dataesr/scientific-paragraphs-categorization huggingface dataset:
Aspergilli genome data mining More than 200 Aspergillus species have been described so far. Several genome projects have been initiated including A. fumigatus, A. flavus, A. niger, A. clavatus and others. Using both annotated and partially completed genomic data and data from other sources (non-redundant GenBank CDS translations +PDB+SwissProt+PIR+PRF), genes coding for a peptide with a strong similarity to the AAL lectin from A. aurantia were identified in A. fumigatus Af293, A1163, Af10 (identical copies in each strain) and Af210 (two single-point mutations at the protein level compared to three other strains), A. flavus NRRL3357 and A. oryzae RIB40. Other homologous sequences were identified in related fungal species from the genera Neosartorya, Penicillium, Trichophyton, Arthroderma, Metarhizium and others (Figure  S1 ).
DENZO and SCALEPACK (Otwinowski & Minor, 1997 ); program(s) used to solve structure: SIR92 (Altomare et al. , 1994) ; program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) ; software used to prepare material for publication: WinGX (Farrugia, 2012).
Initial protein concentrations varied from 20 to 100 M, whereas injectant concentrations were between 0. 4 and 3 mM. Higher injectant concentrations were not possible due to limited solubility of the ligands in aqueous solutions. The heat associated with the binding process was calculated as the difference between the heat of reaction and the corresponding heat of dilution, as obtained from independent titrations of the ligand into buffer. The resulting binding isotherms were analyzed and fitted through non-linear least-squares to an appropriate thermodynamic model with the MicroCal Origin software (MicroCal, Inc. ). Crystallization X-ray Data Collection and Structure Solution-Fra a 1E, Fra a 2, and Fra a 3 proteins were assayed for crystallization by the vapor diffusion method, the High Throughput Crystallization Laboratory of the EMBL Grenoble Outstation  (51)  in the presence and absence of the flavonoid compounds indicated in the previous section.
Fra a 3-catechin crystals were optimized by the vapor diffusion method by mixing 1 l of protein and 1 l of precipitant solution (2. 25 M sodium malonate, pH 7. 0) equilibrating against a reservoir containing 0. 5 ml of precipitant solution. Crystals in the shape of flat hexagonal prisms appeared within 2 days. Crystals were flash-frozen in liquid nitrogen using 15% glycerol as cryoprotectant. The Fra a 2 protein did not produce any crystals, neither alone nor in the presence of any of the mentioned flavonoids. X-ray diffraction data were collected at the ID14-4, ID23-2, and ID14-1 beamlines of the ESRF for Fra a 1E crystal form A, Fra a 3-catechin and Fra a 1 E crystal form B, respectively. Crystallographic data reduction and scaling was carried out with the software XDS  (52). Initial phases were obtained using Phaser (53) by the molecular replacement method using the yellow lupine LIPR-10.
Initial phases for crystal form A of Fra a 1E were obtained by the molecular replacement method using the yellow lupine LIPR-10. 2B protein (Protein Data Bank code 3E85)  (19)  as a search model. The final model was refined to a resolution of 2. 2 Å with an R work and R free of 0. 21 and 0. 25, respectively. The refined model contained two molecules of Fra a 1E in the asymmetric unit. Both molecules showed a similar structure and comprise amino acids 2 to 160. The region corresponding to the ␤3-␤4 loop (amino acids 61-63 and 61-65 in chains A and B, respectively) was disordered and could not be modeled (Fig. 3 ). The three amino acids from the N-terminal purification tag that remain after TEV cleavage were also visible in the structure. As can be appreciated in Fig. 3a , the structure of Fra a 1E conforms to the START fold (2, 9) and consists of a sevenstranded ␤-sheet, two short helical segments between strands 5 and 7, and a long ␣-helix at the C terminus.
* This work was supported in part by the  P-CUBE  project of the  European Commission  (FP7/2007-2013; Grant  227764 ),  Ministerio de Ciencia e Innovacion  Grant  BIO2010-15630  (Spain), and  Deutsche Forschungsgemeinschaft SFB 924 (Germany). Author's Choice-Final version full access. The atomic coordinates and structure factors (codes  4C9C ,  4C94 , and  4C9I ) have been deposited in the Protein Data Bank (http://wwpdb. org/). 1 Both authors contributed equally to this work. 2Recipient of a  Formacion de Personal Investigador (FPI) fellowship  from the  Spanish government.
L. casei and B. breve Induce Increased Expression of Differentiation Genes in m-ICcl2 Cells L. casei and B. breve not only down-regulated cell cycle gene expression, but also induced an increased in expression of genes encoding proteins that characterize a state of higher IEC C: Hierarchical clustering of cell cycle gene expression was performed using dChip software with Euclidian distance and average as a linkage method. Before clustering, expression values for one gene across all samples were standardized to produce a mean of zero. Increased or decreased values were then compared with that mean. Red and blue colors represent expression that is higher or lower than the mean value, respectively. The key for intensity of expression is indicated under the bar. See Table  S2  for the corresponding fold change and p-value of cell cycle modulated genes.
Finally, the arrays were scanned at 570 nm with a resolution of 3 mm/pixel, using a GeneArray scanner from Agilent Technologies. Preprocessing by Robust Multichip Average (RMA) was applied to process individual probe values (perfect match) and to generate summary values for each probe set (transcript)  [45]. The dChip software was used for comparative analysis and for hierarchical clustering with Euclidean distance and average as a linkage method  [46]. Before clustering, expression values for one gene across all samples were standardized to produce a mean of zero. Increased or decreased values were then ranged compared with that mean. For the analysis step, redundant probe set were removed. Data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE37369.
General genetic techniques Standard molecular genetic techniques were used throughout this study  [28]. Restriction enzymes were obtained from New England Biolabs (Ipswich, England). Genomic DNA from yeast transformants was prepared as described by Querol et al. [29]. PCR amplifications were performed in an Eppendorf 2720 thermal cycler with both Taq (Promega, Madison, WI) and Pfu (Stratagene, La Jolla, CA) DNA polymerases, using the primers shown in Table  S2. PCR fragments were purified with a QIAgen Purification Kit (Qiagen, Hilden, Germany), and DNA fragments were recovered from agarose gels with a QIAquick Gel Extraction Kit (Qiagen, Hilden, Germany). The Staden software package was used for gene sequence analysis  [30].
Fluorescence microscopy Images were acquired using a Zeiss Axio Imager M2 microscope (Zeiss, Le Pecq, France) with a 100× objective and Zeiss filters 45 and 46 for fluorescent microscopy. Axiovision 4. 8 software (Zeiss, Le Pecq, France) was used for image acquisition. For visualisation of LBs, BodiPy® Lipid Probe (2. 5 mg/ml in ethanol; Invitrogen) was added to the cell suspension (A 600 of 5) and the samples incubated for 10 min at room temperature.
Construction of the phylogenetic tree The deduced Y. lipolytica protein sequences of YlTgl1 (YALI0E32035g), YlTgl3 (YALI0D17534g) and YlTgl4 (YALI0F10010g) (http://www. genolevures. org/index. html#) were compared with the protein sequences of intracellular lipases and steryl-ester hydrolases from S. cerevisiae (http://www. yeastgenome. org/) and S. pombe (http:// www. pombase. org), using ClustalX  [39]. One-thousand rounds of heuristic search were performed, using the JTT model of amino acid substitution using the phyml_v2. 4. 4 program  [40]. The tree was rooted using the protein sequence of the Y. lipolytica extracellular lipase, Lip2, as an outgroup.
In the absence of approved medicines, anakinra has been used to manage CAPS symptoms; 4-10 however, expert opinion and sparse data suggest that the treatment of CAPS was suboptimal in some patients and compliance may have been limited. For example, refusal of daily treatment was observed in a recent study. 8 oorly treated or untreated CAPS leads to considerable morbidity and impacts education, social relationships, and occupation. 10 The objective of the current study was to quantify the burden of disease on CAPS patients and to characterize patient symptomatology and tolerability of treatment with anakinra. A secondary objective of the study included comparing chart review and patient recall of symptoms and AEs. Due to the subjectivity of CAPS symptoms and the suboptimal treatment many patients receive, it was determined that many patients may not be as forthcoming with physicians regarding their symptoms and AEs.
Data Source and Measurement After Ethics Committee approval in each country, sites recruited patients and obtained informed consent from patients. Data were directly collected from patients during the period June 2009 -August 2009. No patientspecific information that would allow patient identification was recorded. Data were entered onto case report forms by data managers and principal investigators at the sites and by patients remotely. Site record data collection was completed through a chart review over the 12 months prior to patients completing the online surveys. Patients were first asked to recall flares over the previous month on anakinra treatment. The patients individually determined the definition of a flare, generally, in terms of any clinical disease activity due to CAPS and each period of activity counted as a flare.
Descriptive Data Fifty Caucasian patients (32 adults and 18 children) were enrolled from four Centres of Excellence for CAPS. The United Kingdom, Germany, Italy, and France provided 18, 15, 11, and 6 patients, respectively. All 50 patients who were contacted agreed to participate in the study. Patients had a mean age of 29. 0 (standard deviation [SD] 17. 5) years and had been diagnosed with CAPS for a mean of 4. 3 (SD 3. 2) years with the following phenotypes: FCAS/familial cold urticaria syndrome (FCUS) (7), FCAS/FCUS-MWS overlap (1), MWS (32), MWS-NOMID/chronic infantile neurological, cutaneous and articular (CINCA) syndrome overlap (3) and NOMID/CINCA (7) (see Table  1 ).
Acknowledgements We gratefully acknowledge the sponsorship of  Novartis Pharma AG  in this research. We also acknowledge and greatly appreciate the expert assistance of the following individuals in Ethics Committee documentation and data collection:  Thirusha Lane  ( UCL Medical School, UK ),  Signe Risom  ( UCL Medical School, UK ),  Isabelle Marie  ( Hôpital Kremlin Bicêtre, France ),  Sandra Hansmann  ( University Hospital Tübingen, Germany ),  Silvia Federici  ( G. Gaslini Scientific Institute, Italy ) and  Roberta Caorsi  (G. Gaslini Scientific Institute, Italy). We would also like to thank  Hal Hoffman  ( University of California at San Diego ) and  Philip Hawkins  ( UCL Medical School, UK ) for their guidance and  Sarah Evans  ( Arnold Consultancy & Technology LLC at the time of the study ) for data collation and interpretation.
Carrageenans are also important carbon sources for heterotrophic marine bacteria, which degrade cell walls of marine red algae by secreting specific glycoside hydrolases (GHs), referred to as carrageenases  [5]. Based on their substrate specificity, these enzymes are named as k-, iand l-carrageenases, respectively. All described carrageenases are endo-hydrolases and cleave b-1,4 glycosidic bonds of carrageenans yielding oligosaccharide products of the neocarrabiose type  [6] [7] [8]. Based on amino acid sequences, these enzymes belong to distinct GH families, k-carrageenases form a subfamily within the family GH16  [6] , i-carrageenases define the unrelated family GH82  [7] , while l-carrageenases constitute a new GH family  [8] , although it has not been yet classified in the carbohydrate-active enzymes (CAZy) database  [9].
The theoretical molecular mass of the mature CgiA_Ce was 49. 2 kDa which corresponds to the apparent molecular mass of the purified CgiA_Ce (48 kDa). Database search using the BLASTp program showed that this protein shared high sequence identity with the characterized icarrageenases from Alteromonas fortis and Zobellia galactanovorans (39% and 79%, respectively)  [7]. Multiple alignment of family GH82 sequences (Figure  5A ) showed that CgiA_Ce displayed the conserved catalytic residues of this family and the main secondary structures of CgiA_Af, including the flexible domain A  [11]. All these data demonstrated that CgiA_Ce is indeed a new active member of family GH82.
The NH 4 HCO 3 salt was removed by repeated co-evaporation with water under diminished pressure at 50uC. 1 H-and 13 C-NMR were carried out on a JNMECP600 (JEOL) instrument, with 2,2-dimethyl-2silapentane-5-sulfonic acid as the internal standard. Molecular masses of the oligosaccharide products were determined by negative-ion ESI-MS performed on a LTQ Orbitrap XL mass spectrometer (ThermoFisher Scientific, USA). I spray voltage: 3 kV; tube lens: 280 V; capilary temp: 275uC; capilary voltage: 243 V; sheath gas flow rate: 8 arb. Samples were dissolved in CH 3 CN/H 2 O (1:1, v/v), typically at a concentration of 5-10 pmol/ml, of which 5 ml was loop-injected. The data were collected and processed by Xcalibur software.
Bioinformatics Analysis The putative translation frame was identified by the DNATools program, and the theoretical molecular mass and isoelectric point were calculated using the Compute pI/Mw tool (http://web. expasy. org/compute_pi). A functional domain search was performed to determine the protein family and domain organization using the Pfam search server (http://www. sanger. ac. uk/Software/ Pfam) and the NCBI BLAST server (http://blast. ncbi. nlm. nih. gov/Blast. cgi). Pairwise and multiple sequence alignments between CgiA_Ce and other known i-carrageenases were obtained using the CLUSTAL X program  [29]. SWISS-MODEL software (http://swissmodel. expasy. org/) was performed to create the 3D homology models of CgiA_Ce and its derivatives using the crystal structure of CgiA_Af (PDB accession code 1KTW) as the template  [30].
The PyMol molecular Graphics System (DeLano Scientific, San Carlos, USA. http://www. pymol. org) was used to visualize and analyze the modeled structure and to construct graphical presentations and illustrative figures. Using the crystal structure of CgiA_Af complexed with neo-i-carratetraose and neo-i-carrabiose (PDB accession code 1KTW) as a guide, a neo-i-carrabiose with the same configuration was manually docked into the subsites 21 and 22 of modeled structure of CgiA_Ce and positioned.
Acknowledgments The authors wish to thank  Dr Le Forestier  and his  Staff from the ''Photologie'' Department for their help, Cecile Deleine and Stephanie Blandin  for expert technical assistance,  Dr Bara  for his gift of MUC5AC antibodies,  Dr Blache  for providing the  HT29-Cl16E-Sox9  cells,  Dr Dabdoub  for his gift of pCMV6-Myc tag-Hath1 expression vector and  Fabrice Airaud  for help in DNA sequencing. We also thank the  ''tumorotheque de l'IRCNA (CHU de Nantes-Institut de Cancerologie de l'Ouest, Nantes, France)''  for providing tumor samples for DNA analyses.
Live-cell microscopy Images were captured at 37°C using an inverted microscope (Axio Observer. Z1; Carl Zeiss) with a Plan Apochromat 63×/1. 40 NA differential interference contrast oil objective and a camera (AxioCam MR3; Carl Zeiss) equipped with a spinning-disc module. Frames were recorded every 2 s for a maximum of 2 min. A multiple wavelength laser module was used to visualize red fluorescence, and images were processed using AxioVision software (Carl Zeiss). TfnR and Tfn uptake and recycling assays Total cell TnfR levels were measured with and without bafilomycin A1 treatment. Adherent HeLa cells were transfected with siRNA for 72 h. For the final 18 h, cells were incubated with 100 µM bafilomycin A1 (in DMSO diluted to a final concentration of 1 µM; Sigma-Aldrich) or DMSO vehicle and then washed and harvested in cell lysis buffer (300 mM NaCl, 50 mM Tris, pH 8.
0, 5 mM EDTA, pH 8. 0, and 1% [vol/vol] Triton X-100). Samples were analyzed by Western blot analysis, and bands were quantified using ImageJ software. Band intensity values were normalized against actin or GAPDH band intensity to control for loading variations. Cell surface TnfR levels were measured as follows. Adherent HeLa cells were transfected with siRNA for 72 h and then trypsinized, resuspended in Opti-MEM, and incubated on ice with FITC-CD71 (1:5; BD) for 30 min. Cells were washed and then fixed in a solution of 3. 8% formaldehyde in PBS and analyzed using a FACS machine (FACSCalibur; BD). Tfn uptake and recycling assays were performed as previously described  (Peden et al. , 2004). In brief, adherent HeLa cells were transfected with siRNA for 72 h and then trypsinized, resuspended in Opti-MEM, and incubated on ice with Alexa Fluor Tfn-647 (Invitrogen).
4 NA oil immersion objective [Carl Zeiss] with a digital camera [C10600; Hamamatsu Photonics]) and SimplePCI software (HCImage). Images were subsequently processed using Photoshop and Illustrator (Adobe) or ImageJ (National Institutes of In toto immunohistochemistry Whole-mount immunohistochemistry experiments were performed on 26-hpf control and MO spast -and MO IST1 -injected embryos. Embryos were fixed in 4% PFA for 2 h at room temperature, washed four times with PB-T1% (1% Triton X-100 in PBS), permeabilized in a 0. 25% trypsin solution (at 25°C) for 2 min, blocked for 2 h in PB-T1% supplemented with 10% normal goat serum, and subsequently incubated overnight with the znp-1 antibody. After several washes in PB-T1%, embryos were incubated overnight at 4°C with an Alexa Fluor 488 goat anti-mouse (Molecular Probes).
Images were acquired at room temperature using a fluorescent microscope equipped with an ApoTome module (20×/0. 5 NA air objective; Axiovert 200M; Carl Zeiss) and processed using Photoshop software. Primary culture of zebrafish spinal neurons and immunocytochemistry Primary cultures of zebrafish spinal neurons were prepared from 24-hpf embryos as previously described  (Fassier et al. , 2010). In brief, spinal cords of dechorionated control and MO spast -and MO IST1 -injected embryos were isolated by removing the yolk and the head, incubated in a Custom ATV solution (mM: 0. 6 EDTA, 5. 5 glucose, 5. 4 KCl, 136. 8 NaCl, and 5. 5 Na 2 CO 3 ) supplemented with 0. 25% trypsin for 20 min at 27°C and mechanically dissociated with a drawn-out Pasteur pipette in culture medium (50% L-15 medium [Leibovitz's], 49% 10-fold diluted Ringer [mM: 115 NaCl, 2.
4 NA objective (oil immersion, 63×; Leica) with the pixel size set to 60 nm and a z step of 130 nm. Confocal images of SNX1 staining were deconvoluted with the Huygens 3. 6 software (Scientific Volume Imaging) using a theoretical point spread function and the classical maximum likelihood estimation algorithm and adjusted for brightness and contrast with Photoshop software. The number of endosomal tubules and endosomal complex structures was counted in 30 control and morphant growth cones per experiment in three (MO spast ) or five (MO IST1 ) independent analyses and normalized according to the growth cone area.
Acknowledgments This article was written while the authors were supported by the  University of Franche-Comté, "BQR Jeunes chercheurs of University of Franche-Comté" and the Ministère de l'Enseignement Supérieur et de la Recherche (MESR). The authors thank  J. N. Legrand ,  Dr Ramji R. Rajendran MD PhD  ( Elk Grove Village, Illinois, USA ) and  Lisa Oliver PhD  ( INSERM U892 ,  Nantes, France)  for the critical reading of this manuscript and comments.
Repository information Portions of the Leducq dataset approved by local IRBs for central deposit have been uploaded to dbGaP at http://www. ncbi. nlm. nih. gov/projects/gap/cgi-bin/study. cgi?study_id = phs000331. v1. p1. The DARE dataset is held by the International Serious Adverse Events Consortium (iSAEC) and is available on application to the iSAEC data management committee at http://www. saeconsortium. org/.
Quality control and population structure Genotype data from the 264 cases and 1119 drug-exposed and POPRES controls underwent QC as described above. After dropping SNPs with genotyping efficiency #95% or MAF #1%, the final set for initial analysis across all platforms used included 478,055 SNPs. Of the 1383 samples, 46 sample pairs had identityby-descent sharing values. 0. 2 in the Leducq set, and we removed the sample from each pair with the lower overall SNP calling rate. In total, we selected for further analyses 242 cases from all ethnicities (189 from the Leducq set and 53 from the DARE set) and 1094 controls (435 drug-exposed control and 659 POPRES controls). After identifying and removing non-Caucasian subjects by PCA, we investigated the genetic structure of Caucasian cases and drugexposed controls.
This study was supported by  U01HL65962 , the  Pharmacogenomics of Arrhythmia Therapy site of the Pharmacogenetics Research Network , and by a grant from the  Fondation Leducq  ( Trans-Atlantic Network of Excellence ''Alliance Against Sudden Cardiac Death '',  05 CVD 01 ). Genotyping the Leducq samples described in the text was performed by the  RIKEN Center for Genomic Medicine, Yokohama, Japan , which is supported in part by the  BioBank Japan Project  funded by the  Japanese Ministry of Education, Culture, Sports, Science and Technology. The DARE study was funded by the  British Heart Foundation  under special project grant  SP/02/001. The DARE samples were genotyped at  Gene Expression Ltd. Further support was provided by a collaboration with the  International Serious Adverse Events Consortium , whose membership currently includes  Abbott, Amgen, Astra-Zeneca, Cerner, Daiichi-Sankyo ,  GlaxoSmithKline ,  Merck ,  Novartis ,  Pfizer ,  Takeda , and the  Welcome Trust.
Portions of the Leducq dataset have been deposited at dbGaP at http://www. ncbi. nlm. nih. gov/projects/gap/cgi-bin/study. cgi?study_id = phs000331. v1. p1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. study. He was paid for lectures by  Sanofi-Aventis and Boston Scientific. Travel and accommodations have been paid by  Sanofi-Aventis. He is chair of DSMB of a multicenter study co-supported by the  National Heart, Lung, and Blood Institute , and  Medtronic ,  GE , and  Zoll. AJC  has acted as a consultant for  Sanofi, Servier, Daiichi ,  Boehringer Ingelheim ,  Bayer ,  Novartis ,  Gilead  and  Menarini. He  is a member of DSMB for studies funded by  Servier ,  Novartis ,  BMs  and  Pfizer. ALG reports additional funding to his institution by  Gilead Sciences  to study proprietary compounds, but unrelated to the present study.
Acknowledgements Research in the SK and MJB laboratories relevant to the areas discussed is supported by funding from  BBSRC (UK , grants  BB/H019820/1 ,  BB/J004553/1 ,  BB/I019557/1  and  BB/J004553/1 ),  ERC  (proposal 294608), the  John Innes Foundation  and the  Gatsby Charitable Foundation. KY is supported by a  JSPS   Postdoctoral Fellowships for Research Abroad, SR a Marie Curie CIG grant  (contract  334036 ) and DGOS a  Leverhulme Early Career Fellowship.