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  • 1
    In: Clinical Research in Cardiology, Springer Science and Business Media LLC, Vol. 111, No. 8 ( 2022-08), p. 843-858
    Type of Medium: Online Resource
    ISSN: 1861-0684 , 1861-0692
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2218331-0
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  • 2
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 119, No. 7 ( 2023-07-04), p. 1509-1523
    Abstract: Specific fibroblast markers and in-depth heterogeneity analysis are currently lacking, hindering functional studies in cardiovascular diseases (CVDs). Here, we established cell-type markers and heterogeneity in murine and human arteries and studied the adventitial fibroblast response to CVD and its risk factors hypercholesterolaemia and ageing. Methods and results Murine aorta single-cell RNA-sequencing analysis of adventitial mesenchymal cells identified fibroblast-specific markers. Immunohistochemistry and flow cytometry validated platelet-derived growth factor receptor alpha (PDGFRA) and dipeptidase 1 (DPEP1) across human and murine aorta, carotid, and femoral arteries, whereas traditional markers such as the cluster of differentiation (CD)90 and vimentin also marked transgelin+ vascular smooth muscle cells. Next, pseudotime analysis showed multiple fibroblast clusters differentiating along trajectories. Three trajectories, marked by CD55 (Cd55+), Cxcl chemokine 14 (Cxcl14+), and lysyl oxidase (Lox+), were reproduced in an independent RNA-seq dataset. Gene ontology (GO) analysis showed divergent functional profiles of the three trajectories, related to vascular development, antigen presentation, and/or collagen fibril organization, respectively. Trajectory-specific genes included significantly more genes with known genome-wide associations (GWAS) to CVD than expected by chance, implying a role in CVD. Indeed, differential regulation of fibroblast clusters by CVD risk factors was shown in the adventitia of aged C57BL/6J mice, and mildly hypercholesterolaemic LDLR KO mice on chow by flow cytometry. The expansion of collagen-related CXCL14+ and LOX+ fibroblasts in aged and hypercholesterolaemic aortic adventitia, respectively, coincided with increased adventitial collagen. Immunohistochemistry, bulk, and single-cell transcriptomics of human carotid and aorta specimens emphasized translational value as CD55+, CXCL14+ and LOX+ fibroblasts were observed in healthy and atherosclerotic specimens. Also, trajectory-specific gene sets are differentially correlated with human atherosclerotic plaque traits. Conclusion We provide two adventitial fibroblast-specific markers, PDGFRA and DPEP1, and demonstrate fibroblast heterogeneity in health and CVD in humans and mice. Biological relevance is evident from the regulation of fibroblast clusters by age and hypercholesterolaemia in vivo, associations with human atherosclerotic plaque traits, and enrichment of genes with a GWAS for CVD.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1499917-1
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  • 3
    In: ECS Meeting Abstracts, The Electrochemical Society, Vol. MA2022-02, No. 15 ( 2022-10-09), p. 822-822
    Abstract: Two dimensional ultrathin layers are considered promising materials to bring new functionalities in nanotechnologies and candidate to replace 3D materials in existing applications. Among this last category, transition metal dichalcogenides (TMDC) like WS 2 , MoS 2 , WSe 2 are viewed as interesting alternative channels for ultra-scaled CMOS technologies, as silicon is approaching its physical limits. These semiconductor 2D monolayers could bring a decisive advantage in terms of electrostatic control at very low gate length, while maintaining decent carrier transport properties as compared to 3D materials at same dimension. In addition, TMDC should provide improved off current performance as compared to silicon, an important factor to improve the static power efficiency in multibillion transistor chips. Obviously, replacing the channel material of the main device in microelectronics, from silicon to TMDC, comes with a very long list of scientific and technological challenges to be addressed. In this paper we limit our scope to the growth of TMDC, one of the main pillar in this global effort, and share how we addressed some of the challenges related to the formation of 2D semiconductor channels, to enable the fabrication of functioning devices on lab and 300 mm flows. TMDCs thin films grown with metal oxide CVD on substrates with, in some case, the presence of NaCl salts, are demonstrating the largest grain size and the best electrical performance but these processes are hardly compatible with industrial CVD reactors. In contrast we use chemistries more compatible with manufacturing, with the target of growing TMDC on 300 mm substrates. We report on MoS 2 and WS 2 formed with chemistries using metal organic precursors such as Mo(CO) 6 or W(CO) 6 and di-hydrogen sulfide grown in customized epitaxial cross flow 200 and 300 mm reactors [1]. We report basic nucleation and growth studies over a large process domain which show the possibility to control the density of nuclei and the subsequent lateral crystal growth while minimizing secondary nucleation and metal particle defectivity. We study the deposition of MoS 2 an WS 2 on two basic types of substrates defining fundamentally the integration schemes. On one route, dedicated to device performance demonstration, TMDC monolayers are grown on templated substrates like sapphire following a van der Waals epitaxy mode which enables regular orientation of the crystallites and formation of large and oriented domains after grain ripening with reduced defect concentration. The 2D layer is then transferred onto the final substrate for the device formation. With this technique, average mobilities above 30 cm2/Vs have been achieved regularly on MoS 2 backgated devices, and the best devices exhibit currents at transfer curve up to 420 mA/mm [2,3]. On the other flow, recent efforts have aimed at growing WS 2 directly on various types of amorphous substrate layer typically deposited on 300mm wafer, acting either as bottom gate dielectric or sacrificial layer. This scheme doesn’t require subsequent transfer step. However, after integration, these materials demonstrate performance still substantially lower than with material grown on sapphire [4,5]. As the device dimensions has scaled down over the last 20 years, improving the variability at different scales has emerged as major topic in microelectronics. TMDC channels are no exception to this trend despite intrinsic advantage in terms of thickness control. We will share on specific work done on sapphire surface specification and preparation. We have demonstrated that depositing MoS 2 on 1° off-A axis C-plane sapphire substrate reduced the dispersion in mobility as compared to similar materials obtained on C-plane oriented on-axis substrates [6]. We have also worked-out in-situ Cl 2 etch process to remove the superficial islands grown on top of the first layer MoS 2 crystals as this first layer is being closed. The process enables full lateral etching of the secondary layer crystals selectively to the closed first layer. With this process, we observed substantial improvement in the electrostatic control of MoS2 scaled transistors, including threshold voltage variability and improved subthreshold swing control [7]. We continue to work out the TMDC growth process to improve the material quality, impacted by the presence of defects at the grain boundaries or intra-grain, aiming to close the gap with advanced logic requirements. 1-Caymax & al., SSDM, D-1-03, 2019 2-D Lin & al., Symposium on VLSI Technology, 1-2, 2021 3- Wu & al., IEDM, 7.4.1-7.4.4, 2021 4- Asselberghs & al., IEDM, 40.2.1- 40.2.4, 2020 5- Smets & al., IEDM, 34.2.1-34.2.4, 2021 6- Shi & al., ACS nano 15 (6), 9482-9494, 2021 7- Shi & al., IEDM, 37.1.1-37.1.4, 2021
    Type of Medium: Online Resource
    ISSN: 2151-2043
    Language: Unknown
    Publisher: The Electrochemical Society
    Publication Date: 2022
    detail.hit.zdb_id: 2438749-6
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  • 4
    In: Clinical Research in Cardiology, Springer Science and Business Media LLC, Vol. 111, No. 8 ( 2022-08), p. 969-970
    Type of Medium: Online Resource
    ISSN: 1861-0684 , 1861-0692
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2218331-0
    Library Location Call Number Volume/Issue/Year Availability
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