198 research outputs found

    Self-aligned 0.12mm T-gate In.53Ga.47As/In.52Al.48As HEMT Technology Utilising a Non Annealed Ohmic Contact Strategy

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    An InGaAs/InAlAs based HEMT structure, lattice matched to an InP substrate, is presented in which drive current and transconductance has been optimized through a double-delta doping strategy. Together with an increase in channel carrier density, this allows the use of a non-annealed ohmic contact process. HEMT devices with 120 nm standard and self-aligned T-gates were fabricated using the non-annealed ohmic process. At DC, self-aligned and standard devices exhibited transconductances of up to 1480 and 1100 mS/mm respectively, while both demonstrated current densities in the range 800 mA/mm. At RF, a cutoff frequency f/sub T/ of 190 GHz was extracted for the self-aligned device. The DC characteristics of the standard devices were then calibrated and modelled using a compound semiconductor Monte Carlo device simulator. MC simulations provide insight into transport within the channel and illustrate benefits over a single delta doped structure

    Investigating the mechanisms of endometrial cancer risk in polycystic ovary syndrome: can UK biobank help?

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    Background: UK biobank was set up to investigate the respective contributions of genetic predisposition and environmental exposure to the development of disease and recruited participants between 2006 and 2010. Our aim was to investigate the feasibility of using UK biobank for exploring the association between polycystic ovarian syndrome (PCOS) and endometrial cancer, including the role played by serum IGF-1 levels. Methods: Publicly accessible and freely available online data in the resource section of the UK biobank website were used to determine the prevalence of self reported PCOS and for assessing the quality of data on ovarian imaging and serum biomarkers. A literature review was conducted to compare rates of PCOS in UK Biobank with other populations. Results: UK biobank contains 273,469 women (age range 37-73 years) of whom 643 (0.23%) self-reported PCOS. This was compared with values ranging from 3.1 % to 19.9% obtained from 16 studies picked up by our systematic literature search. Conclusion: It is feasible to use UK biobank to conduct research into the role of IGF-1 in explaining the association between PCOS and endometrial cancer. More detailed phenotyping of women recruited into the diagnostic group of PCOS is, however, vital to underpin this research. The resulting resource would be excellent for researchers interested in exploring the long-term health risks associated with PCOS

    Does Prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy?:A subanalysis from the REx Randomised Controlled Trial

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    Background: Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). Methods: Patients scheduled for NACRT, then potentially curative surgery (August 2014–March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13–17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1–2 weeks before surgery. Results: The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI − 3.4 to 83.7) between groups in change from baseline (p = 0.07). Conclusions: Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation

    Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder

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    Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ

    Bridging conventional and molecular genetics of sorghum insect resistance

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    Sustainable production of sorghum, Sorghum bicolor (L.) Moench, depends on effective control of insect pests as they continue to compete with humans for the sorghum crop. Insect pests are a major constraint in sorghum production, and nearly 150 insect species are serious pests of this crop worldwide and cause more than 9% loss annually. Annual losses due to insect pests in sorghum have been estimated to be 1,089millioninthesemiaridtropics(ICRISATAnnualreport1991.InternationalCropResearchInstituteforSemi−aridTropics.Patancheru,AndhraPradesh,India,1992),butdifferinginmagnitudeonaregionalbasis.KeyinsectpestsintheUSAincludethegreenbug,Schizaphisgraminum(Rondani);sorghummidge,Stenodiplosissorghicola(Coquillett);andvariouscaterpillarsintheSouthernareas.Forexample,damagebygreenbugtosorghumisestimatedtocostUSproducers1,089 million in the semiarid tropics (ICRISAT Annual report 1991. International Crop Research Institute for Semi-arid Tropics. Patancheru, Andhra Pradesh, India, 1992), but differing in magnitude on a regional basis. Key insect pests in the USA include the greenbug, Schizaphis graminum (Rondani); sorghum midge, Stenodiplosis sorghicola (Coquillett); and various caterpillars in the Southern areas. For example, damage by greenbug to sorghum is estimated to cost US producers 248 million annually. The major insect pests of sorghum on a global basis are the greenbug, sorghum midge, sorghum shoot fly (Atherigona soccata Rond.), stem borers (Chilo partellus Swin. and Busseola fusca Fuller), and armyworms (Mythimna separata Walk and Spodoptera frugiperda J.E. Smith). Recent advances in sorghum genetics, genomics, and breeding have led to development of some cutting-edge molecular technologies that are complementary to genetic improvement of this crop for insect pest management. Genome sequencing and genome mapping have accelerated the pace of gene discovery in sorghum..

    Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder

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    Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3–2.8, one-sided p = 6.0 × 10−4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ

    Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.

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    Funder: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)Funder: Dalio Foundation; doi: https://doi.org/10.13039/100009834Funder: Wayne and Gladys Valley Foundation; doi: https://doi.org/10.13039/100001370Funder: Robert Wood Johnson Foundation (RWJF); doi: https://doi.org/10.13039/100000867Funder: U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)Funder: The Dalio FoundationBipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ
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