dataesr/scientific-paragraphs-categorization huggingface dataset:
Their head was restrained and equipped with MRI-compatible headphones customized for monkeys (MR Confon GmbH). A radial receive-only surface coil (10 cm diameter) was positioned above the head. Eye position was monitored at 120 Hz during scanning using a pupil-corneal reflection tracking system (Iscan). Animals were rewarded with liquid dispensed by a computer-controlled reward delivery system (Crist) through a plastic tube coming to their mouth. The task, all the behavioral parameters, and the sensory stimulations were monitored by two computers running with MATLAB and Presentation (Neurobehavioural Systems). Visual stimulations were projected onto the screen with a Canon XEED SX60 projector. Tactile stimulations were delivered through Teflon tubing and two articulated plastic arms connected to distant air pressure electro-valves.
1). In all of the three bimodal conditions, the spatial extent of the observed functional activations is only marginally affected by whether the analyses are performed relative to the visual or to the tactile stimuli. Thus, unless stated otherwise, the communication of the results and their discussion refer to the analysis timed on the visual stimuli. Regions-of-interest. We performed regions-of-interest (ROIs) analyses using MarsBar toolbox  (Brett et al. , 2002) , based on the fixed effects individual analyses results. To ensure statistically valid inferences when performing the ROI analysis, we divided, for each individual subject, the functional runs into two independent datasets of equal size. The ROIs were defined on one dataset, using the activations obtained at uncorrected level (t scores Ͼ 3.
1) in the fully predictive bimodal VT condition (VT_Full) versus fixation contrast. For each of these ROIs, the percentage of signal change (PSC) was extracted at their associated coordinates for all the runs belonging to the second dataset, using SPM8 and the MarsBar toolbox (http://marsbar. sourceforge. net; Brett et al. , 2002). Specifically, for each ROI, MarsBar allows to extract the signal intensity at the event of interest in percentage with respect to the whole brain mean (Ev/WholeBrain). Likewise, for each ROI, and each event of interest, it allows to extract the signal intensity at the corresponding reference fixations (i. e. , fixations sampled within the same blocks as the events of interest), again in percentage with respect to the whole brain mean (Fix/ WholeBrain). The PSC we report corresponds to the difference between Ev/WholeBrain and Fix/WholeBrain.
The significance of these PSCs across all runs was assessed using repeated-measures ANOVA and paired t tests, after the data for each ROI was tested for normality (Kolmogorov-Smirnov test). Within these ROIs, we reported superadditive and subadditive interactions to test for multisensory integration processes. Potential covariates. In all analyses, realignment parameters, as well as eye movement traces, were included as covariates of no interest to remove eye movement and brain motion artifacts. However, some of the stimulations might have induced a specific behavioral pattern biasing our analysis, not fully accounted for by the above regressors. For example, airpuffs to the face might have evoked facial mimics (for an analysis of blink-related activations, see  Guipponi et al. , 2015b )  inducing some degree of variability in the point of impact of the air puffs.
The variations of pupil size were analyzed as a function of block condition, to identify possible autonomic markers that the monkeys were interpreting differently each stimulation block, based on the predictive information provided by each block (Fig. 2A ). Specifically, changes in pupil size in time were normalized with respect to the pupil size average of each session. The main pupil size analysis describes the average deviation of pupil size in each block condition with respect to the overall session average, per monkey. Eye movements analyses indicate that fixation behavior did not significantly vary from one block to the other, for each monkey (see next section). As a result, changes in pupil diameter cannot be accounted for by changes in eye movements. Eye movement data analysis. During the MRI scanning sessions, the horizontal ( X) and vertical ( Y) eye position of the monkey was recorded (in degrees).
, Tokyo, Japan) at room temperature for 3 min. The grids were observed by a transmission electron microscope (JEM-1400Plus: JEOL Ltd. , Tokyo, Japan) at an acceleration voltage of 80 kV. Images from light, scanning and tranmission electron microscopy were used to measure cell dimensions and frustule thickness using ImageJ software. Measurements of cell diameter and length from light microscope images of cells in girdle-band orientation were used to calculate surface area and volume, and surface area to volume ratios for individual cells.
Aggregation analysis During the same growth experiment, a sub-sample was taken from each replicate culture and viewed using light microscopy (Olympus BX40). At least 100 cells were counted per sample in triplicate and the number of cells per aggregate was recorded. In addition, the number of cells counted was divided by the number of aggregates counted to give the average number of cells per particle. These data were used to normalise cell abundances obtained by coulter counter for the same cultures. Transcriptome sequencing RNA was extracted from triplicate cultures of nourseothricin cassette alone (NAT) and two independent TSD cell lines harvested during late exponential phase and following 48 h silicon starvation as described under 'Transcript level silacidin expression analysis' (Supplementary Figure  S2 ).
, 2008). Note: Gene ID 23685 features in both Mock_Si and Mock_pH. Genes differentially regulated in all TSD transcriptomes compared with NAT (TSD1+3 E+S). 8615, 3898, 8616, 6681, 7687, 12137 (no annotation) , Gene ID 7353 (IPR000408 Regulator of chromosome condensation, RCC1), Gene ID 6886 (IPR001440 TPR repeat), 7435 (GO terms 0016051: carbohydrate biosynthetic process, 0016758 transferase activity transferring hexosyl groups), 263350 (GO terms 0003899 DNA-directed RNA polymerase activity, 0006350 transcription) 23686 (IPR001678 Bacterial Fmu (Sun)/ eukaryotic nucleolar NOL1/Nop2p), 9840 (GO terms 0003677 DNA binding, 0003700 sequence-specific transcription factor activity, 0005215 transporter activity, 0005634 nucleus, 0006355 regulation of transcription DNA-dependent, 0006810 transport, 0016020 membrane).
Acknowledgements We acknowledge the  Leverhulme Trust  ( F/00204/AP ) and the  Natural Environment Research Council  ( NE/K004530/1 ) for funding. We also acknowledge  EMBO  for a short-term fellowship ( ASTF295. 00-2010 )awarded to AR Kirkham. The T. pseudonana temperature evolution experiment was funded by a PhD studentship from the  School of Environmental Sciences, University of East Anglia  awarded to K Schmidt. We are grateful to  A Toseland  for bioinformatics assistance. E Brunner  gratefully acknowledges financial support from the  Deutsche Forschungsgemeinschaft  ( BR1278/24-1. 2within   FOR 2038 "Nanomee ").
10, 15, 16 However, these trials were generally 8-12 weeks in duration and focused on short-term improvement of lung function outcomes, thus they were unable to assess longer term fluctuations in asthma control and events, such as exacerbations. Moreover, smokers and patients with unstable asthma, who may both have more prominent small airways disease,  4, 17  were typically excluded, as were patients with poor inhaler techniques, who might also benefit from extrafine-particle ICSs. 18 Thus, the question remains whether ICS particle size plays a role in long-term effectiveness of ICS therapy. Non-interventional observational studies using high-quality databases can capture prescribing and medical record information to assess long-term outcomes for patients with asthma often excluded from clinical trials but commonly seen by clinicians, such as smokers, patients with poor inhaler techniques, patients at high risk of exacerbation, and those with comorbidities.
14, 17, 19, 20 Previous database studies in the UK and USA have found in matched cohort analyses that the prescription of extrafine-particle beclomethasone was associated with equal, or better, asthma-related outcomes over a 1-year period, at significantly lower prescribed ICS doses, than standard fine-particle fluticasone. 21, 22 The aim of the current historical cohort study was to compare 1-year asthma-related outcomes between extrafine particle ciclesonide and 2 standard fine-particle ICS, fluticasone and non-extrafine beclomethasone, for patients in the Netherlands prescribed their first ICS.
Patients and study design Patients eligible for this study were aged 12-60 years, had ≥1 full year of baseline and ≥1 full year of outcome data before and after their first recorded prescription of ICS (initiation date), and had received 2 or more prescriptions for asthma at any time in their records in addition to the first ICS prescription, including at least 1 more ICS prescription during outcome (but no ICS during the baseline year); therefore, all patients included received at least 2 ICS prescriptions. We excluded patients >60 years old, those with any other recorded chronic respiratory disease, and those prescribed long-acting muscarinic antagonists or maintenance oral corticosteroid therapy during the baseline year. At the initiation date, patients received a first prescription of ICS delivered using a pMDI as the extrafine-particle ICS ciclesonide (Alvesco ® , Takeda Pharmaceuticals International GmbH, Zurich, Switzerland) or a pMDI fine-particle ICS, either fluticasone propionate (Flixotide ® , GlaxoSmithKline, Brentford, Middlesex, UK) or non-extrafine beclomethasone dipropionate (Supplementary Fig.
Study endpoints Co-primary endpoints were assessed during 1 outcome year after initiation of ICS therapy and included (1) the rate of severe exacerbations, defined as asthma-related hospital admission or acute oral corticosteroid prescription (based on the American Thoracic Society/European Respiratory Society definition  29  excluding emergency department attendance, not available in the database); (2) risk-domain asthma control, defined as the absence of severe exacerbations; and (3) overall asthma control, defined as achieving risk-domain asthma control plus mean daily dose of albuterol of ≤200 µg. Secondary endpoints included the change in therapy and mean daily dose of shortacting β 2-agonists (SABA) during the outcome period (additional detail in the Online Supplement).
Statistical analysis Analyses were carried out using IBM SPSS Statistics version 22, Microsoft Office EXCEL 2007, and SAS version 9. 3. Statistical significance was defined as P<0. 05. Chi-square or Mann Whitney U-tests (unmatched data) and conditional logistic regression (matched data) were used to compare treatment cohorts at baseline. Patients in the 2 cohorts were matched using 1:1 exact-matching methods,  30  described in the Online Supplement. Matching variables were sex, age, baseline risk-domain asthma control, prescribed long-acting β 2-agonist, SABA daily dose, prescribed leukotriene receptor antagonist, prescribed antifungal medication for oral candidiasis, and year of ICS therapy initiation. A conditional Poisson regression model was used to compare the rates of severe exacerbations and hospitalizations for matched patients.
Patients There were 4,064 eligible patients identified in the database during the study period; 1,382 (34%) were prescribed extrafineparticle ciclesonide, and 2,682 (66%) fine-particle ICS. Applying the matching criteria led to 1,244 patients being selected in each treatment cohort (Supplementary Fig. 2 ). After matching, baseline asthma control measures, SABA daily dose, and prior maintenance asthma therapy were comparable between the cohorts (Table  1 ). Asthma-related hospital admissions during the baseline year, while generally infrequent, were significantly more prevalent in the ciclesonide cohort (Table 1); significantly more patients who received ciclesonide had evidence of rhinitis (43% vs 38%; P=0. 004) and were prescribed proton pump inhibitors (41% vs 34%; P<0. 001) than those who received fine-particle ICS.
Finally, our analyses were limited by data availability; for example, smoking history, which may have some impact on effectiveness of ICS,  17, 36  was not available, and nor were body mass index and lung function data. Diagnostic information was inferred from prescribing data. This meant that patients were selected as having asthma based on prescribed therapy, potentially leading to diagnostic misclassification. To mitigate this, we excluded patients with only 1 ICS prescription, which could have been a therapy trial. We were not able to assess current clinical control, but SABA dose (based on prescriptions) served as an indication of symptom control: 83% and 64% of patients in the ciclesonide and fine-particle ICS cohorts, respectively, were prescribed ≤1 puff/day (≤100 µg/day) of SABA on average, well within the definition of good control of asthma from an administrative database.
ACKNOWLEDGMENTS Funds to acquire the dataset from the PHARMO Institute were provided by  Research in Real-Life, Ltd (RiRL). The study data were provided to the  Small Airways Study Group (SASG) , which received financial support to conduct the analyses from  Takeda Pharmaceuticals International GmbH, Zurich, Switzerland. Two Takeda  employees (D. vE. and J. M. K. ) are authors of the paper and participated in developing the study protocol and the manuscript. Members of the SASG were reimbursed for travel expenses to attend meetings to discuss this together with several other projects; they were not otherwise compensated for their advisory role. The authors acknowledge with gratitude the contributions of  Dr. Gene Colice  to study design and interpretation. We acknowledge  Dr. Matthias Binek  for contributions to the study design.
for Pharmacoepidemiology and Pharmacovigilance (ENCePP, study no. 6148 ). • The  University of Groningen  has received money for Professor Dirkje S. Postma regarding an unrestricted educational grant for research from  Astra Zeneca ,  Chiesi. Travel to ERS and/or ATS has been partially funded by  AstraZeneca ,  Chiesi ,  GSK ,  Takeda. Fees for consultancies were given to the  University of Groningen by AstraZeneca ,  Boehringer Ingelheim ,  Chiesi ,  GSK ,  Takeda , and  TEVA. Travel  and lectures in China paid by  Chiesi. Richard Dekhuijzen  has received over the past 3 years (i) fees for speaking, organising education, participation in advisory boards or consulting from  Almirall ,  AstraZeneca ,  Boehringer Ingelheim ,  Chiesi ,  Mundipharma ,  Novartis ,  Pfizer ,  Teva , Zambon; (ii) research grants from  Novartis ,  Boehringer Ingelheim ,  AstraZeneca.
Because of the difficulty in controlling P. vivax, in areas where the two species coexist its incidence appears to decrease more slowly than that of Plasmodium falciparum  [1]. Due to limitations associated with classical malaria control measures, vaccination against malaria is currently considered a potentially valuable cost-effective complement for malaria control activities that would significantly contribute to its elimination  [9]. During the last 2-3 decades, significant efforts have been invested on developing P. falciparum  [10] , and more recently P. vivax vaccines  [11]. However, discovery of new potential vaccine candidates is required. The use of bioinformatics tools has allowed to explore the malaria genome/proteome databases, and to identify parasite proteins containing specific domains with functional importance for the parasite that could be immunologically targeted and therefore represent novel candidate antigens for vaccine development.
Chromatin integrity -SCSA Sperm samples were adjusted to 2 × 10 6 spermatozoa/ mL in PBS to a final volume of 200 μL, to which 400 μl of acid detergent solution (0. 08 M HCl, 15 M NaCl, and 0. 1% Triton ×100, pH 1. 2) was subsequently added. After 30 s of incubation, 1. 2 mL of Acridine Orange (AO) solution was added (6 μg of AO per mL of buffer -0. 037 M citric acid, 0. 126 M Na2HPO4, 1. 1 M EDTA, and 0. 15 M NaCl, pH 6. 0). The samples were read 3 min after the addition of acid detergent, and 10,000 events were assessed  [18]. The assessments were analyzed using the Flowjo® program (Tree Star, Inc. , San Carlos, CA, USA) to obtain the total percentage of sperm with damaged chromatin (% DFI). Positive control samples were incubated in DDT (2 mM) for 45 min. Hydrogen peroxide (2 mM) and ferrous sulfate (1 mM) were then added, and samples were incubated for 60 min.
Statistical analysis Our null hypothesis (H0) was that there were no differences in DNA integrity and types of chromatin damage in cryopreserved sperm from bulls at different ages. The statistical analyses were performed using the SAS software, "Statistical Analysis System" software (release 9. 2. SAS Institute Inc. , Cary, NC, USA, 2008). The percentage data were transformed into arcsine to obtain a normal distribution. The results were examined using the "two-way" ANOVA (bulls × group). The averages were compared by the Duncan test and were considered significant when p < 0. 05. Correlation (r) and determination (r2) coefficients and the regression equation were calculated for selected variables  [19].
Plant Material Two accessions of wild pearl millet (Cenchrus americanus (L. ) Morrone ssp. monodii) were collected in West Africa from populations growing in the most drastic environmental conditions experienced by the species according to bioclimatic data (see details in  Berthouly-Salazar et al. 2016). One accession was collected in the driest environment in Niger (P9A, geographic coordinates: 18 31 0 48 00 N 8 38 0 24 00 E) and the No Excess of Cis-Regulatory Variation Associated with Intraspecific Selection in Cenchrus americanus.
Sequencing and Mapping Genomic DNA was extracted from leaf tissues of the F1 hybrids as previously described in  Mariac et al. (2014). Libraries were constructed using 6-bp barcodes to allow for multiplexing  (Mariac et al. 2014)  and were sequenced at the MGX-Montpellier GenomiX plateform (Montpellier, France) on two Illumina HISeq2500 lanes generating paired-end reads of 2Â125 pb. Demultiplexing based on the 6-bp barcodes was performed using the freely available Perl script Demuladapt (https://github. com/Maillol/demultadapt) with a 1-mismatch threshold. The resulting raw reads were cleaned for remaining adapter sequences using cutadapt  (v. 1. 8, Martin 2011). Reads were filtered based on their length (L > 35 bases) and on their quality mean values (Q > 30) using a freely available Perl script (https:// github.
com/SouthGreenPlatform/arcad-hts/blob/master/scripts/ arcad_hts_2_Filter_Fastq_On_Mean_Quality. pl). The remaining paired-end reads were mapped to the reference genome of cultivated pearl millet (Varshney RK, personal communication) using BWA software (v. 0. 7. 2,  Li and Durbin 2009)  with the MEM algorithm. The resulting SAM file was converted to BAM using  SAMtools (v. 1. 2, Li et al. 2009 ) and duplicated reads were marked using Picard's MarkDuplicates (v. 1. 83, http://broadinstitute. github. io/ picard). The genome mean coverage was estimated using QualiMap (v. 2. 0. 2, Garcia-Alcalde et al. 2012).
ASE Analysis Following the method implemented in the ASEQ tool  (Romanel et al. 2015) , we first performed a binomial test to identify the positions at which the ratio of the two alleles in the transcriptomic data is significantly different from 0. 5. Then we assessed the reference ratio derived from DNA sequencing and tested the difference between the allelic ratios obtained from the DNA and the RNA data using a Fisher exact test. A position was considered as ASE if both the two tests were significant. The rationale of this methodology is as follows: (1) to identify positions showing disequilibrium in read count for one allele compared with the other in the transcriptomic data and (2) among those positions, to exclude sites showing the same pattern of read count disequilibrium at the genomic level.
Indeed, deviation from the expected 0. 5 value of allelic ratio can be observed in genomic data as well as in transcriptomic data due to biases occurring during the mapping step either associated with copy number variation (CNV) or higher mappability of reads carrying the reference allele compared with the one carrying the alternate allele. To avoid no-independence between counts, we only considered SNPs separated by >100 bp. The whole analysis was performed separately for each hybrid. Our analysis enabled the identification of ASE at the level of SNPs. Using the intersect function of bedtools (v2. 25) (http://bedtools. readthedocs. io/; last accessed January 27, 2017), SNPs were assigned to genes identified in the GFF file of cultivated pearl millet (Varshney RK, personal communication). Genes were considered ASE if at least one of their SNPs was identified as ASE.
Study design We conducted a phase II, multicenter, international, randomized, double-blind, placebo-controlled trial (Clinical-Trials. gov identifier: NCT01528345) designed to evaluate the efficacy and safety of dovitinib in combination with fulvestrant in postmenopausal women with HR + , HER2 - locally advanced or metastatic breast cancer who had evidence of disease progression. Enrolled patients were randomized in a 1:1 ratio to receive dovitinib plus fulvestrant or placebo plus fulvestrant, stratified by FGF pathway amplification status (amplified vs nonamplified) and presence of visceral disease (yes vs no). All patients received fulvestrant 500 mg (intramuscular injection once every 4 weeks, with an additional dose 2 weeks after the initial dose) and dovitinib (500 mg) or placebo orally following a weekly 5 days on and 2 days off schedule until death, loss to follow-up, disease progression, or consent withdrawal.
FGF pathway amplification was determined by a designated Clinical Laboratory Improvement Amendments-certified laboratory using a TaqMan PCR assay (Life Technologies, Carlsbad, CA, USA), as previously described  [38]. Positive amplification for each FGF pathway marker tested (i. e. , FGFR1, FGFR2, or FGF3) was defined as a copy number ≥6; copy number was quantified by comparison with a reference gene (human ribonuclease P RNA component H1) and calculated using CopyCaller software (version 1. 1; Applied Biosystems, Foster City, CA, USA). Samples were considered to be FGF pathway-amplified if they had positive amplification of FGFR1, FGFR2, and/or FGF3. Given that the previously defined amplification cutoff of at least six copies for FGFR1 was associated with higher sensitivity to dovitinib monotherapy  [38] , the same cutoff was used in this combination therapy study.
Data analysis The primary endpoint, PFS, was evaluated in each of the treatment arms using three sets of comparisons, following a Bayesian design: (1) all patients regardless of FGF pathway amplification status, (2) FGF pathway-amplified, and (3) FGF pathway-nonamplified (Additional file 1). Patients who did not have a PFS event at the time of analysis or who had received further antineoplastic therapy were censored at the time of the last tumor assessment. Kaplan-Meier plots were generated by treatment arm for the full population, FGF pathway-amplified subpopulation, and FGF pathway-nonamplified subpopulation. The HR of PFS in the full population was estimated using a Cox proportional hazards model stratified by FGF pathway amplification status and presence of visceral disease (yes vs no).