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Mokori, E. B. "The role of pannexin channels in small arteries." Thesis, University of Nottingham, 2016. http://eprints.nottingham.ac.uk/38019/.
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Pannexins (Panx) are membrane bound channels which allow the exchange of molecules, particularly ATP, between the cytoplasm and the extracellular space. Panx channels have been shown to be expressed in the vasculature, and there is evidence suggesting that they are involved in the regulation of vasoconstriction in small arteries. In mice thoracodorsal resistance arteries Panx1 channels are co localized with α1D-adrenoceptors on smooth muscle cells, and have been reported to open after α1D-adrenoceptor stimulation to release ATP which is then responsible for causing vasoconstriction by activating P2 purinoceptors (Billaud et al., 2011). This thesis examined the expression and the role of Panx channels in rat mesenteric and cerebral arteries. Western blotting was used to probe for the presence of pannexin proteins in rat mesenteric and cerebral arteries. The functional role of pannexin channels in the mesenteric and cerebral arterial vasoconstriction was studied using pressure myography. The effects of the pannexin channel inhibitors, mefloquine, probenecid, and carbenoxolone were tested against sympathetic nerve mediated vasoconstriction in 2nd order mesenteric arteries. The effects of purinoceptor antagonists, suramin, and NF449 as well as apyrase an ectonucleotidase that degrades ATP and αβ-MeATP which desensitises P2X1 purinoceptors and mefloquine, probenecid and carbenoxolone were examined against responses to noradrenaline (NA) and potassium chloride (KCl) in pressurized 2nd order mesenteric arteries. The effects of increasing concentrations of pannexin channel inhibitors, mefloquine, probenecid, and carbenoxolone, and purinoceptor antagonists, suramin, and NF449 were also examined against the myogenic tone of 3rd order mesenteric arteries and cerebral arteries. Panx1 siRNAs were used to try to knock down the Panx1 protein in isolated mesenteric arterial smooth muscle cells and mesenteric arteries. Panx1 and Panx2 proteins were detected in rat mesenteric and cerebral arteries, but no Panx3 protein was detected. The activation of the sympathetic nerves in the 2nd order mesenteric arteries resulted in a frequency-dependent vasoconstriction, which was reduced in the presence of all the pannexin channel inhibitors (mefloquine, probenecid and carbenoxolone). Mefloquine caused a significant difference in the vessel diameter, the vessel diameter was 91.00 ± 36.19 µm in the absence of mefloquine and 1.00 ± 0.70 µm in its presence (Student’s t test, p > 0.05). Probenecid caused a significant change in the vessel diameter, at 10Hz the vessel diameter was 60.75 ± 4.59 µm in the absence of probenecid and 26.25 ± 2.83 µm in the presence of probenecid (Student’s t test, p>0.05). Similarly NA and KCl caused a concentration dependent contraction of the 2nd order mesenteric arteries. All the agents tested against the NA mediated responses, pannexin channel inhibitors, purinoceptor antagonists (suramin, NF449), and αβ-MeATP except apyrase resulted in the reduction in the contraction. The concentration that caused a 20% reduction in the vessel diameter in the absence of carbenoxolone was -6.82 ± 0.09 M and it was significantly different in the presence of carbenoxolone, it was -6.22 ± 0.16 M (student’s t test, p>0.05). The concentration that cause a 20% reduction in the vessel diameter, in the absence of suramin was -6.72 ± 0.18 M and it was significantly different in its presence -6.00 ± 0.15 M (Student’s t test, p>0.05). However, mefloquine and probenecid also inhibited the contraction produced by raising extracellular KCl. The myogenic tone of 3rd order mesenteric arteries was reduced by both pannexin channel inhibitors and purinoceptor antagonists. With the exception of mefloquine, none of the agents had any effect on the myogenic tone of cerebral arteries. The attempt to knock down the Panx1 protein in isolated mesenteric arterial smooth muscle cells and mesenteric arteries was unsuccessful, despite demonstrating that the delivery systems worked. In conclusion, Panx1 and Panx2 proteins are expressed in both mesenteric and cerebral arteries. Some of the observations in this study provide evidence that support the role for pannexin channels in sympathetic nerve responses and those to exogenous NA, these include the inhibitory effects seen with the P2 purinoceptor antagonists, suramin, and NF449 as well as αβ-MeATP on exogenous NA. This effect was also mimicked by the pannexin channel inhibitors, mefloquine, probenecid and carbenoxolone which also inhibited the nerve mediated contractions. Thus the data is consistent with the hypothesis that transduction of responses to NA involves the opening of pannexin channels and the release of ATP as an intercellular messenger, to enable synchronized vasoconstriction of the vascular smooth muscle cells. However, some caution needs to be applied since mefloquine and probenecid also reduced the response to raised extracellular KCl indicating that they may not be selective. In the case of the myogenic tone major differences in the effects of the pannexin channel inhibitors were seen between the cerebral and mesenteric arteries showing that probenecid and carbenoxolone were acting selectively, however mefloquine was non-selective. Thus the effects obtained with probenecid and carbenoxolone coupled with those obtained with P2 purinoceptor antagonists, suramin and NF449 on the myogenic tone of mesenteric arteries suggests a role for pannexin channels as the stress/pressure sensor in mesenteric arteries.
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Mruk, Karen. "Small Molecule Investigation of KCNQ Potassium Channels: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/621.
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Voltage-gated K+ channels associate with multiple regulatory proteins to form complexes with diverse gating properties and pharmacological sensitivities. Small molecules which activate or inhibit channel function are valuable tools for dissecting the assembly and function of these macromolecular complexes. My thesis focuses on the discovery and use of small molecules to probe the structure and function of the KCNQ family of voltage-gated K+ channels.
One protein that obligatorily assembles with KCNQ channels to mediate proper assembly, trafficking, and gating is the calcium sensor, calmodulin. Although resolution of the crystal structures of calmodulin associated with isolated peptide fragments from other ion channels has provided some insight into how calmodulin interacts with and modulates KCNQ channels, structural information for calmodulin bound to a fully folded ion channel in the membrane is unknown. In Chapter II, I developed an intracellular tethered blocker approach to determine the location of calmodulin binding with respect to the KCNQ ion-conducting pathway. Using distance restraints from a panel of these intracellular tethered blockers we then generated models of the KCNQ-calmodulin complex. Our model places calmodulin close to the gate of KCNQ channels, providing structural insight into how CaM is able to communicate changes in intracellular calcium levels to KCNQ channel complexes.
In addition to pore blockers, chemical modification of ion channels has been used to probe ion channel function. During my initial attempt to chemically activate KCNQ channels, I discovered that some boronates modulate KCNQ complexes. In Chapter III, the activating derivative, phenylboronic acid, is characterized. Characterization of activation by phenylboronic acid showed that it targeted the ion conduction pathway of KCNQ channels with some specificity over other voltage-gated K+ channels. The commercial availability of thousands of boronic acid derivatives provides a large class of compounds with which to systematically dissect the mechanisms of KCNQ gating and may lead to the discovery of a potent activator of KCNQ complexes for the treatment of channelopathies.
All of the electrophysiological studies presented in this thesis were conducted in Xenopus oocytes. Unexpectedly, during the studies described above, the quality of our Xenopus oocytes declined. The afflicted oocytes developed black foci on their membranes, had negligible electric resting potentials, and poor viability. Culturing the compromised oocytes determined that they were infected with multi-drug resistant Stenotrophomonas maltophilia, Pseudomonas fluorescens and Pseudomonas putida. Antibiotic testing showed that all three species of bacteria were susceptible to amikacin and ciprofloxacin, which when included in the oocyte storage media prevented the appearance of black foci and resulted in oocytes that were usable for electrophysiological recordings. This study provides a solution to a common issue that plagues many electrophysiologists who use Xenopus oocytes.
Taken together, these findings provide new insights into activation of KCNQ channel complexes and provide new tools to study the structure-function relationship of voltage-gated K+ channels.
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Dickinson, Paul. "Approximate Private Quantum Channels." Thesis, University of Waterloo, 2006. http://hdl.handle.net/10012/2944.
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This thesis includes a survey of the results known for private and approximate private quantum channels. We develop the best known upper bound for ε-randomizing maps, n + 2log(1/ε) + c bits required to ε-randomize an arbitrary n-qubit state by improving a scheme of Ambainis and Smith [5] based on small bias spaces [16, 3]. We show by a probabilistic argument that in fact the great majority of random schemes using slightly more than this many bits of key are also ε-randomizing. We provide the first known nontrivial lower bound for ε-randomizing maps, and develop several conditions on them which we hope may be useful in proving stronger lower bounds in the future.
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Vanyushyn, Vladimir. "Innovative Behaviour of Small Firms : Essays on Small Firms' Internationalisation and Use of Online Channels." Doctoral thesis, Umeå universitet, Handelshögskolan vid Umeå universitet, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-43819.
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The spread of information technology and the dissolution of international borders have had a significant impact on the challenges and opportunities faced by today's small and medium-sized enterprises (SMEs). Innovative behaviour on the part of SMEs is a prerequisite for a successful transformation of the opportunities offered by these structural changes into growth and profitability. Thus, the overall aim of this thesis is to advance the understanding of small firms' innovative behaviour as manifested in the adoption of online channels and internationalisation. This doctoral thesis consists of an introductory chapter and six self-contained essays. The introductory section develops a general analytical framework for the thesis by reviewing the literature on innovation and organisational innovativeness and identifying key determinants and processes. The first four essays seek to explain a firm's propensity to adopt online channels and suggest that firm size and a firm's willingness to cannibalise, i.e. a firm's readiness to reduce the actual or potential value of its earlier investments, differentiate between adopters and non-adopters of online channels. Expectations of alienating resellers through online channel adoption may prevent a firm from adopting. Customers' pull, competitors' push and previous use of the Internet turned out to be strong drivers of online channel use. The fourth essay employs a two-wave research design and highlights that changes that occur in the technological and economic environment in which firms operate can, over time, change a firm's pattern of decision-making from innovation adoption to conventional cost-benefit approach. Essays five and six focus on the internationalisation of SMEs. In particular, essay five focuses on the process aspects of internationalisation and suggests that early importing has a modest direct influence on exporting, and that early importing activity indirectly enhances a firm's international experience and capabilities. Essay six investigates how competitive interactions affect internationalisation and suggests that cooperation with competitors, or coopetition, is a noteworthy internationalisation motive. This thesis contributes to the literature on innovation, internationalisation, electronic marketing and small business management and demonstrates that the dynamic forces associated with innovative behaviour affect SMEs adoption of online channels and how they work with customers and suppliers abroad.Spridningen av informationsteknik och en kraftig ökning av handel och samarbete över ländergränser har haft en betydande effekt på de utmaningar och möjligheter som dagens små och medelstora företag (SMF) står inför. De små och medelstora företagens innovationsbeteende är dock en förutsättning för att de framgångsrikt skall kunna ta tillvara de möjligheter som dessa strukturella förändringar skapar för att åstadkomma tillväxt och lönsamhet. Således är det övergripande syftet med denna avhandling att utveckla kunskap om innovationsbeteende i små företag, så som detta manifesteras i användande av onlinekanaler och deltagande i internationaliseringsprocesser. Denna avhandling består av ett inledande kapitel och sex fristående essäer. I det inledande kapitlet utvecklas ett övergripande analytiskt ramverk för avhandlingen, utifrån en litteraturöversikt av begreppen innovation och organisatorisk innovativitet där de viktigaste determinanterna och processerna identifieras. De första fyra essäerna försöker förklara ett företags benägenhet till adoption av onlinekanaler och föreslår att företagets storlek och vilja att kannibalisera, dvs ett företags beredskap att minska det faktiska eller potentiella värdet av dess tidigare investeringar, skiljer sig mellan de som använder respektive de som inte använder kanaler på nätet. Förväntningar att återförsäljare skulle bli negativt inställda om företag börjar använda onlinekanaler kan hindra företag från att investera i dem. Karaktäristika hos kunderna, utmaningar från konkurrenterna och tidigare användning av Internet visade sig vara starka drivkrafter bakom användningen av onlinekanaler. I den fjärde essäen, som baseras på data insamlad under två olika tidsperioder, visas att de förändringar som sker i den tekniska och ekonomiska miljö i vilken företagen är verksamma, kan med tiden innebära att beslutsfattandet skiftar från innovationstänkande till traditionellt kostnads-nyttotänkande. Essä fem och sex fokuserar på internationaliseringsprocesser i små och medelstora företag. Den femte essäen studerar i första hand internationaliseringsprocessen och visar på att tidig erfarenhet från importverksamhet enbart har en mindre inverkan på omfattningen av företagets framtida export. Tidig importerfarenhet har emellertid även en indirekt positiv effekt på företagets proaktiva attityd till internationalisering. Essä sex undersöker hur interaktion med konkurrenter påverkar internationaliseringen och visar att samarbete med konkurrenter, eller ”coopetition”, kan ha en betydande effekt på motiv till internationalisering. Denna avhandling bidrar till litteraturen inom områdena innovation, internationalisering, digital marknadsföring och ledning av små och medelstora företag. Den visar att de dynamiska krafter som ligger bakom innovationsbeteende påverkar små och medelstora företags användning av onlinekanaler samt hur denna företagsgrupp arbetar med kunder och leverantörer utomlands.
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Gawenis, Lara Renee. "Calcium and sodium absorption across the small intestine of cystic fibrosis mice /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3012969.
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D'hoedt, Dieter. "Structure-function analyses of small-conductance, calcium-activated potassium channels." Diss., [S.l.] : [s.n.], 2005. http://edoc.ub.uni-muenchen.de/archive/00006036.
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York, Michael C. "Development of a Nitrogen Dynamics Model for Small Stream Channels." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1282055154.
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Poon, Yan Shuen Mayo Stephen L. Rees Douglas C. "The characterization and structure of mechanosensitive channels of small conductance /." Diss., Pasadena, Calif. : California Institute of Technology, 2008. http://resolver.caltech.edu/CaltechETD:etd-05292008-144531.
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Martin, Callizo Claudi. "Flow Boiling Heat Transfer in Single Vertical Channels of Small Diameter." Doctoral thesis, KTH, Tillämpad termodynamik och kylteknik, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-25797.
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Microchannel heat exchangers present many advantages, such as reduced size, high thermal efficiency and low fluid inventory; and are increasingly being used for heat transfer in a wide variety of applications including heat pumps, automotive air conditioners and for cooling of electronics.However, the fundamentals of fluid flow and heat transfer in microscalegeometries are not yet fully understood. The aim of this thesis is to contribute to a better understanding of the underlying physical phenomena in single-phase and specially flow boiling heat transfer of refrigerants in small channels. For this purpose, well-characterized heat transfer experiments have been performed in uniformly heated, single, circular, vertical channels ranging from 0.64 to 1.70 mm in diameter and using R-134a, R-22 and R-245fa as working fluids. Furthermore, flow visualization tests have been carried out to clarify the relation between the two-phase flow behavior and the boiling heat transfer characteristics. Single-phase flow experiments with subcooled liquid refrigerant have confirmed that conventional macroscale theory on single-phase flow and heat transfer is valid for circular channels as small as 640μm in diameter. Through high-speed flow boiling visualization of R-134a under non adiabatic conditions seven flow patterns have been observed: isolated bubbly flow, confined bubbly flow, slug flow, churn flow, slug-annular flow, annular flow, and mist flow. Two-phase flow pattern observations are presented in the form of flow pattern maps. Annular-type flow patterns are dominant for vapor qualities above 0.2. Onset of nucleate boiling and subcooled flow boiling heat transfer of R-134a has been investigated. The wall superheat needed to initiate boiling was found as large as 18 ºC. The experimental heat transfer coefficients have been compared to predictions from subcooled flow boiling correlationsav ailable in the literature showing poor agreement. Saturated flow boiling heat transfer experiments have been performed with the 640 μm diameter test section. The heat transfer coefficient has been found to increase with heat flux and system pressure and not to change with vapor quality or mass flux when the quality is less than ∼0.5. For vapor qualities above this value, the heat transfer coefficient decreases with vapor quality. This deterioration of the heat transfer coefficient is believed to be caused by the occurrence of intermittent dryout in this vapor quality range. The experimental database, consisting of 1027 data points, has been compared against predictions from correlations available in the literature. The best results are obtained with the correlations by Liu and Winterton (1991) and by Bertsch et al. (2009). However, better design tools to correctly predict the flow boiling heat transfer coefficient in small geometries need to be developed. Dryout incipience and critical heat flux (CHF) have been investigated in detail. CHF data is compared to existing macro and microscale correlations. The comparison shows best agreement with the classical Katto and Ohno (1984) correlation, developed for conventional large tubes.QC 20101101
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Wu, Xuemei. "Monte-Carlo modeling of turbulent dispersion of small particles in channels." Diss., Georgia Institute of Technology, 2001. http://hdl.handle.net/1853/17389.
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Deng, Zhihui. "SMALL CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM (SK) CHANNELS IN MAMMALIAN SPINAL MOTONEURONS." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1237821684.
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BabovicÌ, Mileta. "Enhanced heat transfer to endothermic reactions by catalytic combustion in small channels." Thesis, University of Newcastle Upon Tyne, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289262.
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Barniol, Xicota Marta. "New polycyclic small molecules as ion channel modulators." Doctoral thesis, Universitat de Barcelona, 2017. http://hdl.handle.net/10803/400154.
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L’objectiu de la present tesi doctoral consisteix en desenvolupar molècules policícliques de baix pes molecular que tinguin com a diana tres canals iònics específics: la viroporina A/M2 del virus de la grip, el receptor purinèrgic dependent de lligand P2X7 i el receptor glutamatèrgic dependent de lligand N-metil-D-Aspartat, per tal de modular-los d’una manera tal que n’evitin o millorin el desenvolupament dels processos patogènics associats a aquestes proteïnes i/o que permetin ser emprades com a eines de recerca.
En el capítol 1 es presenta una introducció general del paper dels canals iònics, així com una descripció més específica de cadascun dels 3 canals objecte d’estudi en aquesta Tesi. Els objectius d’aquest treball es detallen en el capítol 2, després del qual, en el capítol 3 es presenten un seguit d’anàlegs per contracció d’anell del fàrmac comercial Amantadina, resultant-ne els primers inhibidors duals del canal M2 del virus de la Influenza A descrits en la bibliografia, actius sobre la soca salvatge (wt) i sobre el mutant resistent a fàrmacs V27A (Rey-Carrizo, M. et al. J. Med. Chem. 2013, 56, 9265). Seguidament en la part A del capítol 4 es gràcies a estudis in silico, s’observa com un dels inhibidors triples presenta un mode d’unió diferent sobre els canals wt i V27A, que podria estar directament relacionat amb el mecanisme de resistència a fàrmacs del mutant V27A (Rey-Carrizo, M., et al. J. Med. Chem. 2014, 57(13), 5738). En el capítol 5 es completa el treball presentant per primera vegada la proba experimental d’una possible explicació del mecanisme de resistència a fàrmacs del mutant V27A. (Barniol-Xicota, M., et al. manuscrit acceptat al J. Med. Chem.).
Com a continuació en el capítol 6 s’explora una diana diferent de la viroporina M2: l’hemaglutinina (HA) (Leiva, R., et al. manuscrit pendent d’enviar a J. Med. Chem.).
El capítol 7 representa el primer treball que marca l’inici de la línia de recerca d’antagonistes del receptor P2X7 en el grup. (Barniol-Xicota, M., et al. manuscrit en revisió al Bioorg. Med. Chem. Lett.).
Finalment, en el capítol 8, es presenten els primers exemples descrits a la bibliografia de multi-target directed ligands (MTDL) amb els receptors NMDA i P2X7 com a dianes. (Karou, O., et al. manuscrit pendent d’enviar a ACS Med. Chem. Lett.).
Deixant de banda la recerca de compostos bioactius en la part B del capítol 4 es descriu un estudi teòric i experimental d’un alquè altament piramidalitzat, derivat de l’estructura d’un compost bioactiu detallat en la part A del mateix capítol. (Rey-Carrizo, M. et al. Angew. Chem. Int. Ed. 2014, 53, 8195).
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Brown, Jennifer Ruth. "Collidial suspension flow and transport behavior in small channels by magnetic resonance microscopy." Diss., Montana State University, 2007. http://etd.lib.montana.edu/etd/2007/brown/BrownJ1207.pdf.
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The research presented addresses colloidal transport issues in small channel systems using Magnetic Resonance Microscopy techniques. In transport phenomena, the interaction between convection or deterministic motions and diffusion or random motions is important in many engineering and natural applications, especially relating to multiphase flows. Magnetic Resonance methods have the ability to separate coherent from incoherent motion, as well as measure spatially resolved velocity, probability distributions of displacement, and microstructure on the pore scale, even within a multiphase colloidal system. A dilute (f < 0.10) suspension of ~2.5 mm Brownian particles under shear flow in a 1 mm diameter glass capillary was investigated using spectrally resolved Pulsed Gradient Spin Echo techniques. The results indicate particle migration inward towards the capillary center. In addition, dispersion coefficients measured via flow-compensated Pulsed Gradient Spin Echo techniques as a function of observation time indicate the onset of irreversible dynamics with increasing total strain. Particle migration and irreversible dynamics are generally not expected to occur in dilute Brownian suspensions and are therefore not considered in the modeling of flow systems. Evidence of these effects, as indicated by the data presented, exhibits the importance of many body hydrodynamics in dilute Brownian suspensions and shows the applicability of chaos theory and non equilibrium statistical mechanics methods to model these systems. Additionally, blood, a well-studied cellular suspension with controllable aggregation properties, was studied when exposed to shear in a small gap cylindrical Couette rheometer. Shear induced particle migration in inhomogeneous shear flows creates non-uniform particle concentrations and cell depletion near the walls of the flow chambers. Non-uniform particle concentrations affect the overall flow characteristics of the suspension and create spatial variation of effective material properties, such as apparent viscosity. Understanding erythrocyte migration away from vessel walls is useful for identifying physiological transport mechanisms, designing filtration devices and designing microfluidic based sensors for blood. As a non-invasive and non-destructive technique with the ability to probe time and length scale displacements non-invasively, Magnetic Resonance Microscopy provides a unique perspective on the study of complex and opaque colloidal suspension flow.
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Watson, Graeme. "The influence of interfacial heat transfer on stable flame propagation in small channels." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114427.
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Flames in heated tubular channels, with radii on the order of the flame thickness, are investigated experimentally and numerically to understand the various effects of flame / wall interfacial heat transfer. First, combustion is studied in a burner-stabilized configuration, with an imposed temperature profile along the tube wall, to isolate and understand the role of flame / wall heat loss, without heat recirculation. The flames are found to be influenced by competition between energy required to preheat the reactants, heat released by combustion, and heat lost to the wall. To model such flames, an extension to the standard 1--D, volumetric formulation is proposed which uses detailed chemistry, mixture-averaged transport, and an interfacial heat transfer sub-model. The interfacial heat transfer sub-model uses a non-linear, radially-varying heat source to account for combustion and captures enhanced interfacial heat transfer inside the reaction zone. The degree of heat loss in the reaction zone is found to be sensitive to non-linear heat release. Heat release, from chemical reactions, acts as a local thermal discontinuity resulting in steep temperature gradients and high heat loss. This is absent in present volumetric formulations and in standard interfacial heat transfer correlations; which do not account for chemical reactions and treat the flow as thermally fully-developed. The model is, then, validated with experiments. In the experiments, strongly burning, axisymmetric methane / air flames, stabilized inside the wall temperature profile, are found to be "flat" for sufficiently small tube dimensions. The extended model is also found to be in agreement with experimental results and gives improved quantitative predictions for flame stabilization position, compared to the standard volumetric approach. Temperature and species profiles are also compared to those obtained from a detailed multi-dimensional formulation; which is assumed to predict the actual structure of the flame. Again, the extended volumetric model shows significant improvement compared to the standard formulation. Deviations between the extended model and the detailed model are also investigated to determine the nature of the unconsidered multi-dimensional effects. Finally, propagation and extinction in a participating channel is modeled to understand the combined effects of flame / wall heat transfer and heat recirculation on burning rate. These phenomena are deemed to be the leading-order effects for this case. The interfacial heat transfer sub-model is reformulated to use a non-linear heat source, for combustion, and radial convection, for flow redirection. The model is evaluated for stoichiometric flames over a range of channel inlet flow velocities and confirms the existence of regimes for fast and slow flame propagation, which have non-monotonic variation for burning rate. Peak heat loss is also found to coincide with peak heat release, rather than the maximum temperature location. The numerical model is, once again, found to give improved quantitative predictions over other approaches which neglect the effects of heat release, without the additional computational cost of multi-dimensional, detailed simulations.Les flammes réalisées à l'intérieur de canaux tubulaires chauffés sont étudiées expérimentalement et numériquement pour comprendre les effets du transfert de chaleur entre la flamme et la paroi. Tout d'abord, le processus de combustion est étudié dans une configuration de brûleur à flamme stabilisée, avec un profil de température imposé le long du tube. Ceci permet d'isoler et de comprendre le rôle de la perte de chaleur de la flamme vers la paroi, sans recirculation de la chaleur. Il est alors observé que les flammes sont influencées parla compétition existant entre l'énergie requise pour le préchauffage des réactifs, la chaleur dégagée par la combustion, et la perte de chaleur. Pour modéliser ces flammes, une extension à la formulation volumétrique et unidimensionnelle, typiquement utilisée, est proposée. Cette nouvelle formulation inclue la chimie détaillée, le transport moyenné du mélange, et un sous-modèle de transfert de chaleur interfaciale. Le sous-modèle de transfert de chaleur interfaciale utilise une source de chaleur non-linéaire pour tenir compte de la combustion, et saisit l'effet de transfert de chaleur interfaciale à l'intérieur de la zone de réaction. La quantité de perte de chaleur dans la zone de réaction se trouve à être sensible au dégagement de chaleur non-linéaire. Le dégagement de chaleur lié aux réactions chimiques agit comme une discontinuité thermique locale, entraînant des gradients de température importants et une perte de chaleur. Ceci est absent des formulations volumétriques typiques et des corrélations de transfert de chaleur standard, qui ne tiennent pas compte des réactions chimiques, et traitent l'écoulement comme thermiquement établi. Le modèle est ensuite comparé à des expériences. Dans les expériences, des flammes axisymétriques à brûlage fort, de méthane et d'air, sont stabilisées le long du profil de température de la paroi. Les flammes sont plates pour les tubes de petites dimensions. Le modèle nouveau est en accord avec les résultats expérimentaux et donne des prédictions améliorées pour la position de la flamme, par rapport à l'approche volumétrique standard. Les profils de température et d'espèces chimiques sont également comparés à ceux obtenus à partir d'une formulation détaillée multidimensionnelle, qui hypothétiquement prédit la structure réelle de la flamme. Encore une fois, le nouveau modèle volumétrique montre une amélioration significative par rapport à la formulation standard. Les écarts entre le nouveau modèle et le modèle détaillé sont également étudiés afin de déterminer la nature des effets multidimensionnels non-considéré.
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Monaghan, Alan S. "Chloride and potassium channels of enterocytes isolated from guinea-pig small intestinal villi." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338067.
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Campbell, Thomas. "The role of voltage-gated sodium channels in non-small cell lung cancer." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/the-role-of-voltagegated-sodium-channels-in-nonsmall-cell-lung-cancer(a65f4c5e-b217-483b-91d3-bb669965eb03).html.
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Various ion channels are expressed in human cancers where they are intimately involved in proliferation, angiogenesis, migration and invasion. Expression of functional voltage-gated sodium (Nav) channels is implicated in the metastatic potential of breast, prostate, colon, cervical and lung cancer cells. However, the cellular mechanisms that regulate Nav channel expression in cancer remain largely unknown. Growth factors are attractive candidates; they not only play crucial roles in cancer progression but are also key regulators of ion channel expression and activity in non-cancerous cells. Here, the role of epidermal growth factor receptor (EGFR) signalling and Nav channels in non-small cell lung cancer (NSCLC) cell lines have been examined. It is shown that functional expression of Nav1.7 promotes invasion in strongly metastatic H460 NSCLC cells. However, in non-invasive A549 NSCLC cells, Nav1.7 is completely absent. Inhibition of Nav1.7 either pharmacologically by tetrodotoxin (TTX) or genetically by small interfering RNA (siRNA) reduces H460 cell invasion by up to 50%. Whilst EGFR signalling enhances proliferation, migration and invasion of H460 cells, EGFR-mediated upregulation of Nav1.7 specifically, is required to promote invasive behaviour in these cells. Examination of Nav1.7 expression at the mRNA, protein and functional levels further reveals that EGFR signalling via the ERK1/2 pathway controls transcriptional regulation of Nav1.7 expression to promote cellular invasion in NSCLC. The role of Nav channels in promoting cancer cell invasion is also unclear. Therefore, the effect of Nav channel activity on two likely downstream contributors to cellular invasion, intracellular calcium concentration, [Ca2+]i, and intracellular pH, pHi, have been examined. It is shown that functional expression of Nav1.7 likely drives H460 NSCLC cell invasion via H+ efflux from the cell in an uncharacterised mechanism potentially involving NHE1, resulting in extracellular acidification of the perimembrane space. However, much more work is needed to understand this Na+-dependent invasive mechanism. Immunohistochemistry (IHC) of patient biopsies confirms the clinical relevance of Nav1.7 expression in NSCLC. Thus, Nav1.7 has significant potential as a novel target for therapeutic intervention, possibly in conjunction with existing EGFR inhibitors, and/or as a diagnostic/prognostic marker in NSCLC.
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Yau, Kwok-hei, and 邱國禧. "Small molecule-based synthetic ion channels modulate smooth muscle contraction and epithelial ion transport." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hdl.handle.net/10722/196079.
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In living systems, ion channels are membrane transport proteins that provide pathways for the passive diffusion of ions through lipid membranes. The flow of ions across membranes is the basis of many important physiological processes, including but not limited to the regulation of membrane potential, transepithelial transport and cell volume. While many efforts have been made to understand the biological roles of natural ion channels, the biological activities of artificial ion channels remain largely unknown. Recently, it was reported that a small molecule 1, which forms synthetic chloride (Cl–) channels in membranes via self-assembly, is capable of modulating vascular functions. In this thesis, novel small molecules that are structurally similar to 1 are shown to form artificial ion channels in membranes. Together with 1, the effects of these small molecules on the contractile activities of smooth muscles and epithelial ion transport are explored. The therapeutic implications of the findings are also discussed.
A collection of small molecules was screened using liposome-based fluorescence assays. In these assays, the ability of the synthetic compounds to modulate membrane potential was monitored. The screening yielded compound 3 that formed synthetic potassium (K+) channels in liposomal membranes, although the liposome-based fluorescence experiments suggested that 3 also transported Cl–. Two derivatives of 3, namely, compounds 2 and 4 were also examined. Single-channel recording experiments suggested that 2 forms synthetic Cl– channels in liposomal membranes.
The effects of compounds 2 and 3 on the functions of the vascular smooth muscle are explored. Using confocal imaging, it was shown that both 2 and 3 counteracted the effects of high-K+ depolarizing solution on membrane potential and intracellular Ca2+ concentration ([Ca2+]i) in cultured vascular smooth muscle cells. 2 and 3 also relaxed mice aortic rings pre-contracted with high-K+ solution. These observations can be explained in terms of the Cl– transporting functions of 2 and 3.
To determine the potential for developing the compounds into bronchodilators, the effects of compounds 1 and 3 on the contractile activities of the airway smooth muscle (ASM) were explored using organ bath technique. The contractile activities of the trachea isolated from Sprague-Dawley (SD) rats were first characterized. Among the contractile agents used, only potassium chloride (KCl), cholinergic agonists, serotonin and endothelin-1 were contractile to the SD rat trachea. 1 and 3 relaxed the ASM pre-contracted with KCl, whereas the contractions induced by other agonists were not affected.
The ability of compounds 2, 3 and 4 to modulate ion transport across cultured epithelia was tested by the short-circuit current measurement technique. It was shown that the compounds were capable of inducing Cl– secretion when applied to the apical side of airway and colonic epithelia. Importantly, the synthetic compounds induced apical Cl– secretion in immortalized cystic fibrosis (CF) bronchial epithelia. This suggests that the synthetic compounds may be used to correct the anion transport defect in CF epithelia.
In summary, the small-molecule based synthetic ion channels demonstrated two important general functions of natural ion channels, namely, the regulation of membrane potential and epithelial ion transport.published_or_final_version
Chemistry
Doctoral
Doctor of Philosophy
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Messer, Matthias. "Pulsed ultrasonic doppler velocimetry for measurement of velocity profiles in small channels and capplilaries." Thesis, Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-09022005-131744/.
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Thesis (M. S.)--Mechanical Engineering, Georgia Institute of Technology, 2006.Cyrus K. Aidun, Committee Member ; Farrokh Mistree, Committee Member ; Yves H. Berthelot, Committee Member ; Philip J. W. Roberts, Committee Member. Includes bibliographical references.
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Mertens, Timothy Edward. "Properties and regulation of small-conductance anion channels in a rat microglia cell line." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0023/MQ40871.pdf.
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Bascone, Davide. "Modelling and optimisation of intensified extraction in small channels for spent nuclear fuel reprocessing." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10058926/.
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Nuclear energy is considered an option for future power supply. Spent Nuclear Fuel (SNF) reprocessing is essential to reduce the volume of nuclear wastes and to recover reusable materials, such as uranium and plutonium. Nowadays, all the commercial plants rely on the Plutonium Uranium Reduction Extraction (PUREX) process, an over 60-year old process. In the present work, a mathematical model for liquid-liquid extraction in small channels has been developed. The model is suitable for SNF reprocessing. Calculations of thermodynamics, hydrodynamics, pressure drop and nuclear criticality are included in the model. Several components and redox reactions, between the various oxidation states of U, Pu and Np, have been considered. Also, to increase the throughput and provide a good flow distribution within the channels, the design of a comb-like manifold has been included into the calculations. The resulting model, posed as optimisation problem, is a mixed-integer differential optimisation problem. The goal is to develop a methodology that allows to explore alternative flowsheets for the nuclear fuel cycle, using the small-scale extractor. Different case studies have been investigated. Firstly, the "codecontamination" section of the PUREX process has been investigated to demonstrate the applicability of the model. Secondly, a novel codecontamination section has been investigated to compare the small-scale extractor and the two main conventional technologies, i.e. pulsed column and mixer-settler. Finally, an alternative flowsheet has been proposed, using the small-scale extractors. This process has been obtained using a superstructure optimisation approach. The flowsheet produces a mixed uranium/plutonium oxide, to preclude the risk of nuclear proliferation. The mathematical model, despite its size and complexity, has been successfully solved in a short computational time. Results have shown that intensified extraction in small channel can provide to several benefits over the conventional technologies, in particular in terms of solvent degradation and mass transfer.
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Bahia, Parmvir Kaur. "A study of small and intermediate conductance calcium-activated potassium channels in sensory neurones." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445301/.
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The role of small and intermediate conductance calcium-activated potassium channels (SK and IK channels) in dorsal root ganglion (DRG) neurones was examined. Sixteen antibodies raised against human or rat SK/IK channel peptide epitopes were tested for their ability to stain cells expressing channel protein. Of sixteen antibodies, 12 (6 to SKI, 1 to SK2, 2 to SK3 and 3 to IK) were deemed suitable for immunohistochemistry in human or rat tissue. Real-time quantitative PCR (qPCR) of rat DRG cDNA was performed to examine SK/IK expression levels. DRG neurones produce mRNA for all SK/IK channels and these mRNA levels were found to increase during development. Antibody staining experiments using DRG neurones cultured from different aged animals produced a positive stain with the anti-SK3 antibody only. The number of cells that stained positively and the intensity of staining for SK3 increased with age. To investigate possible functional roles for SK/IK channels sensory neurones, action potential afterhyperpolarisations (AHPs) were recorded from cultured DRG and nodose cells. The majority of these AHPs proved to be insensitive to the SK channel blocker UCL 1848. Attempts to block medium duration AHPs in DRG cells using IK and calcium channel blockers, also failed in most cases, suggesting that some other potassium conductances) are responsible. The possibility that SK3 is functional at the terminals of primary afferents was examined next. Spinal cord slices stained with SK/EK channel antibodies revealed positive SK3 staining in the outer laminae of the dorsal horn, where small and large diameter DRG fibres are expected to terminate. In vivo experiments (done by Dr Rie Suzuki, Department of Pharmacology, UCL) using UCL 1848 and l-ethyl-2- benzimidazolinone (1-EBIO an SK channel opener) showed that SK channels are likely to be active at these terminals where they have a functional role in mediating innocuous mechanical and nociceptive responses.
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Kukkonen, S. (Soile). "Small impact craters in crater counting:evolution studies of the eastern Hellas outflow channels, Mars." Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526218779.
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Abstract Crater counting is a method which allows us to estimate the surface ages of the planetary bodies, from which the sampling and sample delivery to laboratories on Earth are difficult or impossible. Because the number of craters on a surface unit increases over the time the surface has been exposed to space, old, geologically stable units have more craters than young and active units. When the crater production rate as a function of time is known, the absolute age of the surface unit can be determined based on its crater density. The purpose of this thesis is to investigate the role of small impact craters in crater counts to find out how modern very high-resolution space images can be utilized in age determination of planetary surfaces. The thesis focuses on how reliable crater count based datings are, if only small craters and counting areas are used in age determination. The research is carried out by utilizing crater counts on the outflow channels of Dao, Niger, Harmakhis and Reull Valles, which all are located in the eastern rim region of the Hellas impact basin, on the southern hemisphere of Mars. Crater counts are performed mainly based on the images of ConTeXt Imager (CTX) and High Resolution Imaging Science Experiment (HiRISE) aboard Mars Reconnaissance Orbiter (MRO). The results show that small craters are a very valuable tool to get information about the surface age. Instead of the size-range of counted craters, or the size of counting areas, results are dependent on the variability and scale of the surface modification history. The more variable or larger scale the modification history is, the larger surface area and wider crater diameter range are typically needed to achieve comprehensive age estimations. The crater counts on the eastern Hellas outflow channels support the earlier theories according to which the valles formed during a relatively short time interval, ~ 3.4–3.7 Ga ago. The existence of terrace structures and smaller tributary channels indicate that the outflow channels were filled by several pulses of liquids. The major fluvial activity ended no later than ~ 0.8–1.9 Ga ago, and it was probably controlled by the activity of nearby highland volcanoes. Soon after the declined fluvial activity, the outflow channels were covered by ice-rich deposits. The major reason for this was probably the changed climatic conditions, although in places e.g. impact cratering seems to have contributed to the emplacement of the deposits. The region as a whole was also resurfaced several times because of changes in local climate conditions. The most significant of the resurfacing processes seem to be the episodes of thin ice-rich mantling deposits, the most recent of which dominated the regional modification less than 10 Ma ago. In addition, the region has experienced eolian activity during the last 1 MaOriginal papers The original publications are not included in the electronic version of the dissertation. Kostama, V.-P., Kukkonen, S., & Raitala, J. (2017). Resurfacing event observed in Morpheos basin (Eridania Planitia) and the implications to the formation and timing of Waikato and Reull Valles, Mars. Planetary and Space Science, 140, 35–48. https://doi.org/10.1016/j.pss.2017.04.001 Kukkonen, S., & Kostama, V.-P. (2018). Modification history of the Harmakhis Vallis outflow channel, Mars, based on CTX-scale photogeologic mapping and crater count dating. Icarus, 299, 46–67. https://doi.org/10.1016/j.icarus.2017.07.014 Kukkonen, S., & Kostama, V.-P. (2018). Usability of small impact craters on small surface areas in crater count dating: Analysing examples from the Harmakhis Vallis outflow channel, Mars. Icarus, 305, 33–49. https://doi.org/10.1016/j.icarus.2018.01.004 Kukkonen, S., & Kostama, V.-P. (2018). Mapping and dating based evolution studies of the Niger Vallis outflow channel, Mars. Planetary and Space Science, 153, 54–71. https://doi.org/10.1016/j.pss.2017.12.012 Korteniemi, J., & Kukkonen, S. (2018). Volcanic Structures Within Niger and Dao Valles, Mars, and Implications for Outflow Channel Evolution and Hellas Basin Rim Development. Geophysical Research Letters, 45(7), 2934–2944. https://doi.org/10.1002/2018gl077067 http://jultika.oulu.fi/Record/nbnfi-fe201902226008
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Eldefors, Miriam, and Hanna Rosvall. "Small but mighty : en kvalitativ studie om lokala designföretags marknadskommunikation." Thesis, Linnéuniversitetet, Institutionen för marknadsföring (MF), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-75341.
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Studiens syfte är att redogöra för, samt få en djupare förståelse kring lokala designföretags marknadskommunikation. Forskningsfrågorna lyder som följande; Vilka kanaler för marknadskommunikation använder sig lokala designföretag av? samt Hur arbetar lokala designföretag med innehåll och formspråk i sin marknadskommunikation? Genom en kvalitativ metod med deduktiv ansats, utfördes åtta semistrukturerade intervjuer med både företagare och experter. Vidare genomfördes en innehållsanalys samt strukturerade observationer av fem företags digitala och sociala kanaler. Resultatet visar på att det finns gemensamma aspekter när det kommer till vilka kanaler samt vilket innehåll som företagen använder och publicerar. Det går även att utläsa att samtliga företag har en tydlig produktorientering i sin kommunikation. Formspråket baseras dock på företagens egen estetik. Slutligen presenteras studiens resultat i en modell, som utgår från Shannon-Weavers kommunikationsmodell från 1948 och förslag för framtida forskning tydliggörs.The purpose of this study was to describe, as well as gain a deeper understanding of local design companies' marketing communication. The research questions were as follows: Which channels for marketing communication do local design companies use? and How does local design companies work with content and design languages in their market communication? Through a qualitative method of deduction, eight semistructured interviews were conducted with both entrepreneurs and experts. Furthermore, a content analysis and structured observations were conducted of five companies' digital and social channels. The result shows that there are common aspects when it comes to which channels and what content companies use and publish. It is also possible to read that all companies have a clear product orientation in their communication. The design language is based on the company's own aesthetics. Finally, the study results are presented in a model, based on Shannon-Weaver's communication model from 1948, and proposals for future research are clarified.
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Maråk, Knut Arild. "Condensation Heat Transfer and Pressure Drop for Methane and Binary Methane Fluids in Small Channels." Doctoral thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for energi- og prosessteknikk, 2009. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-5702.
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A conventional heat exchanger consists of fluid channels with diameter larger than approximately 3 mm. Here, the phenomena around heat transfer and pressure drop are more or less well understood and can be well predicted. Newer and more compact heat exchangers use channels with smaller diameter which gives multiple advantages; they occupy less volume, are lighter, may be modular and can be faster and cheaper to produce. However, it is uncertain whether the phenomena affecting heat transfer and pressure drop are the same as in the larger channels. Clarifying this with respect to possible usage in the LNG-industry has been the main purpose of this work. An experimental set-up designed by Dr. Steffen Grohmann has been used in these investigations. A total of 749 measurements in tubes with diameter 1 mm, 0.5 mm and 0.25 mm have been done. Both single and two-phase flow measurements of pure methane, methane/ethane- and methane/nitrogenmixtures have been carried out. The measurements were done over a broad range with respect to pressure, vapour fraction, mass flux and heat flux. Also the pressure drop was measured. The conclusion is that the models concerning heat transfer and pressure drop in conventional channels also can be used in tubes with diameter 1 mm and 0.5 mm. The results from the 0.25 mm tube are burdened with too high uncertainty to be used in the conclusion. The results can also be relevant for non-circular diameters in microscale, e.g. for plate-fin heat exchangers.Konvensjonelle varmevekslarar nyttar kanalar med diameter ned til omlag 3 mm. I desse er fenomena kring varmeovergang og trykktap i stor grad kjende. Nyare og meir kompakte varmevekslarar har kanalar med mindre diameter som inneber ei rekkje fordelar; dei tek mindre plass, er lettare og kan vere raskare og billigare å produsere. Det herskar imidlertid uvisse om fenomena kring varmeovergang og trykktap er dei same som i konvensjonelle kanalar. Å få dette avklart i høve til mogleg bruk i LNG-industrien har vore hovudføremålet med arbeidet. Eit eksperimentelt oppsett designa av Steffen Grohmann vart brukt i undersøkjingane. Tilsaman 749 m˚alingar i røyr med diameter 1 mm, 0.5 mm og 0.25 mm vart utført. Både einfase kjøling og kondensasjon av metan og blandingar av metan/etan og metan/nitrogen vart gjort. Målingane varierte over eit stort omr˚ade med omsyn til trykk, dampfraksjon, massefluks og varmefluks. Ogs˚a trykkfall gjennom røyra vart målt. Resultata viser at varmeovergang i einfase veske kan forutseiast med eksisterande modellar i 1 mm og 0.5 mm røyra. Trykkfallsmålingane for 1 mm royret er som forventa utifr˚a konvensjonelle modellar. For 0.5 mm røyret er trykkfallet høgare enn forventa. For 0.25-mm røyret er uvissa for stor til at resultata kan brukast i ein konklusjon. For kondensering av rein metan kan varmeovergangen i 1 mm-røyret forutseiast med konvensjonelle modellar. I 0.5 mm røyret er varmeovergangen høgare enn berekna. For kondensering av binære blandingar kan varmeovergangen bereknast med konvensjonelle modellar for både 1 mm og0.5 mm royret. For tofasemålingar i 1 mm-røyret er den gjennomsnittlege uvissa for varmeovergang rundt 10 % og hovudsakleg knytt til temperatursensorane. For 0.5 mm røyret er uvissa for kondensering av rein metan litt over 20 %, medan den er rundt 10 % for kondensering av binarblandingane. For 0.5 mm-royet og sarskilt for 0.25 mm-røyret er massestraumsmålaren ei mykje viktigare kjelde til uvisse.
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Ang, Jit Hang Jackie. "Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4.
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Biophysical techniques are widely used to determine the structure, function and ligand binding properties of a protein. However, their application to membrane proteins has been limited due to the difficulty of obtaining sufficient purified sample. In this work, I use such methods to examine the thermostability and ligand binding properties of TREKs, two members of the family of tandem pore domain K+ channels important for the regulation of cellular excitability. Structures of TREK1 and TREK2 are available and thus when combined with such approaches may help guide the design of better ligands. I first successfully optimised the DSF method using the CPM dye for the detection of TREK ligands and found this to be a viable approach. In addition, direct binding detection methods such as SPR, ITC and Biolayer Interferometry were also investigated. A test case of 351 compounds derived from an FDA-approved pharmaceutical agent library were then screened against a range of K2P channels using the CPM assay. Several compounds were identified that appeared to thermostabilize the TREKs. These initial hits were further assessed using label-free DSF and functional studies on channel activity. Two compounds, cilnidipine and rimonabant were identified as a novel inhibitor and activator of TREK2 and TREK1 respectively. The findings are significant for the development of potent and selective binders for the TREKs and other membrane proteins, as they identify a viable workflow for identification of binders using biophysical methods.
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Cai, Shiwei. "The transient receptor potential channel 1 (TRPC1) mediates calcium-regulated differentiation in oral gingival keratinocytes /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/6390.
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Salman, W'el. "Characterisation and modelling of Taylor flow in small circular channels for the purpose of sequential screening." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446770/.
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This work focuses on the characterisation of a commonly encountered flow pattern, Taylor flow, for the purpose of using it in high throughput experimentation (HTE). Taylor flow consists of elongated gas bubbles of equivalent diameter larger than the tube diameter separated by liquid slugs. The bubbles adopt a characteristic capsular shape almost entirely filling the channel cross section. This configuration enhances the mixing within the liquid slugs and significantly decreases axial mixing along the liquid compared to single phase liquid flow. In this work, the characterisation of a Taylor flow reactor was divided into three parts: The first part deals with the hydrodynamics of the flow, identifying the dimensionless parameter governing Taylor flow and the size of forming bubbles in a coaxial inlet arrangement. One of the findings was that a minimum channel size 100 mum exists below which the Taylor flow may becomes non-periodic or unstable. The experimentally observed mechanisms of Taylor bubble formation are reported and a simple model is provided for predicting the most common of the mechanisms. In the second part, two models were developed which enable the prediction of axial mixing and the residence time distribution curves of the Taylor flow reactor. The first model is applicable when Peclet numbers Pe 100. It was used to evaluate existing literature models and then for determining the rate of mixture injection in HTE. The second model is a special extension of the first applicable when Pe 1000 and accounts for forward as well as back mixing. In the third part a model was developed for identifying the flow rates and channel and slug lengths in the Taylor reactor which allow its use for determining kinetics of chemical reactions. An important finding from both axial and the kinetics models is that the slug lengths should be kept to the minimum possible size for best reactor performance.
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Saqar, Wedad Ali. "Characterization of Small Conductance Calcium-Activated Potassium Channels in a Human Lens Epithelium Cell Line (B3)." Wright State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=wright1401279427.
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Firth, Amy. "Cellular mechanisms involved in the regulation of voltage gated potassium channels in rat small pulmonary vasculature." Thesis, University of Bath, 2006. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436807.
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Ro, Seungil. "SK channels : distribution, function and regulation in mouse colonic myocytes /." abstract and full text PDF (UNR users only), 2002. http://0-gateway.proquest.com.innopac.library.unr.edu/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3090879.
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Schmidt, Matthias Rene. "K+ channels : gating mechanisms and lipid interactions." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:51dc4149-d943-4dcd-bf5b-f04130456d84.
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Computational methods, including homology modelling, in-silico dockings, and molecular dynamics simulations have been used to study the functional dynamics and interactions of K+ channels. Molecular models were built of the inwardly rectifying K+ channel Kir2.2, the bacterial homolog K+ channel KirBac3.1, and the twin pore (K2P) K+ channels TREK-1 and TRESK. To investigate the electrostatic energy profile of K+ permeating through these homology models, continuum electrostatic calculations were performed. The primary mechanism of KirBac3.1 gating is believed to involve an opening at the helix bundle crossing (HBC). However, simulations of Kir channels have not yet revealed opening at the HBC. Here, in simulations of the new KirBac3.1-S129R X-ray crystal structure, in which the HBC was trapped open by the S129R mutation in the inner pore-lining helix (TM2), the HBC was found to exhibit considerable mobility. In a simulation of the new KirBac3.1-S129R-S205L double mutant structure, if the S129R and the S205L mutations were converted back to the wild-type serine, the HBC would close faster than in the simulations of the KirBac3.1-S129R single mutant structure. The double mutant structure KirBac3.1-S129R-S205L therefore likely represents a higher-energy state than the single mutant KirBac3.1-S129R structure, and these simulations indicate a staged pathway of gating in KirBac channels. Molecular modelling and MD simulations of the Kir2.2 channel structure demonstrated that the HBC would tend to open if the C-linker between the transmembrane and cytoplasmic domain was modelled helical. The electrostatic energy barrier for K+ permeation at the helix bundle crossing was found to be sensitive to subtle structural changes in the C-linker. Charge neutralization or charge reversal of the PIP2-binding residue R186 on the C-linker decreased the electrostatic barrier for K+ permeation through the HBC, suggesting an electrostatic contribution to the PIP2-dependent gating mechanism. Multi-scale simulations determined the PIP2 binding site in Kir2.2, in good agreement with crystallographic predictions. A TREK-1 homology model was built, based on the TRAAK structure. Two PIP2 binding sites were found in this TREK-1 model, at the C-terminal end, in line with existing functional data, and between transmembrane helices TM2 and TM3. The TM2-TM3 site is in reasonably good agreement with electron density attributed to an acyl tail in a recently deposited TREK-2 structure.
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Fronk, Brian Matthew. "Coupled heat and mass transfer during condensation of high-temperature-glide zeotropic mixtures in small diameter channels." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/52265.
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Zeotropic mixtures exhibit a temperature glide between the dew and bubble points during condensation. This glide has the potential to increase system efficiency when matched to the thermal sink in power generation, chemical processing, and heating and cooling systems. To understand the coupled heat and mass transfer mechanisms during phase change of high-glide zeotropic mixtures, a comprehensive investigation of the condensation of ammonia and ammonia/water mixtures in small diameter channels was performed. Condensation heat transfer and pressure drop experiments were conducted with ammonia and ammonia/water mixtures. Experiments on ammonia were conducted for varying tube diameters (0.98 < D < 2.16 mm), mass fluxes (75 < G < 225 kg m⁻² s⁻¹) and saturation conditions (30 < Tsat < 60°C). Zeotropic ammonia/water experiments were conducted for multiple tube diameters (0.98 < D < 2.16 mm), mass fluxes (50 < G < 200 kgm⁻² s⁻¹) and bulk ammonia mass fraction (xbulk = 0.8, 0.9, and > 0.96). An experimental methodology and data analysis procedure for evaluating the local condensation heat duty (for incremental ∆q), condensation transfer coefficient (for pure ammonia), apparent heat transfer coefficient (for zeotropic ammonia/water mixtures), and frictional pressure gradient with low uncertainties was developed. A new heat transfer model for condensation of ammonia in mini/microchannels was developed. Using the insights derived from the pure ammonia work, an improved zeotropic condenser design method for high-temperature-glide mixtures in small diameter channels, based on the non-equilibrium film theory, was introduced. The key features of the improved model were the consideration of annular and non-annular flow effects on liquid film transport, including condensate and vapor sensible cooling contributions, and accounting for mini/microchannel effects through the new liquid film correlation. By understanding the behavior of these mixtures in microchannel geometries, highly efficient, compact thermal conversion devices can be developed.
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Murphy, Matthew M. "Investigating the Effects of CyPPA on Small-Conductance Calcium-Activated Potassium Channels in SOD1G93A Transgenic Mouse Model." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1589929963490428.
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Gruben, Kathleen H. (Kathleen Hall). "The Role and Contributions of Independent Sales Representatives in the Relationship Between Merchandise Suppliers and Small Retailers: Dynamic Interactions in the Channel." Thesis, University of North Texas, 1998. https://digital.library.unt.edu/ark:/67531/metadc277918/.
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Small retailers are searching for a basis of competitive advantage to compete against larger retailers.
The independent sales representative (rep) may represent such a basis. Little is known about how the role of reps and their performance is perceived by suppliers and retailers. We do not know what is expected from reps, if the reps' performance meets suppliers and retailers expectations, or whether met expectations lead to a basis of competitive advantage. Primarily, the study was designed to identify the role and contributions reps in the interactions between the supplier and retailer in the channel of distribution.
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Pierce, Stephanie Lynn. "The role and regulation of small conductance CA2+ activated K+ channel subtype 3 in myometrial contraction and placental development." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/1059.
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SK3 channels contribute to membrane repolarization and hyperpolarization that leads to both relaxation of smooth muscle and vascular branching. These two distinct properties are intensified in the SK3T/T mice possibly influencing pregnancy by dampening uterine contractions and causing dysfunctional placental development. SK3T/T mice have delayed or hindered parturition, suggesting a role for SK3 channels in labor contractions (Chapter 2 & 3). Based on these findings, we hypothesized that SK3 channel expression must be reduced late in normal pregnancy to enable the uterus to produce the forceful contractions required for parturition. The mechanism(s) downregulating this channel in the uterus during pregnancy is unknown. The SK3 gene promoter region contains two Specificity Protein (Sp) binding sites; Sp1, a transcription factor that enhances transcription of genes in response to estrogen, and Sp3, a factor that competes for the same binding motif as Sp1 to reduce gene expression (Chapter 4). SK3 channels may also be involved in the vascular remodeling that occurs during pregnancy. The SK3 channel is present in vascular endothelial cells and overexpression of this channel leads to abnormal vessel branching and an increase in vessel diameter. During pregnancy, the vascular system must adapt to accommodate dramatic increases in blood volume necessary to sustain the developing fetus. Overexpression of SK3 channels could produce abnormalities in the placental vascular network, similar to the abnormal vessel branching and vasodilatation found in the mesenteric circulation, thus leading to poor fetal outcome (Chapter 5). The aim of this research was to determine the function of the SK3 channel in pregnancy by focusing on its role in myometrial contractility in addition to identifying its role in remodeling the maternal vasculature and its impact on placental blood flow and fetal demise.
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Ghidersa, Brǎduṭ Eugen. "Finite volume-based volume-of-fluid method for the simulation of two-phase flows in small rectangular channels /." Karlsruhe : Forschungszentrum Karlsruhe in der Helmholtz-Gemeinschaft, 2004. http://bibliothek.fzk.de/zb/berichte/FZKA6889.pdf.
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Kye, Min-Jeong. "Regulation of small-conductance, calcium-activated potassium channels (SK) in mouse brain in response to aging and stress." [S.l.] : [s.n.], 2004. http://webdoc.sub.gwdg.de/diss/2004/kye/kye.pdf.
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Ghidersa, Brăduţ Eugen. "Finite volume-based volume of fluid method for the simulation of two-phase flows in small rectangular channels." Karlsruhe FZKA, 2004. http://bibliothek.fzk.de/zb/berichte/FZKA6889.pdf.
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Haghnegahdar, Mohammadreza [Verfasser], U. [Gutachter] Hampel, and J. [Gutachter] Brandner. "Experimental analysis of mass transfer of Taylor bubble flow in small channels / Mohammadreza Haghnegahdar ; Gutachter: U. Hampel, J. Brandner." Dresden : Technische Universität Dresden, 2019. http://d-nb.info/1227198132/34.
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Lowe, Sidney. "Channel strategy for export distribution: towards a channel strategy model for non-multinational manufacturingfirms in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1988. http://hub.hku.hk/bib/B31949319.
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Kittiwongvivat, Wasinee, and Pimonpha Rakkanngan. "Facebooking your dreams : How to make the best use of Social Networking sites asinnovative and cost-effective/ low-budget marketing channels insmall-sized entrepreneurship." Thesis, Mälardalen University, School of Sustainable Development of Society and Technology, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:mdh:diva-9954.
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This study aims to understand and explain how small sized
entrepreneurship currently uses social networking sites
through out the process of launching and marketing
their products. This also includes the use of word of mouth,
which features social networking technology. Lastly, we
intended to give recommendations to problems that small
sized entrepreneurship is facing in order to make the best
use of social networking channels and to ensure that these
channels are used in the most effective way.
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Hillman, David James. "Membrane currents evoked by vasoactive compounds in vascular endothelial cells : contributions of small and intermediate conductance calcium-activated potassium channels." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445578/.
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The contribution of different calcium-activated potassium channel subtypes to agonist-evoked whole-cell currents was studied in cultured pig coronary artery endothelial cells. From a resting membrane potential of-5.9 0.5mV (n=102), 1-lOuM ATP, 1-1 OnM substance P and 1-lOOnM bradykinin hyperpolarised cell rafts to -50.7 1.6mV (n=76), -45.7 4.7mV (n=19) and -59.1 3.5mV (n=16), respectively. In small clusters of cells, 1 OuM ATP evoked outward currents which reversed close to EK and were sensitive to both the SKca channel blocker UCL 1848 (IC5o 1.2nM -65% maximal block) and the IKca/BKca channel blocker charybdotoxin (-85% block at 30-100nM). Surprisingly lOuM clotrimazole, a non selective blocker of IKca channels, abolished ATP-evoked currents in a total of three out of five cells. This requires further study. ImM 1-EBIO, which increases the calcium sensitivity of SKca and IKca channels, activated currents which were sensitive to lOOnM UCL 1848 and luM clotrimazole (blocked by 57.0 15.1% (n=3) and 89.0 1.6% (n=4), respectively). When applied in combination, these two blockers essentially abolished 1-EBIO evoked currents. Buffering intracellular calcium to 1.5uM activated outward currents which were sensitive to lOOnM UCL 1848, lOOnM charybdotoxin and lu.M clotrimazole (blocked by 28.3 5.4% (n=27), 101.2 0.5% (n=3), and 82.6 3.7% (n=22), respectively. Plasma membrane delimited expression of the SK3 channel protein was detected using fluorescence immunohistochemistry. In many vessels endothelium-derived hyperpolarising factor (EDHF)- mediated vasodilation is abolished by a combination of SKca and IKca channel blockers, which are frequently ineffective when applied alone. This has led some to suggest the existence of a novel channel with unusual pharmacology. The present study demonstrates, however, that separate SKca and IKca channels contribute to endothelial cell currents underlying the EDHF pathway. Based on protein expression and UCL 1848-sensitivity it is further proposed that the contributing SKca channels are formed of SK3 subunits.
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Shah, Yousef. "Effects of point mutations on the block of SK3 small-conductance calcium-activated potassium channels expressed in mammalian cell lines." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446491/.
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Small conductance calcium-activated K+ channels (SK channels) form a subfamily of K+ -selective, volt age-insensitive channels that have been recently cloned. This thesis is concerned primarily with an investigation of the pharmacology of these channels. Understanding their pharmacology is of potential clinical importance since SK channels participate in diverse physiological roles, for example, generating neuronal afterhyperpolarizations (that set tonic firing frequencies) and regulating smooth muscle contraction. This thesis consists of two parts. The first is concerned with expressing and establishing recording conditions for rSK3 in mammalian cell lines. This was made difficult because of channel run up and run down. However, some progress was made towards stabilizing channels through MgATP regulation and this allowed progress towards the second part (the major part) of this thesis; a functional characterization of site-directed point mutants that were created to better understand the pharmacology of these channels. First, two mutations were made to examine similarities between the pore structures of the KcsA and Shaker channels and the SK channels. The first of these mutants would be predicted to increase Tetraethylammonium (TEA) affinity to the sub-millimolar range, and the second to provide increased sensitivity to charybdotoxin (CTX) block. Both these predictions were fulfilled suggesting that the KcsA/Shaker pore structure can provide a reasonable model for the SK channel pore. However, an important difference was identified in the TEA sensitive mutant, indicating that although the channels are similar, they are not identical. Three UCL compounds were then studied; UCL 1848, UCL 1684, and UCL 1530 with six channel mutants. The effects of these mutations on blocker affinity provided the basis of a "map" of the channel residues interacting with UCL compounds and establishes that these blockers bind in the channel pore region. Further, experiments co-expressing wildtype (WT) and mutant subunits demonstrate that UCL compounds do not require all four "sensitive" subunits for block, suggesting an asymmetric interaction with the channel outer pore. Finally, some work has also been done to define the possible assembly patterns of SK subunits in forming heteromeric channels. Evidence is presented that SKI and SK3 can co-assemble. Overall, this thesis provides a starting point for understanding the pharmacology of small molecule SK channel blockers at the molecular level.
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Besedina, Oleksandra, and Viktoriia Chernyshova. "Who you are and what they think about you : how to measure brand identity and brand image of a small design company." Thesis, Högskolan på Gotland, Institutionen för humaniora och samhällsvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:hgo:diva-974.
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The idea of this thesis originates from the stand point that the understanding of who you are, who you want to be and what impression you actually make, is the start of a successful reciprocal relationship. The thesis solves two tasks. First, it offers a methodology of measuring brand image and brand identity and therefore contributes to the development of the research base. Second, presenting a case-study of a small scale company it applies the methodology and analyzes the congruency between brand image and brand identity from the communication perspective of SMEs. In a result the developed methodology is tested and a contribution to the deeper understanding of brand nature is made.
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Ariz, Extreme Igor [Verfasser], Jochen S. [Akademischer Betreuer] Hub, Markus [Gutachter] Zweckstetter, and Sebastian [Gutachter] Kruss. "Computational Studies of Small Molecule Permeation across Membrane Channels / Igor Ariz Extreme ; Gutachter: Markus Zweckstetter, Sebastian Kruss ; Betreuer: Jochen S. Hub." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2018. http://d-nb.info/1164764861/34.
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Paret, Taylor York. "To Hear Without and Ear: Mechanosensation in Plants." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1556807284059847.
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Bogoev, Jane. "The interest rate and bank lending channels in a small, open and Euroised economy with fixed exchange rate : the case of Macedonia." Thesis, Staffordshire University, 2011. http://eprints.staffs.ac.uk/1892/.
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This thesis explores the possibility of conducting a more independent monetary policy through the adoption of an inflation targeting regime in a small, open and Euroised transition economy where banks are dependent on foreign financing. The major aim of this research programme is to investigate the effectiveness and determinants of the interest rate and bank lending channels in the case of Republic of Macedonia, since their effectiveness is seen as one of the preconditions for adoption of an inflation targeting regime. This thesis contributes to the existing literature for transition economies in two main ways. Firstly, it investigates the size and determinants of individual bank‟s lending rate adjustments to changes in the „cost of funds‟ rate. Secondly, it examines two loan functions according to the currency disaggregation of loans, and investigates what bank-specific characteristics are the major determinants. The findings with respect to the first research contribution indicate that the size of the short-run adjustment of lending rates to changes in the „cost of funds‟ rate is quite sluggish and heterogeneous among Macedonian banks. Moreover, bank-specific characteristics and macroeconomic variables play different roles in individual bank‟s lending rate setting decisions. These results are consistent with the presence of aggregation bias in previous research that uses sector-level data, due to the suppression of banks‟ heterogeneous behaviour. The results regarding the second research contribution imply that the bank lending channel in Macedonia works mainly through foreign currency loans and the foreign reference rate, whereas the responsiveness of domestic currency loans to the changes in the domestic reference rate is quite low. Moreover, different banks react differently to changes in the domestic and foreign reference rates due to their specific characteristics. These findings suggest that the impact of domestic monetary policy on the Macedonian economy through the interest rate and bank lending channels is quite limited. Therefore, the current monetary policy regime of a fixed exchange rate may be more effective in achieving the price stability aim than adoption of an inflation targeting regime in economies like Macedonia.
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Luong, Ngoc Anh Minh, and Liangqi Wang. "Factors Influencing E-commerce Usage within Internationalisation : A study of Swedish small and medium-sized fashion retailers." Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-387796.
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Purpose − Previous research has shown that Swedish Small-and-Medium enterprises (SMEs) have a relatively low level of digital maturity when it comes to export, thus limiting growth potential in international markets. This study aims at investigating this phenomenon with a focus on e-commerce, as it is among the top digital channels that have a large impact on international expansion. Factors influencing the usage of e-commerce channels within internationalisation by Swedish SME fashion retailers will be investigated. Design/methodology/approach −The overall methodology used in this study is qualitative with an abductive mode of reasoning. The study follows a case study approach using multiple cases with interviews as the primary data source. Based on literature review, thirteen factors are identified to have a certain influence on the usage of e-commerce within internationalisation. Semi-structured interviews are conducted with seven cases to examine the identified factors from literature and explore new factors if possible. Findings − The results present eleven critical factors including eight identified factors from the literature together with five newly discovered factors. They are Relative Advantage, Perceived Usefulness, Compatibility, Costs, Customer Reachability, Branding and Advertising, Time-efficiency, Technology Competence & Configuration, Organisation Size, Competitive Pressure, and Main Product Features. These critical factors have various effects depending on companies’ business operations and the degree of online internationalisation. The results further confirmed that the Uppsala Model is still applicable in the context of Swedish SME fashion retailers internationalising with e-commerce. Value − This study has contributed to the existing research on e-commerce and internationalisation in terms of the influence on firms’ e-commerce usage within internationalisation in the post-adoption phase, and under the specific business context of Swedish small-and-medium sized fashion retailers. Based on the conclusion, practical implications are offered for similar companies in this industry
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Sanches, Jéssica Paezani. "Planejamento e gestão de programas de relacionamento de marketing ao pequeno varejo: um estudo de caso com uma indústria do setor alimentício." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/96/96132/tde-11062015-160048/.
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O relacionamento entre empresas e seus clientes, a durabilidade deste relacionamento, confiança e comprometimento são variáveis fundamentais que interferem no desempenho das empresas e podem gerar ganhos de vantagens competitivas para uma organização. Os programas de relacionamento fazem parte das estratégias para chegar ao consumidor final e para manter um relacionamento produtivo com os membros do canal. Nos mercados emergentes, o pequeno varejo passou a ser um canal de grandes oportunidades para a indústria, no entanto, é um canal que possui flexibilidade no oferecimento de serviços às necessidades variadas dos consumidores. Este estudo buscou entender quais os fatores críticos para o sucesso de um programa de relacionamento realizado pela indústria ao pequeno varejo e também propor um método para sua construção pela perspectiva da indústria. Foram verificados os direcionadores que afetam este relacionamento, caracterizados pelo comprometimento, satisfação, confiança e a sensação de pertencer e exclusividade do pequeno varejista com a indústria fornecedora. O procedimento metodológico utilizado para o desenvolvimento desta pesquisa aplicada é a pesquisa exploratória de caráter qualitativo através do método de estudo de caso único em uma indústria do setor de alimentos. Uma indústria no Brasil do setor de alimentos foi selecionada, e seus programas de relacionamento ao pequeno varejista foram analisados e comparados, através de análise de documentos e entrevistas com colaboradores da indústria e pequenos varejistas que participam destes programas. Deste modo, foi proposto, através do estudo de conceitos teóricos de marketing de relacionamento e programas de relacionamento a canais, e a partir do estudo de caso realizado, um método para elaboração e programa e relacionamento de marketing para pequenos varejistas. Quatro etapas para o método foram sugeridas: análise externa e interna; definição de estratégias e participantes do programa; definição dos indicadores de desempenho e benefícios, e gestão de programas de relacionamento para pequenos varejistas.The relationship between companies and their customers, the durability of this relationship, trust and commitment are key variables that affect the performance of companies in the market in which they operate. The relationship programs are part of the strategies to reach the end consumer and to maintain productive relationships with channel members. In emerging markets, small retailers have become a channel of great opportunities for the industry, however, are a very wide channel and have some flexibility of service differentiation to meet the varying needs of consumers, unexplored question by industries. This study aimed at the understanding of which are the critical factors for the success of relationship programs that are conducted by the industry to the small retail, and also propose a method for its construction. The drivers that affect this relationship, characterized by commitment, satisfaction, confidence and a sense of belonging and exclusivity of the small retailer with the industry were checked. The approach used for the development of this applied research is an exploratory qualitative research study, using the method of case study in a single industry in the food sector. An industry of the food sector in Brazil was selected. Their relationship programs to small retailers were analyzed and compared through documents analysis and interviews with the industry\'s collaborators and small retailers that participate in these programs. Thus, a method was proposed (through the study of theoretical concepts of relationship marketing and relationship programs, and the case study) to elaborate a relationship program for small retailers. The steps suggested are: external and internal analysis; definition of strategies and program participants; definition of performance indicators and benefits, and management of relationship programs for small retailers.