Identification of Novel Druggable Targets in Two Members of Mononegavirales

Measles virus (MeV) is considered one of the most contagious human viruses and has recently been declared endemic again in several countries despite a highly efficacious vaccine. The viral RNA dependent RNA polymerase (RdRP) is a heterologous complex comprised of the large protein (L), which provides all catalytic domains for RNA synthesis, and the phosphoprotein (P), which provides chaperone support for L and mediates the interaction between L and the ribonucleoprotein complex (RNP). Though essential for polymerase function, the interface between P and L remains poorly characterized, as well as the role of P in RdRP advancement along the RNP. Through biochemical interface mapping, functional assays, and domain swapping of P, we have identified a bipartite L binding domain on P. One domain consists of a conserved helical motif upstream of the oligomerization domain (OD), and the second is a face of the P X-domain (PXD). Using stoichiometrically-controlled trans-complementation studies and applied mathematical modeling, we also determined the PXD:L interaction to be mutually exclusive to the PXD:N interaction. These findings suggest a model that centers PXD as a master regulator of RdRP advancement. Rabies virus (RABV) causes a severe and 100% fatal neurological disease that is vaccine preventable and treatable prior to the onset of clinical symptoms. The post-exposure prophylaxis (PEP) for RABV treatment is prohibitively expensive, especially in developing countries where the majority of cases occur and does not confer cross-protection against the newly emerging phylogroup II lyssaviruses. To address the unmet clinical need for cross-protective anti-RABV therapeutics, we developed and implemented an innovative high-throughput screening approach utilizing a novel single cycle RABV reporter strain maintained in BSL-2 laboratory conditions. From our extensive screening library, we have identified the first direct-acting multi-strain RABV entry inhibitor, GRP-60367. Resistance profiling of GRP-60367 revealed escape mutations that accelerate the fusion kinetic of the RABV glycoprotein (G). We have solved two of the feasibility issues with current RABV antiviral drug discovery: i) BSL-2+RABV containment restraints and ii) reliable drug efficacy determination, thus paving the way for future drug discovery campaigns to alleviate the deficit and cost of current therapeutic options against lyssaviruses

Duchamp\u27s Audience

An examination of Marcel Duchamp’s ideas of how art is defined, especially in regards to the role of the audience in determining whether an object is art and his challenges to how art was perceived, as demonstrated by his readymades. The struggle to define art is a significant element of society. With this paper, I argue against Duchamp’s view that the audience has a monopoly on power in the artist-audience relationship, showing that the audience can be persuaded to accept an object as art based on how the object is presented. This manipulation of the audience has meaningful consequences, as the manipulator can affect much more than just the way the audience views art

Personhood & Parenthood: An Experiential Account of Balance & Well-being

Parents are constantly engaging in a balancing act, weighing their own needs with those of their children and family. Helping parents navigate the role of parenthood can promote optimal development in the child, parent, couple and family. Parents engage in various roles and responsibilities essential for family and individual well-being that require balance in order to be effective. Past research on balance has indicated that people are more satisfied with life when they are active in multiple life domains rather than in a single one. This study is interested in two specific life domains: personhood and parenthood, and how parents balance these two roles and identities. Balance between these two domains may operate to develop the individual and collective simultaneously, seeking to satisfy basic human needs. As a result, this fulfillment and balance may contribute to the experience of well-being. The focus of this study is on parents who believe that they have balance between personhood and parenthood. The mission is to bring awareness and understanding to the experiential part of parenting through a qualitative, phenomenological approach. This study explores parent’s personal accounts, experiences and stories through a semi-structured face-to-face interview. Participants included seven American parents of a variety of ages but all of whom were age 26 years and older. The electronic version of this dissertation is accessible at the Ohiolink ETD center http://www.ohiolink.edu/etd

The Effects of Federal Funding Reductions on Emergency Shelters in Urban U.S. Sanctuary Cities.

AbstractWhen the U.S. federal government reduces funding to urban sanctuary cities because of those cities’ refusal to cooperate with federal law enforcement agents this affects the services offered by the municipalities to their residents. The purpose of this study was to provide a better understanding of the effects that withdrawal of federal funds from urban sanctuary cities have on people experiencing homelessness. The social exchange theory provided the theoretical foundation for the study, which featured a qualitative exploratory case study design and involved interviews with four shelter administrators in three mid-Atlantic states. The participants described (a) the effects of reduced federal funding on their services and client population and (b) the strategies they used to address their budget shortfall. Bryman’s four stages of coding were applied to the transcribed data to identify themes and to answer the research questions. The emergency shelter administrators were not aware of the proposed Mobilizing Against Sanctuary Cities Act. They were focused on their mission of helping people experiencing homelessness to return to independence and self-sufficiency while using donations and fundraising to supplement their shelter budgets. A larger sample size across a wider study boundary could have provided more robust data. Still, the study furthers understanding of how some emergency shelter administrators in sanctuary cities perceived their roles and the operations of their shelters. With this knowledge, policy makers may be able to promote positive social change by formulating more equitable policies and practices for the distribution of federal funds to sustain emergency shelters serving the homeless population

Personhood & Parenthood: An Experiential Account of Balance & Well-being

Parents are constantly engaging in a balancing act, weighing their own needs with those of their children and family. Helping parents navigate the role of parenthood can promote optimal development in the child, parent, couple and family. Parents engage in various roles and responsibilities essential for family and individual well-being that require balance in order to be effective. Past research on balance has indicated that people are more satisfied with life when they are active in multiple life domains rather than in a single one. This study is interested in two specific life domains: personhood and parenthood, and how parents balance these two roles and identities. Balance between these two domains may operate to develop the individual and collective simultaneously, seeking to satisfy basic human needs. As a result, this fulfillment and balance may contribute to the experience of well-being. The focus of this study is on parents who believe that they have balance between personhood and parenthood. The mission is to bring awareness and understanding to the experiential part of parenting through a qualitative, phenomenological approach. This study explores parent’s personal accounts, experiences and stories through a semi-structured face-to-face interview. Participants included seven American parents of a variety of ages but all of whom were age 26 years and older. The electronic version of this dissertation is accessible at the Ohiolink ETD center http://www.ohiolink.edu/etd

Black Female Faculty and Professional Socialization: Constraints, Enablements and Enactments.

Professional socialization is the process of learning and employing the cultural perspective of the workplace. Informed by Black Feminist Thought and Critical Race Feminism, this study examines the professional socialization experiences of tenured Black female faculty at four predominately White Research institutions (PWIs). In doing so, this research captures the trajectory from graduate school to associate professor and analyzes how tenured Black women define and enact their role in the academy. Traditional views of professional socialization do not fully explain what happens when a socially subordinated group like Black women enters spaces defined by the experiences of a socially dominant group. Therefore, the theoretical framework for this study considers a) how socially marginalized groups access spaces where the prevailing norms and values disadvantage them, b) how structural and agential factors promote or hinder career advancement, and c) how individuals can alter institutions in ways that are more aligned with their values. Agency, the ability to identify and implement choices to achieve a self-defined goal, allowed the participants to mediate the vestiges of institutional racism. The key agential factors were self-efficacy and self-advocacy (e.g. seeking mentoring). However, structural opportunities were vital to their career success. Key structural factors were (a) recruitment initiatives (e.g. Affirmative Action), (b) critical mass of people of color on campus, and (c) intellectual support. These enabling aspects of structure made accessing PWIs possible and made finding a space for intellectual production less complicated. The participants contributed to their institutions through a series of critical enactments. The term enactment is meant to capture how the participants manifest multiple ways of maneuvering through academe. These enactments are critical because they are concerned with naming and subverting social injustice. The participants embodied critical enactments by employing critical pedagogy, challenging epistemological paradigms and advocating on behalf of the most vulnerable groups in college settings. Essentially, for the participants, professional socialization means enacting norms that are aligned with their standpoint, discarding norms that conflict with their standpoint, and transforming norms to encourage agreement with their standpoint. With this knowledge, institutions can better address norms that undermine the professional development of underrepresented groups.Ph.D.EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/61695/1/vthandis_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/61695/2/vthandis_2.pd

Professional development needs of TVET college lecturers towards remote learning : implications for leadership

Abstract: Rapid technological development has affected the educational sector, prompting it to evolve and embrace technology as part of everyday teaching and learning. The coronavirus outbreak has exacerbated the need for educational institutions to transform from being 100% face-to-face learning institutions to ones that integrate ICT mechanisms as part of teaching and learning. As a result of the COVID-19 lockdown in 2020, universities were forced to suspend all contact learning activities and transition to online learning. However, Technical and Vocational Education and Training (TVET) colleges had to come to a complete halt because they lacked response mechanisms in the form of infrastructure, and experienced and knowledgeable lecturers. In this study, the training and resource needs of TVET college lecturers are investigated. Moreover, lecturer training guidelines for remote learning are proposed for TVET college leaders. Employing a generic qualitative research approach, within the interpretivist worldview, data gathering was undertaken through qualitative surveys and semi-structured interviews. Seventy-three TVET college lecturers participated in the survey and three TVET college Heads of Department (HODs) were interviewed from a TVET college in Ekurhuleni, Gauteng. The findings were presented using a generic qualitative research design and reporting methods. The findings of the study revealed that TVET college leaders need to furnish lecturers with resources and training in the utilisation of remote learning prior to implementation. The appropriate resources and training needed were recommended. The study also found that owing to the differing nature of the vocational subjects offered at TVET colleges, the training and resource needs of lecturers differed and therefore recommended that TVET leaders cater for the individual and subject-related needs of the lecturers. The study also recommended a distributive leadership approach to assist with the resource and training needs of lecturers, through the formation of and reliance on campus and college committees comprising internal and external stakeholders. Furthermore, training guidelines were recommended to ensure that the training of lecturers is adequate, appropriate, accredited and meets global educational standards to make sure that lecturers become 21st-century transformative intellectuals.M.Ed. (Educational Leadership and Management