919 research outputs found

    Mechanisms of growth inhibition of primary prostate epithelial cells following gamma irradiation or photodynamic therapy including senscence, necrosis, and autophagy, but not apoptosis

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    In comparison to more differentiated cells, prostate cancer stem-like cells are radioresistant, which could explain radio-recurrent prostate cancer. Improvement of radiotherapeutic efficacy may therefore require combination therapy. We have investigated the consequences of treating primary prostate epithelial cells with gamma irradiation and photodynamic therapy (PDT), both of which act through production of reactive oxygen species (ROS). Primary prostate epithelial cells were cultured from patient samples of benign prostatic hyperplasia and prostate cancer prior to treatment with PDT or gamma irradiation. Cell viability was measured using MTT and alamar blue assay, and cell recovery by colony-forming assays. Immunofluorescence of gamma-H2AX foci was used to quantify DNA damage, and autophagy and apoptosis were assessed using Western blots. Necrosis and senescence were measured by propidium iodide staining and beta-galactosidase staining, respectively. Both PDT and gamma irradiation reduced the colony-forming ability of primary prostate epithelial cells. PDT reduced the viability of all types of cells in the cultures, including stem-like cells and more differentiated cells. PDT induced necrosis and autophagy, whereas gamma irradiation induced senescence, but neither treatment induced apoptosis. PDT and gamma irradiation therefore inhibit cell growth by different mechanisms. We suggest these treatments would be suitable for use in combination as sequential treatments against prostate cancer

    Usefulness of routine preoperative testing in a developing country: a prospective study

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    Introduction: The assessment of anesthetic risks is an essential component of preoperative evaluation. In developing world, preanesthesia evaluation may be challenging because patient's medical history and records are scare, and language barrier limits physical examination. Our objective was to evaluate the impact of routine preoperative testing in a low-resources setting. Methods: Prospective observational study performed in a French forward surgical unit in Abidjan, Ivory Coast. 201 patients who were scheduled for non urgent surgery were screened with routine laboratory exams during preoperative evaluation. Changes in surgery were assessed (delayed or scheduled). Results: Abnormal hemoglobin findings were reported in 35% of patients, abnormal WBC count in 11,1% of patients, abnormal platelets in 15,3% of patients. Positive HIV results were found in 8,3% of cases. Routine tests represented 43,6% of changes causes. Conclusion: Our study showed that in a developing country, routine preoperative tests showed abnormal results up to 35% of cases, and represented 43,6% of delayed surgery causes. The rate of tests leading to management changes varied widely, from 0% to 8,3%. These results suggested that selected tests would be useful to diagnose diseases that required treatment before non urgent surgery. However, larger studies are needeed to evaluate the cost/benefit ratio and the clinical impact of such a strategy

    pH-dependent modulation of reactivity in Ruthenium(II) organometallics

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    The pH-dependent intramolecular chelation of a tethered sulfonamide ligand in ruthenium(II) arene complexes is demonstrated, a process shown to modulate metal-centered reactivity toward the model ligand guanosine 5′-monophosphate within the physiologically relevant pH region

    Citizen forecasting suggests Macron will win a comfortable victory over Marine Le Pen

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    With the second round of the French presidential election just days away, what can election forecasts tell us about the likely result? Drawing on a citizen forecasting model, Andreas Murr, Yannick Dufresne, Justin Savoie, Bruno Jérôme and Michael S. Lewis-Beck write that Emmanuel Macron looks set to win a comfortable victory over Marine Le Pen

    The Application of Reversible Intramolecular Sulfonamide Ligation to Modulate Reactivity in Organometallic Ruthenium(II) Diamine Complexes

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    Metallation of biomacromolecular species forms the basis for the anticancer activity of many metallodrugs. A major limitation of these compounds is that their reactivity is indiscriminate and can, in principle, occur in healthy tissue as well as cancerous tissue, potentially leading to side effects in vivo. Here we present pH-dependent intramolecular coordination of an arene-tethered sulfonamide functionality in organometallic ruthenium(II) ethylenediamine complexes as a route to controlling the coordination environment about the central metal atom. Through variation of the sulfonamide R group and the length of the tether linking it to the arene ligand the acidity of the sulfonamide NH group, and hence the pH-region over which regulation of metal coordination occurs, can be modulated. Intramolecular sulfonamide ligation controlled the reactivity of complex 4 within the physiologically relevant pH-region, rendering it more reactive towards 5?-GMP in mildly acidic pH-conditions typical of tumour tissue compared to the mildly alkaline pH-conditions typical of healthy tissue. However, the activation of 4 by ring-opening of the chelate was found to be a slow process relative to the timescale of typical cell culture assays and members of this series of complexes were found not to be cytotoxic towards the HT-29 cell line. These complexes provide the basis for the development of analogues of increased potency where intramolecular sulfonamide ligation regulates reactivity and therefore cytotoxicity in a pH-dependent, and potentially, tissue-dependent manner

    Matter-wave laser Interferometric Gravitation Antenna (MIGA): New perspectives for fundamental physics and geosciences

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    The MIGA project aims at demonstrating precision measurements of gravity with cold atom sensors in a large scale instrument and at studying the associated applications in geosciences and fundamental physics. The first stage of the project (2013-2018) will consist in building a 300-meter long optical cavity to interrogate atom interferometers and will be based at the low noise underground laboratory LSBB in Rustrel, France. The second stage of the project (2018-2023) will be dedicated to science runs and data analyses in order to probe the spatio-temporal structure of the local gravity field of the LSBB region, a site of high hydrological interest. MIGA will also assess future potential applications of atom interferometry to gravitational wave detection in the frequency band 0.110\sim 0.1-10 Hz hardly covered by future long baseline optical interferometers. This paper presents the main objectives of the project, the status of the construction of the instrument and the motivation for the applications of MIGA in geosciences. Important results on new atom interferometry techniques developed at SYRTE in the context of MIGA and paving the way to precision gravity measurements are also reported.Comment: Proceedings of the 50th Rencontres de Moriond "100 years after GR", La Thuile (Italy), 21-28 March 2015 - 10 pages, 5 figures, 23 references version2: added references, corrected typo

    Spatial clustering of emergency department visits by asthmatic children in an urban area: south-western Detroit, Michigan

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    Objective This ecological study evaluates the correlation of asthma clusters with outdoor air pollution, race, and household income in South-western Detroit, Michigan. Design To attain this objective (1) a geographic information aystem (GIS) is utilized to evaluate the relationships between rates of emergency department (ED) admissions for asthma, race, and socio-economic status at the neighborhood block group level of analysis; (2) cluster statistical analyses are performed using Geomed software; and (3) the asthma risk from industrial air pollution was evaluated with windrose data and Screen3 air pollution model. Sample Data from five major hospitals with ED admissions of asthma patients (code 493), aged 0–15 years, are used to select a region of analysis with good geographical representation based on the catchment areas of hospitals in the study. A total of 2067 of the reported cases between 1 January 1993 and 30 June 1998, are successfully geocoded to a map, generating a no-match rate of 8.4%. Data on racial characteristics, population density, and household income levels are obtained from neighborhood block groups in the 1990 census report. Locations of major polluting industries within the study area are obtained from the Toxics Release Inventory. Results Spatial analysis identified a local asthma cluster roughly 2 km east (the predominant downwind direction) of the second and third largest air polluters (in terms of tonnage) in Wayne County. Evaluation of the industrial pollution with a focused cluster test, Screen3 air pollution model, and windrose figures, displayed weak association between ED asthma admissions and estimated levels of outdoor air pollution from these two facilities. The neighborhood block groups in the local asthma cluster are more closely correlated with high proportions of African Americans and low median household income. Implications for practice This study illustrates the strengths and weaknesses of GIS in the public health arena. It highlights the difficulty of disentangling the effects of exposure to outdoor air pollutants and socio-economic factors on ED asthmatics (reflecting asthma severity) among an urban population. This study also illustrates the need for population-based, as opposed to hospital-based, asthma data, and the need for block-groups, as opposed to zip codes, as a spatial unit of analysis in the evaluation and analysis of asthma-related risk factors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73994/1/j.1467-0658.2001.00143.x.pd

    SST-GATE: A dual mirror telescope for the Cherenkov Telescope Array

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    The Cherenkov Telescope Array (CTA) will be the world's first open observatory for very high energy gamma-rays. Around a hundred telescopes of different sizes will be used to detect the Cherenkov light that results from gamma-ray induced air showers in the atmosphere. Amongst them, a large number of Small Size Telescopes (SST), with a diameter of about 4 m, will assure an unprecedented coverage of the high energy end of the electromagnetic spectrum (above ~1TeV to beyond 100 TeV) and will open up a new window on the non-thermal sky. Several concepts for the SST design are currently being investigated with the aim of combining a large field of view (~9 degrees) with a good resolution of the shower images, as well as minimizing costs. These include a Davies-Cotton configuration with a Geiger-mode avalanche photodiode (GAPD) based camera, as pioneered by FACT, and a novel and as yet untested design based on the Schwarzschild-Couder configuration, which uses a secondary mirror to reduce the plate-scale and to allow for a wide field of view with a light-weight camera, e.g. using GAPDs or multi-anode photomultipliers. One objective of the GATE (Gamma-ray Telescope Elements) programme is to build one of the first Schwarzschild-Couder prototypes and to evaluate its performance. The construction of the SST-GATE prototype on the campus of the Paris Observatory in Meudon is under way. We report on the current status of the project and provide details of the opto-mechanical design of the prototype, the development of its control software, and simulations of its expected performance.Comment: In Proceedings of the 33rd International Cosmic Ray Conference (ICRC2013), Rio de Janeiro (Brazil). All CTA contributions at arXiv:1307.223
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