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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
581

An integrative approach to the effect of interleukin-6 on adaptation to restraint stress in rats

Viljoen, Monet 12 1900 (has links)
Thesis (MSc (Physiological Sciences))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: Bi-directional communication exists between HPA-axis activation and interleukin-6 (IL-6). However, the relative contribution of centrally versus peripherally secreted IL- 6 remains unclear, especially under psychological stress conditions. We hypothesised that the HPA response to mild psychological stress is dependent on IL- 6, both centrally and peripherally. 120 male Wistar rats were divided into four groups, depending on whether they received an anti-IL-6 antibody (Ab) (2μg/ml/kg body weight) or a placebo (sterile saline) injection and whether or not they were subjected to 1 hour of restraint stress for 1, 2 or 3 days. Rats were euthanized 24 hours after stress exposure. Plasma corticosteroid (GC) levels remained significantly increased 24 hours after a single stress exposure (control placebo (CP) versus stress placebo (SP): p < 0.05). The undetectable plasma IL-6 levels evident across all groups may be explained by the short half-life of IL-6. Plasma IL-1β levels decreased when IL-6 was blocked in unstressed animals (CP versus CAb: p < 0.05), suggesting a role for IL-6 in the maintenance of IL-1β levels under tonic physiological conditions. At tissue level, pituitary gland mass increased significantly at time point 2, independently of stress when blocking IL-6 (CAb: p < 0.05). This suggests that when normal homeostasis is threatened, immediate adaption or at least compensation may occur. It was observed that GR, IL-1β, IL-1βR, IL-6, IL-6R and GABAARα1 showed no response to stress alone in the pituitary. It is therefore more likely that resistance to adaptation exists centrally. IL-1β and IL-1βR (p < 0.05) and GABAARα1 (p < 0.005) expression increased in the CAb group in the pituitary, again suggesting a role for IL-6 under control conditions. In terms of the adrenal, blocking IL-6 resulted in decreased glandular mass at time point 1, independent of stress (CAb and SAb: p < 0.005). The up-regulation in GR expression seen in CAb and SAb (p < 0.05) may be the effect of a compensatory mechanism to increase IL-6 dependent bioactivity of GCs. The fact that expression of IL-6, IL-6R, IL-1β and IL- 1βR consistently increased in the Ab groups, and mostly in the zona fasciculata and zona reticularis, suggests that lack of local direct negative cytokine feedback occurred in response to very low plasma IL-6 levels and that this contributes more than GCs in the down-regulation of inflammatory cytokine release. In conclusion, consistent effects of the Ab were apparent in the tissues investigated, even in control conditions, suggesting that IL-6 plays a role in the maintenance of basal homeostasis, including its regulation of the response to psychological stress. We found differential regulation in terms of cytokines and GCs when comparing peripheral versus central effects of stress and Ab, as well as the levels of cytokines in the blood compartment, compared to within tissues. / AFRIKAANSE OPSOMMING: Daar bestaan twee-rigting kommunikasie tussen HPA-as aktivering en interleukin-6 (IL-6), allhoewel die relatiewe bydrae van sentraal versus perifeer afgeskeide IL-6 nog onduidelik is, veral gedurende sielkundige strestoestande. Ons hipotese is dat die HPA reaksie tot sielkundige stres afhanklik van IL-6 is, beide sentraal en in die periferie. 120 manlike Wistar rotte is in vier groepe verdeel, afhangende van of hulle ‘n anti-IL- 6 teenliggaampie (Ab) (2μg/ml/kg liggaamsgewig) of ‘n plasebo (steriele soutoplossing) inspuiting gekry het, en of hulle onderworpe was aan 1 uur van vaskeer-stres vir 1, 2 of 3 dae. Rotte is 24 uur na blootstelling aan stres aan genadedood onderwerp. Bloed kortikosteroïed (GC) vlakke het beduidend toegeneem binne 24 uur na ‘n eenmalige stres blootstelling (kontrole plasebo (CP) versus stres plasebo (SP): p < 0.05). Die onmeetbaar lae vlakke van IL-6 regoor al die groepe, kan verduidelik word na aanleiding van die kort half-leeftyd van IL-6. Bloed IL-1β vlakke het afgeneem in kontrole rotte wanneer IL-6 geblok is (CP versus CAb: p < 0.05). Dit kan beteken dat IL-6 noodsaaklik is vir die onderhoud van IL-1β vlakke gedurende basale toestande. Op weefselvlak het die hipofise massa toegeneem by tydpunt 2 toe IL-6 geblok is, onafhanklik van stres (CAb: p < 0.05). Dit dui aan dat wanneer normale homeostase bedreig word, daar onmiddelike aanpassing of kompensasie plaasvind. Dit is opvallend dat GR, IL-1β, IL-1βR, IL-6, IL-6R en GABAARα1 geen respons in terme van stres alleen in die hipofise getoon het nie. Na aanleiding daarvan is dit meer waarskynlik dat weerstand tot aanpassing sentraal bestaan. IL-1β and IL-1βR (p <0.05) en GABAARα1 (p < 0.005) uitdrukking in die hipofise het toegeneem in die CAb groep, wat weereens ‘n rol vir IL-6 onder kontrole toestande uitwys. In terme van die bynier, het die blok van IL-6 ‘n afname in massa veroorsaak by tydpunt 1, wat weer onafhanklik van stres was (CAb en SAb: p < 0.005). Die opregulering in die CAb en SAb groepe (p < 0.05), kan wees as gevolg van ‘n kompensasie meganisme om IL-6 afhanklike GC aktiwiteit te verhoog. Die feit dat die uitdrukking van IL-6, IL-6R, IL-1β and IL-1βR in die Ab groepe deurlopend verhoog was, en meeste in die zona fasciculata en zona reticularis, stel voor dat daar ‘n tekort aan plaaslike, direkte sitokien negatiewe terugvoering was, as gevolg van die merkwaardige lae bloed IL-6 vlakke en dat dit meer bydra as GCs in die afregulering van inflammatoriese sitokien vrystelling.
582

Hypothalamic-pituitary-adrenal-axis vs. the sympatho-adrenal medullary system in the acute response to psychological stress

Janse van Vuuren, Marthinus 03 1900 (has links)
Thesis (MSc (Physiological Sciences))--University of Stellenbosch, 2011. / Includes bibliography. / ENGLISH ABSTRACT: The hypothalamic-pituitary-adrenal-(HPA) axis has long been closely associated with psychological stress-induced activation of the adrenal cortex and subsequent glucocorticoid production. Another, less known peripheral limb of the psychological stress response, is the sympatho adrenal medullary pathway. We hypothesized that the sympatho-adrenal medullary system constitutes the primary response to acute psychological stress, with the HPA-axis functioning as a secondary response. We tested our hypothesis by manipulating a model of acute mild psychological stress (restraint) by blocking IL-6, a valuable constituent of the sympatho-adrenal medullary system. Serum corticosterone concentration increased in response to stress (7 ± 3 vs. 57 ± 4 ng/ml; P<0.0001), a response attenuated when IL-6 was blocked (17 ± 7 ng/ml). Stress increased pituitary mass only when IL-6 was blocked (38 ± 3 vs. 65 ± 6 mg; P <0.001). Stress increased left adrenal mass only in the presence of IL-6 (34 ± 1 vs. 73 ± 8 mg; P <0.00001). Stress did not influence the circulating levels of TNF-α, IL-1β or IL-6 significantly. IL-1β and TNF-α concentrations in the unstressed rats were lower when IL-6 was blocked. We then manipulated the stress model by administering S. frutescens extract to elucidate both the central and peripheral effects of acute S. frutescens administration on the psychological stress response. Restraint caused decreases in hippocampal GR levels when compared to respective controls. S. frutescens administration and exposure to restraint synergistically decreased hippocampal GABAAR levels. In addition, exposure to both stress and S. frutescens led to a noteworthy increase in pituitary mass (P = 0.078), as well as pituitary ACTH levels (P < 0.01). Similarly, differences in circulating ACTH levels showed an effect of stress on ACTH secretion only in the presence S. frutescens (P < 0.05). Adrenal mass was significantly increased in S. frutescenstreated animals that were also exposed to restraint (P < 0.05). Adrenal levels of ACTH showed a reciprocal trend to pituitary and circulating ACTH levels. No statistically significant differences were seen in adrenal IL-6 content. However, marked increases in IL-6 levels were seen at this level with administration of S. frutescens stress exposure and a cumulative increase seen with both S. frutescens-treatment and stress exposure. Hippocampal GABAAR, pituitary mass, pituitary ACTH and circulating ACTH levels showed a similar trend towards a synergistic effect of S. frutescens and restraint in activation of the psychological stress response, while adrenal ACTH levels showed an inverse trend. Hippocampal GR did not show any effect of stress or S. frutescens-treatment. The results from these two experiments indicate that the sympatho-adrenal medullary system constitutes the primary response to acute mild psychological stress and that the HPA-axis is only activated during an exacerbated stress response or when the sympatho-adrenal medullary contribution is inadequate. Furthermore, the acute administration of S. frutescens possibly led to a functional shift in GABAergic function, resulting in activation of the stress response. The anecdotal reports of a “docile” effect of S. frutescens most likely results from activation of the mesolimbic dopaminergic system by the hippocampus and amygdala. These results have dramatic consequence in GABA-based anxiety-treatments. / AFRIKAANSE OPSOMMING: Die hipotalamo-pituïtêre-adrenale (HPA)-as is lank bekend as ‘n primêre rolspeler in die respons op emosionele stres en daaropvolgende glukokortikoïed produksie. ‘n Ander, minder bekende arm van die sielkundige stres respons is die simpatiese bynier-medulla-sisteem. Ons hipotese was dat die laasgenoemde simpatiese bynier-medulla-sisteem die primêre respons tot sielkundige stres behartig terwyl die HPA-as ‘n sekondêre respons bied. Ons het ons hipotese getoets deur die manupilering van ‘n beproefde stres model waar ons IL-6, ‘n waardevolle rolspeler in die simpatiese bynier-medulla-sisteem, onderdruk het. In respons op stress, het serum kortikosteroon konsentrasies toegeneem slegs in die teenwoordigheid van IL-6 (7 ± 3 vs. 57 ± 4 ng/ml; P<0.0001), maar nie wanneer IL-6 onderdruk is nie (17 ± 7 ng/ml). Stres het ‘n verhoging in hipofise massa teweeggebring slegs tydens die onderdrukking van IL-6 (38 ± 3 vs. 65 ± 6 mg; P <0.001). Stres het ook linker-byniermassa verhoog slegs wanneer voldoende IL-6 beskikbaar was (34 ± 1 vs. 73 ± 8 mg; P <0.00001). Stres alleen het geen invloed gehad op serum IL-1β, IL-6 of TNF-α nie, maar die onderdrukking van IL-6 het wel ‘n inhiberende effek op basale IL-1β en TNF-α gehad. Daarna het ons weer eens die stresmodel manipuleer deur die rotte ‘n S. frutescens ekstrak te gee in ‘n poging om beide die sentrale en perifere effekte daarvan op die sielkundige stres respons te evalueer. Stres alleen het gelei tot ‘n afname in GR terwyl ‘n kombinasie van stres en S. frutescens administrasie tot ‘n afname in GABAARα1 in die hippokampus gelei het. Hierdie kombinasie het ook tot ‘n merkwaardige toename in hipofise massa (P = 0.078) sowel as ACTH-inhoud van die hipofise (P < 0.01) gelei. ‘n Soortgelyke patroon is waargeneem betreffende sirkulerende ACTH en byniermassa met P < 0.05 vir elk. Bynier ACTH inhoud, aan die ander kant, het ‘n omgekeerd eweredige verhouding met ACTH in die hipofise en in sirkulasie getoon. Bynier IL- 6 inhoud het geen statisties beduidende verskille getoon nie, maar ‘n merkwaardige verhoging is weereens gesien met ‘n kombinasie van stres en S. frutescens administrasie. Die soortgelyke tendens wat waargeneem word in GABAAR in die hippokampus, asook hipofise- en sirkulerende ACTH vlakke, en dui op ‘n samewerkende rol van stres en S. frutescens in die aktivering van die sielkundige stres respons. GR in die hippokampus toon geen veranderinge nie. Die resultate van die twee eksperimente dui op ‘n primêre rol van die simpatiese bynier-medulla-sisteem in die respons op ‘n akute stressor en dat die HPA-as net geaktiveer word tydens ‘n ooreiste stres reaksie of indien die simpatiese bynier-medulla-sisteem onderdruk word. Die waargenome “verdowings”-effek van S. frutescens word moontlik deur aktivering van die mesolimbiese dopamien pad deur die hippokampus en amigdala bewerkstellig. Die resultate mag ook lei tot die heroorweging van GABA-gebaseerde angs medikasies.
583

Einfluss zweier Bandscheibenprothesen auf die Kinematik des C3/C4-Segmentes / Influence of two different types of total disc arthroplasty on the kinematic properties of C3/C4-segments

Wagner, Markus 17 September 2014 (has links)
No description available.
584

Simulations of vertical axis wind turbines with PMSG and diode rectification to a mutual DC-bus

Christoffer, Fjellstedt January 2017 (has links)
Transient simulations were performed with MATLAB Simulink on a mutual wind park topology, where three vertical axis wind turbines equipped with permanent magnet synchronous generators were connected to a mutual DC-bus through passive diode rectification. The aim with the work was to show the effects of two different kinds of loads on the system in respect to generator torque, rotor speed, produced power by the generators and the power on the DC-bus. The loads were a variable voltage source and a resistance with the value 2.0 Ω. It was shown that the transient behavior of the system in respect to both kinds of loads exhibited a high level of stability when the wind speed was altered. It was also shown that the system when equipped with a voltage source load began to oscillate with the natural frequency of a two mass rotating spring system if a sudden increase of the voltage made the DC-bus voltage larger than the peak of the internal induced voltage of the generators. Small variations of the DC voltage however exhibited a stable behavior.
585

Détection des nutriments et contrôle central de la prise alimentaire / Nutrient sensing and central control of food intake

Delaere, Fabien 02 December 2009 (has links)
En relation avec sa position anatomique, la détection portale de nutriments se situe au coeur de l’impact de la composition nutritionnelle d’un repas sur la prise alimentaire et le métabolisme énergétique. Ainsi, la détection portale de glucose, produit par exemple en réponse aux protéines alimentaires, induit un signal nerveux à l’origine d’une induction de la satiété et d’une amélioration de l’homéostasie glucidique. Grâce à des travaux physiologiques et anatomiques chez le rat, nous proposons un modèle pour cette détection dans lequel deux modes interviennent, soit un transport et un catabolisme intracellulaire, soit une détection purement extracellulaire du glucose. La glycémie portale est détectée par l’un ou l’autre de ces mécanismes en fonction de sa différence avec la glycémie artérielle, reflet du statut nutritionnel et métabolique des individus. Un signal nerveux est ensuite initié dans les neurones périportaux, dont les axones aboutissent à proximité de la lumière veineuse. Les études immunohistochimiques réalisées ont permis de montrer que ce signal induit une activation cérébrale étendue en relation avec les effets multiples du glucose portal, dans le tronc cérébral, les systèmes sensoriels et cortico-limbiques, et l’hypothalamus. Dans ce dernier, la nature cellulaire de l’activation conforte notamment l’hypothèse de l’implication du signal glucose portal dans l’effet de satiété induit par les régimes riches en protéines. / Nutrient sensing in the portal vein occurs in a strategic location to relay the effects of the diet on food intake and energy metabolism. The portal sensing of glucose produced for instance in response to dietary proteins initiates a nervous signal that ultimately induces satiety and a better control of glucose metabolism. Our physiological and anatomical approaches enable us to propose a sensing model in which two different mechanisms can occur, involving either the intracellular transport and catabolism of glucose or a direct extracellular detection. Portal glycaemia is detected by one pathway or the other depending on its difference with arterial blood glucose, which reflects the nutritional and metabolic state of the subject. A nervous signal is then initiated in periportal neurons, whose axons terminate close to the venous lumen. Our immunohistochemical studies have shown that this signal induces a widespread activation in the brain that relates to the multiple effects of portal glucose appearance, in the brainstem, the sensory and cortico-limbic systems and the hypothalamus. In this latter area, the cellular nature of the activation supports the hypothesized central role of portal glucose appearance in the satiety effect of high-protein diets.
586

Keck Planet Imager and Characterizer: concept and phased implementation

Mawet, D., Wizinowich, P., Dekany, R., Chun, M., Hall, D., Cetre, S., Guyon, O., Wallace, J. K., Bowler, B., Liu, M., Ruane, G., Serabyn, E., Bartos, R., Wang, J., Vasisht, G., Fitzgerald, M., Skemer, A., Ireland, M., Fucik, J., Fortney, J., Crossfield, I., Hu, R., Benneke, B. 26 July 2016 (has links)
The Keck Planet Imager and Characterizer (KPIC) is a cost-effective upgrade path to the W.M. Keck observatory (WMKO) adaptive optics (AO) system, building on the lessons learned from first and second-generation extreme AO (ExA0) coronagraphs. KPIC will explore new scientific niches in exoplanet science, while maturing critical technologies and systems for future ground-based (TMT, FELT, GMT) and space-based planet imagers (HabEx, LUVOIR). The advent of fast low-noise IR cameras (IR-APD, MKIDS, electron injectors), the rapid maturing of efficient wavefront sensing (WFS) techniques (Pyramid, Zernike), small inner working angle (IWA) coronagraphs (e.g., vortex) and associated low-order wavefront sensors (LOWFS), as well as recent breakthroughs in high contrast high resolution spectroscopy, open new direct exoplanet exploration avenues that are complementary to planet imagers such as VLT-SPHERE and the Gemini Planet Imager (GPI). For instance, the search and detailed characterization of planetary systems on solar-system scales around late-type stars, mostly beyond SPHERE and GPI's reaches, can be initiated now at WMKO.
587

Experimental studies of a small scale horizontal axis tidal turbine

Franchini, Italo 17 November 2016 (has links)
The research in this thesis focuses on the investigation of tidal turbines using a small scale horizontal axis tidal turbine and a 2D hydrofoil testing rig, combining experiments with simulations to provide comprehensive results and to better understand some of the variables that affect their performance. The experimental campaigns were carried out at the University of Victoria fluids research lab and the Sustainable Systems Design Lab (SSDL). The experimental testing rigs were re-designed by the author and are now fully automated, including a friendly graphical user interface for easy implementation. Particle image velocimetry (PIV) technique was used as the quantitative flow visualization method to obtain the time-averaged flow fields. This thesis presents three investigations. The first study aims to quantify the impacts of channel blockage, free surface effects and foundations on hydrokinetic turbine performance, using porous discs and an axial flow rotor. The results were used to cross-validate computational fluid dynamics (CFD) simulations. It was found that as wall blockage increases, thrust and power are incremented with and without the inclusion of free surface deformation. Discrepancies between simulations and experimental results on free surface effects compared to a slip wall were obtained and hence further research is recommended and the author gives some advice on how to proceed in this investigation. The second study determines the performance of four hydrofoil candidates over a range of low Reynolds number (Re), delivering useful information that can be applied to low Re energy conversion systems and, specifically in this case, to improve the performance of the small scale tidal turbine at the SSDL lab. The study combines the 2D hydrofoil test rig along with PIV measurements in order to experimentally obtain lift and drag coefficients. The experiments were carried out in the recirculating flume tank over the range of low Re expected for the small scale rotor rig, in order to provide more accurate results to improve rotor blade design. In addition, numerical simulations using XFOIL, a viscid-inviscid coupled method, were introduced to the study. These results were analysed against experiments to find the most suitable parameters for reliable performance prediction. The final results suggested that adding a numerical trip at a certain chordwise distance produced more reliable results. Finally, an experimental study on turbine rotor performance and tip vortex behavior was performed using again the rotor rig and PIV. Blade design and rotor performance were assessed, showing good agreement with Blade Element Momentum (BEM) simulations, particularly at predicting the tip speed ratio corresponding to the maximum power coefficient point. Regarding the wake structure, tip vortex locations (shed from the blade tips) were captured using PIV in the near wake region, showing evidence of wake expansion. The velocity and vorticity fields are also provided to contribute to the development and validation of CFD and potential flow codes. / Graduate / 0548 / 0547 / 0538 / iafranch@uvic.ca
588

Does prenatal maternal depression predict foetal and infant development? : a study of mothers and infants in rural South India

Fernandes, Michelle Caroline January 2011 (has links)
Introduction: Prenatal maternal depression is associated with an increased risk of psychopathology in childhood. The understanding of the mechanisms underlying this association is limited. Further, despite high rates of prenatal depression in the developing world, no research investigating this issue exists from these settings. Objectives: The primary objectives of this thesis are to study the association between prenatal maternal depression and the following early offspring outcomes in a non-smoking, non-alcohol consuming prenatal sample from rural, South India: Foetal stress responsivity, measured through foetal heart rate (FHR). Infant stress responsivity, measured through infant cortisol response to immunisation. Infant temperament. Methods: 194 pregnant women from Solur, India were assessed for depression. The first 67 mothers with elevated symptoms of prenatal depression and the first 66 controls underwent FHR monitoring to study foetal stress responsivity. 58 mother-infant dyads returned at 1.5-3 months post birth. Infant salivary cortisol was measured before and after immunisation. Information on infant temperament and maternal postnatal depression (PND) was also collected. Results: Twenty nine mothers (14.9%) met a diagnosis of major depression during pregnancy while 67 (34.5%) had elevated symptoms of prenatal depression. Whilst there were no linear association between prenatal depression and foetal responsivity, a curvilinear (U shaped) association existed with the foetuses of mothers with very high and very low levels of prenatal depression having elevated stress responses compared to those with moderate levels of prenatal depression. Prenatal depression predicted infant cortisol responsivity independent of PND (B=13.08, p=0.02).The relationship between infant cortisol responsivity and prenatal depression was also U shaped. There was no association between prenatal depression and infant temperament. Conclusions: This is the first study from the developing world investigating the relationship between prenatal depression and offspring outcomes. It provides evidence suggestive of the programming influence of prenatal depression on the developing offspring.
589

ETHANOL REGULATION OF GLUCOCORTICOID RESPONSIVE GENES

Costin, Blair 18 April 2013 (has links)
Glucocorticoid hormones modulate acute and chronic behavioral and molecular responses to drugs of abuse including psychostimulants and opioids. Acute ethanol activates the hypothalamic pituitary adrenal (HPA) axis causing the release of adrenal glucocorticoid hormones, but following chronic ethanol the HPA axis is dysregulated in both humans and rodents. Thus, there is growing evidence that glucocorticoids might also modulate behavioral and molecular responses to ethanol. Previous microarray studies in the Miles’ laboratory have shown that the well-known glucocorticoid responsive gene, Serum and Glucocorticoid-regulated Kinase 1, Sgk1, is prominently up regulated by acute ethanol (2 g/kg) in the prefrontal cortex (PFC) of DBA/2J mice. Functionally, Sgk1 is an important focal point of intracellular signaling cross-talk through which the cell surface receptors, nuclear receptors, and cellular stress pathways converge to control many cellular processes including receptor or ion channel trafficking, cell proliferation and/or apoptotic responses. In the aforementioned microarray studies, Sgk1 was accompanied by a highly correlated group of genes, many of which are also known to respond to glucocorticoids. This suggests that stress-related signaling events might play an important role in ethanol regulation of the Sgk1 gene network. Prior work by others showed that Sgk1 plays an important role modulating synaptic plasticity occurring in memory. Based on these findings, it is hypothesized that glucocorticoids and glucocorticoid responsive genes are responsible for modulating acute and chronic cellular and behavioral responses to ethanol including locomotor activation and ethanol sensitization. In particular, because Sgk1 is regulated by ethanol, has a well-established role in learning and memory and is responsive to glucocorticoid signaling we hypothesize that Sgk1 is involved in modulating acute and chronic cellular and behavioral responses to ethanol including ethanol sensitization. Our results indicate that the induction of glucocorticoid responsive genes may play a role in regulating acute behavioral and cellular responses to ethanol. Adrenalectomized (ADX) and mifepristone (RU-486) both impaired acute ethanol (2 g/kg) induced locomotor activation in DBA/2J mice without affecting basal locomotor activity. ADX mice showed microarray gene expression changes in the PFC that significantly overlapped with acute ethanol-responsive gene sets derived by our prior microarray studies. Additionally, acute ethanol regulates Sgk1 transcription via glucocorticoid receptor binding to the Sgk1 promoter. Furthermore, increases in Sgk1 may occur to compensate for decreases in SGK1 protein and phosphorylation of SGK1 and its well-known target N-myc downstream-regulated gene 1 (NDRG1) is significantly increased 15 minutes following ethanol administration. Finally, Sgk1 intensifies and prolongs the expression phase of sensitization in D2 mice. Our studies suggest that ethanol’s activation of adrenal glucocorticoid release and subsequent glucocorticoid receptor activation may partially modulate ethanol’s acute locomotor activation in male D2 mice. Furthermore, adrenal glucocorticoid basal tone regulates PFC gene expression. A significant set of acute ethanol-responsive genes are regulated by adrenal glucocorticoid basal tone suggesting that glucocorticoid regulated PFC gene expression may be an important factor modulating acute behavioral responses to ethanol. Sgk1 is acutely regulated following ethanol administration by the glucocorticoid receptor binding to the Sgk1 promoter. Altogether, these results suggest a critical role for the hypothalamic pituitary adrenal axis and Sgk1 in regulating the acute and chronic cellular and behavioral responses to ethanol.
590

Modélisation et simulation du procédé de prépolissage automatique sur centre d'usinage 5 axes / Modeling and simulation of automatic pre-polishing process on 5-axis machining center

Guiot, Anthony 06 December 2012 (has links)
La réalisation de formes complexes comme les moules ou les prothèses médicales nécessite l’utilisation d’opérations de super finition pour obtenir de faibles défauts géométriques, pouvant aller jusqu’au poli-miroir. Ces opérations de pré-polissage et de polissage sont encore régulièrement réalisées manuellement. En effet, malgré des avantages en termes de répétabilité, de productivité et de qualité géométrique, les méthodes de polissage automatique sont peu utilisées car elles nécessitent une mise au point importante. Les travaux de recherche présentés participent à la maîtrise du procédé de polissage automatique tout en contrôlant la qualité géométrique des pièces. Pour parvenir à cette maîtrise, un outil de simulation de l’enlèvement de matière est mis en place. Cet outil permet de simuler l’enlèvement de matière au cours d’une opération de prépolissage réalisée sur centre d’usinage 5 axes. Il se base sur un modèle du contact obtenu entre l’outil de pré-polissage et la pièce, ainsi que sur un modèle du pouvoir abrasif intégrant l’usure et l’encrassement du disque. Cette simulation permet de vérifier la régularité de l’abrasion sur une surface et d’identifier les zones pouvant faire apparaitre des défauts macro-géométriques importants. Une méthode est également proposée pour compenser les variations du pouvoir abrasif au cours du temps. La compensation s’effectue en optimisant les consignes de vitesse d’avance et/ou de fréquence de broche le long de la trajectoire. Cette méthode de pilotage permet d’obtenir un taux d’enlèvement de matière plus constant et ainsi de réduire les défauts géométriques générés pendant une opération de prépolissage. / Complex shapes such as medical implants or injection molds require the use of super-finishing operations to minimize geometrical defects, down to mirror effect finish. These pre-polishing and polishing operations are still regularly performed manually by skilled workers. In spite of advantages in terms of repeatability, productivity and geometrical quality, automatic polishing methods are not widely used because they require systematic and significant developments. The present work contributes to enhance the automatic polishing process compared to the geometric quality of the parts. To achieve this control, a numerical simulation of material removal is implemented. This software simulates the material removal during a pre-polishing operation performed on 5-axis machining center. It is based on a contact model obtained between the pre-polishing tool and the part, as well as an abrasive model including wear of the disc. This simulation allows to check the uniformity of the material removal on the surface and to identify potential areas where macro-geometric defects appear. A method is also proposed to balance variations of the abrasive efficiency. The correction is performed by optimizing the federate and/or the spindle speed along the tool path. This method provides a constant material removal and reduces the geometrical deviations generated during pre-polishing operations.

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