STAT5a/b contribute to sex bias in vascular disease: A neuroendocrine perspective

Previous studies have elucidated a neuroendocrine mechanism consisting of the hypothalamus (growth hormone releasing hormone, GHRH) – pituitary (growth hormone, GH) – STAT5a/b axis that underlies sex-biased gene expression in the liver. It is now established that male vs female patterned secretion of GHRH, and thus of circulating GH levels (“pulsatile” vs “more continuous” respectively), leading to differently patterned activation of PY-STAT5a/b in hepatocytes results in sex-biased gene expression of cohorts of hundreds of downstream genes. This review outlines new data in support of a STAT5a/b-based mechanism of sex bias in the vascular disease pulmonary hypertension (PH). Puzzling observations in PH include its 2-4-fold higher prevalence in women but a male-dominance in many rodent models, and, paradoxically, inhibition of PH development by estrogens in such models. We observed that conditional deletion of STAT5a/b in vascular smooth muscle cells (SMC) in mice converted the male-dominant model of chronic hypoxia-induced PH into a female-dominant phenotype. In human idiopathic PH, there was reduced STAT5a/b and PY-STAT5 in cells in late-stage obliterative pulmonary arterial lesions in both men and women. A juxtaposition of the prior liver data with the newer PH-related data drew attention to the hypothalamus-GH-STAT5 axis, which is the major target of estrogens at the level of the hypothalamus. This hypothesis explains many of the puzzling aspects of sex bias in PH in humans and rodent models. The extension of STAT5-anchored mechanisms of sex bias to vascular disease emphasizes the contribution of central neuroendocrine processes in generating sexual dimorphism in different tissues and cell types

Manufacture and Characterisation of a Novel, Low Modulus, Negative Poisson’s Ratio Composite

Copyright © 2009 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Composites Science and Technology. 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. A definitive version was subsequently published in Composites Science and Technology, Vol. 69 Issue 5 (2009). DOI: 10.1016/j.compscitech.2008.12.016Relatively few negative Poisson’s ratio (auxetic) composites have been manufactured and characterised and none with inherently auxetic phases [Milton G. J. Mech. Phys. Solids 1992;40:1105–37]. This paper presents the use of a novel double-helix yarn that is shown to be auxetic, and an auxetic composite made from this yarn in a woven textile structure. This is the first reported composite to exhibit auxetic behaviour using inherently auxetic yarns. Importantly, both the yarn and the composite are produced using standard manufacturing techniques and are therefore potentially useful in a wide range of engineering applications

The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I trial

No Abstract

A proposal for broad spectrum proof certificates

International audienceRecent developments in the theory of focused proof systems provide flexible means for structuring proofs within the sequent calculus. This structuring is organized around the construction of ''macro'' level inference rules based on the ''micro'' inference rules which introduce single logical connectives. After presenting focused proof systems for first-order classical logics (one with and one without fixed points and equality) we illustrate several examples of proof certificates formats that are derived naturally from the structure of such focused proof systems. In principle, a proof certificate contains two parts: the first part describes how macro rules are defined in terms of micro rules and the second part describes a particular proof object using the macro rules. The first part, which is based on the vocabulary of focused proof systems, describes a collection of macro rules that can be used to directly present the structure of proof evidence captured by a particular class of computational logic systems. While such proof certificates can capture a wide variety of proof structures, a proof checker can remain simple since it must only understand the micro-rules and the discipline of focusing. Since proofs and proof certificates are often likely to be large, there must be some flexibility in allowing proof certificates to elide subproofs: as a result, proof checkers will necessarily be required to perform (bounded) proof search in order to reconstruct missing subproofs. Thus, proof checkers will need to do unification and restricted backtracking search

Statistical Determination of Bulk Flow Motions

We present here a new parameterization for the bulk motions of galaxies and clusters (in the linear regime) that can be measured statistically from the shape and amplitude of the two-dimensional two-point correlation function. We further propose the one-dimensional velocity dispersion (v_p) of the bulk flow as a complementary measure of redshift-space distortions, which is model-independent and not dependent on the normalisation method. As a demonstration, we have applied our new methodology to the C4 cluster catalogue constructed from Data Release Three (DR3) of the Sloan Digital Sky Survey. We find v_p=270^{+433}km/s (also consistent with v_p=0) for this cluster sample (at z=0.1), which is in agreement with that predicted for a WMAP5-normalised LCDM model (i.e., v_p(LCDM=203km/s). This measurement does not lend support to recent claims of excessive bulk motions (\simeq1000 km/s) which appear in conflict with LCDM, although our large statistical error cannot rule them out. From the measured coherent evolution of v_p, we develop a technique to re-construct the perturbed potential, as well as estimating the unbiased matter density fluctuations and scale--independent bias.Comment: 8 pages, 5 figure

First-principles study of stability and vibrational properties of tetragonal PbTiO_3

A first-principles study of the vibrational modes of PbTiO_3 in the ferroelectric tetragonal phase has been performed at all the main symmetry points of the Brillouin zone (BZ). The calculations use the local-density approximation and ultrasoft pseudopotentials with a plane-wave basis, and reproduce well the available experimental information on the modes at the Gamma point, including the LO-TO splittings. The work was motivated in part by a previously reported transition to an orthorhombic phase at low temperatures [(J. Kobayashi, Y. Uesu, and Y. Sakemi, Phys. Rev. B {\bf 28}, 3866 (1983)]. We show that a linear coupling of orthorhombic strain to one of the modes at Gamma plays a role in the discussion of the possibility of this phase transition. However, no mechanical instabilities (soft modes) are found, either at Gamma or at any of the other high-symmetry points of the BZ.Comment: 8 pages, two-column style with 3 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/index.html#ag_pbt

Magnetoresistance of Two-Dimensional Fermions in a Random Magnetic Field

We perform a semiclassical calculation of the magnetoresistance of spinless two-dimensional fermions in a long-range correlated random magnetic field. In the regime relevant for the problem of the half filled Landau level the perturbative Born approximation fails and we develop a new method of solving the Boltzmann equation beyond the relaxation time approximation. In absence of interactions, electron density modulations, in-plane fields, and Fermi surface anisotropy we obtain a quadratic negative magnetoresistance in the weak field limit.Comment: 12 pages, Latex, no figures, Nordita repor