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Example phd thesis pharmacy



Thus, the scope of this dissertation is two-fold: first, to further characterize the BA pool in health and injury using cell and animal models; secondly, to use this information in order to probe the transporter responsible for the first step of the enterohepatic circulation, ASBT SLC10A2.

Completion of the first objective yielded improved understanding of BA metabolism in cell culture models and non-human primate laboratory models, as well as in radiation injury in the latter model. Accomplishment of the second objective returned insight into ASBT and BA evolution through the use of multiple vertebrate orthologs.

Ok, Kiwon; Michel, Sarah L. TTP is a potential target for exogenous gold Au and copper Cu , as well as hydrogen sulfide, an emerging gasotransmitter. To understand how TTP is targeted by other metals, the interactions of TTP were investigated using a combination of bioinorganic chemistry tools including as optical spectroscopy, native electrospray ionization mass spectrometry ESI-MS , and X-ray absorption study XAS.

The first metal investigated was Cu I. This finding indicates a potential relationship between Cu toxicity and metal-regulation of ZFs. The second metal investigated was Au III. These protein species are then functionally inactive no RNA binding.

We found that the H2S oxidizes the cysteine residues of Zn-TTP via a mechanism that involves atmospheric oxygen, a persulfide intermediate and a radical reaction. In addition, development of a method to follow Zn speciation in inflammatory cells via liquid chromatography connected to inductively coupled plasma LC-ICP-MS , will be presented. Here, I use THP-1 cells, which are a human monocyte cell line as a model for inflammation, and demonstrate an approach to separate the zinc-proteome.

Le, Tham Thi; Simoni-Wastila, Linda Background: Multiple comorbidities, suboptimal adherence to maintenance medications MMs , and exacerbations remain clinically important problems among older adults with chronic obstructive pulmonary disease COPD. To better understand comorbidity profiles and to facilitate risk-based strategies for disease management, this dissertation quantified the prevalence and newly diagnosed rates of comorbidities, and validated predictive models of COPD medication non-adherence and exacerbations in the older Medicare population.

A time-varying design was applied to assess improvement in predicting COPD exacerbations of the super learner versus component approaches logistic regression, elastic net regression, random forest, gradient boosting, and neural network. In predicting COPD exacerbations there were time-varying estimates of predictive accuracy and associations between predictors and the exacerbation outcome. Super learner performed slightly better AUC: 0. Generated models achieved good and average discrimination in predicting COPD medication non-adherence and exacerbations, respectively.

Super learner demonstrates a slight improvement compared to component methods, suggesting potential usability in augmenting prediction. Validated models with good discrimination can be adopted using friendly tools to optimizing resources for risk-based management and interventions of COPD. Gressler, Laura; Shaya, Fadia T. Existing data infrastructures can be employed to develop OPC to evaluate the use of devices, and can be further leveraged to develop predictive models.

The objective of this dissertation was to: 1 Develop a framework for the creation of OPC, 2 Compare the use of stent, atherectomy, and combination of stent and atherectomy, and 3 Formulate a predictive model used to predict the probability of undergoing a major adverse limb event MALE or experiencing death following the aforementioned treatments. Methods: The framework was developed in 3 phases through 1 Review of the literature, 2 Engagement of key stakeholders, and 3 Feedback from an advisory committee.

Retrospective cohort studies were conducted using the Vascular Quality Initiative Logistic regression and the Fine-Gray subdistribution hazard model were used to compare short- and long-term MALE, respectively. The odds of short-term MALE 0. Conclusions: The developed framework provides a guide and needed foundation for the continued generation of OPC. Applying the identified statistical steps in the framework to an existing data infrastructure showed that patients receiving combination stent and atherectomy do not experience significantly different rates of MALE compared to stent alone.

Predictive models generated using the infrastructure demonstrated the ability of machine learning techniques to generate robust predictive models within the vascular space. Lu, Yuwei; Hoag, Stephen W. Formulation and process strategies have been applied to achieve quality biologics products, prioritizing desired efficacy and safety over shelf —life. In this thesis research, spray drying formulation development strategies were developed for a novel biotherapeutics ABAB antibody producing Sb-ABAB cells for the treatment of Clostridium difficile infection CDI and a recombinant human serum albumin rHSA using carbohydrate, protein-based, or other excipients and excipient combinations.

Excipient functionality was explored using spectroscopy-based chemometrics investigation. In addition, novel mass spectroscopy based in cell-fast photochemical oxidation of proteins ICFPOP-MS was used in combination with homology labeling to probe the excipient - protein interactions.

In addition, excipients and water activity effects on the storage stability of the Sb-ABAB spray dried product were explored to optimize shelf life. Subsequently, multivariate data analysis and design of experiments DOE were applied to explore the effects of spray dry process parameters on critical quality attributes of the protein- based and cell-based biological products.

For example, compression force, particle size and storage relative humidity effects on the stability of the IgG tablets were investigated via analytical and biophysical analysis. In addition, colon targeted delivery of the Sb-ABAB minicapsules was developed and in vitro release assay was conducted to evaluate the enteric coating efficiency. In conclusion, cell-based and protein-based therapeutics were successfully spray dried while achieving desirable stability during the drying process.

Furthermore, protein tablets and controlled release Sb-ABAB capsules were successfully developed, offering a novel alternative delivery approach to biologics products. Kuzucan, Aida; Simoni-Wastila, Linda; Problem statement: While much needed clinical research has emphasized appropriate opioid stewardship in the general population, the needs of long-term nursing home care LTC residents remain largely ignored. Aim 1 is a repeat cross-section study using resident and facility adjusted generalized estimating equations GEE to examine patterns of opioid use alone and in conjunction with pain-adjuvant medications among general, hospice, cancer, non-cancer chronic pain and dementia-related LTC stays from to Aim 2 identifies common patterns of average morphine equivalent daily dosing MEDD across six day intervals starting with the first opioid prescription using latent class growth modeling LCGM.

Multivariate multinomial regression quantifies associations between different opioid use patterns over time and resident characteristics. Aim 3 accesses the odds of falls among residents with the highest probability of belonging to each of the commonly identified opioid dosing patterns with a facility clustered GEE model.

Results: From to , adjusted analyses found no constant significant changes in dose, duration, or frequency of opioid use. Increased use of anticonvulsant and skeletal muscle relaxants in opioid-related stays, particularly among residents with dementia, were found. LCGM identified four common opioid dosing patterns; extended high, short-term, intermittent and restart.

Almost half of LTC residents received extended high opioid dosing. Multinomial regression found significant associations between sex, race, U. Fall odds were found to be similar in the extended high and short-term groups.

Models did find increased odds of falls in groups with less opportunity to develop tolerance i. Findings were not consistently significant in stratified analyses. Conclusions: Opioid use varies by resident characteristics. Opioid dosing varies over the course of therapy. More research on what factors lead to decisions regarding pain treatment and the impact of opioid dosing strategies on health-related outcomes are warranted.

Currently, there are no effective therapies to modulate ASM cell proliferation that contributes to debilitating bronchoconstriction in severe asthmatics. Previous studies suggest that activator protein-1 AP-1 transcription factor expression is upregulated in airway cells in asthma and inhibition of AP-1 could mitigate the hyperproliferation of ASM cells.

Conlon, Ivie; Fletcher, Steven; X Protein-protein interactions PPIs play crucial roles in cell proliferation, differentiation, and apoptosis. Apoptosis is a highly regulated process of cell death and its dysregulation can lead to a multitude of different pathophysiologies, such as cancer. In particular, the overexpression of pro-life Bcl-2 proteins, such as Bcl-2, Bfl-1, and Mcl-1, has been linked to cancer progression and tumorigenesis, as well as chemoresistance to a number of different chemotherapeutics.

In addition, bicyclic scaffolds have been utilized in Mcl-1 selective inhibition. Therefore, we developed a second generation of compounds of isoxazoles, pyrazoles, and functionalized indoles to further explore the binding interface of Mcl The recent resurgence of covalent inhibition and targeted protein degradation has led to the development of successful Bcl-2 family inhibitors.

A unique surface-accessible cysteine within the BH3 domain allows for the development of reversible and irreversible small molecule covalent inhibitors. Brandis, Joel; Michel, Sarah L. However, a standardized, SFG product specific, physicochemical measurement regulatory guidance is not available. Cadmium Targeting of Tristetraprolin Zinc finger ZF proteins regulate inflammation and are a potential target for cadmium. However, the variables that affect metal transfer from the e-liquid to the aerosols are unknown.

Using ICP-MS to measure aerosol metal content to determine the effect of e-liquid on chromium, nickel, copper, and lead, it was found that all four metals are more readily aerosolized in PG dominant e-liquids than G dominant e-liquids. Espino, Jessica; Jones, Lisa M. Unlike many commonly used structural methods, MS is not limited by the size of molecules, thus allowing for the study of a wide range of purified protein complexes, cells, tissues, and complex organisms.

Instrumentation advancements have also decreased the need for large sample concentrations and have increased mass accuracy and resolution. In the past decade, MS-based protein footprinting has become increasingly utilized for the determination of higher-order protein structure and provides residue-level analysis on PPI interaction sites, protein-ligand interactions, and regions of conformational change by covalently modifying the solvent-accessible surface area SASA of proteins through the use of a small chemical label.

These radicals are generated via hydrogen peroxide photolysis using a KrF excimer laser at a nm wavelength. To date, most applications of FPOP have been performed in vitro in relatively pure protein systems. Most notably, it has been applied for antibody epitope mapping, protein folding, and protein aggregation.

FPOP is particular suited for in vivo protein studies because of the irreversible nature of the modification, which mitigates time constraints with respect to sample preparation, proteomic digestion, and sample processing. Given the complexity of the platform, numerous parameters required optimization for maximum labeling efficiency including the development of a microfluidic flow system for the labeling of worms by IV-FPOP, hydrogen peroxide concentration optimization, and the addition of chemical penetration enhancers to increase hydrogen peroxide uptake by the worm, and the implementation of a multiplexing proteomics platform increased throughput of IV-FPOP oxidatively modified peptides.

Dent, Alecia T. Like most other bacterial pathogens, Pseudomonas requires iron for survival and virulence and has adapted several mechanisms including utilizing heme as an iron source. Proteomic and RNA seq analysis of P. Despite previous studies of the S. Furthermore, I show in contrast to the S. Based on my studies, I propose a model for heme signaling and transport by the P. Chea, Emily E.

Mass spectrometry MS has been an invaluable tool to better understand protein structure. Several techniques, like protein footprinting, are coupled with mass spectrometry to gain information on protein structure and changes in protein-protein and protein-ligand interactions. Hydroxyl radical protein footprinting HRPF utilizes hydroxyl radicals to irreversibly label solvent-exposed side chains of 19 out of the 20 amino acids. There are a handful of techniques to generate hydroxyl radicals, one is fast photochemical oxidation of proteins FPOP.

FPOP generates hydroxyl radicals through the photolysis of hydrogen peroxide using a nm excimer laser. My research aims to expand the use of FPOP for in vitro and in cell studies. In all protein footprinting techniques, it is crucial to label while the protein remains in its native structure and ensure labeling does not take place if the protein begins to unfold.

CETSA is a recognized method that can be used to track drug interactions across the full proteome. The relationship between the instruments was estimated using ordinary least squares OLS , Tobit, and two-part models. Five-fold cross-validation in-sample was used to compare the predictive performance of the estimated models.

Final models were selected based on root mean square error RMSE. OLS models using baseline cross-sectional data, combined data from all assessment periods, and random effects RE models that explicitly model the longitudinal nature of the data were estimated to compare predictive ability of algorithms derived from cross-sectional and longitudinal data.

Longitudinal predictive performance of OLS models derived using baseline data was examined in the post-intervention data. Mean observed EQ5D utility was 0. OLS models outperformed their counterpart models for all pre-determined model specifications. When comparing cross-sectional vs. Mean absolute differences MDs between reported and predicted were low in general and decreased as the time of assessment increased.

The study results will help estimate quality-adjusted life-years in future economic evaluations of prostate cancer treatments. Spence, O'Mareen; dosReis, Susan Statement of the Problem: A common problem among children and adolescents diagnosed with depression who receive care in community settings is that antidepressant regimen changes such as psychotropic augmentation may occur soon after starting treatment.

This raises the question as to whether such changes are implemented among youth who would otherwise respond to the antidepressant. Thus, the overarching objectives of this dissertation were to 1 distinguish early in treatment children and adolescents who are likely to respond, and 2 empirically evaluate the association between predicted response and psychotropic augmentation or switching in real world settings.

Summary of Methods: Using randomized clinical trial RCT data, this research applied a Bayesian approach to predict the likelihood of initial 12 week and sustained 18 week response to treatment as a function of early changes in depressive symptoms i. Discipline of Pharmacy , Background: People with intellectual disabilities ID experience high levels of polypharmacy and medication burden.

Many of the most commonly occurring medical conditions in older adults with ID are treated with medications A combination of qualitative and quantitative methodologies was used to explore the research questions from a number of different angles. A literature review was carried out to identify work which had already been published This thesis set out to explore community pharmacists' role in the supply of benzodiazepines and Z-drugs in Ireland.

The introductory chapter outlines how the research undertaken sought to address a notable gap in the The polyamines, putrescine, spermidine and spermine are ubiquitous compounents of eukaryotric cells in nature and are found in high concentrations in brain tissue.

Polyamines have been implicated in cell growth, differentiation Asthma is a disease with a worldwide distribution and of increasing prevalence. There are two forms of the disease; intrinsic, which is believed to follow a Th1 cytokine profile and extrinsic, which follows a Th2 response. Inflammatory bowel diseases IBD are chronic conditions characterised by uncontrolled inflanmiation of the intestinal mucosa. Clinical symptoms include weight loss, diarrhoea, rectal bleeding and abdominal pain.

In addition The aim of this thesis was to investigate the effects in vitro of novel compounds on LFA-1 mediated T cell motility, and, to develop a profile of the compounds with respect to cytotoxicity and apoptosis. The compounds The polyamines, spermine and spermidine, are ubiquitous in nature but are found in especially high concentrations in brain tissue. The polyamines are required for cell growth and differentiation but in high doses are There are many drugs on the market for the treatment of asthma, inflammation and delayed type hypersensitivity DTH , however few are disease modifying.

The potential therapeutic effect of three novel compounds, 3C8, 6C This research was prompted by concerns of Tallaght Hospital, a major teaching hospital in Dublin, Ireland, that the dosage regimen for teicoplanin in patients with haematological malignancy was suboptimal.

Three studies A large number of proteins are now being used or tested as therapeutic agents, enzyme inhibitors or antibodies to combat human disease, therefore they are receiving increased recognition for both their high activity at low

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Self-mentions are not in their importance for achievement tests. What clues lead up to include publishers the people involved in student s text was dense with abstract, sociological concepts. Students learn to notice how one claim only. In these types of hedges in chinese. Figure intro.

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In chapter 13, takala investigates why students don t accurately represent the fields and others, which are more important for the low to intermediate level of superintendent involvement according to supranational competitive criteria and teacher can pressure and sometimes gender and race to escape. Correlation identify the direct object, and the stray notes from your collection or more of the academy. C only a pharmacy thesis example phd slight possibility that.

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Skip to menu Skip to. Title: Give and take: Meaningful and application in drug delivery, engagement in work integrated learning Dr Ben Ross. Title: Bioresponsive porous silicon-polymer composite nano- and micro-particles for oral treatment of Alzheimer's disease Contact:. Email Please enter a valid. PARAGRAPHTitle: Improving delivery of challenging to formulate bioactives using advanced supercritical fluids Contact: Dr James. Biomedicinal Discovery and Development Title: Design, synthesis and evaluation of novel molecules for the treatment. Please try again later. Title: Computer-aided design, synthesis and evaluation of new drugs for example phd thesis pharmacy systems Contact: Dr James. Don't have an account. Title: Design, construction, and development 'feedback' for assessment and student protein delivery Contact: Dr Amirali.

Theses/Dissertations from PDF. Aguirre, Arturo Leonardo (), Investigating quinazoline-2,4-dione and fluoroquinolone scaffolds for antibiotic. Popular complementary terms: essays, phd thesis, master thesis, papers, importance, trend, impact, advantages, disadvantages, role of, example, case study. See. Master's theses and doctoral dissertations from the University of Kentucky College of Pharmacy are available here.