22 research outputs found

    Nonlinear Transport in a Quantum Point Contact due to Soft Disorder Induced Coherent Mode Mixing

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    We show that the coherent mixing of different transverse modes, due to forward scattering of carriers by soft impurity- or boundary potentials leads to a nonlinear, asymmetric current response of quantum point contacts (QPC). The oscillating contribution to the current is sensitive both to driving voltage and to gate voltage in direct analogy to the electrostatic Aharonov-Bohm effect. Our calculations are in a good agreement with recent experimental data showing small-scale conductivity nonlinearities and asymmetry in QPC.Comment: 4 pages, 2 figures (availiable upon request), REVTEX, Applied Physics Report 93-4

    Resveratrol Targeting of Carcinogen-Induced Brain Endothelial Cell Inflammation Biomarkers MMP-9 and COX-2 is Sirt1-Independent

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    The occurrence of a functional relationship between the release of metalloproteinases (MMPs) and the expression of cyclooxygenase (COX)-2, two inducible pro-inflammatory biomarkers with important pro-angiogenic effects, has recently been inferred. While brain endothelial cells play an essential role as structural and functional components of the blood-brain barrier (BBB), increased BBB breakdown is thought to be linked to neuroinflammation. Chemopreventive mechanisms targeting both MMPs and COX-2 however remain poorly investigated. In this study, we evaluated the pharmacological targeting of Sirt1 by the diet-derived and antiinflammatory polyphenol resveratrol. Total RNA, cell lysates, and conditioned culture media from human brain microvascular endothelial cells (HBMEC) were analyzed using qRT-PCR, immunoblotting, and zymography respectively. Tissue scan microarray analysis of grade I–IV brain tumours cDNA revealed increased gene expression of Sirt-1 from grade I–III but surprisingly not in grade IV brain tumours. HBMEC were treated with a combination of resveratrol and phorbol 12-myristate 13-acetate (PMA), a carcinogen known to increase MMP-9 and COX-2 through NF-κB. We found that resveratrol efficiently reversed the PMA-induced MMP-9 secretion and COX-2 expression. Gene silencing of Sirt1, a critical modulator of angiogenesis and putative target of resveratrol, did not lead to significant reversal of MMP-9 and COX-2 inhibition. Decreased resveratrol inhibitory potential of carcinogen-induced IκB phosphorylation in siSirt1-transfected HBMEC was however observed. Our results suggest that resveratrol may prevent BBB disruption during neuroinflammation by inhibiting MMP-9 and COX-2 and act as a pharmacological NF-κB signal transduction inhibitor independent of Sirt1

    A similarity search algorithm to predict protein structures

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    Accurate prediction of protein structures is very important for many applications such as drug discovery and biotechnology. Building side chains is an essential to get any reliable prediction of the protein structure for any given a protein main chain conformation. Most of the methods that predict side chain conformations use statistically generated data from known protein structures. It is a computationally intractable problem to search suitable side chains from all possible rotamers simultaneously using information of known protein structures. Reducing the number of possibility is a main issue to predict side chain conformation. This paper proposes an enumeration based similarity search algorithm to predict side chain conformations. By introducing &ldquo;beam search&rdquo; technique, a significant number of unrelated side chain rotamers can easily be eliminated. As a result, we can search for suitable residue side chains from all possible side chain conformations.<br /
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