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Articles 2971 - 3000 of 5390
Full-Text Articles in Entire DC Network
Mechanical Behavior And Length Adaptation Of Rabbit Bladder Smooth Muscle, Atheer Almasri
Mechanical Behavior And Length Adaptation Of Rabbit Bladder Smooth Muscle, Atheer Almasri
Theses and Dissertations
Overactive bladder (OAB), involuntary contractions during bladder filling, is a common condition affecting 17% of the adult population worldwide, and in the U.S. ranks ahead of diabetes in a list of the 10 most common chronic disorders (Mullins 2009). Mechanical mechanisms contributing to OAB are not completely understood and because of the unique function and broad volume range of the bladder, there may be mechanical characteristics that distinguish detrusor smooth muscle (DSM) in bladder from other smooth muscles. Recent studies have shown that the length-passive tension curve in DSM exhibits adjustable passive stiffness (APS) characterized by a passive curve that …
The Design And Validation Of A Computational Rigid Body Model Of The Elbow., Edward Spratley
The Design And Validation Of A Computational Rigid Body Model Of The Elbow., Edward Spratley
Theses and Dissertations
The use of computational modeling is an effective and inexpensive way to predict the response of complex systems to various perturbations. However, not until the early 1990s had this technology been used to predict the behavior of physiological systems, specifically the human skeletal system. To that end, a computational model of the human elbow joint was developed using computed topography (CT) scans of cadaveric donor tissue, as well as the commercially available software package SolidWorks™. The kinematic function of the joint model was then defined through 3D reconstructions of the osteoarticular surfaces and various soft-tissue constraints. The model was validated …
The Regulation Of Alternative Splicing By Oncogenic Signaling Pathways., Jacqueline Shultz
The Regulation Of Alternative Splicing By Oncogenic Signaling Pathways., Jacqueline Shultz
Theses and Dissertations
In the presented study, we demonstrate that the alternative splicing of caspase 9 was dysregulated in a large percentage of NSCLC tumors and cell lines. These findings led to the hypothesis that survival pathways activated by oncogenic mutation regulated this mechanism. Indeed, the oncogenic PI3-Kinase/Akt pathway was demonstrated to regulate the alternative splicing of caspase 9. Further mechanistic studies demonstrate that multiple Akt isoforms can regulate the alternative splicing of caspase 9 in NSCLC. Akt was additionally shown to mediate the exclusion of the exon 3,4,5,6 cassette of caspase 9 via the phospho-state of the RNA trans-factor, SRp30a. Mutagenesis studies …
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Theses and Dissertations
Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …
Effect Of Renin Angiotensin System Inhibition On Cardiovascular Sequelae In Elderly Hypertensive Patients With Insulin Resistance, Hala Zreikat
Theses and Dissertations
Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin …
Therapeutic Strategies Aimed To Facilitate Axonal Regeneration And Functional Recovery Following Traumatic Spinal Cord Injury, Woon Chow
Theses and Dissertations
Traumatic spinal cord injury (SCI) is a physically debilitating, emotionally devastating, financially costly, and life-changing condition that afflicts more than 1,000,000 people in the United States alone. Owing to the characteristic neuropathology and low regenerative capacity of the central nervous system, many victims of SCI are left permanently paralyzed. Though the tissue damage caused by the initial insult almost certainly cannot be reversed, intensive research in recent years to elucidate the cellular and molecular events that follows has provided new grounds for optimism. Accordingly, in this dissertation, we present a number of potential treatment strategies aimed to address some of …
Deriving Optimal Composite Scores: Relating Observational/Longitudinal Data With A Primary Endpoint, Rhonda Ellis
Deriving Optimal Composite Scores: Relating Observational/Longitudinal Data With A Primary Endpoint, Rhonda Ellis
Theses and Dissertations
In numerous clinical/experimental studies, multiple endpoints are measured on each subject. It is often not clear which of these endpoints should be designated as of primary importance. The desirability function approach is a way of combining multiple responses into a single unitless composite score. The response variables may include multiple types of data: binary, ordinal, count, interval data. Each response variable is transformed to a 0 to1 unitless scale with zero representing a completely undesirable response and one representing the ideal value. In desirability function methodology, weights on individual components can be incorporated to allow different levels of importance to …
Shafer Court Connections (2009-09)
Shafer Court Connections (2009-09)
Shafer Court Connections, 1994-2010
For alumni of the Academic Campus of Virginia Commonwealth University.
Identification Of Clinical, Laboratory And Genetic Covariates For Pharmacokinetics, Efficacy And Toxicity Of Sorafenib In Patients With Solid Tumors, Lokesh Jain
Theses and Dissertations
The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer …
The Use Of A Tri-Axial Accelerometer To Measure Changes In Lower Extremity Fatigue During Functional Activity, Kristin Morgan
The Use Of A Tri-Axial Accelerometer To Measure Changes In Lower Extremity Fatigue During Functional Activity, Kristin Morgan
Theses and Dissertations
In 2004, the National Collegiate Athletic Association reported ankle sprain as the most frequent injury in soccer, basketball, and volleyball players. Further research found an increased likelihood with fatigue. Measuring fatigue during functional activities has been a longstanding problem. In this study, changes in ankle biomechanics were measured using a tri-axial accelerometer embedded in the shoe as subjects (n=12) performed a fatiguing activity. Data were collected from the accelerometer and from established devices that are considered the industry gold standard. Several kinetic and kinematic accelerometer derived variables were highly correlated with these standards (r2>0.90) and were associated with changes …
Design By Accident, Mengfu Zhang
Design By Accident, Mengfu Zhang
Theses and Dissertations
Accident is a metaphor for life. From an arbitrary point in time, we potentially preview the entirety of existence. There is a Chinese idiom called “ blessing or bane,” which implies that a misfortune may perhaps soon turn into a blessing. Focusing on accident as a design method implies making the best out of a bad situation. An accident reveals invisible circumstances and potentialities in the world, both familiar and unfamiliar. Looking into the unpredictable world, I can begin to release my control, take a breath, and see what might happen if I do not fight the situation. I am …
Marrying Immunotherapy And Chemotherapy: A Cancer Therapy Based On T Lymphocyte Expansion Augmented By Alternate Gamma Chain Cytokines And Gemcitabine-Mediated Inhibition Of Myeloid Derived Suppressor Cells, Esther Cha
Theses and Dissertations
Successful adoptive immunotherapy (AIT) for cancer relies on the infusion of in vitro expanded, tumor-reactive lymphocytes with a goal of generating productive tumor immunity. Previously, our lab has developed a protocol to activate selectively tumor-reactive T lymphocytes in vitro using two pharmacologic agents, bryostatin-1 and ionomycin. Following the pharmacological stimulation, conventionally, IL-2 is added to stimulate in vitro proliferation. In this report, alternate cytokines from the common cytokine receptor γ-chain family, namely IL-7 and IL-15, were explored as the alternative cytokine supplements. We found that tumor DLN cells activated in vitro with B/I and cultured in IL-7/15 alternate common γ-chain …
Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi
Mutagenesis And Spectroscopic Studies Of Mycobacterium Tuberculosis Sterol 14alpha Demethylase., Anuja R. Modi
Theses and Dissertations
P450s are heme containing enzymes which affect oxidation of substrates via catalytic intermediates having transient lifetimes. These oxidative catalytic intermediates are formed by a sequential interplay of electrons and protons at the active site of the enzyme bearing molecular dioxygen. The proton transfer to the active site from bulk solvent is coordinated by an “acid-alcohol” pair of active site residues which are conserved in all P450s. Sterol 14α-demethylases (CYP51) are P450 enzymes which catalyze oxidative deformylation of lanosterol in the cholesterol/ergosterol biosynthetic pathway. Both cholesterol and ergosterol are important regulators of membrane fluidity. CYP51 differs from other P450s in that …
Age-Related Differences In In-Vitro Sensitivity To Inhibition Of Human Red Blood Cell Acetylcholinesterase And Plasma Butyrylcholinesterase By The Cholinesterase Inhibitors Physostigmine (Phys), Pyridostigmine (Pyr), Donepezil (Don) And Galantamine (Gal), David Lee
Theses and Dissertations
Alzheimer’s disease (AD) is a chronic, progressive neurodegenerative disorder, characterized clinically by a progressive loss of memory, cognitive function, ability to care for oneself and psychiatric symptoms. First-line agents for the treatment of AD are ChE inhibitors (DON, GAL), whose modest clinical efficacy and the high incidence of dose-limiting toxicities limit their clinical utility. In addition to AD, ChE inhibitors (PYR) are used for other medical conditions, such as myasthenia gravis (MG). Furthermore, ChE inhibitors (PYR) are used by military personnel prophylactically if impending exposure to chemical warfare agents, e.g., soman, is suspected. The purpose of this research project was …
Creating An Environmentally Sustainable Costume Shop, Katherine Stone
Creating An Environmentally Sustainable Costume Shop, Katherine Stone
Theses and Dissertations
The goal of my thesis is to provide the reader with a better understanding of how to create an environmentally sustainable costume shop. I chose to focus on certain elements of the costume shop that are imperative to the function of the shop, but desperately need to change for the sake of the environment. The elements I focused on were fabric, energy, and chemicals. Armed with a better understanding of why and what needs to be changed, the reader will be able to take this knowledge and apply it to their costume shop and life. We need to change how …
Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng
Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng
Theses and Dissertations
Swelling-activated Cl- current (ICl,swell) is an outwardly rectifying Cl- current that influences cardiac electric activities and acts as a potential effector of mechanoelectrical feedback that antagonizes the effects of stretch-activated cation channels. Persistent activation of ICl,swell has been observed in multiple models of cardiovascular diseases. Previously we showed that angiotensin II (AngII) signaling and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) are involved in the activation of ICl, swell by both beta1-integrin stretch and osmotic swelling. Because endothelin-1 (ET-1) is a potential downstream mediator of AngII and ETA receptor blockade abrogates AngII-induced ROS generation, we studied how ET-1 …