Leung Kin Hong Donald. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 2003-2004, design report." / Includes bibliographical references. / In this book: / Chapter 1. --- About the thesis : New + Old / Chapter 2a. --- Analysis / Chapter 2b. --- Analysis & cases / Chapter 3. --- Site & program / Chapter 4. --- Design & development / Chapter 5. --- Final design / Chapter 6. --- Appendix & reference

Background: Myocardial infarction (MI) results in severe biochemical, physiological, and cellular changes that lead to alterations in the structure and function of the myocardium. Oxidative stress potentiates this remodeling response and is associated with progressive worsening of cardiac function. Accordingly, we used a powerful antioxidant-based therapeutic strategy to improve cardiac health and study redox-dependent signaling. Methods: MI was surgically induced in rats by ligating the left anterior descending coronary artery. Subgroups of MI rats received resveratrol (i.p., 10 mg/kg/day for 28 days beginning immediately post-MI). Cardiac histology and biochemical analyses of genes and proteins implicated in cardiac fibrosis, hypertrophy, and apoptosis, and redox-dependent signaling were analyzed. Results: As expected, MI resulted in profound structural changes to the myocardium. Further, we observed a sharp reduction in nuclear factor-erythroid 2-related factor 2 (Nrf2) and Krüppel-like factor 15 (KLF15), factors that are responsible for maintaining the endogenous antioxidant capacity and regulating cardiac gene expression, respectively. It is likely that disruption of normal KLF15 signaling permitted the expression of several cardiac genes associated with progressive cardiac remodeling. Importantly, daily treatment with resveratrol ameliorated cardiac remodeling, improved redox state, restored Nrf2 expression, and up-regulated KLF15 expression. Further, induction of KLF15 signaling following resveratrol treatment is associated with attenuated expression of several genes implicated in cardiac remodeling. Conclusions: Chronic oxidative stress potentiates cardiac remodeling post-infarct, in part, by suppressing Nrf2 and KLF15 expression. Importantly, we demonstrate that normal KLF15 signaling may be rescued with an antioxidant-based therapy, which may be an attractive therapeutic target to support cardiac health post-MI.

Asthma is a chronic condition characterized by variable airflow obstruction, bronchial hyper-responsiveness, airway inflammation and remodeling. In spite of tremendous advances, the regulatory mechanisms controlling these pathological features have not yet been completely addressed. From an immunological perspective, type 2 inflammation and eosinophilic infiltration are the most striking hallmarks of asthma. At physiological level, structural changes such as increase in smooth muscle mass take the center stage which is usually associated with clinical measures of asthma. There might be some regulatory mediators capable of tuning airway inflammation and remodeling under homeostatic conditions but abrogated in asthmatic conditions. Semaphorin 3E (Sema3E) is an axon guidance molecule that is ubiquitously expressed and plays diverse roles in structural and inflammatory cells such as regulation of cell migration, proliferation and angiogenesis. However, its role in clinical and experimental asthma remains unclear. In this thesis, I have set out to uncover the expression and function of Sema3E in allergic asthma. It is generally hypothesized that Sema3E is down-regulated in allergic asthma which orchestrates the function of inflammatory (dendritic cells and neutrophils) and structural (airway smooth muscle) cells. Replenishment of Sema3E, which is suppressed under asthmatic conditions, could confer protection against allergic asthma by modulation of cellular functions. I began by comparing the expression of Sema3E between allergic asthmatics and healthy subjects. A remarkable down-regulation of Sema3E under asthmatic patients was observed which was further confirmed in a mouse model of the disease. Decreased expression of Sema3E was specifically demonstrated on bronchial epithelial cells obtained from asthmatic patients at both mRNA and protein levels. To address the function of Sema3E in allergic asthma in vivo, I extended my studies to mouse models of the disease and demonstrated that Sema3e gene deletion results in exacerbated allergic asthma pathology induced by allergen exposure. To investigate the translational relevance of my findings, I performed treatment of an asthmatic mouse model with exogenous Sema3E in which its intranasal administration attenuated airway inflammation, remodeling and hyper-responsiveness. The mechanism underlying Sema3E’s role in pathogenesis of allergic asthma was extensively studied indicating a crucial role of this mediator in modulation of dendritic cells and neutrophils functions. Our data demonstrated that both dendritic cells and neutrophils express the Sema3E high affinity receptor, PlexinD1, which makes them responsive to Sema3E treatment. Then, I studied expression and function of PlexinD1 on human airway smooth muscle (ASM) cells. I found that PlexinD1 surface expression was reduced on ASM cells from asthmatic patients. Treatment of ASM cells with Sema3E inhibited their proliferation and migration as the characteristic feature of airway remodeling. Suppression of Rac1 GTPase activity and phosphorylation of Akt/PI3K and ERK/MAPK were found as signaling mechanisms underlying Sema3E’s inhibitory effects. Together, these findings show that Sema3E thereby appears as a novel regulatory mediator, upstream of pro-allergic events, suggestive of a new approach to attenuate allergic asthma deficits. / May 2016

The purpose of this dissertation research was to use markers of activity change to explore the effects of imperial expansion and sociopolitical upset on a population. This study focused on markers such as entheseal remodeling and the development and progression of osteoarthritis that are commonly used in bioarchaeological literature to assess changes in activity over time. Three populations were used, comprised of seven different sites, which are divided into the Late Medieval (pre-Ottoman), Early Modern (post-Ottoman), and Vlach populations. These sites come from both the Adriatic and continental region of Croatia and are curated at the Croatian Academy of Sciences and Arts – Anthropology Center. The skeleton is highly plastic, which allows it to serve as an archive for the lived experiences of the individual. Because of this plasticity, embodiment theory was employed as a lens through which to examine the changing activity of people under Ottoman rule. Historical narratives paint this time period as being rife with conflict, with a large proportion of the Croatian population being displaced, subsumed by the Ottoman threat, or killed. This is reported to have caused drastic changes in the daily lives of all Croatians across the country as they were forced to adapt to new rulers or leave their homes. This was tested by examining entheseal remodeling and osteoarthritis within the different populations. The data indicate that although there were some differences found between the time periods, the changes were not as drastic as what may have been expected from the historical data. This is perhaps due to most Croatian people at the time being serfs, living a rugged lifestyle on the lands of feudal lords. Although the Ottomans may have been relentless rulers, they may not have worked common Croatians more so than their Croatian lords. Most people probably remained in their roles as craftsmen or food producers, which would not have left dramatic changes in the form of activity markers on the skeleton.

Tang Tai Yuen. / "Architecture Department, Chinese University of Hong Kong, Master of Architecture Programme 1997-98, design report." / Includes bibliographical references (leave 50). / Chapter (1) --- Introduction / Chapter 1.1 --- Preface --- p.1 / Chapter 1.2 --- Background --- p.2 / Chapter (2) --- Project Nature / Chapter 2.1 --- Client Profile --- p.3 / Chapter 2.2 --- Target Users --- p.3 / Chapter 2.3 --- Schedule of Accommodation --- p.4 / Chapter (3) --- Project Analysis / Chapter 3.1 --- Existing Problem --- p.5 / Chapter 3.2 --- General Objectives --- p.6 / Chapter 3.3 --- Mission --- p.7 / Chapter 3.4 --- Architectural Objectives --- p.7 / Chapter 3.5 --- Research Methodlogy --- p.8 / Chapter (4) --- Site Aspects / Chapter 4.1 --- Site Options --- p.9 / Chapter 4.2 --- Site Analysis / Chapter (i) --- Contextual Background --- p.10 / Chapter (ii) --- Vehicular & Pedestrian Accessibility --- p.11 / Chapter (iii) --- View --- p.12 / Chapter (iv) --- Visibility --- p.13 / Chapter (v) --- Solar Orientation --- p.14 / Chapter (vi) --- NoiseDisturbance --- p.14 / Chapter (vii) --- Wind effect --- p.14 / Chapter (5) --- Design Process / Chapter 5.1 --- Studies on Diverse Sport Halls --- p.15-16 / Chapter 5.2 --- Prelimary Options --- p.17-19 / Chapter 5.3 --- Schematic Concept --- p.20 / Chapter 5.4 --- Design Development / Chapter (i) --- Building Part Evolution --- p.21 / Chapter (ii) --- Elevation Studies --- p.22 / Chapter (iii) --- Roof Form Studies --- p.23 / Chapter (iv) --- Structure Studies --- p.24 / Chapter (v) --- Glass Wall Detail Studies --- p.25-26 / Chapter (vi) --- Materials and Finishes Studies --- p.27 / Chapter (vi) --- Mechanical and Finishes Studies --- p.28 / Chapter (6) --- Final Product / Chapter 6.1 --- Site Concepts --- p.29-30 / Chapter 6.2 --- Building Concepts --- p.31-32 / Chapter 6.3 --- Building Profile --- p.33 / Chapter 6.4 --- Generic Main Space Layout --- p.34 / Chapter 6.5 --- Building Plans --- p.35 / Chapter 6.6 --- Elevations and Section --- p.36 / Chapter 6.7 --- Squential Interior Perpsective Drawings --- p.37-41 / Chapter 6.8 --- Building Detail --- p.42 / Chapter 6.9 --- Building Model --- p.43 / Appendix / Chapter 1. --- Statutory requirement Response / Chapter (i) --- Outline Zoning Plan --- p.44 / Chapter (ii) --- Lease Conditions --- p.45-46 / Chapter 2. --- Life Safety and Building Services --- p.47 / Chapter 3. --- Builidng Cost Estimate --- p.48 / Chapter 4. --- Program Schedule --- p.49 / Chapter 5. --- Bibliography --- p.50

"Mechanical loads play a pivotal role in the growth, maintenance, remodeling, and disease onset in connective tissues. Harnessing the relationship between mechanical signals and how cells remodel their surrounding extracellular matrix would provide new insights into the fundamental processes of wound healing and fibrosis and also assist in the creation of custom-tailored tissue equivalents for use in regenerative medicine. In 3D tissue models, uniaxial cyclic stretch has been shown to stimulate the synthesis and crosslinking of collagen while increasing the matrix density, fiber alignment, stiffness, and tensile strength in the direction of principal stretch. Unfortunately, the profound fiber realignment in these systems render it difficult to differentiate between passive effects and cell-mediated remodeling. Further, these previous studies generally focus on a single level of stretch magnitude and duration, and they also investigate matrix remodeling under a homogeneous strain conditions. Therefore, these studies are not sufficient to establish key information regarding stretch-dependent remodeling for use in tissue engineering and also do not simulate the complex mechanical environment of connective tissue. We first developed a novel in vitro model system using equibiaxial stretch on fibrin gels (early models of wound healing) that enabled the isolation of mechanical effects on cell-mediated matrix remodeling. Using this system we demonstrated that in the absence of in-plane alignment, stretch stimulates fibroblasts to produce a stronger tissue by synthesizing collagen and condensing their surrounding matrix. We then developed dose-response curves for multiple aspects of tissue remodeling as a function of stretch magnitude and duration (intermittent versus continuous stretch). Our results indicate that both the magnitude and the duration per day of stretch are important factors in mechanically induced cell activity, as evidenced by dose-dependent responses of several remodeling metrics in response to these two parameters (UTS, matrix stiffness, collagen content, cell number). In addition, we found that cellularity, collagen content, and resistance to tension increased when the tissues were mechanically loaded intermittently as opposed to continuously. Finally, we developed a novel model system that produces non-homogeneous strain distribution, allowing for the simultaneous study of strain gradients, strain anisotropy, and strain magnitude in 2D and 3D. Establishing a system that produces complex strain distributions provides a more accurate model of the mechanical conditions found in connective tissue, and also allows for the investigation of cellular adaptations to a changing mechanical environment. "

Thesis. 1977. M.Arch.--Massachusetts Institute of Technology. Dept. of Architecture. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ROTCH. / Bibliography : leaf 23. / M.Arch.

In eukaryotes, the organization of DNA into chromatin is a primary determinant of gene expression. Positioned nucleosomes in promoter regions are frequently found to regulate gene expression by obstructing the accessibility of cis-regulatory elements in DNA to trans-factors. This dissertation focuses on the chromatin structure and remodeling program at the S. cerevisiae PHO5 promoter, extending the use of DNA methyltransferases as in vivo probes of chromatin structure. Our studies address the diversity of histone-DNA interactions in vivo by examining nucleosome conformational stabilities at the PHO5 promoter. We present high-resolution chromatin structural mapping of the promoter, required to relate in vivo site accessibility to nucleosome stability and show that the PHO5 promoter nucleosomes have different accessibilities. We show a correlation between DNA curvature and nucleosome positioning, which is consistent with the observed differences in accessibility/stability. Kinetic analyses of the chromatin remodeling program at PHO5 show that nucleosomes proximal to the enhancer are disrupted preferentially and prior to those more distal, demonstrating bidirectional and finite propagation of chromatin remodeling from bound activators and providing a novel mechanism by which transactivation at a distance occurs.

Extracellular microenvironment, including its components and biophysical parameters such as matrix structure and stiffness, is a crucial determinant of cellular function. There exists interdependency between cellular behaviors and the extracellular matrix (ECM), whereby cells are constantly sensing and modifying their surroundings in response to physical stress or during processes like wound repair, cancer cell invasion, and morphogenesis, to create an environment which supports adaptation. To date, knowledge of the distinct regulatory mechanisms of this complex relationship is little, while the urge is evident as it plays a significant role in understanding tissue remodeling. Cells are observed to align with the parallel arrays of collagen fibrils found in tissues such as bone, tendon, and cornea, suggesting the importance of ordered matrices in defining cell functions. In this study, epitaxial growths of ordered two-dimensional collagen matrices were created, with parallelly aligned fibrils on muscovite mica, and novel triangular pattern matrix on phlogopite mica. Using Fluorescence and Atomic Force Microscopy, we were able to observe cell polarization along with stress fiber formation and matrix deformation at high resolution. Cells were observed to be able to penetrate between collagen fibrils and generate traction anisotropically to polarize. These ordered collagen matrices serve as an excellent model to study cellular remodeling of ECM in vitro, in which this fundamental apprehension of cell-matrix relationship is of crucial importance to manipulate the system and obtain desired cell functions.

C-terminal Binding Protein (CtBP) is a transcriptional co-repressor that plays an important role in mammalian development and tumorigenesis. CtBP is known to interact with Ikaros, an important transcriptional regulator in the pituitary; however CtBP itself has not been examined in this gland. I examined the role of CtBP in pituitary cell growth and survival. Compared to control pituitary GH4 cells, CtBP1-deficient cells exhibit reduced proliferation and de-regulation of genes involved in cell cycle and growth factor signaling. CtBP1-deficient cells were more susceptible to hypoxia-induced apoptosis and showed a reduction in hypoxia-induced Ikaros expression. Interactions between CtBP and Ikaros isoforms were demonstrated in pituitary tumor cell lines. CtBP and Ikaros also bound a common region of the previously characterized Ikaros target, the LDL-R promoter. These results identify oncogenic properties of CtBP1 in the pituitary and set the groundwork for future studies into regulatory roles of CtBP and Ikaros in the pituitary.