NAP (davunetide) rescues neuronal dysfunction in a Drosophila model of tauopathy

Alzheimer’s disease (AD) is a devastating neurodegenerative disease causing irreversible cognitive decline in the elderly. There is no disease-modifying therapy for this condition and the mechanisms underpinning neuronal dysfunction and neurodegeneration are unclear. Compromised cytoskeletal integrity within neurons is reported in AD. This is believed to result from loss-of-function of the microtubule-associated protein tau, which becomes hyper-phosphorylated and deposits into neurofibrillary tangles in AD. We have developed a Drosophila model of tauopathy in which abnormal human tau mediates neuronal dysfunction characterised by microtubule destabilisation, axonal transport disruption, synaptic defects and behavioural impairments. Here we show that a microtubule-stabilising drug, NAPVSIPQ (NAP), prevents as well as reverses these phenotypes even after they have become established. Moreover, it does not alter abnormal tau levels indicating that it by-passes toxic tau altogether. Thus, microtubule stabilisation is a disease-modifying therapeutic strategy protecting against tau-mediated neuronal dysfunction, which holds great promise for tauopathies like AD

Fungal bioremediation of polyethylene:challenges and perspectives

Plastics have become ubiquitous in both their adoption as materials and as environmental contaminants. Widespread pollution of these versatile, man-made, and largely petroleum-derived polymers has resulted from their long-term mass production, inappropriate disposal, and inadequate end of life management. Polyethylene (PE) is at the forefront of this problem, accounting for one third of plastic demand in Europe in part due to its extensive use in packaging (European Parliament, 2020). Current recycling and incineration processes do not represent sustainable solutions to tackle plastic waste, especially once it becomes littered, and the development of new waste-management and remediation technologies are needed. Mycoremediation (fungal-based biodegradation) of PE has been the topic of several studies over the last two decades. The utility of these studies is limited by an inconclusive definition of biodegradation and a lack of knowledge regarding the biological systems responsible. This review highlights relevant features of fungi as potential bioremediation agents, before discussing the evidence for fungal biodegradation of both high- and low-density PE. An up-to-date perspective on mycoremediation as a future solution to PE waste is provided. [Abstract copyright: This article is protected by copyright. All rights reserved.

X-ray standing wave and reflectometric characterization of multilayer structures

Microstructural characterization of synthetic periodic multilayers by x-ray standing waves have been presented. It has been shown that the analysis of multilayers by combined x-ray reflectometry (XRR) and x-ray standing wave (XSW) techniques can overcome the deficiencies of the individual techniques in microstructural analysis. While interface roughnesses are more accurately determined by the XRR technique, layer composition is more accurately determined by the XSW technique where an element is directly identified by its characteristic emission. These aspects have been explained with an example of a 20 period Pt/C multilayer. The composition of the C-layers due to Pt dissolution in the C-layers, Pt$_{x}$C$_{1-x}$, has been determined by the XSW technique. In the XSW analysis when the whole amount of Pt present in the C-layers is assumed to be within the broadened interface, it l eads to larger interface roughness values, inconsistent with those determined by the XRR technique. Constraining the interface roughness values to those determined by the XRR technique, requires an additional amount of dissolved Pt in the C-layers to expl ain the Pt fluorescence yield excited by the standing wave field. This analysis provides the average composition Pt$_{x}$C$_{1-x}$ of the C-layers .Comment: 12 pages RevTex, 10 eps figures embedde

Structure Loaded Vacuum Laser-Driven Particle Acceleration Experiments at SLAC

We present an overview of the future laser-driven particle acceleration experiments. These will be carried out at the E163 facility at SLAC. Our objectives include a reconfirmation of the proof-of-principle experiment, a staged buncher laser-accelerator experiment, and longer-term future experiments that employ dielectric laser-accelerator microstructures

Statistical Pattern Recognition: Application to νμ→ντ\nu_{\mu}\to\nu_{\tau} Oscillation Searches Based on Kinematic Criteria

Classic statistical techniques (like the multi-dimensional likelihood and the Fisher discriminant method) together with Multi-layer Perceptron and Learning Vector Quantization Neural Networks have been systematically used in order to find the best sensitivity when searching for $\nu_\mu \to \nu_{\tau}$ oscillations. We discovered that for a general direct $\nu_\tau$ appearance search based on kinematic criteria: a) An optimal discrimination power is obtained using only three variables ($E_{visible}$, $P_{T}^{miss}$ and $\rho_{l}$) and their correlations. Increasing the number of variables (or combinations of variables) only increases the complexity of the problem, but does not result in a sensible change of the expected sensitivity. b) The multi-layer perceptron approach offers the best performance. As an example to assert numerically those points, we have considered the problem of $\nu_\tau$ appearance at the CNGS beam using a Liquid Argon TPC detector.Comment: 24 pages, 15 figure

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics