dataesr/scientific-paragraphs-categorization huggingface dataset:
Characterization of NP The mean diameter of the magnetic cores (d core , nm) was determined by counting 400 diameters/fields using a transmission electron microscope (CM12; Philips Electron Optics, Zürich, Switzerland) at 45,000× magnification. Hydrodynamic diameter (d H , nm) and zeta potential (Z potential, mV) were measured at pH 7, at an ionic strength of 10 mM NaCl, by dynamic light scattering, using a Malvern NanoZS (Nanosizer 7. 2 software; Malvern Instruments, Malvern, UK) and a theoretical refractive index of magnetite of 2. 42. 32 The saturation magnetization (emu/g) was obtained from lyophilized SPION before PVA coating, using a superconducting quantum interference device. 33 The chemical composition of SPION, (ie, the concentration of iron in mg of Fe per mL), was determined using magnetic susceptibility methods.
statistical analyses Flow cytometry data were analyzed using GraphPad Prism Software (GraphPad Software, Inc. , La Jolla, CA, USA) and are presented as box and whisker plots (whiskers from minimum to maximum), or mean with standard deviation, of at least eight independent experiments. Multiple comparisons were analyzed by one-or two-way analysis of variance as indicated, with Bonferroni's multiple comparison post hoc tests for normally distributed data. Probability values of P,0. 05 were considered to be statistically significant.
Effects of modified a-PVA-grafted-SPION on human immune cells Next, the effects of a-PVA-grafted-SPION (++) on immune cell survival and cytokine secretion were analyzed. As already reported for a-PVA-SPION,  25  we found no significant influence of a-PVA-grafted-SPION (++) on apoptosis or viability of human immune cells at concentrations up to 100 µg/mL (data not shown). Secreted cytokines were analyzed in the supernatants collected from these whole blood viability experiments (n=9) using the Bio-Plex ® Suspension array system. We found significantly increased secretion of the following cytokines in the presence of a-PVA-grafted-SPION (++) (at 100 µg/mL) compared with the untreated control: IL6, IL8, IL10, IL12, IL17, MCP-1, MIP1a, MIP1b, FGF-basic, VEGF, and GM-CSF (Figure  2B ). These effects differed from those observed with a-PVA-SPION;  25  however, cytokine secretion did increase.
Libraries were prepared using 1. 2 g of total RNA, which was processed using a TruSeq RNA sample prep kit according to the Illumina protocol. Large-scale small RNA-Seq was performed using an Illumina HiSeq 2500 instrument, with a read length of 50 nucleotides (nt). RT-qPCR. Quantitative real-time PCRs were established as described previously  (30) , using a Corbett Rotor-gene 6000 real-time PCR system (Qiagen). For mature miRNA analysis, total RNA (100 ng) was first polyadenylated and reverse transcribed by using a miScript II RT system (Qiagen) according to the manufacturer's instructions. The obtained cDNA (2 l of a 10 Ϫ1 dilution) was subjected to RT-qPCR using a miScript SYBR green PCR kit (Qiagen). Primers were the mature miRNA sequence for the forward primers (as indicated at the Sanger miRBase database, v19.
0  [31] ) and the universal miScript primer (Qiagen) for the reverse primer. To check for RT-qPCR efficiency, standard curves were performed using 10-fold dilution series of total RNA from naive Huh7. 5. 1 cells. Data were analyzed using the ⌬⌬C T method, using small nucleolar RNA, C/D box 61 (SNORD61) as an endogenous reference and the noninfected samples as a calibrator  (32). miRNA transfection. Reverse transfection was performed using RNAiMax reagent according to the manufacturer's instructions (Life Technologies). Unless otherwise indicated, all siRNAs and miRNA mimics were used at a concentration of 20 nM, while anti-miRNAs were used at a concentration of 100 nM. Small-molecule inhibitor and DAA treatments. To inhibit nuclear factor kappa B (NF-B) signaling, control or miR-146a-5p-transfected differentiated Huh7 or Huh7.
HCV RNA translation was assessed by measuring intracellular luciferase activity after 4 h  (25, 28, 36). To assess the relevance of miR-146a-5p for viral replication, cells were electroporated with JFH1/⌬E1E2 RNA carrying a firefly luciferase reporter gene  (23). Cells allowing HCV replication were transfected at 48 h postelectroporation, and HCV replication was assessed by measuring intracellular firefly luciferase activity 48 h later. Luciferase activity data were normalized to protein amounts, which were determined for the same lysates by using a DC protein assay (Bio-Rad) according to the manufacturer's instructions. To assess the effect of miR-146a-5p on HCV assembly/egress and infectivity, cells were transfected 48 h prior to infection with HCVcc (Jc1) for 4 h. HCVcc were then removed, and cells were incubated with complete medium for 48 h.
5. 1  (39) , which uses miRBase release 20 and Rfam v. 11. miRNA measures were normalized using DESeq2 software  (40). Only miRNAs present in at least one of the libraries, with a minimum of 10 reads, were kept for further analysis of differential miRNA expression, which was performed using DESeq2 software  (40). Raw data (CEL intensity files) from genome-wide mRNA profiling were extracted from the scanned images by using Affymetrix GeneChip Command Console (AGCC), version 4. 0. CEL files were further processed with Affymetrix Expression Console software, version 1. 3. 1, to calculate probe set signal intensities by use of robust multiarray average (RMA) algorithms with default settings. Differentially expressed genes were selected using the FCROS method  (41) , with the selection error set at 0.
03. Functional annotation and gene network analyses of differentially regulated genes were performed by using Ingenuity Pathway Analysis (IPA; Qiagen) software. In parallel, modulation of molecular pathways under conditions of miR-146a-5p overexpression was determined in Molecular Signature Database (MSigDB; ver. 4. 0) (42) by using gene set enrichment analysis (GSEA)  (43). miRNA targeting analyses were performed using MiRSystem (44), which allows retrieval of both experimentally validated and predicted miRNA targets. Statistical analyses were performed using the GraphPad Prism v. 6 package. The normality of data set distributions was assessed using the D'Agostino and Pearson omnibus and the Shapiro-Wilk normality tests. Data sets with normal distributions are presented as means Ϯ standard deviations (SD) and were analyzed by the unpaired t test with Welch's correction or one-way analysis of variance (ANOVA), as indicated in the figure legends.
siRNA targeting STAT3 was used as a control to inhibit proliferation of hepatocyte-like cells  (61). In contrast to cells silenced for STAT3, which displayed decreased cell proliferation over time, cells overexpressing miR-146a-5p did not show any significant alteration of cell proliferation within 96 h of transfection compared to control-transfected cells (Fig. 2A ). To confirm this finding, we analyzed the cell cycle distribution of hepatocyte-like cells upon miR-146a-5p transfection by flow cytometry. While silencing of STAT3 resulted in markedly lower percentages of cells in the S and G 2 /M phases, overexpressing miR-146a-5p did not affect the overall cell cycle distribution (Fig. 2B ). Taken together, these data suggest that miR-146a-5p does not promote cell proliferation of hepatocyte-like cells.
To investigate the pathways regulated by miR-146a-5p in our model in an unbiased manner, we performed a genome-wide transcriptomic analysis of hepatocyte-like cells upon miR-146a-5p overexpression (Fig. 3 ). Using RT-qPCR, we assessed a consistent increase of miR-146a-5p upon miRNA transfection prior to genome-wide microarray analysis (data not shown). Compared to the results for control cells, enhanced miR-146a-5p expression in hepatocyte-like cells resulted in a significant deregulation of 274 genes, including 63 upregulated and 211 downregulated genes (Fig. 3A ) (P Ͻ 0. 01; FCROS method). Interestingly, the interleukin-1 receptor-associated kinase 1 (IRAK1) and chemokine C-X-C motif chemokine ligand 8 (CXCL8) genes, two known targets of miR-146a-5p, were among the downregulated genes. In line with a previously shown implication of miR-146a-5p and IRAK1 in inflammatory responses in immune cells  (52) , our data suggest a role for miR-146a-5p in inflammation signaling in hepatocyte-like cells.
5. 1 cells at 7 days postinfection were retrieved using the miRsystem tool. The involvement of these target genes in pathways related to inflammation, fibrosis, and cancer was assessed through miRsystem and a systematic screen of the available literature by use of PubMed. ϫ, involvement of miRNA target in the indicated process. maintaining the increased risk of HCC development in patients cured of hepatitis C. Since the upregulation of miR-146a-5p results in the enhancement of fatty acid metabolism, which is instrumental to HCV replication, this piece of data suggests that in addition to modulating pathways associated with liver disease pathogenesis, miR-146a-5p may fine-tune the metabolic activity of hepatocytes upon viral infection and eventually act on the viral replication cycle itself.
Red dots represent mRNAs whose values are considered to be statistically significant (P Ͻ 0. 015; FCROS method). (B) Functional network analysis of genes with modified expression after miR-146a-5p overexpression in hepatocyte-like cells. The IPA toxicity algorithm was used to assess the enrichment of deregulated genes in specific toxicity pathways with altered expression in human disease. P values indicate the significance of enrichment of the input genes for each Tox Function pathway. (C) Coregulated gene networks in miR-146a-5p-overexpressing cells. Modulation of molecular pathways by miR-146a-5p was determined by using the KEGG database and GSEA  (43). Significantly enriched gene networks involved in immune responses (blue), the cell cycle and DNA repair (black), and cell metabolism (gray) are shown.
ACKNOWLEDGMENTS We thank  R. Bartenschlager  ( University of Heidelberg, Germany ) for providing the plasmids for production of HCVcc,  F. Chisari  ( The Scripps Research Institute, La Jolla, CA ) for the gift of Huh7. 5. 1 cells, and  A. Patel  ( MRC Virology Unit, Glasgow, United Kingdom ) for the E2-specific MAb  AP33. We acknowledge  N. Van Renne ,  S. Coassolo , and  A. Mawa  ( Inserm U1110, Strasbourg, France ), as well as  A. Weiss ,  L. Brino , and  D. Dembele  ( IGBMC, Department of Functional Genomics and Cancer, Illkirch, France ), for excellent technical assistance and helpful discussions regarding transfection protocols and computational analyses. We thank  B. Campana  ( Department of Biomedicine, University Hospital Basel, Basel, Switzerland ) for providing clinical information about the patients enrolled in the study.
Differences between one code and another may be explained by at least the following four factors: the choice of the included physics, as a compromise between correctness and feasibility; cross sections that can come from theory, measurements or both (in most cases, the cross section data have a certain uncertainty); numerical and coded implementation, e. g. , numerical integrations, interpolations, roundoff errors and bugs; the performance, as faster codes can run more particles in the same time, which results in more accurate statistics. Even if it is possible in principle to determine the differences between the physical models and between the numerical methods, it may be very complicated (if not impossible) to estimate the uncertainties associated with a certain choice of physical models, to estimate the uncertainty propagation and accumulation of all input through the full multiscale models, and to review all source codes (if available) to find any mistakes and possible numerical problems.
EGS5 EGS5 (Electron-Gamma Shower version 5, developed by  Hirayama et al. , 2005)  is a general purpose software package for the Monte Carlo simulation of the coupled transport of electrons, positrons and photons in an arbitrary geometry. It is the next version after EGS4 that was released by  Nelson et al. (1985)  with a history that dates back to the 1960s. The user controls an EGS5 simulation by means of an input text file for settings and a written FORTRAN user code, to which the rest of the FORTRAN source files are appended and compiled as one. In the user code, several subroutine calls create, establish and initiate the cascade. Two important subroutines, HOWFAR and AUSBGAB, which should be written inside the user code, are used to specify the geometry and the output of the results. EGS5 can simulate particles from a few keV up to several hundred GeV, depending on the material.
FLUKA FLUKA (developed by  Ferrari et al. , 2005 , copyright to INFN and CERN 1989 -2011) , is a general purpose tool for calculations of particle transport and interactions with matter. FLUKA is able to simulate the interaction and propagation in matter of roughly 60 different particles, including photons from 100 eV and electrons and positrons from 1 keV to thousands of TeV, neutrinos, muons of any energy, hadrons of energies up to 20 TeV (up to 10 PeV by linking FLUKA with the DPMJET code) and all the corresponding antiparticles and neutrons down to thermal energies. FLUKA includes recent data sets, published by  Böhlen et al. (2014). The program can handle magnetic and electric fields, although not self-consistently (i. e. , the charged particles do not produce magnetic or electric fields).
The GRanada Relativistic Runaway (GRRR) code Developed by A. Luque at the Astrophysics Institute of Andalusia (IAA-CSIC), the GRanada Relativistic Runaway (GRRR) code was designed to investigate the self-consistent interaction between electrons in the limit of very intense RREAs. This investigation, presented in Luque (2014), concluded that due to the interaction between electrons in the avalanche RREAs saturate into a steady-state propagating relativistic runaway ionization front (RRIF). As the GRRR code was implemented with that specific goal in mind, its scope is narrower than the general purpose codes (EGS5, FLUKA, Geant4) analyzed in this paper. It only follows the evolution of high energy electrons, and includes a limited set of interactions between these electrons and the embedding medium.
Electron ionization and Rutherford scattering are modeled discretely and, in this work, down to a low energy cutoff of 50 keV. The friction for these interactions is uniform and without straggling effect. Bremsstrahlung collisions with nuclei are modeled deterministically by friction; in other words, as continuous radiative losses. The Supplement of  Luque (2014)  contains further details about the physical model underlying the GRRR code. In the Supplement of this work, the input files are given for the presented bench-mark tests. The full source code for GRRR is available at https://github. com/aluque/grrr. However, presently the code is mostly undocumented so we advise potential users to contact the author.
MC-PEPTITA The Monte Carlo model for photon, electron and positron tracking in terrestrial atmosphere (MC-PEPTITA) by  Sarria et al. (2015)  is a Fortran 90 code that simulates the propagations of TGF and associated electron-positron beams within the Earth environment from the production altitude at 10 to 20 km to satellite altitude. To simulate the quasi-exponential atmospheric density profile and the Earth's magnetic field, it uses the NRLMSISE-00 and IGRF-11 models  (Cullen et al. , 1997; Perkins et al. , 1991). It is optimized to run in this environment, whereas some other codes (e. g. , Geant4) can only handle layers of constant density. Concerning the interactions between particles and matter, it mainly uses the EPDL and EEDL cross section sets  (Cullen et al. , 1997; Perkins et al. , 1991) , except for inelastic scattering of electrons and positrons where the GOS model is used.
Performance benchmark As a complement, we also tested how much time the codes needed to complete the simulations. We did not try to do an in-depth performance benchmark of the codes, but we think this is an interesting piece of information for someone who is seeking for a code to be used in the HEAP context. Since the programs are written in different languages (Fortran, C++ and Python) and may be run on different machines with different architectures, we normalized the completion time with respect to a reference computer configuration. The simulation starting with 1 million 1 MeV electrons is used as the test case because it is feasible for all the evaluated codes, and it takes a completion time that is neither too short nor too long. More details are given in the Supplement. The normalized results are discussed in Sect.
MC-PEPTITA simulations can be requested, contact  David Sarria (david. sarria. 89@gmail. com). MC-PEPTITA program was developed under a contract of Centre National D'Edtudes Spatiales (CNES) and Direction Générale de l'Armement (DGA), whose permissions are required in order to get access to the source code. Details of the performance tests are also available in the Supplement. The Supplement related to this article is available online at doi:10. 5194/gmd-9-3961-2016-supplement.
Acknowledgements. Working visits between the European partners were supported by the  ESF  research training network TEA-IS (Thunderstorm Effects on the Atmosphere-Ionosphere System). Casper Rutjes is funded by the  Foundation for Fundamental Research on Matter (FOM) , which is part of the  Netherlands Organisation for Scientific Research (NWO). Alexander Broberg Skeltved is supported by the  European Research Council  under the European Union's  Seventh Framework Programme  ( FP7/2007-2013) / ERC  grant agreement 320839 and the  Research Council of Norway  under contracts  208028/F50 ,  216872/F50 , and  223252/F50  (CoE). Alejandro Luque was supported by the  European Research Council (ERC)  under the European Union's  H2020 programme/ERC  grant agreement  681257  and by the  Spanish Ministry of Economy and Competitiveness ,  MINECO  under projects  ESP2013-48032-C5-5-R  and  FIS2014-61774 -EXP that include EU funding through the  FEDER program.
Bioinformatics analysis of the deep sequencing data revealed that both symptomatic plants accumulated high proportion of viral siRNAs in a total population of 20-25 nt sRNAs (9. 7% in the SeT-ICMV plant and 22% in the SeM-SLCMV plant) (Figure  2d ). In contrast, only trace amounts of viral siRNAs were detected in the SeT-rec plant (0. 07% of the total 20-25 nt sRNAs). Taken together, our findings agree with the findings of Patil and Fauquet  [19] , which showed that recovery from symptoms is not always associated with high siRNA accumulation. The re-emergence of CMD symptoms from recovered plants occurred after the complete loss of the SLCMV-[SeT1] titer and near complete loss of viral siRNAs, and this re-emergence of severe disease symptoms was associated with production of viral siRNAs from ICMV-[SeT4] that replicated efficiently in the absence of SLCMV.
-collected cassava plants (Manihot esculenta Crantz, cultivar Sengutchi) collected from Malappuram and Thiruvananthapuram in June 2009 were propagated as stem cuttings initially in Viruses 2016, 8, 264 3 of 15 the Madurai Kamaraj University (MKU) greenhouse under natural light (12 h light/12 h darkness, 23 to 33 • C). Details of SLCMV and ICMV isolates, their National Center for Biotechnology Information (NCBI) accession numbers, the sizes of their DNA A and DNA B components and the isolates to which the maximum nucleotide sequence identity is seen are presented in Table 1. SLCMV-Sengutchi Malappuram [SeM] DNA A was cloned by polymerase chain reaction (PCR) using abutting primers. SLCMV-[SeM] DNA B, SLCMV-Sengutchi Thiruvananthapuram [SeT1] DNA A, SLCMV-[SeT1] DNA B, ICMV-[SeT4] DNA A and ICMV-[SeT4] DNA B were cloned by rolling circle amplification (RCA).
Acknowledgments: This work was funded by  Indo-Swiss Collaboration in Biotechnology  (ISCB #  CV1. 2 ) which is jointly supported by the  Department of Biotechnology (DBT), Govt. of India and Swiss Agency for Development and Co-operation (SDC). University Grants Commission (UGC), Government of India  is thanked for the  UGC-Basic Scientific Research (BSR)   Faculty Fellowship  (No. F. 18-1 (61)/2014 (BSR)) to  K. Veluthambi. B. Abirami  is acknowledged for her technical support. Author Contributions: K. V. planned and guided N. benthamiana agroinfection experiments; T. H. made the critical interpretation on the recovery of cassava from SLCMV and re-emergence of ICMV; M. M. P. carried out deep sequencing and provided the data on small RNAs in cassava; C. K. made partial dimers of both SLCMV and ICMV, performed agroinfection experiments and wrote the manuscript; B.
Field -collected cassava plants (Manihot esculenta Crantz, cultivar Sengutchi) collected from Malappuram and Thiruvananthapuram in June 2009 were propagated as stem cuttings initially in Viruses 2016, 8, 264 3 of 15 the Madurai Kamaraj University (MKU) greenhouse under natural light (12 h light/12 h darkness, 23 to 33 • C). Details of SLCMV and ICMV isolates, their National Center for Biotechnology Information (NCBI) accession numbers, the sizes of their DNA A and DNA B components and the isolates to which the maximum nucleotide sequence identity is seen are presented in Table 1. SLCMV-Sengutchi Malappuram [SeM] DNA A was cloned by polymerase chain reaction (PCR) using abutting primers. SLCMV-[SeM] DNA B, SLCMV-Sengutchi Thiruvananthapuram [SeT1] DNA A, SLCMV-[SeT1] DNA B, ICMV-[SeT4] DNA A and ICMV-[SeT4] DNA B were cloned by rolling circle amplification (RCA).
Computational fluid dynamics analysis Volumetric meshes were generated using ICEM CFD software package, Version 11. 0 (ANSYS, Canonsburg, Pennsylvania). Meshes were composed of unstructured tetrahedral in the lumen and 6node prism elements near the vessel wall. Smaller tetrahedral elements were used to resolve the stent struts. To ensure CFD simulations independent from mesh element size, in particular around the FDs, a mesh independency analysis was carried out. The convergence criterion of mesh independence was that wall shear stress (WSS) and intra-aneurysmal velocity had to be within 2. 5% from the finest tested mesh. Convergence was reached with an element size around the stent strut of 0. 016 mm, 3 prism layers with a total size of 0. 3 mm defined everywhere but in the region of the FDs  and a global tetrahedral element size of 0.
Data analysis Four hemodynamic variables were analyzed, namely: (1) spatial average of intra-aneurysmal velocity magnitude (velsa), (2) spatial average of wall shear stress on the aneurysm wall (wsssa), (3) spatial average of intra-aneurysmal pressure (pressuresa), and (4) range of intra-aneurysmal pressure (pressurerng), which was defined as the difference between the maximum and minimum intra-aneurysmal pressure. Variable values were recorded at each time step of the cardiac cycle. These variables were chosen for their role in aneurysm occlusion and their relation to aneurysm flow velocity  [26, 27, 7, 10]. For part of the analysis, we highlighted changes in the shape and amplitude of the variables' time curves, and removed information about the absolute reduction, by normalizing variable x by its timeaveraged, or mean, value: x normalized = x/mean(x).
Acknowledgments The study used data collected during by the 6th framework program of the  European Commission @neurIST project  (www. aneurist. org) FP6-IST-2004027703. The authors would like to acknowledge clinicians collecting data in the  Geneva University Hospital of Geneva  ( Vitor Mendes Pereira ,  Hasan Yilmaz ,  Daniel Rfenacht ,  Philippe Bijlenga ,  Karl Schaller ) and the @neurIST project providing the infrastructure to collect and share the data. This research has been partially funded by the  Catalonian Department of Innovation, Universities and Enterprise (DIUE) , through the  EndoTreat  project (exp. VALOR2010-00064 ).