48670 research outputs found
Sort by
The Role Of Neuropilin2a/b And Sema3fa In The Protoglomerular Targeting Of Zebrafish Olfactory Sensory Neurons
Get PDFDuring development, zebrafish olfactory sensory neurons (OSNs) project axons from the olfactory epithelium to neuropil structures in the olfactory bulb (OB) known as protoglomeruli. OSNs expressing either OMP or TRPC2 exclusively project axons to two distinct, complementary sets of protoglomeruli. It is not known how differential protoglomerular targeting of these two populations is maintained. The guidance receptors nrp2a and nrp2b, along with their ligand sema3fa, were identified through RNAseq as potential candidates responsible for differential protoglomerular targeting of OMP- and TRPC2-class OSNs. Nrp2a and nrp2b are expressed in TRPC2-class OSNs, while sema3fa is expressed in OMP-class OSNs and OB. To investigate the involvement of these guidance factors in OSN axon guidance, the protoglomerular targeting fidelity of OSNs expressing OMP:RFP or TRPC2:Venus were assessed in nrp2a, nrp2b, and sema3fa mutants. The roles for these three guidance factors were further investigated through genetic interaction studies and live time-lapse imaging experiments. Targeting fidelity of TRPC2-class OSNs is degraded in nrp2a, nrp2b, and sema3fa mutants with increased rates of misprojecting axons observed in OMP-specific protoglomeruli as well as non-protoglomerular regions within the OB. Genetic interaction experiments suggest that nrp2a and nrp2b are partially redundant and that sema3fa is likely one of multiple guidance cues that acts in the same pathway as nrp2a and nrp2b. Live time-lapse imaging experiments comparing nrp2a and sema3fa mutants to their heterozygous siblings show that the dynamic behavior of TRPC2-class OSN growth cones are altered in mutant animals. The results support a model in which sema3fa functions as a repulsive cue to exclude nrp2a- and/or nrp2b-expressing TRPC2-class OSNs from OMP-specific protoglomeruli as well as form the dorsal-medial OB, adding to a growing list of guidance factors involved in protoglomerular targeting of OSNs. I also describe a protocol for the registration of guidance cue expression data in the 36hpf OB and present an unbiased registration template and model of the 72hpf OB and protoglomeruli. This work highlights the complex interaction of guidance factors involved in protoglomerular targeting of OSNs and lays a foundation for the systematic study of olfactory circuit formation
Institutionalization Of Green Infrastructure Planning For Wastewater And Stormwater Management In The United States
No full textScholars and practitioners have widely advocated the use of green infrastructure for water quality improvements. The United States has witnessed an emphasis on cost-effectiveness and co-benefits as the federal government has enforced green infrastructure planning in some Clean Water Act compliance cases. In addition, planning scholarship generally assumes that a growing number of cities are adopting green infrastructure. How and to what extent cities have integrated green infrastructure into institutional planning, however, is a subject that has received little attention. This dissertation evaluates the status of institutional green infrastructure planning and investigates the impact of federal mandates on the institutionalization. This research consists of two phases: a landscape study to understand the overall status of green infrastructure planning to control stormwater and combined sewer overflows, and an in-depth study to highlight how each federal mandate impacted differences. Phase 1 first characterizes green infrastructure elements in U.S. Environmental Protection Agency consent decrees and the planning documents of 41 local governments. Based on the content analysis findings, I then examined the impact of federal mandates on planning and implementation status. Phase 2 takes a comparative analysis of two cases: the maximum and minimum federal direction cases. I conducted semi-structured interviews to add nuance in actual practice and used Google Street Views to exhibit the differences in mandated projects and changes in pre- and post-construction conditions. The results of the landscape study demonstrate a lack of standardization in federal enforcement as well as local green infrastructure planning to control stormwater and combined sewer overflows. The case studies suggest that green infrastructure may not be a cost-effective and multifunctional solution for sewer authorities, especially in terms of CSO reduction. The findings also indicate room for both regulatory and planning improvements to better institutionalize green infrastructure planning while facilitating desired outcomes. The dissertation concludes with policy and planning recommendations for regulatory bodies and local governments, including a measurable goal setting through a phased approach, an evaluation framework with more frequent performance reviews, a robust and strategic pilot project plan, a community- and project-specific co-benefit analysis, and a cost-sharing scheme
Development Of Novel Vaccination Strategies Against Emerging Bunyaviruses
Get PDFSevere fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic emergent bunyavirus. First isolated in 2009 in China, SFTSV is now endemic to several east Asian countries where high case fatality ratios of 6-30% are reported. The primary tick vector of SFTSV, Haemaphysalis longicornis, has a large range and is a well reported invasive species throughout the world. This, in addition to SFTSV’s ability to spread in the absence of its vector in nosocomial and veterinary settings, suggests SFTSV is well suited to cause widespread lethal outbreaks. Currently no vaccines or therapeutics against SFTSV exist, prompting health agencies to list SFTSV as a high priority pathogen. Here, we first develop a single dose recombinant vesicular stomatitis virus (rVSV) encoding the SFTSV glycoproteins Gn/Gc as a virus vectored vaccine. We demonstrate that this vaccine (rVSV-SFTSV) is safe in immunocompromised mice and not neuropathogenic when delivered intracerebrally. Additionally, this vaccine induces robust antibody responses that are protective from lethal challenge. Furthermore, we demonstrate that this vaccine elicits cross-protective responses against the closely related Heartland virus. We then developed an mRNA vaccine encoding SFTSV Gn/Gc and compared this platform with our rVSV-SFTSV vaccine in single dose, homologous prime-boost, and heterologous prime-boost regimens. We found that mRNA immunizations in single dose and homologous prime-boost regimens achieved the highest neutralizing antibody titers. Immunizations with rVSV-SFTSV also reached high antibody titers though they were the lowest titers of any immunization regimen, with heterologous prime-boost having intermediate titers. When T-cell responses were analyzed, mRNA immunization achieved robust CD4+ and CD8+ responses in single dose and homologous prime-boost regimens. Heterologous vaccine regimens elicited similar responses to homologous mRNA strategies despite weak cellular activity after rVSV-SFTSV prime. Despite some differences in immunogenicity, all vaccines were protective from lethal SFTSV challenge. Overall, this work demonstrates the effectiveness of two vaccine platforms in their ability to elicit robust protective responses against SFTSV
Music After The Cultural Revolution: Transnational Precarity For China\u27s One-Child Generation
Get PDFThis dissertation studies the intergenerational effects of the Chinese Cultural Revolution and the transnational careers of Chinese musicians born and raised during the one-child policy. Bridging scholarship in ethnomusicology and musicology with work in cultural anthropology, East Asian studies, Asian American studies, and literature studies, I examine the palpable memories and traumas from the Cultural Revolution and show that they continually frame individual and collective engagements with music in the People’s Republic of China and the Chinese diaspora. At the core of this research are extensive multi-sited ethnography conducted in the PRC, Taiwan, Canada, and the United States, and archival sources. Using these interdisciplinary methodologies, I address Chinese music-making practices in relation to personal and familial desires, and national transformations. I argue that although some Chinese musicians have achieved the highest levels of institutional success through conservatory training and international performances, they are continually motivated by anxieties of socio-economic precarity and desires for redress from parents who lost musical ambitions during the Cultural Revolution. As a result, Chinese musicians use what I term “strategic citizenship” to create transnational opportunities and seek stable futures for themselves while navigating neoliberal systems that impact their educational pathways and possibilities for new residency in countries such as Canada and the United States
The Underrepresentation of Female Superintendents in New Jersey: What Are the Personal and Societal Considerations and Influences that Contribute to Underrepresentation?
No full textWhile most teachers in U.S. classrooms are women, most superintendents, the highest-ranking position in school districts, are men. Somewhere during educators’ trajectory to superintendent positions, the representation of women diminishes. One might think that women, who make up most of the teachers, should be at least equally represented to men as superintendents. There are some considerations that have contributed to the underrepresentation of women. A review of literature included considerations such as family responsibilities, gender bias, discrimination, access, and mentoring to name a few reasons for the lack of female representation. This study identified and extrapolated meaning from the lived experiences of women in leadership. Study participants included sitting or retired superintendents, aspiring female leaders, and board of education members. While other studies have identified barriers for women in educational leadership, this study differed in that it sought information from three groups of active participants in the journey to the superintendency. The understanding of the underrepresentation of women in the superintendent role can be used for future studies and to inform important policy change, recruitment, and mentoring of aspiring female superintendents
Essays on Corporate Governance and Shareholder Activism
No full textThe goal of this dissertation is to deepen our understanding of corporate governance and shareholder activism. The first chapter, The Roles of Activists in Boardrooms: Advisors and Supervisors , studies the effects of activist directors on firm outcomes. Using a unique hand-collected data set of activist directors\u27 committee appointments, I show that their impacts depend on whether they sit on advisory or monitoring committees. Shareholders benefit from the appointments of activist directors: the average abnormal return increases by 1.9% and 1.4% around the day of advisory and monitoring directors\u27 appointments, respectively. By using close-call director election results in a regression discontinuity design, I provide causal evidence that activist hedge funds perform two distinct governance roles of advising and monitoring, with each role producing different outcomes. Upon being appointed to advisory committees, activist directors increase operating performance by enhancing profitability and internal capital allocation. They also increase corporate innovation, acquisitions, and divestitures to drive long-term growth. Upon their appointments to monitoring committees, activist directors curb agency problems by increasing shareholder payouts, divestitures, CEO turnover, and pay-performance sensitivity while decreasing acquisitions. My findings shed light on the roles of activists as advisors and supervisors. The second chapter, The Aftermath of Settlements: Hedge Fund Activism and Corporate Risk-Taking , studies the effects of activist settlements on corporate risk-taking using board settlements and hand-collected golden leash agreements data. I find causal evidence against the claim that board settlements tilt the direction of management toward short-termism, leading to excessive risk-taking. I identify two mechanisms that explain the decrease in corporate risk-taking: increased board monitoring and change in ownership structure. Taken together, my findings show that activists decrease corporate risk-taking, causing improvements in long-term firm value
An Analytical Framework to Diagnose the Financial Challenges Facing Small Private Liberal Arts Colleges and Specific Turnaround Strategies for Those Institutions
No full textStudent demographic changes, an evolving job market, and educational cost increases are some of the key factors that have shaped today’s operating environment for small private liberal arts colleges (SPLACs). This challenging climate exacerbates many ongoing problems including SPLACs’ suboptimal economy of scale, limited resources, downward pressure on net tuition, and tuition dependency. This research aims to investigate (a) the manageable risk factors contributing to the financial challenges for a tuition-dependent SPLAC and (b) specific turnaround strategies that mitigate the risks contributing to the economic challenges. The investigation adopted a mixed-method approach. First, the study used the grounded theory research approach to derive a literature-based framework that suggests three manageable risk factors are shaping the financial challenges of the sub-group. The risk factors include institutional cost structure and scale, institutional financial stewardship performance, and market-driven value proposition that impacts institutional resources allocation. Second, the risk factors framework was assessed and tested by case study findings involving two colleges sampled from the SPLAC sub-group of total enrollments of less than 1,000 in 2020. Third, the measurable risk factors and their correlation with institutional financial sustainability were statistically tested by regression-based models. The statistical findings suggest that financial stability, measured by institutional equity ratio, is positively correlated with revenue’s investment returns weighting and endowment-to-core expenses ratio, and negatively correlated with tuition dependence. There is a statistically significant correlation between measured financial stability and risk factors. The case study findings further demonstrate the grounded theory-based risk factors framework, which encompasses the statistically tested risk factors. The framework suggests how to address and understand problems and how to create revival strategies for financially challenged tuition-dependent SPLACs. The framework also suggests that reviving SPLACs need to redesign curriculum, match cost structure to revenue mix, and practice diligent financial stewardship to grow the endowment as an offset to tuition and fees over-dependence. Finally, the case study describes the difference that change-adept and professionally competent boards can bring to support leadership teams’ turnaround actions
Optimizing the Design and Implementation of Peer Support Interventions for Adolescents Living with HIV in Sub-Saharan Africa
No full textAdolescents living with HIV (ALHIV) in sub-Saharan Africa (SSA) face multiple challenges which exacerbate their risks for treatment failure and poor psychosocial outcomes. Peer support interventions can be a mechanism to potentially improve their health outcomes. The purpose of this dissertation was to use innovative approaches to design and evaluate peer support interventions for ALHIV in sub-Saharan Africa, which were explored in three ways. First, an integrated review was conducted to understand the state of the science regarding the efficacy of peer support interventions in improving psychosocial and treatment outcomes among ALHIV in SSA. Second, a hybrid inductive-deductive thematic approach was used to identify implementation determinants regarding the peer delivery of a brief psychological intervention (i.e., Friendship Bench) among ALHIV in Gaborone, Botswana. Our findings provide eight implementation determinants (i.e., six barriers and two facilitators) to consider in future adaptations of Friendship Bench for ALHIV. The six barriers identified were client accessibility, parent disapproval, lack of financial resources, counselor psychological wellbeing, client reticence and confidentiality concerns, and scheduling procedures. The two facilitators were counselors’ perceived value of the intervention and peer delivery of counseling. Third, a behavioral economics design approach (i.e., NUDGE) was used to identify behavioral barriers to antiretroviral therapy adherence among ALHIV in Eswatini, and subsequently design intervention prototypes that peer lay health workers (i.e., expert clients) can use to address these barriers. The following barriers were identified and validated by expert clients: fear of public and interpersonal disclosure of HIV status, anger and lack of acceptance related to delayed HIV disclosure among parents, refusal to receive adherence instructions from adults, and psychological barriers related to food insecurity. Lastly, prototype ideas to address these barriers were developed and vetted by expert clients. Overall, expert clients favored four prototype ideas that they believed were feasible to implement at a low cost: commitment contracts, message framing, group regret lotteries, and messenger type interventions. The overall findings and insights from this dissertation provide the preliminary steps for future work utilizing behavioral economics and implementation science to optimize peer support interventions for ALHIV in SSA
Economics Of Information Search And Financial Misreporting
No full textI examine how investors’ search for different types of information affects managers’ reporting decisions. I distinguish investors’ search for information about firm fundamentals (“fundamental search”) from their search for information about managers’ incentives (“incentive search”). Based on a parsimonious model of misreporting, I predict that fundamental search reduces the earnings response coefficient, which reduces a manager’s benefits from misreporting, resulting in less misreporting. In contrast, incentive search increases the earnings response coefficient, which increases the benefits from misreporting, resulting in more misreporting. I test these predictions using an empirical technique that classifies EDGAR downloads as fundamental search or incentive search. Consistent with my theoretical predictions, I find that both fundamental and incentive search are positively associated with measures of price efficiency, but that fundamental (incentive) search is negatively (positively) related to the earnings response coefficients and intentional restatements. I also confirm my findings in the XBRL adoption setting where the costs of fundamental search exogenously decreased, and show that the XBRL adoption increased investors’ search for fundamental information relative to incentive information, decreased the earnings response coefficient, and decreased misreporting. Collectively, the results show that investors’ information demand can shape managers’ reporting decisions, and that its effects can vary depending on the type of information investors search for
Chromosome Stories: How Scientists Tracked Radiation Risk After Hiroshima And Nagasaki
No full textThis dissertation is about the scientists who strived to track radiation risk after Hiroshima and Nagasaki. It focuses on cytogeneticists and epidemiologists at the Atomic Bomb Casualty Commission (ABCC)—later re-institutionalized as the Radiation Effects Research Foundation (RERF)—who devoted their careers to investigating chromosomes drawn from the hibakusha, atomic-bomb survivors, as biological entities. It considers the experiences of these scientists who studied chromosomes, the technologies and infrastructure that facilitated the studies, the complex relationship between the hibakusha and the scientists, as well as the broader community in which the research outcomes shaped the policy and practice of radiation protection. By doing so, it asks how acts of extreme violence that wrought unique biological effects became an opportunity and resource for scientific advancement, and the implications of such a story for our understanding of science, ethics, and social justice. Chromosomes reveal much more than the internal working of the ABCC and RERF, or the development of cytogenetics as a field of scientific inquiry. This dissertation uses the hibakusha chromosomes to contextualize the cytogenetic labor at ABCC/RERF and the aspirations of scientists in the larger history of the atomic age; to highlight the complex relationship between diplomacy and science; to shed light on the extensive global infrastructure of radiobiology as a response to emerging geopolitical risks; and to consider the forms of power and violence that are inextricably linked to the work of science. The dissertation argues that as long as the RERF remains as an institution that primarily serves regulatory bodies, whose ultimate aim is risk estimates at a population level, it does not reconcile with hibakusha who ask the science to serve their individual health. Ultimately, this dissertation shows how studies of chromosome mutations were in themselves mutated forms of scientific violence. The RERF was undoubtedly a critical node in post-WWII global biomedicine—connected to intimate experiences of pain and illness, and to international debates on nuclear weapons and nuclear energy. The contradictions and vexations of this institution reflect its almost impossible agenda—to transform Hiroshima and Nagasaki from sites of violence into sites of knowledge