Opiate Modulation of the Preovulatory Luteinizing Hormone Surge in the Rat

Endogenous opioid peptides have a profound inhibitory influence on the secretion of luteinizing hormone. Recently, it has been proposed that a reduction in the activity of these peptides in the hypothalamus may be the initial neural stimulus for the generation of the preovulatory luteinizing hormone surge which induces ovulation. Furthermore, this action may involve alterations in the activity of monoaminergic neurones which synapse on the luteinizing hormone-releasing hormone neurones in the hypothalamus. This investigation was undertaken to determine the effects of exogenous agonists of various opioid receptor subtypes on, (i) the magnitude of the preovulatory luteinizing hormone surge, and (ii) the activity of monoaminergic neurotransmitters in the hypothalamic areas which contain luteinizing hormone-releasing hormone neurones at the time when the surge is initiated

A first--order irreversible thermodynamic approach to a simple energy converter

Several authors have shown that dissipative thermal cycle models based on Finite-Time Thermodynamics exhibit loop-shaped curves of power output versus efficiency, such as it occurs with actual dissipative thermal engines. Within the context of First-Order Irreversible Thermodynamics (FOIT), in this work we show that for an energy converter consisting of two coupled fluxes it is also possible to find loop-shaped curves of both power output and the so-called ecological function against efficiency. In a previous work Stucki [J.W. Stucki, Eur. J. Biochem. vol. 109, 269 (1980)] used a FOIT-approach to describe the modes of thermodynamic performance of oxidative phosphorylation involved in ATP-synthesis within mithochondrias. In that work the author did not use the mentioned loop-shaped curves and he proposed that oxidative phosphorylation operates in a steady state simultaneously at minimum entropy production and maximum efficiency, by means of a conductance matching condition between extreme states of zero and infinite conductances respectively. In the present work we show that all Stucki's results about the oxidative phosphorylation energetics can be obtained without the so-called conductance matching condition. On the other hand, we also show that the minimum entropy production state implies both null power output and efficiency and therefore this state is not fulfilled by the oxidative phosphorylation performance. Our results suggest that actual efficiency values of oxidative phosphorylation performance are better described by a mode of operation consisting in the simultaneous maximization of the so-called ecological function and the efficiency.Comment: 20 pages, 7 figures, submitted to Phys. Rev.

UK export performance research - review and implications

Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990-2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed

Effective actions with fixed points, (error in derivation of coefficient corrected)

The specific form of the constant term in the asymptotic expansion of the heat-kernel on an axially-symmetric space with a codimension two fixed-point set of conical singularities is used to determine the associated conformal change of the effective action in four dimensions. Another derivation of the relevant coefficient is presented.Comment: 10p,uses JyTeX,MUTP/94/1

Elevated circulating amyloid concentrations in obesity and diabetes promote vascular dysfunction

Diabetes, obesity and Alzheimer’s disease (AD) are associated with vascular complications and impaired nitric oxide (NO) production. Furthermore, increased β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), APP and β-amyloid (Aβ) are linked with vascular disease development and raised BACE1 and Aβ accompany hyperglycemia and hyperlipidemia. However, the causal relationship between obesity and diabetes, raised Aβ and vascular dysfunction is unclear. We report that diet-induced obesity (DIO) in mice raised plasma and vascular Aβ42 that correlated with decreased NO bioavailability, endothelial dysfunction and raised blood pressure. Genetic or pharmacological reduction of BACE1 activity and Aβ42 prevented and reversed, respectively, these outcomes. In contrast, expression of human mutant APP in mice or Aβ42 infusion into control diet-fed mice to mimic obese levels impaired NO production, vascular relaxation and raised blood pressure. In humans, raised plasma Aβ42 correlated with diabetes and endothelial dysfunction. Mechanistically, higher Aβ42 reduced endothelial NO synthase (eNOS), cyclic GMP and protein kinase G (PKG) activity independently of diet whereas endothelin-1 was increased by diet and Aβ42. Lowering Aβ42 reversed the DIO deficit in the eNOS-cGMP-PKG pathway and decreased endothelin-1. Our findings suggest that BACE1 inhibitors may have therapeutic value in the treatment of vascular disease associated with diabetes

py4DSTEM: a software package for multimodal analysis of four-dimensional scanning transmission electron microscopy datasets

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full 2D image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields and other sample-dependent properties. However, extracting this information requires complex analysis pipelines, from data wrangling to calibration to analysis to visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail, and present results from several experimental datasets. We have also implemented a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open source HDF5 standard. We hope this tool will benefit the research community, helps to move the developing standards for data and computational methods in electron microscopy, and invite the community to contribute to this ongoing, fully open-source project

Interacting galaxies in the IllustrisTNG simulations - I : Triggered star formation in a cosmological context

We use the IllustrisTNG cosmological hydrodynamical simulations to investigate how the specific star formation rates (sSFRs) of massive galaxies (M-* > 10(10) M-circle dot) depend on the distance to their closest companions. We estimate sSFR enhancements by comparing with control samples that are matched in redshift, stellar mass, local density, and isolation, and we restrict our analysis to pairs with stellar mass ratios of 0.1 to 10. At small separations (similar to 15 kpc), the mean sSFR is enhanced by a factor of 2.0 +/- 0.1 in the flagship (110.7Mpc)(3) simulation (TNG100-1). Statistically significant enhancements extend out to 3D separations of 280 kpc in the (302.6Mpc)(3) simulation (TNG300-1). We find similar trends in the EAGLE and Illustris simulations, although their sSFR enhancements are lower than those in TNG100-1 by about a factor of two. Enhancements in IllustrisTNG galaxies are seen throughout the redshift range explored (0Peer reviewe

Excreted/secreted Schistosoma mansoni venom allergen-like 9 (SmVAL9) modulates host extracellular matrix remodelling gene expression

AbstractThe Schistosoma mansoni venom allergen-like (SmVAL) protein family consists of 29 members, each possessing a conserved α-β-α sandwich tertiary feature called the Sperm-coating protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain. While the SmVALs have been found in both excretory/secretory (E/S) products and in intra/sub-tegumental (non-E/S) fractions, the role(s) of this family in host/parasite relationships or schistosome developmental processes remains poorly resolved. In order to begin quantifying SmVAL functional diversity or redundancy, dissecting the specific activity (ies) of individual family members is necessary. Towards this end, we present the characterisation of SmVAL9; a protein previously found enriched in both miracidia/sporocyst larval transformation proteins and in egg secretions. While our study confirms that SmVAL9 is indeed found in soluble egg products and miracidia/sporocyst larval transformation proteins, we find it to be maximally transcribed/translated in miracidia and subsequently down-regulated during in vitro sporocyst development. SmVAL9 localisation within sporocysts appears concentrated in parenchymal cells/vesicles as well as associated with larval germinal cells. Furthermore, we demonstrate that egg-derived SmVAL9 carries an N-linked glycan containing a schistosome-specific difucosyl element and is an immunogenic target during chronic murine schistosomiasis. Finally, we demonstrate that recombinant SmVAL9 affects the expression of extracellular matrix, remodelling matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) gene products in both Biomphalaria glabrata embryonic cell (BgMMP1) and Mus musculus bone marrow-derived macrophage (MmMMP2, MmMMP9, MmMMP12, MmMMP13, MmMMP14, MmMMP28, TIMP1 and TIMP2) in vitro cultures. These findings importantly suggest that excreted/secreted SmVAL9 participates in tissue reorganisation/extracellular matrix remodelling during intra-mammalian egg translocation, miracidia infection and intra-molluscan sporocyst development/migration

Standard setting Very Short Answer Questions (VSAQs) relative to Single Best Answer Questions (SBAQs): does having access to the answers make a difference?

Background: We investigated whether question format and access to the correct answers affect the pass mark set by standard-setters on written examinations. Methods: Trained educators used the Angoff method to standard set two 50-item tests with identical vignettes, one in a single best answer question (SBAQ) format (with five answer options) and the other in a very short answer question (VSAQ) format (requiring free text responses). Half the participants had access to the correct answers and half did not. The data for each group were analysed to determine if the question format or having access to the answers affected the pass mark set. Results: A lower pass mark was set for the VSAQ test than the SBAQ test by the standard setters who had access to the answers (median difference of 13.85 percentage points, Z = -2.82, p = 0.002). Comparable pass marks were set for the SBAQ test by standard setters with and without access to the correct answers (60.65% and 60.90% respectively). A lower pass mark was set for the VSAQ test when participants had access to the correct answers (difference in medians -13.75 percentage points, Z = 2.46, p = 0.014). Conclusions: When given access to the potential correct answers, standard setters appear to appreciate the increased difficulty of VSAQs compared to SBAQs