973 resultados para signal transduction, two-component system


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In terms of exact solution of the time-dependent Schrodinger equation. we examine the quantum tunneling process in Bose condensates of two interacting species trapped in a double well configuration. We use the two series of time-dependent SU(2) gauge transformation to diagonalize the Hamilton operator obtain analytic time-evolution formulas of the population imbalance and the berry phase. The particle population imbalance (a(L)(+)a(L) - a(R)(+)a(R)) of species A between the two wells is studied analytically.

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The thermal entanglement in a two-qutrit system with two spins coupled by exchange interaction is investigated in terms of the measure of entanglement called "negativity". It is found that the thermal entanglement is present and evolvements symmetrically between both ferromagnetic and antiferromagnetic exchange couplings with the temperature. Moreover the critical temperature at which the negativity vanishes increases with the exchange coupling constant J. From the temperature and magnetic field dependences we demonstrate that the temperature and the magnetic field can affect the feature of the thermal entanglement significantly.

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This paper discusses a rigorous treatment of the refractive scintillation of pulsar PSR B0833-45 caused by a two-component interstellar scattering medium. It is assumed that the interstellar scattering medium is composed of a thin screen ISM and an extended interstellar medium. We consider that the scattering of the thin screen concentrates in a thin layer presented by a delta function distribution and that the scattering density of the extended irregular medium satisfies the Gaussian distribution. We investigate and develop equations for the flux density structure function corresponding to this two-component ISM geometry in the scattering density distribution and compare our result with that of the Vela pulsar observations. We conclude that the refractive scintillation caused by this two-component ISM scattering gives a more satisfactory explanation for the observed flux density variation of the Vela pulsar than does the single extended medium model. The level of refractive scintillation is strongly sensitive to the distribution of scattering material along the line of sight. The logarithmic slope of the structure function is sensitive to thin screen location and is relatively insensitive to the scattering strength of the thin screen medium. Therefore, the proposed model can be applied to interpret the structure function of flux density observed in pulsar PSR B0833-45. The result suggests that the medium consists of a discontinuous distribution of plasma turbulence embedded in the Vela supernova remnant. Thus our work provides some insight into the distribution of the scattering along the line of sight to the Vela pulsar.

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The nucleation and growth kinetics of CdS nanocrystals in a two-phase synthesis system have been investigated. It was found that the nucleation process is quite lengthy and overlapped with the growth process; nevertheless, as formed nanocrystals show extremely narrow size distribution owing to the unique heterogeneous reacting environment and Ostwald ripening growth. The nucleation and growth kinetics of the nanocrystals were also influenced strongly by the monomer concentration, capping agent concentration, and solvent polarity. It was also found that a high monomer concentration, a low capping agent concentration, and low solvent polarity lead to a higher maximum nucleus concentration and nanocrystal concentration, while high polarity solvents are favorable for the formation of nanocrystals with narrower size distribution and higher photoluminescence quantum yield.

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We uncovered the underlying energy landscape of the mitogen-activated protein kinases signal transduction cellular network by exploring the statistical natures of the Brownian dynamical trajectories. We introduce a dimensionless quantity: The robustness ratio of energy gap versus local roughness to measure the global topography of the underlying landscape. A high robustness ratio implies funneled landscape. The landscape is quite robust against environmental fluctuations and variants of the intrinsic chemical reaction rates.

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We uncover the underlying potential energy landscape for a cellular network. We find that the potential energy landscape of the mitogen-activated protein-kinase signal transduction network is funneled toward the global minimum. The funneled landscape is quite robust against random perturbations. This naturally explains robustness from a physical point of view. The ratio of slope versus roughness of the landscape becomes a quantitative measure of robustness of the network. Funneled landscape is a realization of the Darwinian principle of natural selection at the cellular network level. It provides an optimal criterion for network connections and design. Our approach is general and can be applied to other cellular networks.

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In the investigation of effect of KSCN on the partitioning of lysozyme in PEG2000/ammonium sulfate aqueous two-phase system, it was found that the KSCN could alter the pH difference between the two phases. and thus affect the partition of lysozyme. The relationship between partition coefficients of lysozyme and pH differences between two phases was discussed.

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The effect of potassium thiocyanate on the partitioning of lysozyme and BSA in polyethylene glycol 2000/ammonium sulfate aqueous two-phase system has been investigated. As a result of the addition of potassium thiocyanate to the PEG/ammonium sulfate system, the PEG/mixed salts aqueous two-phase system was formed. It was found that the potassium thiocyanate could alter the pH difference between the two phases, and, thus, influence the partition coefficients of the differently charged proteins. The relationship between partition coefficient of the proteins and pH difference between two phases has been discussed. It was proposed that the pH difference between two phases could be employed as the measurement of electrostatic driving force for the partitioning of charged proteins in polyethylene glycol 2000/ammonium sulfate aqueous two-phase system.

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Interfacial waves propagating along the interface between a three-dimensional two-fluid system with a rigid upper boundary and an uneven bottom are considered. There is a light fluid layer overlying a heavier one in the system, and a small density difference exists between the two layers. A set of higher-order Boussinesq-type equations in terms of the depth-averaged velocities accounting for stronger nonlinearity are derived. When the small parameter measuring frequency dispersion keeping up to lower-order and full nonlinearity are considered, the equations include the Choi and Camassa's results (1999). The enhanced equations in terms of the depth-averaged velocities are obtained by applying the enhancement technique introduced by Madsen et al. (1991) and Schaffer and Madsen (1995a). It is noted that the equations derived from the present study include, as special cases, those obtained by Madsen and Schaffer (1998). By comparison with the dispersion relation of the linear Stokes waves, we found that the dispersion relation is more improved than Choi and Camassa's (1999) results, and the applicable scope of water depth is deeper.

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This paper considers interfacial waves propagating along the interface between a two-dimensional two-fluid with a flat bottom and a rigid upper boundary. There is a light fluid layer overlying a heavier one in the system, and a small density difference exists between the two layers. It just focuses on the weakly non-linear small amplitude waves by introducing two small independent parameters: the nonlinearity ratio epsilon, represented by the ratio of amplitude to depth, and the dispersion ratio mu, represented by the square of the ratio of depth to wave length, which quantify the relative importance of nonlinearity and dispersion. It derives an extended KdV equation of the interfacial waves using the method adopted by Dullin et al in the study of the surface waves when considering the order up to O(mu(2)). As expected, the equation derived from the present work includes, as special cases, those obtained by Dullin et al for surface waves when the surface tension is neglected. The equation derived using an alternative method here is the same as the equation presented by Choi and Camassa. Also it solves the equation by borrowing the method presented by Marchant used for surface waves, and obtains its asymptotic solitary wave solutions when the weakly nonlinear and weakly dispersive terms are balanced in the extended KdV equation.

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Alzheimer’s disease (AD) is an incurable neurodegenerative disorder, accounting for over 60% of all cases of dementia. The primary risk factor for AD is age, however several genetic and environmental factors are also involved. The pathological characteristics of AD include extracellular deposition of the beta-amyloid peptide (Aβ) and intraneuronal accumulation of neurofibrillary tangles (NFTs) made of aggregated paired helical filaments (PHFs) of the hyperphosphorylated tau protein, along with synaptic loss and neuronal death. There are numerous biochemical mechanisms involved in AD pathogenesis, however the reigning hypothesis points to toxic oligomeric Aβ species as the primary causative factor in a cascade of events leading to neuronal stress and dyshomeostasis that initiate abnormal regulation of tau. The insulin and IGF-1 receptors (IR, IGF-1R) are the primary activators of PI3- K/Akt through which they regulate cell growth, development, glucose metabolism, and learning and memory. Work in our lab and others shows increased Akt activity and phosphorylation of its downstream targets in AD brain, along with insulin and insulin-like growth factor-1 signalling (IIS) dysfunction. This is supported by studies of AD models in vivo and in vitro. Our group and others hypothesise that Aβ activates Akt through IIS to initiate a negative feedback mechanism that desensitises neurons to insulin/IGF-1, and sustains activation of Akt. In this study the functions of endogenous Akt, IR, and the insulin receptor substrate (IRS-1) were examined in relationship to Aβ and tau pathology in the 3xTg-AD mouse model, which contains three mutant human transgenes associated with familial AD or dementia. The 3xTg-AD mouse develops Aβ and tau pathology in a spatiotemporal manner that best recapitulates the progression of AD in human brain. Western blotting and immunofluorescent microscopy techniques were utilised in vivo and in vitro, to examine the relationship between IIS, Akt, and AD pathology. I first characterised in detail AD pathology in 3xTg-AD mice, where an age-related accumulation of intraneuronal Aβ and tau was observed in the hippocampal formation, amygdala, and entorhinal cortex, and at late stages (18 months), extracellular amyloid plaques and NFTs, primarily in the subiculum and the CA1 layer of the hippocampal formation. Increased activity of Akt, detected with antibody to phosphoSer473-Akt, was increased in 3xTg-AD mice compared to age-matched non-transgenic mice (non-Tg), and in direct correlation to the accumulation of Aβ and tau in neuronal somatodendritic compartments. Akt phosphorylates tau at residue Ser214 within a highly specific consensus sequence for Akt phosphorylation, and phosphoSer214-tau strongly decreases microtubule (MT) stabilisation by preventing tau-MT binding. PhosphoSer214-tau increased concomitantly with this in the same age-related and region-specific fashion. Polarisation of tau phosphorylation was observed, where PHF-1 (tauSer396/404) and phosphoSer214-tau both appeared early in 3xTg-AD mice in distinct neuronal compartments: PHF-1 in axons, and phosphoSer214-tau in neuronal soma and dendrites. At 18 months, phosphoSer214-tau strongly colocalised with NFTs positive for the PHF- 1 and AT8 (tauSer202/Thr205) phosphoepitopes. IR was decreased with age in 3xTg-AD brain and in comparison to age-matched non-Tg, and this was specific for brain regions containing Aβ, tau, and hyperactive Akt. IRS-1 was similarly decreased, and both proteins showed altered subcellular distribution. Phosphorylation of IRS-1Ser312 is a strong indicator of IIS dysfunction and insulin resistance, and was increased in 3xTg-AD mice with age and in relation to pathology. Of particular note was our observation that abberant IIS and Akt signalling in 3xTg-AD brain related to Aβ and tau pathology on a gross anatomical level, and specifically localised to the brain regions and circuitry of the perforant path. Finally, I conducted a preliminary study of the effects of synthetic Aβ oligomers on embryonic rat hippocampus neuronal cultures to support these results and those in the literature. Taken together, these novel findings provide evidence for IIS and Akt signal transduction dysfunction as the missing link between Aβ and tau pathogenesis, and contribute to the overall understanding of the biochemical mechanisms of AD.

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Deregulation of the Sonic hedgehog pathway has been implicated in an increasing number of human cancers. In this pathway, the seven-transmembrane (7TM) signaling protein Smoothened regulates cellular proliferation and differentiation through activation of the transcription factor Gli. The activity of mammalian Smoothened is controlled by three different hedgehog proteins, Indian, Desert, and Sonic hedgehog, through their interaction with the Smoothened inhibitor Patched. However, the mechanisms of signal transduction from Smoothened are poorly understood. We show that a kinase which regulates signaling by many "conventional" 7TM G-protein-coupled receptors, G protein-coupled receptor kinase 2 (GRK2), participates in Smoothened signaling. Expression of GRK2, but not catalytically inactive GRK2, synergizes with active Smoothened to mediate Gli-dependent transcription. Moreover, knockdown of endogenous GRK2 by short hairpin RNA (shRNA) significantly reduces signaling in response to the Smoothened agonist SAG and also inhibits signaling induced by an oncogenic Smoothened mutant, Smo M2. We find that GRK2 promotes the association between active Smoothened and beta-arrestin 2. Indeed, Gli-dependent signaling, mediated by coexpression of Smoothened and GRK2, is diminished by beta-arrestin 2 knockdown with shRNA. Together, these data suggest that GRK2 plays a positive role in Smoothened signaling, at least in part, through the promotion of an association between beta-arrestin 2 and Smoothened.