dataesr/scientific-paragraphs-categorization huggingface dataset:
Structural analysis highlights, between the two amphipathic α-helices, an interhelical loop whose conformation differs between the monomers forming a given TWISTlcontaining dimer and according to the partner of TWISTl in the dimer (Figure  2 ). We demonstrate that these structural divergences notably reflect differences in residue composition, as they affect the formation of H-bonds involving either residues or DNA bases. Interestingly, the E-loop of the TWIST1/E12 heterodimer forms a unique cavity that might reasonably be targeted in efforts to select specific intercalating molecules for pharmacological purposes. Preliminary docking analysis of the NCI library supports this hypothesis (data not shown). Residues located in the loops of all of the homodimers and heterodimers studied interact with nucleotides À1 to +4 of the E-box sequence (Figures  3 4 5 6 7 8 ), known to be important in bHLH binding  (De Masi et al.
Whole genome sequencing data in conjunction with genomewide association genetics has been shown a promising approach to investigate the diversity of disease resistance QTL in plants and to detect with high resolution common resistance alleles in a given population  [2, 14]. QTL meta-analysis  [15]  have also been shown a useful approach to obtain a synthetic representation of the diversity of loci controlling a trait of interest in plants. It consists of combining results from previous QTL reports into consensus genomic regions, or meta-QTL, associated with the trait variation. The position of these meta-QTL is estimated with higher accuracy compared to position estimates of individual QTL. Statistical methods for meta-analysis of QTL have been implemented in two main software packages, Biomercator  [16]  and Meta-QTL  [17].
Ae-Ps3. 1 LGIIIb Ae-Ps5. 4  Figure  1  (See legend on next page. ) A08_1050 I11_1100 L13_1050 AB140 AB68 AA355 O16_650 R03_800 PLM00_ADI Ae-Ps3. 2 LGVI C14_1600 AD51 AA224b AA200 J14_750 AA31 AA297 O01_700 AD59 AA467 AB71 N14_500 AD60 G04_950 E11_600* A11_850 A19_850 A6 X18_2200 Pl AB125 AC76a K16_900 AA103* AB91 RI02_RRI DI02_ADI1 DI02_ADI2 DI03_ADI1 LS03_ADI1 LS03_ADI1 LS00_ADI2 Ae78 Ae-Ps6. (Figure  1 , Additional file 5). A major QTL, AePs7. 6, previously identified in  [46] , was consistently detected on LGVII from ADI and/or RRI data collected in the 11 field environments studied and for five of the six strains in controlled conditions. The Ae-Ps7. 6 genomic region covered about 35 cM and accounted for the majority of the phenotypic variation, yielding 59. 8% for resistance to the RB84 strain.
Consensus map The consensus marker map was established from the three individual genetic maps (Puget × 90-2079, DSP × 90-2131, Baccara × PI180693/552) using the Meta-QTL software. The map comprised a total of 619 markers (31% SSR; 33% RAPD; 32% AFLP; 2. 4% STS, 1. 6% isozyme or morphological markers) and covered 1513 cM Kosambi (Additional file 10). Eighty-six percent of the markers mapped to only one of the individual maps studied, while 14% mapped to two or three individual maps with consistent marker order and regular distribution on all LG (8 to 22 common markers per LG) with exception of LGI. Fifteen percent of the 619 markers of the consensus map were also mapped on the reference genetic map described by  [53]  and had consistent positions between the two maps.
None of the meta-QTL comprised of a minimum of two initial controlled   a Meta-QTL names are coded as follows : MQTL-Ae = Meta-QTL detected for resistance to A. euteiches; MQTL-Morpho = Meta-QTL detected for morphological and phenological traits (flowering time and plant height). On each Linkage Group (LG), MQTL-Ae and MQTL-Morpho, which co-localize, are mentioned by asterisks. Meta-QTL indicated in bold correspond to the seven main consistent genomic regions identified for resistance to A. euteiches. b QTL position at the LOD (Log of likelihood ratio) score peak, from the first marker of the linkage group in cM Kosambi. c 95% confidence interval of the meta-QTL given by MetaQTL software, in cM Kosambi. d Mean and standard deviation of confidence intervals (estimates according to  [55] ) of all independent QTL belonging to each meta-QTL, in cM Kosambi.
QTL meta-analysis Using all the additive-effect QTL identified for resistance to A. euteiches, earliness and plant height from Puget × 90-2079  [31, 78] , Baccara × PI180693, Baccara x 552  [46]  and DSP × 90-2131 (this study) RIL populations, a QTL meta-analysis was performed using the MetaQTL software version 1. 0  [17]. QTL meta-analysis was conducted in three steps, according to details given in  [21]. For each QTL, data given to the software were the QTL position (LG, position on the LG at the LOD peak), the upper and lower bound and LOD decrease of the QTL confidence interval, the percentage of variation (R 2 ) individually explained by the QTL, the trait related to the QTL and the size of the mapping population used for the QTL detection. First, a single consensus marker map was built by integrating the available genetic maps, based on common markers designated with common names between the maps, using the ConsMap command of the software.
Confidence intervals (CI) of independent QTL were estimated from the QTL R 2 values, using the empirical formula proposed by  [55] : CI ¼ 530 NxR 2 , where N is the population size. This formula usually gives larger confidence intervals than the usual interval length of LOD-1 decrease. Finally, the QTL meta-analysis algorithm, computed in the QTLClust command of the software, was used to determine the most likely number of meta-QTL on a given chromosome and to estimate their corresponding positions and confidence intervals. Meta-QTL considers QTL positions and corresponding confidence intervals in individual experiments, after projection onto the consensus map. We used the -cimode option 4 of QTLClust command that consider the maximum confidence interval between the LOD-1 decrease value reported and the QTL R 2 value estimated by the formula of  [55].
On a given chromosome, projected independent QTL were clustered into all possible numbers of hypothetic clusters of meta-QTL (K), for which a Gaussian mixture model estimates meta-QTL positions and confidence intervals  [17]. The optimal K was determined using the highest weight of evidence values estimated for five information-based criteria  [17] , which were computed for each K. The most frequent optimal K value given by the different criteria was selected, which always corresponded to the optimal K value determined by the Akaike Information Criterion. The position, 95% confidence interval and probability of individual QTL belonging to the meta-QTL, were given by the software for each meta-QTL. Two meta-analysis runs were conducted separately for Aphanomyces resistance QTL data and earliness and plant height QTL data, respectively, resulting in the detection of meta-QTL for two types of traits, which were then compared.
Acknowledgments This work was funded by a  pre-doctoral fellowship  ( Céline Hamon ) from  INRA, Département de Génétique et Amélioration des Plantes (France) ,  MAP  ( Ministère de l'Agriculture et de la pêche, Paris, France ) and  UNIP (Union Nationale Interprofessionnelle des Plantes riches en protéines, Paris, France) , which we greatly acknowledge. We thank the  INRA experimental units of Le Rheu and Dijon-Epoisses, France, UNILET (Union Nationale Interprofessionnelle des Légumes Transformés), Quimperlé, France , for contributing to field experiments. We also acknowledge the technical staff and students from the  Legume group  of  INRA Le Rheu, France --A-M. Jacob ,  T. Dormegnies ,  V. L'Anthoëne ,  J. M. Abelard ,  J. Poisson ,  J. Gautier  --for supporting work on RIL population genotyping with molecular markers, plant material production and field evaluation.
Additional measurements from the tower elevator included high speed (10 Hz) wind from a Gill Windmaster ultrasonic anemometer and H 2 O and CO 2 concentrations from an open path non-dispersive infrared analyzer (Licor 7500) provided by the NOAA Physical Sciences Division. The H 2 O mixing ratio measurements were in excellent agreement with the Picarro measurements once calibrated, as anticipated from the previous work  (Noone et al. , 2011). Temperature measurements on the platform are from a Vaisala HMP 45C sensor, which has a characteristic response time of less than one minute. While vibrations of the elevator are likely to influence the high frequency (faster than 1 Hz) measurements, our analysis focuses on 10 s averages to minimize vibration influences. There were no surface sensible or latent heat flux measurements made during the period of the study, while radiation data show characteristically low energy availability due to the high albedo of snow.
Acknowledgements. We thank  Bruce Vaughn ,  Valerie Morris  and  Jim White  of the  University of Colorado Stable Isotope Laboratory  for providing calibration standards and invaluable advice on sample preparation and laboratory isotopic analysis. We thank  Chris Still  of  University of California at Santa Barbara and Brent Helliker of Penn State  for advice on design of the vacuum cryogenic extraction line. We are indebted to  Emily Graham  and  Peter Blanken  of the  Department of Geography at University of Colorado  for making time for our campaign during their experiment at the  BAO. Support  for this project was from  National Science Foundation Early Career and Climate and Large-scale Dynamics program  ( AGS-0955841 ),  NASA   Atmospheric Composition Program  ( NNX08AR23G ), a grant from the  NASA Jet Propulsion Laboratory  and the  University of Colorado Undergraduate Research Opportunities Program.
Promoting Remyelination-Potential Candidate Drugs How can we intervene to improve remyelination and maintain function in MS patients? All current treatments used to treat MS in clinical practice act primarily on modulating or suppressing the immune system to prevent further relapses, but they do not delay or slow disease progression or affect remyelination. The current licensed treatments (in the UK) are the beta-interferons, glatiramer acetate, natalizumab and fingolimod. Natalizumab (a monoclonal antibody blocking a4 integrin and preventing T cells from crossing the blood-brain barrier) and fingolimod (a sphingosine-1-phosphate receptor modulator preventing T cells from exiting lymph nodes) are both also in clinical trial to test whether they prevent or slow progression of disease (NCT01416181, NCT00731692), but they are not being directly tested for their ability to promote remyelination.
Fingolimod does promote rodent oligodendrocyte process extension and survival in vitro  [61, 62] ; however, it remains unclear how it affects regeneration of myelin, as although increased remyelination has been demonstrated in the multi-cellular environment of ex vivo rodent slice culture preparations  [63] , it was not seen in in vivo rodent studies  [64]. While one human clinical trial has reported no effect of fingolimod on disease progression in RRMS patients  [65] , other trials continue (NCT00731692, NCT01498887). The wealth of other drugs designed to reduce MS relapses (including daclizumab, teriflunomide, ocrelizumab, laquinimod and siponimod), which are in clinical trial, awaiting licensing, or that have received licensing in some countries, have also not been shown to affect disease progression or remyelination.
One possible support for the latter is that cultures of peripheral blood mononuclear cell cultures, in particular T cells, produce increased concentrations of potentially useful neuronal growth factors when treated with alemtuzumab and stimulated with myelin basic protein. In addition, media from these cell cultures promote survival of neurons and OPCs and enhance oligodendrocyte differentiation and myelination  [70]. Future clinical trials are planned using MRI analysis to measure myelin repair for further exploration of the putative neuroprotective and remyelinating potential of alemtuzumab (NCT01307332, NCT01395316).
A recent preclinical study in an immune model of demyelination in rats (MOG-EAE), thus far only published in abstract form, also demonstrates a fivefold reduction of axonal loss in the optic nerve of rats treated with BIIB033 (an anti-LINGO-1 antibody) compared with control antibody, which became more marked (eightfold reduction) in combination with methylprednisolone  [83]. A clinical phase Ib study compared the effect of BIIB033 (an anti-LINGO-1 antibody) in patients with RRMS in a placebocontrolled randomised trial (NCT01244139); this is the first trial targeted at directly improving remyelination in MS. The study was completed in April 2012, showing no serious adverse events, as reported at the American Academy of Neurology annual meeting. A phase II trial is planned and will give additional information with regards to safety, tolerability and efficacy (NCT01864148).
Human Monoclonal IgM Antibody 22 The human monoclonal IgM antibody ). Similar increases in remyelination were reported in MRI studies using the same experimental animal model  [85]. Further research suggests that this pro-remyelination effect of rHIgM22 is independent of immunomodulation  [86]  and is associated with anti-apoptotic signalling in pre-myelinating oligodendrocytes  [87]. Recent data provide evidence of potential mechanisms underpinning the remyelination-enhancing effect of rHIgM22, involving the Src family kinase Lyn and platelet-derived growth factor (PDGF)-receptor alpha signalling  [88, 89]. A phase I clinical trial is now recruiting patients to evaluate safety, tolerability, pharmacokinetics and immunogenicity of a single intravenous dose of rHI-gM22 in patients with MS (NCT01803867).
Acknowledgments  Dr Williams  and  Dr Mu  ¨nzel have no conflicts of interest that are directly relevant to this review, and no funding was received for the paper. AW is currently funded by the  Chief Scientist's Office, Scotland  and EJM by the  Centre for Clinical Brain Sciences, University of Edinburgh. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Phenotypic data on fertility/sterility Two methodologies were employed to determine the overall level of male fertility/sterility of each plant. The spikes from the first, third and fourth tillers were bag isolated at emergence and imposed to self-pollinate. After dehiscence, the spikes were harvested; for each spike, the number of spikelets and the number of seeds were counted. The level of fertility was determined for each spike as a ratio between the number of seeds produced and the total number of spikelets. The value of the three collected spikes was averaged to provide an overall 'seeds per spikelet' (SpS) score. This value is rather provided in its unit value ranging from 0. 0 to 1. 41, or as a percentage value of SpS fertility, where 100 % correspond to the unit value 1. 41 (max value reached in the experiment).
The data on fertility were recorded for each RH plant as well as for three durum control lines (LDN, LDN 3D (3B), and their F progeny) and two hexaploid control lines (CS and the CS deletion bin line 3BL7-0. 63-1. 00). The RH lines, due to their unique karyotype makeup, could only be tested once during winter 2009 without replicates by single plant screening. The control lines, however, were tested in three replicates across four greenhouse seasons in Fargo using a randomized complete block design: winter 2009, spring 2010, winter 2011, and spring 2011; while the hexaploid controls were tested in three replicates solely during the winter 2011 season. Fig. 1  Physiological effects of removing the 3B chromosome from the genome of durum wheat. a An adult wheat spike opening its florets to facilitate crosspollination, because the sterility of the pollen grains prevents self-pollination.
The images of pollen mother cells at the stages from diakinesis to tetrad were captured using an Axiocam HRm CCD camera and imaging software Aixovision Release 4. 5 (Carl Zeiss Light Microscopy, Germany). In aberrant cells, the number of springerproof. sps. co. in:8080/uat_oxe/printpage. php?token=IMyxXLsJCFgw7IMNe2I48A 8/27 bivalents can be measured as (28-number of univalents)/2.
High-quality extracts show a single sharp band in close proximity of the gel wells and such extracts were used for further genotyping. The 3B-RH panel was genotyped using three different classes of markers: PCR-based insertion sitebased polymorphisms (ISBPs, labeled as 'cfp';  Paux et al. 2006 Paux et al. , 2010)) ; simple sequence repeats (SSRs, labeled as 'gwm' and 'wmc';  Somers et al. 2004; Song et al. 2005)  and Diversity Array Technology (DArT, labeled as 'wPt' and 'tPt';  Akbari et al. 2006; Wenzl et al. 2010). The SSR and ISBP markers were primarily used to confirm the genotyping data provided by the DArT markers. PCR amplification and scoring of ISBP and SSR markers were done as described in  Kumar et al. (2012a). For DArT analysis, a total of 245 3B specific DArT markers were selected from earlier studies (175 markers;  Wenzl et al.
Statistical analyses To generate a comprehensive map of chromosome 3B, the retention/deletion data on the 696 RH lines genotyped with 140 markers were run on the Carthagene mapping software v1. 2. 2 (de  Givry et al. 2005) , employing the iterative framework mapping procedure described earlier  (Kumar et al. 2012a). Further details are provided as supplementary material. The calculation of the map resolution provided by this population was computed as suggested by  Kumar et al. (2012a). The SAS 9. 3 environment (SAS Institute, Cary, NC) was used to determine the significant differences of the fertility categories (t test) by procGLM across four growing seasons and then combining (12 replicates) given the absence of statistical significance between seasons. SAS 9. 3 was also employed to calculate the r association between markers and phenotypes.
Acknowledgments The authors wish to thank  Professor Wojtek Pawlowski  ( Cornell University, NY ) for in-depth revision and insightful comments on this manuscript,  Justin Hegstad  and  Allen Peckrul  for their qualified technical help. This work was supported by funding from the  National Science Foundation ,  Plant Genome Research Program (NSF-PGRP ) grant No. IOS-0822100  to SFK. F. M. B was partially supported by  Program Master  and  Back Regione Autonoma della Sardegna and Monsanto Beachell-Borlaug International Scholarship.
Meta-analyses have also been conducted as part of national health technology assessments. In 2009, the German Institute for Quality and Efficiency in Health Care (IQWiG) published their evaluation report on memantine in AD  [18]. In 2010, as part of the National Institute for Health and Clinical Excellence (NICE) review of AD therapies, the independent Peninsula Technology Assessment Group (PenTAG) conducted a systematic review and meta-analysis  [19]. All five meta-analyses incorporated data from the clinical development program for memantine in AD. This comprised six randomized, double-blind, placebo-controlled trials of 6 months duration, designed in line with current recommendations of the European Medicines Agency (EMA). The trials assessed the efficacy of memantine across key AD domains (cognition, ADL, global assessment, and behavior) using standard scales.
The methodologies of the trials were similar but with important differences in the included patient populations, both in terms of AD severity and background treatment with AChEIs (Table  1 ). Another important point is that in distinct populations of varying severities, different scales are sometimes used to measure the same concept. For example, both the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and severe impairment battery (SIB) are used to assess cognition. While these six pivotal registration studies were the main data sources, not all meta-analyses included all trials. Furthermore, one additional trial conducted more recently was included in the meta-analysis conducted by IQWiG: Lu-10116, the pivotal trial for the authorization of memantine in China, assessed memantine as a monotherapy in Chinese patients with moderate to severe AD over a 4-month period  [20].
Acknowledgments SG is a scientific advisor and an investigator to  Lundbeck , and has received financial support to participate in scientific meetings. BR, CM, and CF are employees of Lundbeck. SC received financial support for writing, editorial assistance, and data analyses. The authors have no conflicts of interest. Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
Hardware functional models (similar to hardware accelerators) are used to generate data, and traditional microprocessors are employed for further processing. An example of such a system is the STDP implementation by  Belhadj et al. (2008). Digital neural networks can also be implemented using large networks of embedded microprocessors, such as in the spiNNaker project  (Rast et al. , 2010)  in which ARM processors, running software neuron models, perform the calculations instead of physical silicon neurons. These systems are essentially generalized networks that have been highly optimized for neuron computation.
We chose a memory with a size of 4k × 9 bits = 36k bits, as the size of the on-chip block RAM in the Xilinx Virtex 6 family is either 18 or 36k. Any block memory used has to be constructed from RAMs of these two sizes and any fragments are wasted. To fully utilize the available memory, an implementation with 4096 virtual axons was chosen. Each virtual axon module is updated every 62 µs (4096/66 MHz), and therefore the longest delay the ramp generator can generate is 2 9 × 4096/66 MHz ≈ 32 ms. This value can be easily changed if desired, by either changing the clock frequency or the bit width of the counter. If the output of the ramp generator exceeds the programmed delay, a pre-synaptic spike will be generated with the AER address stored in the SRAM for the configured address. This programmed delay corresponds to one of the four axonal delay paths in each virtual axon module.
Conclusion Giant viruses infecting phagocytic protists represent a major challenge in human pathology, as virological procedures implemented to date have not used appropriate media to allow their culture, and molecular techniques have used filtration steps that likely prevented their detection. The proportion of respiratory or other infections related to these giant viruses in humans is currently unknown and should be the subject of future work. However, there is an increasing body of evidence that mimiviruses might cause pneumonia and that humans carry marseilleviruses, and re-analyses of metagenomic databases have provided evidence that these giant viruses can be common in human samples. In conclusion, giant viruses infecting amoebae are emerging pathogens in humans, and their precise short-and long-term roles remain to be determined.
1 mM to 1. 5 mM), 1 mM GTP, an anti-fading cocktail (2 mg/mL glucose, 80 mg/mL catalase, and 0. 67 mg/mL glucose oxydase), and 1. 5% BSA (Figure  1A ). MT assembly was visualized using an objective-based TIRF microscope (Nikon TE2000-E) and Quantem 512SC camera (Photometrics). Microscope stage was kept warm (32uC) using a warm stage controller (LINKAM MC60). Excitation was achieved using 491 nm and 561 nm lasers (Optical Insigths). Time-lapse microscopy (one frame every 2 s) was performed for 30 min using Metamorph software (Universal Imaging).