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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
101

Electrical Characterization of Cluster Devices

Sattar, Abdul January 2011 (has links)
The aim of the study presented in this thesis is to explore the electrical and physical properties of films of tin and lead clusters. Understanding the novel conductance properties of cluster films and related phenomenon such as coalescence is important to fabricate any cluster based devices. Coalescence is an important phenomenon in metallic cluster films. Due to coalescence the morphology of the films changes with time which changes their properties and could lead to failure in cluster devices. Coalescence is studied in Sn and Pb cluster films deposited on Si$_3$N$_4$ surfaces using Ultra High Vacuum (UHV) cluster deposition system. The conductance of the overall film is linked to the conductance of the individual necks between clusters by simulations. It is observed that the coalescence process in Sn and Pb films follows a power law in time with an exponent smaller than reported in literature. These results are substantiated by the results from previous experimental and Kinetic Monte Carlo (KMC) simulation studies at UC. Percolating films of Sn show unique conductance properties. These films are characterized using various electrode configurations, applied voltages and temperatures. The conductance measurements are performed by depositing clusters on prefabricated gold electrodes on top of Si$_3$N$_4$ substrates. Sn cluster films exhibit a variety of conductance behaviours during and after the end of deposition. It is observed that the evolution of conductance during the onsets at percolation threshold is dependent on the film morphology. Samples showing difference responses in onset also behave differently after the end of deposition. Therefore all samples were categorized according to their onset behaviour. After the end of deposition, when a bias voltage is applied, the conductance of Sn films steps up and down between various well-defined conductance levels. It is also observed that in many cases the conductance levels between which these devices jump are close to integral multiples of the conductance quantum. There are many possible explanations for the steps in conductance. One of the explanations is formation and breaking of conducting paths in the cluster films by electric field induced evaporation and electromigration respectively. The stepping behaviour is similar to that in non-volatile memory devices and hence very interesting to explore due to potential applications.
102

Electronic transport in spin-glasses and mesoscopic wires : correlations of universal conductance fluctuations in disordered conductors / Transport électronique dans des verres de spins et fils mésoscopiques : corrélations de fluctuations universelles de conductance dans des conducteurs désordonnés

Solana, Mathias 29 June 2018 (has links)
Le travail expérimental développé pendant cette thèse se situe à l'interface de deux champs en physique de la matière condensée, à savoir les verres de spins et la physique mésoscopique. Les verres de spins ont été largement étudié et font partie des problèmes les plus débattus au cours des années tant d'un point de vue expérimental que théorique. Cet état est caractérisé par des propriétés très particulières qui se font jour lors d'une transition de phase magnétique à très basses températures qui est elle-même inhabituelle. En effet, cette transition est due à un mélange de frustration et de désordre dans la structure magnétique du système. Ce faisant, c'est un système modèle pour les verres et les systèmes frustrés en général. Après bien des efforts, des travaux théoriques ont réussi à décrire l'état fondamental du système au moyen de deux approches différentes et apparemment incompatibles. Cependant, la question de la vraie nature de la phase verre de spin reste grandement débattue.La physique mésoscopique, de son côté, traite du transport électronique dans les échantillons pour lesquels les électrons gardent leur cohérence de phase. Si les électrons restent cohérents, il est possible de voir des effets d'interférences qui sont des signes quantiques de ce qu'il se passe au niveau atomique. Dans cette thèse, il est utilisé pour sonder le désordre aussi bien magnétique que statique dans un verre de spins.Nous montrons que, contrairement à ce qui est cru, de forts changements se déroulent dans le désordre microscopique même à basses températures. Nous prétendons également que ces changements sont purement structuraux et viennent du fait de systèmes dont la distribution en énergie est très large. / The experimental work developed during this PhD is situated at the interface of two fields of condensed matter physics, namely spin glasses and mesoscopic physics. Spin glasses have been widely studied and are one of the problem that has been the most discussed over the years, both on a theoretical and experimental point of view. This state is characterized by very peculiar properties that come to light as it exhibits a magnetic phase transition at low temperatures that is already unusual. Indeed, this transition is due to a mix of frustration and disorder in the magnetic structure of the system, making it an exceptional model system for glasses and frustrated systems in general. After many efforts, theoreticians managed to described the fundamental state of the system by the mean of two different and apparently incompatible approaches. The first one, called RSB theory, is based on a mean-field approximation and predicts a complex phase space with an unconventional hierarchical organization. The second is based on more phenomenological approach and is named Droplet theory. It points towards a unique ground state and explain all the observation by slow relaxation processes. However, the question of the true nature of the spin glass phase is still heavily debated. Mesoscopic physics, for its part, addresses the question of electronic transport for samples in which the electrons keep their phase coherence. If the electrons remains coherent, it is possible to see interference effects that are quantum signs of what happens at the atomic level. In this work, it is used to probe the magnetic and static disorder in spin glasses. Indeed, it is possible to interpret the change in those interferences as changes in the microscopic disorder configuration and to know exactly how the spin glass state evolves. Some work have already tried to use coherent transport in spin glasses but this remains an open field. This work has then be dedicated to the implementation of transport measurement in spin glasses and mesocopic conductors. The first part will be focused on a the experimental setup that was used to perform very precise transport measurements and on the processing of the data taken out of them. In a second part, we will present some general physical characteristics of our samples such as their resistance dependence to the temperature or magnetic field, before extracting the quantum signature in magnetoresistance measurements. Finally, we will discuss the results obtained. We show that strong changes in the microscopic disorder happen even at low temperatures, in opposition to what is believed. We argue that those observed changes are purely structural and come from systems that are widely distributed in energy.
103

Direct molecular dynamics simulation of piezoelectric and piezothermal couplings in crystals / Simulation directe par dynamique moléculaire des couplages piézoélectrique et piézothermique dans les cristaux

Kassem, Wassim 14 September 2015 (has links)
La thèse est axée sur l'examen de l'effet de la contrainte sur la conductivité thermique des matériaux piézoélectriques. Les matériaux piézoélectriques sont des cristaux qui présentent une déformation mécanique lors de l'application d'un champ électrique. Des exemples de tels systèmes sont ZnO, AlN, et SiO2. En utilisant des simulations de dynamique moléculaire, nous avons calculé la conductivité thermique de cristaux de ZnO et AlN sous contrainte. Nous avons aussi calculé la résistance thermique des interfaces SiO/C et ZnO/C soumis à un champ électrique.Nous commençons par le calcul des propriétés piézoélectriques et élastiques de ZnO. Celles-ci serviront à valider les potentiels interatomiques utilisés, et à montrer l'ampleur de la contrainte qu’il est possible d'appliquer. En utilisant la dynamique moléculaire d'équilibre, nous avons estimé le coefficient élastique c33 de ZnO, qui se trouve être en accord avec les valeurs expérimentales. Il a aussi été déterminé que la limite élastique d'un cristal de ZnO est de 6 GPa, ce qui correspond à une déformation de 6%. Nous avons ensuite établi les coefficients piézoélectriques de ZnO en utilisant la dynamique moléculaire de non-équilibre, et il a été constaté que les coefficients piézoélectriques dij sont en accord avec les valeurs de la littérature.Deuxièmement, nous avons examiné l'effet de la pression sur la conductivité thermique intrinsèque de ZnO et d’AlN. La dynamique moléculaire de non-équilibre inverse a été mise en œuvre pour calculer la conductivité parce que les coûts de calcul sont nettement inférieurs à ceux de la méthode d'équilibre, d’autant plus pour ZnO dont le potentiel inter-atomique contient les interactions Coulombiennes. L'effet de taille sur la conductivité thermique de ZnO et AlN a ensuite été étudié. Nous avons montré que la formule de Schelling peut en effet être mise en œuvre pour les deux cristaux pour différentes valeurs de la contrainte. La conductivité thermique pour un cristal de ZnO de taille infinie est extraite de la formule de Schelling, et elle se révèle être de 410 W/mK. La conductivité thermique de cristaux de ZnO sous contrainte a ensuite été analysée. Nous avons montré que, après correction de l'effet de taille, la conductivité thermique suit une dépendance en loi de puissance à la contrainte uniaxiale. De plus, la conductivité thermique de ZnO est affectée par un champ statique externe en raison de la contrainte induite. La conductivité thermique d'AlN est estimée à 3000 W/mK, l'effet de la contrainte ne modifie pas cette valeur du fait du potentiel inter-atomique utlisé. Par conséquent, AlN n’est pas un matériau pertinent pour faire office de switch thermique.Troisièmement, nous avons exploré l'effet d’un déplacement piézoélectrique sur la conductance thermique d’interface de Si2O/graphène et ZnO/graphène. Utilisant la dynamique moléculaire d’équilibre, la conductivité thermique d'un super-réseau dont la période est composée de silice et de graphène polyfeuillet. Le super-réseau a été évalué pour différentes valeurs du champ électrique externe. Nous avons constaté que l'application d'un champ électrique de 20 MV/m positif parallèle à la direction hors-plan du super-réseau conduit à la réduction de la conductivité thermique d'un facteur deux. D'autre part, aucun changement dans la conductance thermique n’est noté pour le super-réseau ZnO/graphène. Cette différence est due aux différences de déformations induites au niveau des interfaces dans le super-réseau. L'effet est recréé dans un super-réseau Si/Ge en appliquant une déformation pour former les interfaces. Cette approche crée une déformation non uniforme qui est susceptible de diffuser les phonons. / The thesis is focused on investigating the effect of strain on the thermal conductivity of piezoelectric materials. Piezoelectric materials are crystals which display a mechanical deformation upon application of an electric field. Examples of such material are ZnO, AlN, and SiO2. Using Molecular Dynamics simulations, we calculate the thermal conductivity of unstrained and strained ZnO and AlN crystals. We also calculate the thermal resistance of SiO/graphene interfaces under strain.We calculate the piezoelectric and elastic properties of ZnO. These will serve as confirmation of the correctness of the inter-atomic potential used, and will serve to show the magnitude of strain that is possible to apply. Using non-equilibrium molecular dynamics, we determine the elastic coefficient of ZnO c33, and we see that it agrees with experimental values. We also determine that the elastic limit of a perfect ZnO crystal is 6 GPa which corresponds to a 6% strain. We also determine the piezoelectric coefficient of ZnO using NEMD, and we find that the piezoelectric coefficient d33 also agrees with literature values.Second, we look at the effect of strain on the intrinsic thermal conductivity of ZnO and AlN. We use reverse non-equilibrium molecular dynamics to calculate the conductivity because the computational costs are significantly lower than those for the equilibrium method; especially for ZnO whose inter-atomic potential contains Coulomb interaction. We also study the size-effect on the thermal conductivity of ZnO and AlN. We show that the Schelling formula can indeed be implemented to both crystals for different values of strain. The infinite length thermal conductivity for ZnO is extracted from the formula, and it is found to be 410 W/mK. We then calculate the thermal conductivity of strained ZnO crystals. We show that after correcting for the size effect the thermal conductivity follows power-law dependence to uniaxial strain. Also, we demonstrate that the thermal conductivity of ZnO can be affected by a static external field due to the induced strain. The infinite length thermal conductivity of AlN is found to be 3000 W/mK. We show that for the case of AlN the effect of strain does not affect the thermal conductivity due to the different inter-atomic bonding. Hence, AlN might not be a useful material for piezothermal application.Third, we explore the effect of piezoelectric strain on the thermal conductance of SiO2/graphene and ZnO/graphene superlattices. Using EMD we calculate the thermal conductivity of a superlattice composed of silica and graphene monolayers. The thermal conductance of the superlattice was evaluated under different values of external electric field. We find that applying a positive electric field parallel to the Z-direction leads to reduction of the thermal conductance by a factor of 2 for an electric field of 20 MV/m. On the other hand, no change in the thermal conductance is noted for ZnO/graphene superlattice. The effect is due to the non-uniform strain induced at the superlattice junctions. The effect is recreated in Si/Ge superlattice by mechanically applying a non-uniform strain at the interface. This approach might be responsible for the scattering of phonons.
104

Freqüência de polimorfismos do gene CFTR em pacientes portadores de pancreatite crônica alcoólica / Polymorphisms in patients with alcoholic chronic pancreatitis

Marianges Zadrozny Gouvêa da Costa 19 March 2008 (has links)
A dependência de álcool acomete de 10 a 12% da população mundial, estando a associação entre uso abusivo do álcool e pancreatite crônica bem estabelecida. A suscetibilidade pancreática ao álcool é variável e apenas 5 a 10% dos etilistas crônicos desenvolvem pancreatite crônica, sendo o papel dos fatores genéticos neste processo praticamente desconhecido. O gene CFTR (cystic fibrosis transmenbrane conductance regulator) codifica proteína que funciona na membrana plasmática de células epiteliais e que tem papel chave na função pancreática exócrina normal, promovendo a regulação, da secreção de fluídos e bicarbonato, importantes para a diluição e a alcalinização do suco pancreático. Quando a função desta proteína é inadequada, observa-se obstrução de pequenos ductos por rolhas protéicas. Várias pesquisas buscam documentar a associação fibrose cística - pancreatite crônica, porém os resultados são conflitantes. Este trabalho pesquisou a freqüência de polimorfismos no trato de politiminas e poli TGs no intron 8 do gene CFTR em pacientes portadores de pancreatite crônica alcoólica. Foram estudados três grupos de pacientes: Grupo A - adultos alcoolistas com diagnóstico de pancreatite crônica; Grupo B - adultos alcoolistas sem pancreatopatia ou cirrose hepática e Grupo C - adultos sadios não alcoolistas. O DNA genômico para análise do gene CFTR foi extraído do sangue periférico, pesquisando-se a freqüência de polimorfismos no trato de politiminas e poli TGs no intron 8. O genótipo 5T/7T foi mais encontrado no grupo A do que no B (p = 0,0481), não havendo diferença quando comparados os grupos A e C (p = 0,1317). Pacientes com pancreatite crônica por álcool com o genótipo 5T/7T tiveram menor incidência de diabetes melito do que aqueles com outros genótipos (p = 0,0465). A combinação de haplótipos 10TG 7T / 11TG 7T foi mais freqüente nos grupos B e C do que no A e poderia, eventualmente, ser um fator protetor contra o desenvolvimento da pancreatite crônica. (p = 0,0080 e 0,0162). Em conclusão, há diferenças no intron 8 do gene CFTR em pacientes com pancreatite crônica alcoólica, quando comparados com alcoolistas não pancreatopatas e indivíduos com o genótipo 5T/7T teriam maior risco de desenvolver pancreatite crônica quando se tornam alcoolistas crônicos. / The alcohol dependence affects from 10 to 12% of the world-wide population, being the association between alcohol abuse and chronic pancreatitis well established. The pancreatic susceptibility to the alcohol is only 5 to 10%, being the paper of the genetic factors practically unknown. The CFTR gene (cystic fibrosis transmenbrane conductance regulator) codifies a protein that functions in the epithelial cells and has a role in pancreatic exocrine function, promoting regulation of the secretion of fluids and bicarbonate, important for the dilution and the alcalinization of the pancreatic juice. When the function of this protein is inadequate, blockage of small ducts occurs. Some research regist the association cystic fibrosis - chronic pancreatite, however the results are conflicting. This work searched the frequency of polymorphisms in the polyT and poly TGs tracts in intron 8 of CFTR gene in patients with alcoholic chronic pancreatitis. Three groups of patients have been studied: Group A - adult alcoholics with chronic pancreatitis; Group B - adult alcoholics without pancreatic disease or hepatic cirrhosis and Group C - non alcoholics healthy adults. DNA analysis of CFTR gene was made after extraction from peripheral blood samples. The 5T/7T genotype was more frequently found in group A that in B (p = 0.0481), with no difference when compared to group C (p = 0,1317). Patients with alcoholic chronic pancreatitis and 5T/7T genotype had less incidence of diabetes mellitus that those with other genotypes (p = 0,0465). The haplotype combination 10TG 7T / 11TG 7T was more frequent in groups B and C that in A and it could, eventually, be a protective factor against the development of alcoholic chronic pancreatitis. (p = 0,0080 and 0,0162). In conclusion, we found differences when these tree groups are compared and individuals with 5T/7T genotype would have greater risk to develop chronic pancreatitis if they become alcoholics.
105

Microscopie à grille locale comme outil d’extraction des propriétés électroniques locales en transport quantique / Scanning gate microscopy as a tool for extracting electronic properties in quantum transport

Ly, Ousmane 23 November 2017 (has links)
La technique de la microscopie à grille de balayage (SGM) consiste à mesurer la conductance d'un gaz bidimensionnel d'électrons (2DEG) sous l'influence d'une pointe balayant la surface de l'échantillon. Dans ce travail, une approche analytique complétée par des simulations numériques est développée pour étudier la relation entre les mesures SGM et les propriétés électroniques locales dans des systèmes mésoscopiques. La correspondance entre la réponse SGM et la densité locale partielle (PLDOS) est étudiée pour un contact quantique entouré d’un 2DEG en présence ou en absence de désordre, pour une pointe perturbative ou non perturbative. Une correspondance SGM-PLDOS parfaite est trouvée pour des transmissions entières et des pointes locales. La dégradation de la correspondance en dehors de cette situation est étudiée. D’autre part, la liaison entre la réponse SGM et la transformée de Hilbert de la densité locale est discutée. Pour étudier le rôle de la force de la pointe sur la conductance SGM, une formule analytique donnant la conductance totale est obtenue. Dans le cas d'une pointe à taille finie nous proposons une méthode basée sur les fonctions de Green permettant de calculer la conductance en connaissant les propriétés non-perturbées. En plus, nous avons étudié la dépendance des branches de la PLDOS en fonction de l’énergie de Fermi. / The scanning gate microscopy (SGM) technique consists in measuring the conductance of a two dimensional electron gas (2DEG) under the influence of a scanning tip. In this work, an analytical approach complemented by numerical simulations is developed to study the connection between SGM measurements and local electronic properties in mesoscopic devices. The connection between the SGM response and the partial local density of states (PLDOS) is studied for the case of a quantum point contact surrounded by clean or disordered 2DEG for perturbative or non-perturbative, local or extended tips. An SGM-PLDOS correspondence is found for integer transmissions and local tips. The degradation of this correspondence out of these conditions is studied. Moreover, a presumed link between the SGM response and the Hilbert transform of the LDOS is discussed. To study the role of the tip strength, an analytical formula giving the full conductance in the case of local tips is obtained. Furthermore, a Green function method enabling to calculate the quantum conductance in the presence of a finite size tip in terms of the unperturbed properties is proposed. Finally the dependence of the PLDOS branches on the Fermi energy is studied.
106

Transport à travers un canal quantique élémentaire : action du circuit, quantification de la charge et limite quantique du courant de chaleur / Transport across an elementary quantum channel : action of the circuit, charge quantization and quantum limit of heat flow

Jezouin, Sebastien 27 November 2014 (has links)
Ce mémoire de thèse présente trois expériences portant sur le transport quantique dans les conducteurs cohérents à l’échelle élémentaire du canal de conduction. La première étudie comment le transport d’électricité dans un canal est affecté lorsque le canal est inséré dans un circuit modélisé par une impédance linéaire. Nous avons observé empiriquement une loi d’échelle à laquelle obéit la conductance du canal et nous avons démontré expérimentalement une analogie entre ce système et les liquides de Tomonaga-Luttinger. La deuxième s’intéresse à la nature de la charge d’un îlot métallique couplé électriquement au monde extérieur par deux canaux de conduction. Dans le régime de couplage faible, il est bien connu que cette charge est quantifiée en unités de la charge de l’électron. Ici, nous avons caractérisé la transition vers le régime de couplage fort, où la quantification de la charge est détruite par les fluctuations quantiques. La troisième concerne le transport de chaleur dans les conducteurs cohérents. Grâce à un système de mesure de bruit implémenté au cours de ce travail de thèse, nous avons pu, pour la première fois, mesurer quantitativement la conductance thermique d’un unique canal de conduction électronique, que nous avons trouvée en accord avec le quantum de conductance thermique à une résolution de quelques pourcents. / This thesis presents three experiments focusing on quantum transport in coherent conductors at the elementary scale of the conduction channel. The first one studies how electrical transport in a channel is modified when the channel is embedded in a linear circuit characterized by an impedance. We observed empirically that the channel conductance obeys a scaling law and we demonstrated experimentally a mapping of this system to the so-Called Tomonaga-Luttinger liquids. The second one is interested in the charge of a metallic island electrically coupled to the outside world through two conduction channels. In the weak coupling regime, it is well-Known that the island charge is quantized in units of the electron charge. Here we characterized the crossover to the strong coupling regime where charge quantization is destroyed by quantum fluctuations. The third one is about heat transport in coherent conductors. Thanks to a noise measurement setup implemented during this thesis, we were able to measure quantitatively for the first time the thermal conductance of a single electronic channel, which we found in agreement with the thermal conductance quantum to a few % accuracy.
107

The mechanics of valve cooling in internal-combustion engines. Investigation into the effect of VSI on the heat flow from valves towards the cooling jacket.

Abdel-Fattah, Yahia January 2009 (has links)
Controlling the temperature of the exhaust valves is paramount for proper functioning of engines and for the long lifespan of valve train components. The majority of the heat outflow from the valve takes place along the valve-seat-cylinder head-coolant thermal path which is significantly influenced by the thermal contact resistance (TCR) present at the valve/seat and seat/head interfaces. A test rig facility and experimental procedure were successfully developed to assess the effect of the valve/seat and seat/head interfaces on heat outflow from the valve, in particular the effects of the valve/seat interface geometry, seat insert assembly method, i.e. press or shrink fit, and seat insert metallic coating on the operating temperature of the valve. The results of tests have shown that the degree of the valve-seat geometric conformity is more significant than the thermal conductivity of the insert: for low conforming assemblies, the mean valve head temperature recorded during tests on copper-infiltrated insert seats was higher than that recorded during tests on noninfiltrated seats of higher conformance. The effect of the insert-cylinder head assembly method, i.e. shrink-fitted versus press-fitted inserts, has proved negligible: results have shown insignificant valve head temperature variations, for both tin-coated and uncoated inserts. On the other hand, coating the seat inserts with a layer of tin (20-22¿m) reduced the mean valve head temperature by approximately 15°C as measured during tests on uncoated seats. The analysis of the valve/seat and seat/head interfaces has indicated that the surface asperities of the softer metal in contact would undergo plastic deformation. Suitable thermal contact conductance (TCC) models, available in the public domain, were used to evaluate the conductance for the valve/seat and seat/cylinder head interfaces. Finally, a FE thermal model of the test rig has been developed with a view to assess the quality of the calculated TCC values for the valve/seat and seat/head interfaces. The results of the thermal analysis have shown that predicted temperatures at chosen control points agree with those measured during tests on thermometric seats with an acceptable level of accuracy, proving the effectiveness of the used TCC models.
108

A new paradigm for disc-pad interface models in friction brake system

Qiu, L., Qi, Hong Sheng, Wood, Alastair S. January 2014 (has links)
In this paper a 2D coupled thermal-stress finite element model is established and used to predict thermal phenomena at the disc-pad interface of a disc brake system. The importance of certain critical settings and parameters for the 2D FE model has been identified (such as, a limited degree of freedom for a brake pad in place of accepted practice that considers uniform contact), here a non-uniform pressure distribution resulting from friction bending moment effects due to the introduction of a pivot point. These parameters affect the distributions of both interface temperature and pressure. The simulation results show that when the interface conductance h is 10^6 W/m^2K or higher, the interface temperature distribution is no longer sensitive to friction bending moment effects. However, when h is 30000 W/m^2K or lower, the interface temperature distribution and heat partition ratio are significantly affected by the setting used for the rotational degree of freedom of the pad. The simulation results provide a useful reference for a better design of a disc brake system for different applications.
109

Evaluation of NMR structural studies on a family of membrane active channel forming peptides

Herrera, Alvaro Ivan January 1900 (has links)
Doctor of Philosophy / Biochemistry and Molecular Biophysics / Om Prakash / John M. Tomich / As part of the ongoing development of a channel forming peptide with the potential to be used clinically to treat cystic fibrosis, a number of structural studies using solution NMR spectroscopy have been carried out on a number of the test sequences. Given their structural similarities of the monomers it is important to evaluate whether or not there is a compelling need to determine the solution NMR structure of next-generation peptides. The determination of the NMR monomeric solution structure of peptides NK₄-M2GlyR-p22 and NK₄-M2GlyR-p20 T17R S20W in TFE solution and SDS micelles sample shows predominantly alpha-helical conformations for both sequences with an extended conformation for the N-terminal lysine residues. The I[subscript max], K[subscript 1/2] and Hill coefficient, derived from data on ion conductance across monolayers of MDCK cells, were used to compare the ion conductance properties of the peptide sequences. Peptide NK₄ M2GlyR p20 T17R S20W has both a higher I[subscript MAX] (43.8 ± 2.8 μA/cm²) and a lower K[subscript 1/2] (58 ± 8 μM) compared to other M2GlyR derived peptides with calculated NMR structures. All available molecular structures calculated by NMR for M2GlyR derived peptides were compared and the correlation of the structural changes observed in the NMR structures with the ion conductance changes was evaluated. The NMR structures were found to have limited predicting potential over the ion conduction data. NMR determined structures have provided an experimentally based starting point for studies of the channels formed by the family of M2GlyR peptides. Computer simulations account for inter peptide interactions and packing effects that are not experienced by the monomeric form of the peptides in the NMR samples that have been used until now. The determination of the structure of the oligomeric peptide channels is deemed needed to improve the relevance of future use of NMR in this project. The use of larger membrane mimicking agents, isotopically labeled (¹⁵N, ¹³C) samples, 3D NMR experiments and potentially solid state NMR would be required to accomplish that task.
110

Synthetic peptides modulate epithelial junctions

Yi, Sheng January 1900 (has links)
Master of Science / Department of Biochemistry / Bruce D. Schultz / John M. Tomich / Peptides based on the second transmembrane segment of the glycine receptor (M2GlyR) were made to provide a potential therapeutic treatment for cystic fibrosis (CF) and a latent absorption enhancer for drug delivery. For similarity of presentation, unique synthetic peptide sequences have been given alpha-numeric designations. Results are presented from studies focusing on four peptides. In the first study, the contributions of synthetic peptides p1171, p1172 and p1173 to net transepithelial ion transport were measured as a first step toward the goal of testing whether pore length or electrostatics of pore lining residues will affect anion transport. Peptide p1130 exhibits many attributes that make it an ideal synthetic peptide for CF treatment, but has low permselectivity for anions. Therefore, it is used as a platform for modification. Peptide p1171 is doubly substituted with diaminopropionic acid at positions T13 and T17. Peptide p1172 and p1173 are separately one and two helical turn(s) inserted into the p1130 backbone. Apical exposure of MDCK monolayers to these peptides caused a rapid increase in short circuit current (Isc), an indicator of net ion transport. The increase in Isc caused by p1172 or p1173 was accompanied by increase in transepithelial electrical conductance (gte). The electrophysiological results suggested that these modified peptides can assemble in the apical membrane of epithelial cells to form functional ion-conducting pores. Peptide NC-1059, which provides for ion transport across epithelial cells derived from many sources, was studied further to assess cellular changes that account for increased gte. NC-1059 increased Isc, gte and enhanced permeation of dextrans in a concentration dependent manner. Results from previous and current studies show that NC-1059 modulated the epithelial paracellular pathway by altering the distribution and abundance of junctional proteins. Immunoblotting and immunolabeling with confocal microscopy showed that NC-1059 induces reorganization of actin and causes a reduction in F-actin abundance in epithelial cells. The distributions were changed and cellular abundances were reduced of tight junction proteins occludin and ZO-1 and adherens junction proteins E-cadherin and β-catenin by NC-1059. These effects were largely reversed in 24 hr and fully recovered in 48 hr. Therefore, NC-1059 has the therapeutic potential to increase the efficiency of drug delivery across barrier membranes.

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