243 research outputs found

    Single electron emission in two-phase xenon with application to the detection of coherent neutrino-nucleus scattering

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    We present an experimental study of single electron emission in ZEPLIN-III, a two-phase xenon experiment built to search for dark matter WIMPs, and discuss applications enabled by the excellent signal-to-noise ratio achieved in detecting this signature. Firstly, we demonstrate a practical method for precise measurement of the free electron lifetime in liquid xenon during normal operation of these detectors. Then, using a realistic detector response model and backgrounds, we assess the feasibility of deploying such an instrument for measuring coherent neutrino-nucleus elastic scattering using the ionisation channel in the few-electron regime. We conclude that it should be possible to measure this elusive neutrino signature above an ionisation threshold of \sim3 electrons both at a stopped pion source and at a nuclear reactor. Detectable signal rates are larger in the reactor case, but the triggered measurement and harder recoil energy spectrum afforded by the accelerator source enable lower overall background and fiducialisation of the active volume

    Corporate political activity in less developed countries:The Volta River Project in Ghana, 1958-66

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    The article expands existing categorisations of political and economic governance by including literature on less developed countries (LDCs). In four consecutive negotiations between the US multinational Kaisers and the US and Ghana governments in the early 1960s, it is argued that the company reached levels of influence that are at odds with existing explanations. In order to understand corporate political activities in LDCs, analysis needs to go beyond static factors (political risk) and include dynamic factors such as diplomatic relations and 'arenas of power', and consider the role of the investor's home country relative to the host economy

    Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

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    Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

    Peer-provided psychological intervention for Syrian refugees: results of a randomised controlled trial on the effectiveness of Problem Management Plus

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    Background: The mental health burden among refugees in high-income countries (HICs) is high, whereas access to mental healthcare can be limited. Objective: To examine the effectiveness of a peer-provided psychological intervention (Problem Management Plus; PM+) in reducing symptoms of common mental disorders (CMDs) among Syrian refugees in the Netherlands. Methods: We conducted a single-blind, randomised controlled trial among adult Syrian refugees recruited in March 2019-December 2021 (No. NTR7552). Individuals with psychological distress (Kessler Psychological Distress Scale (K10) >15) and functional impairment (WHO Disability Assessment Schedule (WHODAS 2.0) >16) were allocated to PM+ in addition to care as usual (PM+/CAU) or CAU only. Participants were reassessed at 1-week and 3-month follow-up. Primary outcome was depression/anxiety combined (Hopkins Symptom Checklist; HSCL-25) at 3-month follow-up. Secondary outcomes included depression (HSCL-25), anxiety (HSCL-25), post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; PCL-5), impairment (WHODAS 2.0) and self-identified problems (PSYCHLOPS; Psychological Outcomes Profiles). Primary analysis was intention-to-treat. Findings: Participants (n=206; mean age=37 years, 62% men) were randomised into PM+/CAU (n=103) or CAU (n=103). At 3-month follow-up, PM+/CAU had greater reductions on depression/anxiety relative to CAU (mean difference -0.25; 95% CI -0.385 to -0.122; p=0.0001, Cohen's d=0.41). PM+/CAU also showed greater reductions on depression (p=0.0002, Cohen's d=0.42), anxiety (p=0.001, Cohen's d=0.27), PTSD symptoms (p=0.0005, Cohen's d=0.39) and self-identified problems (p=0.03, Cohen's d=0.26), but not on impairment (p=0.084, Cohen's d=0.21). Conclusions: PM+ effectively reduces symptoms of CMDs among Syrian refugees. A strength was high retention at follow-up. Generalisability is limited by predominantly including refugees with a resident permit. Clinical implications: Peer-provided psychological interventions should be considered for scale-up in HICs

    The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells.

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    INTRODUCTION: High cell density is known to enhance adipogenic differentiation of mesenchymal stem cells, suggesting secretion of signaling factors or cell-contact-mediated signaling. By employing microfluidic biochip technology, we have been able to separate these two processes and study the secretion pathways. METHODS AND RESULTS: Adipogenic differentiation of human adipose-derived stem cells (ASCs) cultured in a microfluidic system was investigated under perfusion conditions with an adipogenic medium or an adipogenic medium supplemented with supernatant from differentiating ASCs (conditioned medium). Conditioned medium increased adipogenic differentiation compared to adipogenic medium with respect to accumulation of lipid-filled vacuoles and gene expression of key adipogenic markers (C/EBPα, C/EBPβ, C/EBPδ, PPARγ, LPL and adiponectin). The positive effects of conditioned medium were observed early in the differentiation process. CONCLUSIONS: Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment phase of the differentiation process
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