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University of Kentucky

2011

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The Role Of Co-Infection In The Spread Of Hiv In Sub-Saharan Africa, Diego Fernando Cuadros Jan 2011

The Role Of Co-Infection In The Spread Of Hiv In Sub-Saharan Africa, Diego Fernando Cuadros

Theses and Dissertations--Biology

The cause of the high HIV prevalence in sub-Saharan Africa is incompletely understood, with heterosexual penile-vaginal transmission proposed as the main mechanism. Heterosexual HIV transmission has a very low probability; further, a single estimation of heterosexual probability of HIV transmission fails to reproduce the variation associated with important biological cofactors. In particular, studies of HIV incidence suggest that co-infection with other infectious diseases influence the HIV transmission, and therefore might substantially vary the pattern of the spread of the infection. To assess the effect of co-infection on the spread of HIV, I developed and analyzed several mathematical and statistical models …


Price Levels And Dispersion With Asymmetric Information, Tanmoy Bhattacharya Jan 2011

Price Levels And Dispersion With Asymmetric Information, Tanmoy Bhattacharya

Theses and Dissertations--Economics

In the extensive literature on price dispersions that exists to date, there is a gap in the analysis of how market structure affects prices as well as the degree of dispersion in prices. Specifically, the literature is deficient in analyzing how price levels and price dispersion are affected by the number of firms operating in a market. I use secondary data to look at the prices of prescription drugs at the retail level in nine hundred and seventy pharmacies across one hundred and sixty five markets in Maryland and compare price dispersion across these brick and mortar pharmacies as well …


The Potential And Possibilities For Utilizing Geographic Information Systems To Inform School Library As Place, Melissa P. Johnston, Bradley Wade Bishop Jan 2011

The Potential And Possibilities For Utilizing Geographic Information Systems To Inform School Library As Place, Melissa P. Johnston, Bradley Wade Bishop

Information Science Faculty Publications

Teacher librarians often consider their students and the internal school environment in planning programs and services but ignore the larger community from which learners originate. The purpose of this study was to provide a review of the ongoing discussions related to the school library in the community context and provide implications for utilizing geographic information systems (GIS) to inform the idea of the “school library as place.” This preliminary exploration, a thematic literature review, indicated multiple possibilities for implementing GIS in school libraries that may enable teacher librarians to better facilitate students’ development of a sense of place, support their …


Anton Mangstl: A Tribute, Antoinette Paris Greider Jan 2011

Anton Mangstl: A Tribute, Antoinette Paris Greider

Library Faculty and Staff Publications

No abstract provided.


[Review Of] Organizational Storytelling For Librarians, Jennifer A. Bartlett Jan 2011

[Review Of] Organizational Storytelling For Librarians, Jennifer A. Bartlett

Library Faculty and Staff Publications

No abstract provided.


Mathematical Modeling Of Clostridium Thermocellum’S Metabolic Responses To Environmental Perturbation, Bless Adotey Jan 2011

Mathematical Modeling Of Clostridium Thermocellum’S Metabolic Responses To Environmental Perturbation, Bless Adotey

Theses and Dissertations--Biosystems and Agricultural Engineering

Clostridium thermocellum is a thermophilic anaerobe that is capable of producing ethanol directly from lignocellulosic compounds, however this organism suffers from low ethanol tolerance and low ethanol yields. In vivo mathematical modeling studies based on steady state traditional metabolic flux analysis, metabolic control analysis, transient and steady states’ flux spectrum analysis (FSA) were conducted on C. thermocellum’s central metabolism. The models were developed in Matrix Laboratory software ( MATLAB® (The Language of Technical Computing), R2008b, Version 7.7.0.471)) based on known stoichiometry from C. thermocellum pathway and known physical constraints. Growth on cellobiose from Metabolic flux analysis (MFA) and Metabolic …


Evaluating Algal Growth At Different Temperatures, Keelin Owen Cassidy Jan 2011

Evaluating Algal Growth At Different Temperatures, Keelin Owen Cassidy

Theses and Dissertations--Biosystems and Agricultural Engineering

In recent years, there has been a concern for the amount of carbon dioxide released into the atmosphere and how it will be captured. One way to capture carbon dioxide is with algae. In this study, algae's growth was measured at different temperatures. The first part of the study was to grow Scenedesmus and Chlorella with M8 or urea growth media at a temperature of 25, 30 or 35ºC. It was found that 30ºC had the best growth rates for both algae. The second part studied Scenedesmus growth with urea, more in-depth, and found the optimum growth temperature to be …


Cell And Protein-Based Sensing Systems For The Detection Of Environmentally And Physiologically Relevant Molecules, Kendrick Bruce Turner Jan 2011

Cell And Protein-Based Sensing Systems For The Detection Of Environmentally And Physiologically Relevant Molecules, Kendrick Bruce Turner

Theses and Dissertations--Chemistry

The detection of small molecules in complex sample matrices such as environmental (surface and ground water, sediment, etc.) and biological (blood, serum, plasma, etc.) samples is of paramount importance for monitoring the distribution of environmental pollutants and their patterns of exposure within the population as well as diagnosing and managing diseases. Biosensors have demonstrated a singular ability to sensitively and selectively detect analytes in complex samples without the need for extensive sample preparation and pretreatment. Nature has demonstrated myriad examples of exquisite selectivity in spite of complexity and we seek to take advantage of that attribute in the development of …


The Relationship Between Service Learning And Public Speaking Self-Efficacy: Toward Engaging Today’S Undergraduates, Jami Leigh Warren Jan 2011

The Relationship Between Service Learning And Public Speaking Self-Efficacy: Toward Engaging Today’S Undergraduates, Jami Leigh Warren

Theses and Dissertations--Communication

This study examined the role service learning might play in increasing students’ public speaking self-efficacy in a required public speaking course. By increasing students’ public speaking mastery experiences with real world audiences and by providing them with additional feedback from community professionals in the audience, a service learning approach might potentially raise students’ perceptions of public speaking selfefficacy beyond what is gained from a public speaking course taught in a traditional way. A repeated measures, quasi-experimental study design with a comparison group was utilized in this study. Participants included 274 students enrolled in service learning public speaking courses and 328 …


Molecular And Chemical Dissection Of Cellulose Biosynthesis In Plants, Darby M. Harris Jan 2011

Molecular And Chemical Dissection Of Cellulose Biosynthesis In Plants, Darby M. Harris

Theses and Dissertations--Plant and Soil Sciences

Plant cell walls are complex structures that must not only constrain cellular turgor pressure but also allow for structural modification during the dynamic processes of cell division and anisotropic expansion. Cell walls are composed of highly glycosylated proteins and polysaccharides, including pectin, hemicellulose and cellulose. The primary cell wall polysaccharide is cellulose, a polymer composed of high molecular weight !- 1,4-glucan chains. Although cellulose is the most abundant biopolymer on Earth, there is still a lot to learn about its biosynthesis and regulation. This research began by applying a variety of analytical techniques in an attempt to understand differences in …


Characterization Of Wolbachia And Its Interaction In Host Mosquitoes, Eunho Suh Jan 2011

Characterization Of Wolbachia And Its Interaction In Host Mosquitoes, Eunho Suh

Theses and Dissertations--Entomology

Wolbachia are maternally inherited, obligate, intracellular bacteria inducing a form of sterility known as cytoplasmic incompatibility. Wolbachia based strategies have been proposed for the control of disease vectors. One example is to use a population replacement strategy to drive into natural population a novel Wolbachia that modifies the age structure of a vector population, reducing disease transmission.

In this research, the effects of a life-shortening stain of Wolbachia (popcorn Wolbachia) are transferred into the mosquitoes Aedes albopictus (Chapter Two and Three) and A. aegypti (Chapter Four and Five). In Chapter Two, the Wolbachia symbiosis significantly reduced fecundity and …


Parametric Estimation In Competing Risks And Multi-State Models, Yushun Lin Jan 2011

Parametric Estimation In Competing Risks And Multi-State Models, Yushun Lin

Theses and Dissertations--Statistics

The typical research of Alzheimer's disease includes a series of cognitive states. Multi-state models are often used to describe the history of disease evolvement. Competing risks models are a sub-category of multi-state models with one starting state and several absorbing states.

Analyses for competing risks data in medical papers frequently assume independent risks and evaluate covariate effects on these events by modeling distinct proportional hazards regression models for each event. Jeong and Fine (2007) proposed a parametric proportional sub-distribution hazard (SH) model for cumulative incidence functions (CIF) without assumptions about the dependence among the risks. We modified their model to …


Stochastic Dynamics Of Gene Transcription, Yan Xie Jan 2011

Stochastic Dynamics Of Gene Transcription, Yan Xie

Theses and Dissertations--Statistics

Gene transcription in individual living cells is inevitably a stochastic and dynamic process. Little is known about how cells and organisms learn to balance the fidelity of transcriptional control and the stochasticity of transcription dynamics. In an effort to elucidate the contribution of environmental signals to this intricate balance, a Three State Model was recently proposed, and the transcription system was assumed to transit among three different functional states randomly.

In this work, we employ this model to demonstrate how the stochastic dynamics of gene transcription can be characterized by the three transition parameters. We compute the probability distribution of …


Making Reproductive Health Meaningful: An Anthropological Study Of Planned Parenthood Personnel In Lexington, Ky, Hannah M. Wohltjen Jan 2011

Making Reproductive Health Meaningful: An Anthropological Study Of Planned Parenthood Personnel In Lexington, Ky, Hannah M. Wohltjen

Theses and Dissertations--Anthropology

This thesis focuses on how reproductive health is made meaningful in the context of a Planned Parenthood clinic in Kentucky. Using ethnographic field methods, including participant observation and semi-structured interviews, the paper explores how staff members negotiate definitions of reproductive health as employees of Planned Parenthood health center. The analysis addresses reproductive health discourse among the clinic staff and how reproductive health is used as a site of intervention. It also explores the sociocultural processes and interactions the staff members engage in at the national and local levels and the role these play in shaping the conceptualization of reproductive health …


Factors Affecting Feeder Cattle Prices In The Southeast, Kenneth H. Burdine Jan 2011

Factors Affecting Feeder Cattle Prices In The Southeast, Kenneth H. Burdine

Theses and Dissertations--Agricultural Economics

Traditional factors known to affect feeder cattle prices, such as corn prices, have been questioned recently given the volatile nature of agricultural markets and some recent research findings. This work utilizes two very current and unique datasets to examine feeder cattle pricing relationships from Kentucky internet auctions and Certified Preconditioned for Health (CPH) sales. In addition to examining traditional pricing factors, factors that affect feeder cattle basis were also examined. Basis questions are of great interest in the southeast as transportation costs to major cattle feeding areas have been impacted by rising fuel prices and increased market volatility. Finally, price …


Six Japanese Gardens And Trois Rivières: Delta: An Analysis Of Kaija Saariaho’S Two Major Works For Solo Percussion And Electronics, Bradley Edward Meyer Jan 2011

Six Japanese Gardens And Trois Rivières: Delta: An Analysis Of Kaija Saariaho’S Two Major Works For Solo Percussion And Electronics, Bradley Edward Meyer

Theses and Dissertations--Music

Music for solo multiple-percussion (“multi-percussion”) has been rapidly developing in terms of quantity of and creativity exhibited within works since this genre was established in the late 1950s. It is important to underscore, analyze, and question the music of composers who have helped further multi-percussion towards the highest level of musical excellence possible as the genre continues to expand and mature. Finnish-born composer Kaija Saairaho has achieved international fame and success with her acoustic, electronic, and electro-acoustic (the simultaneous combination of electronic and acoustic elements) compositions. She has a large body of musical works, including two compositions for solo percussionist …


Stability Of Affinity Based Layer-By-Layer Polymeric Self-Assemblies For Oral Wound Applications, Sundar Prasanth Authimoolam Jan 2011

Stability Of Affinity Based Layer-By-Layer Polymeric Self-Assemblies For Oral Wound Applications, Sundar Prasanth Authimoolam

Theses and Dissertations--Chemical and Materials Engineering

Oral mucositis is a painful and debilitating chronic inflammatory condition that can result from chemo and/or radiotherapy. While current treatment strategies which provide temporary relief exist, there is still an unmet clinical need for a robust long active barrier strategy which can simultaneously provide protection and release drug to enhance the wound healing response. It is proposed that an affinity based layer-by-layer self-assembled barrier administered as a series of mouth rinses can allow for wound specific drug delivery, providing an effective regenerative therapy.

In this work, biotinylated poly(acrylic acid) is used to develop LBL assemblies based upon biotin-streptavidin affinity interactions. …


Moisture Control Methodology For Gas Phase Compost Biofilters, Lucas Dutra De Melo Jan 2011

Moisture Control Methodology For Gas Phase Compost Biofilters, Lucas Dutra De Melo

Theses and Dissertations--Biosystems and Agricultural Engineering

Gas phase biofilters are used for controlling odors from animal facilities. Some characteristics can affect their performance and moisture content is one very important. A methodology for controlling and measuring moisture content is required to optimize these systems. An experiment was conducted to determine the appropriate placement of a set of soaker hoses 1.2 m in length for water application. It was found that the soaker hose installed in the lower region of the biofilter coupled with appropriate and timely application of water was able to minimize drying of the compost. Thermal conductance proved to be a reliable indicator for …


Clinical And Functional Assessment Following Autologous Chondrocyte Implantation To The Knee: The Role Of Patient Reported Outcomes, Performance Based Assessment, And Response Shift, Jennifer Sebert Howard Jan 2011

Clinical And Functional Assessment Following Autologous Chondrocyte Implantation To The Knee: The Role Of Patient Reported Outcomes, Performance Based Assessment, And Response Shift, Jennifer Sebert Howard

Theses and Dissertations--Rehabilitation Sciences

Autologous chondrocyte implantation (ACI) is a cell based therapy for the treatment of articular cartilage defects. Numerous studies have reported outcomes following ACI using a variety of patient reported outcomes (PROs), but no clear recommendations exist regarding which PRO is the most responsive to changes following ACI. Few studies have documented changes in performance based assessments (PBAs) following ACI. Response shift theory proposes that residual changes in self-report measures occur over time. Failing to account for response shift may result in over or under reporting of outcomes from which clinical decisions are made. The purposes of this dissertation were 1) …


Studies Of Solubilization Of Poorly Water-Soluble Drugs During In Vitro Lipolysis Of A Model Lipid-Based Drug Delivery System And In Mixed Micelles, Lin Song Jan 2011

Studies Of Solubilization Of Poorly Water-Soluble Drugs During In Vitro Lipolysis Of A Model Lipid-Based Drug Delivery System And In Mixed Micelles, Lin Song

Theses and Dissertations--Pharmacy

Lipid-based drug delivery systems (LBDDSs) are becoming an increasingly popular approach to improve the oral absorption of poorly-water soluble drugs. Several possible mechanisms have been proposed to explain the means by which LBDDSs act in vivo to enhance absorption. The goal of the current dissertation is to provide a better understanding of one proposed mechanism; the capability of lipoidal components in LBDDS formulations to create and maintain a drug in a supersaturated state under simulated GI conditions. Moreover, molecular details of equilibrium solubilization of a drug in a series of model lipid assemblies were examined. The results of these studies …


Fullerenes And Metallofullerenes In Coal-Fired Stoker Fly Ash, Luis F.O. Silva, Katia Daboit, Carmen Serra, Sarah M. Mardon, James C. Hower Jan 2011

Fullerenes And Metallofullerenes In Coal-Fired Stoker Fly Ash, Luis F.O. Silva, Katia Daboit, Carmen Serra, Sarah M. Mardon, James C. Hower

Coal Combustion and Gasification Products Journal Archive

Asuite of high-As, high-C fly ashes from a university-based stoker-fired coal boiler were analyzed by a number of techniques, including high-resolution transmission electron microscopy (HR-TEM), time-of-flight secondary ion mass spectrometry (TOFSIMS), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FE-SEM). The sooty carbon is in the form of nano balls with the major fullerenes at C60 +,C70 +, and C80 +, with species at C2 increments from C56 + to C78 +. Arsenic and Hg, among other metals, are found in association with the fullerenes, but, with our techniques, it is not possible to determine if the metals are …


Geochemical Controls Of Coal Fly Ash Leachate Ph, William R. Roy, Peter M. Berger Jan 2011

Geochemical Controls Of Coal Fly Ash Leachate Ph, William R. Roy, Peter M. Berger

Coal Combustion and Gasification Products Journal Archive

When coal fly ash is initially mixed with water, the initial pH of resulting extract or leachate may be strongly acidic (pH 4) or alkaline (pH12). With time, however, this pH range tends to narrow because of geochemical buffering reactions. Because pH is the major variable that controls the leaching of many potential groundwater contaminants, understanding the long-term pH behavior of fly ash leachate is crucial to evaluating the environmental impacts of fly ash management. Using laboratory extract data, kinetic-geochemical models were created to gain a better understanding of the potential buffering that influences the long-term pH of ash leachate. …


Influence Of Chemical Reagents On Rheological Properties Of Fly Ash-Water Slurry At Varying Temperature Environment, H.K. Nail, M.K. Mishra, Karanam U.M. Rao Jan 2011

Influence Of Chemical Reagents On Rheological Properties Of Fly Ash-Water Slurry At Varying Temperature Environment, H.K. Nail, M.K. Mishra, Karanam U.M. Rao

Coal Combustion and Gasification Products Journal Archive

About 70% of total electrical energy is generated from thermal power plants in India which in turn release about 160 Mt of fly ash as solid waste annually. Transportation and disposal of such a huge amount of fly ash is a major problem faced by the power plants. Presently fly ash is transported as lean slurry in pipe lines requiring about 80 to 85% of water with high energy input. A major impediment in high volume transportation of fly ash is its high specific gravity as compared to that of water. The objective of the present study was to evaluate …


The Leachability Of Major Elements At Different Stages Of Weathering In Dry Disposed Coal Fly Ash, S.A. Akinyemi, A. Akinlua, W.M. Gitari, R.O. Akinyeye, L.F. Petrik Jan 2011

The Leachability Of Major Elements At Different Stages Of Weathering In Dry Disposed Coal Fly Ash, S.A. Akinyemi, A. Akinlua, W.M. Gitari, R.O. Akinyeye, L.F. Petrik

Coal Combustion and Gasification Products Journal Archive

Large quantities of solid residue are generated by coal-fired power stations in many parts of the World. The disposal and management of the unused fly ash remains a major problem to the environment. The weathered dry disposed ash cores comprise of major element constituents such as Al, Si, Ca, Mg, Fe, Mn, Na+ and K+. The mobility patterns and mineralogical associations of major elements in weathered dry disposed ash dumps aged 1-year-old, 8-year-old and 20-year-old from a coalfired power station in South Africa were investigated using a modified sequential extraction scheme. The extraction sequence was as follows: (1) water soluble, …


Predictors Of Readiness To Initiate Insulin Therapy In Patients With Type 2 Diabetes When Oral Medications Fail To Control Hyperglycemia, Pamela Lynn Phares Jan 2011

Predictors Of Readiness To Initiate Insulin Therapy In Patients With Type 2 Diabetes When Oral Medications Fail To Control Hyperglycemia, Pamela Lynn Phares

Theses and Dissertations--Nursing

Type 2 diabetes (T2DM) has reached epidemic levels worldwide during the past two decades. It affects nearly 26 million adults in the U.S. Advances in both the treatments for T2DM and guidelines for its optimal management are extensive. Despite these advances, barely half of type 2 diabetics achieve recommended glycemic targets.

Specific Aims: The specific aims were to:

  1. Describe the available research on clinical inertia and interventions that have been implemented to reduce it.
  2. Analyze various behavioral theories that explain and predict self-care practices in diabetes in order to develop a conceptual model on which to base an investigation …


Co-Disposal Of Dry Fgd By-Product With Coal Gasification Ash And Inorganic Brines, Jabulani S. Mahlaba, P.C. Pretorius, Subal Maharajh, M.P. Augustyn Jan 2011

Co-Disposal Of Dry Fgd By-Product With Coal Gasification Ash And Inorganic Brines, Jabulani S. Mahlaba, P.C. Pretorius, Subal Maharajh, M.P. Augustyn

Coal Combustion and Gasification Products Journal Archive

There is a growing pressure from the environmental authorities and public bodies to reduce anthropogenic pollution. Stringent environmental legislation is being implemented for industries around the world, even more so for coal consuming industries. Control of gaseous emissions is one of the areas that are receiving considerable attention towards sustainable development. Coal combustion in coal-fired power utilities emits SO~x~ to the atmosphere. Dry flue gas desulphurisation (FGD) is a well known technology often used to mitigate sulphur emissions in coal-fired power utilities. It traditionally uses lime to neutralise SO~x~, and forms a mixture of anhydrite (CaSO~4~), and calcium sulphite (CaSO~3~). …


Compaction Of High-Ca Fly Ash-Al- And Al-Alloy-Composites: Evaluation Of Their Microstructure And Tribological Performance, Grigorios Itskos, Angeliki Moutsatsou, Pradeep K. Rohatgi, Nikolaos Koukouzas, Charalampos Vasilatos, Eleni Katsika Jan 2011

Compaction Of High-Ca Fly Ash-Al- And Al-Alloy-Composites: Evaluation Of Their Microstructure And Tribological Performance, Grigorios Itskos, Angeliki Moutsatsou, Pradeep K. Rohatgi, Nikolaos Koukouzas, Charalampos Vasilatos, Eleni Katsika

Coal Combustion and Gasification Products Journal Archive

In this study, highly calcareous and siliceous fly ash particles were utilized for the fabrication of Al- and Al-alloy-based MetalMatrix Composites (MMCs) by means of powder metallurgy. After compacting and sintering Al and Al/Si powders containing 10, 15, and 20wt. % ash particles, the homogenous (and with minimal amount of voids) microstructure of the produced composites was verified by means of Scanning Electron Microscopy (SEM). The composites were tested for their dry sliding wear behavior using a pin-on-disc machine against spheres of alumina. The worn surfaces of composites were then examined by using SEM and Energy Dispersive X-Ray Spectroscopy (EDS). …


Effect Of Additive On The Performance Characteristics Of Centrifugal And Progressive Cavity Slurry Pumps With High Concentration Fly Ash Slurries, Sunil Chandel, S.N. Singh, V. Seshadri Jan 2011

Effect Of Additive On The Performance Characteristics Of Centrifugal And Progressive Cavity Slurry Pumps With High Concentration Fly Ash Slurries, Sunil Chandel, S.N. Singh, V. Seshadri

Coal Combustion and Gasification Products Journal Archive

Slurry pumps that are used in the hydraulic transportation of fly ash slurries through pipes in thermal power plants can be broadly classified into two main categories namely positive displacement and centrifugal pumps. The two types of pumps differ considerably in construction as well as in operating principle compared to the conventional pumps. The present study reports the effect of additive on the performance characteristics of centrifugal and progressive cavity screw pumps with fly ash slurries at high concentrations (above Cw < 50% by weight). Mixture of sodium carbonate and Henko detergent (5:1) at a concentration of 0.2% by weight has been used as an additive. For each type of pump, the effect of additive on the performance characteristics has been experimentally evaluated at rated speed with fly ash slurries in the concentration range of 50 to 70% by weight. The pump total head, overall efficiency and pump input power as a function of flow rate have been measured. The results obtained from the centrifugal slurry pump performance show that at rated speed, the performance of the pump improves with the addition of drag reducing additive. In the case of progressive cavity screw pump, pump performance characteristics and behavior were completely different as compared to the centrifugal slurry pump. At rated speed, the performance of screw pump deteriorates with the addition of drag reducing soap solution.


Impact Of Manufactured Coal Ash Aggregates On Water Quality During Open Pit Restoration: 1. A Statistical Screening Test, Sangchul Hwang, Isomar Latorre Jan 2011

Impact Of Manufactured Coal Ash Aggregates On Water Quality During Open Pit Restoration: 1. A Statistical Screening Test, Sangchul Hwang, Isomar Latorre

Coal Combustion and Gasification Products Journal Archive

Utilization of manufactured coal ash aggregates (MAs) as a subsoil substitute during restoration of an open pit was assessed in a three-factor, two-level factorial analysis. The factors of interest were the MA application rate (2:1 or 1:2 topsoil/MA volume ratio), rainfall intensity (high or low), and aggregate size (2.36–4.75 mm or 4.75–9.53 mm). Among the water quality parameters examined (pH, turbidity, heavy metal content (lead and cadmium), conductivity, and hardness), the last two parameters were significantly higher (p,0.05) in soil amended with MAs than in a control reactor using sand. A low rainfall intensity and larger aggregate size resulted in …


Mechanism And Kinetics Of Covalent Amide-Linked Adduct Formation In Solution And Solid Peptide Formulations, Michael Paul Dehart Jan 2011

Mechanism And Kinetics Of Covalent Amide-Linked Adduct Formation In Solution And Solid Peptide Formulations, Michael Paul Dehart

Theses and Dissertations--Pharmacy

Peptides and proteins are prone to chemical and physical degradation in solutions and solids. One of the most common chemical degradation pathways involves deamidation of asparagine residues through a reactive succinimide intermediate resulting in the formation of aspartyl and isoaspartyl degradation products.

In this work, kinetic studies in aqueous solutions demonstrated that the succinimide intermediate is susceptible to attack by nucleophiles other than water. This may lead to a variety of alternative degradants. In solutions containing high concentrations of ammonia, the succinimide generated in the deamidation of the model peptides Phe-Asn-Gly and Phe-isoAsn-Gly underwent back-reaction with ammonia leading to peptide …