Higgs Doublets, Split Multiplets and Heterotic SU(3)_C x SU(2)_L x U(1)_Y Spectra

A methodology for computing the massless spectrum of heterotic vacua with Wilson lines is presented. This is applied to a specific class of vacua with holomorphic SU(5)-bundles over torus-fibered Calabi-Yau threefolds with fundamental group Z_2. These vacua lead to low energy theories with the standard model gauge group SU(3)_C x SU(2)_L x U(1)_Yand three families of quark/leptons. The massless spectrum is computed, including the multiplicity of Higgs doublets.Comment: 11+1 p

Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator.

Metabotropic glutamate subtype 1 (mGlu1) receptor is thought to play a role in synaptic responses in thalamic relay nuclei. The aim of this study was to evaluate the positive allosteric modulator (PAM) Ro67-4853 as a tool to modulate thalamic mGlu1 receptors on single thalamic neurones in vivo. Ro67-4853, applied by iontophoresis onto ventrobasal thalamus neurones of urethane-anaesthetised rats, selectively enhanced responses to the agonist (S)-3,5-dihydroxy-phenylglycine (DHPG), an effect consistent with mGlu1 potentiation. The PAM was also able to enhance maintained responses to 10 Hz trains of sensory stimulation of the vibrissae, but had little effect on responses to single sensory stimuli. Thus Ro67-4853 appears to be a highly selective tool that can be useful in investigating how mGlu1 receptor potentiation can alter neural processing in vivo. Our results show the importance of mGlu1 in sensory processing and attention mechanisms at the thalamic level and suggest that positive modulation of mGlu1 receptors might be a useful mechanism for enhancing cognitive and attentional processes

Association between environmental tobacco smoke exposure and dementia syndromes

© 2020 The Authors. Published by BMJ. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: http://dx.doi.org/10.1136/oemed-2012-100785Objectives: Environmental tobacco smoke (ETS) has a range of adverse health effects, but its association with dementia remains unclear and with dementia syndromes unknown. We examined the dose-response relationship between ETS exposure and dementia syndromes. Methods: Using a standard method of GMS, we interviewed 5921 people aged ≥60 years in five provinces in China in 2007-2009 and characterised their ETS exposure. Five levels of dementia syndrome were diagnosed using the Automated Geriatric Examination for Computer Assisted Taxonomy instrument. The relative risk (RR) of moderate (levels 1-2) and severe (levels 3-5) dementia syndromes among participants exposed to ETS was calculated in multivariate adjusted regression models. Results: 626 participants (10.6%) had severe dementia syndromes and 869 (14.7%) moderate syndromes. Participants exposed to ETS had a significantly increased risk of severe syndromes (adjusted RR 1.29, 95% CI 1.05 to 1.59). This was dose-dependently related to exposure level and duration. The cumulative exposure dose data showed an adjusted RR of 0.99 (95% CI 0.76 to 1.28) for >0-24 level years of exposure, 1.15 (95% CI 0.93 to 1.42) for 25-49 level years, 1.18 (95% CI 0.87 to 1.59) for 59-74 level years, 1.39 (95% CI 1.03 to 1.84) for 75-99 level years and 1.95 (95% CI 1.34 to 2.83) for ≥100 level years. Significant associations with severe syndromes were found in never smokers and in former/current smokers. There were no positive associations between ETS and moderate dementia syndromes. Conclusions: ETS should be considered an important risk factor for severe dementia syndromes. Avoidance of ETS may reduce the rates of severe dementia syndromes worldwide.Published versio

Eukaryotic Polyribosome Profile Analysis

Protein synthesis is a complex cellular process that is regulated at many levels. For example, global translation can be inhibited at the initiation phase or the elongation phase by a variety of cellular stresses such as amino acid starvation or growth factor withdrawal. Alternatively, translation of individual mRNAs can be regulated by mRNA localization or the presence of cognate microRNAs. Studies of protein synthesis frequently utilize polyribosome analysis to shed light on the mechanisms of translation regulation or defects in protein synthesis. In this assay, mRNA/ribosome complexes are isolated from eukaryotic cells. A sucrose density gradient separates mRNAs bound to multiple ribosomes known as polyribosomes from mRNAs bound to a single ribosome or monosome. Fractionation of the gradients allows isolation and quantification of the different ribosomal populations and their associated mRNAs or proteins. Differences in the ratio of polyribosomes to monosomes under defined conditions can be indicative of defects in either translation initiation or elongation/termination. Examination of the mRNAs present in the polyribosome fractions can reveal whether the cohort of individual mRNAs being translated changes with experimental conditions. In addition, ribosome assembly can be monitored by analysis of the small and large ribosomal subunit peaks which are also separated by the gradient. In this video, we present a method for the preparation of crude ribosomal extracts from yeast cells, separation of the extract by sucrose gradient and interpretation of the results. This procedure is readily adaptable to mammalian cells

POLG2 deficiency causes adult-onset syndromic sensory neuropathy, ataxia and parkinsonism

Objective: Mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative disorders such as ataxia and Parkinson's disease. We describe an extended Belgian pedigree where seven individuals presented with adult-onset cerebellar ataxia, axonal peripheral ataxic neuropathy, and tremor, in variable combination with parkinsonism, seizures, cognitive decline, and ophthalmoplegia. We sought to identify the underlying molecular etiology and characterize the mitochondrial pathophysiology of this neurological syndrome. Methods: Clinical, neurophysiological, and neuroradiological evaluations were conducted. Patient muscle and cultured fibroblasts underwent extensive analyses to assess mitochondrial function. Genetic studies including genome-wide sequencing were conducted. Results: Hallmarks of mitochondrial dysfunction were present in patients' tissues including ultrastructural anomalies of mitochondria, mosaic cytochrome c oxidase deficiency, and multiple mtDNA deletions. We identified a splice acceptor variant in POLG2, c.970-1G>C, segregating with disease in this family and associated with a concomitant decrease in levels of POLG2 protein in patient cells. Interpretation: This work extends the clinical spectrum of POLG2 deficiency to include an overwhelming, adult-onset neurological syndrome that includes cerebellar syndrome, peripheral neuropathy, tremor, and parkinsonism. We therefore suggest to include POLG2 sequencing in the evaluation of ataxia and sensory neuropathy in adults, especially when it is accompanied by tremor or parkinsonism with white matter disease. The demonstration that deletions of mtDNA resulting from autosomal-dominant POLG2 variant lead to a monogenic neurodegenerative multicomponent syndrome provides further evidence for a major role of mitochondrial dysfunction in the pathomechanism of nonsyndromic forms of the component neurodegenerative disorders

O-GlcNAcase:promiscuous hexosaminidase or key regulator of O-GlcNAc signalling?

O-GlcNAc signaling is regulated by an opposing pair of enzymes: O-GlcNAc transferase installs and O-GlcNAcase (OGA) removes the modification from proteins. The dynamics and regulation of this process are only beginning to be understood as the physiological functions of both enzymes are being probed using genetic and pharmacological approaches. This minireview charts the discovery and functional and structural analysis of OGA and summarizes the insights gained from recent studies using OGA inhibition, gene knock-out, and overexpression. We identify several areas of “known unknowns” that would benefit from future research, such as the enigmatic C-terminal domain of OGA

Running coupling: Does the coupling between dark energy and dark matter change sign during the cosmological evolution?

In this paper we put forward a running coupling scenario for describing the interaction between dark energy and dark matter. The dark sector interaction in our scenario is free of the assumption that the interaction term $Q$ is proportional to the Hubble expansion rate and the energy densities of dark sectors. We only use a time-variable coupling $b(a)$ (with $a$ the scale factor of the universe) to characterize the interaction $Q$. We propose a parametrization form for the running coupling $b(a)=b_0a+b_e(1-a)$ in which the early-time coupling is given by a constant $b_e$, while today the coupling is given by another constant, $b_0$. For investigating the feature of the running coupling, we employ three dark energy models, namely, the cosmological constant model ($w=-1$), the constant $w$ model ($w=w_0$), and the time-dependent $w$ model ($w(a)=w_0+w_1(1-a)$). We constrain the models with the current observational data, including the type Ia supernova, the baryon acoustic oscillation, the cosmic microwave background, the Hubble expansion rate, and the X-ray gas mass fraction data. The fitting results indicate that a time-varying vacuum scenario is favored, in which the coupling $b(z)$ crosses the noninteracting line ($b=0$) during the cosmological evolution and the sign changes from negative to positive. The crossing of the noninteracting line happens at around $z=0.2-0.3$, and the crossing behavior is favored at about 1$\sigma$ confidence level. Our work implies that we should pay more attention to the time-varying vacuum model and seriously consider the phenomenological construction of a sign-changeable or oscillatory interaction between dark sectors.Comment: 8 pages, 5 figures; refs added; to appear in EPJ

Aluminium oxide barrier films on polymeric web and their conversion for packaging applications

In recent years, inorganic transparent barrier layers such as aluminium oxide or silicon oxide deposited onto polymer films have emerged as an attractive alternative to polymer based transparent barrier layers for flexible food packaging materials. For this application, barrier properties against water vapour and oxygen are critical. Aluminium oxide coatings can provide good barrier levels at thicknesses in the nanometre range, compared to several micrometres for polymer-based barrier layers. These ceramic barrier coatings are now being produced on a large scale using industrial high speed vacuum deposition techniques, here, reactive evaporation on a 'boat-type' roll-to-roll metalliser. For the thin barrier layer to be useful in its final packaging application, it needs to be protected. This can be either via lamination or via an additional topcoat. This study reports on acrylate topcoats, but also undercoats, on aluminium oxide coated biaxially oriented polypropylene films. The effect of the acrylate layer on barrier levels and surface topography and roughness was investigated. The acrylate was found to smooth the substrate surface and improve barrier properties. Furthermore, the activation energy for water vapour and oxygen permeation was determined in order to investigate barrier mechanisms. The oxide coated film was, additionally, converted via adhesive lamination, which also provided improvement in barrier levels. © 2013 Elsevier B.V. All rights reserved

Inflation, moduli (de)stabilization and supersymmetry breaking

We study the cosmological inflation from the viewpoint of the moduli stabilization. We study the scenario that the superpotential has a large value during the inflation era enough to stabilize moduli, but it is small in the true vacuum. This scenario is discussed by using a simple model, one type of hybrid models.Comment: 17 pages, 7 figure

Variable Geometry Turbocharger Technologies for Exhaust Energy Recovery and Boosting-A Review

As emissions regulations become increasingly demanding, higher power density engine (downsized/downspeeded and increasingly right-sized) requirements are driving the development of turbocharging systems. Variable geometry turbocharging (VGT) at its most basic level is the first step up from standard fixed geometry turbocharger systems. Currently, VGTs offer significant alternative options or complementarity vis-à-vis more advanced turbocharging options. This review details the range of prominent variable geometry technologies that are commercially available or openly under development, for both turbines and compressors and discusses the relative merits of each. Along with prominent diesel-engine boosting systems, attention is given to the control schemes employed and the actuation systems required to operate variable geometry devices, and the specific challenges associated with turbines designed for gasoline engines