Life Sciences Commons^™

Introducing Novel Combinatorial Targeted Therapies In Multiple Types Of Cancer, Mehrad Tavallai

Theses and Dissertations

The cancers of liver, colon and breast are amongst the top five most prevalent and most fatal worldwide. As the Raf/MEK/ERK pathway is frequently deregulated in hepatocellular carcinoma (HCC), sorafenib, a Raf kinase inhibitor, became the first systemic therapy approved for the treatment of patients with HCC. However, sorafenib only produced modest effects with low response rates in the clinic. Similarly, regorafenib, which was approved for the treatment of metastatic colorectal cancer (CRC), has had a poor response rate in the clinic. Since phosphodiesterase type 5 has been reported to be overexpressed in HCC and CRC, we hypothesized that sildenafil, …

Evaluating And Improving The Efficiency Of Software And Algorithms For Sequence Data Analysis, Hugh L. Eaves

Theses and Dissertations

With the ever-growing size of sequence data sets, data processing and analysis are an increasingly large portion of the time and money spent on nucleic acid sequencing projects. Correspondingly, the performance of the software and algorithms used to perform that analysis has a direct effect on the time and expense involved. Although the analytical methods are widely varied, certain types of software and algorithms are applicable to a number of areas. Targeting improvements to these common elements has the potential for wide reaching rewards. This dissertation research consisted of several projects to characterize and improve upon the efficiency of several …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

Upper Thermal Limits Differ Among Component Species In A Host-Parasitoid-Hyperparasitoid System, Kanchan A. Joshi

Theses and Dissertations

Among the predicted impacts associated with global climate change, warming is of special interest because the rates of physiological processes are temperature-dependent. Insects and other ectotherms are likely to be affected due to their limited ability to control body temperature. In this study, I measured the tolerance to extreme high temperatures, i.e., critical thermal maximum (CT_max), of component species in a tri-trophic system, including an herbivore (Manduca sexta), a primary larval parasitoid (Cotesia congregata) and a hyperparasitoid (genus Silochalcis). For wild insects, the parasitoid had the lowest CT_max, the hyperparasitoid had …

Independent Origination Of Floral Zygomorphy, A Predicted Adaptive Response To Pollinators: Developmental And Genetic Mechanisms, Ghadeer Bukhari, Wenheng Zhang

Theses and Dissertations

Observations of floral development indicate that floral organ initiation in pentapetalous flowers more commonly results in a medially positioned abaxial petal (MAB) than in a medially positioned adaxial petal (MAD), where the medial plane is defined by the stem and the bract during early floral development. It was proposed that the dominant MAB petal initiation might impose a developmental constraint that leads to the evolution of limited patterns of floral zygomorphy in Asteridae, a family in which the floral zygomorphy develops along the medial plane and results in a central ventral (CV) petal in mature flowers. Here, I investigate whether …

Applicability Of Lidar Technology In Saltmarshes: Landscape-Scale Predictive Models To Local-Scale Biomass Estimation, James Dean Edwards Jr.

Theses and Dissertations

The management of saltmarshes requires detailed knowledge of the underlying processes driving their distribution in both time and space to make appropriate management decisions. With most of the world’s population living in the coastal zone and rising sea levels, one of our most important natural resources in the coastal zone faces increasing threat of collapse. This study uses the current state of Light Detection and Ranging (LiDAR) technology to model and predict saltmarsh distribution at a landscape-scale and provide evidence that a terrestrial laser scanner (TLS) can be used to estimate saltmarsh biomass for inclusion into existing models.

Land cover …

Role Of Altered Gut Microbiota In Tumor Development, Mucus Production And Inflammation In Apc Min/+ Mouse Model, Kamaljeet Kaur

Theses and Dissertations

The microbiome forms an integral part of the gut microenvironment. Once ignored, the topic has gained momentum in research during the past decade, where studies have strongly suggested the association of microbiota with health and a misbalance thereof, to many disease conditions ranging from inflammation and colitis to diabetes, obesity and colon cancer. The Human Microbiome Project (HMP, NIH common fund - 2008) has used a variety of high throughput analyses in order to study gut microbiota in health. The consortium has so far been able to isolate and characterize more than 1,300 reference bacterial strains from the human body. …

Mislabeling Of Commercial Atlantic Cod (Gadus Morhua) Products In Spain, Joshua Helgoe

Theses and Dissertations

The mislabeling of commercial fish products is a pervasive, worldwide problem. Most consumers of seafood are unaware this issue directly affects them and can even have negative impacts on their health. Mislabeling occurs when a product’s label is inconsistent with its content. Although mislabeling can be unintentional, deliberate mislabeling is a more common trend to increase profits and/or bypass fishing regulations - a form of economic fraud. Unfortunately, oversight, enforcement, and research are vastly insufficient in relation to the global scale of the problem. In order to add to the small knowledge base on European mislabeling rates, determine if overfished …

Exploring Children’S Physical Activity Levels Through Structure And Measurement, Jessica L. Chandler

Theses and Dissertations

The purpose of this dissertation was twofold: 1) to establish best practices for wrist-based accelerometry for 5-11 year old children and 2) to explore the contribution of activity structure to children’s physical activity (PA) levels.

The purpose of study 1 aimed to determine differences in counts/5second epoch produced by the dominant and non-dominant wrist during seated, sedentary activities in 5-11 year old children and ultimately create a cutpoint threshold to distinguish seated sedentary behavior from light physical activity. 167 children, ages 5-11 years, performed up to 8 sedentary activities for 5 minutes while wearing ActiGraph GT3X+ accelerometers on both wrists. …

Exploratory Analysis Of Ptsd Severity And Objective Measures Of Physical Activity Among Combat Veterans, Danny O. Sauceda

Theses and Dissertations

Strong levels of motivation, relatedness and self-determination support the likeliness of participating in habitual exercise. Compared to nationwide estimates, research has demonstrated fitness and performance is significantly lower among those suffering from PTSD. Meeting established recommended daily levels of physical activity (PA) for individuals with PTSD is critical for their physical and mental health status over a lifetime and factors supporting or hindering adherence to habitual exercise are lacking. Furthermore, regular PA among combat Veterans with Posttraumatic Stress Disorder (PTSD) is a viable and substantial treatment option to improve physical health status and cognitive well-being. The purpose of this exploratory …

The Effects Of Tidal Forcing On Nutrient Fluxes In The Tidal, Freshwater James River Estuary, Va, Dana L. Devore

Theses and Dissertations

A 12-month study (January to December 2015) focused on the effects of tidal forcing on nutrient fluxes in the tidal, freshwater segment of the James River Estuary (JRE). Discrete sampling of nutrient chemistry and continuous monitoring of tidal discharge were used to determine the volume and timing of the tides, and differences in nutrient concentrations between incoming and outgoing tides. The goal of this study was to improve understanding of tidal influence on nutrient fluxes and their role in nutrient transport to the lower estuary. Results suggested that differences in nutrient concentrations between incoming and outgoing tides were small throughout …

Genome Wide Epigenetic Analyses Of Araptus Attenuatus, A Bark Beetle, Chitra Seshadri

Theses and Dissertations

Phylogeographic studies have relied on surveying neutral genetic variation in natural populations as a way of gaining better insights into the evolutionary processes shaping present day population demography. Recent emphasis on understanding putative adaptive variation have brought to light the role of epigenetic variation in influencing phenotypes and the mechanisms underlying local adaptation. While much is known about how methylation acts at specific loci to influence known phenotypes, there is little information on the spatial genetic structure of genome-wide patterns of methylation and the extent to which it can extend our understanding of both neutral and putatively adaptive processes. This …

Biodegradation Of Highly Weathered Deepwater Horizon Oil, Joel T. Bostic

Theses and Dissertations

Oil from the Deepwater Horizon (DwH) spill continues to be found on beaches five years post-spill. Understanding the role of microbes in removing DwH oil from sandy beaches is necessary to elucidate the fate of DwH oil in the coastal zone. Oiled sand patties and non-oiled sand were collected from affected beaches five years post- DwH. Biomarkers in oiled sand indicated that sand patties originated from the DwH spill, however the oil was heavily weathered and dominated by oxygenated hydrocarbons. Microbial communities, as measured by phospholipid fatty acids (PLFA), were present on oiled sand patties and distinct from microbes on …

Decadal Salinity Changes In The Oceanic Subtropical Gyres And Connection To Changes In The Global Water Cycle, Bryce Andrew Melzer

Theses and Dissertations

There is evidence that the global water cycle has been undergoing an intensification over several decades as a response to increasing atmospheric temperatures, particularly in regions with skewed evaporation – precipitation (E-P) patterns such as the oceanic subtropical gyres. However, observational data (rain gauges, etc.) can be quite sparse over such areas due to the inaccessibility of open ocean regions. This study utilizes in situ data, reanalysis, and model outputs to infer interannual to decadal scale trends in surface freshwater forcing within remote, evaporation-dominated subtropical regions of the ocean as they pertain to the past and present state of the …

The Role Of Nuclear Factor-Erythroid-2-Related Factor 2 In Sensitivity To Thymidylate Synthase Inhibitors In Colon Cancer Cells, Sarah Ashley Clinton

Theses and Dissertations

Nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors, confers protection against oxidative and electrophilic stress. NRF2 is of great interest in cancer research, due to its role in response to chemotherapy. The class of drugs targeting thymidylate synthase (TYMS) has been useful in the treatment of colorectal cancer, among other cancers. It has long been known that inhibition of TYMS leads to depletion of thymidine levels and the onset of programmed cell death, deriving from the enzyme’s function as the sole de novo source of thymidine for DNA replication and repair. …

Development And Application Of Foraminiferal Carbonate System Proxies To Quantify Ocean Acidification In The California Current, Emily B. Osborne

Theses and Dissertations

The oceanic uptake of anthropogenic carbon has mitigated climate change, but has also resulted in a global average 0.1 decline in surface ocean pH over 20th century known as ocean acidification. The parallel reduction in carbonate ion concentration ([CO32-]) and the saturation state of seawater (Ω) has caused many major calcium carbonate-secreting organisms such as planktonic foraminifera to exhibit impaired calcification. We develop proxy calibrations and down core records that use calcification and geochemical characteristics of planktonic foraminifera as proxies for the marine carbonate system. This study focuses specifically on the surface ocean chemistry of the California Current Ecosystem (CCE), …

The Informational And Emotional Support Needs Of Grandparents Of Children With Pompe Disease, Natasha Lousie Rudy

Theses and Dissertations

The complex roles and experiences of grandparents of children with various diagnoses have been described, but previous studies have not investigated the roles and experiences of grandparents of children with treatable, Mendelian conditions such as Pompe disease. The availability of treatment and heritable nature of Pompe introduce the possibility for unique grandparent roles, experiences and needs. This is a particularly timely investigation given the advent of newborn screening for Pompe. This study aimed to characterize grandparents’ roles and involvement, identify grandparents’ information and emotional support needs, and explore the psychosocial impact felt by grandparents of children with Pompe. An online …