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Articles 1 - 4 of 4
Full-Text Articles in Physical Sciences and Mathematics
Design And Synthesis Of Small Molecular Probes For Cns And Kidney Disorders, Swagat H. Sharma
Design And Synthesis Of Small Molecular Probes For Cns And Kidney Disorders, Swagat H. Sharma
Theses & Dissertations
The G protein regulated inwardly rectifying potassium channels (GIRK) are a family of inwardly rectifying potassium channels and are key effectors in signaling pathways. GIRK 1/2 channel subunit, predominantly found in the brain, is involved pathophysiology of various neurological disorders including, but not limited to, epilepsy, anxiety, Parkinson's, pain, reward, and addiction. Previously, our laboratory had identified a series of urea containing molecules as GIRK1/2 preferring activators. Unfortunately, the urea series suffers from significant PK liabilities (solubility, brain penetration and high clearance). The chapter 1 of the dissertation describes our efforts in developing three new series of activators with improved …
Approximate Likelihood Based Estimations For Joint Models With Intractable Likelihoods, Karl Stessy M. Bisselou
Approximate Likelihood Based Estimations For Joint Models With Intractable Likelihoods, Karl Stessy M. Bisselou
Theses & Dissertations
This dissertation focuses on the development of approximation approaches for the joint modeling (JM) of repeated measures data and time-to-event data in the presence of analytically or numerically intractable likelihoods. Current likelihood-based inferences for JMs show several limitations including (i) intractability of integrals during marginal likelihood derivations due to the complexity in computations, and (ii) the large number of nuisance parameters (unobserved) posing a problem with convergence. The h-likelihood (HL) and synthetic likelihood (SL) are two computationally efficient estimation approaches that overcome these challenges.
In the presence of extremely high censoring rates, the HL can produce bias parameter estimates. We …
Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li
Urinary Bile Acid Indices As Prognostic Biomarkers For The Complications Of Liver Diseases, Wenkuan Li
Theses & Dissertations
Hepatobilary diseases cause the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues, which may lead to an unfavorable prognosis. In this study, we compared the urinary BA profile in 257 patients with hepatobilary diseases during a 7-year follow-up period. We investigated the use of the urinary BA profile to develop logistic regression models to predict the prognosis of hepatobiliary diseases in terms of developing disease-related complications, especially for ascites. The urinary BA profile was characterized by calculating BA indices, which quantify the composition, metabolism, hydrophilicity, and toxicity of the BA profile. All patients had high …
Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner
Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner
Theses & Dissertations
Despite effective regimens of combination antiretroviral therapy, individuals with HIV are still at higher risk for developing forms of cognitive impairment, with one of the most common behavioral abnormalities to manifest being motor dysfunction. This is an important consideration, as deficits in motor control likely contribute to higher-order cognitive impairments, which together, lead to functional dependencies in the ever-growing aging population of HIV-infected adults. While the neuroanatomical bases of motor dysfunction have recently been illuminated in people living with HIV (PLWH), there remains an open question regarding the molecular processes supporting the circuit-level neuronal dynamics that potentially serve these behavioral …