Deletion of Gpr27 in vivo reduces insulin mRNA but does not result in diabetes.

Gpr27 is a highly conserved, orphan G protein coupled receptor (GPCR) previously implicated in pancreatic beta cell insulin transcription and glucose-stimulated insulin secretion in vitro. Here, we characterize a whole-body mouse knockout of Gpr27. Gpr27 knockout mice were born at expected Mendelian ratios and exhibited no gross abnormalities. Insulin and Pdx1 mRNA in Gpr27 knockout islets were reduced by 30%, but this did not translate to a reduction in islet insulin content or beta cell mass. Gpr27 knockout mice exhibited slightly worsened glucose tolerance with lower plasma insulin levels while maintaining similar insulin tolerance. Unexpectedly, Gpr27 deletion reduced expression of Eif4e3, a neighboring gene, likely by deleting transcription start sites on the anti-sense strand of the Gpr27 coding exon. Our data confirm that loss of Gpr27 reduces insulin mRNA in vivo but has only minor effects on glucose tolerance

Transient Thermal Diffusion in Conical Bodies

A numerical solution has been obtained for transient thermal diffusion in a cone in which chemical, electrical or nuclear energy at a constant rate. An implicit method is used to set up the finite difference equations and detailed analysis is carried out to trace the time history of the temperature distribution from the initial stages to the steady state. The effect of the rate of heat generation on the time required to reach steady state thermal distribution has also been depicted

Transient Heat Transfer in Composite Solids with Non-Linear Boundary Condition

Transient heat transfer in composite media with non-linear radiation boundary condition has been studied by implicit finite difference scheme. It is observed that as the diffusivity ratio decreases there is more transfer of heat from radiating surface towards the non-radiating surface

Excitons in boron nitride nanotubes: dimensionality effects

We show that the optical absorption spectra of boron nitride (BN) nanotubes are dominated by strongly bound excitons. Our first-principles calculations indicate that the binding energy for the first and dominant excitonic peak depends sensitively on the dimensionality of the system, varying from 0.7 eV in bulk hexagonal BN via 2.1 eV in the single sheet of BN to more than 3 eV in the hypothetical (2,2) tube. The strongly localized nature of this exciton dictates the fast convergence of its binding energy with increasing tube diameter towards the sheet value. The absolute position of the first excitonic peak is almost independent of the tube radius and system dimensionality. This provides an explanation for the observed "optical gap" constancy for different tubes and bulk hBN [R. Arenal et al., to appear in Phys. Rev. Lett. (2005)].Comment: 5 pages, 2 figure

Discrimination between two mechanisms of surface-scattering in a single-mode waveguide

Transport properties of a single-mode waveguide with rough boundary are studied by discrimination between two mechanisms of surface scattering, the amplitude and square-gradient ones. Although these mechanisms are generically mixed, we show that for some profiles they can separately operate within non-overlapping intervals of wave numbers of scattering waves. This effect may be important in realistic situations due to inevitable long-range correlations in scattering profiles.Comment: 5 pages, 3 figure

Early Results from the Wisconsin H-Alpha Mapper Southern Sky Survey

After a successful eleven-year campaign at Kitt Peak, we moved the Wisconsin H-Alpha Mapper (WHAM) to Cerro Tololo in early 2009. Here we present some of the early data after a few months under southern skies. These maps begin to complete the first all-sky, kinematic survey of the diffuse H-alpha emission from the Milky Way. Much of this emission arises from the Warm Ionized Medium (WIM), a significant component of the ISM that extends a few kiloparsecs above the Galactic disk. While this first look at the data focuses on the H-alpha survey, WHAM is also capable of observing many other optical emission lines, revealing fascinating trends in the temperature and ionization state of the WIM. Our ongoing studies of the physical conditions of diffuse ionized gas will continue from the southern hemisphere following the H-alpha survey. In addition, future observations will cover the full velocity range of the Magellanic Stream, Bridge, and Clouds to trace the ionized gas associated with these neighboring systems.Comment: 4 pages, 2 figures. To appear in "The Dynamic ISM: A celebration of the Canadian Galactic Plane Survey," ASP Conference Serie

Regulation of Proteins Implicated in Alzheimer’s Disease by MicroRNAs

poster abstractAlzheimer’s Disease (AD) is a neurodegenerative disorder characterized by the deposition of Amyloid-Beta (Aβ) peptide in the brain. This toxic peptide is generated by the sequential cleavage of Amyloid Precursor Protein (APP) by Beta-site APP-cleaving enzyme-1 (BACE-1) and γ-secretase. The disorder is also characterized by the perturbation of calcium homeostasis in neurons. MicroRNAs are short, single-stranded RNAs that are able to influence protein expression by targeting the 3’ Untranslated region (UTR) or 5’ UTR of mRNAs. Previous work in our laboratory has shown that miR-101, miR-153 and miR-346 can regulate APP whereas miR-339-5p can lower BACE1 expression. Here, we aim to reduce APP, BACE1 and Aβ levels, in vitro, by the addition of microRNAs that target the 3’ UTR of APP and BACE1. We show that in a human astrocytoma-glioblastoma (U373) cell line, the expression of BACE1 protein is significantly reduced compared to the mock condition upon transfecting miR-298, miR-328 and miR-144. miR-298 also reduces Aβ levels in these cells. Similarly, in HeLa cells, we show that miR-520c, miR-20b and miR-144 produce a reduction in APP expression compared to both mock and a negative control microRNA mimic. Additionally, we observed that knocking down APP using siRNA, but not knocking down BACE1, lowers basal intracellular calcium levels as well as changes the kinetics of Potassium Chloride (KCl)-induced intracellular calcium influx in a human fetal brain (HFB) culture, when compared to control. miR-346 increases basal calcium levels, but does not affect KCl-induced calcium transients in our HFB culture. Taken together, these results show that miRNAs can influence both the protein expression as well as calcium homeostasis in different human cell culture models. By reducing levels of proteins implicated in AD pathology and by reversing calcium dysregulation, our results will benefit AD research and generate possibilities for novel therapeutics

A Whole-Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response.

Insulin production by the pancreatic β-cell is required for normal glucose homeostasis. While key transcription factors that bind to the insulin promoter are known, relatively little is known about the upstream regulators of insulin transcription. Using a whole-genome RNA interference screen, we uncovered 26 novel regulators of insulin transcription that regulate diverse processes including oxidative phosphorylation, vesicle traffic, and the unfolded protein response (UPR). We focused on Spry2-a gene implicated in human type 2 diabetes by genome-wide association studies but without a clear connection to glucose homeostasis. We showed that Spry2 is a novel UPR target and its upregulation is dependent on PERK. Knockdown of Spry2 resulted in reduced expression of Serca2, reduced endoplasmic reticulum calcium levels, and induction of the UPR. Spry2 deletion in the adult mouse β-cell caused hyperglycemia and hypoinsulinemia. Our study greatly expands the compendium of insulin promoter regulators and demonstrates a novel β-cell link between Spry2 and human diabetes

Hypergraphic LP Relaxations for Steiner Trees

We investigate hypergraphic LP relaxations for the Steiner tree problem, primarily the partition LP relaxation introduced by Koenemann et al. [Math. Programming, 2009]. Specifically, we are interested in proving upper bounds on the integrality gap of this LP, and studying its relation to other linear relaxations. Our results are the following. Structural results: We extend the technique of uncrossing, usually applied to families of sets, to families of partitions. As a consequence we show that any basic feasible solution to the partition LP formulation has sparse support. Although the number of variables could be exponential, the number of positive variables is at most the number of terminals. Relations with other relaxations: We show the equivalence of the partition LP relaxation with other known hypergraphic relaxations. We also show that these hypergraphic relaxations are equivalent to the well studied bidirected cut relaxation, if the instance is quasibipartite. Integrality gap upper bounds: We show an upper bound of sqrt(3) ~ 1.729 on the integrality gap of these hypergraph relaxations in general graphs. In the special case of uniformly quasibipartite instances, we show an improved upper bound of 73/60 ~ 1.216. By our equivalence theorem, the latter result implies an improved upper bound for the bidirected cut relaxation as well.Comment: Revised full version; a shorter version will appear at IPCO 2010