| 1. |
- Tang, Ting-Ting, et al.
(författare)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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| 2. |
- Weinstein, John N., et al.
(författare)
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The cancer genome atlas pan-cancer analysis project
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
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Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
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| 3. |
- Baek, Seung Ki, et al.
(författare)
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Quantum Monte Carlo study of the transverse-field quantum Ising modelon infinite-dimensional structures
- 2011
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Ingår i: Physical Review B Condensed Matter. - : American Physical Society. - 0163-1829 .- 1095-3795. ; 84, s. 174419-
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Tidskriftsartikel (refereegranskat)abstract
- In a number of classical statistical-physical models, there exists acharacteristic dimensionality called the upper critical dimension abovewhich one observes the mean-field critical behavior. Instead of constructinghigh-dimensional lattices, however, one can also considerinfinite-dimensional structures, and the question is whether this mean-fieldcharacter extends to quantum-mechanical cases as well. We thereforeinvestigate the transverse-field quantum Ising model on the globally couplednetwork and on the Watts-Strogatz small-world network by means of quantum MonteCarlo simulations and the finite-size scaling analysis. We confirm that bothof the structures exhibit critical behavior consistent with the mean-fielddescription. In particular, we show that the existing cumulant methodhas difficulty in estimating the correct dynamic critical exponent andsuggest that an order parameter based on the quantum-mechanicalexpectation value can be a practically useful numerical observable todetermine critical behavior when there is no well-defined dimensionality.
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| 4. |
- de Faire, Ulf, et al.
(författare)
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Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men : Effects on uptake of oxidized LDL in macrophages as a potential mechanism
- 2010
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 34:2, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL). Methods: From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan. Results: Relative risks (RR) with 95% confidence intervals (Cl) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type 11 diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile I (values below 29.7 U/ml) had a significantly increased RR of 1.96 (Cl 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL Conclusions: Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.
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| 5. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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| 6. |
- Tan, Tianwei, et al.
(författare)
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Cross-linked agarose for separation of low molecular weight natural products in hydrophilic interaction liquid chromatography
- 2010
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Ingår i: Biotechnology Journal. - : Wiley. - 1860-6768. ; 5:5, s. 505-510
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Forskningsöversikt (refereegranskat)abstract
- Following its market introduction in 1982, the cross-linked 12% agarose gel media Superose 12 has become widely known as a tool for size exclusion chromatography of proteins and other biological macromolecules. In this review it is shown that, when appropriate mobile phases are used, Superose possesses adsorption properties similar to that of traditional media for hydrophilic interaction liquid chromatography (HILIC). This is illustrated by the separation and purification of low molecular weight compounds such as polyphenols including active components of traditional Chinese medicinal herbs and green tea. Structural features of the cross-linked agarose that likely cause the observed adsorption effects are discussed aswell. These are identified as being primarily ether bonds acting as strong hydrogen bond acceptors as well as hydrophobic residues originating from the cross-linking reagents.
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| 7. |
- Wang, Hui, et al.
(författare)
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On the Structure of alpha-BiFeO3
- 2013
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 52:5, s. 2388-2392
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Tidskriftsartikel (refereegranskat)abstract
- Polycrystalline and monocrystalline alpha-BiFeO3 crystals have been synthesized by solid state reaction and flux growth method, respectively. X-ray, neutron, and electron diffraction techniques are used to study the crystallographic and magnetic structure of alpha-BiFeO3. The present data show that alpha-BiFeO3 crystallizes in space group PI with a = 0.563 17(1) nm, b = 0.563 84(1) nm, c = 0.563 70(1) nm, alpha = 59.33(1)degrees, beta = 59.35(1)degrees, gamma = 59.38(1)degrees, and the magnetic structure of alpha-BiFeO3 can be described by space group PI with magnetic modulation vector in reciprocal space q = 0.0045a* - 0.0045b*, which is the magnetic structure model proposed by I. Sosnowska(1) applied to the new PI crystal symmetry of alpha-BiFeO3
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| 8. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 9. |
- Yao, Honghong, et al.
(författare)
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Molecular mechanisms involving sigma receptor-mediated induction of MCP-1: implication for increased monocyte transmigration.
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 115:23, s. 4951-62
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Tidskriftsartikel (refereegranskat)abstract
- Cocaine abuse hastens the neurodegeneration often associated with advanced HIV-1 infection. The mechanisms, in part, revolve around the neuroinflammatory processes mediated by the chemokine monocyte chemotactic protein-1 (MCP-1/CCL2). Understanding factors that modulate MCP-1 and, in turn, facilitate monocyte extravasation in the brain is thus of paramount importance. We now demonstrate that cocaine induces MCP-1 in rodent microglia through translocation of the sigma receptor to the lipid raft microdomains of the plasma membrane. Sequential activation of Src, mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3' kinase (PI3K)/Akt and nuclear factor kappaB (NF-kappaB) pathways resulted in increased MCP-1 expression. Furthermore, conditioned media from cocaine-exposed microglia increased monocyte transmigration, and thus was blocked by antagonists for CCR2 or sigma receptor. These findings were corroborated by demonstrating increased monocyte transmigration in mice exposed to cocaine, which was attenuated by pretreatment of mice with the sigma receptor antagonist. Interestingly, cocaine-mediated transmigratory effects were not observed in CCR2 knockout mice. We conclude that cocaine-mediated induction of MCP-1 accelerates monocyte extravasation across the endothelium. Understanding the regulation of MCP-1 expression and functional changes by cocaine/sigma receptor system may provide insights into the development of potential therapeutic targets for HIV-1-associated neurocognitive disorders.
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| 10. |
- Yi, Su Do, et al.
(författare)
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Allometric exponent and randomness
- 2013
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Ingår i: New Journal of Physics. - : Institute of Physics Publishing (IOPP). - 1367-2630. ; 15, s. 043001-
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Tidskriftsartikel (refereegranskat)abstract
- An allometric height-mass exponent gamma gives an approximative power-law relation < M > proportional to H-gamma between the average mass < M > and the height H for a sample of individuals. The individuals in the present study are humans but could be any biological organism. The sampling can be for a specific age of the individuals or for an age interval. The body mass index is often used for practical purposes when characterizing humans and it is based on the allometric exponent gamma = 2. It is shown here that the actual value of gamma is to a large extent determined by the degree of correlation between mass and height within the sample studied: no correlation between mass and height means gamma = 0, whereas if there was a precise relation between mass and height such that all individuals had the same shape and density then gamma = 3. The connection is demonstrated by showing that the value of gamma can be obtained directly from three numbers characterizing the spreads of the relevant random Gaussian statistical distributions: the spread of the height and mass distributions together with the spread of the mass distribution for the average height. Possible implications for allometric relations, in general, are discussed.
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