Design and development of a 5 kV isolated solid state switch

A unique microcircuit intended for use as a shorting switch for large extraterrestrial solar cell arrays is described. The packaging design for the 5 kV isolated hybrid switch is different from most hybrid microcircuits in that it utilizes a compartmentalized plastic case (a portion of which is encapsulated), is not hermetic, and is designed for high voltage operation

Science lives: School choices and ‘natural tendencies’

An analysis of 12 semi-structured interviews with university-based scientists and non-scientists illustrates their life journeys towards, or away from, science and the strengths and impact of life occurrences leading them to choose science or non-science professions. We have adopted narrative approaches and used Mezirow's transformative learning theory framework. The areas of discussion from the result have stressed on three main categories that include ‘smooth transition’, ‘incremental wavering transition' and ‘transformative transition’. The article concludes by discussing the key influences that shaped initial attitudes and direction in these people through natural inclination, environmental inspirations and perceptions of science

TNF receptor signalling in autoinflammatory diseases

Autoinflammatory syndromes are a group of disorders characterised by recurring episodes of inflammation as a result of specific defects in the innate immune system. Patients with autoinflammatory disease present with recurrent outbreaks of chronic systemic inflammation that are mediated by innate immune cells, for the most part. A number of these diseases arise from defects in the tumour necrosis factor (TNF) receptor signalling pathway leading to elevated levels of inflammatory cytokines. Elucidation of the molecular mechanisms of these recently defined autoinflammatory diseases has led to a greater understanding of the mechanisms of action of key molecules involved in TNFR signalling, particularly those involved in ubiquitination, as found in haploinsufficiency of A20 (HA20), otulipenia/otulin-related autoinflammatory syndrome (ORAS) and linear ubiquitin chain assembly complex (LUBAC) deficiency. In this review we also address other TNFR signalling disorders such as (TNF) receptor-associated periodic syndrome (TRAPS), RELA haploinsufficiency, RIPK1-associated immunodeficiency and autoinflammation, X-linked ectodermal dysplasia and immunodeficiency (X-EDA-ID) and we review the most recent advances surrounding these diseases and therapeutic approaches currently used to target these diseases. Finally, we explore therapeutic advances in TNF-related immune based therapies and explore new approaches to target disease-specific modulation of autoinflammatory diseases

Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations

Cystic fibrosis (CF) is one of the most common life-limiting recessive genetic disorders in Caucasians, caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). CF is a multi-organ disease that involves the lungs, pancreas, sweat glands, digestive and reproductive systems and several other tissues. This debilitating condition is associated with recurrent lower respiratory tract bacterial and viral infections, as well as inflammatory complications that may eventually lead to pulmonary failure. Immune cells play a crucial role in protecting the organs against opportunistic infections and also in the regulation of tissue homeostasis. Innate immune cells are generally affected by CFTR mutations in patients with CF, leading to dysregulation of several cellular signalling pathways that are in continuous use by these cells to elicit a proper immune response. There is substantial evidence to show that airway epithelial cells, neutrophils, monocytes and macrophages all contribute to the pathogenesis of CF, underlying the importance of the CFTR in innate immune responses. The goal of this review is to put into context the important role of the CFTR in different innate immune cells and how CFTR dysfunction contributes to the pathogenesis of CF, highlighting several signalling pathways that may be dysregulated in cells with CFTR mutations

The Biotechnology Cluster in Vancouver

There is a strong biotechnology cluster in Vancouver yet there is no major manufacturing facility. The Vancouver cluster is unlike other biotech clusters in that its output is solely intellectual property. This ongoing study not only examines the usual structure of a cluster, but also will focus on the issue of intellectual environment, and seek to determine whether a strong cluster can be built without the presence of a large, globally-competitive, manufacturer

The Highly Damped Quasinormal Modes of dd-dimensional Reissner-Nordstrom Black Holes in the Small Charge Limit

We analyze in detail the highly damped quasinormal modes of $d$-dimensional Reissner-Nordstr$\ddot{\rm{o}}$m black holes with small charge, paying particular attention to the large but finite damping limit in which the Schwarzschild results should be valid. In the infinite damping limit, we confirm using different methods the results obtained previously in the literature for higher dimensional Reissner-Nordstr$\ddot{\rm{o}}$m black holes. Using a combination of analytic and numerical techniques we also calculate the transition of the real part of the quasinormal mode frequency from the Reissner-Nordstr$\ddot{\rm{o}}$m value for very large damping to the Schwarzschild value of $\ln(3) T_{bh}$ for intermediate damping. The real frequency does not interpolate smoothly between the two values. Instead there is a critical value of the damping at which the topology of the Stokes/anti-Stokes lines change, and the real part of the quasinormal mode frequency dips to zero.Comment: 18 pages, 8 figure

Split Tickets? On the Strategic Allocation of Presidential Versus Vice Presidential Visits in 2016

This article analyzes the strategic allocation of presidential campaign visits in 2016. In particular, we test whether each campaign disproportionately targeted its presidential versus vice presidential candidates’ visits toward voters with whom they shared a salient demographic or political characteristic. Our purpose in doing so is to discern whether—and, if so, among which groups—the campaigns perceived the candidates as having a strategic advantage in appealing to affiliated voters. To this end, we analyze an original database of 2016 campaign visits that includes local population characteristics for each host site. Our results indicate that each ticket’s visits were highly coordinated across states, but frequently divergent within states. At the substate level, we find several systematic differences in the populations visited by presidential versus vice presidential candidates—in some cases aligning with a candidate’s personal characteristics. We discuss these findings’ implications with respect to campaign strategy and vice presidential selection

Stable isotopes reveal trophic relationships and diet of consumers in temperate kelp forest and coral reef ecosystems

We explored the use of stable nitrogen (N) isotope analysis to assess trophic position of consumers in two marine ecosystems: the kelp forests of southern California and a coral atoll in the tropical Pacific. The delta N-15 values of consumers in both ecosystems increased from known herbivores (invertebrates and fish) to higher-level consumers (predatory invertebrates and fish). In the absence of data on trophic enrichment in N-15 for our study species, we used the oft-cited value of +3.4 parts per thousand increase in delta N-15 value per trophic level and estimates of the delta N-15 producer baseline value to estimate trophic position. The trophic position of consumers computed using N isotopes compared favorably to published observations of diet. Nitrogen isotope analysis revealed that some of our higher-level fish consumers from rocky reefs (i.e., some rockfish) were feeding largely on invertebrates rather than on fish, as is often assumed. Our analysis also suggests that higher-level consumers on coral reefs may consume more herbivorous prey (i.e., both fishes and invertebrates) than previously reported. Our data support the use of nitrogen isotope values to assess trophic position and, thus, their utility as one metric with which to explore the effects of short- and longer-term natural and human-induced changes on kelp forest and coral reef food webs

Excessive ENaC-mediated sodium influx drives NLRP3 inflammasome-dependent autoinflammation in cystic fibrosis

Cystic Fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and results in defective CFTR-mediated chloride transport, dysregulation of epithelial sodium channels (ENaC) and exaggerated innate immune responses. We tested the hypothesis that upregulation of ENaC drives autoinflammation in this complex monogenic disease.We show that monocytes from patients with CF exhibit a systemic proinflammatory cytokine signature, with associated anti-inflammatory M2-type macrophage deficiency. Cells harboring CF mutations are hyperresponsive to NLRP3 stimulation, as evidenced by increased IL-18, IL-1β, ASC-specks levels in serum and caspase-1 activity in monocytes, and by increased IL-18 production and caspase-1 activity in human bronchial epithelial cells (HBECs). In both cell types there is an associated shift to glycolytic metabolism with succinate release, in response to increased energy requirements. Inhibition of amiloride-sensitive sodium channels partially reverses the NLRP3-dependent inflammation and metabolic shift in these cells. Overexpression of β-ENaC, in the absence of CFTR dysfunction, increases NLRP3-dependent inflammation, indicating a CFTR-independent ENaC axis in CF pathophysiology. Sodium channel modulation provides an important therapeutic strategy to combat lung inflammation in CF.</jats:p