O desgaste é um dos fatores que causam a maior parte das falhas e redução na vida útil de ferramentas, além de resultar em produtos com condições superficiais inadequadas. A crescente demanda da indústria por menores custos, maior produtividade e melhor qualidade estão entre as justificativas para que se busquem maneiras de incrementar o desempenho dessas ferramentas. Neste contexto, o trabalho tem como objetivo avaliar e caracterizar superfícies projetadas para resistência ao desgaste utilizando o processo de aspersão térmica oxicombustível de alta velocidade (HVOF). Fez-se um estudo comparativo de caracterização e comportamento tribológico de um aço ferramenta com deposição por aspersão térmica de dois diferentes revestimentos. O estudo abrange o aço ABNT H13, utilizando o tratamento superficial de aspersão térmica HVOF com revestimentos de Cr3C2-25(NiCr) e WC-10Co-4Cr. A avaliação da superfície e do comportamento tribológico envolveu perfis de microdureza, análise de fases por difração de raios X, metalografias, obtenção da composição química, caracterização da rugosidade, ensaio de abrasão e adesão, pino-disco e ensaio do anel. O objetivo de conseguir aumentar a resistência ao desgaste utilizando um aço ferramenta com deposição via processo de HVOF, bem como o de caracterizar este processo foi alcançado. A utilização do aço ABNT H13 com deposição via aspersão térmica HVOF e revestimentos à base de carboneto de cromo e tungstênio demonstrou-se recomendável para proteção de substratos, fornecendo alta dureza e boa resistência ao desgaste. O revestimento de WC-10Co-4Cr obteve o melhor desempenho geral, apresentando uma microdureza 192% maior frente ao aço sem revestimento, uma redução de 315% do coeficiente de atrito, além de uma adesão maior ao substrato quando comparado com o revestimento Cr3C2-25(NiCr). / Wear is one of the factors that cause most of the failures and reduction of lifespan for tools, it also results in products with no quality in the surface conditions. The increasing demand of the industry for lower costs, higher productivity and better quality are among the justifications for finding ways to increase the performance of these tools. In this context, the objective of this work is to evaluate and characterize surfaces designed for wear resistance using the high velocity oxyfuel (HVOF) thermal spray process. A comparative study of characterization and tribological behavior of a tool steel with thermal spray deposition was performed for two different coatings. The study covers the ABNT H13 steel, using the surface treatment of HVOF thermal spray with coatings of Cr3C2-25(NiCr) and WC-10Co-4Cr. The surface and the tribological behavior evaluation involved microhardness profiles, phase analysis by x-ray diffraction, metallography, chemical composition, roughness characterization, abrasion and adhesion test, pin-on-disk and ring test. The objective of increasing the wear resistance using a tool steel with deposition through HVOF process, as well as to characterize this process was achieved. The use of ABNT H13 steel with chrome and tungsten carbide coatings deposited by thermal spray HVOF has proved to be recommended for substrates protection, providing high hardness and good wear resistance. The WC-10Co-4Crcoating had the best overall performance, presenting a microhardness 192% higher than the steel with no coating, a reduction of 315% of the coefficient of friction, and a higher adhesion to the substrate compared to the Cr3C2-25(NiCr) coating.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-03-20T19:29:07Z No. of bitstreams: 1 WendelAndersonDantasTeixeira_DISSERT.pdf: 3957759 bytes, checksum: cc4a46d4569b9607cedd8a5a5758b525 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-03-21T22:40:07Z (GMT) No. of bitstreams: 1 WendelAndersonDantasTeixeira_DISSERT.pdf: 3957759 bytes, checksum: cc4a46d4569b9607cedd8a5a5758b525 (MD5) / Made available in DSpace on 2017-03-21T22:40:07Z (GMT). No. of bitstreams: 1 WendelAndersonDantasTeixeira_DISSERT.pdf: 3957759 bytes, checksum: cc4a46d4569b9607cedd8a5a5758b525 (MD5) Previous issue date: 2016-11-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Interfaces Metal-WC-Co est?o presentes em opera??es de perfura??o de po?os de petr?leo, onde se utilizam brocas tric?nicas de insertos cer?micos duros. A a??o combinada de corte, esmagamento e desagrega??o de rochas causa a degrada??o das brocas de perfura??o. A degrada??o est? relacionada com o desgaste, fratura total ou parcial do corpo da broca ou dos insertos, choque t?rmico e corros?o. Tamb?m o deficiente encaixe mec?nico dos insertos cer?micos nos cones da broca pode originar o seu destacamento provocando uma s?rie de danos ? broca. O aprimoramento no processo de produ??o de interfaces metal-cer?mica pode eliminar ou minimizar algumas das falhas acima mencionadas nas brocas tric?nicas, otimizando o seu tempo de vida ?til, e portanto, reduzindo o custo m?trico de perfura??o. A brasagem ? uma t?cnica extensivamente utilizada para uni?o de metais e cer?micos, podendo ser uma excelente alternativa ao processo comum de encaixe mec?nico de ?pressfitting? dos insertos cer?micos no corpo de a?o da broca. A metaliza??o das superf?cies WC-Co ? utilizada para melhorar a molhabilidade e ades?o de sistemas M/C. Neste trabalho, pretendeu-se avaliar o efeito da temperatura de brasagem em uni?es de insertos WC-6Co com a?o H13 utilizando ligas de adi??o com base no eut?tico 72Ag28Cu, em um forno com uma condi??o de alto v?cuo. A caracteriza??o mec?nica, microestrutural e morfol?gica das uni?es geradas foi avaliada em ensaios de flex?o de 3 pontos, MEV-EDS e DRX. Os melhores resultados de resist?ncia mec?nica foram encontrados para os sistemas brasados a 880?C com liga de adi??o eut?tica AgCu. / Metal-WC-Co interfaces are present in oil well drilling operations, where tricone drill bits with hard ceramic inserts play an important role. The combination of cutting, crushing and breaking up of rocks results in the degradation of tricone drill bits by wear, total or partial rupture of the drill bit body or the ceramic inserts, thermal shock and corrosion. In addition, the improper pressfitting of the ceramic inserts on the bit body may cause its total detachment, and promote serious damages to the drill bit. The improvement on the production process of metal-ceramic interfaces can eliminate or minimize some of above-mentioned failures presented in tricone drill bits, optimizing their lifetime and so reducing drilling metric cost. Brazing is a widely established technique to join metal-ceramic materials, and may be an excellent alternative to the common mechanical press fitting process of hard ceramic inserts on the steel bit body for tricone drill bit. The metallization of WC-Co surfaces is used to improve the wetting and adhesion of the M/C system, when a liquid phase is present during the brazing process. In this work, the effect of brazing temperature was studied on WC-6Co and H13 steel couples, using 72Ag28Cu eutectic based brazing alloys inside a furnace under high vacuum. Mechanical and microstructure caracterization of the interfaces produced was analysed by 3 point flexural tests, SEM-EDX and XRD techinques.d, and the interfaces produced were analysed by SEM-EDX. Better results for mechanical strenght were found for the systems brazed at 880?C using AgCu eutectic braze alloy.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-08-10T11:24:30Z No. of bitstreams: 1 MeysamMashhadikarimi_TESE.pdf: 7466845 bytes, checksum: 3ec1fdf5f0b341e5aa20ba33dd8d5104 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-08-10T14:09:43Z (GMT) No. of bitstreams: 1 MeysamMashhadikarimi_TESE.pdf: 7466845 bytes, checksum: 3ec1fdf5f0b341e5aa20ba33dd8d5104 (MD5) / Made available in DSpace on 2017-08-10T14:09:43Z (GMT). No. of bitstreams: 1 MeysamMashhadikarimi_TESE.pdf: 7466845 bytes, checksum: 3ec1fdf5f0b341e5aa20ba33dd8d5104 (MD5) Previous issue date: 2017-07-10 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Neste trabalho de pesquisa, foi obtido um compacto de diamante policristalino (PDC), constitu?do de uma camada superior de diamante policristalino sob um substrato de WC-10% em peso de Co e uma interface de WC-20% em peso de Nb/Ni entre as camadas, atrav?s de m?todo de sinteriza??o de alta press?o e alta temperatura (HPHT). Para alcan?ar esse objetivo, foram realizadas tr?s etapas distintas. Na primeira etapa, foi sinterizado o corpo de diamante com um ligante adequado, e foram obtidos os melhores par?metros de sinteriza??o. Na segunda etapa, foi realizado o estudo de diferentes condi??es de sinteriza??o para o substrato de metal duro WC-10% p.Co. E, na terceira e ?ltima etapa, foi produzido, de acordo com os resultados alcan?ados nas etapas anteriores, o compacto de diamante policristalino de camada tripla (PDC). Na primeira etapa, quatro ligantes diferentes foram usados para sinterizar o diamante atrav?s do m?todo HPHT. Os ligantes utilizados foram o Nb/Fe, Nb/Co, Nb/Ni e Nb puro, sendo 10% em peso de ligante utilizado para cada composi??o. A sinteriza??o foi realizada a diferentes temperaturas e sob diferentes press?es e tempos. As amostras obtidas foram analisadas atrav?s das medidas de densidade relativa e dureza, al?m das imagens eletr?nicas de varredura, para encontrar os melhores par?metros de sinteriza??o e ligante. Os estudos mostraram que o Nb apresentou o melhor comportamento, e que os melhores par?metros de sinteriza??o foram: T = 1750 ?C, P = 7,7 GPa, t = 6 minutos. Na segunda etapa, uma mistura em p? de WC-10% em peso de Co foi sinterizado atrav?s de HPHT sob press?o de 7,7 GPa, variando temperatura (1500 ?C, 1600 ?C, 1700 ?C, 1800 ?C, 1900 ?C) e tempo (2 e 3 minutos). As an?lises microestruturais e estruturais foram realizadas atrav?s de MEV/EDS e DRX. Ensaios de dureza, tenacidade (ITF) e de resist?ncia ? compress?o, tamb?m, foram realizados para entender os efeitos de diferentes par?metros de sinteriza??o nas propriedades dos sinterizados, verificando-se densifica??o total das amostras sinterizadas a altas temperaturas. Entretanto, foi observado um crescimento anormal de gr?os para estas mesmas temperaturas. Altos valores de dureza foram observados, aproximadamente, entre 1250 a 1650 HV para todas as amostras sinterizadas. Na terceira etapa, para a obten??o do PDC, uma camada fina de WC-20% em peso de Nb/Ni foi utilizada para a forma??o da interface entre a camada superior de diamante com ligante de Nb pura e o substrato de WC 10% em peso de Co. A sinteriza??o foi feita atrav?s do m?todo HPHT ? temperatura de 1750 ?C sob 7,7 GPa de press?o. Foram utilizados dois tempos diferentes, de 6 min. (tr?s sucessivos 2 minutos) e 9 min. (tr?s sucessivos 3 minutos). A dureza foi medida e os estudos estruturais/microestruturais foram realizados atrav?s de an?lises de MEV/EDS. Em suma, os resultados mostraram que este novo tipo de PDC pode ser produzido com sucesso, usando um novo ligante, o niobio puro, para o diamante, sem qualquer presen?a de grafitiza??o. Verificou-se tamb?m que o uso de uma interface com os mesmos elementos constituintes do substrato e do corpo de diamante sinterizado resultou numa boa ades?o entre as camadas, o que pode resultar em melhor desempenho e melhorar a durabilidade do PDC. / The primary objective of this thesis was to obtain a triple layer polycrystalline diamond compact (PDC) containing a polycrystalline diamond as top layer, a WC 10 wt% Co substrate, and a WC 20 wt% Nb/Ni interface to bond these two layers via high pressure high temperature (HPHT) sintering. To achieve this objective, the project has been done in three different stages. The first stage was producing diamond sintered body with a suitable binder, and finding the best sintering parameters. The second stage of project was done to study the WC 10 wt% Co hardmetal substrate at different sintering conditions, and the third and last stage was done according to the results achieved from previous stages to obtain a triple layer PDC. At the first stage, four different binders were used to sinter diamond under HPHT condition. Binders were Nb/Fe, Nb/Co, Nb/Ni and pure Nb and 10 wt% binder was used. Sintering was carried out at different temperature and under different pressure and holding time. Obtained samples were studies according to relative density, microstructure, and hardness to find the optimum binder and sintering parameters. Studies at this stage showed that Nb is the best binder and T=1750 ?C, 7.7 GPa with holding time more than 6 minutes are the best sintering parameters. At the second stage a powder mixture of WC 10 wt% Co was sintered via HPHT at 1500, 1600, 1700, 1800, and 1900?C under 7.7 GPa pressure for 2 and 3 minutes. Microstructural/structural analyses were performed by SEM/EDS and XRD and hardness, Indentation Fracture Toughness (ITF) and compression tests were also carried out to understand effects of different sintering parameters. At this stage, it was found that full density can achieved for high sintering temperature along with abnormal grain growth. High hardness was observed in range starting from 1250 up to 1650 HV. At the third stage, to obtain PDC, a thin layer of WC 20 wt% Nb/Ni was used as an interface between top layer of diamond with pure Nb binder and WC 10 wt% Co substrate. Sintering was done via HPHT method at 1750?C under 7.7 GPa of pressure. Two different holding time of 6 (three successive 2 minutes) and 9 (three successive 3 minutes) were used. Hardness was measured and microstructural/structural studies were done via SEM/EDS. The overall results showed that this new kind of PDC can successfully produce using a new pure Niobium binder for diamond without any graphitization. It was also found that using an interface having the resemblance to both substrate and sintered diamond body caused good adhesion between layers that can results in enhanced performance and improving durability of PDC.

O desgaste é um dos fatores que causam a maior parte das falhas e redução na vida útil de ferramentas, além de resultar em produtos com condições superficiais inadequadas. A crescente demanda da indústria por menores custos, maior produtividade e melhor qualidade estão entre as justificativas para que se busquem maneiras de incrementar o desempenho dessas ferramentas. Neste contexto, o trabalho tem como objetivo avaliar e caracterizar superfícies projetadas para resistência ao desgaste utilizando o processo de aspersão térmica oxicombustível de alta velocidade (HVOF). Fez-se um estudo comparativo de caracterização e comportamento tribológico de um aço ferramenta com deposição por aspersão térmica de dois diferentes revestimentos. O estudo abrange o aço ABNT H13, utilizando o tratamento superficial de aspersão térmica HVOF com revestimentos de Cr3C2-25(NiCr) e WC-10Co-4Cr. A avaliação da superfície e do comportamento tribológico envolveu perfis de microdureza, análise de fases por difração de raios X, metalografias, obtenção da composição química, caracterização da rugosidade, ensaio de abrasão e adesão, pino-disco e ensaio do anel. O objetivo de conseguir aumentar a resistência ao desgaste utilizando um aço ferramenta com deposição via processo de HVOF, bem como o de caracterizar este processo foi alcançado. A utilização do aço ABNT H13 com deposição via aspersão térmica HVOF e revestimentos à base de carboneto de cromo e tungstênio demonstrou-se recomendável para proteção de substratos, fornecendo alta dureza e boa resistência ao desgaste. O revestimento de WC-10Co-4Cr obteve o melhor desempenho geral, apresentando uma microdureza 192% maior frente ao aço sem revestimento, uma redução de 315% do coeficiente de atrito, além de uma adesão maior ao substrato quando comparado com o revestimento Cr3C2-25(NiCr). / Wear is one of the factors that cause most of the failures and reduction of lifespan for tools, it also results in products with no quality in the surface conditions. The increasing demand of the industry for lower costs, higher productivity and better quality are among the justifications for finding ways to increase the performance of these tools. In this context, the objective of this work is to evaluate and characterize surfaces designed for wear resistance using the high velocity oxyfuel (HVOF) thermal spray process. A comparative study of characterization and tribological behavior of a tool steel with thermal spray deposition was performed for two different coatings. The study covers the ABNT H13 steel, using the surface treatment of HVOF thermal spray with coatings of Cr3C2-25(NiCr) and WC-10Co-4Cr. The surface and the tribological behavior evaluation involved microhardness profiles, phase analysis by x-ray diffraction, metallography, chemical composition, roughness characterization, abrasion and adhesion test, pin-on-disk and ring test. The objective of increasing the wear resistance using a tool steel with deposition through HVOF process, as well as to characterize this process was achieved. The use of ABNT H13 steel with chrome and tungsten carbide coatings deposited by thermal spray HVOF has proved to be recommended for substrates protection, providing high hardness and good wear resistance. The WC-10Co-4Crcoating had the best overall performance, presenting a microhardness 192% higher than the steel with no coating, a reduction of 315% of the coefficient of friction, and a higher adhesion to the substrate compared to the Cr3C2-25(NiCr) coating.

Hintergrund: Die Berlin Fat Mouse Inzuchtlinie (BFMI) ist ein Modell für Adipositas und das metabolische Syndrom. Diese Studie zielte darauf ab, genetische Varianten zu identifizieren, die mit dem gestörten Glukosestoffwechsel assoziiert sind, indem die fettleibigen Linien BFMI861-S1 und BFMI861-S2 verwendet wurden, die genetisch eng verwandt sind, sich aber in mehreren Merkmalen unterscheiden. BFMI861-S1 ist insulinresistent und speichert ektopisches Fett in der Leber, während BFMI861-S2 insulinsensitiv ist. Methoden: Die QTL-Analyse wurde in zwei fortgeschrittenen Intercross-Linien (AIL) in der Generation durchgeführt. Eine AIL wurde aus der Kreuzung BFMI861-S1 x BFMI861-S2 und die zweite AIL aus der Kreuzung BFMI861-S1 x BFMI861-B6N erhalten. Für beide AILs wurden Phänotypen über 25 bzw. 20 Wochen gesammelt. Zur Priorisierung von positionellen Kandidatengenen wurden Gesamtgenomsequenzierung und Genexpressionsdaten der Elternlinien verwendet. Ergebnisse: Für den AIL BFMI861-S1 x BFMI861-S2 wurden überlappende QTL für das Gonadenfettgewebegewicht und die Blutglukosekonzentration auf Chromosom (Chr) 3 (95,8–100,1 Mb) und für das Gonadenfettgewebegewicht, Lebergewicht und Blut nachgewiesen Glukosekonzentration auf Chr 17 (9,5–26,1 Mb). Für die AIL BFMI861-S1 x BFMI861-B6N zeigte ein hochsignifikanter QTL auf Chromosom (Chr) 1 (157–168 Mb) einen Zusammenhang mit dem Lebergewicht. Ein QTL für das Körpergewicht nach 20 Wochen wurde auf Chr 3 (34,1 – 40 Mb) gefunden, der sich mit einem QTL für das scAT-Gewicht überlappte. In einem multiplen QTL-Mapping-Ansatz wurde ein zusätzliches QTL, das das Körpergewicht bei 16 Wochen beeinflusste, auf Chr 6 (9,5–26,1 Mb) identifiziert. Schlussfolgerungen: Die QTL-Kartierung zusammen mit einem detaillierten Priorisierungsansatz ermöglichte es uns, Kandidatengene zu identifizieren, die mit Merkmalen des metabolischen Syndroms in beiden AILs assoziiert sind. / Background: The Berlin Fat Mouse Inbred line (BFMI) is a model for obesity and the metabolic syndrome. This study aimed to identify genetic variants associated with the impaired glucose metabolism using the obese lines BFMI861-S1 and BFMI861-S2, which are genetically closely related, but differ in several traits. BFMI861-S1 is insulin resistant and stores ectopic fat in the liver, whereas BFMI861-S2 is insulin sensitive. Methods: QTL-analysis was performed in two advanced intercross lines (AIL) in generation. One AIL obtained from the cross BFMI861-S1 x BFMI861-S2 and the second AIL from the cross BFMI861-S1 x BFMI861-B6N. For both AILs phenotypes were collected over 25 and 20 weeks, respectively. For prioritization of positional candidate genes whole genome sequencing and gene expression data of the parental lines were used. Results: For the AIL BFMI861-S1 x BFMI861-S2 overlapping QTL for gonadal adipose tissue weight and blood glucose concentration were detected on chromosome (Chr) 3 (95.8-100.1 Mb), and for gonadal adipose tissue weight, liver weight, and blood glucose concentration on Chr 17 (9.5-26.1 Mb). For the AIL BFMI861-S1 x BFMI861-B6N one highly significant QTL on chromosome (Chr) 1 (157–168 Mb) showed an association with liver weight. A QTL for body weight at 20 weeks was found on Chr 3 (34.1 – 40 Mb) overlapping with a QTL for scAT weight. In a multiple QTL mapping approach, an additional QTL affecting body weight at 16 weeks was identified on Chr 6 (9.5-26.1 Mb). Conclusions: QTL mapping together with a detailed prioritization approach allowed us to identify candidate genes associated with traits of the metabolic syndrome in both AILs.

Die Untersuchung von Proteininteraktionen ist unerlässlich um die komplexen Mechanismen der epigenetischen Kontrolle von Zugänglichkeit zum Chromatin und dessen Struktur zu verstehen. Zellspezifizierung während der Entwicklung von Organismen kann nur durch strikte Regulation von Chromatin gewährleistet werden, was auch für den Schutz von Zellenidentitäten im späteren Lebensverlauf wichtig ist. Die Modifizierung von Histon-Proteinen, welche integrale Komponenten des Chromatins sind, fördert entweder positive oder negative Genregulation. Eine Vielzahl von Chromatin regulierenden Proteinen hat jedoch keine enzymatische Aktivität für Histon- Modifikationen, so dass sie nur such Interaktionen mit anderen Proteinen regulatorisch einwirken können. Der Nematode Caenorhabditis elegans eignet sich als ein in vivo System, um die Schutzmechanismen der Zellen basierend auf Chromatinfaktoren zu untersuchen, indem systematisch Protein-Interaktionsnetzwerke bestimmt werden. Diese Dissertation beschriebt zunächst die Etablierung eines optimierten Verfahrens für die quantitative Analyse ohne Markierung von Proteinen in C. elegans, die mittels CRISPR mit einem Epitop fusioniert wurden. Mit Hilfe dieses Verfahrens wurden fünf Chromatin regulierende Proteine, die eine wichtige Rolle beim Schutz von Zellidentitäten spielen, charakterisiert. Es wurden in vivo Proteininteraktions-Netzwerke erstellt und dabei neue funktionsrelevante Interaktionspartner identifiziert. Darüber hinaus wurde eine vertiefende Analyse der Interaktionen des Chromatinfaktors MRG- 1 durchgeführt, das homolog zum humanen MRG15 ist. MRG-1 besitzt eine sogenannte Chromodomäne, um an methylierte Histone zu binden. Diese Studie zeigt, dass die Untersuchung der Proteininteraktionen von epigenetischen Faktoren in einem in vivo System ein bedeutendes Verfahren ist, um wichtige biologische Mechanismen der Schutzfunktion von Zellen zu entschlüsseln. / Elucidating protein-protein interactions has been instrumental to understand the complex mechanisms underlying epigenetic regulations to control chromatin accessibility and structure. Proper development and cell fate specification are established under strict chromatin regulation to safeguard cellular identities throughout an organism's life. Modifications of histone proteins as an integral component of chromatin can promote either positive or negative gene regulation. However, many chromatin-regulation proteins lack enzymatic activity and depend on protein-protein interaction to cooperate with other factors to regulate chromatin through histone modifications. The nematode Caenorhabditis elegans can be used as an in vivo system to study chromatin regulators that safeguard cell identity and offers an attractive model system for mapping in vivo protein interactions. The presented thesis includes establishment of an optimized protocol for a quantitative approach based on label-free interaction proteomics to accurately identify interactions of chromatin-regulating proteins, which were epitope-tagged using CRISPR in C. elegans. This protocol was utilized to reveal the interaction partners of five bait proteins involved in essential chromatin regulation mechanisms during cell fate maintenance. The present study generated an in vivo protein interaction network identifying new interactions of high functional relevance. Moreover, in-depth protein-protein interaction analysis of the chromodomain protein MRG-1, homolog of human MRG15, detected a strong association with the Small Ubiquitin-like Modifier (SUMO), besides previously described and novel interactions with other proteins. In summary, in vivo interactome mapping of epigenetic regulators is a powerful approach that can reveal crucial biological insights into how cell fate decisions are regulated.

Die Regulation der Genexpression ist einer der wichtigsten zellulären Prozesse und steht in Zusammenhang mit der Entstehung diverser Krankheiten. Regulationsmechanismen können mit einer Vielzahl von Methoden experimentell untersucht werden, zugleich erfordert die Integration der Datensätze in umfassende Modelle stringente rechnergestützte Methoden. Ein Teil dieser Methoden modelliert die genomweite Genexpression als (lineares) Gleichungssystem über die Aktivität und Beziehungen von Transkriptionsfaktoren (TF), Genen und anderen Faktoren und optimiert die Parameter, sodass die gemessenen Expressionsintensitäten möglichst genau wiedergegeben werden. Trotz ihrer gemeinsamen Wurzeln in der mathematischen Optimierung unterscheiden sich die Methoden stark in der Art der integrierten Daten, im für ihre Anwendung notwendigen Hintergrundwissen, der Granularität des Regulationsmodells, des konkreten Paradigmas zur Lösung des Optimierungsproblems, und der zur Evaluation verwendeten Datensätze. In dieser Arbeit betrachten wir fünf solcher Methoden und stellen einen qualitativen und quantitativen Vergleich auf. Unsere Ergebnisse zeigen, dass die Überschneidungen der Ergebnisse sehr gering sind, was nicht auf die Stichprobengröße oder das regulatorische Netzwerk zurückgeführt werden kann. Ein Grund für die genannten Defizite könnten die vereinfachten Modelle zellulärer Prozesse sein, da diese vorhandene Rückkopplungsschleifen ignorieren. Wir schlagen eine neue Methode (Florae) mit Schwerpunkt auf die Berücksichtigung von Rückkopplungsschleifen vor und beurteilen deren Ergebnisse. Mit Floræ können wir die Identifizierung von Knockout- und Knockdown-TF in synthetischen Datensätzen verbessern. Unsere Ergebnisse und die vorgeschlagene Methode erweitern das Wissen über genregulatorische Aktivität können die Identifizierung von Ursachen und Mechanismen regulatorischer (Dys-)Funktionen und die Entwicklung von medizinischen Biomarkern und Therapien unterstützen. / Gene regulation is one of the most important cellular processes and closely interlinked pathogenesis. The elucidation of regulatory mechanisms can be approached by many experimental methods, yet integration of the resulting heterogeneous, large, and noisy data sets into comprehensive models requires rigorous computational methods. A prominent class of methods models genome-wide gene expression as sets of (linear) equations over the activity and relationships of transcription factors (TFs), genes and other factors and optimizes parameters to fit the measured expression intensities. Despite their common root in mathematical optimization, they vastly differ in the types of experimental data being integrated, the background knowledge necessary for their application, the granularity of their regulatory model, the concrete paradigm used for solving the optimization problem and the data sets used for evaluation. We review five recent methods of this class and compare them qualitatively and quantitatively in a unified framework. Our results show that the result overlaps are very low, though sometimes statistically significant. This poor overall performance cannot be attributed to the sample size or to the specific regulatory network provided as background knowledge. We suggest that a reason for this deficiency might be the simplistic model of cellular processes in the presented methods, where TF self-regulation and feedback loops were not represented. We propose a new method for estimating transcriptional activity, named Florae, with a particular focus on the consideration of feedback loops and evaluate its results. Using Floræ, we are able to improve the identification of knockout and knockdown TFs in synthetic data sets. Our results and the proposed method extend the knowledge about gene regulatory activity and are a step towards the identification of causes and mechanisms of regulatory (dys)functions, supporting the development of medical biomarkers and therapies.

[EN] The necessity of higher quality tools, due to the increasing competitivity in the machining industry, and in general the need of materials with improved wear resistance, places the hard metal sector in continuous technical renovation. The important improvement of hardness, strength and wear resistance obtained in ultrafine WC-Co grades, as well as the extraordinary properties of nanomaterials, has focused the cemented carbides research in obtaining nanocrystalline powders, and in the development of bulk nanostructured cemented carbides, which remains a technological challenge. In this context, the aim of present research is to contribute on the knowledge of the behaviour sintering of ultrafine and nanocrystalline WC-Co mixtures, and to explore the possibilities of microstructural control that allow manufacturing dense cemented carbides with grain size close to the nanometer scale. Furthermore, the effect of the microstructural refinement in the mechanical behaviour of sintered materials is evaluated. Moreover, due to the poor supply and the high cost of these powders in the market, the fabrication of ultrafine and nanocrystaline WC-Co mixtures by planetary milling is studied. This allows analysing the effect of the powder production method on their densification, microstructural development and final mechanical properties. The results obtained show the problems of the powders fabricated by milling, due to their decarburation, and their fast kinetics of grain growth. Furthermore, the advantages of using nanocrystalline powders, versus the ultrafine ones, on improving the densification and capability of microstructural control, have been demonstrated, allowing a significant increase in the hardness of the sintered samples. The main contribution of the research is the combined use of additives inhibitors and pressure assisted sintering techniques that allow increasing the densification at lower sintering temperature and shorter holding times, thus limiting the grain growth. WC-CoVC / Cr3C2 cemented carbides near fully dense is obtained by SPS and HIP in solid phase at 1100 ºC. The addition of inhibitors, especially VC, is demonstrated to be an efficient method for controlling the grain growth in the solid state, even by rapid sintering processes. The combination of addition of VC and HIP sintering at low temperature has allowed manufacturing near nanostructured materials (120 nm), with an excellent combination of properties, with hardness about 2100 HV30 and fracture toughness values greater than 10 MPa·m1/2. These properties place these materials among the most outstanding cemented carbides of those reported in literature. / [ES] La necesidad de herramientas de mayor calidad, debido a la creciente competitividad en el sector del mecanizado, y, en general, de materiales con resistencia al desgaste mejorada, sitúa al sector del duro metal en continua renovación técnica. La importante mejora de dureza, resistencia mecánica y resistencia al desgaste obtenida en grados WC-Co ultrafinos, y las excepcionales propiedades asociadas a los nanomateriales, ha focalizado la investigación de metal duro en la obtención de polvos nanocristalinos, y en el desarrollo de carburos cementados nanoestructurados, que sigue siendo un reto tecnológico. En esta línea, la presente investigación, pretente contribuir al conocimiento del comportamiento durante la sinterización de mezclas WC-Co ultrafinas y nanocristalinas, explorando posibilidades de control microestructural, que permitan obtener carburos cementados densos con tamaño de grano próximo a la escala nanométrica, y evaluar el efecto del refinamiento microestructural en su comportamiento mecánico. Además, dada la escasa oferta en el mercado de estos polvos y su elevado coste, se analiza su fabricación mediante molienda en planetario, lo que permite analizar el efecto de la vía de obtención del polvo en su densificación, desarrollo microestructural, y propiedades finales. Los resultados obtenidos ponen de manifiesto la problemática de los polvos obtenidos por molienda, debido a su decarburación, y su rápida cinética de crecimiento de grano. Además, se ha demostrado las ventajas del uso de polvos nanocristalinos frente a los ultrafinos, en el aumento de la densificación y posibilidades de control microestructural, lo que se traduce en importantes aumentos de dureza de los sinterizados. La principal aportación de la investigación es el empleo combinado de aditivos inhibidores y técnicas de sinterización asistidas por presión, que permiten aumentar la densificación reduciendo temperatura y tiempo de exposición, limitando así el crecimiento de grano. Se ha demostrado que es posible obtener sinterizados WC-Co-VC/Cr3C2 casi 100% densos a 1100 ºC, mediante HIP y SPS, confirmándose, además, la efectividad de los inhibidores. La combinación de adición de VC y sinterización en HIP a baja temperatura, ha permitido obtener materiales casi nanocristalinos (120 nm), con una excelente combinación de propiedades, con durezas de hasta 2100 HV30 y valores de tenacidad superiores a los 10 MPa·m1/2, lo que sitúa a estos materiales entre los carburos cementados más destacados de los publicados en la literatura. / [CA] La necessitat de ferramentes de major qualitat, degut a la creixent competitivitat en el sector del mecanitzat, i, en general, de materials amb resistència al desgast millorada, situa el sector del metall dur en contínua renovació tècnica. La important millora de duresa, resistència mecànica i resistència al desgast obtinguda en graus WC-Co ultrafins, i les excepcionals propietats associades als nanomaterials, ha focalitzat la investigació de metall dur en l'obtenció de pols nanocristal·lins, i en el desenvolupament de carburs cementats nanoestructurats, que segueix sent un repte tecnològic. En aquesta línia, la present investigació pretén contribuir al coneixement del comportament durant la sinterització de mescles ultrafines i nanocristal·lines, explorant possibilitats de control microestructural, que permeten obtindre carburs cementats densos amb grandària de gra propera a l'escala nanomètrica i avaluar l'efecte del refinament microestructural en el seu comportament mecànic. A més a més, donada l'escassa oferta en el mercat d'aquests pols i el seu elevat cost, s'analitza la seua fabricació mitjançant mòlta en planetari, la qual cosa permet analitzar l'efecte de la via d'obtenció dels pols en la seua densificació, desenvolupament de la seua microestructura, i propietats finals. Els resultats obtinguts posen de manifest la problemàtica dels pols obtesos per mòlta, degut a la seua decarburació, i la seua ràpida cinètica de creixement de gra. Així mateix, s'han demostrat els avantatges de l'ús de pols nanocristal·lins front als ultrafins, en l'augment de la densificació i possibilitats de control microestructural, el que es tradueix en importants augments de duresa dels sinteritzats. La principal aportació de la investigació és l'emprament combinat d'additius inhibidors i tècniques de sinterització assistides per pressió, que permeten augmentar la densificació reduint temperatura i temps d'exposició, limitant així el creixement de gra. S'ha demostrat que és possible obtindre sinteritzats WC-Co-VC/Cr3C2 quasi 100% densos a 1100 ºC, mitjançant HIP i SPS, confirmant-se, a més, l'efectivitat dels inhibidors. La combinació d'addició de VC i sinterització en HIP a baixa temperatura ha permès obtindre materials quasi nanocristal·lins (120 nm), amb una excel·lent combinació de propietats, amb dureses de fins a 2100 HV30 i valors de tenacitat superiors als 10 MPa·m1/2, la qual cosa situa aquests materials entre els carburs cementats més destacats dels publicats en la literatura. / Bonache Bezares, MV. (2016). Obtención, procesado y caracterización de carburos cementados CW-Co basados en polvos ultrafinos y nanocristalinos [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/63222

As light-weighting becomes a priority for the automotive industry, refill friction stir spot welding emerges with enormous potential to supplement or replace conventional spot joining processes. This thesis addresses the limitations of current tooling options by examining materials beyond steel for use in RFSSW. Contained herein is an analysis of weld quality as a function of tool material, a production evaluation of RFSSW using various tool materials, and an assessment of long-term performance of a tungsten carbide tool. Over the course of this research, tungsten carbide emerged as a viable candidate for long-lasting RFSSW tooling.

Thesis (MScEng (Civil Engineering))- -University of Stellenbosch, 2011 / ENGLISH ABSTRACT: The limited water supply and an increasing water demand means that the effective management of water resources becomes much more important than in the past. The implementation of water demand management / water conservation (WDM/WC) projects are usually used as a crisis management tool to reduce immediate water shortage and to allow time for the planning and construction of infrastructure to increase water supply. It is however possible to incorporate WDM/WC into integrated water resource management and to use WDM/WC as an economic viable option for the upgrade of infrastructure to balance supply and demand. Existing economic evaluation methods to compare different options with each other were used to evaluate WDM/WC measures. Literature showed that to perform an economic evaluation of WDM/WC measures, the costs associated with the implementation of the WDM/WC measures, as well as the expected water saving from the implementation of the WDM/WC measure, must be known. Models were developed to estimate the expected water savings from different WDM/WC measures. The economic impacts of specific WDM/WC measures were investigated by using these models. Different economic models were developed to perform an economic evaluation of WDM/WC measures. WDM/WC measures were evaluated in terms of its economic feasibility. Economical evaluations of WDM/WC measures were also done as an alternative to the upgrading of infrastructure. In the last evaluation, the financing of WDM/WC measures through the deferral of capital cost, was investigated. Case studies from literature, where costs as well as water savings were available, were used to evaluate these WDM/WC measures by using the developed economic models. Cost estimates for the upgrading of infrastructure, to supply an equal amount of water as the water saving achieved in each case study, were done. These estimates were used to compare WDM/WC measure with the upgrading of infrastructure. / AFRIKAANSE OPSOMMING: Daar word al hoe meer druk op bestaande hulpbronne geplaas om voldoende water te lewer. Die fokus skuif na effektiewe bestuur van hierdie hulpbronne. Wateraanvraagbestuur/ Waterbewaring (WAB/WB) projekte word geïmplementeer om krisisse van water tekorte aan te spreek en tyd te wen om nuwe hulpbronne te ontwikkel. Dit is wel moontlik om WAB/WB in geïntegreerde waterbron bestuur in te sluit en WAB/WB as ʼn ekonomiese alternatief tot kapitale investering aan te wend. Om die ekonomiese aspekte van WAB/WB te ondersoek, is daar op bestaande ekonomiese evaluerings metodes gefokus om verskillende opsies met mekaar te vergelyk. Uit die literatuur is gevind dat die belangrikste aspekte vir die ontleding van WAB/WB alternatiewe i.t.v. hul ekonomiese waarde, die koste van implementering van die WAB/WB alternatief is en die waterbesparing wat deur die implementering van die WAB/WB alternatief verkry word. WAB/WB modelle is ontwikkel om die verwagte water besparing van bepaalde WAB/WB alternatiewe te beraam. Die moontlike ekonomiese impak van bepaalde WAB/WB alternatiewe is deur die gebruik van hierdie modelle ondersoek. Ekonomiese evaluerings modelle is opgestel om WAB/WB alternatiewe te ontleed. WAB/WB alternatiewe kan as ʼn ekonomiese haalbare projek geïmplementeer word waar die kostes van die waterbesparings meer as die kapitale koste van die projek is. WAB/WB alternatiewe kan ook meer ekonomies as die ontwikkeling van nuwe bronne of opgradering van ʼn bestaande netwerk wees. Laastens is die moontlikheid om WAB/WB as ʼn alternatief te finansier deur die besparing wat bereik kan word deur ʼn kapitale projek uit te stel, ondersoek. Gevalle studies uit die literatuur, waar die kostes en waterbesparings bekend is, is ontleed deur van hierdie ekonomiese evaluerings modelle gebruik te maak. Vir elk van die gevalle studies is ʼn koste vir die opgradering van die infrastruktuur beraam om die ekwivalente hoeveelheid water te voorsien as wat deur die WAB/WB alternatief bespaar is.