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- Matuozzo, D, et al.
(författare)
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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
- 2022
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundWe previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants wasTLR7, with an OR of 27.68 (95%CI:1.5-528.7,P=1.1×10−4), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2],P=2.1×10−4). Adding the recently reportedTYK2COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4];P=3.4×10−3). When these 14 loci andTLR7were considered, all individuals hemizygous (n=20) or homozygous (n=5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0],P=4.7×10−7), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9],P=0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years;P=1.68×10−5).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.
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- Bhattacharyya, Debabrata, et al.
(författare)
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Material aspects for batch integration of PZT thin films using transfer bonding technologies : Q2M development
- 2008
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Ingår i: Proc. 4M 2008 Conference on Multi-Material Micro Manufacture.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Transfer bonding is a reliable cost-efficient and low-temperature CMOS compatible technique which allows batchintegration of materials whose incompatibility with Si makes them unsuitable for monolithic integration. In thisheterogeneous device integration method the material and process incompatibilities inherent in Si IC technology areovercome by fabricating devices on separate substrates and then transferring them onto target (e.g. CMOS) wafers.Transfer bonding has great potential for integrating RF-MEMS devices incorporating, for example, high thermal budgetmaterials such as PZT and PST or non-ferroelectric piezoelectrics such as AlN and ZnO into microwave ICs forenhanced systems performance. This paper presents an overview of technology developments within the EUsponsored project Q2M for the realization of transfer bonded piezoelectrically actuated RF MEMS switches and othercomponents focusing in particular on material factors relating to growth of the piezoelectric films, in this case sol-geldeposited PZT, that restricts the choice of device layers and impact on PZT properties such as microstructure, filmorientation and piezoelectric coefficients. New process developments such as hard masking of PZT pattern during RIEetching and its compatibility with polymer transfer bonding are discussed.
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