Hypersensitivity of BRCA1 heterozygote lymphoblastoid cells to gamma radiation and PARP inhibitors

This article is made available through the Brunel Open Access Publishing Fund. Copyright @ 2013 Bourton EC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PARP inhibitors can be used to induce synthetic lethality in cells with bi-allelic BRCA1 and BRCA2 mutations. However the effect of PARP inhibitors in combination with radiation on cells with mono-allelic mutations of BRCA1 and BRCA2 is unknown. We have examined the cell survival response of lymphoblastoid cells derived from normal individuals and those derived from carriers of BRCA1 and BRCA2 mutations, following exposure to ionising radiation and the PARP inhibitor Olaparib. Two lymphoblastoid cell lines from normal individuals and three with mono-allelic mutations in BRCA1 and BRCA2 were exposed to increasing doses of gamma radiation either alone or in combination with 5 μM Olaparib. Cell survival was measured using the MTT assay. Exposure to increasing doses of gamma radiation caused a reduction in cell survival of all cell types. The combined exposure to gamma radiation and 5 μM Olaparib did not enhance cell kill in normal or BRCA2 heterozygote lymphoblastoid cells but significantly enhanced cell kill in cells derived from BRCA1 carriers (P = 0.02). The treatment of cancer patients carrying mutations in the BRCA1 gene with radiotherapy and the PARP inhibitor Olaparib may significantly enhance radiation induced normal tissue toxicity in these patients.Vidal Sassoon Foundation of America and “The Balls to Cancer” Charity, Coventry, U

Reasons for living following an acquired brain injury: A mixed thematic analysis

Considering the prevalence of acquired brain injury (ABI) and the concerning statistics around the associated risk of problematic substance use, impacted mental health, and suicidality (3-4 greater risk of suicidality in those with TBI), and the lack of qualitative, recent, and UK based research. This study aimed to explore what people’s reasons for living after ABI were. Individuals living with ABI were recruited via BABICM (British Association of Brain Injury and Complex Case Management) to participate in semi-structured interviews. A mixed thematic analysis was conducted on the transcripts using the themes from Knight, Norman and Simpson (2020) as a framework for a deductive analysis and then a reflexive inductive thematic analysis was conducted. The participants (four British males) had experienced a TBI (average time since injury 26 years). Two overarching themes of Lost and maintained sense of self, and ABI is a hidden disability, and five main themes Acceptance, Support networks, Experiences of low mood and suicidality, Protective factors and coping strategies, and Overcoming challenges and posttraumatic growth were identified along with several subthemes. Suicidality was a comparatively minor theme and did not underlie all the other themes as in the Knight et al. paper. The themes that emerged were focused on factors that impact recovery and rehabilitation (positively and negatively), wellbeing and mental health more generally. The data might point toward suicidality in this population being reduced or prevented through a comprehensive package of support, long-term case management, acceptance, and various protective factors

Simulation of a synergistic six-post motion system on the flight simulator for advanced aircraft at NASA-Ames

Motion system drive philosophy and corresponding real-time software have been developed for the purpose of simulating the characteristics of a typical synergistic Six-Post Motion System (SPMS) on the Flight Simulator for Advanced Aircraft (FSAA) at NASA-Ames which is a non-synergistic motion system. This paper gives a brief description of these two types of motion systems and the general methods of producing motion cues of the FSAA. An actuator extension transformation which allows the simulation of a typical SPMS by appropriate drive washout and variable position limiting is described

Home-based rehabilitation: Physiotherapy student and client perspectives

Background. Home-based rehabilitation (HBR) in under-resourced areas in a primary healthcare (PHC) context exposes students to the real-life situations of their clients. There is a scarcity of literature on student and client experiences of HBR in the physiotherapy context. Increased knowledge of HBR could result in an enhanced experience for both student and client. This study sought to discover the perceptions of final-year physiotherapy students and their clients relating to their experiences of HBR during a PHC placement in a resource-constrained setting.Objectives. To explore the experiences and perceptions of physiotherapy students and their clients regarding HBR as part of clinical training in resource-constrained settings. To discover the barriers to and facilitators of effective HBR.Methods. An exploratory case study was performed. A qualitative phenomenologicalresearch design in the interpretivist paradigm was used. Semistructured interviews were conducted with clients (n=7) living in an under-resourced setting, who had received HBR from physiotherapy students. Paired interviews were conducted with final-year physiotherapy students (n=6) after their HBR placement.Results. Clients appreciated the students’ services; however, data revealed communication barriers and unmet expectations. Students reported struggling to adapt to the context, resulting in interventions not being sufficiently client-centred. They voiced a need for language competency and earlier exposure to such contexts.Conclusion. Exposure to real-life situations in under-resourced settings in HBR provides valuable situated and authentic learning opportunities for physiotherapy students. The experience can be useful in preparing graduates to address the needs of the populations they serve during community service

Carrier localization mechanisms in InGaN/GaN quantum wells

Localization lengths of the electrons and holes in InGaN/GaN quantum wells have been calculated using numerical solutions of the effective mass Schr\"odinger equation. We have treated the distribution of indium atoms as random and found that the resultant fluctuations in alloy concentration can localize the carriers. By using a locally varying indium concentration function we have calculated the contribution to the potential energy of the carriers from band gap fluctuations, the deformation potential and the spontaneous and piezoelectric fields. We have considered the effect of well width fluctuations and found that these contribute to electron localization, but not to hole localization. We also simulate low temperature photoluminescence spectra and find good agreement with experiment.Comment: 7 pages, 7 figure

Evaluation of Geologic CO\u3csub\u3e2\u3c/sub\u3e Sequestration Potential and CO\u3csub\u3e2\u3c/sub\u3e Enhanced Oil Recovery in Kentucky

Kentucky gets approximately 95 percent of its electricity from coal-fired power plants, which produce significant amounts of carbon dioxide (CO2). In 2005, Kentucky coal-fired plants vented 102.8 million short tons of CO2 into the atmosphere. The economic vitality of the state will be affected by its ability to develop and apply a portfolio of technologies that will mitigate input of CO2 into the atmosphere. One technology that has the potential to assist in this challenge is geologic carbon storage, which captures CO2 at point sources and injects it into deep rock strata that can store it for tens of thousands of years and longer. Previous studies suggest that Kentucky has the capacity to store up to 1 billion tons of CO2 in underground strata. By necessity, the capacity calculations are high-level estimates, and consequently, actual capacity remains unproved and even speculative. In addition, other factors such as infrastructure, engineering, and economic and regulatory policy will affect the viability of geologic carbon storage in the state. This report is divided into five chapters, each addressing specific technical aspects pertinent to geologic carbon storage, which is the overarching theme. Chapter 1 is an introduction and overview of geologic carbon storage and the data needed to evaluate its potential. Chapter 2 is a geologic evaluation of the potential to use CO2 for enhanced oil recovery. Chapter 3 is an evaluation of subsurface formation-water geochemistry and implications for CO2 sequestration. Chapter 4 is an evaluation of CO2 storage potential with an emphasis along some of the state\u27s major river corridors. Chapter 5 is a geologic evaluation of CO2 storage potential for nominated coal-to-liquids (gasification) sites

Understanding and utilization of Thematic Mapper and other remotely sensed data for vegetation monitoring

The TM Tasseled Cap transformation, which provides both a 50% reduction in data volume with little or no loss of important information and spectral features with direct physical association, is presented and discussed. Using both simulated and actual TM data, some important characteristics of vegetation and soils in this feature space are described, as are the effects of solar elevation angle and atmospheric haze. A preliminary spectral haze diagnostic feature, based on only simulated data, is also examined. The characteristics of the TM thermal band are discussed, as is a demonstration of the use of TM data in energy balance studies. Some characteristics of AVHRR data are described, as are the sensitivities to scene content of several LANDSAT-MSS preprocessing techniques

Cultures of transformation: An integrated framework for transformative action

The challenges posed by climate change have generated many initiatives that seek to implement societal transformations. In most cases, these focus on technology developments, adoption and diffusion but neglect the social and cultural dimensions of a transformation. Insights from systems and behavioural sciences can provide valuable guidance on these aspects, but the utility of this literature is limited by two factors. Firstly, the literature on the intersection between social transformation and psychological processes of behaviour change by individuals is limited. Secondly, the complex technical nature of much of the transition relevant literature limits its accessibility by stakeholders outside academia. We seek to address these challenges through the development of a transdisciplinary Transformation Process Framework for use as a ‘knowledge integration’ tool as part of a co-design process for transformative change. The Framework: (1) develops a systematic narrative of the transformational changes that need to be triggered at multiple scales (from individual to society), (2) generates a map to identify key variables, drivers, and blockers in a transformation process integrating different knowledge from fragmented disciplines; (3) serves as a tool to support the exploration of relevant academic (and other) literature to collate and utilise relevant knowledge. © 2022Suggestion H.P., A.H.S. and A.A.K was supported by the H2020 European Commission Project ‘PARIS REINFORCE’ under grant agreement no. 820846 . This work also originated in, and benefited from, discussions with multiple research and non-governmental organisations. We acknowledge and thank all involved in helping us develop and refine our ideas. We also thank two anonymous referees who provided valuable and insights comments that significantly helped in improving the original manuscript. We also grateful for the constructive and thoughtful comments provided by two anonymous referees

Constraining uncertainty in aerosol direct forcing

The uncertainty in present-day anthropogenic forcing is dominated by uncertainty in the strength of the contribution from aerosol. Much of the uncertainty in the direct aerosol forcing can be attributed to uncertainty in the anthropogenic fraction of aerosol in the present-day atmosphere, due to a lack of historical observations. Here we present a robust relationship between total present-day aerosol optical depth and the anthropogenic contribution across three multi-model ensembles and a large single-model perturbed parameter ensemble. Using observations of aerosol optical depth, we determine a reduced likely range of the anthropogenic component and hence a reduced uncertainty in the direct forcing of aerosol