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The effect of workload and cadence on sagittal plane knee biomechanics in cycling has been widely studied, however few studies have focused on the frontal plane. Frontal plane knee biomechanics, especially knee abduction moment, is closely related to the severity and progression of knee osteoarthritis. The purpose of this study was to investigate the effects of different workloads and cadences on knee frontal plane kinematics and kinetics. Eighteen subjects participated in this study. A motion analysis system was used to collect five cycles of kinematics during two minutes of cycling in eight testing conditions, which included five workload conditions of 0.5, 1, 1.5, 2, and 2.5 kg at 60 revolutions per minute (RPM), and four cadence conditions of 60, 70, 80, and 90 RPM with 1 kg workload. A custom instrumented pedal was used to collect pedal reaction force (PRF). Increased workloads with constant RPM significantly increased knee abduction moment and knee abduction range of motion (ROM), without any change of peak knee adduction angle. Increased workloads also significantly increased medial, posterior, and vertical pedal PRF, and knee extension moment. Increased cadences with constant workload had no effects on knee abduction moment. In addition, increased cadences increased anterior and vertical PRF, and knee flexion moment. We found two patterns of frontal knee moments among our subjects which deserves further investigation. Further study may be needed to demonstrate the efficacy of appropriate level of workload in the knee osteoarthritis and other deceased populations.

Breast cancer is a common form of cancer in women. In Taiwan, breast cancer ranks as the second highest incidence of all cancers and is the fourth leading cause of cancer death for women. Being diagnosed and living with breast cancer involves a series of stressful life events that impact on many aspects of women’s quality of life (QOL). Consequently, many women with breast cancer have developed particular coping strategies and used complementary and alternative medicine (CAM) to enhance their QOL and well being. While research has shown that cultural and contextual factors affect QOL in women with breast cancer, it is unclear how well personal and environmental variables, specifically treatment-related stressors, coping, and CAM use, predict QOL in Taiwanese women with breast cancer. The overall purpose of this study was to identify the predictors of QOL and to explore the role of CAM use in Taiwanese women with breast cancer. A mixed methods two-phased study was used. The study was underpinned by the pragmatist paradigm, and employed a sequenced combination of quantitative approach followed by qualitative inquiry. The complementarity approach was chosen to enhance, enrich and illustrate the results from one method with the results from the other method. Phase One used a predictive survey to identify the relationships between QOL and its hypothesised predictors in a convenience sample of outpatients from a large general hospital in eastern Taiwan. The survey data were collected by face-to-face interviews using structured instruments that comprised: a demographic profile sheet; and five scales, including symptom distress, anxiety and depression, internal health locus of control, use of coping strategies, and QOL; as well as number of individual items in relation to CAM use. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Cancer (EORTC QLQ-C30) was used to measure the QOL. It is composed of five functioning scales, a single scale for global QOL, three symptom scales, and six individual symptom items. A number of multiple regression analyses were undertaken to identify the significant predictors of each of the EORTC QLQ-C30 scales. A total of 240 women were invited to participate in study. The overall response rate was 81.7% (n = 196), which is considered statistically high. The majority of respondents were high school educated, married, Buddhists, not currently employed, and with a mean age of 53 years. The average time since diagnosis was 28 months. Most women were diagnosed with Stage II breast cancer, and had had a mastectomy with no recurrence of the disease. Approximately 74% of the women reported that they were CAM users before and/or after their diagnosis. The women’s perceived QOL was predicted by several independent variables. A combination of the independent predictive QOL variables explained 5.7% to 43.8% of the variance. In particular, symptom distress, anxiety and depression were the most influential variables in the prediction of QOL. Additionally, the use of coping strategies, such as planning coping, denial, humour, venting, and self-distraction, made statistically significant contributions to the prediction of various aspects of QOL. Phase Two of the study used a qualitative exploratory design to describe the role of CAM use in the context of Taiwanese women’s health needs and perceived QOL, from the perspective of women with breast cancer. Various perceptions were integrated and further illustrated the women’s use of CAM. Three major domains were identified: women’s reasons for CAM use; influences on decision making regarding CAM; and effects of CAM use. Within these three domains, eight major categories emerged: dealing with emerging health problems through CAM use; regaining balance in life; fighting cancer to enhance health; family and friends’ influence; communication with health care professionals; beliefs about CAM; living a normal life through using CAM; and building strong social networks. This study supports the stress and coping model proposed by Lazarus and Folkman, that indicated that people use particular coping strategies in response to the situation and context; and these, may affect their adaptation. The findings suggest that the use of certain coping strategies and CAM use may be integrated within the conventional biomedical treatments to help improve breast cancer patients’ well being. Understanding CAM use in women with breast cancer may inform clinical practice and assist health professionals to provide compassionate and comprehensive cancer care, and thus support women in making informed treatment decisions.

Adenosine mediates angiogenesis, the development of new blood vessels from pre-existing vasculature. A critical process in this event is adenosine-induced endothelial cell proliferation which requires activation of extracellular-regulated kinase 1/2 (ERK1/2). Our hypothesis was that in human umbilical vein endothelial cells (HUVEC) an A2 adenosine receptor (AR) subtype mediates the angiogenic effects of adenosine via a signaling pathway activating ERK1/2. This project had 3 specific aims: I. Define the AR subtype involved in ERK1/2 activation; II. Identify the participants in the signaling cascade(s) from the AR subtype to ERK1/2 activation; III. Explore the role of AR activation in HUVEC proliferation. Through a series of extensive pharmacological studies, we identified the A2BAR as the AR subtype responsible for adenosine-mediated ERK1/2 activation in HUVEC. Multiple findings demonstrated that the A2BAR-mediated ERK1/2 activation primarily occurred in a cAMP-dependent yet protein kinase A (PKA)-independent manner. Based on this characterization, focus was placed on the exchange protein directly activated by cAMP (Epac) which is a novel cAMP effector. Epac1 is a guanine nucleotide exchange factor (GEF) for Rap GTPases and may stimulate ERK1/2 activation via the Rap1–B-Raf module. Epac1 activation by 8-CPT-2’-O-Me-cAMP, a cAMP analog selective for Epac1, resulted in ERK1/2 stimulation. Epac1 down-regulation by siRNA abrogated ERK1/2 activation by 8-CPT-2’-O-Me-cAMP and substantially inhibited that by A2BAR activation. Epac1 over-expression enhanced the A2BAR-induced ERK1/2 activation. This is the first demonstration that adenosine signaling employs Epac1 and provides further evidence that stimulation of Epac1 results in ERK1/2 activation. Additional mechanisms involving Ras and Src may in part mediate the A2BAR-mediated ERK1/2 activation, whereas receptor tyrosine kinase transactivation, protein kinase C isoforms and phosphoinositol-3-kinase are not involved. A2BAR activation stimulated HUVEC proliferation and this response required ERK1/2 stimulation. Epac1 over-expression stimulated HUVEC proliferation and this response required the GEF activity of Epac1. Additionally, the proliferative effect of Epac1 over-expression appeared to be cell-type dependent and may be dependent on the availability of the 95 kDa isoform of B-Raf. This is the first time that Epac1 has been shown to regulate cell proliferation.

Empirical economic studies are often confronted by the joint problem of weak instruments and near exogeneity, such as labor economics and empirical economic growth theory. This dissertation presents new evidence and solutions on estimation and inference with weak instruments and near exogeneity. Chapter 1 reexamines the effect of institutions on economic performance in Acemoglu, Johnson and Robinson (2001) where the measurement of current institutions is instrumented by European settler mortality rates. Since many economists argue that the settler mortality rates can possibly affect economic performance through other channels, I reexamine the effect of institutions by considering near exogeneity. I provide some evidence to show that the effect of institutions is not significant in many regression specifications when the settler mortality rates are used as the main instrument.Chapter 2 studies estimation and inference with weak instruments and near exogeneity in a linear simultaneous equations model. I show that near exogeneity can exaggerate asymptotic bias of the TSLS and the LIML estimators. When using critical values from chi-square distributions, Anderson-Rubin and Kleibergen tests under exogeneity have a large size distortion. I propose the delete-d jackknife based Anderson-Rubin and Kleibergen tests to automatically reduce the size distortion in finite samples without a need for any pretest of exogeneity.Chapter 3 extends estimation and inference with weak identification and near exogeneity into a GMM framework with instrumental variables. A GMM framework allows nonlinear and nondifferentiable moment conditions. I examine asymptotic results of one-step GMM estimator, two-step efficient GMM estimator and continuously updating estimator with weak identification and near exogeneity. Near exogeneity can produce relatively large bias for all these estimators. The Anderson-Rubin type and the Kleibergen type tests under near exogeneity converge in distribution to nonstandard distributions, which creates large size distortion when using critical values from chi-square distributions. The delete-d jackknife based approach can reduce the size distortion

The nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus is a 123 amino acid structural protein required for packaging the single stranded RNA genome. In addition to its structural function, we propose that the N protein is also involved in regulation of host cell function during replication. Using enhanced green fluorescent protein as a tag, we identified a highly conserved basic region (residues 43- 60) which is required for N protein nucleolar localization and is capable of directing the nuclear and nucleolar translocation of an otherwise cytoplasmic protein, ~ - galactosidase. Mutation analysis showed that the basic residues Lysine 43 and Lysine 44 are critical for nucleolar targeting of the N protein. N protein nuclear import was enhanced by modifying the phosphorylation of two CK-II sites (threonine 59 and threonine 68). These results demonstrate that N protein contains a functional nucleolar localization signal sequence (residues 43-60) which directs N protein to the cell nucleolus and suggest that CK-II phosphorylation plays a role in the regulation of N protein nucleolar localization.

Curve matching is essential to many design and manufacturing applications as well as in image processing. In this thesis, several techniques are developed to facilitate the three steps involved in the matching process: representation, correspondence and alignment. For representation, a 3D curve is represented as a unit quaternion curve by quaternion mapping. Through the Serret-Frenet frame, a 3D curve can be considered as the combination of successive rotations. The quaternion mapping is the conversion from these rotations to the unit quaternions. Since curves differing only in scaling have the same image in the quaternion space, this new representation facilitates the matching between objects in different scales. Since the quaternion space has the same structure as the rotation group, this new representation enables the development of efficient algorithms for later alignment. For correspondence, instead of the $L\sb2$ norm as commonly used in identifying the corresponding features, an energy minimization model is formulated. With different correspondences, the strain energy which measures the magnitude of deformation between two curves is computed. Since the strain energy only consists of intrinsic properties of curves, the method is independent of initial positions. The best match is defined as the configuration which has the minimal energy. This energy minimization model is formulated as a functional and the solution is derived by solving the Euler-Lagrange equations. It is shown that the energy minimization process is equivalent to finding the shortest path on a surface. Such an energy surface is derived to represent the terrain of the minimization space. This surface not only serves as a visualization tool, it gives a qualitative prediction of the result of matching. For alignment, two new methods which utilize quaternion distance as the metric in the objective functions are offered. These two methods not only provide faster and more accurate results as compared to the existing ones, one of the two always gives a simple closed form solution which greatly reduces the complexity of implementation.