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Punctual Hilbert schemes for Kleinian singularities as quiver varieties
No full textFor a finite subgroup and , we construct the (reduced scheme underlying the) Hilbert scheme of points on the Kleinian singularity as a Nakajima quiver variety for the framed McKay quiver of , taken at a specific non-generic stability parameter. We deduce that this Hilbert scheme is irreducible (a result previously due to Zheng), normal, and admits a unique symplectic resolution. More generally, we introduce a class of algebras obtained from the preprojective algebra of the framed McKay quiver by a process called cornering, and we show that fine moduli spaces of cyclic modules over these new algebras are isomorphic to quiver varieties for the framed McKay quiver and certain non-generic choices of stability parameter
Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer
No full textBackground
Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).
Materials and method
180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.
Results
166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.
Conclusions
Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same
If Boris Johnson is serious about levelling up, he would plan for a 2026 census now
No full textAn extra population survey, on top of next week’s, would provide information the country really need
Ligand-engineered bandgap stability in mixed-halide perovskite LEDs
No full textLead halide perovskites are promising semiconductors for light-emitting applications because they exhibit bright, bandgap-tunable luminescence with high colour purity1,2. Photoluminescence quantum yields close to unity have been achieved for perovskite nanocrystals across a broad range of emission colours, and light-emitting diodes with external quantum efficiencies exceeding 20 per cent—approaching those of commercial organic light-emitting diodes—have been demonstrated in both the infrared and the green emission channels1,3,4. However, owing to the formation of lower-bandgap iodide-rich domains, efficient and colour-stable red electroluminescence from mixed-halide perovskites has not yet been realized5,6. Here we report the treatment of mixed-halide perovskite nanocrystals with multidentate ligands to suppress halide segregation under electroluminescent operation. We demonstrate colour-stable, red emission centred at 620 nanometres, with an electroluminescence external quantum efficiency of 20.3 per cent. We show that a key function of the ligand treatment is to ‘clean’ the nanocrystal surface through the removal of lead atoms. Density functional theory calculations reveal that the binding between the ligands and the nanocrystal surface suppresses the formation of iodine Frenkel defects, which in turn inhibits halide segregation. Our work exemplifies how the functionality of metal halide perovskites is extremely sensitive to the nature of the (nano)crystalline surface and presents a route through which to control the formation and migration of surface defects. This is critical to achieve bandgap stability for light emission and could also have a broader impact on other optoelectronic applications—such as photovoltaics—for which bandgap stability is required
A scenario-based approach to multi-agent optimization with distributed information
No full textIn this paper, we consider optimization problems involving multiple agents. Each agent introduces its own constraints on the optimization vector, and the constraints of all agents depend on a common source of uncertainty. We suppose that uncertainty is known locally to each agent through a private set of data (multi-agent scenarios), and that each agent enforces its scenario-based constraints to the solution of the multi-agent optimization problem. Our goal is to assess the feasibility properties of the corresponding multi-agent scenario solution. In particular, we are able to provide a priori certificates that the solution is feasible for a new occurrence of the global uncertainty with a probability that depends on the size of the datasets and the desired confidence level. The recently introduced wait-and-judge approach to scenario optimization and the notion of support rank are used for this purpose. Notably, decision-coupled and constraint-coupled uncertain optimization programs for multi-agent systems fit our framework and, hence, any distributed optimization scheme to solve the associated multi-agent scenario problem can be accompanied with our a priori probabilistic feasibility certificates
Microbe Profile: dictyostelium discoideum: model system for development, chemotaxis and biomedical research
No full textThe social amoeba Dictyostelium discoideum is a versatile organism that is unusual in
alternating between single-celled and multi-celled forms. It possesses highly-developed
systems for cell motility and chemotaxis, phagocytosis, and developmental pattern formation.
As a soil amoeba growing on microorganisms, it is exposed to many potential pathogens; it
thus provides fruitful ways of investigating host-pathogen interactions and is emerging as
an influential model for biomedical research
Millet consumption in Siberia prior to mid-second millenium BC? A review of recent developments
No full textIn this paper we discuss recent developments in documenting the spread of millet across the Eurasian steppes. We emphasize that, despite a recent proposal that millet consumption in southern Siberia can be attributed to the Early Bronze Age (i.e., the late third to early second millennium BC), at present there are no direct data for southern Siberia indicating the consumption of millet prior to the Late Bronze Age, from the 14th century BC. We also present in full the combined stable isotope and 14C datasets from the Minusinsk Basin to support this conclusion
Undernutrition: a major but potentially preventable cause of poor outcomes in children living with sickle cell disease in Africa
No full textHigher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis
No full textBackground Premorbid body mass index, physical activity, diabetes and cardiovascular disease have been associated with an altered risk of developing amyotrophic lateral sclerosis (ALS). There is evidence of shared genetic risk between ALS and lipid metabolism. A very large prospective longitudinal population cohort permits the study of a range of metabolic parameters and the risk of subsequent diagnosis of ALS.
Methods The risk of subsequent ALS diagnosis in those enrolled prospectively to the UK Biobank (n=502 409) was examined in relation to baseline levels of blood high and low density lipoprotein (HDL, LDL), total cholesterol, total cholesterol:HDL ratio, apolipoproteins A1 and B (apoA1, apoB), triglycerides, glycated haemoglobin A1c (HbA1c) and creatinine, plus self-reported exercise and body mass index.
Results Controlling for age and sex, higher HDL (HR 0.84, 95% CI 0.73 to 0.96, p=0.010) and apoA1 (HR 0.83, 95% CI 0.72 to 0.94, p=0.005) were associated with a reduced risk of ALS. Higher total cholesterol:HDL was associated with an increased risk of ALS (HR 1.17, 95% CI 1.05 to 1.31, p=0.006). In models incorporating multiple metabolic markers, higher LDL or apoB was associated with an increased risk of ALS, in addition to a lower risk with higher HDL or apoA. Coronary artery disease, cerebrovascular disease and increasing age were also associated with an increased risk of ALS.
Conclusions The association of HDL, apoA1 and LDL levels with risk of ALS contributes to an increasing body of evidence that the premorbid metabolic landscape may play a role in pathogenesis. Understanding the molecular basis for these changes will inform presymptomatic biomarker development and therapeutic targeting