dataesr/scientific-paragraphs-categorization huggingface dataset:
For comparative quantification of gene expression, read counts were determined for every CDS. CDS with at least 200 mapped reads were considered for expression analysis. The threshold for a classification as differently expressed was 2-fold. CDS with p<0. 05 were considered significantly deregulated. Moreover, the data allowed also the mapping of 192 transcriptional start sites (S1 Table ). Since the physiological state of the bacteria inside the mouse peritoneum is unknown, we compared the in vivo gene expression to the RNA-Seq data of exponentially growing and of stationary phase cells. This showed that 273 and 223 CDS seemed to be significantly induced and 170 and 154 CDS were repressed in vivo, respectively (S1 Table ). The in vivo induced CDS were then checked by RT-qPCR using 3 independent RNA extractions from cells isolated from the mouse peritoneum and mid-log phase cultures as the comparator to confirm the validity of RNA-Seq data.
We screened our in vivo induced genes database for the presence of the genes encoding these antioxidative activities and noted that it reflects well the former findings. Indeed, the most in vivo induced peroxidase is by far Tpx. Expression of the gene encoding this enzyme is induced 14. 8-fold whereas Npr and AhpCF are more moderately induced (+3. 7-and +3. 2-fold, respectively). The expression of sodA is also somewhat induced in vivo (+3. 2-fold). Moreover, several other genes with known or suspected implications in oxidative stress are present in the in vivo induced gene database such as genes endoding thioredoxin reductase (ef1405; +4. 8-fold), two members of the ferric uptake regulator family, PerR (ef1585; 4. 4-fold)  [52]  and Fur (ef1525; +5. 9-fold), and the Dps family protein (ef3233; +2.
Metabolic activities of E. faecalis during peritoneum infection After infection, bacteria have to proliferate inside the infected host. This is particulary challenging for polyauxotrophic microorganisms like enterococci since these organisms need a large panel of nutrients for growth. Either the bacteria get all these growth factors from the host or they have mechanisms to mobilize them actively. An important question concerns also the energy source used by enterococci inside the host. Therefore we analysed the in vivo expression database to get useful information on the questions if E. faecalis is metabolically active and which substrates are used by this bacterium during the first hours of infection. The data indicate that genes belonging to the category "Metabolism" are part of the second most abundant group of genes (18%) arguing that the bacteria actively adapt to the special nutrient conditions inside the host.
Comparison of the data to previous in vivo transcriptome studies We present in this work the first genome-wide analysis of the E. faecalis transcriptome during peritonitis by high-resolution RNA-Sequencing. Very recently, a microarray-based transcriptome of E. faecalis was conducted with bacteria isolated from a rabbit subdermal abscess infection site  [70]. These analyses revealed that at 2 hours post-inoculation of the subdemal chambers, 222 genes were differentially expressed, with around half of them induced when compared with the initial inoculum. Comparison with our database revealed only 9% overlap with genes differentially expressed in the rabit model. At 8 hours post inoculation of the subdermal chambers, 88% of the differentially expressed genes (total number of 291 genes) were repressed.
Concerning the genes induced in the rabbit model, 19 overlap with our database of in vivo induced genes, amongst others ef0362 encoding the chitin-binding protein, ef0463 encoding the superoxide dismutase, genes encoding stress response proteins like ef1058, lpB, groEL and groES, and 3 lipoproteins (ef0095, ef0176, ef0177). The differences of the animal models, sites of infection, time point of sampling, and the techniques used for the transcriptome analysis could be at the basis of this low overlap between the two datasets. It is of note that bacteria incubated in the subdermal chambers in the rabbit abscess infection model do not survive well in the first hours of incubation with around 10% and 4% of the bacteria still culturable at 2 hours and 8 hours post-inoculation, in contrast to the peritonitis model used in the present study  (S2 Fig).
Before the introduction of microarray and RNA-Seq technologies, identification of upregulated genes has been performed by a recombinant-based in vivo expression technology (RIVET) approach. However, using the above mentioned rabbit subdermal abcess infection model, only very few RIVET clones overlapped with the microarray results. We used the RIVET for the identification of genes activated during bacteremia and peritonitis infections in E. faecalis  [71]. 20 genes grouped in 7 operon structures identified to be induced in vivo in the present study overlap with the 64 genes identified by RIVET (ef0104 to ef0108, ef0162 to ef0164, ef0176-ef0177, ef0185 to ef0187, ef0377-ef0378, ef0525 to ef0528, and ef1677). The Mutants affected in genes highly induced in vivo should be attenuated in virulence Our in vivo expression database identified several operons which are highly induced during peritonitis and hence should be important for the infection process.
Acknowledgments The expert technical assistance of  Maxence Bourin ,  Isabelle Rince ,  Marie-Jeanne Pigny  and  Evelyne Marchand  was greatly appreciated. We would like to thank all members of our labs for helpful discussions. This study was partly supported by grants from the  Agence Nationale de la Recherche  in the frame of a transnational  ERA-NET PathoGenoMics program  ( ANR-08-PATH-008-01 ).
This study was supported by grants from the  Agence Nationale de la Recherche  (http://www. agence-nationale-recherche. fr) in the frame of a transnational  ERA-NET PathoGenoMics program  ( ANR-08-PATH-008-01 ), and the funding was received by AH, TH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Characterization The morphologies of the coatings were observed using scanning electron microscopy (SEM) in their as prepared and post-wear states. Chemical composition of the wear scars and transfer films were obtained through energy dispersive x-ray spectroscopy (EDX). SEM and EDX were performed using a FEI Quanta 600 microscope with a tungsten filament source. An accelerating voltage of 20kV was used. Selected specimens were observed in cross section and were cut with a diamond blade and prepared metallographically. X-ray diffraction (XRD) was used to confirm the phase of the coating. A Bruker Discover D8-2D, fitted with a Co-Kα source, was used in the standard θ-2θ mode on the unworn coatings. Profilometry was performed on the wear scars. An Altisurf 500 confocal microscope coupled with Phénix 2 software was used to obtain the profile maps.
Acknowledgements The authors would like to thank  Dr. Sriraman Rajagopalan ,  Priyadarshi Behera ,  Salim Brahimi  and  Professor Stephen Yue  for their continual support and inputs throughout the experiments. We would also like to thank  Natural Science and Engineering Research Center (NSERC) ,  Boeing Canada, Pratt & Whitney Canada ,  Héroux Devtek ,  Canadian Fastener Institute  and.
Study population This is an observational single-centre cohort study enrolling all successfully ART-treated patients, i. e. with a VL <50 copies/mL, switching to tenofovir/emtricitabine/rilpivirine STR between September 2012 and February 2013. All the patients enrolled in this study gave their written informed consent to have their medical chart recorded in the electronic medical record system Nadis (Fedialis Medica, Marly Le Roi, France, CNIL number: 1171457 May 24 th 2006), designed for the healthcare medical follow-up of HIV-infected patients, that also included their agreement to participate to retrospective studies. All data were analyzed anonymously.
Acknowledgments We are indebted to the following for the data for their assistance in data collection:  E. Bouvet ,  S. Matheron ,  C. Rioux ,  X. Lescure ,  M. Caseris ,  N. Dournon ,  H. Ferrand ,  M. Pichon ,  M. Ahouanto ,  E. Casalino ,  G. Castanedo ,  A. Dia ,  X. Duval ,  Z. Eid ,  S. Fegueux ,  V. Gregoire , E.
Supramolecular structures of Ni II -porphyrin-Tel22 complexes Molecular dynamics (MD) simulations were carried out to give insights into the structures and binding modes of the studied porphyrins to model intramolecular G4: anti-parallel "baskettype" G4 (with Na + , PDB ID: 143D), parallel G4 (with K + , PDB ID: 1KF1) and hybrid G4 (mixed parallel/anti-parallel strands, PDB ID: 2HY9) structures of Tel22. 37, 41, 48 Only 1 : 1 complexes were considered for the sake of computational cost, taking into account the water explicitly (TIP3P model). MD simulations were carried out on a 100 ns timescale, allowing us to explore the movements of a single porphyrin around each G4 type and the possible interaction sites. Five starting conformations were considered, as depicted in Fig. 4. Ni II -TImidP4-G4 complexes.
5b  and S10. † In contrast to inter-actions with anti-parallel G4, Top conformations are accessible since the loops do not cover the G-quartets in this structure. The Groove binding mode is comparable to the one with antiparallel G4, the imidazolium interacting here with dT12 (Fig. 4b ). Note that MD simulations starting from hybrid parallel/anti-parallel G4 folding (PDB ID: 2HY9) yield the same preferential binding modes (Bot, Top, Groove). In this case the Bot conformation shows a π-stacking between Ni II -TImidP4 and 3′-terminal adenine (Fig. S11 † ). Ni II -TMPyP4-G4 complexes. Ni II -TMPyP4 possesses a planar central porphyrin macrocycle, in strong contrast with the saddle shape of Ni II -TImidP4. Furthermore, the cationic pyridinium moieties are located at the four meso positions (Chart 1) while for Ni II -TImidP4 the imidazolium moieties are fused to the β-pyrrolic positions, which lead to different G4 binding modes from MD simulations (Fig.
59, 60 orphyrin parameters are available in the ESI. † Molecular dynamics simulations. Solvated Tel22 G-quadruplex structures were obtained from the PDB structures (antiparallel structure with Na + , PDB ID: 143D; parallel structure with K + : 1KF1; hybrid structure, PDB ID: 2HY9). 37, 48, 61 The FF12SB force field as implemented in the Amber12 package  60  was used to describe G-quadruplex structures. MD simulations were first performed on pure anti-parallel or parallel G-quadruplex structures. Water molecules were described as the "threepoint" TIP3P model. 62, 63 The minimum distance between any atom of the system and the edge of the periodic box was set up at 15 Å. Water molecules were minimized prior to the entire system minimization. Boxes were thermally equilibrated by performing 50 ps heating MD simulation from 0 to 350 K.
Then, 100 ps NPT MD simulations were carried out in order to obtain a solvent box density of 1 g cm -3. Finally, 100 ns NVT MD simulations were carried out. The equilibrated G-quadruplex parallel and anti-parallel structures were used for 1 : 1 metalloporphyrin-G-quadruplexes MD simulations. Five different binding modes were used as initial structures for 1 : 1 metalloporphyrin-anti-parallel/parallel G-quadruplex structures (Fig. 3 ). The same protocol was used to equilibrate 1 : 1 complex structures (i. e. , minimization, heating, and density equilibration). 100 ns MD simulations were then achieved in the (N,V,T ) ensemble. Binding free energy calculations. The MM-GBSA (molecular mechanics-Generalized Born surface area) script as implemented in the Amber12 package was used to calculate the metalloporphyrin binding energies (ΔG binding ).
Acknowledgements This work was supported by the  Fonds de la Recherche Scientifique-FNRS (Belgium)  under the grant no. 2. 4615. 11-BINDER. J. R. -M. is a FNRS post-doctoral researcher and M. S. is a FNRS research associate. M. L. acknowledges  SeRC (Swedish e-Science Research Center)  for funding and  FNRS  for visiting professor position. P. N. and F. D. M. acknowledge financial support from the  Swedish Research Council  (grant no. 621-2010-5014 ). The authors acknowledge SNIC ( Swedish National Infrastructure for Computing ) for providing computer resources. S. R. , S. C. and M. L. are grateful to the  CNRS  and the  Agence Nationale de la Recherche (ANR)  for financial support ( research  project  ANR-09-JCJC-0089-01 ).
Setting and study population Country-level information on malaria is submitted annually to WHO regional offices and then to GMP in Geneva, Switzerland. Validation is performed at country level as well as by the WHO regional and global levels. The results are published annually in the World Malaria Report. Aggregate data on confirmed malaria cases in countries in pre-elimination, elimination, and prevention of reintroduction were included in this study. Countries in pre-elimination, elimination, and prevention of reintroduction can transition between these categories within a few years. For example, a country that was classified as being in elimination in the year 2007 could be classified as being in prevention of reintroduction in the year 2013.
Acknowledgements This research was conducted through the  Structured Operational Research and Training Initiative (SORT IT ), a global partnership led by the  Special Programme for Research and Training in Tropical Diseases  at the  World Health Organization. The model is based on a course developed jointly by the  International Union Against Tuberculosis and Lung Disease  ( The Union ) and Medecins sans Frontieres. The specific SORT IT programme which resulted in this publication was jointly developed and implemented by: The Centre for Operational Research, The Union, Paris, France; The  Operational Research Unit, Medecins Sans Frontieres, Brussels Operational Centre, Luxembourg; The Union, South-East Asia Regional Office, New Delhi, India; and The Centre for International Health, University of Bergen, Norway.
Study population and design Patient and data collection have been already published elsewhere. 4 The sample study was recruited at the Clinic of Genolier (Switzerland). It consisted of 616 consecutive ambulatory patients consulting our center of preventive medicine (www. nescens. com) for a medical checkup between January 1, 2009 and December 31, 2012. Pregnant women and/or individuals with self-reported cardiac failure, who had a cardiac pacemaker, or who had previously undergone limb amputation were not considered. Otherwise, there were not any exclusion criteria. Briefly, Nescens medical checkups are designed in three steps. The first and third steps are dedicated to medical consultations, which are conducted before and after all the complementary investigations. The medical consultation conducted before is dedicated to personal and family medical histories, medications, current complaints, and symptoms, and a complete medical examination is also performed.
In the course of the first consultation, patients were informed about the protocol prior to signing consent forms. The results of the checkup are detailed and discussed during the second consultation. The second step is composed by biological, radiological, and functional investigations. Thus, blood test analyses, including in part the biological data of interest (see below and Table  1  for details), are carried out as well as a large panel of radiology exams such as DEXA scan, angiography by computed tomography scan (CT scan) of the supra-aortic and coronary arteries, and total body CT scan (256-row detector CT scan). In addition, a cardiologist conducts a stress test on electronically braked cycle ergometer in addition to a Doppler echocardiography. In order to avoid any interference due to injection of iodine-based contrast products used for the angiography and total body CT scans, DEXA scans were systematically carried out in first.
Data collection Assessment of body composition. The assessment of body composition was performed with a DEXA scan (Hologic Discovery; Hologic Inc. ). 15 The instrument was calibrated by using a spine phantom daily and a step phantom weekly. All scans were performed 4-5 h after the last meal, at least, and before CT scans. DEXA represents a three-compartment model for estimating body composition, because it can divide the body into three compartments: fat, bone mineral, and all other fat-free mass that does not include bone. Thus, unlike two-compartment models, DEXA is not subject to errors caused by variations in bone density among different ethnicities. DEXA thus provides bone density estimates, and regional estimates of body composition (i. e. , it can estimate the body composition of individual parts of your body), by measuring the body's absorbance of X-rays at two different energies.
7 mmol/L; 210 £ uric acid £ 420 for men and 150 £ uric acid £ 360 for women; and 4. 0 £ HbA1c £ 6. 0 for both genders. Cardiovascular diseases. Medical data and diagnostics of interest leading to identify individuals suffering from metabolic-related cardiovascular complications were collected throughout the two medical consultations from previous reports, personal medical history, and the result of the tests performed during the checkup. Thus, individuals who demonstrate documented hypertension (under treatment or not) and/or a significant coronaropathy (symptomatic or not), atherosclerosis of at least one of the supra-aortic arteries (symptomatic or not) and/or of one large arteries of the body were considered as having cardiovascular diseases. 16 atistical analyses For descriptive analysis, numerical variables are presented as meanstandard deviation (m -SD) and for categorical variables as number and percentage.
Statistical tests used for the unifactorial comparative analysis were chosen according to the type of variable, the sample size under consideration, and the number of group compared. Thus, numerical outcomes were compared using analysis of variance or Kruskal-Wallis test (when > 2 groups), and Student's t or Mann-Whitney test (when 2 groups). For categorical outcomes, chi-squared or Fisher's exact test was used. All these analyses were performed with SAS Ò software (version 9. 3; SAS System, SAS Institute Inc. , Cary, NC). The level of significance was set at p = 0. 05. In addition, receiver-operating characteristic (ROC) curves were computed using SPSS Ò (version 21; SPSS Inc. , Chicago IL). Each point on the ROC curve represents a sensitivity/100-specificity pair corresponding to a particular decision threshold.
Chromatographic apparatus & conditions The liquid chromatograph was an Agilent 1200 HPLC system consisting of a binary pump, a mobile phase degasser, a thermostatic column compartment, an auto-sampler (kept at 4°C) and a fluorescence detector. Agilent ChemStation software was used to control the system and analyze the data. The chromatographic separation was performed on XTerra phenyl ® column (250 × 4. 6 mm, 5 μm; Waters, MA, USA) associated with guard column packed with the same bonded phase. XTerra ® Columns combine the properties of silica and polymeric bonded phases with patented Hybrid Particle which enables chromatographers to perform high pH method development. The temperature of column was controlled at 50°C. The mobile phase consisted of a mixture of glycine buffer/sodium chloride (pH 9.
Statistical analysis The nonparametric regression proposed by Passing-Bablock et al. was used firstly to investigate the anticoagulant and gel separator effect on assay of HCQ and its metabolites, and then to estimate the relationship between two analytical techniques to assay whole blood HCQ concentration  [23]. The regression equation is expressed with the 95% CI for the estimates of slope and intercept. The scatter of the method was visualized according to the recommendations of Bland and Altman  [24]. Statistical analysis was performed using Medcalc ® software, version 7. 3. 0. 1 (Mariakerke, Belgique) after exclusion of the samples below the LLQ of either method. p < 0. 05 was considered statistically significant.
Slides were mounted in DAKO mounting medium supplemented with DAPI (Sigma) and examined at a magnification of 63x using a fluorescence microscope (Zeiss Axio Observer Z1) equipped with an ORCA-ER camera (Hamamatsu). The microscope and camera parameters were set for each series of experiments to avoid signal saturation. Image processing and analysis were performed using ImageJ software (http://rsb. info. nih. gov/ij/).
Cells presenting more than 5 foci were considered positive. Data represent the mean of two independent experiments with similar results. (H) Left. Representative images of BRCA1/RAP80 interaction dots detected with the Proximity Ligation Assay in nuclei (DAPI stained, blue) in FANCC-mutated (PD331 FANCC -/-) and -corrected (PD331corr) cells under untreated conditions or 24 h following MMC exposure (1 g/ml/1 h). White line: 8 m. Right. BRCA1/RAP80 interaction dots quantification 24 h after MMC exposure (1 g/ml/1 h). Histograms represent the pooled data from three independent experiments. Quantification was conducted using ImageJ software. (I) Left. Representative images of BRCA1/CtIP (left) interaction dots detected with the Proximity Ligation Assay in nuclei (DAPI stained, blue) in FANCC-mutated (PD331 FANCC -/-) and -corrected (PD331corr) cells under untreated conditions or 24 hours following MMC exposure (1 g/ml/1 h).
White line: 8 m. Right. BRCA1/CtIP interaction dots quantification 24 h after MMC exposure (1 g/ml/1 h). Histograms represent the pooled data from three independent experiments. Quantification was conducted using ImageJ software. (J) Representative images of FANCD2 foci (red), RAP80 (red) or 53BP1 (green) in PD20 corr (FANCD2-corrected cells), PD20 (FANCD2 -/- cells) and PD20 FANCD2 K561R (PD20 cells expressing a K561R, non-ubiquitinable FANCD2) cells. White line: 2 m. Histograms represent the number of RAP80 (red) and 53BP1 (green) foci in the three different cell lines in the left. Data represent the mean of two independent experiments with similar results. BACH1/FANCJ, which favor HR. By using proximity ligase assay (PLA) technology (Supplemental Figure  S1D ), we observed that, in both untreated and MMC-treated conditions, the frequency of cells containing an elevated number of BRCA1/RAP80 dots per cell is higher in FANCC -/- cells than in FANCC corrected cells (Figure  1H ), whereas the opposite is observed for BRCA1/CtIP dots (Figure  1I ).
Actin is presented as loading control. (F) Representative images of pDNA-PK (red) and MRE11 (green) foci in nuclei (DAPI stained, blue) of FANCCcorrected (corr) or -deficient (FANCC -/-) cells. The cells were pre-treated with DMSO or TSA (5 M) for 5 h before MMC (200 ng/ml) exposure and analyzed 24 h later. White line: 2 m. (G) Quantitative analysis of the data presented in (F). Histograms are the mean of three independent experiments. (H) Western blot analysis of the subcellular distribution of TIP60 in untreated and MMC-treated FANCC-proficient (Ctrl or corr) or -deficient (siFANCC or FANCC -/-) cells 24 h after exposure to MMC (1 g/ml/1 h). GAPDH and LaminB1 are used as loading controls. (I) Quantitative analysis from four independent experiments of TIP60 relocalization to the chromatin in HeLa cells 48 h after siRNA-mediated FANCC downregulation (left panel) or in FANCC-corrected (PD331corr) or deficient (PD331 FANCC -/-) cells (right panel).