Transient but not genetic loss of miR-451 attenuates the development of pulmonary arterial hypertension

<b>Rationale:</b> MicroRNAs are small non-coding RNAs involved in the regulation of gene expression and have recently been implicated in the development of pulmonary arterial hypertension (PAH). Previous work established that miR-451 is up-regulated in rodent models of PAH.<p></p> <b>Objectives:</b> The role of miR-451 in the pulmonary circulation is unknown. We therefore sought to assess the involvement of miR-451 in the development of pulmonary arterial hypertension.<p></p> <b>Methods:</b> Silencing of miR-451 was performed in vivo using miR-451 knockout mice and an antimiR targeting mature miR-451 in rats. Coupled with exposure to hypoxia, indices of pulmonary arterial hypertension were assessed. The effect of modulating miR-451 on human pulmonary artery smooth muscle cell proliferation and migration was analysed.<p></p> <b>Measurements and Main Results:</b> We observed a reduction in systolic right ventricular pressure in hypoxic rats pre-treated with antimiR-451 compared to hypoxia alone (47.7 ± 1.36mmHg and 56.0 ± 2.03mmHg respectively, p<0.01). In miR-451 knockout mice following exposure to chronic hypoxia, no significant differences were observed compared to wild type hypoxic mice. In vitro analysis demonstrated that over-expression of miR-451 in human pulmonary artery smooth muscle cells promoted migration under serum-free conditions. No effect on cellular proliferation was observed.<p></p> <b>Conclusions:</b> Transient inhibition of miR-451 attenuated the development of pulmonary arterial hypertension in hypoxia exposed rats. Genetic deletion of miR-451 had no beneficial effect on indices of pulmonary arterial hypertension, potentially due to pathway redundancy compensating for the loss of miR-451.<p></p&gt

The Imperative of Immigration Reform

Volume 2 - Paper #40_40TheImperativeofImmigrationReform.pdf: 451 downloads, before Oct. 1, 2020

Evaluating the role of a galanin enhancer genotype on a range of metabolic, depressive and addictive phenotypes

Funded by •ERC. Grant Number: 284167 •NIH. Grant Number: 1RO1DK0921127-01 •NWO. Grant Numbers: 463-06-001, 451-04-034Peer reviewedPublisher PD

Lasers incorporating 2D photonic bandgap mirrors

Semiconductor lasers incorporating a 2D photonic lattice as a one end mirror in a Fabry-Perot cavity are demonstrated. The photonic lattice is a 2D hexagonal close-packed array with a lattice constant of 220 nm. Pulsed threshold currents of 110 mA were observed from a 180 μm laser

Note on the importance of hydrocarbon fill for reservoir quality prediction in sandstones

Oil emplacement retarded the rate of quartz cementation in the Brae Formation deep-water sandstone reservoirs of the Miller and Kingfisher fields (United Kingdom North Sea), thus preserving porosity despite the rocks' being buried to depths of 4 km and 120degreesC. Quartz precipitation rates were reduced by at least two orders of magnitude in the oil legs relative to the water legs. Important contrasts in quartz cement abundances and porosities have emerged between the oil and water legs where reservoirs have filled with hydrocarbons gradually over a prolonged period of time (greater than 15 m.y.). The earlier the hydrocarbon fill, the greater is the degree of porosity preservation. Failure to consider this phenomenon during field development could lead to overestimation of porosity and permeability in the water leg, potentially leading in turn to poor decisions about the need for and placement of downflank water injectors. During exploration, the retarding effect of oil on quartz cementation could lead to the presence of viable reservoirs situated deeper than the perceived regional economic basement

Politics makes strange bedfellows: addressing the ‘messy’ power dynamics in design practice

The paper addresses the role of the designer in navigating through politics and power dynamics that can potentially hinder ways in which people have input into a design process. It acknowledges that such obstacles are common to design practices and much is already documented in organisational, business and management frameworks (Best, 2006, p. 97; Jones, 2003). However, the paper draws on the author’s doctoral research that explored how designers work within the complexities of politics and power dynamics and the agency they bring when working within such contexts. Firstly, the paper clarifies its use of the word politics by distinguishing between the Political choices that designers make, to the embedded politics of power dynamics and hidden agendas. It acknowledges how the Political content and intention of design is widely discussed in communication design literature where designers have created political content toward a purposeful political outcome. The paper therefore focuses more on another political aspect to communication design practice that relates to values, relationships and power dynamics. These human aspects of practice are complex, ‘messy’ and are often implicit. The power dynamics within projects can significantly influence the way stakeholders have input into the design process and subsequent project outcome. The politics of the individual, organisation, community or the society can often abruptly and unexpectedly surface through designing. Based on several interviews with a variety of communication design practitioners and project case studies from the author’s research, the paper highlights a role that designers can potentially play in addressing the ‘messy’ politics that can manifest through design projects. The research explored various design interventions to enable a variety of people with different values, opinions and viewpoints within a design project to collectively negotiate them through dialogue. It has discovered that such design interventions can be instrumental in facilitating the dialogic process amongst stakeholders to illuminate differences in values or hidden agendas. The paper proposes that the role of the designer, then, is to facilitate this dialogic process through design interventions to enrich the experience of dialogue and exchange amongst project stakeholders. Keywords: Human-Centred Design; Communication Design; Politics; Power-Dynamics; Design ‘Scaffolds’; Dialogue.</p

The post-investment impact of Business Angels upon their investee companies.

Awarded Small Business Service Award for Best ‘Newcomer’ Paper (£1k). Nominated for Best Paper, ‘Venture Capital and Micro-Finance for SB’ Track, ISBE 2006. Original approach measuring BA impact; employing new indicators (efficiency, survival, profile). Emphasises strategic activities and further financing impact but negative impact of BAs becoming ‘employed’ with investees

East Midlands healthcare and bioscience sector strategy

The healthcare and bioscience sector is one of four priority sectors identified in the regional economic strategy, A Flourishing Region. This document sets out a strategy for maximising the contribution of the healthcare and biosciences sector to the economic development of the East Midlands

Single Point of Entry Long-Term Living Resource System Team Report

Pursuant to House File 451 the Single Point of Entry Long-Term Living Resources System Team, involving several state agencies as well as interested associations, submitted a report to the legislature on recommendations to establish a single point of entry system