Made available in DSpace on 2016-01-26T18:55:35Z (GMT). No. of bitstreams: 1 daniel.pdf: 186929 bytes, checksum: 3b546022c9b10042ce06a35c124600cd (MD5) Previous issue date: 2012-04-13 / The silver staining technique for AgNOR nucleolar organizer regions (NORs) is characterized by marking proteins linked to the ribosomal ribonucleic acid, evaluating cell proliferation. The aim was to study the validity of the AgNOR staining technique in the testicular cell proliferation in crossbred ovine. Was used treis pairs forty crossbred sheep testes between six and ten months old.Wilcoxon and Spearman tests were used with a significance level of 5%. The mean NORs count in cells of the gonads right and left were respectively: spermatogonia (8.77±1.14 and 9.04±0.96), spermatocyte (4.99±2.00 and 6.20±2.07, P<0.05), Leydig (8.05±2.82 and 7.89±2.29) and Sertoli cells (8.07±1.88 and 7.61±2.16; P<0.05). There was a correlation between the mean values for right and left sides for the number of NORs (P<0.05) between Leydig x spermatocytes (0.49); spermatocytes x Sertoli (0.49) and Sertoli x Leydig (0.96). The study demonstrates that the AgNOR staining technique is indicated to evaluate the cell proliferative potential in ovine testis with practical implementation and low cost. / A coloração pela prata das regiões organizadoras de nucléolos (NORs) é caracterizada por marcar proteínas ligadas ao ácido ribonucléico ribossômico, avaliando a proliferação em células normais ou neoplásicas. O objetivo do trabalho foi estudar em testículos de ovinos obtidos em matadouro a validade do uso da técnica de coloração AgNOR na proliferação de células saudáveis da linhagem espermatogênica. Utilizou-se 43 pares de testículos de ovinos mestiços entre seis e 10 meses de idade. Testes de Wilcoxon e Spearman foram empregados, com nível de 5%. As médias das NORs nas células das gônadas direita e esquerda foram respectivamente: espermatogônia (8,77±1,14 e 9,04±0,96), espermatócito (4,99±2,00 e 6,20±2,07; P<0,05), Leydig (8,05±2,82 e 7,89±2,29) e Sertoli (8,07±1,88 e 7,61±2,16; P<0,05). Houve correlação (P<0,05) entre os lados para o número de NORs: espermatócito x Leydig (0,49); espermatócito x Sertoli (0,49) e Leydig x Sertoli (0,96). Conclui-se ser válido o emprego da técnica AgNOR para avaliar o potencial proliferativo das células saudáveis em testículos de ovinos com prática execução e baixo custo.

Made available in DSpace on 2016-07-18T17:53:10Z (GMT). No. of bitstreams: 1 daniel.pdf: 186929 bytes, checksum: 3b546022c9b10042ce06a35c124600cd (MD5) Previous issue date: 2012-04-13 / The silver staining technique for AgNOR nucleolar organizer regions (NORs) is characterized by marking proteins linked to the ribosomal ribonucleic acid, evaluating cell proliferation. The aim was to study the validity of the AgNOR staining technique in the testicular cell proliferation in crossbred ovine. Was used treis pairs forty crossbred sheep testes between six and ten months old.Wilcoxon and Spearman tests were used with a significance level of 5%. The mean NORs count in cells of the gonads right and left were respectively: spermatogonia (8.77±1.14 and 9.04±0.96), spermatocyte (4.99±2.00 and 6.20±2.07, P<0.05), Leydig (8.05±2.82 and 7.89±2.29) and Sertoli cells (8.07±1.88 and 7.61±2.16; P<0.05). There was a correlation between the mean values for right and left sides for the number of NORs (P<0.05) between Leydig x spermatocytes (0.49); spermatocytes x Sertoli (0.49) and Sertoli x Leydig (0.96). The study demonstrates that the AgNOR staining technique is indicated to evaluate the cell proliferative potential in ovine testis with practical implementation and low cost. / A coloração pela prata das regiões organizadoras de nucléolos (NORs) é caracterizada por marcar proteínas ligadas ao ácido ribonucléico ribossômico, avaliando a proliferação em células normais ou neoplásicas. O objetivo do trabalho foi estudar em testículos de ovinos obtidos em matadouro a validade do uso da técnica de coloração AgNOR na proliferação de células saudáveis da linhagem espermatogênica. Utilizou-se 43 pares de testículos de ovinos mestiços entre seis e 10 meses de idade. Testes de Wilcoxon e Spearman foram empregados, com nível de 5%. As médias das NORs nas células das gônadas direita e esquerda foram respectivamente: espermatogônia (8,77±1,14 e 9,04±0,96), espermatócito (4,99±2,00 e 6,20±2,07; P<0,05), Leydig (8,05±2,82 e 7,89±2,29) e Sertoli (8,07±1,88 e 7,61±2,16; P<0,05). Houve correlação (P<0,05) entre os lados para o número de NORs: espermatócito x Leydig (0,49); espermatócito x Sertoli (0,49) e Leydig x Sertoli (0,96). Conclui-se ser válido o emprego da técnica AgNOR para avaliar o potencial proliferativo das células saudáveis em testículos de ovinos com prática execução e baixo custo.

Edvard Grieg (1843-1907) är en viktig nationallromantisk kompositör inom norskmusikhistoria. Den här studien belyser Edvard Griegs Violin Sonata No. 2, Op. 13. Syftet äratt nå en fördjupad förståelse för Edvard Grieg som en nationalromantisk kompositör. I minatvå frågeställningar undersöker jag vad som specifikt karakteriserar Griegs musik som”norsk" i form av hans influenser av norsk folkmusik och hans upplevelser av norsk natur.Med hjälp av instudering och interpretation, litteraturstudier samt experiment har studienssyfte uppfyllts. Resultatet av min egen musikanalys visar på flera exempel där Grieg harinspirerats av norsk folkmusik (halling och springar). Jag belyser även hans strävan attefterlikna den norska hardingfelan i violinstämmans utformning. Dessa resultat bekräftas ilitteraturstudien. Resultat gällande musikelement i sonaten som gestaltar norsk natur tyckerjag mig själv finna stöd för i min egen analys, men jag inser att jag har svårt att frigöra migfrån mina egna upplevelser från den norska naturen och dess kopplingar till Griegs musik.Litteraturstudiens resultat visar på liknande tolkningar, t ex att sonaten har en prägel av sorgoch melankoli, vilket kan tolkas som en reflektion över den norska naturens ödsliga och kargalandskap. I experimentet där 9 deltagare får lyssna på sonaten och välja bland 9 naturtypersom de tycker passar bäst till stycket. Resultatet visar på att ingen väljer den bild som visarnorsk natur (Hardangervidda) men att flera deltagare (5 av 9) väljer naturtyper som kan varaförknippat med ett nordiskt land. I diskussionen ställs frågor om hur det kommer sig attGriegs musik definierar ”ett norskt tonspråk”. Är detta på riktigt eller är det ett resultat avmänniskors konstruktioner med syftet att skapa en nationell identitet i ett politiskt landskapdär Norge strävar efter nationell självständighet från grannländernas flera hundraårigaockupation? / <p>F. Schubert Violinsonat no 4 i A-dur, op. 162, D 574. E. Grieg första satsen ur violinsonat no 2 i G-dur, op 13. E. Ysaye sonat no 3 i d-moll, Ballade, op. 27. (Medverkande Erik Lanninger, piano)</p>

Depuis une vingtaine d'années, l'industrie de la microélectronique et en particulier le marché des mémoires non-volatiles connaît une évolution considérable, en termes d'augmentation de la capacité d'intégration et de diminution du prix de revient. Ceci a permis au grand public d'accéder aux produits électroniques (téléphones portables, baladeurs MP3, clés USB, appareils photos numériques...) qui connaissent actuellement un énorme succès. Cependant, la miniaturisation des mémoires Flash risque de rencontrer des limitations. C'est pourquoi les industriels et les laboratoires recherchent actuellement de nouvelles voies qui permettraient de prolonger la durée de vie de ces dispositifs. Dans ce contexte, l'objectif premier de cette thèse est l'étude expérimentale et théorique des mémoires non-volatiles à nanocristaux de silicium. Nous avons montré les différentes possibilités d'intégration des nanocristaux de silicium à partir d'un procédé de fabrication standard. Un démonstrateur Flash NOR 32 Mb à nanocristaux de silicium a été réalisé à partir d'un produit ATMEL. Nous nous sommes ensuite intéressés à la caractérisation électrique des cellules et matrices mémoires. Une étude exhaustive de l'influence des conditions de programmation ainsi que des paramètres technologiques sur les performances électriques a été menée. La modélisation de l'effacement Fowler-Nordheim et du « gate disturb » a permis de comprendre l'influence de certains de ces paramètres. Concernant l'écriture par porteurs chauds, nous avons étudié l'influence des conditions d'écriture sur la localisation de la charge à l'aide de simulations TCAD et d'un modèle analytique couplé à des mesures expérimentales.

Patienten mit chronischem Nierenversagen leiden sowohl klinisch als auch subklinisch unter Entzündungsepisoden. Um einen Frühindikator der Mikroinflammation zu finden, wurde die Expression funktioneller monozytärer Oberflächenantigene (HLA-DR, CD14, CD16, TLR2 (extra-, intrazellulär), TLR4 (extra-, intrazellulär), CD80, CD86), das Zytokinexpressionsprofil (IL1, IL6, IL10, TNFa, TGFb) und der ultrastruktrurelle Phänotyp des Monozyten in vivo bzw. in vitro untersucht. Dabei wurde strikt zwischen der Membranproteinexpression auf antiinflammatorischen (CD14++CD16-), proinflammatorischen (CD14++CD16+, CD14dimCD16+) und CD14+ bzw. CD16+ Monozyten unterschieden und parallel die Serumspiegel von Parathormon (PTH), C-reaktivem Protein (CRP), Calcium und Phosphor untersucht. Inwieweit monozytäre Aktivierungsmarker zum immunologischen Monitoring geeignet sind, sollte vergleichend zwischen Gesunden, Hämodialyse-(HD)- und Peritonealdialyse-(CAPD)-Patienten untersucht werden. Zusätzlich wurde die Expression in einem in-vitro-Zellkulturmodell vergleichend betrachtet. Der Serum-PTH-Spiegel fiel nach Injektion des Vitamin D-Derivates Paricalcitol, der Serumcalciumspiegel stieg signifikant innerhalb des oberen Referenzbereiches bei Patienten mit sekundärem Hyperparathyroidismus drei Wochen nach Beginn der Therapie. Die HLA-DR, extrazelluläre TLR2, intrazelluläre TLR4, CD80, CD86 Expression fiel nach Paricalcitolinjektion. Paricalcitol erhöhte die Anzahl antiinflammatorischer und erniedrigte die Anzahl proinflammatorischer Monozyten. Beim ultrastrukturellen Vergleich zeigte sich eine deutliche Häufung von elektronendichten Granula bei Paricalcitol-inkubierten Zellen im in-vitro-Versuch. Hierbei handelt es sich mit an Sicherheit grenzender Wahrscheinlichkeit um Lysosomen, was die These einer erhöhten phagolysosomalen monozytären Aktivität unter Paricalcitol-Inkubation stützt. Sowohl bei 48- als auch bei 72-stündiger Inkubation in Primärzellkultur wirkte Paricalcitol antiinflammatorisch, indem es Aktivierungsmarker des Monozyten (HLA-DR, TLR2 (extrazellulär), TLR4 (extrazellulär)), die Anzahl proinflammatorischer Monozyten und die Synthese proinflammatorischer Zytokine (IL1, IL6, TNFa) supprimierte. Dialysepatienten unterliegen einem erhöhten Eintrag von Endotoxin (=LPS) über die Dialysemembran, das in der Regel durch Bindung an den LPS-Rezeptor (=CD14) detoxifiziert wird. Dieser wird nicht nur nach LPS Inkubation, sondern v.a. nach Paricalcitol Inkubation vermehrt exprimiert. LPS erhöhte die Anzahl der proinflammatorischen Monozyten in Zellkultur und reflektierte damit den steady state des HD-Patienten. Aktivierungsmarker von Monozyten unterschieden sich zudem bei vergleichender Betrachtung zwischen CAPD-, HD-Patienten und Gesunden und außerdem im Vergleich vor und nach HD. Die intrazelluläre TLR2 und TLR4 Expression von CAPD-Patienten und HD-Patienten war gegenüber Gesunden erniedrigt, während die CD14 Expression signifikant erhöht war. HD-Patienten zeigten einen erhöhten Anteil proinflammatorischer Monozyten vergleichend zu Gesunden aber auch zu Patienten unter CAPD-Substitutionstherapie. Unmittelbar nach HD fielen die proinflammatorischen Monozyten, während v.a. die Expression von extrazellulärem TLR2, intrazellulärem TLR2 und intrazellulärem TLR4 stieg. Somit unterliegt der HD-Patient einer stärkeren Mikroinflammation als der CAPD-Patient. CAPD-, HD- und auch Patienten mit sekundärem Hyperparathyroidismus zeigen Zeichen einer Mikroinflammation. Dabei war CRP (derzeitiger Routineparameter) kein probates diagnostisches Mittel der Entzündung bei CAPD- und HD-Patienten, des Weiteren nicht geeignet zwischen beiden Patientengruppen zu unterscheiden. Die Verteilung der monozytären Subpopulationen und Expression monozytärer Aktivierungsmarker unterschied sich hinreichend zwischen CAPD- und HD-Patienten. Paricalcitol moduliert funktionelle monozytäre Antigene und Zytokine in vivo und in vitro und wirkt damit der Mikroinflammation und dem Immundefekt des CNI-Patienten entgegen. Der Monozyt wirkt ambivalent und initiiert seine „eigene“ Gegenregulation zur Inflammation, die beim Patienten unter Nierenersatztherapie Endotoxin-vermittelt ist. Vitamin D-Derivate wie Paricalcitol wirken nicht nur auf die Calcium-Phosphat-Homöostase sondern auch immunmodulatorisch, indem sie auf monozytäre Antigene, wie Rezeptoren der angeborenen Immunabwehr, Einfluss nehmen.

Submitted by Ana Sant'Ana (ana.mattos@ufscar.br) on 2016-09-26T13:33:25Z No. of bitstreams: 1 DissCCS.pdf: 2483023 bytes, checksum: 3acdef41810eb8722e4f4c44f4ebb688 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-06T14:03:42Z (GMT) No. of bitstreams: 1 DissCCS.pdf: 2483023 bytes, checksum: 3acdef41810eb8722e4f4c44f4ebb688 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-10-06T14:03:54Z (GMT) No. of bitstreams: 1 DissCCS.pdf: 2483023 bytes, checksum: 3acdef41810eb8722e4f4c44f4ebb688 (MD5) / Made available in DSpace on 2016-10-06T14:04:00Z (GMT). No. of bitstreams: 1 DissCCS.pdf: 2483023 bytes, checksum: 3acdef41810eb8722e4f4c44f4ebb688 (MD5) Previous issue date: 2016-07-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / The endogenous opioids are involved in analgesia, thermoregulation and physiological responses to various stressful stimuli such as infection, psychological stress and hypoxia. The mu and kappa receptors in the hypothalamus play a role in endotoxin-induced fever and hypoxia-induced anapyrexia (opposite response to fever), respectively. In addition, periaqueductal gray (PAG), which express both mu and kappa receptors, is involved in defence and thermoregulatory responses. Thus, our hypothesis is that mu and kappa opioid receptors in the PAG modulate the restraint-induced fever in rats by activating and inhibiting this response, respectively. To this end, body temperature (Tb) and heat loss index (HLI; inference for heat conservation/loss) and oxygen consumption (VO ; inference for thermogenesis) of unanesthetized Wistar rats submitted or not to restraint stress, was monitored before and after intra-PAG microinjection of the selective mu opioid receptor antagonist (CTAP; 1 and 10 μg/ 100 nL/ animal), the selective kappa-opioid receptor antagonist (nor-BNI; 1 and 4 μg/ 100 nL/ animal), or vehicle (saline; 100nL/ animal). CTAP and nor-BNI did not change the Tb or the HLI of the animals in euthermia. During the restraint stress, Tb increased in all groups of animals. However, this effect was significantly lower in animals treated with CTAP, and significantly higher in animals treated with nor-BNI. No treatment affected HLI, but CTAP decreased thermogenesis and nor-BNI increased thermogenesis. The results indicate that the mu and kappa opioid receptors in the PAG of rats play a pyrogenic and antipyretic role, respectively, during fever induced by restraint stress and these receptors in PAG may not be essential for the maintenance of Tb during euthermia. / Os opióides endógenos estão envolvidos na analgesia, termorregulação e respostas fisiológicas a vários estímulos estressantes, como infecção, estresse psicológico e hipóxia. Os receptores mu e kappa no hipotálamo desempenham um papel na febre induzida por endotoxina e anapirexia induzida por hipoxia (resposta oposta à febre), respectivamente. Além disso, a substância cinzenta periaquedutal (PAG), que expressa ambos os receptores mu e kappa, está envolvida na defesa e respostas de termorregulação. Assim, nossa hipótese é que os receptores opióides mu e kappa na PAG modulam a febre induzida por contenção em ratos, ativando e inibindo esta resposta, respectivamente. Para este fim, a temperatura corporal (Tc) e o índice de perda de calor (IPC; inferência para a conservação/perda de calor) e o consumo de oxigênio (VO ; inferência para a termogênese) de ratos Wistar não anestesiados submetidos ou não ao estresse contenção, foi monitorado antes e depois microinjeção intra-PAG do antagonista seletivo do receptor opióide mu (CTAP; 1 e 10 μg/ 100 nL/ animal), antagonista seletivo do receptor opióide kappa (nor-BNI; 1 e 4 μg/ 100 nL/ animal) ou veículo (solução salina; 100 nL / animal). A microinjeção de CTAP ou nor-BNI não alterou a Tc ou IPC dos animais em eutermia. Durante o estresse de contenção, a Tc aumentou em todos os grupos de animais. No entanto, este efeito foi significativamente menor no grupo de animais tratados com CTAP, e significativamente maior em animais tratados com nor-BNI. Nenhum tratamento afetou o IPC, mas o CTAP diminuiu a termogênese e o nor-BNI aumentou a termogênese. Os resultados indicam que os receptores opióides mu e kappa na PAG de ratos desempenham um papel pirogênico e antipirético, respectivamente, durante a febre induzida pelo estresse de contenção e estes receptores na PAG podem não ser essenciais para a manutenção de Tc durante eutermia.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / CHAPTER II: Pequi, Caryocar brasiliense, is one of the species of highlight at the biome of the Brazilian savannah due to its utilization in culinary, popular medicine, industry in general, and iron and steel industry. It presents an elevated index of exploration, being capable of entering the list of the endangered species. In the region of São José do Xingu (MT), a tree of pequi without thorn at the mesocarp was found and this enables to improve pequi not only for consumption, taking advantage of the high appreciation it already has. To detect the existing genomic differences between the pequi with and without the thorn at the endocarp, RADP markers were utilized. The generated polymorphisms were cloned and sequenced in order to identify the sequences responsible for the fenotypical alteration. It was observed that the pequi without thorn is genetically isolated from the other populations of pequi with thorn at the endocarp, proving that this characteristic is related to the genetic divergence of the species. Analysis in BLASTn evidenced the similarity of the Dof1 genes of Zea mays, in the population with thorn, and in the population without thorn, with the gene of phosphinotricin acetyl transferase of Z. mays. In the analysis of BLASTx, the similarity was verified with the proteins responsible for the deficiency in ferric reductase 4, in the pequi without thorn and catalase, in the pequi without thorn. CHAPTER III:The pequi, Cayocar brasiliense Cambess. Is a feature of Brazilian cerrado plant suffering extractive action, mainly for food. It is a plant very appreciated in the regions of Minas Gerais, especially in the north of this state. In the region of Sao Jose do Xingu, Mato Grosso, was found in a plant which had no thorns in the core and this allowed further research to discover the lack of thorns as it is an unwanted feature of the plant. Thus, the cytogenetic study, using conventional Giemsa staining, NOR, banda C, DAPI and CMA3 were used for comparison between the pequi with and without spines in the putamen. It was found that these differences are not attributed to chromosomal differences between the two types of pequi. Both have the same chromosome number, the marking of NOR, C banding was not verified due to the size of chromosomes and differences in staining with DAPI and CMA3 could not be verified although related to these characteristics. CHAPTER IV: The pequi is a species that is gathered and today is seen as a source for the production of biodiesel. The objective of this study was to identify sequences from a cDNA library that are involved in the metabolic pathways for production of pequi fruit, to gain a better understanding of the species and its biological and genetic properties. To do so, a cDNA library was created and the clones were cloned and sequenced. These identified sequences were deposited in GenBank. Most of the sequences found are associated with protection against oxidative stress in plants, some are transcription factors and others provide structural and pathogenic resistance. / CAPÍTULO II: O pequi, Caryocar brasiliense, é uma das espécies de destaque no bioma do Cerrado devido a sua utilização na culinária, medicina popular, indústria e siderurgia. Apresenta índice de exploração elevado, podendo entrar na lista das espécies ameaçadas de extinção. Na região de São José do Xingu (MT) foi encontrada uma árvore produzindo pequi sem espinho no endocarpo, o que levantou a possibilidade de melhorar o pequi para consumo aproveitando a alta apreciação que já possui. Com o objetivo de analisar as diferenças genômicas entre o pequi com e o sem espinho no endocarpo, utilizou-se marcadores RADP (Random Amplified Polymorphism DNA). As bandas polimórficas geradas foram isoladas, clonadas e seqüenciadas, buscando identificar sequências responsáveis pela alteração fenotípica. Observou-se que o pequi sem espinho fica isolado geneticamente das demais populações de pequi com espinho no caroço, comprovando que essa característica está relacionada à divergência genética da espécie. Análises em BLASTn mostraram a similaridade aos genes Dof1 de Zea mays, na população com espinho e com o gene da Acetiltransferase Fosfinotricina de Z. mays, na população sem espinho. As análises em BLASTx revelaram similaridade com as proteínas responsáveis pela Deficiência em Redutase Férrica 4, no pequi sem espinho e com catalase, no pequi com espinho. CAPÍTULO III: O pequizeiro, Cayocar brasiliense Cambess., é uma planta característica do cerrado brasileiro que sofre ação extrativista, principalmente, para a alimentação. É uma planta bastante apreciada em regiões de Minas Gerais, especialmente no Norte desse estado. Na região de São José do Xingu, Mato Grosso, foi encontrada uma planta produzindo pequi sem espinhos no caroço. O estudo citogenético, por meio de coloração convencional de Giemsa, NOR, banda C, DAPI e CMA3 foi utilizado para a comparação entre plantas produtoras de pequi com e sem espinhos no caroço. Verificou-se que essas diferenças não podem ser atribuídas à diferenças cromossômicas entre os dois tipos de pequi. Ambas as plantas têm o mesmo número cromossômico, mesma marcação de NOR. Não foi verificado bandeamento C devido ao tamanho dos cromossomos. Diferenças de coloração com DAPI e CMA3 foram detectadas, porém não é possível afirmar que estejam relacionadas com a presença ou ausência de espinhos no fruto. CAPÍTULO IV: O pequizeiro (Caryocar brasiliense Cambess.) é uma espécie nativa do cerrado brasilieiro e que possui importância alimentar e social para a população que dela depende. É uma espécie que sofre ação extrativista e que, atualmente, é considerada fonte para a produção de biodiesel. Nesse trabalho o objetivo foi identificar, a partir de uma bilbioteca de cDNA, seqüências que estejam envolvidas em vias metabólicas para produção do fruto do pequi, para conhecimento da espécie, suas propriedades biológicas e genéticas. Dessa forma foi construída biblioteca de cDNA e os clones foram clonados e seqüenciados. As sequências identificadas foram depositadas no GenBank. Algumas das sequências encontradas estão relacionadas à proteção contra o estresse oxidativo em plantas, outras são fatores de transcrição e algumas sequências expressas têm funções estruturais e de resistência a patógenos. / Doutor em Genética e Bioquímica

Les récepteurs nucléaires sont des facteurs de transcription régulant l’expression de gènes impliqués dans plusieurs processus physiologiques. En général, ces récepteurs sont activés par une interaction avec un ligand spécifique, mais leur activité peut également être modulée par des modifications post-traductionnelles comme la SUMOylation. Notre laboratoire a récemment trouvé que le récepteur des estrogènes ER est une cible de cette modification sur un site de SUMOylation atypique nommé pSuM. Ce site non-consensus se retrouve également sur Nor-1, un récepteur nucléaire impliqué dans une variété de processus physiologiques comme le métabolisme du glucose, la prolifération cellulaire ainsi que la survie neuronale. Pour l’instant, le rôle de ce motif atypique reste inconnu et aucune évidence n’indique que Nor-1 est SUMOylé dans la littérature. Nos objectifs étaient donc de déterminer le potentiel de SUMOylation de Nor-1 sur son pSuM dans un contexte neuronal et de caractériser l’effet de la SUMOylation sur l’activité transcriptionnelle de Nor-1 ainsi que l’expression de gènes cibles. Nos résultats ont démontré que Nor-1 peut effectivement être SUMOylé sur son pSuM, que cette SUMOylation est dépendante d’une phosphorylation de la sérine-139 et que la voie des MAPK augmente l’état global de SUMOylation de Nor-1 ainsi que son expression protéique. De plus, les résultats ont indiqués que Nor-1 peut conjuguer deux isoformes de SUMO, soit SUMO-1 et SUMO-2. Les résultats démontrent également que la SUMOylation augmente l’activité transcriptionnelle de Nor-1 et que la SUMOylation de son site pSuM est importante pour le maintien de son activité transcriptionnelle basale. Nos résultats préliminaires suggèrent que la SUMOylation du pSuM de Nor-1 affecte l’expression de gènes cibles comme l’énolase-3 ce qui propose un rôle de la SUMOylation de Nor-1 dans la régulation du métabolisme des neurones. En conclusion, les résultats de ce projet permettent d'identifier un nouveau processus de SUMOylation impliqué dans la régulation des récepteurs nucléaires et de Nor-1 suggérant un rôle de ce processus de SUMOylation atypique dans plusieurs réseaux géniques et processus physiologiques. / Nuclear hormone receptors are transcription factors that regulate the expression of many genes implicated in a wide variety of physiological functions. They are generally activated by an interaction with a specific ligand but their activity can also be modulated by post-translational modifications such as SUMOylation. Recently, our laboratory identified ER as a SUMOylation target on an atypical SUMOylation motif named pSuM. This non-consensus SUMOylation motif was also found on Nor-1, a nuclear receptor implicated in physiological processes such as glucose metabolism, cellular proliferation and neuronal survival. Until now, the function of this pSuM motif is still unknown and there are no evidence that Nor-1 is a target of SUMOylation. Therefore, the objectives of this work were to determine the SUMOylation potential of Nor-1 on his pSuM in a neuronal context and to characterize the effect of SUMOylation on Nor-1 transcriptional activity and target genes expression. Our results showed that Nor-1 can indeed be SUMOylated on his pSuM, that this SUMOylation was dependent on serine-139 phosphorylation, and that the MAPK pathway augmented the global SUMOylation state of Nor-1 and its protein expression levels. Furthermore, we demonstrated that Nor-1 can conjugate SUMO-1 and SUMO-2. Our results also indicated that SUMOylation activates the transcriptional activity of Nor-1 and that the pSuM site of Nor-1 was important in maintaining its basal transcriptional activity. Preliminary results suggests that Nor-1 SUMOylation on the pSuM has an impact on the expression of target genes such as enolase-3, suggesting a potential role for Nor-1 in the regulation of the metabolism of neurons. In conclusion, the results presented in this work identify a new SUMOylation process implicated in regulating Nor-1 and nuclear receptors activities, suggesting an extended role of this atypical SUMOylation process in many gene networks and physiological processes.

This thesis presents the modeling and fabrication of a new solid-state device meant to be used for digital logic circuits. Most current logic circuits are based on MOSFETs. The new logic device uses some of the same operating principles, but also relies on optical illumination to provide input power. In order to obtain the desired current-voltage behavior of the new device, the Silvaco (Atlas) device simulation was used to give some insight into the correct doping levels in the semiconductor and device geometries. Prototypes were fabricated on p-type silicon wafers using CMOS fabrication processes including oxide growth, photolithography, precise plasma or chemical wet etching, diffusion processes, and thin film evaporation. Electrical measurements were done by using an HP4156 parameter analyzer to measure several output voltage signals at one time while an illuminating the device with laser light. The current-voltage characteristics under different biasing conditions with an optical illumination condition were measured and showed characteristics similar to an nMOS transistor.

Die enorme Steigerung der Leistungsfähigkeit integrierter Schaltkreise wird seit über 50 Jahren im Wesentlichen durch eine Verkleinerung der Bauelementdimensionen erzielt. Aufgrund des Erreichens physikalischer Grenzen kann dieser Trend, unabhängig von der Lösung technologischer Probleme, langfristig nicht fortgesetzt werden. Diese Arbeit beschäftigt sich mit der Entwicklung und Herstellung neuartiger Transistoren und Schaltungen, welche im Vergleich zu konventionellen Bauelementen funktionserweitert sind, wodurch ein zur Skalierung alternativer Ansatz vorgestellt wird. Ausgehend von gewachsenen und nominell undotierten Silizium-Nanodrähten wird die Herstellung von Schottky-Barrieren-Feldeffekttransistoren (SBFETs) mit Hilfe etablierter und selbst entwickelter Methoden beschrieben und die Ladungsträgerinjektion unter dem Einfluss elektrischer Felder an den dabei erzeugten abrupten Metall–Halbleiter-Grenzflächen analysiert. Zur Optimierung der Injektionsvorgänge dienen strukturelle Modifikationen, welche zu erhöhten ambipolaren Strömen und einer vernachlässigbaren Hysterese der SBFETs führen. Mit dem rekonfigurierbaren Feldeffekttransistor (RFET) konnte ein Bauelement erzeugt werden, bei dem sich Elektronen- und Löcherinjektion unabhängig und bis zu neun Größenordnungen modulieren lassen. Getrennte Topgate-Elektroden über den Schottkybarrieren ermöglichen dabei die reversible Konfiguration von unipolarer Elektronenleitung (n-Typ) zu Löcherleitung (p-Typ) durch eine Programmierspannung, wodurch die Funktionen konventioneller FETs in einem universellen Bauelement vereint werden. Messungen und 3D-FEM-Simulationen geben einen detaillierten Einblick in den elektrischen Transport und dienen der anschaulichen Beschreibung der Funktionsweise. Systematische Untersuchungen zu Änderungen im Transistoraufbau, den Abmessungen und der Materialzusammensetzung verdeutlichen, dass zusätzliche Strukturverkleinerungen sowie die Verwendung von Halbleitern mit niedrigem Bandabstand die elektrische Charakteristik dieser Transistoren weiter verbessern. Im Hinblick auf die Realisierung neuartiger Schaltungen wird ein Konzept beschrieben, die funktionserweiterten Transistoren in einer energieeffizienten Komplementärtechnologie (CMOS) nutzbar zu machen. Die dafür notwendigen gleichen Elektronen- und Löcherstromdichten konnten durch einen modifizierten Ladungsträgertunnelprozess infolge mechanischer Verspannungen an den Schottkyübergängen erzielt und weltweit erstmalig an einem Transistor gezeigt werden. Der aus einem <110>-Nanodraht mit 12 nm Si-Kerndurchmesser erzeugte elektrisch symmetrische RFET weist dabei eine bisher einzigartige Kennliniensymmetrie auf.Die technische Umsetzung des Schaltungskonzepts erfolgt durch die Integration zweier RFETs innerhalb eines Nanodrahts zum dotierstofffreien CMOS-Inverter, der flexibel programmiert werden kann. Die rekonfigurierbare NAND/NOR- Schaltung verdeutlicht, dass durch die RFET-Technologie die Bauelementanzahl reduziert und die Funktionalität des Systems im Vergleich zu herkömmlichen Schaltungen erhöht werden kann. Ferner werden weitere Schaltungsbeispiele sowie die technologischen Herausforderungen einer industriellen Umsetzung des Konzeptes diskutiert. Mit der funktionserweiterten, dotierstofffreien RFET-Technologie wird ein neuartiger Ansatz beschrieben, den technischen Fortschritt der Elektronik nach dem erwarteten Ende der klassischen Skalierung zu ermöglichen. / The enormous increase in performance of integrated circuits has been driven for more than 50 years, mainly by reducing the device dimensions. This trend cannot continue in the long term due to physical limits being reached. The scope of this thesis is the development and fabrication of novel kinds of transistors and circuits that provide higher functionality compared to the classical devices, thus introducing an alternative approach to scaling. The fabrication of Schottky barrier field effect transistors (SBFETs) based on nominally undoped grown silicon nanowires using established and developed techniques is described. Further the charge carrier injection in the fabricated metal to semiconductor interfaces is analyzed under the influence of electrical fields. Structural modifications are used to optimize the charge injection resulting in increased ambipolar currents and negligible hysteresis of the SBFETs. Moreover, a device has been developed called the reconfigurable field-effect transistor (RFET), in which the electron and hole injection can be independently controlled by up to nine orders of magnitude. This device can be reversibly configured from unipolar electron conducting (ntype) to hole conducting (p-type) by the application of a program voltage to the two individual top gate electrodes at the Schottky junctions. So the RFET merges the functionality of classical FETs into one universal device. Measurements and 3D finite element method simulations are used to analyze the electrical transport and to describe the operation principle. Systematic investigations of changes in the device structure, dimensions and material composition show enhanced characteristics in scaled and low bandgap semiconductor RFET devices. For the realization of novel circuits, a concept is described to use the enhanced functionality of the transistors in order to realize energy efficient complementary circuits (CMOS). The required equal electron and hole current densities are achieved by the modification of charge carrier tunneling due to mechanical stress and are shown for the first time ever on a transistor. An electrically symmetric RFET based on a compressive strained nanowire in <110> crystal direction and 12 nm silicon core diameter exhibits unique electrical symmetry. The circuit concept is demonstrated by the integration of two RFETs on a single nanowire, thus realizing a dopant free CMOS inverter which can be programmed flexibly. The reconfigurable NAND/NOR shows that the RFET technology can lead to a reduction of the transistor count and can increase the system functionality. Additionally, further circuit examples and the challenges of an industrial implementation of the concept are discussed.The enhanced functionality and dopant free RFET technology describes a novel approach to maintain the technological progress in electronics after the expected end of classical device scaling.