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Social Stress Modulations of Accumbal Dopamine during Extended Cocaine Binge.
No full textRationale: Increased vulnerability to drug abuse, specifically cocaine abuse, is associated with repeated exposure to stressful events, both in clinical populations and in animal models of drug abuse. Stressful experiences are hypothesized to induce long term neuroadaptations within dopamine rich circuitry which influences physiological and behavioral response to drug exposure. Objective: To examine factors that contribute to the maintenance and termination of extended bouts of cocaine intake, and the extent to which altered dopaminergic response to cocaine may promote sustained bingeing in defeat-experienced rats.Conclusions: These preliminary data offer some insight into potential stress induced differences in mesolimbic DA transmission during extended cocaine binge. Disparity in tonic extracellular DA lends some support to the DA deficiency hypothesis of addiction. However, defeat-experienced animals may also retain DA terminal function following prolonged cocaine exposure, which may facilitate extended bouts of self-administration. Further research is necessary to clarify these potential mechanisms by which stress experience potentiates escalated drug use, and perhaps, a vulnerability towards cocaine use disorder
Teaching Taboo: A Comparative Study of Secondary School Sex Education Curricula and Philosophies.
No full textThe purpose of this research was to understand schools' rationales for teaching sex education to high schoolers and how these schools' values and beliefs about sexuality, relationships, and intimacy consequently influenced the sex education curriculum that the institutions provide. By evaluating three sets of curricula across a range of academic institutions and paying particular attention to the ways in which schools address relationships, safety, and choices in their curricula, I hoped to uncover the principles most important to each school and context then propose evidence about what makes a successful sex education program in cross-comparing the three curricula
In Vitro Characterization of Acute Pain and Wound Healing In a Silk-Based Cornea Model.
No full textThe cornea is the most densely innervated peripheral tissue in the body, as detection of slight changes in the chemical, thermal, and physical environments of the ocular surface is necessary to protect eyesight. Damage to the cornea as a result of caustic chemical exposure can be painful and debilitating, underscoring the need for understanding ocular irritation mechanisms. The 3D in vitro silk-based cornea model developed by Wang et al (2017) is a novel tool for studying pain in the cornea as it is the first engineered cornea model to incorporate epithelium, keratocytes, and human sensory nerves in 3D scaffolding. In these studies this model was used to study the effects of pain and irritation mediated by transient receptor potential (TRP) channels vanilloid 1 and ankyrin 1 (TRPV1, TRPA1) using a variety of stimuli. The results show that this model is a viable tool for studying pain responses in vitro in a holistic, high throughput-like manner and shows promise as a novel and sensitive tool for studying chemical irritation
Identification of Pathogenic Lymphocyte Subsets in Ankylosing Spondylitis.
No full textKiller immunoglobulin-like receptors (KIRs) may play a role in the pathogenesis of ankylosing spondylitis (AS). KIR3DL2 binds to HLA-B27 homodimers and genetic associations with AS have been reported for KIR3DS1/DL1 and KIR2DL5. KIR expression is not limited to Natural Killer (NK) cells and has been demonstrated for other innate and adaptive lymphocyte subsets as well. We hypothesize that the previously described expansion of KIR3DL2 positive CD4+ T cells expressing the pathogenic cytokine IL-17A in HLA-B27+ individuals might be only one of many examples for the disease-promoting modulation of lymphocyte function by AS-associated KIRs in HLA-B27+ individuals. Distinct KIR expression profiles might identify pathogenic lymphocyte subsets in HLA-B27+ patients with AS. A 17-color flow cytometry panel was developed that distinguishes 8 lymphocyte subsets in human PBMCs stimulated with PMA/Ionomycin and permits the analysis of multiple KIRs and cytokines in a single sample. This panel will be used to analyze samples from HLA-B27+ and HLA-B27- healthy individuals in order to examine any correlations between HLA-B27 and KIR expression
Refusing Loyalty: Japanese American Incarceration, the U.S. Government's Racialized Construction of Citizenship, and My Grandfather's Fight for Justice.
No full textMy grandfather, Tadamichi "Joe" Tsuboi, was second-generation Japanese American, born in Covina, California in 1921. Because of early twentieth-century exclusionary naturalization laws that forbade his first-generation parents from attaining U.S. citizenship statuses, my grandfather was educated in Japan to maintain roots in the United States and in Japan. Yet, when Pearl Harbor was bombed in December 1941 and the U.S. entered World War II, in the eyes of the U.S. government, my grandfather's upbringing in Japan confirmed his status as potentially "disloyal" to his country of birth. During World War II, he was incarcerated at age twenty-one at a series of “Assembly Centers” and incarceration camps; he went from the Santa Anita Racetrack “Assembly Center” to the Jerome, Arkansas “Relocation Center” and from there to the Tule Lake, California “Relocation Center,” where he was kept under surveillance because of his status as second-generation Japanese American who were raised and/or educated in Japan, or kibei. Ultimately, at Tule Lake, my grandfather was forced to renounce his U.S. citizenship because he failed to meet the standards of American “loyalty” on the Loyalty Questionnaire. Through archival and ethnographic research, I analyze my grandfather's life: from his family's dynamic immigration history, their decision to send him to Japan for education, this incarceration experience as kibei and subsequent renunciation of U.S. citizenship, and, lastly, the legal battle he endured to restore a status that should have guaranteed him all civil rights
Analysis of Gas Diffusion-Induced Cassie to Wenzel State Transition
No full textAbstract: We develop one- and two-dimensional models for transient diffusion of gas between ridges into a quiescent liquid suspended in the Cassie state above them. In the first case study of the one-dimensional model, we assume that the liquid and gas are initially at the same pressure and that the liquid column is sealed at the top. In the second one, we assume that the gas initially undergoes isothermal compression and that the liquid column is exposed to gas at the top. In the two-dimensional model, we capture the effects of meniscus curvature and domain deformation and numerically solve the governing equations by using a Chebyshev collocation (spectral) method. Our models provide a framework to compute the transient gas concentration field in the liquid, the time when the triple contact line begins to move down the ridges, and the time when menisci reach the bottom of the substrate compromising the Cassie state. At illustrative conditions, we show the effects of geometry, hydrostatic pressure, and initial gas concentration on the Cassie to Wenzel state transition.Thesis (M.S.)--Tufts University, 2018.Submitted to the Dept. of Mechanical Engineering.Advisor: Marc Hodes.Committee: Erica Kemmerling, and Robert Viesca.Keyword: Mechanical engineering
Ceramic 'Pot' Water Filters: Investigations into Manufacturing and Performance
No full textAbstract: Ceramic 'pot' water filters (CWF) are widely used to improve the microbiological quality of drinking water at the point of use. CWFs are manufactured at >50 filter factories worldwide by pressing a mixture of clay and a burn-out material into the filter shape, which is then fired to a ceramic state. Silver is added during this process as a bactericide. In 2011, the Ceramics Manufacturing Working Group (CMWG) developed recommendations to, "provide guidance to assist filter factories in producing the lowest-cost, most-effective ceramic filters possible". The focus of this dissertation was to further this aim. Specifically, to: 1) investigate the effects of silver type, silver concentration, and input materials on CWF performance; 2) evaluate filter distribution programs; 3) develop a framework for evaluating manufacturing quality control protocols; and 4) synthesize research findings through a systematic literature review. Overall, results suggest that in households filtered water quality meets the low-risk guideline and filter use has been associated with a reduction in diarrheal disease. However, local context, including source water quality, time in use and supply chain access, likely influence long-term filter use and can affect in situ technology performance evaluation. Results from laboratory investigations and the systematic review demonstrate filters can achieve ≥2 log reduction in bacteria; however, silver should not be relied on as a principal treatment mechanism for long-term filter performance. Thus, it is recommended that filters be tested for bacteria removal prior to silver application. Burn-out material particle size and clay content (<2µm) are associated with bacteria removal by the porous matrix. Lastly, with participation from factories, a framework for evaluating quality control protocols was developed. CWFs are widely manufactured, promoted and used; thus, there is a need to continue supporting factories in manufacturing high-quality filters and to broadly disseminate research findings.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Civil Engineering.Advisor: Daniele Lantagne.Committee: David Gute, Derek Chitwood, and Kishore Pochampally.Keyword: Environmental engineering
Analysis of the Soluble Geochemistry of Extreme Environments to Assess the Habitability of Mars
No full textAbstract: The research presented here is aimed at evaluating the past and present habitability of Mars and the implications for whether or not life could have developed and evolved to persist on Mars. This work is motivated by the similarities in formation of Earth and Mars as well indications of large quantities of liquid water early in Mars' history. Evidence presented from a direct measurement of Mars through the soluble chemistry of the Tissint meteorite suggests that the conditions necessary to form prebiotic molecules in hydrothermal fluids was present on Mars in the recent past. This work also presents evidence for the persistence of subsurface microbial habitats in some of the most arid locations on Earth, suggesting a mechanism for preservation of life during the prolonged aridification of Mars. The availability of stable liquid water on the surface or in the subsurface remains one the biggest challenges for the persistence of life on Mars. This work evaluates water track features in Antarctica as analogues to recurring slope lineae (RSL) on Mars to evaluate the potential for RSL to be formed by stabilized liquid water in the form of brines. Finally, this work addresses how different environments on Earth can be related to different epochs of Mars and how the soluble chemistry of these environments can be used to inform the search for habitable environments on Mars.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Chemistry.Advisor: Samuel Kounaves.Committee: Yu-Shan Lin, Charles Mace, and Aaron Noell.Keyword: Chemistry
Next-generation DNA sequencing technologies and the study of trinucleotide repeat instability
No full textAbstract: Microsatellite repeats are the source of multiple hereditary diseases in humans. Certain repetitive sequences form unusual DNA structures that differ from standard B-form DNA. As the length of a repeat increases, structures form more frequently and stably. Secondary structures can interfere with numerous cellular processes, leading to expansions and contractions of the repetitive tract, double-strand breaks (DSBs) and complex genomic rearrangements (CGRs). DNA sequencing technologies have developed in leaps and bounds in the previous decade. Large-scale DNA sequencing is now fast and inexpensive. More recently, it has become possible to sequence long stretches of DNA in a single, contiguous read. This has exciting possibilities for the study of microsatellites and CGRs, both of which are difficult to resolve using short-read sequencing technologies. I present here two innovative applications of DNA sequencing technologies used to uncover new mechanisms of microsatellite instability. In Chapter 2, short-read DNA sequencing is central to a novel screening method to identify genes involved in (GAA)n repeat expansion using yeast as a model system. This led to identification of mutants of the polyadenylation gene YSH1, later found to affect transcription-replication collisions that cause DSBs. Chapter 3 also concerns the role of transcription and the effect of nucleosome positioning on (GAA)n repeat expansions. Chapter 1 consists of a review highlighting the importance of using model systems to identify characterize modifiers of microsatellites, revealing molecular mechanisms and potentially informing human health. In Chapter 4, long-read Nanopore sequencing was used to uncover mechanisms leading to CGRs. This approach demonstrates that DNA rearrangements can be captured within individual sequencing reads, revealing the mechanisms by which DNA breakage and repair occur, including the invasion of (GAA)n repeats into other areas of the genome, recombination between repetitive transposable elements, and the use of break-induced replication. This approach can be extended not only to the further study of microsatellite instability and DNA repair, but also to cancer, where CGRs are frequent.Thesis (Ph.D.)--Tufts University, 2018.Submitted to the Dept. of Biology.Advisor: Sergei Mirkin.Committee: Catherine Freudenreich, Mitch McVey, and Shamil Sunyaev.Keywords: Genetics, and Molecular biology