Browsing by Subject "screening"
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Item Novel Evaluation Methods for Complex Systems via Adaptive Sequential Exploration of Variables Interactions(2014-12-01) Al Rashdan, Ahmad Y. M.The complex and coupled behavior of variables in the currently developing Generation IV reactors and Small Modular Reactors is becoming a major incentive to seek efficient design methods. This research develops and validates new methods to evaluate systems with various degrees of variables? interactions using basic knowledge in variables? directions of effect and an adaptive number of experiments. The methods replace the commonly used assumption of negligible interactions with a broader assumption of monotonic variables? effects. The assumption was evaluated using studies of other physical systems? regularities, and is expected to be significantly present in physical systems. Four methods were developed and analyzed in this dissertation. Three of the introduced methods utilized an adaptive sequential spanning tree concept with a method specific criterion to construct piecewise multidimensional surfaces or subtrees. Each method then used a specific approach to project the results within the subtrees. The fourth method is an expansion to an existing method to explore any order of interactions through the introduction of a new domain of parameters. Three of the four methods significantly outperformed the common orthogonal arrays methods that rely on a uniform distribution of experiments in the design domain. Two of the three methods significantly outperformed the third method and were used in the dissertation?s application. The strength of the applicable methods was demonstrated through their application to two examples from literature, each of which has a different degree of variables? monotonic behavior. The most applicable method of the two most effective methods was used to decouple the effects of fourteen variables on six performance characteristics in the design of a Small Modular Reactor version of the Advanced Pressurized Water Reactor AP1000. The methods? application succeeded in finding the most important main effects and interactions of each performance characteristic. The performance of the methods? application to three performance characteristics was compared to the performance of fractional factorial designs. The methods were found to significantly reduce the projection error when the assumption of variables? monotonic behavior is valid.Item Scheduling screening inspections for replaceable and non-replaceable systems(2009-05-15) Aral, BahadirThis dissertation focuses on developing inspection schedules to detect non-self- announcing events which can only detected by inspections. Failures of protective sys- tems ,such as electronic equipments, alarms and stand-by systems, incipient failures and the emergence of certain medical diseases are examples of such events. Inspec- tions are performed at pre-determined times to detect whether or not the event has occurred, and necessary actions are taken upon the detection. In this research, my interest is in developing effective inspection schedules to detect non-self-announcing events that balance system downtime and inspection effort. To evaluate the quality of an inspection schedule, I use the availability (for re- placeable) and the detection delay (for non-replaceable systems) as performance mea- sures. When the monetary cost of inspection and the cost of delay are difficult to determine, non-monetary performance measures become more meaningful. In this research, the focus is on maximizing availability or minimizing detection delay given a limited number of inspections or a limited inspection rate. I show that for replace- able and non-replaceable systems, it is possible to construct inspection schedules that perform better than periodic inspection with respect to our performance measures. The occurrence of the event I would like to detect may be influenced by certain individual characteristics. For instance, the risk of developing a certain type of dis- ease might be different for different subgroups within the population. In this case, because of the non-homogeneity in the population, benefits of performing screening tests may not be fully achieved for each sub-group by using an inspection strategy developed for the entire population. Thus, it may be of value for an individual to learn more information about his/her likehood to have the disease. To address this issue, I analyze the change in the expected delay if schedules are based on the whole population information or the individual information and provide numerical results.Item The Biochemical Investigation and Isolation of Small Molecule Inhibitors for Two Essential Proteins of Mycobacterium tuberculosis H37Rv: IspD and Wag31(2014-06-12) Joseph, SoniaTuberculosis is one of the leading causes of death due to infectious disease. The causative agent, Mycobacterium tuberculosis, is a facultative intracellular parasite with a slow regeneration rate. Though there is a decline in the overall TB incidence since 2005, the emergence of resistant strains that are impervious to existing treatment regimens make the discovery and development of new drug leads crucial. To this end, exploiting key differences between the biology of the host and the pathogen can generate novel lead molecules with minimal side effects. This thesis details the study of two proteins that are essential for the survival of M. tuberculosis (M.tb) but are not present in the host, making them potential drug targets. The first protein, IspD (2-C-methyl-D-erythritol-4-phosphate (MEP) cytidyl transferase), is a part of the non-mevalonate pathway for the synthesis of isoprenoids and catalyzes the condensation of MEP and cytidine triphosphate (CTP) to form 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) and pyrophosphate (PPi). A medium-throughput enzyme assay was developed to identify inhibitors for this protein. It was screened against 3550 compounds drawn from five different M. tb whole-cell active small molecule libraries generating a total of five hits. These molecules were then assessed for their potency against IspD as measured by their IC50, their activity against M. tb whole cells and their cytotoxicity. Of the five hits, two compounds inhibited M. tb whole cell growth at a concentration below 50 ?M while exhibiting no general cytotoxicity to human dermal fibroblasts (HDF). They each had an IC50 of 26.1 ?M and 37.8?M and preliminary SAR studies were performed on the latter. These molecules could prove to be a viable starting point for the rational design of IspD inhibitors. The second protein, Wag31 is a cell division associated protein that regulates mycobacterial cell size and septum formation. Wag31 exhibited a propensity for gel formation both alone and in association with other cellular proteins. A purification strategy was developed to circumvent this tendency and generate soluble protein. It was found that mutations within the wag31 protein coding sequence conferred resistance to a whole-cell active small molecule (MIC99=6.25 ?g/ml) in both M. tuberculosis and M. smegmatis. Moreover, all of the discovered mutations were clustered within the C-terminal coiled-coil domain of the protein. It was established that this compound binds to Wag31 and seems to shift the equilibrium of the protein solution towards gel formation. The mutated protein does not form gel and seems to bind to the compound at a significantly reduced rate. To further confirm that Wag31 was indeed the target of this small molecule, whole cell viability assays were performed to establish whether the over-expression of Wag31 in M. smegmatis would shift the EC50 and MIC99 values. Wag31 over-expression reduced both the EC50 and MIC99 values providing further proof that Wag31 is the target for this compound. The compound appears to act by shifting the equilibrium of the protein towards a gelatinous state which proves inhibitory for cell growth.Item Universal Screening for Behavior: Considerations in the Use of Behavior Rating Scales(2012-08-20) Mason, Benjamin 1972-Universal screening for behavior is the use of a measure of social, emotional or behavioral function across an entire population with a goal of preventing future difficulties by intervening with students identified by the screening protocol. Multiple screening procedures have been used, with most including behavior rating scales in the selection process. The purpose of the present research was to investigate two central questions related to the use of universal screeners for behavior in school settings: first, can scores on universal screeners be used as an outcome measure investigating program based interventions, and second, what evidence of teacher bias exists when an external criterion of behavior is included. The purpose of study one was to determine if differences in teacher-rated behavior could be detected between a sample of students that attended public preschool and a nonattending peer group matched for ethnicity, gender, and a gross measure of socioeconomic status (total n= 138). Results of Study One indicated no significant differences between preschool-attending and nonattending groups (p=.61) or between Hispanic and Caucasian participants. Limitations related to sampling and measurement were discussed. In study two, a best-evidence synthesis of peer-reviewed articles investigating teacher bias in behavior ratings of students was conducted. Strict inclusion criteria were chosen to allow for inferential judgment of teacher accuracy. Results of Study Two found a final total of 25 studies of teacher bias that suggested mixed evidence for bias due to student ethnicity or gender and stronger evidence for bias due to expectancies (disability label), teacher culture, unrelated behaviors (halo effects), and teacher training and experience. Limitations, implications for practice and directions of future research were discussed.