We report the final measurement of the neutrino oscillation parameters Δm322 and sin2 θ23 using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of ...23.76 × 1020 protons on target producing νμ and νμ beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of νμ and the appearance of νe events between the Near and Far detectors yields ... and ... at 68% C.L. for normal (inverted) hierarchy. (ProQuest: ... denotes formulae omited.).
The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma ...remain unclear.
To identify common genetic variants affecting susceptibility to severe asthma.
A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies.
An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance.
The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.
GPR50 is an orphan G protein-coupled receptor (GPCR) located on Xq28, a region previously implicated in multiple genetic studies of bipolar affective disorder (BPAD). Allele frequencies of three ...polymorphisms in GPR50 were compared in case-control studies between subjects with BPAD (264), major depressive disorder (MDD) (226), or schizophrenia (SCZ) (263) and ethnically matched controls (562). Significant associations were found between an insertion/deletion polymorphism in exon 2 and both BPAD (P=0.0070), and MDD (P=0.011) with increased risk associated with the deletion variant (GPR50(Delta502-505)). When the analysis was restricted to female subjects, the associations with BPAD and MDD increased in significance (P=0.00023 and P=0.0064, respectively). Two other single-nucleotide polymorphisms (SNPs) tested within this gene showed associations between: the female MDD group and an SNP in exon 2 (P=0.0096); and female SCZ and an intronic SNP (P=0.0014). No association was detected in males with either MDD, BPAD or SCZ. These results suggest that GPR50(Delta502-505), or a variant in tight linkage disequilibrium with this polymorphism, is a sex-specific risk factor for susceptibility to bipolar disorder, and that other variants in the gene may be sex-specific risk factors in the development of schizophrenia.
In early-stage pancreatic cancer, there are currently no biomarkers to guide selection of therapeutic options. This prospective biomarker trial evaluated the feasibility and potential clinical ...utility of circulating tumor DNA (ctDNA) analysis to inform adjuvant therapy decision making.
Patients considered by the multidisciplinary team to have resectable pancreatic adenocarcinoma were enrolled. Pre- and post-operative samples for ctDNA analysis were collected. PCR-based-SafeSeqS assays were used to identify mutations at codon 12, 13 and 61 of KRAS in the primary pancreatic tumor and to detect ctDNA. Results of ctDNA analysis were correlated with CA19-9, recurrence-free and overall survival (OS). Patient management was per standard of care, blinded to ctDNA data.
Of 112 patients consented pre-operatively, 81 (72%) underwent resection. KRAS mutations were identified in 91% (38/42) of available tumor samples. Of available plasma samples (N = 42), KRAS mutated ctDNA was detected in 62% (23/37) pre-operative and 37% (13/35) post-operative cases. At a median follow-up of 38.4 months, ctDNA detection in the pre-operative setting was associated with inferior recurrence-free survival (RFS) hazard ratio (HR) 4.1; P = 0.002) and OS (HR 4.1; P = 0.015). Detectable ctDNA following curative intent resection was associated with inferior RFS (HR 5.4; P < 0.0001) and OS (HR 4.0; P = 0.003). Recurrence occurred in 13/13 (100%) patients with detectable ctDNA post-operatively, including in seven that received gemcitabine-based adjuvant chemotherapy.
ctDNA studies in localized pancreatic cancer are challenging, with a substantial number of patients not able to undergo resection, not having sufficient tumor tissue for analysis or not completing per protocol sample collection. ctDNA analysis, pre- and/or post-surgery, is a promising prognostic marker. Studies of ctDNA guided therapy are justified, including of treatment intensification strategies for patients with detectable ctDNA post-operatively who appear at very high risk of recurrence despite gemcitabine-based adjuvant therapy.
Cognitive impairment is common among individuals diagnosed with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). It has been suggested that some aspects of ...intelligence are preserved or even superior in people with ASD compared with controls, but consistent evidence is lacking. Few studies have examined the genetic overlap between cognitive ability and ASD/ADHD. The aim of this study was to examine the polygenic overlap between ASD/ADHD and cognitive ability in individuals from the general population. Polygenic risk for ADHD and ASD was calculated from genome-wide association studies of ASD and ADHD conducted by the Psychiatric Genetics Consortium. Risk scores were created in three independent cohorts: Generation Scotland Scottish Family Health Study (GS:SFHS) (n=9863), the Lothian Birth Cohorts 1936 and 1921 (n=1522), and the Brisbane Adolescent Twin Sample (BATS) (n=921). We report that polygenic risk for ASD is positively correlated with general cognitive ability (beta=0.07, P=6 × 10(-7), r(2)=0.003), logical memory and verbal intelligence in GS:SFHS. This was replicated in BATS as a positive association with full-scale intelligent quotient (IQ) (beta=0.07, P=0.03, r(2)=0.005). We did not find consistent evidence that polygenic risk for ADHD was associated with cognitive function; however, a negative correlation with IQ at age 11 years (beta=-0.08, Z=-3.3, P=0.001) was observed in the Lothian Birth Cohorts. These findings are in individuals from the general population, suggesting that the relationship between genetic risk for ASD and intelligence is partly independent of clinical state. These data suggest that common genetic variation relevant for ASD influences general cognitive ability.
ABSTRACT
We analyse a robust sample of 30 near-infrared-faint (KAB > 25.3, 5σ) submillimetre galaxies (SMGs) selected from a 0.96 deg2 field to investigate their properties and the cause of their ...faintness in optical/near-infrared wavebands. Our analysis exploits precise identifications based on Atacama Large Millimeter Array (ALMA) 870-μm continuum imaging, combined with very deep near-infrared imaging from the UKIDSS Ultra Deep Survey. We estimate that SMGs with KAB > 25.3 mag represent 15 ± 2 per cent of the total population brighter than S870 = 3.6 mJy, with a potential surface density of ∼450 deg−2 above S870 ≥ 1 mJy. As such, they pose a source of contamination in surveys for both high-redshift ‘quiescent’ galaxies and very high redshift Lyman-break galaxies. We show that these K-faint SMGs represent the tail of the broader submillimetre population, with comparable dust and stellar masses to KAB ≤ 25.3 mag SMGs, but lying at significantly higher redshifts (z = 3.44 ± 0.06 versus z = 2.36 ± 0.11) and having higher dust attenuation (AV = 5.2 ± 0.3 versus AV = 2.9 ± 0.1). We investigate the origin of the strong dust attenuation and find indications that these K-faint galaxies have smaller dust continuum sizes than the KAB ≤ 25.3 mag galaxies, as measured by ALMA, which suggests their high attenuation is related to their compact sizes. We identify a correlation of dust attenuation with star formation rate surface density (ΣSFR), with the K-faint SMGs representing the higher ΣSFR and highest AV galaxies. The concentrated, intense star formation activity in these systems is likely to be associated with the formation of spheroids in compact galaxies at high redshifts, but as a result of their high obscuration these galaxies are completely missed in ultraviolet, optical, and even near-infrared surveys.
Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae ...has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.
We present sensitive 850 m imaging of the Cosmological Evolution Survey (COSMOS) field using 640 hr of new and archival observations taken with SCUBA-2 at the East Asian Observatory's James Clerk ...Maxwell Telescope. The SCUBA-2 COSMOS survey (S2COSMOS) achieves a median noise level of 850 m = 1.2 mJy beam−1 over an area of 1.6 sq. degree (main; Hubble Space Telescope/Advanced Camera for Surveys footprint), and 850 m = 1.7 mJy beam−1 over an additional 1 sq. degree of supplementary (supp) coverage. We present a catalog of 1020 and 127 sources detected at a significance level of >4 and >4.3 in the main and supp regions, respectively, corresponding to a uniform 2% false-detection rate. We construct the single-dish 850 m number counts at S850 > 2 mJy and show that these S2COSMOS counts are in agreement with previous single-dish surveys, demonstrating that degree-scale fields are sufficient to overcome the effects of cosmic variance in the S850 = 2-10 mJy population. To investigate the properties of the galaxies identified by S2COSMOS sources we measure the surface density of near-infrared-selected galaxies around their positions and identify an average excess of 2.0 0.2 galaxies within a 13″ radius (∼100 kpc at z ∼ 2). The bulk of these galaxies represent near-infrared-selected submillimeter galaxies and/or spatially correlated sources and lie at a median photometric redshift of z = 2.0 0.1. Finally, we perform a stacking analysis at submillimeter and far-infrared wavelengths of stellar-mass-selected galaxies (M = 1010-1012 M ) from z = 0-4, obtaining high-significance detections at 850 m in all subsets (signal-to-noise ratio, S/N = 4-30), and investigate the relation between far-infrared luminosity, stellar mass, and the peak wavelength of the dust spectral energy distribution. The publication of this survey adds a new deep, uniform submillimeter layer to the wavelength coverage of this well-studied COSMOS field.
An advanced backcross population between an accession of Oryza rufipogon (IRGC 105491) and the U.S. cultivar Jefferson ( Oryza sativa ssp. japonica) was developed to identify quantitative trait loci ...(QTLs) for yield, yield components and morphological traits. The genetic linkage map generated for this population consisted of 153 SSR and RFLP markers with an average interval size of 10.3 cM. Thirteen traits were examined, nine of which were measured in multiple environments. Seventy-six QTLs above an experiment-wise significance threshold of P < 0.01 (corresponding to an interval mapping LOD > 3.6 or a composite interval mapping LOD > 3.9) were identified. For the traits measured in multiple environments, 47% of the QTLs were detected in at least two environments. The O. rufipogon allele was favorable for 53% of the yield and yield component QTLs, including loci for yield, grains per panicle, panicle length, and grain weight. Morphological traits related to the domestication process and/or weedy characteristics, including plant height, shattering, tiller type and awns, were found clustered on chromosomes 1 and 4. Comparisons to previous studies involving wild x cultivated crosses revealed O. rufipogon alleles with stable effects in multiple genetic backgrounds and environments, several of which have not been detected in studies between Oryza sativa cultivars, indicating potentially novel alleles from O. rufipogon. Some O. rufipogon-derived QTLs, however, were in similar regions as previously reported QTLs from Oryza sativa cultivars, providing evidence for conservation of these QTLs across the Oryza genus. In addition, several QTLs for grain weight, plant height, and flowering time were localized to putative homeologous regions in maize where QTLs for these traits have been previously reported, supporting the hypothesis of functional conservation of QTLs across the grasses.
We present deep, high-resolution (0 03, 200 pc) ALMA Band 7 observations covering the dust continuum and C ii λ157.7 m emission in four z ∼ 4.4-4.8 sub-millimeter galaxies (SMGs) selected from the ...ALESS and AS2UDS surveys. The data show that the rest-frame 160 m (observed 345 GHz) dust emission is consistent with smooth morphologies on kpc scales for three of the sources. One source, UDS 47.0, displays apparent substructure, but this is also consistent with a smooth morphology-as indicated by simulations showing that smooth exponential disks can appear clumpy when observed at the high angular resolution (0 03) and depth of these observations ( Jy beam−1). The four SMGs are bright C ii emitters. We extract C ii spectra from the high-resolution data, and recover ∼20%-100% of the C ii flux and ∼40%-80% of the dust continuum emission, compared to the previous lower-resolution observations. When tapered to 0 2 resolution, our maps recover ∼80%-100% of the continuum emission, indicating that ∼60% of the emission is resolved out on ∼200 pc scales. We find that the C ii emission in high-redshift galaxies is more spatially extended than the rest-frame 160 m dust continuum by a factor of 1.6 0.4. By considering the / ratio as a function of the star formation rate surface density ( ), we revisit the C ii deficit and suggest that the decline in the / ratio as a function of is consistent with local processes. We also explore the physical drivers that may be responsible for these trends and can give rise to the properties found in the densest regions of SMGs.
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