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1
Dugan, Aisling Siobhan. „The interactions between BK virus and host cell receptors“. View abstract/electronic edition; access limited to Brown University users, 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3318311.
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2
Floyd, Hayley. „Cobalt, chromium implant wear : investigating interactions between products and the local environment and presenting an approach for mapping tissues“. Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8366/.
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Modern cobalt-chromium (CoCr) alloy compositions, for hip implants, were developed to resist the issues of wear and corrosion; however they still succumb to degradation. While the literature is vast, there is still a lack of understanding of the variability in implant-metal derivatives generated, and the effect such products can have on biological components other than just cells. In this thesis the effect of Co ions on type I collagen (main component of the extracellular matrix) was investigated. The conformation of the triple-helix was maintained, however the time taken for fibril formation to complete increased with Co concentration. In addition, with increasing Co, the collagen matrix became more heterogeneous and cellular attachment and proliferation was reduced. It is likely that Co ions are interacting with a C-O (hydroxyl) group. An overlooked population of degradation products was also investigated. They were found to be highly dependent upon the local environment. Media composition resulted in changes to the morphology, while pH directed the initiation of precipitation. A pH < 5 resulted in no observed pellet. In addition, the presence of Co ions in the media resulted in a change of Cr speciation. Finally, an approach is presented for sub-micron (600nm) x-ray absorption near edge spectroscopy (XANES) mapping of ex vivo tissue. Sub-micron XANES maps contained at least 4 spectra, determined through principal component analysis and clustering. A 5x5 pixel region was averaged for comparison to the 3μm beam approach. Both spectra contained similar features representative of chromium phosphate suggesting that XANES with a micron-sized beam (standard approach) cannot represent the full chemical variability present within the tissue.
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Monnot, Pauline. „Rôle des interactions mécaniques entre tissus dans la mise en place du circuit olfactif du poisson-zèbre“. Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS113.
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Alors que les signaux biochimiques impliqués dans la croissance axonale et la migration neuronale sont largement étudiés, la contribution des signaux mécaniques dans la formation des circuits neuronaux reste peu explorée in vivo. Nous cherchons à étudier comment les forces mécaniques contribuent à la formation du circuit olfactif du poisson-zèbre. Ce circuit se développe durant la morphogénèse de la placode olfactive (PO), par le mouvement passif des corps cellulaires qui s’éloignent de l’extrémité de leurs axones. Mes travaux de thèse s’intéressent à la contribution mécanique de l’œil, qui se forme sous la PO par des mouvements d’évagination et d’invagination, à cette migration passive des neurones et à l’extension de leurs axones. L'analyse quantitative des mouvements cellulaires a tout d’abord révélé que les mouvements des cellules de la PO et de l’œil sont corrélés. Chez des embryons dans lesquels l’œil ne se développe pas, les mouvements des cellules de la PO sont affectés, ce qui produit des PO plus fines et des axones plus courts, et la tension mécanique dans la direction d’élongation des axones dans la PO est réduite. Enfin, la matrice extracellulaire s’accumule à l’interface oeil/PO et sa dégradation enzymatique réduit la corrélation entre les mouvements des cellules de la PO et de l’œil. Ces résultats suggèrent que l’œil en formation exerce des forces de traction sur la PO, transmises par la matrice, entrainant le mouvement des neurones et l’extension des axones. Ce travail apporte un éclairage nouveau sur le rôle des forces mécaniques échangées entre les neurones en développement et les tissus environnants dans la formation des circuits neuronaux in vivoWhereas the biochemical signals guiding axon growth and neuronal migration are extensively studied, the contribution of mechanical cues in neuronal circuit formation is still poorly explored in vivo. We aim at investigating how mechanical forces influence the construction of the zebrafish olfactory circuit. This circuit forms during the morphogenesis of the olfactory placode (OP) by the passive displacement of neuronal cell bodies away from the tip of their axons. My PhD work focuses on the mechanical contribution of the adjacent eye tissue, which develops underneath the OP through extensive evagination and invagination movements, to this passive neuronal migration and to their associated axon elongation. Quantitative live cell imaging analysis during OP morphogenesis first revealed that OP and eye cells undergo correlated movements. In embryos lacking eyes, the movements of OP cell bodies are affected, resulting in thinner placodes and shorter axons, and the mechanical stress along the direction of axon elongation within the OP is reduced. Finally, extracellular matrix was observed to accumulate at the eye/OP interface, and its enzymatic degradation decreased the correlation between OP and eye cell movements. Altogether, these results suggest that the developing eye exerts traction forces on the OP through extracellular matrix, mediating proper neuronal movements and axon extension. This work sheds new light on the role of mechanical forces exchanged between developing neurons and surrounding tissues in the sculpting of neuronal circuits in vivo
4
Hollville, Enzo. „Impact du type de surface sur la réponse à l’exercice : du muscle au mouvement Interactions between fascicles and tendinous tissues in gastrocnemius medialis and vastus lateralis during drop landing How surface properties affect fascicle-tendon interactions during drop landing? Muscle-tendon interactions in jumping: influence of surface properties“. Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCB018.
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Les propriétés des surfaces sportives peuvent impacter directement la performance et le risque de blessure en modulant la part d’énergie transmise à l'athlète lors de l'impact du pied sur la surface. Les pelouses naturelle et synthétique sont couramment utilisées sur les terrains de football et de rugby. Depuis quelques années, une nouvelle génération de pelouse dite naturelle renforcée a fait son apparition dans les clubs professionnels mais son influence sur la biomécanique du geste sportif est encore mal connue. Cette thèse vise à évaluer l'influence de trois types de surfaces (gazon naturel renforcée, gazon synthétique et tartan) sur les interactions muscle-tendon et les coordinations neuromusculaires des muscles gastrocnemius medialis (GM) et vastus lateralis (VL) lors de mouvements de réception uni et bilatérale ainsi que de saut. L’analyse des données échographiques dynamiques, de cinématique 2D et d’activité musculaire nous a permis de montrer que : i) les propriétés mécaniques des surfaces peuvent altérer les interactions entre les faisceaux musculaires et les tissus tendineux ainsi que l’amplitude d’activation musculaire ; ii) la pelouse naturelle renforcée semble avoir des propriétés plus optimales que la pelouse synthétique lors de sauts et réceptions ; iii) il existe des différences de comportement marquées entre le GM et VL qui dépendent du type de surface, du type de mouvement et de son intensité. Cela souligne l’importance de ne pas se limiter à l’étude des propriétés mécaniques des surface pour comprendre leur influence sur le mouvement sportif. Par ailleurs, l’étude des comportements musculo-tendineux in vivo en condition écologique permet de mieux comprendre les interactions complexes entre l’homme et la surfaceSports surface properties can substantially alter the overall performance and risk of injury. Surface mechanical properties influence the loading of the human musculoskeletal system by modulating the amount of foot-impact energy transmitted to the athlete. Natural grass and synthetic turf are commonly used pitches in football and rugby. More recently, reinforced natural grass technology has been used at the elite-level facilities, but its influence on player is not well defined. This thesis aimed at evaluating the influence of three different surfaces (reinforced natural grass, synthetic turf and athletic track) on the muscle-tendon interactions and neuromuscular coordination of gastrocnemius medialis (GM) and vastus lateralis (VL) muscles during landings and jumping tasks. Analysis of dynamic ultrasound imaging, 2D kinematics and electromyographic data showed that: i) surface mechanical properties influenced muscle-tendon interactions as well as the level of muscle activity; ii) the reinforced natural grass surface seems to optimize the muscular response during the movement and iii) GM and VL muscles displayed specific behaviors relative to the type of movement, its intensity and the type of surface. This emphasizes that the human response cannot be predicted by only analyzing the mechanical surface properties and highlights the important role of in vivo ecological testing to better understand player-surface interaction
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Shapero, Kayle Sarah. „Interactions between valvular cells: implications for heart valve tissue engineering“. Thesis, Boston University, 2013. https://hdl.handle.net/2144/11048.
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Thesis (Ph.D.)--Boston UniversityApproximately 1 in 1000 children are born with congenital cardiovascular defects yearly in the US, including many abnormalities in heart valves. Tissue engineered heart valves (TEHVs) offer a solution for replacement or repair of affected valves. However, its therapeutic application is limited, and in ovine models, no TEHV has performed satisfactorily in vivo for longer than twenty weeks, in part due to the absence of supporting data for selection of the appropriate cell type(s) to be incorporated into the construct. This partially owes to the lack of a full understanding of the cells that inhabit the valve, which includes valve interstitial cells (VICs) and valve endothelial cells (VECs), and on the molecular mechanism underlying their interactions that maintain valve homeostasis. During embryonic valve development, the vast majority of VICs are derived from VECs via endothelial to mesenchymal transformation (EMT). EMT in postnatal valves is rare but it has been implicated in diseased valves. Yet, relatively little is known about VECs and VICs in post-natal valves in terms of specialized features, and how VECs and VICs might influence each other. This lack of knowledge has made it difficult to determine what type of cells should be used to create a TEHV. In order to achieve the optimal construction of a tissue engineered heart valve we look to the native valve as our guide for proper valve structure and function. Examination of the native valve leaflets can contribute to our understanding of the proper cellular environment and how disruption of this environment affects the valves. Many common mitral valve pathologies including mitral valve prolapse are characterized by thickening of the valve spongiosa, the presence of activated myofibroblasts, and excessive remodeling of the extracellular matrix. By examining the cell-cell interactions in healthy native valves, and comparing this with observations from pathogenic valves, a greater understanding can be achieved and then applied to the field of TEHV. In this thesis we explored the cell dynamics of the heart valve as related to natural homeostasis, disease progression, and tissue engineering. Using an in vitro co-culture model we revealed a novel two-way communication between mitral valve endothelial and interstitial cells. We propose that this communication promotes a healthy valve phenotype and function by inhibiting EndMT and suppressing VIC activation. We made a similar observation in the aortic valve, where VEC-VIC communication may prevent the process of an EndMT mediated osteogenesis in the context of calcific aortic valve disease. We have also used the VEC-VIC co-culture model to identify possible candidate cell sources for a tissue engineered heart valve. And finally, we show that cells that populated a tissue engineered pulmonary valve leaflet, created using an acellular scaffold, are phenotypically and functionally similar to native valve cells. These studies contribute to an understanding of the dynamics of the cellular interactions between VECs and VICs, and provide a new framework for identifying and testing the functionality of appropriate cell sources for building a TEHV with the ability to grow with the child, maintain homeostasis, and prevent fibrosis and calcification.
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Carlsson, Karin. „Tissue Factor in Complex : Studies of interactions between blood coagulation proteins“. Doctoral thesis, Linköpings universitet, Biokemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-63688.
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Many biological processes rely on specific protein-protein interactions, for example immune responses, cell signaling, transcription, and blood coagulation. Blood coagulation is initiated when a vessel wall is damaged, exposing tissue factor (TF) to the circulating factor VII/factor VIIa (FVII/FVIIa) which results in the formation of the TF:FVIIa complex and thereby the initiation of blood coagulation. One of the substrates for the TF:FVIIa complex is factor X (FX), which is activated to factor Xa (FXa), subsequently leading to a series of reactions resulting in clot formation. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of the sTF:FVIIa complex, involved in regulation of coagulation by forming the TF:FVIIa:FXa:TFPI complex. Occasionally, the blood coagulation mechanism malfunctions, resulting in conditions such as the inability to stop bleeding or thrombosis. The fact that TF is the main initiator of the coagulation makes this an interesting protein to study, in the hunt for means to interfere with players involved in the blood clotting process. Throughout the studies included in this thesis the site-directed labeling technique is utilized to attach spectroscopic probes to cysteines, introduced at specific positions by mutagenesis, in the protein of interest. These fluorescent or spin-probes are sensitive for changes in their immediate environment and can thus, for example be used to monitor protein-protein complex formation and conformational changes. No complete structure has been obtained as yet for the large complex involving sTF, FVIIa, FXa, and TFPI. Therefore, we introduced a fluorescent probe at specific positions in soluble tissue factor (sTF) and the changes in fluorescence emission were detected upon sTF:FVIIa:FXa:TFPI complex formation. From these measurements it was concluded that not only parts of the C-terminal domain of sTF (TF2), but also residues in the N-terminal domain (TF1) are involved in binding to FXa in the quaternary complex. In order to investigate conformational changes occurring in the extended interface between sTF and FVIIa upon binding of different inhibitors spectroscopic probes were introduced in sTF, in the vicinity of the interaction region. From the obtained data it was concluded that the exosite-binding inhibitor E-76 induces equivalent structural changes at the interface of sTF and the protease domain (PD) of FVIIa, as do the active-site inhibitors FFR and TFPI, i.e. makes the region around the active-site more compact. Binding of these inhibitors shows similar effects despite their differences in size, binding site, and inhibitory mechanism. In addition, the Ca2+ dependence of the formation of the sTF:FVIIa complex was studied. Association between sTF and FVIIa during Ca2+ titration begins by Ca2+ binding to the first EGF-like domain of FVIIa. However, Ca2+ saturation of the γ-carboxyglutamic acid-rich (Gla) domain of FVIIa is required for complete sTF:FVIIa complex formation, and we were also able to detect that a Gla domain with vacant Ca2+ sites hinders the docking to sTF. Finally, we investigated the structural changes of free inhibited FVIIa upon sTF and Ca2+ binding by FRET and quenching measurements. From this it was concluded that inhibited FVIIa does not seem to undergo large global structural changes upon binding to sTF, when taking the dynamics of free FVIIa into account. However, Ca2+ binding induces minor local conformational changes in the active-site region of the PD of inhibited FVIIa and subsequent binding of sTF causesfurther structural rearrangements in this area.
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Sim, Richard James. „Characterisation of the interaction between Neisseria meningitidis and the human host“. Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246497.
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Neisseria meningitidis is an important cause of septicaemia and meningitis, yet can be found colonising the nasopharynx of up to 20% of healthy individuals. The aim of my work was to provide detailed characterisation of the cellular location of meningococcal carriage and subsequently select suitable models to investigate the molecular and cellular basis of the mechanisms by which the bacterium interacts with the human upper respiratory tract. This is the fundamental microbial-host interaction underlying the commensalism of Neisseria meningitidis. A survey of meningococcal carriage in tonsillar tissue was undertaken using IHe techniques that detect PorA, a protein unique to Neisseria meningitidis. This showed that carriage rates are higher than those described with nasopharyngeal swabbing, and that the bacterium occupies a site deep to the epithelium in the carrier state. To identify genes that are required to reach sub-epithelial sites, air-interface organ culture models were used to screen bacteria subjected to signature tagged mutagenesis. Ten potentially colonisation deficient mutants were isolated and further analysed. This is the first time that such a screen has been undertaken in tissue of human origin. Additionally, homologues of two genes essential for intracellular survival in Legionella pneumophila (macrophage infectivity potentiator and an unknown virulence protein) were identified in Neisseria meningitidis and mutants containing specific genetic deletions constructed.
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Qui, Lin. „Interaction between vascular endothelial cells and surface textured biomaterials“. Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8854.
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A promising approach to overcome thrombus and neointima formation on vascular grafts is to create a functional, quiescent monolayer of endothelial cells on the surface of implants. Surface topography of these implants is proven to enhance cell attachment and to reduce the inflammation associated with a smooth surface. Photoembossing is a relatively new, simple, environment-friendly and cost-effective technique to create surface topographies, since there is no etching step or mould needed. In this study, photopolymer films are photoembossed through contact mask photoembossing, while fibres are photoembossed through holographic lithography. Surface relief textures of ridges and grooves with various pitch sizes and heights are successfully obtained through both methods. Furthermore, we introduce this technique to fabricate, for the first time, reproducible surface textures on electrospun fibres. Human umbilical vein endothelial cells (HUVECs) are used in the study. Three different systems are investigated: non-degradable PMMA-TPETA, semi-degradable PLGA-TPETA and fully degradable PLGA-PEGDA-DTT, for different applications and therapeutic requirements. Both non-degradable PMMA-TPETA photopolymer and semi-degradable PLGA-TPETA photopolymer are shown to improve biocompatibility compared to PMMA and PLGA, respectively. Photoembossed films made from these two photopolymers show significantly improved cell attachment and proliferation, IV with a water contact angle around 70º. It is shown that the pitch size of surface topographies affects cell adhesion and migration in the wound healing assay study. Interaction between HUVECs and fibres shows that cells grow from their initial locations at fibre crossings. Focal adhesions are seen to be more aggregated on the surface textured fibres, while those on the glass cover slips are more dispersed near the edge of the cell membrane. The appearance of F-actin in the cytoplasm is also seen to be influenced by the surface topography, where changes in the diameter of the fibre and its surface texture result in F-actin rearrangement. Our study shows that a surface textured, fully degradable, gel-like photopolymer PLGA-PEGDA-DTT has great potential to be further developed for tissue engineering applications.
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Aziz, Khalil Abdul. „Influence of GM-CSF and G-CSF on the mutual interactions between platelets and neutrophils“. Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241473.
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10
Hockey, Verity Irena. „Characterising the molecular interaction between tissue factor pathway inhibitor and protein S“. Thesis, Imperial College London, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.530472.
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11
Fisher, Brian T. „Investigation of interactions between the 193-nm argon-fluoride excimer laser and corneal tissue“. [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0008220.
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12
Nixon, Mark. „Interactions between glucocorticoid metabolism and inflammation in obesity and insulin resistance“. Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5593.
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Inflammation plays a key role in the underlying pathogenesis of obesity and its associated health risks, with increased markers of inflammation evident in both liver and adipose tissue. In parallel, there is dysregulation of glucocorticoid metabolism in obesity, with increased adipose levels of the glucocorticoid-regenerating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and increased hepatic levels of 5α-reductase type 1 (5αR1), which catalyses the reduction of glucocorticoids. Both the mechanisms and consequences of this glucocorticoid metabolism dysregulation remain unclear, however, there is evidence that it may be related to inflammation. In vitro studies have demonstrated that pro-inflammatory markers upregulate 11βHSD1 expression in adipocytes, potentially explaining increased expression of this enzyme in obesity. Previous work has also demonstrated that the glucocorticoid metabolites produced by 5αR1 lack the metabolic effects of the parent glucocorticoid, but retain its anti-inflammatory properties, indicating that increased expression of hepatic 5αR1 may serve to dampen down inflammation in the liver. The hypotheses addressed in this thesis are that in obesity, inflammation regulates adipose glucocorticoid metabolism through 11βHSD1, and that hepatic glucocorticoid metabolism regulates the inflammatory state of the liver through 5αR1. The role of inflammation in the regulation of 11βHSD1 was assessed in vivo in mice treated with the anti-inflammatory compound sodium salicylate (salicylate). In diet-induced obese mice, salicylate downregulated 11βHSD1 expression and activity selectively in visceral adipose tissue, alongside improved glucose tolerance, reduced plasma non-esterified fatty acids, and changes in adipose lipid metabolism. 11βHSD1-deficient mice fed a high-fat diet were resistant to the insulin sensitising effects of salicylate treatment. These results indicate a novel role for 11βHSD1 down-regulation in mediating the insulin sensitising effect of anti-inflammatory treatment. The mechanisms underpinning the anti-inflammatory properties of 5α-reduced glucocorticoids were explored in vitro and in vivo. In lipopolysaccharide-stimulated murine macrophages, both 5α-reduced glucocorticoid metabolites tested, namely 5α-dihydrocorticosterone (5αDHB) and 5α-tetrahydrocorticosterone (5αTHB), suppressed tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) release, although to a lesser extent than corticosterone (B). Similar to B, both 5αDHB and 5α THB suppressed phosphorylation of intra-cellular inflammatory signalling mitogen-activated protein kinases (MAPK) proteins c-Jun N-terminal kinase (JNK) and p38, as well as increasing protein expression of MAPK phosphatase-1 (MKP-1). Treatment of phorbol ester-stimulated HEK293 kidney cells with these 5α-metabolites revealed that 5αDHB suppressed nuclear factor κB (NFκB) and activator protein-1 (AP-1) activation to a similar extent to that of B, whilst 5αTHB increased activation of these pro-inflammatory transcription factors, indicating cell-specific effects of 5αTHB. In conclusion, reduced intra-adipose glucocorticoid regeneration by 11βHSD1 mediates the insulin sensitising effects of salicylate, suggesting that altered glucocorticoid metabolism may reflect altered intra-adipose inflammation in obesity. Furthermore, these data support the concept that this enzyme provides a therapeutic target in obesity-related metabolic disorders. 5α-reduced metabolites of glucocorticoids have similar anti-inflammatory properties to the parent glucocorticoid, indicating that the elevated hepatic levels of 5α-reductase in obesity may be a protective mechanism to limit the adverse metabolic effects of glucocorticoids upon the liver, but maintain the beneficial anti-inflammatory properties. These 5α-reduced glucocorticoid metabolites may provide a potential therapeutic treatment as selective glucocorticoid receptor modulators for inflammatory conditions.
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Hsiao, Chan-Chih. „INTERACTION BETWEEN THE METABOLISM OF KETONE BODIES IN BRAIN TISSUE AND NEUROLOGICAL DISORDERS“. Cleveland State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=csu1600291498945814.
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14
Bäck, Karolina. „Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues“. Doctoral thesis, Linköpings universitet, Cellbiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-71892.
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Insulin and insulin-like growth factor I (IGF-I) are two related peptides with similar structure. They mediate their effects by binding to their respective receptor, the insulin receptor (IR) and the IGF-I receptor (IGF-IR) and induce intracellular signalling cascades resulting in metabolic or mitogenic effects. The relative abundance of IR and IGF-IR is of importance for the type of effect that is the outcome of the signal. There are few studies investigating the relative receptor abundance and its effects in human cells and tissues. In this thesis we wanted to study abundance and regulation of insulin and IGF-I receptors in different human cells and tissues and examine the effects of variations in insulin and IGF-I receptor abundance between different cells and tissues. We examined IR and IGF-IR gene and protein expression and the effects of insulin and IGF-I on receptor phosphorylation, DNA synthesis and glucose transport. Our results show that there is a large variation in the distribution of IR and IGF-IR in different human cells and tissues. Renal artery intima-media expressed predominantly IGF-IR while in liver IR was the predominant receptor type. Differentiation of human preadipocytes results in a change in relative expression of IGF-IR to IR. Mature adipocytes express almost 10-fold more IR than IGF-IR while preadipocytes express almost the same amounts of both receptors. Mature tissues, such as liver, skeletal muscle, myometrium and renal artery intima-media, express predominantly IR-B. Preadipocytes express IR-A and the expression of IR-B is induced during differentiation. We could show the presence of insulin/IGF-I hybrid receptors in preadipocytes but not in mature adipocytes. Cultured endothelial cells express mostly IGF-IR and insulin/IGF-I hybrid receptors and these cells respond mainly to IGF-I. Due to the large abundance of IR mature adipocytes are sensitive to insulin but insensitive to IGF-I whereas preadipocytes expressing equal amounts of both receptors respond to both insulin and IGF-I. Insulin and IGF-I are only partial agonists to each other’s receptors in human preadipocytes and adipocytes. The overall results indicate that differential expression of IGF-IR and IR is a key mechanism in regulation of growth and metabolism.
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Toy, William. „Electrophysiological interactions between disopyramide and its major metabolite, mono-N-dealkyldisopyramide, in canine ventricular tissue“. Thesis, McGill University, 1990. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=59865.
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Mono-N-dealkyldisopyramide (MND), the major metabolite of disopyramide, reaches significant concentrations in patients; however, little is known about its electrophysiological effects. We therefore assessed its activity in canine ventricular tissue superfused in vitro. MND produced a concentration and rate dependent increase in the magnitude of V$ sb{ rm max}$ depression. MND shortened all phases of repolarization in Purkinje fibers but prolonged action potential duration and effective refractory period in ventricular muscle.We then assessed the effects of the combination of disopyramide and MND at clinically relevant concentrations. The combination produced additive effects on depression of V$ sb{ rm max}.$ MND accentuated the shortening of action potential duration in Purkinje fibers and the prolongation of refractory periods in both Purkinje fibers and ventricular muscle produced by disopyramide at normal heart rates.
In contrast, at slow stimulation rates and under redisposing electrolyte conditions, disopyramide produced a reverse use-dependent prolongation of action potential duration which led to the development of early afterdepolarizations and triggered activity in Purkinje fibers. Mexiletine and pacing abolished triggered activity, while MND shifted the incidence of triggered activity to longer cycle lengths.
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Kandasamy, Kodi Isparan. „Tissue culture studies on the interactions between the yam anthracnose pathogen and Dioscorea alata L“. Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321759.
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17
Young, Nathan Price. „Tissue-specific interactions between oncogenic K-ras and the p19A̳r̳f̳_p53 pathway determine susceptibility to transformation“. Thesis, Massachusetts Institute of Technology, 2010. http://hdl.handle.net/1721.1/58199.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2010.In title on title page, doubled underscored "Arf" appears as superscript. Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
Tumor development is a multi-step process driven by the collective action of gain-of-function mutations in oncogenes and loss-of-function alterations in tumor suppressor genes. The particular spectrum of mutations in a given cancer is rarely the result of random chance but instead derives from the intimate connections between proliferative networks and those suppressing growth and transformation. Specifically, hyper-active oncogenes directly engage tumor suppressor programs, such that cells harboring oncogenic lesions frequently must acquire secondary mutations that disable these anti-proliferative responses before progressing to overt transformation. This tight coupling represents a critical checkpoint protecting against tumor formation. Whether different cell types exhibit variability in the extent and/or timing of this oncogene-induced tumor suppression is largely unknown. The ability of oncogenic Ras to induce the tumor suppressive p1 9 Arf-p5.3 pathway and cause irreversible cell cycle arrest typifies this phenomenon. Using this-well established interaction as model, we investigated the cell-type specificity of oncogene-induced tumor suppression. By combining K-rasL mice with a reporter for p19Arf expression (Ar FP), we identify a tissue-specific, onocogenic K-ras-dependent expression pattern of 19Arfin lung tumors and sarcomas that correlates with each tissue's genetic requirements for tumorigenesis. Lung tumors, which can arise in the presence of p19Arf and show modest increases in tumor progression in its absence, exhibit very minimal p19 Arf induction. Conversely, sarcomas, which depend on p19 f-p53 mutation for tumor formation, display robust p 1 9 Af up-regulation. While previous studies proposed oncogene levels as the main determinant of p19A induction, we find equivalent signaling levels and instead highlight tissue-specific differences in the epigenetic regulation of Ink4a/Arf Using in vivo RNAi, we implicate Polycomb group (PcG) proteinmediated repression in lung tumors and SWI/SNF-dependent activation in sarcomas as being critically important for each tissue's unique expression pattern of p1 9 Arf During normal tumor progression, mutations in oncogenes and tumor suppressors occur in a sequential fashion, although whether unique orders of mutations dictate distinct phenotypes is unknown. The requirement for complete p53 pathway abrogation during oncogenic K-rasdependent sarcomagenesis suggested that tumor development in the muscle critically depends on early p53 mutation. To test this we generated a Flp-inducible allele of K-rasG12D (K-rasFSF-G12D) that when combined with established reagents for Cre-dependent p53 deletion permits the separate regulation of K-ras activation and p53 loss. Strikingly, although simultaneous mutation results in robust tumor formation, delaying p53 deletion relative to oncogenic K-ras expression
(cont.) significantly diminishes tumor penetrance. This indicates that the tumorigenic capacity of KrasG12D mutant muscle cells is rapidly and severely compromised by a strong p53-dependent response, which is entirely different from the mode of action of p53 during lung tumorigenesis. Further genetic analysis implicates the p53 target gene p21 in this suppression, implying that p53 irreversibly constrains sarcoma development through cell cycle arrest mechanisms. Together, these results highlight tissue-specific variability in the relationship of oncogenic K-ras and the p53 pathway. Robust pathway up-regulation, as seen in muscle cells, affords potent inhibition of tumor initiation, while modest induction, such as in lung cells, permits tumor development and only hinders more advanced stages of progression. These differences might help explain the spectrum of tumors associated with K-Ras mutations as well as the overall frequency of difference cancer types.
by Nathan Price Young.
Ph.D.
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Zhou, Yinghong. „Interactions between undifferentiated and osteogenically differentiated mesenchymal stromal cells during osteogenesis“. Thesis, Queensland University of Technology, 2013. https://eprints.qut.edu.au/63002/1/Yinghong_Zhou_Thesis.pdf.
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The body of work presented in this dissertation has demonstrated that the interactions between donor cells and host cells are critical for bone repair and regeneration. The donor cells secrete VEGF which activates the downstream PI3K/Akt signaling pathway, ultimately leading to host cell recruitment and robust bone regeneration. The findings from this dissertation may provide a scientific rationale for the development of novel therapeutic strategies in the treatment and management of bone defects.
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Schivell, Amanda Elizabeth. „Biochemical and functional characterization of the interaction between the synaptic vesicle proteins SV2 and synaptotagmin /“. Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/10634.
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Ismail, Ayshe. „Interactions between human embryonic stem cell and foetal femur derived cell populations : development of strategies for tissue regeneration“. Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/375470/.
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Mundy, Christina Maria. „The Interaction Between Connective Tissue Growth Factor and Bone Morphogenetic Protein-2 During Osteoblast Differentiation and Function“. Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/269581.
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Cell BiologyPh.D.
Connective tissue growth factor (CTGF/CCN2) and bone morphogenetic protein (BMP)-2 are both produced and secreted by osteoblasts. Both proteins have been shown to have independent effects in regulating osteoblast proliferation, maturation and mineralization. However, how these two proteins interact during osteoblast differentiation remains unknown. In Chapters 2 and 3, we utilized two cell culture model systems, osteoblasts derived from CTGF knockout (KO) mice and osteoblasts infected with an adenovirus, which over-expresses CTGF (Ad-CTGF), to investigate the effects of CTGF and BMP-2 on osteoblast development and function in vitro. To observe differences in osteoblast maturation and mineralization, we performed alkaline phosphatase (ALP) staining and activity and alizarin red staining, respectively. Contrary to a previously published report, osteoblast maturation and mineralization were similar in osteogenic cultures derived from KO and wild type (WT) calvaria in the absence of BMP-2 stimulation. Interestingly, in KO and WT osteoblast cultures stimulated with BMP-2, the KO osteoblast cultures exhibited increased alkaline phosphatase staining and activity and had larger, fused nodules stained with alizarin red than WT osteoblast cultures. This increase in osteoblast differentiation was accompanied by increased protein levels of phosphorylated Smad 1/5/8 and mRNA expression levels of bone morphogenetic protein receptor Ib. These data confirm enhanced osteoblast maturation and mineralization in BMP-2 induced KO osteoblast cultures. We also examined osteoblast differentiation in cultures that were infected with Ad-CTGF and in control cultures. Continuous over-expression of CTGF resulted in decreased ALP staining and activity, alizarin red staining, and mRNA expression of osteoblast markers in both unstimulated and BMP-2 stimulated cultures. Impaired osteoblast differentiation in cultures over-expressing CTGF was accompanied by decreased protein levels of phosphorylated Smad 1/5/8. In addition to the functional assays that we performed on WT and KO osteoblast cultures, we performed ChIP assays to investigate differences in binding occupancy of transcription factors on the Runx2 and Osteocalcin promoters in BMP-2 induced WT and KO osteoblast cultures. We demonstrate that in BMP-2 induced WT and KO osteoblast cultures, there was greater Smad 1 and JunB occupancy on the Runx2 promoter and Runx2 occupancy on the Osteocalcin promoter in BMP-2 induced KO osteoblast cultures compared to WT cultures. Collectively, the data demonstrate that CTGF acts to negatively regulate BMP-2 induced signaling and osteoblast differentiation. In Chapter 4, we synthesized an active His-tagged BMP-2 recombinant protein to track surface binding of BMP-2 in CTGF WT and KO osteoblasts. We amplified mature BMP-2 in genomic DNA, which was inserted correctly into a pET-28b(+) vector. We ran a SDS-PAGE gel and stained with Coomassie blue to show that we successfully induced BMP-2 in bacteria cells, extracted the protein using urea, and purified and eluted the protein using Nickel charged agarose beads and imidazole elution buffer. Furthermore, by Western blot analysis using anti-His antibody, we confirmed the presence of the His-tag on the BMP-2 protein. Lastly, ALP staining on osteoblast cultures stimulated with our synthesized BMP-2 exhibited increased staining compared to the unstimulated osteoblast cultures, which confirmed the activity of our His-tagged BMP-2 protein. Future studies utilizing this protein will demonstrate that CTGF acts as an extracellular antagonist by limiting the amount of BMP-2 available for receptor binding.
Temple University--Theses
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Augustine, Robin. „Electromagnetic modelling of human tissues and its application on the interaction between antenna and human body in the BAN context“. Phd thesis, Université Paris-Est, 2009. http://tel.archives-ouvertes.fr/tel-00499255.
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Les réseaux BAN (Body Area Network) révolutionnent le concept de la surveillance et de la prise en charge à distance de la santé du patient. Le BAN fournit des informations sur l'état de santé du patient en temps réel quelque soit l'endroit où il se trouve. Dans le « télé monitoring », des capteurs de mouvement, de respiration ou du rythme cardiaque placés à l'intérieur ou sur le corps humain transmettent des données via le réseau sans fil constituant le BAN, une antenne étant associée à chaque nœud du réseau. La communication peut être in/on, on/on ou on/off selon que les antennes sont placées à l'intérieur, sur ou à l'extérieur du corps. Le développement des BAN nécessite la réalisation de modèles (ou fantômes) simulant au mieux les propriétés électromagnétiques du corps humain. Des antennes portables, miniaturisées doivent être réalisées avec des contraintes d'intégration d'une part (aux vêtements, à des objets type montre ou badge), des contraintes de résistance ou de prise en compte de l'influence du corps d'autre part. La réduction de l'impact des antennes sur les tissus en terme de SAR (Specific Absorption Rate) doit également être considérée. Dans ce travail, l'objectif est de développer des fantômes valables pour les communications dans et sur le corps. Les matériaux de base sélectionnés sont d'origine biologique (biocéramiques et biopolymères) avec des propriétés proches de celles des tissus humains. Ces fantômes étant biocompatibles, ils sont essentiellement non toxiques alors que les fantômes usuels le sont en général. D'autre part, différents types d'antennes conformables, fonctionnant dans la bande ISM 2.4 GHz ont été développées et étudiées dans la perspective du BAN. Les antennes voient leur adaptation et leur efficacité chuter au contact ou à proximité du corps, ce qui constitue un écueil majeur pour établir une bonne communication. Différentes méthodes permettant de réduire l'influence du corps (plan de masse à l'arrière, surface haute impédance, feuille de ferrite polymère) sont testés et leurs avantages et inconvénients développés. Des mesures de SAR permettent aussi de démontrer l'efficacité de ces méthodes sur la réduction de la puissance absorbée par les tissus. Au final, ce travail apporte une contribution à l'étude théorique et expérimentale de l'interaction entre corps humain et antenne dans le cadre des réseaux BAN appliqués à la télésurveillance de la santé
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Castillo, Yvette S. „DESIGN OF EXPERIMENTATION TO SYSTEMATICALLY DETERMINE THE INTERACTION BETWEEN ELECTROSPINNING VARIABLES AND TO OPTIMIZE THE FIBER DIAMETER OF ELECTROSPUN POLY (D,L-LACTIDE-CO-GLYCOLIDE) SCAFFOLDS FOR TISSUE ENGINEERED CONSTRUCTS“. DigitalCommons@CalPoly, 2012. https://digitalcommons.calpoly.edu/theses/780.
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Cardiac disease causes approximately a third of the deaths in the United States. Furthermore, most of these deaths are due to a condition termed atherosclerosis, which is a buildup of plaque in the coronary arteries, leading to occlusion of normal blood flow to the cardiac muscle. Among the methods to treat the condition, stents are devices that are used to restore normal blood flow in the atherosclerotic arteries. Before advancement can be made to these devices and changes can be tested in live models, a reliable testing method that mimics the environment of the native blood vessel is needed. Dr. Kristen Cardinal developed a tissue engineered blood vessel mimic to test intravascular devices.
Among the scaffolding material used, electrospun poly (lactide-co-glycolide) (PLGA) has been used as an economic option that can be made in house. PLGA is a biodegradable co-polymer, and when electrospun, creates a porous matrix with tailorable properties. Currently, the standard PLGA electrospinning protocol produces consistent fibrous scaffolds with a mean fiber diameter of 5-6 microns. Research indicates that cell adhesion is more successful in fibrous matrices with a mean fiber diameter at the nanometer level. However, because previous work in the Tissue Engineering Laboratory at Cal Poly sought to ensure a consistent fibrous, there was no model or equation to determine how to change the electrospinning parameter settings to create scaffolds with an optimal mean fiber diameter.
To fill this need, biomedical engineering senior Steffi Wong created a design of experiment to systematically approach the electrospinning variables and determine how they interacted with each other, as well as their effect on fiber diameter. The aims of this thesis were to perform the said design of experiments and determine a model to predict the resulting mean fiber diameter of a scaffold based on the electrospinning parameters as well as to determine what combination of parameters would lead to a scaffold with an optimal mean fiber diameter between 100-200 nanometers. The variables tested were solution concentration, gap distance, flow rate, and applied voltage. Each scaffold was imaged and a mean fiber diameter was calculated and used as the predicted variable in a regression analysis, with the variables indicated above as the predictors. The goal of 100-200 nanometer mean fiber diameter was not reached. The smallest mean fiber diameter calculated was 2.74 microns—half of that of the standard protocol. The regression analysis did result in a model to describe how the voltage, gap distance, and flow rate affected the fiber diameter.
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Heyde, Sandrina [Verfasser]. „The role of Leishmania major proliferation for the interaction between the parasite and its tissue environment in vivo / Sandrina Heyde“. Magdeburg : Universitätsbibliothek Otto-von-Guericke-Universität, 2019. http://d-nb.info/1220034843/34.
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Clausson, Carl-Magnus. „Making Visible the Proximity Between Proteins“. Doctoral thesis, Uppsala universitet, Science for Life Laboratory, SciLifeLab, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-217772.
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Genomic DNA is the template of life - the entity which is characterized by a self-sustaining anatomical development, regulated signaling processes, the ability to reproduce and to respond to stimuli. Through what is classically known as the central dogma, the genome is transcribed into mRNA, which in turn is translated into proteins. The proteins take part in most, if not all, cellular processes, and it is by unraveling these processes that we can begin to understand life and disease-causing mechanisms. In vitro and in vivo assays are two levels at which protein communication may be studied, and which permit manipulation and control over the proteins under investigation. But in order to retrieve a representation of the processes as close to reality as possible, in situ analysis may instead be applied as a complement to the other two levels of study. In situ PLA offers the ability to survey protein activity in tissue samples and primary cell lines, at a single cell level, detecting single targets in their natural unperturbed environment. In this thesis new developments of the in situ PLA are described, along with a new technique offering in situ enzyme-free detection of proximity between biomolecules. The dynamic range of in situ PLA has now been increased by several orders of magnitude to cover analogous ranges of protein expression; the output signals have been modified to offer a greater signal-to-noise ratio and to limit false-positive-rates while also extending the dynamic range further; simultaneous detection of multiple protein complexes is now possible; proximity-HCR is presented as a robust and inexpensive enzyme-free assay for protein complex detection. The thesis also covers descriptions on how the techniques may be simultaneously applied, also together with other techniques, for the multiple data-point acquisition required by the emerging realm of systems biology. A future perspective is presented for how much more information may be simultaneously acquired from tissue samples to describe biomolecular interactions in a new manner. This will allow new types of biomarkers and drugs to be discovered, and a new holistic understanding of life.
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Gretenkort, Marie A. „Studies of the expression of the interaction between Leptosphaeria maculans (Desm.) Ces & de Not. and cultured tissue of Brassica napus L. ssp. oleifera (Metzg.) sinsk“. Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317661.
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Altamimy, Raed Adill Hannon. „Interactions between coronary artery endothelial cells and leukocyte MPs shed in response to E. coli lipopolysaccharide : in-vitro and ex-vivo studies of the impact of vascular ageing and of high glucose“. Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ024/document.
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Les microparticules (MP) sont des vésicules de la membrane plasmique émises après stress cellulaire. Nous avons étudié le rôle des MPs leucocytaires extraites de la rate de rats comme marqueur du vieillissement et effecteurs de la senescence et de la dysfonction endothéliales induites par les fortes concentrations de glucose (HG). L’émission basale de MP augmente avec l’âge qui favorise leur génération en réponse au LPS ou au PMA/ionophore A23187 (MPLPS, MPPMA/I). Les MP de rats âgés mais pas de jeunes induisent la sénescence de cellules endothéliales primaires d’artères coronaires (AC) de porc. MPLPS ou MPPMA/I de rats jeunes, mais pas MPCTL (cellules non traitées) réduisent la relaxation dépendante de l’endothélium d’anneaux d’AC en réponse à la bradykinine avec sous-expression de eNOS, surexpression de COX2, ICAM-1, VCAM-1. HG favorise l’émission des MP de rate. Dans les AC en HG, la vasoconstriction en réponse au U46619l est diminuée de manière dépendante du SGLT1/2 et de l’EDHFMicroparticles (MP) are plasma membrane vesicles shed from stimulated cells. We investigated whether leukocyte MP extracted from rat spleen are reliable markers of aging and effectors of high glucose (HG)-induced endothelial senescence and dysfunction. Data indicate that ageing enhances MP shedding from spleen cells of middle-age and aged rats and raises MP release in response to LPS, or to PMA and ionophore A23187. Of note, MP from aged but not young rats induced senescence of porcine coronary artery primary endothelial cells. In young rats, MPLPS, MPPMA/I but not from resting cells (MPCTL) reduced the endothelial-dependent relaxation of coronary artery rings (CAR) in response to bradykinin with down-regulation of eNOS, up-regulation of COX-2, ICAM-1, VCAM-1. HG enhanced early and late MP release from spleen cells. Prolonged exposure to HG potentiated endothelial dysfunction in CAR and altered vasoconstriction in response to U46619l in a SGLT1/2 and EDHF dependent manner
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Wagner, Alison F. Lysle Donald T. „Interactions between intracerebral human immunodeficiency virus-1 glycoprotein 120 and systemic heroin on expression of messenger ribonucleic acid mRNA of inducible nitric oxide synthase, interleukin-1[beta], tumor necrosis factor-[alpha], and cyclooxygenase-2 in hippocampus and cortex brain tissue of the Lewis rat“. Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2008. http://dc.lib.unc.edu/u?/etd,1893.
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Thesis (M.A.)--University of North Carolina at Chapel Hill, 2008.Title from electronic title page (viewed Dec. 11, 2008). "... in partial fulfillment of the requirements for the degree of Master of Arts in the Department of Psychology Behavioral Neuroscience." Discipline: Psychology; Department/School: Psychology. On t.p. and in abstract, [alpha] and [beta] are the Greek letters.
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Ortiz-Colón, Guillermo. „Investigation of adipogenic differences between bovine intramuscular and subcutaneous preadipocyctes“. Diss., 2006.
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Huang, Sheng-Yi, und 黃勝義. „Study of Interaction Effect between Antenna Far-field Electromagnetic Radiation and Human Similar Tissue“. Thesis, 2012. http://ndltd.ncl.edu.tw/handle/9n4452.
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博士國立臺北科技大學
電腦與通訊研究所
101
The Specific Absorption Rate (SAR) is generally evaluated by using the near-field measurement method, which is to measure the E-field strength deposited into the human similar tissue with the E-probe and/or to measure the thermal energy deposited on the surface of the human similar tissue with the thermal camera. Furthermore, it is worthy of studying the absorption of EM radiation energy deposited into the human similar tissue by using the far-field measurement system. Therefore, we propose a new measurement method to evaluate the far-field whole-body SAR, which is different from the near-field measurement method. The far-field measurement method is considering the absorption limit of the EM radiation power absorbed by the human similar tissue. There are two process steps to evaluate the absorption limit: (1) Taking the far-field measurement system measures the EM radiation powers of a radiation source such as antenna placed in free space and in neighbor of phantom respectively. (2) Taking the Wheeler Cap method evaluates the lost EM radiation power. According to the law of conservation of energy, most of the lost EM radiation power is absorbed by the human similar tissue and a little portion is losing in the stage of EM propagation. Therefore, the far-field whole-body SAR can be calculated while the total radiated power and the input power of a radiation source are known. The evaluated far-field whole-body SAR is compared to the ref. [4.9], which the relative error is within 14 %. According to the measured results, the EM radiation interaction effect can be greatly reduced approximately by 70 % when the separation distance of the EM radiation source and the human similar tissue is more than 170 mm. The measured results of the antenna efficiency are compared to the simulated results, which the relative errors are between 13 % and 3 %. The proposed new method has the good advantages of simplicity, rapidity, and saving time, which means that a small quantity number of data collection is necessary to evaluate the interaction effect between antenna far-field EM radiation and human similar tissue. The measured results have the good agreement with the simulated results.
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Alhaddad, A. G., Khairun N. Ramli, Raed A. Abd-Alhameed und Dawei Zhou. „Interaction Between Electromagnetic Field and Human Body for Dual Band Balanced Antenna Using Hybrid Computational Method“. 2010. http://hdl.handle.net/10454/4788.
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yesThis paper describes a hybrid computational method which efficiently models the interaction between a small antenna placed in proximity with the human body. Results for several test cases of placed in different locations on the body are presented and discussed. The near and far fields were incorporated into the study to provide a full understanding of the impact on human tissue. The cumulative distribution function of the radiation efficiency and absorbed power is also provided. The antennas are assumed to be operating over the 2.4 GHz and 5.2 GHz WLAN frequencies.