The potential role of environmental exposures and genomic signaling in development of central nervous system tumors

The etiology of central nervous system tumors (CNSTs) is mainly unknown. Aside from extremely rare genetic conditions, such as neurofibromatosis and tuberous sclerosis, the only unequivocally identified risk factor is exposure to ionizing radiation, and this explains only a very small fraction of cases. Using meta-analysis, gene networking and bioinformatics methods, this dissertation explored the hypothesis that environmental exposures produce genetic and epigenetic alterations that may be involved in the etiology of CNSTs. A meta-analysis of epidemiological studies of pesticides and pediatric brain tumors revealed a significantly increased risk of brain tumors among children whose mothers had farm-related exposures during pregnancy. A dose response was recognized when this risk estimate was compared to those for risk of brain tumors from maternal exposure to non-agricultural pesticides during pregnancy, and risk of brain tumors among children exposed to agricultural activities. Through meta-analysis of several microarray studies which compared normal tissue to astrocytomas, we were able to identify a list of 554 genes which were differentially expressed in the majority of astrocytomas. Many of these genes have in fact been implicated in development of astrocytoma, including EGFR, HIF-1α, c-Myc, WNT5A, and IDH3A. Reverse engineering of these 554 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme (GBM) were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. Lastly, bioinformatics analysis of environmental databases and curated published results on GBM was able to identify numerous potential pathways and geneenvironment interactions that may play key roles in astrocytoma development. Findings from this research have strong potential to advance our understanding of the etiology and susceptibility to CNSTs. Validation of our ‘key genes’ and pathways could potentially lead to useful tools for early detection and novel therapeutic options for these tumors.

Reverse Engineering of Modified Genes by Bayesian Network Analysis Defines Molecular Determinants Critical to the Development of Glioblastoma

In this study we have identified key genes that are critical in development of astrocytic tumors. Meta-analysis of microarray studies which compared normal tissue to astrocytoma revealed a set of 646 differentially expressed genes in the majority of astrocytoma. Reverse engineering of these 646 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I–IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. All of these genes were up-regulated, except MPP2 (down regulated). These 10 genes were able to predict tumor status with 96–100% confidence when using logistic regression, cross validation, and the support vector machine analysis. Markov genes interact with NFkβ, ERK, MAPK, VEGF, growth hormone and collagen to produce a network whose top biological functions are cancer, neurological disease, and cellular movement. Three of the 10 genes - EGFR, COL4A1, and CDK4, in particular, seemed to be potential ‘hubs of activity’. Modified expression of these 10 Markov Blanket genes increases lifetime risk of developing glioblastoma compared to the normal population. The glioblastoma risk estimates were dramatically increased with joint effects of 4 or more than 4 Markov Blanket genes. Joint interaction effects of 4, 5, 6, 7, 8, 9 or 10 Markov Blanket genes produced 9, 13, 20.9, 26.7, 52.8, 53.2, 78.1 or 85.9%, respectively, increase in lifetime risk of developing glioblastoma compared to normal population. In summary, it appears that modified expression of several ‘key genes’ may be required for the development of glioblastoma. Further studies are needed to validate these ‘key genes’ as useful tools for early detection and novel therapeutic options for these tumors.

Fiber Scaffolds of Poly (glycerol-dodecanedioate) and its Derivative via Electrospinning for Neural Tissue Engineering

Peripheral nerves have demonstrated the ability to bridge gaps of up to 6 mm. Peripheral Nerve System injury sites beyond this range need autograft or allograft surgery. Central Nerve System cells do not allow spontaneous regeneration due to the intrinsic environmental inhibition. Although stem cell therapy seems to be a promising approach towards nerve repair, it is essential to use the distinct three-dimensional architecture of a cell scaffold with proper biomolecule embedding in order to ensure that the local environment can be controlled well enough for growth and survival. Many approaches have been developed for the fabrication of 3D scaffolds, and more recently, fiber-based scaffolds produced via the electrospinning have been garnering increasing interest, as it offers the opportunity for control over fiber composition, as well as fiber mesh porosity using a relatively simple experimental setup. All these attributes make electrospun fibers a new class of promising scaffolds for neural tissue engineering. Therefore, the purpose of this doctoral study is to investigate the use of the novel material PGD and its derivative PGDF for obtaining fiber scaffolds using the electrospinning. The performance of these scaffolds, combined with neural lineage cells derived from ESCs, was evaluated by the dissolvability test, Raman spectroscopy, cell viability assay, real time PCR, Immunocytochemistry, extracellular electrophysiology, etc. The newly designed collector makes it possible to easily obtain fibers with adequate length and integrity. The utilization of a solvent like ethanol and water for electrospinning of fibrous scaffolds provides a potentially less toxic and more biocompatible fabrication method. Cell viability testing demonstrated that the addition of gelatin leads to significant improvement of cell proliferation on the scaffolds. Both real time PCR and Immunocytochemistry analysis indicated that motor neuron differentiation was achieved through the high motor neuron gene expression using the metabolites approach. The addition of Fumaric acid into fiber scaffolds further promoted the differentiation. Based on the results, this newly fabricated electrospun fiber scaffold, combined with neural lineage cells, provides a potential alternate strategy for nerve injury repair.

An interactive environmental site assessment audit for Wagner Creek river basin clean up project

The primary purpose of this thesis was to design and create an Interactive Audit to conduct Environmental Site Assessments according to American Society of Testing Material's (ASTM) Phase I Standards at the Wagner Creek study area. ArcPad and ArcIMS are the major software that were used to create the model and ArcGIS Desktop was used for data analysis and to export shapefile symbology to ArcPad. Geographic Information Systems (GIS) is an effective tool to deploy these purposes. This technology was utilized to carry out data collection, data analysis and to display data interactively on the Internet. Electronic forms, customized for mobile devices were used to survey sites. This is an easy and fast way to collect and modify field data. New data such as land use, recognized environmental conditions, and underground storage tanks can be added into existing datasets. An updated map is then generated and uploaded to the Internet using ArcIMS technology. The field investigator has the option to generate and view the Inspection Form at the end of his survey on site, or print a hardcopy at base. The mobile device also automatically generates preliminary editable Executive Reports for any inspected site.

Time, Cost, and Environmental Impact Analysis for Sustainable Design at Multiple Building Levels

Construction projects are complex endeavors that require the involvement of different professional disciplines in order to meet various project objectives that are often conflicting. The level of complexity and the multi-objective nature of construction projects lend themselves to collaborative design and construction such as integrated project delivery (IPD), in which relevant disciplines work together during project conception, design and construction. Traditionally, the main objectives of construction projects have been to build in the least amount of time with the lowest cost possible, thus the inherent and well-established relationship between cost and time has been the focus of many studies. The importance of being able to effectively model relationships among multiple objectives in building construction has been emphasized in a wide range of research. In general, the trade-off relationship between time and cost is well understood and there is ample research on the subject. However, despite sustainable building designs, relationships between time and environmental impact, as well as cost and environmental impact, have not been fully investigated. The objectives of this research were mainly to analyze and identify relationships of time, cost, and environmental impact, in terms of CO2 emissions, at different levels of a building: material level, component level, and building level, at the pre-use phase, including manufacturing and construction, and the relationships of life cycle cost and life cycle CO2 emissions at the usage phase. Additionally, this research aimed to develop a robust simulation-based multi-objective decision-support tool, called SimulEICon, which took construction data uncertainty into account, and was capable of incorporating life cycle assessment information to the decision-making process. The findings of this research supported the trade-off relationship between time and cost at different building levels. Moreover, the time and CO2 emissions relationship presented trade-off behavior at the pre-use phase. The results of the relationship between cost and CO2 emissions were interestingly proportional at the pre-use phase. The same pattern continually presented after the construction to the usage phase. Understanding the relationships between those objectives is a key in successfully planning and designing environmentally sustainable construction projects.

An Exergy Based Engineering and Economic Analysis of Sustainable Building

To achieve the goal of sustainable development, the building energy system was evaluated from both the first and second law of thermodynamics point of view. The relationship between exergy destruction and sustainable development were discussed at first, followed by the description of the resource abundance model, the life cycle analysis model and the economic investment effectiveness model. By combining the forgoing models, a new sustainable index was proposed. Several green building case studies in U.S. and China were presented. The influences of building function, geographic location, climate pattern, the regional energy structure, and the technology improvement potential of renewable energy in the future were discussed. The building’s envelope, HVAC system, on-site renewable energy system life cycle analysis from energy, exergy, environmental and economic perspective were compared. It was found that climate pattern had a dramatic influence on the life cycle investment effectiveness of the building envelope. The building HVAC system energy performance was much better than its exergy performance. To further increase the exergy efficiency, renewable energy rather than fossil fuel should be used as the primary energy. A building life cycle cost and exergy consumption regression model was set up. The optimal building insulation level could be affected by either cost minimization or exergy consumption minimization approach. The exergy approach would cause better insulation than cost approach. The influence of energy price on the system selection strategy was discussed. Two photovoltaics (PV) systems – stand alone and grid tied system were compared by the life cycle assessment method. The superiority of the latter one was quite obvious. The analysis also showed that during its life span PV technology was less attractive economically because the electricity price in U.S. and China did not fully reflect the environmental burden associated with it. However if future energy price surges and PV system cost reductions were considered, the technology could be very promising for sustainable buildings in the future.

Mitigating Social Risk in the Extractive Sector: Developing Intercultural Competence as a Tool for Negotiating Western-Indigenous Perspectives within the Undergraduate Mining Engineering Curriculum

Drawing upon critical, communications, and educational theories, this thesis develops a novel framing of the problem of social risk in the extractive sector, as it relates to the building of respectful relationships with indigenous peoples. Building upon Bakhtin’s dialogism, the thesis demonstrates the linkage of this aspect of social risk to professional education, and specifically, to the undergraduate mining engineering curriculum, and develops a framework for the development of skills related to intercultural competence in the education of mining engineers. The knowledge of social risk, as well as the level of intercultural competence, of students in the mining engineering program, is investigated through a mixture of surveys and focus groups – as is the impact of specific learning interventions. One aspect of this investigation is whether development of these attributes alters graduates’ conception of their identity as mining engineers, i.e. the range and scope of responsibilities, and understanding of to whom responsibilities are owed, and their role in building trusting relationships with communities. Survey results demonstrate that student openness to the perspectives of other cultures increases with exposure to the second year curriculum. Students became more knowledgeable about social dimensions of responsible mining, but not about cultural dimensions. Analysis of focus group data shows that students are highly motivated to improve community perspectives and acceptance. It is observed that students want to show respect for diverse peoples and communities where they will work, but they are hampered by their inability to appreciate the viewpoints of people who do not share their values. They embrace benefit sharing and environmental protection as norms, but they mistakenly conclude that opposition to mining is rooted in a lack of education rather than in cultural values. Three, sequential, threshold concepts are identified as impeding development of intercultural competence: Awareness and Acknowledgement of Different Forms of Knowledge; Recognition that Value Systems are a Function of Culture; Respect for varied perceptions of Social Wellbeing and Quality of Life. Future curriculum development in the undergraduate mining engineering program, as well as in other educational programs relevant to the extractive sector, can be effectively targeted by focusing on these threshold concepts.

GiveMe Shelter: a people-centred design process for promoting independent inquiry-led learning in engineering

It has become increasingly common for tasks traditionally carried out by engineers to be undertaken by technicians and technologist with access to sophisticated computers and software that can often perform complex calculations that were previously the responsibility of engineers. Not surprisingly, this development raises serious questions about the future role of engineers and the education needed to address these changes in technology as well as emerging priorities from societal to environmental challenges. In response to these challenges, a new design module was created for undergraduate engineering students to design and build temporary shelters for a wide variety of end users from refugees, to the homeless and children. Even though the module provided guidance on principles of design thinking and methods for observing users needs through field studies, the students found it difficult to respond to needs of specific end users but instead focused more on purely technical issues.

Developing an engineering approach for migrating from prescriptive to performance-based specification for concrete

The integral variability of raw materials, lack of awareness and appreciation of the technologies for achieving quality control and lack of appreciation of the micro and macro environmental conditions that the structures will be subjected, makes modern day concreting a challenge. This also makes Designers and Engineers adhere more closely to prescriptive standards developed for relatively less aggressive environments. The data from exposure sites and real structures prove, categorically, that the prescriptive specifications are inadequate for chloride environments. In light of this shortcoming, a more pragmatic approach would be to adopt performance-based specifications which are familiar to industry in the form of specification for mechanical strength. A recently completed RILEM technical committee made significant advances in making such an approach feasible.
Furthering a performance-based specification requires establishment of reliable laboratory and on-site test methods, as well as easy to perform service-life models. This article highlights both laboratory and on-site test methods for chloride diffusivity/electrical resistivity and the relationship between these tests for a range of concretes. Further, a performance-based approach using an on-site diffusivity test is outlined that can provide an easier to apply/adopt practice for Engineers and asset managers for specifying/testing concrete structures.

Assessing Potential Laser Strike Protection Engineering Control for United States Coast Guard Aircraft

Thesis (Master's)--University of Washington, 2016-06

Application of gas hydrate equilibria prediction in process engineering

Desde hace cerca de dos siglos, los hidratos de gas han ganado un rol importante en la ingeniería de procesos, debido a su impacto económico y ambiental en la industria -- Cada día, más compañías e ingenieros ganan interés en este tema, a medida que nuevos desafíos muestran a los hidratos de gas como un factor crucial, haciendo su estudio una solución para un futuro próximo -- Los gases de hidrato son estructuras similares al hielo, compuestos de moléculas huéspedes de agua conteniendo compuestos gaseosos -- Existen naturalmente en condiciones de presiones altas y bajas temperaturas, condiciones típicas de algunos procesos químicos y petroquímicos [1] -- Basado en el trabajo doctoral de Windmeier [2] y el trabajo doctoral the Rock [3], la descripción termodinámica de las fases de los hidratos de gas es implementada siguiendo el estado del arte de la ciencia y la tecnología -- Con ayuda del Dortmund Data Bank (DDB) y el paquete de software correspondiente (DDBSP) [26], el desempeño del método fue mejorado y comparado con una gran cantidad de datos publicados alrededor del mundo -- También, la aplicabilidad de la predicción de los hidratos de gas fue estudiada enfocada en la ingeniería de procesos, con un caso de estudio relacionado con la extracción, producción y transporte del gas natural -- Fue determinado que la predicción de los hidratos de gas es crucial en el diseño del proceso del gas natural -- Donde, en las etapas de tratamiento del gas y procesamiento de líquido no se presenta ninguna formación, en la etapa de deshidratación una temperatura mínima de 290.15 K es crítica y para la extracción y transporte el uso de inhibidores es esencial -- Una composición másica de 40% de etilenglicol fue encontrada apropiada para prevenir la formación de hidrato de gas en la extracción y una composición másica de 20% de metanol en el transporte

Exergetic, energetic, economic and environmental evaluation of concentrated solar power plants in Libya

The PhD project addresses the potential of using concentrating solar power (CSP) plants as a viable alternative energy producing system in Libya. Exergetic, energetic, economic and environmental analyses are carried out for a particular type of CSP plants. The study, although it aims a particular type of CSP plant – 50 MW parabolic trough-CSP plant, it is sufficiently general to be applied to other configurations. The novelty of the study, in addition to modeling and analyzing the selected configuration, lies in the use of a state-of-the-art exergetic analysis combined with the Life Cycle Assessment (LCA). The modeling and simulation of the plant is carried out in chapter three and they are conducted into two parts, namely: power cycle and solar field. The computer model developed for the analysis of the plant is based on algebraic equations describing the power cycle and the solar field. The model was solved using the Engineering Equation Solver (EES) software; and is designed to define the properties at each state point of the plant and then, sequentially, to determine energy, efficiency and irreversibility for each component. The developed model has the potential of using in the preliminary design of CSPs and, in particular, for the configuration of the solar field based on existing commercial plants. Moreover, it has the ability of analyzing the energetic, economic and environmental feasibility of using CSPs in different regions of the world, which is illustrated for the Libyan region in this study. The overall feasibility scenario is completed through an hourly analysis on an annual basis in chapter Four. This analysis allows the comparison of different systems and, eventually, a particular selection, and it includes both the economic and energetic components using the “greenius” software. The analysis also examined the impact of project financing and incentives on the cost of energy. The main technological finding of this analysis is higher performance and lower levelized cost of electricity (LCE) for Libya as compared to Southern Europe (Spain). Therefore, Libya has the potential of becoming attractive for the establishment of CSPs in its territory and, in this way, to facilitate the target of several European initiatives that aim to import electricity generated by renewable sources from North African and Middle East countries. The analysis is presented a brief review of the current cost of energy and the potential of reducing the cost from parabolic trough- CSP plant. Exergetic and environmental life cycle assessment analyses are conducted for the selected plant in chapter Five; the objectives are 1) to assess the environmental impact and cost, in terms of exergy of the life cycle of the plant; 2) to find out the points of weakness in terms of irreversibility of the process; and 3) to verify whether solar power plants can reduce environmental impact and the cost of electricity generation by comparing them with fossil fuel plants, in particular, Natural Gas Combined Cycle (NGCC) plant and oil thermal power plant. The analysis also targets a thermoeconomic analysis using the specific exergy costing (SPECO) method to evaluate the level of the cost caused by exergy destruction. The main technological findings are that the most important contribution impact lies with the solar field, which reports a value of 79%; and the materials with the vi highest impact are: steel (47%), molten salt (25%) and synthetic oil (21%). The “Human Health” damage category presents the highest impact (69%) followed by the “Resource” damage category (24%). In addition, the highest exergy demand is linked to the steel (47%); and there is a considerable exergetic demand related to the molten salt and synthetic oil with values of 25% and 19%, respectively. Finally, in the comparison with fossil fuel power plants (NGCC and Oil), the CSP plant presents the lowest environmental impact, while the worst environmental performance is reported to the oil power plant followed by NGCC plant. The solar field presents the largest value of cost rate, where the boiler is a component with the highest cost rate among the power cycle components. The thermal storage allows the CSP plants to overcome solar irradiation transients, to respond to electricity demand independent of weather conditions, and to extend electricity production beyond the availability of daylight. Numerical analysis of the thermal transient response of a thermocline storage tank is carried out for the charging phase. The system of equations describing the numerical model is solved by using time-implicit and space-backward finite differences and which encoded within the Matlab environment. The analysis presented the following findings: the predictions agree well with the experiments for the time evolution of the thermocline region, particularly for the regions away from the top-inlet. The deviations observed in the near-region of the inlet are most likely due to the high-level of turbulence in this region due to the localized level of mixing resulting; a simple analytical model to take into consideration this increased turbulence level was developed and it leads to some improvement of the predictions; this approach requires practically no additional computational effort and it relates the effective thermal diffusivity to the mean effective velocity of the fluid at each particular height of the system. Altogether the study indicates that the selected parabolic trough-CSP plant has the edge over alternative competing technologies for locations where DNI is high and where land usage is not an issue, such as the shoreline of Libya.

An investigation of environmental conditions experienced during the life of high-value wood components and products

Australian forest industries have a long history of export trade of a wide range of products from woodchips (for paper manufacturing), sandalwood (essential oils, carving and incense) to high value musical instruments, flooring and outdoor furniture. For the high value group, fluctuating environmental conditions brought on by changes in temperature and relative humidity, can lead to performance problems due to consequential swelling, shrinkage and/or distortion of the wood elements. A survey determined the types of value-added products exported, including species and dimensions packaging used and export markets. Data loggers were installed with shipments to monitor temperature and relative humidity conditions. These data were converted to timber equilibrium moisture content values to provide an indication of the environment that the wood elements would be acclimatising to. The results of the initial survey indicated that primary high value wood export products included guitars, flooring, decking and outdoor furniture. The destination markets were mainly located in the northern hemisphere, particularly the United States of America, China, Hong Kong, Europe (including the United Kingdom), Japan, Korea and the Middle East. Other regions importing Australian-made wooden articles were south-east Asia, New Zealand and South Africa. Different timber species have differing rates of swelling and shrinkage, so the types of timber were also recorded during the survey. Results from this work determined that the major species were ash-type eucalypts from south-eastern Australia (commonly referred to in the market as Tasmanian oak), jarrah from Western Australia, spotted gum, hoop pine, white cypress, black butt, brush box and Sydney blue gum from Queensland and New South Wales. The environmental conditions data indicated that microclimates in shipping containers can fluctuate extensively during shipping. Conditions at the time of manufacturing were usually between 10 and 12% equilibrium moisture content, however conditions during shipping could range from 5 (very dry) to 20% (very humid). The packaging systems incorporated were reported to be efficient at protecting the wooden articles from damage during transit. The research highlighted the potential risk for wood components to ‘move’ in response to periods of drier or more humid conditions than those at the time of manufacturing, and the importance of engineering a packaging system that can account for the environmental conditions experienced in shipping containers. Examples of potential dimensional changes in wooden components were calculated based on published unit shrinkage data for key species and the climatic data returned from the logging equipment. The information highlighted the importance of good design to account for possible timber movement during shipping. A timber movement calculator was developed to allow designers to input component species, dimensions, site of manufacture and destination, to see validate their product design.

Engineering the transition from non-living to living matter

Re-creating and understanding the origin of life represents one of the major challenges facing the scientific community. We will never know exactly how life started on planet Earth, however, we can reconstruct the most likely chemical pathways that could have contributed to the formation of the first living systems. Traditionally, prebiotic chemistry has investigated the formation of modern life’s precursors and their self-organisation under very specific conditions thought to be ‘plausible’. So far, this approach has failed to produce a living system from the bottom-up. In the work presented herein, two different approaches are employed to explore the transition from inanimate to living matter. The development of microfluidic technology during the last decades has changed the way traditional chemical and biological experiments are performed. Microfluidics allows the handling of low volumes of reagents with very precise control. The use of micro-droplets generated within microfluidic devices is of particular interest to the field of Origins of Life and Artificial Life. Whilst many efforts have been made aiming to construct cell-like compartments from modern biological constituents, these are usually very difficult to handle. However, microdroplets can be easily generated and manipulated at kHz rates, making it suitable for high-throughput experimentation and analysis of compartmentalised chemical reactions. Therefore, we decided to develop a microfluidic device capable of manipulating microdroplets in such a way that they could be efficiently mixed, split and sorted within iterative cycles. Since no microfluidic technology had been developed before in the Cronin Group, the first chapter of this thesis describes the soft lithographic methods and techniques developed to fabricate microfluidic devices. Also, special attention is placed on the generation of water-in-oil microdroplets, and the subsequent modules required for the manipulation of the droplets such as: droplet fusers, splitters, sorters and single/multi-layer micromechanical valves. Whilst the first part of this thesis describes the development of a microfluidic platform to assist chemical evolution, finding a compatible set of chemical building blocks capable of reacting to form complex molecules with endowed replicating or catalytic activity was challenging. Abstract 10 Hence, the second part of this thesis focuses on potential chemistry that will ultimately possess the properties mentioned above. A special focus is placed on the formation of peptide bonds from unactivated amino acids, despite being one of the greatest challenges in prebiotic chemistry. As opposed to classic prebiotic experiments, in which a specific set of conditions is studied to fit a particular hypothesis, we took a different approach: we explored the effects of several parameters at once on a model polymerisation reaction, without constraints on hypotheses on the nature of optimum conditions or plausibility. This was facilitated by development of a new high-throughput automated platform, allowing the exploration of a much larger number of parameters. This led us to discover that peptide bond formation is less challenging than previously imagined. Having established the right set of conditions under which peptide bond formation was enhanced, we then explored the co-oligomerisation between different amino acids, aiming for the formation of heteropeptides with different structure or function. Finally, we studied the effect of various environmental conditions (rate of evaporation, presence of salts or minerals) in the final product distribution of our oligomeric products.