4,581 research outputs found
Quantum Spin Hall Insulator State in HgTe Quantum Wells
Recent theory predicted that the Quantum Spin Hall Effect, a fundamentally
novel quantum state of matter that exists at zero external magnetic field, may
be realized in HgTe/(Hg,Cd)Te quantum wells. We have fabricated such sample
structures with low density and high mobility in which we can tune, through an
external gate voltage, the carrier conduction from n-type to the p-type,
passing through an insulating regime. For thin quantum wells with well width d
< 6.3 nm, the insulating regime shows the conventional behavior of vanishingly
small conductance at low temperature. However, for thicker quantum wells (d >
6.3 nm), the nominally insulating regime shows a plateau of residual
conductance close to 2e^2/h. The residual conductance is independent of the
sample width, indicating that it is caused by edge states. Furthermore, the
residual conductance is destroyed by a small external magnetic field. The
quantum phase transition at the critical thickness, d = 6.3 nm, is also
independently determined from the magnetic field induced insulator to metal
transition. These observations provide experimental evidence of the quantum
spin Hall effect.Comment: 16 pages, 5 figure
Response to combination therapy with interferon alfa-2a and ribavirin in chronic hepatitis C according to a TNF-alpha promoter polymorphism
Background. Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of chronic active hepatitis C. Polymorphisms in the promoter region of the TNF-alpha gene can alter the TNF-alpha expression and modify the host immune response. The present study aimed at the correlation of the G308A TNF-alpha polymorphism with the response to antiviral combination therapy in chronic hepatitis C. Patients and Methods: 62 patients with HCV and 119 healthy unrelated controls were genotyped for the G308A TNF-alpha promoter polymorphism. The patients received 3 x 3 million units of interferon alfa-2a and 1,0001,200 mg ribavirin daily according to their body weight. A response was defined as absence of HCV-RNA and normalization of S-ALT after 6 months of combination therapy. Results:With respect to the allele and genotype frequency, a significant difference was not observed between controls and patients with chronic hepatitis C. Furthermore, such a difference was also not observed if responders and non-responders to antiviral therapy were compared. Conclusions: The promoter polymorphism of the TNF-alpha gene investigated herein is equally distributed in healthy individuals and patients with hepatitis C and does not seem to predict the response to therapy with interferon alfa-2a and ribavirin. Copyright (C) 2003 S. Karger AG, Basel
304Nuclear targeting apelin induces phenotypic transition of vascular smooth muscle cells
Background: Apelin, and its receptor APJ, are a peptidic system playing a crucial role in vascular diseases. However, the role of apelin in atherogenesis and smooth muscle cell (SMC) proliferation remains unclear. We isolated 2 distinct SMC phenotypes from porcine coronary artery: spindle-shaped (S) and rhomboid (R). Biological features of R-SMCs (i.e. enhanced proliferative and migratory activities as well as poor level of differentiation) explain their capacity to accumulate into the intima. S100A4 is a marker of R-SMCs in vitro and of intimal SMCs, both in pig and human. S100A4 is a Ca2+-binding protein that can also be secreted; it has extracellular functions probably via the receptor for advanced glycation end products (RAGE). Purpose: Investigate the effects of apelin on SMC phenotypic transition and S100A4 expression and release. Methods and Results: We observed that apelin was highly expressed in R-SMCs particularly in their nucleus. P-SORT software analysis of preproapelin sequence suggested that N-terminal truncated apelin may target the nucleus, and we confirmed this in SMCs by overexpression of mutated preproapelin-His-tag. Transfection of mutated preproapelin-His-tag encoding plasmid in differentiated S-SMCs induced a transition towards a R-phenotype associated with increased proliferative activity, downregulation of SMC differentiation markers (i.e. alpha-smooth muscle actin), and increased nuclear expression and release of S100A4. In contrast, transfection of S-SMCs with wild type preproapelin-His-tag encoding plasmid did not induce nuclear targeting of Apelin or S100A4, and did not change the S-phenotype. Stimulation of S-SMCs with PDGF-BB, known to induce a transition to the R-phenotype, yielded nuclear targeting of both apelin and S100A4. In vivo, Apelin was expressed in SMC nuclei of stent-induced intimal thickening while its expression in the media was mainly cytoplasmic. Conclusions: Our results suggest that nuclear targeting of apelin in SMCs acts on S100A4 expression and release, cell proliferation and differentiation. The pathophysiological consequences of this retargeting could be instrumental in the understanding of artherosclerosi
Chemical synthesis of site-selective advanced glycation end products in α-synuclein and its fragments
\ua9 2024 The Royal Society of Chemistry.Advanced glycation end products (AGEs) arise from the Maillard reaction between dicarbonyls and proteins, nucleic acids, or specific lipids. Notably, AGEs are linked to aging and implicated in various disorders, spanning from cancer to neurodegenerative diseases. While dicarbonyls like methylglyoxal preferentially target arginine residues, lysine-derived AGEs, such as N(6)-(1-carboxymethyl)lysine (CML) and N(6)-(1-carboxyethyl)lysine (CEL), are also abundant. Predicting protein glycation in vivo proves challenging due to the intricate nature of glycation reactions. In vitro, glycation is difficult to control, especially in proteins that harbor multiple glycation-prone amino acids. α-Synuclein (aSyn), pivotal in Parkinson\u27s disease and synucleinopathies, has 15 lysine residues and is known to become glycated at multiple lysine sites. To understand the influence of glycation in specific regions of aSyn on its behavior, a strategy for site-specific glycated protein production is imperative. To fulfill this demand, we devised a synthetic route integrating solid-phase peptide synthesis, orthogonal protection of amino acid side-chain functionalities, and reductive amination strategies. This methodology yielded two disease-related N-terminal peptide fragments, each featuring five and six CML and CEL modifications, alongside a full-length aSyn protein containing a site-selective E46CEL modification. Our synthetic approach facilitates the broad introduction of glycation motifs at specific sites, providing a foundation for generating glycated forms of synucleinopathy-related and other disease-relevant proteins
PopulaçÔes de plantas e estratégias de manejo de irrigação na cultura da soja.
Este trabalho teve por objetivo verificar o efeito do manejo da irrigação e da população de plantas sobre o rendimento de grĂŁos em soja semeada apĂłs a Ă©poca recomenda. O experimento foi conduzido de janeiro a maio de 2005 na Universidade Federal de Santa Maria. O delineamento experimental utilizado foi blocos ao acaso com parcelas subdivididas e quatro repetiçÔes. Nas parcelas principais foram distribuĂdos trĂȘs manejos de irrigação: 1) nĂŁo-irrigado; 2) irrigado todo o ciclo; e 3) irrigado nos perĂodos crĂticos. Nas subparcelas foram distribuĂdas duas populaçÔes de plantas (250.000 e 400.000 plantas ha-1). Para as plantas irrigadas todo o ciclo ou somente nos perĂodos crĂticos, o rendimento de grĂŁos nĂŁo diferiu entre as populaçÔes testadas. O rendimento de grĂŁos das plantas nĂŁo-irrigadas teve um incremento de 21% com o aumento da população de plantas para 400.000 plantas ha-1
Synchronized dynamics of cortical neurons with time-delay feedback
The dynamics of three mutually coupled cortical neurons with time delays in
the coupling are explored numerically and analytically. The neurons are coupled
in a line, with the middle neuron sending a somewhat stronger projection to the
outer neurons than the feedback it receives, to model for instance the relay of
a signal from primary to higher cortical areas. For a given coupling
architecture, the delays introduce correlations in the time series at the
time-scale of the delay. It was found that the middle neuron leads the outer
ones by the delay time, while the outer neurons are synchronized with zero lag
times. Synchronization is found to be highly dependent on the synaptic time
constant, with faster synapses increasing both the degree of synchronization
and the firing rate. Analysis shows that presynaptic input during the
interspike interval stabilizes the synchronous state, even for arbitrarily weak
coupling, and independent of the initial phase. The finding may be of
significance to synchronization of large groups of cells in the cortex that are
spatially distanced from each other.Comment: 21 pages, 11 figure
A human MAP kinase interactome.
Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps
Castaing Instability and Precessing Domains in Confined Alkali Gases
We explore analogy between two-component quantum alkali gases and
spin-polarized helium systems. Recent experiments in trapped gases are put into
the frame of the existing theory for Castaing instability in transverse channel
and formation of homogeneous precessing domains in spin-polarized systems.
Analogous effects have already been observed in spin-polarized and
mixtures systems. The threshold effect of the confining
potential on the instability is analyzed. New experimental possibilities for
observation of transverse instability in a trap are discussed.Comment: 6 RevTex pages, no figure
Slow Noncollinear Coulomb Scattering in the Vicinity of the Dirac Point in Graphene
The Coulomb scattering dynamics in graphene in energetic proximity to the Dirac point is investigated by polarization resolved pump-probe spectroscopy and microscopic theory. Collinear Coulomb scattering rapidly thermalizes the carrier distribution in k directions pointing radially away from the Dirac point. Our study reveals, however, that, in almost intrinsic graphene, full thermalization in all directions relying on noncollinear scattering is much slower. For low photon energies, carrier-optical-phonon processes are strongly suppressed and Coulomb mediated noncollinear scattering is remarkably slow, namely on a ps time scale. This effect is very promising for infrared and THz devices based on hot carrier effects
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