dataesr/scientific-paragraphs-categorization huggingface dataset:
Analysis of Population Subdivision by Country The HIV-1 B CAR pol sequences from Haiti identified here were aligned with B CAR sequences from Haiti (n = 12) and the Dominican Republic (n = 123) previously characterized  (Cabello et al. , 2014). A Bayesian phylogenetic tree of the B CAR dataset from Hispaniola was reconstructed under the best-fit nucleotide substitution model (GTR + I + G) using the MrBayes program  (Ronquist et al. , 2012). Two chains were run for 25 × 10 6 generations, and stationarity (constant mean and variance of trace plots) and good mixing (effective sample size > 200) for all parameter estimates were assessed using TRACER v1. 7  (Rambaut et al. , 2018). The degree of phylogenetic mixing of B CAR sequences obtained from both countries was then quantified using the BaTS program  (Parker et al.
Phylodynamic Analyses The evolutionary rate, the age of the most recent common ancestor (T MRCA ), the spatial diffusion pattern, and the rate of population growth (r, year -1 ) of B CAR lineages in Hispaniola were jointly estimated using a Bayesian Markov Chain Monte Carlo (MCMC) approach implemented in BEAST v1. 8  (Drummond et al. , 2002; Drummond and Rambaut, 2007). Regression analyses using the TempEst program  (Rambaut et al. , 2016)  revealed that the B CAR pol dataset compiled here did not contain a sufficient temporal signal for reliable timescale estimations [X-intercept (T MRCA ) < 1910]. Thus, Bayesian MCMC analyses were performed using a relaxed uncorrelated lognormal molecular clock model  (Drummond et al. , 2006)  with a uniform prior distribution on the substitution rate (1.
No significant differences were observed in the frequency of  To investigate the phylogeographic structure of the HIV-1 epidemic within Hispaniola, B CAR pol sequences from Haiti here identified (n = 91) were combined with Haitian (n = 12) and Dominican (n = 123) B CAR pol sequences identified in a previous study  (Cabello et al. , 2014)  and analyzed using BaTS. Analyses of population subdivision rejected the null hypothesis of panmixis (i. e. , complete intermixing of sequences from Haiti and the Dominican Republic) (Supplementary Table  S4 ), demonstrating that despite frequent viral intermixing between both countries, the geographic subdivision of the HIV-1 B CAR sequences from Hispaniola was greater than expected by chance. The same dataset of B CAR pol sequences from Haiti (n = 103) and the Dominican Republic (n = 123) was then subjected to Bayesian phylogeographic analyses.
We estimate that nearly 55% of B CAR infections in the Dominican Republic probably occurred within local transmission networks. Previous evolutionary analyses  (Gilbert et al. , 2007; Junqueira et al. , 2011; Worobey et al. , 2016)  support that the HIV-1 subtype B arrived in Haiti earlier than in any other American country. Here, we tested the hypothesis of the Haitian origin of subtype B epidemic by using for the first time a geographically balanced HIV-1 B CAR dataset of Haitian (n = 103) and Dominican (n = 123) sequences. Our Bayesian phylogeographic analysis traced the root location of the B CAR epidemic into Haiti and the Dominican Republic with the same posterior probability. This result revealed the complexity to uncover the geographic origin of the subtype B epidemic within Hispaniola by using only genetic data, probably due to the continuous cross-border viral movements between countries since the very early epidemic times.
In summary, this study highlights that the HIV-1 epidemic in Haiti is mainly driven by dissemination of early divergent non-pandemic B CAR strains. Our findings revealed that the HIV-1 B CAR epidemics in Haiti and the Dominican Republic are highly connected by intensive bidirectional viral dispersal since the early 1970s and that local B CAR transmission was already established in both countries when the first AIDS cases were officially recognized. Despite the use of a geographically balanced B CAR dataset, probabilistic Bayesian phylogeographic models cannot uncover the root of the subtype B epidemic in Hispaniola by using only genetic sequence information. Our findings support that both national and bi-national coordinated prevention measures are necessary to further control the HIV-1 dissemination in Haiti and the Dominican Republic.
The displacement and loading rate were set at 70 mm and 150 mm/min respectively for the four independent actuators. Images of the specimen surface at increasing stretches were stored at a frequency equal to 5 Hz with a IDS camera equipped with a 55 mm telecentric objective. The charge-coupled device (CCD) of the camera has 1920 × 1200 joined pixels. The Digital Image Correlation (DIC) technique is used to determine the displacement field at the specimen surface. The software used for the correlation process was SeptD  (Vacher et al. 1999) , and a uniform cold lighting was ensured by a home-made LED lamp. The spatial resolution, defined as the smallest distance between two independent points was equal to 4 pixels corresponding to 0. 343mm. The Region Of Interest (ROI) and the grid used for the digital correlation is represented in Figure  3.
Data Collection An electronic registry of deidentified medical and laboratory data was compiled for patients who underwent a first allo-HCT procedure between January 1, 2013, and September 30, 2015, at a participating center. For each patient, the following information was entered into the registry: date of allo-HCT, patient age at allo-HCT, sex, stem cell source, graft manipulation, underlying disease for allo-HCT, donor type, type of induction/conditioning regimen, and vital status (alive or dead). All patient records were also reviewed for any AdV-positive tests (ie, polymerase chain reaction, antigen, virus isolation) within the 6 months after allo-HCT, regardless of the biological specimen analyzed (ie, stool, blood, respiratory secretion, or urine). Separate and additional registries were created for patients with a positive AdV test result to capture detailed baseline and follow-up information, to examine the natural history of disease and the management of AdV infection for up to 1 year after transplantation.
Data collated for these patients included: all AdV test results and the thresholds for AdV detection, demographic data, patient height and weight, other laboratory test findings including coinfections, AdV organ involvement, anti-AdV treatment or interventions received, hospitalizations during follow-up, clinical outcomes (eg, GVHD, relapse of underlying disease, graft failure, additional allo-HCT), and vital status. Data extraction was done by a clinical research assistant at Analytica Laser (New York, NY) or by hospital personnel at each center. Analytica Laser oversaw the data collection process to minimize the possibility of missing or poorÀquality data. Data collection and use were in accordance with local and national laws.
Other factors could include the differences in the patient profiles between younger and adult patients, or the relatively underdeveloped acquired immunity in younger patients. Our study design limited the possible analyses in this study, as we were only able to evaluate the predictive power only of those factors prespecified in the data collection protocol. For example, because GVHD information was collected only in subjects with AdV infection, we could not include it as a potential prognostic factor for the incidence of AdV viremia with 1000 copies/mL. We also used historical medical record data; the quality and completeness of which cannot be confirmed. Centers may have used various AdV screening, analysis, and treatment protocols, as well as different post-transplant immunosuppressive regimens.
ACKNOWLEDGMENTS The authors thank the patients and investigators at each of the AdVance study sites. Sites and principle investigators are listed in Supplemental Material 1. Financial disclosure: This study was supported by  Chimerix  and conducted by  Analytica Laser. Medical writing support for this manuscript was funded by  Chimerix  and provided by  Jennifer Bodkin  of  Engage Scientific, Horsham, UK. Conflict of interest statement: M. R. has previously received research grants from  Neovii ,  Novartis , and  Sanofi. A. C. is an employee of Analytica Laser. E. V. , T. B. , E. M. , and G. N. are employees of Chimerix. P. Sedl a cek, T. P. ,  P. Sivaprakasam , and S. V. have no conflicts of interest to report.
Metabolic profiling For metabolome studies in mice, blood was sampled between 9 and 11a. m. , either in nonfasted animals, i. e. fed ad libitum, or after an overnight fast. For FXS controls and patients, sera were obtained from nonfasted individuals. NMR experiments were carried out using a Bruker Avance spectrometer (Bruker GmbH, Rheinstetten, Germany) operating at 600 MHz as described previously  [22]. Structural assignment was performed using data from literature, HMDB (http:// www. hmdb. ca/), S-Base (Bruker GmbH, Rheinstetten, Germany) and in-house databases  [23]. 1 H NMR spectra were pre-processed and exported into Matlab for multivariate statistical analyses using orthogonal partial least square discriminant analysis (O-PLS-DA) as previously reported  [24].
Liver proteome analysis Livers from 4 months-old overnight fasted animals were quickly collected after cervical dislocation, snapped frozen in liquid nitrogen and kept at À80 C until further analysis. Proteins were digested by insolution digestion and measured on an EASY-nLC 1200 coupled to an Orbitrap Elite mass spectrometer (Thermo Fisher Scientific). All acquired MS data were processed with the MaxQuant software suite  [30, 31]  version 1. 5. 2. 8 against the complete mouse UniProt database (taxonomy ID10090). Comparison analysis for individual protein levels between genotype was run on normal rank-based inverse logtransformed label-free quantification (LFQ) values and individual FDR were calculated. GO analysis was performed using String (v10. 5) [32]  and Panther (v12. 0) expression analysis tools  [33, 34].
Metabolic network analysis MetaboSignal R package  [40, 41]  was used to build the shortest paths network from FMRP to the metabolites of interest (Table  S5 ), integrating the proteins dysregulated in the liver as extra nodes to the network (Table  S6 ). Pivotal betweenness was then computed (Table  S7 ). 2. 14. Immunoaffinity (IA) capture of FMRP complexes in FL83B cells or liver extracts FL83B cells or Fmr1-WT and -KO liver were homogenized in IA buffer (10 mM Tris pH 7. 4, 150 mM NaCl, 1. 25 mM MgCl2, 0. 5% NP40, 1 mM DTT, 5 U/mL RNasin (Invitrogen)). The lysates were centrifuged at 10,000 g for 15 min at 4 C. The collected supernatant was then raised to 400 mM NaCl and 30 mM EDTA  [37]. For each IA assay, 500 mg of proteins from FL83B cells or liver extract was incubated in the presence of 60 mg of anti-FMRP IgY#C10 antibodies or nonimmune IgY immobilized on 15 mL of anti-chicken IgY agarose beads (Gallus Immunotech Inc.
Cumulative glycemia calculated over the course of the GTT and ITT were also significantly decreased in Fmr1-KO animals (Figure  2C, D ). We further investigated the insulin response at the molecular level in Fmr1-KO and WT liver. Injection of a bolus of insulin triggered activation and autophosphorylation of the insulin receptor (InsR) in the liver, leading to an increased phosphorylation at Tyr 1146 and Tyr 1150/ 1151 in both groups. In Fmr1-KO animals, the phosphorylation of InsR was increased both in basal conditions and upon insulin injection when compared to Fmr1-WT liver (Figure  2E ). We then monitored the phosphorylation status of Akt at Ser 473. Following insulin injection, the increase in Akt phosphosphorylation was significantly steeper in the Fmr1-KO liver (Figure  2E ). These data suggested that loss of FMRP in the liver was accompanied by an increased response to insulin stimulation.
Nuclei were counterstained with DAPI (blue) and merge images are shown in the last panel. The same exposure time was used for image captures of shFmr1-and shCtl transduced cells. (E) Translation monitoring assay using puromycin-labeled proteins in the shFmr1-or shControl (shCtl)-inactivated cells. Cells were labeled with puromycin for 15 and 30 min. Cell homogenates were analyzed by SDS-PAGE and proteins transferred to nitrocellulose membranes. Separated proteins were stained with Red Ponceau followed by immuno-blotting with an anti-puromycin antibody (a-Puro) that labels neosynthesized peptides. (F) Densitometric analysis of puromycin signal in (E). Data were normalized to total protein Ponceau signal, adjusted to average signal in shCtl cells at 15 min and presented as means AE cSEM; n ¼ 6 independent measures/group, except for WT 30 min, n ¼ 5; 2-way ANOVA: p(shRNA) < 0.
ACKNOWLEDGEMENTS We thank  N. Durand  and the IPMC animal facility for expert animal care. We acknowledge  H. Van Esch  for help with patient recruitment and are very grateful to the families and patients who have participated in this study. We thank the Anexplo phenotyping platform (Genotoul, Rangueil, Toulouse). LD thanks the generous support of  FRAXA Research Foundation ,  Agence Nationale de la Recherche  ( ANR JCJC SVE6 MetaboXFra ), Conseil Général  06 ,  Fondation Jérôme Lejeune  and the  CNRS PICS program. LD and MED acknowledge the support of the  Royal Society-CNRS   International Exchange Program  ( IE120728 ). LD, BM and MED are grateful to the European Community 7th Framework Program under Coordinated  Action NEURON-ERANET  (grant agreement  291840 ). The MED lab is funded by  METACARDIS  ( HEALTH-F4-2012-305312 ) and the  UK Medical Research Council  ( MRC grant   MR/M501797/1 ).
RFK and AVD have received grants from  FRAXA Research Foundation  and  Jérôme Lejeune Foundation. EWK was supported by grants from the  CIHR  and  NSERC. JAJB and JLM thank  Region Centre-Val de Loire  ( ARD2020   BiomedicamentseGPCRAb ) and the  Labex MabImprove  for financial support and the  Experimental Unit PAO  # 1297  ( EU0028 ) of  INRA Centre Val de Loire  for animal housing.
Isolation and cryo-EM analyses of EpsD and ExeD secretins The full-length forms of EpsD and ExeD were produced in a cell-free system  [6]  in the presence of liposomes, extracted as intact multimers, and purified to homogeneity in Zwittergent 3-14 (Zw3-14). SDS-PAGE and negative stain EM analyses of both EpsD and ExeD showed that they remained multimeric after purification (Fig  2   The grids were imaged using a Polara (FEI) electron microscope working at 300 kV and movies were recorded using a direct electron detector camera. For each sample, 2D image classification (Fig  2 ) was performed using Relion  [32]. Cryo-EM data collection and refinement statistics can be found in S1 Table. Analyses of top views of class averages (Fig 2, S2 and S3 Figs) revealed that, for both secretins, symmetry is unambiguously pentadecameric (C15 symmetry) (Fig  3 ).
Cryo-EM Samples were frozen with a Vitrobot Mark IV (FEI) at 100% humidity and 2 seconds of blotting time, force 1. Holey carbon grids (QUANTIFOIL) were used with an extra continuous 2 nm thick layer of amorphous carbon in order to have more particles presenting side-views. Without the extra carbon layer, we observed almost exclusively top-view particles. A Tecnai Polara (FEI) electron microscope working at 300 KV with a magnification of 41,322 was used to automatically collect images with a K2-summit direct electron detector camera in counting mode using the Latitude S software (Gatan Inc). Movie beam induced motion correction was performed with the motioncor2 software  [51]  and CTF estimation with Gctf  [52]. The pixel size at the detector level was 1. 21 Å. For each sample, semi-automated particle picking with EMAN boxer  [53]  was performed followed by 2D image classification by using Relion  [32]  on ~5,000 manually boxed particles.
With the obtained 2D class averages (S3 Fig) a low-resolution ab-initio 3D model was obtained by using RIco  [54]  (S6 Fig). 3D Image processing then followed the standard Relion protocol  [32]  with the need of a 3D classification step to reduce the excess of top-views. C15 symmetry was imposed. From a total of 2,021 micrographs of EpsD, 46,126 particles were kept in the final 3D reconstruction at 3. 4 Å resolution (FSC 0. 143). For ExeD, 2,247 micrographs were collected and 51,960 particles were kept in the final 3D reconstruction at 3. 7 Å resolution (FSC 0. 143). Model building was performed using Buccaneer  [55]  and Coot  [56]  based on secretins with PDB codes 5WQ8 and 5WQ7 for EpsD and ExeD, respectively. Refinement was performed with Refmac  [57].
EpsS crystallization, data collection, and structure solution Initial crystallization conditions for purified EpsS were obtained by the HTX platform (ISBG, Grenoble, France). Subsequently, urchin-like crystals were improved manually, and improved crystals were grown using the vapor diffusion method in a hanging drop setup by mixing 1 μl of EpsS (in 25 mM HEPES pH 7. 5, 150 mM NaCl at 5. 5 mg/ml) with 1 μl of 0. 1 M Tris-HCl pH 7. 5, 1. 9 M Ammonium Sulfate, 2. 5% (v/v) PEG 400. After one month of growth at 20 ˚C, crystals were fished and soaked in the crystallization solution supplemented with 25% (v/v) ethylene glycol and then flash cooled with a cryo-loop in liquid nitrogen. X-ray data collection was performed under a cold stream of nitrogen at 100 K at the European Synchrotron Radiation Facility (ESRF, Grenoble, France) on beamline ID30A-3.
Data were recorded to 1. 6 Å on an Eiger X 4M detector. X-ray diffraction data were analyzed, indexed and scaled with XDS  [60]  and then imported into the CCP4 program suite  [61]. Crystals belong to space group I222; due to the high resolution of the data set, we employed Arcimboldo Schredder  [44]  to solve the structure using AspS as an initial model (PDB: 4FTF). Arcimboldo Schredder was run in the laboratory's Linux OpenSuSE HTCondor v8. 6. 6 cluster  [62]  with 68 CPUs. ARP/wARP  [45]  was used to rebuild the solved model and reduce bias. COOT  [56]  and REFMAC5  [57]  were subsequently employed to manually build and refine EpsS. TLS definition was introduced at the later REFMAC refinements step  [63]. The quality of EpsS model was determined with MolProbity  [64]  and PROCHECK  [65].
Acknowledgments We acknowledge the platforms of the Grenoble Instruct-ERIC center (ISBG;  UMS 3518 CNRS-CEA-UGA-EMBL ) supported by the  French Infrastructure for Integrated Structural Biology Initiative, FRISBI  ( ANR-10-INSB-05-02 ) and by the  Grenoble Alliance for Integrated Structural Cell Biology, GRAL  ( ANR-10-LABX-49-01 ) within the  Grenoble Partnership for Structural Biology  (PSB). The electron microscope facility is supported by the  Rhone-Alpes Region , the  Fondation Recherche Medicale (FRM) , the  Fonds FEDER , the  Centre National de la Recherche Scientifique (CNRS) , the  CEA , the  University of Grenoble Alpes, EMBL , and the  GIS-Infrastrutures en Biologie Santeet Agronomie (IBISA). We would like to thank  Lionel Imbert  and  Jerome Boisbouvier  for assistance with and access to the Cell Free platform (ISBG) and  George Katselis ,  Canadian Centre for Health and Safety in Agriculture Mass Spectrometry Facility , for MS analysis and identification of proteins isolated from  SDS-PAGE gels.
Results Rietveld refinement is carried out using FullProf program  21, 22  and the refined pattern is shown in Fig. 1(a). The refined structure is tetragonal with P4 2 /mnm space group (No. 136) and all the respective Bragg diffraction positions are shown in Fig. 1(a). The lattice parameters are a = 4. 68 Å = b and c = 3. 06 Å and the respective crystal structure is shown in Fig. 1(b). The structure consists of NiF 6 octahedra, sharing edges along the c -direction and corners in the a-b plane. The position of nickel and fluorine atoms are (0 0 0) and (0. 30183 0. 30183 0. 00000) in the unit cell  20. The theoretically computed lattice parameters are a = 4. 70 Å and c = 3. 12 Å, in good agreement with refined structural parameters, and consistent with the reported literature  23, 24. The transition atom is coordinated with six fluorine atoms which form the distorted octahedral symmetry because of two different Ni atomic sites, leading to different Ni-F bond lengths (Fig.
Methods and Characterization Commercial powder of NiF 2 (97% anhydrous) was obtained from Alfa Aesar. Phase identification of NiF 2 was carried out by powder XRD using a Smartlab, Rigaku X-ray diffractometer. The X-ray generator was operated at 40 kV and 30 mA. Diffraction data were collected by step scanning method over an angular range of 20-80° with a step range of 0. 01°. The magnetization measurements were carried out using a PPMS-VSM (Model: 6000, Quantum Design, USA). For the dielectric measurements, the powder was pressed in a pelletizer under a pressure of 6 Ton using a 20 Ton hydraulic press. The resultant pellet has a thickness of 1. 25 mm and 13 mm in diameter. For dielectric measurements, the conducting layer of silver was deposited on both the sides of the pellets to have better ohmic contacts.
Acknowledgements The author S. A. acknowledges the funding agencies of  DST (SERB, FIST, PURSE) ,  RUSA  and  UGC-DAE Consortium for Scientific Research (Indore, Kolkata)  for the financial support. Author A. D. acknowledges  UGC-DAE Consortium for Scientific Research, Gov. of India  through project number  UDCSR/MUM/AO/ CRS-M-221/2016/722  for this work. Author P. S. would like to thank  UGC-BSR-RFSMS-SRF  for the meritorious fellowship.
Acknowlegments This work was performed, in partnership with the SAS PIVERT, within the frame of the  French Institute for the Energy Transition (Institut pour la Transition Energétique (ITE) P. I. V. E. R. T. (www. institut-pivert. com)selected as an  Investment for the Future ("Investissements d'Avenir "). This work was supported, as part of the Investments for the Future, by the  French Government  under the reference  ANR-001-01.
Ca 2+ measurements The cytosolic calcium concentration was measured using FURA-2loaded HT-1080 cells. The glass coverslip was mounted in a chamber on a Zeiss microscope equipped for fluorescence (excitation wavelengths: 350-80 nm, emission wavelength: 510 nm). Acquisitions were performed using a Cool SNAP HQ camera (Princeton Instruments, Evry, France) and Metafluor software (version 7. 1. 7. 0) was used for acquisition and analysis. The [Ca 2+ ] i concentration was derived from the ratio of the fluorescence intensities for each of the excitation wavelengths (F 350 /F 380 ), and from the Grynkiewicz equation. The cells were continuously perfused with saline solution and EDPs were added as 50 µg/mL via a whole chamber perfusion system. The flow rate of the whole cell chamber perfusion system was set to 1 mL min -1 and the chamber volume was 500 mL.
Real-time imaging and analysis For live imaging, the HT-1080, GFP-Hsp90 HT-1080 and mCherry-MLC HT-1080 cells were grown on µ-dish 35 mm and stimulated with 50 µg/mL EDPs. Cells were placed directly on a heated stage and supplemented with 5% CO 2. Images were acquired using Axio Observer (Carl ZEISS SAS) coupled with confocal Yokogawa spinning disk (Roper Scientific, Evry, France) through a 63 × NA1. 40 oil immersion objective. The system was drived by Metamorph Imaging software (Roper Scientific) and signals were collected with EM-CCD Camera EVOLVE (Photometrics). The whole fluorescent cell bodies were captured in Z-stack with 0. 5 µm step between optical sections. Each Z-stacks were acquired in ∼22 s intervals during 20 min. The experimental results show representative cells from a minimum of 10 different experiments.