dataesr/scientific-paragraphs-categorization huggingface dataset:
Boundary conditions and experiment design for climate simulations Data from the Atmospheric GCM HadAM3H developed by the Hadley Center was used to drive the MM5 regional model. The HadAM3H model resolution is 1. 25º latitude by 1. 875º longitude. Details of the model characteristics can be found in  Pope et al. (2000). The HadAM3H present-climate simulations from 1961 to 1990 were initialized with atmospheric and land surface conditions from the Coupled Ocean-Atmosphere Global Climate Model (HadCM3) and forced with observed sea surface temperature (SST) and sea-ice distribution from the Hadley Centre HadISST dataset  (Rayner et al. , 2003). This database shows a mixture of global monthly sea surface temperature and sea-ice concentration at 1º horizontal resolution from 1871. The MM5 model requires initial and time evolving boundary conditions for wind components, temperature, geopotential height, relative humidity and surface pressure.
Validation data For the validation of monthly mean precipitation and surface air temperature, the Climate Research Unit (CRU) dataset  (Mitchell et al. , 2003)  from East Anglia University has been used. CRU is available over a 0. 5º × 0. 5º horizontal grid. The NCEP/NCAR reanalysis  (Kalnay et al. , 1996)  was used for validation of the circulation variables (zonal and meridional winds).
Over the western Andes the model overestimates the mean temperature compared to the CRU Fig. 4. Same as in Figure  3 , but for surface air temperature. Units are in ºC. database; in contrast the simulated temperature is underestimated over the eastern side of the Andes. Similar results were found by  Marengo et al. (2009b)  and  Solman et al. (2007). The positive bias over the center of Argentina and over the subtropical region of South America is a feature that has also been found in others  (Chou et al. , 2012   Furthermore, the positive bias over the subtropical region of South America is consistent with results by  Misra et al. (2002 Misra et al. ( , 2003) )  and  Chou et al. (2012) , and the magnitude of temperature bias is similar to that obtained with the RegCM3 model, documented in  Fernández et al.
Acknowledgments We would like to thank the  Hadley Centre  for providing the HadAM3H data. This work was partially supported by  UBACYT-Y028 ,  CLAR-IS-LPB (A Europe-South America Network for Climate Change Assessment and Impact Studies in La Plata Basin  [http://www. claris-eu. org/]) and  CONICET  grants  PIP 112-201101-00189  and  PIP 112-200801-00195.
In particular, the analysis mainly focuses on four innovations pertaining to the Greek language, namely genitive-dative syncretism, the loss of infinitive, the formation of the periphrastic perfect and the dislocation of clitics. The dissertation aims at tracing these changes back to their starting points and taking a close look at their further evolution. Data have been collected by creating a corpus of circa 300 private letters on papyrus, which were chosen among already published collections of letters or non-literary papyrus documents: testimonies were brought together and translated.
Acknowledgments Limited funding was provided by  Nordic Pharma Europe  to facilitate panel members' travel to meetings they were not already attending, and to provide administrative support from  Michel Bordier  in literature searching, providing papers for review, and minuting expert panel discussions. Corvus Communications received support for AMC's time in critique and development of the manuscript as part of the expert panel. Prior to submission, Nordic Pharma Europe was sent a copy of the final manuscript but did not comment. Without the support from  Nordic Pharma Europe , the project would not have been able to be as thorough.
Acknowledgments We would like to thank  Dr. Richard A. Van Etten  for the MSCV-BCR/ABL (p210)-IRES-GFP vector. Support of this project was from  NIH  grant  1R01CA172268 ,  Leukemia & Lymphoma Society Awards LLS # 1024-14  and LLS# 6024-14-01 ,  CPRIT RP140402 , and  Taishan Scholar Program.
Procedures All individuals aged ≥6 months were invited to participate in the surveys. Individual informed consent was obtained from adults, and parental consent was obtained for children aged <16 years. Demographic data and symptom information were collected from each person, and the tympanic temperature, weight, and height were measured. A venous blood specimen (volume, 3 mL) was collected from all individuals aged ≥5 years, and 500-µL blood specimens were obtained from children aged ≥6 months to 5 years. Sample processing for quantitative uPCR analysis included separation of plasma, buffy coat, and packed red blood cells, which were then frozen and stored at -80°C and transported to the laboratory in Bangkok, Thailand, for DNA extraction and quantitative uPCR analysis  [11, 12]. All samples obtained for molecular analyses were handled and processed according to the standard operating procedures developed specifically for these studies  [12].
Acknowledgments. We thank the communities and their representatives and our many colleagues who helped conduct these surveys. Financial support. This work was supported by the  Wellcome Trust  (strategic award  101148 ) and the  Bill and Melinda Gates Foundation  ( OPP1081420 ) and was part of the  Wellcome Trust Mahidol University Oxford Tropical Medicine Research Programme. Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the  ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Statistical analyses Analyses were performed on all available data from patients participating in the OLE study. OLE data are presented according to the intervention received during the double-blind study period (control-active and active-active). The following (differences in) effects on the exploratory NTB memory domain scores were statistically tested: a) between-group comparisons including control-active group versus active-active group in the total 48 week and 24-48 week intervals and the comparison of the baseline-24 week interval in the active-active group versus the 24-48 week interval in the control-active group, and b) within-group comparisons including within the control-active group the comparison of the active intervention (week 24-48) versus control intervention (baseline-week 24), within the active-active group the comparison of the baselineweek 24 interval versus the week 24-48 interval and both within the control-active and active-active groups the change from 24 to 48 weeks.
In addition, two exploratory key groups of interest were defined for the analysis of effects on the NTB memory domain score: 1) patients who did not start using AD medication during the OLE study, and 2) patients with a large study gap. See supplementary material for detailed information. Comparisons were statistically tested using t-tests and/or by using a mixed model for repeated measures (MMRM) in which time was treated as a categorical variable and represented by dummies. Correction for multiple testing was not applied due to the explorative nature of this study, the small sample size, and the high correlation between outcome parameters. Statistical analyses were performed using SAS ® statistical software (SAS Enterprise Guide 4. 3 for Windows, SAS Institute Inc. , Cary, NC, USA).
Overall, the current data support results of previous studies and indicate that 48-week use of Souvenaid is safe and well-tolerated. Good compliance to an intervention is of particular importance in clinical practice, where adherence to AD therapies is often poor and represents a major problem  [28]. This OLE study reported a high product intake adherence (≥95%), which is line with previous studies  [18] [19] [20]  and supported by biochemical data. Although intake adherence is likely to be higher in a clinical trial population compared with a real-world clinical setting, high compliance was further supported by the low rate of discontinuation and these observations highlight the potential of Souvenaid as a useful intervention for AD in clinical practice. The main efficacy assessment from the RCT, the NTB memory domain z-score, was continued as an exploratory outcome measure in the OLE.
ACKNOWLEDGMENTS We sincerely thank the patients and their caregivers for their participation in the study and are indebted to the other investigators of the Souvenir II OLE study group:  Dr. F. H. Bouwman ;  Dr. P. L. J. Dautzenberg ;  Dr. W. M. W. Sipers ;  Dr. D. van Asselt ;  Dr. M. Stevens ;  Dr. P. Tack ;  Dr. P. Bourgeois ;  Dr. E. Mulleners ;  Dr. med. R. Horn ;  Prof. Dr. med. H-J. Gertz ;  Prof. Dr. med. J. Schröder; PD Dr. med. K-C. Steinwachs;  Dr. P. G. Gil ;  Dr. M. R. Boada ;  Prof. P. Mecocci ;  Prof. G. Rodriguez ;  Dr. P-J. Ousset ;  Dr. M. M. Vercelletto ;  Prof. M. P. M. Ceccaldi. Study design and conduct (collection, management, analysis and interpretation of the data, and preparation, review, and approval of the manuscript) were carried out in conjunction with the sponsor, Nutricia Research, on behalf of  Nutricia Advanced Medical Nutrition.
This could be of great value when monitoring tumors in patients treated by virotherapy. Note: a NCT references can be viewed at https://clinicaltrials. gov/ Abbreviations: Ad, adenovirus; GM-CSF, granulocyte-macrophage colony-stimulating factor; iL2, interleukin-2; MPM, malignant pleural mesothelioma; PD, progressive disease; PR, partial remission; SD, stable disease; VV, vaccinia virus; TCiD, tissue culture infective dose.
18 months Ad. hiFN-α2b Pilot 9 MPM 2 intrapleural injections well tolerated 34 (SCH 721015) (3-day interval) Neutralizing antibodies (3×10 11 -1×10 12 particles) 1 PR and 2 SD Ad. hiFN-α2b i/ii MPM 2 intrapleural injections Ongoing NCT01119664 a (SCH 721015) + 4-6 cycles of chemotherapy Ad. hiFN-α2b i MPM 2 intrapleural injections Ongoing NCT01212367 a (SCH 721015) (3-day interval) Ad5-D24-GMCSF Unspecified 2 MPM After chemotherapy well tolerated 54 Single intrapleural injection Tumor-specific and virus- (2. 5×10 11 -3×10 11 particles) specific immunity 1 SD and 1 PD Ad5/3-D24-GMCSF i 1 MPM After chemo-/radiotherapy T CD8 + tumor infiltration 65 (ONCOS-102) 4 intratumoral injections Th1 polarization (3×10 11 particles) + cyclophosphamide (daily) Poxvirus VV-iL2 6 MPM intratumoral injection well tolerated 21 No tumor regression JX-594 i 1 metastatic MPM After chemotherapy PR over 10 weeks 16 (pexastimogene Single intravenous injection devacirepvec) (1.
5×10 7 particles) GL-ONC1 i Malignant pleural effusions intrapleural injection Ongoing NCT01766739 a (primary, metastases, and MPM) Reovirus Reolysin i 1 MPM Pretreatment with docetaxel Minor response 48 intravenous injection 23% size decrease for (1×10 9 -3×10 10 TCiD 50 ) 1 invaded lymph node Up to 8 cycles (every 21 days) of 5 daily injections Measles virus MV-NiS i MPM intrapleural injections Ongoing NCT01503177 a Up to 6 cycles (every 28 days) Herpesvirus HSV-1716 i/iia MPM Single/multiple intrapleural Ongoing NCT01721018 a injections.
The data exported from the patients' files for analysis included: age, histologic subtype, maximum tumor size, number of LNs involved, SBR grade, ER, PgR expression, HER2 overexpression, date of diagnosis, date of relapse, date of death and date of last news. This study is reported according to the REMARK criteria  [23]  and was done according to French regulations and approved by the ethics committee of the Centre Léon Bérard.
Statistical analysis The correlation between TIF1γ, TGFβ1, SMAD4 expression and clinico-pathologic characteristics, was determined using Pearson's chi square test (or Fisher's exact test) for categorical variables and Student's T test for numerical variables. Disease-free survival (DFS) was defined as the time from the date of diagnosis of breast cancer to the date of any cancer recurrence (local or distant or contralateral), or death. Distant metastasis free survival (DMFS) was defined as the time from the date of diagnosis of breast cancer to the date of distant metastasis or death. Overall survival (OS) was defined as the time from the date of diagnosis of breast cancer to the date of death. To account for the heterogeneous follow up period resulting from different dates of diagnoses and last follow up visits, we locked the database at a maximum of 12 years of follow up and patients without events at 12 years were censored.
Survival curves, median DMFS, DFS and OS (if reached) in addition to 8 year DMFS, DFS and OS rate (with 95 % CIs) were derived from Kaplan-Meier estimates and the curves were compared using log-rank test  [25]. Hazard ratios and 95 % CIs were calculated using cox regression model  [26]. Cox multivariate analysis was performed using cox regression model to determine whether a factor is an independent predictor of DMFS, DFS or OS after adjusting for other significant factors at the univariate level. All statistical tests were two-sided, and the p value was considered statistically significant if less than 5 %. The statistical analyses were performed using SPSS 17. 0 statistics package (SPSS Inc, Chicago, IL).
Acknowledgments This work was supported by grants from  INSERM ; CNRS; the  Ligue Nationale contre le Cancer (Savoie ; grant to RR) and  Fondation ARC (Association pour la Recherche sur le Cancer ; grant to RR). LK received a research grant from  Novartis  oncology. LF was supported by fellowships from  MESR  ( Ministere de l'Enseignement Superieur et de la Recherche ) and next from  Fondation ARC. MD is supported by fellowships from the  Ligue Nationale contre le Cancer.
Statistical analysis normal distribution and homogeneity of the parameters tested were verified using the Shapiro-Wilk procedure. The tested parameters were not normally distributed and non-parametric statistical tests were therefore applied. Non-parametric paired Wilcoxon tests were carried out for each group (R and c) to assess within-group differences between V1 and V2. A non-parametric Mann-Whitney test was carried out to compare the characteristics of both groups. this test was also used to compare the percentage change in the functional test scores between groups. The significance level was fixed at p < 0. 05 for all statistical analyses. All the statistical analyses were carried out using Statistica ® version 7. 1 software. data from the clinical evaluation were described quantitatively and not analysed statistically because the scales used were ordinal (MAS and MRc).
Methods Patients and families. Written informed consent was obtained for all individuals enrolled in this study and approved by the Institutional Review boards at the University of Paris Descartes and at the University of Michigan. Homozygosity mapping, exome sequencing and mutation calling. Homozygosity mapping in families NPH302 and A4336 was performed using 'Human Mapping 250k NspI' array and parametric logarithm of odds scores were calculated with MERLIN software  43  for NPH302, and GENEHUNTER 2. 1 (ref. 44) ALLEGRO  45  for A4336, assuming autosomal-recessive inheritance. WES in patients A4336-22 and NPH302-23 were performed as follow. In brief, genomic DNA was isolated from blood lymphocytes and subjected to exome capture using Agilent SureSelect human exome capture arrays (Life Technologies) followed by next generation sequencing on the Illumina sequencing platform.
Paired-end reads were generated (75 þ 35 for SOLiD, 100 þ 100 for HiSeq) and sequences were aligned to the reference human genome hg19 with Illumina's processing software ELAND (CASAVA 1. 8. 2), the Burrows-Wheeler Aligner (Illumina) or mapread (SoliD). Downstream processing for WES in NPH302-23 and ciliome in NPH579-22, NPH638-21 and NPH1110-22 was carried out with the Genome Analysis Toolkit (GATK), SAMtools, and Picard Tools, following documented best practices (http:// www. broadinstitute. org/gatk/guide/topic?name=best-practices). All variants were annotated using a software system developed by the Paris Descartes University Bioinformatics platform  47. The mean depth of coverage obtained was greater than Â 90, and 489% of the exome was covered at least Â 15. Different filters were applied to exclude all variants located in non-exonic regions, pseudogenes, untranslated regions or known polymorphic variants with a frequency above 1%, that is present in databases such as dbSNP, 1000 genome projects and all variants identified by in-house exome sequencing (5,150 exomes and 1,020 ciliomes).
The functional consequence of missense variants was predicted using SIFT (http://sift. jcvi. org/www/SIFT_enst_submit. html), CADD/PHRED2 (http://cadd. gs. washington. edu/) and PolyPhen2 software (http://genetics. bwh. harvard. edu/pph2/). For A4336-22, SAMtools37 was used to call single-nucleotide variants and insertion/deletion at targeted bases. Variants with minor allele frequencies o1% in the Yale (1,972 European subjects), NHLBI GO Exome Sequencing Project (4,300 European and 2,202 African American subjects), dbSNP (version 135) or 1,000 Genomes (1,094 subjects of various ethnicities) databases were selected and annotated for impact on the encoded protein and for conservation of the reference base and amino acid among orthologs across phylogeny. Sequence reads were mapped to the human reference genome assembly (GRCh37/hg19) using CLC Genomics Workbench (version 4.
5 buffer containing 250 mM sucrose, 5 mM b-mercaptoethanol, 10 mM KCl, 1. 5 mM MgCl 2 and protease inhibitor cocktail (Roche) and then purified in large scale as described above. Circular dichroism spectroscopy. Secondary structure content was analysed on a Jasco J-715 spectropolarimeter at 4 °C using 0. 1 mg ml À 1 of recombinant purified proteins in a 0. 1-cm quartz cuvette. The measurements were performed in 10 mM HEPES 7. 5, 100 mM NaCl, 10% glycerol and 5 mM DTT. Data were obtained and processed using the Spectra Manager v2. 06 software from Jasco. The measured curves were buffer corrected and secondary structure assignments were done using the CONTIN fitting method and SMP56 as the reference protein set. Melting curves were measured continuously from 10 to 90 °C, with additional full spectra taken in 10 °C steps.
Data analysis was performed in Spectra Manager v2. 06. Zebrafish strains and morpholinos. Adult zebrafish were maintained at 28 °C, in system water with a conductivity of 500 mS and a pH of 7. Embryos were cultured at 28 °C in embryo medium with 0. 1% w/v methylene blue. The elipsa tp49d mutant, which encodes a premature stop codon at position 195 (previously described  13  ) was obtained as a gift from J. Malicki. Heterozygous sibling embryos were used as controls for all experiments using the elipsa mutant line. An anti-sense morpholino targeting traf3ip1 (previously published  13  ) was used for knock-down experiments. Knock-down of map4 was performed using an ATG translation-blocking morpholino (5 0 -GGCATCACGTAAACTAAAGTCCATC-3 0 ) and a 5-base-pair mismatch (5 0 -GACATAACGTAAAATAAAATCAATC-3 0 ) control, designed by and ordered from Genetools, LLC.
Wild-type Tu ¨:AB fish were used for all morpholino experiments unless stated otherwise. To rescue the elipsa/traf3ip1 knock-down phenotype, full-length zebrafish ift54 coding sequence was amplified by reverese transcription PCR (RT-PCR). Site-directed mutagenesis was then used to introduce mutations at the desired locations. The resulting products were then cloned into the pGEM-T Easy vector and constructs were linearized and transcribed using the SP6/T7 mMessage mMachine kit (Ambion). Approximately 100 pg of mRNA was injected into embryos at the 1-cell stage. Effects of RNA injections (WT and mutated RNAs) were evaluated based on severity of body curvature, analysis of pronephric cilia, presence or absence of pronephric cysts and surface area of the retina. Body curvature was quantified by measuring the internal angle of each larva using ImageJ software.
Fibroblasts were obtained from skin biopsies of patients and cultured in Optimem supplemented with 10% FBS, 100 U ml À 1 penicillin and 100 mg ml À 1 streptomycin (all from Life Technologies). Fibroblasts were then cultured up to 10 passages. Ciliogenesis was induced by starving the cells in serum-free Optimem for 24 h. HEK293T cells (from ATCC) were cultured in DMEM supplemented with 10% FBS, 100 U ml À 1 penicillin and 100 mg ml À 1 streptomycin. Antibodies. The following antibodies were used in the study: acetylated a-tubulin (6-11-B-1, used at 1:10,000 to detect cilia and 1:1,000 to detect cytoplasmic microtubules) and a-tubulin (T5168, used at 1:1,000 for immunofluorescence (IF) and 1:50,000 for western blot) from Sigma; EB1 (610534, used at 1:200), b-catenin (610153, used at 1:200) and anti-PKAc (610980, used at 1:200) from BD biosciences; acetylated a-tubulin (ab24610, used at 1:500) and a-tubulin (ab18251, used at 1:500) from Abcam; IFT54 (HPA037858, Atlas Antibodies, used at 1:50 for IF and 1:1,000 for WB); ZO1 (61-7300, used at 1:100) from Life Technologies; ARL13B (17711-1-AP, Proteintech, used at 1:400); Gp135 (AF1556, R&D, used at 1:200 for IF and 1:1000 for WB); g-tubulin (DQ-19, Sigma, used at 1:500); g-tubulin (C-20, used at 1:200), MAP4 (H-300 and G-10, used at 1:400 for IF and 1:1,000 for WB) and ACIII (C-20, used at 1:200) from Santa Cruz; GAPDH (MAB374, used at 1:4000 for WB) from Millipore.
DNA was stained with Dapi or Hoechst (Life Technologies) (except for STED imaging). Confocal images were taken on either Zeiss LSM 700 or LEICA SP8 microscopes. Images were analysed with ImageJ. Alternatively, super resolution images were acquired using a LEICA SP8 gSTED microcoscope, equipped with a 660-nm laser that quenches the fluorescence outside the centre of the focus. Images were then deconvoluted using Huygens software. Ciliogenesis analyses were performed on a CV7000 confocal microscope from YOKOGAWA with Â 40 long distance. Z-stacks were acquired with identical acquisition settings (gain, offset, laser power) and all measurements of fluorescence intensity were performed on maximum intensity projection, calculated with the Yokogawa software. For all cilia numerical values (frequency, length), we developed one specific pipeline using CellProfiler software  51.
In brief, nuclei were detected as primary objects using Otsu Adaptive two-class thresholding. For cilia length, a mask was constructed by applying MoG global thresholding on ARL13B staining, followed by measurement of the major axis length. Cilia frequency was calculated by dividing cilia and nuclei counts. All data points are performed in duplicate with four fields acquired per well, and an average of 300 cells per field. Cell profiler pipeline was run using the Linux cluster interface JENKINS. Spheroids were directly analysed using the ZEN 2011 software (Zeiss). Calcium switch assay and TER measurement. mIMCD3 cells grown on 65-mm Transwell filters (Corning) for 7 days were subjected to Ca 2 þ switch as described in Straight et al. 52  Briefly, cells were washed with PBS-4 mM EGTA and Ca 2 þ free DMEM (Life Technologies) containing 4 mM EGTA was added to the cells for 45 min to disrupt cell junctions.
1% sodium dodecyl sulfate and protease inhibitor cocktail (Roche). Protein quantification was then performed using the BCA protein assay kit (Ther-moScientific). A measure of 30-50 mg of proteins were loaded on 8 or 10% acrylamide gels, blotted on PVDF membrane (Millipore) and the membrane was incubated using the indicated antibodies. Western blots were then analysed with Bioprofil software. qPCR. Total cellular mRNA was isolated using Qiagen Extraction Kit and treated with DNase I. 1 mg of total RNA was reverse-transcribed using Superscript II (Life Technologies). Relative expression levels of the TRAF3IP1 or MAP4 mRNAs were determined by real-time PCR using either Absolute SYBR Green ROX Mix (ABgene) or TaqMan Gene Expression Assay (Applied Biosystems) with specific primers (Supplementary Table  3 ).