Digital Commons Network^™

Examples Of Population Pharmacokinetic Modeling In Drug Development Using Nonmem, Julie M. Jones

Open Access Dissertations

The population approach to pharmacokinetic analysis, and its application to the identification of patient characteristics that affect a drug's pharrnacokinetic parameters, is achieving greater prominence in the drug development process. Specifically, population analyses are a way to gather information that might be difficult to capture in some subpopulations. In the fall of 1997, the Food and Drug Administration proposed new legislation, commonly known as the ''Pediatric Rule". This new legislation required pharmaceutical companies to collect pediatric data for drugs with indications applicable to children before the compound would be approved. Other than conducting traditional pharrnacokinetic clinical trials, another way to …

Optimizing Parameters For Efficient Introduction Of Transgenes Into Turfgrass, Chhandak Basu

Open Access Dissertations

Embryogenic callus was generated from seeds of turfgrass species (creeping bentgrass, cv. Penn A4 and Providence) on tissue culture medium. After 12 weeks, embryogenic calli were identified and used for bombardment with chimeric gene constructs that confer phosphinothricin resistance (bar) as a selectable marker and β-glucuronidase (GUS) as a reporter gene. After bombardment, the calli were transferred to selection medium and then to regeneration medium. Putative transgenic turfgrass plants were generated and molecular analysis (PCR) was performed to confirm presence of the transgene (bar, GUS). We analyzed reporter gene (GUS) expression in turfgrass cells over a developmental time period of …

Neuronal Control Of Nematocyst Discharge In Hydra, A. A. Scappaticci Jr.

Open Access Dissertations

This dissertation research seeks to understand how the neuronal circuitry of the battery cell complex in hydra functions in order to accomplish the basic biological necessity of food acquisition through its effector organelles, the nematocysts. A behavioral assay was used to discharge individual nematocysts from the tentacles of Hydra vulgaris. Cnidocils were mechanically deflected using a piezoelectrically driven glass probe. Standard immunohistochemical methods were used to localize the N-methyl-D-aspartate receptor in hydras tissues. Desmonemes and stenoteles differentially responded to imposed forces on the cnidocil. Desmonemes discharged when the cnidocil was struck with a force of at least 3.7 × 10−3 …

Sources, Transport, And Fates Of Particulate Trace Metals In The Gulf Of Maine-Scotian Shelf And Labrador Sea, Sarah Elizabeth Weinstein

Open Access Dissertations

This dissertation research describes three studies examining of the role of particulate metals in the northwest Atlantic Ocean. Manuscript 1 provides a discussion of the distribution of a suite of size-fractionated particulate trace metals (Al, Fe, Sr, Ba, Mn, Pb, Cu, V, and Co) in the Gulf of Maine, Scotian Shelf and Labrador Sea. An important facet of this study is the demonstration that the Challenger Oceanic Systems and Services large-volume in-situ pump is a valuable tool for the collection of size-fractionated particulate metals in the marine environment. In Manuscript 2, an empirical approach to quantify the downward flux of …

The Dec1 Transcription Factor: Oncogenic Involvement And Molecular Mechanisms On Transcription Regulation, Yuxin Li

Open Access Dissertations

The basic helix-loop-helix (bHLH) proteins are intimately associated with developmental events such as cell differentiation and lineage commitment. The HLH domain in the bHLH motif is responsible for dimerization whereas the basic region mediates sequence specific DNA binding. Human DEC, mouse STRA and rat SHARP proteins represent a new c lass of bHLH proteins. In each species, two members are identified with a sequence identity of>90% in the bHLH region and - 40% in the total protein, respectively. Based on sequence alignment and domain analysis, DEC/STRA/SHARP proteins show high s imilarities (- 40%) to Drosoph ila Hairy and E(spl) …

Micropropagation Of Carnivorous Plants, Kenneth Stephen Uhnak

Open Access Dissertations

A simple, efficient system for seed surface disinfestation and in vitro germination was developed for the carnivorous pitcher plants Darlingtonia californica and Sarracenia leucophylla. Of the disinfectants tested, hydrogen peroxide or 10% Clorox® were most effective for disinfesting seeds of D. californica, while concentrated sulfuric acid worked best for S. leucophylla. Differences in the effectiveness of sterilants were associated by differences in seed coat morphology. Seeds of D. californica imbibed at 4-7°C in sterile deionized water with surfactant and gibberellin germinated earlier than seeds without exposure to gibberellin. Unimbibed seeds of S. leucophylla germinated …

Gaba B Receptors In The Ventral Tegmental Area Regulate Morphine-Induced Motor Sensitization And Accumbal Fos Expression In C57bl/6 Mice, Kimberly Anne Leite-Morris

Open Access Dissertations

Mesolimbic dopamine (A10) neurons have a central role in mediating opiate-induced motor sensitization and are implicated in drug addiction. This dissertation examines the hypotheses that GABAB receptors are located in the ventral tegmental area (VTA), that morphine sensitization occurs via A10 neuronal activation, and that GABAB receptor activation in the VTA inhibits the development and expression of morphine-induced sensitization. Dopaminergic neurons projecting from the VTA to the nucleus accumbens (NAc) of the forebrain are involved in mediating behavioral sensitization to morphine. GABA B receptor activation in the VTA leads to inhibition of dopaminergic transmission and inhibition of opiate actions. Sensitization …

The Regulation And Function Of Inositol Phosphorylceramide Synthase In The Yeast Saccharomyces Cerevisiae, Angeleah Arlene Browdy

Open Access Dissertations

IPC Synthase has been shown to be an essential membrane bound enzyme in yeast that catalyzes the transfer of PI to ceramide to yield the primary sphingolipid found in yeast, Inositolphosphorylceramide. A biochemical approach was taken to investigate the biological factors that regulate IC synthase activity in order to better understand the sphingolipid synthesis. A highly purified IPC synthase was purified over 1000-fold from the yeast Saccharomyces cerevisiae by a procedure that included Triton X-100 solubilization, as well as a series of ion exchange and hydrophobic column chromatography steps. The highly purified enzyme fraction contained three major bands at 45, …

Geomagnetic Sensitivity And Orientation In Eastern Garter Snakes (Thamnophis Sirtalis), Douglas Eliot Smith

Open Access Dissertations

Thirteen eastern garter snakes (Thamnophis sirtalis) were each kept in a terrarium for 10 to 15 days inside a solenoid made of electrical wire and attached to a DC power source. When activated, the solenoid reduced the intensity and reversed the direction of the ambient magnetic field inside the aquarium. Food was placed in an L-shaped corridor attached to the aquarium before the solenoid was turned on. The time between activation of the solenoid and the first strike at the food was measured. Snakes that were exposed to the magnetic cue learned to associate it with the presence of food …

Functional Characterization Of The Pregnane X Receptor, He Zhang

Open Access Dissertations

Cytochrome P450 3A enzymes (CYP3A) are involved in the metabolism of two thirds of drugs and other xenobiotics, and highly induced by structurally diverse xenobiotics. Induction of CYP3A causes many drug-drug interactions, and an orphan nuclear receptor, the pregnane X receptor (PXR) is established to mediate the induction of CYP3A in mouse and human. Structurally, the PXR has a N-terminal uncharacterized domain, a conserved DNA binding domain (DBD) and a diverse C-terminal ligand binding domain (LBD). The purpose of the studies described in this dissertation is to characterize the role of the N-terminal domain and the LBD in PXR-mediated signaling …

Breast Cancer Experiences: Women's Reflections Years After Diagnosis, Margaret Barton-Burke

Open Access Dissertations

Many women diagnosed with breast cancer m the last decade are either living with active treatment for the disease or are classified as cured but living with the sequelae of the disease or treatment. Most research has been on the physical aspects of the disease and conducted during or immediately after active treatment. Information beyond the physical dimension of women's experiences is small and narrowly focused, and research beyond 5 years is almost nonexistent. A full depiction of the multidimensional nature of being diagnosed with, treated for, recovering from, and living with the aftermath of breast cancer is lacking. The …

Peer Group Instructional Conversation: Collaboration In Context, Linda Greene Capalbo

Open Access Dissertations

American schools traditionally have reflected and promoted societal values of autonomy and independence in the development of the individual child. This limited perspective on how humans come to know focuses on the accrued cultural capital of each learner and neglects the role of 'the other' in the construction of meaning. Such a view can be especially debilitating for students who have been identified as marginal learners. This study examines how social interaction organizes participation opportunities and strategies for members of a peer learning group, including a student designated language learning disabled. The study documents the development and negotiation of individual …

Lagrangian Studies Of Oxygen Variability In The North Atlantic Ocean, Peter Lazarevich

Open Access Dissertations

During 1997-2000, our research group participated in a major field study to determine the absolute circulation of the Subpolar North Atlantic. We successfully tracked 50 isopycnal RAFOS floats which measured pressure, temperature, and dissolved oxygen. The floats were ballasted for the 27.5 σ &thetas; density surface, which is found in the lower subtropical thermocline waters of the North Atlantic. A comparison of our field results to historical hydrography for the region shows that the oxygen sensors provided an accuracy of about 5% over periods exceeding one year. One of our goals was to understand the conspicuous difference between the hydrographically …

Rational Approaches To The Regulation Of Nonprescription Medicines, Anand S. Achanta

Open Access Dissertations

In recent years, self-medication products have undergone a dramatic change due to the advent of herbal medicines, dietary supplements, nutraceuticals and health foods in addition to traditional nonprescription medicines and the increasing societal preferences towards greater individual control over the use of medicines. Globally, the role and importance of nonprescription medicines in healthcare delivery is also rapidly increasing due to the potential cost-savings. Hence, this area is beginning to receive much attention from regulatory authorities, academia and professional/industry/trade organizations.

This dissertation presents a comprehensive analysis of the classification of nonprescription medicines and Rx-to-OTC switch criteria/policy in the United States, United …

New England Salt Marsh Pools: Analysis Of Geomorphic And Geographic Parameters, Macrophyte Distribution And Nekton Use, Susan C. Adamowicz

Open Access Dissertations

Salt marsh pools are shallow, steep-sided depressions that remain flooded throughout a tidal cycle and provide important habitat for nekton (fish and decapod crustaceans). Although New England pools are relatively unstudied, efforts are underway to expand pool habitat through an open marsh water management technique know as ditch plugging. The purpose of this study was to quantify pool geomorphic and geographic characteristics, to determine distribution of vegetative cover types and nekton species, and to evaluate effects of ditch plugging on nekton use of pools.

Over 30 ditched and unditched marshes were surveyed from the Connecticut shore of Long Island Sound …

Development Of A Numerical Model For Shallow Marine Ecosystems With Application To Greenwich Bay, Rhode Island, Mark James Brush

Open Access Dissertations

Numerical models have become increasingly important tools for the study of marine ecosystems. While these models serve as valuable research and heuristic tools, they are not yet to the point of producing reliable predictions upon which to base management decisions. Further, most existing models of coastal systems have been constructed for relatively deep estuaries rather than shallow, nearshore systems which receive the bulk of anthropogenic nutrient loading and experience the most extreme degradation in water quality. A numerical model was developed for shallow marine ecosystems which contain both pelagic and benthic compartments of the food web. A series of innovations …

Effects Of Mobile Fishing Gear On The Benthic Megafauna And Production Of Georges Bank, Jerome Michael Hermsen Jr.

Open Access Dissertations

Although the effects of mobile fishing gear on the habitat and productivity of the sea bottom has warranted attention for several centuries, recent concern has fueled an upsurge in research into the ecosystem effects of fishing over the last decade. This dissertation addresses the effects of mobile fishing gear disturbance on the benthic megafaunal productivity, scavenging amphipods and isopods, and benthic habitat-mediated survival of juvenile cod ( Gadus morhua). Using baited traps, scavenging amphipod and isopod populations were sampled at deep and shallow sites in disturbed and undisturbed areas on the northern part of Georges Bank and in the Great …

Leftist Literature And The Ideology Of Eugenics During The American Depression, Sarah Catherine Holmes

Open Access Dissertations

This dissertation examines both literary and non-literary works to illustrate how leftist writing was profoundly influenced by notions of eugenics which circulated widely in Depression-era America, though often just beneath the surface. One of the most popular movements during the Great Depression was the attempt to prove that certain groups of the American population were "unfit" and that society should take intentional steps to intervene in citizens' reproductive rights. This eugenics doctrine was so pervasive that it became embodied in a variety of texts, including many "leftist" texts, thereby producing an ideological crisis for many of these writers. Leftist literature …

The Nature Of Infant Relinquishment As Described By Two Voices: The Relinquishing Mother And The Obstetrical Nurse, Linda Jean Kobokovich

Open Access Dissertations

Little is known about the relinquishment experience and nursing interventions for infant relinquishment. The purpose of this study was to first, describe in the birth mother's voice, the relinquishment experience and her perception of nursing interventions, while second, creating an inventory of nursing interventions. Kim's (2000) Practice Domain provided the theoretical background. This two-phase study used an inductive, qualitative approach and employed a mixed method design of semi-structured interview and focus group interview. The interview was crafted upon the interview style of McCracken (1988) and Spradley (1969) while focus group methodology as detailed by Morgan (1993, 1996) guided the second …

A Proposed Model Of Medical Staff-Family Communication In The Context Of Cancer: Psychometric, Model And Mediational Testing, Dana Anne Gionta

Open Access Dissertations

This dissertation extends our knowledge of the relationships among complex communication variables involved in medical staff-family member communication in the context of adult cancer. It does this in three ways. First, communication variables are quantified using qualitative data from previous studies in the area of cancer, communication and the family to provide a more systematic means of studying these variables. Manuscript 1 examines the psychometric soundness of these instruments with results indicating a single factor structure for each instrument, preliminary evidence for construct and content validity and good to excellent internal consistency (.77, .91, .93., .97). Second, a model of …

Genetic Transformation Of Bentgrasses For Fungal Disease Resistance, Yuexia Wang

Open Access Dissertations

Genetic transformation of cultivated plants is a new tool that could be used to improve plants for higher yield, better quality, and enhanced stress tolerance. To establish a stable and efficient biolistic-mediated genetic transformation system for bentgrass trait improvement, this research focused on: (1) comparing growth media for embryogenic callus induction and plantlet regeneration; (2) transferring bar, chitinase, glucanase and barnase genes into embryogenic calli of creeping and velvet bentgrasses, and regenerating transgenic plants from the transformed calli; (3) evaluating the transgenic plants by using herbicide glufosinate, polymerase chain reaction (PCR), Southern blot and northern blot hybridization assays; and (4) …

Fish Landmarks For Chromosome 11 Of Bombyx Mori: An In Situ Analysis, Charles Eugene Mcgovern

Open Access Dissertations

Fluorescence in situ hybridization (FISH) has been used to simultaneously identify the positions of the ribosomal DNA and the Sericin genes on chromosome 11 of Bombyx mori. The ribosomal DNA genes were detected using biotin labeled plasmid pBmR 161 and avidin-Texas Red and the Sericin 2 gene was detected using digoxigenin labeled plasmid 2002 and anti-digoxigenin-fluorescein. The position of the Sericin 1 gene was identified using the ribosomal DNA genes as a chromosomal landmark. Sericin 1 was detected using digoxigenin labeled bacterial artificial chromosome 9HJD and anti-digoxigenin-fluorescein. The chromosomal spreads were counterstained with diamindino-phenyl-indole (DAPI). The signals from the sericin …

Market Information And Fisheries Management: Improving Efficiency In Private Property Right Management Systems, Eyjolfur Gudmundsson

Open Access Dissertations

Fisheries economics concentrates on solving the problem of economic overexploitation in fisheries. The field took its first steps, as a specialized study area within economics, in the early 1950s. The approach since then, for solving the problem of overexploitation, has mostly been one of neo-classical economics, with emphasis on the production side of the problem. A potential solution to the overexploitation problem is the privatization of fisheries in order to maximize long-term economic benefits. Recent studies have shown that prices and certain product characteristics are an important factor for determining the optimal management of fisheries. This study tries to establish …

Regulation And Mechanisms Of Excitation-Contraction Coupling In The Ventricular Myocardium Of The Surf Clam, Spisula Solidissima, Leon Paul Collis

Open Access Dissertations

Extensive research has previously examined the extrinsic, neural regulation of the bivalve myocardium, via the action of such neurotransmitters as acetylcholine, serotonin and the tetrapeptide, FRMFamide. This investigation was performed in order to identify any intrinsic, autoregulatory (mechanical or pharmacological) processes, which attenuate or amplifier cardiac activity. For this purpose, the ventricular muscle of the bivalve, Spisula solidissima , was used. The ultrastructure was described in order to explain specific excitation-contraction (EC) coupling mechanisms that were elucidated in this study. Manuscript 1 identified and characterized shortening deactivation in ventricular trabeculae of the surf clam. This is defined as the loss …

The Ecology And Morphology Of Eelgrass (Zostera Marina L.) And Its Associated Macrophyte Community In Relation To Environmental Variables, Joanne C. Bintz

Open Access Dissertations

Shallow coastal lagoons are subject to anthropogenic nutrient enrichment and disturbances that result in loss of seagrass ecosystems. These losses have generated a desire by coastal managers for tools to monitor existing seagrass meadows, and to restore those that have been lost. The following Chapters in this dissertation address aspects of these issues. Chapter 1 documents a nearly 16 month study of Zostera marina seasonal and year-to-year leaf and rhizome morphology and growth in Ninigret Pond, R.I. Individual shoots produced approximately 0.11 leaves per day from March to December. Shoot surface area and the length of the longest leaf on …

Analysis And Simulation Of Skeletonema Costatum (Grev.) Cleve Annual Abundance Patterns In Lower Narragansett Bay 1959 To 1996, David Gerald Borkman

Open Access Dissertations

A 38-year time series (1959 to 1996) of weekly observations of abundance of the marine diatom Skeletonema costatum and related plankton habitat parameters in lower Narragansett Bay, Rhode Island was analyzed. A phytoplankton growth model was then developed for investigation of Skeletonema annual abundance pattern regulating mechanisms. A ca. 45% decline in Skeletonema abundance was detected, from 2,292 cells ml−1 (prior to September 1974) to 1,263 cells ml−1 (after August 1980). Winter-spring decreases were greatest, with declines in March Skeletonema abundance from near 3,400 cells ml−1 before a 1977 change-point to mean abundance of ca. 1,000 cells ml−1 after 1977. …

Individual Differences In Toddler Emotion Coping: The Impact Of Temperament And Socialization Experiences On Regulation Development, Elena Mirsky

Open Access Dissertations

The current study explores the expression of emotion coping behaviors in the developmental context of temperamental and socialization experiences. 45 30- month-olds, whose families were involved in a larger longitudinal study, participated in a laboratory assessment including 4 contexts designed to provide an experience of stress for the child. Child coping behaviors were coded according to a system by Grolnick (1996) which rates behaviors along a continuum of adaptiveness from focusing on the course of frustration, to self-comforting and other-directed behaviors, to behavior that is re-oriented toward the environment. Correlations were run between coping data and data on child temperament …

A Comprehensive Mass Balance Of A Watershed Under Steady State Conditions, Oran Joseph Viator Jr.

Open Access Dissertations

Blackstone River water quality data collected during three dry weather surveys of the river was used in a comprehensive mass balance of selected water quality constituents for the river under steady state conditions, and to develop a method that can be applied to separate point and non-point source loads to the river. Mass balances for the river reaches between each dry weather sampling station were completed which isolated point sources, resulting in the identification of those reaches that were major contributors of pollutant loads to the river. These non-point sources, and the point sources, were ranked according to their dry …

An Alternate To Chromate Conversion Coatings For The Corrosion Protection Of Aluminum 2024-T3, Ruiguang Guo

Open Access Dissertations

Corrosion of high-strength aluminum alloys used for airspace application is an expensive and serious problem. The most significant environmental factor contributing to the corrosion of these alloys is water condensed from humid air and contaminated with soluble chloride salts. The Al 2024 series used for aircraft are particularly susceptible to corrosion in aqueous chloride solutions due to alloying constituents such as copper and other impurities. Chromates are efficient inhibitors of corrosion of aluminum in near neutral aqueous environments containing aggressive anions such as chlorides. Usually, aluminum alloys are initially protected by chromate conversion coatings. Additional polymer coatings are sometimes added …

Heat Shock Proteins And Osmotic Shock In Atlantic Salmon (Salmo Salar), Feng Pan

Open Access Dissertations

Heat shock proteins are molecular chaperones. Atlantic salmon is a major aquaculture species in the world, their anadromous nature made them encounter osmotic shock twice in the life cycle. Salmon prior treated with a mild thermal shock observed a significantly higher survival rate upon transfer to hyperosmotic seawater than control fish. Heat shock protein 70 was prominently induced and persisted up to 24 hours after initial heat shock. Fish with prior heat shock treatment exhibited significant higher rate of protein synthesis over control after transfer to seawater. Hsp90 is known to enhance the fidelity of glucocorticoid hormone and receptors. Northern …