dataesr/scientific-paragraphs-categorization huggingface dataset:
Generation of P. berghei transgenic line PbBCKDH-E1a sequence was retrieved from the online Plasmodium genome database, (PBANKA_141110, www. plasmodb. org). To generate the PbBCKDH-E1a knockout (Pbe1a_ko), primers 3835 and 2482 were used to amplify a 2 kb region of homology at the 5'end of the PbBCKDH-E1a locus (Table  S2 ). The PCR fragment was cloned between KpnI and ApaI restriction sites of the pBS-DHFR vector containing the T. gondii dhfr conferring pyrimethamine resistance  [60]. The 3' flanking region 2 kb was amplified using primers 3836 and 2483 and cloned between EcoRV and BamHI restriction sites of pBS-DHFR. The final construct was linearized with NotI prior to transfection. Complementation of Pbe1a_ko by P. falciparum BCKDH-E1a was performed using a knock-in strategy in the promoter region of PbBCKDH-E1a still present in Pbe1a_ko parasites.
Parasites were harvested after 4 h and metabolites extracted as above. Changes in the mass isotopologue abundances of key intermediates in central carbon metabolism were assessed by GC-MS or LC-MS analysis. The level of labelling of individual metabolites was calculated as the percent of the metabolite pool containing one or more 13 C atoms after correction for natural abundance and amount of 13 C-carbon source compared to 12 Ccarbon source in the culture medium (as determined by GC-MS analysis). The mass isotopologue distributions (MIDs) of individual metabolites were corrected for the occurrence of natural isotopes in both the metabolite and, in GC-MS experiments, the derivatisation reagent  [69]. An untargeted metabolome-wide isotope analysis was performed on high resolution LC-MS data to detect all labelled metabolic products of 13 C-U-glucose or 13 C-U-leucine/ 13 C-U-isoleucine/ 13 C-U-valine according to the method previously described  [70].
Following 24 h of growth in glucose-depleted environment, glucose was added back to the media and rescue of the parasite's growth was assessed. Data are represented as means 6 SD from three independent biological replicates. (E) The apicoplast targeting sequence of TgPDH-E1a (aa 1-225, ABE76506) and mitochondrial targeting sequence of TgBCKDH-E1a (aa 1-73, XP_002366588) were replaced with the mitochondrial transit peptide of the superoxide dismutase 3 (SOD3) and myc-tagged [71]  to direct the expression of the fusion protein in the mitochondrion of Tge1a_ko parasites for complementation (creating pTub8-SOD3mycPDHE1a and pTub8-SOD3mycBCKDHE1a respectively). Immunofluorescence assay shows localization of SOD3mycPDHE1a and SOD3mycBCKDHE1a in the single tubular mitochondrion (anti-myc (in green), anti-GAP45 (pellicle marker in red)).
The project was supported by the  Swiss National Foundation  ( FN3100A0-116722 ), the  Swiss SystemsX. chinitiative, grant  LipidX-2008/011  and is part of the activities of the  BioMalPar and EVIMalaR European Networks of Excellence  ( LSHP-CT-2004-503578  and No. 242095 ). Work at the Sanger Institute was funded by a  Wellcome Trust  grant ( 098051 ) and by the  Medical Research Council  ( G0501670 ). DSF is an  International Scholar  of the  Howard Hughes Medical Institute. MJM is a  NH&MRC Principal Research Fellow. DJC is a  NHMRC Biomedical Training Fellow. RDO is supported by the  iGE3 program  from the  University of Geneva  and by the  Ozmalnet Travel Award from Evimalar. The authors declare that they have no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
1B ). The observation was reversible by complementation with a plasmid expressing tolC pACYC184-tolC which reduced the fluorescence to the level of the tolC+ strain (Fig. S1 ). To determine whether the observed fluorescence corresponded to increased accumulation of PPIX, we examined cells by fluorescence HPLC. Cells were grown in LB broth to OD 600 of 1 in the presence of arabinose to induce yfeX overexpression. Cells were collected by centrifugation and porphyrins were extracted from soluble fractions by solvent treatment. Figure  1C  shows that both strains tolC+ (pBAD24-yfeX) and tolC (pBAD24-yfeX) contained PPIX. However, the tolC mutant accumulated 9 times more PPIX than the corresponding tolC+ strain. In the absence of yfeX induction, the COPI, COPIII, and PPIX levels were also higher in the tolC mutant than in the tolC+ strain (data not shown).
We next introduced pBAD24-yfeX into acrAB mutant, also expressing the various pumps. Upon arabinose induction, all strains were fluorescent (data not shown). YfeX production was determined by western blot and showed similar levels of the protein in the various strains (data not shown). YfeX-driven PPIX overproduction failed to change the ERY MIC values of acrAB strain carrying acrAB, mdtEF, acrEF, and emrAB on pBAD33 (Table  2 ). In contrast, PPIX production reduced the ERY MIC value of acrAB (macAB) to the level of the acrAB mutant (Table  2 ). Excessive PPIX production also reduced the MIC of other tested antibiotics (azythromycin, NOV, and deoxycholate) expelled by the MacAB-TolC pump (Fig. S2 ). Since MacAB is the only pump strongly inhibited by PPIX overproduction, it is unlikely that PPIX inhibits physiological function required for drug efflux.
All strains were grown in LB medium + 0. 2% arabinose to induce the efflux pump genes on pBAD33 and yfeX on pBAD24. Strains with YfeX overproduction (+YfeX) carry pBAD24-yfeX. Strains without YfeX (ÀYfeX) carry pBAD24 without insert. Strains without Yfex carrying pBAD24 without insert were also grown in LB + 0. 2% arabinose with or without 5-ALA to overproduce COPIII. MIC was determined as described in Experimental Procedures. pump (data not shown). We also tested the effect of COPIII overproduction on MacAB-TolC macrolide efflux capacities. Strain acrAB (pBAD33-macAB) was grown in the presence of 10 lg mL À1 5-ALA plus or minus arabinose to induce the MacAB pump. Unlike PPIX accumulation, 5-ALA driven COPIII accumulation did not change the macrolide MIC (Table  2 ).
Wild type and mutant cells did not show any CFU decrease when incubated in dark during the 2 h experiments. Survival was measured at time point 0; 5 and 10 J/cm 2. All experiments were done five times with standard deviations of 10% of the values indicated in the table. It is the maximal observed standard deviation. Cells were grown overnight in LB medium in the dark and 100-fold-diluted in the morning and kept in the dark. When they reached an OD 600 of 0. 5, Dip was added at the final concentration of 100 lmol/L. Cells were harvested still in the dark, when growth stopped and bacterial cultures were diluted in PBS for the same OD 600. This is time 0 of the experiments. measured as the % of bacterial viable cells (CFU) after light irradiation compared to the CFU in dark. No toxicity was observed in the dark (data not shown) or in the absence of arabinose (Table  3 ).
Laboratory assessments Plasma (EDTA) samples were collected from ALS subjects prior to collection of open muscle biopsy samples and aliquots dispensed and frozen at -80°C. Frozen samples were shipped to The Doctors Laboratory (TDL) and an exploratory analysis performed for lactate dehydrogenase (LDHI2), creatinine (CREJ2) and creatine kinase (CK) using the Roche Cobas system. Note that sample stability data was not available to cover the storage time (>1 year) or conditions (-80°C) for these samples. Non parametric Mann Whitney test was carried out to find the correlation between increased CK levels and muscle fibre necrosis and inflammation.
Acknowledgements The authors thank  Mrs Mary Davitt  for her efforts to prepare the manuscript and  Dr Istvan Bodi  for his technical help to produce the photographs. We are grateful for all the  ALS centres at, The Neurosciences clinical centre, Pitie-Salpetriere, Paris ,  The John Hopkins medical school, Baltimore, USA  and the  Neuroscience centre at Institute of Psychiatry, Psychology and Neurosciences ( IOPNN) at Kings College London, UK  for recruiting the patients for this study.
Circular Dichroism (CD) CD experiments were performed to obtain information on the DNA strands orientation. Experiments were run on a Jasco J-815 spectrophotometer using a quartz cell of 2 mm path length. All spectra shown here are the sum of three scans, acquired at 20°C with a scan speed of 50 nm/min and a 2 nm bandwidth. The CD data were normalized to molar circular-dichroic absorption (Δε) based on DNA concentration using the following Equation, Δε ¼ θ 32980 Â c Â l ð1Þ where θ is the CD ellipticity in milidegrees, c is DNA concentration in mol L -1 (5×10 -6 mol. L -1 ), and l is the pathlength in cm (0. 2 cm).
Acknowledgments The authors thank  Frédéric Rosu  and  Miguel Garavis  for fruitful discussion, the  Structural Biophysico-chemistry Platform of the IECB (CNRS UMS   3033  and  Inserm   US 001 ) for access to the MS instruments,  Kevin Giles  and  Jonathan Williams  ( Waters, Manchester, UK ) for assistance in performing the IMS experiments on the Synapt  G2S , and  Christian Bleiholder  and  Mike Bowers  ( UC Santa Barbara ) the opportunity to measure the drift tube CCS of the new calibrants. This work was funded by the  Inserm (ATIP-Avenir) , the  EU (Marie Curie CIG) , and the  Conseil Régional Aquitaine  (Crédits d'installation). A. M. has a Ph. D. fellowship from  Inserm  and  Conseil Régional Aquitaine.
Acknowledgments This work is supported by  Agence Nationale de la Recherche  ( OSMOTUS ANR-2011 -BS0301001 ). We thank our colleagues,  Loïc Morvan  and  Daniel Dolfi , from  THALES Research and Technology  for providing the active gain medium and  Grégoire Pillet ,  Antoine Rolland ,  Steve Bouhier  and  Anthony Carré  for fruitful discussion.
2) Data collection The method used for collecting data relies on interviews and document studies. Semi-structured and in-depth interviews were conducted with the main actors. In total, 18 interviews were made. The interviewees were asked to describe the way they coped with the uncertainties and the tools they used. (3) Data analysis Data analysis was in two steps. Firstly initial uncertainties in each project were assessed from the point of view of sources and types of uncertainty. The end result is given: (i) Projects 2, 3 and 4 suffered unforeseen technological uncertainty. In terms of market, the three projects supported foreseen market uncertainty. (ii) Project 1 mainly dealt with unforeseen market uncertainty. (iii) Project 5 had to deal with unforeseen technological uncertainty and market uncertainty.
In a Phase II study (VITAL), 346 GT-2 and GT-3 naïve patients are randomized in five groups with different doses of ALV only or in combination with RBV with or without PEG-INF. In the three IFN-free arms, 22%, 23%, and 34% of the patients reach RVR and are therefore maintained on the IFN-free regimen until week 24. Twelve weeks after cessation of treatment, the SVR rates range from 82% to 93% (see Future GT-2 treatment). As for GT-2 patients, this data suggests that the majority of GT-3 patients may soon be cured with a short course of DAA combination with or without RBV. However, for some patients, combination therapy with PEG-INF and RBV is still required.
1 MJ/Nm 3 ) 0. 5 of n-heptane, aromatic malthenes -to aromatic hydrocarbon solvents (18. 15 MJ/m 3 ) 0,5 of toluene. Therefore, when polymers are selected for making the bitumen-polymer compounds one may take into account in the first approximation the solubility data of a particular polymer as the basis in the hydrocarbon solvent or by oil swell. Thus, the bitumen compatibility with TPR was determined using toluene simulating the malthenes portion of bitumen.
MAIN PART In our work, the solubility parameter value was determined to assess the bitumen compatibility with mixed thermoplastic rubber. 10% solutions of thermoplastic rubber were prepared in hydrocarbon solvents. The time of a homogeneous solution formation was determined at the temperature of 25 °C. TPR dissolution (in corresponding solvent) period was used as a benchmark parameter. The data obtained are shown in Fig. (1) , which demonstrate that the curves have a pronounced minimum at δ = 16,5 (MJ/m 3 ) 0. 5.
For superstrings, the reconnection probability can be less than unity (10 -4 < p < 1  [23] ) while field theory simulations show that topological strings will essentially always reconnect. This is partly due to the fact that fundamental strings interact probabilistically. Furthermore, superstring models have extra spatial dimensions so that even though two strings may meet in three dimensions, they miss each other in the extra dimensions. When a string intercommutes with itself, a closed loop breaks off. The loop oscillates, radiates gravitationally, and decays. Cosmic string loops can form cusps, points along the string with large Lorentz boosts, that produce powerful bursts of gravitational radiation  [24]. This Letter reports on the search for such GW transient signatures from cosmic strings in data from the LIGO and Virgo gravitational wave detectors.
GW bursts from cosmic string cusps. This Letter presents a different approach to constrain cosmic string parameters, with a targeted search for transient cusp signatures in LIGO and Virgo data. This approach was previously tested in Ref. [32]  over a short period of about 2 weeks of live time with detectors less sensitive by about a factor of 2. For this work we have analyzed all available LIGO and Virgo data collected between 2005 and 2010, at design sensitivity. Moreover, the search pipeline includes new postprocessing techniques, described in this Letter, offering the tightest observational constraints achievable from first generation ground-based GW interferometers. The possibility of direct detection of GW bursts from cosmic string cusps was first suggested in 2000 by Berezinsky et al.
The search. The LIGO-Virgo detector network  [35, 36]  is composed of four kilometer-scale Michelson interferometers: H1 (4 km) and H2 (2 km) share the same location at Hanford, Washington, USA, L1 (4 km) is in Livingston Parish, Louisiana, USA, and V1 (3 km) is located near Pisa, Italy. We analyze data collected between November 2005 and October 2010, at times when at least two detectors were operating simultaneously in stable conditions. This corresponds to a total of 625 days of observation time. The search for GW bursts from cosmic strings begins with a matched-filter analysis of strain data from each detector separately  [37]. It consists of projecting the whitened data onto an overpopulated  [38]  template bank defined by a set of cusp waveforms with a highfrequency cutoff spanning from 75 up to 8192 Hz.
Results. The LIGO-Virgo data set was divided into 24 time segments, which are analyzed independently. In particular, the training sets S and B are generated for each segment to account for the noise nonstationarities and the evolution of the detector sensitivities. The principal outcome of this search is shown in Fig. 1. The upper plot in Fig. 1  shows the combined cumulative event rate as a function of the ranking statistic Λ( x). The highestranked event of the search occurred on May 10, 2007 at 16:27:15 UTC and is detected simultaneously by the three LIGO interferometers. The ranking value of this event is less than 1σ away from the expected background distribution from time-shifted data, shown on the same plot. Therefore, we cannot claim this event to be a GW signal produced by cosmic strings.
Conclusion. We found no evidence for GW bursts produced by cosmic (super)string cusps in LIGO-Virgo data collected between 2005 and 2010. In the absence of a detection, we place significant constraints on cosmic string models, surpassing existing limits from CMB data. The next generation of ground-based GW detectors will probe the cosmic string parameter space further, including, for instance, superstring loops with junctions  [45] , as the improved sensitivity of Advanced LIGO  [41]  and Advanced Virgo  [46]  will allow us to search for cosmic strings with an order of magnitude lower tension. p, where g1, g2 and nc are numerical factors of O(1). The gray regions, in different shades for four reconnection probability values, are rejected by our analysis at a 90% level. The black lines show the bounds derived from the GW stochastic background spectrum for p = 10 -3 and for a small loop scenario (CMB, pulsar and LIGO data).
Acknowledgments. The authors gratefully acknowledge the support of the  United States National Science Foundation  for the construction and operation of the  LIGO Laboratory , the  Science and Technology Facilities Council of the United Kingdom , the  Max-Planck-Society , and the  State of Niedersachsen/Germany  for support of the construction and operation of the GEO600 detector, and the  Italian Istituto Nazionale di Fisica Nucleare  and the  French Centre National de la Recherche Scientifique  for the construction and operation of the Virgo detector. The authors also gratefully acknowledge the support of the research by these agencies and by the  Australian Research Council , the  International Science Linkages pro-gram of the Commonwealth of Australia , the  Council of Scientific and Industrial Research of India , the  Istituto Nazionale di Fisica Nucleare of Italy , the  Spanish Ministerio de Economía y Competitividad , the  Conselleria d'Economia Hisenda i Innovació of the Govern de les Illes Balears , the  Foundation for Fundamental Research on Matter  supported by the  Netherlands Organisation for Scientific Research , the  Polish Ministry of Science and Higher Education , the  FOCUS Programme of Foundation for Polish Science , the  Royal Society , the  Scottish Funding Council , the  Scottish Universities Physics Alliance , The  National Aeronautics and Space Administration, OTKA of Hungary , the  Lyon Institute of Origins (LIO) , the  National Research Foundation of Korea, Industry Canada  and the  Province of Ontario  through the  Ministry of Economic Development and Innovation , the  National Science and Engineering Research Council Canada , the  Carnegie Trust , the  Leverhulme Trust , the  David and Lucile Packard Foundation , the  Research Corporation , and the  Alfred P.
Acknowledgments We thank the members of the  ETM Collaboration  for making their gauge field configurations publicly available. Numerical computations are performed using the HPC resources of IDRIS Orsay, thanks to the computing time given to us by  GENCI  ( 2013-056808 ). We also thank  C. Bouchard ,  A. Khodjamirian  and  A. Radyushkin  for correspondence related to their respective works.
From 7th European Conference on Rare Diseases and Orphan Products (ECRD 2014) There is currently very little information available about the disabilities encountered by rare disease (RD) patients. Orphanet [http://www. orpha. net], the international database and portal on RDs and orphan drugs, has developed various projects to improve the knowledge and visibility of disabilities associated with RDs, and to provide tools to help the stakeholders. First, we have added content to the texts of the Orphanet Encyclopaedia for the General Public (133 texts) about the daily difficulties associated with the disease and its management. This information is provided through three questions: "What disabilities result from the disease?", "What resources are available to limit and prevent the disability?" and "Living with: the disability on a daily basis".
Through a questionnaire sent to medical experts, disability specialists and patient organisations, we collect data for each RD: the activity limitations and participation restrictions, their temporality during the course of the disease (permanent or transient difficulty, delay, loss of abilities), their severity and respective frequency in the patient population with current standard management, and important environmental factors. The collected data is analysed and standardised to constitute the Orphanet Functioning Database. 857 RDs are already indexed and 540 more are in progress, thanks to the contribution of hundreds of people and organisations from 43 countries. These RD disability core sets, which can be integrated into information systems, will be freely available in 7 languages. In addition, we will map the "Body structures" and the "Body functions" domains of the ICF-CY to the Human Phenotype Ontology  [2] , enabling us to list the anatomical structures and physiological functions impaired for each RD.
Settings and Cohorts The South African cohorts form part of the International Epidemiologic Databases to Evaluate AIDS Southern African (IeDEA-SA) collaboration  [16]. Data were restricted to the four cohorts, out of eight cohorts in South Africa, that were able to link to the NPR (Table  S1 ). These cohorts include government primary-care clinics in Cape Town, hospital clinics in Johannesburg and Durban, and a rural program in KwaZulu-Natal Province. The ART Cohort Collaboration (ART-CC) brings together cohorts of treatment-naı ¨ve adult patients from Europe and North America  [17]. Data were included from six North American and nine European cohorts (see collaborating centres).
Loss to Follow-up and Mortality Ascertainment Loss to follow-up (LTF) was determined by closing the analysis for each cohort six months before database closure, and defining patients with no recorded death or visit in the window between analysis and database closure as being lost at their last visit. Patients with no outcome before analysis closure were censored at analysis closure. The primary outcome was death from all causes. For each of the South African cohorts, civil identification numbers, where available, were crosschecked with the NPR prior to data transfer to confirm or ascertain dates of death. The European and North American cohorts recently described the frequency of death registry linkage as well as their own assessments of the completeness of mortality ascertainment  [13]. All of the North American cohorts link to a population-based death registry at least annually, while only three of the European cohorts reported regular searching of a registry for unrecorded deaths (one cohort annually for patients ,65 years old, and one each every two and three years, respectively).
Statistical Methods Patient characteristics at ART initiation (categorized or as medians with interquartile ranges) were described by region, including gender, age, CD4 count (within 6 months prior to initiation), viral load, mode of transmission (men who have sex with men, injection drug use, heterosexual, blood, other, or unknown), and year of ART initiation (Table  1 ). Although HIV in South Africa is predominantly heterosexually acquired  [21, 22] , data on mode of transmission were not available at an individual patient level for the South African patients. Clinical stage was characterised as advanced if WHO stage III or IV (South Africa) or CDC stage C (Europe and North America). Missing baseline values were multiply imputed by a chained equations approach and all resulting estimations were combined across five imputed datasets using Rubin's rules  [23, 24].
The imputation model included baseline gender, CD4 count, viral load, year of ART initiation, HIV clinical stage, cohort, and region as well as the outcomes of duration of follow-up (continuous time) and mortality (see Textbox S1). The absence of data on hepatitis C (HCV) in South Africa precluded its inclusion in any combined analyses. Among patients LTF in South Africa, those with civil identification numbers and therefore linkable to the NPR were up-weighted to represent all patients lost: within each cohort we took the inverse of the modelled probability (based on age, gender, CD4 count, year of ART initiation, and duration on ART when lost) of having a civil identifier as the weight for each linkable patient, in order to account for any differences between linkable and other patients LTF (Table  S2 ).