954 research outputs found
American Forum Non Conveniens in Light of the Hague Convention on Choice-of-Court Agreements
Little Grill Guy, LLP, (LGG) is a small Pittsburgh firm whose primary business is making and selling high-end gas grills for outdoor use. Recently, a famous chef used LGG’s top-of-the-line model when preparing a meal on a very popular Japanese cooking game show. As often happens when American culture is injected into the Japanese limelight, Japanese consumers have been clamoring for LGG products since the episode aired. LGG has started negotiations with Tokyo-Mart, Inc., the largest commercial retailer in Japan. Despite its recent fame in Japan, LGG is still a small firm in a small industry and has relatively little bargaining power compared to the retail giant.\u
Investigation of Pulse Detonation Engines: the Effect of Variable Blockage Ratio on the Deflagration to Detonation Transition
Detonation and constant volume combustion is well known to be thermodynamically more efficient than the typically utilized constant pressure. There have been numerous approaches of achieving detonation through deflagration-to-detonation transition most of which use evenly spaced obstacles with a specified constant blockage ratio to generate turbulence and pressure fluctuations. There have been few efforts to study effects of varying blockage ratio as a function of axial distance. This research analyzes the effect of variable blockage ratio on deflagration-to-detonation transition in ethylene-air mixtures. The experiments show that with certain blockage ratio functions detonation is more repeatable and produces a smaller variation in both peak pressure and wave velocity representative of consistently stable detonations
Remote Neutron Spectroscopy on Mars
Remote neutron spectroscopy is an important technique in planetary science that allows for classification of the amount of light elements in a planetary regolith. It is especially suited for studying hydrogen abundances and elements with high thermal neutron absorption cross sections in the top ~1 meter of regolith. The Mars Science Laboratory rover Curiosity carries the first rover based neutron spectrometer Dynamic Albedo of Neutrons (DAN) in Gale crater, Mars. As the DAN instrument operates in passive mode, it is sensitive to neutrons produced through Galactic Cosmic Ray interactions and neutrons generated by the rover\u27s Multi-Mission Radioisotope Thermoelectric Generator. In this work, we develop an appropriate simulation strategy and data analysis methods to interpret passive data from the DAN instrument. Furthermore, the methods are used to estimate water equivalent hydrogen abundances in the shallow regolith of Gale crater along the traverse route of Curiosity from landing to the base of Mt. Sharp. Hydrogen is shown to have large variability on a scale of a few meters, much smaller than the spatial footprint of previous orbital investigations. Strong correlations between WEH content and surface properties are not observed. While in passive operation, DAN also observes diurnal variations in the martian neutron leakage fluxes. These diurnal variations are investigated and shown to possibly be a consequence of a combination of instrumental effects and environmental effects, most notably preferential shielding of alpha particles by the martian atmosphere leading to increased neutron production in the regolith as the surface atmospheric pressure changes throughout the sol
A Phenomenological Study Examining the Experiences of Female High School Career and Technical Education Completers Who Participated in a Technology-Based Program of Study
The purpose of this phenomenological study was to investigate how female high school students who earned Career and Technical Education (CTE) completer status in a technology-based program of study (POS) in Virginia describe their experiences. CTE completer status is defined as having met the Virginia Department of Education’s CTE completer requirements in a technology-based POS. This study was guided by three theories: Self-efficacy theory was applied as it relates to the participants’ status as completers in a technology-based CTE POS; Role-congruity theory suggests that men and women occupy social roles with attendant stereotypes which contributed to how participants described their experience in a technology-based POS; Social cognitive career theory focuses on the factors influencing occupational choice-making. Using interviews, electronic discussion boards, and photo essays, the experiences of 12 participants who earned Virginia CTE completer status in a technology-based POS were examined to address the central research question: How do female high school students who earned CTE completer status in Virginia describe their experiences in a technology-based POS? Participants were selected through criterion sample. The data in this study was analyzed using the procedures of a transcendental phenomenology to gain a complete understanding of the participants\u27 shared experiences as females who earned completer status in a technology-based CTE POS. After thorough analysis of the data, three themes emerged: (a) instructor influence on program and participant goals; (b) the impact of collaboration; and (c) guidance and support focused on the individual
Engineering a minimal G protein to facilitate crystallisation of G protein-coupled receptors in their active conformation
G protein-coupled receptors (GPCRs) modulate cytoplasmic signalling in response to extracellular stimuli, and are important therapeutic targets in a wide range of diseases. Structure determination of GPCRs in all activation states is important to elucidate the precise mechanism of signal transduction and to facilitate optimal drug design. However, due to their inherent instability, crystallisation of GPCRs in complex with cytoplasmic signalling proteins, such as heterotrimeric G proteins and β-arrestins, has proved challenging. Here, we describe the design of a minimal G protein, mini-Gs, which is composed solely of the GTPase domain from the adenylate cyclase stimulating G protein Gs. Mini-Gs is a small, soluble protein, which efficiently couples GPCRs in the absence of Gβγ subunits. We engineered mini-Gs, using rational design mutagenesis, to form a stable complex with detergent-solubilised β1-adrenergic receptor (β1AR). Mini G proteins induce similar pharmacological and structural changes in GPCRs as heterotrimeric G proteins, but eliminate many of the problems associated with crystallisation of these complexes, specifically their large size, conformational dynamics and instability in detergent. They are therefore novel tools, which will facilitate the biochemical and structural characterisation of GPCRs in their active conformation
Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces
G protein-coupled receptors (GPCRs) regulate cellular signalling through heterotrimeric G proteins and arrestins in response to an array of extracellular stimuli. Structure determination of GPCRs in an active conformation bound to intracellular signalling proteins has proved to be highly challenging. Nonetheless, three new structures of GPCRs in an active state have been published during the last year, namely the adenosine A2A receptor (A2AR) bound to an engineered G protein, opsin bound to visual arrestin and the m opioid receptor (mOR) bound to a G protein-mimicking nanobody. These structures have provided novel insight into the sequence of events leading to GPCR activation, and have highlighted both similarities and differences in the structure of the interface between GPCRs and different signalling proteins
New insights into GPCR coupling and dimerisation from cryo-EM structures
Over the past three years (2020–2022) more structures of GPCRs have been determined than in the previous twenty years (2000–2019), primarily of GPCR complexes that are large enough for structure determination by single-particle cryo-EM. This review will present some structural highlights that have advanced our molecular understanding of promiscuous G protein coupling, how a G protein receptor kinase and β-arrestins couple to GPCRs, and GPCR dimerisation. We will also discuss advances in the use of gene fusions, nanobodies, and Fab fragments to facilitate the structure determination of GPCRs in the inactive state that, on their own, are too small for structure determination by single-particle cryo-EM
Confronting Institutional Discrimination in a Color-Blind World
This article builds on the scholarship on color-blind ideology by examining discourse challenging two cases of institutional discrimination (the criminalization of unauthorized immigrants and sports teams’ use of Native American symbolism). Our research questions are first, what general options do anti-racists have for navigating norms of color-blindness in the public sphere? Second, how does context influence how people confront institutional discrimination? Based on an ethnographic content analysis of 165 letters to the editor published in American newspapers, we find that opponents of institutional discrimination have the choice of addressing one of four laminations. In each lamination, authors acknowledge framings of racial discrimination that are unacknowledged in previous ones. In the abstraction lamination, authors do not recognize race and ethnicity. In the pigmentation lamination, authors identify race and ethnicity, but not discrimination. Authors in the discrimination lamination acknowledge the practice is harmful to a particular racial or ethnic group, and the contextualization lamination lends added dimensionality to the discourse. A comparison of the laminations of pro-immigrant and anti-mascot letters demonstrates varying willingness to acknowledge racial discrimination. Namely, the pro-immigrant discourse was more color-blind than anti-mascot criticism. We consider the potential causes of these findings and offer suggestions for future research in the conclusio
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