As the son of parents of the "baby boomer" generation I foresee the immanent increased demand for assisted living for the elderly. By 2030 an estimated 20 percent - one in five Americans - will be 65 or older. Unless attention is paid now to advancing the designs and opportunities for assisted-living, there will either be a distinct lack of available options, or worse, the continuation of out-dated designs that simply will not be a marketable. Contemporary thinking with regard to the design of places of residence for the elderly has changed dramatically from the days of outdated structures and philosophies. In my research, I have seen a shift toward the concept of community rather than institution. Owing to cultural change that will surely be the future of assisted living design strategy. Yet, the shift is still in the rut of scaling designs to accommodate up to only a few dozen individuals. While I understand the rationale of such designs, I foresee a shortcoming to that approach. If the design idea is the drive toward the feeling of "home" then I feel it to be conceivable for an expansion of the current model to include multiple neighborhoods of residences, subsidiary structures, and more connection to a feeling of neighborhood and social interaction; the attributes of a true "community." What are missing are the environments that appeal to younger citizens. Baby boomers, easily described as much more educated, well-informed, well traveled, financially successful and much more discerning will not find the traditional options appealing or acceptable. My primary method of research for such an endeavor falls under the classification of Qualitative Research; the category that focuses on personal and informal social science. My design intention is not to separate and isolate the population of those seeking assisted living. Instead, offer more than just a place to live. I intend to discover validity for the concept of a larger networked residential community with more opportunity for social interaction and active lifestyle extending beyond what currently exists.

The Great Basin is a region of the Basin and Range Physiographic Province, which is completely isolated hydrologically from the sea. All precipitation that falls within the Great Basin is lost from the land surface or from the surf ace of closed inland lakes through evapotranspiration. Playas are often found at the base of these undrained basins. This study focuses on subsurface groundwater flow patterns in closed basins. Because all discharge from the basins occurs via evapotranspiration on and near the playa, the water table of the aquifer beneath the playa is often just below the ground surface. Fluctuations of the water table due to climatic events cause the water table to rise and dissolve the salts on the playa surface. This mass transfer can produce density gradients that in turn cause flow. This study is an extension of the work performed by Duffy and Al-Hassan (Duffy and Al-Hassan 1988) in which numerical experiments were used to show that the free convection, caused by the variation in density of the bulk fluid propenies, appears to play an important role in determining the patterns of groundwater flow beneath the playa. Their work considered only homogeneous, isotropic porous media in symmetric basins. The effects of anisotropy, periodic stratification, and asymmetric basins on the groundwater flow and transport patterns was studied here. Dimensionless parameters, the Rayleigh number and the salt nose length, L0*, were defined for each of the systems incorporated and were shown to be linearly related. The implication of this relationship is that the Rayleigh number can be used to predict basin-scale circulation patterns in the hypothetical closed basins studied. It was also determined that an equivalent anisotropic system could be defined for a horizontally stratified aquifer in order to predict basin-scale circulation patterns. An equivalent isotropic system was defined for each anisotropic system in a similar manner.

Diseases such as epilepsy, pain, and neurodegenerative disorders are associated with changes in neuronal dysfunction due to an imbalance of excitation and inhibition. This work details a novel electroconvulsive seizure assay for C. elegans using the well characterized cholinergic and GABAergic excitation and inhibition of the body wall muscles and the resulting locomotion patterns to better understand neuronal excitability. The time to recover normal locomotion from an electroconvulsive seizure could be modulated by increasing and decreasing inhibition. GABAergic deficits and a chemical proconvulsant resulted in an increased recovery time while anti-epileptic drugs decreased seizure duration. Successful modulation of excitation and inhibition in the new assay led to the investigation of a cGMP-dependent protein kinase (PKG) which modulates potassium (K+) channels, affecting neuronal excitability, and determined that increasing PKG activity decreases the time to recovery from an electroconvulsive seizure. The new assay was used as a forward genetic screening tool using C. elegans and several potential genes that affect seizure susceptibility were found to take longer to recover from a seizure. A naturally occurring polymorphism for PKG in D. melanogaster confirmed that both genetic and pharmacological manipulation of PKG influences seizure duration. PKG has been implicated in stress tolerance, which can be affected by changes in neuronal excitability associated with aging, so stress tolerance and locomotor behavior in senescent flies was investigated. For the first time, PKG has been implicated in aging phenotypes with high levels of PKG resulting in reduced locomotion and lifespan in senescent flies. The results suggest a potential new role for PKG in seizure susceptibility and aging. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2019. / FAU Electronic Theses and Dissertations Collection

The type Iα cGMP-dependent protein kinase (PKG Iα) is an essential regulator of vascular tone and systemic blood pressure. Located in the smooth muscle of resistance vessels, PKG Iα stimulates vasodilation through the phosphorylation of multiple intracellular substrates. Its primary regulator is the small molecule, 3',5'-cyclic guanosine monophosphate (cGMP); however, the Iα isoform can also be activated by oxidation. Despite the established physiological importance of PKG Iα, the structural underpinnings of these two activation mechanisms are largely unknown. The work presented in this dissertation demonstrates the importance of the cGMP-binding domain A (CBD-A) in regulating both of these mechanisms of PKG Iα activation. Using a monomeric, N-terminally truncated form of PKG Iα (Δ53), Chapter 2 investigates the mechanism of inhibition through the autoinhibitory domain and the influence of dimerization on cooperative cGMP-dependent activation and cyclic nucleotide selectivity. We observed that autoinhibition occurs in cis, whereas cooperativity requires interprotomer contacts facilitated by the N-terminal dimerization domain. Furthermore, the loss of selectivity for cGMP over cAMP of this construct suggests the dimerization domain plays a critical role in preventing cross-reactivity with cAMP-dependent signaling. These observations culminate into an overarching model wherein binding of cGMP to CBD-A is necessary and sufficient for activation and cooperativity is driven by the dimerization domain. Chapter 3 investigates the cysteine residues that mediate oxidation-dependent activation of PKG Iα. Using PKG Iα constructs with point mutations at specific cysteine residues, it was found that oxidation-dependent activation is driven by C117 in CBD-A. Furthermore, the interprotomer disulfide bond that forms in the dimerization domain at C42 does not contribute to this mechanism. Finally, we propose a model wherein the disulfide bond that forms between C117 and the adjacent cysteine at position 195 acts as a protective mechanism to prevent activation and higher oxidation states form contacts with nearby residues in the linker region of PKG Iα to disrupt binding of the adjacent autoinhibitory domain to the catalytic domain. Finally, Chapter 4 provides a discussion of the results presented herein in context with previous studies and suggests future directions for the PKG field.

Abstract not available

Although considered a substanially preventable disease, Type 2 diabetes is reaching epidemic status within the Maori population. This study sought to investigate factors that positively and negatively influenced levels of physical activity for Maori within Otepoti/Dunedin, and to discuss ideas and potential initiatives that could increase levels of physical activity and aid in the prevention of Type 2 diabetes. Eighteen Maori (9 males; 9 females) from this rohe (area) participated in a four hour focus group interview (groups of three) and were also invited to attend an evaluation hui. A Maori-centered research orientation was used throughout the research process. Individual transcripts from focus groups, debriefing discussion and content from the evaluation hui were inductively analysed to identify the main themes. The 'active' participants were physically active because of the benefits they attained for health and longevity, and to undertake task-oriented activity such as gathering kai. Barriers to physical activity (i.e., family, work), a contemporary societal shift towards inactivity, and negative personal attitudes and perceptions towards physical activity detrimentally affected levels of physical activity. Initiatives to increase levels of physical activity included community, educational and work-based initiatives. A key element of each proposed initiative was a 'by Maori for Maori' approach, with a focus on strengthening whānau and iwi networks, a comfortable environment and social support. While education was believed to be a key component for Type 2 diabetes prevention, an avoidance barrier and fatalistic attitudes could negatively affect any attempt to prevent Type 2 diabetes and increase levels of physical activity. The results indicated that to strengthen Maori identity, increase levels of physical activity and prevent Type 2 diabetes, positive changes (taking responsibility for health), cultural changes (a shift towards a stronger identity and belief in the taonga [treasure] of being Maori), societal changes ( a more positive view of Maori, better role models and education), and social economic changes (better access to exercise facilities, healthy food and education for those in the lower deprivation indices) were needed.

Classical immunoglobulin transgenic (Ig-Tg) mouse models such as the MD4 anti-hen egg lysozyme (-HEL) Ig-Tg line have been used extensively to study B cell responses in tolerance and immunity. This thesis describes a new generation of gene-targeted mice (designated SWHEL mice) whereby the VH10 Ig variable gene encoding the HyHEL-10 specificity of the original anti-HEL Ig-Tg mouse was targeted to the Ig heavy chain locus. B cells in the SWHEL mouse are therefore capable of undergoing class switch recombination (CSR) and somatic hypermutation (SHM), representing a major advance on the original MD4 mouse model. SWHEL mice were found to not only contain a large population of HEL-specific (HEL+) B cells but also a significant population of non-HEL-binding (HEL-) B cells generated by VH gene replacement. HEL+ SWHEL B cells were found to belong to the B2 lineage and displayed high levels of surface IgM. Nevertheless, they matured normally and colonised the primary B cell follicle and marginal zone (MZ) of the spleen. The SWHEL model thus provided an opportunity to re-examine some of the original observations made in the MD4 system and also to extend these observations, particularly with regard to the regulation of CSR by self-reactive B cells. As expected, analysis of SWHEL B cells exposed to high avidity membrane-bound HEL revealed that they underwent clonal deletion in the bone marrow (BM). More interestingly, analysis of HEL+ B cells exposed to low avidity soluble HEL revealed that they were able to emigrate from the BM to the spleen as anergic B cells. However, unlike anergic MD4 B cells, anergic SWHEL B cells were reduced in frequency, displayed an immature B cell phenotype, were excluded from the follicle and had a reduced lifespan. Direct measurement of B cell antigen receptor (BCR) occupancy by HEL and the frequency of HEL- competitor B cells was combined with mixed BM irradiation chimeras to demonstrate unequivocally that the difference in phenotype and fate of HEL+ B cells in the two systems was due solely to competition from HEL- B cells. In addition, the SWHEL model of B cell self-tolerance was used to show that while self-reactive B cells were hypo-responsive to BCR stimulation, BCR-independent signals delivered via anti-CD40 plus IL-4 or lipopolysaccharide could trigger them to undergo CSR and secretion of potentially pathogenic isotype-switched autoantibodies. Finally, the SWHEL model was used to study the responses of adoptively transferred follicular (Fo) and MZ B cells to in vivo activation with HEL conjugated to sheep red blood cells (HEL-SRBC). These studies revealed that both HEL+ MZ and Fo B cells were capable of mounting a robust T cell-dependent IgG1 antibody response to HEL-SRBC. However, HEL+ MZ B cells did not efficiently localise to the T cell-B cell border following antigen engagement and preferentially migrated to the bridging channels and red pulp. In contrast, HEL+ Fo B cells rapidly localised to the T cell-B cell border and subsequently colonised numerous germinal centres. As a result, the rate and pattern of SHM by HEL+ Fo and MZ B cells was shown to be distinct, with preferential targeting of mutations to the second complementarity-determining region in the former and to the second framework region in the latter. Together these data indicate illustrate the value of the SWHEL model and its potential to greatly advance the current understanding of B cell responses in tolerance and immunity.

"September, 2002." / Bibliography: leaves 93-106. / 106 leaves : ill. (some col.), plates ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / In this thesis the biochemical and genetic characterization of Fkh2p identifies it as a major component of SFF. It has been shown to bind DNA in an Mcm1p dependent manner and the Fkh2p DNA binding domain is essential for this interaction. The protein interaction domain of Mcm1p has been demonstrated to be essential for ternary complex formation. Fkh2p, along with a functionally redundant protein Fkh1p, has been show to control the periodic expression of the CLB2 cluster genes. The functional characterisation of the Fkh2p domains reveals an important role for both the Forkhead associated domain and the C-terminus. Ndd1p. another protein important for mitotic progression, is shown to be important for CLB2 cluster regulation by de-repressing Fkh2p and activating gene expression. The role of cdk activity is shown to act through the CLB2 cluster upstream activating sequences, possibly through Ndd1p. / Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2003

Thesis (Ph.D.)--University of Nevada, Reno, 2005. / "December, 2005." Includes bibliographical references (leaves 168-219). Online version available on the World Wide Web.

<p>This paper argues that there is a finiteness distinction in Hdi and that the notion is of value for a description of the language. The definition of finiteness suitable for the language has been suggested to be the one given by Anderson (2007) combined with Bisang (2007). The finite clauses are argued to be the pragmatically independent ones while the non-finite clauses are argued to be the pragmatically dependent. However, no morphological reductions were found in the non-finite clauses relative to the finite ones. What is more, negation in Hdi shows a nontypical behaviour regarding finiteness properties as there are aspectual distinctions made for dependent clauses that are not made for independent. Verbless clauses and imperatives may be viewed as finite and non-finite depending on their capacity to licence independent predication or, alternatively, they may be viewed as not displaying finiteness properties at all. The latter is argued to be preferred in order to avoid a redundant definition of finiteness.</p>