Integrative Biology Commons^™

Novel Mechanisms For The Neural Control Of Breathing In Acute Lung Injury, Kajal Kamra

Theses & Dissertations

Acute lung injury (ALI) triggers inflammation that disrupts the normal alveolar-capillary endothelial barrier, impairing gas exchange and causing hypoxemia, which reflexively increases respiration. An elevated respiratory rate (fR) usually develops within hours to days following ALI. This acute respiratory failure disorder affects approximately 200,000 new cases annually in the US and accounts for 10% of ICU admissions, with high morbidity and mortality. The neural mechanisms underlying respiratory dysfunction post-ALI are not fully understood. My doctoral dissertation aimed to investigate the mediators of abnormal ventilation during ALI. Systemic hypoxia stimulates the carotid body (CB) chemoreflex, a crucial protective reflex that maintains …

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …

Development Of A Muc16-Targeted Near-Infrared Antibody Probe For Fluorescence-Guided Surgery Of Pancreatic Cancer, Madeline T. Olson

Theses & Dissertations

Pancreatic cancer (PDAC) is an extremely lethal disease with an overall survival rate of 10%. Surgery remains the only potentially curative treatment option, but resections are complicated by infiltrative disease, proximity of critical vasculature, peritumoral inflammation, and dense stroma. Surgeons are limited to tactile and visual cues to differentiate cancerous tissue from normal tissue. Furthermore, translating preoperative images to the intraoperative setting poses additional challenges for tumor detection, and can result in undetected and unresected lesions. Thus, PDAC has high rates of incomplete resections, and subsequently, disease recurrence. Fluorescence-guided surgery (FGS) has emerged as a method to improve intraoperative detection …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

Development Of A Long-Acting Nanoformulation Of Dolutegravir For Prevention And Treatment Of Hiv-1 Infection, Brady Sillman

Theses & Dissertations

Dolutegravir (DTG) is a potent human immunodeficiency virus type 1 (HIV-1) integrase strand-transfer inhibitor (INSTI) with a high barrier to viral drug resistance. However, opportunities to improve its profile abound. These include extending the drug’s apparent half-life, increasing penetrance to “putative” viral reservoirs, and reducing inherent toxicities. These highlight, in part, the need for long-acting, slow effective release antiretroviral therapy (LASER ART) delivery schemes. A long-acting (LA) DTG was made by synthesizing a hydrophobic and lipophilic prodrug encased with poloxamer (P407) surfactant. This modified DTG (MDTG) reduced systemic metabolism and polarity, increased lipophilicity and membrane permeability, improved encapsulation, and formed …

Role Of Transforming Growth Factor (Tgf) – Β Signaling In Craniofacial Development, Malignancies And Regeneration, Jingpeng Liu

Theses & Dissertations

The transforming growth factor (TGF) – β signaling pathway regulates a diversity of fundamental cellular processes such as cell growth and proliferation, cell differentiation, migration, apoptosis and other biological functions, both during embryogenesis and in adult tissue homeostasis. TGF-β is known to play a critical role in palatal development as in TGF-β knockout murine models, TGF-β deficiency causes cleft palate, a common craniofacial deformity in humans due to the abnormality of growth, elevation or fusion of the two palatal shelves. In order to investigate the mechanisms of how TGF-β regulates palatogenesis, we generated TGF-β3 knockout (-/-) murine models, performed systematic …

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …