1,543 research outputs found
Success Through Community Cultural Wealth: Reflections From Black Female College Athletes at a Historically Black College/University (HBCU) and a Historically White Institution (HWI)
The purpose of this study was to explore the experiences of Black female college athletes at a Division I historically Black college/university (HBCU) and historically White institution (HWI) and identify key influences that facilitated their academic achievement and positive educational experiences. Two focus groups and eight individual interviews were conducted with three Black female college athletes at a HBCU and five Black female college athletes at a HWI. An 8-item demographic questionnaire was administered to obtain information related to the participantsâ personal backgrounds. Yossoâs (2005) community cultural wealth framework was incorporated to highlight individual and environmental influences that contributed to participantsâ positive educational and developmental outcomes. Findings revealed participants accessed and leveraged various forms of familial, resistant, aspirational, social, and navigational capital to overcome challenges and excel in college. Implications for policy and practice are discussed
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Defining the Role of Tyrosine Nitration in Biology with Genetic Code Expansion
The buildup of reactive oxygen species (ROS) and reactive nitrogen and oxygen species (RNS) is known as oxidative stress. Oxidative stress results in a wide variety of modification to biological macromolecules including nucleic acids, lipids, and proteins. For at least 30 years it has been known that high levels of oxidative stress leads to damage to cellular components resulting in cell death via apoptosis and necrosis. In perhaps the last 10 years it has become clear that ROS and RNS also mediate âredox signalingâ via specific macromolecule modifications. The formation of the oxidative post-translational modification (Ox-PTM) 3-nitrotyrosine (nitroTyr) in proteins serves as the main biomarker of oxidative stress and is present in over 50 disease pathologies. In the vast majority of these diseases it is not known if the nitroTyr is simply a bystander or is playing an active role driving disease progression. Genetic code expansion (GCE) has emerged as a method to install noncanonical amino acids (ncAAs) into proteins of interest. Here we develop several GCE systems for the incorporation of nitroTyr to address the role of tyrosine nitration in biology.
This dissertation presents studies aimed to both improve and develop GCE systems for encoding nitroTyr in E. coli and eukaryotic cells, and to apply this ability to studying the effect of tyrosine nitration on the calcium (Ca²âş) regulatory protein calmodulin (CaM). Four chapters of original work are presented in this dissertation and include one review and three primary research reports. Three of the chapters (Chapters 2, 3, and 5) focus on the development and optimization of GCE systems for the incorporation of the nitroTyr, and the other chapter (Chapter 4) focuses on the application of the GCE systems to evaluate the nitroTyr Ox-PTMs in the regulatory hub protein, CaM, as the first report of regulating a protein function with the nitroTyr PTM. Chapters 2 and 3 are published; Chapters 4 and 5 are at the stage of manuscripts in preparation for submission. These central chapters are bookended by a brief introduction to oxidative stress and GCE (Chapter 1) and concluding remarks on my summary of the impact of this work, and perspective on future directions (Chapter 6).
In the first research chapter (Chapter 2), I review the strengths and weaknesses of GCE for the study of Ox-PTMs, provide an overview of the Ox-PTMs that have been genetically encoded and applications of GCE to the study of Ox-PTMs. The GCE systems for nitroTyr reviewed in Chapter 2, show clear phenotypic evidence that they cannot match the efficiency of natural translational systems, however the root causes of these efficiencies were unknown. In Chapter 3, I correlate the efficiency of in vivo GCE with kinetic constants derived from the in vitro aminoacylation reactions carried out by several nitrotyrosyl-aminoacyl-tRNA synthetases (nitrotyrosyl-aaRS-tRNA) derived from the Methanocaldococcus janaschii (M. jannaschii) tyrosyl-aaRS-tRNA. On the basis of these measurements I report that certain modifications made to the tRNA sequence thought to be necessary for maintaining translational fidelity are not necessary and negatively impact the efficiency of the system.
With these optimized tools in hand I applied them to addressing a major outstanding question in the oxidative stress field in chapter 4; can the oxidative stress induced nitrotyrosine PTM regulate protein function? As a way to address the question I investigated the effect of tyrosine nitration on the regulatory hub protein CaM. Tyrosine phosphorylation of CaM is known to modulate its regulation of intracellular Ca²⺠signling. Proteomic studies have also revealed that both tyrosines in CaM are nitrated in vivo, although the impact of this modification is unknown. The effect of tyrosine nitration on the CaM target protein endothelial nitric oxide synthase (eNOS) is of particular interest as this signaling protein can generate the oxidants that result in tyrosine nitration, potentially indicating a feedback loop and signaling microdomain. Using GCE I show that tyrosine nitration alters CaM regulation with regard to eNOS function in vitro and in eukaryotic cell lysate.
To extend this research further, I developed a system to genetically encode tyrosine nitration directly into proteins in eukaryotic cells (Chapter 5). This is an empowering technology for studying the impact of tyrosine nitration on regulation/dysregulation of cellular function in the native context of the modification. This technology is also of particular utility for the study of nitrated transmembrane proteins that need to be studied in eukaryotic cell culture or animal models
Effects of Self-Generated Noise on Estimates of Detection Threshold in Quiet for School-Age Children and Adults
Detection thresholds in quiet become adult-like earlier in childhood for high than low frequencies. When adults listen for sounds near threshold, they tend to engage in behaviors that reduce physiologic noise (e.g., quiet breathing), which is predominantly low frequency. Children may not suppress self-generated noise to the same extent as adults, such that low-frequency self-generated noise elevates thresholds in the associated frequency regions. This possibility was evaluated by measuring noise levels in the ear canal simultaneous with adaptive threshold estimation
Deep Space Habitat Wireless Smart Plug
NASA has been interested in technology development for deep space exploration, and one avenue of developing these technologies is via the eXploration Habitat (X-Hab) Academic Innovation Challenge. In 2013, NASA's Deep Space Habitat (DSH) project was in need of sensors that could monitor the power consumption of various devices in the habitat with added capability to control the power to these devices for load shedding in emergency situations. Texas A&M University's Electronic Systems Engineering Technology Program (ESET) in conjunction with their Mobile Integrated Solutions Laboratory (MISL) accepted this challenge, and over the course of 2013, several undergraduate students in a Capstone design course developed five wireless DC Smart Plugs for NASA. The wireless DC Smart Plugs developed by Texas A&M in conjunction with NASA's Deep Space Habitat team is a first step in developing wireless instrumentation for future flight hardware. This paper will further discuss the X-Hab challenge and requirements set out by NASA, the detailed design and testing performed by Texas A&M, challenges faced by the team and lessons learned, and potential future work on this design
Existential Risk and Equal Political Liberty
Rawls famously argues that the parties in the original position would agree upon the two principles of justice. Among other things, these principles guarantee equal political libertyâthat is, democracyâas a requirement of justice. We argue on the contrary that the parties have reason to reject this requirement. As we show, by Rawlsâ own lights, the parties would be greatly concerned to mitigate existential risk. But it is doubtful whether democracy always minimizes such risk. Indeed, no one currently knows which political systems would. Consequently, the partiesâand we ourselvesâhave reason to reject democracy as a requirement of justice in favor of political experimentalism, a general approach to political justice which rules in at least some non-democratic political systems which might minimize existential risk
Education in the working-class home: modes of learning as revealed by nineteenth-century criminal records
The transmission of knowledge and skills within the working-class household greatly troubled social commentators and social policy experts during the first half of the nineteenth century. To prove theories which related criminality to failures in working-class up-bringing, experts and officials embarked upon an ambitious collection of data on incarcerated criminals at various penal institutions. One such institution was the County Gaol at Ipswich. The exceptionally detailed information that survives on families, literacy, education and apprenticeships of the men, women and children imprisoned there has the potential to transform our understanding of the nature of home schooling (broadly interpreted) amongst the working classes in nineteenth-century England. This article uses data sets from prison registers to chart both the incidence and âsuccessâ of instruction in reading and writing within the domestic environment. In the process, it highlights the importance of schooling in working-class families, but also the potentially growing significance of the family in occupational training
Discriminative stimulus properties of 1.25 mg/kg clozapine in rats: Mediation by serotonin 5-HT2 and dopamine D4 receptors
The atypical antipsychotic drug clozapine remains one of most effective treatments for schizophrenia, given a lack of extrapyramidal side effects, improvements in negative symptoms, cognitive impairment, and in symptoms in treatment-resistant schizophrenia. The adverse effects of clozapine, including agranulocytosis, make finding a safe clozapine-like a drug a goal for drug developers. The drug dis- crimination paradigm is a model of interoceptive stimulus that has been used in an effort to screen experimental drugs for clozapine-like atypical antipsychotic effects. The present study was conducted to elucidate the receptor-mediated stimulus properties that form this clozapine discriminative cue by testing selective receptor ligands in rats trained to discriminate a 1.25 mg/kg dose of clozapine from vehicle in a two choice drug discrimination task. Full substitution occurred with the 5-HT2A inverse agonist M100907 and the two preferential D4/5-HT2/Îą1 receptor antagonists Lu 37-114 ((S)-1-(3-(2-(4- (1H-indol-5-yl)piperazin-1-yl)ethyl)indolin-1-yl)ethan-1-one) and Lu 37-254 (1-(3-(4-(1H-indol-5-yl) piperazin-1-yl)propyl)-3,4-dihydroquinolin-2(1H)-one). Partial substitution occurred with the D4 re- ceptor antagonist Lu 38-012 and the Îą1 adrenoceptor antagonist prazosin. Drugs selective for 5-HT2C, 5-HT6 muscarinic, histamine H1, and benzodiazepine receptors did not substitute for clozapine. The present findings suggest that 5-HT2A inverse agonism and D4 receptor antagonism mediate the dis- criminative stimulus properties of 1.25 mg/kg clozapine in rats, and further confirm that clozapine produces a complex compound discriminative stimulus
Delays in Leniency Application: Is There Really a Race to the Enforcer's Door?
This paper studies cartelsâ strategic behavior in delaying leniency applications, a take-up decision that has been ignored in the previous literature. Using European Commission decisions issued over a 16-year span, we show, contrary to common beliefs and the existing literature, that conspirators
often apply for leniency long after a cartel collapses. We estimate hazard and probit models to study the determinants of leniency-application delays. Statistical tests find that delays are symmetrically affected by antitrust policies and macroeconomic fluctuations. Our results shed light on the design of
enforcement programs against cartels and other forms of conspiracy
Multiabsorber Transition-Edge Sensors for X-Ray Astronomy
We are developing arrays of position-sensitive microcalorimeters for future x-ray astronomy applications. These position-sensitive devices commonly referred to as hydras consist of multiple x-ray absorbers, each with a different thermal coupling to a single-transition-edge sensor microcalorimeter. Their development is motivated by a desire to achieve very large pixel arrays with some modest compromise in performance. We report on the design, optimization, and first results from devices with small pitch pixels (<75 m) being developed for a high-angular and energy resolution imaging spectrometer for Lynx. The Lynx x-ray space telescope is a flagship mission concept under study for the National Academy of Science 2020 decadal survey. Broadband full-width-half-maximum (FWHM) resolution measurements on a 9-pixel hydra have demonstrated E(FWHM) = 2.23 0.14 eV at Al-K, E(FWHM) = 2.44 0.29 eV at Mn-K, and E(FWHM) = 3.39 0.23 eV at Cu-K. Position discrimination is demonstrated to energies below <1 keV and the device performance is well-described by a finite-element model. Results from a prototype 20-pixel hydra with absorbers on a 50-m pitch have shown E(FWHM) = 3.38 0.20 eV at Cr-K1. We are now optimizing designs specifically for Lynx and extending the number of absorbers up to 25/hydra. Numerical simulation suggests optimized designs could achieve 3 eV while being compatible with the bandwidth requirements of the state-of-the art multiplexed readout schemes, thus making a 100,000 pixel microcalorimeter instrument a realistic goal
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