Introduction Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor ...genes strongly contribute to idiopathic and familial PAH. Objective To explore the genetic bases of SScâeuro"PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods TGFβ receptor genes, BMPR2, ALK1 , TGFR2 and ENG , were sequenced in 10 SScâeuro"PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SScâeuro"PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SScâeuro"PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SScâeuro"PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SScâeuro"PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SScâeuro"PAH using both sequencing and genotyping methods.
Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory ...rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10-5 were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10-8, OR = 0.69, 95% CI 0.60-0.79; rs6457617, P = 1.14×10-7 and rs9275245, P = 1.39×10-7. Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10-5, OR = 1.36 1.18-1.56) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10-5) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10-10, OR:1.25), TNIP1 (P = 4.68×10-9, OR:1.31), and RHOB loci (P = 3.17×10-6, OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis.
Advances in ultrafast plasmonics Alemayehu Nana Koya; Romanelli, Marco; Kuttruff, Joel ...
arXiv (Cornell University),
11/2022
Paper, Journal Article
Open access
In the past twenty years, we have reached a broad understanding of many light-driven phenomena in nanoscale systems. The temporal dynamics of the excited states are instead quite challenging to ...explore, and, at the same time, crucial to study for understanding the origin of fundamental physical and chemical processes. In this review we examine the current state and prospects of ultrafast phenomena driven by plasmons both from a fundamental and applied point of view. This research area is referred to as ultrafast plasmonics and represents an outstanding playground to tailor and control fast optical and electronic processes at the nanoscale, such as ultrafast optical switching, single photon emission and strong coupling interactions to tailor photochemical reactions. Here, we provide an overview of the field, and describe the methodologies to monitor and control nanoscale phenomena with plasmons at ultrafast timescales in terms of both modeling and experimental characterization. Various directions are showcased, among others recent advances in ultrafast plasmon-driven chemistry and multi-functional plasmonics, in which charge, spin, and lattice degrees of freedom are exploited to provide active control of the optical and electronic properties of nanoscale materials. As the focus shifts to the development of practical devices, such as all-optical transistors, we also emphasize new materials and applications in ultrafast plasmonics and highlight recent development in the relativistic realm. The latter is a promising research field with potential applications in fusion research or particle and light sources providing properties such as attosecond duration.
BIONETS architecture: from networks to SerWorks De Pellegrini, F.; Miorandi, D.; Linner, D. ...
2007 2nd Bio-Inspired Models of Network, Information and Computing Systems,
2007-Dec.
Conference Proceeding
This paper presents the networking framework as conceived within the European project BIONETS. The case for such a framework comes from the idea of a ldquoDisappearing Networkrdquo paradigm. In the ...disappearing network, the network ceases to exist as an independent entity and becomes an appendix of the distributed services running on user devices. The overall BIONETS system exploits the presence of embedded devices to provide context-awareness and leverages peer-to-peer interactions among mobile devices in order to ensure system-wide dissemination of data and services. Some of the current networking solutions developed within the project are also presented, highlighting the use of bio-inspired techniques and tools. The paper presents then a first version of the SerWorks architecture, which takes a unifying view on networks and services. In SerWorks, the network becomes a set of particular services, aimed at general connectivity purposes, which can be created and modified at runtime in order to accommodate for specific system conditions and higher-level constraints.
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