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1
McGarry, Anthony. "Evaluation of the Tracer CAD and T ring prosthetic shape capture systems." Thesis, University of Strathclyde, 2009. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=11251.
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SONI, HARSHIT. "DESIGN AND STUDY OF NANOSCALE TRENCHED GATE MOSFET." Thesis, DELHI TECHNOLOGICAL UNIVERSITY, 2020. http://dspace.dtu.ac.in:8080/jspui/handle/repository/18379.
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This Project presents T-CAD simulation of buffered trench gate MOSFET (BTG-MOSFET),
and GaN buffered trench gate MOSFET (GaN-BTG MOSFET). The electrical attributes of
the devices are contrasted with conventional trench gate MOSFET (CTG-MOSFET). A
comparative study between various performance factors, for example, electric field, electron
velocity, electron mobility, the threshold voltage (Vth), and sub-threshold swing (SS) of the
devices has been performed. Results uncover a 43.85% improvement in SS and 9.83%
decrement in Vth for GaN-BTG-MOSFET. Further in this report, GaN-BTG-MOSFET’s
parameters are concentrated with variation in channel length, Effective Oxide thickness (tox),
and Doping concentration. Thermal reliability of GaN- BTG-MOSFET for application in
Integrated Circuits (ICs) at high temperatures (300K to 600 K) is examined. An intensive
near examination of electrical characteristics GaN-BTG-MOSFET has been carried out.
GaN-BTG MOSFET acts as a promising structure for further downsizing of the trenched gate
MOSFET and guarantees better performance for sub-micrometer MOSFET.
Thermal reliability of GaN-BTG-MOSFET for application in Integrated Circuits
(ICs) at high temperatures (300K to 600K). An intensive relative investigation of electrical
characteristics, for example, transconductance, transfer characteristics, leakage current, and
the electric field of the designed devices have been performed using the TCAD Atlas tool. A
detailed discussion is introduced on the thermal stability of the device at high temperatures
(300-600K). Report additionally presents the performance factors, for example, On-
Resistance (Ron), leakage current, and threshold voltage (Vth). Results recommend that the
introduction of GaN instead of silicon in a trenched gate structure not just improves the
device’s performance at room temperature (300K) yet additionally enhances the thermal
stability of the device. The performance of GaN-BTG-MOSFET at high temperatures when
contrasted with CTG MOSFET suggests that it tends to be utilized in ICs and shows
preferred thermal stability than silicon-based devices.
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Ferrari, Giacomo. "Metodi numerici per superfici T-Spline." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amslaurea.unibo.it/5913/.
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Questo lavoro di tesi riguarda lo studio e la realizzazione dei principali algoritmi di rappresentazione e modellazione di superfici T-Spline. In particolare si è cercato di determinare i vantaggi e gli svantaggi che queste superfici presentano rispetto alle superfici NURBS, utilizzate nei software CAD.
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Font, Andreu Jordi. "Impacto tecnológico del CAD en la docencia de la expresión gráfica en la Ingeniería." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/1263.
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El presente trabajo de investigación tiene por objeto analizar el impacto tecnológico del Diseño Asistido por Ordenador en la docencia de la Ingeniería Gráfica. El trabajo se centra en los cambios metodológicos y en las más importantes consecuencias que ha comportado la aparición de una nueva herramienta de diseño respecto a la práctica y los contenidos del Área de conocimiento de Ingeniería Gráfica.Se han tratado datos disponibles de los centros públicos del territorio español desde la implantación de los planes de estudios de 1993.
Para el presente estudio se han tenido en cuenta los acontecimientos más importantes producidos en el entorno universitario nacional, entre los que cabe destacar los siguientes:
· Elaboración y aplicación de los nuevos planes de estudios
· Reducción de las horas lectivas por asignatura (de veintiocho semanas por curso en el plan de 1964 a 15 semanas en los planes posteriores a 1993).
· Incorporación de la docencia del Dibujo Asistido por Ordenador en aplicación de los descriptores del Boletín Oficial del Estado (BOE), a partir de 1993.
· Expansión del Diseño Asistido por Ordenador (CAD 3D) paramétrico, a raíz de la migración de estaciones de trabajo a ordenadores personales a mediados de 1995.
· Introducción paulatina de las nuevas Tecnologías de la Comunicación y de la Información (TIC) en las aulas.
· Instalación de aulas informáticas con acceso a Internet.
· Proliferación de Aplicaciones Didácticas Interactivas (ADI) como recurso metodológico en la docencia y el aprendizaje.
· Reformas realizadas de los planes de estudios vigentes para la adaptación al Proceso de Bolonia.
Dichas transformaciones en el marco de la enseñanza han propiciado que se revisen los objetivos, los contenidos y los métodos empleados en la docencia, para dar respuesta a las necesidades que se promueven desde las instituciones, la industria y el conjunto de la sociedad en general.
Se detalla la programación de las asignaturas de Ingeniería Gráfica a partir de la localización de las guías académicas disponibles de los centros donde se imparten ingenierías. Se analizan los objetivos y los contenidos de dichas asignaturas en los centros docentes que se han tomado de referencia. Se muestran ejercicios de prácticas y se exponen los contenidos necesarios para resolverlos mediante herramientas manuales y digitales, con la finalidad de destacar los diferentes métodos empleados. Se describen los contenidos utilizados en el modelado geométrico 3D y se estudian los métodos empleados en el sistema diédrico en combinación con los propios del CAD 3D. Por último, se muestran los cuerpos y superficies más habituales en el estudio de la geometría, así como los elementos constructivos y las operaciones más comunes en la generación de los modelos en 3D.
En las conclusiones se recogen las consecuencias más relevantes del impacto del CAD en la docencia de la Ingeniería Gráfica. Se exponen los argumentos que se desprenden del análisis de los datos aportados y que corroboran los objetivos y las hipótesis formuladas. Se plantean y se apuntan posibles líneas de investigación a desarrollar en un futuro.
"The technological impact of CAD on the teaching of Graphic Expression in Engineering"
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This study focuses on the methodological changes brought about by the appearance of the new design tool CAD 3D and the very important consequences it has had on brought about by the appearance of the new design tool CAD 3D regarding the practice and the contents of the field of Graphic Engineering.
The syllabi of the Graphic Engineering courses in engineering schools are described. The aims and the contents of said subjects are analysed. Typical practical exercises from the courses are shown and their solution using both manual and digital tools is discussed with the aim of reflecting on and analysing the differences between the methods employed.
The materials used in 3D geometric modelling are described, and the methods employed by the dihedral system are studied in combination with those used by CAD 3D. Lastly, the construction elements and the most common operations used in the generation of 3D models are shown.
The most relevant consequences of the impact of CAD on the teaching of Graphic Engineering are detailed in the conclusion. The ideas born from the analysis ofA discussion of the results shows that the data collected and which corroborate the aims and the hypotheseis of the thesis are defended. Possible avenues for future research to develop are suggested.
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BESERRA, Simone Ataíde. "Influência do tipo e do tempo de duração de cura nas propriedades mecânicas de concretos de alto desempenho (CAD) produzidos em períodos quente (t>25°C) e de baixa umidade relativa do ar (h<50%)." Universidade Federal de Goiás, 2005. http://repositorio.bc.ufg.br/tede/handle/tde/686.
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Previous issue date: 2005-06-07In the case of conventional concrete, small constructive defects, variations of mix proportion or even inadequate curings can not compromise significantly the material. No longer HPC demands a severity in the control since its dosage until the execution, therefore any imperfection can bring serious damages to the material or the structure. Amongst the relative aspects most important to the total quality of any concrete it is the curing, that becomes basic when is about HPC. The curing of the high performance concrete constitutes in a controversial subject in the technician area as well as the type and duration of it, therefore the necessity of a deeper refined study on this subject. This research verifies the influence of the type and time of duration of curing in the mechanical properties of the HPC (compressive strength, flexion tensile strength and module of deformation), produced in Goiânia in hot period (t>25ºC) and of low relative humidity of air (h<50%) situation this considered critical for NBR 14931/2003 and predominant in the months of May the September in this region. In the experimental study were produced HPC of target compressive strength 60, 80 and 100MPa, from the Furnas Mix Proportion Method, using cement CP II-F-32, silica fume, polycarboxylate based superplasticizer, natural sand and crushed stones nº 0 of the granulite. 14 cures of different type and times of duration had been applied: curing with permanence of 1, 3, 7, 14, and 28 days inside of the humid chamber; curing with aspersion of water during 1, 3, 7, 14 and 28 days; chemical curing based on paraffin and chemical curing based on chloride rubber; cure for aspersion of water during 7 days and later sealing of the part with membrane of curing based on chloride rubber and air curing. For concretes of target compressive strength to the 28 days of 60 MPa and 80 MPa, the best type of curing was "saw humid" (curing in humid chamber and curing with aspersion of water) and the best time of duration humid was 7 days. For the one of 100 MPa the best type of curing also was "saw humid", however the duration time was 14 days. According to the chemical curing, some times the results had been even though less than to the one of reference (air curing). Among the two types of used chemical curing, difference in the results of compressive strength was not verified, despite the chemical membrane based on paraffin has an inferior cost to the chloride rubber base.
No caso de concreto convencional, pequenos defeitos construtivos, variações de dosagem ou mesmo curas inadequadas podem não comprometer significativamente o material. Já no CAD exige-se um rigor no controle desde sua dosagem até a execução, pois qualquer falha pode trazer sérios prejuízos ao material ou a estrutura. Dentre os aspectos mais importantes relativos à qualidade total de qualquer concreto está a cura, o que se torna fundamental quando se trata de CAD. A cura do concreto de alto desempenho constitui assunto polêmico no meio técnico assim como o tipo e duração desta, por isso a necessidade de um estudo mais apurado sobre este tema. Esta pesquisa verifica a influência do tipo e tempo de duração de cura nas propriedades mecânicas do CAD (resistência à compressão, resistência à tração na flexão e módulo de deformação), produzidos em Goiânia em período quente (t>25ºC) e de baixa umidade relativa do ar (h<50%), situação esta considerada crítica pela norma NBR 14931 (ABNT, 2003) e predominante nos meses de maio a setembro na região. No estudo experimental foram produzidos CAD de resistência à compressão estimada 60, 80 e 100MPa, a partir do Método de Dosagem de Furnas, utilizando cimento CP II-F-32, sílica ativa, superplastificante à base de éter carboxilato, areia natural e brita 0 de granulito. Foram aplicados 14 curas de diferentes tipos e tempos de duração: cura com permanência de 1, 3, 7, 14, e 28 dias dentro da câmara úmida; cura através de aspersão de água durante 1, 3, 7, 14 e 28 dias; cura química com membrana à base de parafina e à base de borracha clorada; cura através de aspersão de água durante 7 dias e depois selagem da peça com membrana de cura à base de borracha clorada e cura ao ar. Para os concretos de resistência estimada aos 28 dias de 60 MPa e de 80 MPa, o melhor tipo de cura foi via úmida (cura em câmara úmida e cura através de aspersão de água) e o melhor tempo de duração foi 7 dias. Para o de 100 MPa o melhor tipo de cura também foi via úmida , porém o tempo de duração foi 14 dias. Quanto à cura química, algumas vezes os resultados foram até mesmo inferiores ao de referência (cura ao ar). Dentre os dois tipos de curas químicas utilizados não verificouse diferença nos resultados de resistência à compressão, salientando-se que a membrana química à base de parafina tem custo inferior à base de borracha clorada.
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Samakai, Elsie. "TRANSCRIPTIONAL CONTROL OF Ca2+ SIGNALING IN T CELLS." Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/466164.
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BiochemistryPh.D.
Antigen presentation to T cells results in their activation through T Cell Receptor (TCR) stimulation, resulting in sustained elevation of cytosolic Ca2+ concentration critical for T cell activation. Sustained Ca2+ signals are important for the activation of Nuclear Factor of Activated T cells (NFAT), which is a key regulator of T cell activation through its transcriptional control of genes in multiple process including cytokine production, proliferation and differentiation(Rao, Luo, & Hogan, 1997). Recently it was shown that Stromal Interaction Molecule 1 (STIM1) inhibits plasma membrane Ca2+/ATPase 4 (PMCA4) function during T cell activation resulting in sustained elevation of Ca2+ signals(Ritchie, Samakai, & Soboloff, 2012). This interaction requires upregulation of both STIM1 and PMCA4. In this thesis, I hypothesize that changes in Ca2+ signals arising from transcriptional changes of STIM1 and PMCA are important for the efficient activation of T cells. In the first part of this thesis, I assess the transcriptional regulation of STIM1 and PMCA4. My in vitro studies show that expression of both proteins is regulated by the EGR family members, EGR1 and EGR4. Additionally, transcriptional regulation of PMCA inhibition by EGR1 and EGR4 is required for efficient activation of T cells. Interestingly, whereas significant roles for EGR1, EGR2 and EGR3 in T cell development and function have been established, a role for EGR4 has not, hitherto been elucidated. In the second half of this thesis, using qPCR, I reveal that EGR4 expression is stimulated by TCR engagement in primary double positive, CD4 and CD8 positive murine T cells. Further, EGR4-null mice exhibit shifts in early thymic development, although this does not affect the relative number of double or single positive T cells in the thymus. Interestingly, EGR4-null primary T cells exhibit normal Ca2+ entry, but fail to exhibit activation-induced inhibition of Ca2+ clearance. Although not all subsets of EGR1 and EGR4 null primary T cells exhibited decreased STIM1 expression, significant defects in proliferation, migration and/or cytokine production were observed upon stimulation in all populations, albeit to different extents. These findings reveal a two-faceted role in which EGRs regulate T cell development and function through both Ca2+-dependent and independent methods. I believe that these findings have important implications towards the general understanding of transcriptional control of Ca2+ signaling, as well as having a possible impact in the quest to advance therapies targeting immunological disorders.
Temple University--Theses
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Serrano, Daniel. "GIMAP5 influence la survie des cellules T naïves en participant à la régulation du calcium emmagasiné dans les organites." Thèse, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/11088.
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La survie des cellules T naïves est essentielle au bon fonctionnement du système immunitaire à long terme. Les rats BBDP (Bio-breeding Diabetes prone) sont caractérisés par une haute prédisposition au développement du diabète ainsi que par une diminution significative du nombre de cellules T naïves. Ces rats comportent une mutation de type décalage de lecture dans le gène codant pour «GTPase Immunity-Associated Protein 5» (Gimap5) ce qui entraine l’apoptose des lymphocytes T. Le mécanisme par lequel la déficience de la protéine GIMAP5 conduit les cellules T à la mort est actuellement méconnu. GIMAP5 a également été associée à différentes maladies auto-immunes, ce qui suggère son influence dans l'homéostasie des lymphocytes T. Des résultats antérieurs de notre groupe de recherche ont montré que l'absence de GIMAP5 entraîne une diminution du flux de Ca2+ ainsi qu’une réduction de la capacité mitochondriale à emmagasiner du Ca2+ suite à la stimulation du TCR. Cependant, GIMAP5 n'est pas une protéine mitochondriale. Afin de mieux comprendre le rôle de GIMAP5 dans la biologie des cellules T, au cours de mes études doctorales, je me suis concentré sur la localisation cellulaire de la protéine ainsi que sur son rôle dans l'homéostasie du Ca2+. Comme modèle d’étude, j'ai établi des lignées cellulaires HEK293T stables pour l’expression de GIMAP5, ainsi que pour différents mutants et variantes de la protéine. Ceci m’a permis d’élucider l'importance du domaine transmembranaire (TM) pour la localisation et le rôle physiologique de GIMAP5 ainsi que la différence entre les deux variantes de cette protéine.
Mes résultats ont permis de montrer que l'expression de Gimap5 ne semble pas être nécessaire après l’activation des lymphocytes T. En parallèle, j'ai confirmé nos observations antérieures qui démontrent l’influence de GIMAP5 dans l'homéostasie du Ca2+ et sa colocalization avec les microtubules. En outre, j'ai montré que GIMAP5 se trouve dans des structures de type vésiculaire, particulièrement dans la membrane lysosomale où son domaine TM est essentiel à son bon fonctionnement et localisation. Mes résultats suggèrent que les mitochondries exhibent un défaut dans leur capacité à emmagasiner du Ca2+ au niveau basal, ainsi que suite à l’activation du TCR. Enfin, j'ai démontré pour la première fois, que l'influence de GIMAP5 sur le stockage de Ca2+ lysosomal peut avoir un impact sur la survie des lymphocytes T. D’après ces observations, une des fonctions probables de GIMAP5 serait d’empêcher la fermeture prématurée des canaux de relâche calcique. Finalement, GIMAP5 pourrait être engagé dans des mécanismes visant à prolonger et raffiner la signalisation du Ca2+ dans les cellules T. Bref, la régulation du Ca2+ lysosomal médié par GIMAP5 est essentielle à la survie de cellules T naïves.Abstract: Healthy and long-term survival of naïve T cells is essential for proper functioning of the immune system. In bio-breeding diabetes prone (BBDP) rats, there is a critical decrease in the number of naïve T cells. In these rats, a recessive frameshift mutation in the GTPase of Immune-Associated Protein 5 (Gimap5) gene induces lymphocytes to undergo spontaneous apoptosis. The death of T cells driven by a deficiency of the GIMAP5 is currently not fully understood. Interestingly, different autoimmune diseases have shown an association with perturbations in the Gimap5 gene, which further suggests its influence in basal lymphocyte homeostasis. Previous findings by our group have shown that the absence of GIMAP5 results in a decrease calcium flux following TCR stimulation and an impaired capacity of the mitochondria to buffer calcium entry. However, GIMAP5 is not a mitochondrial protein. During my Ph.D. studies, I focused on clarifying the cellular localization of GIMAP5 as well as its function in Ca2+ homeostasis in order to further understand its role in T cell biology. As a model, I established HEK293T cells stable for the expression of the different mutants and variants of the GIMAP5 protein. Where I uncovered the importance of the transmembrane domain (TM) for GIMAP5 localization and physiological role, as well as the differences between the two variants of GIMAP5. The results obtained show that the expression of Gimap5 is no longer needed after T cells activation. Moreover, our previous observations were confirmed and expanded upon regarding GIMAP5’s influence on Ca2+ homeostasis and colocalization with the cytoskeleton. It was also shown that GIMAP5 localizes to vesicular-like structures, particularly to the lysosomal membrane, where its TM domain is critical for proper functioning and localization. My results suggest that the mitochondria might be impaired to uptake as well as retain Ca2+ at their full capacity in the absence of GIMAP5. Finally, I observed for the first time that GIMAP5’s influence on lysosomal Ca2+ storage could impact lymphocyte survival. These results suggest that GIMAP5 may work as a backup mechanism to prevent premature closure of Ca2+ channels and Ca2+ influx or as a mechanism to prolong and refine Ca2+ signaling in T cells.
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Li, Qince. "Mathematical modelling of intracellular Ca2+ alternans in atrial and ventricular myocytes." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/mathematical-modelling-of-intracellular-ca2-alternans-in-atrial-and-ventricular-myocytes(54ff4d2a-f820-43b6-a572-4706850f28ec).html.
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During excitation-contraction coupling, Ca2+ transient induced by the depolarization of membrane potential is the trigger of mechanical contraction in cardiac myocytes, which is responsible for the pumping function of the heart. However, mechanisms underlying intracellular Ca2+ regulation and the coupling between Ca2+ transient and membrane potential are not completely understood. Abnormalities in intracellular Ca2+ regulation have been observed during heart failure and cardiac arrhythmias, such as intracellular Ca2+ alternans and T-tubule disorganization. In this project, intracellular Ca2+ dynamics in different types of cardiac myocytes were investigated by using computer modelling. For atrial myocytes, a biophysically detailed computer model was developed to describe the observations of Ca2+ alternans and Ca2+ wave propagation in cardiac myocytes lacking T-tubules. The model was validated by its ability to reproduce experimental observed Ca2+ wave propagation under normal condition and the influences on spatial Ca2+ distribution by modifying various aspects of Ca2+ cycling, such as Ca2+ influx, SR Ca2+ uptake and SR Ca2+ release in cardiac myocytes lacking T-tubules. Mechanisms underlying the genesis of Ca2+ alternans in this type of cell were investigated by the model. Furthermore, a spontaneous second Ca2+ release was observed in response to a single voltage stimulus pulse with enhanced Ca2+ influx as well as SR Ca2+ overload. For the ventricular myocytes, an existing canine model was used to study the genesis of APD and intracellular Ca2+ alternans under various conditions. The genesis of Ca2+ alternans was investigated by analyzing the relationship between systolic Ca2+ concentration and SR Ca2+ content. On the other side, the roles of SR Ca2+ regulation and action potential restitution in the genesis of intracellular Ca2+ and APD alternans were also examined under various conditions. In addition, it was shown that spatially discordant Ca2+ alternans was generated when the Ca2+-dependent inactivation of ICa,L was strong. It tended to be concordant for weak Ca2+-dependent inactivation of ICa,L. For the sinoatrial node cells, a mathematical model was developed to simulate stochastic opening of unitary L-type Ca2+ channel and single RyR channel, thereby reproducing experimental observed local Ca2+ release during diastolic depolarization phase of the action potential. Simulation results of ionic channel block and modifications of SR Ca2+ regulation suggested a limited role of intracellular Ca2+ in the automaticity of central SA node cells.
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Malik, Aqsa. "Functional characterization of T-type calcium channels in area CA3 of the hippocampus." Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55100.
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Calcium (Ca²+) entry through voltage-gated Ca²+ channels in dendrites of hippocampal pyramidal cells (PCs) contributes to synaptic depolarization and activation of downstream pathways that regulate many aspects of synaptic and cellular function. Activated by small depolarizing changes in voltage, T-type Ca²+ channels mediate low-threshold spikes (LTS) that drive the resting membrane potential towards action potential threshold. T-type Ca²+ channels are hypothesized to contribute to subthreshold synaptic depolarization in the CA3 subfield of the hippocampus due to the stratified nature of inputs on CA3 dendrites. While T-type Ca²+ channels are densely expressed in area CA3, their functional characteristics and interactions with postsynaptic receptors are not well understood and LTS have not been reported in CA3 PCs. In Chapter 3, using whole-cell electrophysiology, we demonstrate that LTS in CA3 PCs can be evoked by somatic current injection. LTS were only evoked when 4AP was applied to depress A-type K+ channels. Using specific pharmacological blockers, we show that Cav3.2 channels mediate LTS in CA1 and CA3 PCs. In Chapter 4, using two-photon Ca²+ imaging, we map the subcellular distribution of Cav3.2 channels in hippocampal PCs. Our results show that Cav3.2 channel expression is restricted to the soma and proximal dendrites in CA1 PCs, while Ca²+ influx from Cav3.2 channel activation occurs in distal (>50 μm) regions of CA3 PC dendrites. In Chapter 5, we demonstrate that mAChR stimulation potentiates LTS amplitude and such amplification of Ca²+ influx through Cav3.2 channels is dependent on M-current inhibition. Furthermore, we show that application of t-ACPD causes potent and rapid inhibition of LTS propagation. This inhibition occurs exclusively through mGlu₁ receptors and downstream activation of PKC is necessary for this process. Lastly, in Chapter 6, we show boosting of subthreshold synaptic signals by T-type Ca²+ channels in PCs within area CA3 but not CA1. Taken together, our data identify a new T-type mediated Ca²+ signaling pathway in CA3 PC dendrites that is unlocked by A-type K+ channel blockade, potentiated by mAChR activation, and inhibited by mGluR₁ activation. Furthermore, our study highlights the important involvement of T-type Ca²+ channels in enhancing dendritic depolarization in CA3 PCs.Medicine, Faculty of
Graduate
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Kinoshita, Hideyuki. "T-Type Ca2+ Channel Blockade Prevents Sudden Death in Mice With Heart Failure." Kyoto University, 2010. http://hdl.handle.net/2433/120614.
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Catherinet, Claire. "Etude des effecteurs de la voie Ca2+/Calmoduline dans les leucémies aiguës lymphoblastiques T." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC293/document.
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Les leucémies aigües lymphobastiques (LAL) représentent un tiers des leucémies et constituent le cancer pédiatrique le plus fréquent chez l’enfant. Les LAL de type T (LAL-T)sont caractérisées par l’expansion anormale de progéniteurs de lymphocytes T. Aujourd’hui,la réponse curative aux traitements est proche de 80% chez l’enfant et 50% chez l’adulte. La rechute reste donc fréquente et souvent de mauvais pronostic. Pour ces raisons,l’identification de nouvelles voies de signalisation en vue de développer de nouvelles stratégies thérapeutiques est cruciale afin d’améliorer le traitement des LAL-T.Les résultats précédents du laboratoire ont révélé l’activation soutenue de la voie calcineurine (Cn)/NFAT dans des échantillons humains de lymphomes et de LAL, ainsi que dans des modèles murins de ces pathologies. Le laboratoire a ensuite montré que Cn est intrinsèquement requise pour la capacité des cellules leucémiques de LAL-T à propager la maladie (activité LIC « Leukemia Initiating Cells ») dans un modèle murin de LAL-T induit parun allèle activé de NOTCH1 (ICN1). Puisque l’inhibition pharmacologique de Cn induit de nombreux effets secondaires, la recherche de cibles thérapeutiques en aval de Cn constitue un axe de recherche important. J’ai participé à une étude du laboratoire montrant que l’expression à la surface cellulaire de CXCR4 est régulée par Cn et requise pour la migration des cellules de LAL-T, mais non suffisante pour rétablir le potentiel de ré-initiation suggérant que d’autres effecteurs doivent être impliqués dans cette activité.Les facteurs de transcription NFAT (NFAT1, NFAT2 et NFAT4) sont des effecteurs importants de Cn en réponse à la signalisation calcique lors du développement des thymocytes, mais également dans les lymphocytes T. L’essentiel de ce travail de thèse a utilisé des LAL-T induites par ICN1 dans lesquelles l’inactivation génique des trois facteurs NFAT par recombinaison homologue. Nous avons ainsi montré que (i) les facteurs NFAT sont requis en aval de Cn pour le potentiel LIC des LAL-T-ICN1 in vivo, (ii) leur inactivation altère la survie, la prolifération et la migration des cellules de LAL-T in vitro, (iii) NFAT1,NFAT2 et NFAT4 ont une fonction largement redondante dans les LAL-T. Nous avons également par une approche transcriptomique identifié deux gènes dont l’expression estsous contrôle des facteurs NFAT et impliqués dans la régulation de la survie et de la prolifération des LAL-T in vitro : CDKN1A et MAFB.Tout comme la voie Cn/NFAT, les CaMKs sont des protéines kinases activées en aval de la signalisation calcique dans les lymphocytes T. Nous avons montré par une approche pharmacologique que l’inhibition des CaMKs dans les LAL-T-ICN1 in vitro altère la survie etla prolifération des cellules leucémiques. L’inhibition spécifique par une approche d’ARN interférence de deux isoenzymes CaMKIIγ et CaMKIIδ suggèrent que ces protéines jouent dans le maintien des cellules leucémiques in vitroT cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of T cell progenitors. Despite initial response to chemotherapy, relapses remain frequent in children and adults. Previous results identify sustained activation of Calcineurin (Cn)/NFAT signaling pathway in human T-ALL and murine T-ALL models. Importantly, they also demonstrated Cn is essential for T-ALL Leukemia Initiating Cells (LIC) activity in a murine model of T-ALL induced by an activated allele of NOTCH1 (ICN1). Since pharmacologic inhibition of Cn induces side effects, we aim to identify downstream effectors involved in T-ALL. NFAT (Nuclear Factor of Activated T cells) factors play crucial roles downstream Cn during development and activation of T cells. To address their role in T-ALL, we generated mouse ICN1-induced T-ALL in which NFAT genes can be inactivated either single or in combination following Cre-mediated gene deletion. We demonstrated that (i) NFAT factors are required downstream Cn for LIC activity in T-ALL in vivo (ii) ex vivo NFAT factors deletion alters survival, proliferation and migration of T-ALL (iii) NFAT1, 2 and 4 have a largely redundant function in T-ALL. Moreover, the NFAT-dependant transcriptome allowed to identify important targets (CDKN1A, MAFB) involved in T-ALL survival and proliferation in vitro. Calmodulin-dependant kinases (CaMK) are kinases activated by calcium signaling in T cells. We showed that pharmacologic inhibition of CaMKs in ICN1-induced T-ALL alters survival and proliferation of T-ALL in vitro. Beside, specific inhibition by RNA interference of CaMKIIg and CaMKIId suggests a putative role of these kinases in T-ALL maintenance
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Johnson, Emily Louise. "The role of thioredoxin and T-type Ca2+ channels in vascular smooth muscle cell proliferation." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/15679/.
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Elevated vascular smooth muscle cell (VSMC) proliferation is a feature of various cardiovascular conditions including restenosis, abdominal aortic aneurysm (AAA) and atherosclerosis. Voltage-gated T-type Ca2+ channels are implicated in VSMC proliferation as their expression is markedly up-regulated in proliferative phases of the VSMC cell-cycle (Kuga et al., 1996). The Thioredoxin (Trx) system is also associated with proliferative disorders of the heart and vasculature, e.g. Trx concentrations are elevated in AAA (Martinez-Pinna et al., 2010) and atherosclerosis (Okuda et al., 2001). Trx has recently been shown to regulate T-type Ca2+channels (Boycott et al., 2013). This PhD has investigated the hypothesis that VSMC proliferation is modulated by interactions between Trx and T-type Ca2+ channels. Proliferation assays revealed that the T-type Ca2+ channel inhibitor NNC55-0396 (NNC, 1-3μM) decreased A7r5, HEK293/CaV3.1 and HEK293/CaV3.2, but not wt HEK293, cell proliferation. In contrast the L-type Ca2+ channel inhibitor nifedipine (2μM) was without effect. The Trx inhibitors PX-12 (1μM) and auranofin (AuF, 300nM) preferentially inhibited the proliferation of CaV3.2-expressing cells, i.e. A7r5 and HEK293/CaV3.2 cells. Basal Ca2+ influx in A7r5 cells was also significantly reduced by NNC (3μM) and AuF (3μM). Whole-cell patch-clamp recordings in recombinant cells revealed that PX-12 (1-300μM) inhibited CaV3.1 and CaV3.2 currents with similar sensitivities. In contrast, Trx (4μg.ml-1) enhanced CaV3.2, but not CaV3.1, peak current amplitude. Similarly, AuF (3μM) selectively reduced the current-density of HEK293/CaV3.2 cells. Data suggest that CaV3.2 channels are positively and selectively regulated by Trx, yet PX-12 could inhibit T-type Ca2+ channels independently of Trx. The sensitivity of CaV3.2 channels to Trx was found to be dependent on an extracellular histidine residue at position 191 (H191), especially as mutation to a glutamine (Q) residue (H191Q) abolished Trx-sensitivity. In summary, these data indicate that interactions between Trx and CaV3.2 channels can regulate the proliferation of CaV3.2–expressing cells.
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Schwarzmann, Nadine. "Funktion der Ryanodin-Rezeptoren innerhalb der Ca2+-Signaltransduktion in T-Lymphozyten funktionaler Knock-down des Ryanodin-Rezeptors in Jurkat-T-Lymphozyten durch Antisense-Technologie /." [S.l.] : [s.n.], 2002. http://deposit.ddb.de/cgi-bin/dokserv?idn=968560830.
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Johnsen, Anke [Verfasser], and Andreas H. [Akademischer Betreuer] Guse. "2-Methoxyestradiol and its derivatives decrease Ca2+ entry in human (Homo sapiens) and rat (Rattus norvegicus) T lymphocytes by inhibiting Ca2+ release-activated Ca2+ channels / Anke Johnsen ; Betreuer: Andreas H. Guse." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2018. http://d-nb.info/1173899294/34.
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Chapman, Briese C. "The Consistency of Ratings on the Cab-T Executive Functioning Scale as Compared to the Brief." TopSCHOLAR®, 2016. http://digitalcommons.wku.edu/theses/1577.
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Executive functioning is an umbrella term used to describe abilities that include self-monitoring, goal-setting, planning, organization, attention, and working memory. Broadband behavior rating scales are commonly used by school psychologists and the instruments often now include an executive functioning scale. It is unknown, however, how these scales, based on a few items, compare to more extensive rating scales that solely measure executive functioning. The current study examined the overall consistency between the executive functioning scale on one broadband instrument to another instrument that assesses multiple areas of executive functioning by having teachers complete both instruments at the same point in time. The comparisons revealed statistically significant correlations, but significantly different mean scores between the executive functioning CAB-T score and the overall BRIEF score. Furthermore, classification consistency (i.e., scores from the two scales are both in the average range or clinically significant range) only occurred approximately two-thirds of the time. Thus, concerns were raised about the use of the scale from the broadband instrument as a general measure of executive functioning.
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Bernardes, Celene Fernandes. "Alterações no fluxo de Ca2+ mitocondrial causadas por T. Butil hidroperoxido e pelo antibiotico X-537a." [s.n.], 1986. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314432.
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Orientador : Lucia Pereira da SilvaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Mitocôndrias isoladas de fígado de rato, energizadas pela oxidação de succinato ou pela hidrólise de ATP apresentam um aumento transitório na velocidade de efluxo de Ca2+ concomitante com a oxidação do NAD(P)H pelo hidroperóxido, quando suspensas em um meio contendo ATP 3mM, Mg2+ 4mM, acetato como ânion permeante e moderada concentração de Ca2+. Isto ocorre paralelamente a um aumento no estado de fluxo constante da concentração de Ca2+ extramitocondrial, decréscimo de, aumento na velocidade de respiração e inchamento mitocondrial. Com exceção do inchamento todos os outros eventos eram reversíveis. Se o movimento cíclico de Ca2+ era prevenido por vermelho de rutênio, o decréscimo de, a velocidade de respiração e a extensão do inchamento mitocondrial eram significantemente diminuídos. Nessas condições, não houve decréscimo significativo no conteúdo de nucleotídeos de piridina mitocondriais e o acoplamento mitocondrial era preservado após um ciclo de efluxo e recaptação de Ca2+. Por outro lado, mitocôndrias de fígado de rato incubadas na presença do antibiótico X-537A, apresentam uma maior captação de Ca2+, baixando o estado de fluxo constante da concentração extramitocondrial do íon; um aumento de e inibição do efluxo de Ca2+ induzido por hidroperóxido ou vermelho de rutênio. ...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital
Abstract: Isolated rat liver mitochondria, energized either by succinate oxidation or ATP hydrolysis present a transient increase in the rate of Ca2+ efflux concomitant to NAD(P)H oxidation by hydroperoxides when suspended in a médium contaning 3mM ATP, 4mM Mg2+, acetate as permeant anion and moderate Ca2+ concentrations. This is paralelled by an increase in the steady state concenration of extramitochondrial Ca2+, a decrease in, an increase in the rate of respiration and mitochondrial swelling. With the exception of mitochondrial swelling all other events were found to be reversible. If Ca2+ cycling was prevented by ruthenium red, the decrease in , the rate of respiration and the extent of mitochondrial swelling were significantly diminished. In addition, the was no significant decrease in the content of mitochondrial pyridine nucleotides. Mitochondrial coupling was preserved after a cycling of Ca2+ release and reuptake under these experimental conditions. On the other hand, rat liver mitochondria incubated in the presence of antibiotic X-537A present a decrease in the steady state concentration of extramitochondrial Ca2+, an increase in and inhibition of ruthenium red or hydroperoxide-induced Ca2+ efflux. The results indicate that alterations in the t-butyl hydroperoxide and X-537A induced Ca2+ flux are related with structural changes of mitochondria, changing the membrane permeability to the cation. ...Note: The complete abstract is available with the full electronic digital thesis or dissertations
Mestrado
Bioquimica
Mestre em Ciências Biológicas
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Duckles, Hayley. "The vascular smooth muscle T-type Ca2+ channel : an anti-proliferative target for heme oxygenase-1." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/4846/.
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Pathological proliferation of vascular smooth muscle cells (VSMC) is a central feature of vascular disorders such as atherosclerosis and restenosis. During such proliferative conditions the expression of the T-type Ca2+ channel is increased, providing an important route for Ca2+ entry. The inducible stress-response protein, heme oxygenase-1 (HO-1), is also up-regulated during vascular disorders. This enzyme confers cytoprotective effects via the breakdown of free heme to produce iron, biliverdin, and carbon monoxide (CO). CO has been shown to be anti-inflammatory, anti-apoptotic, and anti-proliferative at low concentrations. Furthermore, CO is emerging as a modulator of various ion channels, and our research group has recently found that CO inhibits the T-type Ca2+ current via whole-cell patch clamp recordings. Therefore, the aim of this thesis was to investigate whether the VSMC T-type Ca2+ channel could act as an anti-proliferative target for HO-1-derived CO. HEK293 cells over-expressing the Cav3.2 T-type Ca2+ channel produced higher basal [Ca2+]i and displayed an augmented proliferative response. [Ca2+]i and proliferation were both reduced by T-type Ca2+ channel inhibition, CO exposure, and HO-1 induction. T-type Ca2+ channel inhibition and HO-1 induction reduced [Ca2+]i and proliferation in the rat aortic VSMC line, A7r5. Exogenous CO exposure decreased [Ca2+]i in A7r5 cells, but conferred insignificant anti-proliferative effects, which correlated to a relatively low expression of the T-type Ca2+ channel. T-type Ca2+ channel inhibition, CO exposure, and HO-1 induction all have anti-proliferative effects in human VSMCs, yet simultaneous HO-1 induction and T-type Ca2+ channel inhibition do not cause additive inhibitory effects on proliferation. These data provide evidence that CO is anti-proliferative, and that CO potentially acts via the T-type Ca2+ channel. This pathway could be a novel therapeutic target for vascular disorders involving excessive smooth muscle cell proliferation.
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He, Yang. "Modelling the spatio-temporal dynamic of iIntracellular Ca2+ handling system in cardiac cells." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/modelling-the-spatiotemporal-dynamic-of-intracellular-ca2-handling-system-in-cardiac-cells(f1a1b52a-f9f1-4837-aa0f-9d5df1f54d6f).html.
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The intracellular Ca2+ handling system in a cardiac myocyte is of crucial importance. It regulates the contraction and relaxation of the myocyte during the excitation-contraction (EC) coupling. A normal intracellular Ca2+ handling system keeps the contraction of the heart orderly, which represents a powerful force to pump blood to the whole body. However, disarrayed or remodelled cellular structure associated with the intracellular Ca2+ handling system at the subcellular level, such as loss of T-tubule network in diseased conditions, may promote abnormal cardiac EC coupling, leading to genesis of cardiac arrhythmias impairing cardiac mechanical functions. Up to date, it is still incompletely understood how the intracellular Ca2+ handling system is altered by changes in subcellular structures of Ca2+ handling systems. In this thesis, biophysically detailed computational models for the intracellular Ca2+ handling system of a cardiac cell were developed, providing a powerful platform to investigate the spatio-temporal complexity associated with the intracellular Ca2+ handling, and its role in generating abnormal cardiac EC coupling. First, a well-validated single cell model was used to investigate how the diastolic and systolic Ca2+ concentration responded to alterations in the model parameters related to the Ca2+ handling system, from which the mechanisms underlying the rate-dependence of EC coupling were analysed. Then, a novel single cell model, with a 2D presentation of the spatial structures of subcellular Ca2+ handling and membrane action potential, of a sheep atrial myocyte was developed for simulating the abnormal intracellular Ca2+ regulation system due to the loss of T-tubules during atrial fibrillation. Variant scenarios of T-tubule loss were considered to investigate the role of the T-tubule in affecting the intracellular Ca2+ regulation. Furthermore, membrane currents' alterations due to the electrical remodelling arising from atrial fibrillation were considered together with the loss of T-tubule. Three typical types of abnormal Ca2+ cycling phenomenon, namely intracellular Ca2+ alternans, spontaneous Ca2+ sparks and intracellular Ca2+ waves were observed in AF conditions. The relationship between T-tubule loss, AF-remodelling and the genesis of delayed afterdepolarizations (DADs) was also investigated. It was shown that the loss of T-tubule in AF condition played an important role in disturbing the Ca2+ regulation system, which increases the risk for a cell to generate impaired contraction.
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Гребіник, Сергій Миколайович. "Продукування активних форм кисню та зміна рівня цитозольного Ca2+ у трансформованих T-клітинах за дії фотозбудженого фулерену C60." Diss. of Candidate of Biological Sciences, М-во освіти і науки, молоді та спорту України, Київ. нац. ун-т ім. Т. Шевченка, 2012.
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Pereira, Lucas Borges. "Caracterização da apirase do parasita P. falciparum e análise do papel do Ca2+ no egresso de T. gondii." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-17082016-151526/.
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Plasmodium falciparum e Toxoplasma gondii são protozoários parasitas pertencentes ao filo Apicomplexa. Apirases são enzimas metabolizadoras de nucleotídeos extracelulares. Nesta tese mostramos pela primeira vez a presença de um membro desta família de enzimas em P. falciparum, o qual foi capaz de degradar ATP extracelular. Análises por RT-qPCR revelaram a expressão da apirase durante todo o ciclo intraeritrocítico. A adição de inibidores desta classe de enzimas foi capaz de prejudicar o desenvolvimento dos parasitas e a invasão de novas hemácias pelos merozoitos, sugerindo assim um papel da apirase nestes processos. A via de sinalização por Ca2+ é universal e vital para todas as células. Para melhor entender a fisiologia celular de P. falciparum construímos uma nova linhagem de parasitas transgênicos, PfGCaMP3, que nos tornam capazes de monitorar a dinâmica de Ca2+ sem o uso de protocolos invasivos de marcação. De modo semelhante utilizamos uma nova linhagem de T. gondii expressando de forma estável o indicador de Ca2+ GCaMP3 para estudar o papel deste íon na saída da célula. T. gondii possui o Ca2+ necessário para promover este processo, entretanto Ca2+ extracelular age como um fator intensificador neste passo essencial do ciclo lítico.Plasmodium falciparum and Toxoplasma gondii are protozoan parasites that belong to phylum Apicomplexa. Apirases are metabolizing enzymes of extracellular nucleotides. In this work we show for the first time the presence of an apyrase in P. falciparum, which was able to degrade extracellular ATP. RTqPCR analysis revealed the expression of apyrase throughout the intraerythrocytic cycle. Addition of apyrase inhibitors was able to impair the development of the parasites and the invasion of new erythrocytes by merozoites, thus suggesting a role of apyrase in these processes. Calcium signaling is universal and vital to all cells. To better understand the cellular physiology of P. falciparum we construct a new strain of transgenic parasites, PfGCaMP3, which enable us to monitor the Ca2+ dynamics without using invasive protocols. Similarly we use a new strain of T. gondii that stably express the Ca2+ indicator GCaMP3 to study the role Ca2+ in parasite egress. T. gondii has the Ca2+ required to promote this process, however extracellular Ca2+ acts as an enhancer factor in this crucial step of the lytic cycle.
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Kozlov, Andriy. "T-type Ca channels as pathways of Ca2+ entry into the cell. : Role of ion-channel interactions in channel gating." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13186.
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Freitas, Claudia Mercedes. "Regulation of Immune Cell Activation and Functionby the nBMPp2 Protein andthe CD5 Co-Receptor." BYU ScholarsArchive, 2019. https://scholarsarchive.byu.edu/etd/8257.
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According to the centers for disease control and prevention (CDC) and the world healthorganization (WHO), heart disease and immune related diseases such as diabetes and cancer areamong the leading causes of death around the world. Thus, the regulation of the function ofimmune cell plays a key role in health and disease. Calcium (Ca2+) ions play a critical role inimmune cell activation, function and in a robust immune response. Defects in Ca2+ signalinginfluences the development of cardiac disease, Alzheimer disease, immune cell metabolism,muscle dysfunction, and cancer. Each immune cell is unique in its activation and function,making it relevant to understand how activation of each type of immune cell is regulated. Herewe describe the role of the nBMP2 protein in macrophage activation and function and the role ofthe CD5 co-receptor in helper T cell activation and function.The nuclear bone morphogenetic protein 2 (nBMP2) is the nuclear variant of the bonemorphogenetic protein 2 (BMP2), a growth factor important in heart development, neurogenesis,bone, cartilage and muscle development. To better understand the function of nBMP2, transgenicnBMP2 mutant mice were generated. These mice have a slow muscle relaxation and cognitivedeficit caused in part by abnormal Ca2+ mobilization. Mutant nBMP2 mice also have an impairedsecondary immune response to systemic bacterial challenge. Here we have further characterizedmacrophage activation and function from mutant nBMP2 mice before and after bacterialinfection. We describe how nBMP2 influences the Ca2+ mobilization response and phagocytosisin macrophages, revealing a novel role of the nBMP2 protein in immune cell regulation.CD5 is a surface marker on T cells, thymocytes, and the B1 subset of B cells. CD5 isknown to play an important role during thymic development of T cells. CD5 functions as anegative regulator of T cell receptor (TCR) signaling and fine tunes the TCR signaling response.Here we describe our characterization of CD5 regulation of Ca2+ signaling in naïve helper Tcells. We also outline our findings examining how CD5-induced changes in helper T cellactivation influence other biological processes such as immune cell metabolism, the diversity ofthe gut microbiome, and cognitive function and behavior. Thus, this work elucidates theinfluence of the CD5 co-receptor on the functional outcomes in multiple systems when CD5 isaltered.
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Finnigan, Gordon Thomas. "Arbitrary Degree T-Splines." Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2453.pdf.
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Viegas, Vinicius Nery. "Avalia??o das varia??es da transfer?ncia do planejamento virtual e sobre prot?tipos biom?dicos para a instala??o de implantes dent?rios pela t?cnica cir?rgica guiada." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2008. http://tede2.pucrs.br/tede2/handle/tede/999.
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Previous issue date: 2008-09-09A cirurgia guiada em Implantodontia consta de etapas que integram diagn?stico por imagem, planejamento virtual, bioprototipagem e aplica??o cir?rgica. O objetivo desta pesquisa foi avaliar as varia??es na transfer?ncia do planejamento virtual e sobre prot?tipos biom?dicos para o procedimento de instala??o de implantes dent?rios por meio desta t?cnica. O experimento foi realizado em 11 r?plicas id?nticas de mand?bula humana ed?ntula. A defini??o do posicionamento dos implantes foi padronizada e realizada em software espec?fico, a partir de imagens de tomografias computadorizadas cone-beam pr?-operat?rias. Para cada uma das mand?bulas, foram confeccionados biomodelos e guias cir?rgicos pelo m?todo de estereolitografia. Inicialmente, foram realizadas cirurgias simuladas com a coloca??o e remo??o dos implantes nos prot?tipos. Em seguida, os implantes foram instalados nas r?plicas de mand?bula. Para an?lise dos resultados, foram realizadas tomografias p?s-operat?rias e obtidos cortes padronizados nos prot?tipos e nas r?plicas, que possibilitaram a visualiza??o dos leitos dos implantes. A sobreposi??o dos modelos tridimensionais pr? e p?s-operat?rios permitiu a avalia??o da dist?ncia linear e do ?ngulo formado pelos longo-eixos dos implantes planejados e executados. Medidas lineares realizadas diretamente sobre os modelos foram utilizadas para avaliar a validade de procedimentos simulados em prot?tipos na fase de planejamento em Implantodontia. As varia??es das dist?ncias entre as regi?es coronais, centrais e apicais dos 22 implantes avaliados nesta pesquisa apresentaram valores m?dios inferiores ? 0,41 mm. Quanto ? angula??o, os implantes instalados no lado direito das r?plicas apresentaram varia??es de 1,45 ? 0,89 graus e os do lado esquerdo, de 0,70 ? 0,30 graus. A aplica??o do teste t de Student, para comparar as amostras com um valor de refer?ncia zero, indicou diferen?a estatisticamente significativa para todas as medidas analisadas (p<0,05). A correla??o entre o posicionamento dos leitos dos implantes, em cada mand?bula, apresentou valores considerados razo?veis a muito bons, de acordo com a dist?ncia analisada e o m?todo de interpreta??o utilizado. De acordo com os resultados desta pesquisa, as varia??es observadas na transfer?ncia para o campo operat?rio do posicionamento de implantes dent?rios, determinado durante o planejamento virtual e obtido em cirurgia simulada sobre prot?tipo biom?dico, indicam a confiabilidade da utiliza??o da t?cnica de cirurgia guiada em Implantodontia. A margem de seguran?a do m?todo, considerando a varia??o na posi??o dos implantes e a superestima??o ou subestima??o de medidas em procedimentos simulados em biomodelos, deve ser melhor avaliada em estudos cl?nicos.
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Tandl, Dominique [Verfasser], Gerhard [Akademischer Betreuer] Thiel, and Alexander [Akademischer Betreuer] Löwer. "X-ray irradiation triggers via ROS production a canonical Ca2+-dependent immune response in T-lymphocytes / Dominique Tandl ; Gerhard Thiel, Alexander Löwer." Darmstadt : Universitäts- und Landesbibliothek, 2021. http://d-nb.info/1228537410/34.
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Sonehara, Ieda Yuriko. "Estudos de identificação de possíveis alvos para nitro-compostos azometínicos ou oxadiazolínicos com atividade antifúngica e anti-T. cruzi." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/9/9135/tde-11012010-212622/.
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Este trabalho teve como objetivo a realização de estudos de Relações Quantitativas Tridimensionais Estrutura-Atividade, QSAR 3D, com identificação de alvos potenciais para compostos 5-nitro-heterocíclicos com estruturas azometínica ou oxadiazolínica com bioatividade dual, antifúngica e anti-T. cruzi, visando à identificação de novos compostos que possam ser aproveitados como possíveis candidatos a fármaco ou como compostos-líderes para novos estudos de modificação molecular. Os compostos estudados pertencem a quatro séries intimamente relacionadas, a saber: Série AzoO: 5-nitro-2-furfurilideno benzidrazidas 4-substituídas; Série AzoS: 5-nitro-2-tiofilideno benzidrazidas 4-substituídas; Série OxaO: 3-acetil-oxadiazolina 2,5-furfurilideno benzidrazidas 4-substituídas e Série OxaS: 3-acetil-oxadiazolina 2,5-tiofilideno benzidrazidas 4-substituídas. A utilização de forma integrada de ferramentas pertencentes às áreas de química farmacêutica, quimioinformática e bioinformática permite a caracterização de cavidades catalíticas de proteínas e a identificação das propriedades físico-químicas consideradas essenciais para a interação adequada entre ligante e biomacromolécula-alvo. Por outro lado, permitem também a identificação de alvos a partir da comparação de estruturas químicas, com as propriedades físico-químicas associadas, entre ligantes conhecidos e possíveis alvos; este procedimento de comparação de perfis moleculares, conhecido como virtual profiling, parte do princípio de que moléculas semelhantes a ligantes conhecidos de proteínas têm o potencial de interagir com essa mesma proteína, onde o grau de semelhança é determinado não somente pela estrutura química, mas também pela distribuição de características físico-químicas. As ferramentas utilizadas em estudos in silico incluem também análise de descritores topológicos que permitem a caracterização de propriedades físico-químicas considerando sua distribuição espacial em relação à estrutura química de uma dada molécula. O uso destes descritores permite a determinação do grau de semelhança entre moléculas ou partes de moléculas (fragmentos moleculares), e encontra-se na base das metodologias de triagem e de caracterização de sítios catalíticos de proteínas. Dentro da proposta de trabalho foram realizados estudos envolvendo virtual profiling, análise de fragmentos moleculares com base em descritores físico-químicos capazes de caracterizar superfícies de proteínas e ligantes, caracterização de cavidade catalítica de possível alvo e docking dos compostos a alvos putativos. Foi também realizada a determinação de atividade antifúngica e análise de resultados de QSAR 3D, levando finalmente à construção de uma hipótese quanto ao possível alvo biológico para os compostos azometínicos e oxadiazolínicos. O procedimento de virtual profiling apontou como possíveis alvos as enzimas CYP19A (aromatase), CYP3A4, CYP3A5 e CYP3A7. Embora estas enzimas não estejam diretamente envolvidas com as atividades biológicas testadas para os compostos até o momento, existem estudos que demonstram a interação de compostos azólicos de ação antifúngica, cujo alvo é CYP51 (14α-desmetilase), também com CYP19A e CYP3A4. Em conjunto com a análise da caracterização das propriedades físico-químicas com uso de descritores topológicos e a própria dualidade da atividade biológica, concluiu-se que seria possível a interação dos compostos das séries estudadas com CYP51, sendo esta enzima alvo não somente de antifúngicos azólicos, como também de compostos com ação anti-T. cruzi. A caracterização da cavidade catalítica de CYP51, tanto em termos de descritores de propriedades físico-químicas como de características estereoquímicas, associada ao estudos de QSAR 3D, confirmaram a possibilidade de interação da série oxadiazolínica com a CYP51, em orientação semelhante à dos antifúngicos azólicos. A série azometínica, que apresenta a mesma atividade dual da série oxadiazolínica, embora com potências diferentes, não possui conformação adequada para a interação da forma proposta. Existem, no entanto, dados que indicam a possibilidade de interação de compostos no sítio catalítico da enzima de forma diferente em relação a compostos oxadiazolínicos e antifúngicos azólicos.This study had as objective the study of Tridimensional Quantitative Structure-Activity Relationships, 3D QSAR, and the identification of potential targets for 5-nitro-heterocyclic compounds with azomethynic or oxadiazolynic structures presenting dual antifungal and anti-T. cruzi bioactivity, aiming the discovery of new compounds to be used as possible drug candidates or lead compounds. The studied compounds belong to four closely related series: AzoO series: 4-substituted 5-nitro-2-furfurylidene benzhydrazides; AzoS Series: 4-substituted 5-nitro-2-thiophylidene benzhydrazides; OxaO Series: 4-substituted 3-acetyl-oxadiazolyne 2,5-furfurylidene benzhydrazides; and OxaS Series: 4-substituted 3-acetyl-oxadiazolyne 2,5-thiophilydene benzhydrazides. The integrated use of tools belonging to the areas of medicinal chemistry, chemoinformatics, and bioinformatics allow for the characterization of catalytic cavities of proteins and the identification of physicochemical properties considered essential for the adequate interaction between ligand and target biomacromolecule. In addition to this, they also make possible the identification of targets through the comparison of chemical structures, with their associated physicochemical properties, of known ligands and their possible targets; this approach, known as virtual profiling, is based on the principle that molecules similar to known ligands of proteins can potentially interact with this same protein, with the similarity degree being determined not only by chemical structure but also through the distribution of physicochemical characteristics. The tools used in studies in silico also include the analysis of topological descriptors that can be used to analyse physicochemical characteristics considering their spacial distribution in relation to the chemical structure of a given molecule. The use of these descriptors makes possible the determination of the similarity degree between molecules or part of molecules (molecular fragments), and is the basis for methodologies of screening and characterization of the catalytic sites or proteins. Considering the proposed objective, studies were carried involving virtual profiling, analysis of molecular fragments based on physicochemical descriptors able to characterize the surface of ligands and proteins, characterization of the catalytic site of a possible target, and docking of the compounds to putative targets. The antifungal activity of compounds was determined and 3D QSAR results analysed, leading to the formulation of a hypothesis for the possible biological target for the azomethynic and oxadiazolynic compounds. Virtual profiling results pointed as possible targets the P450 enzymes CYP19A (aromatase), CYP3A4, CYP3A5, and CYP3A7. Although these enzymes are not directly involved with the currently tested biological activities for these compounds, there are studies reporting the interaction of azole antifungal compounds, whose target is CYP51 (14α-demethylase), with CYP19A and CYP3A4. Taken together with the analysis of physicochemical characteristics based on topological descriptors, and considering the duality of determined biological activities, it was concluded that the interaction of the studied compounds with CYP51 was possible since this enzyme is the target nor only for azole antifungals, but also for anti-T. cruzi compounds. Characterization studies of CYP51 catalytic cavity considering not only physicochemical properties descriptors but also stereochemical characteristics, associated to the results of 3D QSAR, confirmed the possibility of interaction of compounds from the oxadiazolynic series with CYP51, in an orientation similar to azole antifungals. The azomethynic series, that also presents the same dual biological activity though with different potency, does not present an adequate conformation for the ineraction proposed for the oxadiazolynic series; however, there are reports indicating the possibility of interaction of compounds in the catalytic site of the enzyme in a different way from that of antifungal azoles and the proposed interaction of oxadiazolynic compounds.
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Oliveira, Karen Fantine Silva Souza de. "Os acidentes de trabalho e os valores humanos em operadores de uma f?brica de cal?ados." Universidade Federal do Rio Grande do Norte, 2004. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17497.
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Previous issue date: 2004-09-13The study present analyzes the relation between work accident and human values. It was developed with the sample of 156 operators of a factory, through to an application of structured questionnaires. The data were submitted to quantitative analyses (for example, analyses of frequency distributions, Chi-Square, test t). It was verified that 27 employees that filled out the questionnaires suffered work accidents. The results evidence that there aren?t significant differences between the people s values that suffered work accidents and those that did not suffer. The employees presented a hierarchy of different values comparing with the others Brazilian studies. It was observed that the work accidents varies for organizational sectors. So, we get the conclusion, the occurrence of the work accidents is not associated to the values, but they are probably associated to work conditions
O presente estudo analisa a rela??o entre os acidentes de trabalho e os valores humanos. Foi desenvolvido com uma amostra de 156 operadores de uma f?brica, atrav?s da aplica??o de question?rios estruturados. Os dados foram submetidos a an?lises quantitativas (por exemplo, an?lises das distribui??es de freq??ncia, teste t e qui-quadrado). Verificou-se que 27 funcion?rios que preencheram os question?rios sofreram acidentes de trabalho. Os resultados apontam que n?o h? diferen?as significativas entre os valores daqueles que sofreram acidentes e os que n?o sofreram. Os participantes apresentaram uma hierarquia de valores diferente de outras amostras pesquisadas nos Brasil. Constataram-se diferen?as de freq??ncia de acidentes por setores da empresa. Verificou-se, ent?o, que, a ocorr?ncia dos acidentes de trabalho n?o est? associada aos valores, mas mais provavelmente ?s condi??es de trabalho
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Taha, Hanafi Omneya [Verfasser]. "Electrophysiological characterization of Na+ and T-type Ca2+ channel alterations and their impact on action potential generation in rodent models of neuropathic pain / Omneya Taha Hanafi." Bonn : Universitäts- und Landesbibliothek Bonn, 2014. http://d-nb.info/1080561129/34.
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Adelstrand, Carl, and Emil Brostedt. "Creating Competitive Advantage by Rethinking B2B Software Pricing." Thesis, KTH, Industriell marknadsföring, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-188510.
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The choice of pricing model for software products is a complex procedure due to the different characteristics compared to physical products. This thesis investigates and compares software pricing models in a B2B setting, and describes how KAM plays a role in executing a pricing model. The research has been conducted as an opportunist case study on Adebro, a technology company in the B2B sector. The thesis have come to the following conclusions, with data from interviews and literature: Perpetual license is, and will continue to be, an attractive pricing model for Adebro. However, a subscription-based usage independent pricing model is also attractive for the future. Implications of switching pricing model would be largest when changing between a perpetual and subscription model, where revenue will have the most visual impact. The most important task for KAM is to communicate the change to current and new customers. KAM and the pricing model must also be structured to support each other to be successful. The thesis contributes to science by providing research on pricing models for manufacturing related software. However, studies concerning the weighting of importance for different pricing parameters would be of interest for the future.
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Ratliff-Rang, Christine Annette. "The Hypercapnic Ventilatory Response and Behavior in Ca2+-Activated K+ (BK) Channel Knock Out Mice And T-Cell Death-Associated Gene 8 (TDAG8) Receptor Knock Out Mice." Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1491907677483129.
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Pereira, Maria N?bia Gomes de Lucena. "Avalia??o da aprendizagem no Curso T?cnico em Agroind?stria, no IFCE- Campus Iguatu, atrav?s do desenvolvimento de atividades em um projeto de pesquisa com umbu-caj?" Universidade Federal Rural do Rio de Janeiro, 2010. https://tede.ufrrj.br/jspui/handle/jspui/2350.
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This work has analyzed the contribution of the development of activities of a research project applied in the teaching-learning process, hoping that the students of the Technical Course in Agroindustry of the Federal Institute of Education, Science and Technology ? Campus Iguatu, in the class of fruits and vegetables processing as active agents, comprehend and solidify their knowledge. In that sense, students of the Technical Course in Agroindustry produced teaching materials that could be used for the capacity of the producers of Vila Cajazeiras, with formulation techniques that could assemble value to the fruit of umbucaj? (Spondias sp). To evaluate the pedagogical process, two groups of 16 students have been created. The first group consisted of students from the Technical Course in Agroindustry with the curriculum in the integrated course (test group) and the second, students from the Technical Course in Agroindustry with the curriculum in the modulated course (control group). These students had already taken the class of fruits and vegetables processing the semester before. The evaluation method used was to evaluate the attitude of the individual, building a questionnaire about the umbu-caj? fruit with affirmatives referent to the necessary concepts and knowledge to comprehend these steps. This instrument has been applied in three different steps. For the control group, the instrument has been applied only once. In the extension activity, 16 people from the community have participated. The students were evaluated by the producers that participated in the extension activity. The processed product, nectar of umbu-caj?, has been evaluated referencing the physical-chemical, sensorial and microbiological parameters. In the physical-chemical determinations, the current legislation has been used to compare the results. In the sensorial evaluations, accepting tests have been used. As for the teaching-learning process, it has been observed that the test scores for each subject have been gradually rising as the learning would materialize, reaching the final test with more homogeneous answers. The medium scores were 4,8; 5,2 and 6,9 for T1, T2 and T3, respectively. As the students were being inserted in the context of the contemplated units of the class, it has been noted that the developed activities contributed to elevate their knowledge. In the control group the learning level was lower than in the test group. The results of the second group (control group) indicate that the students of the first group (test group) obtained higher comprehension of the proposed activities in this project, making this student search for interdisciplinary, produce his own learning, establish non-traditional pedagogical relations and learn new methods to assimilate new information and processing technologies of the umbu-caj? fruit, to better support its proposed work. Therefore, this work was important to link the student to the researching world, making him an active agent of all the process, assigning him with responsibility and making it possible for him to create different ways of constructing his own knowledge.
O presente trabalho analisou a contribui??o do desenvolvimento de atividades de um projeto de pesquisa aplicado no processo de ensino-aprendizagem, esperando-se que os estudantes do Curso T?cnico em Agroind?stria do Instituto Federal de Educa??o, Ci?ncia e Tecnologia - Campus Iguatu, da disciplina de processamento de frutos e hortali?as, como agentes ativos, compreendessem e solidificassem o conhecimento. Nesse sentido, estudantes do Curso T?cnico em agroind?stria produziram o material did?tico que pudesse ser utilizado para a capacita??o dos produtores da Vila Cajazeiras, com t?cnicas de formula??es para que eles pudessem agregar valor ao fruto do umbu-caj? (Spondias sp). Para avaliar o processo pedag?gico, foram constitu?dos dois grupos de 16 estudantes, sendo o primeiro do Curso T?cnico em Agroind?stria da matriz curricular do Curso integrado (Grupo Teste) e o segundo, por alunos do Curso T?cnico em Agroind?stria da matriz curricular do curso modulado (Grupo Controle). Esses alunos j? haviam cursado a disciplina de processamento de frutos e hortali?as no semestre anterior. Utilizou-se o m?todo de avalia??o de atitude do indiv?duo construindo-se question?rio relativo ao fruto do umbu-caj? com afirmativas referentes aos conceitos e conhecimentos necess?rios para compreender estas etapas. Esse instrumento foi aplicado em tr?s etapas diferentes. Para o Grupo controle, o instrumento foi aplicado apenas uma vez. Na atividade de extens?o participaram 16 pessoas da comunidade. Os alunos foram avaliados pelos produtores que participaram da atividade de extens?o. O produto processado, n?ctar de umbu-caj?, foi avaliado em rela??o aos par?metros f?sico-qu?micos, sensoriais e microbiol?gicos. Nas determina??es f?sico-qu?micas, para comparar os resultados, utilizou-se a legisla??o vigente. Nas avalia??es sensoriais, utilizaram-se testes de aceita??o. Quanto ao processo de ensino-aprendizagem, verificou-se que a m?dia para cada sujeito foi aumentando gradativamente nos testes, ? medida que a aprendizagem se concretizava, chegando ao ?ltimo teste com uma maior homogeneidade nas respostas, cujas m?dias foram 4,8; 5,2 e 6,9 para T1, T2 e T3, respectivamente. Na medida em que os alunos foram sendo inseridos no contexto das unidades contempladas na disciplina, verificou-se que as atividades desenvolvidas contribu?ram para elevar seu n?vel de conhecimento. O Grupo Controle o n?vel de aprendizagem foi menor do que no grupo teste. Os resultados obtidos no segundo grupo (grupo controle) indicaram que os estudantes do primeiro grupo (grupo teste) obtiveram melhor compreens?o das atividades propostas neste projeto, proporcionando a esse aluno buscar a interdisciplinaridade, produzir seus pr?prios conhecimentos, estabelecer rela??es pedag?gicas n?o-tradicionais e aprender outro m?todo para assimilar novos conhecimentos e tecnologias de processamento do fruto de umbu-caj?, para melhor fundamentar a sua proposta de trabalho. Portanto, o trabalho foi importante para vincular o estudante ao mundo da pesquisa, fazendo-o um agente ativo de todo o processo, atribuindo-lhe responsabilidade e possibilitando-lhe um modo diferente de construir seu pr?prio conhecimento.
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Feij?, Thatiane Fernandes de Melo. "Fatores que afetam a satisfa??o e a fidelidade do consumidor: um estudo com usu?rios de cal?ado esportivo (t?nis), na Regi?o Sul da cidade de Natal." Universidade Federal do Rio Grande do Norte, 2008. http://repositorio.ufrn.br:8080/jspui/handle/123456789/14907.
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Previous issue date: 2008-10-29This paper aims to investigate the factors that influence the satisfaction and fidelity of tennis?s users with the region southern city of Natal, capital of Rio Grande do Norte as the area of analyzing , using the national satisfaction index models as a tool to study. In this study was used the questionnaire as a tool for collecting data based on the new Norwegian customer satisfaction barometer model proposed by Johnson et. al. (2001). The data collection took place during the months of May and June 2008, when 450 tennis?s users were interviewed. The main results obtained by multiple regression analysis and logistic regression showed that the users' satisfaction with the tennis?s brand is influenced by the quality, comfort, material used in the manufacture and price, while fidelity is potentized by the image of the brand and the satisfaction degree with the user's tennis and with the brand of tennis. In relation to user satisfaction with the tennis, that satisfaction is influenced by the quality, comfort, weight and the material used, while fidelity is potentized by the satisfaction with the tennis?s brand, with the possibility of paying the same amount again and the emotional commitment. As the processing of claims there was no direct influence on satisfaction and consumers fidelity due to the low number complaints
Este trabalho tem como objetivo investigar os fatores que influenciam a satisfa??o e a fideliza??o dos usu?rios de t?nis tendo como ?rea de analise a regi?o sul da cidade de Natal, capital do Rio Grande do Norte, utilizando-se como ferramenta de estudo os modelos nacionais de ?ndice de satisfa??o. No presente trabalho foi utilizado o question?rio como instrumento de coletas de dados baseado no novo modelo Noruegu?s proposto por Johnson et. al. (2001). A coleta de dados ocorreu durante o m?s de maio e junho de 2008, onde foram entrevistados 450 usu?rios de t?nis. Os principais resultados obtidos pela regress?o linear m?ltipla e pela regress?o log?stica, revelam que, a satisfa??o dos usu?rios com a marca do t?nis ? influenciada pela qualidade, conforto, material utilizado na fabrica??o e pelo pre?o, enquanto que a fidelidade ? potencializada pela imagem da marca e pelo grau de satisfa??o do usu?rio com o t?nis e com a marca do t?nis. J? com rela??o ? satisfa??o dos usu?rios com o t?nis, esta satisfa??o ? influenciada pela qualidade, conforto, peso do t?nis e material utilizado, enquanto que a fidelidade ? potencializada pela satisfa??o com a marca do t?nis, com a possibilidade de pagar novamente o mesmo valor e pelo compromisso afetivo. Quanto ao tratamento de reclama??es verificou-se n?o haver influencia direta na satisfa??o e fideliza??o do consumidor devido ao baixo n?mero reclama??es
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Melnitzki, Marcelo Lima. "As regras espirituais s?o t?o exatas e positivas como as das ci?ncias materiais: as representa??es sobre a ci?ncia no Jornal Esp?rita. Porto Alegre, d?cada de 1930." Pontif?cia Universidade Cat?lica do Rio Grande do Sul, 2010. http://tede2.pucrs.br/tede2/handle/tede/2428.
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Previous issue date: 2010-06-25In this thesis we tried to analyze the representations of science articles and editorials in the Journal Spiritist in Porto Alegre, in the 1930s. From the methodology of content analysis (CA) seek to identify the arguments used by newspaper writers to (re) asserting the scientific spiritism, closely linked to how sought to represent his doctrine as a scientific knowledge of the similarity of Sciences accurate. Through this approach we can see that this focus on the spiritual doctrine kept relations with the historical context marked by a strong rationalist bias, and what transpired in the intensive reading of the arguments of members of the newspaper Paul Hecker. Taken as a source / object of study in the Journal Spiritist also allowed a better understanding of the local impact of a broader discussion, linked to the history of Spiritualism in the country, marked by division between scientists and mystics.
Nesta disserta??o procuramos analisar as representa??es sobre a ci?ncia nos artigos e editoriais do Jornal Esp?rita, em Porto Alegre, na d?cada de 1930. A partir da metodologia da An?lise de Conte?do (AC) buscamos identificar os argumentos utilizados pelos articulistas do jornal para (re)afirmar a cientificidade do Espiritismo, estreitamente ligados a forma como procuravam fazer representar a sua doutrina, como um conhecimento cient?fico a semelhan?a das ci?ncias exatas. Atrav?s desta abordagem conseguimos perceber que este enfoque sobre a doutrina esp?rita guardava rela??es com contexto hist?rico marcado por um forte vi?s racionalista, e que transpareceu na leitura intensiva dos argumentos dos colaboradores do jornal de Paulo Hecker. Tomado como fonte/objeto deste estudo o Jornal Esp?rita nos permitiu, tamb?m, uma melhor compreens?o da repercuss?o a n?vel local de uma discuss?o mais ampla, ligada a hist?ria do Espiritismo no pa?s, marcada pela divis?o entre cient?ficos e m?sticos.
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Rosa, Silas Luis Sartori Paschoal da Silva. "Estudo da correlação entre os resultados de testes e a aplicação dos conceitos de Gerenciamento de Projetos para omodelamento matemático da durabilidade de um componente automotivo." Instituto de Matemática, 2012. http://repositorio.ufba.br/ri/handle/ri/21349.
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Existem inúmeras ferramentas para auxliar os engenheiros de CAE no desenvolvimento de novos produtos, como por exemplo: CAD (computer aided design), CAE (computer aided engineering), CAM (computer aided manufacturing), QFD e TRIZ, entre outros. Este trabalho apresenta uma aplicação dos conceitos de gerenciamento de projetos para a simulação computacional da durabilidade virtual afim de auxiliar os profissionais da área de CAE no design de componentes automotivos. Neste trabalho, foram aplicados os conceitos do dFmea para aprimorar os resultados obtidos na utilização dos conceitos do QFD e da TRIZ. Em adicional, serão aplicados os conceitos do diagrama P, matriz morfológica e matriz de Pugh. O método apresentado para aperfeiçoar a durabilidade utiliza a simulação computacional para correlacionar os resultados obtidos com a aplicação das ferramentas de gerenciamento de projetos. Para realizar a simulação computacional foi utilizado o software MSC_Nastran 2004 R2, Sol 103 (modos normais). Apresenta tambem as diferenças entre dois tipos de modelamentos matemáticos utilizando os pontos de fixação da peça avaliada de maneiras diferentes. Por fim, apresenta os resultados dos testes de laboratório, com o objetivo de comprovar a abordagem teórica apresentada nesta dissertação.
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Okom, Camille Inès Alexandra [Verfasser], Detlev [Akademischer Betreuer] [Gutachter] Schild, and André [Gutachter] Fiala. "Structural and functional characterisation of M/T cells using Ca2+ Imaging and Activity Correlation Imaging in dendritic networks of the developing Xenopus brain / Camille Inès Alexandra Okom ; Gutachter: Detlev Schild, André Fiala ; Betreuer: Detlev Schild." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2016. http://d-nb.info/1122348819/34.
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Perez-Rodriguez, Jacqueline. "ROLE OF OXIDATIVE STRESS AND T CELL HOMING IN THE DEVELOPMENT OF MURINE SYNGENEIC GRAFT-VERSUS-HOST DISEASE." UKnowledge, 2009. http://uknowledge.uky.edu/gradschool_diss/804.
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Syngeneic graft-versus-host disease (SGVHD) is induced by reconstituting lethally irradiated mice with syngeneic BM cells followed by a 21 day treatment with the immunosuppressive agent cyclosporine A (CsA). Clinical symptoms of the disease appear 2-3 weeks following cessation of CsA therapy and disease-associated inflammation occurs primarily in the colon and liver.
The development of SGVHD is a complex process resulting from the cooperative interaction of multiple effector cell populations including NK cells, T cells and macrophages. TH1 cytokines (IL-12, TNF-α, IFN- γ), produced by these effector cells, serve as inflammatory mediators contributing to the pathogenesis of SGVHD. The SGVHD conditioning agents, irradiation and CsA, are both required for the development of disease and contribute to the production of oxidative stress. Time course studies revealed increased reactive oxygen and nitrogen species (ROS/RNS), as well as, increased colon mRNA levels for TNF-α and iNOS in CsA-treated versus control BMT animals. Since ROS/RNS are known to mediate CsA toxicity, studies were undertaken to determine the effect of oxidative stress on the induction of SGVHD. In vivo treatment with the antioxidant MnTBAP caused a reduction in colon mRNA levels for iNOS and TNF-α, as well as delayed disease development, suggesting a role for oxidative stress in the development of SGVHD.
In addition, CD4+ T cells have been shown to play an important role in the inflammatory response observed in the gut of SGVHD mice. Time course studies revealed significant increases in the migration of CD4+ T cells as early as day 14 post- BMT into the colon of CsA mice as well as significant elevated mRNA levels of cell adhesion molecules. Homing studies revealed that a labeled CD4+ T cell line, generated from SGVHD mice, migrated in larger numbers into the gut of CsA-treated mice compared to control animals. This study demonstrated that CD4+ T cells responsible for the pathogenesis observed in murine SGVHD are present early after BMT in colons of CsA-treated mice, suggesting that during the 21 days of immunosuppression therapy functional mechanisms are in place that result in increased homing of effector cells to colons of CsA-treated mice.
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Bandeira, Raquel Duarte da Costa Cunha. "Desenvolvimento e valida??o de metodologia na detec??o e quantifica??o de Ocratoxina A no caf? verde e torrado utilizando a t?cnica cromatografia l?quida acoplada a espectrometria de massas aplicando os conceitos da metrologia qu?mica." Universidade Federal Rural do Rio de Janeiro, 2010. https://tede.ufrrj.br/jspui/handle/jspui/2349.
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Coffee is an extremely complex food matrix and has an important role in the world?s economy, especially in producing and exporting countries like Brazil. However this product may suffer from technical barriers imposed for exportation because of the possible presence of ochratoxin A, which is nefrotoxic and carcinogenic mycotoxin found in many foods including coffee. The aim of this study was to implement chemical metrology concepts in the development and validation of Liquid Chromatography with Mass Spectrometry in tandem (CLAE-EM/EM) method for identification and quantification of ochratoxin A in green and roasted coffee estimating uncertainty of measurement according to directive 2002/657/EC and Inmetro guidelines (DOC-CGCRE-2010). The extraction method was based on Pittet (1998) and chromatographic parameters were: flow rate of 0.3 mL/min, mobile phase 80:20 water trifluoracetic acid 0.05 %: methanol trifluoracetic acid 0.05 %, injection volume of 50 PL, injection mode Full loop, isocratic mode. The column was Synergi Hydro C18. The mass spectrometry parameters were optimized and transitions selected based on the colision energies monitored were m/z 404 >358 (-10.5 V) and m/z 404 >239 (-20.5 V). From the validation procedure, methods were considered seletive. The evaluation and verification of matrix effect was performed by comparing variances and averages using F and t test. Value of Fcalculated for green coffee (25.2152) and roasted coffee (104.0353), were higher than Ftable (4.0426). Value of t calculated for green (5.0214) and roasted coffee (10.1997) were higher than ttable (2.0106). Both methods were considered linear in the working range of calibration curve with linear correlation coefficients (r) of 0.98188 and 0.91754 for green and roasted coffee, respectively.The quantification and detection limits were 1.2 Pg/kg and 3.0 Pg/kg; 0.36 Pg/kg and 1.0 Pg/kg, for green and roasted coffee respectively. The average recoveries, RSDr and RSDR were in range of 90.45 ? 108.81 %, 5.39 ? 9.94 % and 2.20 ? 14.34 % for green coffee and 89.02 ? 108.85 %, 2.43 ? 13.73 % and 12.57 ? 17.84 % for roasted coffee. All results obtained were considered within acceptable levels according to literature. Measurement value and expanded uncertainties (U) for ochratoxin A were mass fraction w = (11.50 ? 1.11) and w = (4.63 ? 0.63) for green coffee and roasted coffee. Both methods developed and validated using a high sensitivity technique, that allowed detection, confirmation and quantification of ochratoxin A in green and roasted coffee with a estimated uncertainty of measurement, and in the future these methods can be used to help overcome possible technical barriers imposed for exportation of Brazilian coffee.
O caf? constitui uma matriz extremamente complexa e tem importante papel na economia mundial, especialmente nos pa?ses produtores e exportadores como o Brasil. No entanto tem sido alvo de barreiras t?cnicas devido a uma subst?ncia denominada ocratoxina A, micotoxina potencialmente nefrot?xica e nefrocarcinog?nica encontrada em muitos alimentos inclusive o caf?. O presente trabalho tem como objetivo implantar os conceitos da metrologia qu?mica no desenvolvimento, e valida??o do m?todo para identifica??o e quantifica??o de ocratoxina A no caf? verde e caf? torrado estimando a incerteza da medi??o e utilizando a t?cnica de Cromatografia L?quida acoplada a Espectrometria de Massas em s?rie (CLAE-EM/EM) seguindo os crit?rios da diretiva EC-657/2002 e o documento orientativo do Inmetro (DOCCGCRE- 2010). A metodologia de extra??o baseou-se em Pittet (1998) e os par?metros cromatogr?ficos foram: fluxo de 0,3 mL/min, fase m?vel 80:20 ?gua ?cido trifluoroac?tico 0,05%: metanol ?cido trifluoroac?tico 0,05 %, volume de inje??o de 50 PL, com o modo de inje??o Full loop e sistema de elui??o isocr?tico. A coluna utilizada foi Synergi Hydro C18. As condi??es do espectr?metro de massas foram otimizadas e a transi??o selecionada de acordo com suas energias de colis?o foram m/z 404 >358 (-10,5 V) e m/z 404 >239 (-20,5 V). A partir da valida??o os m?todos propostos foram considerados seletivos, a avalia??o e comprova??o do efeito matriz foi realizada atrav?s da compara??o das vari?ncias e das m?dias atrav?s do teste F e teste t. O Fcalculado para o m?todo caf? verde (25,2152) e caf? torrado (104,0353), apresentaram valores maiores que o Ftabelado (4,0426). O tcalculado para o caf? verde (5,0214) e torrado (10,1997) apresentaram valores superiores ao ttabelado (2,0106). Os m?todos foram considerados lineares em toda a faixa de trabalho da curva de calibra??o com os coeficientes de determina??o linear (r) de 0,98188 e 0,91754 para matriz caf? verde e caf? torrado, respectivamente. O limite de quantifica??o e detec??o para os m?todos propostos foram de 1,2 Pg/kg e 3,0 Pg/kg para caf? verde e 0,36 Pg/kg e 1,0 Pg/kg para caf? torrado. Os valores das recupera??es m?dias, DPRr e DPRR variaram na faixa de 90,45 - 108,81 %, 5,39 - 9,94 % e 2,20 - 14,34 % para caf? verde; e de 89,02 - 108,85 %, de 2,43 - 13,73 % e 12,57 - 17,84 %, para caf? torrado. Todos os resultados obtidos encontram-se dentro dos limites comumente aceit?veis na literatura. Todos os resultados de medi??o e as incertezas expandidas (U) para ocratoxina A foram as fra??es m?ssicas W = (11,50 ? 1,11) Pg/kg e W = (4,63 ? 0,63) Pg/kg para caf? verde e caf? torrado, respectivamente. Os m?todos desenvolvidos e validados utilizaram t?cnica de elevada sensibilidade, permitindo a detec??o, confirma??o e a quantifica??o de ocratoxina A no caf? verde e caf? torrado com c?lculo da incerteza, podendo auxiliar futuramente na supera??o das barreiras t?cnicas para exporta??o do caf? brasileiro.
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Rong, Yiping. "Bcl-2 Regulates Proapoptotic Calcium Signals by Interacting with the Inositol 1, 4, 5-Trisphosphate Receptor." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1228322705.
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Edin, Sofia. "Calmodulin mediated regulation of NF-kappaB in lymphocytes." Doctoral thesis, Umeå : Univ, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1895.
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Gonçalves, Fabricio Mota. "Evapotranspiração e coeficientes de cultivo (KC) da cana-de-açúcar irrigada por gotejamento subsuperficial." reponame:Repositório Institucional da UFC, 2010. http://www.repositorio.ufc.br/handle/riufc/18596.
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GONÇALVES, Fabricio Mota. Evapotranspiração e coeficientes de cultivo (KC) da cana-de-açúcar irrigada por gotejamento subsuperficial. 2010. 64 f. Dissertação (Mestrado em engenharia agrícola)- Universidade Federal do Ceará, Fortaleza-CE, 2010.Submitted by Elineudson Ribeiro (elineudsonr@gmail.com) on 2016-06-21T18:44:18Z No. of bitstreams: 1 2010_dis_fmgoncalves.pdf: 3909193 bytes, checksum: b818df330f21fcd52b71e61d84782c03 (MD5)
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Sugar cane is one of the crops with the highest level of water consumption, with a high evapotranspiration demand throughout most of its cycle. Knowledge of the sugar cane water demand, the time that irrigation should be applied, and how to irrigate the crop are becoming increasingly important for the sustainable development of irrigated sugar cane cultivation, especially in areas of low water availability, as it is the case in northea stern Brazil. The experiment was carried out at the Curu Experimental Field (property of the Embrapa Tropical Agroindustry), located in the Curu-Paraipaba Irrig ation Project, city of Paraipaba-CE (3 ° 29 '20''S, 39 ° 9' 45''W and elevation 30m), in order to determine the evapotrans piration and crop coefficients (Kc) of sugarcane (Saccharum L. officinarium), subsurface drip-irrigated. It was used the SP 6949 sugar cane variety, planted in a spacing of 1.8 m between double rows and 0.4 m between rows within the double row. As to t he irrigation, we used one lateral water line for each double row, buried at a depth of 0.15 m, w ith self-compensating drip emitters, with a flow rate of 1 L h-1, spaced 0.5 m on the water line. The crop was irrigated daily and there were three fertigations per week. The irrigation de pth was periodically adjusted, keeping the soil water potential between -8 kPa to -20 kPa. The crop evapotranspiration (ETc) was determined using a wei ghing lysimeter with a surface area of 2.25 m 2. The reference evapotranspiration (ETo) was estimated by the FAO Penman-Monteith method. The durations of the phenological stages of cane sugar were estimated through analysis of soil cover, with the use of digital images. Durations of 31, 49, 237 and 118 days were observed, respectively for initial, crop development, mid-season and late season stages. The yields achieved within and outside the lysimeter were respectively 144.4 and 108.8 t ha -1 . The total ETc observed during the cycle of the sugar cane was 1074.1 m m, with maximum values of 6.6 mm d-1 during the mid-season stage. Observed Kc values for initial, mid-season and late season stages were respectively 0.23, 1 .03 and 0.50. In the crop development stage, the relationship between Kc and the (crop) soil cover was represented with good accuracy by a negative quadratic model.
A cana-de-açúcar é uma das culturas com maior consumo de água, apresentando uma alta demanda evapotranspirativa ao longo da maior parte do seu ciclo. O conhecimento das necessidades hídricas da cana-de-açúcar, do momento de aplicação da água requerida pela mesma e a forma de aplicação torna-se cada vez mais importante para o desenvolvimento sustentável da sua produção irrigada, principalmente em regiões de pouca disponibilidade hídrica, como é o caso da região Nordeste do Brasil. O experimento foi conduzido no Campo Experimental do Curu, pertencente à Embrapa Agroindústria Tropical localizado no Perímetro Irrigado Curu-Paraipaba, município de Paraipaba-CE (3° 29’ 20’’ S, 39° 9’ 45’’ W e altitude de 30 m), com o objetivo de determinar a evapotranspiração e os coeficientes de cultivo (Kc) da cana-de-açúcar (Saccharum officinarium L.), irrigada por gotejamento subsuperficial. Utilizou-se a variedade de cana SP 6949, plantada no espaçamento de 1,8 m entre fileiras duplas e 0,4 m entre linhas dentro da fileira dupla. Na irrigação utilizou-se uma linha lateral para cada fileira dupla, enterrada na profundidade de 0,15 m, com gotejadores autocompensantes, com vazão de 1 L h-1, espaçados de 0,5 m na linha. A cultura foi irrigada com freqüência diária e foram realizadas três fertirrigações por semana. A lâmina de irrigação foi ajustada periodicamente, mantendo-se o potencial de água no solo entre -8 kPa e -20 kPa. A evapotranspiração da cultura (ETc) foi determinada utilizando-se um lisímetro de pesagem com área superficial de 2,25 m2. A evapotranspiração de referência (ETo) foi estimada pelo método FAO Penman-Monteith. As durações das fases fenológicas da cana-de-açúcar foram estimadas por meio da análise da cobertura do solo pela cultura, determinada com o uso de imagens digitais. Foram observadas durações de 31, 49, 237 e 118 dias, para as fases inicial, de desenvolvimento, intermediária e final, respectivamente. A produtividade alcançada dentro e fora do lisímetro foi de 144,4 e 108,8 t ha-1, respectivamente. A ETc total observada durante o ciclo da cana-de-açúcar foi de 1.074,1 mm, com valores máximos da ordem de 6,6 mm d-1 durante a fase intermediária. Foram observados valores de Kc iguais a 0,23, 1,03 e 0,50, para as fases inicial, intermediária e final, respectivamente. Na fase de desenvolvimento vegetativo a relação entre o Kc e a cobertura do solo pela cultura foi representada com bastante exatidão por um modelo quadrático negativo.
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Hýl, Petr. "Slovinské národní divadlo v Lublani." Master's thesis, Vysoké učení technické v Brně. Fakulta architektury, 2009. http://www.nusl.cz/ntk/nusl-215582.
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"Interoperability of Geometric Dimension & Tolerance Data between CAD Systems through ISO STEP AP 242." Master's thesis, 2016. http://hdl.handle.net/2286/R.I.40224.
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abstract: There is very little in the way of prescriptive procedures to guide designers in tolerance specification. This shortcoming motivated the group at Design Automation Lab to automate tolerancing of mechanical assemblies. GD&T data generated by the Auto-Tolerancing software is semantically represented using a neutral Constraint Tolerance Feature (CTF) graph file format that is consistent with the ASME Y14.5 standard and the ISO STEP Part 21 file. The primary objective of this research is to communicate GD&T information from the CTF file to a neutral machine readable format. The latest STEP AP 242 (ISO 10303-242) “Managed model based 3D engineering“ aims to support smart manufacturing by capturing semantic Product Manufacturing Information (PMI) within the 3D model and also helping with long-term archiving of the product information. In line with the recommended practices published by CAx Implementor Forum, this research discusses the implementation of CTF to AP 242 translator. The input geometry available in STEP AP 203 format is pre-processed using STEP-NC DLL and 3D InterOp. While the former is initially used to attach persistent IDs to the topological entities in STEP, the latter retains the IDs during translation to ACIS entities for consumption by other modules in the Auto-tolerancing module. The associativity of GD&T available in CTF file to the input geometry is through persistent IDs. C++ libraries used for the translation to STEP AP 242 is provided by StepTools Inc through the STEP-NC DLL. Finally, the output STEP file is tested using available AP 242 readers and shows full conformance with the STEP standard. Using the output AP 242 file, semantic GDT data can now be automatically consumed by downstream applications such as Computer Aided Process Planning (CAPP), Computer Aided Inspection (CAI), Computer Aided Tolerance Systems (CATS) and Coordinate Measuring Machines (CMM).Dissertation/Thesis
Masters Thesis Mechanical Engineering 2016
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Fudge, Daniel. "A CAD-free and a CAD-based geometry control system for aerodynamic shape optimization." 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=94851&T=F.
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Manohararajah, Valavan. "Area optimizations in FPGA architecture and CAD." 2005. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=370927&T=F.
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Peers, C., Jacobo Elies, and N. Gamper. "Novel ways to regulate T-type Ca2+ channels." 2014. http://hdl.handle.net/10454/12203.
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Elies, Jacobo, J. L. Scragg, S. Huang, M. L. Dallas, D. Huang, D. MacDougall, J. P. Boyle, N. Gamper, and C. Peers. "Hydrogen sulfide inhibits Cav3.2 T-type Ca2 channels." 2014. http://hdl.handle.net/10454/12207.
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NoThe importance of H2S as a physiological signaling molecule continues to develop, and ion channels are emerging as a major family of target proteins through which H2S exerts many actions. The purpose of the present study was to investigate its effects on T-type Ca2+ channels. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS (10 μM−1 mM) selectively inhibits Cav3.2 T-type channels heterologously expressed in HEK293 cells, whereas Cav3.1 and Cav3.3 channels were unaffected. The sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ with N,N,N′,N′-tetra-2-picolylethylenediamine prevented channel inhibition by H2S and also reversed H2S inhibition when applied after H2S exposure, suggesting that H2S may act via increasing the affinity of the channel for extracellular Zn2+ binding. Inhibition of native T-type channels in 3 cell lines correlated with expression of Cav3.2 and not Cav3.1 channels. Notably, H2S also inhibited native T-type (primarily Cav3.2) channels in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2, and suggest that such modulation cannot account for the pronociceptive effects of this gasotransmitter.
This work was supported by the British Heart Foundation, the Medical Research Council, and the Hebei Medical University
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Mangassarian, Hratch. "Pseudo-Boolean satisfiability and quantified Boolean formulas in CAD for VLSI." 2008. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=772091&T=F.
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Yeh, Szu-En, and 葉思恩. "Simulation studies of T +T− feedback control on cardiac alternans in Ca2+ coupled model." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/efeeqw.
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碩士國立中央大學
生物物理研究所
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Nowadays, sudden cardiac (SCD) death is one of top 10 causes of death. Most of them, such as ventricular fibrillation (VF), have a dynamical origin. For example, Ventricular fibrillation has been described as ”chaotic asynchronous fractionated activity of the heart”. According to the non-linear dynamics, that cardiac dynamic would undergo period doubling alternans before getting into chaos. As a result, we could try to reduce the alternans in order to avoid VF. We use single cell and 1-dimension fiber Shiferaw-Fox model, with APD-calcium coupling, to simulate the dynamics of heartbeat and the T +T− feedback control to suppress cardiac alternans. According to the result of our simulations, we found some relationships among basic cycle length, control fraction and critical control strength, and these findings could improve our control to avoid SCD.
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Elies, Jacobo, J. L. Scragg, M. L. Dallas, D. Huang, S. Huang, J. P. Boyle, N. Gamper, and C. Peers. "Inhibition of T-type Ca2+ channels by hydrogen sulfide." 2015. http://hdl.handle.net/10454/12224.
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NoT-type Ca2+ channels are a distinct family of low voltage-activated Ca2+ channels which serve many roles in different tissues. Several studies have implicated them, for example, in the adaptive responses to chronic hypoxia in the cardiovascular and endocrine systems. Hydrogen sulfide (H2S) was more recently discovered as an important signalling molecule involved in many functions, including O2 sensing. Since ion channels are emerging as an important family of target proteins for modulation by H2S, and both T-type Ca2+ channels and H2S are involved in cellular responses to hypoxia, we have investigated whether recombinant and native T-type Ca2+ channels are a target for modulation by H2S. Using patch-clamp electrophysiology, we demonstrate that the H2S donor, NaHS, selectively inhibits Cav3.2 T-type Ca2+ channels heterologously expressed in HEK293 cells, whilst Cav3.1 and Cav3.3 channels were unaffected. Sensitivity of Cav3.2 channels to H2S required the presence of the redox-sensitive extracellular residue H191, which is also required for tonic binding of Zn2+ to this channel. Chelation of Zn2+ using TPEN prevented channel inhibition by H2S. H2S also selectively inhibited native T-type channels (primarily Cav3.2) in sensory dorsal root ganglion neurons. Our data demonstrate a novel target for H2S regulation, the T-type Ca2+ channel Cav3.2. Results have important implications for the proposed pro-nociceptive effects of this gasotransmitter. Implications for the control of cellular responses to hypoxia await further study.
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Elies, Jacobo, E. Johnson, J. P. Boyle, J. L. Scragg, and C. Peers. "H2S does not regulate proliferation via T-type Ca2+ channels." 2015. http://hdl.handle.net/10454/12205.
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NoT-type Ca2+ channels (Cav3.1, 3.2 and 3.3) strongly influence proliferation of various cell types, including vascular smooth muscle cells (VSMCs) and certain cancers. We have recently shown that the gasotransmitter carbon monoxide (CO) inhibits T-type Ca2+ channels and, in so doing, attenuates proliferation of VSMC. We have also shown that the T-type Ca2+ channel Cav3.2 is selectively inhibited by hydrogen sulfide (H2S) whilst the other channel isoforms (Cav3.1 and Cav3.3) are unaffected. Here, we explored whether inhibition of Cav3.2 by H2S could account for the anti-proliferative effects of this gasotransmitter. H2S suppressed proliferation in HEK293 cells expressing Cav3.2, as predicted by our previous observations. However, H2S was similarly effective in suppressing proliferation in wild type (non-transfected) HEK293 cells and those expressing the H2S insensitive channel, Cav3.1. Further studies demonstrated that T-type Ca2+ channels in the smooth muscle cell line A7r5 and in human coronary VSMCs strongly influenced proliferation. In both cell types, H2S caused a concentration-dependent inhibition of proliferation, yet by far the dominant T-type Ca2+ channel isoform was the H2S-insensitive channel, Cav3.1. Our data indicate that inhibition of T-type Ca2+ channel-mediated proliferation by H2S is independent of the channels’ sensitivity to H2S.
This work was supported by the British Heart Foundation (PG/11/84/29146).