Diminished Intracellular Invariant Chain Expression Following Vaccinia Virus Infection

Vaccinia virus (VV) has been used as a vaccine to eradicate smallpox and as a vaccine for HIV and tumors. However, the immunoevasive properties of VV, have raised safety concerns. VV infection of APC perturbs MHC class II-mediated Ag presentation. Exposure of human B cell lines to VV induced a dramatic reduction in cellular expression of the class II chaperone, invariant chain (Ii) during the late stages (i.e. 8–10 h) of infection. Yet, cell viability and surface expression of MHC class II molecules were maintained up to 24 h after exposure to virus. Reductions in Ii and class II mRNA levels were detected as early as 6 h after VV infection of APC. To examine whether VV was acting solely to disrupt host protein synthesis, B cells were treated with an inhibitor of translation, cycloheximide (CHX). Within 1 h of B cell CHX treatment, Ii protein expression decreased coupled with a loss of class II presentation. Analysis of Ii degradation in VV or CHX treated cells, revealed on-going Ii proteolysis contributing to reduced steady state Ii levels in these APC. Yet in contrast with CHX, VV infection of APC altered lysosomal protease expression and Ii degradation. Virus infection induced cellular cathepsin L expression while reducing the levels of other lysosomal proteases. These results demonstrate that at late stages of VV infection, reductions in cellular Ii levels coupled with changes in lysosomal protease activity, contribute in part to defects in class II presentation

State Constitutional Remedy Provisions and Article I, Section 10 of the Washington State Constitution: The Possibility of Greater Judicial Protection of Established Tort Causes of Action and Remedies

Several state courts interpret their states\u27 constitutional remedy provisions as justifying heightened judicial scrutiny of legislative alterations in tort law. This confers greater protection of tort causes of action and remedies established at the time of the state constitution\u27s adoption. This Comment considers whether article I, section 10 of the Washington constitution can support such an interpretation. Additionally, the author discusses the existing interpretations of other states\u27 remedy provisions and suggests a heightened scrutiny model that best balances the interest in retaining already recognized tort remedies against the interest in fostering positive change

Ownership motivation and strategic planning in small business

This study investigates whether strategic planning in small businesses is related to the business ownership motivations of operators. In particular, the study compares the propensity of operators motivated by financial versus personal/non-financial goals to engage in strategic planning for their businesses

Fidelity Assessment in Community Programs: An Approach to Validating Simplified Methodology.

Fidelity to intervention protocol is linked to best outcomes for individuals with autism spectrum disorder (ASD; see Boyd & Corley [Autism 5(4):430-441, 2001]; Pellecchia et al. [J Autism Dev Disord 45(9):2917-2927, 2015]); however, fidelity measurement tools that are both accurate and feasible for community use are often not available. In this paper we explore methods for validated simplification of fidelity assessment procedures toward the goal of increased use in clinical practice. Video recordings (n = 36) of therapists working with children with ASD were coded using three variations of fidelity assessment methodology (trial-by-trial, 5-point Likert Scale, and 3-point Likert Scale), and the results were compared for exact agreement, mastery criterion agreement, and overall reliability. The results indicated overall a very high percentage of exact agreement (mean 99.44%, range 94.4-100%) and excellent reliability (mean Krippendorff's alpha [Kα] 1.0) between the trial-by-trial and 5-point Likert Scale across all components; however, the 3-point method may be viewed as being the more feasible strategy within community programs

Explaining the lack of strategic planning in SMEs: The importance of owner motivation

Considerable evidence shows that strategic planning leads to increased firm performance. Yet, the majority of SMEs do not plan and the reasons why are not well understood. This article questions the common approach to understanding this problem based on identifying business barriers to planning. For the majority of SME owner operators, business performance often ranks far behind intangible goals such as autonomy, personal satisfaction and lifestyle. Strategic planning may therefore have little value to owner-operators driven by such motivators. This article presents an alternative perspective to the issue by arguing that owner aspirations are integral to whether or not SMEs strategically plan

An Unusual Cause of Acute Hypercapneic Respiratory Failure

We present a rare cause of hypercapneic respiratory failure through this case report of a 72-year-old man presenting with progressive dyspnea and dysphagia over two years. Hypercapneic respiratory failure was acute on chronic in nature without an obvious etiology. Extensive workup for intrinsic pulmonary disease and neurologic causes were negative. Laryngoscopy and diagnostic imaging confirmed the diagnosis of diffuse idiopathic skeletal hyperostosis, also known as DISH, as the cause of upper airway obstruction leading to hypercapneic respiratory failure

Pascalammetry with operando microbattery probes: Sensing high stress in solid-state batteries.

Energy storage science calls for techniques to elucidate ion transport over a range of conditions and scales. We introduce a new technique, pascalammetry, in which stress is applied to a solid-state electrochemical device and induced faradaic current transients are measured and analyzed. Stress-step pascalammetry measurements are performed on operando microbattery probes (Li2O/Li/W) and Si cathodes, revealing stress-assisted Li+ diffusion. We show how non-Cottrellian lithium diffusional kinetics indicates stress, a prelude to battery degradation. An analytical solution to a diffusion/activation equation describes this stress signature, with spatiotemporal characteristics distinct from Cottrell's classic solution for unstressed systems. These findings create an unprecedented opportunity for quantitative detection of stress in solid-state batteries through the current signature. Generally, pascalammetry offers a powerful new approach to study stress-related phenomena in any solid-state electrochemical system

Pairing flavours and the temporal order of tasting

There can be little doubt that plating food beautifully is becoming ever more important in the world of high-end cuisine. However, there is a very real danger that all the attention to how a dish looks (or photographs) can end up obscuring the importance of temporal order to flavour perception. That is, there is an increasing tendency to prioritize plating elements in a dish so that they please the eyes of the beholder, rather than necessarily because they deliver the optimum balance of sensations to the palate. Relevant here is the fact that certain combinations of ingredients taste better when sampled simultaneously, or in a particular sequence, than when sampled in a different order. In this review, we examine the importance of sequencing and pairing taste/flavour sensations, both in the design of the meal itself, and when attempting to combine (or match) food and drink. We address the chemical, psychological, and computational strategies that have been suggested by those wishing to combine flavours for maximal impact. We evaluate three general principles of flavour matching: similarity - matching components based on common flavour compounds (or similar flavour profiles); contrast - combinations that are purposely chosen because they differ from each other (a strategy that is more common in the cuisine of some countries than others), and synergy (or emergence) – those combinations that together deliver new flavour experiences, or else harmonize with one another. We argue that the psychological account (informed by an awareness of cultural differences), and to a lesser extent the chemical account, provide meaningful suggestions as far as effectively combining flavours is concerned

Towards a Real-Time Data Driven Wildland Fire Model

A wildland fire model based on semi-empirical relations for the spread rate of a surface fire and post-frontal heat release is coupled with the Weather Research and Forecasting atmospheric model (WRF). The propagation of the fire front is implemented by a level set method. Data is assimilated by a morphing ensemble Kalman filter, which provides amplitude as well as position corrections. Thermal images of a fire will provide the observations and will be compared to a synthetic image from the model state.Comment: 5 pages, 4 figure