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Sökning: WFRF:(Gustafsson Ulf)

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1.
  • Björklund, Elisabet, et al. (författare)
  • Film och historia : exemplet Erik Hedling
  • 2020
  • Ingår i: Historiska fiktioner : En antologi om film, tv och historia - En antologi om film, tv och historia. - 9789189063310 ; , s. 9-23
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Artikel om relationen mellan film och historia med betoning på den forskning som Erik Hedling, professor i filmvetenskap vid Lunds universitet, har bedrivit.
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2.
  • Abbasi, Saeed (författare)
  • Characterisation of airborne particles from rail traffic
  • 2011
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Since the investigation of wear particles in rail transport started in late-1910s, the high mass concentration of these particles has raised worries among researchers concerned with air quality. However, effective action has yet to be taken because of lack of relevant knowledge. This thesis provides applicable information for the airborne wear particles in rail transport. Some aspects of their characteristics such as diameter size, mass concentration, number concentration, and morphology of particles were investigated in field tests and laboratory tests.The effects on particle characterisations from different operational conditions in the field tests, and applying different braking materials, conducting tests in different applied loads or sliding velocities in the laboratory tests were studied. The main advantage of conducting laboratory tests was to focus on studying particles from one source. The possibility of repetition, using high sensitive instruments and conducting tests at low costs are the other advantages of laboratory studies. Paper A describes how a pin-on-disc machine was used to reproduce similar real operational conditions during mechanical braking in a train. The results were validated by comparing the field tests results with the laboratory studies. The particles morphology and size distribution were also studied.Paper B presents a summary of field tests results. The effects of curve negotiating and applying braking in different real conditions were investigated with an on-board measurement.The element composition of the particles and their potential sources were also investigated outside of the particles morphologies.Paper C presents comprehensive results from laboratory studies on airborne particles from different braking materials. The differences in the particle characteristics in similar test conditions were attributable to different material compositions and dominant wear mechanisms. A new index was introduced in this paper and is suggested to be used as a qualitative factor with regard to the airborne wear particle emission rate.Paper D is a review of the recent studies of exhaust emission and non-exhaust emission from rail vehicles. A summary of results, measurements, adverse health effects, and proposed or applied solutions are reviewed in this paper.
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3.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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4.
  • Bonagas, Nadilly, et al. (författare)
  • Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
  • 2022
  • Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
  • Tidskriftsartikel (refereegranskat)abstract
    • The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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5.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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6.
  • Folkersen, Lasse, et al. (författare)
  • Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease
  • 2017
  • Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.
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7.
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8.
  • Gustafsson, Mats, et al. (författare)
  • Effekter av vinterdäck : en kunskapsöversikt
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Choice of winter tyres has, from mainly being a matter of safety and economic costs for wearing of road pavements, during later years also become a matter of inhalable particles formed during pavement wear from studded tyres and their negative effects on public health. Further, the tyres' effects on environment and noise have been illustrated in several studies. The issue is also complicated by the fact that tyre choice effects on traffic safety have several components, including such diverging parameters as friction and behaviour. Finally all aspects have to be evaluated from a socioeconomic point of view for society to be able to decide which kind of distribution of tyre types that is the most profitable. This report is a summary of current knowledge in this complex research field.
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9.
  • Gustafsson, Nils, et al. (författare)
  • Associations among Periodontitis, Calcified Carotid Artery Atheromas, and Risk of Myocardial Infarction
  • 2020
  • Ingår i: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 99:1, s. 60-68
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular disease is a common cause of morbidity and premature mortality. Cardiovascular disease can be prevented when risk factors are identified early. Calcified carotid artery atheromas (CCAAs), detected in panoramic radiographs, and periodontitis have both been associated with increased risk of cardiovascular disease. This case-control study aimed to 1) investigate associations between periodontitis and CCAA detected in panoramic radiographs and 2) determine the risk of future myocardial infarctions due to CCAA combined with periodontitis. We evaluated 1,482 participants (738 cases and 744 controls) with periodontitis and CCAAs recruited from the PAROKRANK study (Periodontitis and Its Relation to Coronary Artery Disease). Participants were examined with panoramic radiographs, including the carotid regions. Associations between myocardial infarction and periodontitis combined with CCAA were evaluated in 696 cases and 696 age-, sex-, and residential area-matched controls. Periodontitis was evaluated radiographically (as degree of bone loss) and with a clinical periodontal disease index score (from clinical and radiographic assessments). We found associations between CCAA and clinical periodontal disease index score among cases (odds ratio [OR], 1.51; 95% CI, 1.09 to 2.10; P = 0.02) and controls (OR, 1.70; 95% CI, 1.22 to 2.38; P < 0.01), although not between CCAA and the degree of bone loss. In a multivariable model, myocardial infarction was associated with CCAA combined with periodontitis, as assessed by degree of bone loss (OR, 1.75; 95% CI, 1.11 to 2.74; P = 0.01). When the cohort was stratified by sex, only men showed a significant association between myocardial infarction and CCAA combined with periodontitis. Participants with clinically diagnosed periodontitis exhibited CCAA in panoramic radiographs more often than those without periodontitis, irrespective of the presence of a recent myocardial infarction. Participants with combined periodontitis and CCAA had a higher risk of having had myocardial infarction as compared with participants with either condition alone. These findings implied that patients in dental care might benefit from dentists assessing panoramic radiographs for CCAA-particularly, patients with periodontitis who have not received any preventive measures for cardiovascular disease.
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10.
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