3,032 research outputs found
Abrupt Rise of the Longitudinal Recoil Ion Momentum Distribution for Ionizing Collisions
We report on the experimental observation of an abrupt rise in the longitudinal momentum distribution of recoil ions created in proton helium collision. The details of this structure can be related to electrons traveling with the velocity of the projectile [electron capture to the continuum (ECC)]. The longitudinal as well as the transverse distribution of the recoil ions can be explained as a continuation of the momentum distribution from ions resulting from electron capture illustrating the smooth transition from the capture to bound states of the projectile to the ECC.Fil: Weber, Th.. Institut für Kernphysik; AlemaniaFil: Khayyat, Kh.. Institut für Kernphysik; AlemaniaFil: Dörner, R.. Universität Freiburg; AlemaniaFil: Rodríguez Chariarse, Vladimir Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Física de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Física de Buenos Aires; ArgentinaFil: Mergel, V.. Institut für Kernphysik; AlemaniaFil: Jagutzk, O.. Institut für Kernphysik; AlemaniaFil: Schmidt, L.. Institut für Kernphysik,; AlemaniaFil: Müller, K. A.. Institut für Kernphysik; AlemaniaFil: Afaneh, F.. Institut für Kernphysik; AlemaniaFil: Gonzalez, A.. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; ArgentinaFil: Schmidt-Böcking, H.. Institut für Kernphysik; Alemani
Effects of oxidized low density lipoprotein, lipid mediators and statins on vascular cell interactions
The integrin heterodimer CD11b/CD18 (alpha M beta 2, Mac-1, CR3) expressed on monocytes or polymorphonuclear leukocytes (PMN) is a receptor for iC3b, fibrinogen, heparin, and for intercellular adhesion molecule (ICAM)-1 on endothelium, crucially contributing to vascular cell interactions in inflammation and atherosclerosis. In this report, we summarize our findings on the effects of lipid mediators and lipid-lowering drugs. Exposure of endothelial cells to oxidized low density lipoprotein (oxLDL) induces upregulation of ICAM-1 and increases adhesion of monocytic cells expressing Mac-1. Inhibition experiments show that monocytes use distinct ligands, i.e. ICAM-1 and heparan sulfate proteoglycans for adhesion to oxLDL-treated endothelium. An albumin-transferable oxLDL activity is inhibited by the antioxidant pyrrolidine dithiocarbamate (PDTC), while 8-epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) or lysophosphatidylcholine had no effect, implicating yet unidentified radicals. Sequential adhesive! and signaling events lead to the firm adhesion of rolling PMN on activated and adherent platelets, which may occupy areas of endothelial denudation. Shear resistant arrest of PMN on thrombin-stimulated platelets in flow conditions requires distinct regions of Mac-1, involving its interactions with fibrinogen bound to platelet alpha llb beta 3, and with other platelet ligands. Both arrest and adhesion strengthening under flow are stimulated by platelet-activating factor and leukotriene B4, but not by the chemokine receptor CXCR2. We tested whether Mac-1-dependent monocyte adhesiveness is affected by inhibitors of hydroxy-methylglutaryl-Coenzyme A reductase (statins) which improve morbidity and survival of patients with coronary heart disease. As compared to controls, adhesion of isolated monocytes to endothelium ex vivo was increased in patients with hypercholesterolemia. Treatment with statins decreased total and low density lipoprotein (LDL) cholesterol plasma levels, surface expression of Mac-1, and resulted in a dramatic reduction of Mac,mediated monocyte adhesion to endothelium. The inhibition of monocyte adhesion was reversed by mevalonate but not LDL in vitro,indicating that isoprenoid precursors are crucial for adhesiveness of Mac-1. Such effects may crucially contribute to the clinical benefit of statins, independent of cholesterol-lowering, and may represent a paradigm for novel, anti-inflammatory mechanisms of action by this class of drugs
The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine
Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT.
Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine.
Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists.
Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum.
Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions.
Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal
Colossal magnetocapacitance and scale-invariant dielectric response in phase-separated manganites
Thin films of strongly-correlated electron materials (SCEM) are often grown
epitaxially on planar substrates and typically have anisotropic properties that
are usually not captured by edge-mounted four-terminal electrical measurements,
which are primarily sensitive to in-plane conduction paths. Accordingly, the
correlated interactions in the out-of-plane (perpendicular) direction cannot be
measured but only inferred. We address this shortcoming and show here an
experimental technique in which the SCEM under study, in our case a 600
Angstrom-thick (La1-yPry)0.67Ca0.33MnO3 (LPCMO) film, serves as the base
electrode in a metal-insulator-metal (MIM) trilayer capacitor structure. This
unconventional arrangement allows for simultaneous determination of colossal
magnetoresistance (CMR) associated with dc transport parallel to the film
substrate and colossal magnetocapacitance (CMC) associated with ac transport in
the perpendicular direction. We distinguish two distinct strain-related
direction-dependent insulator-metal (IM) transitions and use Cole-Cole plots to
establish a heretofore unobserved collapse of the dielectric response onto a
universal scale-invariant power-law dependence over a large range of frequency,
temperature and magnetic field.Comment: 32 pages, 4 figures, Supplementary section included, Submitted to
Nature Physic
Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation
We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis
Strong Interactions of Single Atoms and Photons near a Dielectric Boundary
Modern research in optical physics has achieved quantum control of strong
interactions between a single atom and one photon within the setting of cavity
quantum electrodynamics (cQED). However, to move beyond current
proof-of-principle experiments involving one or two conventional optical
cavities to more complex scalable systems that employ N >> 1 microscopic
resonators requires the localization of individual atoms on distance scales <
100 nm from a resonator's surface. In this regime an atom can be strongly
coupled to a single intracavity photon while at the same time experiencing
significant radiative interactions with the dielectric boundaries of the
resonator. Here, we report an initial step into this new regime of cQED by way
of real-time detection and high-bandwidth feedback to select and monitor single
Cesium atoms localized ~100 nm from the surface of a micro-toroidal optical
resonator. We employ strong radiative interactions of atom and cavity field to
probe atomic motion through the evanescent field of the resonator. Direct
temporal and spectral measurements reveal both the significant role of
Casimir-Polder attraction and the manifestly quantum nature of the atom-cavity
dynamics. Our work sets the stage for trapping atoms near micro- and
nano-scopic optical resonators for applications in quantum information science,
including the creation of scalable quantum networks composed of many
atom-cavity systems that coherently interact via coherent exchanges of single
photons.Comment: 8 pages, 5 figures, Supplemental Information included as ancillary
fil
Linear-response theory and lattice dynamics: a muffin-tin orbital approach
A detailed description of a method for calculating static linear-response
functions in the problem of lattice dynamics is presented. The method is based
on density functional theory and it uses linear muffin-tin orbitals as a basis
for representing first-order corrections to the one-electron wave functions. As
an application we calculate phonon dispersions in Si and NbC and find good
agreement with experiments.Comment: 18 pages, Revtex, 2 ps figures, uuencoded, gzip'ed, tar'ed fil
Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles
BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection
Assessing the efficiency and significance of Methylated DNA Immunoprecipitation (MeDIP) assays in using in vitro methylated genomic DNA
<p>Abstract</p> <p>Background</p> <p>DNA methylation contributes to the regulation of gene expression during development and cellular differentiation. The recently developed Methylated DNA ImmunoPrecipitation (MeDIP) assay allows a comprehensive analysis of this epigenetic mark at the genomic level in normal and disease-derived cells. However, estimating the efficiency of the MeDIP technique is difficult without previous knowledge of the methylation status of a given cell population. Attempts to circumvent this problem have involved the use of <it>in vitro </it>methylated DNA in parallel to the investigated samples. Taking advantage of this stratagem, we sought to improve the sensitivity of the approach and to assess potential biases resulting from DNA amplification and hybridization procedures using MeDIP samples.</p> <p>Findings</p> <p>We performed MeDIP assays using <it>in vitro </it>methylated DNA, with or without previous DNA amplification, and hybridization to a human promoter array. We observed that CpG content at gene promoters indeed correlates strongly with the MeDIP signal obtained using <it>in vitro </it>methylated DNA, even when lowering significantly the amount of starting material. In analyzing MeDIP products that were subjected to whole genome amplification (WGA), we also revealed a strong bias against CpG-rich promoters during this amplification procedure, which may potentially affect the significance of the resulting data.</p> <p>Conclusion</p> <p>We illustrate the use of <it>in vitro </it>methylated DNA to assess the efficiency and accuracy of MeDIP procedures. We report that efficient and reproducible genome-wide data can be obtained via MeDIP experiments using relatively low amount of starting genomic DNA; and emphasize for the precaution that must be taken in data analysis when an additional DNA amplification step is required.</p
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