Emerging infectious diseases continue to threaten human health and healthcare resources across the world, and with the sustained emergence of some like Lyme disease, this trend is only expected to get worse. Even though some research has examined the spread of Lyme disease in different parts of the United States, focusing on its origin, spread, surveillance, and reporting, there has been minimal research on the recent spread of Lyme disease into and within Central and Southern Appalachia. This is an important gap, considering that this region is at the edge of the disease's expanding incidence and range. Considering this factor and the consequences that this disease may have on the residents of Appalachia who already face an array of underlying problems like chronic conditions, decreased access to health care, and exposure through outdoor work like resource extraction, addressing this gap will be important in understanding the current and future spatial range and impacts of the continued emergence of Lyme disease in Appalachia. This study thus sought to examine the extent of the emergence of Lyme disease in Appalachia between 2000 and 2019 using spatial scan statistic. This type of analysis uses spatiotemporal information to quantify disease emergence and diffusion using retrospective case and location data within a GIS environment; hence it helped quantify the spatial distribution and diffusion of Lyme disease into and within Appalachia and identify additional areas that can be targeted with public health prevention measures. We found five statistically significant clusters of Lyme disease across the contiguous US, indicating that the disease expanded spatially over the study period. Lyme disease has more than tripled across the US, with the number of counties with RR>1 increasing from 130 in 2000 to 453 by 2019. Lyme disease also increased more than eightfold in Appalachia, with spread southwards into and within Appalachia. The number of Appalachian counties with RR>1 increased from 16 in 2000 to 127 in 2019. These findings are important in understanding the current and future spatial range and the impacts of the continued emergence of Lyme disease in Appalachia. With this understanding, we can minimize the misdiagnosis of Lyme disease and inform public health action to reduce public vulnerability. / Master of Science / Emerging infectious diseases are diseases that have not been present, the persistence of diseases that were previously unknown, or those diseases that are rapidly increasing in a given location. These diseases continue to threaten human health and healthcare resources across the world, and with the sustained emergence of some like Lyme disease, this trend is only expected to get worse. Even though some research has investigated the spread of Lyme disease in different parts of the United States, focusing on its origin, spread, monitoring, and reporting, there has been minimal research on the recent spread of Lyme disease in Central and Southern Appalachia. This is an important gap, considering that this region is next to areas where the disease has recently spread, thereby making it vulnerable to continued spread. Considering this factor and the consequences that this disease may have on the residents of Appalachia who already face many underlying problems like long-term conditions, decreased access to health care, and exposure through outdoor work like resource extraction, addressing this gap will be important in understanding the current and future geographic occurrence and impacts of the continued spread of Lyme disease in Appalachia. This study thus sought to investigate the extent of the spread of Lyme disease in Appalachia between 2000 and 2019 using statistics and identification of places with a higher than expected number of cases. This type of analysis uses location information to quantify disease occurrence and spread using past case and location data using GIS software; hence it helped identify the distribution and spread of Lyme disease into and within Appalachia and identify additional areas that can be targeted with public health prevention measures. We found five areas with higher than expected number of Lyme disease cases across the contiguous US, indicating that the disease increased over the study period. Lyme disease has more than tripled across the US, with the number of counties with higher cases than expected increasing from 130 in 2000 to 453 by 2019. Lyme disease also increased more than eightfold in Appalachia, with spread southwards into and within Appalachia. The number of Appalachian counties with higher than expected Lyme disease cases increased from 16 in 2000 to 127 in 2019. These findings are important in understanding the current and future spread and the impacts of this continued spread of Lyme disease in Appalachia. With this understanding, we can properly detect Lyme disease and inform public health action to reduce public vulnerability.

The fate of nanoparticulate cerium oxide from the diesel fuel catalyst Envirox was studied from its presence in the additive to its transformations during combustion through its exposure to plants and soils using a broad range of analytical techniques. Envirox is a fuel-borne catalyst comprised of nanoparticles of cerium oxide suspended in kerosene. The particles suspended in Envirox were confirmed by synchrotron X-ray diffraction, dynamic light scattering, and electron microscopy to be 5-7 nm crystals of CeO2 present as 15 nm aggregates. Significant changes to the particles were induced by the combustion process, resulting in 50-300 nm euhedral crystals of CeO2 in the exhaust as discovered using high resolution transmission electron microscopy. Single particle electron diffraction of the emitted cerium oxide particles showed evidence of ordered oxygen vacancies, indicative of a superstructure. Variations in the engine operating load resulted in no significant differences in the emitted cerium oxide particles. The mobility through soils and impacts on the plant Brassica napus (dwarf essex rape) of the emitted cerium oxide were compared to small and large CeO2 nanoparticles as well as diesel particulate matter emissions with very low cerium. The small CeO2 nanoparticles exhibited high mobility through soils and significant uptake and translocation in the plants. The large CeO2 nanoparticles showed extremely low mobility in soils and no significant increase in cerium anywhere in the plants. Cerium emissions from a diesel engine utilizing Envirox was found to have moderate mobility through the soils as well as an increased association with the roots of the plants, though translocation of the cerium into the aboveground biomass was not statistically significant. Despite uptake and translocation of some materials by B. napus, exposure to these cerium sources at 100 ppm Ce in the topsoil showed no significant impacts on the growth or overall health of the plants when compared to unexposed control samples. This dissertation shows that CeO2 nanoparticles employed as catalysts suspended in diesel fuel are altered during their use resulting in changes to their mobility and interaction upon entering the environment. This dissertation lays the groundwork for a new approach to nanotoxicology. / Ph. D.

Plants produce secondary (or specialized) metabolites to respond to a variety of environmental changes and threats. Especially, volatile compounds released by plants facilitate short and long distance interaction with both beneficial and harmful organisms. Comparatively little is known about the organization and role of specialized metabolism in root tissues. In this study, we have investigated the root-specific formation and function of volatile terpenes in the model plant Arabidopsis. As one objective, we have characterized the two root-specific terpene synthases, TPS22 and TPS25. Both enzymes catalyze the formation of several volatile sesquiterpenes with (E)-β-farnesene as the major product. TPS22 and TPS25 are expressed in the root in distinct different cell type-specific patterns and both genes are induced by jasmonic acid. Unexpectedly, both TPS proteins are localized to mitochondria, demonstrating a subcellular localization of terpene specialized metabolism in compartments other than the cytosol and plastids. (E)-β-Farnesene is produced at low concentrations suggesting posttranslational modifications of the TPS proteins and/or limited substrate availability in mitochondria. We hypothesize that the mitochondrial localization of TPS22 and TPS25 reflects evolutionary plasticity in subcellular compartmentation of TPS proteins with emerging or declining activity. Since (E)-β-farnesene inhibits Arabidopsis root growth in vitro, mitochondrial targeting of both proteins may fine tune (E)-β-farnesene concentrations to prevent possible autotoxic or inhibitory effects of this terpene in vivo. We further investigated the role of volatile terpenes in Arabidopsis roots in interaction with the soil-borne oomycete, Pythium irregulare. Infection of roots with P. irregulare causes emission of the C11-homoterpene (or better called C4-norterpene) 4,8-dimethylnona-1,3,7-triene (DMNT), which is a common volatile induced by biotic stress in aerial parts of plants but was not previously known to be produced in plant roots. We demonstrate that DMNT is synthesized by a novel, root-specific pathway via oxidative degradation of the C30-triterpene, arabidiol. DMNT exhibits inhibitory effects on P. irregulare mycelium growth and oospore germination in vitro. Moreover, arabidiol and DMNT biosynthetic mutants were found to be more susceptible to P. irregulare infection and showed higher rates of Pythium colonization in comparison to wild type plants. Together, our studies demonstrate differences and plasticity in the metabolic organization and function of terpenes in roots in comparison to aboveground plant tissues. / Ph. D.

Virginia's temperate climate is suitable for several mosquito species capable of transmitting pathogens to humans. In southwest Virginia, La Crosse encephalitis and West Nile fever are most prominent. The objective of this research, which uses the Health Belief Model (HBM) as a theoretical framework, is to assess knowledge of mosquito-borne disease in southwest Virginia, as well as perceptions and practices of mosquito prevention. Given that several cases of La Crosse encephalitis have been reported in Wise and Tazewell counties, they were selected as study sites to conduct surveys. Five demographic and socioeconomic variables (gender, age, income, education level and length of time one has lived in the county) were used as predictor variables in logistic regression analyses. Gender, age, and length of residence time in the county were found to be statistically significant predictors of specific health-related behaviors. Within the framework of the HBM, barriers to removing standing water around the home and wearing insect repellent were highlighted. Knowledge of mosquito-borne diseases within the area was generally low, with only one individual correctly identifying La Crosse encephalitis as a threat in the region. Higher numbers (6%) were aware of West Nile virus, while 4% reported malaria in the region, demonstrating a disconnect between actual and perceived risk. These results can enhance existing public health programs by increasing knowledge, addressing public uncertainty about insect repellent safety, and addressing ways to make recommended practices more effective with the knowledge of how different aspects are perceived by varying groups within the community. / Master of Science

WN virus has spread for over 60 years creating endemic and epidemic areas throughout Africa, Asia, and Europe, affecting human, bird, and equine populations. Its 1999 appearance in New York shows the ability of the virus to cross barriers and travel great distances, emerging into new territories previously free of infection. Spreading much faster than expected, WN virus has infected thousands of birds, equine, and humans throughout the conterminous United States (US). Case and serological studies performed in the Eastern hemisphere prior to 1999 offer detailed descriptions of endemic and epidemic locations in regards to geography, land cover, land use, population, climate, and weather patterns. Based on the severity of WN activity within each study area, the patterns associated with these environmental factors allow for the identification of values associated with different levels of risk. We can then model the landscape of the disease within the US and identify areas of high risk for infection. State and county public health officials can use this model as a decision-making tool to allocate funding for disease prevention and control. Dynamic factors associated with increased transmission, such as above average temperature and precipitation, can be closely monitored and measures of prevention can be implemented when necessary. In turn, detailed information from higher resolution analyses can be documented to an online GIS (Geographic Information System) that would contribute to a global collaboration on outbreaks and prevention of disease. / Master of Science

Yes / Enteropathogenic Escherichia coli (EPEC) is usually associated with outbreaks and sporadic cases of severe infantile diarrhoea in the developing world, and less commonly with sporadic cases in developed countries. Very little evidence indicates that EPEC is a food-borne pathogen for adults. In a previous study, two groups of adult travellers became ill, and eae+ E. coli of serogroup O111 was isolated from affected individuals and epidemiologically linked to food consumption. Here the strain responsible was further investigated and characterized as an unusual atypical EPEC. PCR analysis of the designated type isolate showed the presence of the rorf1 and espB genes of the LEE pathogenicity island, which was inserted at the chromosomal selC locus. The isolate was negative for the enteroaggregative E. coli EAST-1 toxin present in other strains of EPEC associated with food-borne outbreaks. The strain adhered sparsely to HEp-2 cell monolayers in a diffuse manner, but fluorescent actin staining demonstrated that it was capable of inducing polymerization of actin at the sites of bacterial attachment. Strain P2583 is the first EAST-negative EPEC to be confirmed as a cause of outbreaks of infection in adults following the consumption of contaminated food or water.

This study evaluates the roles of temperature variability and disease awareness in the emergence of Chagas disease (American trypanosomiasis). Chagas disease is endemic in Latin America and primarily spreads to humans directly via the triatomine vector. Hosts for most triatomine species are mainly rodents and occasionally dogs. The disease itself is caused by a parasitic protozoan, Trypanosoma cruzi (T. cruzi) which is found in the triatomine's feces and is often spread while the triatomine is consuming a blood meal. T. cruzi from feces enters the body via an abrasion on the skin, the mucous membranes, conjunctivae, or through consumption. To determine the risk of Chagas disease transmission one must define qualities that make the triatomine an effective disease vector as well as investigate the level of disease awareness among physicians and the population within the vector's range. This thesis maps triatomine species within the U.S. that harbor T. cruzi naturally and that exhibit qualities of domesticity. These qualities are defined by whether the species bites humans and dogs as well as reports that the species has been found in the domestic setting. Ranges illustrating temperature thresholds for increased triatomine activity for 2000 and 2030 are also depicted. Additionally, outcomes of a physician survey are presented to gauge the status of Chagas disease awareness in areas at higher risk for disease transmission. Results reveal limited consideration of Chagas disease in physician diagnosis despite the higher risk range which extends through the southern U.S. and is predicted to expand significantly by 2030. / Master of Science

Dans cette thèse, nous menons une étude dans le cadre de la théorie de l'information sur deux questions importantes de la communication sans fil : l'amélioration du débit de données dans les réseaux avec interférence grâce à la coopération entre utilisateurs et le renforcement de la sécurité des transmissions à l'aide d'un signal de rétroaction.Dans la première partie de la thèse, nous nous concentrons sur le modèle le plus simple qui intègre à la fois l'interférence et la coopération, le canal à relais et interférence ou IRC (Interference Relay Channel). Notre objectif est de caractériser dans un nombre fixe de bits la région de capacité du IRC gaussien. À cette fin, nous dérivons une nouvelle limite supérieure de la capacité et deux stratégies de transmission. La limite supérieure est notamment obtenue grâce à une extension non triviale que nous proposons, de la classe de canaux semi-déterministe et injective à l'origine dérivée par Telatar et Tse pour le canal à interférence.Dans la seconde partie, nous étudions le canal avec espion et rétroaction généralisée ou WCGF (Wiretap Channel with Generalized Feedback). Notre objectif est de développer une stratégie de transmission générale qui englobe les résultats existants pour les différents modèles de rétroaction trouvés dans la littérature. À cette fin, nous proposons deux stratégies de transmission différentes sur la capacité du WCGF sans mémoire. Nous dérivons d'abord une stratégie qui est basée sur le codage source-canal conjoint. Nous introduisons ensuite une seconde stratégie où le signal de rétroaction est utilisé pour générer une clé secrète qui permet de chiffrer le message partiellement ou totalement. / In this thesis, we conduct an information-theoretic study on two important aspects of wireless communications: the improvement of data throughput in interference-limited networks by means of cooperation between users and the strengthening of the security of transmissions with the help of feedback.In the first part of the thesis, we focus on the simplest model that encompasses interference and cooperation, the Interference Relay Channel (IRC). Our goal is to characterize within a fixed number of bits the capacity region of the Gaussian IRC, independent of any channel conditions. To do so, we derive a novel outer bound and two inner bounds. Specifically, the outer bound is obtained thanks to a nontrivial extension we propose of the injective semideterministic class of channels, originally derived by Telatar and Tse for the Interference Channel (IC).In the second part of the thesis, we investigate the Wiretap Channel with Generalized Feedback (WCGF) and our goal is to provide a general transmission strategy that encompasses the existing results for different feedback models found in the literature. To this end, we propose two different inner bounds on the capacity of the memoryless WCGF. We first derive an inner bound that is based on the use of joint source-channel coding, which introduces time dependencies between the feedback outputs and the channel inputs through different time blocks. We then introduce a second inner bound where the feedback link is used to generate a key that encrypts the message partially or completely.

Dans cette thèse, nous menons une étude dans le cadre de la théorie de l'information sur deux questions importantes de la communication sans fil : l'amélioration du débit de données dans les réseaux avec interférence grâce à la coopération entre utilisateurs et le renforcement de la sécurité des transmissions à l'aide d'un signal de rétroaction.Dans la première partie de la thèse, nous nous concentrons sur le modèle le plus simple qui intègre à la fois l'interférence et la coopération, le canal à relais et interférence ou IRC (Interference Relay Channel). Notre objectif est de caractériser dans un nombre fixe de bits la région de capacité du IRC gaussien. À cette fin, nous dérivons une nouvelle limite supérieure de la capacité et deux stratégies de transmission. La limite supérieure est notamment obtenue grâce à une extension non triviale que nous proposons, de la classe de canaux semi-déterministe et injective à l'origine dérivée par Telatar et Tse pour le canal à interférence.Dans la seconde partie, nous étudions le canal avec espion et rétroaction généralisée ou WCGF (Wiretap Channel with Generalized Feedback). Notre objectif est de développer une stratégie de transmission générale qui englobe les résultats existants pour les différents modèles de rétroaction trouvés dans la littérature. À cette fin, nous proposons deux stratégies de transmission différentes sur la capacité du WCGF sans mémoire. Nous dérivons d'abord une stratégie qui est basée sur le codage source-canal conjoint. Nous introduisons ensuite une seconde stratégie où le signal de rétroaction est utilisé pour générer une clé secrète qui permet de chiffrer le message partiellement ou totalement. / In this thesis, we conduct an information-theoretic study on two important aspects of wireless communications: the improvement of data throughput in interference-limited networks by means of cooperation between users and the strengthening of the security of transmissions with the help of feedback.In the first part of the thesis, we focus on the simplest model that encompasses interference and cooperation, the Interference Relay Channel (IRC). Our goal is to characterize within a fixed number of bits the capacity region of the Gaussian IRC, independent of any channel conditions. To do so, we derive a novel outer bound and two inner bounds. Specifically, the outer bound is obtained thanks to a nontrivial extension we propose of the injective semideterministic class of channels, originally derived by Telatar and Tse for the Interference Channel (IC).In the second part of the thesis, we investigate the Wiretap Channel with Generalized Feedback (WCGF) and our goal is to provide a general transmission strategy that encompasses the existing results for different feedback models found in the literature. To this end, we propose two different inner bounds on the capacity of the memoryless WCGF. We first derive an inner bound that is based on the use of joint source-channel coding, which introduces time dependencies between the feedback outputs and the channel inputs through different time blocks. We then introduce a second inner bound where the feedback link is used to generate a key that encrypts the message partially or completely.

Dans cette thèse, les réseaux coopératifs sont étudiés sous cette hypothèse que la source est incertain par rapport le canal en opération. Dans le premier chapitre, des stratégies coopératives sont développées pour les canaux à relais simultanés (SRC) lesquelles se composent d'un ensemble de deux canaux à relais parmi lesquels le canal en opération est choisi. Cela est équivalent au canal de diffusion à relais (BRC). Les bornes sur la région de capacité de BRC général sont dérivées. Les résultats de capacité sont obtenus pour les cas particuliers du canal à relais simultané semi-dégradé et dégradé Gaussien. Dans le deuxième chapitre, le canal à relais composite est considéré où le canal est tiré aléatoirement d'un ensemble de la distribution conditionnelle. Le débit est fixé en dépit du canal actuel et la probabilité d'erreur (EP) asymptotique est caractérisée. Une nouvelle stratégie de codage sélectif (SCS) est introduit permettant aux relais de choisir -selon leur mesurage du canal - la meilleur schéma de codage entre Décoder-et-Transmettre (DF) et Comprimer-et-Transmettre (CF). Les théorèmes de codage de réseau bruit généralisées sont démontrés pour le cas de réseau unicast général où les relais utilisent soit DF soit CF. Dans le troisième chapitre, le spectre asymptotique de EP est introduit en tant que nouvelle mesure de performance pour réseaux composites. Il est démontré que chaque code avec le débit hors de la borne cut-set, abouti à EP égal à un et le spectre asymptotique de EP coïncide avec la probabilité d'outage pour les réseaux satisfaisant la converse forte.