The role of insulin receptor substrate 2 in hypothalamic and β cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

Boundary element formulations for the numerical solution of two-dimensional diffusion problems with variable coefficients

This is the post-print version of the final paper published in Computers & Mathematics with Applications. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2012 Elsevier B.V.This paper presents new formulations of the radial integration boundary integral equation (RIBIE) and the radial integration boundary integro-differential equation (RIBIDE) methods for the numerical solution of two-dimensional diffusion problems with variable coefficients. The methods use either a specially constructed parametrix (Levi function) or the standard fundamental solution for the Laplace equation to reduce the boundary-value problem (BVP) to a boundary–domain integral equation (BDIE) or boundary–domain integro-differential equation (BDIDE). The radial integration method (RIM) is then employed to convert the domain integrals arising in both BDIE and BDIDE methods into equivalent boundary integrals. The resulting formulations lead to pure boundary integral and integro-differential equations with no domain integrals. Furthermore, a subdomain decomposition technique (SDBDIE) is proposed, which leads to a sparse system of linear equations, thus avoiding the need to calculate a large number of domain integrals. Numerical examples are presented for several simple problems, for which exact solutions are available, to demonstrate the efficiency of the proposed approaches

Herschel-ATLAS: The angular correlation function of submillimetre galaxies at high and low redshift

Original article can be found at: http://www.aanda.org/ Copyright The European Southern ObservatoryWe present measurements of the angular correlation function of galaxies selected from the first field of the H-ATLAS survey. Careful removal of the background from galactic cirrus is essential, and currently dominates the uncertainty in our measurements. For our 250 μm-selected sample we detect no significant clustering, consistent with the expectation that the 250 μm-selected sources are mostly normal galaxies at z 1. For our 350 μm and 500 μm-selected samples we detect relatively strong clustering with correlation amplitudes A of 0.2 and 1.2 at 1', but with relatively large uncertainties. For samples which preferentially select high redshift galaxies at z~2–3 we detect significant strong clustering, leading to an estimate of r0 ~ 7–11 h-1 Mpc. The slope of our clustering measurements is very steep, δ ~ 2. The measurements are consistent with the idea that sub-mm sources consist of a low redshift population of normal galaxies and a high redshift population of highly clustered star-bursting galaxies.Peer reviewe

Pond canopy cover: a resource gradient for anuran larvae

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72395/1/j.1365-2427.2005.01497.x.pd

Flavor changing Z-decays from scalar interactions at a Giga-Z Linear Collider

The flavor changing decay Z -> d_I \bar{d}_J is investigated with special emphasis on the b \bar{s} final state. Various models for flavor violation are considered: two Higgs doublet models (2HDM's), supersymmetry (SUSY) with flavor violation in the up and down-type squark mass matrices and SUSY with flavor violation mediated by R-parity-violating interaction. We find that, within the SUSY scenarios for flavor violation, the branching ratio for the decay Z -> b \bar{s} can reach 10^{-6} for large \tan\beta values, while the typical size for this branching ratio in the 2HDM's considered is about two orders of magnitudes smaller at best. Thus, flavor changing SUSY signatures in radiative Z decays such as Z -> b \bar{s} may be accessible to future ``Z factories'' such as a Giga-Z version of the TESLA design.Comment: 27 pages, 15 figures, REVTeX4. A new section added and a few minor corrections were made in the tex

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Striatal mRNA expression patterns underlying peak dose L-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson’s disease (PD). With prolonged treatment (⩾5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kg s.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 min after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence

Lepton flavor violating Z boson decays induced by scalar unparticle

We predict the branching ratios of the lepton flavor violating Z boson decays Z\to e^{\pm} \mu^{\pm}, Z\to e^{\pm} \tau^{\pm} and Z\to \mu^{\pm} \tau^{\pm} in the case that the lepton flavor violation is carried by the scalar unparticle mediation. We observe that their BRs are strongly sensitive to the unparticle scaling dimension and the branching ratios can reach to the values of the order of 10^{-8}, for the heavy lepton flavor case, for the small values of the scaling dimension.Comment: 15 pages, 5 figures, 1 tabl