Adequately preparing for and responding to potential terrestrial (land-based) chemical spills are critical to the protection of human health and ecology. In this research, an environmental risk management system is developed to support analysis and facilitate decision-making for terrestrial chemical spill planning and response. This system is designed to serve a variety of stakeholders, including managers and policy-makers, who would benefit from generating screening level environmental risk assessments without requiring a technical background or collection of detailed environmental and chemical data. Areas of potential application include transportation routing, industrial zoning, environmental regulatory compliance and enforcement, spill response, and security planning. The system leverages geographic information systems (GIS) technology to assess and delineate the immediate threat to human and environmental receptors from terrestrial chemical spills. It characterizes a spilled chemicals ability to immediately impact human health, groundwater, surface water, and soil resources, and incorporates these four receptors into an overall measure of terrestrial chemical risk. The methodology driving this characterization is a risk index model, which is supported by a comprehensive database containing information on chemical properties and environmental resources. This model differs from previous environmental risk indices in that it: 1) accounts for attributes of the local environment and contaminant in question, 2) requires almost no data input or scientific knowledge from the user, 3) creates an easy-to-understand visual output that supports the decision process, and 4) has the potential for transferability to sites throughout the United States. In establishing proof of concept, the system is applied to a case study of a representative area in the United States. The potential terrestrial spill of several different chemicals is considered across all areas of Geauga County in the State of Ohio. Utilizing the system, risk assessment results are generated and visually displayed. The implications of these results are discussed in terms of how they impact decisions involving transportation routing, industrial zoning, environmental regulatory compliance and enforcement, spill response, and security planning.

How visual targets are selected for eye movements is a fundamental neural coding problem for all animals that see with a fovea. The strength of the model of the neuron as a coincidence detector suggests neural synchrony is a plausible, if not intrinsic, part of the cortical code. Moreover, synchrony has been proposed as a neural mechanism for the allocation of attention in visual processing. To investigate a synchronous ensemble code for saccadic target selection in the frontal eye field (FEF), the gravity algorithm was applied to simultaneously recorded neurons in a macaque monkey performing color singleton search. In addition to developing an original measure of statistical significance for the gravity method, this thesis demonstrates the existence of synchrony in the search process. The functional influence of synchrony in the distribution of visual attention, however, or in gating broad population responses in FEF, requires further interpretation.

This dissertation examined the use and variations of African American Language by middle school students. It focused on the relationships of African American Language to the social and cultural identities and academic achievements of students in educational settings. A second focus examined the educational complexities surrounding the uses of African American Language use by students in traditional classroom environments. Over a seven-month period, data were collected on interactions involving the use of African American Language in an eighth grade language arts classroom. Key classroom events and student interviews were examined utilizing the cultural analysis of discourse, thematic, and microethnographic analysis. Also examined were the cultural models for the use and meaning of African American Language and for cultural identity held by five African American Language student speakers. The study also examined the central role of prosody in signaling particular social and cultural identities and explored the significance of students adopting such identities across varying spaces in and outside of the classroom as a means to navigate social existences in a predominantly African American school community.

This research aimed to measure the operational impact of various strategies for utility loading behavior for commercial spent nuclear fuel (CSNF), as well as thermal design parameters involving waste transportation and emplacement of CSNF during the pre-closure period at Yucca Mountain, NV (YM). Specific objectives included: (1) generation of probable scenarios for waste stream quantities and thermal properties, (2) identification of performance trade-offs in surface facility design parameters and operating decisions, and (3) evaluation of safety and throughput implications of pre-closure strategies. These objectives were accomplished by modeling the pre-closure phase of YM operations as an integrated waste management system. Through application of this model, a better understanding was gained of how various waste management strategies influence facility design assumptions. Advantages and disadvantages of various operating strategies were identified in terms of safety considerations and throughput of surface facilities. This led to an opportunity for making recommendations that have potential to result in improved performance. Strategies that required fewer canisters to be aged and those that contained fewer dual-purpose canisters (DPCs) resulted in lower frequencies of dropped canisters and spent nuclear fuel assemblies. Results indicate that DOE estimates are within the likely range of frequencies for a drop event that is generated by this analysis. The consequences of these events are low enough that their frequency will not likely impact the ability to meet regulatory requirements. Still, DOE could strengthen its preliminary hazards analyses by adopting a probabilistic approach to estimating the drop frequency in evaluating pre-closure safety. This would help to communicate the risk posed by the drop events, and allow for an analysis that is less reliant on deterministic estimates of waste stream quantities and crane drop rates. Pending future agreements between waste generators and the Department of Energy, the capacity of the Wet Handling Facility may need to be increased in order to efficiently handle assemblies arriving in DPCs and bare-fuel transportation casks. Furthermore, because design goals for throughput have been defined in terms of surface buildings as opposed to functional needs, there is a redundancy in functional capability of the Canister Receipt and Closure Facility and the Receipt Facility which should be taken into account in order to design a more efficient system. An alternative design for throughput requirements, based on functional demands of the system, is proposed.

INTERDISCIPLINARY STUDIES: NEUROGENETICS ASSOCIATION STUDY OF TWO SLC6A4 POLYMORPHISMS WITH AUTISM JACQUELYN RECKTENWALD Thesis under the direction of Professor James Sutcliffe Autism is a heritable neurodevelopmental disorder characterized by impairments in language development and use, social interaction and repetitive behaviors, restricted interests and resistance to change. Serotonergic system dysregulation is implicated in autism since ~25% of individuals with autism have blood platelet hyperserotonemia, selective serotonin reuptake inhibitors are efficacious in treating repetitive behaviors, anger and anxiety in autism, and PET studies indicate children with autism have less capacity for CNS serotonin synthesis than children without autism. These findings indicate the serotonin transporter (SERT) as a strong candidate susceptibility gene and studies point toward linkage in a region containing the SERT gene (SLC6A4) locus with autism. Two SLC6A4 repeat polymorphisms, HTTLPR and VNTR, are located in the promoter region upstream of SLC6A4 and in the second intron, respectively, and regulate SERT expression. Association studies of HTTLPR or VNTR polymorphisms with autism are inconclusive. We hypothesized that there would be preferential transmission of an HTTLPR polymorphism, VNTR polymorphism and a haplotype containing these polymorphisms to affected individuals in our sample. We found no association of any HTTLPR polymorphisms or VNTR polymorphisms with autism in our sample and further we did not find any association of a haplotype containing these polymorphisms with autism in our sample. Paternal inheritance of VNTR alleles was associated with the social intent and milestones (p =.02 and p = .05, respectively) components of the ADI-R, however, these two association results may be due to chance.

<p>This research discovers if there are early indicators of the conduct of clinical trials that related to predicting the success of a clinical trial. Successful trials were those achieving at least 100% of the minimum projected accrual goal necessary to statistically support the scientific objective. Two primary aspects of a clinical trial are investigated that influence success are identified as 1) factors related to the design and development stage of a trial and 2) factors that are observed once a clinical trial is implemented, or available for patient enrollment. The research is conducted using National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) sponsored trials for all therapeutic Phase I, I/II, II and III trials between January 1, 2000 and December 31, 2007. </p> <p>Overall observations of the trials in the sample uncover that approximately two out of every five therapeutic studies conducted through NCI-CTEP will fail to achieve the minimum accrual goal. Furthermore, it is observed that phase III clinical trials are unique from non-phase III clinical trials; Phase III trials have longer development times, greater trial size with respect to accrual goals, and a higher rate failure in terms of inability to achieve the accrual goal. </p> <p>The findings of the research suggest that studies with shorter development time have a higher likelihood of achieving accrual success at trial closure; inversely, studies with longer development time have a decreased likelihood of achieving accrual success. Both the time-to-first accrual and the accrual performance at the expected period are both identified as potential accrual milestone indicators of predicting eventual accrual success. Finally, clinical trial characteristics, particularly the number of scientific reviews, can be used to explain the variance in the development time. </p>

The development phase of systems engineering is one of the most critical phases in the entire life of a project because it is at that point the majority of the projects technology and committed costs are determined (Buede 2000). Yet, the decision tools available to assist systems engineers in choosing between technology alternatives at this phase are extremely limited, consisting mainly of the financial models of net present value and return on investment. Conceptually, if we view the alternatives available as a portfolio of cost, performance, and schedule options, then we can extend the financial portfolio model of Real Options Analysis (ROA) into system engineering. Such an extension is the first element of my research. However, because there is a need to extend beyond strictly the financial realm, I then introduce an advanced performance model, Technology Options Analysis (TOA), which is employed to address a systems performance options. Technology options, while similar to financial options, use performance dimensions such as availability of current and future technologies, technology risks, and industry clock speeds (Fine 1998). The purpose of Technology Options Analysis is to provide a tool that decision makers can use to understand the value of waiting to make a technology selection until some or all of a technologys performance uncertainty has been resolved. Finally, to create a more complete picture of the decision trade space, I combined Real Options and Technology Options into a unified algorithm that incorporates both performance and cost uncertainty into the decision making process. The aspect of schedule is beyond the scope of this dissertation and is left for future research. Applicability of the models are illustrated in the context of one case study.

This study examines the relationship between firm and facility characteristics and environmental compliance rates. A framework to help analyze this relationship is provided by deterrence theory which suggests that given the same level of government monitoring and enforcement, facilities with higher compliance costs will have lower compliance rates. The literature implies that firms and facilities with certain characteristics face higher costs to ensure compliance with regulations. For example, it has been proposed that plants that are part of large firms, multi-facility firms, or publicly traded firms will incur higher agency costs monitoring employees to make sure they are complying with regulations. Similarly, it is thought that large facilities and facilities located in a different state than the firms headquarters will also face higher agency costs. In addition, it is suggested that foreign-owned plants will confront higher costs developing the expertise to comply with domestic regulations. Understanding the nature of these costs and how they relate to firm and facility characteristics could assist policymakers with developing more targeted environmental compliance strategies. The current study uses data collected on a sample of chemical facilities to analyze whether these characteristics affect facility violation rates, as measured by compliance with air permits. The results suggest that plants with more employees and plants that are part of multi-facility firms are more likely to be out of compliance. Plants that are part of firms with out-of- state headquarters were unexpectedly found to have lower violation rates. None of the other firm and facility characteristics were found to be significant predictors of facility violation rates.

This dissertation develops and applies an integrated framework for embedding flexibility in an engineered system architecture. Systems are constantly faced with unpredictability in the operational environment, threats from competing systems, obsolescence of technology, and general uncertainty in future system demands. Current systems engineering and risk management practices have focused almost exclusively on mitigating or preventing the negative consequences of uncertainty. This research recognizes that high uncertainty also presents an opportunity to design systems that can flexibly respond to changing requirements and capture additional value throughout the design life. There does not exist however a formalized approach to designing appropriately flexible systems. <p>This research develops a three stage integrated flexibility framework based on the concept of architecture options embedded in the system design. Stage One defines an eight step systems engineering process to identify candidate architecture options. This process encapsulates the operational uncertainty though scenario development, traces new functional requirements to the affected design variables, and clusters the variables most sensitive to change. The resulting clusters can generate insight into the most promising regions in the architecture to embed flexibility in the form of architecture options. Stage Two develops a quantitative option valuation technique, grounded in real options theory, which is able to value embedded architecture options that exhibit variable expiration behavior. Stage Three proposes a portfolio optimization algorithm, for both discrete and continuous options, to select the optimal subset of architecture options, subject to budget and risk constraints. Finally, the feasibility, extensibility and limitations of the framework are assessed by its application to a reconnaissance satellite system development problem. Detailed technical data, performance models, and cost estimates were compiled for the Tactical Imaging Constellation Architecture Study and leveraged to complete a realistic proof-of-concept.

Multiple sclerosis (MS) is characterized as an autoimmune neurodegenerative disease. The disease manifests as demyelination or degradation of the myelin sheath in the central nervous system. The Major Histocompatibility Complex (MHC) was associated with MS in the mid-1970s; the association was later refined to the HLA-DRB1*1501-DQB*0602 haplotype. The MHC region is riddled with complicating factors including high gene content, extreme levels of polymorphism, and a dense pattern of linkage disequilibrium (LD). These characteristics make this region difficult for differentiating whether a single allele or an entire haplotype contributes to disease association. Despite these challenges it is clear that the MHC region harbors MS susceptibility loci in addition to the HLA-DRB1*1501 region. Using the strong LD in this region we can test a model that predicts residual odds ratios (ORs) for a marker in LD with a disease allele such as HLA-DRB1*1501. Comparing the correlation between the observed OR and the calculated OR for multiple SNPs in the MHC region, we hypothesize those SNPs that appear as outliers are suggestive of additional effects independent from the HLA-DRB1*1501 region. We examined ~2,300 SNPs in 1,479 cases and 1,482 controls in the 28 Mb to 36 Mb region on chromosome 6 containing the MHC. The ORs for the SNPs were grouped based on the amount of LD with the HLA-DRB1 surrogate SNP (rs3135388). We identified nine outlying SNPs, which had observed ORs much larger than the calculated OR. These nine SNPs are in six different genes that suggest susceptibility to MS independent of HLA-DRB1*1501.