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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Lokalisation, Isolierung und in vitro Generierung von Assemblierungsintermediaten des humanen 20S Proteasoms

Fricke, Benjamin 25 August 2006 (has links)
Das 20S Proteasom bildet den Protein degradierenden Teil des Ubiquitin-Proteasom-Systems (UPS) und ist damit an wichtigen zellulären Prozessen wie Genexpressionskontrolle, Zellzykluskontrolle, Apoptose, Peptidgenerierung zur MHC Klasse I Präsentation und Degradation fehlgefalteter Proteine beteiligt. Die einzelnen Schritte der Biogenese des 20S Proteasoms in Eukaryoten sind bisher nur in Ansätzen verstanden. In dieser Arbeit wird die Untereinheitenzusammensetzung von Biogeneseintermediaten und ihre subzelluläre Lokalisation und Organisation in humanen Zelllinien untersucht. Durch die Etablierung eines in vitro Systems konnten distinkte Assemblierungsintermediate humaner Proteasomen generiert werden und ein (-Ring als früheres Intermediat im in vitro System nachgewiesen werden. Aufschluss über den weiteren Vorgang der Assemblierung wurden durch in vivo Experimente mit radioaktiv markierten HeLa Zellextrakten gewonnen. So konnten vor allem neu synthetisierte und zuletzt eingebaute Untereinheiten identifiziert werden. Hierzu gehören die Untereinheiten ?1 und (7, die aufgrund ihrer in trans agierenden C-terminalen Verlängerungen einen Dimerisierungsprozess zweier Halbproteasom-Vorläuferkomplexe forcieren. Darüber hinaus kann die Untereinheit (1 aufgrund der gewonnen Erkenntnisse als die wahrscheinlich den (-Ring schließende Untereinheit im Vorläuferkomplex postuliert werden. Proteasomale Assemblierungsintermediate konnten außerdem durch immuncytochemische und biochemische Methoden am ER von humanen Zelllinien lokalisiert werden. Dabei scheint dem Assemblierungsfaktor POMP eine Schlüsselrolle zuzukommen, da dieser eine Assoziation der Vorläuferkomplexe mit dem ER erst ermöglicht. In dieser Arbeit sind weitere Schritte des komplexen Biogenese-Vorgangs konstitutiver 20S Proteasomen in humanen Zelllinien aufgeklärt worden und es konnte erstmals die subzelluläre Lokalisation für Assemblierungsintermediate in humanen Zellen beschrieben werden. / The 20S Proteasom represents the protein degrading part of the Ubiquitin- Proteasom- System and is therefore a participant in important cellular processes like gene expression, cell cycle control, apoptosis, peptide generation for MHC class I presentation and degradation of misfolded proteins. Only the beginnings of the individual steps of the 20S proteasome biogenesis in eucaryotes are so far understood. Tis work examines the subunit composition of assembly intermediates and their subcellular localisation and organisation in eucaryotic cells. Distinct assembly intermediates of human proteasomes have been generated by establishing an in vitro system. As an earlier intermediate in the in vitro system an (-ring could be identified. In vivo experiments using radioactive marked total lysates of HeLa cells shed light on the following sequence of assembly. Thus new synthesised and finally incorporated subunits could be indentified. Two of this subunits are (1 and (7 which could force the dimerisation process of two half-proteasome-precursor by their trans acting c-terminal extensions. Furthermore the (1 subunit has been identified as the (-ring completing subunit in the precursor complex. In addition it was possible to detect proteasomal assembly intermediates through immuncytochemical and biochemical methods on the ER of human cell lines. Thereby the assembly factor POMP plays a key role as it allows in the first place the precursor association with the ER. This work clarifies further steps of complex procedure of biogenesis of constitutive 20S proteasomes in human cell lines and allows the characterisation of the subcellular localisation of assembly intermediates in human cells for the first time.
2

O Ateneu e a nostalgia na forma

Ara?jo, Francisco Magno Silva de 25 May 2011 (has links)
Made available in DSpace on 2014-12-17T15:06:52Z (GMT). No. of bitstreams: 1 FranciscoMSA_DISSERT.pdf: 1003537 bytes, checksum: b8ce002ce1c22594454d46863041567e (MD5) Previous issue date: 2011-05-25 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The actual study proposes Raul d‟?vila Pomp?ia‟s O Ateneu (1888) among the most significant works in Brazilian Literature panorama, according to the perspective of verbal materiality of the Romanesque genre under a form nostalgia sign that, in its turn, ascends to the archaic origin poetry of fable. Along with large rereading of pertinent bibliography, it is gone here toward narrator Sergio‟s cr?nica de saudades on pursuit of showing it, firstly, as poetic language allegory updated in the novel technique; secondly, as radical metalanguage that still renders problematic several aspects of modern fictional prose / O presente estudo prop?e O Ateneu (1888) de Raul d‟?vila Pomp?ia dentre as obras mais significativas no panorama da Literatura Brasileira, segundo a perspectiva de materialidade verbal do g?nero romanesco sob o signo de uma nostalgia da forma que, por sua vez, remonta ? poesia da origem arcaica da f?bula. A par de ampla releitura da bibliografia pertinente, envereda-se aqui pela cr?nica de saudades do narrador S?rgio em busca de mostr?-la, primeiro, como alegoria da linguagem po?tica atualizada na t?cnica do romance; segundo, como metalinguagem radical que ainda problematiza v?rios aspectos da moderna prosa de fic??o
3

Dynamique de la formation de nanostructures périodiques par impulsions laser ultrabrèves sur une surface métallique / Dynamics of periodic nanostructure formation on metal surfaces by ultrashort laser pulses

Bounhalli, Mourad 15 December 2011 (has links)
La surface d’un matériau exposé à une irradiation laser à une fluence proche de son seuil d'ablation laisse apparaître des structures périodiques LIPSS (Laser Induced Periodic Surface Structure) d’orientation dépendant de la polarisation de faisceau incident et dont la période est de l'ordre de la longueur d'onde. Les causes de ce phénomène qui suscite l'attention des chercheurs depuis plus d’une trentaine d’années sont maintenant bien connues. Cependant, son étude dans le cadre de l'utilisation récente de lasers à impulsions ultra-brèves fait surgir de nouvelles interrogations et relance l'intérêt pour le sujet. Ce travail est consacré à l’étude dynamique de la formation des nanostructures sur une surface métallique suite à une interaction laser femtoseconde. Nous nous intéressons aux mécanismes responsables de la formation de ces structures et nous proposons des explications permettant de comprendre leur origine. Dans le premier chapitre on présente une étude de l’état de l’art sur la formation des LIPSS, on y aborde les paramètres influant sur la formation de ces structures ainsi que les différents modèles explicatifs élaborés par les chercheurs. Ce chapitre traite également de l’interaction laser matière et de ses différents processus. Le deuxième chapitre met l’accent sur les dispositifs expérimentaux réalisés dans ce cadre. Le troisième chapitre présente, quant à lui une étude expérimentale permettant de rendre compte du rôle de l’excitation du plasmon de surface dans la formation de LIPSS. Dans le quatrième chapitre on analyse les résultats relatifs à l’influence du couplage électron phonon sur la formation des LIPSS. Enfin, le cinquième et dernier chapitre met en évidence le rôle de la relaxation électron-phonon sur la formation des LIPSS à l’aide d’une expérience pompe-sonde / When a material is irradiated with laser fluency close to its ablation threshold, periodic surface structures LIPSS (Laser Induced Periodic Surface Structure) appears on its surface. These structures are dependent of the polarization vector of incident electric field and their periods are close to the laser wavelength. They have been extensively studied for more than thirty years, and their origins are quite well understood. However, the recent use of ultra-short laser sources has renewed the subject. Present work is dedicated to the dynamics study of the nanostructures formation on a metal surface by femtosecond laser irradiation. We are interested in mechanisms responsible for the formation of these structures and we propose an explanation of their origin. The first chapter presents a literature review on the formation of LIPSS. Here, the parameters affecting the formation of these structures as well as a different models developed by researchers will be discussed. This chapter also addresses the laser material interaction and its processes. The second chapter focuses on the experimental devices used in this context. The third chapter deals with the experimental study concerning the role of excitation of surface plasmon in the formation of LIPSS. In the fourth chapter, the results on the influence of electron phonon coupling on the formation of LIPSS are analyzed. Finally, the last chapter highlights the role of electron-phonon relaxation on the formation of LIPSS using pump-probe experiments
4

Genetic and Molecular Studies of Two Hereditary Skin Disorders

Dahlqvist, Johanna January 2011 (has links)
Monogenic disorders, i.e., disorders caused by mutations in a single gene, are rare and clinically heterogeneous conditions. Identification of the genetic cause of monogenic traits can bring new insights into molecular pathways and disease mechanisms. The aims of the present study were to identify the mutant genes in two autosomal recessive skin disorders and to characterize the functions of the mutated genes.  In order to identify candidate genes for the two disorders whole-genome SNP analysis, homozygosity mapping and gene sequencing were used. Autosomal recessive congenital ichthyosis (ARCI) is a group of disorders characterized by extensive scaling and redness of the skin.  A subgroup of ARCI patients (n=27) was selected based on specific ultrastructural aberrations in their skin, revealed by electron microscopy. Mutations were identified in the Ichthyin gene in 93% of the selected patients, indicating a strong association between mutant Ichthyin and the specific morphological abnormalities. Ichthyin mRNA levels were shown to increase during keratinocyte differentiation in cells from healthy and affected individuals. Electron microscopy revealed a localization of ichthyin protein to keratins and desmosomes in epidermis. Staining of epidermal lipids identified aberrant lipid aggregates in skin sections of patients with Ichthyin mutations, indicating a role for Ichthyin in epidermal lipid metabolism. In twelve KLICK syndrome patients with ichthyosis, palmoplantar keratoderma and keratotic striae on joints, a single-nucleotide deletion was identified in the 5’ region of the proteasome maturation protein (POMP) gene.  The deletion caused an increase in the proportion of POMP transcripts with long 5’ UTR’s in patient keratinocytes.  Immunohistochemical analysis of differentiated skin cell layers revealed aberrant expression of POMP, proteasome subunits and the skin protein filaggrin in patients. CHOP expression, associated with endoplasmic reticulum stress, was increased in the same layers. siRNA silencing of POMP in cell cultures reduced proteasome subunit levels and induced expression of CHOP.  The results indicate that the mutation in KLICK patients causes POMP and proteasome insufficiency with subsequent cellular stress. This study conclusively contributes to the understanding of epidermal physiology and the pathogenesis of two inherited skin diseases.
5

A nostalgia da forma po?tica do romance: alegoriza??o barroca e tradi??o ret?rica n'O Ateneu de Raul Pomp?ia

Ara?jo, Francisco Magno Silva de 20 February 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-04-11T19:30:44Z No. of bitstreams: 1 FranciscoMagnoSilvaDeAraujo_TESE.pdf: 1713229 bytes, checksum: 18e387f2df272def69ee51d15c6438c0 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-04-12T19:39:16Z (GMT) No. of bitstreams: 1 FranciscoMagnoSilvaDeAraujo_TESE.pdf: 1713229 bytes, checksum: 18e387f2df272def69ee51d15c6438c0 (MD5) / Made available in DSpace on 2018-04-12T19:39:16Z (GMT). No. of bitstreams: 1 FranciscoMagnoSilvaDeAraujo_TESE.pdf: 1713229 bytes, checksum: 18e387f2df272def69ee51d15c6438c0 (MD5) Previous issue date: 2017-02-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O presente estudo prop?e analisar a primazia estil?stica d?O Ateneu (1888) de Raul Pomp?ia, buscando mostr?-lo como romance que elege a poesia como mat?ria de cria??o, motivo pelo qual se revela uma das obras mais modernas da Literatura Brasileira. A par de ampla releitura da bibliografia pertinente, que parte da revis?o da fortuna cr?tica do livro em correspond?ncia com a teoria da recep??o, busca-se mostrar a mec?nica da ?cr?nica de saudades? de S?rgio por meio de tr?s procedimentos: primeiro, como transposi??o aleg?rica da realidade para a f?bula; segundo, como metalinguagem po?tica atualizada na forma do romance; e, por fim, como reciclagem barroca de antigos c?digos ret?ricos na moderna prosa de fic??o. / The present study proposes to analyze the stylistic primacy of Raul Pomp?ia?s O Ateneu (1888), seeking to show it as a novel that elects poetry as the creative material, making of it one of the most significant works within the Brazilian literary panorama. Along with a broad re-reading of the pertinent bibliography, which starts from the review of the book's critical fortune in correspondence with the reception theory, it seeks to show the mechanics of S?rgio's "chronic of homesickness" through three procedures: first, as an allegorical transposition of reality into the fable; second, as a poetic meta-language updated in the form of the novel; and, finally, as baroque recycling of old rhetorical codes in modern fictional prose.
6

A atividade comercial nas ruas Pompeia, Chegan?a e Boa Sorte no contexto da produ??o do espa?o urbano da Zona Norte de Natal/RN-Brasil

Costa, Soneide Moura da 07 March 2017 (has links)
Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T20:01:57Z No. of bitstreams: 1 SoneideMouraDaCosta_DISSERT.pdf: 3498124 bytes, checksum: 09aee87d5cfa03d848c0113f06976399 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-06T22:32:13Z (GMT) No. of bitstreams: 1 SoneideMouraDaCosta_DISSERT.pdf: 3498124 bytes, checksum: 09aee87d5cfa03d848c0113f06976399 (MD5) / Made available in DSpace on 2017-06-06T22:32:13Z (GMT). No. of bitstreams: 1 SoneideMouraDaCosta_DISSERT.pdf: 3498124 bytes, checksum: 09aee87d5cfa03d848c0113f06976399 (MD5) Previous issue date: 2017-03-07 / Sendo o bin?mio com?rcio e cidade, indissoci?vel, empreende-se que a produ??o do espa?o urbano pode ser entendida ? luz da atividade comercial ao passo que este, ou seja, o espa?o, influencia na produ??o e localiza??o do com?rcio. Desta forma, a pesquisa enveredou pela discuss?o do processo de expans?o urbana de Natal/RN em dire??o ? Zona Norte via pol?tica habitacional e o percurso assumido pelo com?rcio tradicional nas ruas Pomp?ia, Chegan?a e Boa Sorte. O trabalho est? embasado em pesquisa bibliogr?fica, documental e pesquisa de campo. Do ponto de vista te?rico-metodol?gico, adotou-se o m?todo regressivo-progressivo proposto por Lefebvre (2000), cuja perspectiva de investiga??o est? organizada em tr?s momentos: descritivo; anal?tico-regressivo e hist?rico-gen?rico. A an?lise desenvolvida revelou que a atividade comercial na Pomp?ia, Chegan?a e Boa Sorte apresenta um car?ter de proximidade f?sica e social, uma vez que, al?m de atender a demanda de consumo local e de bairros pr?ximos a estas, tamb?m mant?m uma clientela fidedigna no que concernem ?s rela??es de compra com o comerciante da rua. Outrossim, mesmo n?o se configurando como grandes corredores de passagem na Zona Norte, estas ruas se constituem em l?cus de representa??o s?cio-espacial embasada, por um lado na l?gica de reprodu??o hegem?nica e por um lado na reprodu??o da vida. Ainda que inserido no contexto da crise econ?mica, tamb?m vivenciada no Rio Grande do Norte e que repercute em altas taxas de desemprego, o com?rcio da Pomp?ia, Chegan?a e Boa Sorte apresenta perspectivas de crescimento, principalmente no tocante ao com?rcio informal, sendo este ?ltimo uma possibilidade de garantia de renda familiar alternativa. / Understanding the binomial commerce and city, inseparable, it is realized that the production of the urban space can be understood from the commercial activity whereas this, that is, the space, influences in the production and location of the commerce. In this way, the research began by discussing the process of urban expansion of Natal / RN towards the North Zone through housing policy and the path taken by the traditional commerce in the streets Pompeia, Chegan?a and Boa Sorte. The dissertation is based on bibliographical research, documentary and field research. From the theoretical-methodological point of view, the regressiveprogressive method proposed by Lefebvre (2000) was adopted. The research perspective of this method is organized in three moments: descriptive; analyticregressive and historical-generic. The analysis revealed that the commercial activity in Pompeia, Chegan?a and Boa Sorte has a physical and social proximity, because it meets the demand of local consumption and neighborhoods close to them and maintains a trustworthy clientele in relation to the purchase relations with The street merchant. Moreover, even though they are not configured as major passageways in the North Zone, these streets constitute a locus of socio-spatial representation based on the logic of hegemonic reproduction and reproduction of life. Although in the context of the economic crisis, also experienced in Rio Grande do Norte and which has a high unemployment rate, the commercial activity in the streets of Pompeia, Chegan?a and Boa Sorte presents growth prospects, especially with regard to informal commerce, which is a possibility to guarantee alternative family income.
7

Die proteasomale Homöostase

Heink, Sylvia 03 August 2005 (has links)
Das Proteasom spielt eine zentrale Rolle beim Proteinabbau und der Antigen-Generierung für die adaptive Immunantwort. Vertebraten exprimieren zwei Typen des proteolytischen 20S-Kernkomplexes: das konstitutive c20S (mit den aktiven Untereinheiten beta 1, 2, 5) und das Immunoproteasom i20S (mit den Immunountereinheiten LMP2, MECL-1, LMP7). Die i20S-Expression wird durch Interferon_gamma (IFNg) induziert, was die Antigen-Präsentation auf MHC Klasse I und die Immunantwort gegen infizierte bzw. maligne entartete Zellen durch cytotoxische T-Zellen steigert. Proteasomen werden über komplexe, bisher unvollständig verstandene Biogenese-Prozesse formiert. Die initialen Schritte der humanen 20S-Formation wurden in dieser Arbeit untersucht und eine Methode zur Isolation früher Assemblierungsintermediate (EPIs) etabliert. Die 20S-Biogenese bedarf der Assistenz von Hilfsfaktoren wie dem Proteasom-Maturierungsprotein POMP. Diese Komponente von Precursorkomplexen stellt das erste Substrat gereifter c20S dar. In dieser Arbeit konnte erstmalig gezeigt werden, dass POMP ebenfalls die i20S-Formation vermittelt und sich die Biogenese von c20S und i20S hinsichtlich der Maturierungskinetik unterscheidet. POMP wird durch IFNg induziert und interagiert mit der Immunountereinheit LMP7. Dieses molekulare Zusammenspiel bewirkt eine schnellere Maturierung von i20S- im Vergleich zu c20S- Precursorkomplexen, wodurch POMP einem schnelleren Abbau unterliegt. Die forcierte i20S-Biogenese ist eine intrinsische Eigenschaft und unabhängig von weiteren, IFNg-induzierten Faktoren. Nur die LMP7_E2-Variante vermittelt die schnelle Degradation von POMP, während das nicht funktionelle LMP7_E1 mit einer anderen Prosequenz nicht in i20S-Vorläufer inkorporiert wird. Somit führt die alleinige LMP7_E1-Expression in IFNg-stimulierten Carcinom-Zellen zu einer i20S-Defizienz, was eine mögliche Immunevasions-Strategie darstellt. Weiterhin besitzen beide 20S-Typen unterschiedliche Halbwertszeiten: i20S sind, unabhängig von weiteren IFNg-induzierten Proteinen, signifikant instabiler als c20S. Somit werden i20S sowohl schneller formiert als auch zügiger wieder abgebaut als c20S, womit sie typische Eigenschaften cytokin-regulierter Proteine aufweisen. Die i20S-Formation ist also eine transiente Antwort und stellt ein effizientes Instrument zur schnellen Reaktion auf immunologische Herausforderungen wie z.B. eine Infektion dar. Nach einer wirksamen Immunantwort erlaubt die geringere i20S-Stabilität eine schnelle Rückkehr zur standardmäßigen c20S-Expression. / The proteasome plays a crucial role in protein degradation and antigen generation for the adaptive immune response. Vertebrates express two types of the proteolytic 20S core complex: the constitutive proteasome c20S (with the active subunits beta 1, 2 and 5) and the immunoproteasome i20S (with the immunosubunits LMP2, MECL-1 and LMP7). Interferon_gamma (IFNg) induces the i20S expression, that supports a more efficient MHC class I antigen presentation and an effective immune response against infected or malignant cells by cytotoxic T-cells. Proteasomes are formed by a complex and not well understood biogenesis program. The initial steps in the human 20S formation have been analyzed in this thesis and a method for the isolation of ´early proteasome assembly intermediates´ (EPIs) has been established. The 20S biogenesis requires the assistance of accessory factors like the proteasome maturation protein POMP. This component of precursor complexes becomes the first substrate of the matured c20S. The described experiments demonstrate for the first time that POMP mediates the i20S formation and that biogenesis of c20S and i20S differ in their maturation kinetics. POMP is induced by IFNg and interacts with the immunosubunit LMP7. This molecular interplay provokes a faster maturation of i20S compared to c20S precursor complexes, whereby POMP becomes subject to a faster degradation. The accelerated i20S biogenesis is an intrinsic characteristic and independent of additional IFNg-induced factors. Exclusively the LMP7_E2 variant causes the rapid degradation of POMP, whereas the non-functional LMP7_E1 bearing another prosequence is not incorporated into i20S precursor complexes. Thus, LMP7_E1 expression in IFNg-stimulated carcinoma cells leads to a i20S deficiency pointing out a possible immune evasion strategy. In addition, both 20S types display different half-life values: i20S are, independent of other IFNg-induced proteins, significantly less stable than c20S. Thus, i20S are not only faster assembled, but also more quickly decomposed compared to c20S, showing typical attributes of proteins regulated by cytokines. Consequently, i20S formation is a transient response and represents an efficient instrument for a rapid adjustment to varying immunological challenges like an infection. Once the immune response has been effective, the lower stability of i20S permits an expeditious return to the standard c20S expression.
8

The impact of [beta] 5i-deficiency on structure and function of 20S proteasomes in Listeria monocytogenes infection

Joeris, Thorsten 26 March 2009 (has links)
Das Proteasomsystem ist die Hauptquelle von Peptiden für die MHC Klasse I Antigen-Präsentation. In Vertebraten kann dieses durch die Expression verschiedener Subtypen des 20S Proteasoms moduliert werden. Die häufigsten Subtypen sind konstitutive Proteasomen (c20S) mit den katalytischen Untereinheiten beta1, beta2 und beta5 und Immunoproteasomen (i20S) mit den Immunountereinheiten beta1i, beta2i und beta5i. Die Expression von i20S optimiert in der Regel die MHC Klasse I Antigen-Präsentation, indem die Bildung von Peptiden mit hoher Affinität zu MHC I Molekülen verstärkt wird. Die Bildung von i20S wird momentan durch ein Modell der kooperativen Assemblierung erklärt, das auf der präferentiellen Interaktion zwischen den Immunountereinheiten beruht. In dieser Arbeit wurde die Assemblierung von 20S Proteasomen in beta5i defizienten Mäusen nach Infektion mit Listeria monocytogenes analysiert. In diesem Modell konnte keine präferentielle Interaktion zwischen den Untereinheiten festgestellt werden. Stattdessen zeigen die Ergebnisse, daß die Integration von konstitutiven oder Immunountereinheiten durch direkte Kompetition reguliert wird. Des Weiteren wurde während der Infektion eine beta5i-abhängige Zunahme der zellulären Proteasommenge festgestellt und somit ein neuer Mechanismus zur Regulation des zellulären Proteasomgehaltes entdeckt. Funktionell führt die beta5i-Defizienz zu einer verringerten MHC I Expression auf antigenpräsentierenden Zellen und zu einer verminderten Prozessierung des bakteriellen Antigens LLO296-304. Bei der Analyse der LLO296-304 spezifischen CD8 T Zell Antwort konnte jedoch kein Unterschied zwischen Wildtyp- und beta5i defizienten Mäusen festgestellt werden .Die Kontrolle der Infektion in den beta5i defizienten Mäusen ist jedoch in der Leber verzögert. Dies deutet darauf hin, dass die Erkennung und Elimination infizierter Zellen durch cytotoxische CD8 T Zellen auf Grund der geringeren MHC Klasse I Präsentation bakterieller Antigene behindert wird. / The proteasome-system is the main source of peptides for MHC class I antigen presentation. In vertebrates this system can be modulated by the expression of different subtypes of the 20S proteasome. The most common subtypes are constitutive proteasomes (c20S) with the catalytic subunits beta1, beta2 and beta5 and immunoproteasomes (i20S) with the immunosubunits beta1i, beta2i and beta5i. Expression of i20S generally optimizes MHC class I antigen presentation by increasing the generation of peptides with high affinity to MHC class I molecules. Currently, the formation of i20S is explained by a model of cooperative proteasome assembly, which is based on preferential interactions among the immunosubunits. Here, the assembly of 20S proteasomes was analysed in beta5i deficient mice during an ongoing infection with Listeria monocytogenes. In this model, no preferential interactions among constitutive subunits or immunosubunits could be determined. Instead, the results show that the integration of constitutive subunits or immunosubunits is regulated by direct competition. Further, a beta5i-dependent increase in cellular proteasome quantity was observed following infection. This reveals a novel mechanism for the regulation of cellular proteasome quantity, which is based on the differential expression of beta5i. Functionally, the deficiency in beta5i results in a reduced MHC class I cell surface expression on professional antigen presenting cells and a drastically diminished processing of the bacterial antigen LLO296-304. However, the analyses of LLO296-304 specific CD8 T cells did not reveal differences in the frequencies of these T cells between wild-type and beta5i deficient mice. Still, the control of infection in the liver of beta5i deficient mice was delayed. This phenotype suggests that the recognition and elimination of infected target cells by cytotoxic CD8 T cells is constrained due to the lowered MHC class I presentation of bacterial antigens.
9

Optimal sizing and operation of pumping systems to achieve energy efficiency and load shifting

Zhang, He 22 September 2011 (has links)
This dissertation presents a pumping system operation efficiency improvement solution that includes optimal selection and control of the water pump. This solution is formulated based on the performance, operation, equipment and technology (POET) framework. The focus is on the minimization of the operational energy cost. This efficiency improvement solution is divided into three stages in accordance with the operation category of the POET framework. The first stage is to select the optimal pump capacity by considering both energy efficiency and load shifting requirements. The second stage is to develop a flexible pump controlling strategy that combines and balances the contributions from energy efficiency and load shifting. The last stage is to improve the robustness of the control system using the closed-loop model predictive control approach. An optimal pump capacity selection model is formulated. In this model, additional capacity requirements for load shifting are considered along with the traditional energy efficiency requirements. By balancing the contributions from load shifting and energy efficiency, the operational energy cost can be reduced by up to 37%. An optimal pump control is formulated. The objective of this control model is to balance the energy efficiency and load shifting contributions during the operation and minimize the operational energy cost. This control model is tested under different operational conditions and it is compared to other existing control strategies. The simulation and comparison results show that the proposed control strategy achieves the lowest operational energy cost in comparison to other strategies. This optimal pump control model is further modified into the closed-loop model predictive control format to increase the robustness of the control system under operation uncertainties. A mixed integer particle swarm optimization algorithms is employed to solve the optimization problems in this research. AFRIKAANS : Hierdie verhandeling bied ’n verbeterde oplossing vir die operasionele doeltreffendheid van pompstelsels wat die optimale keuse en beheer van die waterpomp insluit. Hierdie oplossing is geformuleer op ’n raamwerk wat werkverrigting, bedryf, toerusting en tegnologie in ag neem. Die oplossing fokus op die vermindering van bedryfsenergie koste. Hierdie oplossing is onderverdeel in drie fases soos bepaal deur die bedryfskategorie gegrond op die bogenoemde raamwerk: Die eerste fase is die keuse van die optimale pompkapasiteit deur beide energiedoeltreffendheid en lasverskuiwing in ag te neem. Die tweede fase is om ’n buigbare pompbeheer strategie te ontwikkel wat ’n goeie balans handhaaf tussen die onderskeie bydraes van energiedoeltreffendheid en lasverskuiwing. Die derde fase is om die stabiliteit van die beheerstelsel te verbeter deur gebruik te maak van ’n geslote-lus beheermodel met voorspellende beheer (Predictive Control). ’n Model vir die keuse van optimale pompkapasiteit is geformuleer. In hierdie model word vereistes vir addisionele pompkapasiteit vir lasverskuiwing sowel as vereistes in terme tradisionele energiedoeltreffendheid in ag geneem. Deur die regte verhouding tussen die onderskeie bydraes van energiedoeltreffendheid en lasverskuiwing te vind kan ’n besparing van tot 37% op die energiekoste verkry word. Optimale pompbeheer is geformuleer. Die doel van die beheermodel is om die bydraes van energiedoeltreffendheid en lasverskuiwing te balanseer en om die bedryfsenergie koste te minimiseer. Hierdie beheermodel is getoets onder verskillende bedryfstoestande en dit is vergelyk met ander bestaande beheerstrategiee. Die simulasie en vergelyking van resultate toon dat die voorgestelde beheerstrategie die laagste bedryfsenergie koste behaal in vergelyking met ander strategiee. Hierdie optimale pomp beheermodel is verder aangepas in ’n geslote beheermodel met voorspellende beheerformaat om die stabiliteit van die beheerstelsel te verbeter onder onsekere bedryfstoestande. ’n Gemende heelgetal partikel swerm optimisasie (Mixed interger particle swarm optimization) algoritme is gebruik om die optimiseringsprobleme op te los tydens hierdie navorsingsoefening. / Dissertation (MEng)--University of Pretoria, 2011. / Electrical, Electronic and Computer Engineering / Unrestricted
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低レベル熱源からの化学的冷熱生成に関する基礎研究

松田, 仁樹, 板谷, 義紀, 渡辺, 藤雄 03 1900 (has links)
科学研究費補助金 研究種目:基盤研究(B)(2) 課題番号:08458123 研究代表者:松田 仁樹 研究期間:1996-1997年度

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