Movement Effects on the Flow Physics and Nutrient Delivery in Engineered Valvular Tissues

Mechanical conditioning has been shown to promote tissue formation in a wide variety of tissue engineering efforts. However the underlying mechanisms by which external mechanical stimuli regulate cells and tissues are not known. This is particularly relevant in the area of heart valve tissue engineering (HVTE) owing to the intense hemodynamic environments that surround native valves. Some studies suggest that oscillatory shear stress (OSS) caused by steady flow and scaffold flexure play a critical role in engineered tissue formation derived from bone marrow derived stem cells (BMSCs). In addition, scaffold flexure may enhance nutrient (e.g. oxygen, glucose) transport. In this study, we computationally quantified the i) magnitude of fluid-induced shear stresses; ii) the extent of temporal fluid oscillations in the flow field using the oscillatory shear index (OSI) parameter, and iii) glucose and oxygen mass transport profiles. Noting that sample cyclic flexure induces a high degree of oscillatory shear stress (OSS), we incorporated moving boundary computational fluid dynamic simulations of samples housed within a bioreactor to consider the effects of: 1) no flow, no flexure (control group), 2) steady flow-alone, 3) cyclic flexure-alone and 4) combined steady flow and cyclic flexure environments. We also coupled a diffusion and convention mass transport equation to the simulated system. We found that the coexistence of both OSS and appreciable shear stress magnitudes, described by the newly introduced parameter OSI-t , explained the high levels of engineered collagen previously observed from combining cyclic flexure and steady flow states. On the other hand, each of these metrics on its own showed no association. This finding suggests that cyclic flexure and steady flow synergistically promote engineered heart valve tissue production via OSS, so long as the oscillations are accompanied by a critical magnitude of shear stress. In addition, our simulations showed that mass transport of glucose and oxygen is enhanced by sample movement at low sample porosities, but did not play a role in highly porous scaffolds. Preliminary in-house in vitro experiments showed that cell proliferation and phenotype is enhanced in OSI-t environments.

Understanding Ten-Eleven Translocation-2 in Hematological and Nervous Systems

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems. In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA sequencing (RNA-Seq) of hematopoietic stem/progenitor cells to determine whether the deletion of Tet2 can affect the abundance of 5hmC at myeloid, T-cell and B-cell specific gene transcription start sites, which ultimately result in various hematological malignancies. Subsequent Exome sequencing (Exome-Seq) showed that disease-specific genes are mutated in different types of tumors, which suggests that TET2 may protect the genome from being mutated. The direct interaction between TET2 and Mutator S Homolog 6 (MSH6) protein suggests TET2 is involved in DNA mismatch repair. Finally, in vivo mismatch repair studies show that the loss of Tet2 causes a mutator phenotype. Taken together, my data indicate that TET2 binds to MSH6 to protect genome integrity. In Part II, I intended to better understand the role of Tet2 in the nervous system. 5-hydroxymethylcytosine regulates epigenetic modification during neurodevelopment and aging. Thus, Tet2 may play a critical role in regulating adult neurogenesis. To examine the physiological significance of Tet2 in the nervous system, I first showed that the deletion of Tet2 reduces the 5hmC levels in neural stem cells. Mice lacking Tet2 show abnormal hippocampal neurogenesis along with 5hmC alternations at different gene promoters and corresponding gene expression downregulation. Through the luciferase reporter assay, two neural factors Neurogenic differentiation 1 (NeuroD1) and Glial fibrillary acidic protein (Gfap) were down-regulated in Tet2 knockout cells. My results suggest that Tet2 regulates neural stem/progenitor cell proliferation and differentiation in adult brain.

Theoretical Investigation of Intra- and Inter-cellular Spatiotemporal Calcium Patterns in Microcirculation

Microcirculatory vessels are lined by endothelial cells (ECs) which are surrounded by a single or multiple layer of smooth muscle cells (SMCs). Spontaneous and agonist induced spatiotemporal calcium (Ca2+) events are generated in ECs and SMCs, and regulated by complex bi-directional signaling between the two layers which ultimately determines the vessel tone. The contractile state of microcirculatory vessels is an important factor in the determination of vascular resistance, blood flow and blood pressure. This dissertation presents theoretical insights into some of the important and currently unresolved phenomena in microvascular tone regulation. Compartmental and continuum models of isolated EC and SMC, coupled EC-SMC and a multi-cellular vessel segment with deterministic and stochastic descriptions of the cellular components were developed, and the intra- and inter-cellular spatiotemporal Ca2+ mobilization was examined. Coupled EC-SMC model simulations captured the experimentally observed localized subcellular EC Ca2+ events arising from the opening of EC transient receptor vanilloid 4 (TRPV4) channels and inositol triphosphate receptors (IP3Rs). These localized EC Ca2+ events result in endothelium-derived hyperpolarization (EDH) and Nitric Oxide (NO) production which transmit to the adjacent SMCs to ultimately result in vasodilation. The model examined the effect of heterogeneous distribution of cellular components and channel gating kinetics in determination of the amplitude and spread of the Ca2+ events. The simulations suggested the necessity of co-localization of certain cellular components for modulation of EDH and NO responses. Isolated EC and SMC models captured intracellular Ca2+ wave like activity and predicted the necessity of non-uniform distribution of cellular components for the generation of Ca2+ waves. The simulations also suggested the role of membrane potential dynamics in regulating Ca2+ wave velocity. The multi-cellular vessel segment model examined the underlying mechanisms for the intercellular synchronization of spontaneous oscillatory Ca2+ waves in individual SMC. From local subcellular events to integrated macro-scale behavior at the vessel level, the developed multi-scale models captured basic features of vascular Ca2+ signaling and provide insights for their physiological relevance. The models provide a theoretical framework for assisting investigations on the regulation of vascular tone in health and disease.

Investigating the Outcomes of a Physical Activity Program offered to Older Adults in South Florida and Understanding the Correlates of Completion

Despite the well-known benefits of physical activity, in 2012, only 37.5% of older adults aged 60 years or older met recommended aerobic physical activity levels and 16.1% met muscle-strengthening guidelines. Effective exercise programs can help combat the problem of inactivity but 50% of those who start participating in an exercise program drop out within first few weeks, preventing them from gaining any health benefits. Since fall 2008, the Healthy Aging Regional Collaborative of South Florida has offered EnhanceFitness (EF), an evidence-based physical activity program to older adults. This dissertation compared EF effectiveness at 4-, 8-, and 12-months and examined the factors that were associated with program completion. A paired sample t-test identified changes at 4-months and repeated measures design was used to identify changes from baseline to 4-, 8-, and 12- months. Logistic regression was used to identify correlates associated with completion. Between October 1, 2008 and December 31, 2012, 4,531 older adults (>=60 years) attended one or more EF sessions. Participants showed significant improvement in the number of chair stands performed in 30-seconds with mean change of 1.7, 1.6, and 2.0 respectively at 4-,8-,and 12- months (pp<0.001). Results suggest Black, non-Haitian men were less likely to complete the program when compared to white, non-Hispanic men (OR=0.41, p=0.02). Men who self-reported having at least one risk factor were more likely to complete the program (OR=1.81, p= 0.03). In addition, women who lived in Miami-Dade County (OR=2.13, ppppp<0.01). Effectiveness results revealed that all participants improved on outcome measures. However, improvement is more than double for those who completed recommended sessions (p

The effectiveness of an intelligent tutoring system on the attitude and achievement of developmental mathematics students in a community college

This study examined the effectiveness of intelligent tutoring system instruction, grounded in John Anderson's ACT theory of cognition, on the achievement and attitude of developmental mathematics students in the community college setting. The quasi-experimental research used a pretest-posttest control group design. The dependent variables were problem solving achievement, overall achievement, and attitude towards mathematics. The independent variable was instructional method. Four intact classes and two instructors participated in the study for one semester. Two classes (n = 35) served as experimental groups; they received six lessons with real-world problems using intelligent tutoring system instruction. The other two classes (n = 24) served as control groups; they received six lessons with real-world problems using traditional instruction including graphing calculator support. It was hypothesized that students taught problem solving using the intelligent tutoring system would achieve more on the dependent variables than students taught without the intelligent tutoring system. Posttest mean scores for one teacher produced a significant difference in overall achievement for the experimental group. The same teacher had higher means, not significantly, for the experimental group in problem solving achievement. The study did not indicate a significant difference in attitude mean scores. It was concluded that using an intelligent tutoring system in problem solving instruction may impact student's overall mathematics achievement and problem solving achievement. Other factors must be considered, such as the teacher's classroom experience, the teacher's experience with the intelligent tutoring system, trained technical support, and trained student support; as well as student learning styles, motivation, and overall mathematics ability.

Racial/ethnic differences on the body image perceptions and weight concerns of fourth grade girls

The purpose of this study was to determine the racial and ethnic differences on body image perceptions and weight concerns of fourth grade girls. A purposive sample of 182 fourth grade girls were eligible to participate, 166 were included in the data analysis. The Children's Eating Attitude Test (ChEAT) and a Dieting and Demographic Questionnaire (DDQ) were used to determine eating attitudes of fourth grade girls. A pictoral instrument that was modified from the original was used to assess body image. Anthropometric data was assessed and body mass index (BMI) values were used to classify subjects into percentiles. Results revealed that 56% of all fourth grade girls studied wanted to be thinner and 53% had tried to lose weight. Significantly more non-Hispanic white (NHW) girls reported wanting to be thinner than non-Hispanic black (NHB) and H girls (65.5% vs.32% and 47%, respectively, P=0.005) No significant racial/ethnic differences were revealed for the ChEAT scores. However, 19% of all subjects studied fell into the category indicative of anorexia nervosa. H girls who were less than the 85" %tile for BMI chose significantly smaller figures as their perceived body image (3.5±0.7) than both NHB and NHW girls (4.0±0.6 and 3.9±0.5, respectively, P<0.01). These findings demonstrated that weight concerns were prevalent among girls ages 9- 11 years. NHW and H girls may have more concerns about their body size and shape than their NHB counterparts. Implementing intervention programs at an early age may prevent eating disorders in adolescence and adulthood.

Intracellular Signaling and Trafficking in Cancer: Role of Rab5-GTPase in Migration and Invasion of Breast Cells

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases, are small signaling molecules and critical in the regulation of many cellular processes including cell migration, growth via the endocytic pathway. This research involves the role of Rab GTPases, specifically Rab5 and its guanine exchange factors (GEFs), in the promotion of cancer cell migration and invasion. Two important questions abound: Are IGFR stimulation and downstream effect involved the endocytic pathway in carcinogenesis? What role does Rab5 play in cell migration and invasion of cancer cells? The hypothesis is that growth factor signaling is dependent on Rab5 activity in mediating the aggressiveness of cancer cells. The goal is to demonstrate that IGF-1 signaling is dependent on Rab5 function in breast cancer progression. Here, the results thus far, have shown that while activation of Rab5 may mediate increased cell proliferation, migration and invasion in breast cancer cells, the Rab5 GEF, RIN1 interacts with the IGFR thereby facilitating migration and invasion activities in breast cells. Furthermore, endocytosis of the IGFR in breast cancer cells seems to be caveolin dependent as the data has shown. This taken together, the data shows that IGF-1 signaling in breast cancer cells relies on IGF-1R phosphorylation, caveolae internalization and sequestration to the early endosome RIN1 function and Rab5 activation.

Petrologic and geochemical study of crustal xenoliths from Calbuco Volcano, Chile (latitude 41°20ʹS)

Twenty Four samples of xenoliths and country rocks from the 1961 lava flow of Calbuco volcano have been studied. Fourteen samples have been analyzed for major elements and P, Ni, Ba, Cr, V, Zr, Sc, Y, and Sr. Five of these samples were further analyzed for Sm, Nd, Sr, and Pb isotope ratios. Seventeen samples were studied under the microscope and three samples were analyzed by microprobe for their pyroxene compositions. Based on petrographic studies xenoliths were divided into three groups. Fine grained xenoliths (groups I and II) probably formed from metamorphosed MORB-like basalts, whereas coarse grained xenoliths (group III) were apparently derived from cumulate minerals that crystallized from the Calbuco magma. The fine grained xenoliths were probably entrained in magma at intermediate levels of the crust, near the stability limit of amphibole to form pyroxene and plagioclase. In the coarse grained xenoliths amphibole that formed at depth dehydrated as the xenoliths were brought to the surface. The country rocks are apparently unrelated to the xenoliths.

An analysis of Venezuela's foreign policy during the period of the Betancourt doctrine and Caldera's ideological pluralism

This thesis examines the foreign policy of Venezuela during the period of the Betancourt Doctrine (1945-1948 and 1959-1963), and Caldera's Ideological Pluralism (1969-1973). The study seeks to determine whether, and to what extent the pursuit of political and economic interests and ideology determined Venezuela's foreign policy. Based on primary and secondary sources, this study examines political economy and ideology and how these affected the outcome of Venezuela's foreign policy. The major finding of this thesis is that Venezuelan foreign policy was a pragmatic one but it was rationalized within an ideological framework. In fact, Venezuela was most concerned in pursuing its domestic economic and political interests but these were hidden behind an ideological facade.

The influence of simulated disability slides and audiotape messages on college students' attribution of personality characteristics

The purpose of this study was to examine the attitudes college students have toward those with physical disabilities and what personality characteristics they attribute to physical appearance. One-hundred-one introductory psychology students at FIU were randomly assigned to one of three groups: control--no disability group, a group that viewed five slides of peers with disabilities, and a group that viewed the disability slides and heard their voices. All subjects rated the individuals' perceived personality. A one-way ANOVA revealed that those in the visual and audio disability group rated those with disabilities significantly higher in friendliness, attractiveness, and assertiveness than those who rated the individuals without disabilities. Those in the visual and audio disability group rated them higher in self-esteem than those in the visual only disability group. Since voice can have such positive effects on first impression, an occupational therapist can work on improving communication skills of those with disabilities.

Nutrient cycling in Alaskan tundra in response to experimental manipulation of growing season length and soil temperature : a climate change scenario

Climate change in the Arctic is predicted to increase plant productivity through decomposition-related enhanced nutrient availability. However, the extent of the increase will depend on whether the increased nutrient availability can be sustained. To address this uncertainty, I assessed the response of plant tissue nutrients, litter decomposition rates, and soil nutrient availability to experimental climate warming manipulations, extended growing season and soil warming, over a 7 year period. Overall, the most consistent effect was the year-to-year variability in measured parameters, probably a result of large differences in weather and time of snowmelt. The results of this study emphasize that although plants of arctic environments are specifically adapted to low nutrient availability, they also posses a suite of traits that help to reduce nutrient losses such as slow growth, low tissue concentrations, and low tissue turnover that result in subtle responses to environmental changes.

Analysis of fractured terrain using remote sensing and geographic information systems : establishing a correlation between fracture network properties and vegetation

This research analyzed the spatial relationship between a mega-scale fracture network and the occurrence of vegetation in an arid region. High-resolution aerial photographs of Arches National Park, Utah were used for digital image processing. Four sets of large-scale joints were digitized from the rectified color photograph in order to characterize the geospatial properties of the fracture network with the aid of a Geographic Information System. An unsupervised landcover classification was carried out to identify the spatial distribution of vegetation on the fractured outcrop. Results of this study confirm that the WNW-ESE alignment of vegetation is dominantly controlled by the spatial distribution of the systematic joint set, which in turn parallels the regional fold axis. This research provides insight into the spatial heterogeneity inherent to fracture networks, as well as the effects of jointing on the distribution of surface vegetation in desert environments.

Development of the Sphere Overlap Scale (SOS) : compartmentalization and the spillover hypothesis

The purpose of this study was to create a scale that could measure compartmentalization. In the first of two studies 311 working undergraduates were asked to indicate agreement with 119 items that measured compartmentalization. The resulting scale's reliability and validity were evaluated by having a second sample of 312 working students complete the items that comprise a sphere overlap scale, two measures of spillover, and a measure of personality, coping, and demoralization. Although the study's original goal was not realized, its procedures were successful in developing a short (10-item) measure of work-to-home spillover whose items loaded on a single factor. Structural equation modeling indicated that SOS items were correlated with existing measures of spillover and could be discriminated from related concepts of personality and coping. The SOS was also more highly correlated with demoralization than existing measures of spillover in hierarchical analyses that controlled for demographic factors, personality characteristics, and coping style. It is concluded that the SOS shows enough promise to warrant the cost of its appraisal as an alternative measure of spillover in a longitudinal study.

The knowledge and use of critical thinking teaching strategies of faculty in associate degree nursing education programs

The purpose of this study was to determine the knowledge and use of critical thinking teaching strategies by full-time and part-time faculty in Associate Degree Nursing (ADN) programs. Sander's CTI (1992) instrument was adapted for this study and pilottested prior to the general administration to ADN faculty in Southeast Florida. This modified instrument, now termed the Burroughs Teaching Strategy Inventory (BTSI), returned reliability estimates (Cronbach alphas of .71, .74, and .82 for the three constructs) comparable to the original instrument. The BTSI was administered to 113 full-time and part-time nursing faculty in three community college nursing programs. The response rate was 92% for full-time faculty (n = 58) and 61 % for part-time faculty (n = 55). The majority of participants supported a combined definition of critical thinking in nursing which represented a composite of thinking skills that included reflective thinking, assessing alternative viewpoints, and the use of problem-solving. Full-time and part-time faculty used different teaching strategies. Fulltime faculty most often used multiple-choice exams and lecture while part-time faculty most frequently used discussion within their classes. One possible explanation for specific strategy choices and differences might be that full-time faculty taught predominately in theory classes where certain strategies would be more appropriate and part-time faculty taught predominately clinical classes. Both faculty types selected written nursing care plans as the second most effective critical thinking strategy. Faculty identified several strategies as being effective in teaching critical thinking. These strategies included discussion, case studies, higher order questioning, and concept analysis. These however, were not always the strategies that were used in either the classroom or clinical setting. Based on this study, the author recommends that if the profession continues to stress critical thinking as a vital component of practice, nursing faculty should receive education in appropriate critical teaching strategies. Both in-service seminars and workshops could be used to further the knowledge and use of critical thinking strategies by faculty. Qualitative research should be done to determine why nursing faculty use self-selected teaching strategies.

The adoption of retail electronic commerce: an empirical investigation

The purpose of this study was to empirically investigate the adoption of retail electronic commerce (REC). REC is a business transaction which takes place over the Internet between a casual consumer and a firm. The consumer has no long-term relationship with the firm, orders a good or service, and pays with a credit card. To date, most REC applications have not been profitable. To build profitable REC applications a better understanding of the system's users is required. The research model hypothesizes that the level of REC buying is dependent upon the Buying Characteristics of Internet Use and Search Experience plus the Channel Characteristics of Beliefs About Internet Vendors and Beliefs About Internet Security. The effect of these factors is modified by Time. Additional research questions ask about the different types of REC buyers, the differences between these groups, and how these groups evolved over time. To answer these research questions I analyzed publically available data collected over a three-year period by the Georgia Institute of Technology Graphics and Visualization Unit over the Internet. Findings indicate the model best predicts Number of Purchases in a future period, and that Buyer Characteristics are most important to this determination. Further, this model is evolving over Time making Buyer Characteristics predict Number of Purchases better in more recent survey administrations. Buyers clustered into five groups based on level of buying and move through various levels and buy increasing Number of Purchases over time. This is the first large scale research project to investigate the evolution of REC. This implications are significant. Practitioners with casual consumer customers need to deploy a finely tuned REC strategy, understand their buyers, capitalize on the company reputation on the Internet, install an Internet-compatible infrastructure, and web-enable order-entry/inventory/fulfillment/ shipping applications. Researchers might wish to expand on the Buyer Characteristics of the model and/or explore alternative dependent variables. Further, alternative theories such as Population Ecology or Transaction Cost Economics might further illuminate this new I.S. research domain.