La nucléoline, une des protéines non-ribosomique les plus abondantes du nucléole, semble être impliquée dans de nombreux aspects du métabolisme de l'ADN en plus de son rôle dans la régulation de la transcription par l'ARN polymérase I, la maturation du pré-ARNr et l’assemblage des ribosomes. L'objectif de cette thèse est d'étudier l'interaction de la nucléoline avec la chromatine, et de déchiffrer la fonction de la nucléoline dans la régulation de l’expression génique. Il a été rapporté que la nucléoline est nécessaire pour la transcription des gènes codant pour l'ADN ribosomal in vivo, mais le mécanisme par lequel la nucléoline module la transcription d’ARN polymérase I (Pol I) est inconnue. Dans cette thèse, je montre que l’inhibition de l’expression de la nucléoline par siRNAconduit dans les gènes de l’ADNr à une augmentation de la marque hétérochromatine et une diminution des marques caractéristiques de l’euchromatine. La nucléoline est associée à des gènes ADNr non méthylés et ChIP-seq montrent un fort enrichissement de la nucléoline dans le promoteur et la région codante de l'ADNr. La nucléoline est capable d'interférer avec la liaison de TTF-1 sur le terminateur T0 proches du promoteur inhibant ainsi le recrutement du sous-unité NoRC TIP5 et HDAC1 et la création d'un état répressif hétérochromatine. Cette invasion de macroH2A1 dans le nucléole joue un rôle majeur dans l'inhibition de la transcription par la RNA Polymérase I en l'absence de la nucléoline. Ces résultats révèlent l'importance de la nucléoline pour le maintien de l'état euchromatien de l'ADNr et le rôle de macroH2A1 dans la régulation de la transcription de l'ADNr. / Besides the well-known role of the nucleolus in ribosome biogenesis, nucleoli play important roles in the regulation of many fundamental cellular processes, including cell cycle regulation, apoptosis, telomerase production, RNA processing and therefore it is not surprising that many nucleolar proteins appear to be multifunctional proteins. Nucleolin, one of the most abundant non-ribosomal proteins of the nucleolus, has been the focus of many studies since it was first described 35 years ago. It seems to be involved in many aspects of DNA metabolism, chromatin regulation and appeared to be a good pharmacological target for drug development in addition to its role in RNA polymerase I transcription and pre-ribosomal processing and assembly in pre-ribosomes. In eukaryotic cells, DNA is packed into nucleosomes to form chromatin in the nucleus. The cells develop a variety of strategies to overcome the nucleosomal barriers. These strategies include DNA methylation, histone post-translational modifications, incorporation of histone variants and ATP dependent chromatin remodeling. The aim of this thesis is to study the interaction of nucleolin with chromatin, and to decipher the mechanism of nucleolin in gene regulation. It was reported that nucleolin possesses a histone chaperone activity, helps the transcription through nucleosomes, and it is required for ribosomal DNA gene (rDNA) transcription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (Pol I) transcription is unknown. In the thesis it is shown that nucleolin knockdown results in an increase of the heterochromatin mark H3K9me2 and a decrease of H4K12Ac and H3K4me3 euchromatin histone marks in rDNA genes. Nucleolin is associated with unmethylated rDNA genes and ChIP-seq experiments identified a strong enrichment of nucleolin in the promoter and coding regions of rDNA. Nucleolin is able to interfere with the binding of TTF-1 on the promoter-proximal terminator T0 thus inhibiting the recruitment of the nucleolar remodeling complex (NoRC) subunit TIP5 and HDAC1 and the establishment of a repressive heterochromatin state. In addition, in absence of nucleolin or after inhibition of Pol I by actinomycin D, a strong relocalization of the histone variant macroH2A1 to the nucleolus and on the rDNA genes was observed. This invasion of macroH2A1 in the nucleolus plays a major role in the inhibition of Pol I transcription in absence of nucleolin, as knockdown of macroH2A1 eliminates the repressive effect of nucleolin depletion. These results reveal the importance of nucleolin for the maintenance of the euchromatin state of rDNA required for an efficient production of ribosomal RNAs and the role of macroH2A1 in rDNA transcription.

Oocyte development in Xenopus laevis spans six morphologically distinct stages (stage I-VI), and is associated with a decrease in protein O-GlcNAc levels. As a first step in elucidating the role of O-GlcNAc in developing oocytes, initial efforts were focused on isolation and identification of fifteen modified proteins that decrease during oocyte development. Stage I oocytes due to their high amounts of these proteins, were used as starting material for purification. Multiple affinity and specific antibody based purification technique were initially used in an attempt to enrich the O-GlcNAc proteins. Due to the unique properties of the proteins ultimately identified, these techniques were unable to provide sufficient material for sequencing. However, differential centrifugation coupled with 2D-gel electrophoresis was highly successful. The majority of isolated proteins were strongly basic in nature with pIs 8-10. Coomassie stained bands from 2D-analysis were trypsin digested, and peptides were sequenced by mass spectroscopy (Finnigan LCQ). Mass data were interpreted by Bioworks software, and protein sequences were compared to multiple protein databases. Initially, six proteins were identified as Thesaurin a (42Sp50), cytoplasmic mRNA binding protein p54, y-box homolog, Xp 54 (ATP dependent RNA helicase p54), Vg1 RNA binding protein variant A, Zygote arrest 1(Zar1) and Poly (A) binding protein (PABP). Thesaurin a, the main component of 42S particle of previtellogenic oocytes (stages I-III) is involved in tRNA storage and possess low tRNA transfer activity; y-box factor homolog and Xp54 are present in oocyte mRNA storage ribonucleoprotein particles; Vg1 RBP variant A associates mVg1 RNA to microtubules in order to translocate to the vegetal cortex; Zar1 is involved in oocyte-to-embryo transition; and PABP initiates mRNA translation. This study is the first to characterize these oocyte specific proteins as O-GlcNAc modified proteins. Overall, the presence of several O-GlcNAc proteins in oocytes, the reduction in their levels/ O-GlcNAc levels, and the variation in maturation time in the presence of HBP-flux modulators in developing oocyte indicates O-GlcNAc may play important roles in metabolism, cell growth and cell division of X. laevis oocytes. Therefore, identifying the remainder of these proteins and elucidating the O-GlcNAc role in their function is a worthwhile pursuit.

時間序列分析發展至今,常常發現動態資料的走勢,隨著時間過程而演變.所以傳統的模式配適常無法得到很好的解釋,因此許多學者提出不同的模型建構方法.但是對於初始模式族的選擇,卻充滿相當的主觀與經驗認定成份.本文針對時變型時間序列分析,考慮利用知識庫,由模式庫來判斷初始模式.再藉由遺傳演算法的觀念,建立模式參數的遺傳關係.我們把這種遺傳演算法,稱之為時變遺傳演算法.針對台灣省國中數學教師人數,分別以時變遺傳演算法,狀態空間,與單變量ARIMA來建構模式,並作比較.比較結果發現,時變遺傳演算法較能掌握資料反轉的趨勢,且預測值增加較為平緩.因此時變遺傳演算法在模式建構上將是個不錯的選擇. / In time series analysis, we find often the trend of dynamic data changingwith time. Using the traditional model fitting can't get a good explanationfor dynamic data. Therefore, many savants developed a lot of methods formodel construction. However, these methods are usually influenced by personal viewpoint and experience in model base selection. In this thesis, we discussedtime-variant time series analysis. First, we builded a model base to judge inial models by knowledge base. Then, we set up the genetic relations of themodels' parameter. This method is called Time Variant Genetic Algorithm. We use the data if the number of junior high school mathematic teachers in Taiwan to ccompare the predictive performance of Time Variant Genetic Algorithmwith State Space and ARIMA. The forecasting performance shows the Time VariantGenetic Algorithm takes a better prediction result.

Ce mémoire est dédié à l'étude de la synthèse de l'estimation d'état en temps fini par une approche algébrique (les techniques développées au sein de l'équipe ALIEN) pour les systèmes linéaires à paramètres invariant dans le temps (LTI) sujets à des perturbations extérieures inconnues, les systèmes linéaires à paramètres variant dans le temps (LTV) et les systèmes linéaires à commutation en temps continu (SLC). Pour les systèmes LTI et LTV, une expression formelle de l'état en fonction des intégrales itérées des sorties et de l'entrée a été donnée. Pour les systèmes linéaires à commutation, en combinant les résultats de l'estimation d'état pour les systèmes LTI et de la détection de l'instant de commutation en temps réel présentée dans le chapitre 4, nous donnons la démarche principale de l'estimation en temps réel du mode courant et l'état continu du système. Pour ce faire, on applique certains outils mathématiques : la transformation de Laplace, les outils issus du calcul opérationnel et la théorie des distributions

<p>software product line is a set of software-intensive systems that share a common, managed set of features satisfying the specificneeds of a particular market segment or mission. The main attractive part of SPL is developing a set of common assets which includes requirements, design, test plans, test cases, reusable software components and other artifacts. Tools for the development of softwareproduct line are very few in number. The purpose of these tools is to support the creation, maintenance and using different versions ofproduct line artifacts. This requires a development environment that supports the management of assets and product development,processes and sharing of assets among different products.</p><p>The objective of this master thesis is to investigate the available tools which support Software Product Line process and itsdevelopment phases. The work is carried out in two steps, in the first step available Software Product Line tools are explored and a list of tools is prepared, managed and a brief introduction of each tool is presented. The tools are classified into different categoriesaccording to their usage, relation between the tools is established for better organization and understanding. In the second step, two tools Pure::variant and MetaEdit+ are selected and the quality factors such as Usability, Performance, Reliability, MemoryConsumption and Capacity are evaluated.</p>

<p>Oncogenic human papillomaviruses (HPVs) are implicated in 99.7 % of cervical cancer cases but require the co-operation of other factors. To investigate potential genetic risk factors we have typed the HLA class II DRB1 and DQB1 loci in 478 women diagnosed with cervical carcinoma in situ and in 608 age-matched controls. Quantitative measurements of HPV 16, HPV 18/45 and HPV 31 were obtained. The DRB1*1501 and DQB1*0602 alleles were found to increase the risk of HPV 16 infection. Carriers of DRB1*1501 and DQB1*0602 were also shown to have an increased risk of a higher viral load compared to non-carriers. The DRB1*1301 and DQB1*0603 alleles were found to protect from HPV 18/45 and 31 infections as well as resulting in a lower viral load in carriers compared to non-carriers. Women with a high HPV 16, 18/45 or 31 viral load were more prone to long-term infections and women with a low HPV 16 viral load were more prone to short-term infections. Carriers of DRB1*1501 and DQB1*0602 alleles were also shown to have an increased risk of long-term infections compared to short-term infections. We also tested if an HPV susceptibility locus found for epidermodysplasia verruciformis (EV) was also linked to HPV susceptibility in cervical cancer. We did not find any linkage to this locus in a set of 77 families, each with at least three cases diagnosed with cervical carcinoma in situ. Other potential risk factors tested were HPV 16 E6 variants together with a p53 codon 72 polymorphism and HLA class II alleles. We found an association between the E6 L83V variant and the HLA DR4-DQ3 haplotype, as well as an increased frequency of Arg homozygosity of p53 in women infected with the L83V variant. These results show that alleles at HLA class II loci represents risk factors for persistent HPV infection and thereby also contribute to the risk of development of cervical carcinoma <i>in situ</i>.</p>

Die Orientierung am Kunden und dessen individuellen Wünschen ist heutzutage von großer Bedeutung. Mit Hilfe eines Produktkonfigurationssystems ist es möglich, Produkte nach bestimmten Regeln aus bestimmten Bauteilen virtuell zu entwickeln [1] und somit die gewünschten Leistungsmerkmale der Kunden auf ihre Durchführbarkeit hin zu überprüfen. In der vorliegenden Marktuntersuchung wurden die Leistungsfähigkeit von Konfiguratoren sowohl in ERP-/PPS-Systemen als auch als Stand-alone-Lösung untersucht und darauf überprüft, inwiefern sie zur Bewältigung komplexer und variantenreicher Produktgestaltungsaufgaben geeignet sind. / Market research : configurators in ERP-/PPS-Systems: <br><br> Today customer orientation is of great importance. With the help of a product-configuration-system it is possible to develop products virtually under specific rules and therefore to prove the customer capability characteristics for their practicability. In the present market research the capability of configurators in ERP-/PPS-systems as well as in stand-alone-solutions were checked and it was tested to what extend they are suitable to cope with complex product implementation.<br> -------<br> © GITO mbH Berlin

Oncogenic human papillomaviruses (HPVs) are implicated in 99.7 % of cervical cancer cases but require the co-operation of other factors. To investigate potential genetic risk factors we have typed the HLA class II DRB1 and DQB1 loci in 478 women diagnosed with cervical carcinoma in situ and in 608 age-matched controls. Quantitative measurements of HPV 16, HPV 18/45 and HPV 31 were obtained. The DRB1*1501 and DQB1*0602 alleles were found to increase the risk of HPV 16 infection. Carriers of DRB1*1501 and DQB1*0602 were also shown to have an increased risk of a higher viral load compared to non-carriers. The DRB1*1301 and DQB1*0603 alleles were found to protect from HPV 18/45 and 31 infections as well as resulting in a lower viral load in carriers compared to non-carriers. Women with a high HPV 16, 18/45 or 31 viral load were more prone to long-term infections and women with a low HPV 16 viral load were more prone to short-term infections. Carriers of DRB1*1501 and DQB1*0602 alleles were also shown to have an increased risk of long-term infections compared to short-term infections. We also tested if an HPV susceptibility locus found for epidermodysplasia verruciformis (EV) was also linked to HPV susceptibility in cervical cancer. We did not find any linkage to this locus in a set of 77 families, each with at least three cases diagnosed with cervical carcinoma in situ. Other potential risk factors tested were HPV 16 E6 variants together with a p53 codon 72 polymorphism and HLA class II alleles. We found an association between the E6 L83V variant and the HLA DR4-DQ3 haplotype, as well as an increased frequency of Arg homozygosity of p53 in women infected with the L83V variant. These results show that alleles at HLA class II loci represents risk factors for persistent HPV infection and thereby also contribute to the risk of development of cervical carcinoma in situ.

The utilization of ferromagnetic shape memory alloys (FSMAs) in small scale devices has attracted considerable attention within the last decade. However, the lack of sufficient studies on their reversible shape change mechanisms, i.e, superelasticity, magnetic field-induced martensite variant reorientation and martensitic phase transformation, at the micron and submicron length scales prevent the further development and the use of FSMAs in small scale devices. Therefore, investigating the size effects in these mechanisms has both scientific and technological relevance. Superelastic behavior of Ni54Fe19Ga27 shape memory alloy single crystalline pillars was studied under compression as a function of pillar diameter. Multiple pillars with diameters ranging between 200 nm and 10 µm were cut on a single crystalline bulk sample oriented along the [110] direction in the compression axis and with fully reversible two-stage martensitic transformation. The results revealed size dependent two-stage martensitic transformation which was suppressed for pillar sizes of 1 µm and below. We also demonstrated that the reduction in pillar diameter decreases the transformation temperature due to the difficulty of martensite nucleation in small scales. Size effects in the magnetic field-induced martensite variant reorientation were investigated in the Ni50Mn28.3Ga21.7 single crystals oriented along the [100] direction of the austenite phase. Single crystalline compression pillars were fabricated on the martensite twins between the sizes of 630 nm and 20 µm. It was found that the stress-induced and magnetic field-induced martensite variant reorientation are size dependent and became more difficult with the reduction in sample size. Surprisingly, it was still possible to magnetically activate the shape change in the micropillars which indicates the fact that magnetocrystalline anisotropy energy increases with the reduction in sample dimensions. Ni45Mn36.6Co5In13.4 pillars between the 600 nm and 10 µm diameters were investigated along the [100] direction of the austenite to study the size effects in the magnetic field-induced phase transformation (MFIPT). MFIPT was obtained down to 5 µm size in these pillars with reasonable magnetic field levels similar to their bulk counterparts.

自先秦《詩經》成了四言體裁集大成作品之後，討論者眾，繁華過盡，後世以四言體裁為研究對象者遂寡，使得四言體裁成為詩歌學術討論相對較缺乏關愛之一環，甚為可惜。晉代摯虞與梁代劉勰不約而同界定四言體裁詩歌為「正體」，正體與四言詩的關係，在先秦《詩‧大序》僅約略可見「正」與「變」的對舉，在漢代以前則呈現正變不明的情況，四言體詩歌可以說是到了摯虞才正式被稱為「正體」。究竟四言體詩歌有何特殊風格與地位？詩論家何以將之標舉為「正體」？而此一「正體」說法，對於魏晉時期的四言詩又有什麼影響？本文透過南朝以前的詩歌論述與詩歌流變，進行詳細且深入的探討。 四言詩歌在魏晉時期與五言詩歌同時並存，其間的消長遂成為當時詩歌流變的脈絡。本文參酌以五言詩為對象進行之討論與其建立的魏晉時期五言詩歌譜系，透過對魏晉時期四言詩脈絡進行詳細歸納整理，並且藉由對四言詩歌作品完整且細密的分類，以嚴謹架構出當時四言詩歌的內在質素。此外，從類型由來與區分的探究中，進一步剖析四言詩之所以被形塑為「正體」依據的緣由，以深入探勘魏晉時期所闕漏的四言詩歌討論，希冀確立四言詩在詩歌史之定位。本研究並在四言詩歌類型的篩選與討論上，透過量化分析方式，藉由創作類型比例的高低作為另一客觀的討論基礎，同時依憑數據化的討論，揭示、呈現四言詩歌在魏晉時期完整且確然的狀態。 / In Jin and Liang Dynasties, Zhi Yu (摯虞) and Liu Xie (劉勰) both defined four-word poetry as " Zheng Ti" (Classical Form). Actually, the form of four-word poetry was called "Zheng Ti" until Zhi Yu. Why those critics called the four-word poetry with classical form? What could we figure out the special type and cultural level of "Zheng Ti"? And the thought of classical form compared what kind of imagination in the four-word poetry during Wei and Jin Dynasties? In this paper, the reasons why four-word poetry associated with "Zheng Ti" were discovered through the Southern Dynasties poetry discussion with variation in prosody. The four-word and five-word poetry both coexist in the Wei and Jin Dynasties. The growth and decline between the two forms composed of the poetry changed at that time. In this paper, the four-word poetry classifications system was established and the qualities were found through the researches about five-word poetry classifications and the system of five-word poetry in Wei and Jin Dynasties. Besides, the research through screening and discussion of four-word poetry, based on quantitative analysis, the proportion of every type in the classifications system from high to low could be an objective basis for discussion. Relied upon a discussion of the data, this paper will render the complete and mature condition of four-word poetry, and fill up the lake of discussion in four-word poetry history of positioning in Wei and Jin Dynasties.