Life Sciences Commons^™

Elucidating Cellular Signaling Pathways That Contribute To The Immunopathogenesis Of Aplastic Anemia, Christina M. Kuksin

Doctoral Dissertations

Aplastic Anemia is a rare immune mediated bone marrow failure disease that is mediated by autoreactive T cells that cause destruction to the stem, progenitor, and stromal cells in the bone marrow. Because little is known about the etiology of the disease, our lab has developed a major MHC mismatch GVHD model to examine cellular pathways in autoreactive T cells that contribute to disease. We examined three pathways that are important in T cell activation and differentiation and asked if they were important in the development of Aplastic Anemia. First, we were able to show that expression of active PKCθ …

Dried Whole Plant Artemisia Annua As A Novel Antimalarial Therapy, Mostafa A. Elfawal

Doctoral Dissertations

Dried Whole plant Artemisia annua as a novel antimalarial therapy September 2014 Mostafa Ahmed Elfawal Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor Stephen M. Rich Malaria is one of the worst vector-borne parasitic diseases in the developing world. The World Health Organization (WHO) estimated that 215 million cases of malaria occurred, with >655,000 deaths; half the world’s population is at risk of contracting the disease. Drugs are primary weapons for reducing malaria in human populations. Successful drugs are highly efficacious and inexpensive to manufacture synthetically. However, emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that …

Evaluating Predictors Of An Individual’S Dietary Intake Latent Value Under Different Mixed Models, Shuli Yu

Doctoral Dissertations

The accurate estimation of an individual’s usual dietary intake is important since the estimates are essential to uncover the diet-disease relationships. This study explores a more accurate method to estimate an individual’s latent value of usual dietary intake when it is repeatedly measured using a 24-hour dietary recall (24HR) and seven day dietary recall (7DDR), accounting for random measurement error and bias. The performance of the (empirical) predictor of subject’s latent value obtained under the finite population mixed model (FPMM) framework is compared with those obtained under the usual mixed model and the measurement error model through a simulation study. …

Ligand-Receptor Interactions For Supramolecular Disassembly With Applications In Screening And Drug Delivery, Diego Amado Torres

Doctoral Dissertations

Proteins have the capacity to bind specific sets of compounds known as ligands, these are small molecules with a recurrent theme in their molecular design that is a characteristic exploited here to (i) identify particular affinities of small molecules for proteins with the aim of using them as ligands, inhibitors, or targeting moieties in more complex systems by means of a methodology that screens small molecules based on protein affinity; (ii) decorate a self-assembling supramolecular system at different positions, making it responsive to a complementary protein with the aim of exploring differences in disassembly and sensitivity of the release of …

Associations Of Total Activity Counts And Physical Activity Intensity Levels With The Metabolic Syndrome: A Structural Equation Modeling Approach, Dana Lizbeth Wolff

Doctoral Dissertations

To clarify the protective benefits of physical activity (PA), epidemiologists and public health researchers continue to seek improved methods of assessing PA. In particular, accelerometers have gained acceptance with researchers as they provide reliable estimates of PA and can record both the amount and intensity of ambulatory movement. However, there is concern that accelerometer data reduction techniques may not provide quantitatively accurate measurements of time spent in various PA intensity categories. One way to circumvent these inaccuracies is to use the accelerometer-derived total activity counts (TAC), which is a more direct expression of what the monitor records.

In order to …

Cd4 Silencing In Thymocytes Is Opposed By The Enforced Association Of P300 Hat, Hdac1 Or Suv39h1 With Runx Transcription Factors, Christyne Ayne Kane

Doctoral Dissertations

The transcription factors Runx1 and Runx3 are required for permanent silencing of CD4 in maturing CD8+ thymocytes. Runx binding to consensus sites within the CD4 silencer region is required for CD4 silencing post-positive selection. The Runx nuclear matrix targeting sequence (NMTS) is required for CD4 silencing and is implicated in binding to the histone acetyltransferase (HAT) p300, histone deacetylases (HDAC), and histone methyltransferase (HMT) SUV39H1 proteins. Epigenetic modifications of chromatin or post-translational modifications of Runx itself as a result of Runx association with these enzymes may be important for establishment of long-term CD4 silencing. In this study, we show that …

Exploration Of Breastfeeding Concepts Among Current And Future Parents: Results Of Questionnaires Administered To Chinese And Us University Students And To New Mothers In China, Zixin Lou

Doctoral Dissertations

The objectives were to explore breastfeeding knowledge, attitudes, and intention of future parents, and to investigate indicators and causes of perceived insufficient milk (PIM) supply among Chinese mothers. Objectives were accomplished using a cross-sectional study design. Two questionnaires were developed, one targeting Chinese and US undergraduates, and a second targeting Chinese mothers. In total, 597 undergraduates (395 Chinese; 202 US) and 392 Chinese mothers participated in the study. Data cleaning resulted in a final sample size of 572 for undergraduates (383 Chinese; 189 US) and 341 for Chinese mothers. Results showed that undergraduates in both countries possessed some breastfeeding knowledge …

Functional Analysis Of Corazonin And Its Receptor In Drosophila Melanogaster, Kai Sha

Doctoral Dissertations

Corazonin (Crz) is an amidated undecapeptide originally isolated from the American cockroach. It has been shown to affect diverse physiological functions in a species-specific manner. However, the functionality of Crz in Drosophila melanogaster has not yet been determined. To gain insight into the role of Crz signaling in vivo, Crz and CrzR null alleles were obtained by transposable element mobilization. Flies carrying a deficiency uncovering Crz and pr-set7 loci were generated via P-element excision, and the latter was rescued by wild-type pr-set7 transgene. A mutation of Crz receptor (CrzR) was generated by Minos-element mobilization from …

The Measurement Of Auditory Interhemispheric Transfer Time (Ihtt) In Children With Normal Auditory Processing Abilities, Brittany Suzanne Keahey

Doctoral Dissertations

Interhemispheric transfer time (IHTT) is the time it takes for information to be transmitted from one hemisphere to the other. The goal of this study was to determine if differences existed in the IHTT of children 6 to 9 years of age with normal auditory processing abilities by the use of an objective measure (auditory late evoked potentials [ALEPs]), specifically waves P1, N1 and P2. It was hypothesized that there would be no difference in IHTT between the groups due to the age range of participants being tested. The 16 participants were divided into two groups based on age and …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …

A Description Of The Movement Of The Canine Pelvic Limb In Three Dimensions Using An Inverse Dynamics Method, And A Comparison Of Two Techniques To Surgically Repair A Cranial Cruciate Ligament Deficient Stifle, Jason Headrick

Doctoral Dissertations

The purposes of the dissertation were: 1) to describe three-dimensional (3D) motion of the canine pelvic limb using an inverse dynamics method, and 2) to compare these motion patterns between normal, healthy dogs and those that have had their stifles stabilized by one of two surgical methods approximately five years earlier.

Twenty-five dogs were allocated to three groups; healthy control dogs, dogs that had received the tibial plateau leveling osteotomy (TPLO), and dogs that had received the lateral fabellar suture (LFS) stabilization technique. Both surgical techniques were performed approximately five years prior on stifles with surgically induced cranial cruciate ligament …

A Factor Analysis Of The Health, Safety, And Welfare In The Built Environment Toward Interior Design As Perceived By Building Industry Professionals, Dana Marie Moody

Doctoral Dissertations

This research study created, piloted, and field tested a new instrument designed to collect perceptions toward an interior designer’s impact on the health, safety, and welfare of the public. It also established an initial profile of perceptions within building industry professionals, identified the salient factors within those perceptions, and determined the level of these factors through a factor analysis. The Health, Safety, & Welfare in the Built Environment instrument was developed using a Table of Specifications based on the subject content that interior designers must be familiar with in regards to protecting the health, safety, and welfare of the public …

Effects Of Increased Step Width On Knee Joint Biomechanics In Healthy And Knee Osteoarthritis Older Adults During Stair Descent, Maxime Robert Paquette

Doctoral Dissertations

Stair negotiation is one of the most challenging tasks for older adults especially for those suffering from knee osteoarthritis (OA). To date, no studies have investigated the effects of increased step width (SW) on knee joint biomechanics. The purpose of Study One was to investigate the effects of increased SW on peak internal knee abduction moment and other lower extremity variables during stair descent in healthy older adults. The purpose of Study Two was to investigate the effects of increased SW on peak internal knee abduction moment, knee pain and other lower extremity variables during stair descent in medial compartment …

“It Was Fight Or Flight...And Flight Was Not An Option”: An Existential Phenomenological Investigation Of Military Service Members’ Experience Of Hand-To-Hand Combat, Peter Richard Jensen

Doctoral Dissertations

Hand-to-hand combat is one of the more psychologically challenging performance environments for those in the military (Grossman, 1995). Even with the technological advances of modern warfare military leaders still believe hand-to-hand combat is an important and relevant challenge for service members (Blanton, 2007; Clark, 2009; Collins, 2007; Wojdakowski, 2007; Wood & Micaelson, 2000). Despite its importance, the hand-to-hand combat experience has, to date, attracted very little research attention. Therefore, the purpose of this study was to explore military service members’ experiences of hand-to-hand combat. To accomplish this objective, phenomenological interviews were conducted with 17 male military service members. Each participant …

A Geospatial Based Decision Framework For Extending Marssim Regulatory Principles Into The Subsurface, Robert Nathan Stewart

Doctoral Dissertations

The Multi-Agency Radiological Site Survey Investigation Manual (MARSSIM) is a regulatory guidance document regarding compliance evaluation of radiologically contaminated soils and buildings (USNRC, 2000). Compliance is determined by comparing radiological measurements to established limits using a combination of hypothesis testing and scanning measurements. Scanning allows investigators to identify localized pockets of contamination missed during sampling and allows investigators to assess radiological exposure at different spatial scales. Scale is important in radiological dose assessment as regulatory limits can vary with the size of the contaminated area and sites are often evaluated at more than one scale (USNRC, 2000). Unfortunately, scanning is …

Chemical Tools To Characterize Membrane-Protein Binding Interactions Using Synthetic Lipid Probes, Meng Meng Rowland

Doctoral Dissertations

Signaling lipids such as diacylglycerol (DAG) and the phosphatidylinositol polyphosphates (PIP_ns) play crucial roles in numerous cellular pathways. However, characterization of their activities is hindered by the complexity of associated signaling pathways and of the membrane environment. To address this issue, we have developed lipid probes that are effective for characterizing biological events using different applications, including activity-based probing (PIP_ns and DAG) and microarray analysis (PIP_ns). The activity-based probes have been applied to label receptor targets in multiple cancer cell proteomes through photocrosslinking followed by click reactions. The probes were found to label several …

Development Of An Autonomous Mammalian Lux Reporter System, Daniel Michael Close

Doctoral Dissertations

Since its characterization, the definitive shortcoming of the bacterial luciferase (lux) bioluminescent reporter system has been its inability to express at a functional level in the eukaryotic cellular background. While recent developments have allowed for lux function in the lower eukaryote Saccharomyces cerevisiae, they have not provided for autonomous function in higher eukaryotes capable of serving as human biomedical proxies. Here it is reported for the first time that, through a process of poly-bicistronic expression of human codon-optimized lux genes, it is possible to autonomously produce a bioluminescent signal directly from mammalian cells. The low background of …

Stem Cell Biology And Strategies For Therapeutic Development In Degenerative Diseases And Cancer, Angel A. Alvarez '98

Doctoral Dissertations

Stem cell biology is an exciting field that will lead to significant advancements in science and medicine. We hypothesize that inducing the expression of stem cell genes, using the embryonic stem cell gene nanog, will reprogram cells and dedifferentiate human mesenchymal stem cells into pluripotent stem cells capable of neural differentiation. The aims of initial studies are as follows:

Aim 1: Demonstrate that forced expression of the embryonic stem cell gene nanog induces changes in human mesenchymal stem cells to an embryonic stem cell-like phenotype.

Aim 2: Demonstrate that induced expression of nanog up-regulates the expression of multiple embryonic stem …

Diagnosis And Management Of Horses With Equine Metabolic Syndrome (Ems), Kelly Ann Chameroy

Doctoral Dissertations

In horses, a painful and often debilitating disease known as laminitis can result in impaired function and, in severe cases, euthanasia. Equine Metabolic Syndrome (EMS) is a syndrome in horses that results in development of laminitis and is characterized by the presence of general and/or regional adiposity (“cresty neck”), aberrations in blood lipid concentrations, insulin resistance (IR) and/ or hyperinsulinemia. Therapies have focused on improving the state of obesity and insulin resistance with the goal of diminishing the likelihood of laminitis development. A definitive cause for laminitis has not been established, but hyperinsulinemia and IR are likely candidates as experimental …

The Effect Of Body Mass Index On Pedometer Accuracy In A Free-Living Environment, Brian Matthew Tyo

Doctoral Dissertations

The purpose of this dissertation was to determine if the New Lifestyles NL-2000 (NL) and the Digi-Walker SW-200 (DW), waist-mounted devices, yield similar daily step counts as compared to the StepWatch 3 (SW), an ankle-mounted device, worn by adults and children in the free-living environment.

For the first study, fifty-six adults (32.7 + 14.5 y) wore the devices for seven consecutive days. There were 20 normal weight, 18 overweight, and 18 obese participants. The NL and DW undercounted (pedometer error) similarly in the normal weight and overweight groups (-15.4% to -18.2%, respectively). However, the DW undercounted more than the NL …

Methicillin Resistance In Staphylococcus Pseudintermedius, Chad Christopher Black

Doctoral Dissertations

Staphylococcus pseudintermedius affecting dogs is analogous to S. aureus on humans, acting as both normal flora and opportunistic pathogen. Methicillin resistance in S. pseudintermedius is recent, with the first documented occurrence of an isolate bearing the methicillin resistance gene, mecA, in 1999. This gene encodes penicillin binding protein 2a, which renders all beta-lactam drugs ineffective and functions as a “gateway” antibiotic resistance determinant. In the presence of ineffective antibiotics, opportunities for mutational events and acquisition of mobile genetic elements increase as microbial densities increase, often leading to multi-drug resistance. Methicillin-resistant S. pseudintermedius (MRSP) infections have become increasingly common. For …

Associative Pattern Mining For Supervised Learning, Harpreet Singh

Doctoral Dissertations

The Internet era has revolutionized computational sciences and automated data collection techniques, made large amounts of previously inaccessible data available and, consequently, broadened the scope of exploratory computing research. As a result, data mining, which is still an emerging field of research, has gained importance because of its ability to analyze and discover previously unknown, hidden, and useful knowledge from these large amounts of data. One aspect of data mining, known as frequent pattern mining, has recently gained importance due to its ability to find associative relationships among the parts of data, thereby aiding a type of supervised learning known …

Feline Lentivirus: Molecular Analysis And Epidemiology In Southern African Lions, Hayley Rebecca Adams

Doctoral Dissertations

Feline immunodeficiency virus is a retrovirus of domestic cats causing significant lifelong infection. Infection has also been detected in nondomestic species, including African lions. It is endemic in certain populations in east and southern Africa. Infection leads to immunologic dysfunction and immunosuppressive disease in domestic cats; however, little research exists about the pathogenic effects of infection in lions and its epidemiological impact on free-ranging and captive populations. Little is known about the lentivirus in these populations at the molecular and host level. Analysis of the virus from these populations is necessary for development of detection assays that are both sensitive …

The Effects Of Augmented Attentional Focus On The Performance With Practice Of A Closed Perceptual-Motor Task For Individuals Who Differ In Task Mastery, John Allen Richards

Doctoral Dissertations

The purpose of this study was to investigate the effects of augmented attentional focus on the performance with practice, of a closed perceptual-motor task for individuals who differ in task mastery. Sixty-four male volunteers were assigned to either the beginning or advanced task mastery group (n = 32) based on bowling averages (≤ 130, ≥ 150 respectively). Each subject in the task mastery groups was randomly assigned to one of four augmented focus of attention conditions, i.e., focus on: (a) environmental results of the movement that was performed (KR); (b) the movement that was performed (KP); (c) self via presence …

X-Ray-Induced Specific-Locus Mutation Rates In Newborn And Young Mice, Paul Bruce Selby

Doctoral Dissertations

The specific-locus mutation frequency resulting from 300 R of acute X irradiation has been determined for the germ cells present in male mice at 0, 2, 4, 6, 8, 10, 14, 21, 28, and 35 days of age and also for female mice at 0 days of age, Sample size was much larger for the males irradiated on day 0 than for other age groups but in all groups it was large enough to insure that an extremely high rate would be noticed. At 35 days of age the testis is histologically similar to that of the adult. It was …