1,635 research outputs found

    Ponderomotive scattering of an electron-bunch before injection into a laser wakefield

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    For the purpose of laser wakefield acceleration, it turned out that also the injection of electron bunches longer than a plasma wavelength can generate accelerated femtosecond bunches with relatively low energy spread. This is of high interest because such injecting bunches can be provided, e.g., by state-of-the-art photo cathode RF guns. Here we point out that when an e-bunch is injected in the wakefield it is important to take into account the ponderomotive scattering of the injecting bunch by the laser pulse in the vacuum region located in front of the plasma. At low energies of the injected bunch this scattering results in a significant drop of the collection efficiency. Larger collection efficiency can by reached with lower intensity laser pulses and relatively high injection energies. We also estimate the minimum trapping energy for the injected electrons and the length of the trapped bunch.Comment: 12 pages, 5 figures, submitted to Phys. Rev.

    The investigational CFTR potentiator, VX-770, potentiated multiple CFTR forms in vitro

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    Stepwise Design and Evaluation of a Values-Oriented Ambient Intelligence Healthcare Monitoring Platform

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    Contains fulltext : 251562.pdf (Publisher’s version ) (Open Access)OBJECTIVES: The majority of all developed digital health technologies do not reach successful implementation. A discrepancy among technology design, the context of use, and user needs and values is identified as the main reason for this failure. Value-sensitive design (VSD) is a design method enabling to align design with user values by embedding values in technology, yet the method is lacking clear heuristics for practical application. To improve the successful design and implementation of digital health, we propose and evaluate a stepwise approach to VSD. METHODS: The approach consists of the phases: experiment, demonstrate, and validate. Experiment takes place in an office to create makeshift solutions. Demonstrate takes place in a mock-up environment and aims to optimize design requirements through user feedback. The validate phase takes place in an authentic care situation and studies how the novel technology affects current workflows. RESULTS: We applied the stepwise VSD approach to the design of a hospital-based ambient intelligence solution for remotely and continuously monitoring quality and safety of patient care. We particularly focused on embodiment of the values of safety, privacy, and inclusiveness in the design. Design activities of the experiment and demonstrate phase are discussed. CONCLUSIONS: A stepwise approach to VSD enables a design to optimally meet the values of all users involved, while aligning the design process with the practical limitations of healthcare institutions. We discuss some benefits and challenges related to VSD and the potential for transfer of this approach to other digital health solutions

    Australian Veterinary History Record No. 32

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    Australian Veterinary Associatio

    Ethical considerations for alcohol researchers in their relation towards policy makers

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    Alcohol policy research all over the world is often funded by national or local governments. Researchers involved may be confronted with several ethical questions. These questions can have quite a different character. Ethical questions may have a severe character that can be quite “clear” for the researchers involved. Miller et al. [1] for instance recently studied interference of funders, like governments or industrial and charitable organizations, in addiction research. Results show that activities occur such as censorship of research outputs, interference with the wording in reports and articles and interventions in when and how findings are released. Governments funding policy research may interfere in a way as described by Miller et al. [1]. but also less obvious ethical issues may occur: What if the research question is formulated in a “questionable” or “suggestive” way? What if policy makers deliberately ignore results of scientific research? The purpose of this contribution is to elaborate on these less obvious ethical issues, not primarily to give clear-cut answers but to raise consciousness and stimulate reflection and debate among researchers and policy makers

    Hypomagnesemia in persons with type 1 diabetes:associations with clinical parameters and oxidative stress

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    Background: Among persons with type 1 diabetes mellitus (T1DM) low concentrations of magnesium have been reported. Previous (small) studies also suggested a relation of hypomagnesemia with (poor) glycaemic control and complications. We aimed to investigate the magnitude of hypomagnesemia and the associations between magnesium with parameters of routine T1DM care in a population of unselected outpatients. Methods: As part of a prospective cohort study, initially designed to measure quality of life and oxidative stress, data from 207 patients with a mean age of 45 [standard deviation (SD) 12] years, 58% male, diabetes duration 22 [interquartile range (IQR) 16, 31] years and glycated haemoglobin (HbA1c) of 60 (SD 11) mmol/mol [7.6 (SD 1.0)%] were examined. Hypomagnesemia was defined as a concentration below Results: Mean magnesium concentration was 0.78 (SD 0.05) mmol/l. A deficiency was present in 4.3% of participants. Among these persons, mean concentration was 0.66 (SD 0.03) mmol/l. There was no correlation between magnesium and HbA1c at baseline (r = -0.014, p = 0.843). In multivariable analysis, free thiols (reflecting the degree of oxidative stress) were significantly and negatively associated with magnesium concentrations. Conclusion: In this cohort of T1DM outpatients, the presence of hypomagnesemia was infrequent and, if present, relative mild. Magnesium was not associated with glycaemic control nor with presence of micro- and macrovascular complications. Although these results need confirmation, in particular the negative association of magnesium with free thiols, this suggests that hypomagnesemia is not a relevant topic in routine care for people with T1DM

    Systemic oxidative stress and antioxidant capacity in cancer patients

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    Various factors impact the outcome of patients with the diagnosis of cancer. Common treatment modalities of cancer, including surgery, radiation therapy and cytostatic agents, all lead to a systemic inflammatory reaction. In particular, this reaction is of physiological importance as it is crucial for patient recovery. However, in some patients, a self-perpetuating inflammatory response develops due to the presence of unfavorable risk factors, several of which are still unknown, but might lead to a worse disease prognosis. Inflammation has been intimately associated with oxidative stress, that is characterized by an imbalance between pro-oxidants, also termed reactive species, and antioxidants. Systemically, oxidative stress can be quantified by measuring thiols (R-SH, sulfhydryl compounds), which are considered to be regulatory nodes within the extracellular antioxidant network. Most importantly, thiol measurements in serum or plasma form a robust and powerful read-out of the in vivo reduction-oxidation (redox) status as thiols are highly redox-active and thus readily oxidized by circulating reactive species. Therefore, systemic quantification of thiols might be a valuable addition to the clinically available diagnostic and prognostic armamentarium as it is able to reliably capture the overall balance between oxidants and the antioxidant capacity of patients. In this review, we summarized the currently available literature on thiol levels as amendable markers for oxidative stress in patients with lung, prostate and colorectal cancer. Total thiols, native (free) thiols and disulfide levels are significantly altered in these patients compared to healthy individuals. In general, these findings indicate that the extracellular antioxidant capacity is severely affected in patients with these types of cancer. Moreover, lower thiol levels are associated with a lowered overall survival. Future research should focus on exploration of the clinical significance of thiols in cancer

    Baja tasa de infecciĂłn por COVID-19 en zonas a gran altura

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    Severe acute respiratory syndrome (SARS) is an acute infectious disease that spreads mainly via the respiratory route. A distinct coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Recently, a metallopeptidase named angiotensin-converting enzyme 2 (ACE2) has been identified as the functional receptor for SARS-CoV. Although ACE2 mRNA is known to be present in virtually all organs, its protein expression is largely unknown. Since identifying the possible route of infection has major implications for understanding the pathogenesis and future treatment strategies for SARS, the present study investigated the localization of ACE2 protein in various human organs (oral and nasal mucosa, nasopharynx, lung, stomach, small intestine, colon, skin, lymph nodes, thymus, bone marrow, spleen, liver, kidney, and brain). The most remarkable finding was the surface expression of ACE2 protein on lung alveolar epithelial cells and enterocytes of the small intestine. Furthermore, ACE2 was present in arterial and venous endothelial cells and arterial smooth muscle cells in all organs studied. In conclusion, ACE2 is abundantly present in humans in the epithelia of the lung and small intestine, which might provide possible routes of entry for the SARS-CoV. This epithelial expression, together with the presence of ACE2 in vascular endothelium, also provides a first step in understanding the pathogenesis of the main SARS disease manifestations. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd

    Spatiotemporal regulation of hydrogen sulfide signaling in the kidney

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    Hydrogen sulfide (H2S) has long been recognized as a putrid, toxic gas. However, as a result of intensive biochemical research in the past two decades, H2S is now considered to be the third gasotransmitter alongside nitric oxide (NO) and carbon monoxide (CO) in mammalian systems. H2S-producing enzymes are expressed in all organs, playing an important role in their physiology. In the kidney, H2S is a critical regulator of vascular and cellular function, although the mechanisms that affect (sub)cellular levels of H2S are not precisely understood. H2S modulates systemic and renal blood flow, glomerular filtration rate and the renin-angiotensin axis through direct inhibition of nitric oxide synthesis. Further, H2S affects cellular function by modulating protein activity via post-translational protein modification: a process termed persulfidation. Persulfidation modulates protein activity, protein localization and protein-protein interactions. Additionally, acute kidney injury (AKI) due to mitochondrial dysfunction, which occurs during hypoxia or ischemia-reperfusion (IR), is attenuated by H2S. H2S enhances ATP production, prevents damage due to free radicals and regulates endoplasmic reticulum stress during IR. In this review, we discuss current insights in the (sub)cellular regulation of H2S anabolism, retention and catabolism, with relevance to spatiotemporal regulation of renal H2S levels. Together, H2S is a versatile gasotransmitter with pleiotropic effects on renal function and offers protection against AKI. Unraveling the mechanisms that modulate (sub)cellular signaling of H2S not only expands fundamental insight in the regulation of functional effects mediated by H2S, but can also provide novel therapeutic targets to prevent kidney injury due to hypoxic or ischemic injury
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