dataesr/scientific-paragraphs-categorization huggingface dataset:
Third, we did not collect any data on the incidence of positive Aspergillus cultures or the total number of ICU admissions to the participating centers over the study period. Thus, we could not evaluate the burden of this disease among critically ill patients. Importantly, IA remains a rare disease. It was reported in 1% to 2% of ICU patients in a large international database  [10]. Fourth, we did not record laboratory data in detail, which might have been useful to better characterize the cohort. We also did not collect data on daily corticosteroid dose and could not fully explore the impact of dose or duration on mortality. Importantly, we did not collect the amount of antibacterial drugs that patients received before IA diagnosis or whether this may have influenced the development of the disease.
Acknowledgements This study was supported by an unrestricted educational grant from  Pfizer Belgium  and a research grant from  Ghent University. SB holds a research mandate from  Ghent University. The  AspICU  project is endorsed by the  European Critical Care Research Network of the European Society of Intensive Care Medicine. The funding bodies had no role in the collection, analysis or interpretation of the data and were not involved in the writing or approval of the final manuscript.
Competing interests This study was supported by an unrestricted educational grant from Pfizer Belgium and a research grant from Ghent University. SB holds a research mandate from Ghent University. The AspICU project was endorsed by the European Critical Care Research Network of the European Society of Intensive Care Medicine. The authors declare that they have no other competing interests. Authors' contributions FST contributed to data acquisition and analyses and interpretation of the results and drafted the manuscript. AMVDA contributed to acquisition of the data and interpretation of the results and revised the paper for important intellectual content. PB contributed to acquisition of the data, interpretation of the results and revision the paper for important intellectual content. BM contributed to the conception and design of the study, acquisition of the data, interpretation of the results and revision of the paper for important intellectual content.
1 NA) water immersion objective. We monitored intracellular [Ca 2+ ] changes with Oregon green BAPTA-5N added to presynaptic pipette solution. All experiments were performed at room temperature (22 C-24 C). Data analysis was performed with IgorPro 6. 3 (WaveMetrics) using NeuroMatic. Deconvolution of EPSCs was performed as describe previously  (Sakaba and Neher, 2001; Taschenberger et al. , 2005). All values in the text and figures are given as means ± SEM unless otherwise indicated. Numerical Simulations Ca 2+ Reaction-Diffusion and Vesicular Release Ca 2+ diffusion and binding with Oregon green BAPTA-5N and buffers in the vicinity of VGCC clusters was simulated using a finite-difference method  (Di-Gregorio et al. , 1999; DiGregorio et al. , 2007)  in order to predict spot-detected Ca 2+ transients.
ACKNOWLEDGMENTS We thank  Taro Ishikawa ,  Shinichi Iwasaki ,  Masahiro Kimura ,  Florian Mueller , and  Tetsuhiro Tsujimoto  for their contributions during the early stage of this study. We also thank  Tetsuya Hori  for helping with the pipette perfusion experiments,  Hee-Sup Shin  for providing Ca v 2. 1 knockout mice,  Masahiko Watanabe  for providing Ca v 2. 1 antibodies, and  Steven Aird  for editing the paper. This work was supported by the  Core Research for Evolutional Science and Technology (CREST) of Japan Science and Technology Agency  to T. T. and R. S. ; by the funding provided by  Okinawa Institute of Science and Technology (OIST)  to T. T. and Y. N. ; by  JSPS  Core-to- Core Program ,  A. Advanced Networks  to T. T. ; by the  Grant-in-Aid for Young Scientists  from the  Japanese Ministry of Education, Culture, Sports, Science and Technology  (# 23700474 ) to Y.
N. ; by the  Centre National de la Recherche Scientifique  through the  Actions Thematiques et Initatives sur Programme ,  Fondation Fyssen, Fondation pour la Recherche Medicale, Federation pour la Recherche sur le Cerveau ,  Agence Nationale de la Recherche  ( ANR-2007-Neuro-008-01  and  ANR-2010-BLAN-1411-01 ) to D. D. and Y. N. ; and by the  European Commission Coordination Action ENINET  ( LSHM-CT-2005-19063 ) to D. D. and R. A. S. R. A. S. and J. S. R. were funded by  Wellcome Trust Senior  ( 064413 ) and Principal ( 095667 )  Research Fellowship  and an  ERC   advance grant  ( 294667 ) to RAS. The authors declare no competing financial interests. Accepted: November 14, 2014 Published: December 18, 2014.
We note that the variant at the TP53INP1 locus on chromosome 8 (rs896854, lying in intron 1) associated with T2D in GWAS studies (Voight et al, 2010) appears to lead to impaired b-cell function (i. e. reduced insulin secretion), as measured by a decrease in HOMA-B (Voight et al, 2010) and unchanged insulin sensitivity. Moreover, dysglycemia necessarily involves a failure in pancreatic insulin secretion. The present data may suggest that, as well as being more insulin resistant, TP53INP1-deficient mice also possess b-cells which may be more susceptible to the effects of global lipid dysregulation. Interestingly, there are also decreases in miRNAs that regulate TP53INP1 in human diabetic islets  (Kameswaran et al, 2014) , suggesting that over-expression of TP53INP1 may occur in b-cells in diabetes.
Pancreas Pancreases from 3-month-old TP53INP1 WT (n = 4) and KO (n = 4) male mice were spread into flat embedding cassettes, fixed with 4% paraformaldehyde, paraffin embedded and longitudinally sectioned through the pancreatic head-to-tail axis (4 lm thickness). Three pancreatic sections per mouse, separated by at least 100 lm, were stained with hematoxylin/eosin and scanned using a NanoZoomer slide scanner (Hamamatsu Photonics, Hamamatsu City, Japan). The islet numbers were quantified, and the area of each islet was measured with the NDP. view software, version 1. 2.
Flow cytometry MEFi were incubated during 10 min at 37°C with 5 lM MitoSOX TM Red (Life Technologies #M36008) or 200 nM MitoTracker â Deep Red (Life Technologies #M22426) diluted in HBSS (Hank's buffered salt solution; Life Technologies). Cells were trypsinized and rinsed by centrifugation (1,200 g, 5 min) with PBS. They were then analyzed on a FACSCalibur flow cytometer (BD Biosciences, Le Pont de Claix, France). Data analysis was performed using FlowJO (Treestar, Olten, Switzerland) software.
Transmission electron microscopy (TEM) MEFi were seeded in 10-cm dishes (7. 5 × 10 6 cells) 48 h before treatment. Cells were then rinsed twice with PBS and fixed for 1 h in cacodylate sodium buffer 0. 2 M, pH 7. 2, containing 2. 5% glutaraldehyde, 8% paraformaldehyde and 0. 01% CaCl 2. Samples were then treated as described previously (Baron  Gaillard et al, 2011). Observations were performed on an EM 912 electron microscope (Zeiss) at 100-kV acceleration equipped with a BioScan camera (Model 792; Gatan, Warrendale, PA, USA). Images were acquired with the Digital Micrograph software (Gatan). Quantification of the number of mitochondria, mitophagic vacuoles and lipid droplets normalized by cytoplasmic surface area was done by counting these structures on 40 images for which surface occupied by cell cytoplasm has been determined.
High-resolution respirometry High-resolution respirometry was performed using a 2-ml chamber OROBOROS â Oxygraph 2K (Oroboros Instruments, Innsbruck, Austria) at 37°C. Respiration rates were calculated as the time derivative of oxygen concentration measured in the closed respirometer and expressed per million viable cells and corrected by nonmitochondrial oxygen consumption (antimycin A). The amplified signal was recorded in a computer with online display of the calibrated oxygen concentration and oxygen flux (DatLab software for data acquisition and analysis; Oroboros Instruments). Intact cells (0. 5 × 10 6 cells/ml) were analyzed in their respective bioenergetic substrate-containing cultivation medium. ROUTINE respiration (no additions), LEAK respiration (oligomycin-inhibited, 8 lg/ml) and ETS capacity (maximum non-coupled respiration induced by stepwise (typically 2-3 steps) titration of carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), 0.
Stéphane Garcia for support in histological analysis, and to Lionel Chasson (Histology Platform of CIML) for support in confocal microscopy analyses. We also thank Rose-Patricia Spoto for preparation of tail of mice DNA for genotyping, Thomas Bonacci for help in Western blotting, Jacques Nunès and Marie-Christine Alessi for advices in HFD protocol, and Mathias Chamaillard and Fatima Mechta-Grigoriou for helpful discussions. The authors were supported by Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut National du Cancer, Association pour la Recherche sur le Cancer and La Ligue Nationale contre le Cancer. This work was also supported by grants from the University of Nice, the Programme Hospitalier de Recherche Clinique (Centre Hospitalier Universitaire of Nice), charities (Association Française pour l'Etude du Foie (AFEF/LFB) to PG, European Foundation for the study of Diabetes EFSD/Lilly to PG) and by the French Government (National Research Agency, ANR) through the 'Investments for the Future' LABEX SIGNALIFE: program reference #ANR-11-LABX-0028-01.
Acknowledgements We are grateful to the IBDML electron microscopy facilities (PICsL platform), to  Laurence Borge  (cell culture platform of Marseille/Luminy), to  Karim Sari ,  Régis Vitestelle  and  Romain Magro  for assistance with the use of the animal housing facility, to  Fabrice Gianardi  and  Gilles Warcollier  for assistance with the use of the  Laboratoire d'Exploration Fonctionnelle de Luminy , to  Marie-Noëlle Lavaut.
and Stéphane Garcia for support in histological analysis, and to Lionel Chasson (Histology Platform of CIML) for support in confocal microscopy analyses. We also thank Rose-Patricia Spoto for preparation of tail of mice DNA for genotyping, Thomas Bonacci for help in Western blotting, Jacques Nunès and Marie-Christine Alessi for advices in HFD protocol, and Mathias Chamaillard and Fatima Mechta-Grigoriou for helpful discussions. The authors were supported by Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Institut National du Cancer, Association pour la Recherche sur le Cancer and La Ligue Nationale contre le Cancer. This work was also supported by grants from the University of Nice, the Programme Hospitalier de Recherche Clinique (Centre Hospitalier Universitaire of Nice), charities (Association Française pour l'Etude du Foie (AFEF/LFB) to PG, European Foundation for the study of Diabetes EFSD/Lilly to PG) and by the French Government (National Research Agency, ANR) through the 'Investments for the Future' LABEX SIGNALIFE: program reference #ANR-11-LABX-0028-01.
Our study has several limitations. Its observational design with non-consecutive patients could engender a selection bias. The study population is small given the monocentric screening and the stringent inclusion criteria. Even if only a single experienced operator performed TTE, a post hoc analysis by an independent expert could have confirmed the hemodynamic data obtained by blinded practitioners. Similarly, data were obtained by TTE and not TEE, which, in the context of HFOV, could cast doubts on the accuracy of the results. Yet, TTE-obtained data are consistent with those found by TPTD (e. g. , LVOT VTI and TPTD CI both decreased by 13 % on HFOV) and comparable to those obtained by  Guervilly et al. with TEE [11]. Another limitation of the study is the lack of assessment of a potential preload decrease during HFOV.
Chemiluminescence monitoring and determination of standardized ADRB index Chemiluminescence was measured as described previously  [19]  using opaque 96-well plates (Berthold), and a MicroLumat Plus 96 luminometer (Berthold). Briefly, merozoite pellets (40 µL) were incubated with 10 µL of test or control sera for at least 30 min at 37 °C. PMN (100 µL at 1-5 × 10 7 cells mL -1 ) and isoluminol (100 µL of 1:100 dilution in PBS of 4 mg mL -1 stock in DMSO) were loaded rapidly using an Eppendorf multipipette 4780. To facilitate rapid handling, only 40-50 wells per plate were used using the HIS as systematic internal control in the first and last wells. Plate reading started immediately, and continued for 1 h. Data are presented as standardized activity index of merozoite ADRB calculated as where rlu maximum HIS is an average of the first and last wells on the plate.
Anti-PyMSP1p19 Fig. 4  ADRB activity of a set of 24 sera in the solid-phase assay using PfMSP1p19-coated plates. Histograms of ADRB activity measured using PfMSP1p19-coated in 9, 11 and 4 sera from Ndiop (light grey), Dielmo (medium grey) and urban malaria (dark grey), respectively, plotted in increasing order of ADRB units, respectively. The sera were chosen irrespective of their level of antibodies to PfMSP1p19 antigen antibodies contributing to ADRB were however observed in naïve as well as vaccinated mice after a primary infection, suggesting that infection elicits such antibodies  [20]. Second, the data show that the baculovirus recombinant PfMSP1p19 recapitulates here the functional triggering activity of the merozoite-displayed native antigen. This is important information for vaccine development.
Acknowledgements We are particularly grateful to  Dr S Longacre  who substantially contributed to the design and the execution of this work and generously provided the PfMSP1p19 antigen as well as to  Prof B Crabb  who kindly provided the isogenic P. falciparum D10 lines. We thank  Prs A Dieye ,  L Diakhate  and  Dr M Delepierre  and  O Niass  for helpful discussions and  G Milon  for reviewing the manuscript. S Rosario  prepared the purified PfMSP1p19 antigen. We are grateful to the villagers from Ndiop and Dielmo who participated in this study. The work was supported by grants from the  Institut Pasteur Foundation , the  French Ministère de la Recherche et de la Technologie  ( Programme VIHPAL ), the  Fonds dédiés programme: Combatting Parasitic Diseases (Sanofi Aventis/ Ministère de l'Enseignement Supérieur et de la Recherche)  and the 7th European Framework Programme, FP7/2007-2013, contract  242095 , Evimalar.
ACKNOWLEDGMENTS We thank  Sabine Jungwirth ,  Sarah Niggemeyer , and  Patricia Schittenhelm  for animal caretaking;  Doris Chen ,  Thomas Penz ,  Michael Schuster , and  Christoph Bock  from the  Biosequencing Facility at CeMM ;  Matxus Perugorria Montiel  for advice on culturing primary mouse hepatocytes; and  Vivien Holecska ,  Michael Kolta , and  Berend Snijder  for technical assistance. We also thank  Mathias Mu  ¨ller and  Birgit Strobl  ( University of Veterinary Medicine, Vienna, Austria ) for Irf7 À/À and Stat1 À/À mice,  Ulrich Kalinke (Paul-Ehrlich-Institut, Langen, Germany ) for Ifnar1 fl/fl mice,  Pierre Chambon  ( Institut de Genetique et de Biologie Moleculaire et Cellulaire, Illkirch, France ) for Cre-Alb ERT2 mice,  Arturo Zychlinski  ( Max-Planck Institute of Infection Biology, Berlin, Germany ) for Sod1 À/À mice backcrossed to  C57BL/6J , and  Karl S.
Outcome events In ICSS major outcome events were adjudicated by an independent endpoint committee that was unaware of treatment allocations. Stroke was defined as a rapidly developing clinical syndrome of focal disturbance of cerebral function lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin. Stroke was considered procedural if the event occurred at any time between initiation of the revascularisation (day 0) and day 30 after revascularisation. Stroke was classified as disabling if there was an increase in the modified Rankin score to 3 or more, attributable to the event 30 days after onset. For the present analysis, the technical data forms completed by the surgeon or interventionist at the time of the procedure were reviewed along with the carotid and brain imaging to determine the most likely mechanism of stroke.
The technical forms recorded the techniques used for endarterectomy or stenting and also recorded complications occurring during the procedure or immediately afterwards, including complications such as hypotension or asystole. In addition, the available clinical data describing the stroke together with carotid and brain imaging were interrogated. For procedures performed with the patient under general anaesthesia, stroke was considered intraprocedural if the cerebral deficit presented before the patient fully emerged from anaesthesia. Stroke was determined to have occurred after the procedure if the onset of the stroke occurred after full and asymptomatic awakening from anaesthesia including a clear symptom-free interval between the intervention and onset of symptoms. For procedures performed under local anaesthesia, stroke was considered intraprocedural if the cerebral deficit was noticed in the intervention room during the procedure and determined to have occurred after the procedure if the patient left the intervention room before the deficit was noted (Fig.
Classification of stroke mechanism To determine the pathophysiological mechanism of procedural stroke, a correlation was made between the onset of neurological symptoms and available data on intra-and postprocedural haemodynamic complications, reported technical difficulties, and observed carotid patency. The topography of the procedural infarct (or haemorrhage) was assessed using available brain imaging. Two investigators (AH and DC) analysed separately all available data described above to assess the likely procedural stroke mechanism according to the pre-defined following classification, in ischaemic stroke: (1) carotidembolic, (2) haemodynamic, (3) thrombosis or occlusion of the carotid artery, (4) hyperperfusion, (5) cardio-embolic, (6) multiple, or (7) undetermined. In haemorrhagic stroke, it was determined whether stroke was related to: (1) hyperperfusion or (2) no hyperperfusion/ undetermined.
5 × 10 13 and 1. 6 × 10 15 ions cm -2 , respectively. In the following these samples are referred with the adjective either low-or high-fluence. More details about the irradiation process can be found in Refs. [1, 34]. As discussed before, for studying the irradiation-induced defects, the irradiated samples are annealed under helium atmosphere at a temperature of 400 K for about two hours. At this temperature no modifications are induced in non-irradiated MnAs thin films  [41]. Before and after annealing (but also before the irradiation), the samples properties are characterised by X-ray diffraction (XRD) and magnetometry. The XRD data are obtained at room temperature, where the two phases of MnAs are normally visible. We use two different instruments, both using the CuKα emission: a PANalytical XPert MRD diffractometer (without monochromator) and a Rigaku Smartlab diffractometer with a copper rotating anode and a two-reflection monochromator.
Acknowledgments This work was partially supported by  French  state funds managed by the  ANR  within the  Investissements d'Avenir programme  under reference  ANR-11-IDEX-0004-02 , and more specifically within the framework of the Cluster of Excellence MATISSE led by  Sorbonne Universités. V. Gafton  acknowledges support from the strategic grant  POSDRU/159/1. 5/S/137750 ,Project, "Doctoral and Post-doctoral programs support for increased competitiveness in Exact Sciences research" co financed by the  European Social Found  within the  Sectoral Operational Program Human Resources Development 2007-2013.
Overall Monitoring Scheme To ensure the collection of valid data, there was a culture of monitoring from the field sites up to the level of the DSMB. Investigators monitored one another to ensure the accuracy, completeness of AE forms, and also timeliness of the SAE reporting. SAE reports were checked for accuracy and compliance with the protocol by the responsible CRO. A different CRO performed periodic monitoring visits to the study sites, where they compared the source documents with what was recorded on the SAE report forms and/or case report forms, to reconcile any discrepancy. The frequency of the visits was determined by the nature of the study and the quantity of data to be monitored. The sponsors also employed the services of an experienced safety consultant who helped set up the SAE system and during the course of studies clarified terms and important dates and resolved differences in understanding.
However, when some subjects inadvertently became pregnant, they were monitored until delivery, and any events in the mother or the newborn were documented. Because women of childbearing age are susceptible to group A meningococcal disease, this raised a dilemma. Consequently, a detailed risk-benefit analysis was conducted, based on burden and impact of the disease in pregnant women, data from nonclinical studies, and experience with similar vaccines, which justified the use of the vaccine in pregnant women during the postlicensure use of the vaccine  [19]. PsA-TT (MenAfriVac) has now been given postlicensure to >217 million people aged 1-29 years  [20] ; hence, women of childbearing age constitute a significant proportion. A study follows up the safety of MenAfriVac in pregnant women and pregnancy outcomes, and data confirm that the vaccine has no adverse effect on pregnant women and their infants  [21].
Acknowledgments. We acknowledge  Samba O. Sow ,  Brown Okoko ,  Abraham Hodgson ,  Adebayo Akinsola ,  Siddhivinayak Hirve ,  Aldiouma Diallo ,  Nilima Kshirsagar ,  Thatt Urmila ,  Naidu Mur ,  Etard Jean-Francois ,  Aissat Diarra ,  Lorna Renner ,  Rebecca Grais ,  Andy Hall ,  Mrudula Phadke  for their contributions. Supplement sponsorship. This article appears as part of the supplement "The Meningitis Vaccine Project: The  Development, Licensure, Introduction, and Impact of a New Group A Meningococcal Conjugate Vaccine for Africa ," sponsored by the  Meningitis Vaccine Project  through a grant from the  Bill & Melinda Gates Foundation. Potential conflicts of interest. F. M. L. is the former director of the Meningitis Vaccine Project. S. V. received institutional support from  PATH Europe  for this article, and also has received fees for consulting from  Bionet-Asia, Thailandia, PATH Seattle , and  Takeda Vaccines (Switzerland) ; has received grant support from  Grand Challenges Gates Foundation ; and holds stock options in Sanofi Pasteur.
To further investigate this, we assessed the capacities of SYN oligomers, ribbons and fibrils to seed endogenous SYN and to propagate, leading to long-term functional effects. We inoculated 40 µg of SYN assemblies divided over 3 injection sites in rat striatum in combination with rAAV-SYN overexpression (Fig. 3a ) or not (Extended Fig. 6 ). Large amounts of sarkosyl-insoluble rodent SYN were detected after 60 days throughout the striatonigral pathway for ribbons and fibrils (Fig. 3a  and Extended Fig. 6 ) although the inoculated human SYN was undetected after sarkosyl extraction in animals injected only with SYN assemblies (Extended Data Fig. 7 ). This implies that exogenous SYN strains seed the assembly of endogenous SYN overcoming the species barrier. In addition, the Proteinase K resistance of sarkosyl-insoluble SYN extracted from the brains of animals overexpressing SYN inoculated with either ribbons or fibrils differed (Fig  3b ).