<p>Adherens junctions are calcium-dependent cell-cell contacts formed during epithelial morphogenesis that link neighboring cells via cadherin receptors. Coordinated regulation of the actin cytoskeleton by the Rho GTPases is required for the formation and dissolution of adherens junctions, however the pathways that link cadherin signaling to cytoskeletal regulation remain poorly defined. The Abl family of tyrosine kinases have been shown to modulate cytoskeletal reorganization downstream of various extracellular signals including growth factor receptors and integrins.</p><p>Here we use pharmacological inhibition and RNA interference to identify the Abl family kinases as critical mediators of cadherin-mediated adhesion. Endogenous Abl family kinases, Abl and Arg, are activated and are required for Rac activation following cadherin engagement, and regulate the formation and maintenance of adherens junctions in mammalian cells. Significantly, we show that Abl-dependent regulation of the Rho-ROCK-myosin signaling pathway is critical for the maintenance of adherens junctions. Inhibition of the Abl kinases in epithelial sheets results in activation of Rho and its downstream target ROCK, leading to enhanced phosphorylation of the myosin regulatory light chain. These signaling events result in enhanced stress fiber formation and increased acto-myosin contractility, thereby disrupting adherens junctions. Conversely, Arg gain-of-function promotes adherens junction formation through a Crk-dependent pathway in cells with weak junctions. These data identify the Abl kinases as a novel regulatory link between the cadherin/catenin adhesion complex and the actin cytoskeleton through regulation of Rac and Rho during adherens junction formation.</p><p>Unexpectedly, we identified a requirement for Abl and Crk downstream of Rac in the regulation of adherens junctions. Therefore, Abl functions both upstream and downstream of Rac in regulating adherens junctions, which suggests the possibility of a positive feedback loop consisting of Abl-Crk-Rac.</p><p>Finally, we identified the Abl kinases as critical mediators of epithelial cell response to HGF. Pharmacological inhibition of Abl kinase activity resulted in impaired dissolution of adherens junctions downstream of HGF stimulation of the Met receptor. Additionally, we observed decreased phosphorylation of the Met receptor itself, along with Gab1 and Crk, downstream effectors of Met signaling. Taken together, these data suggest a requirement for Abl kinases in both adherens junctions formation and turnover.</p> / Dissertation

<p>Abstract</p><p>The trefoil factor family of secreted proteins contains three members; trefoil factor 1 or TFF1, trefoil factor 2 or TFF2, and trefoil factor 3 or TFF3. These three proteins share a conserved 42-43 amino acid domain containing 6 cysteine residues resulting in three disulfide bonds that holds the protein in a characteristic three-loop or "trefoil structure" known as the P domain. TFF1 is primarily localized to the stomach and secreted by the gastric mucosa while TFF2 and TFF3 are primarily localized to the colon and duodenum and secreted by the goblet cells. All three of these proteins play a protective role in the gastrointestinal tract where they are normally localized and have been identified as possible tumor suppressors, however, these proteins are also upregulated in cancer within tissues where they are not normally expressed including the breast, pancreas, prostate, and liver. The mechanisms by which two of these factors, TFF1 and TFF3, promote tumorigenesis remain largely undefined. In this dissertation we will attempt to elucidate these mechanisms as well as the regulation of these two proteins in both pancreatic and prostate cancer. Many of the underlying genetic and molecular mechanisms involved in the development of both pancreatic and prostate cancer remain largely unknown and as a result, therapeutic and diagnostic tools for treating these diseases are not as effective as they could be. By deciphering the role of TFF1 and TFF3 in these cancers, they could potentially serve as new therapeutic targets or biomarkers for treating both diseases.</p><p>Chapter 2 of this dissertation will examine the functional role of TFF1 promoting tumorigenesis in pancreatic and prostate cancer. We will show that TFF1 expression is critical for the viability of both pancreatic and prostate cancer cells and that reduction of TFF1 expression in these cells results in decreased tumorigenicity when implanted in immunocompromised mice. It will also be demonstrated that TFF1's function in promoting tumorigenicity is its ability to assist tumor cells overcome the tumor suppressive barrier of senescence. Thirdly, we show that the form of senescence that TFF1 assists in allowing the cells overcome is oncogene-induced senescence (OIS). Lastly, a cell cycle array identifies the potential downstream target p21CIP, a cyclin-dependent kinase inhibitor and OIS marker, whose expression is induced by loss of TFF1 expression.</p><p>In Chapter 3 of this work, we examine the role of another trefoil factor family member, TFF3, and its role in promoting prostate tumorigenesis. Just as with TFF1, it appears that TFF3 3 expression is critical for prostate cancer cell viability and tumorigenicity using the same experimental techniques used in Chapter 2. Using a genetically defined model of prostate cancer, a PI3-kinase-dependent regulatory mechanism of TFF3 emerges in this prostate cancer context. Using this system we begin to see a divergence in both regulation and function of TFF1 and TFF3 in prostate cancer. Finally, a mouse model expressing TFF3 was developed to monitor the histopthological changes associated with expression of this protein. Initial characterization of this model suggests a hyperplastic phenotype coinciding with TFF3 expression in the prostate.</p><p>The two studies in this dissertation establish a role of TFF1 and TFF3 in both prostate and pancreatic tumorigenesis and demonstrate that ablation of expression of both proteins is a potent inhibitor of tumorigenesis. With this knowledge, it is possible that TFF1 and TFF3 may become a potential therapeutic target or diagnostic marker for better treatment of prostate and pancreatic cancer.</p> / Dissertation

Nerve autografts are widely used clinically to repair nerve grafts. However, nerve grafts have many limitations, such as, availability of donor nerve grafts, and loss of function at donor site. To overcome these problems, we have used a tissue engineering approach to design three-dimensional (3D) agarose scaffolds containing gradients of laminin-1 (LN-1) and nerve growth factor (NGF) to mimic in vivo conditions to promote nerve regeneration in rats. To determine the effect of LN-1 gradients on neurite extension in vitro, dorsal root ganglia (DRG) from chick embryos were cultured in 3D hydrogels. A gradient of LN-1 molecules in agarose gels was made by diffusion technique. LN-1 was then immobilized to the agarose hydrogels using a photo-crosslinker, Sulfo-SANPAH (Sulfosuccinimidyl-6-[4-azido-2-nitrophenylamino] hexanoate). Anisotropic scaffolds with three different slopes of LN-1 gradients were used. Isotropic scaffolds with uniform concentrations of LN-1, at various levels, were used as a positive control. DRG cultured in anisotropic scaffolds with optimal slope of LN-1 gradient extended neurites twice as fast as DRG in optimal concentration in isotropic scaffolds. Also, in the anisotropic scaffolds the faster growing neurites were aligned along the direction of LN-1 gradient. To promote nerve regeneration in vivo, tubular polysulfone guidance channels containing agarose hydrogels with gradients of LN-1 and NGF (anisotropic scaffolds) were used to bridge 20-mm nerve gaps in rats. Nerve autografts were used as positive controls and isotropic scaffolds, with uniform concentration of LN-1 and NGF, were used as negative controls. After 4-months, the rats were sacrificed and nerve histology was done to test for nerve regeneration. Only anisotropic scaffolds and nerve autografts contained evidence of axonal regeneration. Both groups had similar numbers of myelinated axons and similar axonal-diameter distribution. However, nerve graft group performed better in functional outcome as measured by relative gastrocnemius muscle weight (RGMW) and electrophysiology. Optimization of performance of anisotropic scaffolds by varying the LN-1 and NGF concentration gradients might lead to development of scaffolds that can perform as well as nerve auotgrafts for nerve regeneration over long nerve gaps.

This study constructs a cross-market risk model based upon local multi-factor risk models of Taiwan and China equity markets. We employ world, country, industry, and global risk factors to build a structural model which could explain the relationship between local factors across markets by further decomposing local factor returns. Under the structure, this model allows each local market to adopt different local factors rather than force all local markets to use one parsimonious set of factors. Therefore, this model could provide both in-depth and broad coverage analysis of international equity portfolios. The innovative methodology is first introduced by Barra as the Integrated Model. Moreover, we build a simple portfolio and its corresponding benchmark to illustrate the power of our model. Once the contents of a portfolio are decided, this model could provide not only the risk estimation and decomposition in advance but also the performance attribution compared with the benchmark after the portfolio is realized. The analytical viewpoint could also easily change with different numeraire perspectives. The result demonstrates that this model is practical and flexible for international equity portfolio analysis.

The objective of this study is to discover the non-linear effect of market sentiment to characteristic factor returns. We run ¡¥Quantile Regression¡¦ to help us extract useful information and design an effective strategy. Based on the quantitative investment method, using the platform of Multi-Factor Model (MFM), we attempt to construct a portfolio and enhance portfolio performance. If the market-sentiment variable increases performance, we could conclude that some characteristic factors in a high sentiment period will perform better or worse in the next period. What is the market or investor sentiment? It is still a problem in the finance field. There is no co-definition or consensus so far. We do our best to collect the indirect data, such as transaction data, price and volume data, and some indicators in other studies, VIX, put/call ratio and so on. Then, we test the proxy variables independently, and obtain some interesting results. The market turnover, the ratio of margin lending on funds/ margin lending on securities, and the growth rate of consumer confidence index have significant effects on some of the characteristic factors. This holds that some market sentiment variables could influence stocks with certain characteristics, and the factor timing approach could improve portfolio performance under examination by information ratio.

In recent years, the economic exchanges between China and Taiwan have become more frequent, hence the Chinese financial market is the main target that we should research and participate in actively. This study refers to Barra Multi-Factor Modeling process to construct a China Multi-Factor Model. We then apply MFM to establish a Shanghai Stock Exchange 50 enhanced index fund. The first objective of this study is to discover significant factors which can explain excess return of securities. The second is to identify significant factors to forecast stock returns and show the alpha effect in an Enhanced Index Fund via a new weight allocating model developed by this study. The result shows that the eight significant factors are Earning Quality, Efficiency, Growth, Momentum, Size, Trading Activity, Value, and Volatility. The performance of Enhanced Index Fund is better than that of the benchmark. Information ratio is 0.86, and turnover rate is 213%, which is acceptable.

Recently, with the escalating demands for optical communications, the need for bandwidth in optical communication network has increased. The technology breakthrough indry fiber fabrication opens the possibility for fiber bandwidth form 1.3 to 1.6 £gm. Cr4+:YAG double-clad crystal fiber (DCF) grown by the co-drawing laser-heated pedestal growth method has a strong spontaneous emission spectum form 1.3 to 1.6 £gm. Such fiber is therefore, eminently suitable for optical coherence tomography (OCT), broadband optical amplifier, amplifier spontaneous emission (ASE) light source, and tunable solid-state laser applications. In this thesis, multilayer dielectric thin films were directly deposited by E-gun coating onto the end faces of the Cr4+:YAG DCF. To improve the thin-film quality, to increase transmittance of laser output, and to design for the high power laser. For broadband optical amplifier in dual-pump and double-pass scheme, a 3.0-dB gross gain, a 3.0-dB insertion loss, and a 0-dB net gain at 1.4-£gm signal wavelength have been successfully developed with HR coating onto one of the Cr4+:YAG DCF end faces. In addition, we have successfully developed the Cr4+:YAG DCF laser by direct HR coatings onto fiber end faces and increase transmittance of laser output. A record-low threshold of 31.2 mW with a slope efficiency of 7.5% was achieved at room temperature.

The objective of this study is to build a complete process of quantitative stockselection model construction that combines a Multi-Factor Model and informationanalysis. Based on the quantitative stock selection model, we construct anenhanced index fund that uses the Taiwan 50 index as its benchmark. Stock prices change for a multitude of reasons, and these reasons may changeover time. In this study, we use a Multi-Factor Model and information analysis to find the relationship between stock price behavior and a factor‟s condition. Wecan use this relationship as a basis for stock selection. Moreover, the purpose of this study is to construct an enhanced index fund,hence we need to control the tracking error. We use an intuitive portfolio construction method, the original weight retention rate of the benchmark, to control tracking error. In addition, the turnover rate of a portfolio is also a significant problem as it may cause the profit of a portfolio to decreasesignificantly. In this study, we use the smoothing alpha score method to control the turnover rate of our portfolio.

In the thesis, LED driver circuits which are applied in low power lighting LED with constant output current and Power Factor Correction are presented. The non-isolated Buck converter are used for the LED drivers. According to different operating mode of inductance current, Power Factor Correction are realized with both the method of Voltage Follower Approach Control under Discontinuous Conduction Mode and the method of Nonlinear Carrier Control under Continuous Conduction Mode. NLC doesn¡¦t need the multiplier which is used in traditional power factor correction, therefore NLC can reduce the system cost. The designed circuits are verified by simulation of IsSpice software and practical experiments. From simulation and experimental results, it shows the proposed approaches achieve the goal with high power factor and constant output current.

Abstract In 1972, Taiwan¡¦s first squid jigging vessel ¡§YUNG CHUNG¡¨ succeeded in developing fishing ground at Sea of Japan. Since that time, Taiwanese squid jigging vessels keep succeeding in developing new Squid fishing grounds in New Zealand, North Pacific Ocean, and Southwest of the Atlantic Ocean. Because the squid catch continued to grow, Taiwan began to export squid products to China, Japan, South Korea, North America, and Europe. In volumes, the top three countries of catching squids are Taiwan, China and South Korea vessels at present. However, in reality, even the freezing ability and catching quality of Taiwanese jigging vessels are much better than the other two countries, the export price for Taiwanese catch are the lowest. The major factor is because the packaging weight has not been standardized. It reduces the purchase willingness and the selling price in the overseas markets for Taiwanese catches. Currently, Taiwan now has 105 squid jigging vessels, but each vessel process the catch in their own way. Therefore, it makes the crew difficult to follow the work procedures which influence the efficiency, and result in inconsistent of the packaging weight. This research we use ¡§Analytical Hierarchy Process¡¨. Through consulting with the experts and studying based from the historical documents, we try to establish the key factors on the construction and design of our questionnaire. We then collect the answers from the fishery companies in Taiwan and sea food processing factories in China, and then we confirm the results trough the statistical analysis. We hope through a dependable data and solid research, we can provide concrete recommendations to squid fishery companies, processing factories, and Fisheries Agency of the Government on benefits of packaging weight standardization. We then hope that the ultimate goal is to help raise the Taiwanese squid price in overseas markets.