dataesr/scientific-paragraphs-categorization huggingface dataset:
3. 2. 2. Fusion of water. The enthalpies of fusion of water in the hydrated annealed samples were calculated as explained below, and expressed per mole of CA(1-7)M(2-9). For the sample with h = 4. 51, a straight line and a secondorder curve were fitted to the C p data between 214 and 227 K and between 274 and 302 K, respectively. For the sample with h = 0. 49, two straight lines were fitted to the C p data between 214 and 221 K and between 270 and 300 K, respectively. The baseline heat capacities were determined by extrapolating the lower fitted function up to and the upper fitted function down to the melting points of ice (272. 5 and 265. 0 K, respectively, for each of the samples). The enthalpies of fusion were calculated by subtracting the contribution of the base line heat capacity from the total enthalpy change.
Acknowledgements The experiments at LLB were supported by the  European Commission  through the  Access Activities of the Integrated Infrastructure Initiative for Neutron Scattering and Muon Spectroscopy  ( NMI3 ), supported by the  European Commission  under the  6th Framework Program  through the  Key Action: Strengthening the European Research Area, Research Infrastructures , Contract no. :  RII3-CT-2003-505925. Thanks are also due to Fundaça ˜o para a  Ciencia e Tecnologia  for financial support to  CIQ(UP)  through the strategic project  Pest-C/QUI/ UI0081/2011. MB would like to thank  Patrick R. Connelly  for.
Then, blots were probed with the rabbit polyclonal anti-IGAP1 antibody (1:3000), or the mouse monoclonal anti-VE-cadherin antibody (1:1000) or the rabbit polyclonal anti-b-catenin antibody (1:1000) overnight at 4uC. After washing, the secondary peroxi-  dase-labeled goat anti-rabbit antibody (1:15,000) or goat antimouse antibody (1:10000) was applied for 1 h at room temperature. Immunoreactive detection was performed by chemiluminescence (ECL Plus Western Blotting Chemiluminescent Substrate, GE Healthcare) and the signal intensity was quantified using Image J software.
In situ Proximity Ligation Assay (PLA) The Duolink TM in situ PLA allows the detection and the quantification of IQGAP1 interactions with the AJ proteins VEcadherin and b-catenin. Briefly, PDECs exposed or not (control) to flow were rinsed with PBS, fixed with 4% PFA for 20 min at room temperature, permeabilized with 0. 1% Triton X100 for 1 min and incubated in blocking buffer (1% BSA (w/v), 1% FCS (v/v) in PBS) for 15 min. Cells were immunolabeled with the same primary antibodies as those described above. Then, PDECs were incubated for 2 h at 37uC with secondary antibodies with attached PLA probes, supplied in the Duolink kit. The subsequent procedure was the same as that described in the manufacturer's instruction. Finally, cells were mounted under a cover slip with ProLong containing DAPI (Invitrogen -Molecular Probes) and images were taken and analyzed using the TCS SPE confocal microscope and LASAF software (Leica, Wetzlar, Germany).
Results High content screening and analysis (HCSA). Protein citrullination. Human lung epithelial (A549) cells and phagocytic (THP-1) cells were exposed to various SWCNTs concentrations (1, 5, 10 mg/ml) for 6 h and 24 h, and HCSA was carried out to quantify the induction of protein citrullination. The data (Figure  1A ) indicated a significant increase in protein citrullination in both cell lines in a time-and dose-dependent manner, with maximum effects seen at 24 h and at the highest dose (10 mg/ml) tested. Immunofluorescent images of cells exposed to chemically-treated SWCNTs (Figure  1B ) showed citrullinated proteins in the cytoplasm and around the nucleus after 24 exposure, thus validating that citrullinated proteins were expressed. By increasing the complexity of the SWCNT's functionalization (p-SWCNTs , p SWCNTs/BSA , f-SWCNTs , f-SWCNTs/BSA), the induction of citrullinated proteins decreased.
Protein citrullination was quantified using the dual area object analysis module of the IN Cell Investigator software (GE Healthcare, Buckinghamshire, UK). The module allows for simultaneous quantification of subcellular inclusions that are marked by different fluorescent labels and measures fluorescence intensity associated with predefined nuclear and cytoplasmic compartments. Cells exposed to peptidylarginine diminase (PAD) were used as positive control (P/T). Cytotoxicity assay: Following exposure to SWCNTs for 3, 6 and 24 h, a multiparametric cytotoxicity assay was performed using HCS reagent HitKit TM as per manufacturer's instructions (Thermo Fisher Scientific Inc. , USA). Briefly, this kit enable to measure cell viability, cell membrane permeability and lysosomal mass/ pH, which are toxicity-linked cellular markers.
Cell exposed to LPS were used as positive control (P/T). Statistical analysis. A two-way analysis of variance (ANOVA) followed by a Bonferroni post-test analysis was carried out for all HCSA and ELISA assays (Prism; Graph-Pad Software Inc. , USA). p , 0. 05 was considered statistically significant. The entire list of p values can be found as Supplementary Tables S1-S22 online. HCSA and ELISA data, as well as the protein citrullination results, are presented as mean values (n test 5 2) 6 standard error of the mean and normalized to the negative control. Due to the large amount of information acquired by HCSA, a data mining and exploration platform was used (KNIME (http://KNIME. org, 2. 0. 3) in combination with a HiTS screening module (http://code. google. com/p/hits 0. 3. 0) in order to screen and normalize all parameters under investigation as previously reported  27, [36] [37] [38].
Acknowledgments This work was supported by the  EU   FP7   NAMDIATREAM  project ( NMP-2009-LARGE-3-246479 ), and  CRANN (CRANN Pathfinder  to D. M. ), A. K. for the financial support under  EU   FP7   NANOINTERACT  project ( NMP4-CT-2006-033231 ), HEA PRTLI cycles III-IV. B. M. M. for the financial support under MULTIFUN ( NMP-2010-LARGE-4-246979 ) and INTERREG  CAN  project ( INTERREG 4A IRELAND-WALES ).
Cell lines were regularly screened and are free from mycoplasma contamination. Growth inhibition assay. Growth inhibition assays were performed as previously described  (Pasquier et al, 2010). After 72-hdrug incubation, metabolic activity was detected by addition of Alamar blue and spectrophotometric analysis. Cell proliferation was determined and expressed as a percentage of untreated control cells. The determination of IC 50 values was performed using GraphPad Prism 4 software (GraphPad Sofware Inc, La Jolla, CA, USA). Combination indexes (CI) were calculated for all tested drug concentrations according to the Chou and Talalay method  (Chou and Talalay, 1984; Chou, 2010). In vitro Matrigel assay. Matrigel (BD Biosciences, North Ryde, New South Wales, Australia) assay was used to examine the antiangiogenic effects of b-blockers alone and in combination with chemotherapy, as previously described  (Pasquier et al, 2011).
Cells were treated with different drug solutions 20 min after seeding on Matrigel, and photographs were taken after 8-h-drug incubation using the Â 5 objective of an Axiovert 200 M fluorescent microscope coupled to an AxioCamMR3 camera driven by the AxioVision 4. 7 software (Carl Zeiss, North Ryde, New South Wales, Australia). The anti-angiogenic effects were then quantitatively evaluated by measuring the total surface area of capillary tubes formed in at least 10 view fields per well using AxioVision 4. 7 software. Cell cycle analysis and apoptosis detection. For cell cycle analysis, adherent and floating cells were harvested, fixed in 80% ethanol and incubated 15 min in the dark with 100 mg ml À 1 propidium iodide (PI), immediately before analysis. Amount of DNA present was measured by flow cytometry (FACSCalibur, BD Biosciences) and cytogram analysis was done with FlowJo software version 7.
6. 5 (Tree Star, Ashland, OR, USA). For apoptosis detection, adherent and floating cells were harvested and incubated for 15 min in the dark with PI and Annexin V-FITC (BD Biosciences), followed immediately by flow cytometry analysis (FACSCalibur, BD Biosciences). Cytogram analysis was performed with Cell Quest Pro software (BD Biosciences), as previously described  (Pasquier et al, 2004). Mitochondrial network. Fluorescence labelling of mitochondria was performed by stably transfecting neuroblastoma SK-N-SH cells with the mitochondrial-targeted DsRed (mtDsRed)  (Savry et al, 2013). The dynamic localisation of mitochondria was analysed in living cells after a 6-h incubation with propranolol alone, vincristine alone or their combination. Cells were observed using the Â 40 objective of a Leica DM-IRBE microscope driven by Metamorph software (Princeton Instrument, Trenton, NJ, USA), and 600 cells were analysed for each experimental condition to determine the percentage of cells with a fragmented mitochondrial network.
ACKNOWLEDGEMENTS We would like to thank  Marie-Pierre Montero  ( INSERM UMR 911 ),  Claudia Flemming  ( Children's Cancer Institute Australia ) and  Dr Maria Sarris  ( Faculty of Medicine, University of New South Wales, Australia ) for their assistance with the fluorescence labelling of mitochondria, the radiolabelled drug accumulation assay and the CD31 staining analysis, respectively. This work was supported by the  Children's Cancer Institute Australia for Medical Research , which is affiliated with the  University of New South Wales and Sydney Children's Hospital , and by grants from the  Balnaves Foundation (EP) , ' LN la vie' (NA) and 'Enfance et Sante & SFCE' (NA ). EP was supported by a  Cancer Institute New South Wales  ' Early Career Development' Fellowship  (no. 07-ECF-1-21 ) and MK is supported by a  National Health and Medical Research Council Senior Research Fellowship  (no.
Acknowledgements We thank  Mike Tyers  and  Matthias Peter  for providing reagents, and  Gabriella Alexandru  and  Satpal Virdee  for critical reading of the manuscript. We also thank the  MRC-Protein Phosphorylation Unit (PPU) DNA Sequencing Service  (coordinated by  Nicholas Helps)  and the  Division of Signal Transduction Therapy (DSTT)  protein and antibody purification teams (coordinated by  Hilary McLauchlan  and  James Hastie). G. R. is funded by  INSERM  and  Rennes Metropole. This work was supported by an  ERC   Starting Investigator Grant  to T. K. , by a  European Regional Development Fund Grant for an Innovation Pipeline for Translational Science  (grant number  LUPS/ERDF/2008/2/1/ 0429 ), by a grant from the  Scottish Government  to the  Scottish Institute  for Cell Signalling and by the pharmaceutical companies supporting the  Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer-Ingelheim ,  GlaxoSmithKline ,  Merck KGaA ,  Janssen Pharmaceutica and Pfizer ).
Statistical analysis Data are presented as mean ± SD. Expression of profibrotic cytokines was evaluated using ANOVA followed by Bonferroni-Dunn post hoc test. Nonparametric Mann-Whitney U test (Systat, version 7. 0, SPSS, Chicago, IL) was used to evaluate significance in differential phosphorylation of MAPK. Values of p < 0. 05 were considered statistically significant.
PET data acquisition FMZ (RO15-1788) was radiolabeled with 11 C using methylation  (Maziere et al. , 1984). PET scans were acquired using an Exact ECAT HR+ scanner (Siemens, Erlangen, Germany) in the high sensitivity three-dimensional mode with a spatial resolution of about 5 mm full with half maximum (FWHM) measured with 18 F according to the NEMA protocol  (Brix et al. , 1997). For the purpose of attenuation correction, a 68 Ge transmission scan was acquired. [ 11 C]FMZ (2. 775 MBq/kg) and unlabelled FMZ (0. 01 mg/kg) were simultaneously injected  (Delforge et al. , 1995). Starting at injection, dynamic three-dimensional emission images were collected as twelve consecutive temporal frames over 55 min and reconstructed as sixty-three contiguous slices with 2. 42 mm slice thickness and a voxel size of either 1.
Pharmacists, who are in direct contact with patients, identified stocking 'color' and 'fragility' as key issues for users. Subsequently, 12 items covering all of the domains were selected for inclusion in the questionnaire. Simple and comprehensive questions were generated. Patient opinion on compressive stockings was captured using visual numeric scales, from 0 to 10 (0 = very unacceptable/very difficult; and 10 = very good/very easy). To highlight the underlying constructs through these items, an explanatory factor analysis (principal-axis factoring method) of data from compressive stockings currently used by the patients was performed. Since correlations between latent traits may exist, an oblique promax rotation after an orthogonal varimax rotation was chosen. The most parsimonious model yielded to two factors with a correlation coefficent, r, of 0.
For categorical variables, intergroup comparisons were performed with the c 2 test or Fisher's exact test. Comparisons between groups were performed using the Student's t-test or the Wilcoxon and Mann-Whitney test for quantitative variables. Intragroup comparisons of scores were performed with paired Student's t-test or signed rank Wilcoxon U test when the conditions necessary for the application of this test were not met. The level of significance was set at 5%. Data were analyzed using SAS ® software version 9. 3 (SAS Institute Inc. , NC, USA) on Windows hardware. The following subgroup analyses were conducted as secondary end points: patients who did not wear stockings daily due to difficulty in putting them on/taking them off; patients with osteoarthritis; obese patients; and unemployed patients.
Patient demographics A total of 222 French women were originally included in the study. However, two patients did not provide responses to all of the survey items, so were excluded from the final analysis. Therefore, the final survey analysis included 220 evaluable French women (group 1: n = 102; group 2: n = 118). Baseline sociodemographic data are presented in table 1. Overall, the mean age of patients was 55. 5 ± 13. 6 years, with a mean BMI of 27. 0 ± 6. 6. In the total population, approximately half of all patients (48. 9%) were in paid employment, and 60% of patients were married, with approximately 30% of these patients having children. Patients had a mean of 8. 0 ± 4. 5 comorbidities, with 105 (47. 7%) patients experiencing osteoarthritis (hip: 31%; knee: 58%; hand: 61%; and fingers: 48%).
Immunofluorescence analyses Log phase cells were fixed with formaldehyde as described before  (Bringaud et al. , 1998). Slides were incubated with rabbit anti-TDH (diluted 1:100) and Mitotracker ® , or mouse anti-PDH-E1 (diluted 1:50) and rabbit anti ASCT (diluted 1:100)  (Riviere et al. , 2004)  followed by ALEXA Fluor ® 594conjugated goat anti-mouse secondary antibody (diluted 1:100) and/or ALEXA Fluor ® 488-conjugated goat anti-rabbit secondary antibody (diluted 1:100) (Molecular Probes), depending on the analysed cell. Cells were viewed with a Leica DM5500B microscope and images were captured by an ORCA ® -R 2 camera (Hamamatsu) and Leica MM AF Imaging System software (MetaMorph ® ) and merged in Adobe Photoshop on a Macintosh iMac computer.
Acknowledgements We are extremely grateful to TIGR and the  Wellcome Trust Sanger Institute  for the chromosome sequences accessible on the T. brucei genome database (http://www. genedb. org/genedb/tryp/). This work was supported by the  Agence Nationale de la Recherche (ANR)  through grant  ACETOTRYP  of the ANR-BLANC-2010 call to FB and PM; FB is also supported by the  Centre National de la Recherche Scientifique (CNRS) , the  Université Bordeaux Segalen , the  Conseil Régional d'Aquitaine , the  Laboratoire d'Excellence (LabEx) ParaFrap   ANR-11-LABX-0024 ; FB and MPB are also supported by the  ParaMet PhD programme of Marie Curie Initial Training Network  ( FP7 ). MPB is partly supported by the  Wellcome Trust  through The  Wellcome Trust   Centre for Molecular Parasitology , which is supported by core funding from the  Wellcome Trust  (Grant  085349 ).
AON design AON-5 (5 0 -CCA GCC ACU CGG GCU GAG AAG ACA A-3 0 ) and AON-6 (5 0 -AAG UGG UCU GAG CAU CUG UGA UGU G-3 0 ) target ESE motifs in exon 5 or exon 6 of Mybpc3, respectively. The motifs were identified using the ESE prediction program "ESE finder 3. 0"  (Cartegni et al, 2003; Smith et al, 2006). To test the specificity of the AONs (25-mers) 2 0 -O-methyl RNA with a full-length phosphorothioate 2OMePS backbone was synthesized (Eurogentec).
Acknowledgements We thank  Julie Johnston  ( Penn Vector Core, University of Pennsylvania, PA, USA ) for supplying the recombinant AAV vector pE5/9,  Evelyn Bendrat  and  Michaela Miehe  ( UKE-HEXT, Hamburg, Germany ) for AAV6 production. We thank  Siegfried Labeit  ( Heidelberg, Germany ) for providing the anti-titin Z1 antibody and  Sakthivel Sadayappan  ( Loyola University Chicago, IL, USA ) for providing antibodies directed against cMyBP-C-2-14aa, Ser273-, and Ser-302-cMyBP-C. We thank  Vincent Christoffels  and  Malou van den Boogaard  ( Amsterdam, The Netherlands ) for providing embryonic mouse heart samples. We also thank  Cyriaque Beley  ( Inserm U974, Paris, France ) for supplying the pAAV-U7 plasmid, as well as  June Uebeler  ( UKE-Pharmacology, Hamburg, Germany ) for technical help.
Total and active forms of MMP-2 and MMP-9 were calculated using standards provided by the kit and expressed as ng/mL. The amount of total protein in the culture supernatants was measured using the Bio-Rad protein assay (Bio-Rad). Data for total and active MMP-2 and MMP-9 in the culture media were normalized against the total protein content of the culture supernatants. The detection limits of the assay are 0. 19-12 ng/mL for MMP-2 and 0. 125-16 ng/mL for MMP-9. All experiments were performed in duplicate.
Acknowledgments We are most grateful to all of the patients who participated in the present study. We thank  Professors Jean-Luc Pouly  and  Michel Canis , and  Doctor Revaz Botchorishvili  ( Department of Gynecology, CHU Estaing, CHU Clermont-Ferrand ) who allowed us to collect samples. We thank  Ms. Chrsitelle Picard  for excellent technical assistance. We also thank the staff at the  Department of Gynecology  and operating room,  CHU Estaing, CHU Clermont-Ferrand. We are also indebted to the staff in the  Department of Pathology, CHU Estaing, CHU Clermont-Ferrand. Disclaimer Presented in part at the 28 th Annual Meeting of the  European Society of Human Reproduction and Embryology, Istanbul, Turkey , July 1 to 4, 2012, and at the 68 th Annual Meeting of the  American Society for Reproductive Medicine ,  San Diego CA ,  October 20  to 24, 2012.
 Competitive environment In this section we will review drugs potentially useful for the treatment of autonomic dysfunction in PD. Full searches were conducted in Pubmed, Clinicaltrials. gov and Movement Disorders Society International congress from 2002 up to 2012. We focused on drugs with insufficiently documented efficacy or for which there are clinical trials either planned or ongoing. Inefficacious or unsafe drugs will be briefly mentioned. Results are summarized in Table  2.
Behavioral therapy The intervention consisted in training patients to control their pelvic muscles  [82]. Computer-assisted anorectal (or vaginal) dual-channel EMG biofeedback was used to help participants identify pelvic floor muscles and teach them to contract and relax these muscles in isolation while keeping rectus abdominis muscles relaxed. Participants were given guidance regarding fluid management (decrease caffeine, A randomized, blinded study including 60 patients is underway to further test the efficacy and safety of the intervention (NCT01520948).
 Solifenacin succinate Solifenacin is a M3 muscarinic receptor antagonist which has shown efficacy for the treatment of overactive bladder in the general population  [83]. A randomized, double-blind, placebo-controlled clinical trial in a reduced number of PD patients testing the efficacy and safety of solifenacin succinate up to 10 mg/day is underway (NCT01018264).
Fipamezole (JP-1730) is a potent alpha2-adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease. [68]. The acute hemodynamic effects of fipamezole were evaluated in a double blind placebo controlled study in 21 PD patients [70]. Blood pressure was evaluated during an acute intravenous levodopa challenge. Continuous levodopa treatment significantly decreased mean blood pressure (P<0. 01). Compared to placebo, fipamezole returned blood pressure to preinfusion values in a dose-dependent fashion (p<0. 01). A clinical trial is underway to confirm these results (NCT00758849).  Partial weight supported treadmill gait training Partial weight supported treadmill gait training is sometimes used in rehabilitation in PD. Its cardiovascular effects have been recently evaluated in a controlled openlabel study [71].
Photobleaching events were minimized with a FluoArc system and an ND75 filter (Carl Zeiss), which reduce the excitation light of a 100-watt mercury lamp. FAs located at the leading edge were selectively chosen, and their turnover was quantified using Metamorph software (Molecular Devices, Sunnyvale, CA) as described previously  (20). Briefly, mature FAs were manually outlined as well as their surrounding cytoplasmic area, and adhesions were manually tracked from their nucleation to their disassembly. The mean fluorescence intensity in the adhesion area was subtracted from the cytoplasmic background value. From these data, a shaped bell curve denoting FA turnover was obtained, allowing the measurements of FA assembly and disassembly rates as well as FA lifetime. Image Analysis-Cells were imaged on a nonlinear optics LSM510 inverted confocal and biphoton laser-scanning microscope equipped with a ϫ63, numerical aperture 1.
A dose-escalation phase I clinical trial (NCT01239134) with agonist anti-GITR mAb (TRX518) was recently initiated. Third possibility is to repress the activity of enzymes (IDO, ARG-1, iNOS) that were shown to inhibit the immune response. Data from first clinical trials using IDO inhibitors, notably the isomers of 1-methyl-tryptophan (1MT), were disappointing, but these studies may suffer from lack of potent and selective IDO inhibitors. New compounds recently entered clinical trials  [167]. A phase II study of IDO inhibitor INCB024360 is currently recruiting patients with biochemical-recurrent-only EOC following complete remission with first-line chemotherapy (clinical trial: NCT01685255). In addition, inhibitors of phosphodiesterase(PDE)-5, e. g. sildenafil, were reported to increase intracellular concentrations of cGPM, resulting in the inhibition of both ARG-1 and iNOS.
For imaging experiments, culture medium was substituted by extracellular saline (10 23 mol/ liter: NaCl, 137; KCl, 4; CaCl 2 , 1. 8; MgCl 2 , 1; glucose, 10; HEPES, 10; pH 7. 4). Cells were treated or not with 10 28 M aldosterone, 10 26 M torasemide (Sigma, St. Louis, MO) and 10 26 M spironolactone (Sigma, St. Louis, MO) and images were acquired every 2 minutes (min) for one hour. Total and nuclear fluorescence intensity was analyzed frame by frame in individual cells using the manufacturers software (Olympus). Data processing and curve fitting were performed using Igor Pro (Wavemetrics, Lake Oswego, OR).
This work was supported by grants from  INSERM (Institut National pour la Santeet Recherche Medicale) , a  CEVA company research grant , the  ''Centre de Recherche Industrielle et Technique''  and the  Ministerio de Economı ´a y Competitividad (Spain) , grant  BFU2010-16265  to D. A. R. B. G. and A. T. were recipients of PhD grant from the  French Ministry of Research. R. J. - C. is supported by a predoctoral fellowship from  Cajacanarias (Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. As mentioned in the funding sources, this work was partly supported by a grant from the  CEVA company.