Cross-sections of large-angle hadron production in proton-- and pion--nucleus interactions VIII: aluminium nuclei and beam momenta from {\pm}3 GeV/c to {\pm}15 GeV/c

We report on double-differential inclusive cross-sections of the production of secondary protons, charged pions, and deuterons, in the interactions with a 5% {\lambda}int thick stationary aluminium target, of proton and pion beams with momentum from \pm3 GeV/c to \pm15 GeV/c. Results are given for secondary particles with production angles between 20 and 125 degrees. Cross-sections on aluminium nuclei are compared with cross-sections on beryllium, carbon, copper, tin, tantalum and lead nuclei.Comment: 71 pages, 16 figures, 47 table

Exploiting Parallel R in the Cloud with SPRINT

BACKGROUND: Advances in DNA Microarray devices and next-generation massively parallel DNA sequencing platforms have led to an exponential growth in data availability but the arising opportunities require adequate computing resources. High Performance Computing (HPC) in the Cloud offers an affordable way of meeting this need. OBJECTIVES: Bioconductor, a popular tool for high-throughput genomic data analysis, is distributed as add-on modules for the R statistical programming language but R has no native capabilities for exploiting multi-processor architectures. SPRINT is an R package that enables easy access to HPC for genomics researchers. This paper investigates: setting up and running SPRINT-enabled genomic analyses on Amazon’s Elastic Compute Cloud (EC2), the advantages of submitting applications to EC2 from different parts of the world and, if resource underutilization can improve application performance. METHODS: The SPRINT parallel implementations of correlation, permutation testing, partitioning around medoids and the multi-purpose papply have been benchmarked on data sets of various size on Amazon EC2. Jobs have been submitted from both the UK and Thailand to investigate monetary differences. RESULTS: It is possible to obtain good, scalable performance but the level of improvement is dependent upon the nature of algorithm. Resource underutilization can further improve the time to result. End-user’s location impacts on costs due to factors such as local taxation. Conclusions: Although not designed to satisfy HPC requirements, Amazon EC2 and cloud computing in general provides an interesting alternative and provides new possibilities for smaller organisations with limited funds

Cross-Sections of Large-Angle Hadron Production in Proton- and Pion-Nucleus Interactions III: Tantalum Nuclei and Beam Momenta from +/-3 Gev/c to +/-15 Gev/c

We report on double-differential inclusive cross-sections of the production of secondary protons, charged pions, and deuterons, in the interactions with a 5% nuclear interaction length thick stationary tantalum target, of proton and pion beams with momentum from +/-3 GeV/c to +/-15 GeV/c. Results are given for secondary particles with production angles between 20 and 125 degrees. They are of particular relevance for the optimization of the design parameters of the proton driver of a neutrino factory.Comment: 68 pages, 12 figures, corrections in v2: added 'HARP -CDP group' to author name, corrected two typos in Table 4 (last two p values for 65-90 degrees were all 0.972

Исследование подавления роста опухоли, экспрессирующей раково-эмбриональный антиген, новым высокотехнологичным препаратом карплазмин (CAR-T-терапия) у мышей линии Balb/c nude

Introduction. Adoptive immunotherapy based on chimeric antigen receptors (CAR) is considered as a promising direction in the treatment of solid malignant tumors. To produce genetically modified human T-lymphocytes, lenti/retroviral transduction is currently most often used. However, safety concerns associated with the viral vector production and possible unwanted genome modification limit the clinical utility of CAR-T cells. Therefore, non-viral transfection methods, in particular electroporation, using of DNA or RNA vectors, are being actively studied as a method for producing CAR-T lymphocytes.Aim. To evaluate in vivo antitumor activity of the new high-tech drug carplasmin, intended for CAR-T therapy of tumors expressing carcinoembryonic antigen (CEA). Materials and methods. Carplasmin was obtained by electroporation of activated human lymphocytes with plasmid DNA carrying the third generation CAR gene specific to CEA. The study was performed on a human colorectal cancer xenograft model obtained by intraperitoneal injection of CEA-positive HCT116 cell line to athymic Balb/c nude mice. Carplasmin treatment was carried out once a week, starting from the third day after HCT116 cell inoculation. Mice in the two control groups were treated with either electroporated lymphocytes without plasmid addition (pulse-lymphocytes) or RPMI-1640 culture medium (group without treatment).Results. In vivo, carplasmin demonstrated a pronounced antitumor effect. Seven weekly injections of the drug to inoculated mice led to a prominent effect of antitumor therapy: 80 % of the animals in the experimental group survived (with 40 % of the mice had a complete remission without signs of a detectable tumor), compared to 100 % death in the control group (without treatment).Conclusion. The results of preclinical efficacy studies demonstrate that carplasmin is a promising drug for the treatment of CEA-positive intraperitoneal tumors.Введение. Адоптивная иммунотерапия на основе химерных антигенных рецепторов (CAR) рассматривается как перспективное направление в лечении солидных злокачественных опухолей. Для получения генетически модифицированных Т-лимфоцитов человека в настоящее время чаще всего используется ленти-/ретровирусная трансдукция. Однако проблемы безопасности, связанные с продукцией вирусного вектора и возможной нежелательной модификацией генома, ограничивают клиническую применимость CAR-Т-клеток. Поэтому невирусные методы трансфекции, в частности электропорация с использованием ДНК- или РНК-векторов, активно исследуются как подход для получения CAR-T-лимфоцитов.Цель исследования – оценка противоопухолевой активности in vivo нового высокотехнологичного лекарственного средства карплазмин, предназначенного для CAR-T-терапии опухолей, экспрессирующих раково-эмбриональный антиген (РЭА).Материалы и методы. Карплазмин получен методом электропорации активированных лимфоцитов человека плазмидной ДНК, несущей ген CAR 3-го поколения, специфичный к РЭА. Исследование выполнено на модели ксенотрансплантата колоректального рака человека, полученной при интраперитонеальном введении РЭА-положительных клеток линии HCT116 бестимусным мышам линии Balb/c nude. Введение карплазмина проводили 1 раз в неделю, начиная с 3-го дня после прививания клеток HCT116. Мышам 2 контрольных групп вводили либо лимфоциты, подвергнутые электропорации без внесения плазмиды (пульс-лимфоциты), либо культуральную среду RPMI-1640 (группа без лечения).Результаты. In vivo карплазмин демонстрировал выраженное противоопухолевое действие. Семь еженедельных введений препарата привитым мышам привели к выраженному эффекту противоопухолевой терапии: 80 % животных в экспериментальной группе выжили (при этом у 40 % мышей наблюдалась полная ремиссия без признаков определяемой опухоли), тогда как в контрольной (без лечения) группе 100 % животных погибли.Заключение. Результаты доклинических исследований эффективности демонстрируют, что карплазмин является перспективным препаратом для терапии РЭА-позитивных интраперитонеальных опухолей

New constraints on oscillation parameters from Ve appearance and Vu disappearance in the NOvA experiment

For full abstract please refer to Official URL link”, or if there is a document attached which contains the abstract, “For full abstract please refer to attached documen

Measurement of neutrino-induced neutral-current coherent π⁰ production in the NOvA near detector

The cross section of neutrino-induced neutral-current coherent π⁰ production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ = 13.8±0.9(stat)±2.3(syst)×10⁻⁴⁰ cm²/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π⁰ production in the few-GeV neutrino energy region

Measurement of neutrino-induced neutral-current coherent π⁰ production in the NOvA near detector

The cross section of neutrino-induced neutral-current coherent π⁰ production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ = 13.8±0.9(stat)±2.3(syst)×10⁻⁴⁰ cm²/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π⁰ production in the few-GeV neutrino energy region

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesOver the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) <1.15).We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls).We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P = 9 × 10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23.This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental-related genes such as EXT1, ASTN2, MACROD2, and HDAC4.National Institutes of Mental Health (NIMH, USA) ACE Network Autism Genetic Resource Exchange (AGRE) is a program of Autism Speaks (USA) The Autism Genome Project (AGP) from Autism Speaks (USA) Canadian Institutes of Health Research (CIHR), Genome Canada Health Research Board (Ireland) Hilibrand Foundation (USA) Medical Research Council (UK) National Institutes of Health (USA) Ontario Genomics Institute University of Toronto McLaughlin Centre Simons Foundation Johns Hopkins Autism Consortium of Boston NLM Family foundation National Institute of Health grants National Health Medical Research Council Scottish Rite Spunk Fund, Inc. Rebecca and Solomon Baker Fund APEX Foundation National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) endowment fund of the Nancy Pritzker Laboratory (Stanford) Autism Society of America Janet M. Grace Pervasive Developmental Disorders Fund The Lundbeck Foundation universities and university hospitals of Aarhus and Copenhagen Stanley Foundation Centers for Disease Control and Prevention (CDC) Netherlands Scientific Organization Dutch Brain Foundation VU University Amsterdam Trinity Centre for High Performance Computing through Science Foundation Ireland Autism Genome Project (AGP) from Autism Speak

Measurement of neutrino-induced neutral-current coherent π0 production in the NOvA near detector

The cross section of neutrino-induced neutral-current coherent π0 production on a carbon-dominated target is measured in the NOvA near detector. This measurement uses a narrow-band neutrino beam with an average neutrino energy of 2.7 GeV, which is of interest to ongoing and future long-baseline neutrino oscillation experiments. The measured, flux-averaged cross section is σ=13.8±0.9(stat)±2.3(syst)×10−40cm2/nucleus, consistent with model prediction. This result is the most precise measurement of neutral-current coherent π0 production in the few-GeV neutrino energy region

Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders

Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways