178 research outputs found

    Enhanced Integrin α4β1-Mediated Adhesion Contributes to a Mobilization Defect of Endothelial Progenitor Cells in Diabetes.

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    Diabetes is associated with a deficit of circulating endothelial progenitor cells (EPCs), which has been attributed to their defective mobilization from the bone marrow. The basis for this mobilization defect is not completely understood, and we sought to determine if hyperglycemic conditions enhanced EPC adhesion. We found that culturing EPCs in high glucose media increased adhesion to bone marrow stromal cells. This enhanced adhesion was associated with decreased expression of protein kinase A regulatory subunit 1β (PRKAR1β), activation of protein kinase A (PKA), and phosphorylation of α4-integrin on serine 988. This potentiated adhesion was reversed by treatment with a PKA inhibitor, overexpression of PRKAR1β, or expression of a phosphorylation-defective α4-integrin variant (α4[S988A]). Using a model of type 1 diabetes, we showed that α4(S988A)-expressing mice have more circulating EPCs than their wild-type counterparts. Moreover, diabetic α4(S988A) mice demonstrate enhanced revascularization after hind limb ischemia. Thus, we have identified a novel signaling mechanism activating PKA in diabetes (downregulation of an inhibitory regulatory subunit) that leads to deficits of circulating EPCs and impaired vascular repair, which could be reversed by α4-integrin mutation

    Impact of Stark Shifts on the Radiation Cooling of Cu-Dominated Plasmas

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    We study the impact of Stark line shifts reported recently for Cu I transitions on the radiative cooling of Cu-dominated plasmas. The observed detuning in absorption between the hot core and cold shell of the arc leads to a reduction in radiation reabsorption compared to the case where Stark line shifts are neglected. Using a modeling based on a phenomenological treatment of the Stark line shift, we show that this reduction is below 2%

    Premenstrual tension syndrome: Diagnostic criteria and selection of research subjects

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    The investigation of premenstrual tension syndrome (PMTS) has been hampered by several methodological problems, particularly an inadequate definition of study subjects. Diagnostic criteria for PMTS that use both interview and self-report information were tested in 24 symptomatic female volunteers. Each woman subsequently completed daily reports of emotional and somatic symptoms for 1 menstrual cycles. Symptom profiles from subjects meeting the diagnostic criteria for PMTS were compared with profiles from subjects who failed to meet the criteria. This study demonstrated that the diagnostic instruments used could identify a group of women with a severe and time-limited premenstrual psychological disturbance and distinguish them from women with milder and more temporally diffuse changes. The need for such instruments and their importance for further research into this disorder are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25197/1/0000636.pd

    Light Neutralinos as Dark Matter in the Unconstrained Minimal Supersymmetric Standard Model

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    The allowed parameter space for the lightest neutralino as the dark matter is explored using the Minimal Supersymmetric Standard Model as the low-energy effective theory without further theoretical constraints such as GUT. Selecting values of the parameters which are in agreement with present experimental limits and applying the additional requirement that the lightest neutralino be in a cosmologically interesting range, we give limits on the neutralino mass and composition. A similar analysis is also performed implementing the grand unification constraints. The elastic scattering cross section of the selected neutralinos on 27^{27}Al and on other materials for dark matter experiments is discussed.Comment: Submitted to Astroparticle Physics, 19 Feb. 96, Latex 23 pages with 24 figures in a gzip compressed file FIGURE.PS.GZ available via anonymous ftp from ftp://iws104.mppmu.mpg.de/pub/gabutt

    Investigation of Vacuum Arc Anode Temperatures of Cu-Cr and Pure Cu Contacts

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    The present contribution reports on investigations of electrode temperatures for pure Cu electrodes and Cu–Cr electrodes of different diameters exposed to vacuum arcs with sinusoidal currents of 5-15 kA and an axial magnetic field up to 180 mT. It is found that surface temperatures of pure Cu electrodes are significantly lower than for Cu–Cr electrodes of the same diameter. This must be explained by different thermal properties of both materials. Reducing the diameter of Cu–Cr electrodes it is found that surface temperatures increase, but moreover it is shown that the enthalpy stored in the electrode bulk material may effect electrode temperatures on timescales much longer than the current pulse width, particularly if there is no effective heat dissipation after current zero

    Nuclear recoil measurements in Superheated Superconducting Granule detectors

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    The response of Superheated Superconducting Granule (SSG) devices to nuclear recoils has been explored by irradiating SSG detectors with a 70Me ⁣\!V neutron beam. In the past we have tested Al SSG and more recently, measurements have been performed with Sn and Zn detectors. The aim of the experiments was to test the sensitivity of SSG detectors to recoil energies down to a few ke ⁣\!V. In this paper, the preliminary results of the neutron irradiation of a SSG detector made of Sn granules 15-20μ\mum in diameter will be discussed. For the first time, recoil energy thresholds of \sim1ke ⁣\!V have been measured.Comment: 7pages in Latex format, Preprint Bu-He 93/6 (University of Berne, Switzerland), four figures available upon request via [email protected] or [email protected]

    Dynamic Behavior in Piezoresponse Force Microscopy

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    Frequency dependent dynamic behavior in Piezoresponse Force Microscopy (PFM) implemented on a beam-deflection atomic force microscope (AFM) is analyzed using a combination of modeling and experimental measurements. The PFM signal comprises contributions from local electrostatic forces acting on the tip, distributed forces acting on the cantilever, and three components of the electromechanical response vector. These interactions result in the bending and torsion of the cantilever, detected as vertical and lateral PFM signals. The relative magnitudes of these contributions depend on geometric parameters of the system, the stiffness and frictional forces of tip-surface junction, and operation frequencies. The dynamic signal formation mechanism in PFM is analyzed and conditions for optimal PFM imaging are formulated. The experimental approach for probing cantilever dynamics using frequency-bias spectroscopy and deconvolution of electromechanical and electrostatic contrast is implemented.Comment: 65 pages, 15 figures, high quality version available upon reques

    Towards local electromechanical probing of cellular and biomolecular systems in a liquid environment

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    Electromechanical coupling is ubiquitous in biological systems with examples ranging from simple piezoelectricity in calcified and connective tissues to voltage-gated ion channels, energy storage in mitochondria, and electromechanical activity in cardiac myocytes and outer hair cell stereocilia. Piezoresponse force microscopy (PFM) has originally emerged as a technique to study electromechanical phenomena in ferroelectric materials, and in recent years, has been employed to study a broad range of non-ferroelectric polar materials, including piezoelectric biomaterials. At the same time, the technique has been extended from ambient to liquid imaging on model ferroelectric systems. Here, we present results on local electromechanical probing of several model cellular and biomolecular systems, including insulin and lysozyme amyloid fibrils, breast adenocarcinoma cells, and bacteriorhodopsin in a liquid environment. The specific features of SPM operation in liquid are delineated and bottlenecks on the route towards nanometer-resolution electromechanical imaging of biological systems are identified.Comment: 37 pages (including refs), 8 figure

    Post-myocardial infarction heart failure dysregulates the bone vascular niche

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    The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post-infarction heart failure on the bone vascular cell composition. We demonstrate an age-independent loss of type H endothelium in heart failure after myocardial infarction in both mice and humans. Using single-cell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium, showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Endothelial-specific overexpression of MYC was sufficient to induce type H bone endothelial cells, whereas inhibition of NLRP3-dependent IL-1β production partially prevented the post-myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of bone vascular function in ischemic heart disease
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