966 research outputs found

    Spin Hall Conductance of the Two Dimensional Hole Gas in a Perpendicular Magnetic Field

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    The charge and spin Hall conductance of the two-dimensional hole gas within the Luttinger model with and without inversion symmetry breaking terms in a perpendicular magnetic field are studied, and two key phenomena are predicted. The sign of the spin Hall conductance is modulated periodically by the external magnetic field, which means a possible application in the future. Furthermore, a resonant spin Hall conductance in the two-dimensional hole gas with a certain hole density at a typical magnetic field is indicated, which implies a likely way to firmly establish the intrinsic spin Hall effect. The charge Hall conductance is unaffected by the spin-orbit coupling.Comment: accepted for publication in Phys. Rev. B; 6 pages, 4 figure

    Development and application of operational techniques for the inventory and monitoring of resources and uses for the Texas coastal zone

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    The author has identified the following significant results. Four LANDSAT scenes were analyzed for the Harbor Island area test sites to produce land cover and land use maps using both image interpretation and computer-assisted techniques. When evaluated against aerial photography, the mean accuracy for three scenes was 84% for the image interpretation product and 62% for the computer-assisted classification maps. Analysis of the fourth scene was not completed using the image interpretation technique, because of poor quality, false color composite, but was available from the computer technique. Preliminary results indicate that these LANDSAT products can be applied to a variety of planning and management activities in the Texas coastal zone

    NADPH as a potential intrinsic probe for tumour margin estimation

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    The fluorescent properties of the reduced coenzyme NADH and its phosphorylated derivative (NADPH) have been explored in order to assess their potential as an intrinsic probe for cancer surgery. NADPH production is increased in cancer cells to quench reactive oxygen species and meet higher demands for biosynthesis, and has attractive fluorescent properties such as emission towards the visible part of the spectrum and a relatively long fluorescence lifetime upon binding to enzymes (~ 1 – 6.5 ns) that helps discriminate against other endogenous species. Different environmental effects on NAD(P)H fluorescence are reported here, including an increase in lifetime upon oxygen removal, an ability to retain its fluorescent properties in a complex medium (a silica phantom) and its fluorescence lifetime also being distinguishable in a cell environment. In addition, the development of a miniaturized liquid light guide filter-based timecorrelated single photon counting fluorescence lifetime system is reported as a step towards time-resolved visual imaging in cancer surgery. This system has been demonstrated as being capable of accurately measuring NAD(P)H fluorescence lifetimes in both simple solvent and cellular environments

    Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis.

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    INTRODUCTION Streptococcus pneumoniae (pneumococcus) meningitis is a serious disease with substantial lethality and long-term disability in survivors. Loss of synaptic staining in the superficial layers of the neocortex in rodent models and in humans, and pneumolysin (a major pneumococcal toxin)-dependent dendritic spine collapse in brain slices have been described. It remains unclear how deep in the neocortex more discrete changes are present, how soon after disease onset these changes occur, and whether other properties of dendrites are also affected. METHODS Using a mouse model of pneumococcal meningitis, we studied changes in the neocortex shortly (3-6 h) after the onset of clinical symptoms via modified Golgi-Cox silver staining. RESULTS Dendritic changes were present in areas with otherwise unchanged cell numbers and no signs of necrosis or other apparent neuronal pathology. Mature dendritic spines were reduced in the pyramidal neurons running through layers 1-5. Additionally, spine morphology changes (swelling, spine neck distortion), were also observed in the deeper layers 4 and 5 of the neocortex. Immature spines (filopodia) remained unchanged between groups, as well as the dendritic arborization of the analyzed neurons. In a third of the animals with meningitis, massive mechanical distortion of the primary dendrites of most of the pyramidal neurons through layers 1-5 was observed. This distortion was reproduced in acute brain slices after exposure to pneumolysin-containing bacterial lysates (S. pneumoniae D39 strain), but not to lysates of pneumolysin-deficient bacteria, which we explain by the tissue remodeling effect of the toxin. Experimental mechanical dendrite distortion in primary neural cultures demonstrated diminished FRAP diffusion of neuronally-expressed enhanced green fluorescent protein (eGFP), indicative of disturbed dendritic diffusion. DISCUSSION Our work extends earlier knowledge of synaptic loss in the superficial cortical layers during meningitis to deeper layers. These changes occurred surprisingly early in the course of the disease, substantially limiting the effective therapeutic window. Methodologically, we demonstrate that the dendritic spine collapse readout is a highly reliable and early marker of neural damage in pneumococcal meningitis models, allowing for reduction of the total number of animals used per a group due to much lower variation among animals

    Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis.

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    In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia to Streptococcus pneumoniae lysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization. Here we identify the cholesterol-dependent cytolysin pneumolysin as a pro-endocytotic factor in lysates, its elimination reduces their proinflammatory effect. Only pore-competent pneumolysin enhances endocytosis in a dynamin-, phosphatidylinositol-3-kinase- and potassium-dependent manner. Endocytic enhancement is limited to toxin-exposed parts of the membrane, the effect is rapid and pneumolysin permanently alters membrane dynamics. In a murine model of pneumococcal meningitis, mice treated with chlorpromazine, a neuroleptic with a complementary endocytosis inhibitory effect show reduced neuroinflammation. Thus, the dynamin-dependent endocytosis emerges as a factor in pneumococcal neuroinflammation, and its enhancement by a cytolysin represents a proinflammatory control mechanism

    Mechanism for zirconium oxide atomic layer deposition using bis(methylcyclopentadienyl)methoxymethyl zirconium

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    The mechanism for zirconium oxide atomic layer deposition using bis(methylcyclopentadienyl)methoxymethyl zirconium and H(2)O was examined using ab initio calculations of hydrolysis energies to predict the order of ligand loss. These predictions were tested using in situ mass spectrometric measurements which revealed that the methyl ligand, and 65% of the methylcyclopentadienyl ligands are lost during the zirconium precursor adsorption. The remaining 35% of the methylcyclopentadienyl ligands and the methoxy ligand are lost during the subsequent H(2)O exposure. These measurements agree very well with the predictions, demonstrating that thermodynamic calculations are a simple and accurate predictor for the reactivities of these compounds. (c) 2007 American Institute of Physics. (DOI: 10.1063/1.2824814

    Exploiting the MDM2-CK1 alpha Protein-Protein Interface to Develop Novel Biologics That Induce UBL-Kinase-Modification and Inhibit Cell Growth

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    Protein-protein interactions forming dominant signalling events are providing ever-growing platforms for the development of novel Biologic tools for controlling cell growth. Casein Kinase 1 α (CK1α) forms a genetic and physical interaction with the murine double minute chromosome 2 (MDM2) oncoprotein resulting in degradation of the p53 tumour suppressor. Pharmacological inhibition of CK1 increases p53 protein level and induces cell death, whilst small interfering RNA-mediated depletion of CK1α stabilizes p53 and induces growth arrest. We mapped the dominant protein-protein interface that stabilizes the MDM2 and CK1α complex in order to determine whether a peptide derived from the core CK1α-MDM2 interface form novel Biologics that can be used to probe the contribution of the CK1-MDM2 protein-protein interaction to p53 activation and cell viability. Overlapping peptides derived from CK1α were screened for dominant MDM2 binding sites using (i) ELISA with recombinant MDM2; (ii) cell lysate pull-down towards endogenous MDM2; (iii) MDM2-CK1α complex-based competition ELISA; and (iv) MDM2-mediated ubiquitination. One dominant peptide, peptide 35 was bioactive in all four assays and its transfection induced cell death/growth arrest in a p53-independent manner. Ectopic expression of flag-tagged peptide 35 induced a novel ubiquitin and NEDD8 modification of CK1α, providing one of the first examples whereby NEDDylation of a protein kinase can be induced. These data identify an MDM2 binding motif in CK1α which when isolated as a small peptide can (i) function as a dominant negative inhibitor of the CK1α-MDM2 interface, (ii) be used as a tool to study NEDDylation of CK1α, and (iii) reduce cell growth. Further, this approach provides a technological blueprint, complementing siRNA and chemical biology approaches, by exploiting protein-protein interactions in order to develop Biologics to manipulate novel types of signalling pathways such as cross-talk between NEDDylation, protein kinase signalling, and cell survival

    Defining the role of elastic lubricants and micro textured surfaces in lubricated, sliding friction

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    Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (p. 203-204).Solutions for reducing friction in sliding, lubricated systems include modifying lubricant rheology using polymers and adding a micro-scale texture to the sliding surfaces, but the mechanism of how lubrication properties and surface texturing interact is poorly understood. This thesis presents a study of lubricant elasticity and surface micro texturing and explains the mechanisms for the resulting altered frictional profile on the Stribeck diagram. In this work, isolating non-Newtonian effects in the lubrication flow is shown to normalize the frictional profiles of elastic and Newtonian lubricants. These non-Newtonian effects were determined to be the shear rate-dependent lubricant viscosity and the added normal stresses of the elastic lubricant undergoing shear flow. A modified Gumbel number is presented that includes the shear rate-dependent viscosity and scales the normal stress using the Deborah number. Experimental results from testing both elastic and inelastic lubricants using a triborheometer support the use of the new modified Gumbel number in place of the traditional Gumbel number for normalizing the effects of lubricant elasticity on the Stribeck diagram. To analyze the effect of surface micro texturing on the frictional profile, step-bearing theory and assumptions about the surface/lubricant interaction are used to develop scaling parameters for the transition velocities between lubrication regimes on the Stribeck diagram. These parameters indicate how the surface texture geometry can be altered to induce or delay transition between lubrication regimes. Micro textured surfaces are fabricated using photolithography and electroless nickel plating techniques, and friction testing indicates that the new scaling parameters successfully capture the trends of the related transition velocities.by Sara J. Hupp.Ph.D
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