for the MEL/MFI case. 28 However, the synthesis of an MTT/TON intergrowth is typically performed by using the dual-OSDA approach, hindering the control of phase fraction. 29 However, fine-tuning the synthesis conditions may direct the formation of these zeolites and the corresponding intergrowth. Although synthesis parameters cannot be selected purely through simulations, past literature outcomes and machine learning models trained on them may guide the exploration of synthesis routes. 25,30 Interestingly, since MTT has a slightly smaller unit cell than TON, variations of binding energy with respect to shape depend on the commensurability of the OSDA within the framework (Fig. 3d). At a value of 4 Å for Finally, we show that the method can also be applied to large-pore, three dimensional zeolites. One example is the BEC/ISV intergrowth, which is often only obtained in the presence of germanium or fluoride in the synthesis media. 31 Despite the challenge usually associated to predicting OSDAs for zeolites with intersecting pores, the design principles successfully recover the literature results for phase selectivity in BEC and ISV. Figure 4 shows the proposed OSDAs for the synthesis of this intergrown structure. Reference OSDAs for the selective synthesis of BEC are indeed more favorable towards this framework compared to ISV (Fig. 4a,c). Furthermore, the red area towards OSDAs with longer Axis 1 in Fig. 4d recover the fact that longer OSDAs favor BEC zeolite, since the unit cells of BEC and ISV have very similar a and b lattice parameters, but ISV has a c lattice parameter 1% smaller than the c in the BEC unit cell. Similarly to the MTT/TON example, this indicates that the commensurability between the OSDA and the zeolite is a useful parameter when predicting phase selectivity. From these insights and the results from Fig. 4d, we suggest that OSDAs with an Axis 1 between 9 and 10 Å lie in the phase boundary between BEC and ISV, and could be used to direct a zeolite intergrowth.</p><p>Since this rationale can be extended to any pair of zeolites that are individually templated by OSDAs, bi-selective OSDAs leading to other intergrown structures can be predicted.</p><p>In Figs. S3-10 in the Supporting Information, we show the applicability of this method towards many other intergrowths, including known disordered structures such as SBS/SBT, FAU/EMT, MEL/MFI, ITH/ITR, RTH/ITE, and ERI/OFF. In cases such as MEL/MFI or RTH/ITE (Figs. S3,4), the difficulty in distinguishing between phase boundaries may explain why these phases are typically found as intergrowths even when a single OSDA is used. As the shapes of the cavities are very similar, bi-selectivity is more easily achieved compared to other intergrowths. In other cases such as FAU/EMT, ITH/ITR, ERI/OFF, AFS/BPH (Figs. S5-8), the shape boundaries are more subtle, and often dominated by one of the end members. This suggests that balancing phase competition between the polymorphs could require tuning other synthesis conditions in addition to the OSDA. This is also the case of SBS/SBT (Fig. S9), whose intergrowth can be tuned beyond the use of bi-selective ISV Energy (kJ/mol Si) OSDAs by selecting inorganic structure-directing agents that cooperate to crystallize the disordered structure. 32 Finally, OSDAs for realizing the hypothetical intergrowth AEI/SAV (Fig. S10) is proposed. Whereas SAV is typically synthesized as a zeotype, synthesizing an aluminosilicate SAV framework intergrown with SSZ-39 (AEI framework) may be interesting for catalytic applications such as NO x -SCR beyond pure AEI or CHA/AEI intergrowths.</p><p>In summary, we combined simulations, data mining, and design principles to propose bi-selective OSDAs for intergrowth zeolites. By visualizing the OSDAs according to their phase competition and shape matching metrics, we designed promising bi-selective candidates for cost-efficient synthesis of intergrowth zeolites. The method was demonstrated for small-, medium-, and large-pore zeolites, and extended towards several known intergrowths. Furthermore, we proposed OSDAs that could realize a hypothetical intergrowth. This work is expected to accelerate discovery of intergrown zeolites using computation.</p>\n\nSupporting Information Available\n<p>Computational methods, visualizations and comparisons of binding modes/metrics for proposed OSDAs in CHA/AFX zeolites, and proposed OSDAs for 8 intergrowth zeolite pairs. of organic structure-directing agents for zeolites using nature-inspired ant colony optimization. Chemical Science 2020, 11, 8214-8223.</p>", "role": "user" }, { "content": "Zeolites are inorganic materials with wide industrial applications due to their topological diversity. Tailoring confinement effects in zeolite pores, for instance by crystallizing intergrown frameworks, can improve their catalytic and transport properties, but controlling zeolite crystallization often relies on heuristics. In this work, we use computational simulations and data mining to design organic structure-directing agents (OSDAs) to favor the synthesis of intergrown zeolites. First, we propose design principles to identify OSDAs which are selective towards both end members of the disordered structure. Then, we mine a database of hundreds of thousands of zeolite-OSDA pairs and downselect OSDA candidates to synthesize known intergrowth zeolites such as CHA/AFX, MTT/TON, and BEC/ISV. The computationally designed OSDAs balance", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nPGC-1alphaproteinwasnotdetectedinwholecell(Figure1E)ornuclearproteinextracts(unpublisheddata)isolatedfromBATofPGC-1alpha-/-miceunderbasalconditionsorinresponsetocoldexposure,aconditionknowntomarkedlyinducetheexpressionofPGC-1alphainBAT.", "role": "user" }, { "content": "[\"protein\", \"protein\"]", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: An efficient algorithm for obtaining near real-time disparity maps comparable to state-of-the-art approaches\n\nKeywords: stereo matching images paragraph-level\n\nDataset Information:\nFord Campus Vision and Lidar Data Set: Ford Campus Vision and Lidar Data Set is a dataset collected by an autonomous ground vehicle testbed, based upon a modified Ford F-250 pickup truck. The vehicle is outfitted with a professional (Applanix POS LV) and consumer (Xsens MTI-G) Inertial Measuring Unit (IMU), a Velodyne 3D-lidar scanner, two push-broom forward looking Riegl lidars, and a Point Grey Ladybug3 omnidirectional camera system.\nMiddlebury 2014: The Middlebury 2014 dataset contains a set of 23 high resolution stereo pairs for which known camera calibration parameters and ground truth disparity maps obtained with a structured light scanner are available. The images in the Middlebury dataset all show static indoor scenes with varying difficulties including repetitive structures, occlusions, wiry objects as well as untextured areas.\nNAB: The First Temporal Benchmark Designed to Evaluate Real-time Anomaly Detectors Benchmark The growth of the Internet of Things has created an abundance of streaming data. Finding anomalies in this data can provide valuable insights into opportunities or failures.\nMiddlebury: The Middlebury Stereo dataset consists of high-resolution stereo sequences with complex geometry and pixel-accurate ground-truth disparity data. The ground-truth disparities are acquired using a novel technique that employs structured lighting and does not require the calibration of the light projectors.\n\nAvailable Datasets: A: Ford Campus Vision and Lidar Data Set B: Middlebury 2014 C: NAB D: Middlebury", "role": "user" }, { "content": "Middlebury", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nin a recent issue of the british journal of anaesthesia , moloney and griffiths reviewed basic issues surrounding the ongoing debate on ventilator induced / associated lung injury ( vili ) and the implications for patient care .\nthe potential importance of vili / biotrauma is not only that it can aggravate ongoing lung injury but also that it may have important systemic consequences , and may explain why most patients with acute respiratory distress syndrome ( ards ) who go on to die , succumb to multiple organ failure ( mof ) . vili / biotrauma offers a clinically relevant window of therapeutic opportunity in the management of ards / acute lung injury ( ali ) .\noften the process of systemic inflammatory response syndrome has been initiated hours if not days before admission to the intensive care unit .\nin contrast , we know exactly when vili / biotrauma begins with intubation and initiation of mechanical ventilation\n. a full understanding of the mechanisms that mediate lung injury may permit potential strategies directed at reducing the incidence of vili - induced mof to be instituted early in the course of illness .\nthis is no small issue for a syndrome with an incidence of 64.2 cases per 105 person - years and with a 4050% mortality rate .\nresults from the ardsnet trial have underscored the potential importance of biotrauma in the management of ards : the results from that large multicenter trial showed a relative risk reduction of 22% in patients ventilated with the lower tidal volume .\nthis improvement in mortality in patients ventilated with low tidal volumes was not due to a decrease in barotrauma between groups .\nit is postulated that injurious strategies of mechanical ventilation can cause pulmonary inflammation with release of various cytokines / mediators biotrauma .\nthe initial insult ( pneumonia , acid aspiration , or contusion are a few examples ) ' primes ' the lung .\na ' second hit ' , or subsequent insult , such as mechanical ventilation , leads to an overwhelming pulmonary inflammatory response .\nloss of pulmonary compartmentalization allows for important mediators to escape the confines of the lung and gain access to the systemic circulation .\nrecent experiments have shown that this is associated with apoptosis of cells in distal organs ( kidney , villi of colon ) and end - organ dysfunction ( kidney ) , which potentially underlies the development of mof . in a randomized controlled trial conducted in 44 patients , ranieri and coworkers demonstrated that a lung protective strategy attenuated the levels of proinflammatory cytokines in plasma and bronchoalveolar lavage fluid , and was associated with a lower incidence of mof .\nhowever , the measurement of proinflammatory cytokines does not address the issue of maintenance of alveolar epithelial barrier integrity .\nin a recent study conducted by eisner and coworkers , circulating levels of surfactant protein ( sp)-a and sp - d were evaluated in plasma samples from participants in the ardsnet randomized trial .\nbaseline plasma sp - a levels were not found to be related to clinical outcome .\nin contrast , higher baseline plasma sp - d levels were associated with a greater risk for death ( odds ratio 1.21 per 100 ng / ml increment ; 95% confidence interval 1.08 to 1.35 ) as well as higher overall morbidity .\nin addition , use of a lower tidal volume strategy significantly attenuated the rise in plasma sp - d levels ( p = 0.0006 ) .\nbecause injury to the alveolar epithelial barrier is a hallmark of ali , levels of circulating sps may not only represent a potential biomarker for ali / ards but they may also , in the future , be used to gauge the effects of treatment .\nample evidence supports the use of a relatively low tidal volume , but what about the use of a open lung strategy ( e.g. recruitment maneuvers , positive end - expiratory pressure [ peep ] , proning ) ?\nthe alveoli study ( prospective , randomized , multi - center trial of higher end - expiratory lung volume / lower fio2 versus lower end - expiratory lung volume / higher fio2 ventilation in acute lung injury and acute respiratory distress syndrome ) , performed by the ardsnet investigators to study the use of higher peep levels , was discontinued prematurely because of lack of efficacy .\naccumulating evidence from both animals and human experiments suggest that not all patients are recruitable ; moreover , if improved oxygenation does not seem to affect outcome , then should recruitment be pursued for the sole purpose of decreasing atelectrauma ?\ndata have been reported that suggest that recruitment maneuvers may be deleterious if sufficient peep is not used to maintain recruitment .\nrepeated de - recruitments accentuate lung injury during mechanical ventilation , and it has also been suggested that allowing the lung to remain in a state of de - recruitment may mitigate biotrauma .\none of the mechanisms for upregulation of cytokines during mechanical ventilation of acutely injured lungs is alteration in alveolar mechanics ( i.e. the dynamic change in alveolar size and shape during ventilation ) \nalveolar instability and recruitment / de - recruitment . using direct visualization of subpleural alveoli , schiller and\ncoworkers demonstrated that normal alveoli are extremely stable with minimal movement during mechanical ventilation .\nin contrast , surfactant deactivation ( also a classic finding in ards ) causes a continuum of altered alveolar mechanics seen as repetitive collapse of alveoli at end - expiration and re - inflation at end - inspiration . in a recent follow - up study ,\nsteinberg and coworkers demonstrated that alveolar instability can mechanically injure the lung independent of inflammatory damage .\nmoreover , the application of peep in this animal model was sufficient to stabilize the alveoli .\nthat group also noted that alveolar instability was associated with modest increases in interleukin-6 levels after 4 hours of mechanical ventilation , even in the absence of neutrophil infiltration , and that this increase could be attenuated by the application of peep .\nthese data suggest that mechanical injury alone is sufficient to cause a rise in tissue and bronchoalveolar lavage levels of proinflammatory cytokines , and that stabilization of alveoli is a key issue in reducing atelectrauma .\nthis probably occurs via a direct attenuation of the mechanical injury to the capillary alveolar membrane , thereby limiting the effects of mechanotransduction ( the response of cells to mechanical force ) on cellular molecular physiology .\npreliminary evidence suggests that use of strategies that stabilize alveoli are lung protective , but definitive clinical outcome data are not yet available .\nfurther research is required to determine whether alveolar stabilization is achievable , measurable , and desirable .\nagain , the answer is probably ' yes ' , both as a consequence of mechanical injury and as the mechanism underlying the development of mof in this patient population .\nhowever , as pointed out by moloney and griffiths , a definitive answer to this latter question requires a study that monitors outcomes after specifically targeting certain mediator(s ) .\nali = acute lung injury ; ards = acute respiratory distress syndrome ; mof = multiple organ failure ; peep = positive end - expiratory pressure ; sp = surfactant protein ; vili = ventilator - induced / associated lung injury . 1", "role": "user" }, { "content": "in a recent issue of the british journal of anaesthesia , moloney and griffiths reviewed clinically pertinent issues surrounding the management of the acute respiratory distress syndrome ( ards ) patient , particularly as it pertains to the treatment of ventilator induced / associated lung injury ( vili ) . \n in addition to highlighting the important observations that have contributed to further our understanding of the relationship between the mechanical ventilator and inflammatory lung injury , the authors also offer a concise reappraisal of the clinical strategies used to minimize vili in ards . \n special emphasis is placed on the theory of biotrauma , which attempts to explain how multi - organ failure may develop in patients who ultimately succumb to this syndrome .", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: High-Assurance Separation Kernels: A Survey on Formal Methods \nChapter Title: Overall Comparison \n1. Abstract of Cited Paper (BIB001): We revisit the classical notion of noninterference for state-based systems, as presented by Rushby in 1992. We strengthen his results in several ways, in particular clarifying the impact of transitive vs. intransitive policies on unwinding. Inspired partially by Mantel’s observations on unwinding for event systems, we remove the restriction on the unwinding relation to be an equivalence and obtain new insights in the connection between unwinding relations and observational preorders. \n2. Abstract of Cited Paper (BIB002): Separation of processes is the foundation for security and safety properties of systems. This paper reports on a collaborative effort of Government, Industry and Academia to achieve high confidence in the separation of processes. To this end, this paper will discuss (1) what a separation kernel is, (2) why the separation of processes is fundamental to security systems, (3) how high confidence in the separation property of the kernel was obtained, and (4) some of the ways government, industry, and academia cooperated to achieve high confidence in a separation kernel. ::: ::: i>What is separationq Strict separation is the inability of one process to interfere with another. In a separation kernel, the word i>separation is interpreted very strictly. Any means for one process to disturb another, be it by communication primitives, by sharing of data, or by subtle uses of kernel primitives not intended for communication, is ruled out when two processes are separated. ::: ::: i>Why is separation fundamentalq Strict separation between processes enables the evaluation of a system to check that the system meets its security policy. For example, if a red process is strictly separated from a black process, then it can be concluded that there is no flow of information from red to black. ::: ::: i>How was high confidence achievedq We have collaborated and shared our expertise in the use of SPECWARE. SPECWARE is a i>correct by construction method, in which high level specifications are built up from modules using specification combinators. Refinements of the specifications are made until an implementation is achieved. These refinements are also subject to combinators. The high confidence in the separation property of the kernel stems from the use of formal methods in the development of the kernel. ::: ::: i>How did we collaborateq Staff from the Kestrel Institute (developers of SPECWARE), the Department of Defense (DoD), and Motorola (developers of the kernel) cooperated in the creation of the Mathematically Analyzed Separation Kernel (MASK). DoD provided the separation kernel concept, and expertise in computer security and high confidence development. Kestrel provided expertise in SPECWARE. Motorola combined its own the expertise with that of DoD and Kestrel in creating MASK. \n3. Abstract of Cited Paper (BIB003): While intransitive noninterference is a natural property for any secure OS kernel to enforce, proving that the implementation of any particular general-purpose kernel enforces this property is yet to be achieved. In this paper we take a significant step towards this vision by presenting a machine-checked formulation of intransitive noninterference for OS kernels, and its associated sound and complete unwinding conditions, as well as a scalable proof calculus over nondeterministic state monads for discharging these unwinding conditions across a kernel's implementation. Our ongoing experience applying this noninterference framework and proof calculus to the seL4 microkernel validates their utility and real-world applicability. \n4. Abstract of Cited Paper (BIB004): We present an in-depth coverage of the comprehensive machine-checked formal verification of seL4, a general-purpose operating system microkernel. We discuss the kernel design we used to make its verification tractable. We then describe the functional correctness proof of the kernel's C implementation and we cover further steps that transform this result into a comprehensive formal verification of the kernel: a formally verified IPC fastpath, a proof that the binary code of the kernel correctly implements the C semantics, a proof of correct access-control enforcement, a proof of information-flow noninterference, a sound worst-case execution time analysis of the binary, and an automatic initialiser for user-level systems that connects kernel-level access-control enforcement with reasoning about system behaviour. We summarise these results and show how they integrate to form a coherent overall analysis, backed by machine-checked, end-to-end theorems. The seL4 microkernel is currently not just the only general-purpose operating system kernel that is fully formally verified to this degree. It is also the only example of formal proof of this scale that is kept current as the requirements, design and implementation of the system evolve over almost a decade. We report on our experience in maintaining this evolving formally verified code base. \n5. Abstract of Cited Paper (BIB005): Protecting the confidentiality of information manipulated by a computing system is one of the most important challenges facing today's cybersecurity community. A promising step toward conquering this challenge is to formally verify that the end-to-end behavior of the computing system really satisfies various information-flow policies. Unfortunately, because today's system software still consists of both C and assembly programs, the end-to-end verification necessarily requires that we not only prove the security properties of individual components, but also carefully preserve these properties through compilation and cross-language linking. In this paper, we present a novel methodology for formally verifying end-to-end security of a software system that consists of both C and assembly programs. We introduce a general definition of observation function that unifies the concepts of policy specification, state indistinguishability, and whole-execution behaviors. We show how to use different observation functions for different levels of abstraction, and how to link different security proofs across abstraction levels using a special kind of simulation that is guaranteed to preserve state indistinguishability. To demonstrate the effectiveness of our new methodology, we have successfully constructed an end-to-end security proof, fully formalized in the Coq proof assistant, of a nontrivial operating system kernel (running on an extended CompCert x86 assembly machine model). Some parts of the kernel are written in C and some are written in assembly; we verify all of the code, regardless of language.\n\nReview Chapter:", "role": "user" }, { "content": "We give an overall comparison of formal methods application on separation kernels in this subsection. We compare the related work on aspects of the target of formal methods application, development processes covered by the formal methods used according to CC, verification approaches, estimated EAL in CC according to Table III , and scale of formal methods application in Table XII . In addition to the normative definitions of EALs, the CC standard defines the possibility of intermediate levels of security when a requirement is evaluated at a higher level than that required by the target level. The addition of the symbol \"+\" represents this kind of evaluation. Formal verification of ED, PikeOS, and PROSPER does not have low-level design. They either prove the conformance Properties TP 4+ + Noninterference [Rushby 1992; BIB002 BIB004 Properties TP 4+ ++ MASK BIB001 BIB003 Low-level model R, TP, CG 7 ? MPS between the high-level design and the implementation or use software model checking to analyze the implementation. The highest assurance level of CC (EAL 7) requires formal methods application on the lowlevel design but not on the implementation. Aiming at security/safety of separation kernels as far as possible, a few research works have provided formal proof of refinement between the low-level design and the implementation, such as seL4 [Murray et al. 2013] and mCertiKOS BIB006 . Targeting at the source code by formal methods always means that they are applied on the implementation, which has overstepped the demand of EAL 7 in CC and estimated as EAL 7+ in Table XII . Compared to the high cost of CC certification, formal verification on implementation is a low-cost way to provide more assurance of separation kernels as stated in [Klein et al. 2009] . Few work provides an estimation of time and cost of formal methods application on separation kernels. Thus, we cannot clearly compare them. A notable viewpoint is that the industry rules-ofthumb for CC EAL 6 certification is of $1k/LOC, although it provides less assurance than formal verification BIB005 .", "role": "assistant" } ]

[ { "content": "Examine the abstracts provided from a main scientific article and its cited works. Craft a narrative that synthesizes the key insights and contributions, emphasizing their interconnections. Employ numerical citations such as [1], [2], etc., to reference the cited works.\n\nMain Article Summary:\nUnderstanding the semantic characteristics of the environment is a key enabler for autonomous robot operation. In this paper, we propose a deep convolutional neural network (DCNN) for the semantic segmentation of a LiDAR scan into the classes car, pedestrian or bicyclist. This architecture is based on dense blocks and efficiently utilizes depth separable convolutions to limit the number of parameters while still maintaining state-of-the-art performance. To make the predictions from the DCNN temporally consistent, we propose a Bayes filter based method. This method uses the predictions from the neural network to recursively estimate the current semantic state of a point in a scan. This recursive estimation uses the knowledge gained from previous scans, thereby making the predictions temporally consistent and robust towards isolated erroneous predictions. We compare the performance of our proposed architecture with other state-of-the-art neural network architectures and report substantial improvement. For the proposed Bayes filter approach, we show results on various sequences in the KITTI tracking benchmark.\n\nCited Works Summary:\n[1]: Convolutional networks are powerful visual models that yield hierarchies of features. We show that convolutional networks by themselves, trained end-to-end, pixels-to-pixels, exceed the state-of-the-art in semantic segmentation. Our key insight is to build “fully convolutional” networks that take input of arbitrary size and produce correspondingly-sized output with efficient inference and learning. We define and detail the space of fully convolutional networks, explain their application to spatially dense prediction tasks, and draw connections to prior models. We adapt contemporary classification networks (AlexNet [20], the VGG net [31], and GoogLeNet [32]) into fully convolutional networks and transfer their learned representations by fine-tuning [3] to the segmentation task. We then define a skip architecture that combines semantic information from a deep, coarse layer with appearance information from a shallow, fine layer to produce accurate and detailed segmentations. Our fully convolutional network achieves state-of-the-art segmentation of PASCAL VOC (20 relative improvement to 62.2 mean IU on 2012), NYUDv2, and SIFT Flow, while inference takes less than one fifth of a second for a typical image.\n\n[2]: State-of-the-art approaches for semantic image segmentation are built on Convolutional Neural Networks (CNNs). The typical segmentation architecture is composed of (a) a downsampling path responsible for extracting coarse semantic features, followed by (b) an upsampling path trained to recover the input image resolution at the output of the model and, optionally, (c) a post-processing module (e.g. Conditional Random Fields) to refine the model predictions.,,,,,, Recently, a new CNN architecture, Densely Connected Convolutional Networks (DenseNets), has shown excellent results on image classification tasks. The idea of DenseNets is based on the observation that if each layer is directly connected to every other layer in a feed-forward fashion then the network will be more accurate and easier to train.,,,,,, In this paper, we extend DenseNets to deal with the problem of semantic segmentation. We achieve state-of-the-art results on urban scene benchmark datasets such as CamVid and Gatech, without any further post-processing module nor pretraining. Moreover, due to smart construction of the model, our approach has much less parameters than currently published best entries for these datasets.", "role": "user" }, { "content": "Focusing on the task of semantic segmentation using 2D images, one of the initial architectures was proposed by long_shelhamer_fcn [1] . They proposed an encoder-decoder style, fully convolutional network (FCN) architecture and other architectures since then have followed the same paradigm. jegou2017one [2] proposed a dense block based DCNN for the task of semantic segmentation. The main differences between our DCNN and theirs is that we use depth separable convolution layers for dense blocks in the decoder. To down-sample the feature maps they proposed a transition down block comprising of a composite function implementing different operations. We replace this block with a single max-pooling operation and show that instead of a composite function, this single operation is sufficient. In the presented ablation study, we justify these proposed changes.", "role": "assistant" } ]

[ { "content": "Analyze the given text to identify specific entities. Focus on extracting relevant data.\n\nProvide your findings in JSON format. Each category should list the entities found.\n\nText:\n\nHomogeneous palladium-catalyzed asymmetric hydrogenation. The transition metal catalyzed asymmetric hydrogenation of unsaturated compounds arguably presents one of the most attractive methods for the synthesis of chiral compounds. Over the last few decades, Pd has gradually grown up as a new and popular metal catalyst in homogeneous asymmetric hydrogenation the same as traditional Ru, Rh and Ir catalysts. Much progress has been successfully achieved in the asymmetric reduction of imines, enamines, olefins, ketones and heteroarenes. It was also found that palladium catalyzed asymmetric hydrogenation could be used as a key step in tandem reactions to quickly synthesize chiral compounds. This tutorial review intends to offer an overview of recent progress in homogeneous palladium catalyzed asymmetric hydrogenation and should serve as an inspiration for further advances in this area.", "role": "user" }, { "content": "{\"Chemical\": [\"Ir\", \"Ru\", \"enamines\", \"ketones\", \"olefins\", \"Rh\", \"palladium\", \"heteroarenes\", \"imines\", \"Pd\"]}", "role": "assistant" } ]

[ { "content": "Examine the following abstract and identify distinct entities. Focus on extracting entities related to participants, interventions, and outcomes.\n\nPresent your findings in a JSON format like: {\"Participant\": [\"example entity\", ...], \"Intervention\": [\"example entity\", ...], \"Outcome\": [\"example entity\", ...]}. If no entities are found for a category, use an empty list.\n\nAbstract Content:\n\n[ Psychoexperimental studies on the effect of a valepotriate combination as well as the combined effects of valtratum and alcohol ] .", "role": "user" }, { "content": "{\"Intervention\": [\"valtratum and alcohol ]\", \"valepotriate combination\"], \"Outcome\": [], \"Participant\": [\"valepotriate combination as well as the combined effects of valtratum and alcohol\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We present a novel method for image retrieval using an embedding approach. We first introduce a function approximation based\n\nKeywords: image retrieval images\n\nDataset Information:\nOxford5k: Oxford5K is the Oxford Buildings Dataset, which contains 5062 images collected from Flickr. It offers a set of 55 queries for 11 landmark buildings, five for each landmark.\nCMD: Consists of the key scenes from over 3K movies: each key scene is accompanied by a high level semantic description of the scene, character face-tracks, and metadata about the movie. The dataset is scalable, obtained automatically from YouTube, and is freely available for anybody to download and use.\nHIGGS Data Set: The data has been produced using Monte Carlo simulations. The first 21 features (columns 2-22) are kinematic properties measured by the particle detectors in the accelerator.\nEPIC-KITCHENS-100: This paper introduces the pipeline to scale the largest dataset in egocentric vision EPIC-KITCHENS. The effort culminates in EPIC-KITCHENS-100, a collection of 100 hours, 20M frames, 90K actions in 700 variable-length videos, capturing long-term unscripted activities in 45 environments, using head-mounted cameras.\n\nAvailable Datasets: A: Oxford5k B: CMD C: HIGGS Data Set D: EPIC-KITCHENS-100", "role": "user" }, { "content": "Oxford5k", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\na 55-year - old man , presented to our hospital , complained of a large pelvic mass , which was found incidentally during a routine ultrasonography .\nthe patient had no history of abdominal or pelvic discomfort , nor any abdominal or pelvic surgery .\nin addition , the patient had no relevant medical or family history except for diabetes mellitus . upon a digital rectal examination , a large mass with a stone - like hardness was palpated at 5 - 6 cm above the anal verge .\na single - phase helical ct ( lightspeed ultra ; ge healthcare , milwaukee , wi ) , spanning the whole abdominopelvic cavity , was performed .\nthe ct scanning parameters included a beam collimation of 8 1.25 mm , a reconstruction interval of 1.25 mm , a pitch of 1.35 , a rotation time of 0.8 seconds , a table speed of 13.5 mm / rotation , 120 kv and 160 mas .\ntransverse ct images were obtained 70 seconds after the intravenous injection of non - ionic contrast material ( 120 ml ) at a rate of 3 ml / sec ( ultravist 300 ; bayer schering pharma , berlin , germany ) .\nthe ct images revealed a large , well - defined mass in the presacral space of the pelvic cavity , which seemed to have a long stalk arising from the left gluteus medius muscle ( fig .\nthe stalk traversed along the surface of the left iliac bone , and proceeded through the left sciatic foramen , and ended up connecting with the mass .\nthe ct attenuation generated an easily recognizable mass , which was mainly composed of fatty tissue and calcification , with most of the stalk becoming calcified .\nsome focal areas of intermediate attenuation were identified as a mixture between fatty tissue and calcification , and occupied only a limited portion of the mass .\nmr imaging ( horizon 1.5 t ; ge healthcare , milwaukee , wi ) was also performed with the use of a torso coil . on both the t1-weighted ( 366/8 , echo train length of zero , 5-mm slice thickness , 2-mm gap , 256192 matrix , 24-cm field of view , 2 signal acquired , and sequence duration of 3 - 4 minutes ) and t2-weighted ( 4300/84 , echo train length of ten , 5-mm slice thickness , 2-mm gap , 512256 matrix , 24-cm field of view , 2 signal acquired , and sequence duration of 3 - 4 minutes )\nmr images , the mass was revealed to mainly consist of the hyperintense and signal void areas that represent fatty tissue and calcification , respectively ( fig .\n1c - e ) . also seen are the focal areas of intermediate signal intensity , as shown on the ct images .\nthe gadolinium - enhanced t1-weighted mr images obtained 30 seconds , 60 seconds , and 3 minutes after the intravenous injection of contrast material ( gadovist ; bayer schering pharma , berlin , germany ) , and the focal areas of the intermediate signal intensity around the calcifications observed at 30 and 60 seconds post - injection , became isointense as the surrounding fat tissue at 3 minutes post - injection .\nthe main mass was resected using a transabdominal approach , whereas the stalk was removed through the sciatic foramen .\nthe surgical specimen consisted of a 13 cm , well - circumscribed , hard mass , with a severely calcified external surface .\nthe cut surface of the resected specimen revealed a mass mixed with fatty tissue and calcification ( fig .\na histopathological examination revealed that the mass was composed of lipoma with chondroid metaplasia ( fig .\nthe term mesenchymoma was originally defined by stout ( 7 ) in 1948 to describe tumors containing at least two mesenchymal tissues not normally found together .\nthe tumors can be classified as benign or malignant , and most of the benign varieties have been called angiomyolipomas , angiolipomas , chondrolipomas , osteolipomas , and other names depending on the predominant tissue form in the tumor .\nhowever , fibrous tissue is found in all mesenchymal tumors , and is not counted as one of the elements ( 6 ) .\nconversely , if a mesenchymal tumor is well - defined or encapsulated and composed predominantly of one type of mesenchymal tissue , along with one or more minor element , the diagnosis should reflect the predominant mesenchymal tissue ( 6 ) . in our case ,\nthe diagnosis of a chondrolipoma was appropriate , since the mass was composed of a sufficiently high proportion of both fatty tissue and extensively calcified chondroid tissue , though it was well - defined and encapsulated .\ntwo possible explanations for the pathogenesis of cartilage and bone formation in benign mesenchymomas have been proposed ( 5 , 6 , 8 , 9 ) .\nthe first is that cartilage arises from chondro - osseous metaplasias of adipose tissue , presumably as a result of mechanical stress or trophic disturbance .\nthe close proximity or contact with bone and a large joint , myxoid background , or a lipodystrophy - like change , which are often associated with these tumors , suggest a metaplastic process caused by a trophic disturbance or mechanical stress ( 8 - 10 ) .\na previous immunohistochemical study supported the explanation that the pattern of expression for growth factor- , latent transforming growth factor- binding protein-1 transforming , and bone morphogenetic protein might play an important role in the transformation of multipotential cells into the chondrolipoma ( 11 ) .\nconsidering the proximity of the identified chondrolipoma to the iliac bone of our case study , we agree with the first explanation of chondroid - osseous metaplasia , which states that the mass may be a result of a micro - trauma .\nour mass occupied both the inside and outside of the pelvic cavity ; however , we could not clarify whether its primary site was the pelvic cavity or the left buttock . according to previously reported cases\nthe only reported case of an abdominal chondrolipoma in a human occurred in the small bowel ( 8) , whereas a chondrolipoma was once documented in the pelvic cavity of a dog ( 12 ) . considering these reports , we thought that in our case , a chondrolipoma in the buttock might be extended to the pelvic cavity through the sciatic foramen , though the proportion of the mass in the pelvis was greater than in the buttock .\nthere are few reports pertaining to the imaging features of chondrolipomas of various organs , with most cases describing their mr features ( 5 , 9 , 13 , 14 ) . for these reports ,\nchondroid and fatty tissues were described as intermediate and high signal intensity areas on t1-weighted images , respectively .\nboth chondroid and fatty tissues were identified as having a higher signal intensity area than the surrounding muscle , whereas chondroid tissue was depicted as having a higher signal intensity area than fatty tissue on t2-weighted images .\nsignal void areas corresponding to calcifications were only found in a small portion of these reported cases . for the ct images ,\nfatty tissue was depicted as a low attenuation area ( less than -30 hounsfield units ) , whereas chondroid tissue was depicted as an intermediate attenuation area . in our case ,\nthe mass was depicted to be primarily composed of fatty tissue and calcification , which matched the ct attenuation and mr signal intensity .\nalso , we found that additional focal areas of intermediate attenuation or signal intensity corresponded to chondroid tissue .\nthese findings were different from those described in previously reported cases whereby , in our case , the calcification was much more extensive , and the signal intensity of chondroid tissue on the t2-weighted images was intermediate\n. moreover , we found extensive calcification located peripherally in a linear and rosary pattern .\na previous report also cited the observation of chondroid tissue in a rosary pattern ( 9 ) . despite the very limited number of reported cases , we propose that the rosary pattern of either the chondroid tissue or calcification could be a characteristic finding of chondrolipomas , and in our case , the calcification in a rosary pattern was likely a consequence of the dystrophic change involving the chondroid tissue .\nmoreover , the signal intensity of chondroid tissue was intermediate on the t2-weighted images , and could be explained by the presence of fibrous tissue within the chondroid tissue ( fig .\n1i ) , which reduced the signal intensity of chondroid tissue below the fatty tissue .\nit is interesting that the focal areas of intermediate signal intensity around the calcifications showed delayed enhancement on the gadolinium - enhanced mr images .\n( 9 ) described the presence of enhancing foci between the fatty tissue and chondroid tissue in a chondrolipoma , without clarifying the histopathological findings .\nalso , there have been no reports of chondrolipomas with delayed enhancement . in our case ,\nhowever , keeping in mind that the location of these focal areas corresponded to chondroid tissue , and that chondroid tissue is usually not enhanced , even on the delayed phase , the delayed enhancement of these focal areas may be attributed due to sufficient fibrous tissue within the chondroid tissue . despite the characteristic imaging findings of chondrolipomas , fatty tumors such as lipomas or liposarcomas , which contain chondro - osseous differentiation ,\nthe treatment of choice for chondrolipomas is surgical excision ( 5 , 8 , 14 ) .\nconclusively , we experienced the only reported human case of a chondrolipoma in the pelvic cavity , and found that it had characteristic imaging features consistent with fatty tissue and calcification , as well as the areas corresponding to cartilage .", "role": "user" }, { "content": "a chondrolipoma is an extremely rare form of a benign mesenchymal tumor containing mature cartilage and fatty tissue . \n chondrolipomas may be found in almost any part of the body , particularly in the connective tissue of the breast , head and neck area , as well as in the skeletal muscle . \n however , to the best of our knowledge , chondrolipomas located in the pelvic cavity have not been reported . in this case report \n , we describe a case of a chondrolipoma in the pelvis , and show that it has its own characteristic imaging findings , which included the composition of fatty tissue and calcification in most parts , as well as some focal areas of chondroid tissue based on the ct and mr findings .", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: Densovirus Is a Mutualistic Symbiont of a Global Crop Pest (Helicoverpa armigera) and Protects against a Baculovirus and Bt Biopesticide\nContent:\nAbstract:\nMutualistic associations between symbiotic bacteria and their hosts are common within insect systems. However, viruses are often considered as pathogens even though some have been reported to be beneficial to their hosts. Herein, we report a novel densovirus, Helicoverpa armigera densovirus-1( HaDNV-1) that appears to be beneficial to its host. HaDNV-1 was found to be widespread in wild populations of H. armigera adults( >67% prevalence between 2008 and 2012). In wild larval populations, there was a clear negative interaction between HaDNV-1 and H. armigera nucleopolyhedrovirus( HaNPV), a baculovirus that is widely used as a biopesticide. Laboratory bioassays revealed that larvae hosting HaDNV-1 had significantly enhanced resistance to HaNPV( and lower viral loads), and that resistance to Bacillus thuringiensis( Bt) toxin was also higher at low doses. Laboratory assays indicated that the virus was mainly distributed in the fat body, and could be both horizontally- and vertically-transmitted, though the former occurred only at large challenge doses. Densovirus-positive individuals developed more quickly and had higher fecundity than uninfected insects. We found no evidence for a negative effect of HaDNV-1 infection on H. armigera fitness-related traits, strongly suggesting a mutualistic interaction between the cotton bollworm and its densovirus.\nIntroduction:\nThe interactions between symbiotic species and their hosts are becoming increasingly understood within insect systems[1],[2],[3]. Symbionts form diverse evolutionary relationships that influence the life history of their host, from mutualistic, by protecting them from natural enemies or increasing their host's fitness though a variety of means[1],[4],[5],[6],[7],[8], to parasitic, either by decreasing their resistance to harmful microorganisms or their tolerance to environmentally harmful factors, or by killing them directly[9],[10],[11]. There is a growing literature on the mutualistic interactions between intracellular bacterial symbionts, such as Wolbachia and their insect hosts, in which the symbionts spread through the host population by increasing the fitness of infected hosts[1],[6],[12],[13]. However, viral mutualistic symbioses have rarely been reported. This may be because, as obligate symbionts, viruses have long been considered harmful to their host and are usually isolated from cadavers killed by the virus. Moreover, until relatively recently, laboratory techniques only had the capacity to shed light on overtly pathogenic viruses, and not covert beneficial ones[14],[15],[16]. The development of molecular and sequencing technology facilitates the discovery and analysis of non-pathogenic virus species, using techniques such as suppression subtractive hybridization( SSH) and RNA-seq[17],[18]. Generally, viruses isolated from healthy individuals may be conditionally beneficial to their hosts. Recently, these ‘good viruses’ have attracted more attention, largely due to the prospect of using them in applications such as gene therapy and as tools for gene manipulation[2],[19]. As defined by Roossinck, there are few examples of viral mutualistic symbioses in insects( identified as conveying benefit to the host without any detectable fitness costs)[2]. The cotton bollworm moth, Helicoverpa armigera, is a major migratory pest of cotton and other economically-important crops throughout Asia, Africa, Europe and Australasia[20],[21],[22]. In China, the introduction of Bt-cotton in the 1990s has seen a dramatic decline in the H. armigera moth population. However, there are signs of Bt-resistance emerging[23],[24], fueling renewed interest in other forms of biological pest control, including the use of host-specific viral pesticides, derived from densoviruses[25], small RNA viruses[26] and baculoviruses[27],[28],[29],[30],[31]. Previously, we reported a novel densovirus( HaDNV-1, from the family Parvoviridae) in H. armigera moths that possesses a monosense genome that is 4926 nucleotides in length and clustered with the members of the genus Iteravirus in phylogenetic analysis[32]. This has allowed further investigation into the interactions between HaDNV-1 and its host H. armigera, which we report here. The main objective of this study was to establish the ecological significance of this virus within the migratory H. armigera system. Specifically, we undertook experiments to determine the transmission strategies of HaDNV-1, the impact of HaDNV-1 infection on host fitness, including its capacity to modulate resistance to potentially lethal biopesticides, and the prevalence of HaDNV-1 in field populations of H. armigera. Our results show that HaDNV-1 can be both horizontally- and vertically-transmitted in H. armigera; that HaDNV-1 infection increases host-fitness by increasing larval/pupal development rate, female lifespan and egg/offspring production; and that it also enhances larval resistance to H. armigera nucleopolyhedrovirus( HaNPV), a widely-used biopesticide. Resistance to Bt Cry1Ac protoxin was also enhanced, but only at relatively low toxin concentrations. Overall, we found no evidence for a negative effect of densovirus infection on H. armigera fitness-related traits, strongly suggesting a mutualistic interaction between the cotton bollworm and HaDNV-1.\nDiscussion:\nIn conclusion, our studies to date suggest a mutualistic relationship between the cotton bollworm and HaDNV-1, in which the cotton bollworm appears to benefit from HaDNV-1 infection, with all host fitness parameters so far tested( larval growth rate, larval and pupal development rate, fertility, adult female lifespan, and resistance to baculovirus and low doses of Bt toxin) enhanced at no detectable cost. The study of beneficial viruses in both vertebrate and invertebrate systems has only relatively recently attracted researchers' attention[2], predominantly due to the explosion of new technologies that now make the detection of such organisms possible. It should be noted that the coevolution between viral mutualistic symbionts and their hosts could be an important factor to consider when studying the adaptability of insect host species. Illuminating the function of such viral symbionts may offer novel insights for future pest management strategies.", "role": "user" }, { "content": "The old world cotton bollworm , Helicoverpa armigera , is one of the most significant pests of crops throughout Asia , Europe , Africa and Australia . Herein , we report a novel densovirus ( HaDNV-1 ) which was widely distributed in wild populations of H . armigera and was beneficial to its host by increasing larval and pupal development rates , female lifespan and fecundity , suggesting a mutualistic interaction between the cotton bollworm and HaDNV-1 . The cotton bollworm is currently widely controlled by the biopesticides Bacillus thuringiensis ( Bt ) toxin and the baculovirus HaNPV . It is therefore important to estimate the risk that the symbiotic virus will negatively impact on the efficiency of these biopesticides . Field and laboratory results suggest that HaDNV-1 infection significantly increases larval resistance to HaNPV and Bt toxin . These results have important implications for the selection of biopesticides for this species , and highlight the need for greater research into the elegant microbial interactions that may impact host individual and population dynamics .", "role": "assistant" } ]

[ { "content": "Given the full text of a scientific research paper, write an abstract section for the paper. Your response should contain only the abstract without any other text.\n\nArticle text:\nwhen photometric properties of star clusters are compared to the predictions of population synthesis models , it is common to find that the scatter among the observed colors and the difference between these colors and the model predictions , are larger than allowed by the observational errors .\nthis is particularly true for intermediate age clusters in optical - ir colors , like @xmath0 , but to a lesser extent the scatter is also large in @xmath1 .\nfig 1 illustrates this point . in a recent paper , maraston et al .\n( 2001 ) show that the population synthesis models of maraston ( 1998 ) reproduce quite well the @xmath0 colors of the cluster population observed in ngc 7252 at an age between 400 and 600 myr . in these models , built on the fuel consumption theorem ( renzini & buzzoni 1986 )\n, the contribution of agb stars to the bolometric light in the synthetic population has been increased over that expected from stellar evolution theory , in such a way as to reproduce the empirical values determined by frogel et al .\n( 1990 ) for a sample of lmc clusters as a function of swb class . even though this is a valid procedure , in this paper\ni show that the optical and optical - ir colors of the intermediate age clusters of the lmc and ngc 7252 are consistent with the colors expected from models ( bruzual & charlot 2001 ; bruzual 2000 , 2001 ) based on current stellar evolution theory , if stochastic fluctuations in the number of stars in sparsely populated evolutionary stages are properly included into the models . in\nwhat follows i use the montecarlo technique pioneered by barbaro & bertelli ( 1977 ) , chiosi et al .\n( 1988 ) , girardi et al .\n( 1995 ) , santos & frogel ( 1997 ) , and cervio , luridiana & castander ( 2000 ) , to study the role that stochastic effects on the initial mass function ( imf ) have on star cluster colors .\ni follow the santos & frogel ( 1997 ) approach to study the lmc and ngc 7252 cluster samples .\nthe derivation below follows closely santos & frogel ( 1997 ) .\nthe imf @xmath2 normalized as usual , @xmath3 obeys , @xmath4 , and @xmath5 @xmath6 can be interpreted as a probability distribution function which gives the probability that a random mass @xmath7 is in the range between @xmath8 and @xmath9 .\n@xmath6 can be transformed into another probability distribution function @xmath10 , such that the probability of occurrence of the random variable @xmath11 within @xmath12 and the probability of occurrence of the random variable @xmath7 within @xmath13 is the same , @xmath14 where @xmath15 is a single - valued function of @xmath8 . from ( 1 )\n, @xmath16 is a cumulative distribution function which gives the probability that the mass @xmath7 is less or equal to @xmath8 , and using ( 4 ) , it follows that @xmath17 @xmath10 is thus a uniform distribution for which any value is equally likely in the interval @xmath18 . if we sample @xmath15 using a random number generator ( press et al .\n1992 ) , from ( 5 ) we can obtain @xmath8 as a function of @xmath15 , @xmath19^{- { 1 \\over x } } .\\ ] ] for each star of mass @xmath8 generated in this way , we obtain its observational properties from the log @xmath20 and log @xmath21 corresponding to this mass in the isochrone at the age of interest .\nwe repeat the procedure until the cluster mass , i.e. the sum of @xmath8 for all the stars generated , including dead stars , reaches the desired value . adding the contribution of each star to the flux in different photometric bands , we obtain the cluster magnitude and colors in these bands . throughout this paper\ni use @xmath22 ( salpeter 1955 ) , and for the lower and upper mass limits of star formation , i assume @xmath23 and @xmath24 m@xmath25 , respectively .\nfigs 2 to 6 show the results of the montecarlo simulations . for reasons of space\nthe details of each figure given in the caption are not repeated in the text . from figs 2 and 3\nit is apparent that the fluctuations in the colors become larger as the cluster mass decreases .\nthe number of stars in the @xmath26 m@xmath25 cluster may be unrealistically small , and some evolutionary stages are not sampled .\nthere are not enough high mass ms stars in the @xmath26 m@xmath25 and @xmath27 m@xmath25 clusters to make them as blue in @xmath28 at early ages as the model computed with the analytical imf ( equivalent to infinite number of stars ) . in the @xmath29 m@xmath25 case the upper ms\nis well sampled and both models are equally blue in @xmath28 .\nfig 3 shows that the lower mass cluster models at early ages are bluer in @xmath0 than the analytic model because the lower ms is over populated with respect to the short lived phases with redden this color . for the @xmath29 m@xmath25 cluster\nthe agreement is good at early ages .\nthe expected fluctuations in @xmath0 for a @xmath27 m@xmath25 cluster amount to almost 2 magnitudes , in close agreement with the range of colors observed at a given age , and is considerably broader than for the @xmath27 m@xmath25 case .\nfig 4 shows an enlargement of the diagrams for the @xmath27 m@xmath25 star cluster . at the intermediate ages the models are redder in @xmath0 than the analytic imf model because of a larger number of agb stars , which appear naturally as a consequence of stochastic fluctuations in the imf .\nthe regions in these planes occupied by the observations and the cluster simulations overlap quite well .\nthis comparison seems to favor a not very large mass for these clusters , if stochastic fluctuations are responsible of the color variations .\nthis conclusion is supported by fig 5 in which i plot @xmath30 vs @xmath0 at the distance of the lmc .\nthe region covered by the @xmath27 m@xmath25 clusters matches the region covered by the observations very well .\nthis is not the case for the @xmath29 m@xmath25 clusters , which show a much lower dispersion in color for the same @xmath30 magnitude than the observations and the lower mass simulations .\neven though the montecarlo technique used in this paper has been used successfully before to explain cluster colors , i have revisited it in this paper to show that there is no need to introduce ad - hoc assumptions into population synthesis models ( maraston 1998 , maraston et a. 2001 ) , which represent a departure from our current understanding of stellar evolution theory , in order to explain the observed range of values of cluster colors and magnitudes . in this paper\ni have briefly summarized the results of simple simulations which show clearly how the range of colors observed in intermediate age star clusters can be understood on the basis of current stellar evolution theory , if we take into account properly the expected variation in the number of stars occupying sparsely populated evolutionary stages due to stochastic fluctuations in the imf . our preliminary conclusion that cluster masses in the range around @xmath27 m@xmath25 are preferred , as well as the dependence on this mass of the fluctuations in magnitude and colors will be explored in detail by bruzual & charlot ( 2001 ) .\nthe interested reader may request results for other quantities equally sensitive to stochastic fluctuations , like the number of ionizing photons from a young stellar population , not shown here for lack of space ( see also cervio , luridiana & castander 2000 ) .\nbarbaro , g. & bertelli , g. 1977 , a&a , 54,243 bruzual a. , g. 2000 , in proceedings of the xi canary islands winter school of astrophysics on `` galaxies at high redshift '' , eds . i. prez - fournon and f. snchez , cambridge contemporary astrophysics , in press , ( bc2000 , astro - ph/0011094 )", "role": "user" }, { "content": "in this paper i combine the results of a set of population synthesis models with simple montecarlo simulations of stochastic effects in the number of stars occupying sparsely populated stellar evolutionary phases , to show that the scatter observed in the magnitudes and colors of lmc and ngc 7252 star clusters can be understood in the framework of current stellar evolution theory , without the need to introduce ad - hoc corrections ( e.g. artificially increasing the number of agb stars ) . # 1_#1 _ # 1_#1 _ = # 1 1.25 in .125 in .25 in", "role": "assistant" } ]

[ { "content": "Analyze the given research paper excerpts and address the question provided. Extract the necessary information directly from the text. Your answer should be formatted as a JSON object with the following structure:\n\n\"answer\": A list of text segments from the paper that directly respond to the question.\n\"evidence\": A list of text segments from the paper where the answer can be found.\n\nIf the question cannot be answered with the given text, return \"null\".\n\nDocument: Global Greedy Dependency Parsing\n\nMost syntactic dependency parsing models may fall into one of two categories: transition- and graph-based models. The former models enjoy high inference efficiency with linear time complexity, but they rely on the stacking or re-ranking of partially-built parse trees to build a complete parse tree and are stuck with slower training for the necessity of dynamic oracle training. The latter, graph-based models, may boast better performance but are unfortunately marred by polynomial time inference. In this paper, we propose a novel parsing order objective, resulting in a novel dependency parsing model capable of both global (in sentence scope) feature extraction as in graph models and linear time inference as in transitional models. The proposed global greedy parser only uses two arc-building actions, left and right arcs, for projective parsing. When equipped with two extra non-projective arc-building actions, the proposed parser may also smoothly support non-projective parsing. Using multiple benchmark treebanks, including the Penn Treebank (PTB), the CoNLL-X treebanks, and the Universal Dependency Treebanks, we evaluate our parser and demonstrate that the proposed novel parser achieves good performance with faster training and decoding.\n\nThe General Greedy Parsing\nThe global greedy parser will build its dependency trees in a stepwise manner without backtracking, which takes a general greedy decoding algorithm as in easy-first parsers.\nUsing easy-first parsing's notation, we describe the decoding in our global greedy parsing. As both easy-first and global greedy parsing rely on a series of deterministic parsing actions in a general parsing order (unlike the fixed left-to-right order of standard transitional parsers), they need a specific data structure which consists of a list of unattached nodes (including their partial structures) referred to as “pending\". At each step, the parser chooses a specific action $\\hat{a}$ on position $i$ with the given arc score score($\\cdot $), which is generated by an arc scorer in the parser. Given an intermediate state of parsing with pending $P=\\lbrace p_0, p_1, p_2, \\cdots , p_N\\rbrace $, the attachment action is determined as follows:\nwhere $\\mathcal {A}$ denotes the set of the allowed actions, and $i$ is the index of the node in pending. In addition to distinguishing the correct attachments from the incorrect ones, the arc scorer also assigns the highest scores to the easiest attachment decisions and lower scores to the harder decisions, thus determining the parsing order of an input sentence.\nFor projective parsing, there are exactly two types of actions in the allowed action set: ATTACHLEFT($i$) and ATTACHRIGHT($i$). Let $p_i$ refer to $i$-th element in pending, then the allowed actions can be formally defined as follows:\n$\\bullet $ ATTACHLEFT($i$): attaches $p_{i+1}$ to $p_i$ , which results in an arc ($p_i$, $p_{i+1}$) headed by $p_i$, and removes $p_{i+1}$ from pending.\n$\\bullet $ ATTACHRIGHT($i$): attaches $p_i$ to $p_{i+1}$ , which results in an arc ($p_{i+1}$, $p_i$) headed by $p_{i+1}$, and removes $p_i$ from pending.\n\nGlobal Greedy Parsing Model\nOur proposed global greedy model contains three components: (1) an encoder that processes the input sentence and maps it into hidden states that lie in a low dimensional vector space $h_i$ and feeds it into a specific representation layer to strip away irrelevant information, (2) a modified scorer with a parsing order objective, and (3) a greedy inference module that generates the dependency tree.\n\nGlobal Greedy Parsing Model ::: Training Objectives\nTo parse the syntax tree $y$ for a sentence $x$ with length $l$, the easy-first model relies on an action-by-action process performed on pending. In the training stage, the loss is accumulated once per step (action), and the model is updated by gradient backpropagation according to a preset frequency. This prohibits parallelism during model training lack between and within sentences. Therefore, the traditional easy-first model was trained to maximize following probability:\nwhere $\\emph {pending}_i$ is the pending list state at step $i$.\nWhile for our proposed model, it uses the training method similar to that of graph-based models, in which the arc scores are all obtained in one-shot. Consequently, it does not rely on the pending list in the training phase and only uses the pending list to promote the process of linear parsing in the inference stage. Our model is trained to optimize the probability of the dependency tree $y$ when given a sentence $x$: $P_\\theta (y|x)$, which can be factorized as:\nwhere $\\theta $ represents learnable parameters, $l$ denotes the length of the processing sentence, and $y^{arc}_i$, $y^{rel}_i$ denote the highest-scoring head and dependency relation for node $x_i$. Thus, our model factors the distribution according to a bottom-up tree structure.\nCorresponding to multiple objectives, several parts compose the loss of our model. The overall training loss is the sum of three objectives:\nwhere the loss for arc prediction $\\mathcal {L}^{arc}$ is the negative log-likelihood loss of the golden structure $y^{arc}$:\nthe loss for relation prediction $\\mathcal {L}^{rel}$ is implemented as the negative log-likelihood loss of the golden relation $y^{rel}$ with the golden structure $y^{arc}$,\nand the loss for parsing order prediction $\\mathcal {L}^{order}$:\nBecause the parsing order score of each layer in the tree increases by 1, we frame it as a classification problem and therefore add a multi-class classifier module as the order scorer.\n\nGlobal Greedy Parsing Model ::: Non-Projective Inference\nFor non-projective inference, we introduce two additional arc-building actions as follows.\n$\\bullet $ NP-ATTACHLEFT($i$): attaches $p_{j}$ to $p_i$ where $j > i$, which builds an arc ($p_i$, $p_{j}$) headed by $p_i$, and removes $p_{j}$ from pending.\n$\\bullet $ NP-ATTACHRIGHT($i$): attaches $p_{j}$ to $p_i$ where $j < i$ which builds an arc ($p_i$, $p_j$) headed by $p_i$, and removes $p_j$ from pending.\nIf we use the two arc-building actions for non-projective dependency trees directly on $s_{final}$, the time complexity will become $O(n^3)$, so we need to modify this algorithm to accommodate the non-projective dependency trees. Specifically, we no longer use $s_{final}$ directly for greedy search but instead divide each decision into two steps. The first step is to use the order score $s_{order}$ to sort the pending list in descending order. Then, the second step is to find the edge with the largest arc score $s_{arc}$ for this node in the first position of the pending list.\n\nExperiments\nWe evaluate our parsing model on the English Penn Treebank (PTB), the Chinese Penn Treebank (CTB), treebanks from two CoNLL shared tasks and the Universal Dependency (UD) Treebanks, using unlabeled attachment scores (UAS) and labeled attachment scores (LAS) as the metrics. Punctuation is ignored as in previous work BIBREF18. For English and Chinese, we use the projective inference, while for other languages, we use the non-projective one.\n\nExperiments ::: Treebanks\nFor English, we use the Stanford Dependency (SD 3.3.0) BIBREF37 conversion of the Penn Treebank BIBREF38, and follow the standard splitting convention for PTB, using sections 2-21 for training, section 22 as a development set and section 23 as a test set. We use the Stanford POS tagger BIBREF39 generate predicted POS tags.\nFor Chinese, we adopt the splitting convention for CTB BIBREF40 described in BIBREF19. The dependencies are converted with the Penn2Malt converter. Gold segmentation and POS tags are used as in previous work BIBREF19.\nFor the CoNLL Treebanks, we use the English treebank from the CoNLL-2008 shared task BIBREF41 and all 13 treebanks from the CoNLL-X shared task BIBREF42. The experimental settings are the same as BIBREF43.\nFor UD Treebanks, following the selection of BIBREF23, we take 12 treebanks from UD version 2.1 (Nivre et al. 2017): Bulgarian (bg), Catalan (ca), Czech (cs), Dutch (nl), English (en), French (fr), German (de), Italian (it), Norwegian (no), Romanian (ro), Russian (ru) and Spanish (es). We adopt the standard training/dev/test splits and use the universal POS tags provided in each treebank for all the languages.\n\nExperiments ::: Implementation Details ::: Hyperparameters\nThe character embeddings are 8-dimensional and randomly initialized. In the character CNN, the convolutions have a window size of 3 and consist of 50 filters. We use 3 stacked bidirectional LSTMs with 512-dimensional hidden states each. The outputs of the BiLSTM employ a 512-dimensional MLP layer for the arc scorer, a 128-dimensional MLP layer for the relation scorer, and a 128-dimensional MLP layer for the parsing order scorer, with all using ReLU as the activation function. Additionally, for parsing the order score, since considering it a classification problem over parse tree layers, we set its range to $[0, 1, ..., 32]$.\n\nExperiments ::: Main Results\nWe now compare our model with several other recently proposed parsers as shown in Table TABREF9. Our global greedy parser significantly outperforms the easy-first parser in BIBREF14 (HT-LSTM) on both PTB and CTB. Compared with other graph- and transition-based parsers, our model is also competitive with the state-of-the-art on PTB when considering the UAS metric. Compared to state-of-the-art parsers in transition and graph types, BIAF and STACKPTR, respectively, our model gives better or comparable results but with much faster training and decoding. Additionally, with the help of pre-trained language models, ELMo or BERT, our model can achieve even greater results.\nIn order to explore the impact of the parsing order objective on the parsing performance, we replace the greedy inference with the traditional MST parsing algorithm (i.e., BIAF + parsing order objective), and the result is shown as “This work (MST)\", giving slight performance improvement compared to the greedy inference, which shows globally optimized decoding of graph model still takes its advantage. Besides, compared to the standard training objective for graph model based parser, the performance improvement is slight but still shows the proposed parsing order objective is indeed helpful.\n\nExperiments ::: CoNLL Results\nTable TABREF11 presents the results on 14 treebanks from the CoNLL shared tasks. Our model yields the best results on both UAS and LAS metrics of all languages except the Japanese. As for Japanese, our model gives unsatisfactory results because the original treebank was written in Roman phonetic characters instead of hiragana, which is used by both common Japanese writing and our pre-trained embeddings. Despite this, our model overall still gives 1.0% higher average UAS and LAS than the previous best parser, BIAF.\n\nExperiments ::: UD Results\nFollowing BIBREF23, we report results on the test sets of 12 different languages from the UD treebanks along with the current state-of-the-art: BIAF and STACKPTR. Although both BIAF and STACKPTR parsers have achieved relatively high parsing accuracies on the 12 languages and have all UAS higher than 90%, our model achieves state-of-the-art results in all languages for both UAS and LAS. Overall, our model reports more than 1.0% higher average UAS than STACKPTR and 0.3% higher than BIAF.\n\nConclusion\nThis paper presents a new global greedy parser in which we enable greedy parsing inference compatible with the global arc scoring of graph-based parsing models instead of the local feature scoring of transitional parsing models. The proposed parser can perform projective parsing when only using two arc-building actions, and it also supports non-projective parsing when introducing two extra non-projective arc-building actions. Compared to graph-based and transition-based parsers, our parser achieves a better tradeoff between parsing accuracy and efficiency by taking advantages of both graph-based models' training methods and transition-based models' linear time decoding strategies. Experimental results on 28 treebanks show the effectiveness of our parser by achieving good performance on 27 treebanks, including the PTB and CTB benchmarks.\n\nFigure 1: A fully built dependency tree for “The test may come today.” including part-of-speech (POS) tags and root token.\n\nFigure 2: Overview for our global greedy parser.\n\nTable 1: Comparison of results on the test sets. “T”, “G” and “E” indicate transition-based, graph-based and easy-first models, respectively. The “G + E” represents the graph-based training while the easy-first algorithm is used for inference. Acronyms used: (g) – greedy, (b) – beam search, (re) – re-ranking, (3rd) – 3rd-order, (1st) – 1st-order. The “*” in the upper right corner of the results is because the original ELMo (Peters et al. 2018) has no Chinese version. We instead used the multilingual version “HIT-ELMo” pre-trained by (Che et al. 2018).\n\nTable 2: UAS and LAS on 14 treebanks from CoNLL shared tasks, together with several state-of-the-art parsers. Bi-Att is the bi-directional attention based parser (Cheng et al. 2016), and NeuroMST is the neural MST parser (Ma and Hovy 2017). “Best Published” includes the best results in recent years among (Koo et al. 2010), (Martins et al. 2011), (Martins, Almeida, and Smith 2013), (Lei et al. 2014), (Zhang et al. 2014), (Zhang and McDonald 2014), (Pitler and McDonald 2015), and (Cheng et al. 2016) in addition to the ones we listed above.\n\nTable 4: Training time and decoding speed. The experimental environment is on the same machine with Intel i9 9900k CPU and NVIDIA 1080Ti GPU.\n\nTable 3: UAS and LAS on test datasets of 12 treebanks from UD Treebanks, together with BIAF and STACKPTR for comparison.\n\nInquiry: What are performance compared to former models?", "role": "user" }, { "content": "{\"answer\": [\"model overall still gives 1.0% higher average UAS and LAS than the previous best parser, BIAF\", \"our model reports more than 1.0% higher average UAS than STACKPTR and 0.3% higher than BIAF\"], \"evidence\": [\"Table TABREF11 presents the results on 14 treebanks from the CoNLL shared tasks. Our model yields the best results on both UAS and LAS metrics of all languages except the Japanese. As for Japanese, our model gives unsatisfactory results because the original treebank was written in Roman phonetic characters instead of hiragana, which is used by both common Japanese writing and our pre-trained embeddings. Despite this, our model overall still gives 1.0% higher average UAS and LAS than the previous best parser, BIAF.\", \"Following BIBREF23, we report results on the test sets of 12 different languages from the UD treebanks along with the current state-of-the-art: BIAF and STACKPTR. Although both BIAF and STACKPTR parsers have achieved relatively high parsing accuracies on the 12 languages and have all UAS higher than 90%, our model achieves state-of-the-art results in all languages for both UAS and LAS. Overall, our model reports more than 1.0% higher average UAS than STACKPTR and 0.3% higher than BIAF.\"]}", "role": "assistant" } ]

[ { "content": "Transform the provided sections of a biomedical research paper into a digestible summary for a general audience. Focus on simplifying complex ideas while retaining key scientific insights.\n\nResearch Title: A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis\nContent Overview:\nAbstract:\nPrevious works suggested that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor. We did a pilot clinical investigation, including a nonrandomized( 57 patients with large HCC) and a randomized controlled( 20 patients with large HCC) study. The patients were treated with transarterial chemoembolization( TACE) with or without bicarbonate local infusion into tumor. In the nonrandomized controlled study, geometric mean of viable tumor residues( VTR) in TACE with bicarbonate was 6. 4-fold lower than that in TACE without bicarbonate( 7. 1%[95% CI: 4. 6%–10. 9%] vs 45. 6%[28. 9%–72. 0%]; p<0. 0001). This difference was recapitulated by a subsequent randomized controlled study. TACE combined with bicarbonate yielded a 100% objective response rate( ORR), whereas the ORR treated with TACE alone was 44. 4%( nonrandomized) and 63. 6%( randomized). The survival data suggested that bicarbonate may bring survival benefit. Bicarbonate markedly enhances the anticancer activity of TACE. Funded by National Natural Science Foundation of China. ChiCTR-IOR-14005319.\nIntroduction:\nWe recently found that Lactic acidosis could effectively protect cancer cells against glucose starvation or deprivaiton( Wu et al., 2012; Xie et al., 2014). First, lactic acidosis dramatically reduces glycolysis rate with little wasting glucose to lactate, as such, a limited amount of glucose could support cancer cells for a relatively long time otherwise would be exhausted quickly. Second, when glucose was deprived, lactic acidosis transformed cancer cells to a ‘dormant’ state, via arresting cells at G0/G1 phase, initiating autophagy, inhibiting apoptosis, etc. The protective function relies on co-presence of lactate and proton, depriving either of which would abolish the function( Wu et al., 2012; Xie et al., 2014). When converting lactic acidosis to lactosis by a base, the protective function is gone; similarly, removing lactate, acidosis conferred cancer cells with little resistance to glucose deprivation. The significance of intratumoral lactic acidosis in tumor biology has been extensively revealed by many other investigators. Clinical studies showed that high level of lactate was a strong prognostic indicator of increased metastasis and poor overall survival( Gatenby and Gillies, 2004; Brizel et al., 2001; Walenta et al., 2000; Schwickert et al., 1995; Walenta et al., 1997; Yokota et al., 2007; Paschen et al., 1987). The work of Gillies and Gatenby group demonstrated that systematic and tumor pHe alkalization could inhibit carcinogenesis, tumor invasion and metastasis, and they also provided integrated models that can predict the safety and efficacy of buffer therapy to raise tumour pHe( Silva et al., 2009; Robey et al., 2009; Ibrahim-Hashim et al., 2012) and related theoretical work( Martin et al., 2012, Martin et al., 2011). Furthermore, many studies reported that lactic acidosis played multifaceted roles in skewing macrophages( Colegio et al., 2014) and inhibiting the function of cytotoxic T cells( Haas et al., 2015), altering cancer cell metabolism( Chen et al., 2008; Sonveaux et al., 2008), inducing chromosomal instability( Dai et al., 2013), and promoting tumor angiogenesis( Gatenby and Gillies, 2004; Végran et al., 2011). According to the guideline of Barcelona Clinic Liver Cancer( BCLC) staging and treatment strategy, HCC larger than 3 cm in diameter is not suitable for curative therapy( surgical resection, liver transplantation, and ablation) and the recommended treatment is TACE( Forner et al., 2012; El-Serag, 2011; Knox et al., 2015). But sadly, it is recognized that TACE is not effective to treat large tumors( Sieghart et al., 2015). This leaves the patients with large HCC without choice of effective therapy, as also pointed out by Sieghart et al, “maximal restriction of patients selection for TACE would otherwise only improve the results of the treatment modality per se but again would leave those more advanced patients within the intermediate stage without treatment options. ”( Sieghart et al., 2015) TACE is for local control of the targeted tumor. TEX equation checkTACE kills HCC via 2 mechanisms, delivering concentrated anticancer drugs locally into tumor and occluding tumor feeding arteries to deprive nutrients to starve cancer cells. We would focus on the second mechanism. Occluding tumor feeding arteries effectively deprive nutrients including glucose. The problem is that embolization-created hypoxia condition would stimulate cancer cells to emit strong signals to initiate angiogenesis( Knox et al., 2015) to reestablish tumor vasculature to bypass the occluded tumor feeding arteries. If the tumor cells cannot be rapidly eliminated, tumor vasculature would be re-established, and a certain amount of tumor( ranging from a few percent of the original tumor to even a larger tumor known as progressive disease) would survive and thrive. The lactate concentrations in HCC biopsies were around 20 mM( unpublished data), suggesting a lactic acidosis condition. After TACE, lactic acidosis would be trapped in embolized tumor and it would potentially attenuate the therapeutic efficacy of TACE. If it were true, locally infusion of bicarbonate to neutralize it would result in a severer necrosis in the embolized area.\nDiscussion:\nIn this clinical investigation, we carried out 2 studies sequentially, the first one is a nonrandomized controlled study, which demonstrated a remarkable therapeutic improvement of TILA-TACE, based on which, a randomized controlled study was designed and carried out, and again it demonstrated a superior anticancer activity of TILA-TACE. The most striking point is that the numbers reflecting the therapeutic improvements by TILA-TACE from the 2 studies were nearly identical( 81. 1% and 80. 1%). This confirms the consistency of anticancer activities of cTACE as well as TILA-TACE with respect to local control of large HCC. We compared the ORR in our cTACE practice with those reported globally. The average objective tumor response to TACE is 35%( range, 16%–61%), as systematically reviewed by LIovet and Bruix for the Barcelona-Clinic Liver Cancer Group in 2002( Llovet and Bruix, 2003). In 2012, Forner, LIovet, and Bruix summarized that more than 50% of patients had an objective response to TACE( Forner et al., 2012), suggesting that the objective tumor response to TACE in the 10-year period( 2002–2012) had been increased for about 15%. The complete tumor response to TACE is rare( 0-4. 8%)( Jansen et al., 2005). Obviously, the results obtained from our cTACE practice were similar to those reported globally. TACE is for local control of the targeted tumor. Many previous studies have confirmed that better local control was an independent prognostic indicator for patient survival( Kim et al., 2015; Jung et al., 2013; Kim et al., 2013; Shim et al., 2012; Riaz et al., 2011; Gillmore et al., 2011; Riaz et al., 2010). Kim et al and Shim et al( Kim et al., 2015; Shim et al., 2012) further demonstrated a clear prognostic difference between CR, PR, stable disease and progressive disease. The current study demonstrated that TILA-TACE achieved a remarkable improvement of local tumor control and suggested an early sign of improved survival for patients with large HCCs( Figure 5A). It is noted that, during follow up, 16 patients in the TILA-TACE arm( Figure 5A), eventually exhibited progressive disease, including 11 patients with new foci in the liver, 1 with new liver foci and lung metastasis, and 3 with lung metastasis, and 1 with bone metastasis, all of which may account for the death( Supplementary file 2). These observations suggest that fast CR and timely control of recurrent tumors in the liver would likely improve the survival of patients, especially those with large tumor burden and low liver reserve. Nevertheless, the work is limited by the study design. The randomized controlled study designed in this investigation was for local tumor control, not for survival. Although the small sample size allowed us to evaluate the local tumor control, we did not expect that such small sample size would yield statistically significant data for cumulative survival. Evaluation of survival is a matter much more complicated than evaluation of local control. There are many more factors affecting the survival of patients than those affecting the local tumor control, e. g., tumor characteristics, liver function reserve, tumor staging, disease complications, vascular invasion, metastasis, etc., all of which must be well controlled. While we acknowledged these limitations of the present small RCT, the preliminary survival data allowed us to rationally calculate the sample size for a subsequent large RCT for evaluating the survival difference between cTACE and TILA-TACE. We are planning a large-scale RCT to further confirm the therapeutic advantage of TILA-TACE with respect to overall and progression-free survival of patients with large HCCs. There was no significant difference of adverse effect between TILA-TACE and cTACE( Tables 3 and 4), i. e., TILA-TACE was as tolerable as cATCE. It was within our expectation, as locally administration of bicarbonate into tumor is safe. Taken together, this pilot study demonstrated that bicarbonate infusion locally into HCC can markedly enhance anticancer activity of TACE, supporting the notion that neutralizing intratumoral lactic acidosis combined with glucose deprivation may deliver an effective approach to control tumor.", "role": "user" }, { "content": "Surgery is the main treatment for liver cancer , but the most common liver cancer – called hepatocellular carcinoma – can sometimes become too large to remove safely . An alternative option to kill the tumor is to block its blood supply via a process called embolization . This procedure deprives the tumor cells of oxygen and nutrients such as glucose . However , embolization also prevents a chemical called lactic acid – which is commonly found around tumors – from being removed . Lactic acid actually helps to protect cancer cells and also aids the growth of new blood vessels , and so the “trapped” lactic acid may reduce the anticancer activity of embolization . Previous works suggested that neutralizing the acidic environment in a tumor while depriving it of glucose via embolization could become a new treatment option for cancer patients . Chao et al . now report a small clinical trial that tested this idea and involved patients with large hepatocellular carcinomas . First , a group of thirty patients received the embolization treatment together with an injection of bicarbonate – a basic compound used to neutralize the lactic acid – that was delivered directly to the tumor . The neutralization killed these large tumors more effectively than what is typically seen in patients who just undergo embolization Chao et al . then recruited another twenty patients and randomly assigned them to receive either just the embolization or the embolization with bicarbonate treatment . This randomized trial showed that the tumors died more and patients survived for longer if they received the bicarbonate together with the embolization treatment compared to those patients that were only embolized . In fact , four patients initially assigned to , and treated in , the embolization-only group subsequently asked to cross over to , and indeed received , the bicarbonate treatment as well . These data indicate that this bicarbonate therapy may indeed be effective for patients with large tumors that are not amenable to surgery . In future , larger clinical trials will need to be carried out to verify these initial findings .", "role": "assistant" } ]

[ { "content": "Read the provided biomedical research paper and create a concise abstract. Ensure the abstract captures the main points of the paper.\n\nFull Paper:\nthe terms phase iii and multiple sclerosis were used for a pubmed search with no time restriction in march 2014 .\nstudies were eligible for inclusion if they ( 1 ) were phase iii trials of dmds in pwrms and ( 2 ) reported the rate of neoplasms and cancers observed .\nconference abstracts were excluded as were studies investigating only an acute dose effect or follow - up studies of previously published phase iii trials .\nthe proportion of pwrms who developed cancer was extracted from each study . in trials where multiple doses were tested ,\ngiven the relatively short and very similar duration of analyzed studies , the proportion of pwrms in whom cancer occurred was used as an estimate of the rate of cancer .\nthe cancer rate in the treatment group of clarity was first compared to the combined cancer rate of all treatment groups of placebo - controlled phase iii trials of other dmds .\nthe cancer rate in the placebo group of clarity was then compared to the combined cancer rate of the placebo groups of all other phase iii trials .\nstudy heterogeneity was calculated using test and publication bias was assessed using a funnel plot .\nstatistical analysis was performed using graphpad prism , revman , and stata 13.1 ( statacorp , college station , tx ) .\nanalysis was similarly done using the cancer rates reported in a recently completed phase iii trial on the effect of oral cladribine on time to conversion to clinically definite ms in patients with a first demyelinating event ( oracle ms ) .\nfurthermore , meta - analysis pooling using a random - effects model was performed based on risk difference to assess any excess risk from cladribine .\nrisk difference was selected as a measure rather than the more commonly used measures of relative risk or relative odds because when incidence rates are low and the comparator arm has zero cases ( as in clarity ) , these latter measures are not reliably estimated .\nthe terms phase iii and multiple sclerosis were used for a pubmed search with no time restriction in march 2014 .\nstudies were eligible for inclusion if they ( 1 ) were phase iii trials of dmds in pwrms and ( 2 ) reported the rate of neoplasms and cancers observed .\nconference abstracts were excluded as were studies investigating only an acute dose effect or follow - up studies of previously published phase iii trials .\nthe proportion of pwrms who developed cancer was extracted from each study . in trials where multiple doses were tested ,\ngiven the relatively short and very similar duration of analyzed studies , the proportion of pwrms in whom cancer occurred was used as an estimate of the rate of cancer .\nthe cancer rate in the treatment group of clarity was first compared to the combined cancer rate of all treatment groups of placebo - controlled phase iii trials of other dmds .\nthe cancer rate in the placebo group of clarity was then compared to the combined cancer rate of the placebo groups of all other phase iii trials .\nstudy heterogeneity was calculated using test and publication bias was assessed using a funnel plot .\nstatistical analysis was performed using graphpad prism , revman , and stata 13.1 ( statacorp , college station , tx ) .\nanalysis was similarly done using the cancer rates reported in a recently completed phase iii trial on the effect of oral cladribine on time to conversion to clinically definite ms in patients with a first demyelinating event ( oracle ms ) .\nfurthermore , meta - analysis pooling using a random - effects model was performed based on risk difference to assess any excess risk from cladribine .\nrisk difference was selected as a measure rather than the more commonly used measures of relative risk or relative odds because when incidence rates are low and the comparator arm has zero cases ( as in clarity ) , these latter measures are not reliably estimated .\nincluding clarity , a total of 11 phase iii trials in pwrms were eligible for inclusion in the analysis .\ndmds investigated in these studies were cladribine , dimethyl fumarate , fingolimod , teriflunomide , natalizumab , alemtuzumab , and glatiramer acetate .\nthe combirx trial ( interferon [ ifn]--1a plus glatiramer acetate ) was excluded because malignant and nonmalignant neoplasms were not reported separately .\nseven of the included studies compared dmd with placebo ; 4 compared dmd with ifn--1a .\none trial compared natalizumab as an add - on to ifn--1a with placebo added to ifn--1a .\nstudy characteristics , references , and annualized cancer rate of dmds included in the analysis are provided in table e-1 at neurology.org/nn .\nthe cancer rate in the clarity treatment group was 0.34% and thus not different from all other treatment groups of placebo - controlled trials ( 0.6% , p = 0.4631 ) . among these treatment groups ,\nthe cancer rate in clarity was the third lowest observed ( figure 1 ) . among placebo groups ,\nthe cancer rate of zero in clarity was the lowest observed and significantly lower than the combined cancer rate of all other placebo groups ( 1.19% , p = 0.0159 ; figure 2 ) .\nforest plot of malignancy rates in treatment groups from phase iii trials with a placebo group .\nforest plot of malignancy rates in placebo groups of phase iii trials . comparing all trials ( i.e.\n, placebo - controlled and active comparator ifn--1a controlled ) , no difference was detected in the cancer rate of clarity treatment arms vs all other trial arms ( 0.67% , p = 0.3669 ; figure 3 ) . no difference in cancer rate\nwas detected between treatment arms of clarity and oracle ms ( 0.34% vs 0.49% , p = 0.6546 ) ; both trials used identical doses of cladribine .\ncomparison of the total neoplasm rate ( including both malignant and nonmalignant neoplasms ) in clarity treatment arms ( 1.13% ) vs oracle ms treatment groups ( 0.98% ) did not reveal any difference ( p = 1 ) .\nthe clarity placebo group had a lower neoplasm rate ( 0% ) than the oracle ms placebo group ( 2.91% , p = 0.0012 ) .\nrandom - effects pooling based on risk difference indicated a cancer risk profile from the clarity trial comparable to that of other dmds ( cladribine had a lower risk difference compared to 4 other trials ; figure 4 ) .\nwe further noted that the clarity trial did not indicate a higher risk difference than the other \ninduction dmd , alemtuzumab , in previously untreated pwrms in the cohen 2012 trial . given the heterogeneity of treatments , significant heterogeneity between trials was detected ( i = 56.3% , p = 0.009 ) .\nalem = alemtuzumab ; ci = confidence interval ; clad = cladribine ; dime = dimethyl fumarate ; fing = fingolimod ; nata = natalizumab ; teri = teriflunomide .\nthe main findings of this study are that ( 1 ) the rate of cancer was similar between the only phase iii trial of cladribine and all other phase iii trials of dmds in pwrms , and ( 2 ) a significant difference emerged when comparing the placebo groups of clarity ( no cancers ) with the placebo arms of all other phase iii trials included in this study .\nthese findings were corroborated by a cancer rate difference in clarity that was comparable to that of all other phase iii trials for dmds for pwrms .\nfocusing on cancers observed in pwrms treated with cladribine in clarity ( and oracle ms ) might lead to the suspicion that cladribine plays a causative role , given the fact that 3 pwrms on cladribine developed cancer whereas none on placebo did .\nhowever , comparison with other dmds shows that the number of malignancies in clarity was not increased .\nindeed , the cancer rate in clarity was among the lowest observed for any treatment group , suggesting that the cancers developed on cladribine are a reflection of the background risk in the population\n. moreover , the short latency between initiation of treatment and cancer diagnosis in clarity ( 18 months ) renders a causal relationship unlikely .\nwe also note that in contrast to the trials of alemtuzumab , cladribine was compared with placebo ( rather than an active comparator ) .\ninvestigations of the general risk of cancer among pwrms in large cohorts reported conflicting results . in a danish study using population - based registers of ms and cancer\n, there was no evidence of an overall increased risk of cancer after a diagnosis of ms ; however , they did report a small excess risk of breast cancer among women .\na recent systematic review of the incidence and prevalence of cancer in ms reported substantial variation in reported estimates between studies .\noverall , the risk of any cancer was most commonly reported to be lower in pwrms compared to the general population .\ncancer risk appeared to be higher for malignant brain tumors and for cancers affecting the urinary tract system .\nhowever , potential surveillance bias and variation of age and sex of pwrms across studies stand in the way of more definitive conclusions .\nthe data from our meta - analysis of dmds in pwrms are supported by the long - term outcome of people with leukemia treated with cladribine . in a 20-year follow - up\nreport of 88 patients diagnosed with hairy cell leukemia before the age of 40 , no increase in the incidence of secondary malignancies was detected . according to the preliminary report of the 96-week phase ii \noral cladribine as add - on to ifn- therapy in patients with active multiple sclerosis \n( onward ) trial , in which oral cladribine ( dose 3.5 mg / kg ) was compared vs placebo as an add - on to interferon - beta treatment , 1 of 124 patients , a 57-year - old woman with a 25-year smoking history , developed squamous cell carcinoma about 2 years following first cladribine exposure .\ncladribine administered as an injection or infusion has previously been investigated in placebo - controlled phase ii trials of varying dosages , with results demonstrating reduced disease activity ( clinically and on mri ) with no reported cancer signal\n. limitations of our study include the inevitable variation between trials in terms of sample size , inclusion criteria , follow - up period , and dosing regimens ; the fact that not all phase iii trials for approved dmds in pwrms reported data on cancer rates ; and the fact that all cancers were considered together , i.e. , regardless of affected organ(s ) . furthermore , clarity was 2 months shorter than most of the other trials included , which lasted 2 years .\nmathematically , a slightly lower number of cancers would therefore be expected in clarity due to the shorter observation period . however , there is no indication that this difference had any material impact on the results of our meta - analysis .\nwe also acknowledge that in a randomized trial such as clarity , if the cancer rate is truly low , \nit should also have been low relative to the placebo group in its own trial .\nhowever , the apparently high risk in clarity relative to placebo may be due to the use of the risk ratio rather than the risk difference ; the former is inappropriate in this context because of the zero cases in the clarity placebo group .\nour meta - analysis of risk differences , which does not require arbitrary substitutions for the zeros , suggests that the risk difference for several other comparable drugs is higher than that in clarity .\nour data suggest that although current evidence can not rule out an increased risk of cancer on cladribine , it also can not confirm that such a risk exists .\na more definitive assessment of cancer risk will only be feasible through long - term follow - up , be it of people treated with cladribine ( prospective observational long - term safety registry of multiple sclerosis patients who have participated in cladribine clinical trials \nthe results of our meta - analysis should encourage further investigation into the potential use of cladribine as a dmd for pwrms .\nk.s . has been supported by a higher education funding council for england ( hefce ) clinical senior lectureship .\naltmann consulted for merck & co and received research support from multiple sclerosis society of great britain and northern ireland .\nturner is on the scientific advisory board for biogen , novartis , and sanofi aventis .\nm. marta received travel funding from biogen and abbott laboratories and received research support from merck - serono .\nd. baker has a patent filed concerning the treatment of multiple sclerosis with cladribine and other compounds ; has consulted for canbex therapeutics ; received research support from genzyme sanofi , national multiple sclerosis society , and academic entities ; has stock options from canbex therapeutics ; and provided legal consult for teva .\nj. chataway is on the scientific advisory board for novartis ; received travel funding and/or speaker honoraria from novartis , teva , and sanofi ; and received research support from novartis , uk mrc , and uk national institute of health research ( nihr ) university college london hospitals / ucl biomedical research centres funding scheme .\nk. schmierer is a principal investigator of trials sponsored by novartis , roche , and teva .\nhe has received speaking honoraria from , and served on advisory boards for , biogen , novartis , teva , merck - serono , and merck inc ; and received research support from novartis , the multiple sclerosis society of great britain & northern ireland , the national ms society , the royal college of radiologists , and barts charity .", "role": "user" }, { "content": "objective : to compare the cancer risk of cladribine and other disease - modifying drugs ( dmds ) in trials of people with relapsing multiple sclerosis ( pwrms).methods : meta - analysis of phase iii trials of licensed dmds for pwrms and a phase iii trial of cladribine ( clarity ) . \n cancer rates were compared using fisher exact test.results:eleven trials were included . investigated treatments included cladribine , dimethyl fumarate , fingolimod , teriflunomide , natalizumab , alemtuzumab , and glatiramer acetate . \n the cancer rate in the clarity treatment group ( 0.34% ) was not increased compared to all other treatment groups , whether including placebo - controlled trials only ( 0.6% , p = 0.4631 ) or all trials , i.e. , including those with an active comparator arm ( 0.67% , p = 0.3669 ) . \n no cancer was reported in the clarity placebo group , whereas the combined cancer rate of all other placebo groups was 1.19% ( p = 0.0159 ) . \n the cancer rate of zero in the clarity placebo group was also lower than that in the phase iii trial of cladribine in people with clinically isolated syndrome ( oracle ms , 2.91% , p = 0.0012 ) . \n in fact , no difference was detected between cancer rates in the treatment groups of clarity ( 0.34% ) and oracle ms ( 0.49% ) ( p = 0.6546).conclusions : our study does not support an increased cancer risk from cladribine in the doses used in clarity and oracle ms , which previously contributed to refusal of market authorization of cladribine in europe . longer - term follow - up is required to assess the safety profile of cladribine , as well as currently licensed dmds , to definitively assess cancer risk .", "role": "assistant" } ]

[ { "content": "Craft a concise summary for a chemistry research paper using the provided title and selected text segments.\n\nHeading:\nDivalent Metal Ion Triggered Activity of a Synthetic Antimicrobial in Cardiolipin Membranes\n\nContent Extracts:\n\n<p>Antimicrobial peptides (AMPs) have broad spectrum killing activity against prokaryotes but not against eukaryotes, and consequently are considered promising antibiotic candidates. However, these peptides are typically large (–up to 80 amino acid residues), structurally complex, and expensive to produce. As a result, much effort has been focused on developing synthetic analogs,1 or antimicrobial oligomers (AMOs). Recent human clinical data indicate that this is a promising approach.1h There is general agreement that these antimicrobial molecules interact with the cell membrane, which can have complex distributions of lipids,2a–e including lipids with non-zero intrinsic curvature,2f such as unsaturated-phosphatidylethanolamine (PE),2g and cardiolipin (CL).2g–i Bacterial membranes have a significantly higher population of negative intrinsic curvature (NIC) lipids compared to mammalian membranes, and it was recently shown that these differences are one mechanism by which AMOs can differentially kill bacteria over mammalian cells.2d, 2e, 2j–l</p><p>The specific relationship between PE and AMO 2 was recently described for E. coli.2d, 2j While this readily explained the potent activity against Gram-negative bacteria (MIC of 0.1 µg/mL against E. coli), it did not explain this AMOs activity against Gram-positive bacteria like S. aureus (0.2 µg/mL) since this organism is known to contain no PE lipid.3 In addition, it was demonstrated that although antimicrobial activity is largely ablated in PE-knock-out strains of E. coli,4 residual antimicrobial activity still remains. Moreover, the previous results specifically implicated PE lipid, although it was hypothesized that NIC lipids were more important than any specific binding between the AMO and PE.</p><p>Here, we examine how a prototypical synthetic antimicrobial interacts with cardiolipin (CL), which is the major lipid component in most Gram-positive bacteria. We show the structural requirement needed for membrane activity of AMO 2 is the existence of NIC lipids, in this case CL. A central feature of CL is that its intrinsic curvature is influenced by the bound cations and can be tuned between zero intrinsic curvature (C0 ~ 0) in the presence of monovalent salts and negative intrinsic curvature (C0 < 0) when bound to divalent cations like the biologically prevalent Ca2+ or also Mg2+ (SI, Figure S1). The presence of NIC lipids is one of the ingredients that facilitate pore formation.2d–e, 2j–l AMO 2 activity against CL membranes, with and without divalent metal ions (Ca2+, Mg2+) was evaluated using both calcein dye leakage assays (DLA) and small angle x-ray scattering (SAXS).</p><p>The ability of AMO 2 to induce calcein dye leakage from CL vesicles depends strongly on the presence of divalent cations. For example, leakage increased from 5% without divalent cations to 60% in the presence of 2.0 mM Mg2+ or 1.0 mM Ca2+ ions (Figure 1A, 1B). Importantly the presence of 2.0 mM Ca2+ ion alone caused no leakage of entrapped calcein dye (SI, Figure S2). Further, the presence of Ca2+ ions have no influence on the leakage activity of 20/80 PG/PE vesicles caused by AMO 2 (Figure 1C). These three data sets highlight the necessity of NIC lipids for AMO 2 to induce calcein release. For the PG/PE vesicles which already have a large volume fraction of NIC lipids, the addition of Ca2+ does not enhance leakage. In contrast, AMO 2 has limited activity toward CL vesicles until a reasonable concentration of divalent cations is added to the solution. Because most Gram-positive bacteria's plasma membranes are not composed solely of CL lipid, we also examined the dependence of AMO 2 induced leakage in PG (phosphatidylglycerol)/CL vesicles. Again, leakage was dependent on the presence of divalent cations as shown in Figure 1D. Not surprisingly, a higher concentration of divalent cation was required to exhibit dye leakage in this PG/CL system compared to pure CL vesicles.</p><p>To further explore the relationships between AMO 2 and CL-rich membranes, we employed SAXS. Recent work showed that the induction of an inverted hexagonal HII phase in PE-rich membranes by AMOs is correlated with dye leakage and bacterial growth inhibition.2d, 2j Here, we map out the structural tendency of CL-rich membranes to re-organize in the presence of AMO 2 and Mg2+ ions. Figure 2A shows SAXS data for pure CL in the presence of increasing [Mg2+]. Consistent with previous results,2i, 5 CL can form an inverted hexagonal phase at sufficiently high [Mg2+] concentrations (1–4 mM) in the absence of the AMO.</p><p>As Gram-positive bacterial membranes contain a mixture of CL and PG lipids, SAXS experiments were also performed on mixed lipid compositions. The addition of anionic PG lipids to a CL membrane is expected to decrease the tendency to form negative curvature by reducing the local concentration of NIC CL. SAXS data (SI, Figure S5, SAXS data without AMO's and other control experiments are described in the SI) is consistent with this expectation as DOPG/CL vesicles with 4.0 mM [Mg2+] show no peaks corresponding to the inverted hexagonal phase in contrast to Figure 2A. Meanwhile, Figure 2B shows SAXS data from complexes formed by AMO 2 and DOPG/CL = 32/68 vesicles in the presence of different [Mg2+] concentrations (0 mM, 0.5 mM, 4.0 mM), with AMO to lipid molar ratios fixed at A/L = 1/5. Consistent with the DLA results which showed some leakage [(See Figure 1D], AMO 2 can induce a phase with hexagonal symmetry without Mg2+ ions as indicated by peak positions at the characteristic ratio of 1:√3:2. However, the presence of divalent Mg2+ increases the structural tendency to form this phase, as evidenced by stronger diffraction peaks. Also consistent with this, the phase with hexagonal symmetry forms at significantly lower [Mg2+] in the presence of AMO 2 than for pure CL vesicles (Compare Figure 2A and 2B, specifically [Mg2+] = 0.5 mM).</p><p>Electron density reconstructions (SI, Figure S6) from the above SAXS data confirm that an inverted hexagonal HII phase is formed, as well as allow an estimate of the number of AMO and Mg2+ ions in the HII water channels. From the reconstructed electron density profiles, we find the calibrated average electron density at the hydrophilic surface to be 0.58, 0.57, and 0.55 (e/Å3) for complexes formed at [Mg2+] of 0, 0.5, and 4.0 mM, respectively. For complexes with a high A/L ratio of 1/5 and without Mg2+ ions, we estimate ~ 4 AMO 2 molecules per 4 nm length of the water channel (thickness of a lipid bilayer) embedded near the hydrophilic region of the membrane, using a procedure described previously.2j From the reconstructed electron density profiles of complexes formed at high [Mg2+] and pure CL vesicles with no added AMO, we estimate that each CL molecule binds ~ 0.6 Mg2+ ions (See SI).</p><p>This information was used to examine the self-assembly of AMO 2 with PG/CL membranes in the presence of Mg2+. Using the working hypothesis that the number of bound Mg2+ ions per CL for DOPG/CL = 32/68 is the same as that of CL vesicles, it was estimated that the number of AMO 2 molecules per 4 nm of channel length is ~ 3.6 and ~ 3.2 for complexes at [Mg2+] of 0.5 mM and 4 mM. Interestingly this observed channel occupancy of AMO 2 molecules are quite close to that found in DOPG/DOPE = 20/80 at high A/L ratios.2j These results suggest that, with the help from curvature generating divalent Mg2+ ions, CL-rich membranes have ~ 3 AMO 2 molecules embedded into their hydrophilic surface lining per 4 nm length of water channel. These results are also consistent with recent work that shows that bacterial mutants with cardiolipin-rich membranes can be killed by AMO 2 in the presence of Mg2+ ions.2j This suggests that CL, in the presence of Mg2+, acts as a NIC lipid and functions as a structural substitute for PE during the membrane interaction by AMO 2. It is likely that both are able to play a structural role in forming the negative curvature necessary for the circumferential barrel of the transmembrane pore.2d</p><p>These results indicate that the presence of NIC lipids is important for pore formation by this class of AMO molecules: In Gram-positive bacteria, CL and divalent metal cations like Ca2+ and Mg2+ are needed. This is completely consistent with the role of PE lipid in Gram-negative bacteria, where AMO antimicrobial activity is dependent on the NIC of PE, rather than a specific interaction with PE. These results lead to the conclusion that influencing curvature either directly, or indirectly by targeting NIC lipids, can be a new approach for antibiotic design.</p>", "role": "user" }, { "content": "One member of a prototypical class of antimicrobial oligomers was used to study pore formation in cardiolipin rich membranes. Using both vesicle dye-leakage assays and small angle x-ray scattering, bilayer remodeling was studied. The results indicate that the presence of negative intrinsic curvature (NIC) lipids is essential for pore formation by this class of molecules: In Gram-positive bacteria, cardiolipin and divalent metal cations like Ca2+ and Mg2+ are needed. This is completely consistent with the role of phosphatidylethanolamine (PE) lipid in Gram-negative bacteria, where antimicrobial activity is dependent on the negative intrinsic curvature of PE, rather than a specific interaction with PE.", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: A novel clustering algorithm based on region segmentation is proposed.\n\nKeywords: clustering images\n\nDataset Information:\nADAM: ADAM is organized as a half day Challenge, a Satellite Event of the ISBI 2020 conference in Iowa City, Iowa, USA. The ADAM challenge focuses on the investigation and development of algorithms associated with the diagnosis of Age-related Macular degeneration (AMD) and segmentation of lesions in fundus photos from AMD patients.\nVOT2018: VOT2018 is a dataset for visual object tracking. It consists of 60 challenging videos collected from real-life datasets.\nNewSHead: The NewSHead dataset contains 369,940 English stories with 932,571 unique URLs, among which there are 359,940 stories for training, 5,000 for validation, and 5,000 for testing, respectively. Each news story contains at least three (and up to five) articles.\nORL: The ORL Database of Faces contains 400 images from 40 distinct subjects. For some subjects, the images were taken at different times, varying the lighting, facial expressions (open / closed eyes, smiling / not smiling) and facial details (glasses / no glasses).\n\nAvailable Datasets: A: ADAM B: VOT2018 C: NewSHead D: ORL", "role": "user" }, { "content": "ORL", "role": "assistant" } ]

[ { "content": "Write an abstract for the research paper below. Your response should only include the abstract and no additional text.\n\nArticle text:\nour increasing ability to carry out unquenched simulations means that the quenched approximation is no longer required .\nthere is an outstanding issue associated with the quenched continuum limit , however , which we address here . at the same time we point out the ingredients that are necessary to obtain an accurate result in the continuum limit , since these ingredients will also be important for unquenched simulations .\nthe outstanding issue is the question of whether all quark formulations give the same result in the quenched continuum limit .\nit is relatively trivial to demonstrate that they should , because this is the limit in which it is easy to analyse the formulations . at lattice 2000 , however , it seemed not to be the case @xcite .\na plot was made of the ratio of nucleon to vector meson mass at a fixed physical quark mass , as a function of the lattice spacing .\nthe physical quark mass was chosen as the point at which the pseudoscalar meson mass divided by the vector meson mass was 0.5 ( in those days quite a low mass to reach ) .\nthe lattice spacing was given in units of the vector meson mass . because of the instability of vector mesons this is not a plot that allows for a precision test against experimental results , even if it used a quark mass value from the real world and was not in the quenched approximation .\nhowever , it can be used as a comparison of different formalisms , provided the results have good statistical precision and are on large enough volumes .\nthe original plot showed a 6@xmath1 disagreement between the results extrapolated to @xmath2 from the wilson formulation @xcite and the unimproved staggered formulation @xcite .\nthe wilson results were extrapolated linearly in @xmath0 and the staggered results quadratically .\nclover results were also included but their variation suggests a statistical error that means they are not particularly useful so we drop those results in this discussion .\nthe disagreement , if true , would represent a major problem for lattice calculations and call the whole approach into question . with\nmany large dynamical quark projects well underway and others planned , it is therefore time to readdress this issue , following on from @xcite .\nin addition , there are more quark formulations in widespread use than there were in 2000 , so the comparison of results can be significantly extended .\nfigure [ fig : aokisq ] shows an updated plot of the wilson and unimproved staggered results from lattice 2000 , along with new results from improved staggered ( asqtad ) quarks on improved glue @xcite and the perfect action @xcite .\nthe new results were chosen for small statistical errors , being available at the quark mass required here ( with interpolation ) , for more than one value of the lattice spacing and with a reasonably large physical volume .\nnote that the @xmath3 axis is now @xmath4 instead of @xmath0 .\nthe lines represent a simultaneous fit to all the data with a single continuum limit imposed .\na good @xmath5 is obtained .\nthe fit allows for leading and higher order polynomials in @xmath0 appropriate to each formulation ( i.e even powers for all except wilson ) with a constraint placed upon the coefficients to avoid losing control of the fit .\nthe effectiveness of this bayesian approach @xcite has been widely demonstrated for fitting correlators , chiral extrapolations etc . \nall situations in which a critical issue is the systematic error in the final result which arises from leaving out higher order terms in an expansion . in all these cases we have a good physical understanding of the expansion and can therefore place constraints on the higher order terms .\ntaking the continuum limit is just such a case .\nwe expect the scale of discretisation errors to be set by the size of internal momenta inside the hadron\n. this should be roughly a few hundred mev . here the priors on the coefficients in the polynomial in @xmath6 were taken to be @xmath70.5 , and 5 terms were included in the expansion for each formulation ( a constant plus 4 appropriate powers ) .\nthe result for the joint continuum limit is 1.373(10 ) , 2@xmath1 below the previous unimproved staggered continuum limit but well above the wilson one .\nwith hindsight this is not surprising because a purely linear fit to wilson results neglects terms which are not small for these results .\nwe would expect the quadratic terms to appear as , say , @xmath8 and this is 5% for the coarsest lattice used .\na systematic error has to be added to a purely linear extrapolation to take this into account . for the improved formalisms\nthis is not so much of an issue because the terms neglected by a leading order extrapolation are @xmath9@xmath10 , 1% for the improved staggered and perfect actions at their coarsest spacing . in all cases , however ,\na bayesian analysis allowing for higher order terms is useful in assessing the systematic errors .\nwe now turn to other scaling plots , figures [ fig : rho ] and [ fig : nuc ] , for which a lot more data is available .\nthese are plots of @xmath11 and @xmath12 in units of @xmath13 , vs @xmath14 @xcite .\nwe include results from wilson @xcite , clover @xcite , perfect action @xcite and domain wall quarks @xcite as well as a variety of staggered results with improved and unimproved glue .\nagain a good fit with a single continuum limit is readily obtained and the curves for this are shown .\nthe results are for a fixed quark mass given by @xmath15 using @xmath16 in the quenched continuum limit @xcite .\nthe authors would welcome additional results for any of these graphs .\nwe show , reassuringly , that all current quark formalisms give the same answer for nucleon and rho masses , at fixed arbitrary quark mass , in the quenched continuum limit .\nwe used an analysis of discretisation effects which allows the inclusion of leading _ and _ higher order terms in the lattice spacing .\nthis is particularly necessary for unimproved actions , emphasising once again the importance of the improvement programme in reducing systematic errors in lattice calculations .\n99 s. aoki , nucl .\n* 94 * ) ( 2001 ) 3 .\net al _ , cp - pacs , phys .\nlett . * 84 * ( 2000 ) 238 . c. bernard _\net al _ , milc , phys .\nrev . d*58 * ( 1998 ) 014503 , hep - lat/9712010 .\nk. jansen , nucl .\n. suppl . * 129 * ) ( 2004 ) 3 .\nnote there is an error in the figure caption for figure 3 . c. bernard _\net al _ , phys .\nrev . d*64 * ( 2001 ) 054506 , hep - lat/0104002 ; c. aubin _ et al _ , hep - lat/0402030 . c. gattringer _\nal _ , bgr , nucl .\nphys . b*677 * ( 2004 ) 3 , hep - lat/0307013 , p. hasenfratz _\net al _ , in preparation .\ng. p. lepage _ et al _ , nucl .\n. suppl . * 106 * ) ( 2002 ) 12 .\nd. toussaint , nucl .\n. suppl . * 106 * ) ( 2002 ) 111 ; c. bernard _ et al _ , phys .\nrev . d*61 * ( 2000 ) 111502 , hep - lat/9912018 .\ns. collins _ et al _ , nucl .\n. suppl . * 53 * ) ( 1997 ) 877 .\nk. c. bowler _\net al _ , phys .\nrev . d*62 * ( 2000 ) 054506 .\net al _ , phys .\nrev . d*69 * ( 2004 ) 074502 , hep - lat/0007038 .", "role": "user" }, { "content": "we show that all current formalisms for quarks in lattice qcd are consistent in the quenched continuum limit , as they should be . \n we improve on previous extrapolations to this limit , and the understanding of lattice systematic errors there , by using a constrained fit including both leading and sub - leading dependence on @xmath0 .", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nLong Short-Term Memory (LSTM) is one of the most powerful sequence models.\nDespite the strong performance, however, it lacks the nice interpretability as in state space models.\nIn this paper, we present a way to combine the best of both worlds by introducing State Space LSTM (SSL), which generalizes the earlier work \\cite{zaheer2017latent} of combining topic models with LSTM.\nHowever, unlike \\cite{zaheer2017latent}, we do not make any factorization assumptions in our inference algorithm.\nWe present an efficient sampler based on sequential Monte Carlo (SMC) method that draws from the joint posterior directly.\nExperimental results confirms the superiority and stability of this SMC inference algorithm on a variety of domains.\nState space models (SSMs), such as hidden Markov models (HMM) and linear dynamical systems (LDS), have been the workhorse of sequence modeling in the past decades From a graphical model perspective, efficient message passing algorithms BID34 BID17 are available in compact closed form thanks to their simple linear Markov structure.\nHowever, simplicity comes at a cost: real world sequences can have long-range dependencies that cannot be captured by Markov models; and the linearity of transition and emission restricts the flexibility of the model for complex sequences.A popular alternative is the recurrent neural networks (RNN), for instance the Long Short-Term Memory (LSTM) BID14 ) which has become a standard for sequence modeling nowadays.\nInstead of associating the observations with stochastic latent variables, RNN directly defines the distribution of each observation conditioned on the past, parameterized by a neural network.\nThe recurrent parameterization not only allows RNN to provide a rich function class, but also permits scalable stochastic optimization such as the backpropagation through time (BPTT) algorithm.\nHowever, flexibility does not come for free as well: due to the complex form of the transition function, the hidden states of RNN are often hard to interpret.\nMoreover, it can require large amount of parameters for seemingly simple sequence models BID35 .In\nthis paper, we propose a new class of models State Space LSTM (SSL) that combines the best of both worlds. We\nshow that SSLs can handle nonlinear, non-Markovian dynamics like RNNs, while retaining the probabilistic interpretations of SSMs. The\nintuition, in short, is to separate the state space from the sample space. In\nparticular, instead of directly estimating the dynamics from the observed sequence, we focus on modeling the sequence of latent states, which may represent the true underlying dynamics that generated the noisy observations. Unlike\nSSMs, where the same goal is pursued under linearity and Markov assumption, we alleviate the restriction by directly modeling the transition function between states parameterized by a neural network. On the\nother hand, we bridge the state space and the sample space using classical probabilistic relation, which not only brings additional interpretability, but also enables the LSTM to work with more structured representation rather than the noisy observations. Indeed\n, parameter estimation of such models can be nontrivial. Since\nthe LSTM is defined over a sequence of latent variables rather than observations, it is not straightforward to apply the usual BPTT algorithm without making variational approximations. In BID35\n, which is an instance of SSL, an EM-type approach was employed: the algorithm alternates between imputing the latent states and optimizing the LSTM over the imputed sequences. However,\nas we show below, the inference implicitly assumes the posterior is factorizable through time. This is\na restrictive assumption since the benefit of rich state transition brought by the LSTM may be neutralized by breaking down the posterior over time.We present a general parameter estimation scheme for the proposed class of models based on sequential Monte Carlo (SMC) BID8 , in particular the Particle Gibbs BID1 . Instead\nof sampling each time point individually, we directly sample from the joint posterior without making limiting factorization assumptions. Through\nextensive experiments we verify that sampling from the full posterior leads to significant improvement in the performance.Related works Enhancing state space models using neural networks is not a new idea. Traditional\napproaches can be traced back to nonlinear extensions of linear dynamical systems, such as extended or unscented Kalman filters (Julier & Uhlmann, 1997), where both state transition and emission are generalized to nonlinear functions. The idea of\nparameterizing them with neural networks can be found in BID12 , as well as many recent works BID22 BID2 BID15 BID23 BID18 thanks to the development of recognition networks BID20 BID32 . Enriching the\noutput distribution of RNN has also regain popularity recently. Unlike conventionally\nused multinomial output or mixture density networks BID4 , recent approaches seek for more flexible family of distributions such as restricted Boltzmann machines (RBM) BID6 or variational auto-encoders (VAE) BID13 BID7 .On the flip side, there\nhave been studies in introducing stochasticity to recurrent neural networks. For instance, BID30 and\nBID3 incorporated independent latent variables at each time step; while in BID9 the RNN is attached to both latent states and observations. We note that in our approach\nthe transition and emission are decoupled, not only for interpretability but also for efficient inference without variational assumptions.On a related note, sequential Monte Carlo methods have recently received attention in approximating the variational objective BID27 BID24 BID29 . Despite the similarity, we emphasize\nthat the context is different: we take a stochastic EM approach, where the full expectation in E-step is replaced by the samples from SMC. In contrast, SMC in above works is aimed\nat providing a tighter lower bound for the variational objective.\nIn this paper we revisited the problem of posterior inference in Latent LSTM models as introduced in BID35 .\nWe generalized their model to accommodate a wide variety of state space models and most importantly we provided a more principled Sequential Monte-Carlo (SMC) algorithm for posterior inference.\nAlthough the newly proposed inference method can be slower, we showed over a variety of dataset that the new SMC based algorithm is far superior and more stable.\nWhile computation of the new SMC algorithm scales linearly with the number of particles, this can be naively parallelized.\nIn the future we plan to extend our work to incorporate a wider class of dynamically changing structured objects such as time-evolving graphs.", "role": "user" }, { "content": "We present State Space LSTM models, a combination of state space models and LSTMs, and propose an inference algorithm based on sequential Monte Carlo.", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: A survey on Hamilton cycles in directed graphs \nChapter Title: Tournaments \n1. Abstract of Cited Paper (BIB001): The so-called Kelly conjecture1 A proof of the Kelly conjecture for large k has been announced by R. Haggkvist at several conferences and in [5] but to this date no proof has been published.states that every regular tournament on 2k+1 vertices has a decomposition into k-arc-disjoint hamiltonian cycles. In this paper we formulate a generalization of that conjecture, namely we conjecture that every k-arc-strong tournament contains k arc-disjoint spanning strong subdigraphs. We prove several results which support the conjecture:If D = (V, A) is a 2-arc-strong semicomplete digraph then it contains 2 arc-disjoint spanning strong subdigraphs except for one digraph on 4 vertices.Every tournament which has a non-trivial cut (both sides containing at least 2 vertices) with precisely k arcs in one direction contains k arc-disjoint spanning strong subdigraphs. In fact this result holds even for semicomplete digraphs with one exception on 4 vertices.Every k-arc-strong tournament with minimum in- and out-degree at least 37k contains k arc-disjoint spanning subdigraphs H1, H2, . . . , Hk such that each Hi is strongly connected.The last result implies that if T is a 74k-arc-strong tournament with speci.ed not necessarily distinct vertices u1, u2, . . . , uk, v1, v2, . . . , vk then T contains 2k arc-disjoint branchings $$F^{ - }_{{u_{1} }} ,F^{ - }_{{u_{2} }} ,...,F^{ - }_{{u_{k} }} ,F^{ + }_{{v_{1} }} ,F^{ + }_{{v_{2} }} ,...,F^{ + }_{{v_{k} }}$$ where $$F^{ - }_{{u_{i} }}$$ is an in-branching rooted at the vertex ui and $$F^{ + }_{{v_{i} }}$$ is an out-branching rooted at the vertex vi, i=1,2, . . . , k. This solves a conjecture of Bang-Jensen and Gutin [3].We also discuss related problems and conjectures. \n2. Abstract of Cited Paper (BIB002): We show that every sufficiently large regular tournament can a lmost completely be decomposed into edge-disjoint Hamilton cycles. More precisely, for each � > 0 every regular tournament G of sufficiently large ordern contains at least (1/2 �)n edge-disjoint Hamilton cycles. This gives an approximate solution to a conjecture of Kelly from 1968. Our result also extends to almost regular tournaments. \n3. Abstract of Cited Paper (BIB003): In this paper we give an approximate answer to a question of Nash-Williams from 1970: we show that for every \\alpha > 0, every sufficiently large graph on n vertices with minimum degree at least (1/2 + \\alpha)n contains at least n/8 edge-disjoint Hamilton cycles. More generally, we give an asymptotically best possible answer for the number of edge-disjoint Hamilton cycles that a graph G with minimum degree \\delta must have. We also prove an approximate version of another long-standing conjecture of Nash-Williams: we show that for every \\alpha > 0, every (almost) regular and sufficiently large graph on n vertices with minimum degree at least $(1/2 + \\alpha)n$ can be almost decomposed into edge-disjoint Hamilton cycles.\n\nReview Chapter:", "role": "user" }, { "content": "A tournament is an orientation of a complete graph. It has long been known that tournaments enjoy particularly strong Hamiltonicity properties: Camion showed that we only need to assume strong connectivity to ensure that a tournament has a Hamilton cycle. Moon strengthened this by proving that every strongly connected tournament is even pancyclic. It is easy to see that a minimum semidegree of n/4 forces a tournament on n vertices to be strongly connected, leading to a better degree condition for Hamiltonicity than that of (3n − 4)/8 for the class of all oriented graphs. 4.1. Edge-disjoint Hamilton cycles and decompositions. A Hamilton decomposition of a graph or digraph G is a set of edge-disjoint Hamilton cycles which together cover all the edges of G. Not many examples of graphs with such decompositions are known. One can construct a Hamilton decomposition of a complete graph if and only if its order is odd (this was first observed by Walecki in the late 19th century). Tillson proved that a complete digraph G on n vertices has a Hamilton decomposition if and only if n = 4, 6. The following conjecture of Kelly from 1968 (see Moon ) would be a far-reaching generalization of Walecki's result: Conjecture 16 (Kelly) . Every regular tournament on n vertices can be decomposed into (n − 1)/2 edge-disjoint Hamilton cycles. In BIB003 we proved an approximate version of Kelly's conjecture. Moreover, the result holds even for oriented graphs G which are not quite regular and whose 'underlying' undirected graph is not quite complete. Theorem 17 (Kühn, Osthus and Treglown BIB003 ). For every η 1 > 0 there exist n 0 = n 0 (η 1 ) and η 2 = η 2 (η 1 ) > 0 such that the following holds. Suppose that G is an oriented graph on n ≥ n 0 vertices such that δ 0 (G) ≥ (1/2 − η 2 )n. Then G contains at least (1/2 − η 1 )n edge-disjoint Hamilton cycles. We also proved that the condition on the minimum semidegree can be relaxed to δ 0 (G) ≥ (3/8+η 2 )n. This is asymptotically best possible since the construction described in Figure 3 is almost regular. Some earlier support for Kelly's conjecture was provided by Thomassen [63] , who showed that the edges of every regular tournament can be covered by at most 12n Hamilton cycles. In this paper, we improve this to an asymptotically best possible result. We will give a proof (which relies on Theorem 17) in Section 6.1. Theorem 18. For every ξ > 0 there exists an integer n 0 = n 0 (ξ) so that every regular tournament G on n ≥ n 0 vertices contains a set of (1/2 + ξ)n Hamilton cycles which together cover all the edges of G. Kelly's conjecture has been generalized in several ways, e.g. Bang-Jensen and Yeo BIB002 conjectured that every k-edge-connected tournament has a decomposition into k spanning strong digraphs. A bipartite version of Kelly's conjecture was also formulated by Jackson BIB001 . Thomassen made the following conjecture which replaces the assumption of regularity by high connectivity. Conjecture 19 (Thomassen ). For every k ≥ 2 there is an integer f (k) so that every strongly f (k)-connected tournament has k edge-disjoint Hamilton cycles. A conjecture of Erdős (see ) which is also related to Kelly's conjecture states that almost all tournaments G have at least δ 0 (G) edge-disjoint Hamilton cycles. Similar techniques as in the proof of the approximate version of Kelly's conjecture were used at the same time in BIB004 to prove approximate versions of two long-standing conjectures of Nash-Williams on edge-disjoint Hamilton cycles in (undirected) graphs. One of these results states that one can almost decompose any dense regular graph into Hamilton cycles. Theorem 20 (Christofides, Kühn and Osthus BIB004 ). For every η > 0 there is an integer n 0 = n 0 (η) so that every d-regular graph on n ≥ n 0 vertices with d ≥ (1/2 + η)n contains at least (d − ηn)/2 edge-disjoint Hamilton cycles. In Section 6.1 we deduce the following analogue of Theorem 18: Theorem 21. For every ξ > 0 there is an integer n 0 = n 0 (ξ) so that every dregular graph G on n ≥ n 0 vertices with d ≥ (1/2+ξ)n contains at most (d+ξn)/2 Hamilton cycles which together cover all the edges of G.", "role": "assistant" } ]

[ { "content": "Transform the following sections from a biomedical study into a simple summary for the general public. Focus on making the information accessible and easy to understand.\n\nResearch Heading: SINE RNA Induces Severe Developmental Defects in Arabidopsis thaliana and Interacts with HYL1 (DRB1), a Key Member of the DCL1 Complex\nContent:\nAbstract:\nThe proper temporal and spatial expression of genes during plant development is governed, in part, by the regulatory activities of various types of small RNAs produced by the different RNAi pathways. Here we report that transgenic Arabidopsis plants constitutively expressing the rapeseed SB1 SINE retroposon exhibit developmental defects resembling those observed in some RNAi mutants. We show that SB1 RNA interacts with HYL1( DRB1), a double-stranded RNA-binding protein( dsRBP) that associates with the Dicer homologue DCL1 to produce microRNAs. RNase V1 protection assays mapped the binding site of HYL1 to a SB1 region that mimics the hairpin structure of microRNA precursors. We also show that HYL1, upon binding to RNA substrates, induces conformational changes that force single-stranded RNA regions to adopt a structured helix-like conformation. Xenopus laevis ADAR1, but not Arabidopsis DRB4, binds SB1 RNA in the same region as HYL1, suggesting that SINE RNAs bind only a subset of dsRBPs. Consistently, DCL4-DRB4-dependent miRNA accumulation was unchanged in SB1 transgenic Arabidopsis, whereas DCL1-HYL1-dependent miRNA and DCL1-HYL1-DCL4-DRB4-dependent tasiRNA accumulation was decreased. We propose that SINE RNA can modulate the activity of the RNAi pathways in plants and possibly in other eukaryotes.\nIntroduction:\nShort Interspersed Elements( SINEs) are repetitive sequences, present in the genome of most eukaryotes and ancestrally derived from small functional RNAs( tRNAs, 7SL RNAs or 5S RNAs)[1]. SINEs can be transcribed by the RNA polymerase III( polIII) machinery[2]. They propagate in genomes following reverse transcription and integration due to their capacity to interact efficiently with the translation products of Long Interspersed Elements( LINEs)[3],[4], a family of active retrotransposons. SINEs copy number usually ranges from several hundred to several thousand in most eukaryotic species, except in mammals where tens of thousands up to millions of copies can be found[1]. Evaluating SINE impact on genome structure and gene expression has been the subject of numerous investigations in the past 20 years( reviewed in[1],[5]–[7]). Most of these studies have been conducted at the DNA level, by evaluating how SINE copies affect chromatin structure, DNA recombination, replication and transcription. The effect of SINE sequences in mRNAs and the corresponding impacts on splicing, editing, degradation and translation processes have also been evaluated. Recently, several SINE polIII-specific transcripts were shown to act as noncoding riboregulators of basic cellular processes, including transcription and translation, in stress situations or in specific tissues. In rodents, following heat shock, several members of the SINE B2 family are actively transcribed[8],[9]. The B2 SINE RNA was shown to interact with and inhibit the RNA polymerase II complex, leading to a general repression of gene transcription in this stress situation[8],[9]. The polIII-specific transcription of human Alu, rodent B1 and silkworm Bm1 SINEs can also be activated by several biotic and abiotic stresses[10]–[15]. Alu RNA was proposed to regulate translation either by modulating the activity of the Protein Kinase R( PKR), a double-stranded RNA binding protein( dsRBP) that down-regulates translation in stress situations[10], or by a PKR-independent process[16],[17]. Recently, human Alu RNA was also shown to act as a modular transacting repressor of mRNA transcription during heat shock[18]. The rodent BC1 and human BC200 SINE-related elements are transcribed specifically in neurons where they regulate translation. BC1 and BC200 RNAs could potentially act as guides for the RNA-binding FMRP protein and regulate the translation of a small subset of neuron mRNAs[19],[20] although this mode of action was recently contested[21]. These RNAs can also have a more general impact on neuron translation by trapping essential translation factors such as eIF4B and PABPs[22],[23]. These different examples reveal that certain SINE loci produce non-coding regulatory RNA molecules that act on basic cellular functions. In this respect, SINE RNAs are similar to other polIII-transcribed riboregulators such as the cellular 7SK RNA regulating transcription elongation[24] and the viral VA1 and EBER1 RNAs regulating translation by interacting with PKR[25]. The Arabidopsis thaliana genome possesses six different SINE families representing a total of 334 repeated copies[26],[27]. In a previous study, we introduced a single copy of a Brassica napus SINE founder locus( SB1) under the control of its natural promoter in Arabidopsis and followed SINE RNA production and maturation in two independent transgenic lines[28]. Here we present evidence that the constitutive production of SINE RNA in these Arabidopsis lines can induce severe developmental defects. The SINE-induced phenotypes are similar to several RNAi mutant phenotypes. We show that SINE RNAs interact with a subset of highly divergent dsRBPs and affect the production of different families of small RNAs and the accumulation of their corresponding mRNA targets. Our results suggest that SINE RNAs influence the activity of a subset of dsRBPs and consequently, influence a variety of basic cellular processes including RNAi.\nDiscussion:\nSB1 expressing lines display a diversity of phenotypes, suggesting that many important developmental transition steps are affected in these plants. The variable phenotypic penetrance within each line also suggests a stochastic effect of the RNA on these transition steps. Although we do not know the precise molecular mechanism( s) responsible for these phenotypes, our data raise the possibility that an interaction between SB1 SINE RNA and a subset of dsRBPs, some of which are involved in RNAi, could contribute to the developmental defects. Using a double-stranded RNA binding domain from Xenopus laevis ADAR1, we have shown that SB1 RNA is fit to bind highly divergent dsRBPs, and therefore many dsRBPs could be affected by SINE RNA expression. Not all Arabidopsis dsRBPs are known to be involved in RNAi. For example, FIERY2 is a dsRBP involved in transcriptional regulation[44], while two other dsRBPs of unknown function( At1g48650, at5g04895) contain a helicase domain. Therefore SB1 RNA potentially affects basic cellular processes other than RNAi, and this in turn could affect plant development. Based on our in vitro studies, we propose that SB1 RNAs interact in vivo with HYL1, and consequently modify the steady-state level of several miRNAs and tasiRNAs. In this scenario, tasiRNA accumulation would be indirectly affected because tasiRNA biogenesis relies on miRNA-guided cleavage( miR173 targets TAS1 and TAS2 and miR390 targets TAS3)[45]( Figure 5B). DCL4-DRB4-dependent miRNA accumulation is unaffected in SB1 transgenic lines( see Figure 5C), consistent with the inability of SB1 RNA to bind DRB4 in gel retardation experiments. The SB1/HYL1 interaction and its molecular consequences on the miRNA pathway are unlikely to be solely responsible for the observed SB1-induced phenotype. Indeed, the global reduction of miRNA levels in SINE-expressing lines is generally moderate to low( from 0. 5 to 0. 8 of the initial amount) and this level of reduction does not always correlate with detectable increases in corresponding mRNA target levels( for examples see[46]). These relatively modest changes might be because several of these miRNAs derive from multigene families and thus potentially arise from several RNA precursors. In such cases, SINE RNAs would need to compete with several differently structured RNA precursors to limit effectively miRNA production. Also, in vivo, such competitions likely are influenced by the varying tissue/spatial distributions of different miRNAs:HYL1 complexes, which would probably effect the capacity of SINE RNA to modulate the production of a given miRNA in a given tissue. In conclusion, we propose that SB1 RNA compete for several dsRBPs, not only HYL1, and that these competitions likely accounts for the extent and unusual characteristics( such as the variable penetrance) of the SINE-induced phenotype. We observed that, in vitro, HYL1 binds efficiently different imperfect double-stranded RNA molecules, including the rapeseed SB1( Figures 2 and 3) and the Arabidopsis SB2( Figure S1) SINE RNAs, while DRB4 only binds perfect RNA duplexes( Figures 2 and 3). These results are fully compatible with the known natural substrates of these two proteins. In vivo, HYL1 is known to interact with pri- and pre-miRNAs, which are organized as stem-loops containing mismatches and bulges( see the miRBase http://microrna. sanger. ac. uk/ for examples of pre-miRNA structures). On the other hand, DRB4 binds perfect linear RNA duplexes formed by the action of RDR6 on a single stranded primary transcript[36]. The fact that HYL1 does not play a major role in double-stranded RNA-induced posttranscriptional gene silencing( PTGS)[46] further suggests that, in vivo, HYL1 preferentially interacts with imperfect double-stranded pri- and pre-miRNAs and not perfect double-stranded PTGS precursors. Based on our RNase V1 mapping results, the basis of this selectivity could be the capacity of HYL1 to interact with single-stranded RNA regions( Figures 3 and 4). Indeed, the binding specificity of other eukaryotic dsRBPs, such as ADARs and Staufen, was shown to depend on their ability to interact with single-stranded RNA loops[47]. We therefore suggest that HYL1 has intrinsic RNA binding specificities distinct from DRB4, and that these specificities dictate different in vivo binding preferences. We also observed that upon binding RNA HYL1 has the general capacity to force single-stranded regions to adopt a more organized, helix-like configuration( Figures 3, 4 and Figure S1). In vivo, HYL1 mainly is involved in promoting processing steps from pri-miRNA to pre-miRNA in association with DCL1, another dsRBP[38],[39]. HYL1 also influences the cleavage positioning of DCL1 on the pre-miRNA to generate the mature miRNA[40]. Consequently, in the hyl1-2 null mutant, pri-miRNAs accumulate and misplaced cleavages of pre-miRNAs were observed in some cases[38]–[40],[46]. However, HYL1 is not fully necessary for plant miRNA processing by DCL1 because the hyl1-2 mutant retains some ability to accumulate wild type miRNAs, although the accumulation level is reduced. Also, this reduction is variable depending on the different miRNAs[46],[48]. HYL1 may therefore promote, to variable extents, the processing activity of DCL1. Based on our observations, one way HYL1 could do this is by inducing a conformational change in the RNA structure, forcing key single stranded regions to adopt organized, helix-like, configurations, including non Watson-Crick base pairing. This could in turn be important for promoting the cleavage activity of DCL1 on pri-miRNAs or for helping to precisely define the cleavage site on pre-miRNAs to generate mature products. It remains to be determined whether the chaperoning-like activity of HYL1 is important for miRNA production. We recently observed that related structural motifs are present in most SINE RNAs from mammals, fishes and plants, suggesting common selective constraints imposed at the SINE RNA structural level[33]. Using a double-stranded RNA binding domain from Xenopus laevis ADAR1, we have shown here that the plant SB1 RNA is fit to bind highly divergent dsRBPs. Therefore, the common trend of structural evolution observed for tRNA-related SINE could result in similar constraints imposed by a subset of dsRBPs across eukaryote species. If true, this predicts that SINE RNAs are under selective pressure to keep intact their capacity to interact with some dsRBPs. This would in turn forge the SINE RNA structure and impose, as observed[33], a common evolutionary history for most eukaryote tRNA-related SINEs. The reason why SINE RNA/dsRBP interaction would be under positive selective pressure is unclear, but precise and punctual expression of SINEs during a key development step or in a stress situation, could induce genetic and/or epigenetic variations and increase diversity and/or adaptability. It is interesting to note that SINE-specific expression in their natural host is highly regulated at the transcriptional and post-transcriptional levels by complex genetic and epigenetic processes( reviewed in[1],[10],[28]). SINEs are non-autonomous in their mobility and need the activation of an autonomous LINE partner to retrotranspose. Therefore, based on our results, we suggest that the main purpose of limiting SINE-specific transcription is not to prevent its mobility( the control of LINEs is sufficient to achieve this) but to preserve cell homeostasis by preventing SINE RNA to interact with a large subset of dsRPBs.", "role": "user" }, { "content": "Short interspersed elements ( SINEs ) are transposable elements in eukaryotic genomes that mobilize through an RNA intermediate . Recently , mammalian SINE RNAs were shown to have roles as noncoding riboregulators in stress situations or in specific tissues . Mammalian SINE RNAs modulate the level of mRNAs and proteins by interacting with key proteins involved in gene transcription and translation . Here we show that constitutive production of a plant SINE RNA induces developmental defects in Arabidopsis thaliana and that this SINE RNA interacts with HYL1 , a double-stranded RNA-binding protein required for the production of microRNA and trans-acting small interfering ( tasi ) RNA . We mapped the binding site of HYL1 to a SINE RNA region that mimics the hairpin structure of microRNA precursors . We also found that HYL1 induces conformational changes upon binding to RNA substrates . These data suggest that SINE RNAs modulate the activity of RNAi pathways in Arabidopsis .", "role": "assistant" } ]

[ { "content": "Examine the provided biomedical abstract. Identify and list entities based on the specified categories: [\"Brand\", \"Drug\", \"DrugGroup\", \"UnapprovedDrug\"].\n\nFormat your findings as a JSON object: {\"Brand\": [\"Aspirin\", ...], \"DrugGroup\": [\"Salicylate\", ...], \"Drug\": [\"Phenobarbital\", ...], \"UnapprovedDrug\": [\"Heroin\", ...]}. Each key represents an entity type, and the corresponding value is a list of entities. If no entities are found for a type, use an empty list [].\n\nFocus solely on producing the JSON object.\n\nSource Text:\n\nWhen administered concurrently, the following drugs may interact with amphotericin B: Antineoplastic agents: may enhance the potential for renal toxicity, bronchospasm and hypotension. Antineoplastic agents (e. g., nitrogen mustard, etc.) should be given concomitantly only with great caution. Corticosteroids and Corticotropin (ACTH): may potentiate amphotericin B- induced hypokalemia which may predispose the patient to cardiac dysfunction. Avoid concomitant use unless necessary to control side effects of amphotericin B. If used concomitantly, closely monitor serum electrolytes and cardiac function. Digitalis glycosides: amphotericin B-induced hypokalemia may potentiate digitalis toxicity. Serum potassium levels and cardiac function should be closely monitored and any deficit promptly corrected. Flucytosine: while a synergistic relationship with amphotericin B has been reported, concomitant use may increase the toxicity of flucytosine by possibly increasing its cellular uptake and/or impairing its renal excretion. Imidazoles (e. g., ketoconazole, miconazole, clotrimazole, fluconazole, etc.): in vitro and animal studies with the combination of amphotericin B and imidazoles suggest that imidazoles may induce fungal resistance to amphotericin B. Combination therapy should be administered with caution, especially in immunocompromised patients. Other nephrotoxic medications: agents such as aminoglycosides, cyclosporine, and pentamidine may enhance the potential for drug-induced renal toxicity, and should be used concomitantly only with great caution. Intensive monitoring of renal function is recommended in patients requiring any combination of nephrotoxic medications . Skeletal muscle relaxants: amphotericin B-induced hypokalemia may enhance the curariform effect of skeletal muscle relaxants (e.g., tubocurarine). Serum potassium levels should be monitored and deficiencies corrected. Leukocyte transfusions: acute pulmonary toxicity has been reported in patients receiving intravenous amphotericin B and leukocyte transfusions.", "role": "user" }, { "content": "{\"Brand\": [], \"Drug\": [\"Flucytosine\", \"pentamidine\", \"cyclosporine\", \"miconazole\", \"fluconazole\", \"clotrimazole\", \"amphotericin B\", \"ketoconazole\", \"nitrogen mustard\", \"Corticotropin\", \"flucytosine\", \"tubocurarine\"], \"DrugGroup\": [\"ACTH\", \"skeletal muscle relaxants\", \"Digitalis glycosides\", \"Corticosteroids\", \"Skeletal muscle relaxants\", \"Antineoplastic agents\", \"aminoglycosides\", \"Imidazoles\", \"imidazoles\", \"digitalis\"], \"UnapprovedDrug\": [\"leukocyte transfusions\", \"Leukocyte transfusions\"]}", "role": "assistant" } ]

[ { "content": "Explore the following research question and associated terms. Identify the most suitable dataset from the list provided. Use the dataset descriptions to guide your choice.\n\nInquiry: We examine how graph representation learning methods affect the link prediction performance of a neural network classifier and a\n\nKeywords: biomedical link prediction graphs\n\nDataset Information:\nOGB-LSC: OGB Large-Scale Challenge (OGB-LSC) is a collection of three real-world datasets for advancing the state-of-the-art in large-scale graph ML. OGB-LSC provides graph datasets that are orders of magnitude larger than existing ones and covers three core graph learning tasks -- link prediction, graph regression, and node classification.\nPROTEINS: PROTEINS is a dataset of proteins that are classified as enzymes or non-enzymes. Nodes represent the amino acids and two nodes are connected by an edge if they are less than 6 Angstroms apart.\nBioGRID: BioGRID is a biomedical interaction repository with data compiled through comprehensive curation efforts. The current index is version 4.2.192 and searches 75,868 publications for 1,997,840 protein and genetic interactions, 29,093 chemical interactions and 959,750 post translational modifications from major model organism species.\nChickenpox Cases in Hungary: Chickenpox Cases in Hungary is a spatio-temporal dataset of weekly chickenpox (childhood disease) cases from Hungary. It can be used as a longitudinal dataset for benchmarking the predictive performance of spatiotemporal graph neural network architectures.\n\nAvailable Datasets: A: OGB-LSC B: PROTEINS C: BioGRID D: Chickenpox Cases in Hungary", "role": "user" }, { "content": "BioGRID", "role": "assistant" } ]

[ { "content": "Analyze the following sentence to identify chemical entities of interest. List these entities in a JSON array format. If no entities are found, return an empty array.\n\nText to Analyze:\nOurstudiesofPGC-1alpha-/-micedemonstratethatPGC-1alphaisnotabsolutelyrequiredforprenatalviabilityincludingmitochondrialbiogenesis.", "role": "user" }, { "content": "[]", "role": "assistant" } ]

[ { "content": "Examine the provided biomedical text and determine the answer to the question. Your response should be either \"yes\" or \"no\" based on the information given.\n\nQuestion: Is Tranexamic acid effective for intracerebral haemorrhage?\n\nText: Tranexamic acid did not increase the risk of post-intracerebral haemorrhage seizures in the first 90 days.\nThe primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.INTERPRETATION: Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications.\nCONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect.\nINTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events.\nOf these, two randomised controlled trials (RCTs) comparing intravenous tranexamic acid to placebo (n = 54) reported no significant difference in death or dependency. Three observational studies (n = 281) suggested less haematoma growth with rapid tranexamic acid infusion.", "role": "user" }, { "content": "no", "role": "assistant" } ]

[ { "content": "Review the provided sections from a computer science paper and distill the primary contribution into a single sentence. Provide only the summary sentence.\n\nSections:\n\nWe investigate the extent to which individual attention heads in pretrained transformer language models, such as BERT and RoBERTa, implicitly capture syntactic dependency relations.\nWe employ two methods—taking the maximum attention weight and computing the maximum spanning tree—to extract implicit dependency relations from the attention weights of each layer/head, and compare them to the ground-truth Universal Dependency (UD) trees.\nWe show that, for some UD relation types, there exist heads that can recover the dependency type significantly better than baselines on parsed English text, suggesting that some self-attention heads act as a proxy for syntactic structure.\nWe also analyze BERT fine-tuned on two datasets—the syntax-oriented CoLA and the semantics-oriented MNLI—to investigate whether fine-tuning affects the patterns of their self-attention, but we do not observe substantial differences in the overall dependency relations extracted using our methods.\nOur results suggest that these models have some specialist attention heads that track individual dependency types, but no generalist head that performs holistic parsing significantly better than a trivial baseline, and that analyzing attention weights directly may not reveal much of the syntactic knowledge that BERT-style models are known to learn.\nPretrained Transformer models like OpenAI GPT BID9 and BERT BID1 have shown stellar performance on language understanding tasks.\nBERT and BERTbased models significantly improve the state-ofthe-art on many tasks such as constituency parsing BID5 , question answering BID11 , and have attained top positions on the GLUE leaderboard .\nAs BERT becomes a staple component of many NLP models, many researchers have attempted to analyze the linguistic knowledge that BERT has learned by analyzing the BERT model BID3 or training probing classifiers on the contextualized embeddings of BERT BID12 .BERT\n, as a Transformer-based language model, computes the hidden representation at each layer for each token by attending to all the tokens in an input sentence. The\nattention heads of Transformer have been claimed to capture the syntactic structure of the sentences BID13 . Intuitively\n, for a given token, some specific tokens in the sentence would be more linguistically related to it than the others, and therefore the selfattention mechanism should be expected to allocate more weight to the linguistically related tokens in computing the hidden state of the given token. In this work\n, we aim to investigate the hypothesis that syntax is implicitly encoded by BERT's self-attention heads. We use two\nrelation extraction methods to extract dependency relations from all the self-attention heads of BERT. We analyze\nthe resulting dependency relations to investigate whether the attention heads of BERT implicitly track syntactic dependencies significantly better than chance, and what type of dependency relations BERT learn.We extract the dependency relations from the self-attention heads instead of the contextualized embeddings of BERT. In contrast\nto probing models, our dependency extraction methods require no further training. Our experiments\nsuggest that the attention heads of BERT encode most dependency relation types with substantially higher accuracy than our baselines-a randomly initialized Transformer and relative positional baselines. Finetuning BERT\non the syntax-oriented CoLA does not appear to impact the accuracy of extracted dependency relations. However, when fine-tuned\non the semantics-oriented MNLI dataset, there is a slight improvement in accuracy for longer-term clausal relations and a slight loss in accuracy for shorter-term relations. Overall, while BERT models\nobtain non-trivial accuracy for some dependency types such as nsubj, obj, nmod, aux, and conj, they do not substantially outperform the trivial right-branching trees in terms of undirected unlabeled attachment scores (UUAS). Therefore, although the attention\nheads of BERT reflect a small number of dependency relation types, it does not reflect the full extent of the significant amount of syntactic knowledge BERT is shown to learn by the previous probing work.\nIn this work, we investigate whether the attention heads of BERT exhibit the implicit syntax depen- dency by extracting and analyzing the dependency relations from the attention heads of BERT at all layers.\nWe use two simple dependency relation extraction methods that require no additional training, and observe that there are attention heads of BERT that track more than 75% of the dependency types with higher accuracy than our baselines.\nHowever, the hypothesis that the attention heads of BERT track the dependency syntax is not well-supported as the linguistically uninformed baselines outperform BERT on nearly 25% of the dependency types.\nAdditionally, BERT's performance in terms of UUAS is only slightly higher than that of the trivial right-branching trees, suggesting that the dependency syntax learned by the attention heads is trivial.\nAdditionally, we observe that fine-tuning on the CoLA and MNLI does not affect the pattern of self-attention, although the fine-tuned models shows different performance from BERT on the GLUE benchmark.", "role": "user" }, { "content": "Attention weights don't fully expose what BERT knows about syntax.", "role": "assistant" } ]

[ { "content": "Craft a cohesive chapter for a literature review using the abstracts provided. Focus on the chapter's theme, weaving together insights and findings from the abstracts. Highlight key points and note any research gaps.\nLiterature Review Title: Adversarial Attack and Defense on Graph Data: A Survey \nChapter Title: Application \n1. Abstract of Cited Paper (BIB001): Deep learning on graph structures has shown exciting results in various applications. However, few attentions have been paid to the robustness of such models, in contrast to numerous research work for image or text adversarial attack and defense. In this paper, we focus on the adversarial attacks that fool the model by modifying the combinatorial structure of data. We first propose a reinforcement learning based attack method that learns the generalizable attack policy, while only requiring prediction labels from the target classifier. Also, variants of genetic algorithms and gradient methods are presented in the scenario where prediction confidence or gradients are available. We use both synthetic and real-world data to show that, a family of Graph Neural Network models are vulnerable to these attacks, in both graph-level and node-level classification tasks. We also show such attacks can be used to diagnose the learned classifiers.\n\nReview Chapter:", "role": "user" }, { "content": "In this section, we will introduce the main tasks on graph data, including node-level application, graph-level application and link-level application. Node-Level Application The node-level application is the most popular one in both academia and industry. A classic example is labelling the nodes in webs and social network graphs, which may contain millions of nodes, such as Facebook and Twitter. Most existing papers BIB001 BIB002 ] focus on the node-level applications. All of these papers study node classification in the transductive learning setting whose objective function can be formulated by modifying Eq.1: where f , c i currently is the representation of node target and its associated graph G ci is set as a single graph G. Few existing works have discussed the node-level applications in the inductive leaning setting. However, these applications frequently appear in the real life. For example, the first party only has several large and public network information, such as Facebook and Twitter. The second party has private unlabeled graph data in which the nodes can be predicted by using the information from the first party. In this case, the node-level classification task is no longer transductive learning, but inductive learning. It can be easily formulated by modifying Eq.1: where f and c i currently is the representation of node target. Link-Level Application Link prediction on dynamic graphs is one of the most common linklevel applications. The link prediction tries to predict missing links in current networks, and new or dissolution links in future networks. The corresponding attacks have been discussed in . Compared with node classification tasks, link predication tasks still use node features, but target at the missing or unlabelled links in the graph. Therefore, we can formulate the link predication task by slightly changing the Eq.2 and 3, where c i is the representation of link target, and y i ∈ {0, 1}. Graph-Level Application Graph-level applications are frequently used in the chemistry or medical area, such as drug molecule graphs and brain graphs. In BIB002 , the whole graph is used as the sample instance. Different from this setting, some other graph-level applications use the sub-graphs information of a large graph for several special tasks. Compared with the existing works on node classification and link predication, graph classification use the graph-structure representation as the features to classify the unlabelled graph instances. Therefore, we can formulate the graph classification task by slightly changing the Eq.2 and 3, by setting c i as the representation of graph target. Other potential attacks on different tasks under diverse settings Several works study the adversarial attack on node classification under transductive learning. Chen et al. study link predication tasks with same setting. Different from other works, Dai et al. BIB002 study the attack on classification tasks under the inductive learning. Many different settings of various graph applications have not been discussed and studied. For example, we can study the node classification/link prediction tasks under inductive learning, and graph classification under transductive learning.", "role": "assistant" } ]

[ { "content": "Examine the given text from a research paper in the field of NLP. Your task is to identify the role of the citation within the context provided. Focus on understanding the intent behind the citation and classify it accordingly.\n\nSection Title:\nrelated work\n\nText Before Citation:\nThere has also been work focused upon determining the political leaning (e.g., “liberal” vs. “conservative”) of a document or author, where most previously-proposed methods make no direct use of relationships between the documents to be classified (the “unlabeled” texts) (Laver et al., 2003; Efron, 2004; Mullen and Malouf, 2006). Politically-oriented text Sentiment analysis has specifically been proposed as a key enabling technology in eRulemaking, allowing the automatic analysis of the opinions that people submit (Shulman et al., 2005; Cardie et al., 2006; Kwon et al., 2006).\n\nCitation Text:\nThere has also been work focused upon determining the political leaning ( e.g. , `` liberal '' vs. `` conservative '' ) of a document or author , where most previously-proposed methods make no direct use of relationships between the documents to be classified ( the `` unlabeled '' texts ) ( Laver et al. , 2003 ; Efron , 2004 ; Mullen and Malouf , 2006 ) .\n\nText After Citation:\nAn exception is Grefenstette et al. (2004), who experimented with determining the political orientation of websites essentially by classifying the concatenation of all the documents found on that site. Others have applied the NLP technologies of near-duplicate detection and topic-based text categorization to politically oriented text (Yang and Callan, 2005; Purpura and Hillard, 2006). Detecting agreement We used a simple method to learn to identify cross-speaker references indicating agreement. More sophisticated approaches have been proposed (Hillard et al., 2003), including an extension that, in an interesting reversal of our problem, makes use of sentimentpolarity indicators within speech segments (Galley et al., 2004).", "role": "user" }, { "content": "Background", "role": "assistant" } ]