968 resultados para k channels
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BoltzmannPoissonKKK
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<p>This dissertation describes studies of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) using unnatural amino acid mutagenesis to gain high precision insights into the function of these important membrane proteins.</p> <p>Chapter 2 considers the functional role of highly conserved proline residues within the transmembrane helices of the D2 dopamine GPCR. Through mutagenesis employing unnatural -hydroxy acids, proline analogs, and N-methyl amino acids, we find that lack of backbone hydrogen bond donor ability is important to proline function. At one proline site we additionally find that a substituent on the proline backbone N is important to receptor function.</p> <p>In Chapter 3, side chain conformation is probed by mutagenesis of GPCRs and the muscle-type nAChR. Specific side chain rearrangements of highly conserved residues have been proposed to accompany activation of these receptors. These rearrangements were probed using conformationally-biased -substituted analogs of Trp and Phe and unnatural stereoisomers of Thr and Ile. We also modeled the conformational bias of the unnatural Trp and Phe analogs employed.</p> <p>Chapters 4 and 5 examine details of ligand binding to nAChRs. Chapter 4 describes a study investigating the importance of hydrogen bonds between ligands and the complementary face of muscle-type and 44 nAChRs. A hydrogen bond involving the agonist appears to be important for ligand binding in the muscle-type receptor but not the 44 receptor.</p> <p>Chapter 5 describes a study characterizing the binding of varenicline, an actively prescribed smoking cessation therapeutic, to the 7 nAChR. Additionally, binding interactions to the complementary face of the 7 binding site were examined for a small panel of agonists. We identified side chains important for binding large agonists such as varenicline, but dispensable for binding the small agonist ACh.</p> <p>Chapter 6 describes efforts to image nAChRs site-specifically modified with a fluorophore by unnatural amino acid mutagenesis. While progress was hampered by high levels of fluorescent background, improvements to sample preparation and alternative strategies for fluorophore incorporation are described.</p> <p>Chapter 7 describes efforts toward a fluorescence assay for G protein association with a GPCR, with the ultimate goal of probing key protein-protein interactions along the G protein/receptor interface. A wide range of fluorescent protein fusions were generated, expressed in Xenopus oocytes, and evaluated for their ability to associate with each other.</p>
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<p>Three separate topics, each stimulated by experiments, are treated theoretically in this dessertation: isotopic effects of ozone, electron transfer at interfaces, and intramolecular directional electron transfer in a supramolecular system.</p> <p> The strange mass-independent isotope effect for the enrichment of ozone, which has been a puzzle in the literature for some 20 years, and the equally puzzling unconventional strong mass-dependent effect of individual reaction rate constants are studied as different aspects of a symmetry-driven behavior. A statistical (RRKM-based) theory with a hindered-rotor transition state is used. The individual rate constant ratios of recombination reactions at low pressures are calculated using the theory involving (1) small deviation from the statistical density of states for symmetric isotopomers, and (2) weak collisions for deactivation of the vibrationally excited ozone molecules. The weak collision and partitioning among exit channels play major roles in producing the large unconventional isotope effect in "unscrambled" systems. The enrichment studies reflect instead the non-statistical effect in "scrambled" systems. The theoretical results of low-pressure ozone enrichments and individual rate constant ratios obtained from these calculations are consistent with the corresponding experimental results. The isotopic exchange rate constant for the reaction ^(16)O + ^(18)O ^(18)O+ ^(16)O ^(18)O + ^(18)O provides information on the nature of a variationally determined hindered-rotor transition state using experimental data at 130 K and 300 K. Pressure effects on the recombination rate constant, on the individual rate constant ratios and on the enrichments are also investigated. The theoretical results are consistent with the experimental data. The temperature dependence of the enrichment and rate constant ratios is also discussed, and experimental tests are suggested. The desirability of a more accurate potential energy surface for ozone in the transition state region is also noted.</p> <p>Electron transfer reactions at semiconductor /liquid interfaces are studied using a tight-binding model for the semiconductors. The slab method and a z-transform method are employed in obtaining the tight-binding electronic structures of semiconductors having surfaces. The maximum electron transfer rate constants at Si/viologen^(2-/+) and InP /Me_(2)Fc^(+/O) interfaces are computed using the tight-binding type calculations for the solid and the extended-Huckel for the coupling to the redox agent at the interface. These electron transfer reactions are also studied using a free electron model for the semiconductor and the redox molecule, where Bardeen's method is adapted to calculate the coupling matrix element between the molecular and semiconductor electronic states. The calculated results for maximum rate constant of the electron transfer from the semiconductor bulk states are compared with the experimentally measured values of Lewis and coworkers, and are in reasonable agreement, without adjusting parameters. In the case of InP /liquid interface, the unusual current vs applied potential behavior is additionally interpreted, in part, by the presence of surface states.</p> <p>Photoinduced electron transfer reactions in small supramolecular systems, such as 4-aminonaphthalimide compounds, are interesting in that there are, in principle, two alternative pathways (directions) for the electron transfer. The electron transfer, however, is unidirectional, as deduced from pH-dependent fluorescence quenching studies on different compounds. The role of electronic coupling matrix element and the charges in protonation are considered to explain the directionality of the electron transfer and other various results. A related mechanism is proposed to interpret the fluorescence behavior of similar molecules as fluorescent sensors of metal ions.</p>
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As espcies reativas de oxignio (ERO) so geradas durante o metabolismo celular normal e podem produzir vrios danos oxidativos no DNA, tais como leses nas bases nitrogenadas ou stios apurnico/apirimidnico (AP). Essas leses podem acarretar acmulo de stios de mutaes, caso esses danos no sejam reparados. Entretanto, as bactrias possuem vrios mecanismos de defesa contra as ERO que desempenham um importante papel na manuteno da fisiologia. O objetivo deste trabalho foi o de avaliar se sistemas enzimticos, como o reparo por exciso de bases (BER), sistema SOS e SoxRS, interferem em respostas como a sensibilidade aos antibiticos, aderncia das clulas bacterianas a superfcies biticas ou abiticas e formao de biofilme. Os mutantes utilizados no presente estudo so todos derivados de Escherichia coli K-12 e os resultados obtidos mostraram que, dos mutantes BER testados, o nico que apresentou diferena no perfil de sensibilidade aos antimicrobiamos em relao cepa selvagem (AB1157) foi o mutante xthA- (BW9091), deficiente em exonuclease III. No teste de aderncia qualitativo realizado com linhagem de clulas HEp-2 (originria de carcinoma de laringe humana) foi observado que onze cepas da nossa coleo, apresentaram um padro denominando like-AA, contrastando com o que era esperado para as cepas de E. coli utilizadas como controle negativo, que apresentam aderncia discreta sem padro tpico. A aderncia manose-sensvel via fmbria do tipo I avaliada nesse estudo mostrou que essa fimbria, possui um papel relevante na intensidade da aderncia e filamentao nessas cepas estudas. A filamentao uma resposta SOS importante para que o genoma seja reparado antes de ser partilhado pelas clulas filhas. Alm disso, com relao formao de biofilme, oito cepas apresentaram um biofilme forte sendo que essa resposta no foi acompanhada pelo aumento da intensidade de filamentao. Nossos resultados em conjunto sugerem o envolvimento de estresse oxidativo na definio de parmetros como sensibilidade a antimicrobianos, padro e intensidade de aderncia, filamentao e formao de biofilme nas amostras de E. coli K-12 avaliadas neste trabalho. Sugerimos que a aderncia gera estresse oxidativo causando danos no DNA, o que leva a induo do sistema SOS resultando na resposta de filamentao observada.
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The properties of a five-level K-type system are investigated. With the controlling fields, the properties of the dispersion and absorption of the system are changed greatly. The system can produce anomalous dispersion regions with absorption and normal dispersion regions with absorption or transparency. Furthermore, the group velocity can be varied from subluminal to superluminal by varying the intensity of the controlling field and the probe detunings in principle. (C) 2008 Elsevier B.V. All rights reserved.
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Short morphological observations are given for the Cyanophyceae Oscillatoria Agardhii, Oscillatoria prolifica and Oscillatoria rubescens.
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The composition of the food of the European grayling and the character of its feeding has been studied fully enough, but this knowledge is scattered in the literature and often contradictory. rare exceptions, analysis of the results of different investigations. Therefore the proposed short outline of the history of the study of the problem with a description of the basic data on the feeding of the grayling in different geographical areas is presented as expedient and opportune, primarily in relation to the determination of immediate problems and the trend of research.
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The design and construction of four experimental channels at Grassholme reservoir in Teesdale, County Durham (UK) are briefly described. The problem of obtaining valid replication between channels is examined using published data obtained for previous experiments in the channels. It is concluded that replication may be obtained by careful experimental design. The limitations of the existing configuration of pipework and channel design are discussed and solutions suggested. Finally a list of the main components of the channels and suppliers is appended. Alternative materials and suppliers could well be found for most items. (PDF contains 23 pages)
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Adjustment of experimental channels to give any specified pattern of water depth or velocity is complex and tedious because it involves a number of variables. Since some variables are not controllable and variables may interact, valve settings of the Grassholme channels were initially determined on an ad hoc basis to suit individual experiments. This method was used during 1982 but additional observations were made in order to gain more detailed understanding of the channel system and, as far as possible, to develop a guide to future short-cuts in attaining suitable channel settings for any given purpose. This report describes calibration of the Grassholme channels (using water of the Grassholme Reservoir) for the biological experiments of spring - summer 1982. The main variables that are discussed are valve turns and discharge and velocity and depth. It also seeks to establish relationships which will be of value in future managment of the channels for experimental purposes.
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<p>Electronic Kl x-ray isotope shifts have been measured for Sn 116-124, Sm 148-154, W 182-184, W 184-186, and W 182-186 using a curved crystal Cauchois spectrometer. The analysis of the measurements has included the electrostatic volume effect, screening by the transition electron as well as the non-transition electrons, normal and specific mass shifts, dynamical nuclear qudrupole polarization, and a radiative correction effect of the electron magnetic moment in the nuclear charge radii are obtained. Where other experimental data are available, the agreement with the present measurements is satisfactory. Comparisons with several nuclear model predictions yield only partial agreement. </p>
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<p>This study is concerned with some of the properties of roll waves that develop naturally from a turbulent uniform flow in a wide rectangular channel on a constant steep slope . The wave properties considered were depth at the wave crest, depth at the wave trough, wave period, and wave velocity . The primary focus was on the mean values and standard deviations of the crest depths and wave periods at a given station and how these quantities varied with distance along the channel.</p> <p>The wave properties were measured in a laboratory channel in which roll waves developed naturally from a uniform flow . The Froude number F (F = u<sub>n</sub>/gh<sub>n</sub>, u<sub>n</sub> = normal velocity , h<sub>n</sub> = normal depth, g =acceleration of gravity) ranged from 3. 4 to 6. 0 for channel slopes S<sub>o</sub> of . 05 and . 12 respectively . In the initial phase of their development the roll waves appeared as small amplitude waves with a continuous water surface profile . These small amplitude waves subsequently developed into large amplitude shock waves. Shock waves were found to overtake and combine with other shock waves with the result that the crest depth of the combined wave was larger than the crest depths before the overtake. Once roll waves began to develop, the mean value of the crest depths h<sub>nmax</sub> increased with distance . Once the shock waves began to overtake, the mean wave period T<sub>av</sub> increased approximately linearly with distance.</p> <p>For a given Froude number and channel slope the observed quantities h<sup>-</sup><sub>max</sub>/h<sub>n</sub> , T' (T' = S<sub>o</sub> T<sub>av</sub> g/h<sub>n</sub>), and the standard deviations of h<sup>-</sup><sub>max</sub>/h<sub>n</sub> and T', could be expressed as unique functions of l/h<sub>n</sub> (l = distance from beginning of channel) for the two-fold change in h<sub>n</sub> occurring in the observed flows . A given value of h<sup>-</sup><sub>max</sub>/h<sub>n</sub> occurred at smaller values of l/h<sub>n</sub> as the Froude number was increased. For a given value of h /hh<sup>-</sup><sub>max</sub>/h<sub>n</sub> the growth rate of h<sup>-</sup><sub>max</sub>/h<sup>-</sup><sub>max</sub>l of the shock waves increased as the Froude number was increased.</p> <p>A laboratory channel was also used to measure the wave properties of periodic permanent roll waves. For a given Froude number and channel slope the h<sup>-</sup><sub>max</sub>/h<sub>n</sub> vs. T' relation did not agree with a theory in which the weight of the shock front was neglected. After the theory was modified to include this weight, the observed values of h<sup>-</sup><sub>max</sub>/h<sub>n</sub> were within an average of 6.5 percent of the predicted values, and the maximum discrepancy was 13.5 percent.</p> <p>For h<sup>-</sup><sub>max</sub>/h<sub>n</sub> sufficiently large (h<sup>-</sup><sub>max</sub>/h<sub>n</sub> > approximately 1.5) it was found that the h<sup>-</sup><sub>max</sub>/h<sub>n</sub> vs. T' relation for natural roll waves was practically identical to the h<sup>-</sup><sub>max</sub>/h<sub>n</sub> vs. T' relation for periodic permanent roll waves at the same Froude number and slope. As a result of this correspondence between periodic and natural roll waves, the growth rate h<sup>-</sup><sub>max</sub>/h<sup>-</sup><sub>max</sub>l of shock waves was predicted to depend on the channel slope, and this slope dependence was observed in the experiments.</p>
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<p>The cross sections for the two antiproton-proton annihilation-in-flight modes,</p> <p>p + p <sup>+</sup> + <sup>-</sup></p> <p>p + p k<sup>+</sup> + k<sup>-</sup></p> <p>were measured for fifteen laboratory antiproton beam momenta ranging from 0.72 to 2.62 GeV/c. No magnets were used to determine the charges in the final state. As a result, the angular distributions were obtained in the form [d/d (<sub>C.M.</sub>) + d/d ( <sub>C.M.</sub>)] for 45 <sub>C.M.</sub> 135. </p> <p>A hodoscope-counter system was used to discriminate against events with final states having more than two particles and antiproton-proton elastic scattering events. One spark chamber was used to record the track of each of the two charged final particles. A total of about 40,000 pictures were taken. The events were analyzed by measuring the laboratory angle of the track in each chamber. The value of the square of the mass of the final particles was calculated for each event assuming the reaction</p> <p>p + p a pair of particles with equal masses.</p> <p>About 20,000 events were found to be either annihilation into <sup></sup>-pair or k <sup></sup>-pair events. The two different charged meson pair modes were also distinctly separated.</p> <p>The average differential cross section of p + p <sup>+</sup> + <sup>-</sup> varied from ~ 25 b/sr at antiproton beam momentum 0.72 GeV/c (total energy in center-of-mass system, s = 2.0 GeV) to ~ 2 b/sr at beam momentum 2.62 GeV/c (s = 2.64 GeV). The most striking feature in the angular distribution was a peak at <sub>C.M.</sub> = 90 (cos <sub>C.M.</sub> = 0) which increased with s and reached a maximum at s ~ 2.1 GeV (beam momentum ~ 1.1 GeV/c). Then it diminished and seemed to disappear completely at s ~ 2.5 GeV (beam momentum ~ 2.13 GeV/c). A valley in the angular distribution occurred at cos <sub>C.M.</sub> 0.4. The differential cross section then increased as cos <sub>C.M.</sub> approached 1.</p> <p>The average differential cross section for p + p k<sup>+</sup> + k<sup>-</sup> was about one third of that of the <sup></sup>-pair mode throughout the energy range of this experiment. At the lower energies, the angular distribution, unlike that of the <sup></sup>-pair mode, was quite isotropic. However, a peak at <sub>C.M.</sub> = 90 seemed to develop at s ~ 2.37 GeV (antiproton beam momentum ~ 1.82 GeV/c). No observable change was seen at that energy in the <sup></sup>-pair cross section.</p> <p>The possible connection of these features with the observed meson resonances at 2.2 GeV and 2.38 GeV, and its implications, were discussed. </p>
