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Sökning: WFRF:(Passarella D)

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2.
  • van Rheenen, W, et al. (författare)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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3.
  • Adamczak, Desiree, et al. (författare)
  • Influence of synthetic pathway, molecular weight and side chains on properties of indacenodithiophene-benzothiadiazole copolymers made by direct arylation polycondensation
  • 2021
  • Ingår i: Journal of Materials Chemistry C. - : Royal Society of Chemistry (RSC). - 2050-7534 .- 2050-7526. ; 9:13, s. 4597-4606
  • Tidskriftsartikel (refereegranskat)abstract
    • Atom-economic protocols for the synthesis of poly(indacenodithiophene-alt-benzothiadiazole) (PIDTBT) are presented in which all C-C coupling steps are achieved by direct arylation. Using two different synthetic pathways, PIDTBT copolymers with different side chains (hexylphenyl, octylphenyl, dodecyl, methyl/2-octyldodecylphenyl, 2-octyldodecylphenyl/2-octyldodecylphenyl) and molecular weight (MW) are prepared. Route A makes use of direct arylation polycondensation (DAP) of indacenodithiophene (IDT) and 4,7-dibromo-2,1,3-benzothiadiazole (BTBr2) leading to PIDTBT in high yields, with adjustable MW and without indications for structural defects. Route B starts from a polyketone precursor also prepared by DAP following cyclization. While route B allows introduction of asymmetric side chains at the IDT unit, polymer analogous cyclization gives rise to defect formation. The absorption coefficient of PIDTBT with alkylphenyl side chains made by route A increases with MW. Field-effect hole mobilities around similar to 10(-2) cm(2) V-1 s(-1) are molecular weight-independent, which is ascribed to a largely amorphous thin film morphology. PIDTBT with linear dodecyl side (C12) chains exhibits a bathochromic shift (20 nm), in agreement with theory, and more pronounced vibronic contributions to absorption spectra. In comparison to alkylphenyl side chains, C12 side chains allow for increased order in thin films, a weak melting endotherm and lower energetic disorder, which altogether explain substantially higher field-effect hole mobilities of similar to 10(-1) cm(2) V-1 s(-1).
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4.
  • Danieli, B, et al. (författare)
  • Synthesis and biological evaluation of paclitaxel-thiocoichicine hybrids
  • 2004
  • Ingår i: Chemistry and Biodiversity. - : Wiley. - 1612-1872 .- 1612-1880. ; 1:2, s. 327-345
  • Tidskriftsartikel (refereegranskat)abstract
    • The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was surprisingly devoid of tubulin activity, acting on a distinct and yet to identify molecular target.
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5.
  • Lagerspetz, E., et al. (författare)
  • Pervasive Communities in the Internet of People
  • 2018
  • Ingår i: 2018 IEEE International Conference on Pervasive Computing and Communications Workshops, PerCom Workshops 2018. - : Institute of Electrical and Electronics Engineers Inc.. - 9781538632277 ; , s. 40-45
  • Konferensbidrag (refereegranskat)abstract
    • The Internet has traditionally been a device-oriented architecture where devices with IP addresses are first-class citizens, able to serve and consume content or services, and their owners take part in the interaction only through those devices. The Internet of People (IoP) is a recent paradigm where devices become proxies of their users, and can act on their behalf. To realize IoP, new policies and rules for how devices can take actions are required. The role of context information grows as devices act autonomously based on the environment and existing social relationships between their owners. In addition, the social profiles of device owners determine e.g. how altruistic or resourceconserving they are in collaborative computing scenarios. In this paper we focus on community formation in IoP, a prerequisite for enabling collaborative scenarios, and discuss main challenges and propose potential solutions. © 2018 IEEE.
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