Solution structure of polyglutamine tracts in GST-polyglutamine fusion proteins

AbstractAggregation of expanded polyglutamine (polyQ) seems to be the cause of various genetic neurodegenerative diseases. Relatively little is known as yet about the polyQ structure and the mechanism that induces aggregation. We have characterised the solution structure of polyQ in a proteic context using a model system based on glutathione S-transferase fusion proteins. A wide range of biophysical techniques was applied. For the first time, nuclear magnetic resonance was used to observe directly and selectively the conformation of polyQ in the pathological range. We demonstrate that, in solution, polyQs are in a random coil conformation. However, under destabilising conditions, their aggregation behaviour is determined by the polyQ length

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

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

Multi-Calorimetry in Light-based Neutrino Detectors

International audienceNeutrino detectors are among the largest photonics instruments built for fundamental research. Since its inception, neutrino detection has been inexorably linked to the challenging detection of scarce photons in huge instrumented volumes. Many discoveries in neutrino physics, including the neutrino itself, are inseparable from the evolution of the detector photonics interfaces, i.e. photo-sensors and readout electronics, to yield ever higher precision and richer detection information. The measurement of the energy of neutrinos, referred to as calorimetry, is pursued today to reach permille level systematics control precision, thus leading to further innovation in specialised photonics. This publication describes a novel articulation that detectors may be endowed with multiple photonics interfaces for simultaneous light detection to yield unprecedented high-precision calorimetry. This multi-calorimetry approach opens the novel notion of dual-calorimetry detectors as an evolution from the single-calorimetry setups used over several decades for most experiments so far. The dual-calorimetry design exploits unique response synergies between photon counting and photon-integration detection systems, including correlations and cancellations between calorimetric responses, to yield the unprecedented mitigation of the dominant response systematic effects today for the possible improved design of a new generation of neutrino experiments

Multi-Calorimetry in Light-based Neutrino Detectors

International audienceNeutrino detectors are among the largest photonics instruments built for fundamental research. Since its inception, neutrino detection has been inexorably linked to the challenging detection of scarce photons in huge instrumented volumes. Many discoveries in neutrino physics, including the neutrino itself, are inseparable from the evolution of the detector photonics interfaces, i.e. photo-sensors and readout electronics, to yield ever higher precision and richer detection information. The measurement of the energy of neutrinos, referred to as calorimetry, is pursued today to reach permille level systematics control precision, thus leading to further innovation in specialised photonics. This publication describes a novel articulation that detectors may be endowed with multiple photonics interfaces for simultaneous light detection to yield unprecedented high-precision calorimetry. This multi-calorimetry approach opens the novel notion of dual-calorimetry detectors as an evolution from the single-calorimetry setups used over several decades for most experiments so far. The dual-calorimetry design exploits unique response synergies between photon counting and photon-integration detection systems, including correlations and cancellations between calorimetric responses, to yield the unprecedented mitigation of the dominant response systematic effects today for the possible improved design of a new generation of neutrino experiments

Multi-Calorimetry in Light-based Neutrino Detectors

International audienceNeutrino detectors are among the largest photonics instruments built for fundamental research. Since its inception, neutrino detection has been inexorably linked to the challenging detection of scarce photons in huge instrumented volumes. Many discoveries in neutrino physics, including the neutrino itself, are inseparable from the evolution of the detector photonics interfaces, i.e. photo-sensors and readout electronics, to yield ever higher precision and richer detection information. The measurement of the energy of neutrinos, referred to as calorimetry, is pursued today to reach permille level systematics control precision, thus leading to further innovation in specialised photonics. This publication describes a novel articulation that detectors may be endowed with multiple photonics interfaces for simultaneous light detection to yield unprecedented high-precision calorimetry. This multi-calorimetry approach opens the novel notion of dual-calorimetry detectors as an evolution from the single-calorimetry setups used over several decades for most experiments so far. The dual-calorimetry design exploits unique response synergies between photon counting and photon-integration detection systems, including correlations and cancellations between calorimetric responses, to yield the unprecedented mitigation of the dominant response systematic effects today for the possible improved design of a new generation of neutrino experiments

Multi-Calorimetry in Light-based Neutrino Detectors

International audienceNeutrino detectors are among the largest photonics instruments built for fundamental research. Since its inception, neutrino detection has been inexorably linked to the challenging detection of scarce photons in huge instrumented volumes. Many discoveries in neutrino physics, including the neutrino itself, are inseparable from the evolution of the detector photonics interfaces, i.e. photo-sensors and readout electronics, to yield ever higher precision and richer detection information. The measurement of the energy of neutrinos, referred to as calorimetry, is pursued today to reach permille level systematics control precision, thus leading to further innovation in specialised photonics. This publication describes a novel articulation that detectors may be endowed with multiple photonics interfaces for simultaneous light detection to yield unprecedented high-precision calorimetry. This multi-calorimetry approach opens the novel notion of dual-calorimetry detectors as an evolution from the single-calorimetry setups used over several decades for most experiments so far. The dual-calorimetry design exploits unique response synergies between photon counting and photon-integration detection systems, including correlations and cancellations between calorimetric responses, to yield the unprecedented mitigation of the dominant response systematic effects today for the possible improved design of a new generation of neutrino experiments