dataesr/scientific-paragraphs-categorization huggingface dataset:
RELATED RESEARCH When a top-level ASR system encounters requests in more than one language, LID can either be fed to the system externally by the user or it can be done automatically. Niesler et al. apply LID to South-African languages by combining acoustic and language modeling using HMMs trained over audio (speech) data  [14]  and achieve an accuracy of about 81%. Most recently, Gonzalez-Dominguez et al. developed a multilingual ASR architecture to recognize speech in several languages that works simultaneously with LID  [7]. The system relies on pre-selected languages indicated by the user. Based on user input, LID recognizes the spoken language and an ASR system for each language is deployed to decode the input signal. On average, the LID system achieves an accuracy of 80% across languages on Google 5M LID corpus.
g. French and Canadian French). Thirdly, we combined the most prevalent Indian languages (e. g. Hindi, Bengali) into an łIndian" class and Chinese languages into an aggregated łChinese" class. We also excluded the comments marked as abusive or moderated, filtered out all comments less than 5 words or 20 characters in length (e. g. łOk"), auto-generated (łShared on Google+"), spammy (URLs) and long comments (more than 10,000 characters) that are usually machine generated. Our final training data contains approximately 10M videos and has 41 language classes. The top 6 languages (English, Spanish, Portuguese, Russian, German and French) represent approximately 80% of all the training data, with mean number of comments of 41.
Golden Dataset According to the CV experiments, we can accurately predict the user-assigned labels. However, since such labels may not represent the actual audio language of the video, we verified our approach by constructing a golden label set with the correct languages assigned by human raters. We chose the top 21 languages from our training data set excluding the aggregated Indian and Chinese classes. For each language, we randomly sampled 50 videos and sent them to 3 human raters. After the labeling, we reconstructed our test set by assigning the language to the video (with majority agreement of the human raters). We reconstructed our full training set by excluding the videos that were in the golden set. Then, we trained the same models as in our CV experiments on this training set. The overall accuracy on golden set is 97% for Forest 10 and 96.
This approach allowed us to identify 11036 lncRNAs expressed amongst our CN-AML patients. Among them, 8526 were new lncRNAs that had not been previously reported in the RefSeq, UCSC or ENCODE databases (GRCh37/hg19). Unsupervised analysis of the 11036 CN-AML lncRNAs using hierarchical clustering (Figure  2A ) segregated the samples into two main groups. When different criteria [namely French-American-British classification (FAB) status, age and presence of mutations] were evaluated in order to define the two groups, the main observation was that NPM1-mutated patients were largely enriched in the first group (80%) compared to the second group (8%) (P=6x10 -6 ). This result suggested there is an lncRNA expression profile that is specific to NPM1-mutated patients.
XLOC_109948 lncRNA expression serves as a prognostic biomarker in CN-AML Although the lncRNAs identified in the minimal signature were differentially expressed between NPM1-mutated and NPM1-wild-type patients, we noticed a heterogeneous expression among patients. We asked whether one of them could be used as a prognostic biomarker. To this end, we selected patients who matched the following criteria: 1) those who had received intensive chemotherapy; and 2) those for whom we had clinical data available. This accounted for 25 of the 40 patients in Cohort 1 and all 134 patients in Cohort 2 (Figure  1  and Online Supplementary Table  S6 ). We used ROC curves to predict the best cut off (-ΔCt value) for each lncRNA for event-free survival (EFS) in Cohort 1. This cut off was then used to define subgroups with a high or low expression of each lncRNA and the log-rank test was used to compare the survival distrihaematologica | 2017; 102(10)  bution in the two groups.
MB was supported by a fellowship from ARC (Association pour la Recherche sur le Cancer). EDC was supported by a fellowship from LABEX. This work was also supported by the Fondation ARC pour la Recherche sur le Cancer, the Association Laurette Fugain, the Ligue Régionale Contre le Cancer (Comités du Gers et de la Haute-Garonne), the Institut Universitaire de France (PB) and by the Associazione Italiana per la Ricerca sul Cancro (AIRC, IG 2013 n. 14595). Distinctive LncRNA profile in NPM1-mutated AML.
Acknowledgements We gratefully acknowledge the assistance from the  bilateral Program ''Russian-German Laboratory'' at HZB BESSY II  and thank  Dmitry Smirnov  for valuable assistance. We gratefully acknowledge the financial support by  Helmholtz Zentrum Berlin (HZB)  and also thank  HZB  for the allocation of synchrotron radiation beamtime. The authors gratefully also acknowledge the  employees of the Centre ''Physical methods of surface investigation '' of the  Research park of St. Petersburg State University. This work was supported by  RFBR  grant  16-32-00276 mol_a.
Purpose-Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in ~20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with anti-tumor activity in FGFR1 amplified SQCLC cell lines and patient-derived xenografts. Design-Based on these data, we performed a phase 1 study of AZD4547 in patients with previously treated stage IV FGFR1 amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included anti-tumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses. Results-15 FGFR1 amplified patients were treated.
Data were collected using the nCounter digital analyser. nCounter data were normalized through an internally developed Pipeline Pilot Tool (NAPPA, publicly available on the Comprehensive R Archive Network, CRAN, Harbron & Wappett (2014) R package: NAPPA http://CRAN. R-project. org/package=NAPPA). In brief, data were log 2 transformed after being normalized in two steps: raw nanoString counts were first background adjusted with a Truncated Poisson correction using internal negative controls followed by a technical normalization using internal positive controls. Data was then corrected for input amount variation through a Sigmoid shrunken slope normalization step using the mean expression of housekeeping genes. A transcript was designated as not detected if the raw count was below the average of the 8 internal negative control raw counts plus 2 standard deviations reflecting approximately a 95% confidence interval.
Still others showed a fragmented expression pattern  (Patient 4C and 11). With regard to FGFR1 in particular, gene expression was relatively low in most patients' tumors. We did identify heterogeneity in FGFR1 mRNA expression in one patient who had two sites of disease available for testing, commensurate with the heterogeneous protein expression detected by IHC (Patient 2A and B). Overall, protein expression did match gene expression where material was available for both assays. Importantly, however, neither occurred at high level in any tumor sample. MYC mRNA expression was also assessed in 8 patients, and while present in all tested cases, was not overexpressed relative to FGFR1 in any case (data not shown).
AZD4547 pharmacokinetics The plasma concentration of AZD4547 was assessed on day 1 of cycles 2 and 3 pre-dose and during prespecified time windows post-dose. There was variability in the PK between patients, in part because of dose reductions from 80mg to 40mg bid in one patient, making specific correlative assessments difficult (Supplementary File 6). Overall, across the histologic expansion arms of the study (Part C), the predose geometric mean concentrations were similar at cycle 2 and cycle 3, ranging from 92. 5-182. 2ng/mL and 56. 8-170. 3ng/mL, respectively, suggesting stability in the PK of AZD4547 over time. There was no clear correlation between C2D1 or C3D1 PK data and response, either by RECIST or unidimensional shrinkage (Supplementary Figure  2 ).
Discussion This is, to our knowledge, the first prospective study of FGFR1 inhibition in patients with FGFR1 amplified stage IV squamous cell lung cancers to report relatively comprehensive data on the molecular landscape of these tumors, with an eye towards elucidating the relationship between gene, RNA, and protein expression. While pre-clinical studies provided a strong rationale for kinase inhibition in this setting, the clinical data to date show only modest efficacy in this study as well as studies of the pan-FGFR inhibitor BGJ398 and the multi-kinase inhibitor dovitinib. (7, 8)  Correlative studies performed by us suggest two possible explanations for this. First, while all patient tumors exhibited FGFR1 amplification by FISH, only a subset was found to have amplification by sequencing.
Notch1 repression was also associated with the induction of FGF1, 3, 4, and 5 mRNA and protein suggesting that autocrine production of FGFR1activating ligands may determine the degree to which FGFR1 is an oncogenic driver. This is in keeping with data from Malchers and colleagues  (9) , who identified autocrine production of FGF2 as a potential mediator of response to FGFR1 inhibition in an FGFR1 amplified SQCLC model. While MYC expression was also assessed, Patients 6 and 7 (-20%, -35% response) had insufficient tumor material for testing, preventing us from ruling-out lack of MYC expression as a potential sensitizer. (9)  Finally, paired pre-treatment/post-treatment tumor biopsies were not obtained in this study, precluding a direct assessment of FGFR1 pathway inhibition. That said, the observed elevation in serum phosphate is a well-characterized on-target effect of the drug attributable to inhibition of FGF23 signaling through FGFR1 in the kidney.
Statement of Translational Relevance Initial attempts at identifying targeted therapies for patients with squamous cell lung cancers (SQCLC) have largely failed, despite relatively detailed knowledge of the somatic events that occur in these cancers. The reasons for this are not clear. Current hypotheses center around the functional validity of the current panel of biomarkers and the role of genomic complexity as it relates to bypass pathways. None of this has been shown to be clinically relevant to date. We present clinical and molecular data that show that targeted therapy development for FGFR1 amplified SQCLCs will need to adjust for the molecular complexity of these tumors in a more comprehensive fashion for existing and future trials, with implications for other targeted efforts in this disease.
In 2013, the Group on Earth Observations Biodiversity Observation Network (GEO BON) developed the frame-work of Essential Biodiversity Variables (EBVs), inspired by the Essential Climate Variables (ECVs). The EBV framework was developed to distill the complexity of biodiversity into a manageable list of priorities and to bring a more coordinated approach to observing biodiversity on a global scale. However, efforts to address the scientific challenges associated with this task have been hindered by diverse interpretations of the definition of an EBV. Here, the authors define an EBV as a critical biological variable that characterizes an aspect of biodiversity, functioning as the interface between raw data and indicators. This relationship is clarified through a multi-faceted stock market analogy, drawing from relevant examples of biodiversity indicators that use EBVs, such as the Living Planet Index and the UK Spring Index.
This paper was financed by the EU BON project that is a 7th Frame-work Programme funded by the European Union under Contract No. 308454. IRG contributed in the frame of the Labex OT Med (no. ANR-11-LABX-0061) funded by the French Government through the A*MIDEX project (no. ANR-11-IDEX-0001-02). The funding bodies had no role in the design, interpretation, or writing of this paper.
Results We recruited a group of 20 control subjects. Behavioral data strictly replicated our previous results 3 (see Fig. 2 ). A main effect of memory was found (F(1,943) = 51. 87; p < 10 -11 ), as well as a main effect of condition(F(1,980) = 6. 71; p = 0. 009). Crucially, the critical and predicted interaction between memory and condition was significant (F(1,992) = 11. 14; p < 0. 001): while no difference of spreads was observed between RCR and RRC conditions for forgotten items (t(19) = -0. 57; p = 0. 6), the spread was significantly larger in the RCR condition than in the RRC condition for remembered items (t(19) = 3. 11; p = 0. 005). These subjects' memory performance was at 45. 7% (± 13. 5) correctly remembered items. We then turned to fMRI analyses and first verified that our task engaged the brain value system  [12] [13] [14]  by identifying regions whose activity correlated with subjects' ratings (in Rating 1 session, see SI).
Stimuli and procedure. Experiment 1: Behavior and fMRI in controls. Overview. The experiment was composed of 5 consecutive blocks, during which fMRI data were acquired: two rating blocks (Rating 1 and 2) and two Choice blocks (Choice 1 and 2) and one repetition detection block. Finally, a memory test and a familiarity assessment were performed after the scanning sessions. Stimuli. Stimuli consisted of 120 colored images of potential vacation destinations. In Rating blocks and in the repetition detection block, one image was presented at the center of the screen with the destination name printed below the image (font size = 30) in each trial. In Choice blocks, two images and their respective names were presented to the left and to the right of the screen, in each trial. The order in which stimuli were presented within each block was random.
Acknowledgements This work has been supported by the  Fondation pour la Recherche Médicale  ('Equipe FRM 2015' grant to L. N. ), by an  AXA Research Fund  grant to I. E. K. , and by the  IHU-A-ICM  (' Investissement d'avenir' program ,  ANR-10-IAIHU-06 ). We thank our colleagues  Laurent Cohen ,  Benjamin Rohaut  and  Vadim Axelrod , as well as the two Reviewers and the Editorial Board member for their very constructive remarks.
Efficacy of TCVs Proof-in-principle of TCV efficacy is derived from trials of the US NIH Vi-rEPA vaccine, and data from these trials were reviewed to inform future trial designs. Efficacy of up to 92% at 24 months and 89% at 46 months has been demonstrated in trials of the Vi-rEPA vaccine carried out in Vietnam, when given as a two-dose schedule in 2-5 year olds  [32, 33]. A post hoc analysis of trial participants administered a single dose of the Vi-rEPA vaccine indicated a protective efficacy of approximately 88%  [34]. However, these trials do not address the issues of TCV efficacy in children under the age of 2 years. Whilst efficacy data are available for Vi-rEPA, it is unclear whether similar results would be observed with TCVs that use other carrier proteins, such as tetanus toxoid.
Measuring outcomes The selection of robust outcome measures will be central to the design of TCV effectiveness studies. The outcome recorded due to the vaccination will affect the generalizability of data generated. Whilst there is no perfect outcome measure, some have clear advantages. The primary outcome of TCV effectiveness studies should be to measure the impact on the burden of typhoid disease using the incidence of blood-culture positive cases as a fixed endpoint. Clinically defined endpoints are problematic due to the nonspecific case presentation of typhoid and range of alternate diagnoses  [48] [49] [50] [51]. A careful clinical case definition for enrolment and collection of blood cultures will have to be defined. Exploratory diagnostics (e. g. antibody in lymphocyte supernatant (ALS), culture-PCR) could be used to broaden the case-definition in some cases, as secondary/exploratory endpoints.
Identification of ASP3 substrates using N-terminome analysis The phenotypic consequences of ASP3 depletion suggest that this protease contributes to the processing of proteins implicated in rhoptry discharge and host PM lysis. Given its localization in the vicinity of the ELC, we hypothesized a plausible role as maturase for MICs, ROPs and RONs, known to undergo maturation along the secretory pathway, prior to accumulation in their respective secretory organelles. To determine the in vivo repertoire of ASP3 substrates and their precise cleavage sites, we quantitatively compared the N-terminome of ASP3ty-iKD parasites +ATc/-ATc using Terminal Amine Isotopic Labelling of Substrates (TAILS) (Figure  2 -figure supplement 1)  (Kleifeld et al. , 2010; Kleifeld et al. , 2011). The TAILS datasets yielded 32594 peptide spectrum match (PSM), which could be assigned to 9169 T.
gondii-specific peptide groups representing 1529 proteins contained in ToxoDB. Among the identified peptides, we found 1487 N-terminal peptides (~16%) supported by 8103 PSMs. 615 of these terminal peptides were acetylated (supported by 2597 PSMs) and therefore represent natural N-termini. The remaining 872 peptide groups were labelled with TMT on the alpha amine group (Figure  2A ). As expected, the total proteome (pre-TAILS data, 1236 annotated proteins) overlapped with the proteins identified by the TAILS dataset (887 proteins), but enrichment for N-terminal peptides also identified 293 additional proteins (Figure  2B ). Normalized log2 abundance ratios (+ATc/-ATc) were calculated for each peptide group to identify ASP3-dependent cleavages. Among the 872 labelled peptide groups, we identified 65 showing either <0.
22 or >2 +ATc/-ATc ratios in the ASP3 depleted condition, representing 17 and 29 proteins (41 unique proteins combined), respectively (Figure  2C , Table  1 , Supplementary files 1 and 3). 26 of the 41 unique proteins with putative ASP3-dependent processing profiles are annotated as secreted proteins in ToxoDB. A more relaxed +ATc/-ATc ratio threshold of <0. 5 expanded this candidate dataset by 42 proteins to 59 (Supplementary file 2). Strikingly, concordant with the egress and invasion phenotypes of ASP3 depletion, the majority of proteins are annotated as MICs, RONs and ROPs, some of which were previously shown to be processed post-Golgi. (Detailed analysis of the TAILS and the criteria for substrate selection is described in Appendix 1).
In this context, toxolysin 4 (TLN4) is a metalloproteinase stored in the micronemes, extensively processed prior to secretion and previously reported to participate in invasion and egress  (Laliberteand Carruthers, 2011). When expressed as a HA-tagged second copy in ASP3ty-iKD, TLN4 exhibited an altered pattern of processing upon ASP3 depletion (Figure  3E ). PLP1 is the only microneme protein implicated in egress and for which a peptide is found enriched in the TAILS data set, which is consistent with the reported N-terminal processing of PLP1 prior to exocytosis  (Kafsack et al. , 2009; Lagal et al. , 2010). Since parasites lacking PLP1 remain trapped into host cells and still surrounded by the PMV, we also assessed the processing of PLP1 in ASP3ty-iKD +/-ATc by C-terminal tagging at the endogenous locus.
Given the severe defect in invasion caused by ASP3 depletion, we assessed whether unprocessed RONs would be affected in their assembly as a complex. Co-immunoprecipitation experiments confirmed that the RON2 and RON4. Global analysis of MS data and peptide ratios. (A) All measured spectra (65'900) minus those with low quality attributes leave 32'594 high quality spectra (9169 peptide groups) for the analysis. The graphical representation depicts proportions of N-terminal peptides in the pre-TAILS and TAILS datasets (blue pie charts) and corresponding N-acetyl modifications (ochre pie charts). N-termini in the TAILS fraction are enriched by >10 fold (69% vs 6%) over internal peptides (generated by trypsin cleavage). (B) Graphical representation of the 1529 proteins in the combined datasets.
Novel rhoptry proteins identified as ASP3 substrates by the TAILS analysis To further validate the TAILS analysis, we explored 8 hypothetical proteins (named TAILS1-8) from the TAILS dataset (relaxed stringency, with either >2 and <0. 5 ratios), selected based on their expression profile, fitness score  (Sidik et al. , 2016)   and conservation (Table 1, Supplementary files  1-3  and Figure 5-figure supplement 1 ). Epitope-tagging of the candidates at the endogenous locus in ASP3myc-iKD revealed that 5 out of the 8 gene products localized to the rhoptries, overlapping with ARO, a known marker of the rhoptries (Figure  5B, D, F, H, J ). This is consistent with the cell cycle dependent expression profile of their transcripts  (Behnke et al. , 2010)  (Figure  5 -figure supplement 1). While TAILS1 (TGME49_202870) has a nuclear localization, TAILS4 (TGME49_239050) appears to be cytosolic (data not shown).
Overall, these results led to the identification of 5 novel rhoptry proteins, validating further the robustness of the TAILS analysis as a powerful technique for protease substrates identification. Table  1. List of peptides detected in the combined TAILS datasets with +ATc/-ATc peptide ratios < 0. 22 (green columns) and >2 (red columns). The ethylamine scaffold based compound 49c recapitulates ASP3 depletion phenotypes Aspartyl proteases qualify as attractive targets for chemotherapy against pathogens and have been the focus of intense research toward the identification of antimalarial drugs. Interestingly, 49c belongs to a series of antimalarials based on a hydroxyethylamine scaffold, and designed to inhibit the malaria Plasmepsin II  (Boss et al. , 2003; Ciana et al. , 2013)  (Figure  6A ).
PLP1 was identified in the TAILS analysis and WB performed in absence of ASP3 indicates slight alternation of the processing pattern that might result in a partial dysfunction of the perforin activity  (Roiko and Carruthers, 2013). The TAILS dataset identified several hypothetical proteins and 5 out of the 8 candidates analyzed further, were confirmed as bona fide rhoptry proteins and ASP3 substrates. Functional characterization of these and other TAILS candidates should help identifying the factor critical for the initial step of invasion and implicated in rhoptry discharge. Invasion and egress are key events for survival and dissemination of the Apicomplexa and an aspartic protease essential for these two steps constitutes an attractive target for drug intervention. Antimalarials primarily target apicoplast or food vacuole that are hosting metabolic pathways and ensuring parasite growth.
LC-MS analysis Peptides were analyzed on an Orbitrap Fusion Tribrid Mass Spectrometer (Thermo Scientific) operated in line with an EASY-nLC 1000 Liquid Chromatography system (Thermo Scientific) in data dependent analysis mode (DDA). In brief, we separated peptides by reverse phase (RP) chromatography on custom made 150 cm x 75 mm ID frit columns packed with Reprosil-Pur 120 C18-AQ, 1. 9 mm (Dr. Maisch GmbH). The liquid phase was mixed from 0. 1% FA in water (A) and 0. 1% FA in ACN (B) both obtained in MS-grade from Biosolve. For separation, peptides were directly loaded onto the analytical column and resolved by applying a linear gradient from 2% to 35% B in 120 min at a constant flow rate of 300 nl/min. The analytical column was heated to 50˚C by an electronic column heater for fused silica columns (PST).