4,815 research outputs found
Mechanisms of dysregulation of low-density lipoprotein receptor expression in vascular smooth muscle cells by inflammatory cytokines
Objective - Although inflammation is a recognized feature of atherosclerosis, the impact of inflammation on cellular cholesterol homeostasis is unclear. This study focuses on the molecular mechanisms by which inflammatory cytokines disrupt low-density lipoprotein (LDL) receptor regulation.Methods and Results - IL-1 beta enhanced transformation of vascular smooth muscle cells into foam cells by increasing uptake of unmodified LDL via LDL receptors and by enhancing cholesterol esterification as demonstrated by Oil Red O staining and direct assay of intracellular cholesterol concentrations. In the absence of IL-1 beta, a high concentration of LDL decreased LDL receptor promoter activity, mRNA synthesis and protein expression. However, IL-1 beta enhanced LDL receptor expression, overriding the suppression usually induced by a high concentration of LDL and inappropriately increasing LDL uptake. Exposure to IL-1 beta also caused overexpression of the sterol regulatory element binding protein ( SREBP) cleavage-activating protein ( SCAP), and enhanced its translocation from the endoplasmic reticulum to the Golgi, where it is known to cleave SREBP, thereby enhancing LDL receptor gene expression.Conclusions - These observations demonstrate that IL-1 beta disrupts cholesterol-mediated LDL receptor feedback regulation, permitting intracellular accumulation of unmodified LDL and causing foam cell formation. The implication of these findings is that inflammatory cytokines may contribute to intracellular LDL accumulation without previous modification of the lipoprotein
Tunneling magnetoresistance in Fe3Si/MgO/Fe3Si(001) magnetic tunnel junctions
published_or_final_versio
A review of physical supply and EROI of fossil fuels in China
This paper reviews China’s future fossil fuel supply from the perspectives of physical output and net energy output. Comprehensive analyses of physical output of fossil fuels suggest that China’s total oil production will likely reach its peak, at about 230 Mt/year (or 9.6 EJ/year), in 2018; its total gas production will peak at around 350 Bcm/year (or 13.6 EJ/year) in 2040, while coal production will peak at about 4400 Mt/year (or 91.9 EJ/year) around 2020 or so. In terms of the forecast production of these fuels, there are significant differences among current studies. These differences can be mainly explained by different ultimately recoverable resources assumptions, the nature of the models used, and differences in the historical production data. Due to the future constraints on fossil fuels production, a large gap is projected to grow between domestic supply and demand, which will need to be met by increasing imports. Net energy analyses show that both coal and oil and gas production show a steady declining trend of EROI (energy return on investment) due to the depletion of shallow-buried coal resources and conventional oil and gas resources, which is generally consistent with the approaching peaks of physical production of fossil fuels. The peaks of fossil fuels production, coupled with the decline in EROI ratios, are likely to challenge the sustainable development of Chinese society unless new abundant energy resources with high EROI values can be found
Effects of Shielding on Properties of Eddy Current Probes with Ferrite Cup Cores
In eddy current inspection the ability to detect small defects depends on the sensitivity of the system and on the relative sizes of the probe and the defect. To detect defects on the opposite surface the probe radius should be at least as great as the thickness of the material. This limits the sensitivity to small defects that can be achieved by decreasing the probe size. Assuming the instrumentation is a given, further sensitivity can be achieved by improving the sensitivity of the probe itself.</p
On absolute continuity of the spectrum of a periodic magnetic Schr\"odinger operator
We consider the Schr\"odinger operator in , , with
the electric potential and the magnetic potential being periodic
functions (with a common period lattice) and prove absolute continuity of the
spectrum of the operator in question under some conditions which, in
particular, are satisfied if
and , .Comment: 25 page
Emergence of scale-free leadership structure in social recommender systems
The study of the organization of social networks is important for
understanding of opinion formation, rumor spreading, and the emergence of
trends and fashion. This paper reports empirical analysis of networks extracted
from four leading sites with social functionality (Delicious, Flickr, Twitter
and YouTube) and shows that they all display a scale-free leadership structure.
To reproduce this feature, we propose an adaptive network model driven by
social recommending. Artificial agent-based simulations of this model highlight
a "good get richer" mechanism where users with broad interests and good
judgments are likely to become popular leaders for the others. Simulations also
indicate that the studied social recommendation mechanism can gradually improve
the user experience by adapting to tastes of its users. Finally we outline
implications for real online resource-sharing systems
An Adaptive Finite Element Method for the Eddy Current Model with Circuit/Field Couplings
Retinoic acid induces HL-60 cell differentiation via the upregulation of miR-663
<p>Abstract</p> <p>Background</p> <p>Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.</p> <p>Methods</p> <p>Using bioinformatics and <it>in vitro </it>experiments, we identified the microRNA gene expression profile of HL-60 cells during ATRA induced granulocytic differentiation.</p> <p>Results</p> <p>Six microRNAs were upregulated by ATRA treatment, miR-663, miR-494, miR-145, miR-22, miR-363* and miR-223; and three microRNAs were downregulated, miR-10a, miR-181 and miR-612. Additionally, miR-663 expression was regulated by ATRA. We used a lentivirus (LV) backbone incorporating the spleen focus forming virus (SFFV-F) promoter to drive miR-663 expression, as the CMV (Cytomegalovirus) promoter is ineffective in some lymphocyte cells. Transfection of LV-miR-663 induced significant HL-60 cell differentiation <it>in vitro</it>.</p> <p>Conclusions</p> <p>Our results show miR-663 may play an important role in ATRA induced HL-60 cell differentiation. Lentivirus delivery of miR-663 could potentially be used directly as an anticancer treatment in hematological malignancies</p
The p.V37I Exclusive Genotype Of GJB2: A Genetic Risk-Indicator of Postnatal Permanent Childhood Hearing Impairment
Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%–0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10−10; OR 62.92, 95% CI 21.27–186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI
Mutations and SNPs of human cardiac sodium channel alpha subunit gene (SCN5A) in Japanese patients with Brugada syndrome
Background: Brugada syndrome is an inherited arrhythmogenic disease characterized by right bundle branch block pattern and ST segment elevation, leading to the change of V1 to V3 on electrocardiogram, and an increased risk of sudden cardiac death resulting from ventricular fibrillation. The sodium channel alpha 5 subunit (SCN5A) gene encodes a cardiac voltage-dependent sodium channel, and SCN5A mutations have been reported in Brugada syndrome. However, single nucleotide polymorphisms (SNPs) and gene mutations have not been well investigated in Japanese patients with Brugada syndrome.
Methods and Results: The SCN5A gene was examined in 58 patients by using PCR and the ABI 3130xl sequencer, revealing 17 SNP patterns and 13 mutations. Of the 13 mutations, 8 were missense mutations (with amino acid change), 4 were silent mutations (without amino acid change), and one case was a mutation within the splicing junction. Six of the eight missense mutations were novel mutations. Interestingly, we detected an R1664H mutation, which was identified originally in long QT syndrome.
Conclusion: We found 13 mutations of the SCN5A gene in 58 patients with Brugada syndrome. The disease may be attributable to some of the mutations and SNPs
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