7,002 research outputs found

    Positive surface charge of GluN1 N-terminus mediates the direct interaction with EphB2 and NMDAR mobility.

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    Localization of the N-methyl-D-aspartate type glutamate receptor (NMDAR) to dendritic spines is essential for excitatory synaptic transmission and plasticity. Rather than remaining trapped at synaptic sites, NMDA receptors undergo constant cycling into and out of the postsynaptic density. Receptor movement is constrained by protein-protein interactions with both the intracellular and extracellular domains of the NMDAR. The role of extracellular interactions on the mobility of the NMDAR is poorly understood. Here we demonstrate that the positive surface charge of the hinge region of the N-terminal domain in the GluN1 subunit of the NMDAR is required to maintain NMDARs at dendritic spine synapses and mediates the direct extracellular interaction with a negatively charged phospho-tyrosine on the receptor tyrosine kinase EphB2. Loss of the EphB-NMDAR interaction by either mutating GluN1 or knocking down endogenous EphB2 increases NMDAR mobility. These findings begin to define a mechanism for extracellular interactions mediated by charged domains

    GPER-induced signaling is essential for the survival of breast cancer stem cells.

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    G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

    Exact Master Equation and Quantum Decoherence of Two Coupled Harmonic Oscillators in a General Environment

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    In this paper we derive an exact master equation for two coupled quantum harmonic oscillators interacting via bilinear coupling with a common environment at arbitrary temperature made up of many harmonic oscillators with a general spectral density function. We first show a simple derivation based on the observation that the two-harmonic oscillator model can be effectively mapped into that of a single harmonic oscillator in a general environment plus a free harmonic oscillator. Since the exact one harmonic oscillator master equation is available [Hu, Paz and Zhang, Phys. Rev. D \textbf{45}, 2843 (1992)], the exact master equation with all its coefficients for this two harmonic oscillator model can be easily deduced from the known results of the single harmonic oscillator case. In the second part we give an influence functional treatment of this model and provide explicit expressions for the evolutionary operator of the reduced density matrix which are useful for the study of decoherence and disentanglement issues. We show three applications of this master equation: on the decoherence and disentanglement of two harmonic oscillators due to their interaction with a common environment under Markovian approximation, and a derivation of the uncertainty principle at finite temperature for a composite object, modeled by two interacting harmonic oscillators. The exact master equation for two, and its generalization to NN, harmonic oscillators interacting with a general environment are expected to be useful for the analysis of quantum coherence, entanglement, fluctuations and dissipation of mesoscopic objects towards the construction of a theoretical framework for macroscopic quantum phenomena.Comment: 35 pages, revtex, no figures, 2nd version, references added, to appear in PR

    Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

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    Endothelial dysfunction contributes to the development of acute kidney injury (AKI) in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC) and soluble thrombomodulin (sTM) levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr) and urine output criteria (AKI UO). We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC) and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78). The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89), which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02) and PC levels independently predicted mortality/non-renal recovery (p=0.04). In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI

    Sudden Death of Entanglement of Two Jaynes-Cummings Atoms

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    We investigate entanglement dynamics of two isolated atoms, each in its own Jaynes-Cummings cavity. We show analytically that initial entanglement has an interesting subsequent time evolution, including the so-called sudden death effect.Comment: 3 pages, 3 figure

    Effects of Residue Background Events in Direct Dark Matter Detection Experiments on the Determination of the WIMP Mass

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    In the earlier work on the development of a model-independent data analysis method for determining the mass of Weakly Interacting Massive Particles (WIMPs) by using measured recoil energies from direct Dark Matter detection experiments directly, it was assumed that the analyzed data sets are background-free, i.e., all events are WIMP signals. In this article, as a more realistic study, we take into account a fraction of possible residue background events, which pass all discrimination criteria and then mix with other real WIMP-induced events in our data sets. Our simulations show that, for the determination of the WIMP mass, the maximal acceptable fraction of residue background events in the analyzed data sets of O(50) total events is ~20%, for background windows of the entire experimental possible energy ranges, or in low energy ranges; while, for background windows in relatively higher energy ranges, this maximal acceptable fraction of residue background events can not be larger than ~10%. For a WIMP mass of 100 GeV with 20% background events in the windows of the entire experimental possible energy ranges, the reconstructed WIMP mass and the 1-sigma statistical uncertainty are ~97 GeV^{+61%}_{-35%} (~94 GeV^{+55%}_{-33%} for background-free data sets).Comment: 27 pages, 22 eps figures; v2: revised version for publication, references added and update

    Finite-Time Disentanglement via Spontaneous Emission

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    We show that under the influence of pure vacuum noise two entangled qubits become completely disentangled in a finite time, and in a specific example we find the time to be given by ln(2+22)\ln \Big(\frac{2 +\sqrt 2}{2}\Big) times the usual spontaneous lifetime.Comment: revtex, 4 pages, 2 figure

    Modulated Entanglement Evolution Via Correlated Noises

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    We study entanglement dynamics in the presence of correlated environmental noises. Specifically, we investigate the quantum entanglement dynamics of two spins in the presence of correlated classical white noises, deriving Markov master equation and obtaining explicit solutions for several interesting classes of initial states including Bell states and X form density matrices. We show how entanglement can be enhanced or reduced by the correlation between the two participating noises.Comment: 9 pages, 4 figures. To be published in Quantum Information Processing, special issue on Quantum Decoherence and Entanglemen
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