dataesr/scientific-paragraphs-categorization huggingface dataset:
We began by automatically clustering the unaffected and affected juvenile parasites based on their differential phenotypic response. The existence of such a clustering and the fact that it could be identified without manual intervention, not only provided a rigorous and objective basis for the subsequent expert analysis, but also allowed us to quantify and visualize the phenotypic response space of the parasite. For the above automated analysis, photographic images were taken at each time point and compound concentration using a Zeiss Axiovert 40 C inverted microscope and a Zeiss Axio-Cam MRc digital camera controlled by AxioVision 40 (version 4. 8. 1. 0) software, as previously described  [20, 55, 69]. The images were segmented (i. e. , individual parasites were differentiated from background) using the Asarnow-Singh segmentation algorithm  [64] , to yield a total of 4,125 parasites (1,047 control and 3,078 drug treated) across the entire study.
Molecular modeling of the ATP-binding site of SmPLK1 To understand whether residues in the SmPLK1 ATP-binding site will accommodate the human benzimidazole thiophene PLK1 inhibitors, we built a homology model of SmPLK1 from the human ortholog's structure (PDB ID: 2YAC). The homology model was constructed using the software PRIME (v. 3. 9; Schrödinger Inc). GSK benzimidazole thiophene inhibitors, GSK461364, GSK1030058, GSK326090 and GSK483724 were built using Maestro's Edit/Build panel (v. 10. 1; Schrödinger Inc). LigPrep (v. 3. 3; Schrödinger Inc. ) was used to minimize the ligand structures. We docked the ligands using Glide (v. 6. 6; Schrödinger Inc. ) with the standard-precision docking scoring function. To compare the docking mode of the ligand GSK461364, we also docked it against the human PLK1 structure.
Similar binding pose of a benzimidazole thiophene in the ATP-binding sites of human and schistosome PLK1 In order to assess the binding mode of the benzimidazole thiophenes, we docked a representative inhibitor, the clinical Phase I drug candidate, GSK461364, in the ATP-binding site of the huPLK1 structure (pdb id: 2yac) and in an homology model of SmPLK1. The predicted binding poses, shown in Fig  5A , are very similar (0. 7Å heavy atom RMSD), as are the Glide-SP docking scores, which were -9. 3 and -9. 6 for the human and S. mansoni enzymes, respectively. Thus, the data from the molecular modeling calculations suggest that the current benzimidazole thiophenes bind to the SmPLK1 without undue energy penalties, as observed by their similar docking scores and predict that the binding orientation will be very similar between huPLK1 and SmPLK1.
Acknowledgments We are indebted to  KC Lim  for decades of expert and patient technical assistance with the schistosome life-cycle. We thank  Roopa Ramamoorthi  of  BIO Ventures for Global Health  for facilitating initial interactions with GSK. JChem for Excel (version 6. 0. 3. 947;2013; ChemAxon (http://www. chemaxon. com. )) was used to draw chemical structures.
After a median of 12•7 years of follow-up, tamoxifen signifi cantly reduced all new breast cancer events by 29%, with a signifi cant impact on ipsilateral DCIS recurrence and contralateral tumours, but no eff ect on ipsilateral invasive recurrence. 8 ntil now no data have been available on the use of aromatase inhibitors for DCIS. Two trials of very similar design have been conducted. Both compared anastrozole with tamoxifen in postmenopausal women with ERpositive or PgR-positive DCIS. The NSABP B-35 results will be reported elsewhere. 10 Here, we report the fi rst results from the International Breast Cancer Intervention Study-II DCIS (IBIS-II DCIS).
Randomisation and masking Participants were randomly assigned in a 1:1 ratio to receive 1 mg/day oral anastrozole or 20 mg/day oral tamoxifen. Randomisation was stratifi ed by major centre or hub. Randomised blocks (six, eight, or ten) were used to maintain balance and randomisation was performed centrally by electronic contact with the main trials centre. All treatment was given on a daily basis for 5 years and all women took two tablets per day (tamoxifen and anastrozole placebo, or anastrozole and tamoxifen placebo). All IBIS-II DCIS personnel, participants, and clinicians were masked to treatment allocation, except for the IBIS-II DCIS trial statistician, who had access to unblinded data, and the independent data monitoring committee, who reviewed interim data for safety purposes.
Adherence was calculated using the Kaplan-Meier method, censoring at breast cancer recurrence, death, or 5 years of follow-up. All p values were two-sided. We estimated a required sample size of 4000 on the basis of a 1•6% annual recurrence rate for tamoxifentreated patients with a 16•7% relative reduction for anastrozole to show non-inferiority, and a 33% reduction to show superiority with 5-year median follow-up. Recruitment to the trial closed on Feb 8, 2012, after enrolment of 2980 of the 4000 planned participants. During the course of the trial, local recurrences occurred at less than half the rate anticipated in the analysis plan, due largely to improvements in the surgical treatment of DCIS. Consequently, the required numbers of events anticipated in the protocol would not be reached for a number of years, and the IBIS-II steering committee, with the agreement of the independent data monitoring committee, took the decision to analyse and report the results at this stage; data were collected up to the cutoff date of Sept 30, 2015.
Acknowledgments This study was funded in part by  Cancer Research UK  ( C569/A5032 ,  C569/A16891 ,  C8162/A26893 ), the  National Health and Medical Research Council Australia  ( GNT300755 ,  GNT569213 ), and the  Breast Cancer Research Fund. Support was also provided by  AstraZeneca , who also provided anastrozole, tamoxifen, and matching placebos, and  Aventis Sanofi  who supported the bone density study. The  IBIS-II study  was sponsored by  Queen Mary University of London, UK.
The aim was to recruit XSL • FO RenderX a total of 1540 participants (220 participants per center) to allow for a potential 20% dropout rate, planned using a priori power calculation  [25]. Power calculations were conducted in Minitab and based on glucose and omega-3 fatty acid concentrations within European adult populations  [25]. The study had ethical approval from the corresponding committees of all participating centers (Germany, Greece, Ireland, the Netherlands, Poland, Spain, and the United Kingdom) and was conducted from August 2012 to March 2014. The Food4Me trial was registered as a randomized control trial (NCT01530139) at Clinicaltrials. gov. The dietary feedback system, described in this paper, was used to deliver PN advice to participants randomized to receive Level 1 PN only (n=414).
Development of a Gradation System for Coding of Nutrient Intakes Dietary intake data were collected throughout the Food4Me study using the recently developed and validated Web-based Food4Me FFQ  [26, 27]. Previous evidence has shown the Food4Me FFQ to have good agreement with the EPIC-Norfolk FFQ and moderate agreement with a 4-day weighed food record for the assessment of both nutrient and food group intakes, rendering it a useful tool for ranking individuals based on nutrient and food group intakes  [26, 27]. The Institute of Medicine (IOM) dietary reference intakes were used as a basis for developing a gradation system to categorize nutrient intakes automatically after completion of the Web-based Food4Me FFQ by participants  [28, 29]. Institute of Medicine reference values were used because (1) they were the most up-to-date values available and (2) recommendations vary across Europe with a need to find standardized reference intakes.
Automation of the Dietary Feedback Nutrient intake analysis was automated for use in the Food4Me study, with the nutrient-related goals and feedback messages derived manually (using the priority system and decision trees) by Food4Me researchers using their own judgment to overrule the feedback system when appropriate. After completion of the Food4Me intervention study, the feedback system was automated by Creme Global (Dublin, Ireland). Therefore, a comparison of the automated and manual-based approaches was possible. The system was automated by firstly capturing the manual decision process for selecting priority nutrients, based on nutrient intake analysis, in a computer algorithm (written in the PHP programming language). Second, the decision trees for selection of feedback messages were encoded in table-like data structures and stored in a relational database (MySQL).
Analysis The first part of the analysis examines the manual use of the feedback system during the Food4Me PoP study. Descriptive statistics were computed to describe the general characteristics of participants across each of the 7 centers using general linear model analysis with least significant difference post hoc. Nutrient-related goal selection frequency was examined across each of the 7 countries. All statistical analyses were conducted using IBM SPSS Statistics version 20, and P<. 05 was considered statistically significant. The second part of the analysis compares the dietary feedback provided by researchers during the Food4Me PoP study with feedback generated automatically by the computerized algorithms and messaging system for participants in Level 1 of the intervention. The level of agreement between the manual (researcher) and automated systems was assessed for both nutrient-related goal selection and feedback advice using baseline data for Level 1 participants, as illustrated in Figure  3.
Agreement was categorized as either "complete agreement," "complete disagreement," or "partial agreement" (data not shown). Overall agreement for feedback advice message was computed by summing the number of participants categorized into the 3 agreement groups for each nutrient-related goal across the countries. Steps taken to compare the level of agreement between the manual and automated systems for nutrient-related goals and feedback advice. The agreement between the 2 systems in selecting the 3 nutrient-related goals was assessed for each participant. Nutrient-related goal agreement between the 2 systems was also evaluated for all 3 nutrient-related goals in random order. Where there was agreement between the 2 systems for nutrient goal selection, agreement in the feedback advice message(s) selected was then assessed between the two systems.
Material and Methods: The screen was performed in 384-well plates by using a pipetting robot and a flow cytometer equipped with a plate loader. REH leukemia suspension cells were treated with the LOPAC 1280 and Selleck Cambridge cancer 384 compound libraries in the presence and absence of the Wee1 inhibitor MK1775 (4h, 400nM), stained with the DNA-stain Hoechst and the DNA damage marker yH2AX, and analyzed by flow cytometry using the FlowJo software. In addition to drugs present in the compound libraries, three additional Chk1-inhibitors (LY60638, MK8776 and UCN01) were included in subsequent validation experiments.
Snow avalanche data in the French Alps and Pyrenees have been recorded for more than 100 years in several databases. The increasing amount of observed data required a more integrative and automated service. Here we report the comprehensive web-based Snow Avalanche Information System newly developed to this end for three important data sets: an avalanche chronicle (Enquête Permanente sur les Avalanches, EPA), an avalanche map (Carte de Localisation des Phénomènes d'Avalanche, CLPA) and a compilation of hazard and vulnerability data recorded on selected paths endangering human settlements (Sites Habités Sensibles aux Avalanches, SSA). These data sets are now integrated into a common database, enabling full interoperability between all different types of snow avalanche records: digitized geographic data, avalanche descriptive parameters, eyewitness reports, photographs, hazard and risk levels, etc.
g. ,  Laternser and Schneebeli, 2002; Eckert et al. , 2010a, c; Corona et al. , 2012; Castebrunet et al. , 2014). Most of the countries exposed to avalanche risk perform a regular registration of avalanche activity  (Bonnefoy-Demongeot et al. , 2014). In Switzerland, avalanche data have been systematically collected since 1950 by the WSL Institute for Snow and Avalanche Research SLF. Two types of data are stored: the Avalanche Observations (AO) database which provide data of general avalanche activity (number, size and impact), including the specification of the triggering mechanism, and the Destructive Avalanche Database (DADB, also known as ADB) covering more than 10 000 individual avalanches that caused property damage or affected people  (Laternser and Schneebeli, 2002; Techel and Zweifel, 2013).
Avalanche data in the United States were initially compiled into avalanche atlases at local scale  (Frutiger, 1964; Miller et al. , 1976; Armstrong and Armstrong, 1977, 2006). A generalized long-term Westwide Avalanche Published by Copernicus Publications on behalf of the European Geosciences Union. E. Bourova et al. :  A web-based information system for snow avalanches in France Network (WWAN) database of weather, snowpack and avalanche information has been available since 1967  (Williams, 1994; Tremper, 1996). The WWAN database contains records for both natural and controlled avalanches, providing daily data on the number and size of avalanches  (Birkeland and Mock, 2001). In Canada, the Information Exchange (InfoEx) database of the Canadian Avalanche Association (CAA) provides daily avalanche occurrences since 1991 submitted by avalanche industry professionals  (Haegeli and McClung, 2007; Haegeli et al.
, 2014). In Europe, the observational, topographical and meteorological data for extreme or deflected avalanche events are available in the EU CADZIE database  (Domaas et al. , 2002). A large campaign of avalanche observations was conducted in the former Soviet Union from 1974 to 1991. These observations were compiled into the Avalanche Cadastre of the USSR divided into 20 volumes and covering wide areas of important avalanche activity  (Gidrometeoizdat, 1984 (Gidrometeoizdat, -1991)). Several databases provide geolocalized information about avalanche paths. In the Catalan Pyrenees, avalanche data are stored into the Avalanche Database of Catalonia (ADBC) with more than 17 000 mapped avalanche paths  (Oller et al. , 2006). In the Italian Alps, the avalanche cadastre includes 3000 avalanche paths with accurately plotted borders  (Debernardi and Segor, 2013).
Spatial characteristics of approximately 2300 avalanches were recently obtained in Japan from aerial photographs  (Akiyama and Ikeda, 2013). Current advances in computer technologies allow for using relational databases, Geographic Information System (GIS) tools and web applications to store snow avalanche observations and share them via the Internet  (Tremper, 1996; Bründl et al. , 2004; Scott, 2007; Duclos et al. , 2008; Scott, 2009; Ekker et al. , 2013). Web-based applications represent also a suitable software solution to assist the observers in their daily work of data collection and validation. They are used to support simultaneous access for a wide range of users with different roles. Such new web-based tools with computer assisted workflow have been recently implemented to support the forecasters in producing avalanche bulletins in Switzerland  (Ruesch et al.
However, the management of the increasing amount of available data as well as new research and operational needs that progressively emerged made the development of a new integrated information system unavoidable. It should guarantee the interoperability among the different data sets as well as a modulable multi-user and multi-level accesses. In a first attempt to this purpose, a web application has been designed for the EPA and SSA tools with a multi-user access and a common database  (Vidaud-Barral et al. , 2010). However, the CLPA was not integrated in this work because the needs were not fully defined at that time. In this paper, we present a generalized web-based snow avalanche information system that includes all CLPA, EPA and SSA modules. We also illustrate the main technical advantages of this new system: (1) it provides a computer assisted homogeneous workflow for observers, accessible from everywhere; (2) it creates a real time multi-user collaboration platform; (3) it insures the data consistency, interoperability and security; (4) the system is built on a stable framework that can be easily maintained and can be further extended to include additional components and services.
In what follows, in Sect. 2, we describe the avalanche data available in our database and the corresponding acquisition processes. In Sect. 3, we summarize the main requirements of the system and the user's needs. On this basis, we present in Sect. 4 the new modular architecture that enables a full interoperability among its different components: EPA, CLPA and SSA. Finally, in Sect. 5, as an illustrative example, we detail the implementation of the web platform through key operations for the CLPA workflow.
Avalanche chronicle: EPA The EPA initially started in Savoie  (Mougin, 1922)  but has been rapidly extended to the whole French Alps and Pyrenees. Nowadays, the EPA database contains nearly 100 000 avalanche events on around 3900 paths. A key strength of the EPA data set consists in the fact that it provides a long temporal series of avalanche observations on well-specified paths. Some of EPA paths have been observed for more than 100 years. The data are continuously updated by observers through annual campaigns that start in September and end in August. An EPA path is placed under permanent or intermittent observation. The EPA paths with easy access are permanently visited by the observer after each snowfall. For hardly accessible areas, the observer visits a path at least once in a winter.
The observation of such paths is considered as intermittent. To decide whether an occurred avalanche event is representative enough for a path, an observation threshold and an alert threshold are defined. The choice of these thresholds is based on expert judgement considering geomorphological characteristics of each site. Important avalanche events that reach the observation threshold are regularly registered into the database. Smaller avalanches stopped above the observation threshold are generally not registered. However, sometimes such small avalanches can also be recorded if the observer considers them significant for some reasons (important snow volume, damages, victims). Major avalanches that reach the alert threshold are recorded in the database with a special alert status. For these events, the observer has to alert the National Forest Office and IRSTEA within 48 h for possible additional investigations.
A map and a photograph of the EPA path number 7 in Molines-en-Queyras township. The observation threshold is plotted as a solid blue line. The alert threshold is drawn as a dashed blue line. For this path, the observation threshold is chosen near a large rock block while the alert threshold corresponds to a cross-country ski track. Both thresholds are easily visible and can be identified by an observer from the observation point. The EPA database stores all avalanche events that reached at least the observation threshold. Figs. 1  and 2. The EPA path limits, the positions of observation and alert thresholds, the thalweg and the observation point (i. e. , the exact place that the observer has to visit regularly) are plotted in Fig. 1. Figure  2  shows the list of recent avalanche events recorded on this path.
If required, these data can be completed by aerial photo analysis realized by a photo-interpreter. Eyewitness account and aerial photo-interpretation techniques are used independently and plotted on the CLPA map as layers of different colors. An observer collects available data for each CLPA avalanche path in the zone under his responsibility. The data for a given path are summarized into a so-called CLPA sheet (Fig. 5 ). On the basis of the collected evidences, the observer decides whether the existing avalanche limits should be extended on the CLPA map or not. Thus, a CLPA sheet supplies a complementary textual description of a path to its geographical limits. It contains the following details: information about the inquiry (type, opening and closure dates, investigation zone); information about the studied avalanche path (path number, path label, location, ski resorts, corresponding EPA paths, protection structures); proof (or testimony) of an avalanche study, which contains an avalanche description in text format and should be based on at least one of the following sources: a witness, a photograph or an archival document; identification number (idGis) of the geographic object corresponding to the avalanche path limits in the geographic information system.
Modifications of avalanche limits proposed by the observer are systematically cross-checked by the CLPA manager, who plays the role of observer in charge of control. The collected evidences and proposed CLPA modifications are usually also cross-checked by other concerned participants depending on the CLPA study (municipality officers, technical services, other CLPA and EPA observers). The CLPA manager validates the new edition of the CLPA and closes the inquiry. After the inquiry closure, no more modification can be applied to CLPA sheets or avalanche limits. When the acquisition process is finished, the data distributor prepares an official distribution of the CLPA. He sends updated CLPA materials in paper format (maps, sheets, mountain massif description, etc. ) to all stakeholders concerned by the current modification of avalanche limits.
Classification of inhabited sites exposed to avalanches: SSA The SSA database is an inventory of 1431 inhabited sites exposed to snow avalanches in France. The SSA inventory classifies the dangerousness of each site accordingly to three categories: strong, doubtful and low. The SSA concerns only the avalanche paths threatening inhabited buildings during winter seasons. The data acquisition for the inventory has been performed from 2003 to 2009 by the French National Forest Office following the method developed at IRSTEA by  Rapin et al. (2006). No new data are collected at present. The data contain detailed information about the vulnerability, morphology, history and snow-climatology of each SSA site and provide a complementary information to the EPA and CLPA data sets. The SSA data are useful during high-risk situations -for example, to prioritize evacuation of people living at most exposed locations.
, 2014). Finally, we used the conceptual data model and system specifications to create a database model and to design the architecture of the generalized system. We defined the specifications of the avalanche information system through regular meetings with the EPA, CLPA and SSA managers and observers. One of the most important requirements was the workflow homogenization for the observers from different affiliations (IRSTEA, French National Forest Office, partners). In the past, the observers from the French National Forest Office used to send a paper report to a manager in IRSTEA who copied the obtained data into a Microsoft Access database via a desktop application. Then, the observers from IRSTEA performed the data entry in a local copy of the Microsoft Access database that was later synchronized with the central database.