Novel genetic susceptibility loci for diabetic end-stage renal disease identified through robust naive Bayes classification

Aims/hypothesis: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel genetic variants associated with diabetic nephropathy and ESRD. Methods: We exploited a novel algorithm, ‘Bag of Naive Bayes’, whose marker selection strategy is complementary to that of conventional genome-wide association models based on univariate association tests. The analysis was performed on a genome-wide association study of 3,464 patients with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study and subsequently replicated with 4,263 type 1 diabetes patients from the Steno Diabetes Centre, the All Ireland-Warren 3-Genetics of Kidneys in Diabetes UK collection (UK–Republic of Ireland) and the Genetics of Kidneys in Diabetes US Study (GoKinD US). Results: Five genetic loci (WNT4/ZBTB40-rs12137135, RGMA/MCTP2-rs17709344, MAPRE1P2-rs1670754, SEMA6D/SLC24A5-rs12917114 and SIK1-rs2838302) were associated with ESRD in the FinnDiane study. An association between ESRD and rs17709344, tagging the previously identified rs12437854 and located between the RGMA and MCTP2 genes, was replicated in independent case–control cohorts. rs12917114 near SEMA6D was associated with ESRD in the replication cohorts under the genotypic model (p < 0.05), and rs12137135 upstream of WNT4 was associated with ESRD in Steno. Conclusions/interpretation: This study supports the previously identified findings on the RGMA/MCTP2 region and suggests novel susceptibility loci for ESRD. This highlights the importance of applying complementary statistical methods to detect novel genetic variants in diabetic nephropathy and, in general, in complex diseases.

On subspace lattices II. Continuity of Lat

We study the continuity of the map Lat sending an ultraweakly closed operator algebra to its invariant subspace lattice. We provide an example showing that Lat is in general discontinuous and give sufficient conditions for the restricted continuity of this map. As consequences we obtain that Lat is continuous on the classes of von Neumann and Arveson algebras and give a general approximative criterion for reflexivity, which extends Arvesonâ??s theorem on the reflexivity of commutative subspace lattices.

Relative energetics and structural properties of zirconia using a self-consistent tight-binding model

We describe an empirical, self-consistent, orthogonal tight-binding model for zirconia, which allows for the polarizability of the anions at dipole and quadrupole levels and for crystal field splitting of the cation d orbitals, This is achieved by mixing the orbitals of different symmetry on a site with coupling coefficients driven by the Coulomb potentials up to octapole level. The additional forces on atoms due to the self-consistency and polarizabilities are exactly obtained by straightforward electrostatics, by analogy with the Hellmann-Feynman theorem as applied in first-principles calculations. The model correctly orders the zero temperature energies of all zirconia polymorphs. The Zr-O matrix elements of the Hamiltonian, which measure covalency, make a greater contribution than the polarizability to the energy differences between phases. Results for elastic constants of the cubic and tetragonal phases and phonon frequencies of the cubic phase are also presented and compared with some experimental data and first-principles calculations. We suggest that the model will be useful for studying finite temperature effects by means of molecular dynamics.

An analogue of the Magnus problem for associative algebras

We prove an analogue of Magnus theorem for associative algebras without unity over arbitrary fields. Namely, if an algebra is given by $n+k$ generators and $k$ relations and has an $n$-element system of generators, then this algebra is a free algebra of rank $n$.

Orbits of operators commuting with the Volterra operator

Asymptotic estimates of the norms of orbits of certain operators that commute with the classical Volterra operator V acting on L-P[0,1], with 1 0, but also to operators of the form phi (V), where phi is a holomorphic function at zero. The method to obtain the estimates is based on the fact that the Riemann-Liouville operator as well as the Volterra operator can be related to the Levin-Pfluger theory of holomorphic functions of completely regular growth. Different methods, such as the Denjoy-Carleman theorem, are needed to analyze the behavior of the orbits of I - cV, where c > 0. The results are applied to the study of cyclic properties of phi (V), where phi is a holomorphic function at 0.

Decompositions of spaces of measures

Let M be the Banach space of sigma-additive complex-valued measures on an abstract measurable space. We prove that any closed, with respect to absolute continuity norm-closed, linear subspace L of M is complemented and describe the unique complement, projection onto L along which has norm 1. Using this fact we prove a decomposition theorem, which includes the Jordan decomposition theorem, the generalized Radon-Nikodym theorem and the decomposition of measures into decaying and non-decaying components as particular cases. We also prove an analog of the Jessen-Wintner purity theorem for our decompositions.

Sequentially continuous non-linear fundamental systems of solutions of affine equations in locally convex spaces

According to the Mickael's selection theorem any surjective continuous linear operator from one Fr\'echet space onto another has a continuous (not necessarily linear) right inverse. Using this theorem Herzog and Lemmert proved that if $E$ is a Fr\'echet space and $T:E\to E$ is a continuous linear operator such that the Cauchy problem $\dot x=Tx$, $x(0)=x_0$ is solvable in $[0,1]$ for any $x_0\in E$, then for any $f\in C([0,1],E)$, there exists a continuos map $S:[0,1]\times E\to E$, $(t,x)\mapsto S_tx$ such that for any $x_0\in E$, the function $x(t)=S_tx_0$ is a solution of the Cauchy problem $\dot x(t)=Tx(t)+f(t)$, $x(0)=x_0$ (they call $S$ a fundamental system of solutions of the equation $\dot x=Tx+f$). We prove the same theorem, replacing "continuous" by "sequentially continuous" for locally convex spaces from a class which contains strict inductive limits of Fr\'echet spaces and strong duals of Fr\'echet--Schwarz spaces and is closed with respect to finite products and sequentially closed subspaces. The key-point of the proof is an extension of the theorem on existence of a sequentially continuous right inverse of any surjective sequentially continuous linear operator to some class of non-metrizable locally convex spaces.

On weak and strong Peano theorems

We say that the Peano theorem holds for a topological vector space $E$ if, for any continuous mapping $f : {\Bbb R}\times E \to E$ and any $(t(0), x(0))$ is an element of ${\Bbb R}\times E$, the Cauchy problem $\dot x(t) = f(t,x(t))$, $x(t(0)) = x(0)$, has a solution in some neighborhood of $t(0)$. We say that the weak version of Peano theorem holds for $E$ if, for any continuous map $f : {\Bbb R}\times E \to E$, the equation $\dot x(t) = f (t, x(t))$ has a solution on some interval. We construct an example (answering a question posed by S. G. Lobanov) of a Hausdorff locally convex topological vector space E for which the weak version of Peano theorem holds and the Peano theorem fails to hold. We also construct a Hausdorff locally convex topological vector space E for which the Peano theorem holds and any barrel in E is neither compact nor sequentially compact.