In pregnancy, the maternal cardiovascular and placental circulation undergoes structural and functional changes to accommodate the growing fetus, but the mechanisms involved are not fully understood. Nitric oxide (NO) increases in normal pregnancy and lack of NO has been implicated in pregnancy related complications, preeclampsia and fetal growth restriction. Thus, the objective of the thesis was to determine if cardiovascular, uteroplacental and fetoplacental changes observed in human pregnancy also occur in mice and to assess the obligatory role of eNOS in mediating these changes. I showed that like humans, mice exhibit increases in maternal cardiac output, stroke volume, plasma volume, and uterine arterial blood flow, and a transient decrease in arterial pressure during pregnancy. Importantly, I showed that endothelial nitric oxide synthase (eNOS) plays an important role in promoting the progressive increase in maternal cardiac chamber dimensions and output and the enlargement of the aorta during pregnancy in mice. Another novel finding was that eNOS plays an important role in remodeling of the uterine and umbilical vasculatures during pregnancy. The remodeling of the uterine vasculatures, including the uterine and spiral arteries, were blunted in the eNOS KO mice with ko fetuses (KO(ko)) and this likely contributed to elevated vascular resistance and reduced perfusion of the uterine circulation during pregnancy. Impaired spiral artery remodeling may be caused by a deficiency in decidual uterine natural killer cells. Fetal placental vascularization was also impaired in eNOS KO(ko) mice, which likely increased vascular resistance and thereby reduced fetoplacental perfusion. Reduced vascularization may be due to decreased VEGF mRNA and protein expression in KO(ko) placentas. Decreased perfusion in both the uterine and umbilical circulations most likely contributed to elevated placental and fetal hypoxia in the eNOS KO(ko) mice. Interestingly, despite placental hypoxia, eNOS KO(ko) mice do not show the classical signs of preeclampsia including hypertension and proteinuria nor are maternal plasma sFlt1 levels elevated. Nevertheless, eNOS KO(ko) pups are growth restricted at term, and this is mainly due to the fetal genotype. These findings suggest that eNOS plays an essential role during pregnancy in remodeling of the maternal heart, aorta, and uterine and umbilical vasculatures thereby augmenting blood flow to the maternal and fetal sides of the placenta and thereby promoting fetal growth in mice.

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Home builders are supplying mass housing projects which are designed without taking into consideration the specific needs and expectations of residents. As well, house are not produced with enough flexibility to enable homeowners to perform easy adaptations that would express their own choices and accommodate their particular requirements. On the other hand, due to economic constraints, most first-time home buyers usually cannot afford the professional services of architects in order to have a house specifically designed to suit their needs and aspirations. / This research explores the different types of modifications that occupants of affordable single-family housing in Montreal make to their residences upon occupancy. / The survey revealed a high level of user intervention--93.6% of the residents made the modifications by themselves. This demonstrates that residents fully engage in housing adaptations when they are given the opportunity to do so, as is the case in the researched houses which offered some type of flexibility in the form of an open and unfinished basement. 108 of the 141 households took advantage of the originally unfinished basement by finishing it and adapting it to their needs and desires. / The author concludes that a house should be adaptable and flexible enough to respond to residents' demands, allowing them to adapt their living spaces according to their personal choices and requirements, as well as to personalise it. As well, the author, convinced that houses do not need to be entirely finished since residents will modify them in any event, suggests certain guidelines and provides recommendations on how affordable single-family houses in Montreal can best be designed to allow for post-occupancy adaptation and user intervention. (Abstract shortened by UMI.)

Myocardial infarctions induce a maladaptive ventricular remodeling process that independently contributes to heart failure. In order to develop effective treatments, it is necessary to understand the way and extent to which the heart undergoes remodeling over the course of healing. There have been few studies to produce any data on the in-vivo material properties of infarcts, and much less on the properties over the time course of healing. In this paper, the in-vivo passive material properties of an infarcted porcine model were estimated through a combined use of magnetic resonance imaging, catheterization, finite element modeling, and a genetic algorithm optimization scheme. The collagen fiber orientation at the epicardial and endocardial surfaces of the infarct were included in the optimization. Data from porcine hearts (N=6) were taken at various time points after infarction, specifically 1 week, 4 weeks, and 8 weeks post-MI. The optimized results shared similarities with previous studies. In particular, the infarcted region was shown to dramatically increase in stiffness at 1 week post-MI. There was also evidence of a subsequent softening of the infarcted region at later time points post infarction. Fiber orientation results varied greatly but showed a shift toward a more circumferential orientation.

Asthma is a chronic disorder highlighted by intermittent airway inflammation and characterized by paroxysmal dyspnea and airway hyperresponsiveness (AHR). A key feature of severe asthma is the development of airway wall remodeling, which is thought to occur through repeated rounds of inflammation and tissue repair. Remodeling includes structural changes such as increased mass of airway smooth muscle (ASM), and excessive collagen deposition. ASM cells contribute to airway remodeling via the expression and secretion of extracellular matrix (ECM) proteins. This is particularly driven by inflammatory processes, which include mediators such as transforming growth factor (TGF)-β1 and damage associated molecular pattern (DAMP) proteins, such as high mobility group box 1 (HMGB1). HMGB1 is ubiquitously expressed as a non-histone DNA-binding protein that can regulate gene expression, but can also be released in response to stress to underpin inflammation and tissue repair. In this study we tested the hypothesis that extracellular HMGB1 induces signaling pathways that control responses linked to progression of airway inflammation, remodeling and hyperresponsiveness in human ASM cells. We used primary cultured ASM cells as well as hTERT-immortalized human ASM cells. With immunoblotting we demonstrate that exogenous HMGB1 (10 ng/mL) can induce rapid and sustained phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) that is comparable to that induced by a potent mitogen, platelet derived growth factor (PDGF-BB, 10 ng/mL). We also found that TGF-β1 (2.5 ng/mL) promotes the accumulation of secreted HMGB1 in culture medium in a time line concomitant with expression of ECM proteins, collagen and fibronectin, suggesting a role for HMGB1 in pro-fibrotic effects of TGF-β1. By lentiviral delivery, we induced stable expression of short hairpin RNA (shRNA) that silenced expression of endogenous HMGB1 or mammalian diaphanous 1 (mDia1), a cytoplasmic scaffold protein that is required for HMGB1-induced cell responses through one of its receptors, receptor for advanced glycation end products (RAGE). Immunoblot analyses revealed that silencing of mDia1 was associated with markedly decreased induction of p42/p44 MAPK phosphorylation by exogenous HMGB1. In HMGB1-silenced human ASM cells, we observed significantly reduced synthesis and secretion of collagen A1 and fibronectin in response to TGF-β1 (2.5 ng/mL, 0-48 hrs). However, exogenous HMGB1 was not sufficient to rescue ECM synthesis in response to TGF-β1 in HMGB1-silenced cells - this suggests that intracellular, but not necessarily secreted HMGB1, regulates ECM expression and secretion in response to TGF-β1. Consistent with this interpretation, exogenous HMGB1 alone was not sufficient to induce ECM synthesis or secretion in primary cultured ASM cells. In conclusion, we show that though in human ASM cells extracellular HMGB1 alone can activate MAPK signaling, likely via mDia1-dependent pathways involving RAGE. it is not capable of prompting ECM protein expression. Recombinanat exogenous HMGB1 does not appear to directly affect ECM synthesis, rather intracellular (nuclear) HMGB1 likely modulates activity of genes that are affected by TGF-β1. Overall, HMGB1 has potential to regulate tissue repair processes involving ASM through intracellular and extracellular mechanisms, thus our findings support further work to elucidate the role of HMGB1 in pathogenesis of obstructive airway disease.

The propose of this thesis was to develop an adaptive reuse proposal for the Wendell L. Willkie High School in Elwood, Indiana. The building, an excellent example of Richardsonain Romanesque Style Architecture, has been vacant since 1973. Listed in the National Register of Historic Places because of its architectural and historical significance, the building merits the attention to develop an appropriate renovation scheme.The proposal includes: the building’s history; a written and photographic description of the existing conditions; the adaptive reuse proposal consisting of text, architectural drawings and the related cost estimates; a series of case studies on similar projects; and the economic incentives associated with historic preservation.The proposal renovation is designed to comply with local building odes and State and Federal standards for rehabilitation. It is hoped that this study will emphasize the value and potential of this magnificent architectural and historical landmark by showing that preservation is a practical and economical alternative in today’s building industry. / Department of Architecture

The project examines the architectural and financial feasibility of adaptive reuse of the Pennsylvania Station at Fort Wayne, Indiana, as an international cultural center and railroad passenger station. The project summarizes the results of primary research which determined the history of the station's original construction and subsequent alterations, as well as the property's associations with the history of Fort Wayne. The narrative also provides an illustrated summary of the current physical condition of the site and its two structures. The proposal for adaptive reuse includes an Amtrak rail passenger facility, shops, a restaurant, and classroom and dormitory areas to be used as a campus of the International Education Center, a school based in Tokyo, Japan. The proposed rehabilitation work is described in terms of its impact upon the historic features of the property, and the design issues involved are stated, as well as the major elements of the proposed work. An itemized budget for all proposed construction is provided.Based upon current rents in the project area, financial comparison of the investment needed with projected returns determined that the project would provide an acceptable acceptable rate of return on the required investment. The study concluded that the project would be both financially and architecturally viable. / Department of Architecture

This thesis will present information on the economic feasibility of rehabilitating an older building into office and living space. Data will show that the outlined rehabilitation project can be carried out at a lower dollar cost than new construction for a comparable amount of useable floor space.The rehabilitation project outlined in this thesis had to meet the following criteria. The current owners proposed future use of the building. All proposed modifications to the structure had to meet the Secretary of the Interior's Standards for Rehabilitation to take fullest advantage of the Tax Reform Act of 1976, and local building and zoning regulations. Rehabilitation of the building must provide the owner with enough income to completely off-set the total cost of the project within a ten year period. All of the proposed work on the building would have to meet the current owner's desire to retain as much of the building's original "character" while creating contemporary work/living space. / Department of Architecture

In this thesis, an environmentally sound and human scale set of design principles, which values ideas like environmental friendliness, human comfort and locality, is formulated, examined and justified. These principles are inspired by experiences in Latin America and South Asia and their universal significance is illustrated through case studies from several countries around the world.In the design project, these principles are applied in a local setting, in this case a residential hall on the Ball State University campus in Muncie, Indiana. The design embraces a ‘green’ approach to campus facility renovation as part of the holistic movement to make the campus more sustainable.The design focus will be on the reuse and revitalization of materials thrown away on campus. Projects in which economic limitations enhance this specific creativity serve as role models. Through the reuse of material, the renovation process of campus facilities can be linked to the recycling program and the curriculum of the university. / Department of Architecture

In order to find a plausible adaptive reuse solution for the former Federal Building and Post Office In Muncie, Indiana, which has been vacant and deteriorating since 1979 despite its significance, the characteristics of the building are analyzed in regards to the concept of historic preservation. A substantial graphical presentation is employed to assist the analysis.Five alternatives are identified as appropriate forms of adaptive reuse for the building. These alternatives, ranked in order of appropriateness, are:museumcultural-study centerart galleryconference center with office spaces showroom-office buildingImproving the reuse probability of the building is provided in five categories:adding usable floor areaupgrading building's thermal controlprovision of proper vertical transportationimproving historical integrityutilizing the advantageous environmentA proposal for converting the former Federal Building into a facility for the Ball State University Art Gallery is also included in the thesis in the form of spatial layouts, conversion work and cost estimation. The probable cost in converting the building according to the proposed plans is in the range of $1,307,516 - $1,451,812 or $40.26 - $44.70 per square foot. / Department of Architecture