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Dipeptidyl peptidáza-IV a Fibroblastový aktivační protein v gliomagenezi. / Dipeptidyl peptidase-IV and Fibroblast activation protein in gliomagenesis.Trylčová, Jana January 2018 (has links)
"Dipeptidyl peptidase-IV Activity and/or Structure Homologues"(DASH) represent a newly defined group of multifunctional molecules, typically bearing dipeptidyl peptidase-IV- like hydrolytic activity. Dipeptidyl peptidase-IV (DPP-IV) cleaves out X-Pro dipeptides from the N-terminus of peptides. Other molecules carrying similar enzyme activity, such as Fibroblast activation protein (FAP), DPP-II, DPP8 and DPP9 or even DPP-IV structure-like but hydrolytically inactive molecules (DPP6 and DPP10) also belong to this group. Recent knowledge suggest a substantial role of DASH in cancer pathogenesis. The aim of this study is a preparation of a biological model and its use for understanding the mechanisms of interaction(s) between transformed glial cells and stroma in the processes of origin and development of tumors derived from neuroectoderm. Stable transfected human glioblastoma cell lines with inducible gene expression of DPP-IV, Fibroblast activation protein and their enzymatically inactive mutated forms, were prepared within the project. Prepared cell lines are used as a tool for studying not only the "autocrine" importance of DPP-IV and FAP for the expressing cells in in-vitro, but also for their potential "paracrine" effect(s) within the tumor microenvironment after homotopic implantation into the...
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Mechanisms of priming and elongation during ubiquitin chain formationLips, Christian 10 January 2020 (has links)
Die Interaktion von RING-finger-Ubiquitin (Ub)-Ligasen (E3-Enzyme) mit Ub-konjugierenden Enzymen (E2-Enzyme) bestimmt wie schnell ein Zielprotein mit einer Ub-Modifikation versehen wird. In dieser Arbeit wird die Stimulation der E2-Enzyme Ubc6 und Ubc7 durch die E3-Enzyme Hrd1 und Doa10 untersucht. Es wird gezeigt, dass Ubc6~Ub-Konjugate bereitwilliger sogenannte "closed conformations" annehmen als Ubc7~Ub-Konjugate, was wiederum die Tendenz, Ub zu übertragen, steigert. Die katalytische Aktivität von Ubc7 kann durch RING-Domänen stimuliert werden. Durch einen allosterischen Mechanismus, der linchpin allostery, werden Ubc7~Ub-Intermediate in "closed conformations" gedrängt. Zusätzlich werden spezifische Kontakte zwischen RING-finger-Domänen und der Ub-Einheit in einem E2~Ub-Konjugat identifiziert. Diese schränken die Flexibilität des Konjugates weiter ein und begünstigen dadurch die Reaktivität des E2~Ub-Intermediates. Dieser Mechanismus scheint weit verbreitet zu sein und wurde schon bei anderen Ub-Ligasen beobachtet.
Poly-Ub-Signale werden in mehreren Schritten generiert. In einer Priming genannten Reaktion wird die erste Ub-Einheit auf das Zielprotein übertragen. Dieser Vorgang erfordert sehr flexible Enzyme, die in diversem Umfeld Akzeptorstellen finden und mit Ub modifizieren. Die zweite Reaktion, die elongation, umfasst das schrittweise Anheften weiterer Ub-Moleküle an die erste Einheit. Im Gegensatz zum Priming, beruht die Bildung einheitlicher Ketten auf der wiederholten und robusten Konjugation von Ub-Molekülen in gleichbleibendem Milieu. Ub-Ligasen verwenden verschiedene Strategien, um die unterschiedlichen Herausforderungen dieser Reaktionen zu bewältigen. Während Doa10 je ein E2-Enzym pro Reaktion nutzt, kann Hrd1 ein einzelnes E2-Enzym durch linchpin allostery ausreichend stimulieren, um beide Prozesse durchzuführen, wie diese Arbeit zeigt. / The interaction of RING-finger ubiquitin (Ub) ligases (E3 enzymes) with Ub conjugating enzymes (E2 enzymes) dictates how fast a Ub modification is synthesized on a client protein. This thesis addresses the catalytic stimulation of the E2 enzymes Ubc6 and Ubc7 by their cognate E3 enzymes Hrd1 and Doa10. Results show that Ubc6~Ub conjugates adopt closed conformations more readily than Ubc7~Ub conjugates, indicative for an inherently higher propensity to transfer Ub. The catalytic activity of Ubc7 can be stimulated by a RING domain which relies on so-called linchpin allostery. This drives Ubc7~Ub intermediates into a closed conformation. In addition, specific contacts of the RING-finger domain and the Ub moiety in an E2~Ub conjugate were identified which further restrict the flexibility of the conjugate and thereby increase the reactivity of the E2~Ub intermediate. This seems to represent a common mechanism for the stimulation of E2 enzymes because similar contacts of RING-finger proteins with Ub have been observed for other Ub ligases.
Poly-Ub signals on proteins are generated in successive steps. The first reaction, called "priming", comprises the attachment of an initial Ub moiety to the target. This requires high flexibility of the involved enzymes to modify acceptor sites in a versatile environment. The second step is the sequential addition of Ub to previously attached Ub molecules in a process termed elongation. In contrast to priming, the formation of uniform Ub chains relies on the repeated and robust conjugation of Ub moieties in a mostly invariant setting. Ub ligases employ different strategies to meet the divergent requirements of these reactions. Doa10 uses separate E2 enzymes for priming and elongation. This thesis shows that Hrd1 efficiently stimulates a single E2 enzyme for the catalysis of both steps via linchpin allostery.
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台北市集合住宅管理維護模式之研究洪子茵 Unknown Date (has links)
住戶對其居家環境每日必需的管理維護工作通常有兩大類選擇:住戶自行負責或委託管理維護公司。目前國內集合住宅在管理維護執行上的現況,係「自行管理」佔了68﹪,「委託管理」佔32﹪,這樣的比例與香港及日本的集合住宅大部分係屬委託管理的情形相差甚遠。為何台灣集合住宅委託管理的情形較不普遍?究竟是什麼因素在影響住戶對管理維護模式的選擇?而不同的管理模式其管理維護的效果有何不同?又是哪一種管理維護模式最能讓住戶感到滿意?此乃本研究關注之焦點。
實證結果發現,集合住宅的「規模」與「價格」是影響管理模式選擇的關鍵,當戶數規模與管理費用越足夠,選擇委託管理模式的機率將越大。平均而言,高層大廈與社區,選擇委託管理較自行管理的勝算分別為公寓的6.357倍與4.245倍。此外,當戶數規模平均每增加10戶,選擇委託管理模式的機率就會增加3.9﹪;而當管理費用平均每坪增加10元時,選擇委託管理模式的機率亦會增加6.5﹪。
至於管理維護模式與住戶滿意度的探討,委由管理維護公司來維護社區的結果均比自行管理來得讓住戶滿意,而「部分委託管理模式」則是四種模式中滿意度最高者。究其原因,管理公司雖有其專業知能與經驗的優勢,但也可能存在著代理問題,受到這二者相互權衡(trade-off)的影響,全部委託管理的滿意度便不如部分委託管理。
為使理論實證結果能與實務連結,本研究對「規模」與「價格」做門檻值推估,發現委託大樓管理業者的社區,住戶至少每月每坪需繳交70元的管理費,且該社區的總戶數應該在100戶左右,由此可知,台北市集合住宅的平均戶數可能因未達經濟規模門檻值(因為目前已報備管理組織的公寓大廈有八成其戶數都在百戶以下),致使台北市委託管理的情形並不普遍。此外,集合住宅內生存在的協商困難與外部性問題,也是委託管理比例偏低的原因,建議政府應藉租稅優惠方式來使外部效果內部化,並直接或委託民間非營利團體協助輔導集合住宅管理組織之報備,減少其中的協商成本。
關鍵字:集合住宅、管理維護、管理模式、住戶滿意度、戶數與管理費門檻值 / Households typically manage their living environment using one of two modes. Under the first, household conducts all of the basic and day-to-day management functions. Under the second approach, the household hires a property management company to provide and monitor a number of services such as repair and maintenance quality control.
In Taiwan, the current proportion of the implementation of condominium ( collective housing ) management and maintenance is 68% of owner management and 32@/o of company management. Comparing to Hong Kong and Japan where the company management is more common than owner management, this proportion is far behind.
This research is focus on the reason of less popular of company management in Taiwan collective housing and the factors of affecting the choice of management mode. Moreover this research also discusses the results and effects of different management modes and which management mode can provides the highest degree of satisfaction.
The empirical results show that the main factors of selections between different management modes are the "scale" and the "price" of the condominium. On average, comparing company management and owner management, the possibility of choosing company management is 6.357 times more in high-rise buildings (above 13 floor) than in apartment (under 5 floor) and 4.245 times more in the community (large projects) than in apartment. Besides, when the scale of the quantity increases additional ten units averagely, the possibility of choosing company management will increase 3.9% ; and when the management cost averagely goes up extra ten dollars per Pin, the possibility of choosing company management will also increase 6.5 % .
As for the discussion of the relationship between the management modes and the household satisfaction, general speaking, the household can get more satisfaction from the result of appointing building management & maintenance companies. Moreover, the outcome of "part company management mode" is the most outstanding one in the four types. The reason is that although the company has the professional knowledge and superior management skills, there does also exist the problem of agency. Due to the trade-off relationship, the satisfaction of complete company management mode is less than part company management mode.
In order to relate the theoretical model to the practice, this research infers the thresholds of "scale" and "price". The results show that every household in the community which has hired the building management & maintenance industry has to pay 70 NT$ per Pin-Month in average; furthermore, the number of its households should be approximate 100 units. Therefore it can be said because of the fact that the average number of the household in condominium in Taipei might not excess the threshold of economic scale, company management is not very common in Taipei.( note that at this stage 80% of the registered condominium is less than hundred households.). Besides, the reason of low proportion of company management is that there does exist the difficulty in negotiations and externalities. Consequently, it is suggested that government should use the effect of tax policy to intemalize the externalities. It is also recommended that government can direct or indirectly authorize the non-profit organizations to assist home owners associations to register, so that the cost of negotiations can be reduced.
keywords: condominium、 management & maintenance 、 management mode、household satisfaction 、 thresholds of "scale" & "price"
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Akce VK a její průběh v želivském klášteře z pohledu Náboženské matice / Operation "VK" and its process in Želiv Monastery from the perspective of Náboženská maticeMašková, Tereza January 2017 (has links)
Diplomová práce Abstract: Operation "VK" and its process in Želiv Monastery from the perspective of Náboženská matice. Master's thesis presents the fate of Želiv Monastery in 1950s caused by operation code named "VK" (monasteries deportation). Operation's purpose was to terminally prevent formation of economical and above all, cultural influence of Roman Catholic Church in recently founded Socialist country. According to unmapped documents from Náboženská matice's archive which is currently placed in National Archive in Prague, I would like to present means in which the communist regime handled monastery property, belongings and people which were interned as prisoners in the monastery. The goal of this thesis is to present profound consequences of monastery abolition using Church archive with roots of legal personality going back to reign of Joseph II. Keywords: Operation "VK", Želiv Monastery, Náboženská matice, Communism, Roman Catholic Church, Internment, Property seizure, "Church Six" Communist Party Central Committee
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Neoprávněné ekonomické aktivity ukrajinských migrantů v ČR / Unauthorized economic activities of Ukrainian migrants in the Czech RepublicMarečková, Veronika January 2019 (has links)
This diploma thesis deals with the issue of unauthorized economic activities of Ukrainian migrants in the Czech Republic, which in this case are understood as all the economic activities of these migrants, which are in some way contrary to the valid legislation - i.e. both completely illegal and quasi-legal activities. The thesis builds on a number of important theories and concepts, such as the dual labour market theory, network theory, institutional theory, client system, or precarisation. The main objective of this diploma thesis is to describe and structure the phenomenon of unauthorized economic activities of Ukrainian migrants in the Czech Republic. First, the thesis presents the statistical data concerning the studied phenomenon and outlines the legislative anchoring the employment of Ukrainian migrants within the Czech labour market. This is followed by the description of general context of Ukrainian labour migration to the Czech Republic, its main reasons and associated risk factors. Then attention is paid to the very phenomenon of unauthorized economic activities with a main focus on its causes, forms, consequences and possible solutions. In the research part of this diploma thesis, the data are mainly drawn from interviews with experts on the given issue working in different areas -...
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