Current optical space telescopes rely upon silicon charge-coupled devices (CCDs) to detect and image the incoming photons. The performance of a CCD detector depends on its ability to transfer ...electrons through the silicon efficiently, so that the signal from every pixel may be read out through a single amplifier. This process of electron transfer is highly susceptible to the effects of solar proton damage (or non-ionizing radiation damage). This is because charged particles passing through the CCD displace silicon atoms, introducing energy levels into the semiconductor band gap which act as localized electron traps. The reduction in charge transfer efficiency (CTE) leads to signal loss and image smearing. The European Space Agency's astrometric Gaia mission will make extensive use of CCDs to create the most complete and accurate stereoscopic map to date of the Milky Way. In the context of the Gaia mission CTE is referred to with the complementary quantity charge transfer inefficiency (CTI = 1-CTE). CTI is an extremely important issue that threatens Gaia's performances: the CCDs are very large so that the electrons need to be transferred a long way; the focal plane is also very large and difficult to shield; the mission will operate at second Lagrange point where the direct solar protons are highly energetic (penetrating) and the science requirements on image quality are very stringent. In order to tackle this issue, in depth experimental studies and modelling efforts are being conducted to explore the possible consequences and to mitigate the anticipated effects of radiation damage. We present here a detailed Monte Carlo model that has been developed to simulate the operation of a damaged CCD at the pixel electrode level. This model implements a new approach to both the charge density distribution within a pixel and the charge capture and release probabilities, which allows the reproduction of CTI effects on a variety of measurements for a large signal level range in particular for signals of the order of a few electrons.
The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A ...series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4‘-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4‘-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4‘-position leads to increased uterine stimulation in vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1−10 mg/kg.
We propose a new approach to forming an estimate of a target track in a distributed sensor system using very limited sensor information. This approach uses a central fusion system that collects only ...the peak energy information from each sensor and assumes that the energy attenuates as a power law in range from the source. A geometrical invariance property of the proximity of the distributed sensors relative to a target track is used to generate potential target track paths. Numerical simulation examples are presented to illustrate the practicality of the technique.
Recloser and fuses are the main overcurrent protective devices on distribution systems. Poor coordination adversely impacts the overall power quality especially from the momentary voltage ...interruption and voltage sag perspectives. Therefore, the purpose of this paper is to develop a novel approach to detect and identify which protective devices operate to clear a short-circuit condition using power-quality waveform measurement data. The proposed approach is intended to evaluate performance coordination of overcurrent protective devices and help locate faults on the feeder. The effectiveness of the techniques is demonstrated using simulation and real-world data. Results indicate a promising potential for real-world deployment and applications.
The EPIC focal plane imaging spectrometers on XMM-Newton use CCDs to record the images and spectra of celestial X-ray sources focused by the three X-ray mirrors. There is one camera at the focus of ...each mirror; two of the cameras contain seven MOS CCDs, while the third uses twelve PN CCDs, defining a circular field of view of 30′ diameter in each case. The CCDs were specially developed for EPIC, and combine high quality imaging with spectral resolution close to the Fano limit. A filter wheel carrying three kinds of X-ray transparent light blocking filter, a fully closed, and a fully open position, is fitted to each EPIC instrument. The CCDs are cooled passively and are under full closed loop thermal control. A radio-active source is fitted for internal calibration. Data are processed on-board to save telemetry by removing cosmic ray tracks, and generating X-ray event files; a variety of different instrument modes are available to increase the dynamic range of the instrument and to enable fast timing. The instruments were calibrated using laboratory X-ray beams, and synchrotron generated monochromatic X-ray beams before launch; in-orbit calibration makes use of a variety of celestial X-ray targets. The current calibration is better than 10% over the entire energy range of 0.2 to 10 keV. All three instruments survived launch and are performing nominally in orbit. In particular full field-of-view coverage is available, all electronic modes work, and the energy resolution is close to pre-launch values. Radiation damage is well within pre-launch predictions and does not yet impact on the energy resolution. The scientific results from EPIC amply fulfil pre-launch expectations.
Intersexuality occurs in a diverse range of animals, and its study offers insights into basic reproductive biology. Investigations in amphipods suggest intersexuality results from incomplete ...feminisation caused by sex-distorting parasites. It has also been noted that 2 intersex phenotypes occur in males of the amphipod Echinogammarus marinus, an external phenotype, in which males possess rudimentary brood plates, and an internal phenotype, in which only an ovotestis is present. This study examines the relationship between these phenotypes and finds their prevalences are independent. In addition, a cross-species microarray reveals the testicular transcriptomes of the intersex phenotypes are distinct from that of normal males and, most crucially, each other. Furthermore, the internal intersex phenotype, unlike the external phenotype, shows no correlation with infection by known feminising parasites. These findings suggest the male intersex phenotypes should not be considered stages on a single spectrum of intersexuality. Rather, they support the hypothesis that internal and external intersexuality are divergent phenotypes with separate causal mechanisms and point to the existence of a distinct and geographically widespread form of amphipod intersexuality caused by an unknown factor.
The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. ...In vivo structure−activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (1) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-β3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489, 4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.
Objective To study the association of clarithromycin with cardiovascular events in the setting of acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia.Design ...Analysis of two prospectively collected datasets.Setting Chronic obstructive pulmonary disease dataset including patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011; Edinburgh pneumonia study cohort including patients admitted to NHS Lothian Hospitals between 2005 and 2009.Population 1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia.Main outcome measures Hazard ratios for cardiovascular events at one year (defined as hospital admissions with acute coronary syndrome, decompensated cardiac failure, serious arrhythmia, or sudden cardiac death) and admissions for acute coronary syndrome (acute ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). Secondary outcomes were all cause and cardiovascular mortality at one year.Results 268 cardiovascular events occurred in the acute exacerbations of chronic obstructive pulmonary disease cohort and 171 in the community acquired pneumonia cohort over one year. After multivariable adjustment, clarithromycin use in acute exacerbations of chronic obstructive pulmonary disease was associated with an increased risk of cardiovascular events and acute coronary syndrome—hazard ratios 1.50 (95% confidence interval 1.13 to 1.97) and 1.67 (1.04 to 2.68). After multivariable adjustment, clarithromycin use in community acquired pneumonia was associated with increased risk of cardiovascular events (hazard ratio 1.68, 1.18 to 2.38) but not acute coronary syndrome (1.65, 0.97 to 2.80). The association between clarithromycin use and cardiovascular events persisted after matching for the propensity to receive clarithromycin. A significant association was found between clarithromycin use and cardiovascular mortality (adjusted hazard ratio 1.52, 1.02 to 2.26) but not all cause mortality (1.16, 0.90 to 1.51) in acute exacerbations of chronic obstructive pulmonary disease. No association was found between clarithromycin use in community acquired pneumonia and all cause mortality or cardiovascular mortality. Longer durations of clarithromycin use were associated with more cardiovascular events. Use of β lactam antibiotics or doxycycline was not associated with increased cardiovascular events in patients with acute exacerbations of chronic obstructive pulmonary disease, suggesting an effect specific to clarithromycin.Conclusions The use of clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation in other datasets.
Arc flash is an important consideration for personnel safety. This paper shows test results for overhead arc flash scenarios and arc flash in a padmounted switch. Both scenarios result in more ...incident energy than expected. For overhead arc scenarios, longer arc lengths are considered when analyzing arc flash. For the padmounted switch, an equation is developed to help coordinate protective clothing with minimum approach distances and upstream protective relaying.
New cobalt(III) Schiff base complexes with antifungal activity against a range of fungal pathogens are reported in this work. In addition, these compounds showed no cytotoxicity against mammalian ...cells and no toxicity in vivo against Galleria mellonella at high concentrations. More information can be found in the Full Paper by A. Frei, M. A. T. Blaskovich, et al. on page 2021.
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