The Genetic Landscape of Renal Complications in Type 1 Diabetes

Diabetes is the leading cause of end stage renal disease. Despite evidence for a substantial heritability of diabetic kidney disease, efforts to identify genetic susceptibility variants have had limited success. We extended previous efforts in three dimensions, examining a more comprehensive set of genetic variants in larger numbers of subjects with type 1 diabetes characterized for a wider range of cross-sectional diabetic kidney disease phenotypes. In 2,843 subjects, we estimated that the heritability of diabetic kidney disease was 35% ( p=6x10-3 ). Genome-wide association analysis and replication in 12,540 individuals identified no single variants reaching stringent levels of significance and, despite excellent power, provided little independent confirmation of previously published associated variants. Whole exome sequencing in 997 subjects failed to identify any large-effect coding alleles of lower frequency influencing the risk of diabetic kidney disease. However, sets of alleles increasing body mass index ( p=2.2×10-5) and the risk of type 2 diabetes (p=6.1x10-4 ) were associated with the risk of diabetic kidney disease. We also found genome-wide genetic correlation between diabetic kidney disease and failure at smoking cessation ( p=1.1×10-4 ). Pathway analysis implicated ascorbate and aldarate metabolism ( p=9×10-6), and pentose and glucuronate interconversions ( p=3×10-6) in pathogenesis of diabetic kidney disease. These data provide further evidence for the role of genetic factors influencing diabetic kidney disease in those with type 1 diabetes and highlight some key pathways that may be responsible. Altogether these results reveal important biology behind the major cause of kidney disease.  

Recent advances in laser-driven neutron sources

Due to the limited number and high cost of large-scale neutron facilities, there has been a growing interest in compact accelerator-driven sources. In this context, several potential schemes of laser-driven neutron sources are being intensively studied employing laser-accelerated electron and ion beams. In addition to the potential of delivering neutron beams with high brilliance, directionality and ultra-short burst duration, a laser-driven neutron source would offer further advantages in terms of cost-effectiveness, compactness and radiation confinement by closed-coupled experiments. Some of the recent advances in this field are discussed,
showing improvements in the directionality and flux of the laser-driven neutron beams.

Two problems from the Polishchuk and Positselski book on Quadratic algebras

In the book ’Quadratic algebras’ by Polishchuk and Positselski [23] algebras with a small number of generators (n = 2, 3) are considered. For some number r of relations possible Hilbert series are listed, and those appearing as series of Koszul algebras are specified. The first case, where it was not possible to do, namely the case of three generators n = 3 and six relations r = 6 is formulated as an open problem. We give here a complete answer to this question, namely for quadratic algebras with dimA_1 = dimA_2 = 3, we list all possible Hilbert series, and find out which of them can come from Koszul algebras, and which can not. As a consequence of this classification, we found an algebra, which serves as a counterexample to another problem from the same book [23] (Chapter 7, Sec. 1, Conjecture 2), saying that Koszul algebra of finite global homological dimension d has dimA_1 > d. Namely, the 3-generated algebra A given by relations xx + yx = xz = zy = 0 is Koszul and its Koszul dual algebra A^! has Hilbert series of degree 4: HA! (t) = 1 + 3t + 3t^2 + 2t^3 + t^4, hence A has global homological dimension 4.