Electrical and network neuronal properties are preferentially disrupted in dorsal, but not ventral, medial entorhinal cortex in a mouse model of Tauopathy

The entorhinal cortex (EC) is one of the first areas to be disrupted in neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. The responsiveness of individual neurons to electrical and environmental stimuli varies along the dorsal-ventral axis of the medial EC (mEC) in a manner that suggests this topographical organization plays a key role in neural encoding of geometric space. We examined the cellular properties of layer II mEC stellate neurons (mEC-SCs) in rTg4510 mice, a rodent model of neurodegeneration. Dorsoventral gradients in certain intrinsic membrane properties, such as membrane capacitance and afterhyperpolarizations, were flattened in rTg4510 mEC-SCs, while other cellular gradients [e.g., input resistance (Ri), action potential properties] remained intact. Specifically, the intrinsic properties of rTg4510 mEC-SCs in dorsal aspects of the mEC were preferentially affected, such that action potential firing patterns in dorsal mEC-SCs were altered, while those in ventral mEC-SCs were unaffected. We also found that neuronal oscillations in the gamma frequency band (30-80 Hz) were preferentially disrupted in the dorsal mEC of rTg4510 slices, while those in ventral regions were comparatively preserved. These alterations corresponded to a flattened dorsoventral gradient in theta-gamma cross-frequency coupling of local field potentials recorded from the mEC of freely moving rTg4510 mice. These differences were not paralleled by changes to the dorsoventral gradient in parvalbumin staining or neurodegeneration. We propose that the selective disruption to dorsal mECs, and the resultant flattening of certain dorsoventral gradients, may contribute to disturbances in spatial information processing observed in this model of dementia. SIGNIFICANCE STATEMENT: The medial entorhinal cortex (mEC) plays a key role in spatial memory and is one of the first areas to express the pathological features of dementia. Neurons of the mEC are anatomically arranged to express functional dorsoventral gradients in a variety of neuronal properties, including grid cell firing field spacing, which is thought to encode geometric scale. We have investigated the effects of tau pathology on functional dorsoventral gradients in the mEC. Using electrophysiological approaches, we have shown that, in a transgenic mouse model of dementia, the functional properties of the dorsal mEC are preferentially disrupted, resulting in a flattening of some dorsoventral gradients. Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia

Schottky Diodes on ZnO Thin Films Grown by Plasma-Enhanced Atomic Layer Deposition

Enhancement of the properties of zinc oxide (ZnO)-based Schottky diodes has been explored using a combination of plasma-enhanced atomic layer deposition (PE-ALD) ZnO thin films and silver oxide Schottky contacts deposited by reactive radio-frequency sputtering. The electrical properties of the ZnO thin films were systematically tuned by varying the deposition temperature and oxygen plasma time during PE-ALD to optimize the performance of the diode. Low temperature (80 °C) coupled with relatively long oxygen plasma time (>30 s) PE-ALD is the key to produce ZnO films with net doping concentration lower than 10 17 cm -3 . Under the optimal deposition conditions identified, the diode shows an ideality factor of 1.33, an effective barrier height of 0.80 eV, and an ON/OFF ratio of 3.11 × 10 5

Superconducting, Insulating, and Anomalous Metallic Regimes in a Gated Two-Dimensional Semiconductor-Superconductor Array

The superconductor-insulator transition in two dimensions has been widely investigated as a paradigmatic quantum phase transition. The topic remains controversial, however, because many experiments exhibit a metallic regime with saturating low-temperature resistance, at odds with conventional theory. Here, we explore this transition in a novel, highly controllable system, a semiconductor heterostructure with epitaxial Al, patterned to form a regular array of superconducting islands connected by a gateable quantum well. Spanning nine orders of magnitude in resistance, the system exhibits regimes of superconducting, metallic, and insulating behavior, along with signatures of flux commensurability and vortex penetration. An in-plane magnetic field eliminates the metallic regime, restoring the direct superconductor-insulator transition, and improves scaling, while strongly altering the scaling exponent

Spatial heterogeneity of habitat suitability for Rift Valley fever occurrence in Tanzania: an ecological niche modelling approach

Despite the long history of Rift Valley fever (RVF) in Tanzania, extent of its suitable habitat in the country remains unclear. In this study we investigated potential effects of temperature, precipitation, elevation, soil type, livestock density, rainfall pattern, proximity to wild animals, protected areas and forest on the habitat suitability for RVF occurrence in Tanzania. Presence-only records of 193 RVF outbreak locations from 1930 to 2007 together with potential predictor variables were used to model and map the suitable habitats for RVF occurrence using ecological niche modelling. Ground-truthing of the model outputs was conducted by comparing the levels of RVF virus specific antibodies in cattle, sheep and goats sampled from locations in Tanzania that presented different predicted habitat suitability values. Habitat suitability values for RVF occurrence were higher in the northern and central-eastern regions of Tanzania than the rest of the regions in the country. Soil type and precipitation of the wettest quarter contributed equally to habitat suitability (32.4% each), followed by livestock density (25.9%) and rainfall pattern (9.3%). Ground-truthing of model outputs revealed that the odds of an animal being seropositive for RVFV when sampled from areas predicted to be most suitable for RVF occurrence were twice the odds of an animal sampled from areas least suitable for RVF occurrence (95% CI: 1.43, 2.76, p < 0.001). The regions in the northern and central-eastern Tanzania were more suitable for RVF occurrence than the rest of the regions in the country. The modelled suitable habitat is characterised by impermeable soils, moderate precipitation in the wettest quarter, high livestock density and a bimodal rainfall pattern. The findings of this study should provide guidance for the design of appropriate RVF surveillance, prevention and control strategies which target areas with these characteristics

Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel.In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime: we compute the two-point correlation functions for the linearized Einstein tensor and for the metric perturbations. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a quasi-static black hole.Comment: 75 pages, no figures, submitted to Living Reviews in Relativit

Lonely but avoidant—the unfortunate juxtaposition of loneliness and self-disgust

Loneliness is prevalent worldwide and is a known risk factor for numerous physical and mental health outcomes. The health consequences of chronic loneliness coupled with the cost on public health care has necessitated the development of interventions and campaigns to end loneliness globally. According to a recent meta-analysis, such interventions focus on improving social skills, increasing opportunities for social contact/support (i.e., reducing social isolation) or addressing maladaptive cognition (e.g., irrational thoughts, self-defeating, and self-blame thoughts). The results showed that changing maladaptive thoughts offer “the best chance” for alleviating feelings of loneliness. In accordance with the latter approach, this paper proposes a new paradigm in understanding and treating loneliness that takes into account self-disgust, an aversive self-conscious affective state that reflects disgust directed towards the self. Based on findings from published and unpublished data, it is argued that interventions against loneliness that focus exclusively on improving social skills and increasing opportunities for social contact may be ineffective because lonelier people experience more self-disgust, which makes them more socially inhibited and reluctant to connect with other people. Future interventions should consider self-disgust in the treatment of loneliness and explore ways to counter feelings of self-disgust

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Systematic review of reduced therapy regimens for children with low risk febrile neutropenia

PURPOSE: Reduced intensity therapy for children with low-risk febrile neutropenia may provide benefits to both patients and the health service. We have explored the safety of these regimens and the effect of timing of discharge. METHODS: Multiple electronic databases, conference abstracts and reference lists were searched. Randomised controlled trials (RCT) and prospective observational cohorts examining the location of therapy and/or the route of administration of antibiotics in people younger than 18 years who developed low-risk febrile neutropenia following treatment for cancer were included. Meta-analysis using a random effects model was conducted. I (2) assessed statistical heterogeneity not due to chance. Registration: PROSPERO (CRD42014005817). RESULTS: Thirty-seven studies involving 3205 episodes of febrile neutropenia were included; 13 RCTs and 24 prospective observational cohorts. Four safety events (two deaths, two intensive care admissions) occurred. In the RCTs, the odds ratio for treatment failure (persistence, worsening or recurrence of fever/infecting organisms, antibiotic modification, new infections, re-admission, admission to critical care or death) with outpatient treatment was 0.98 (95% confidence interval (95%CI) 0.44-2.19, I (2) = 0 %) and with oral treatment was 1.05 (95%CI 0.74-1.48, I (2) = 0 %). The estimated risk of failure using outpatient therapy from all prospective data pooled was 11.2 % (95%CI 9.7-12.8 %, I (2) = 77.2 %) and using oral antibiotics was 10.5 % (95%CI 8.9-12.3 %, I (2) = 78.3 %). The risk of failure was higher when reduced intensity therapies were used immediately after assessment, with lower rates when these were introduced after 48 hours. CONCLUSIONS: Reduced intensity therapy for specified groups is safe with low rates of treatment failure. Services should consider how these can be acceptably implemented