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Purpose To determine the role of eukaryotic translation initiation factor 5A (eIF5A) in TNF-alpha-induced apoptosis of lamina cribrosa (LC) cells. Methods LC cells were isolated from optic nerve heads of eyes of two human donors. The cells were treated with TNF-alpha and camptothecin, a TNF synergist, and the incidence of apoptosis was scored by Hoechst staining. Expression of eIF5A protein in response to camptothecin or a combination of camptothecin and TNF-alpha was determined by Western blot analysis. The ability of small inhibitory (si)RNAs directed against eIF5A to protect LC cells from TNF-alpha-induced apoptosis was determined by Hoechst and TUNEL staining of transfected LC cells. Results TNF-alpha and camptothecin synergized to induce greater than two times more apoptosis in LC cells than when the cells were treated with TNF-alpha or camptothecin separately. Expression of eIF5A protein increased significantly after 8 hours of exposure to TNF-alpha and camptothecin, but not in response to camptothecin alone. siRNAs directed against eIF5A reduced apoptosis of LC cells in response to TNF-alpha and camptothecin by between 35% and 69%, as determined by Hoechst staining. An siRNA against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also reduced apoptosis of LC cells by 42%. TUNEL of transfected LC cells treated with TNF-alpha and camptothecin revealed an 80% reduction in apoptosis with siRNA against eIF5A. Conclusions TNF-alpha, in synergy with camptothecin, induces apoptosis in human LC cells. eIF5A is upregulated by LC cells in response to TNF-alpha, and siRNAs against eIF5A protect LC cells from apoptosis. Thus, eIF5A appears to be a novel proapoptotic protein in the TNF pathway and a possible target for treatment of glaucoma.

This research attempts to evaluate temporary urban regeneration potential by integrating two systems that make up an interim intervention which addresses an observed problem. The research proposes a systematic approach for a multi-system life cycle assessment model which lays out the process of working with two separate systems to provide a pathway for temporary urban development strategies. To achieve this, the research starts with identifying parameters of temporary urban regeneration through a systematic review of the literature. Key parameters are categorized based on objectives, indicators, as well as, physical characteristics of the literature explored case studies. Then, the findings are utilized to guide the proposed model of connecting two given systems to assess their joint impacts on a temporary urban regeneration system. The proposed MSLCA framework utilizes a holistic modeling structure with a process to integrate and analyze separate systems and quantify results for overall sustainability performance. Finally, the model is used to evaluate a case study involving two systems that address observed problems and provide urban services. The results explore the environmental impacts of the proposed intervention and highlight the effects of individual components on both systems. Through the implementation of the model, decisions on temporary urban intervention are guided by hotspots in the results. The findings reveal an opportunity for future research to expand the model's application to other processes and further its scope beyond environmental indicators. Subsequent studies can investigate opportunities for a holistic approach that includes economic and social aspects. Doctor of Philosophy The way we live in cities is heavily influenced by how they are planned. Improvident city planning could deny residents opportunities to enjoy some basic urban amenities. These problems could be self-induced as they are often a result of planning, policies, or personal habits and choice. Planners, urban designers, and regulators are constantly experimenting with different tools of urban regeneration to rediscover genuine urban experiences. This research sets out to investigate opportunities for temporary urban interventions on vacant lands in the city of Riyadh through repurposing idle shipping containers as a tool. This is to address the issues of a lack of urban services within residential subdivisions in the city, the high prevalence of vacant lands, and a wide availability of decommissioned shipping containers. The use of shipping containers for non-cargo purposes has seen an increased interest among architects and designers for their versatility and accessibility. Empty container accumulation is often a result of an unbalanced trading system which is mainly an issue of import-based countries. Therefore, the upcycling potential of intermodal containers can extend their life cycles and take advantage of their structure. It also maximizes the environmental returns of their raw materials. Through such processes of circular economy, potential waste objects can be repurposed as resources into usable structures and thus avoids the use and extraction of new raw materials. It is generally thought that the repurposing of shipping containers into building structures introduces environmental advantages when compared to traditional construction. Similarly, vacant lands are a valuable and well-established resource that can provide the setting for temporary urban interventions. Finding a joint productive use of these systems is at the center of this research as it attempts to assess the urban regeneration value of their merged utility during their idle stage. This helps address a key challenge that most urban area suffers from which is the lack of easily accessible and timely deployable temporary urban intervention to serve a particular use. This research aims to create a model that evaluates the lifecycles of temporary uses based on the joint intersection of contributing systems. The proposed Multi-System Life Cycle Assessment (MSLCA) model is to be applied to assess temporary urban regeneration interventions and help make decisions regarding appropriate approaches. The goal of the model is to propose a value-based approach based on characteristics from two systems. The resulting MSLCA model answers questions on how to apply LCA processes to a transitional intervention with new processes. In doing so, it highlights parameters for systems integration and processes for planning appropriate scenarios for urban interventions. It also highlights the need for unique system boundaries and specifies approaches for system assessment and interpretation. Finally, it provides broader impact categories beyond environmental impacts to consider specific economic and social indicators.

In light of today's technological developments, the world has become more interested in everything that is quantifiable. In the field of architecture, this phenomenon has affected the design process, in terms of neglect human requirements related to the lived experience. This research is concerned with studying the intersection between what is quantifiable and what could contribute to improve the living experience. Research in disciplines such as art, architecture, and psychology assert that geometries with pure mathematical expression are visually pleasing. The present research aims to integrate these geometric relationships with daylight when formed by the edge of light and shadow, resulting from direct sunlight entering a room through roof openings and presenting on a northern wall. The goal of this research is to develop an initial prototype for a proof of concept that enables architects to consider humanistic, aesthetic criteria for geometry and daylight. The research progresses through three stages. First, the researcher describes a method to assess the geometry of lines resulting from the boundary between light and shadow when falling on a sunlit wall. Second, the researcher applies the described method to a random sample of roof opening configurations using digital modeling and a simulation of the sun's movement. Thirdly, the researcher extracts a regression equation that describes the relationship between the resulting shadow lines on the walls and the configuration of the roof openings. This regression analysis will form an initial step to developing a decision-support tool that predicts the purity of shadow lines during the early stages of the design process. Doctor of Philosophy Many architects acknowledge that the buildings we design today lack beauty. This research discusses the possibility of creating a program that considers visual beauty in architectural design. Many disciplines have offered praise about pure geometric shapes. The aim of this research is to develop a prototype that helps architects use these geometric shapes in architectural design specifically in the use of daylight inside rooms. To elaborate, when the sun moves, in its rising and setting, lines of shadows appear within the space that belong to pure geometric shapes. These pure forms are a source of visual beauty because they are derived from nature; as a result, our bodies have a physiological and psychological response when seeing them. The study is based on testing a hypothesis that asserts the higher the degree of purity of the lines used in the design of a room, namely the north-facing wall and roof openings, the higher will be the purity of the shadow lines resulting from the movement of the sun.

Computational Fluid Dynamics (CFD) refers to numerical methods for simulating the movement of fluid. Due to its efficiency, CFD has been widely used in aerospace engineering and automotive design since the 1970s. It also has potential in architectural design since airflow has been an important player in the design process. However, the CFD users in the building industry tend to be limited to researchers and engineers rather than architectural designers due to the complexity of the simulations including the extensive knowledge required for the processing. The benefit of using CFD would be maximized through its early application by architectural designers since the key design decisions are made in the early stages. In response to this, simulation tools specialized for the early stages of architectural design are developed recently, which offer more user-friendly interfaces. Within this context, the present study aimed to introduce and test the simulation tools for the early stages of design and establish a framework for supporting architectural designers to utilize CFD. Under this objective, a mixed-method approach was employed that includes quantitative and qualitative assessments of simulation tools, development of a knowledge set that can help the users to understand the simulation processes and results, an immersive case study for structuring the procedural model, and a Delphi method for evaluating and reaching a consensus on the proposed framework. Doctor of Philosophy Computational Fluid Dynamics (CFD) is a computer simulation method for automating the calculations of the complex equations on the flow of a fluid, such as air or water, and visualizing the calculation results. CFD has been widely used in designing aircraft and cars since the 1970s because of the efficiency of this method compared to physical experiments. CFD also has potential in architectural design since airflow has been an important player in the design process. However, the CFD users in the building industry tend to be limited to researchers and engineers rather than architectural designers due to the complexity of the simulations including the extensive knowledge required for the processing. In response to this situation, more user-friendly simulation tools for non-experts, including designers, are developed recently. Considering this context, the present study tried to introduce and test the simulation tools for designers and develop a framework for supporting architectural designers to utilize CFD in their design processes. Under this objective, both quantitative and qualitative studies were conducted, including the review of relevant articles, computer simulations, a case study with an architectural project example, designed by the author, and a Delphi method in which the recruited experts in architectural design evaluate the proposed framework.