321 research outputs found

    An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma

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    The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer

    MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation

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    Contains fulltext : 87376.pdf (publisher's version ) (Open Access)BACKGROUND: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTK-driven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. RESULTS: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. CONCLUSIONS: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma

    Adiabatic population transfer via multiple intermediate states

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    This paper discusses a generalization of stimulated Raman adiabatic passage (STIRAP) in which the single intermediate state is replaced by NN intermediate states. Each of these states is connected to the initial state \state{i} with a coupling proportional to the pump pulse and to the final state \state{f} with a coupling proportional to the Stokes pulse, thus forming a parallel multi-Λ\Lambda system. It is shown that the dark (trapped) state exists only when the ratio between each pump coupling and the respective Stokes coupling is the same for all intermediate states. We derive the conditions for existence of a more general adiabatic-transfer state which includes transient contributions from the intermediate states but still transfers the population from state \state{i} to state \state{f} in the adiabatic limit. We present various numerical examples for success and failure of multi-Λ\Lambda STIRAP which illustrate the analytic predictions. Our results suggest that in the general case of arbitrary couplings, it is most appropriate to tune the pump and Stokes lasers either just below or just above all intermediate states.Comment: 14 pages, two-column revtex style, 10 figure

    STIRAP transport of Bose-Einstein condensate in triple-well trap

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    The irreversible transport of multi-component Bose-Einstein condensate (BEC) is investigated within the Stimulated Adiabatic Raman Passage (STIRAP) scheme. A general formalism for a single BEC in M-well trap is derived and analogy between multi-photon and tunneling processes is demonstrated. STIRAP transport of BEC in a cyclic triple-well trap is explored for various values of detuning and interaction between BEC atoms. It is shown that STIRAP provides a complete population transfer at zero detuning and interaction and persists at their modest values. The detuning is found not to be obligatory. The possibility of non-adiabatic transport with intuitive order of couplings is demonstrated. Evolution of the condensate phases and generation of dynamical and geometric phases are inspected. It is shown that STIRAP allows to generate the unconventional geometrical phase which is now of a keen interest in quantum computing.Comment: 9 pages, 6 figures. To be published in Laser Physics (v. 19, n.4, 2009

    Observation of coherent transients in ultrashort chirped excitation of an undamped two-level system

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    The effects of Coherent excitation of a two level system with a linearly chirped pulse are studied theoretically and experimentally (in Rb (5s - 5p)) in the low field regime. The Coherent Transients are measured directly on the excited state population on an ultrashort time scale. A sharp step corresponds to the passage through resonance. It is followed by oscillations resulting from interferences between off-resonant and resonant contributions. We finally show the equivalence between this experiment and Fresnel diffraction by a sharp edge.Comment: 4 pages, 4 figures, to appear in PR

    Sub-Doppler cooling of three-level A Atoms in space-shifted standing light waves

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    We present an investigation of an alternative mechanism for sub-Doppler cooling of atoms, based on coherent population transfer in three-level LAMBDA systems. The mechanism considered is that of a LAMBDA atom interacting with two standing light waves with a mutual spatial phase shift phi not-equal 0. The spatial dependence of the level populations of the LAMBDA atom for different values of phi is presented. For phi not-equal 0, this clearly demonstrates coherent population transfer in an atom with transverse motion along the space-shifted nodes and antinodes of the two standing waves. We show that this allows translational temperatures well below the Doppler limit T(D) = hgammaBAR/k(B) to be achieved

    Quantum computation with trapped polar molecules

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    We propose a novel physical realization of a quantum computer. The qubits are electric dipole moments of ultracold diatomic molecules, oriented along or against an external electric field. Individual molecules are held in a 1-D trap array, with an electric field gradient allowing spectroscopic addressing of each site. Bits are coupled via the electric dipole-dipole interaction. Using technologies similar to those already demonstrated, this design can plausibly lead to a quantum computer with 104\gtrsim 10^4 qubits, which can perform 105\sim 10^5 CNOT gates in the anticipated decoherence time of 5\sim 5 s.Comment: 4 pages, RevTeX 4, 2 figures. Edited for length and converted to RevTeX, but no substantial changes from earlier pdf versio

    Feshbach-Stimulated Photoproduction of a Stable Molecular Condensate

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    Photoassociation and the Feshbach resonance are, in principle, feasible means for creating a molecular Bose-Einstein condensate from an already-quantum-degenerate gas of atoms; however, mean-field shifts and irreversible decay place practical constraints on the efficient delivery of stable molecules using either mechanism alone. We therefore propose Feshbach-stimulated Raman photoproduction, i.e., a combination of magnetic and optical methods, as a viable means to collectively convert degenerate atoms into a stable molecular condensate with near-unit efficiency.Comment: 5 pages, 3 figures, 1 table; v3 includes few-level diagram of scheme, and added discussion; transferred to PR

    Security and Privacy Issues in Wireless Mesh Networks: A Survey

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    This book chapter identifies various security threats in wireless mesh network (WMN). Keeping in mind the critical requirement of security and user privacy in WMNs, this chapter provides a comprehensive overview of various possible attacks on different layers of the communication protocol stack for WMNs and their corresponding defense mechanisms. First, it identifies the security vulnerabilities in the physical, link, network, transport, application layers. Furthermore, various possible attacks on the key management protocols, user authentication and access control protocols, and user privacy preservation protocols are presented. After enumerating various possible attacks, the chapter provides a detailed discussion on various existing security mechanisms and protocols to defend against and wherever possible prevent the possible attacks. Comparative analyses are also presented on the security schemes with regards to the cryptographic schemes used, key management strategies deployed, use of any trusted third party, computation and communication overhead involved etc. The chapter then presents a brief discussion on various trust management approaches for WMNs since trust and reputation-based schemes are increasingly becoming popular for enforcing security in wireless networks. A number of open problems in security and privacy issues for WMNs are subsequently discussed before the chapter is finally concluded.Comment: 62 pages, 12 figures, 6 tables. This chapter is an extension of the author's previous submission in arXiv submission: arXiv:1102.1226. There are some text overlaps with the previous submissio
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