Forward Genetic Screening In Human Haploid Cells To Identify Host Factors Required For Virus And Toxin Entry

My dissertation research has focused on identifying host cellular factors required by the bunyavirus Rift Valley fever virus (RVFV), an RNA virus that causes disease in humans and animals, and the secreted Toxin B (TcdB) from Clostridium difficile, a bacterial pathogen that causes severe antibiotic-associated diarrheal disease. In 2015, the WHO named the ten emerging diseases most likely to cause severe outbreaks in the near future, and three are caused by bunyaviruses (including RVFV). Concern is likewise mounting about the increasing incidence, virulence, and antibiotic-resistance of C. difficile infection worldwide. A better understanding of the molecular details of the pathogenesis of these diseases is urgently needed in order to inform the development and application of therapeutic interventions. The data presented in this thesis summarize the results of two independent screening projects, each utilizing a strategy of forward genetic screening in a mutagenized human haploid cell library. Our RVFV screen identified a suite of enzymes involved in glycosaminoglycan biogenesis and transport, including several components of the cis-oligomeric Golgi (COG) complex. In addition, we identified the gene PTAR1, disruption of which led to RVFV resistance and reduced heparan sulfate surface levels. Biochemical and genetic approaches were utilized to show that both pathogenic and attenuated RVFV strains require GAGs for efficient infection in some cell types, with the block to infection being at the level of virion attachment. Our TcdB screen identified the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) complex as a host cellular factor supporting TcdB intoxication. Involvement of the WASH complex in TcdB entry was validated by pharmacologic inhibition of recycling endosomes and the use of mouse fibroblasts lacking a functional WASH complex due to genetic ablation of the core WASH1 gene. The host factors supporting TcdB internalization and transport are largely unknown, and our data help to elucidate the mechanism of intoxication of this important and poorly-characterized virulence factor

Successful science teaching in a rural setting

Quality programs require lengthy commitments

A computer-based instrumentation system for measurement of breath-by-breath oxygen consumption and carbon dioxide production in exercising humans

Call number: LD2668 .T4 1984 R516Master of Scienc

The feasibility of a solar powered sorption dehumidification system applied to grain drying

Call number: LD2668 .T4 1984 R515Master of Scienc

Application programming interface guided QA plan generation and analysis automation

PURPOSE: Linear accelerator quality assurance (QA) in radiation therapy is a time consuming but fundamental part of ensuring the performance characteristics of radiation delivering machines. The goal of this work is to develop an automated and standardized QA plan generation and analysis system in the Oncology Information System (OIS) to streamline the QA process. METHODS: Automating the QA process includes two software components: the AutoQA Builder to generate daily, monthly, quarterly, and miscellaneous periodic linear accelerator QA plans within the Treatment Planning System (TPS) and the AutoQA Analysis to analyze images collected on the Electronic Portal Imaging Device (EPID) allowing for a rapid analysis of the acquired QA images. To verify the results of the automated QA analysis, results were compared to the current standard for QA assessment for the jaw junction, light-radiation coincidence, picket fence, and volumetric modulated arc therapy (VMAT) QA plans across three linacs and over a 6-month period. RESULTS: The AutoQA Builder application has been utilized clinically 322 times to create QA patients, construct phantom images, and deploy common periodic QA tests across multiple institutions, linear accelerators, and physicists. Comparing the AutoQA Analysis results with our current institutional QA standard the mean difference of the ratio of intensity values within the field-matched junction and ball-bearing position detection was 0.012 ± 0.053 (P = 0.159) and is 0.011 ± 0.224 mm (P = 0.355), respectively. Analysis of VMAT QA plans resulted in a maximum percentage difference of 0.3%. CONCLUSION: The automated creation and analysis of quality assurance plans using multiple APIs can be of immediate benefit to linear accelerator quality assurance efficiency and standardization. QA plan creation can be done without following tedious procedures through API assistance, and analysis can be performed inside of the clinical OIS in an automated fashion

Profile and Functional Properties of Seed Proteins from Six Pea (Pisum sativum) Genotypes

Extractability, extractable protein compositions, technological-functional properties of pea (Pisum sativum) proteins from six genotypes grown in Serbia were investigated. Also, the relationship between these characteristics was presented. Investigated genotypes showed significant differences in storage protein content, composition and extractability. The ratio of vicilin: legumin concentrations, as well as the ratio of vicilin + convicilin: Legumin concentrations were positively correlated with extractability. Our data suggest that the higher level of vicilin and/or a lower level of legumin have a positive influence on protein extractability. The emulsion activity index (EAI) was strongly and positively correlated with the solubility, while no significant correlation was found between emulsion stability (ESI) and solubility, nor between foaming properties and solubility. No association was evident between ESI and EAI. A moderate positive correlation between emulsion stability and foam capacity was observed. Proteins from the investigated genotypes expressed significantly different emulsifying properties and foam capacity at different pH values, whereas low foam stability was detected. It appears that genotype has considerable influence on content, composition and technological-functional properties of pea bean proteins. This fact can be very useful for food scientists in efforts to improve the quality of peas and pea protein products

Facilities management: the development of a model for building condition assessment surveys conducted at Fort Riley, Kansas

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references.The purpose of this study is to document the research and design of a condition assessment system for buildings by utilizing case study methods for the facilities located at Fort Riley, Kansas, an Army military installation. The design of the assessment or auditing system incorporates the following procedures: (1) identification of building components, (2) identification of building sub-components, (3) utilization of decision-tree logic diagrams to manage the information, and (4) production of inspection condition criteria and scoring for each sub-component (by visual inspection techniques) . The system was used by multiple inspectors to assess the buildings at Fort Riley. The inspectors received training in the system scoring and methodology. To verify the system's accuracy, ten percent (10%) of the buildings were re-inspected by the developers of the system (quality control) . The analysis of the system included a random sample of 20 buildings from the data collected. The data were analyzed for accuracy and consistency on the component and sub-component recognition and the inspection condition score (as compared to the quality control results) The actual inspection time was monitored to record the inspection efficiency. Statistical testing was conducted which did the following: (1) analyzed the data pair means for any significant differences, and (2) analyzed the strength of the pair relationships. From the data analysis the following was found: (1) the components and sub-components were recognized accurately and consistently, (2) the actual scores seemed to be accurate and consistent (after conducting the statistical test (T-Test) some of the means did indicate that there were some significant differences, while others indicated there were no significant differences) , (3) the data indicated that there was correlation between the data pairs. Also, it was found that this system provides reasonable inspection time and cost restraints. The building assessments are incorporated into an information system that assists the user in establishing priorities. The cost factors for each sub-component are based on building models that relate the quantities of the different sub-components to the actual floor area of the buildings. From these building models conceptual estimates can be generated and used as a tool to budget, justify, and anticipate maintenance and repair costs