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Sökning: WFRF:(van der Vorst M.)

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  • Trappe, N., et al. (författare)
  • Next Generation Sub-millimetre Wave Focal Plane Array Coupling Concepts - An ESA TRP project to develop multichroic focal plane pixels for future CMB polarisation experiments
  • 2016
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9781510602076 ; 9914:Part 1, s. UNSP 991412-
  • Konferensbidrag (refereegranskat)abstract
    • The main objective of this activity is to develop new focal plane coupling array concepts and technologies that optimise the coupling from reflector optics to the large number of detectors for next generation sub millimetre wave telescopes particularly targeting measurement of the polarization of the cosmic microwave background (CMB). In this 18 month TRP programme the consortium are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays which will be demanded to reach the required sensitivity of future CMB polarization missions. One major development was to have multichroic operation to potentially reduce the required focal plane size of a CMB mission. After research in the optimum telescope design and definition of requirements based on a stringent science case review, a number of compact focal plane architecture concepts were investigated before a pixel demonstrator consisting of a planar mesh lens feeding a backend Resonant Cold Electron Bolometer RCEB for filtering and detection of the dual frequency signal was planned for manufacture and test. In this demonstrator the frequencies of the channels was chosen to be 75 and 105 GHz in the w band close to the peak CMB signal. In the next year the prototype breadboards will be developed to test the beams produced by the manufactured flat lenses fed by a variety of antenna configurations and the spectral response of the RCEBs will also be verified.
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  • Trappe, N., et al. (författare)
  • Next generation sub-millimetre wave focal plane array coupling concepts: An ESA TRP project to develop multichroic focal plane pixels for future CMB polarisation experiments
  • 2018
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10708
  • Konferensbidrag (refereegranskat)abstract
    • © 2018 SPIE. In this activity, we develop novel focal plane detector pixels for the next generation CMB B mode detection missions. Such future mission designs will require focal plane pixel technologies that optimizes the coupling from telescope optics to the large number of detectors required to reach the sensitivities required to measure the faint CMB polarization traces. As part of an ESA Technical Research Programme (TRP) programme we are tasked with developing, manufacturing and experimentally verifying a prototype multichroic pixel which would be suitable for the large focal plane arrays to reduce the focal plane size requirement. The concept of replacing traditional single channel pixels with multi frequency pixels will be a key driver in future mission design and the ability to couple radiation effectively over larger bandwidths (30-100%) is a real technical challenge. In the initial part of the programme we reviewed the science drivers and this determined the technical specifications of the mission. Various options for focal plane architectures were considered and then after a tradeoff study and review of resources available, a pixel demonstrator was selected for design manufacture and test. The chosen design consists of a novel planar mesh lens coupling to various planar antenna configurations with Resonant Cold Electron Bolometer (RCEB) for filtering and detection of the dual frequency signal. The final cryogenic tests are currently underway and a final performance will be verified for this pixel geometry.
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  • Haghikia, A., et al. (författare)
  • Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism
  • 2022
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:6, s. 518-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism. Methods and results Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe(-/-)) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe(-/-) mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels. Conclusion Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs.
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  • Gencer, S, et al. (författare)
  • Endothelial ACKR3 drives atherosclerosis by promoting immune cell adhesion to vascular endothelium
  • 2022
  • Ingår i: Basic research in cardiology. - : Springer Science and Business Media LLC. - 1435-1803 .- 0300-8428. ; 117:1, s. 30-
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerosis is the foundation of potentially fatal cardiovascular diseases and it is characterized by plaque formation in large arteries. Current treatments aimed at reducing atherosclerotic risk factors still allow room for a large residual risk; therefore, novel therapeutic candidates targeting inflammation are needed. The endothelium is the starting point of vascular inflammation underlying atherosclerosis and we could previously demonstrate that the chemokine axis CXCL12–CXCR4 plays an important role in disease development. However, the role of ACKR3, the alternative and higher affinity receptor for CXCL12 remained to be elucidated. We studied the role of arterial ACKR3 in atherosclerosis using western diet-fed Apoe−/− mice lacking Ackr3 in arterial endothelial as well as smooth muscle cells. We show for the first time that arterial endothelial deficiency of ACKR3 attenuates atherosclerosis as a result of diminished arterial adhesion as well as invasion of immune cells. ACKR3 silencing in inflamed human coronary artery endothelial cells decreased adhesion molecule expression, establishing an initial human validation of ACKR3’s role in endothelial adhesion. Concomitantly, ACKR3 silencing downregulated key mediators in the MAPK pathway, such as ERK1/2, as well as the phosphorylation of the NF-kB p65 subunit. Endothelial cells in atherosclerotic lesions also revealed decreased phospho-NF-kB p65 expression in ACKR3-deficient mice. Lack of smooth muscle cell-specific as well as hematopoietic ACKR3 did not impact atherosclerosis in mice. Collectively, our findings indicate that arterial endothelial ACKR3 fuels atherosclerosis by mediating endothelium-immune cell adhesion, most likely through inflammatory MAPK and NF-kB pathways.
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  • Auriacombe, Olivier, 1989, et al. (författare)
  • 325 GHz and 650 GHz Dual-polarisation receivers Concept
  • 2022
  • Ingår i: 32nd International Symposium of Space Terahertz Technology, ISSTT 2022.
  • Konferensbidrag (refereegranskat)abstract
    • The integrated dual-polarisation receivers utilize a dual probe concept, efficiently integrating the antenna and MMIC package environment which allows for polarisation discrimination without the use of bulky and lossy external orthomode transducers. This concept increases the sensitivity of the instrument and reduces its size, enabling the development of future earth observation arrays. Omnisys Instruments AB (Sweden) and Chalmers University of Technology (Sweden) are working to demonstrate state-of-the-art dual polarisation capability with two integrated receiver modules at 325 GHz and 650 GHz.
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  • Mauersberger, C, et al. (författare)
  • Loss of soluble guanylyl cyclase in platelets contributes to atherosclerotic plaque formation and vascular inflammation
  • 2022
  • Ingår i: Nature cardiovascular research. - : Springer Science and Business Media LLC. - 2731-0590. ; 1:12, s. 1174-1186
  • Tidskriftsartikel (refereegranskat)abstract
    • Variants in genes encoding the soluble guanylyl cyclase (sGC) in platelets are associated with coronary artery disease (CAD) risk. Here, by using histology, flow cytometry and intravital microscopy, we show that functional loss of sGC in platelets of atherosclerosis-prone Ldlr−/− mice contributes to atherosclerotic plaque formation, particularly via increasing in vivo leukocyte adhesion to atherosclerotic lesions. In vitro experiments revealed that supernatant from activated platelets lacking sGC promotes leukocyte adhesion to endothelial cells (ECs) by activating ECs. Profiling of platelet-released cytokines indicated that reduced platelet angiopoietin-1 release by sGC-depleted platelets, which was validated in isolated human platelets from carriers of GUCY1A1 risk alleles, enhances leukocyte adhesion to ECs. Importantly, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in atherosclerosis-prone Ldlr−/− mice. Therefore, pharmacological sGC stimulation might represent a potential therapeutic strategy to prevent and treat CAD.
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