dataesr/scientific-paragraphs-categorization huggingface dataset:
8% of hypothetical proteins (294 of the 491 predicted proteins). Table  1  describes the PSI-BLAST predictions for 23/29 ORFs tentatively classified as ORFans (79. 3%) and highlights the presence of atypical viral proteins such as ORF 337, which was predicted to encode a cytochrome C-like protein, previously described in mimiviruses but not in marseilleviruses. Furthermore, we found that ORFs which were tentatively classified as ORFans could be predicted to encode a methyltransferase-like protein (ORF-L46), which may be associated with gene transcription regulation; a cysteine protease ATG4B-like protein (ORF-R86), which could be associated with cytoplasmic vacuole transport (Cvt) and/or autophagy; a cytidine and deoxy-cytidylate deaminase-like protein (ORF-L94), which is thought to be involved in the binding of the catalytic zinc ion; a protein-L-isoaspartate O-methyl transferase-like protein (ORF-R123), which may be involved in the repair and/or reduction of damaged proteins resulting from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues; a N-acetylneuraminic acid mutarotase-like protein (L324) which, in bacteria, accelerates the equilibration of the alpha-and beta-anomers of the sialic acid, N-acetylneuraminic acid, which in turn is used as a source of carbon; and others (Table  1 ).
polyphaga but can replicate in A. castellanii. In contrast, replication of BrMV is restricted to the tested A. castellanii strains and no cytopathic effects or viral titers were detected in the A. polyphaga cells infected with this virus. When comparing the replication profile of BrMV and the Marseillevirus prototype in A. castellanii cells, we observed similarities in terms of replication and the achieved viral titers (data not shown). The BrMV genome has the second largest gene content of the Marseilleviridae family. Moreover, its genome was predicted to encode 29 new ORFans, defined as ORFs without detectable homology, although six of them were absent only from the predicted repertoires of gene products of other marseilleviruses. Moreover, we identified 16 ORFs less than 100 aa in length (pseudoORF), without detectable homology with any sequence in the NCBI nr database.
The presence of such short pseudoORF may be a mere annotation artefact, or may represent novel short transcripts. We had identified 47 short ORFs encoding less than 100 amino acids with some correspondence in the NCBI nr database. It is worth mentioning that pseudoORF BrMV sequences were not identified in other marseillevirus genomes. Furthermore, we used the PSI-BLAST tool to detect distant relationships between ORFans and.
The presence of such short pseudoORF may be a mere annotation artefact, or may represent novel short transcripts. We had identified 47 short ORFs encoding less than 100 amino acids with some correspondence in the NCBI nr database. It is worth mentioning that pseudoORF BrMV sequences were not identified in other marseillevirus genomes. Furthermore, we used the PSI-BLAST tool to detect distant relationships between ORFans and proteins in the NCBI nr database. We were able to identify 23/29 (79. 3%) putative homology for ORFans encoded by BrMV. These proteins, identified as encoded by marseilleviruses, have no described function yet, and were probably acquired by horizontal gene transfer HGT) events, which involved vertebrates, bacteria, fungi and viruses. This chimerical profile was previously described by  Boyer et al.
Acknowledgments: We would like to thank our colleagues from  GEPVIG (Grupo de Estudo e Prospecção de Vírus Gigantes)  and  Laboratório de Vírus of Universidade Federal de Minas Gerais. In addition,  CNPq  ( Conselho Nacional de Desenvolvimento Científico e Tecnológico) ,  CAPES  ( Coordenação de Aperfeiçoamento de Pessoal de Nível Superior)  and  FAPEMIG (Fundação de Amparo à Pesquisa do estado de Minas Gerais). We want to acknowledge  Emeline Baptiste  and  Khalid El Karkouri  for their helpful advice in phylogenetic analyses. This work was in part funded by the  Fondation Institut Hospitalo-Universitaire Méditerranée Infection foundation. Author Contributions: Fabio P. Dornas performed virus isolation; Felipe L. Assis performed genomic analysis; Sarah Aherfi performed phylogenetic analysis; Thalita Arantes performed biological experiments;  Jonatas S.
Methods This is a phase III, multicenter, placebo-controlled, double-blind, randomized (1:1), two parallel arm clinical trial conducted in 17 public hospitals in Thailand (see Fig. 1 ). The list of locations is available at Clini-calTrials. gov Identifier NCT01745822. The primary objective is to assess the efficacy of TDF for the prevention of MTCT of HBV at 6 months of age. Important secondary objectives are to assess the risk of postpartum hepatic disease exacerbation after antiviral discontinuation, and infant growth through 12 months of age as part of the safety assessments. Pregnant women are tested for the presence of HBsAg at their first antenatal care visit as standard of care in Thailand. At each site, all pregnant women aged 18 years or older with a positive HBsAg test were informed about the study and invited to provide their informed consent for participation.
Discussion This phase III randomized placebo-controlled doubleblind trial will assess the efficacy and safety of a short course antiviral treatment to prevent mother-to-child transmission of HBV. Enrollment was opened in January 2013 and accrual was completed on August 19, 2015 with no significant operational issues. The data collection for the primary endpoint is scheduled to be completed in August 2016. Primary efficacy results are expected soon afterwards. The efficacy and safety study results will help clarify whether this strategy can play a significant role in the prevention of mother-to-child HBV transmission in highly viremic women.
Flow cytometry and transcriptional analyses Cell suspensions were incubated for 40 min with cold PBS (Life Technologies) containing 10% FCS, FcR block (2. 4G2), a viability dye (eFluor 506; eBioscience #65-0866-14) and fluorochrome-bound Abs. To detect intracellular Ags, cells were fixed for 40 min with 2% paraformaldehyde, followed by a permeabilization/staining step for transcription factors and/ or cytokines with the Foxp3 permeabilization kit (eBioscience). The following Abs were used: CD3 (17A2), CD4 (RM4-5), NK1. 1 (PK136), CD127 (A7R34), CD117 (2B8), ROR, IL-22 (IL22JOP), NKp46 (29A1. 4), CCR6 (29-2L17), T-bet (ebio4B10), MHC class II (M5/114. 15. 2), CD49a (Ha31/8), Ki67 (SoIA15), DNAX accessory molecule (DNAM; 10E5). All of the samples were acquired on an LSR FORTESSA (BD), and data were analyzed with FlowJo software (TreeStar; version 9.
Purpose: This retrospective review examined visual acuity (VA) in subjects with neovascular age-related macular degeneration and identified early and delayed response to ranibizumab. Procedures: MARINA, ANCHOR, HARBOR, and CATT published data were examined for response with monthly versus individualized dosing and predictors of early versus delayed response. Results: Data were available for 1,631 subjects; 18-29% were early gainers and 15-16% were delayed gainers. Of the early gainers, 72-83% maintained their bestcorrected VA gain at month 12 with monthly or individualized dosing. Delayed gainers in HARBOR almost reached the same level of response as early gainers by 12 months who were able to maintain their response. The main predictor of response was baseline VA. Conclusion: There are two distinct types of ranibizumab response; some responded by month 3, while others took up to 12 months.
In addition, data are lacking on how the pattern of response may change with different treatment regimens (e. g. , monthly dosing versus an individualized approach). To address these limitations, we conducted this review using data from HARBOR  [7, 10]  and CATT  [8, 9]  , as well as from MARINA  [5]  and ANCHOR  [6]. Each of these four randomized controlled trials included subjects who were treated in a similar manner to those seen in clinical practice, with either fixed monthly dosing (MARINA and ANCHOR) or individualized monthly or PRN dosing in HARBOR and CATT that was based on individual response. We also examined the pattern of VA response (defined as a gain of ≥ 15 letters) to identify subjects with nAMD who had an early or delayed response to ranibizumab treatment. Early responders were defined as those who gained ≥ 15 letters from baseline as measured at month 3 and delayed responders defined as subjects who did not gain ≥ 15 letters from baseline at month 3, but subsequently gained ≥ 15 letters from baseline as measured at month 12  [16].
Statistical Analysis Data were analyzed at month 3 to identify those subjects who achieved early VA gains with treatment, and at month 12 to identify those with a delayed response who achieved VA gains between BCVA data, as assessed by the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart, were analyzed in subjects treated for 12 months with monthly ranibizumab 0. 3/0. 5 mg (pooled group) in ANCHOR ( n = 279) and MARINA ( n = 478), or with monthly as well as individualized dosing of ranibizumab 0. 5 mg in HARBOR ( n = 275 each) and CATT ( n = 301 in monthly, n = 298 in PRN). Using these data, the percentage of early and delayed ≥ 15-letter gainers were determined and then compared between the monthly and PRN dosing groups. Where available, data on baseline characteristics such as age, sex, VA gains, previous AMD therapy, lesion type, and anatomy were also compared between early 15-letter gainers and delayed 15-letter gainers to identify potential baseline predictors of response.
cerevisiae's RPD3. These genes are now designated as RPD31 and RPD32. The current annotation of these genes has given rise to some confusion, with discrepancies between the original publication  (Srikantha et al. , 2001)  and the current annotation in the Candida Genome  Database (CGD; Assembly 22,. Table  1  presents updated information on the gene and protein accession numbers. Hos1 was first identified and cloned 15 years ago in C. albicans, but its functional role has remained elusive  (Srikantha et al. , 2001). Hos2 was initially described in the CGD as a Class III enzyme with sirtuin activity  (Karthikeyan et al. , 2013) , but it is now presented as a member of the class I family  (Kim et al. , 2015). In vitro analysis of the enzymatic activity of recombinant Hos2 showed it to be inactive on acetylated histones but capable of deacetylating acetylated tubulin  (Karthikeyan et al.
ACKNOWLEDGMENTS MCh is supported by a fellowship from the  Région Rhône Alpes (France). MCo and JG's groups received funding from the  ANR  trough the FungiBET  ANR-14-CE16-0027-02  program. JG's group has also received support from  French National Agency for Research (ANR)  through the EpiGam  ANR-11-PDOC-0011  and the  FP7 Marie Curie Action  " Career Integration Grant "  EpiGam2 304003.
Combination antiretroviral therapy (ART) based on ≥3 antiretroviral drugs including either a protease inhibitor (PI), nonnucleoside reverse transcriptase inhibitor (NNRTI), or integrase inhibitor has substantially improved the prognosis of human immunodeficiency virus type 1 (HIV-1)-infected patients since its introduction in high-income settings in 1996  [1]. ART suppresses HIV-1 replication, leading to declines in plasma HIV-1 RNA, increased CD4 T-cell counts, and, eventually, decreased morbidity and mortality  [2]. Because patients have now been treated with ART for up to 20 years, it is of major interest to explore predictors of long-term prognosis. The Antiretroviral Therapy Cohort Collaboration (ART-CC) was initiated in 2000 by investigators from HIV cohort studies in North America and Europe, to assemble datasets that were sufficiently large to study the prognosis of HIV-1-infected patients who started ART.
Study Sample The ART-CC, which is described in detail elsewhere (http://www. art-cohort-collaboration. org)  [10] , is an international collaboration of HIV cohort studies from North America and Europe that combines data on HIV-infected individuals aged ≥16 years who were antiretroviral-naive when they started ART with a combination of at least 3 drugs. Eligible regimens include at least 1 PI, NNRTI, or integrase inhibitor and 2 nucleoside-analogue reverse transcriptase inhibitors (NRTIs). The present study included data from 18 cohorts, which are listed in the Supplementary Appendix. All were approved by local ethics committees. The National Health Service Health Research Authority South West-Cornwall and Plymouth Research Ethics Committee, United Kingdom, approved the study (REC reference 12/SW/0253).
Statistical Analysis We categorized CD4 counts into 6 groups (0-49, 50-99, 100-199, 200-349, 350-499, and ≥500 cells/µL); viral loads into 3 groups (0-9999, 10 000-99 999, and ≥100 000 copies/µL); age at baseline into 5 groups (16-29, 30-39, 40-49, 50-59, and ≥60 years); year of starting ART into 3 groups  (1996-1997, 1998-1999, and 2000-2001) ; and ART regimen into 5 groups (NNRTI-based, PI-based, NRTI including abacavir, other NRTI not including abacavir, and other regimens). Patients were followed up from the date of starting ART ("baseline") to the earliest of the date of death, loss to follow-up, or administrative censoring. Patients were considered lost to follow-up at their last clinical observation if it was more than a year before the cohort-specific close date of the database. Data were analyzed as intent to continue treatment, ignoring treatment changes and interruptions.
We used unadjusted (Kaplan-Meier) and adjusted estimates of cumulative mortality to examine whether CD4 count at start of ART was prognostic for mortality. The adjusted estimates were for a typical patient: men who have sex with men (MSM) aged 30-39 years, who started ART between 1998 and 1999 in the French Hospital Database on HIV (FHDH) cohort without a diagnosis of AIDS, and with high viral load (HIV-1 RNA > 100 000 copies/µL). We used Poisson models to estimate crude mortality rates (MRs) with 95% confidence intervals (CIs), for all patients and by baseline CD4 count. We then estimated MRs separately according to duration of time on ART (<0. 5, 0. 5-0. 9, 1-2. 9, 3-4. 9, 5-9. 9, and ≥10 years after ART start), overall, and by baseline CD4 count. We used Cox models stratified by cohort to estimate crude and adjusted (for sex, age, transmission risk group, AIDS at baseline, baseline viral load, and year of starting ART) MRRs by baseline CD4 group with 200-349 cells/µL as the reference category, overall and separately according to time on ART.
Relative survival models based on generalized linear models (modified Poisson models) were used to account for variation in background population mortality  [11]. Expected death rates for each country split by sex and 5-year age group were obtained from the Human Mortality Database (www. mortality. org). We estimated adjusted (for the same set of covariates) relative MRR, overall and according to duration of time on ART. The prognostic value of baseline CD4 count according to time since start of ART was compared by estimating the adjusted MRR per CD4 count category (assuming a log-linear relationship with MR across the CD4 categories). All analyses were performed using Stata software version 13 (StataCorp, College Station, Texas).
We tested our model at a range of [Ca 2+ ]'s between 0. 001 and 10 μM for five SL's ranging from 1. 85 to 2. 25 μm. Single overlap length x max increases with SL according to the formulation of Rice et al  [22] , the equations of which are presented in the S1 Appendix (Eq A1-A3). The parameters C s , C f and K CaTn0 were varied so that the sum of the squared differences between the experimental data by Dobesh and the solution of the differential equation (Eq 9) was minimal. The minimization was performed on each individual curve. The Hill-type model with parameters EC 50 , S max , and n H was fitted to the same experimental data. For the MechChem and Hill-type models, the residual errors were assessed to find systematic differences between model and measurement. Additionally, the root mean squared error (RMSE) was calculated for all individual curves (Eq 11).
Model limitations The model presented here assumes that when an area on the thin filament becomes unblocked, XB's are automatically formed. Thus, the fraction of unblocking is proportional to the XBforce developed along the strand. The assumption that XB's form automatically when RU's are activated is not physiologically accurate. We expect this to be corrected upon the explicit incorporation of the different steps of the XB cycle. However, the experimentally measured tension in skinned muscle preparations is obtained after the steady state has been reached. Hence, the experimental data is time-independent. The current model results are limited to the [Ca 2+ ]-tension relationship. The introduction of dynamics such as the XB cycle requires additional assumptions to be made and additional unknown parameters added.
The greatest asset of such an approach is its unbiased nature, which does not focus on preselected regulatory circuits and conditions. Simultaneously, it allows comprehensive and precise mapping of all transcriptome parts such as transcription units, non-coding RNA species, and transcription start sites. Taking the aforementioned B. subtilis data set as an example, the approach provides at least three useful pieces of information that jointly contribute to the discrimination between direct and indirect regulatory effects. First, the observed co-expression patterns can complement results obtained in more targeted experiments  [20]. Second, the data facilitate detection of new regulatory RNA molecules  [21]. Third, the detailed information on transcription units and transcription start sites facilitates the search for potential regulator binding sites  [22].
To elucidate the main physiological adaptations caused by the biological conditions of our study, we conducted a Principal Component Analysis (PCA). This approach allowed assessing the general relationships between the 156 RNA samples in terms of expression profiles composed of aggregated values for all annotated genes and newly discovered RNA features (Fig  2A , Text E in S1 Data). The percentage of total variance captured by the successive axes revealed a major first axis (48. 9%) followed by minor axes of smoothly decreasing importance such that 67. 3% of the total variance is captured with 3 axes, but 13 axes are needed to reach 90%. To Each panel shows from top-to-bottom (i) the original GenBank annotation, (ii) a selection of 30 representative expression profiles (horizontal black lines show for each strand the chromosome median, and the associated 5-fold and 10-fold cut-offs) colored according to the position of the hybridization in 3D PCA, (iii) the detected up-shifts, the associated transcription units, and the down-shift positions, (iv) the new annotation with unannotated expressed segments colored according to the classification based on the transcriptional context.
The different categories of terminal regions are 5'UTR (green boxes) and three classes of 3' regions: 3'UTR (red) ending with a defined termination site, 3'NT (orange) without defined termination site, and 3'PT (old yellow) downstream a site of partial termination. Two categories of intergenic regions are distinguished: intra (dark blue) for strictly intracistronic regions, and inter (light blue) for regions where the downstream gene can be transcribed from its own promoter. Finally, depending of the presence or absence of a defined termination site, independent segments decompose into two categories: indep (black) and indep-NT (brown). Transcription segments overlapping (100bp or 50%) GenBank annotated genes on the opposite strand are referred to as antisense (AS). The left subpanel shows a 3D representation of the relationships between the 156 RNA samples.
The complete results are available in S6 Our study identified nearly all (48/50) of the (predicted) non-coding RNAs of S. aureus NCTC 8325 from the Rfam database  [53] , including the generic RNAs 6S RNA, 4. 5S RNA, tmRNA, RNase P, 33 cis-acting 5'-UTRs, and 11 small regulatory RNAs (sRNAs) including RNAIII  [54]  and SprD  [55]. In addition, a multitude of non-coding RNAs of S. aureus has been predicted and/or experimentally identified by different global approaches, mostly for S. aureus N315  [56] [57] [58] [59] [60] [61] [62]. The RNA-seq based study by Beaume et al. [62]  confirmed almost all non-coding RNAs from earlier studies  [63]. We therefore referred to previously known noncoding RNAs of S. aureus by mapping the 186 intergenic transcripts, including 25 antisense RNAs (ASRNAs), of N315 reported by Beaume et al.
The remaining sRNA, S414, exhibited very low expression levels under all conditions tested in our study except for growth in human plasma. The identification of these new sRNA candidates will likely facilitate the identification of new components of the regulatory network of S. aureus since recent studies revealed important roles of sRNAs in the regulation of metabolism and virulence (reviewed in  [64] ). ASRNAs accounted for 145 of the 1192 RNA features identified by our study (Table  1 , S6 Table ) and occurred at a rate of 51 per Mbp. With respect to the coding genes, 5. 6% (159/2836) of all GenBank annotated genes were overlapped by ASRNAs under the set of growth conditions applied and these genes showed a trend towards lower expression levels compared to all genes (Figure C in S1 Data).
Transcription factor binding site analysis to predict new regulon members Coordinated regulation of promoter activities is summarized in the promoter correlation tree and the associated clustering: 1242 up-shifts (82%) belonged to 16 activity clusters with 15 members defined by a cutoff on average Pearson correlation set to 0. 6 (Fig  3 ). The largest cluster (B1) alone gathered 46% of all the up-shifts. We used the known information on transcription factor (TF) regulons to better understand the contribution of TFs other than SigB to the regulation underlying these correlations. In particular we relied on the experimentally identified and manually curated inferred binding sites of 47 TFs from the RegPrecise database  [68]  for the identification of additional potential TF binding sites (TFBSs).
aureus and a few other Staphylococcus species. According to the SHOW CDS prediction software  [71]  the confidence probability associated with this putative CDS is also very low (value of 0. 18). For these reasons we assume that S596 may be a trans-encoded sRNA rather than a cis-encoded ASRNA. Indeed, the occurrence and role of Fur-dependent sRNAs was reported for several bacterial species (reviewed in  [72] ). Target prediction for S596 using CopraRNA  [73]  revealed enrichment of genes encoding iron-containing proteins and of genes with functions in cofactor metabolism. Potential targets of this sRNA also included arlRS encoding a virulence-associated two-component system (Table E in S1 Data). Termination of TUs identified in the S. aureus wild-type is predominantly Rho-independent Specific sequence elements, typically encoding a hairpin structure followed by a U-rich tract, direct dissociation of the RNA polymerase from the DNA template at intrinsic termination sites.
Applying a 30 bp distance cut-off, these elements were searched using the TransTermHP software  [48]. They were found for 67% of the 1261 identified high-confidence down-shifts (Figure I in S1 Data, S7 Table ) suggesting that intrinsic, also known as Rho-independent, termination determines the 3'-end of a majority of the TUs with defined termination sites in S. aureus. Most down-shift sites were also found associated with predicted intrinsic terminators in B. subtilis, where the transcription termination factor Rho was shown to be involved in termination of a particular class of TUs lacking a defined 3'-end. These TUs were characterized by slowly decreasing expression, apparently due to the lack of an efficient intrinsic terminator (categories 3'PT and 3'NT comprising 3'-extended mRNAs, and category Indep-NT)  [13] , and they often overlapped the antisense strand of annotated genes.