Exploring a SNR/Molecular Cloud Association Within HESS J1745-303

HESS J1745-303 is an extended, unidentified VHE (very high energy) gamma-ray source discovered using HESS in the Galactic Plane Survey. Since no obvious counterpart has previously been found in longer-wavelength data, the processes that power the VHE emission are not well understood. Combining the latest VHE data with recent XMM-Newton observations and a variety of source catalogs and lower-energy survey data, we attempt to match (from an energetic and positional standpoint) the various parts of the emission of HESS J1745-303 with possible candidates. Though no single counterpart is found to fully explain the VHE emission, we postulate that at least a fraction of the VHE source may be explained by a supernova-remnant/molecular-cloud association and/or a high-spin-down-flux pulsar.Comment: 11 pages, 4 figures, Accepted for publication in Astronomy & Astrophysic

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Statins in community acquired pneumonia: Evidence from experimental and clinical studies

SummaryStatins are widely used to lower cholesterol and prevent complications of cardiovascular disease. The non-lipid lowering (pleiotropic) effects of statins may also have applications to the management of infections. These include effects on endothelial function, inflammation and coagulation pathways. Several observational studies have shown a significant reduction in 30-day mortality associated with prior statin therapy in hospitalised patients with sepsis and community acquired pneumonia.This article explores the evidence for statins as novel therapy in community acquired pneumonia. Experimental and animal studies suggest statins attenuate acute lung injury by modulating neutrophil function, reducing pro-inflammatory cytokine release and reducing vascular leak. Statins reduce endothelial dysfunction and have anti-thrombotic effects that improve outcome from pneumonia and sepsis in animal models. Clinical studies have provided conflicting results, but many suggest that statins may have a role in preventing pneumonia, or improving prognosis in hospitalised patients with community-acquired pneumonia

Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites

CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1’s enhancement of resting T-cell recruitment are discussed

Experimental energy balance during the first cycles of cyclically loaded specimens under the conventional yield stress

This paper, as an extension of Maquin and Pierron (Mech Mater 41(8):928–942, 2009), presents an experimental procedure developed to macroscopically estimate the energy balance during the very first cycles of a uniaxially loaded metallic specimen at low stress levels. This energy balance is performed by simultaneously measuring the plastic input energy using a load cell and a strain gauge, and the dissipative energy using the temperature field provided by an infrared camera. Some experimental limitations led to restrain the present procedure to positive stress ratios, and to complement this energy balance by a second measurement while the material plastic work per cycle is negligible compared to the dissipative energy. Some results obtained on a cold rolled low carbon steel specimen are presented. First, a sensitivity study is undertaken to precisely determine the detection threshold on both thermal and plastic energies. Then, after having verified the homogeneity of the dissipative source fields, energy balances have been performed at different stress levels. It was thus confirmed that the slow variations of the dissipative sources occurring during the first cycles are due to micro-plastic adaptation, and that the dissipative sources remaining after some hundreds of cycles are due to viscoelastic (internal friction) phenomena. This procedure provides a better understanding of dissipation based approaches to fatigue found in the literature and an advanced tool to study viscoelastic phenomena in uniaxial loadin

Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL‑1 Binding Sites

CCL19 and CCL21 are chemokines involved in the trafficking of immune cells, particularly within the lymphatic system, through activation of CCR7. Concurrent expression of PSGL-1 and CCR7 in naive T-cells enhances recruitment of these cells to secondary lymphoid organs by CCL19 and CCL21. Here the solution structure of CCL19 is reported. It contains a canonical chemokine domain. Chemical shift mapping shows the N-termini of PSGL-1 and CCR7 have overlapping binding sites for CCL19 and binding is competitive. Implications for the mechanism of PSGL-1’s enhancement of resting T-cell recruitment are discussed

Architecture and performance of the KM3NeT front-end firmware

The KM3NeT infrastructure consists of two deep-sea neutrino telescopes being deployed in the Mediterranean Sea. The telescopes will detect extraterrestrial and atmospheric neutrinos by means of the incident photons induced by the passage of relativistic charged particles through the seawater as a consequence of a neutrino interaction. The telescopes are configured in a three-dimensional grid of digital optical modules, each hosting 31 photomultipliers. The photomultiplier signals produced by the incident Cherenkov photons are converted into digital information consisting of the integrated pulse duration and the time at which it surpasses a chosen threshold. The digitization is done by means of time to digital converters (TDCs) embedded in the field programmable gate array of the central logic board. Subsequently, a state machine formats the acquired data for its transmission to shore. We present the architecture and performance of the front-end firmware consisting of the TDCs and the state machine