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Articles 9301 - 9330 of 12202
Full-Text Articles in Entire DC Network
Identifying Risk And Protective Factors Of Preparatory And Non-Preparatory Students In Agricultural Education Programs Of A Rural Kentucky High School, Randy J. Adams
Theses and Dissertations--Community & Leadership Development
Today there is an increased demand for secondary agriculture education programs to prepare students to be college and career ready through a program of study. The purpose of this study was to identify risk and protective factors of preparatory and non-preparatory students within an agriculture education program at Anderson County High School in Lawrenceburg, Kentucky. The results of this study did not determine that there was a difference in risk and protective factors between preparatory and non-preparatory students within agriculture education courses. The study concluded that students among both categories were equally exposed to risks such as family conflict and …
Impact Of Transformational Leadership: Exploring The Transformational Leadership Qualities Of Selected Secondary Agriculture Teachers, Ryan H. Thomas
Impact Of Transformational Leadership: Exploring The Transformational Leadership Qualities Of Selected Secondary Agriculture Teachers, Ryan H. Thomas
Theses and Dissertations--Community & Leadership Development
The purpose of this study is to determine if transformational leadership styles of agriculture teachers in Jessamine County has an impact on successful transitions of program completers. To be more specific, the focus was to look at agriculture teachers at Jessamine Career and Technology Center (JCTC) to see if they exhibit components of transformational leadership. If so, does transformational leadership of those teachers assist students with successful transitions after graduation? Successful transition is deemed by the Kentucky Department of Education as students that seek post-secondary education, employed full-time or enlist in a branch of armed services.
The population for this …
Analyzing Healthy, Local Food Systems: A Case Study Of Owensboro, Kentucky, Callie Hayden
Analyzing Healthy, Local Food Systems: A Case Study Of Owensboro, Kentucky, Callie Hayden
Theses and Dissertations--Community & Leadership Development
Across the US, support is ever-growing for the local food movement. This growing trend promotes food security, supports farming families, ensures universal access to safe and healthy food products, enhances local economies, and encourages environmental and social well-being. People around the US are implementing sustainable local food systems as a means of meeting their individual community’s needs. While this movement is being popularized dramatically around the world, many cities and regions have yet to address it. This study reviews the existing literature on local food system models in an effort to answer the research question: What are the “ingredients” of …
Evaluation Of Motivation And Professional Development Of Curriculum For Agricultural Science Education (Case) Lead And Master Teachers, Miranda Rose Chaplin
Evaluation Of Motivation And Professional Development Of Curriculum For Agricultural Science Education (Case) Lead And Master Teachers, Miranda Rose Chaplin
Theses and Dissertations--Community & Leadership Development
Curriculum for Agricultural Science Education™ (CASE) is an instructional system of support that provides professional development, curriculum, and assessments to agricultural educators. Through the CASE model, two CASE Lead or Master Teachers facilitate professional development, known as a CASE Institute. This study utilizes three sets of surveys to describe the motivation for CASE certified teachers applying to become CASE Lead and Master Teachers, determine the effectiveness of the professional development provided to Lead and Master Teachers during the Lead Teacher Orientation, and determine the Lead and Master Teachers’ demographic information.
Investigation Of Media Ingredients And Water Sources For Algae Co2 Capture At Different Scales To Demonstrate The Correlations Between Lab-Scale And Large-Scale Growth, Tabitha Graham
Theses and Dissertations--Biosystems and Agricultural Engineering
As energy use increases globally the environmental burdens increase alike. Many accusations have been made that carbon dioxide is a culprit of climate change. The University of Kentucky and Duke Energy Power have partnered to test carbon capture technology in a large scale project. To this end, the objective of this thesis is to investigate potential water media sources and nutrient sources at different volume scales for algae cultivation to help create a more environmentally viable and economically feasible solution. This work will conduct a life cycle assessment of water media sources and the effects of the inputs and outputs …
Alkaline Hydrogen Peroxide Pretreatment For Its Use In An On-Farm Bioprocessing Facility, Mary Kathryn Gray
Alkaline Hydrogen Peroxide Pretreatment For Its Use In An On-Farm Bioprocessing Facility, Mary Kathryn Gray
Theses and Dissertations--Biosystems and Agricultural Engineering
Pretreatment is an essential step in biofuel production from lignocellulose. Disruption of the lignin structure gives enzymes and fermentation organisms access to long chains of cellulose and hemicellulose. For this project’s purposes, the pretreatment must work within the framework of an on-farm butanol bioprocessing facility. Alkaline hydrogen peroxide (AHP) is a delignification method that potentially provides several advantages. At the alkaline pH, powerful hydroxyl radicals are formed; which attack lignin. The objectives of this study were to determine if AHP removes substantial lignin for the feedstocks, corn stover, wheat straw, switchgrass and miscanthus, and to determine if AHP acts as …
Nutrients Recycling Strategy For Microalgae-Based Co2 Mitigation System, Xinyi E
Nutrients Recycling Strategy For Microalgae-Based Co2 Mitigation System, Xinyi E
Theses and Dissertations--Biosystems and Agricultural Engineering
Coal-fired electricity production is the major emitter of CO2 and other greenhouse gases including NOx and SOx. Microalgae-based CO2 mitigation systems have been proposed to reduce the net CO2 emission from coal-fired power plants. This study focused on developing an optimum culture media and exploring the possibilities for recycling nutrients, which were added as commercial mineralized chemicals at the beginning of cultivation.
In order to release the nutrients embedded in the cells so that they can be used as a nutrient source for new cells, Scenedesmus biomass was digested by anaerobic bacteria. Results showed …
On T Cell Fate Decisions: Retinol, Metabolism And Itreg Differentiation, Gavin I. Ellis
On T Cell Fate Decisions: Retinol, Metabolism And Itreg Differentiation, Gavin I. Ellis
Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics
The mammalian immune system is equipped to both eliminate pathogenic microorganisms and tumors, while remaining in homeostasis with commensal species at mucosal surfaces and tolerant towards self. Suppressor regulatory T cells (Tregs) are a major sentinel of this immunological tolerance. Induced Tregs (iTregs) arise in the periphery following the integration of cues from the metabolites, cytokines, etc. which make up its milieu. Dysregulation of iTreg development, function or homing underlies the etiology of many autoimmune diseases and immunopathologies. The amelioration or prevention of multiple murine disease models by boosting Treg cell numbers foreshadows clinical efficacy of iTreg therapy, but an …
Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne
Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne
Theses and Dissertations--Neuroscience
Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.
Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …
Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps
Molecular And Cellular Characterization Of Dopamine Neuron Stimulating Peptides, Kristen Kelps
Theses and Dissertations--Neuroscience
Parkinson’s disease, the second most common neurodegenerative disease, is characterized by the loss of dopaminergic neurons within the substantia nigra. Currently, the treatments available for PD are symptomatic treatments that do not stop the progression of the disease. Trophic molecules, such as glial cell-line derived neurotrophic factor (GDNF), have been evaluated as potential therapeutic molecules that could stop the loss of neurons and potentially restore some of the neurons that have already been lost. However, these trophic molecules are large making them difficult to produce and delivery. Here we characterize three peptides (DNSP-5, DNSP-11, and DNSP-17) to determine it they …
Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe
Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe
Theses and Dissertations--Neuroscience
Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role …
Molecular Mechanisms By Which C-Abl And Arg Mediate Melanoma Invasion And Metastasis, Sourik S. Ganguly
Molecular Mechanisms By Which C-Abl And Arg Mediate Melanoma Invasion And Metastasis, Sourik S. Ganguly
Theses and Dissertations--Pharmacology and Nutritional Sciences
Metastasis is one of the main causes of death in cancer patients. Metastatic melanoma is a death sentence, as chemotherapeutic agents have a 5% success rate or do not extend survival beyond 10 months. The lack of effective chemotherapeutic agents for treating metastatic melanoma indicates a dire need to identify new drug targets and develop new therapies. Our lab has previously shown that the kinase activity of Abelson family of non-receptor tyrosine kinases (c-Abl and Arg) is elevated in invasive breast cancer cell lines as compared to non-invasive cell lines. Previous studies from our lab have shown that Abl …
Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel
Changes In Sleep Architecture And Cognition With Age And Psychosocial Stress: A Study In Fischer 344 Rats, Heather M. Buechel
Theses and Dissertations--Pharmacology and Nutritional Sciences
Changes in both sleep architecture and cognition are common with age. Typically these changes have a negative connotation: sleep fragmentation, insomnia, and deep sleep loss as well as forgetfulness, lack of focus, and even dementia and Alzheimer’s disease. Research has shown that psychosocial stressors, such as isolation from family and friends or loss of a loved one can also have significant negative effects on sleep architecture and cognitive capabilities. This leaves the elderly in a particularly vulnerable situation: suffering from cognitive decline and sleep dysregulation already, and more likely to respond negatively to psychosocial stressors. Taking all of these factors …
Inhibition Of Calpains By Calpastatin: Implications For Cellular And Functional Damage Following Traumatic Brain Injury, Kathleen M. Schoch
Inhibition Of Calpains By Calpastatin: Implications For Cellular And Functional Damage Following Traumatic Brain Injury, Kathleen M. Schoch
Theses and Dissertations--Physiology
Traumatic brain injury (TBI) is a devastating health problem based on its high incidence, economic burden, and lack of effective pharmacological treatment. Individuals who suffer an injury often experience lifelong disability. TBI results in abrupt, initial cell damage leading to delayed neuronal death. The calcium-activated proteases, calpains, are known to contribute to this secondary neurodegenerative cascade. Prolonged activation of calpains results in proteolysis of numerous cellular substrates including cytoskeletal components, membrane receptors, and cytosolic proteins, contributing to cell demise despite coincident expression of calpastatin, the specific inhibitor of calpains.
A comprehensive analysis using two separate calpastatin transgenic mouse lines was …
Sex Differences In Cell Death And Steroid Hormone Receptors In Cortical Explants, Amanda L. Trout
Sex Differences In Cell Death And Steroid Hormone Receptors In Cortical Explants, Amanda L. Trout
Theses and Dissertations--Physiology
Estrogens, such as the biologically active 17-b estradiol (E2) have many actions in the male and female brain. Not only does E2 regulate reproductive behavior in adults, it organizes and activates the brains of younger animals in a sex-specific manner. In addition, many human studies have shown E2 to provide protection against a variety of neurological disorders, including stoke. These studies have been controversial and depend largely on the type and timing of hormone replacement. Animal studies are much less controversial and clearly demonstrate a neuroprotective role for E2 following ischemic brain injury. Because much of E2 neuroprotection requires sex …
Evaluation Of Insulin-Like Growth Factor-1 As A Therapeutic Approach For The Treatment Of Traumatic Brain Injury, Shaun W. Carlson
Evaluation Of Insulin-Like Growth Factor-1 As A Therapeutic Approach For The Treatment Of Traumatic Brain Injury, Shaun W. Carlson
Theses and Dissertations--Physiology
Traumatic brain injury (TBI) is a prevalent CNS neurodegenerative condition that results in lasting neurological dysfunction, including potentially debilitating cognitive impairments. Despite the advancements in understanding the complex damage that can culminate in cellular dysfunction and loss, no therapeutic treatment has been effective in clinical trials, highlighting that new approaches are desperately needed. A therapy that limits cell death while simultaneously promoting reparative mechanisms, including post-traumatic neurogenesis, in the injured brain may have maximum effectiveness in improving recovery of function after TBI. Insulin-like growth factor-1 (IGF-1) is a potent growth factor that has previously been shown to promote recovery of …
Glutamate Dysregulation And Hippocampal Dysfunction In Epileptogenesis, Seth R. Batten
Glutamate Dysregulation And Hippocampal Dysfunction In Epileptogenesis, Seth R. Batten
Theses and Dissertations--Medical Sciences
Epileptogenesis is the complex process of the brain developing epileptic acitivity. Due to the role of glutamate and the hippocampus in synaptic plasticity a dysregulation in glutamate neurotransmission and hippocampal dysfunction are implicated in the process of epileptogenesis. However, the exact causal factors that promote epileptogenesis are unknown.
We study presynaptic proteins that regulate glutamate neurotransmission and their role in epileptogenesis. The presynaptic protein, tomosyn, is believed to be a negative regulator of glutamate neurotransmission; however, no one has studied the effects of this protein on glutamate transmission in vivo. Furthermore, evidence suggests that mice lacking tomosyn have a …
High-Activity Mutants Of Human Butyrylcholinesterase For Cocaine Abuse Treatment, Liu Xue
High-Activity Mutants Of Human Butyrylcholinesterase For Cocaine Abuse Treatment, Liu Xue
Theses and Dissertations--Pharmacy
Cocaine is a widely abused drug without an FDA-approved medication. It has been recognized as an ideal anti-cocaine medication to accelerate cocaine metabolism producing biologically inactive metabolites via a route similar to the primary cocaine-metabolizing pathway, i.e. butyrylcholinesterase (BChE)-catalyzed hydrolysis. However, the native BChE has a low catalytic activity against cocaine. We recently designed and discovered a set of BChE mutants with a high catalytic activity specifically for cocaine. An ideal, therapeutically valuable mutant of human BChE should have not only a significantly improved catalytic activity against cocaine, but also certain selectivity for cocaine over neurotransmitter acetylcholine (ACh) such …
Computational Modeling, Design, And Characterization Of Cocaine-Metabolizing Enzymes For Anti-Cocaine Medication, Lei Fang
Theses and Dissertations--Pharmacy
Cocaine is a widely abused and addictive drug, resulting in serious medical and social problems in modern society. Currently, there is no FDA-approved medication specific for cocaine abuse treatment. The disastrous medical and social consequences of cocaine abuse have made the development of an anti-cocaine medication a high priority. However, despite decades of efforts, traditional pharmacodynamic approach has failed to yield a truly useful small-molecule drug due to the difficulties inherent in blocking a blocker like cocaine without affecting the normal functions of the transporters or receptors. An alternative approach, i.e. pharmacokinetic approach, is to interfere with the delivery of …
Expression Of Rna Nanoparticles Based On Bacteriophage Phi29 Prna In Escherichia Coli And Bacillus Subtilis, Le Zhang
Theses and Dissertations--Pharmacy
Currently, most of the RNAs used in lab research are prepared by in vitro transcription or chemical synthesis, which can be costly. In vivo expression in bacterial cells is another approach to RNA preparation that allows large scale production at a lower cost. However, there are some obstacles in bacterial expression, including RNA degradation in host cell, as well as RNA extraction and purification. tRNA and 5S RNA have been reported as scaffolds to circumvent the degradation problem. These scaffolds can not only make the RNA product survive in the cell but also increase the stability after extraction.
The packaging …
Acculturative Stress And Depressive Symptoms Among Korean Immigrant Elders Residing In Non-Korean Ethnic Enclaves, Stephanie Lyu Rhee
Acculturative Stress And Depressive Symptoms Among Korean Immigrant Elders Residing In Non-Korean Ethnic Enclaves, Stephanie Lyu Rhee
Theses and Dissertations--Social Work
Few studies have examined the relationships among personal factors, acculturative stress, coping resources, and depression of Korean immigrant elders residing in areas without any Korean ethnic enclave. Based on the stress and coping model and the sociocultural model of stress, coping, and adaptation, this cross-sectional study examined the relationships among acculturative stress, coping, and depression in 111 non-institutionalized Korean immigrant elders aged 60 and older residing in areas without any Korean ethnic enclaves in three neighboring states of Southwestern Ohio, North Central Region of Kentucky, and Southern Indiana. A majority of convenience and snowball sample participated in self-administered mailed surveys, …
A Framework For Understanding The Public's Perspectives Of Mining Applied To The Kentucky Coal Industry, Joshua M. Hoffman
A Framework For Understanding The Public's Perspectives Of Mining Applied To The Kentucky Coal Industry, Joshua M. Hoffman
Theses and Dissertations--Mining Engineering
People’s perceptions of mining are heavily based on the media they consume and the messages therein. News outlets ordinarily report on mining only when there is an accident or environmental concern. When messages that the public is exposed to are negative, it is no wonder that there are negative perceptions about mining.
Current public relations campaigns on the behalf of specific companies or select sectors do exist; however, this is often a reactionary move in response to recent shifts in the socio-political environment. The details of these campaigns are often tied up in proprietary information or withheld by public relations …
Enhanced Phosphate Flotation Using Novel Depressants, Lingyu Zhang
Enhanced Phosphate Flotation Using Novel Depressants, Lingyu Zhang
Theses and Dissertations--Mining Engineering
Froth flotation is the most efficient method for phosphate separation, which is a physic-chemical separation process based on the difference of surface properties between the valuable minerals and unwanted gangue minerals. However, the presence of clay slimes in the slurry after grinding consumes a large amount of reagents, decreases the collision probability between bubbles and minerals, prevents phosphate particle attachment to air bubbles, and thus considerably reduces flotation recovery and concentrate grade. Georgia Pacific Chemical, LLC has recently developed novel depressants, i.e., clay binders, which are a series of low molecular weight specialty polymers to help improve phosphate flotation performance …
Cerium Oxide (Ceo2) Promoted Oxygen Carrier Development And Scale Modeling Study For Chemical Looping Combustion, Fang Liu
Theses and Dissertations--Mechanical and Aerospace Engineering
According to IPCC reports, the greenhouse gas CO2 is responsible for global climate change. Studies show that CO2 concentration reached a level of 400 ppm in 2013, or 40 % above pre-industrial levels. The contribution of CO2 from industrial activity to increasing global CO2 concentrations is widely accepted and points to the need to reduce the emission of this greenhouse gas.One possible combustion technology that shows promise for reducing CO2 emissions is chemical looping combustion (CLC). It is an oxy-fuel technology, but has the advantages of in situ oxygen separation, low NOx emissions and …
Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach
Nmda Receptors In The Dorsal Vagal Complex Of Normal And Diabetic Mice, Eva C. Bach
Theses and Dissertations--Physiology
The dorsal vagal complex (DVC), containing the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus nerve (DMV), plays a pivotal role in autonomic regulation. Afferent fibers from peripheral organs and higher brain centers synapse in the NTS, which integrates these synaptic connections as well as information from systemically circulating hormones and metabolites. The integrated information is relayed to the dorsal motor nucleus of the vagus nerve (DMV), which in turn, projects motor fibers to elicit parasympathetic control of digestive and other viscera. Physiological functions mediated by the DVC are disrupted in diabetic patients and …
Defining The Role Of Reactive Oxygen Species, Nitric Oxide, And Sphingolipid Signaling In Tumor Necrosis Factor - Induced Skeletal Muscle Weakness, Shawn Stasko
Theses and Dissertations--Physiology
In many chronic inflammatory diseases, patients suffer from skeletal muscle weakness, exacerbating their symptoms. Serum levels of tumor necrosis factor-alpha (TNF) and sphingomyelinase are increased, suggesting their possible role in the progression of this weakness. This dissertation focuses on the role that reactive oxygen species (ROS) and nitric oxide (NO) play in mediating TNF-induced skeletal muscle weakness and to what extent sphingolipid signaling mediates cellular response to TNF.
The first aim of this work was to identify which endogenous oxidant species stimulated by TNF contributes to skeletal muscle weakness. In C57BL/6 mice (n=38), intraperitoneal injection of TNF elicited a 25% …
Influence Of Coping Styles On Emotional State, Illness Perception, And Information Sources Of Men With Prostate Cancer, Gwendolyn M. Hooper
Influence Of Coping Styles On Emotional State, Illness Perception, And Information Sources Of Men With Prostate Cancer, Gwendolyn M. Hooper
Theses and Dissertations--Nursing
Prostate cancer (PCa) has been the leading cause of cancer death in men since1930. While studies pertaining to PCa have primarily focused on the disease and the subsequent side effects of treatment, psychological distress in this group has yet to be adequately addressed. The purpose of this dissertation was to: 1) conceptualize health related quality of life (HRQL) and health seeking behavior of men by describing lifestyle, cultural and health risks associated with being male, 2) evaluate the psychometric properties of the SF-12 Health Survey (SF-12) combined with the urinary and sexual portions of the UCLA PCa Index (UCLA-PCI), 3) …
Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami
Diet-Induced Obesity: Dopaminergic And Behavioral Mechanisms As Outcomes And Predictors, Vidya Narayanaswami
Theses and Dissertations--Pharmacy
Obesity and drug abuse share common neural circuitries including the mesocoticolimbic and striatal dopamine reward system. In the current study, a rat model of diet-induced obesity (DIO) was used to determine striatal dopamine function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. For the outcome study, rats were randomly assigned a high-fat (HF) or a low-fat (LF) diet for 8 wk. Following the 8-wk HF-diet exposure, rats were segregated into obesity-prone and obesity-resistant groups based on maximum and minimum body weight gain, respectively, and neurobehavioral outcomes were evaluated. For the predictor study, neurobehavioral antecedents were evaluated prior to …
High Dose Simvastatin As A Potential Anticancer Therapy In Leukemia Patients, Tamer Ahmed
High Dose Simvastatin As A Potential Anticancer Therapy In Leukemia Patients, Tamer Ahmed
Theses and Dissertations--Pharmacy
Simvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that is used for the treatment of hyperlipidemia. Simvastatin has recently been studied for its potential use in cancer therapy. In-vitro studies have shown that simvastatin displays anticancer activity, but at concentrations unlikely to be achieved in patients being receiving typical antihyperlipidemic treatment doses. Thus, several clinical trials were conducted to study the tolerability of high dose statins in cancer patients. The maximum tolerated dose of simvastatin was determined to be 15 mg/kg/day, 25-fold higher than a typical dose. However, it is not known if simvastatin plasma concentrations can reach those …
Synthesis And Stability Studies Of Prodrugs And Codrugs Of Naltrexone And 6-Β-Naltrexol, Joshua A. Eldridge
Synthesis And Stability Studies Of Prodrugs And Codrugs Of Naltrexone And 6-Β-Naltrexol, Joshua A. Eldridge
Theses and Dissertations--Pharmacy
The present study was divided between two different drug delivery goals, each involving naltrexone (NTX) or its active metabolite, 6-β-naltrexol (NTXOL). First, amino acid esters of NTX and NTXOL were prepared in order to test their candidacy for microneedle-enhanced transdermal delivery. Second, a 3-O-(-)-cytisine-naltrexone (CYT-NTX) codrug was prepared for screening as a potential oral delivery form of NTX and (-)-cytisine (CYT). The amino acid prodrugs were intended for the treatment of alcohol abuse, while the codrug was designed as a single agent for the treatment of alcoholism and tobacco-dependency co-morbidities. One hypothesis of this work was that prodrugs …