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  • Hedenqvist, Mikael, et al. (författare)
  • Extrusion of protein plastics
  • 2017
  • Ingår i: Abstracts of Papers of the American Chemical Society. - : American Chemical Society (ACS). - 0065-7727. ; 253
  • Tidskriftsartikel (övrigt vetenskapligt)
  • Huang, Joyce Y., et al. (författare)
  • Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)
  • 2020
  • Ingår i: ; 146:9, s. 2394-2405
  • Tidskriftsartikel (refereegranskat)abstract
    • Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all p(trend) < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.
  • Johansson, Ann-Sofi, et al. (författare)
  • Cytotoxicity of Superoxide Dismutase 1 in Cultured Cells Is Linked to Zn2+ Chelation
  • 2012
  • Ingår i: PLoS ONE. - 1932-6203 .- 1932-6203. ; 7:4, s. e36104-
  • Tidskriftsartikel (refereegranskat)abstract
    • Neurodegeneration in protein-misfolding disease is generally assigned to toxic function of small, soluble protein aggregates. Largely, these assignments are based on observations of cultured neural cells where the suspect protein material is titrated directly into the growth medium. In the present study, we use this approach to shed light on the cytotoxic action of the metalloenzyme Cu/Zn superoxide dismutase 1 (SOD1), associated with misfolding and aggregation in amyotrophic lateral sclerosis (ALS). The results show, somewhat unexpectedly, that the toxic species of SOD1 in this type of experimental setting is not an aggregate, as typically observed for proteins implicated in other neuro-degenerative diseases, but the folded and fully soluble apo protein. Moreover, we demonstrate that the toxic action of apoSOD1 relies on the protein's ability to chelate Zn2+ ions from the growth medium. The decreased cell viability that accompanies this extraction is presumably based on disturbed Zn2+ homeostasis. Consistently, mutations that cause global unfolding of the apoSOD1 molecule or otherwise reduce its Zn2+ affinity abolish completely the cytotoxic response. So does the addition of surplus Zn2+. Taken together, these observations point at a case where the toxic response of cultured cells might not be related to human pathology but stems from the intrinsic limitations of a simplified cell model. There are several ways proteins can kill cultured neural cells but all of these need not to be relevant for neurodegenerative disease.
  • Johansson, Björn, et al. (författare)
  • Distributed Model Predictive Consensus
  • 2006
  • Ingår i: Proceedings of the 17th International Symposium on Mathematical Theory of Networks and Systems. ; , s. 2438-2444
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we consider the problem of designing a distributed control strategy such that a linear combination of the states of a number of vehicles coincide at a given time. The vehicles are described by linear difference equations and are subject to convex input constraints. It is demonstrated how primal decomposition techniques and incremental subgradient methods allow us to find a solution in which each vehicle performs individual planning of its trajectory and exchanges critical information with neighbors only. We explore various communication, computation, and control structures, and demonstrate the performance of the algorithms by numerical examples.
  • Johansson, Björn, et al. (författare)
  • On decentralized negotiation of optimal consensus
  • 2008
  • Ingår i: Automatica. - 0005-1098 .- 1873-2836. ; 44:4, s. 1175-1179
  • Tidskriftsartikel (refereegranskat)abstract
    • A consensus problem consists of finding a distributed control strategy that brings the state or output of a group of agents to a common value, a consensus point. In this paper, we propose a negotiation algorithm that computes an optimal consensus point for agents modeled as linear control systems subject to convex input constraints and linear state constraints. By primal decomposition and incremental subgradient methods, it is shown that the algorithm can be implemented such that each agent exchanges only a small amount of information per iteration with its neighbors.
  • Johansson, Björn, et al. (författare)
  • Subgradient methods and consensus algorithms for solving convex optimization problems
  • 2008
  • Ingår i: Decision and Control, 2008. CDC 2008. 47th IEEE Conference on. - : IEEE. - 9781424431236 ; , s. 4185-4190
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we propose a subgradient method for solving coupled optimization problems in a distributed way given restrictions on the communication topology. The iterative procedure maintains local variables at each node and relies on local subgradient updates in combination with a consensus process. The local subgradient steps are applied simultaneously as opposed to the standard sequential or cyclic procedure. We study convergence properties of the proposed scheme using results from consensus theory and approximate subgradient methods. The framework is illustrated on an optimal distributed finite-time rendezvous problem.
  • Kachuri, Linda, et al. (författare)
  • Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
  • 2016
  • Ingår i: Carcinogenesis. - 0143-3334 .- 1460-2180. ; 37:1, s. 96-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000x) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73x10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64x10(-6)), rs112290073 (OR = 1.85, P = 1.27x10(-5)), rs138895564 (OR = 2.16, P = 2.06x10(-5); among young cases, OR = 3.77, P = 8.41x10(-4)). In addition, we found that rs139852726 (P = 1.44x10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84x10(-7)) and lung cancer (P = 2.37x10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
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