No description available.

No description available.

This research effort aims to compare car-following models when the models are calibrated to individual drivers with the naturalistic data. The models used are the GHR, Gipps, Intelligent Driver, Velocity Difference, Wiedemann, and the Fritzsche model. This research effort also analyzes the Wiedemann car-following model using car-following periods that occur at different speeds. The Wiedemann car-following model uses thresholds to define the different regimes in car following. Some of these thresholds use a speed parameter, but others rely solely upon the difference in speed between the subject vehicle and the lead vehicle. This research effort also reconstructs the Wiedemann car-following model for truck driver behavior using the Naturalistic Truck Driving Study's (NTDS) conducted by Virginia Tech Transportation Institute. This Naturalistic data was collected by equipping 9 trucks with various sensors and a data acquisition system. This research effort also combines the Wiedemann car-following model with the GHR car-following model for trucks using The Naturalistic Truck Driving Study's (NTDS) data. / Master of Science

Made available in DSpace on 2014-08-20T13:32:53Z (GMT). No. of bitstreams: 1 dissertacao_augusto_schneider.pdf: 2025669 bytes, checksum: bde04bd1476df3f35564859c10477bca (MD5) Previous issue date: 2008-11-28 / In non-ovarian tissues GHR expression is regulated by insulin concentrations and is correlated to IGF-I expression. In the ovary IGF-I expression is also related to insulin levels, however no correlation with GHR was demonstrated until now. The aim of this study was to investigate the effect of fasting or insulin administration on blood concentrations of glucose, nonsterified fatty acids, insulin, insulin like growth factor I (IGF-I) and estradiol and on follicular expression of growth hormone receptor (GHR) and IGF-I mRNA in ewes. Fifteen ewes received an intravaginal progesterone releasing device that was removed 6 days later (Day 0). In Day -2 the ewes were divided in: control group, which received maintenance diet, insulin group, which received insulin injections every 12 hours from Day -2 to 2 and fasting group, which was submitted to fasting from Day -2 to 2. The results of the current study revealed that insulin administration or fasting during the development of a follicular wave did not affect (P=0.22) follicular diameter, although insulin injection increased (P=0.02) estradiol production. There was no difference among groups for GHR or IGF-I mRNA expression in granulosa (P=0.62, 0.43) or theca cells (P=0.92, 0.43). For fasting group there was a positive correlation between glucose and estradiol (r=0.97, P=0.006) and granulosa cell IGF mRNA (r=0.96, P=0.03). For insulin group estradiol was positive correlated to follicular diameter (r=0.93, P=0.02) and granulosa cell GHR (r=0.87, P=0.05) and IGF-I mRNA (r=0.79, P=0.10). In conclusion, exogenous insulin or fasting did not affect follicular diameter and expression of GHR and IGF-I mRNA in the pre-ovulatory follicle, although exogenous insulin increased estradiol production. / Em tecidos não ovarianos a expressão do receptor do hormônio do crescimento (GHR) é regulada pelas concentrações de insulina e está correlacionada a expressão de fator de crescimento semelhante a insulina tipo I (IGF-I). No ovário a expressão de IGF-I também está relacionada aos níveis de insulina, porém ainda não foi demonstrada sua correlação com a expressão de GHR. O objetivo deste estudo foi investigar o efeito do jejum ou administração de insulina nos níveis de glucose, ácidos graxos não esterificados, uréia, IGF-I, insulina e estradiol e na expressão folicular de RNAm para GHR e IGF-I em ovelhas. Quinze ovelhas receberam um dispositivo intravaginal liberador de progesterona, que foi removido após seis dias (Dia 0). No Dia -2 as ovelhas foram dividas em: grupo controle, que recebeu uma dieta de manutenção; grupo insulina, que recebeu injeções de insulina a cada 12 horas do Dia -2 ao Dia 2 e grupo jejum, que foi submetido à dieta hídrica do Dia -2 ao Dia 2. Os resultados revelaram que a administração de insulina ou o jejum durante o desenvolvimento de uma onda folicular não influenciaram (P=0,22) o diâmetro folicular, no entanto a administração de insulina aumentou (P=0,02) a produção de estradiol. Não houve diferença entre os grupos para a expressão de RNAm para GHR e IGF-I nas células da granulosa(P=0,62; 0,43) ou teca (P=0,92; 0.43). Para o grupo jejum houve uma correlção positiva entre glucose e estradiol (r=0,97, P=0,006) e RNAm IGF-I nas células da granulosa (r=0,96, P=0,03). Para o grupo insulina o estradiol foi positivamente correlacionado ao diâmetro folicular (r=0,93, P=0,02) e expressão de RNAm para GHR (r=0,87, P=0,05) e IGF-I (r=0,79, P=0,10)nas células da granulosa. Em conclusão, a insulina exógena ou o jejum não afetaram o diâmetro folicular e a expressão de mRNA para GHR e IGF-I no folículo pré-ovulatório, apesar da insulina exógena ter aumentado a produção de estradiol.

No description available.

Wachstumshormon (GH) besteht aus 191 Aminosäuren, hat eine Molekülmasse von 22kD und ist essentiell für postnatales Wachstum. Es wird aus der Adenohypophyse freigesetzt. GH bindet an einen GH-Rezeptor (GHR) und aktiviert somit über intrazelluläre Signalvorgänge Zielgene, insbesondere das, welches für die Kodierung von insulin-like growth factor (IGF-1) zuständig ist. IGF-1 vermittelt den Großteil aller GH-Signale. Zusammen mit den bereits bekannten GH Mutanten R77C und D112G ist in dieser Studie der neue GH Mutant d188-190 charakterisiert worden. Alle drei Mutanten wurden in heterozygoter Form in kleinwüchsigen Patienten identifiziert. Diesen Patientendaten zu Folge schien es möglich, dass d188-190 eine GH-antagonistische Wirkung besitzt. Zusätzlich wurde die extrem konservierte C-terminale Disulfidbrücke des GH im Mutanten d188-190 unterbrochen vorgefunden. Die Auswirkung der Unterbrechung wurde durch Substitution einer oder beider involvierter Cysteine durch Alanine untersucht. Alle Mutanten und Wildtypen des GH wurden in menschlichen embryonalen Nierenzellen (HEK-293) angezüchtet und eine Reihe von in vitro Experimenten sind für deren Charakterisierung etabliert worden. Es zeigte sich, dass d188-190 keine GH-antagonistische Wirkung besitzt. Im Vergleich zum Wildtyp weist der Mutant eine verminderte Bindungsaffinität zu GH, schwächere biologische Aktivität und höhere Stabilität auf. R77C und D112G sind dem Wildtyp GH sehr ähnlich. Die Disulfidbrücke ist wichtig für die Rezeptorbindung und für die biologische Aktivität von GH. Wenn ein Cystein entfernt wird vermindert sich die Stabilität des Moleküls. Dieser Effekt kann durch Entfernen des zweiten Cysteins wieder rückgängig gemacht werden. Die in dieser Studie etablierten Experimente können Verwendung finden in der Charakterisierung bislang nicht bekannter GH Mutanten und können darüber hinaus zur Behandlung von Patienten eingesetzt werden. / Growth hormone (GH) is a 22 kD, 191-aa, pituitary-derived peptide hormone that is essential for postnatal growth. GH signals via binding to GH receptor (GHR), which initiates intracellular signal transduction pathways. This leads to activation of target genes, most importantly the one encoding insulin-like growth factor (IGF)-1, which mediates most GH action. In this study a novel GH mutant, d188-190, was characterized along with previously reported GH mutants R77C and D112G. All of these mutants had been identified in heterozygous form in patients with retarded growth. Based on patient data, d188-190 was thought to be a GHR antagonist. Moreover, the extremely conserved C-terminal disulfide bridge of GH was disrupted in mutant d188-190 and its role was studied by substituting one or both of the involved cysteines with alanines. All mutants and wild type (wt) GH were produced in human embryonic kidney (HEK)-293 cells and an array of in vitro experiments was established for their characterization. It turned out that the novel d188-190 mutant is not a GHR antagonist after all. It has a diminished binding affinity to GHR, low biological activity and high stability compared to wt GH. R77C and D112G are rather similar to wt GH. The disulfide bridge is important for receptor binding and biological activity of GH. If one of the cysteines is removed the stability of the molecule drops but this can be reversed by removing both cysteines. If further GH mutants are to be identified, the established array of experiments will be useful for their fast characterization and could even contribute to correct treatment of patients.

No description available.

L'hormone de croissance (GH) est une hormone paradoxale. Historiquement reconnue comme responsable de la croissance post-natale, elle est actuellement considérée comme une véritable cytokine, synthétisée en de nombreux sites extra-hypophysaires et impliquée, lorsque dérégulée, dans les processus de tumorigénèse. Le travail présenté dans cette thèse a permis de caractériser et localiser par RT-PCR in situ, les cellules capables de synthétiser la GH dans le système immunitaire du fœtus et du rat adulte, puis dans les différents systèmes de prolifération cellulaire du carcinome canalaire mammaire humain montrant ainsi que la GH, par son action autocrine / paracrine est non seulement impliquée dans le développement embryonnaire mais participe à la progression tumorale. Nos travaux in vitro montrent que l'internalisation et la translocation nucléaire de la GH complexée à son récepteur sont indépendantes de l'activation de JAK2 « Janus Kinase 2 », cependant indispensable à son exportation hors du noyau. L'étude du système de régulation négative du signal induit par la GH nous a permis de mettre en évidence une surexpression de la protéine CIS « Cytokine-Inducible SH2-containing protein », dans les zones de prolifération tumorale des différents carcinomes étudiés et dans 8 lignées tumorales mammaires. La surexpression de CIS, in vitro, inhibe la voie de signalisation JAK/STAT « Signal Transducer and Activator of Transcription » et active la voie des MAPK « Mitogen Activated Protein Kinases ». Nous avons pour finir, corrélé l'activation prédominante de CIS à la synthèse de GH « autocrine » dans les cellules tumorales mammaires MCF-hGH. La localisation tant nucléaire que cytoplasmique de la GH et de toutes les molécules informatives laisse entrevoir des mécanismes de régulation encore inconnus. Les travaux futurs tenteront de répondre à la question maintenant cruciale : la GH, hormone de jouvence ou véritable oncogène ?

Toutes les actions biologiques de l'hormone de croissance (GH) sont initiées par l'interaction de l'hormone avec un homodimère de son récepteur spécifique (GHR2) présent au niveau de la surface de ses cellules-cibles. Cette association conduit à l'activation de différentes voies de transduction du signal intracellulaire ainsi qu'à l'internalisation du complexe GH-GHR2, notamment au niveau de la mitochondrie. L'objectif de cette étude est de montrer le mécanisme et l'implication de l'internalisation par les cavéoles dans la régulation de l'action de la GH au niveau de la fonction mitochondriale. Nous avons montré l'importance de la boîte 1 du GHR dans la stimulation de l'activité respiratoire globale ; le transport de la GH par la voie des cavéoles dans la mitochondrie ; l'importance de la localisation intramitochondriale de la GH dans la régulation des complexes II et IV de la chaîne respiratoire. Ces résultats suggèrent une nouvelle voie d'action directe de la GH sur la mitochondrie

Made available in DSpace on 2014-08-20T13:32:47Z (GMT). No. of bitstreams: 1 dissertacao_lucas_teixeira_hax.pdf: 388762 bytes, checksum: c93c16af033ccd2aa4ff52ec81723de9 (MD5) Previous issue date: 2013-02-27 / The genes of the somatotropic axis, which act regulating the metabolism and physiology of the mammals, present polymorphism associated to some characteristics of economical interest, such as reproductive performance and milk production. Such factors may be influenced by the mutation on only one nucleotide in the base sequence of the gene of the growth hormone receptor (GHR), which may alter the density of GHR on the hepatic tissue. Changes in the coupling of the growth hormone (GH) in the hepatic tissue alter the serum concentration of the insulin-like growth factor 1 (IGF-I), as IGF-I is produced mainly by the liver when it is stimulated by the growth hormone. Different studies have evaluated the effect of polymorphisms in the gene responsible for encoding IGF-I on the reproductive performance and milk production of high production dairy cows. Among other functions, the IGF-I mediates the effects of gonadotropins on the follicular cells, stimulating the growth and differentiation of theca and granulosa follicular cells, playing also a significant role on the final growth and maturation of the dominant follicle. Furthermore, high serum IGF-I concentrations are associated with a earlier return to cyclicity post partum in high yield dairy cows. Thus, the objective of this study was to evaluated the relevance of the mutations in GHR and IGF-I on the calving conception interval, number of inseminations per pregnancy and milk production in Holstein cows. One hundred and fifty five Holstein cows, submitted to a semi extensive management system, subjected to fixed-time artificial insemination (TAI) that got pregnant up to 250 days in milk in 2011, were selected. Among the animals tested, 29% presented GHR AluI (+ / +), 57.5% AluI (+ / -) and 13.5% AluI (- / -) genotype. 34.9% presented IGF-I SnaBI (+ / +), 45.8% SnaBI (+ / -) and 19.3% SnaBI (- / -) genotype. No association was observed between GHR AluI and IGF-I SnaBI genotypes and calving conception interval, number of inseminations per pregnancy and milk yield (P> 0.05). Likewise, there was no association between the interaction of GHR AluI and IGF-I SnaBI genotypes and calving conception interval, number of inseminations per pregnancy and milk yield (P> 0.05). Finally, further studies are necessary to better understand the relevance of GHR AluI and IGF-I SnaBI genotypes to the calving conception interval number of inseminations per pregnancy and milk production in Holstein cows. / Os genes do eixo somatotrópico, que atuam na regulação do metabolismo e fisiologia dos mamíferos, apresentam polimorfismos associados a algumas características de interesse econômico, como desempenho reprodutivo e produção de leite. Tais fatores podem ser influenciados por mutações de apenas um nucleotídeo na sequência de bases do gene do receptor do hormônio do crescimento (GHR), que podem alterar a expressão do GHR no tecido hepático. Mudanças no acoplamento do hormônio do crescimento (GH) no tecido hepático alteram a concentração sérica de fator de crescimento semelhante à insulina tipo1 (IGF-I), visto que o IGF-I tem sua produção endócrina principalmente no fígado mediante estimulação do hormônio do crescimento. Diversos trabalhos têm estudado o efeito de polimorfismos no gene que codifica para IGF-I no desempenho reprodutivo e produção de leite de vacas leiteiras de alta produção. Entre outras funções, o IGF-I atua como mediador dos efeitos das gonadotrofinas nas células foliculares, estimulando o crescimento e diferenciação das células da teca e da granulosa foliculares, apresentando também um importante papel no crescimento final e na maturação do folículo dominante. As altas concentrações sanguíneas de IGF-I estão também associadas a um retorno à ciclicidade mais precoce de vacas leiteiras pós-parto de alta produção. Dessa forma, o objetivo deste estudo foi avaliar a importância de mutações no GHR e IGF-I no desempenho zootécnico, IPC, número de inseminações por prenhez e produção de leite em vacas da raça Holandês. Foram avaliadas 155 vacas da raça Holandês em sistema semi extensivo submetidas à inseminação artificial em tempo fixo (IATF) e que conceberam até 250 dias em lactação no ano de 2011. Entre os animais analisados, 29% apresentaram o genótipo GHR AluI, (+/+), 57,5% AluI (+/-) e 13,5% AluI (-/-). Já para o IGF-I SnaBI 34,9% apresentaram o genótipo IGF-I SnaBI (+/+), 45,8% SnaBI (+/-) e 19,3% SnaBI (-/-). Não foi observada associação entre os genótipos GHR AluI e IGF-I SnaBI e o intervalo parto-concepção, número de inseminações por prenhez e produção de leite (P>0,05). Da mesma forma, não houve associação entre a interação dos genótipos de GHR AluI e IGF-I SnaBI e o intervalo parto-concepção, número de inseminações por prenhez e produção de leite (P>0,05). Finalmente, novos estudos avaliando uma maior população de animais são necessários para elucidar a importância dos genótipos de GHR AluI e IGF-I SnaBI no intervalo parto-concepção, número de inseminações por prenhez e produção de leite.