Orientador: Helio Waldman / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica e Computação / Made available in DSpace on 2018-08-07T03:14:56Z (GMT). No. of bitstreams: 1 Mello_DarliAugustodeArruda_D.pdf: 2229379 bytes, checksum: e813cff8c9fed2550e1d237c195fd740 (MD5) Previous issue date: 2006 / Resumo: A tese propõe conceitos e ferramentas matemáticas para a alocação eficiente de conexões com habilidade de sobrevivência diferenciada. Utilizamos a disponibilidade como critério na escolha dos mecanismos de proteção e restauração que atuam no controle da habilidade de sobrevivência. Diante da carência de métodos de estimação de disponibilidade acurados, propusemos aproximações baseadas em um modelo markoviano. Obtivemos também limitantes à disponibilidade que permitem calcular erros de estimação. Desenvolvemos então um algoritmo para a alocação de conexões com disponibilidade garantida. Com ele verificamos, usando simulações, a aplicabilidade da proteção por compartilhamento de caminhos de reserva (SBPP) e da proteção de caminho dedicada (DPP) em redes de dimensões nacionais (rede italiana) e continentais (rede estadunidense). Em redes de dimensões nacionais a SBPP oferece ganhos de compartilhamento. Em redes de dimensões continentais a SBPP e a DPP mostraram-se inviáveis devido às restrições de disponibilidade. Por fim, sugerimos utilizar a distribuição da disponibilidade de intervalo e da duração de períodos de inoperância na formulação de contratos de níveis de serviço. Computamos a distribuição das duas métricas por métodos numéricos existentes, e analiticamente, respectivamente / Abstract: This thesis proposes concepts and mathematical formulations for the efficient allocation of connections with differentiated survivability. We use availability to found the choice of adequate protection or restoration mechanisms for survivability differentiation. Given a lack of accurate methods for availability estimation, we proposed approximations based on Markov models. We also derived bounds to the availability that allow to calculate estimation errors. We then developed an algorithm for allocating connections with guaranteed availability. It allowed us to verify the applicability of the shared backup path protection (SBPP) and dedicated path protection (DPP) schemes in networks of national (Italian network) and continental (American NSFNet) dimensions. In networks of national dimensions SBPP allows capacity gains. In networks of continental dimensions the use of both SBPP and DPP has shown to be impractical due to availability constraints. Finally, we suggested to employ the interval availability and outage duration distributions for the elaboration of service level agreements. We computed the distributions using existing numerical methods, and analytically, respectively / Doutorado / Telecomunicações e Telemática / Doutor em Engenharia Elétrica

O diabetes mellitus do tipo 1 (DM1) é uma doença autoimune caracterizada pela destruição seletiva de células pancreáticas produtoras de insulina. Existem diversas formas de tratamento do DM1, tais como administração de insulina, imunossupressores, transplantes de pâncreas ou de ilhotas pancreáticas, porém todos se mostram ineficientes em algum aspecto. Recentemente, uma nova classe de medicamentos, os inibidores da enzima dipeptidil peptidase 4 (iDPP-4), demonstrou eficiência terapêutica e segurança no tratamento de pacientes com diabetes mellitus do tipo 2 devido ao aumento do hormônio peptídeo-1 semelhante ao glucagon (GLP-1, do inglês glucagon-like peptide-1). Além disso, o uso de inibidores de DPP-4 em modelos experimentais de DM1 demonstrou proteção das células pancreáticas contra apoptose, estimulação de neogênese de ilhotas pancreáticas e melhora do controle homeostático da glicose. Esse presente projeto teve como objetivo avaliar o perfil imunológico e endocrinológico da administração do inibidor de DPP-4 (MK0431) em DM1 experimental quimicamente induzido por estreptozotocina em camundongos C57Bl/6. Os animais diabéticos foram tratados com ração controle ou ração contendo inibidor de DPP-4 (4g MK0431/Kg de ração) ad libitum durante 30 e 90 dias. Durante o tratamento os animais tiveram glicemia, peso e teste de tolerância oral à glicose avaliados. Ao final do tratamento, os animais foram eutanasiados e o sangue, baço, timo, linfonodos pancreáticos e pâncreas foram coletados. Após 30 dias de tratamento com inibidor, foi observado um aumento do hormônio GLP-1 no soro, além de um padrão imunológico favorável. Dentre os mecanismos imunológicos, foi possível observar um aumento de células T reguladoras (CD4+CD25+Foxp3+) no baço e uma diminuição da citocina IFN- no homogenato pancreático. Após 90 dias de tratamento com inibidor, também foi detectado um aumento de insulina e GLP-1 séricos e uma diminuição nos níveis glicêmicos dos animais tratados. Observou-se uma redução no padrão inflamatório no microambiente pancreático, caracterizado pela diminuição das citocinas TNF- e IFN- no homogenato pancreático e por uma redução da freqüência de macrófagos CD11b+ nos linfonodos pancreáticos. Os resultados obtidos neste projeto contribuíram para validar a eficácia terapêutica da administração de inibidor de DPP-4 no tratamento do DM1 experimental, bem como os mecanismos imunológicos e endocrinológicos envolvidos. Sem a ocorrência de efeitos tóxicos relevantes, o uso de inibidores de DPP-4 pode se tornar uma alternativa terapêutica para o tratamento do DM1 em humanos, que constitui uma doença crônica associada à baixa qualidade de vida em longo prazo e necessidade de tratamento de alto custo. / Davanso, M.R. Immunoendocrinological analyses after administration of dipeptidyl-peptidase-4 inhibitor on experimental type 1 diabetes. 2012. 105p. Thesis (Masters Degree) School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 2012. Type 1 Diabetes Mellitus (DM1) is an autoimmune disease characterized by the selective destruction of the insulin-producing pancreatic cells. Several forms of treatment for DM1 are current known such as insulin administration, immunosuppressors, pancreas or pancreatic islets transplantation, however, they all are inefficient in some aspect. Recently, a new class of drugs, the dipeptidyl-peptidase-4 inhibitors (iDPP-4) showed therapeutic efficacy and safety in the treatment with type 2 diabetes mellitus patients due to an increase in the glucagon-like peptide-1 (GLP-1). In addition, the use of DPP-4 inhibitors in experimental models of DM1 has demonstrated a protection of pancreatic cells against apoptosis, stimulation of pancreatic islets neogenesis and improvement in the glucose homeostatic control. This project evaluated the immunological and endocrinological profile of the DPP-4 (MK0431) inhibitor administration in experimental chemically induced DM1 by streptozotocin in C57BI/6 mice. The diabetic animals were treated with either a normal chow diet or diet containing DPP-4 inhibitor (4g MK0431/Kg of diet) ad libitum during 30 and 90 days. During the treatment the animals were evaluated regarding glycemia, weight, and oral glucose tolerance test. At the end of the treatment, the animals were killed and the blood, spleen, thymus, pancreatic lymph nodes and pancreas were collected. After 30 days of treatment with inhibitor, it was observed an increase in the hormone GLP-1 in the serum, besides a favorable immunological pattern. Among the immunologic mechanisms, it was possible to observe an increase in the regulator T cells (CD4+CD25+Foxp3+) of the spleen and a decrease in the cytokine IFN- in the pancreatic homogenate. After 90 days of treatment with inhibitor, it was also noticed an increase in the insulin and serum GLP-1 levels as well as a decrease in the glycemic levels in the treated animals. It was observed a reduction in the inflammatory pattern in the pancreatic microenvironment characterized by a decrease in the cytokines TNF- and IFN- in the pancreatic homogenate and by a reduction in the frequency of CD11b+ macrophages in the pancreatic lymph nodes. The results obtained in this project contributed to validate the therapeutic efficacy of the DPP-4 inhibitor administration in the treatment of experimental DM1, as well as the immunological and endocrinological mechanisms involved. Without the occurrence of relevant toxic effects, the use of DPP-4 inhibitors may become a therapeutic alternative for the treatment of DM1 in humans, which constitutes a chronic disease associated to low life quality and need for high cost treatment.

<p>Cardiovascular diseases (CVD) and their risk factors remain the leading cause of morbidity and mortality in North America. Food-derived bioactive peptides (BAP) have been shown to play a role in regulating physiological pathways of CVD risk factors including hypertension, diabetes, and chronic inflammation. Common sources of BAP include dairy and plant proteins. In addition to being an alternative protein source, it is now accepted that edible insect proteins can also confer health benefits beyond nutrition. However, as with any novel protein source, allergenicity remains a major concern surrounding edible insect consumption. </p> <p>This dissertation aimed to: 1) Evaluate the bioactive potential of peptides from an edible cricket species and; 2) determine the effects of BAP production methods on immunoreactivity. First, peptide-rich extracts were generated from farmed food-grade crickets via enzymatic hydrolysis techniques with the commercial protease Alcalase™. To measure the <i>in vitro</i> bioavailability, cricket peptides were also subject to simulated gastrointestinal digestion (SGD). Peptides and their digests were tested for relevant bioactivities and active groups were further fractionated by chromatographic methods to identify the major peptides responsible for the bioactivity. When tested for <i>in vitro</i> antihypertensive and anti-glycemic properties, cricket peptides were found to inhibit the activities of angiotensin converting enzyme, dipeptidyl peptidase-4, α-amylase, and α-glucosidase. The anti-inflammatory potential was expounded using RAW-264.7 macrophages and human umbilical vein endothelial cells (HUVEC). Cricket peptides (after SGD) effectively lowered NF-κB, MCP-1, and IL-6 production in cells without affecting their viability. Proteomic analyses identified 18 sequences from the enriched cationic peptide fraction that showed the highest activity. Three novel peptides were identified via molecular docking, as potent ACE-inhibitors and binding was similar to that of the commercial drug captopril. Key binding characteristics included interaction with hydrophobic amino acids (Phe, Pro, Leu) near the C-terminal position and coordination with Zn (II) ions near the ACE active site.</p> <p>Immunological reactivity was measured by IgE-binding from shrimp-allergenic patient sera to antigens present within cricket peptides. Our studies demonstrate that immunoreactivity was impacted by enzymatic hydrolysis, depending on the conditions and heating source used. Tropomyosin (a major shrimp allergen) was extracted from both untreated crickets and protein hydrolysates, and verified as the major reactive protein. Tropomyosin reactivity decreased (under both partial and extensive hydrolysis) or retained (under conditions which prevented epitope cleavage). However, using microwave-assisted enzymatic hydrolysis was effective at decreasing tropomyosin reactivity in all immunoassays tested (IgG and IgE). Proteomic and immunoinformatic analyses revealed prominent allergen binding regions of cricket tropomyosin available for cleavage during enzymatic hydrolysis. Conserved antigen regions showed greater homology with other crustacean species, but not with other well studied allergenic insect proteins (i.e., cockroach). Lastly, LC-MS/MS and FT-Raman spectrometry suggests that reactivity was affected due to distinct epitope cleavage within the protein instead of decreased antigen extractability/solubility. </p> <p>The findings of this dissertation support that edible cricket proteins are a potential source of bioactive peptides for functional food or nutraceutical development. Additionally, using protein extraction methods such as microwave-assisted hydrolysis seems a promising tool for minimizing the immunoreactivity of the allergen present in this edible cricket species.</p>

Morphogens are secreted signalling molecules that are expressed in restricted groups of cells within the developing tissue. From there, they are secreted and travel throughout the target field and form concentration gradients. These concentration profiles endow receiving cells with positional information. A number of experiments in Drosophila demonstrated that the morphogen Decapentaplegic (Dpp) forms activity gradients by inducing the expression of several target genes above distinct concentration thresholds at different distances from the source. This way, Dpp contributes to developmental fates in the target field such as the Drosophila wing disc. Although the tissue distribution as well as the actual shape and size of the Dpp morphogen concentration gradient has been visualized, the cell biological mechanisms through which the morphogen forms and maintains a gradient are still a subject of debate. Two hypotheses as to the dominant mechanism of movement have been proposed that can account for Dpp spreading throughout the Drosophila wing imaginal target tissue: extracellular diffusion and planar transcytosis, i. e. endocytosis and resecretion of the ligand that is thereby transported through the cells. Here, I present data indicating that implications of a theoreticalanalysis of Dpp spreading, where Dpp transport through the target tissue is solely based on extracellular diffusion taking into account receptor binding and subsequent internalization, are inconsistent with experimental results. By performing Fluorescence Recovery After Photobleaching (FRAP) experiments, I demonstrate a key role of Dynamin-mediated endocytosis for Dpp gradient formation. In addition, I show that most of GFP-Dpp traffics through endocytic compartments at the receiving epithelial cells, probably recycled through apical recycling endosomes (ARE). Finally, a Dpp recycling assay based on subcellular photouncage of ligand is presented to address specifically the Dpp recycling event at the receiving cells.

Two major projects involving the use of solution processed blended semiconductors for organic field effect transistors (OFET) were explored. The first incorporated unsorted single walled carbon nanotubes (SWCNTs) into a diketopyrrolopyrrole-quarterthiophene (DPP-QT) semiconductor to enhance the mobility of the OFET. 2 wt % SWCNT was found to be the optimal blend ratio, nearly doubling the device mobility (0.6 to 0.98 cm^2/V·s). Beyond this ratio, the metallic content of the SWCNT’s dropped the on/off ratio below acceptable levels. When source drain metals who’s work function poorly matched that of the DPP-QT semiconductors highest occupied molecular orbital (HOMO) were used, the SWCNT could dramatically reduce the charge injection ratio with best results achieved for Al, dropping the contact resistance from 10^5 to 45 MΩ. The second project explored the addition of small molecule additives into a UV-sensitive semiconductor 2,7-dipentyl[1]benzothieno[3,2-b][1] benzothiophene (C5-BTBT) mixed with a polymethyl methacrylate (PMMA) polymer binder. We generated a C5-BTBT based phototransistor sensitive to UV-A light. The HOMO and lowest unoccupied molecular orbital (LUMO) of C5-BTBT and the various additives were measured and discovered to play a critical role in how the device operates. We discovered if an additive has a LUMO lower in energy than C5-BTBT, it can act as a charge trap for a photogenerated electron. Electron deficient additives were found to retain a trapped electron for an extended period of time, allowing the device to remain in a high current state for an extended period of time (>1 hour). This provides an opportunity for the device to be used as an optical memory system or photoswitch. The best system could detect UV-A with a Pill > 10^5 and a photoresponsivity of 40 A/W at a Pinc of 0.0427 mW/cm^2. / Thesis / Doctor of Philosophy (PhD) / An emerging field of electronics is the use of organic materials that can be solution processed, to reduce manufacturing costs and make new and interesting products. Here we used unsorted carbon nanotubes blended into the semiconductor layer of a transistor, providing a bridge for the energy mismatch between the electrodes and the semiconductor. This allowed us the freedom to choose different metals to act as our electrodes when making electronic devices. Additionally through the correct choice of semiconductor, we added device functionality, making it responsive to UV-A light. This produced a device that could act as a UV-A sensor, logic switch or memory device. These devices are air stable and solution processable, a necessity if they are to be used in real world applications.

No description available.

Die Notwendigkeit von Bx42 für Drosophila Entwicklung und seine Beteiligung an unterschiedlichen zellulären Prozessen wurde mit Hilfe von RNA Interference (RNAi) demonstriert. Das ubiquitäre Ausschalten oder die Reduktion der Bx42 Expression mittels RNAi führte dabei zu embryonaler Letalität. Weiterhin führte eine gewebespezifische Induktion von Bx42 in Abhängigkeit der verwendeten Treiberlinien bei unterschiedlichen Temperaturen zu mehreren verschiedenen adulten Phänotypen. Diese Phänotypen waren die Grundlage für die Annahme, dass Bx42 eine Rolle in der Regulation mehrerer verschiedener Zellsignalwege spielt. In der Tat interagiert Bx42 mit den Proteinen des Notch-Signalweges Suppressor of hairless [Su(H)] und Notch intracellular domain (N-IC). Zusätzlich werden bei einer Verminderung von Bx42 die Notch Zielgene cut (ct) und enhancer of split m8 [e(Spl)m8] reprimiert (Negeri et al., 2002). In dieser Arbeit wurde die Beteiligung von Bx42 am TGF-ß/Dpp Signalweg untersucht. Es wurde gezeigt, dass Bx42 mit den TGF-ß/Dpp-Signalweg Proteinen Mad und Medea sowohl in vitro als auch in vivo interagiert. Die dabei verwendeten Methoden waren das Hefe-Zwei Hybrid-Sytem und Ni-NTA-Pulldown-Assays. Domänen der Smad Proteine (Mad und Medea), die für die Interaktion mit Bx42 notwendig sind, wurden mit Hilfe von Deletionskonstrukten untersucht. Es konnte gezeigt werden, dass die stark konservierte MH2-Domäne dieser Proteine für die Interaktion notwendig ist. Zudem belegten Versuche die genetische Interaktion zwischen Bx42 und Medea, in denen ein Bx42-RNAi-Phänotyp durch die gleichzeitige Überexpression von Medea gerettet werden konnte. Es ist bekannt, dass das humane Bx42-Homolog Skip sowohl mit den Proteinen Smad2 und 3 des TGF-ß/Activin Signalweg, als auch mit den Onkogenen Sno und Ski interagiert. Skip wirkt hier als Antagonist der Ski/Sno-Wirkung auf den TGF-ß/Activin-Signalweg und fungiert als Koaktivator (Leong et al., 2001). Die Interaktion zwischen Bx42 und der TGF-ß/Activin-Signalweg Komponente dSmad2, sowie mit dem Onkogen dSno konnte in dieser Arbeit auch für Drosophila bewiesen werden. Die Bedeutung dieser Wechselwirkung muss noch in weiteren Arbeiten analysiert werden. Der Einfluss der Bx42-RNAi-Induktion auf die TGF-ß/Dpp Zielgene distal-less (dll), optomotor blind (omb) und spalt (sal) wurde anhand von Reportergen Untersuchungen mit enhancer-trap-Linien und RNA in situ Hybridisierung untersucht. Es konnte gezeigt werden, dass das Ausschalten von Bx42 die Expression dieser Gene in ähnlicher Weise reprimiert, wie eine Elimination des TGF-ß/Dpp-Signals. Diese Ergebnisse unterstützen die Annahme, dass Bx42 in der Lage ist, TGF-ß/Dpp Zielgene durch eine Wechselwirkung mit Mad und Medea zu aktivieren. / The importance of Bx42 in Drosophila development was demonstrated using Bx42-RNA interference. The ubiquitous downregulation of Bx42 generated embryonic lethality, indicating the importance of this protein in early development. The tissue specific induction of Bx42-RNAi resulted in several different phenotypes depending on the driver line and the temperature at which animals were raised. The phenotypes obtained were the key point for the assumption that Bx42 may play a role in the regulation of a number of different cellular signalling pathways. Indeed, within the Notch signalling pathway Bx42 interacts genetically with Suppressor of hairless [Su(H)] and Notch intracellular domain (N-IC). Additionally, the reduction of Bx42 negatively affected the expression of the Notch target Genes cut (ct) and enhancer of split m8 [e(Spl)m8] (Negeri et al., 2002). In this work, the involvement of Bx42 in the Dpp signalling pathway was investigated. It was shown that Bx42 interacts both in vitro and in vivo, as demonstrated by yeast two hybrid protein-protein studies and Ni-NTA pull-down assays, with the TGF-ß/ Dpp components Mad and Medea. Domains of Smads (Mad and Medea) required for Bx42 interaction were examined using deletion constructs of Smads and the importance of the well conserved MH2 domains of Mad and Medea for this interaction was revealed. Moreover, the rescue of the Bx42-RNAi phenotype by the simultaneous overexpression of Medea demonstrated the genetic interaction between Bx42 and Medea. Furthermore, evidences for the interaction of Bx42 with the TGF-ß/Activin pathway component dSmad2 and with the oncogene protein dSno were obtained from interaction assays. The human homologue of Bx42, Skip, also interacts with Smad2/3 or Sno. The meaning of this interaction in Drosophila has yet to be analysed. The influence of Bx42-RNAi induction on the expression of Dpp target genes distal less (dll), optomotor blind (omb) and spalt (sal) was also investigated using enhancer trap lines and RNA in situ hybridisation. In this way it was proven that these genes are suppressed as they are by elimination of Dpp signalling. These results suggest that Bx42 may be able to modulate positively TGF-ß/Dpp signalling through an interaction with the signalling transducer Mad and Medea.

This thesis presents novel materials for photovoltaic conversion. The materials described are solution-processable organic semiconductors and have been used in the fabrication of organic photovoltaic cells (OPVs). The widely used PEDOT:PSS layer was investigated in P3HT and PTB7 photovoltaics. By doping, the efficiencies recorded were amongst the highest reported in the field using a conventional architecture. Two low band-gap BODIPY-based polymers were introduced and shown to have properties favourable for optoelectronics. Photovoltaics consisting solely of the polymers as the active component surpassed the performance expected without the use of an acceptor, indicating ambipolar behaviour, which was verified by charge carrier mobility measurements. When blended with an acceptor, the devices demonstrated a short-circuit current density similar to that of P3HT, a well-studied and successful OPV material. They also revealed a broad spectral response and were shown to operate as photodiodes. Two small molecules containing diketopyrrolopyrrole (DPP) and BODIPY were introduced and characterised. The addition of thiophenes red shifted the absorption but did not result in a sufficient bathochromic shift. Instead, a propensity to aggregate limited the performance. PLQY measurements showed the aggregation to quench luminescence. The study demonstrated the importance of controlling aggregation for efficient devices. Two solution-processable small molecules with a germanium-bridged spiro centre were investigated, and the molecular, electrochemical and optical properties discussed. The small molecule with shorter conjugation length exhibited an interesting packing motif shown to be favourable for charge transport. The mobility measurements were an order of magnitude higher than those reported for sexithiophene, a small molecule analogue, and the same order of magnitude as P3HT. The two-dimensional charge transporting nature of the material was verified with two independent techniques: time of flight (TOF) and organic field-effect transistor (OFET) measurements. The mobility of the material was found to vary with annealing, a result of morphological changes. These were studied with optical, electron and scanning probe microscopies. By controlling the morphology with the implementation of a well-defined annealing method, it was possible to improve the performance of OFETs and planar-heterojunction OPVs. Solution-processed bulk-heterojunction OPVs were fabricated, characterised and optimised with Ge spiro molecules. A PCE similar to that of P3HT, 2.66 %, was achieved for the one, whilst a PCE of 1.60 % was obtained for the other. The results are encouraging, and there is scope for improvement by increasing the overlap between the absorption and solar spectrum, for example.

本研究的目的在於使用心理學與政治學當中，與組織變革相關的理論與實務研究，來探索在政黨歷經組織變革的過程．研究對象為國內第一大反對黨─民進黨． 本研究選擇了與心理學中有關的變項：次團體之間的互動，即民進黨中派系的互動；組織變革中領導者的角色；另外則是華人社會中受儒家思想影響極大的關係主義．由於派系之間的互動不論是在心理學或是政治學中的研究，都極為匱乏，對於民進黨的派系現象更是缺乏系統性的探討，因此本論文嘗試從質的研究著手，以派系互動為主要的變項，領導行為與關係主義為干涉變項，探索這些因素對於民進黨在組織變革過程中的影響．綜合以上，研究者提出兩個問題：第一，中國人是以情感為分類基礎，和研究對象主要以派系為分類基礎，其中的機制有何不同．第二，民進黨的黨主席屬於某一個派系，造成和部屬的互動對組織變革的影響，並探討五倫關係在此所扮演的角色為何． 使用方法以文件研究與半結構式的訪談為主，輔以研究者的參與觀察．經過半年的研究期間，得到的研究結果可分為五個方面：1.派系形成的原因與分析當中的結構因素；2.探索派系之間互動之前，先交代各別派系的基本特質，如成立的背景、結合的機制、組織的特色、代表人物等等；3.派系互動則以資源分配為例來討論；4.派系互動對組織變革的影響，根據Burke-Litwin的組織績效與變革模式當中的各因素，探討在民進黨的組織變革當中的調整或改變，並討論兩大干涉變項的影響；5.使用組織心理學對組織變革的研究回顧民進黨． 研究結論認為，每一個派系都有其組織的文化，而華人社會使用許久的五倫關係在當中必然有其影響，只是有程度上與優先順序上的不同．而這些不同也造成了在成員的屬性、私人關係的頻率、派系衝突解決方式、派系的約束力與對代表人的認同上的差異，這些派系差異所形成的競爭與合作，在仍處於反對黨的前提之下，原則上仍會以黨的整體利益為最優先的考量． 即使黨主席做為民進黨的領導者，也不能違反黨的最高精神──程序正義與公開透明．在這樣的原則之下，五倫關係就會適時地發揮其潤滑作用；反之，若黨主席以五倫關係作為決策的第一考量，則受到黨內各派系抵制的機會將會增加．由於在制度上刻意弱化黨主席權限，因此以黨主席為主的內外團體現象並不明顯．

為了探討與分析長期以來存在，關於行政院高階政務官、事務官員調動的「普遍說」與「特殊說」爭議，並且探究哪些制度性、組織性因素，對於行政院的高階政務、事務官員更替，會有所影響。本研究嘗試在制度的代理人理論架構，以及相關理論預設之下，以一九八八年第一季到兩千零一十年第四季，時序橫跨李登輝、陳水扁、馬英九等三位總統主政期間，包括行政院本部暨所屬三十二個部會的高階政務、事務官員，作為研究對象，進行實證的分析。 在本文的第一到第四章，我們分別說明了研究動機與背景、進行相關文獻回顧、探討研究理論，以及說明研究問題與模型。而在第五章則是分析、探討，台灣於一九九零年代初期，到一九九零年代中期，因為持續進行憲法增修條文的制訂，進而使得總統在憲法本文，以及憲法增修條文，所構成的憲政制度上，獲得了行政院高階行政官員的人事任免權。而且總統在取得了這個制度上的重要權力之後，行政院高階行政官員的任命、調動，就成為總統掌控行政體系的重要制度性工具，同時更是高階行政官員控制的重要手段。 此外，我們更進一步在第六章，分析了台灣從一九八零年代晚期，到兩千零一十年間，分別在不同階段，先後掌權的李登輝、陳水扁、馬英九等三位總統，對行政院高階行政官員，所採取以高階行政官員任命、調動，作為手段的控制模式，並且探討於第四章所提出的假設一、假設二、假設三，分別獲得實證資料支持的情況。至於第七章則是先透過總體資料的分析，探究假設四到假設十一，能否獲得實證資料的支持，同時更以部會為單位的季度別資料，建構縱橫資料的多元迴歸模型，用以分析哪些因素，對於行政院高階行政官員的更替，是有所影響的。 然而，在相關的實證分析之後，我們可以確切的認為，以往關於行政院高階行政官員控制上，所存在的「普遍說」與「特殊說」的爭論，是以普遍說可以獲得理論上，以及實證資料的支持。而就各種可能對於行政院的高階政務、事務官員更替，會有所影響的制度性、組織性因素而言，總統處在什麼樣的政治時機、面對哪些性質的部會，將會是關鍵。當總統必須更為重視行政體系的穩定，以及施政品質時，必然會選擇壓抑行政官員控制的強度。反之，當總統所面對的是，委託代理人難題疑慮的攀升，且有較大的空間容忍行政體系的不穩定時，那麼可以預期的是，大範圍、數量龐大的高階行政官員清洗，將會接踵而至。 最後，透過相關資料的分析，我們也發現了，在一次、二次政黨輪替，於西元兩千年到兩千零八年，相繼的發生，以及相應出現範圍廣泛、人數繁多，全面性高階行政官員清洗，也使台灣社會，在短期間之內，必須付出可觀的政治交易成本。這樣的情況，也使得台灣民眾的民主信念，是有所動搖，同時這也對於台灣的民主政治發展，是一個不容被忽視的隱憂。 / This reasearch offers an analysis of the long-standing discourse on transferal patterns of government officials in Taiwan, with the focus on the much-debated “general theory” vs. “special theory” approach. We will look at the systemic and organizational factors that influence the appointment, replacement, and transferal of both administrative and executive officers in the higher echelons of government. Specifically, this paper examines the time period from 1988 to 2010, employing a systematic agent framework in combination with related theoretical parameters to explore the concrete situation in the Executive Yuan and its 32 ministries, commissions, and other agencies under three consecutive administrations (i.e. presidents Lee Teng-hui, Chen Shui-bian, and Ma Ying-jeou). In the first four chapters, we will outline background and motive of this paper, give an overview of past research on this topic, scrutinize relevant theoretical approaches, and illustrate research problems and models. In the fifth chapter, we explore and analyze the period from the early to the mid-1990s, a time that saw repeated amendments and additions to the constitution that gave the president increasingly greater powers of appointment and removal of cabinet members. These powers have become one of the most important political tools the president wields, allowing the nation’s leader to exert highly effective and immediate control over the Executive Yuan, in particular over its highest-ranking officials. In the sixth chapter, we will cover the entire period from the late 1980s to the 2010. During this time, three presidents were successively at the helm (Lee from 1988-2000, Chen from 2000-2008, Ma since 2008), and we will scrutinize the different appointment and transferal modes applied during their terms, in particular as regards their use as a tool of political control. In addition, we will further discuss the first three hypotheses initially proposed in chapter four, and show if and how they are borne out by the data and facts assembled in this research. Chapter seven contains a comprehensive analysis of the entire set of data to facilitate our discussion of hypotheses four to eleven as first proposed in chapter four, and to determine whether or not these are supported by the empirical data. At the same time, we look at the quarterly figures from Executive Yuan ministries and commissions to create a multiple regression model of the cross-section data, which will help us to analyze which specific factors influence the substitution and transferal of high-ranking officials. After a thorough analysis of the empirical data, we will find that of the two theories usually applied to the problem of systemic and political control over the higher echelons of the executive, i.e. the general and the special theory mentioned above, the general theory is in fact better supported by the relevant set of data. As for which particular systemic and organizational factors may influence the replacement or substitution of high-ranking administrative and executive cabinet members, the crucial parameters affecting this question are the larger political climate that the president faces, as well as the type and political weight of the concerned ministries and commissions. At times when administrative stability and quality are the paramount considerations, the president will necessarily deemphasize his control over the executive and refrain from making too many personnel changes, while in times of political crisis, or when there is growing concern over the competence and suitability of his entrusted agents (i.e. leading members of the Executive Yuan’s subdivisions) and thus more tolerance for change, one will almost always see large-scale cabinet reshuffles as the president attempts to flush out unfit or unwanted elements. Finally, an analysis of the overall data also shows that the two transitions of power Taiwan has seen in 2000 and 2008 respectively were—as a matter of course—accompanied by extensive personnel changes as numerous high-ranking government officials were removed from office to make place for new faces. These far-reaching waves of “political purging” and complete reorganization of the cabinet within short periods of time have come at a considerable political cost for Taiwan’s society as a whole. This has somewhat shaken the population’s faith in democracy as a political system, and here lies a significant potential concern for the future development of Taiwan’s democracy.