| 1. |
- Aad, G., et al.
(författare)
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Studies of the performance of the ATLAS detector using cosmic-ray muons
- 2011
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 71:3
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Tidskriftsartikel (refereegranskat)abstract
- Muons from cosmic-ray interactions in the atmosphere provide a high-statistics source of particles that can be used to study the performance and calibration of the ATLAS detector. Cosmic-ray muons can penetrate to the cavern and deposit energy in all detector subsystems. Such events have played an important role in the commissioning of the detector since the start of the installation phase in 2005 and were particularly important for understanding the detector performance in the time prior to the arrival of the first LHC beams. Global cosmic-ray runs were undertaken in both 2008 and 2009 and these data have been used through to the early phases of collision data-taking as a tool for calibration, alignment and detector monitoring. These large datasets have also been used for detector performance studies, including investigations that rely on the combined performance of different subsystems. This paper presents the results of performance studies related to combined tracking, lepton identification and the reconstruction of jets and missing transverse energy. Results are compared to expectations based on a cosmic-ray event generator and a full simulation of the detector response.
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| 2. |
- Aad, G., et al.
(författare)
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The ATLAS Simulation Infrastructure
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 823-874
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Tidskriftsartikel (refereegranskat)abstract
- The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.
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| 3. |
- Aad, G., et al.
(författare)
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The ATLAS Inner Detector commissioning and calibration
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 787-821
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS Inner Detector is a composite tracking system consisting of silicon pixels, silicon strips and straw tubes in a 2 T magnetic field. Its installation was completed in August 2008 and the detector took part in data-taking with single LHC beams and cosmic rays. The initial detector operation, hardware commissioning and in-situ calibrations are described. Tracking performance has been measured with 7.6 million cosmic-ray events, collected using a tracking trigger and reconstructed with modular pattern-recognition and fitting software. The intrinsic hit efficiency and tracking trigger efficiencies are close to 100%. Lorentz angle measurements for both electrons and holes, specific energy-loss calibration and transition radiation turn-on measurements have been performed. Different alignment techniques have been used to reconstruct the detector geometry. After the initial alignment, a transverse impact parameter resolution of 22.1 +/- 0.9 mu m and a relative momentum resolution sigma (p) /p=(4.83 +/- 0.16)x10(-4) GeV(-1)xp (T) have been measured for high momentum tracks.
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| 4. |
- Aad, G., et al.
(författare)
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Commissioning of the ATLAS Muon Spectrometer with cosmic rays
- 2010
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 70:3, s. 875-916
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Tidskriftsartikel (refereegranskat)abstract
- The ATLAS detector at the Large Hadron Collider has collected several hundred million cosmic ray events during 2008 and 2009. These data were used to commission the Muon Spectrometer and to study the performance of the trigger and tracking chambers, their alignment, the detector control system, the data acquisition and the analysis programs. We present the performance in the relevant parameters that determine the quality of the muon measurement. We discuss the single element efficiency, resolution and noise rates, the calibration method of the detector response and of the alignment system, the track reconstruction efficiency and the momentum measurement. The results show that the detector is close to the design performance and that the Muon Spectrometer is ready to detect muons produced in high energy proton-proton collisions.
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| 5. |
- Dahl-Jensen, D., et al.
(författare)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 6. |
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| 7. |
- Matic, L. P., et al.
(författare)
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Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
- 2018
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
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Tidskriftsartikel (refereegranskat)abstract
- Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.
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| 8. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 9. |
- Buunen, M, et al.
(författare)
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COLOR II. A randomized clinical trial comparing laparoscopic and open surgery for rectal cancer.
- 2009
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Ingår i: Danish medical bulletin. - 1603-9629 .- 0907-8916. ; 56:2, s. 89-91
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Laparoscopic resection of rectal cancer has been proven efficacious but morbidity and oncological outcome need to be investigated in a randomized clinical trial. Trial design: Non-inferiority randomized clinical trial. METHODS: The COLOR II trial is an ongoing international randomized clinical trial. Currently 27 hospitals from Europe, South Korea and Canada are including patients. The primary endpoint is loco-regional recurrence rate three years post-operatively. Secondary endpoints cover quality of life, overall and disease free survival, post-operative morbidity and health economy analysis. RESULTS: By July 2008, 27 hospitals from the Netherlands, Belgium, Germany, Sweden, Spain, Denmark, South Korea and Canada had included 739 patients. The intra-operative conversion rate in the laparoscopic group was 17%. Distribution of age, location of the tumor and radiotherapy were equal in both treatment groups. Most tumors are located in the mid-rectum (41%). CONCLUSION: Laparoscopic surgery in the treatment of rectal cancer is feasible. The results and safety of laparoscopic surgery in the treatment of rectal cancer remain unknown, but are subject of interim analysis within the COLOR II trial. Completion of inclusion is expected by the end of 2009. Trial registration: Clinicaltrials.gov, identifier: NCT00297791 (www.clinicaltrials.gov).
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| 10. |
- Hermansson, Andreas, et al.
(författare)
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Immunotherapy with tolerogenic apolipoprotein B-100–loaded dendritic cells attenuates atherosclerosis in hypercholesterolemic mice
- 2011
-
Ingår i: Circulation. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 1524-4539.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by a massive intimal accumulation of low-density lipoprotein that triggers chronic vascular inflammation with an autoimmune response to low-density lipoprotein components. METHODS AND RESULTS: To dampen the inflammatory component of atherosclerosis, we injected hypercholesterolemic huB100(tg) × Ldlr(-/-) mice (mice transgenic for human apolipoprotein B100 [ApoB100] and deficient for the low-density lipoprotein receptor) intravenously with dendritic cells (DCs) that had been pulsed with the low-density lipoprotein protein ApoB100 in combination with the immunosuppressive cytokine interleukin-10. DCs treated with ApoB100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-γ, and increased de novo generation of regulatory T cells in vitro. Spleen cells from mice treated with DCs plus ApoB100 plus interleukin-10 showed diminished proliferative responses to ApoB100 and significantly dampened T-helper 1 and 2 immunity to ApoB100. Spleen CD4(+) T cells from these mice suppressed activation of ApoB100-reactive T cells in a manner characteristic of regulatory T cells, and mRNA analysis of lymphoid organs showed induction of transcripts characteristic of these cells. Treatment of huB100(tg) × Ldlr(-/-) mice with ApoB100-pulsed tolerogenic DCs led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4(+) T-cell infiltration and signs of reduced systemic inflammation. CONCLUSIONS: Tolerogenic DCs pulsed with ApoB100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis.
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| 11. |
- Klingenberg, Roland, et al.
(författare)
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Depletion of FOXP3(+) regulatory T cells promotes hypercholesterolemia and atherosclerosis
- 2013
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 123:3, s. 1323-1334
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Tidskriftsartikel (refereegranskat)abstract
- Atherosclerosis is a chronic inflammatory disease promoted by hyperlipidemia. Several studies support FOXP3-positive regulatory T cells (Tregs) as inhibitors of atherosclerosis; however, the mechanism underlying this protection remains elusive. To define the role of FOXP3-expressing Tregs in atherosclerosis, we used the DEREG mouse, which expresses the diphtheria toxin (DT) receptor under control of the Treg-specific Foxp3 promoter, allowing for specific ablation of FOXP3(+) Tregs. Lethally irradiated, atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice received DEREG bone marrow and were injected with DT to eliminate FOXP3(+) Tregs. Depletion of Tregs caused a 2.1-fold increase in atherosclerosis without a concomitant increase in vascular inflammation. These mice also exhibited a 1.7-fold increase in plasma cholesterol and an atherogenic lipoprotein profile with increased levels of VLDL. Clearance of VLDL and chylomicron remnants was hampered, leading to accumulation of cholesterol-rich particles in the circulation. Functional and protein analyses complemented by gene expression array identified reduced protein expression of sortilin-1 in liver and increased plasma enzyme activity of lipoprotein lipase, hepatic lipase, and phospholipid transfer protein as mediators of the altered lipid phenotype. These results demonstrate that FOXP3(+) Tregs inhibit atherosclerosis by modulating lipoprotein metabolism.
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| 12. |
- Lundberg, Anna, et al.
(författare)
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Activation-induced FOXP3 isoform profile in peripheral CD4+T cells is associated with coronary artery disease
- 2017
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Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 267, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The expression of FOXP3 isoforms affects regulatory T (Treg) cell function. Reduced Treg cell function has been associated with coronary artery disease (CAD). However, alternative splicing of FOXP3 in CAD has not been investigated. Methods: FOXP3 splice variants and IL17A transcripts in peripheral blood mononuclear cells from stable CAD patients and healthy controls were quantified, and FOXP3 isoform expression in response to T cell receptor (TCR) stimulation or LDL was analyzed by flow cytometry. Results: Compared to healthy controls, CAD patients expressed significantly more FOXP3 transcripts that included exon 2, whereas alternative splicing of exon 7 in correlation with IL17A expression was reduced. Moreover, TCR stimulation, as well as exposure to LDL, decreased alternative splicing of FOXP3 in CD4+ T cells in vitro. Conclusions: Our results demonstrate that blood mononuclear cells in stable CAD patients express a ratio of FOXP3 isoforms that is characteristic for activated CD4+ T cells. (C) 2017 Elsevier B.V. All rights reserved.
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| 13. |
- Nilsson, Jan, et al.
(författare)
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Immunomodulation of Atherosclerosis. Implications for Vaccine Development.
- 2005
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 25:1, s. 18-28
-
Forskningsöversikt (refereegranskat)abstract
- A number of studies have shown activation of the immune system throughout various stages of atherosclerosis. Recent observations have suggested that activation of immune responses may promote atherosclerosis on one hand by inducing and perpetuating arterial inflammation, whereas on the other hand, selective activation of certain immune functions may inhibit atherosclerosis and arterial inflammation. These observations suggest the possibility that selective suppression of proatherogenic immune responses or selective activation of antiatherogenic immune responses may provide new approaches for atherosclerosis prevention and treatment. Several antigens activating immune responses affecting development of atherosclerosis have been identified. These immune responses may be modulated by presenting the antigens together with different types of adjuvants as well as through the route of administration. In this review, we summarize recent experimental studies using immunomodulatory approaches for treatment of atherosclerosis.
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| 14. |
- Sakamoto, K., et al.
(författare)
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Interaction of metastable molecular oxygen with the dangling bonds of a Si(111)-(7×7) surface
- 2001
-
Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - 0368-2048 .- 1873-2526. ; 114-116, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the interaction between metastable molecular oxygen and the adatom dangling bonds modified by the adsorption of atomic oxygen into the back-bonds of a Si(111)-(7×7) surface. Ultraviolet photoelectron spectroscopy shows that the metastable states increase in intensity faster but with a decrease in its saturated intensity as the coverage of atomic oxygen increases. This result suggests that the number of modified dangling bonds is not the only important factor for the adsorption process of metastable oxygen. Taking into account the observation of modified dangling bonds with different density of states in scanning tunneling microscopy, we conclude that the adsorption of the metastable oxygen species correlates closely with the density of states of the dangling bond.
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| 15. |
- Wilhelmson, Anna S K, et al.
(författare)
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Testosterone Protects Against Atherosclerosis in Male Mice by Targeting Thymic Epithelial Cells.
- 2018
-
Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 38:7, s. 1519-1527
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Tidskriftsartikel (refereegranskat)abstract
- Androgen deprivation therapy has been associated with increased cardiovascular risk in men. Experimental studies support that testosterone protects against atherosclerosis, but the target cell remains unclear. T cells are important modulators of atherosclerosis, and deficiency of testosterone or its receptor, the AR (androgen receptor), induces a prominent increase in thymus size. Here, we tested the hypothesis that atherosclerosis induced by testosterone deficiency in male mice is T-cell dependent. Further, given the important role of the thymic epithelium for T-cell homeostasis and development, we hypothesized that depletion of the AR in thymic epithelial cells will result in increased atherosclerosis.Prepubertal castration of male atherosclerosis-prone apoE-/- mice increased atherosclerotic lesion area. Depletion of T cells using an anti-CD (cluster of differentiation) 3 antibody abolished castration-induced atherogenesis, demonstrating a role of T cells. Male mice with depletion of the AR specifically in epithelial cells (E-ARKO [epithelial cell-specific AR knockout] mice) showed increased thymus weight, comparable with that of castrated mice. E-ARKO mice on an apoE-/- background displayed significantly increased atherosclerosis and increased infiltration of T cells in the vascular adventitia, supporting a T-cell-driven mechanism. Consistent with a role of the thymus, E-ARKO apoE-/- males subjected to prepubertal thymectomy showed no atherosclerosis phenotype.We show that atherogenesis induced by testosterone/AR deficiency is thymus- and T-cell dependent in male mice and that the thymic epithelial cell is a likely target cell for the antiatherogenic actions of testosterone. These insights may pave the way for new therapeutic strategies for safer endocrine treatment of prostate cancer.
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| 16. |
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| 17. |
- Duteil, F., et al.
(författare)
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Er/O doped Si1-xGex alloy layers grown by MBE
- 2001
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Ingår i: Optical materials (Amsterdam). - 0925-3467 .- 1873-1252. ; 17:1-2, s. 131-134
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Silicon-based light emitting diodes (LEDs) containing an Er/O-doped Si1-xGex active layer have been studied. The structures were grown by molecular beam epitaxy (MBE), with Er and O concentrations of 5 × 1019 and 1 × 1020 cm-3, respectively, using Er and silicon monoxide sources. The microstructure has been studied by X-ray diffraction (XRD) and cross-sectional transmission electron microscopy, and it is found that Er/O-doped Si0.92Ge0.08 layers of high crystalline quality, can be obtained. Electroluminescence (EL) measurements have been performed on reverse-biased Er/O doped diodes both from the surface and from the edge and the emission at 1.54 µm associated with the Er3+ ions has been studied at 300 K and lower temperatures. To evaluate the possibility to use a Si1-xGex layer for waveguiding in Si-based optoelectronics, studies of the refractive index n of strained Si1-xGex as a function of the Ge concentration have been done by spectroscopic ellipsometry in the range 0.3-1.7 µm. At 1.54 µm the refractive index increases monotonically with the Ge concentration up to n = 3.542 for a Ge concentration of 21.3%. © 2001 Elsevier Science B.V.
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| 18. |
- Duteil, F., et al.
(författare)
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Luminescence and microstructure of Er/O co-doped Si structures grown by MBE using Er and SiO evaporation
- 2000
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Ingår i: Materials Science in Semiconductor Processing. - 1369-8001 .- 1873-4081. ; 3:5-6, s. 523-528
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Tidskriftsartikel (refereegranskat)abstract
- Er and O co-doped Si structures have been prepared using molecular-beam epitaxy (MBE) with fluxes of Er and O obtained from Er and silicon monoxide (SiO) evaporation in high-temperature cells. The incorporation of Er and O has been studied for concentrations of up to 2×1020 and 1×1021 cm-3, respectively. Surface segregation of Er can take place, but with O co-doping the segregation is suppressed and Er-doped layers without any indication of surface segregation can be prepared. Si1-xGex and Si1-yCy layers doped with Er/O during growth at different substrate temperatures show more defects than corresponding Si layers. Strong emission at 1.54µm associated with the intra-4f transition of Er3+ ions is observed in electroluminescence (EL) at room temperature in reverse-biased p-i-n-junctions. To optimize the EL intensity we have varied the Er/O ratio and the temperature during growth of the Er/O-doped layer. Using an Er-concentration of around 1×1020 cm-3 we find that Er/O ratios of 1:2 or 1:4 give higher intensity than 1:1 while the stability with respect to breakdown is reduced for the highest used O concentrations. For increasing growth temperatures in the range 400-575 °C there is an increase in the EL intensity. A positive effect of post-annealing on the photoluminescence intensity has also been observed.
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| 19. |
- Farias, Fabiana H. G., et al.
(författare)
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A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27, s. 432-441
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-U1-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.
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| 20. |
- Folkersen, Lasse, et al.
(författare)
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Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease
- 2010
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Ingår i: Circulation. - 1942-325X .- 1942-3268. ; 3:4, s. 365-373
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. METHODS AND RESULTS: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. CONCLUSIONS: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
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| 21. |
- Hansson, Göran K., et al.
(författare)
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Developing a vaccine against atherosclerosis
- 2020
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Ingår i: Nature Reviews Cardiology. - : Springer Science and Business Media LLC. - 1759-5002 .- 1759-5010. ; 17:8, s. 451-452
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Tidskriftsartikel (refereegranskat)
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| 22. |
- Jarrick, Arne, et al.
(författare)
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Prisade forskare visar oss vägen
- 2015
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Ingår i: Svenska Dagbladet. - 1101-2412. ; :10/12
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 23. |
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| 24. |
- Levin, Malin, 1973, et al.
(författare)
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Rip2 deficiency leads to increased atherosclerosis despite decreased inflammation.
- 2011
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Ingår i: Circulation research. - 1524-4571. ; 109:11, s. 1210-8
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Tidskriftsartikel (refereegranskat)abstract
- The innate immune system and in particular the pattern-recognition receptors Toll-like receptors have recently been linked to atherosclerosis. Consequently, inhibition of various signaling molecules downstream of the Toll-like receptors has been tested as a strategy to prevent progression of atherosclerosis. Receptor-interacting protein 2 (Rip2) is a serine/threonine kinase that is involved in multiple nuclear factor-κB (NFκB) activation pathways, including Toll-like receptors, and is therefore an interesting potential target for pharmaceutical intervention.
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| 25. |
- Liu, Shu Ming
(författare)
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Regulation of endothelial transport
- 1996
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A major role of endothelial cells is to control the influx of solutes into tissues. The aim of the research presented in this thesis was to gain knowledge about the regulation of endothelial transport in relation to the structure of the endothelial cytoskeleton and to elucidate the possible mechanisms of regulation.The transcellular transport of hydrophilic molecules was found to occur viavesicles arranged as chains stretching between the luminal surface and the interior of the cell, and also from the cell interior to the abluminal surface. Intact microtubules were required for this transport, and actin filaments acted as a hinder. In addition, the vesicular transport was stimulated by hydrogen peroxide (H20z) and phorbol myristate acetate (PMA), and the effect of PMA was dependent on reactive oxygen species.The structure of filamentous actin and the permeability were closely associated during stimulation with H20z and PMA. An increase in actin dense peripheral bands (DPBs) was correlated with a decrease in penneability during the first hour of exposure to PMA. For the next 5 h, disruption of DPBs was correlated with an increase in permeability. A low concentration of HzOz (10-5 M) had no effect on either DPBs or permeability, whereas 104 M HzOz disrupted DPBs and increased permeability.Nitric oxide (NO) was involved in the redistribution ofF-actin and the alteration of permeability induced by Hz02 and PMA. Addition of L-arginine, a substrate of NO, increased the number of DPBs and maintained low permeability for up to 6 h in PMAtreated cells. The increase in permeability and disruption of DPBs induced by 10-4 M H202 could be prevented by L-arginine. On the other hand, nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO, disrupted DPBs and caused a direct increase in permeability in PMA-treated cells and in cells treated with both concentrations of Hz02.The involvement of NO in the regulation of endothelial transport by HzOz was cGMP-dependent. An analogue of cGMP, 8-Br-cGMP, prevented the disruption of DPBs and the increase in permeability induced by HzOz even when the production of NO was inhibited by L-NAME.The present findings indicate that the endothelial transport of solutes is associated with the cytoskeleton and that it can be regulated by H20 2 and PMA. The endogenous production of NO appears to be involved in this process via a cGMP-dependent pathway.
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| 26. |
- Ljungberg, Jessica K., et al.
(författare)
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A Longitudinal Study of Memory Advantages in Bilinguals
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e73029-
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Tidskriftsartikel (refereegranskat)abstract
- Typically, studies of cognitive advantages in bilinguals have been conducted previously by using executive and inhibitory tasks (e.g. Simon task) and applying cross-sectional designs. This study longitudinally investigated bilingual advantages on episodic memory recall, verbal letter and categorical fluency during the trajectory of life. Monolingual and bilingual participants (n= 178) between 35-70 years at baseline were drawn from the Betula Prospective Cohort Study of aging, memory, and health. Results showed that bilinguals outperformed monolinguals at the first testing session and across time both in episodic memory recall and in letter fluency. No interaction with age was found indicating that the rate of change across ages was similar for bilinguals and monolinguals. As predicted and in line with studies applying cross-sectional designs, no advantages associated with bilingualism were found in the categorical fluency task. The results are discussed in the light of successful aging.
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| 27. |
- Ljungberg, Jessika K., et al.
(författare)
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The effect of language skills on dementia in a Swedish longitudinal cohort
- 2016
-
Ingår i: Linguistic Approaches to Bilingualism. - : John Benjamins Publishing Company. - 1879-9264 .- 1879-9272. ; 6:1-2, s. 190-204
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Tidskriftsartikel (refereegranskat)abstract
- Recent findings indicate that bilingualism delay the onset of dementia. Using data from the Betula longitudinal cohort study on memory, health and aging (www.betula.su.se) the issue of a possible protective effect of bilingualism was addressed. Monolingual (n = 736) and bilingual (n = 82) participants (= 60 years) without dementia at inclusion were followed for incident dementia over a time-period up to 10 years. In total, 112 participants developed dementia. Analyses were performed with Cox proportional hazards regression adjusted for age, sex, and presence/absence of the Apolipoprotein E (APOE) epsilon 4 allele, with dementia outcome as the dependent variable. Results showed no delayed onset of dementia in bilinguals compared to monolinguals. However, because of the findings from a study using participants from the same population showing beneficial longitudinal effects of bilingualism on episodic memory; we argue that our results may depend on the frequency of use of the second language after retirement.
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| 28. |
- Nagy, Edit, et al.
(författare)
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Valvular osteoclasts in calcification and aortic valve stenosis severity
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 168:3, s. 2264-2271
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bone remodeling in calcified aortic valves is thought to originate from microfractures at multiple sites of the valve, at which osteoclasts and osteoblasts are recruited. The aim of the present study was to assess circulating mediators of bone homeostasis, correlate them to the severity of stenosis and explore the spatio-temporal distribution of bone turnover in different parts of calcified aortic valve tissue.METHODS AND RESULTS: Plasma and explanted aortic valves were obtained from 46 patients undergoing aortic valve replacement surgery. Plasma levels of tartrate-resistant acid phosphatase (TRAP), receptor activator of nuclear-κB (RANK) ligand and Runt-related transcription factor 2 (Runx2/Cbfa1) exhibited a significant correlation to the severity of aortic stenosis. mRNA levels in normal, thickened and calcified parts of aortic valves assessed by quantitative real-time PCR were significantly elevated in calcified parts of valves for TRAP (5.08 ± 1.6-fold, P<0.001) RANK ligand (8.6 ± 4.2-fold, P<0.001) and RANK (1.98 ± 0.78-fold, P=0.015). In an age, gender and aortic valve anatomy-adjusted multivariable regression analysis the local transcript levels of TRAP correlated significantly with echocardiographic parameters quantifying stenosis severity in early stages, whereas the expression level of Runx2/Cbfa1 was a predictor of the stenosis severity in advanced stages.CONCLUSIONS: These findings suggest a critical role of bone turnover as a determinant of aortic stenosis severity.
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| 29. |
- Nahi, Hareth, et al.
(författare)
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Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden
- 2021
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Ingår i: Acta Haematologica. - : S. Karger AG. - 0001-5792 .- 1421-9662. ; 144:5, s. 519-527
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. Objective: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. Methods: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. Results: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- A nd third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). Conclusions: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.
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| 30. |
- Nilsson, Jan, et al.
(författare)
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Vaccination Strategies and Immune Modulation of Atherosclerosis
- 2020
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 126:9, s. 1281-1296
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive as well as innate immune responses contribute to the development of atherosclerosis. Studies performed in experimental animals have revealed that some of these immune responses are protective while others contribute to the progression of disease. These observations suggest that it may be possible to develop novel therapies for cardiovascular disease by selectively modulating such atheroprotective and proatherogenic immunity. Recent advances in cancer treatment using immune check inhibitors and CAR (chimeric antigen receptor) T-cell therapy serve as excellent examples of the possibilities of targeting the immune system to combat disease. LDL (low-density lipoprotein) that has accumulated in the artery wall is a key autoantigen in atherosclerosis, and activation of antigen-specific T helper 1-type T cells is thought to fuel plaque inflammation. Studies aiming to prove this concept by immunizing experimental animals with oxidized LDL particles unexpectedly resulted in activation of atheroprotective immunity involving regulatory T cells. This prompted several research groups to try to develop vaccines against atherosclerosis. In this review, we will discuss the experimental and clinical data supporting the possibility of developing immune-based therapies for lowering cardiovascular risk. We will also summarize ongoing clinical studies and discuss the challenges associated with developing an effective and safe atherosclerosis vaccine.
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| 31. |
- Nordenfelt, E, et al.
(författare)
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Hepatitis C virus infection in hemodialysis patients in southern Sweden: epidemiological, clinical, and diagnostic aspects
- 1993
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Ingår i: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 40:4, s. 266-270
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Tidskriftsartikel (refereegranskat)abstract
- A prevalence of hepatitis C virus (HCV) antibodies of 12% was found in 276 patients from 11 dialysis units. Between zero and 22% of the patients in the different units were anti-HCV positive. The epidemiology of HCV was studied in two units during a 2 year period by antibody assays and the polymerase chain reaction and correlated with clinical manifestations. Two types of epidemiologic patterns were found that may explain the wide difference of HCV prevalence described in different dialysis units. In one unit there was no evidence of spread within the unit, and the prevalence of HCV was dependent on the status of the patients entering for treatment. In the other unit, a clustering of infected patients could be seen in which 13 of 36 were infected during a 3 year period. Some patients who had not received blood transfusions were among the infected. Hepatitis C infection was the most common explanation for repeated abnormal transferase levels. Most of the HCV-infected patients reacted both for anti-HCV and HCV RNA. HCV RNA was in general detected earlier than anti-HCV seroconversion. Among 20 HCV RNA-positive serum samples that were anti-HCV ELISA-positive 18 had indeterminate and two negative reactions by immunoblot (RIBA 2). Thus the RIBA 2 test should be used with caution as a confirmatory antibody test in this group of patients.
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| 32. |
- Olofsson, Peder S., et al.
(författare)
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CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice
- 2008
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Ingår i: Circulation. - Baltimore, Md. : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 117:10, s. 1292-1301
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Tidskriftsartikel (refereegranskat)abstract
- Background— Atherosclerosis is a multifactorial disease in which inflammatory processes play an important role. Inflammation underlies lesion evolution at all stages, from establishment to plaque rupture and thrombosis. Costimulatory molecules of the tumor necrosis factor superfamily such as CD40/CD40L and OX40/OX40L have been implicated in atherosclerosis. Methods and Results— This study shows that the tumor necrosis factor superfamily members CD137 and CD137 ligand (CD137L), which play a major role in several autoimmune diseases, may constitute a pathogenic pair in atherogenesis. We detected CD137 protein in human atherosclerotic lesions not only on T cells but also on endothelial cells and showed that CD137 in cultured endothelial cells and smooth muscle cells was induced by proinflammatory cytokines implicated in atherosclerosis. Activation of CD137 by CD137L induced adhesion molecule expression on endothelial cells and reduced smooth muscle cell proliferation. In addition, treatment of atherosclerosis-prone apolipoprotein E–deficient mice with a CD137 agonist caused increased inflammation. T-cell infiltration, mainly of CD8+ cells, and expression of the murine major histocompatibility complex class II molecule I-Ab increased significantly in atherosclerotic lesions, as did the aortic expression of proinflammatory cytokines. Conclusions— Taken together, these observations suggest that CD137-CD137L interactions in the vasculature may contribute to the progression of atherosclerosis via augmented leukocyte recruitment, increased inflammation, and development of a more disease-prone phenotype.
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| 33. |
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| 34. |
- Ovchinnikova, Olga, et al.
(författare)
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Osteoprotegerin promotes fibrous cap formation in atherosclerotic lesions of ApoE-deficient mice--brief report.
- 2009
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 29:10, s. 1478-1480
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Osteoprotegerin (OPG) is a tumor necrosis factor receptor-related cytokine, initially found to inhibit osteoclastogenesis. In the present study we investigated the effect of OPG treatment on atherosclerosis. METHODS AND RESULTS: Hypercholesterolemic apoe(-/-) mice were treated with recombinant 15 mg/kg OPG or vehicle injections twice a week for 10 consecutive weeks. Mice treated with OPG showed increased amounts of smooth muscle cells and collagen within the atherosclerotic lesions. OPG treatment did not affect atherosclerotic lesion size (8.2% versus 7.6%) or total vessel area but led to a 250% increase in lesion collagen, formation of mature collagen fibers in subendothelial fibrous caps, and upregulated mRNA for lysyl oxidase that promotes collagen crosslinking. In cell culture studies, OPG promoted cell proliferation in rat aortic smooth muscle cells. In contrast, OPG treatment did not affect markers of vascular or systemic inflammation. CONCLUSIONS: OPG treatment promotes smooth muscle accumulation, collagen fiber formation, and development of fibrous caps but does not affect inflammatory properties of atherosclerotic lesions. Its effects may contribute to plaque stabilization.
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| 35. |
- Ovchinnikova, Olga, et al.
(författare)
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T-Cell Activation Leads to Reduced Collagen Maturation in Atherosclerotic Plaques of Apoe−/− Mice
- 2009
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Ingår i: American Journal of Pathology. - : Elsevier. - 0002-9440 .- 1525-2191. ; 174:2, s. 693-700
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Tidskriftsartikel (refereegranskat)abstract
- Rupture of the collagenous, fibrous cap of an atherosclerotic plaque commonly causes thrombosis. Activated immune cells can secrete mediators that jeopardize the integrity of the fibrous cap. This study aimed to determine the relationship between T-cell-mediated inflammation and collagen turnover in a mouse model of experimental atherosclerosis. Both Apoe(-/-) x CD4dnT beta RII mice with defective transforming growth factor-beta receptors in T cells (and hence released from tonic suppression of T-cell activation) and lesion size-matched Apoe(-/-) mice were used. Picrosirius red staining showed a lower content of thick mature collagen fibers in lesions of Apoe(-/-) x CD4dnT beta RII mice, although both groups had similar levels of procollagen type I or M mRNA and total collagen content in lesions. Analysis of both gene expression and protein content showed a significant decrease of lysyl oxidase, the extracellular enzyme needed for collagen cross-linking, in aortas of Apoe(-/-) - CD4dnT beta RII mice. T-cell-driven inflammation provoked a selective and limited increase in the expression of proteinases that catabolize the extracellular matrix. Atheromata of Apoe(-/-) - CD4dnT beta RII mice had increased levels of matrix metalloproteinase-13 and cathepsin S mRNAs and of the active form of cathepsin S protein but no increase was detected in collagen fragmentation. our results suggest that exaggerated T-cell-driven inflammation limits collagen maturation in the atherosclerotic plaque while having little effect on collagen degradation.
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| 36. |
- Paramel, Geena, 1985-, et al.
(författare)
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CARD8 gene encoding a protein of innate immunity is expressed in human atherosclerosis and associated with markers of inflammation
- 2013
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Ingår i: Clinical Science. - London, United Kingdom : Portland Press. - 0143-5221 .- 1470-8736. ; 125:8, s. 401-407
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a key factor in the development of atherosclerotic coronary artery disease. It is promoted through the inflammasome, a molecular machine that produces IL (interleukin)-1 beta in response to cholesterol crystal accumulation in macrophages. The CARD8 (caspase recruitment domain 8) protein modulates this process by suppressing caspase 1 and the transcription factor NF-kappa B (nuclear factor kappa B). The expression of CARD8 mRNA was examined in atherosclerotic vascular tissue and the impact on MI (myocardial infarction) of a polymorphism in the CARD8 gene determined. CARD8 mRNA was analysed by microarray of human atherosclerotic tissue and compared with transplant donor arterial tissue. Microarray analysis was performed for proximal genes associated with the rs2043211 locus in plaque. The CARD8 rs2043211 polymorphism was analysed by genotyping of two Swedish MI cohorts, FIA (First Myocardial Infarction in Northern Sweden) and SCARF (Stockholm Coronary Atherosclerosis Risk Factor). The CRP (C-reactive protein) level was measured in both cohorts, but the levels of the pro-inflammatory cytokines IL-1 beta, IL-18, TNF (tumour necrosis factor) and MCP-1 (monocyte chemoattractant protein) were measured in sera available from the SCARF cohort. CARD8 mRNA was highly expressed in atherosclerotic plaques compared with the expression in transplant donor vessel (P < 0.00001). The minor allele was associated with lower expression of CARD8 in the plaques, suggesting that CARD8 may promote inflammation. Carriers of the minor allele of the rs2043211 polymorphism also displayed lower circulating CRP and lower levels of the pro-atherosclerotic chemokine MCP-1. However, no significant association could be detected between this polymorphism and MI in the two cohorts. Genetic alterations in the CARD8 gene therefore seem to be of limited importance for the development of MI.
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| 37. |
- Paramel Varghese, Geena, 1985-, et al.
(författare)
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NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis
- 2016
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Ingår i: Journal of the American Heart Association. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: The NLR family, pyrin domain containing 3 (NLRP3) inflammasome is an interleukin (IL)-1β and IL-18 cytokine processing complex that is activated in inflammatory conditions. The role of the NLRP3 inflammasome in the pathogenesis of atherosclerosis and myocardial infarction is not fully understood.Methods and Results: Atherosclerotic plaques were analyzed for transcripts of the NLRP3 inflammasome, and for IL-1β release. The Swedish First-ever myocardial Infarction study in Ac-county (FIA) cohort consisting of DNA from 555 myocardial infarction patients and 1016 healthy individuals was used to determine the frequency of 4 single nucleotide polymorphisms (SNPs) from the downstream regulatory region of NLRP3. Expression of NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 (CASP1), IL1B, and IL18 mRNA was significantly increased in atherosclerotic plaques compared to normal arteries. The expression of NLRP3 mRNA was significantly higher in plaques of symptomatic patients when compared to asymptomatic ones. CD68-positive macrophages were observed in the same areas of atherosclerotic lesions as NLRP3 and ASC expression. Occasionally, expression of NLRP3 and ASC was also present in smooth muscle cells. Cholesterol crystals and ATP induced IL-1β release from lipopolysaccharide-primed human atherosclerotic lesion plaques. The minor alleles of the variants rs4266924, rs6672995, and rs10733113 were associated with NLRP3 mRNA levels in peripheral blood mononuclear cells but not with the risk of myocardial infarction.Conclusions: Our results indicate a possible role of the NLRP3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis.
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| 38. |
- Robbie, K., et al.
(författare)
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Formation of Ni-graphite intercalation compounds on SiC
- 2001
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 64, s. 155401-15540111
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Tidskriftsartikel (refereegranskat)
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| 39. |
- Robbie, K, et al.
(författare)
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Study of contact formation by high temperature deposition of Ni on SiC
- 2000
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Ingår i: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 338-3, s. 981-984
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Tidskriftsartikel (refereegranskat)abstract
- We report the observation, by scanning tunneling microscopy (STM), scanning electron microscopy (SEM), Auger electron spectroscopy (AES), and atomic force microscopy (AFM), of island formation on SIC during high temperature deposition and annealing of thin Ni films. Ni films with a nominal thickness of 2.5 monolayers were sputter deposited onto H-2-etched single crystal 6H-SiC (0001) substrates heated to 600 degreesC in an ultrahigh vacuum STM system. After the substrates were annealed to 800-1000 degreesC, island formation was observed by STM. The islands were 0.1-0.5 mum in diameter, similar to 30 nm high, and separated by similar to2 mum from each other, with an exceptionally flat top with a peculiar 'stitched' surface structure. A second type of island, similar to1.5 mum in diameter, similar to 10 nm high, and separated by similar to 10 mum from each other, was observed by ex situ AFM and SEM. Microspot AES showed that the first islands are composed of Ni and C, while the second islands are composed of Ni, C, and Si. AES lineshape studies showed that the carbon in both types of islands is graphitically bound as opposed to the carbon in the substrate which is carbidically bound. From comparisons to literature, we believe that the first islands are a new type of graphite intercalation compound. An indexing of Ni on the top graphite sheets is presented for each anneal temperature.
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| 40. |
- Robinson, I.K., et al.
(författare)
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Resonant scattering in delta-doped heterostructures
- 2001
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 79:18, s. 2913-2915
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the utility of resonant x-ray scattering in probing the structure of doping layers at a heterostructure interface. The positions of germanium layers inserted at the interface of a silicon epitaxial film assert a strong influence of the phase of the scattered intensity along the crystal truncation rods. The phase of the scattering, and hence the internal structure of the layers, can be determined conveniently by analyzing its energy dependence in the vicinity of the Germanium absorption edge at 11.103 keV. © 2001 American Institute of Physics.
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| 41. |
- Rosenquist, K, et al.
(författare)
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Oral status, oral infections and some lifestyle factors as risk factors for oral and oropharyngeal squamous cell carcinoma: A population-based case-control study in southern Sweden
- 2005
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 125:12, s. 1327-1336
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Tidskriftsartikel (refereegranskat)abstract
- Conclusion. Our results show that average and poor oral hygiene and inadequate dental status are independent risk factors for oral and oropharyngeal squamous cell carcinoma ( OOSCC), irrespective of tobacco and alcohol consumption. Objective. To evaluate a possible relationship between oral cancer, oral hygiene, dental status, oral mucosal lesions and some lifestyle factors in a population- based case- control study. Material and methods. Between September 2000 and January 2004, 132/ 165 ( 80%) of all incident cases of OOSCC and 320/ 396 ( 81%) of the intended eligible matched controls participated in the study. Cases and controls were subjected to an identical oral examination. A standardized protocol specially designed for the study was used. Results. After adjusting for tobacco and alcohol consumption, average oral hygiene ( OR 2.0; 95% CI 1.1 - 3.6) and poor oral hygiene ( OR 5.3; 95% CI 2.5 - 11.3) emerged as significant risk factors for OOSCC. More than 20 lost teeth ( OR 3.4; 95% CI 1.4 - 8.5), > 5 defective teeth ( OR 3.1; 95% CI 1.2 - 8.2) and poorly fitting or defective complete dentures ( OR 3.8; 95% CI 1.3 - 11.4) were significant risk factors. Regular dental check- ups were associated with a decreased risk of OOSCC ( OR 0.4; 95% CI 0.2 - 0.6).
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| 42. |
- Sirsjö, Allan, et al.
(författare)
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Deficiency of nitric oxide synthase 2 results in increased neointima formation in a mouse model of vascular injury
- 2003
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Ingår i: Journal of Cardiovascular Pharmacology. - : Lippincott Williams & Wilkins. - 0160-2446 .- 1533-4023. ; 41:6, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Restenosis frequently occurs after arterial interventions. The inducible form of nitric oxide synthase (NOS2) may both promote and inhibit neointima formation. This study investigated the role of NOS2 for neointima formation in a mouse model of carotid artery injury. The common carotid artery was ligated in anesthetized mice. Homozygous NOS2 knockout mice were compared with wild-type B6/129 mice or wild-type mice treated with the pharmacologic NOS2 inhibitor aminoguanidine given orally daily after ligation (n = 6-8 in each group). Vessels were harvested for quantification of lesion size 4 weeks later, or serially after ligation for tissue analysis. mRNA for NOS2 increased 1-4 days after ligation of the carotid artery. Cell proliferation could be visualized with an antibody against proliferating cell nuclear antigen. An intimal smooth muscle cell layer, confirmed by an alpha-actin antibody, was observed in the lumen 4 weeks after injury. Inhibition of NOS2 by either pharmacologic or genetic approaches tended to increase the area of intima formation (P = 0.13 or P less than 0.05, respectively) and increased the intima/media ratio (P = 0.14 and P less than 0.01, respectively). Inhibition of NOS2 by two different approaches increased neointima formation in a mouse model of mechanical vessel injury, indicating that the NOS2 expressed in the injured vessel wall is beneficial.
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| 43. |
- Sirsjö, Allan, et al.
(författare)
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Retinoic Acid Inhibits Nitric Oxide Synthase-2 Expression through the Retinoic Acid Receptor-alpha
- 2000
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 270:3, s. 846-851
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Tidskriftsartikel (refereegranskat)abstract
- Retinoids are multipotent modulators of cellular functions and suppress cytokine-induced production of nitric oxide (NO) in several cell types. We have explored the mechanisms by which retinoic acid (RA) regulates NO production in rat aortic smooth muscle cells (VSMC), which express NOS2 in response to proinflammatory cytokines. RA inhibited interleukin-1beta (IL-1beta)-induced NOS2 mRNA expression and NO production. These effects were attenuated by the retinoic acid receptor (RAR) antagonist CD3106, indicating that they were mediated through retinoic acid receptors (RARs). The synthetic retinoid agonists CD336 (which specifically binds RARalpha) and CD367 (which binds all RARs) but not agonists specific for RARbeta, RARgamma, or RXRs reduced IL-1beta-induced NOS2 expression and NO production. When transfecting VSMC with a 1570-bp NOS2 promoter fragment fused to a luciferase reporter gene, the NOS2 promoter activity was inhibited by RA. These results indicate that retinoids modulate NO production in VSMC via RARalpha, which inhibits the transcription of the NOS2 gene.
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| 44. |
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| 45. |
- Söderström, Leif, et al.
(författare)
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Increased carotid artery lesion inflammation upon treatment with the CD137 agonistic antibody 2A
- 2017
-
Ingår i: Circulation Journal. - 1346-9843. ; 81:12, s. 1945-1952
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased inflammatory activity destabilizes the atherosclerotic lesion and may lead to atherothrombosis and symptomatic cardiovascular disease. Co-stimulatory molecules, such as CD137, are key regulators of inflammation, and CD137 activity regulates inflammation in experimental atherosclerosis. Here, we hypothesized that CD137 activation promotes carotid artery inflammation and atherothrombosis. Methods and Results: In a model of inducible atherothrombosis with surgical ligation of the right carotid artery and a subsequent placement of a polyethene cuff, elevated levels of CD137 and CD137 ligand mRNA in atherothrombotic vs. non-atherothrombotic murine carotid lesions was observed. Mice treated with the CD137 agonistic antibody 2A showed signs of increased inflammation in the aorta and a higher proportion of CD8+ T cells in spleen and blood. In carotid lesions of 2A-treated mice, significantly higher counts of CD8+ and major histocompatibility (MHC)-class II molecule I-Ab+ cells were observed. Treatment with the CD137 agonistic antibody 2A did not significantly affect the atherothrombosis frequency in 16-week-old mice in this model. Conclusions: Levels of CD137 and CD137 ligand mRNA were higher in advanced atherosclerotic disease compared to control vessels, and treatment with the CD137 agonistic antibody 2A, in a murine model for inducible atherothrombosis promoted vascular inflammation, but had no significant effect on atherothrombosis frequency at this early disease stage.
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| 46. |
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| 47. |
- Vasur, Jonas, et al.
(författare)
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Synthesis of cyclic β-glucan using Laminarinase 16A glycosynthase mutant from the basidiomycete Phanerochaete chrysosporium
- 2010
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 132:5, s. 1724-1730
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Tidskriftsartikel (refereegranskat)abstract
- Glycosynthases are precise molecular instruments for making specifically linked oligosaccharides. X-ray crystallography screening of ligands bound to the 1,3(4)-β-d-glucanase nucleophile mutant E115S of Phanerochaete chrysosporium Laminarinase 16A (Lam16A) showed that laminariheptaose (L7) bound in an arch with the reducing and nonreducing ends occupying either side of the catalytic cleft of the enzyme. The X-ray structure of Lam16A E115S in complex with α-laminariheptaosyl fluoride (αL7F) revealed how αL7F could make a nucleophilic attack upon itself. Indeed, when Lam16A E115S was allowed to react with αL7F the major product was a cyclic β-1,3-heptaglucan, as shown by mass spectrometry. NMR confirmed uniquely β-1,3-linkages and no reducing end. Molecular dynamics simulations indicate that the cyclic laminariheptaose molecule is not completely planar and that torsion angles at the glycosidic linkages fluctuate between two energy minima. This is the first report of a glycosynthase that joins the reducing and nonreducing ends of a single oligosaccharide and the first reported synthesis of cyclic β-glucan.
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| 48. |
- Wilbe, Maria, et al.
(författare)
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Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 250-254
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Tidskriftsartikel (refereegranskat)abstract
- The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.
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| 49. |
- Wuttge, Dirk M., et al.
(författare)
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CXCL16/SR-PSOX is an interferon-gamma-regulated chemokine and scavenger receptor expressed in atherosclerotic lesions
- 2004
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 24:4, s. 750-755
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Atherosclerosis is an inflammatory disease. Several chemokines are important for monocyte/macrophage and T-cell recruitment to the lesion. CXCL16 is a recently discovered chemokine that is expressed in soluble and transmembrane forms, ligates CXCR6 chemokine receptor, and guides migration of activated Th1 and Tc1 cells. It is identical to scavenger receptor SR-PSOX, which mediates uptake of oxidized low-density lipoprotein. We investigated whether CXCL16 expression is controlled by interferon-gamma (IFN-gamma)-cytokine abundant in atherosclerotic lesions. METHODS AND RESULTS: CXCL16 and CXCR6 expression was identified by polymerase chain reaction and histochemistry in atherosclerotic lesions from humans and apolipoprotein-E-deficient mice. In vitro IFN-gamma induced CXCL16 in human monocytic THP-1 cells and primary human monocytes, which led to increased uptake of oxidized low-density lipoprotein in THP-1 cells, which could be blocked by peptide antibodies against CXCL16. In vivo IFN-gamma induced CXCL16 expression in murine atherosclerotic lesions. CONCLUSIONS: We demonstrate a novel role of IFN-gamma in foam cell formation through upregulation of CXCL16/SR-PSOX. CXCR6 expression in the plaque confirms the presence of cells able to respond to CXCL16. Therefore, this chemokine/scavenger receptor could serve as a molecular link between lipid metabolism and immune activity in the atherosclerotic lesion.
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| 50. |
- Wuttge, Dirk M., et al.
(författare)
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Induction of CD36 by all-trans retionic acid : retinoic acid receptor signaling in the pathogenesis of atherosclerosis
- 2001
-
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 15:7, s. 1221-3
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Tidskriftsartikel (refereegranskat)abstract
- Scavenger receptors mediating the uptake of oxidized low-density lipoproteins (oxLDL) by macrophages play a crucial role in foam cell formation during atherosclerosis. One member of this receptor family, the thrombospondin receptor CD36, has recently been shown to mediate a major part of the oxLDL-induced aggravation of atherosclerotic lesions. Here, we show that the expression of CD36 protein and mRNA in human monocytic THP-1 cells is increased by alltrans retinoic acid (atRA), a derivative of the essential Vitamin A, which leads to increased uptake of oxLDL. CD3106, a specific antagonist at the retinoic acid receptor (RAR), inhibited the atRA-induced CD36 expression, whereas the RAR-specific agonist CD367 induced CD36 to the same degree as atRA. This indicates an RAR-mediated CD36 induction. AtRA and oxLDL had synergistic effects in up-regulating CD36 when in both THP-1 cells and primary monocytes. Applying a sensitive RAR-GAL-4 reporter assay, we could demonstrate RAR ligands in human atherosclerotic lesions. In addition, immunohistochemistry showed RAR- which indicates that atRA may contribute to foam cell formation and the progress of atherosclerosis.
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