dataesr/scientific-paragraphs-categorization huggingface dataset:
(c) Execution and implementation of workflows Implementing the large-scale execution of workflows for EBV data production requires appropriate computing infrastructure. This probably requires workflow management systems that allow an automated execution of data-intensive scientific workflows on distributed computing infrastructures by multiple users  (Deelman et al. , 2009; Liu et al. , 2015; Hardisty et al. , 2016). Since infrastructure providers want to be flexible in terms of which computing environment and technologies they use, a workflow solution neutral to specific hardware architectures and execution models is needed. The particular software for managing these workflows is less critical than the use of a standard execution-independent mechanism of workflow representation. An open question is who can take on the responsibility and cost of implementing specific EBV workflows.
It is probably not the role of data publishers, and few existing biodiversity research infrastructures are currently well funded, sustained and able to do this. Two basic options for the technical production cycle exist. The first option is a 'create-on-demand' process that requires ready access to relevant raw data, the workflow and processing capacity at any time of interest. It requires that the source data for computing EBV data products are compliant with technical and semantic interoperability standards to allow on-demand machine translation and mapping of algorithms. The second option is a periodic and systematic production of EBV data products (e. g. annually). This reflects that EBV data products are published/archived as an ever-extending data archive that can be consulted for a specific place or area of interest (local, regional, national) at the time of interest.
VI. METADATA AND DATA-SHARING STANDARDS (1) The need for standardized metadata to describe EBV data products The development of EBV data products from multi-source observation data in a workflow-oriented e-infrastructure depends on standardized metadata to make data findable, accessible, interoperable and reusable (FAIR principles;  Wilkinson et al. , 2016). When a community agrees to such standardization efforts, the result is consistently presented information that can be searched using known terms. Together with controlled vocabularies (i. e. carefully selected lists of words and phrases) and ontologies (i. e. formal statements of relationships among concepts represented by vocabulary terms) this facilitates sharing and discovery of biodiversity data because it allows consistency for interoperability and machine reasoning  (Thessen & Patterson, 2011; Michener & Jones, 2012).
The ideal metadata for assessing fitness-for-purpose of potential EBV-useable data sets (cf. Fig. 3 ) would provide information about the extent, resolution, measurement units and uncertainties of spatial, temporal and taxonomic data dimensions. This would allow machine-readable discovery and aggregation of large numbers of candidate data sets  (Wilkinson et al. , 2016). For a data set to be considered EBV-ready (see Fig. 3 ), its structure needs to be transformed and harmonized into interoperable formats and units. Furthermore, the often-complex workflows required to consistently reproduce derived and modelled EBV data products (see Fig. 3 ) must document data provenance, i. e. a record of the data's origin and what has been done with it. This includes recording the modelling and processing steps in a consistent manner.
2) Current standards for sharing biodiversity data To date, there is no agreed schema for documenting EBV data products, but there are many ongoing efforts that can facilitate the capture of metadata for ecological data (e. g. Michener et al. , 1997; Fegraus et al. , 2005; Wieczorek et al. , 2012; Walls et al. , 2014). Here, we summarize the most relevant existing standards related to species distribution and abundance EBVs (Table  6 ). (a) The Darwin Core standard and the Event Core The Darwin Core (DwC) provides a set of terms that facilitate the exchange of information about the occurrence of organisms in nature and the resulting specimens in biological collections  (Wieczorek et al. , 2012). As originally conceived, it is a data and metadata standard for reporting incidental observations or specimens (summarized under 'opportunistic incidence records' in Section IV.
1). To help organize the 169 terms currently in the standard, these are grouped into several categories or classes. A list of terms and descriptions is available at http://rs. tdwg. org/dwc/terms/. Until recently, the DwC has been insufficient to provide detailed reporting on many aspects of inventories because no DwC terms existed to report the scope, effort and completeness of surveys (which is critical information for assessing potential absence of species). New DwC terms have begun to close these gaps, including better capture of quantities found within sampling units. These include biomass or number of individuals as proxies of abundance, capture of sample effort reporting and identifiers relating parent-child relationships between events to represent hierarchical sampling designs. In addition, a new organization of the data in the DwC has recently been proposed that is particularly suitable for EBV data products.
The vast majority of records in DwC format are 'occurrence core' records that have broad use for reporting opportunistic incidence records in that profile format. However, there is now the possibility to make the 'event' the core, and to place occurrence records as related to that event  (Wieczorek et al. , 2014). This enables data holders to share structured survey data such as population time series or presence-absence data (GEO BON, 2016), for instance through GBIF's Integrated Publishing Toolkit (IPT) (http://www. gbif. org/sites/default/files/ gbif_IPT-sample-data-primer_en. pdf ). However, standard details about sampling method and effort are not required in these 'Event Core' fields. One possible option is to utilize extensions for various kinds of inventories, with the caveat that this may create new challenges with heterogeneous data and interpretation.
g. based on taxonomic criteria without downloading and inspecting large data sets). Other EML modules describe methods and protocols of sampling or processing or contain information on responsible persons and organizations, software resources, or access rules. EML metadata and DwC data files can be bundled into DwC archives, which are self-describing zip files produced during data publication. These are ultimately harvested by data aggregators such as GBIF. For this, data publishers use EML standard fields to describe ownership, creation and licensing  (Robertson et al. , 2014).
(c) Other specifications and standards A number of other specifications and standards can serve the need for metadata associated with EBV workflows. Several ontologies have been developed with the aim of improving data aggregation and integration across the biodiversity domain, including the Biological Collections Ontology (BCO)  (Walls et al. , 2014) , the Population and Community Ontology (PCO)  (Walls et al. , 2014) , the Environmental Ontology (ENVO)  (Buttigieg et al. , 2016)  and genomic standards such as the Minimum Information about any (x) Sequence (MIxS)  (Yilmaz et al. , 2011). For in situ biotic inventory processes, the Humboldt Core provides a vocabulary for describing spatial, temporal, environmental and taxonomic information (https://mol. org/humboldtcore/). It includes methodology and effort reporting and a way to assess how a survey and inventory was performed and what was collected (e.
g. abundance information and how it was recorded). Other ontologies for describing observations and measurements based on digital or material sample evidence include the Observation and Measurements ontology (O&M) and the Extensible Observation Ontology (OBOE) (Table  6 ). For Earth observation data, the ISO 19115/19157 metadata standard allows detailed documentation of spatial and temporal data characteristics, measurement units, legal and licensing restrictions, data quality and provenance. The ISO standard is widely used to describe satellite products and other environmental data, and is a core component of the Global Earth Observing System of Systems (GEOSS). These standard reporting mechanisms may themselves be linked to general models for provenance such as PROV  (Missier, Belhajjame & Cheney, 2013)  to assure both human and machine-readable information about provenance.
(3) Metadata standards for EBV data products Practical integration of the above-mentioned standards must still be achieved in the context of the species distribution and abundance EBVs. Lack of such integration was evident when investigating the four example projects (see Section V). However, aggregators such as GBIF already provide workflow services that utilize community-developed standards for expression of occurrence data, e. g. by creating a centralized resource in DwC format with additional complementary metadata files in EML  (Robertson et al. , 2014). This includes the steps needed to produce EBV-ready data sets (workflow steps 4-6 in Fig. 3 ), e. g. to combine and join data sets of opportunistic incidence records using a shared taxonomic backbone, and with capacity to perform geographic quality checks (e.
We further thank  Antonio Torralba Silgado ,  Juan Miguel González Aranda ,  Jesús Miguel Santamaría ,  Clara Luján ,  Alfonso Herrera , the  University of Seville , and the  Joint Research Unit LifeWatch Spain-JRU LW. ES for supporting our second workshop in Sevilla, Spain, from  13-15 June 2016. Financial support came from the  European Commission  (grant  654003 ). C. A. additionally received funding from the  LifeWatchGreece infrastructure  ( MIS 384676 ), funded by the  Greek Government  under the  General Secretariat of Research and Technology (GSRT) ,  ESFRI Projects and National Strategic Reference Framework (NSRF). M. O. was supported by the  Swedish LifeWatch  project funded by the  Swedish Research Council  (Grant no. 829-2009-6278 ), and J. E. by the  Australian Research Council  (grant  FT0991640 ).
Statistical Analysis We report the average (mean) and the standard deviation (SD) from at least three experimental values. In Figures  2B  and 4B , we report the ratio R3 (±SD3) of two numbers R1 ± SD1 and R2 ± SD2, with R3 = R2 R1 and SD3 R3 = SD1 R1 2 + SD2 R2 2. The statistical significance of differences between two averages was determined by a Student's t-test (two independent samples, with two-tailed distribution) using GraphPad Prism software. 1.
Of note, we observed this phenomenon when the cells were grown at both 25 and 37 • C. We verified that the lower amount of YcgZ in the wild type was not due to a lesser expression of ycgZ by quantifying ycgZ messenger levels. RT-qPCR experiments showed that ycgZ was similarly expressed in both strains (see Supplementary Table  S8 ), suggesting that the higher level of YcgZ protein observed in the lon mutant is likely due to a higher stability of the protein in the absence of Lon. Our data illustrated in Figure  6A  also shows similar amounts of YmgA and YmgC proteins when overexpressed in the wild type and in the lon strains. We could not detect significant amount of YmgB in any of the strains tested even though high level of ymgB messenger was measured by RT-qPCR in both strains (data not shown).
Adenoviral transduction and FACS analysis Cell transduction with adenoviral vector was performed using 1×10 5 U2OS cells seeded into 24-well plates. Cells were pre-treated with 100 μM CilioD for 30min or with 10mM of 3'MA or 50μM of Chloroquine for 3h or DMSO and DMF as vehicle control. Cells were transduced with 50 physical particles per cell of either GFP expressing WT or M1 in the presence of drugs followed by medium replacement with drug-free medium after 3h. Cells were analyzed 24h later by flow cytometry for GFP expression. Acquisitions were done on a FACSCantoII cytometer (BD Biosciences) and the data were processed and analyzed by the FACSDIVA software (BD Biosciences). U2OS depleted cells (siGAL3/8/9, siCTRL, shATG5/p62/NDP52 and shCTRL) were transduced following the same procedure.
Confocal microscopy, live-cell imaging and image analysis Confocal images were taken on a Leica SP5 confocal microscope equipped with Leica software and analyzed as detailed in SI. For quantitative image analysis we analyzed for each condition/ time point at least 10 cells with >50 virus particles each (n>500). Live cell imaging was performed as described previously  [39]. Briefly, cells were seeded in ibidi μ-slide VI 0. 4 (Ibidi), and images were acquired using a Leica spinning-disk microscopy system equipped with an environmental chamber heating the whole optical system to 37˚C. Frames were taken every second (x100 objective) for each color channel and recorded using MetaMorph software and assembled in ImageJ.
Raw data were recorded in MetaMorph and assembled and processed using ImageJ software. (AVI) S2 Movie. Related to Fig 10: Intracellular trafficking of LC3-positive AdV. Live-cell imaging showing intracellular trafficking of LC3 positive WT virus to the perinuclear region. Stable expressing U2OS-LC3-GFP cells were infected with Alexa594 coupled WT viruses and imaged using spinning-disk confocal microscopy at a rate of 1 frame/sec for each channel. Raw data.
Acknowledgments We would like to thank  M. Priault ,  M. Djavaheri-Mergny ,  N. Ktistakis  for reagents and antibodies. We would like to thank  S. Boulant ,  E Chevet , and all members of the  Club d'autophagy bordelais (CAB)  for valuable discussions and  I. Seiliez  for critically reading of the manuscript. We thank the members of the  Plateforme de Vectorologie and Cytometrie (FR Transbiomed)  for the preparation of the lentiviral vectors and FACS analysis. The microscopy was done in the  Bordeaux Imaging Center , a service unit of the  CNRS-INSERM and Bordeaux University , member of the national infrastructure France BioImaging. H. W. is an INSERM fellow.
This work was in part supported through  Agence national de recherche  ( ANR grant ) ( ANR 14 IFEC 0003-04 ,  Infect-ERA ; project eDEVILLI, HW), through the  Initiative de excellence of the Bordeaux University (IdEX-FAC  grant, project  BRCAvir, HW ) and through a  PICS CNRS grant ,  HW ). The funders had no role in study design, data collection and removal.
epidemiological analysis Epidemiological data concerning animal and human rabies cases were collected from published bibliographical references and epidemiological reports issued by the competent public authorities, and more especially those of Morocco's National Food Safety Office (ONSSA) for animal rabies cases and the Ministry of Health for human cases. In the event of contradictory data from different sources, the highest figure has been chosen due to the substantial risk of underreporting  (13). The epidemiological characteristics of animal rabies in Morocco are discussed for the period from 1928 to 2015. There follows a presentation and discussion of the rabies patterns in Morocco (reservoir, animal species affected, seasonal changes, and geographical distribution) as well as measures taken at different times to tackle the disease and the suggestions of various authors in order to improve the situation.
Mapping of the evolution of the number of animal rabies cases in the Moroccan provinces was performed using ArcGIS 10. 1 software. The number of human rabies cases reported annually from 1974 to 2015 is analyzed and discussed. There is a discussion on the geographical distribution of cases of human rabies. The provided PEP protocol is discussed as well as the laboratory diagnosis. Propositions of improvement are formulated. A review of the genetic characterization of rabies virus isolates in Morocco is realized. Molecular epidemiology data are compared with classical epidemiology findings.
Moroccan Dog Population It is crucial to remain informed about the dog population in order to draw up a realistic and effective canine rabies control plan. A synthesis of the studies that are interested in the size of the Moroccan canine population is carried out in order to have an estimate of this population. This is based on a comparison between the results of estimations of the dog population in the framework of an amendment to the 1993 rabies control plan, the NRCP of 2001-2010 and other international studies or studies in Maghreb countries. The data are extrapolated depending on the human:dog ratio chosen in order to estimate the size of the dog population. Demographic data were provided by official Moroccan authorities (Health Ministry website: http://www. sante. gov. ma). The current state of dog population control and suggestions for improvement are also presented.
Vaccination coverage of the Dog Population The vaccination coverage of the dog population is estimated by combining data on vaccination in urban areas by private veterinarians with that in rural areas following government-run mass vaccination campaigns. Dog population data are related to the estimated human:dog ratio. Vaccination coverage is analyzed and suggestions put forward on how to improve the situation. Data on vaccination in urban areas were extrapolated from the number of doses of rabies vaccine sold between 2009 and 2015 to veterinarians in the private sector. The data were obtained from veterinary pharmaceutical companies with a rabies vaccine registered in Morocco 2 during the same period. Propositions for dog population vaccination coverage amelioration are formulated with reference to Moroccan experiments in oral dog rabies vaccination.
acKnOWleDgMenTs The authors want to acknowledge the following people for their contribution and advice. From ANSES: Nancy Laboratory for Rabies and Wildlife: Jacques Barrat, Evelyne Picard-Meyer, Marie José Duchêne. From Morocco: Id Sidi Yahia Khadija, Ettair Mina, Zine Hind, El Aounia Kebdi, Sahnoune Saadia, El Ghafki Amina, Lhor Youssef, Lazaar Yassir, and Azami Ahmed. The authors thank Michel Aubert and François-Xavier Meslin for hard involvement and support in dog rabies control in Morocco and Delphine Libby-Claynrough for English editing.
The study was coordinated by the coordinating center (CC) based at the University Hospital (CHU), Bordeaux. The study was conducted in accordance with the international guidelines for Good Clinical Practice and the principles of the Declaration of Helsinki. Patients provided written informed consent. The study was approved by the regional ethics committee ("CPP Sud-Ouest Outre-Mer", N˚2005/09) and registered on Clinicaltrials. gov: NCT00241254.
Randomization and masking Patients were allocated to receive either CPM or MP using a web-based secured system according to a randomization list generated and kept confidential by the statistician of the Clinical Trials Unit (CTU, CHU Bordeaux) using SAS 9Á1 ©. Randomization, with a 1:1 ratio, was stratified by centre, with blocks of size four for small sites and size six for others. All study personnel were blinded to group allocation, including the neurologists and nurses administrating the treatments. Because the study drugs have potential adverse effects that may make patients and clinicians guess the treatment received, outcome assessments were performed by an evaluating neurologist (EN); the treating neurologist (TN) evaluated the clinical state, safety and tolerability. Study drugs were prepared in hospital pharmacies in similar infusion vials that precluded the identification of the group assignment by patients and study personnel.
Key secondary outcomes were the proportion of patients with sustained EDSS progression at 2 years, MS Functional Composite (MSFC) z scores progression, the relapse rate, and the proportion of relapse-free patients. When patients refused to go on with their follow-up visits during the course of the trial, efforts were made for obtaining the outcome criteria at their two-year visit. Treatment failure was defined as either EDSS progression at 2 years or missing data on EDSS at 2 years due to early discontinuation of treatment because of adverse events. Adverse events were collected according to a standardized method using the EudraVigilance database.
Statistical analysis For the main analysis of the primary endpoint (time to sustained accumulation of disability over 16 weeks), an intention-to-treat strategy was employed. A survival frailty model that considered sites as random effects was first fitted. If the variance of the random effect was found to be negligible, a Cox model was fitted with and without adjustment  [26]. Adjustment covariates were the presence of relapses in the year preceding the trial and the disease duration. The interaction between treatment effect and relapses was tested. The time to confirmed EDSS progression was censored whenever patients stopped follow-up before progression. Due to the high number of treatment discontinuations the statistical analysis plan was revised and validated before the database freeze and treatment unblinding, including a preplanned secondary analysis jointly modelling delays of early discontinuation of treatment and of confirmed EDSS progression, using a multistate model of the "illness-death" type  [27, 28]  with and without adjustment, which was fit using the SmoothHazard R package  [29].
Secondary endpoints were analyzed using logistic regression for dichotomous outcomes, linear regression for continuous outcomes. Comparisons were adjusted on covariates with sites as random effects when possible. The R package msm, and more complex models with disability progression occurrence made possible after treatment discontinuation, were used as robustness analyses for the main multistate model  [28] [29]. In the analyses of secondary endpoints, missing data due to early discontinuation of treatment because of adverse events were considered treatment failures as were progressions. Based upon the sample size that there was little power to test the interaction effect. All analyses were performed by the biostatistician from the CTU. Except for multistate models, SAS 9Á2 1 was used. Type I error was fixed at 5%.
Patient characteristics One hundred and forty-eight patients were included between 11/16/2005 and 07/16/2009, when recruitment closed. Due to a low recruitment rate, it was decided to stop the study at this stage. Seventy-two patients were randomly allocated to receive CPM and 66 to receive MP treatment. Table  1  summarizes the baseline characteristics of the patients. Fifty-five patients overall discontinued treatment, more frequently in the CPM than the MP arm (Fig  1 ). Among the 33 patients who discontinued treatment in the CPM arm, 20 did so because of adverse events, compared to five out of 22 in the MP group. A high proportion of patients discontinuing treatment also stopped coming to follow-up visits (29 out of 33 in the CPM group and 18 out of 20 in the MP group), generating missing data on the primary outcome.
In particular, no other therapeutic trial was conducted at the same time. Because of the high number of treatment discontinuations, a secondary analysis was planned (before database freeze and treatment unblinding) using a multistate model that could estimate the hazard of transition to disability progression in both randomization groups while taking into account at the same time the possible transition to early discontinuation of treatment. Hence, as indicated by ITT principles, all patients were analysed in their randomization group, although the transition toward disability progression was estimated only in a patient subgroup, those who did not discontinue treatment. All sensitivity analyses with different multistate models and statistical packages found a significant effect of CPM in delaying disability progression compared to MP.