Background Endothelial dysfunction plays a key role in atherogenesis. We investigated whether AMP-activated protein kinase (AMPK) activity is a downstream mediator of the beneficial effects of ...cilostazol on vascular endothelial cells and whether cilostazol might reverse endothelial dysfunction in diabetic rats. Methods and Results Treatment of human umbilical vein endothelial cells (HUVECs) with cilostazol resulted in time-dependent activation of AMPK, as monitored by phosphorylation of AMPK and its down-stream target, acetyl-CoA carboxylase (ACC). Activation of AMPK by cilostazol was through signaling pathway independent of cyclic AMP and caused phosphorylation of endothelial nitric oxide synthase (eNOS), leading to increased production of nitric oxide (NO), while inhibiting cytokine-induced nuclear factor-κB (NF-κB) activation, leading to suppression of VCAM-1 gene expression. Significantly reduced eNOS activity and NO production in response to cilostazol and attenuation of cilostazol-induced inhibition of NF-κB activation were observed in cells treated with AMPK siRNA. We also demonstrated that administration of cilostazol to diabetic rats significantly restored endothelium-dependent vasodilation. Furthermore, treatment of diabetic rats with cilostazol increased tetrahydrobiopterin (BH4) levels in the aorta. Thus, recovery of BH4 following administration of cilostazol might also contribute to restoration of endothelial function in diabetic rats. Conclusions Our findings suggest that the beneficial effects of cilostazol on endothelial function may be due to AMPK activation. Restoration of endothelial dysfunction in diabetic rats by cilostazol is at least partly attributed to amelioration of biopterin metabolism in the aorta.
A (11)C molecular production/separation system (CMPS) has been developed as part of an isotope separation on line system for simultaneous positron emission tomography imaging and heavy-ion cancer ...therapy using radioactive (11)C ion beams. In the ISOL system, (11)CH4 molecules will be produced by proton irradiation and separated from residual air impurities and impurities produced during the irradiation. The CMPS includes two cryogenic traps to separate specific molecules selectively from impurities by using vapor pressure differences among the molecular species. To investigate the fundamental performance of the CMPS, we performed separation experiments with non-radioactive (12)CH4 gases, which can simulate the chemical characteristics of (11)CH4 gases. We investigated the separation of CH4 molecules from impurities, which will be present as residual gases and are expected to be difficult to separate because the vapor pressure of air molecules is close to that of CH4. We determined the collection/separation efficiencies of the CMPS for various amounts of air impurities and found desirable operating conditions for the CMPS to be used as a molecular separation device in our ISOL system.
Abstract We perform three-dimensional global non-ideal magnetohydrodynamic simulations of a protoplanetary disk containing the inner dead-zone edge. We take into account realistic diffusion ...coefficients of the Ohmic resistivity and ambipolar diffusion based on detailed chemical reactions with single-size dust grains. We found that the conventional dead zone identified by the Elsässer numbers of the Ohmic resistivity and ambipolar diffusion is divided into two regions: “the transition zone” and “the coherent zone.” The coherent zone has the same properties as the conventional dead zone, and extends outside of the transition zone in the radial direction. Between the active and coherent zones, we discover the transition zone, the inner edge of which is identical to that of the conventional dead zone. The transition zone extends out over the regions where thermal ionization determines diffusion coefficients. The transition zone has completely different physical properties than the conventional dead zone, the so-called undead zone, and the zombie zone. The combination of amplification of the radial magnetic field owing to the ambipolar diffusion and a steep radial gradient of the Ohmic diffusivity causes the efficient evacuation of the net vertical magnetic flux from the transition zone within several rotations. Surface gas accretion occurs in the coherent zone but not in the transition zone. The presence of the transition zone prohibits mass and magnetic flux transport from the coherent zone to the active zone. Mass accumulation occurs at both edges of the transition zone as a result of mass supply from the active and coherent zones.
Summary
Respiratory disease is the most important health concern for the swine industry. Genetic improvement for disease resistance is challenging because of the difficulty in obtaining good ...phenotypes related with disease resistance; however, identification of genes or markers associated with disease resistance can help in the genetic improvement of pig health. The purpose of our study was to investigate whether quantitative trait loci (QTL) associated with disease resistance were segregated in a purebred population of Landrace pigs that had been selected for meat production traits and mycoplasmal pneumonia of swine (MPS) scores over five generations. We analysed 1395 pigs from the base to the fifth generation of this population. Two respiratory disease traits MPS scores and atrophic rhinitis (AR) scores and 11 immune‐capacity traits were measured in 630–1332 animals at 7 weeks of age and when the animal's body weight reached 105 kg. Each of the pigs, except sires in the base population, was genotyped using 109 microsatellite markers, and then, QTL analysis of the full‐sib family population with a multi‐generational pedigree structure was performed. Variance component analysis was used to detect QTL associated with MPS or AR scores, and the logarithm of odds (LOD) score and genotypic heritability of the QTL were estimated. Five significant (LOD > 2.51) and 18 suggestive (LOD > 1.35) QTL for respiratory disease traits and immune‐capacity traits were detected. The significant QTL for Log‐MPS score, located on S. scrofa chromosome 2, could explain 87% of the genetic variance of this score in this analysis. This is the first report of QTL associated with respiratory disease lesions.
The Cosmic Infrared Background Experiment (CIBER) is a suite of four instruments designed to study the near infrared (IR) background light from above the Earth's atmosphere. The instrument package ...comprises two imaging telescopes designed to characterize spatial anisotropy in the extragalactic IR background caused by cosmological structure during the epoch of reionization, a low resolution spectrometer to measure the absolute spectrum of the extragalactic IR background, and a narrow band spectrometer optimized to measure the absolute brightness of the zodiacal light foreground. In this paper we describe the design and characterization of the CIBER payload. The detailed mechanical, cryogenic, and electrical design of the system are presented, including all system components common to the four instruments. We present the methods and equipment used to characterize the instruments before and after flight, and give a detailed description of CIBER's flight profile and configurations. CIBER is designed to be recoverable and has flown four times, with modifications to the payload having been informed by analysis of the first flight data. All four instruments performed to specifications during the subsequent flights, and the scientific data from these flights are currently being analyzed.
Previous studies on unilateral neglect have shown that there are at least two types of neglect-i.e., body-centered and stimulus-centered neglect. These symptoms suggest that the human brain has at ...least two different reference frames for processing external space. It is unknown, however, whether these two frames are represented independently in the brain and if so, which areas (or networks) of the brain are responsible for each frame of reference.
To determine whether body-centered neglect and stimulus-centered neglect can be dissociated in patients with brain injury.
New figure discriminative cancellation tasks were designed to simultaneously assess body-centered neglect and stimulus-centered neglect. Two neglect patients with lesions located in different anatomic regions were required to circle every complete figure and to cross out every figure with a missing portion on a sheet of white (29.7 x 42 cm) paper.
Patient 1 omitted leftward stimuli on the paper, but the stimuli he found were correctly circled or crossed out. On the other hand, Patient 2 marked stimuli across the paper although he mistakenly circled stimuli that were missing a portion of their left side. Neither patient manifested interaction between the two types of neglect.
The results of this study clearly showed double dissociation between the two types of neglect. Furthermore, it not only provides evidence that there are two distinct systems of reference frame for external space in the human brain, but also adds new knowledge indicating that these two systems function independently, at least in part.
Abstract Objective To develop the immunohistochemistry specific for meconium in the placenta, fetal membrane and umbilical cord. Study design We previously reported the specific presence of zinc ...coproporphyrin I (ZnCP-I) in human meconium and demonstrated the possible diagnostic use of an elevation in maternal plasma ZnCP-I levels in cases of amniotic fluid embolism. In this study, we developed a new specific monoclonal antibody for ZnCP-I and applied it to the immunostaining of meconium in the placenta, fetal membrane, and umbilical cord. Results Immunoreactivity of ZnCP-I clearly and specifically identified meconium in the placenta, fetal membrane, and umbilical cord. It was especially useful in cases of severe chorioamnionitis to detect meconium in the macrophages surrounded by numerous neutrophils. In more than half of the cases, meconium was detected in clear amniotic fluid at delivery, suggesting previous exposure. Conclusions Immunohistochemical detection of ZnCP-I is a highly sensitive histological diagnosis of meconium.
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