by Charles Chun Chan Wong. / Thesis (M.B.A.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references. / TABLE OF CONTENTS --- p.ii / LIST OF ILLUSTRATIONS --- p.v / LIST OF TABLES --- p.vi / ACKNOWLEDGMENTS --- p.vii / Chapter I. --- BACKGROUND --- p.1 / Foreword --- p.1 / The Modern-day Electronics Industry and the IC Industry --- p.2 / The Semiconductor IC Industry in Asia --- p.5 / RCL Semiconductors Ltd. and the Scope of the Report --- p.6 / Chapter II. --- RELATED LITERATURE --- p.7 / Critique --- p.7 / Periodicals --- p.7 / Report --- p.12 / Thesis --- p.17 / Bibliography --- p.19 / Books --- p.19 / Periodicals --- p.19 / Report --- p.21 / Thesis --- p.21 / Chapter III. --- METHODOLOGY --- p.22 / Research Design --- p.22 / Primary Research --- p.22 / Data collection method --- p.22 / Sampling --- p.23 / Secondary Research --- p.23 / Data collection method --- p.23 / Analysis --- p.23 / Chapter IV. --- FINDINGS --- p.25 / "RCL, the Company" --- p.25 / Background of RCL --- p.25 / Founding of RCL --- p.25 / The Chinese Connection --- p.27 / RCL's Current Status --- p.28 / RCL's Products --- p.29 / RCL's Customer Profile --- p.29 / RCL's Market Profile --- p.31 / Market Conditions for the Semiconductor IC Industry in General --- p.31 / Market Conditions for the Semiconductor IC Industry in Hong Kong --- p.32 / Market Size and Share --- p.33 / RCL's Competition --- p.33 / RCL's Immediate Competitors --- p.33 / Japan --- p.33 / Korea --- p.35 / Taiwan --- p.35 / Hong Kong --- p.36 / Hua Ko Electronics Inc --- p.36 / Vitelic(HK)Ltd --- p.37 / RCL's Potential Competitors --- p.37 / China (The People's Republic of China) --- p.37 / Singapore --- p.38 / ASEAN countries --- p.38 / Chapter V. --- SUMMARY AND IMPLICATIONS --- p.39 / Summary --- p.39 / Industry Attractiveness --- p.39 / RCL's Competitive Advantages --- p.40 / "RCL's ""China Card""" --- p.40 / RCL's Technological Edge over Hua Ko --- p.40 / RCL's Constraints --- p.41 / External Factors --- p.41 / Investment Environment --- p.41 / Low-end Competition --- p.41 / Internal Factors --- p.41 / Implications --- p.42 / Short Term Strategies for RCL --- p.42 / Short Term Overall Strategy --- p.42 / Short Term Competitive Strategy: Externally Focused --- p.43 / Short Term Tactics: Internally Focused on Company's Organization --- p.43 / Long Term Strategy for RCL --- p.43 / Long Term Overall Strategy --- p.43 / Long Term Competitive Strategy --- p.44 / Conclusions --- p.44 / APPENDIX --- p.47 / Chapter I. --- SURVEY QUESTIONNAIRES FOR RCL'S MANAGEMENT --- p.47 / Chapter II. --- SURVEY QUESTIONNAIRES FOR RCL'S CUSTOMERS --- p.56 / Chapter III. --- SURVEY QUESTIONNAIRES FOR SEMICONDUCTOR INDUSTRY EXPERTS --- p.64 / Chapter IV. --- KENICHI OHMAE'S BUSINESS PORTFOLIO MATRIX --- p.73 / Chapter V. --- MICHAEL E. PROTER'S GENERIC STRATEGIES --- p.74 / Chapter VI. --- MICHAEL E. PROTER'S ELEMENTS OF INDUSTRY STRUCTURE --- p.74

<p>Inhibitors belonging to the serpin (serine protease inhibitor) family control proteases involved in various physiological processes. All serpins have a common tertiary structure based on the dominant b-sheet A, but they have different inhibitory specificity. The specificity of a serpin is determined by the Pl-Pl’ peptide bond acting as a bait for the target protease which is made up of an exposed reactive centre loop (RCL). The serpin plasminogen activator inhibitor type-1 (PAI-1) is the main physiological inhibitor of urokinase-type and tissue-type plasminogen activators (uPA and tPA, respectively). Elevated plasma levels of PAI-l have been correlated with a higher risk of deep venous thrombosis, and PAI-1 is a risk factor for recurrent myocardial infarction. Furthermore, PAI-1 has a role in cell migration and has been suggested to regulate tumor growth and angiogenesis. PAI-1 is unique among the serpins in that it can spontaneously and rapidly convert into its latent form. This involves full insertion of the RCL into b-sheet A. </p><p>There were two partially overlapping goals for this thesis. The first was to use latent PAI-1 as model for development of a fluorescence-based method, Donor-Donor Energy Migration for intramolecular distance measurements. The second goal was to use DDEM, together with other biochemical methods, to reveal the structure of the PAI-1/uPA complex, the conformation of the RCL in active PAI-1, and molecular determinants responsible for the conversion of PAI-1 from the active to the latent form.</p><p>The use of molecular genetics for introduction of fluorescent molecules enables the use of DDEM to determine intramolecular distances in a variety of proteins. This approach can be applied to examin the overall molecular dimensions of proteins and to investigate structural changes upon interactions with specific target molecules. In this work, the accuracy of the DDEM method has been evaluated by experiments with the latent PAI-1 for which X-ray structure is known. Our data show that distances approximating the Förster radius (57±1 Å) obtained by DDEM are in good agreement (within 5.5 Å) with the distances obtained by X-ray crystallography.</p><p>The molecular details of the inhibitory mechanism of serpins and the structure of the serpin/protease complex have remained unclear. To obtain the structural insights required to discriminate between different models of serpin inhibition, we used fluorescence spectroscopy and cross-linking techniques to map sites of PAI-1/uPA interaction, and distance measurement by DDEM to triangulate the position of the uPA in the complex. The data have demonstrated clearly that in the covalent PAI-1/uPA complex, the uPA is located at the distal end of the PAI-1 molecule relative to the initial docking site. This indicates that serpin inhibition involves reactive center cleavage followed by full loop insertion, whereby the covalently linked protease is translocated from one pole of the inhibitor to the opposite one. </p><p>To search for molecular determinants that could be responsible for conversion of PAI-1 to the latent form, we studied the conformation of the RCL in active PAI-1 in solution. Intramolecular distance measurements by DDEM, the newly a developed method based on probe quenching and biochemical methods revealed that the RCL in PAI-1 is located much closer to the core of PAI-1 than has been suggested by the recently resolved X-ray structures of stable PAI-1 mutants, and it can be partially inserted. This possibly explains for the ability of PAI-1 to convert spontaneously to its latent form. </p>

Inhibitors belonging to the serpin (serine protease inhibitor) family control proteases involved in various physiological processes. All serpins have a common tertiary structure based on the dominant b-sheet A, but they have different inhibitory specificity. The specificity of a serpin is determined by the Pl-Pl’ peptide bond acting as a bait for the target protease which is made up of an exposed reactive centre loop (RCL). The serpin plasminogen activator inhibitor type-1 (PAI-1) is the main physiological inhibitor of urokinase-type and tissue-type plasminogen activators (uPA and tPA, respectively). Elevated plasma levels of PAI-l have been correlated with a higher risk of deep venous thrombosis, and PAI-1 is a risk factor for recurrent myocardial infarction. Furthermore, PAI-1 has a role in cell migration and has been suggested to regulate tumor growth and angiogenesis. PAI-1 is unique among the serpins in that it can spontaneously and rapidly convert into its latent form. This involves full insertion of the RCL into b-sheet A. There were two partially overlapping goals for this thesis. The first was to use latent PAI-1 as model for development of a fluorescence-based method, Donor-Donor Energy Migration for intramolecular distance measurements. The second goal was to use DDEM, together with other biochemical methods, to reveal the structure of the PAI-1/uPA complex, the conformation of the RCL in active PAI-1, and molecular determinants responsible for the conversion of PAI-1 from the active to the latent form. The use of molecular genetics for introduction of fluorescent molecules enables the use of DDEM to determine intramolecular distances in a variety of proteins. This approach can be applied to examin the overall molecular dimensions of proteins and to investigate structural changes upon interactions with specific target molecules. In this work, the accuracy of the DDEM method has been evaluated by experiments with the latent PAI-1 for which X-ray structure is known. Our data show that distances approximating the Förster radius (57±1 Å) obtained by DDEM are in good agreement (within 5.5 Å) with the distances obtained by X-ray crystallography. The molecular details of the inhibitory mechanism of serpins and the structure of the serpin/protease complex have remained unclear. To obtain the structural insights required to discriminate between different models of serpin inhibition, we used fluorescence spectroscopy and cross-linking techniques to map sites of PAI-1/uPA interaction, and distance measurement by DDEM to triangulate the position of the uPA in the complex. The data have demonstrated clearly that in the covalent PAI-1/uPA complex, the uPA is located at the distal end of the PAI-1 molecule relative to the initial docking site. This indicates that serpin inhibition involves reactive center cleavage followed by full loop insertion, whereby the covalently linked protease is translocated from one pole of the inhibitor to the opposite one. To search for molecular determinants that could be responsible for conversion of PAI-1 to the latent form, we studied the conformation of the RCL in active PAI-1 in solution. Intramolecular distance measurements by DDEM, the newly a developed method based on probe quenching and biochemical methods revealed that the RCL in PAI-1 is located much closer to the core of PAI-1 than has been suggested by the recently resolved X-ray structures of stable PAI-1 mutants, and it can be partially inserted. This possibly explains for the ability of PAI-1 to convert spontaneously to its latent form.

被動元件產業向來是台灣在扮演資訊電子製造業王國角色上的重要推手，對於現有業者與企盼進入的業者而言，在市場需求快速成長的吸引下，極需要一個經營策略的指導方針才能在競爭激烈的市場上佔得一席之地。本研究主要的目的在於針對積層陶瓷電容器產品，利用個案公司之營運策略與規劃，提出相關建議以作為有志深耕於此領域之業者的參考，同時供後續研究者進一步的探討。 本研究的主要根據Aaker的理論架構基礎來進行內在與外在分析，同時探討研擬策略規劃方向。整個研究架構分為四個階段：一、探討相關的文獻，以作為研究的原則基礎。二、進行內外在分析，以界定外在環境中可能發生的機會與威脅，並確認出該產業的關鍵成功因素，同時分析個案公司所擁有的優勢與劣勢。三、根據前述的分析結果歸納出個案公司所面臨的問題。四、提出可行的策略方向與目標，並擬定個案公司之競爭策略和營運策略。

SerpinA12 (vaspin) is thought to be mainly expressed in adipose tissue and has multiple beneficial effects on metabolic, inflammatory and atherogenic processes related to obesity. KLK7 (kallikrein 7) is the only known protease target of vaspin to date and is inhibited with a moderate inhibition rate. In the crystal structure, the cleavage site (P1-P1′) of the vaspin reactive centre loop is fairly rigid compared with the flexible residues before P2, possibly supported by an ionic interaction of P1′ glutamate (Glu379) with an arginine residue (Arg302) of the β-sheet C. A P1′ glutamate seems highly unusual and unfavourable for the protease KLK7. We characterized vaspin mutants to investigate the roles of these two residues in protease inhibition and recognition by vaspin. Reactive centre loop mutations changing the P1′ residue or altering the reactive centre loop conformation significantly increased inhibition parameters, whereas removal of the positive charge within β-sheet C impeded the serpin–protease interaction. Arg302 is a crucial contact to enable vaspin recognition by KLK7 and it supports moderate inhibition of the serpin despite the presence of the detrimental P1′ Glu379, which clearly represents a major limiting factor for vaspin-inhibitory activity. We also show that the vaspin-inhibition rate for KLK7 can be modestly increased by heparin and demonstrate that vaspin is a heparin-binding serpin. Noteworthily, we observed vaspin as a remarkably thermostable serpin and found that Glu379 and Arg302 influence heat-induced polymerization. These structural and functional results reveal the mechanistic basis of how reactive centre loop sequence and exosite interaction in vaspin enable KLK7 recognition and regulate protease inhibition as well as stability of this adipose tissue-derived serpin.