• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 510
  • 117
  • 68
  • 54
  • 36
  • 31
  • 21
  • 10
  • 10
  • 8
  • 7
  • 5
  • 4
  • 4
  • 4
  • Tagged with
  • 1047
  • 83
  • 79
  • 73
  • 68
  • 63
  • 58
  • 57
  • 51
  • 49
  • 49
  • 48
  • 48
  • 46
  • 45
  • 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.
521

Die ontwerp van 'n kultuursensitiewe beroepskeuse-instrument vir graad 12-leerders / Marjorie Grimbeek

Grimbeek, Marjorie January 2001 (has links)
The purpose of this study was to develop an economic career choice instrument for grade 121earners, which conforms with the requirements of cultural fairness, validity and reliability. The various facets of adolescent development were analysed from the literature. Self-knowledge (identity) and career knowledge were analysed from various theoretical perspectives. The various facets of adolescent development had a direct influence on the career choice of learners. These facets served as a basis for the development of the different sections for the career choice instrument. In the empirical study a survey was conducted involving 321 grade 12 learners randomly selected from secondary schools in the Potchefstroom region. These learners completed the newly developed instrument. The reliability of the career choice instrument was determined by using the Cronbach Alpha Coefficient. Factor analysis were used to determine the validity of each section of the instrument. In order to determine whether the career choice instrument was culturally fair, a series of one-way ANOVAS, followed by Tukey tests were performed, whereafter effect sizes were determined. In the study good reliability indices were obtained for all sections of the measuring instrument. The reliability indices obtained from the Cronbach Alpha Coefficients, coincided relatively well with the reliability indices obtained for the MB-10 (Meyer Interest Questionnaire), the Jung Personality questionnaire and the LISRES-Y. Concerning the cultural aspect, the different race groups, white, black and coloured learners, differed significantly in respect of social development and values. Recommendations for further research for the use of the instrument in teaching practice are formulated from the research results, in particular with reference to the designing of a career choice instrument. / Thesis (Ph.D. (Education))--Potchefstroom University for Christian Higher Education, 2001
522

Regional neurochemical characterization of the flinders sensitive line rat with regard to glutamate-nitric oxide and cGMP signalling pathways / Estella Lily Minnaar.

Minnaar, Estella Lily January 2008 (has links)
The serious nature of MDD has intensified the need to identify and elucidate new neurobiological targets for antidepressant drug action. Depression presents with evidence for degenerative pathology that relates to disturbances in excitatory glutamatergic pathways, particularly the N-methyl-D-aspartate (NMDA) receptormediated release of the pleiotropic molecule, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The contribution of the glutamate-NO/cGMP pathway may realize great importance as a fundamental substrate underlying the pathophysiology of major depression. In the next generation of antidepressant drugs, the nitric oxide pathway could playa dynamic role in addressing urgent therapeutic needs. In this study, we have used a genetic model of depression, the Flinders Sensitive Line (FSL) rat, to investigate the surrogate markers of the NO/cGMP pathway. The aim was to determine whether the depressive-like behaviour of the hypercholinergic FSL rat is accompanied by altered activation of the NO/cGMP pathway. To this end, the extent to which the FSL and Flinders Resistant Line (FRL) rats differ neurochemically with regard to basal hippocampal and frontal cortical NOS-activity, as well as nitric oxide (NO) and cGMP accumulation, were determined. Additionally, select behavioural assessments were performed to confirm the anxiogenic phenotype of the FSL strain. For neurochemical determinations a sensitive fluorometric reversed phase highperformance liquid chromatographic (HPLC) assay was developed to analyze total nitrite and nitrate in brain tissue. Nitrate was enzymatically converted to nitrite before derivatization with 2,3-diaminonaphthalene (DAN). The stable and highly fluorescent product, 2,3-naphthotriazole (NAT), was quantified. Secondly, the quantity of the amino acid L-citrulline was measured by HPLC with electrochemical detection after o-phthalaldehyde (OPA) derivatization. L-citrulline formation was used as an index for nNOS activity. Finally, a direct, competitive enzyme immunoassay kit was used to determine the downstream activity of the NO-pathway in brain tissue. FSL rats were compared to FRL rats with respect to sensitivity to serotonin 5-HT1A . receptor-mediated hypothermia under our lab-conditions. The Open Field Test (OFT) behavioural assessment was performed to compare FSL with FRL groups under baseline conditions according to their level of inherent anxiety. The parameters used to measure anxiety were number of line crosses (locomotor activity), time spent in middle blocks and social interaction time between pairs of rats. As an additional behavioural assessment, the Forced Swim Test (FST) was performed to assess behavioural restraint measured as time of immobility. Basal cGMP levels in the frontal cortex were found to be significantly less in FSL than in FRL rats, whereas the levels in the hippocampus did not differ significantly. No other significant differences with respect to NO and nNOS activity were apparent in either of the brain areas. The hypothermia test confirmed a significantly greater decrease in temperature in the FSL rat than the FRL rat. The FST did not confirm any differences in immobility time between the two rat strains. In the OFT, FSL rat groups exhibited behaviour that indicated significantly more anxiety than FRL rats. Under basal conditions, FSL rats do not present with significant changes in markers of the NO cascade in the hippocampus and frontal cortex compared to FRL controls, including NOS activity as well as NO accumUlation. However, cGMP levels were found to be significantly lower in the frontal cortex of FSL rats versus FRL rats, although not in the hippocampus. Since the FSL rat is known to be hypercholinergic, these data support an interaction between the NO/cGMP pathway and the cholinergIc system in the frontal cortex but not hippocampus of FSL animals. The mechanisms and implications of such a mutual involvement need further clarification. Further, this anatomical differentiation may have important implications for understanding the role of NO in the depressive-like behaviour of the FSL rat and, indeed, may reveal more on the neurobiology and treatment of depression. Through the performed behavioural assessments, the FSL and FRL rats were successfully separated with respect to their anxiety phenotype as well as their heightened response to serotonergic challenge, thus confirming a contribution of both the serotonergic and cholinergic systems to the depressogenic nature of these animals. As concluding remark can be said that under normal basal conditions markers of the NO/cGMP signalling cascade are not altered in FSL vs FRL rats, although cGMP levels are reduced in the frontal cortex of FSL rats, supportive of an NO-independent mechanism of cGMP regulation, possibly involving ACh. / Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.
523

Regional neurochemical characterization of the flinders sensitive line rat with regard to glutamate-nitric oxide and cGMP signalling pathways / Estella Lily Minnaar.

Minnaar, Estella Lily January 2008 (has links)
The serious nature of MDD has intensified the need to identify and elucidate new neurobiological targets for antidepressant drug action. Depression presents with evidence for degenerative pathology that relates to disturbances in excitatory glutamatergic pathways, particularly the N-methyl-D-aspartate (NMDA) receptormediated release of the pleiotropic molecule, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The contribution of the glutamate-NO/cGMP pathway may realize great importance as a fundamental substrate underlying the pathophysiology of major depression. In the next generation of antidepressant drugs, the nitric oxide pathway could playa dynamic role in addressing urgent therapeutic needs. In this study, we have used a genetic model of depression, the Flinders Sensitive Line (FSL) rat, to investigate the surrogate markers of the NO/cGMP pathway. The aim was to determine whether the depressive-like behaviour of the hypercholinergic FSL rat is accompanied by altered activation of the NO/cGMP pathway. To this end, the extent to which the FSL and Flinders Resistant Line (FRL) rats differ neurochemically with regard to basal hippocampal and frontal cortical NOS-activity, as well as nitric oxide (NO) and cGMP accumulation, were determined. Additionally, select behavioural assessments were performed to confirm the anxiogenic phenotype of the FSL strain. For neurochemical determinations a sensitive fluorometric reversed phase highperformance liquid chromatographic (HPLC) assay was developed to analyze total nitrite and nitrate in brain tissue. Nitrate was enzymatically converted to nitrite before derivatization with 2,3-diaminonaphthalene (DAN). The stable and highly fluorescent product, 2,3-naphthotriazole (NAT), was quantified. Secondly, the quantity of the amino acid L-citrulline was measured by HPLC with electrochemical detection after o-phthalaldehyde (OPA) derivatization. L-citrulline formation was used as an index for nNOS activity. Finally, a direct, competitive enzyme immunoassay kit was used to determine the downstream activity of the NO-pathway in brain tissue. FSL rats were compared to FRL rats with respect to sensitivity to serotonin 5-HT1A . receptor-mediated hypothermia under our lab-conditions. The Open Field Test (OFT) behavioural assessment was performed to compare FSL with FRL groups under baseline conditions according to their level of inherent anxiety. The parameters used to measure anxiety were number of line crosses (locomotor activity), time spent in middle blocks and social interaction time between pairs of rats. As an additional behavioural assessment, the Forced Swim Test (FST) was performed to assess behavioural restraint measured as time of immobility. Basal cGMP levels in the frontal cortex were found to be significantly less in FSL than in FRL rats, whereas the levels in the hippocampus did not differ significantly. No other significant differences with respect to NO and nNOS activity were apparent in either of the brain areas. The hypothermia test confirmed a significantly greater decrease in temperature in the FSL rat than the FRL rat. The FST did not confirm any differences in immobility time between the two rat strains. In the OFT, FSL rat groups exhibited behaviour that indicated significantly more anxiety than FRL rats. Under basal conditions, FSL rats do not present with significant changes in markers of the NO cascade in the hippocampus and frontal cortex compared to FRL controls, including NOS activity as well as NO accumUlation. However, cGMP levels were found to be significantly lower in the frontal cortex of FSL rats versus FRL rats, although not in the hippocampus. Since the FSL rat is known to be hypercholinergic, these data support an interaction between the NO/cGMP pathway and the cholinergIc system in the frontal cortex but not hippocampus of FSL animals. The mechanisms and implications of such a mutual involvement need further clarification. Further, this anatomical differentiation may have important implications for understanding the role of NO in the depressive-like behaviour of the FSL rat and, indeed, may reveal more on the neurobiology and treatment of depression. Through the performed behavioural assessments, the FSL and FRL rats were successfully separated with respect to their anxiety phenotype as well as their heightened response to serotonergic challenge, thus confirming a contribution of both the serotonergic and cholinergic systems to the depressogenic nature of these animals. As concluding remark can be said that under normal basal conditions markers of the NO/cGMP signalling cascade are not altered in FSL vs FRL rats, although cGMP levels are reduced in the frontal cortex of FSL rats, supportive of an NO-independent mechanism of cGMP regulation, possibly involving ACh. / Thesis (M.Sc. (Pharmacology)--North-West University, Potchefstroom Campus, 2009.
524

Modeling and analysis of quantum cryptographic protocols

Ware, Christopher J 29 August 2008 (has links)
In this thesis we develop a methodology for the modeling and analysis of quantum security protocols, and apply it to a cheat sensitive quantum bit commitment protocol. Our method consists of a formalization of the protocol in the process algebra CQP, a conversion to the PRISM modeling language, verification of security properties, and the quantitative analysis of optimal cheat strategies for a dishonest party. We also define additional syntax and operational semantics for CQP to add decision making capability. For a two party protocol involving Alice committing a bit to Bob, we show that the protocol favors a dishonest Alice over a dishonest Bob. When only one party is dishonest, and uses an optimal cheat strategy, we also show that the probability of cheat detection is bounded at 0.037 for Bob and 0.076 for Alice. In addition, a dishonest Alice is able to reveal an arbitrary commit bit with probability 1 while a dishonest Bob is only able to extract the correct bit before it is revealed with probability 0.854. This bias is interesting as it gives us insight into how the overall protocol functions and where its weaknesses are. By identifying these weaknesses we provide a foundation for future improvements to the protocol to reduce cheating bias or increase cheat detection. Finally, our methodology reveals the weakness of PRISM in modeling quantum variables to their full power and as a result we propose the development of a new modeling tool for quantum protocols.
525

Achieving Quality of Service Guarantees for Delay Sensitive Applications in Wireless Networks

Abedini, Navid 2012 August 1900 (has links)
In the past few years, we have witnessed the continuous growth in popularity of delay-sensitive applications. Applications like live video streaming, multimedia conferencing, VoIP and online gaming account for a major part of Internet traffic these days. It is also predicted that this trend will continue in the coming years. This emphasizes the significance of developing efficient scheduling algorithms in communication networks with guaranteed low delay performance. In our work, we try to address the delay issue in some major instances of wireless communication networks. First, we study a wireless content distribution network (CDN), in which the requests for the content may have service deadlines. Our wireless CDN consists of a media vault that hosts all the content in the system and a number of local servers (base stations), each having a cache for temporarily storing a subset of the content. There are two major questions associated with this framework: (i) content caching: which content should be loaded in each cache? and (ii) wireless network scheduling: how to appropriately schedule the transmissions from wireless servers? Using ideas from queuing theory, we develop provably optimal algorithms to jointly solve the caching and scheduling problems. Next, we focus on wireless relay networks. It is well accepted that network coding can enhance the performance of these networks by exploiting the broadcast nature of the wireless medium. This improvement is usually evaluated in terms of the number of required transmissions for delivering flow packets to their destinations. In this work, we study the effect of delay on the performance of network coding by characterizing a trade-off between latency and the performance gain achieved by employing network coding. More specifically, we associate a holding cost for delaying packets before delivery and a transmission cost for each broadcast transmission made by the relay node. Using a Markov decision process (MDP) argument, we prove a simple threshold-based policy is optimal in the sense of minimum long-run average cost. Finally, we analyze delay-sensitive applications in wireless peer-to-peer (P2P) networks. We consider a hybrid network which consists of (i) an expensive base station-to-peer (B2P) network with unicast transmissions, and (ii) a free broadcast P2P network. In such a framework, we study two popular applications: (a) a content distribution application with service deadlines, and (b) a multimedia live streaming application. In both problems, we utilize random linear network coding over finite fields to simplify the coordination of the transmissions. For these applications, we provide efficient algorithms to schedule the transmissions such that some quality of service (QoS) requirements are satisfied with the minimum cost of B2P usage. The algorithms are proven to be throughput optimal for sufficiently large field sizes and perform reasonably well for finite fields.
526

KATP Channel Action in Vascular Tone Regulation During Septic Shock: Beyond Physiology

Shi, Weiwei 23 March 2009 (has links)
Septic shock is a major cause of deaths resulting from uncontrolled inflammation and circulatory failure. Recent studies suggest that the vascular isoform of ATP-sensitive K+ (KATP) channels is an important contributor to septic susceptibility. To understand the molecular mechanisms for channel regulation during sepsis, we performed studies in isolated endothelium-denuded mesenteric rings. Lipopolysaccharides (LPS) induced vascular relaxation and hyporeactivity to phenylephrine. The LPS-treated aortic smooth muscle cells displayed hyperpolarization and augmentation of KATP channel activity. Both were due to an up-regulation of Kir6.1 and SUR2B surface expression. The up-regulation relied on transcriptional and translational mechanisms, in which nuclear factor-¦ÊB (NF-¦ÊB) and Protein kinase A (PKA) played a critical role. Oxidative stress occurs during sepsis and may act as another regulatory mechanism affecting KATP channel activity and vascular contractility. We found that micromolar concentrations of H2O2 impaired the pinacidil-induced vasodilation. The effect attributed to the suppression of KATP channel activity, which can be fully produced by reactivity oxidants. Unlike the Kir6.1/SUR2B channel, the Kir6.2/SUR2B channel was insensitive to 1mM H2O2, indicating that the modulation sites are located in Kir6.1. Site-directed mutational analysis showed that three cysteine residues located in N-terminus and the core region of Kir6.1 were likely to mediate the redox-dependent channel modulation. Arginine vasopressin (AVP) is a vasoconstrictor that is successfully applied to manage sepsis. However, the downstream target of AVP is uncertain. Our studies show that AVP-induced vasoconstriction depended on V1a receptor, Protein kinase C (PKC) and KATP channel. Additionally, AVP decreased Kir6.1/SUR2B channel activity through V1a receptor. The inhibitory effect was caused by a suppression of the channel open state probability. The channel inhibition was mediated by phosphorylation of the channel protein by PKC. The widespread involvement of the vascular KATP channel in vascular responses to endotoxemia strongly suggests that the temporospatial control of channel activity may constitute an important intervention to vascular tone, blood pressure and organ-tissue perfusion in septic shock. Such a control appears feasible by targeting several modulatory mechanisms of intracellular signaling, Kir6.1/SUR2B expression, redox state and channel protein phosphorylation as demonstrated in this dissertation.
527

Segregation within afferent pathways in primate vision

Roy, Sujata January 2009 (has links)
The current knowledge of the visual pathways in primates includes the patterns of projection from the retina through the dorsal lateral geniculate nucleus (dLGN) to the striate cortex (V1) and the extra-striate projections towards the dorsal and ventral streams. Cells with short wavelength sensitive cone (S-cone) inputs in the dLGN have been studied extensively in New World marmosets but not in Old World macaques. This thesis presents results from studies in the macaque monkey which are more relevant to humans since humans are closer in evolution to Old World than New World monkeys. / The spatial, temporal, chromatic and orientation preferences of neurons in the dLGN of the macaque were investigated by electrophysiological methods. The physiological findings of cells with S-cone inputs were compared to cells with opponent inputs from the long and medium wavelength sensitive cones (L-cones & M-cones, respectively). The cells receiving S-cone inputs (blue-yellow or B-Y cells) preferred lower spatial frequencies than the cells with opponent L-cone and M-cone inputs (red-green or R-G cells). Orthodromic latencies from optic chiasm stimulation were measured where possible to distinguish differences in conduction velocity between the cell groups. Although the B-Y cells usually had longer latencies than R-G cells, there wasconsiderable overlap between the cell groups. / The recorded cells were localised through histological reconstruction of dLGN sections stained for Nissl substance. The distribution of B-Y cells within the dLGN was compared to the distribution of R-G cells. The majority of B-Y cells were located within the intercalated koniocellular layers as well as the koniocellular bridges (extensions of the koniocellular layers into the adjacent parvocellular layers). The B-Y cells were also largely segregated within the middle dLGN layers (K3, P3, K4 & P4). The R-G cells were mainly concentrated within the parvocellular layers (P3, P4, P5 & P6) and were evenly distributed throughout the middle and outer layers of the dLGN. / The study also included recordings from the extra-striate middle temporal area (MT) to determine whether a fast S-cone input exists from the dLGN to area MT which bypasses V1. The pattern of cone inputs to area MT neurons was investigated before and during inactivation of V1. The inactivation was done through reversible cooling with a Peltier thermocouple device or focal inactivation with y-amino butyric acid (GABA) iontophoresis. Precise inactivation of V1 to the topographically matching visual fields of the recording sites in area MT revealed a preservation of all three coneinputs in many cells. The subcortical sources of these preserved inputs are discussed with their relevance to blindsight, which is the limited retention of visual perception after V1 damage. Analysis of the latencies of area MT cells revealed a rough segregation into latencies faster or slower than 70 ms. Cells both with and without a significant change in response during V1 inactivation were present in each group. The findings reported in this thesis indicate that some of the preserved inputs in area MT during V1 inactivation may be carried by a direct input from the dLGN which bypasses V1.
528

Σχεδίαση και ανάπτυξη κινητής εφαρμογής σε χώρο πολιτισμού / Designing and developing a mobile application for cultural spaces

Καρπαθιωτάκη, Μαρία 13 October 2013 (has links)
Η εξέλιξη της τεχνολογίας στον τομέα του κινητού και διάχυτου υπολογισμού έχει δημιουργήσει πολλές δυνατότητες για πρόσβαση μέσω φορητών συσκευών σε πληροφορίες που σχετίζονται με συγκεκριμένο χώρο και αντικείμενα. Οι τεχνολογίες αυτές είναι ιδιαίτερα ελκυστικές για χώρους πολιτισμού όπου μπορούν να αποτελέσουν το υπόβαθρο για μαθησιακές εμπειρίες με παιγνιώδη χαρακτηριστικά. Η διπλωματική αυτή εργασία, που εκπονήθηκε στο Εργαστήριο της Ερευνητικής Ομάδας Αλληλεπίδρασης Ανθρώπου Υπολογιστή, του Τμήματος Ηλεκτρολόγων Μηχανικών και Τεχνολογίας Υπολογιστών του Πανεπιστημίου Πατρών, υπό την επίβλεψη του καθηγητή Νικόλαου Αβούρη, περιγράφει τη μελέτη, ανάπτυξη και αξιολόγηση μίας κινητής εφαρμογής σε χώρο πολιτισμού. Συγκεκριμένα, αφορά το Benaki MuseumScrabble (BMS), ένα χώρο-ευαίσθητο παιχνίδι για φορητές συσκευές, το οποίο απευθύνεται σε επισκέπτες του Μουσείου Μπενάκη. Στόχος του παιχνιδιού είναι να εμπλέξει τους παίχτες σε μια διαδικασία παιγνιώδους εξερεύνησης της έκθεσης του μουσείου και να αναδείξει τα εκθέματα αλλά και υλικό που ανήκει στο τμήμα της συλλογής που δεν εκτίθεται. / Location sensitive mobile games, are usually ludic multiplayer activities where engaging the physical space in the game is of particular importance. They are designed to be played in specific physical spaces, using mobile devices, leading to a strong interplay between physical and virtual spaces. These games have features such as motion and action in physical space, awareness of the surroundings of the player, interaction between players, as well as interaction with objects of the real world in different ways. These characteristics make them particularly attractive for learning activities in real space and have been used in recent years in cultural spaces where social, experiential and situated learning can take place [de Souza, 06]. The basic idea is that such games motivate players to associate information with physical activity, and are attractive as learning tools because they help the integration of the physical and social space with the digital dimension. In this context, it is interesting to explore the design process of an activity of this type, the rules of the game and the development of the corresponding technology (software, appliances, etc.), as well as the involvement of a museum's collection and the related digital information. The objective of this thesis is to describe the design and development of Benaki MuseumScrabble (BMS), a location sensitive game for mobile devices, aimed for young visitor and designed for part of the collection of the Benaki Historical Museum, in Athens.
529

Etudes moléculaires du canal potassique sensible a l'ATP : "gating", pathologie et optogénétique / Molecular studies of ATP-sensitive potassium channels : gating, pathology, and optogenetics

Reyes Mejia, Gina Catalina 23 September 2016 (has links)
Les canaux potassiques sensibles à l’ATP (KATP) sont des canaux omniprésents liant excitabilité et énergie cellulaire. Ils fonctionnent en captant le niveau relatif des nucléotides ATP et ADP à l’intérieur des cellules: Les premiers bloquant le canal et les derniers l’activant. De plus le phospholipide phosphatidylinositol4,5-bisphosphate (PIP2) est connu pour être un puissant régulateur des canaux KATP. Ceux-ci sont présents dans la plupart des tissus excitables et sont impliqués dans un grand nombre de fonctions physiologiques. L’objectif de ma thèse consiste à désigner un bloc dépendant de la lumière au niveau de ces KATP, afin de contrôler son activité optiquement tout en gardant ses propriétés natives. Cela a été accompli par la mutation de différents résidus en cystéine. Ce canal KATP complètement dépendant de la lumière, pourrait être utilisé pour réguler les actions de potentiels via la lumière afin de piloter différents aspects d’électrophysiologie cellulaire mais aussi de développer des applications de photo-traitements.J’ai également réalisé la cartographie fonctionnelle des résidus impliqués dans le gating du canal Kir6.2 sous le contrôle de protéines membranaires interagissant avec le domaine N-terminal. Cela a été réalisé par le design d’un canal artificiel Kir6.2 formé par la fusion du C-terminal d’un RCPG avec le N-terminal du canal. Des structures cristallographiques et des caractérisations fonctionnelles des canaux potassiques ont permis de mettre en évidence la présence de deux portes dans les domaines transmembranaires : le filtre de sélectivité et le « gate A » à l’interface cytoplasmique, et le troisième « gate » dans le domaine cytoplasmique du canal Kir connu sous le nom de « G loop gate ». Enfin j’ai caractérisé de mutations dans le gène ABCC9 codant pour SUR2A et associé au syndrome de Cantu (CS). Ces mutations sont localisées dans le domaine transmembranaire 0 (TMD0) de SUR2A, un domaine essentiel dans l’interaction entre Kir6.2 et SUR dans le complexe KATP. Les résultats suggèrent que les deux mutations cause une hyperactivité du canal via 2 mécanismes distincts : (1) Une diminution de la sensibilité de l’ATP affectant la modulation du PIP2, mais qui n’affecte pas l’activation par le Mg-ADP ou (2) aucun effets en réponse à l’ATP ou Mg-ADP, mais une sensibilité accrue au PIP2. Ces découvertes soulignent le rôle essentiel du TMD0 dans la modulation du « gating » de Kir6.2. En particulier, cela démontre qu’il y a un contrôle de la réponse du canal par des effecteurs intracellulaires qui se fixent sur Kir6.2, impliquant des interactions très liées entre Kir6.2 et la région TMD0. / ATP-sensitive K+ (KATP) channels are ubiquitous channels designed to couple excitability to cellular energy. They perform this function by sensing the relative levels of the intracellular nucleotides ATP and ADP; with ATP blocking the channel and ADP activating it. Additionally, the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) is known to be a strong regulator of KATP channels. These channels are present in many excitable tissues and involved in many physiological functions. The aim of this thesis is to design a light dependent block of the KATP channel, in order to control its activity and have it under optical control while at the same time retaining its native properties. This was accomplished by mutating specific residues to cysteines. This light dependent blocked KATP channel, could be used to regulate action potentials with light to tune diverse aspects of cellular electrophysiology and potentially photo-pharmacology treatment. We also performed a functional mapping of the Kir6.2 channel gate(s) under the control of membrane proteins interacting with the N-terminal domain. This was performed by using a unique artificial gate Kir6.2 channel formed by fusing a GPCR C-terminus to the Kir6.2 N terminus. Crystallographic structures and functional characterizations of potassium channels demonstrated the presence of two gates in the transmembrane domains: the selectivity filter and the "A" gate at the cytoplasmic interface, and a third gate in the cytoplasmic domain of Kir channels known as the G loop gate. Unexpectedly, our results demonstrated that several gates could be involved suggesting a concerted mechanism. Finally, we characterized two single-point mutations in the ABCC9 gene encoding SUR2, that are associated with Cantu syndrome (CS). These mutations are localized in transmembrane domain 0 (TMD0) of SUR2A, an essential domain which mediates the interaction between Kir6.2 and SUR within the K-ATP channel complex. Results suggest that the two mutations cause KATP channel hyperactivity through two divergent mechanisms: (1) a decreased sensitivity to ATP inhibition and affecting the modulation by PIP2, and that does not affect activation by Mg-ADP or (2) any effect on the response to ATP and Mg-ADP, but more sensitive to activation by PIP2. These discoveries underline the essential role of TMD0 in the gating modulation of Kir6.2. They demonstrate in particular that it can control the response of the channel to intracellular effectors that bind to Kir6.2, implying tight interactions between Kir6.2 and the TMD0 region.
530

A fotografia sem câmera : revelações de especificidades da fotografia através do quimigrama

Gonçalves, Myra Adam de Oliveira January 2007 (has links)
Esta dissertação foca um processo de criação de imagens fotográficas a partir de manipulações químicas feitas sobre superfícies fotossensíveis, diretamente sobre o papel ou negativo, sem utilizar para isso o aparato tecnológico – a câmera. A partir dessa abordagem, a dissertação analisa os limites daquilo que conhecemos como fotografia. A pesquisa convergiu para a investigação das possibilidades fotográficas inerentes às superfícies sensíveis e fotossensíveis, às soluções fotoquímicas e para o cruzamento dessas possibilidades fotográficas com outras linguagens artísticas. O trabalho confrontou a fotografia com suas especificidades e buscou desvendar os domínios da fotograficidade, que se configurou como um lugar apropriado para vasculhar as certezas e incertezas do que é a fotografia. As reflexões teóricas foram instituídas pelo trabalho plástico. / This dissertation aims at a photographic images creation process from chemistry manipulations made over light sensitive surfaces, directly on the paper or negative, without the camera. From this point of view the dissertation analyses the limits of which we know as photograph. The research converged to an investigation of the inherent photographic possibilities to sensitive and light sensitive surfaces, to photochemical solutions and to an approaching of these photographic possibilities to other kinds of artistic languages. The creation process faced photograph and its unique features and, by dealing with them, tried to reveal the photographs unique characteristics, which showed a specific place to search the certainties and uncertainties of what photography is. The theoretic reflections were established by the artistic work.

Page generated in 0.0625 seconds