dataesr/scientific-paragraphs-categorization huggingface dataset:
RNA extraction and reverse transcriptase quantitative PCR Cells were lysed in Trizol reagent (Invitrogen) and total RNA was purified using QIAmp Mini Spin columns (Qiagen) following manufacturer's recommendations. Complementary DNAs were prepared from total RNA using the Maxima First Strand cDNA Synthesis kit for reverse transcription quantitative polymerase chain reaction (RT-qPCR) (ThermoScientific). Quantitative PCR was performed using the LightCycler 480 SyberGreen I Master kit (Roche) and the LightCycler 480 System (Roche). Three reference genes (β2 microglobulin, ubc and β-actin) were used for data normalization. The following primers were used: Pim2 (forward 5 -GCCTCACAGATCGACTCCAG-3 , reverse 5 -CTGAGTCTGACAAGGGGGAC-3 ); ubc (forward 5 -ATTTGGGTCGCAGTTCTTG-3 , reverse 5 -TGCCTTGA-CATTCTCGATGGT-3 ), β-actin (forward 5 -TCCCTGGA-GAAGAGCTACG-3 , reverse 5 -AGCACTGTGTTGGCGTA-CAG-3 ), β2m (forward 5 -CCACTGAAAAAGATGAGT-ATGCCT-3 , reverse 5 -CAAACCTCCATGATGCTGAT-TACA-3 ).
Interestingly, the first 30 amino acids of Pim2 corresponding to the region before the kinase domain appear to be unstructured in Pim2 isoform 3  [9]. Analysing isoforms 1 and 2 that have not been crystallized and possess longer N-terminal parts using the PSIPRED v3. 3 / DISOPREP2 software (http://bioinf. cs. ucl. ac. uk/psipred/) shows that these extended domains are completely disordered (Supplementary Figure  S2 ). Moreover, this analysis suggests that the C-terminal part of the molecule could also be disordered although to a lesser extent. Thus, we suggest that the disordered N-terminus domains of Pim2 isoforms are directly recognized by the proteasome although with different efficiencies that could account for the differences of stability among the three isoforms. To sustain this hypothesis, we incubated partially purified Pim2 molecules with purified 20S proteasome.
An attractive hypothesis would be that these terminal domains contribute to direct proteasome targeting while providing means to specifically control the stability of each Pim kinase through association with different partners. Pim2 is an important pro-survival mediator in myeloma cells, at least in part by its contribution to mTORC1 activation  [5, 7]. Accordingly, several Pim inhibitor molecules such as AZD 1208 or PIM447 (formerly LGH447) are currently tested in phase 1 clinical trials for multiple myeloma therapy (https://clinicaltrials. gov). Bortezomib (Velcade) and other proteasome inhibitors inhibit the growth of myeloma cells and induce their apoptosis  [49]. These drugs are commonly used for myeloma therapy  [50, 51] , although most patients relapse. Drug combinations targeting different pathways important for myeloma cell survival are currently tested  [52].
Viability assay Viability experiments were performed in 384-well format in seven replicates per dose using the Promega Cell-Titer Glo ATP-based assay per the manufacturer's instructions. Leukemia cell line viability was evaluated at day 6 post-treatment with PRT062607 and BAY61-3606 in a two-fold dilution to establish the drug concentrations that reduced cell viability to 50 percent of the vehicle controls (IC50). Values for IC50 were calculated by interpolating a natural cubic spline fit to the measured viability data in R (using the spline function).
Staining was conducted with 1:100 anti-pY323 SYK (Epitomics, Inc. , EP574-3; now Abcam, Ab62338, Cambridge, MA, USA) for 1 hour, followed by washing and staining with rabbit ENVISION (DAKO) and diaminobenzidine (DAB) chromogen kit (DAKO) as per the manufacturer's instructions. As shown in Supplemental Figure  1  for 6 representative patient samples, immunohistochemical staining for P-SYK was reproducible across duplicate staining runs. Slides were counterstained with Harris haematoxylin (Polyscientific, Bay Shore, NY, USA). Micrographs were imaged using a Nikon Eclipse 80i microscope, with a Nikon Plan Apo 40_/0. 95 air objective and captured using a Nikon DS-F digital camera with NISElements D 3. 1 software, with manipulation in CorelDRAWX3.
P-SYK Y323 measurement P-SYK Y323 protein expression, assayed by Envision+ disclosed immunopositivity, was measured automatically using an Aperio Scan Scope XT workstation, with ImageScope software (Vista, CA, USA). The Aperio Color Deconvolution v9 algorithm, which measures the optical density per unit area, was used to measure total cellular P-SYK staining, after potential areas of staining artefact such as bone fragments, tissue wrinkles/folding and background debris were excluded from the analysis. P-SYK staining was specific to blasts. Because there is no universal AML blast marker consistently expressed across AML subtypes, dual staining to identify blasts was not possible. Instead, blasts were identified morphologically by pathological examination of the analyzed images. Measurements were performed using the Aperio Image Analysis system.
Micrographs were imaged using a Nikon Eclipse 80i microscope, with a Nikon Plan Apo 40_/0. 95 air objective and captured using a Nikon DS-F digital camera with NISElements D 3. 1 software, with manipulation in CorelDRAWX3. Aperio determines the percentage of positive (brown) staining within the area with haematoxylin-stained tissue and segregates it into 0, 1+, 2+, 3+ based on optical density thresholds for intensity of staining (representative images at each intensity are shown in Supplemental Figure  2A , and 2C respectively, together with total SYK staining in Supplemental Figure  2D. Total, weak (1+), medium (2+) and strong (3+) staining percentage values for each individual case are shown in Supplemental Table  1. Additionally, an H-score (0-300) was calculated from these percentages using the formula H = (3× percentage positivity at 3+) + (2× percentage positivity at 2+) + (1× percentage positivity at 1+), together with a modified H-score in which 1+ staining was aggregated with negative staining, using the formula Mod-H = (3× percentage positivity at 3+) + (2× percentage positivity at 2+) + (0× percentage positivity at 1+) (Supplemental Table  1 ).
ACKNOWLEDGMENTS All authors contributed to research design, or acquisition, analysis and interpretation of data. All authors contributed to drafting and editing the manuscript and all approved the final version submitted. Specifically: KB and AP designed and performed the research, collected, analyzed and interpreted the data and wrote the manuscript; MB performed the research and collected data; GA, CFB and PS undertook laboratory experiments, collected, analyzed and interpreted the data; ET provided clinical liaison and constructed the tissue microarray and its clinical annotation; KS, RJB, and SR designed the research, analyzed and interpreted all data and wrote the manuscript.
Data Collection The following data were collected from the (1) the upper limb from the shoulder joint to hand, (2) ribs and/or spine, (3) pelvis, including the sacrum and tumors in both the pelvis and hip, and (4) lower limb from the hip joint to foot, including tumors in both the leg and hip. The oncologic grade of the tumors was subdivided into 1, 2 or 3 (French FNCLCC grading system) for STTs and a low or high grade (Enneking grading system) for BTs. Antibiotic therapy given for postoperative surgical site infections was subdivided in  (1)  monotherapy for each bacterial isolate, ( combination therapy for all isolated bacteria, (3) the antibiotic spectrum not covering all infectious bacteria, (4) probabilistic antibiotic therapy with negative microbiological cultures or (5) no antibiotic therapy.
ACKNOWLEDGMENTS No funding or sponsorship was received for this study or publication of this article. Part of this data was presented as an abstract at the 54th  Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) , September 2014, Washington, DC,  USA. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole and have given final approval for the version to be published.
To test whether RCCs similarly to UCP-3 upregulate other mitochondrial uncoupling proteins, UCP-1 and UCP-2 protein abundance was determined by immunoblotting in the RCC resection material (Suppl Fig. IIA ). The results suggested downregulation of UCP-1 by all and upregulation of UCP-2 by some of the tested RCCs. In addition, the ccRCC database of The Cancer Genome Atlas (TCGA) was queried for UCP-1, -2, and 3 mRNA expression of the tumor and survival of the ccRCC patients (Suppl. Fig. IIB, C ). The TCGA data suggest co-occurrence of high abundant UCP-2 and UCP3 mRNA in the ccRCC specimens (data not shown) as well as shorter survival of ccRCC patients with high UCP-2 or UCP-3 mRNA abundance in the tumors as compared to the patients with "middle-rate" UCP expressions (Suppl. Fig. IIB, C ). High abundance of UCP-1 mRNA, by contrast, was not associated with altered survival of the ccRCC patients.
Since subgroup analysis concerning tumor staging, treatment regimes, etc. could not be performed, the conclusions drawn from the TCGA data is constrained. Nevertheless, the observed associations might point to a prognostic value of the UCP-3 or UCP-2 expression by the ccRCC. In addition, the data might hint to a functional redundancy of UCP-2 and UCP-3. H/R-adapted cultures exhibit higher resistance against ionizing radiation. Finally, we tested the possibility whether adaptation to H/R is accompanied by increased resistance against anti-cancer therapies such as radiation therapy. To this end, control and H/R-adapted cultures were irradiated under normoxia with a single dose of 0, 5, or 10 Gy, and subG 1 population was recorded by flow cytometry (DNA staining of propidium iodide-permeabilized cells applying the Nicoletti protocol) as a measure of cell death 24 h and 48 h thereafter.
4). In the present study, some RCC specimens exhibited elevated UCP-2 protein amounts as compared to normal renal tissue. UCP-1 protein, in sharp contrast, was downregulated in the RCCs. UCP-2 might exert a function in RCC similar to that proposed for UCP-3. This might be deduced from the TCGA database query of the present study which suggested that-likewise UCP-3-high RCC UCP-2 expression might be associated with bad prognosis. In the present study, adaptation to H/R was accompanied by partial radioresistance. Knockdown of UCP-3 did, however, only slightly increase radiation-induced cell death of the H/R-adapted PT cultures. Upon UCP-3 knockdown the radiation-induced cell death of the control cultures was still much higher than in the selected cultures (see Fig. 7E ) suggesting that radioresistance in the H/R-adapted PT cultures was substantially mediated by upregulation of DNA-repair and other oxidative defense mechanisms (see Suppl.
Transfection efficiency and viability was determined by transfecting the cells with 400 nM green fluorescence siGLO siRNA (ThermoScientific Dharmacon) followed by propidium iodide exclusion dye and flow cytometric analysis (data not shown). Immediately after transfection, cells were cultured either under normal conditions or hypoxic (48 h)/reoxygenation (24 h). Downregulation of UCP-3 was controlled by immunoblotting. Immunoblotting. Following normoxia or hypoxia (48 h)/reoxygenation (24 h) H/R-adapted and control PT cultures as well as frehly frozen specimens from dissected human renal cell carcinoma with adjacent normal renal tissue. Patients gave informed consent and the experiments were approved by the ethical committee of the Faculty of Medicine, University of Tübingen (Ethik-Kommission der Medizinischen Fakultät und am Universitätsklinikum Tübingen, Gartenstrasse 47, 72074 Tübingen, Germany) and carried out in accordance with the approved guidelines.
Antibody binding was detected with a horseradish peroxidase-linked goat anti-rabbit or horse anti-mouse IgG antibody (Cell Signaling #7074 and #7076, New England Biolabs GmbH, Frankfurt am Main, Germany, 1:1000 and 1:2000 dilution in TBS-Tween/5% milk, respectively) incubated for 1 h at room temperature and enhanced chemoluminescence (ECL Western blotting analysis system, GE Healthcare/Amersham-Biosciences, Freiburg, Germany). Where indicated protein levels were quantified by densitometry using ImageJ software (ImageJ 1. 40 g NIH, USA). UCP-3 expression of the tumor samples were categorized using an arbitrary score from 0 (not expressed, see Fig. 6B , 1 st lane) to 4 (highest expression, see Fig. 6B , 8 th lane).
Acknowledgements This work was supported by grants from the  Wilhelm-Sander-Stiftung  awarded to SH ( 2011. 083. 1 ) and from the  Deutsche Krebshilfe  awarded to MB ( D30. 11089 ). We thank  Ilka Müller  and  Heidrun Faltin  for excellent technical assistance. D. K. was supported by the  DFG International Graduate School 1302  ( TP T9 SH ).
Study population 9] [20]  As patients are subjected to the routine assays performed during the 3 week they spent at the Clinique du Château de Vernhes (i. e. anthropometry and body composition, lipid-lipoprotein, and haemodynamic measures), they only gave their written informed consent to the use of data collected. Thus, because of this specific design, this study could not be defined as a clinical trial per se but as a retrospective one. None of the women had identified disease (e. g. cardiomyopathy; endocrine disorders, which may cause irregular menstrual cycles; or orthopaedic limitations that could affect physical activity). Women on medication that could influence outcome-mainly β-blockers, sympathomimetic drugs, cholesterol-lowering drugs (including statins), antihypertensive drugs, and thyroxin, for which a dosage change occurred during the previous 6 months or was expected during the course of the institutionalized weightreducing programme-were excluded from this observational and retrospective study.
Statistical analysis Data are expressed as the mean ± SD. A non-paired Student's t-test was used for the comparison between groups (N-SO vs. SO), at baseline and at the end of the 3 week programme. An analysis of variance (ANOVA) with repeated measures was used to detect changes in response to the treatment condition (pre-vs. post-weight reducing programme) and between groups. Analyses were performed using SPSS 17. 0 (Chicago, IL). A p value of less than 0. 05 was considered significant.
Acknowledgements Thanks are expressed to all staff members of the  Clinique du Château de Vernhes, Bondigoux (France)  and to his owner and director,  Dr F. Sanguignol , who allowed us to use the data collected during the short weight-reducing programme routinely performed in his specialized medical institution. The cooperation of patients was greatly appreciated. This observational and retrospective study was supported by the  Conseil Régional Midi-Pyrénées. Mylène Aubertin-Leheudre  is supported by  FRQS  and  Sébastien Barbat-Artigas  is supported by  CIHR. The authors of this manuscript certify that they comply with the ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia, and Muscle 2010;1:7-8 (von Haehling S,  Morley JE ,  Coats AJ , and  Anker SD ).
It is derived from NEUT-Y on XE instruments and few data are available relating the value of this parameter to infection disease/sepsis management  [4, 5]. NEUT-WY represents the width of the neutrophil scattergram in the WDF channel on the fluorescence axis. This parameter is calculated according to distribution width as it represents the range of the distribution in fluorescence of the major population, excluding outliers below 20% peak height in the distribution curve. It is then representative of heterogeneous fluorescence signal in this population related to either band cells or activated neutrophils. First, we studied a large group of patients to determine the normal ranges of these new structural parameters. Then, we analysed the potential contribution of these parameters on interpreting IG count in blood samples collected from patients without any haematological disease.
Treatment planning using RapidArc® A maximum dose rate of 600 MU/min and 6 MV photon beams were used. The optimization process started with the constraints obtained with the IMRT plans. RapidArc® (RA, Eclipse software version 10. 0. 28, Helios, Varian, Palo Alto, CA) was delivered with two partial coplanar arcs (less than 240°of rotation) sharing the same isocenter and optimized independently and simultaneously. These two arcs were delivered with opposite rotations (clockwise and counterclockwise) so that the off-treatment time between the two beams was minimized to about 25 s. The field size and collimator rotation were determined using the automatic tool from Eclipse software to encompass the PTV. The first clockwise arc used a 45°collimator rotation in order to avoid the tongue-and-groove effect.
Acknowledgements We thank  Dr Julie Courraud  for her editorial assistance. Author details 1  Radiation Oncology Department, Institut régional du Cancer de Montpellier (ICM) ,  Val d'Aurelle, 208 avenue des Apothicaires ,  34298 , Montpellier cedex 5, France. 2  Radiotherapy Department, Mulhouse Hospital, Mulhouse, France.
Statistical analysis Prism version 6. 0 (GraphPad, San Diego, CA) and JMP v11. 0. 0 (SAS, Grégy-sur-Yerres, France) were used for statistical analysis. Unless otherwise indicated, data are expressed as the mean ±SEM. Normality was assessed by d'Agostino-Pearson omnibus test. Comparisons between fatty acid profiles were assessed by multiple unpaired two tailed t-test, with false discovery rate set to 10%. Differences in fatty acid ratios between groups were analyzed by one-way ANOVA followed by Fisher's least significant difference test, or by Kruskal-Wallis test followed by Dunn's multiple comparisons test. Receiver-operator characteristic (ROC) curves were used to study sensitivity and specificity of SCD indices when discriminating between ALS patients and controls. Non-parametric Mann-Withney test was used to assess differences in circulating biochemical parameters.
This work was supported by funds from  Thierry Latran Foundation ,  European Community 's  Health Seventh Framework Programme  under grant agreement No. 259867  ( Euro-MOTOR ), " Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres Maladies du Motoneurone" (ARSLA) , " André combat la SLA " and " Association pour la Recherche et le Développement de Moyens de Lutte contre les Maladies Neurodégénératives" (AREMANE). The funders had no role in study patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs. design, data collection and analysis, decision to publish, or preparation of the manuscript.
Data analysis Data were analyzed using IBM SPSS Statistics Version 21. 0 (IBM Corp, Armonk, NY) and Matlab 7. 10 (Matworks, Natwick, MA). To assess the habituation effect in the baseline condition we performed a regression (B = angular coefficient) using the subjective NRS ratings (pain/distress) as dependent variable and time as independent variable, pooling the data from all subjects. To verify whether TMS stimulation affected the habituation, we first performed a preliminary 2 (time: first and last timepoint) x 6 (location: baseline, AFz, Fz, FCz, Cz, CPz) repeated measure ANOVA. The interaction time by location, if significant, was further explored by means of regression analysis for each location individually. To assess the immediate effect of TMS on pain and distress, we computed for each session a paired sample Wilcoxon test, comparing the scores gathered before (t = 3 min) and just after (t = 7 min) stimulation.
ALE meta-analysis The ALE (Activation Likelihood Estimation) analysis is a quantitative meta-analytic method that can be used to estimate consistent activation across different imaging studies  [24]. ALE maps of co-activations are derived based on patterns of foci of interest where multiple studies have reported statistically significant peak activation. Furthermore, it comprises a method to calculate the above chance clustering between experiments (i. e. , random effects analysis) rather than between foci (fixed effects analysis). To obtain a list of neuroimaging papers that investigated pain rating as a variable, we sent a query to the BrainMap database using Sleuth 2. 2  [25]. The exact query was: ½Subjects½Diagnosis ¼ NormalsAND½Conditions½External Variable ¼ Pain Rating ð1Þ The results of the query were 28 papers (fMRI, PET), 440 subjects, 130 experiments, 1397 foci.
Regarding the fact that prospective randomized trials were not able to demonstrate different outcomes following the use of either perfusion solution, the main reason for that is in our view, the underpower of most studies regarding their primary end point. In the recent review and meta-analysis by O'Callaghan et al  (2)  of 16 randomized control trials, no study arm exceeded 148 grafts. Accordingly, the limited number of patients included was unlikely able to demonstrate any influence of a single factor such as the type of preservation solution among the multiple factors affecting the outcome of LT. Registry data are subject to selection bias but, conversely, include a very large number of patients, and that allows demonstration of such an effect, after careful correction for confounders. Moreover, it is not an effect of hazard that, for example, only two databases as large as those of the United Network for Organ Sharing (17 428 grafts from 2004 to 2008) and the European Liver Transplant Registry (42 869 grafts, from 2003 to 2012) were able to converge on the deleterious effect of histidinetryptophan-ketoglutarate (HTK) solution compared with other solutions.
(2009)  investigated interhemispheric and intrahemispheric reorganization in epilepsy patients using the data-driven method allowing to assess interindividual variability. These authors used fMRI to collect data from 45 patients with TLE during performance of an auditory task; several interhemispheric and intrahemispheric patterns of organization were observed; temporal regions showed an intrahemispheric organization, particularly in the postero-superior temporal sulcus (MNI coordinates, 52, 72, 10) adjacent to classical temporal language areas. Interestingly, it was the youngest patients and patients with the shortest duration of epilepsy who showed an intrahemispheric pattern. These results suggest that several factors may affect the emergence of a specific compensatory pattern. Clearly, the atypical representation of language occurs more frequently in epilepsy patients than in healthy subjects  (Rasmussen and Milner, 1977; Adcock et al.
Possible models of language reorganization All previously mentioned factors make a complex contribution to cerebral organization of language. Crucially, Two separate random-effect group analyses with the contrast images (lexico-semantic vs. control; phonology vs. control) from the individual analyses by using one-sample t test were performed. Subsequently, predefined masks from the WFU PickAtlas allowed us to define two symmetrical (left and right) ROIs: IFG and STG. By comparing with healthy controls, our results suggest that patients with left EZ showed stronger recruitment of right STG; this involvement was stronger for phonological task than for lexico-semantic task. Similarly, patients with right EZ showed stronger bilateral involvement of STG region in both phonological and lexico-semantic tasks.