6,040 research outputs found

    MicroRNA-9 represses sirtuin 1 (SIRT1) in human keratinocytes

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    The protein deacetylase sirtuin 1 (SIRT1) is an established regulator of diverse physiological processes and one of several promising targets for pharmacologic modulation of ageing and longevity. In normal human keratinocytes, SIRT1 has been shown to inhibit proliferation and promote differentiation. MicroRNAs (miRNAs), small non-coding RNA molecules that negatively regulate gene expression, have been shown to regulate SIRT1 expression in several cell types. Using western blotting, we show that miR-9 represses SIRT1 expression in the HaCaT human keratinocytes. The attenuation of SIRT1 levels in response to ectopic miR-9 occurred in a dose-dependent manner. As miR-9 expression is known to be under epigenetic control, the effect of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was examined. Levels of mature miR-9 increased 8-fold following TSA treatment of HaCaT keratinocytes. Expression of the primary transcripts from which miR-9 is derived was also raised in HaCaT keratinocytes exposed to TSA, with a 7-fold elevation of pri-miR-9-1 and 4-fold increase of pri-miR-3. In contrast the DNA methyl transferase inhibitor 5-deoxy-azacytidine (DAC) had little effect on miR-9 or primary miR-9 expression. Together, our findings point to a role for chromatin remodelling in regulating miR-9 levels in human keratinocytes and in turn modulation of SIRT1 expression by miR-9

    Low frequency sound propagation in activated carbon

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    Activated carbon can adsorb and desorb gas molecules onto and off its surface. Research has examined whether this sorption affects low frequency sound waves, with pressures typical of audible sound, interacting with granular activated carbon. Impedance tube measurements were undertaken examining the resonant frequencies of Helmholtz resonators with different backing materials. It was found that the addition of activated carbon increased the compliance of the backing volume. The effect was observed up to the highest frequency measured (500 Hz), but was most significant at lower frequencies (at higher frequencies another phenomenon can explain the behavior). An apparatus was constructed to measure the effective porosity of the activated carbon as well as the number of moles adsorbed at sound pressures between 104 and 118 dB and low frequencies between 20 and 55 Hz. Whilst the results were consistent with adsorption affecting sound propagation, other phenomena cannot be ruled out. Measurements of sorption isotherms showed that additional energy losses can be caused by water vapor condensing onto and then evaporating from the surface of the material. However, the excess absorption measured for low frequency sound waves is primarily caused by decreases in surface reactance rather than changes in surface resistance

    MicroRNA-184 and its lncRNA sponge uca1 are induced in wounded keratinocytes in a store-operated calcium entry-dependent manner.

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    There remains a significant need for therapeutic interventions for wound healing as the clinical and socioeconomic challenges presented by the ageing population and associated rise in non-healing wounds persist, exerting enormous pressure on health services. MicroRNAs (miRNAs) are short ≈22 nucleotide non-coding RNA molecules that fine-tune gene expression by degradation of mRNA targets. Several miRNAs promote keratinocyte migration, including miR-21, miR-31 and miR-132 (reviewed in 3 ), hence miRNA-dependent migration is emerging as a framework for wound healing. This article is protected by copyright. All rights reserved

    Development Needs of Middle Managers In Higher Education Institutions: A Case Study of A Post 1992 New University in UK

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    Development of staff by Human Resources (HR) department in any organisation is crucial to implement its strategy, operations, goals and for eventual success. Similarly, in Higher Education Institutions (HEIs) the Middle Managers (MM) are drivers who execute organisation vision, mission and contribute towards its desired attainment. MM job titles at faculty level include Deans, Head of Departments, Subject leaders and Principle lecturers/Programme leaders. However, evidenced from contemporary literature, changes and challenges transpiring in HEIs sector is influencing and generating tremendous pressures and workloads for MM to work effectively and efficiently in their respective roles. Therefore, the fortitude of this study is to explore this phenomenon and capture true MM Development Needs (DN) and propose a conceptual model. In stage one (qualitative stage), a semi structured interview protocol was derived from 2 pilot semi structured interviews and literature review theoretical model. A meso case study (sub cases and individual embedded cases) of a UK Post 1992 university was conducted with 23 semi-structured interviews lasting an hour each. 14 interviews were analysed in rich detail. The major findings depict 251 themes from the qualitative data analysis categorised under 6 main categories. To validated and cross compare the themes, 9 collected interviews were audio listened to verify and validate the findings. In summary, based on stage 1 results, there is a gap in the development programmes provided by HR in HEIs, and MM requirements. Future study in Stage two (quantitative stage), will further explore MM development needs via pilot testing a survey questionnaire in the same post 1992 HEI before disseminating it externally to 141 UK HEIs providers (Gov. UK, 2017) for validation prior to proposing the final development model

    Development of a best practice statement on the use of ankle-foot orthoses following stroke in Scotland

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    A National Health Service Quality Improvement Scotland (NHS QIS) scoping exercise in 2007 identified the use of ankle-foot orthoses (AFOs) following stroke as a clinical improvement priority, leading to the development of a best practice statement (BPS) on AFO use after stroke. This paper outlines the development process of the BPS which is available from NHS QIS. The authors were involved in the development of the BPS as part of a working group that included practitioners from the fields of orthotics, physiotherapy, stroke nursing and bioengineering, and staff of NHS QIS and a patient representative. In consultation with an NHS QIS health services researcher, the authors undertook a systematic literature review to evidence where possible the recommendations made in the BPS. Where evidence was unavailable, consensus was reached by the expert working group. As the BPS was designed for the non-specialist and non-orthotic practitioner the authors also developed educational resources which were included within the BPS to aid the understanding of the principles underpinning orthotic design and prescription. The BPS has been widely distributed throughout the health service in Scotland and is available electronically at no cost via the NHS QIS website. At part of an ongoing evaluation of the impact of the BPS on the quality of orthotic provision, NHS QIS has invited feedback regarding successes and challenges to implementation

    Haemorrhage control of the pre-hospital trauma patient.

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    . This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

    Probabilistic Analysis of Optimization Problems on Generalized Random Shortest Path Metrics

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    Simple heuristics often show a remarkable performance in practice for optimization problems. Worst-case analysis often falls short of explaining this performance. Because of this, "beyond worst-case analysis" of algorithms has recently gained a lot of attention, including probabilistic analysis of algorithms. The instances of many optimization problems are essentially a discrete metric space. Probabilistic analysis for such metric optimization problems has nevertheless mostly been conducted on instances drawn from Euclidean space, which provides a structure that is usually heavily exploited in the analysis. However, most instances from practice are not Euclidean. Little work has been done on metric instances drawn from other, more realistic, distributions. Some initial results have been obtained by Bringmann et al. (Algorithmica, 2013), who have used random shortest path metrics on complete graphs to analyze heuristics. The goal of this paper is to generalize these findings to non-complete graphs, especially Erd\H{o}s-R\'enyi random graphs. A random shortest path metric is constructed by drawing independent random edge weights for each edge in the graph and setting the distance between every pair of vertices to the length of a shortest path between them with respect to the drawn weights. For such instances, we prove that the greedy heuristic for the minimum distance maximum matching problem, the nearest neighbor and insertion heuristics for the traveling salesman problem, and a trivial heuristic for the kk-median problem all achieve a constant expected approximation ratio. Additionally, we show a polynomial upper bound for the expected number of iterations of the 2-opt heuristic for the traveling salesman problem.Comment: An extended abstract appeared in the proceedings of WALCOM 201
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