Linear-Accelerator Program

Contains reports on one research project

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

In-situ monitoring of surface post-processing in large aperture fused silica optics with Optical Coherence Tomography

Optical Coherence Tomography is explored as a method to image laser-damage sites located on the surface of large aperture fused silica optics during post-processing via CO{sub 2} laser ablation. The signal analysis for image acquisition was adapted to meet the sensitivity requirements for this application. A long-working distance geometry was employed to allow imaging through the opposite surface of the 5-cm thick optic. The experimental results demonstrate the potential of OCT for remote monitoring of transparent material processing applications

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on three research projects

Aesthetics of self-scaling: parallaxed transregionalism and Kutluğ Ataman's art practice

This article examines relations of ethnography, contemporary art-practice, globalisation and scalar geopolitics with particular reference to Kutluğ Ataman’s artworks. Having been shortlisted for the Turner Prize at the Tate and awarded the prestigious international Carnegie Prize in 2004 with his forty-screen video installation Küba (2004), Ataman became an extremely well-known, globally acclaimed artist and filmmaker. Self-conscious of their global travel and critically attentive to the contemporary ethnographic turn in the visual arts scene, Ataman’s video-works perform a conscientious failure of representing cultural alterity as indigeneity. Concentrating on the artist’s engagement with ethnography, this article contains three main parts. Analyses of the selection of videos in each part will give an account of different scalar aspects of Ataman’s artworks. It will first revisit a previous study (Çakirlar 2011) on the artist’s earlier work of video-portraits including Never My Soul! (2002) and Women Who Wear Wigs (1999). A detailed discussion of Küba follows, which may be taken as the ‘hinge - work’ in Ataman’s oeuvre that marks a scalar transition in his critical focus - from body and identity to community and geopolitics. The discussion will then move to a brief analysis of the series Mesopotamian Dramaturgies, including the screen-based sculptures Dome (2009), Column (2009), Frame (2009), English as a Second Language (2009), and The Complete Works of William Shakespeare (2009). Rather than addressing scale as a differential concept, this article aims to demonstrate the ways in which Ataman’s art-practice produces self-scaling, self-regioning subjects that unsettle the hierarchical constructions of scale and facilitates a critique of the scalar normativity within the global art world’s regionalisms and internationalisms

DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling. NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on two research projects

Going Solo: findings from a survey of women ageing without a partner and who do not have children

Greater longevity in the UK population has led to the increasing diversity of women experiencing ageing in a multitude of ways. Internationally gender inequalities within ageing are still relatively invisible within both government policy and everyday life for particular groups of women. This paper explores the concept of women growing older ‘solo’ by which we mean women who find themselves non partnered and ageing without children as they move into later life. We report on the findings from a mixed-methods survey of 76 solo women in the UK aged 50 years and over, used to provide a broader overview of the issues and challenges they face as they move into later life. Qualitative data from the survey captured respondents’ perspectives about the links between their relationships status and wellbeing in later life and highlighted specific cumulative disadvantages emerging for some women as a result of their solo lifestyles. We discuss two key themes were identified; ‘solo-loneliness’ and ‘meaningful futures’ in conjunction with the relevant literature and make suggestions for future research within gender and ageing studies that could enhance more positive approaches to solo lifestyles

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far