| 1. |
- Abelev, Betty, et al.
(författare)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
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Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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| 2. |
- Abelev, Betty, et al.
(författare)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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| 3. |
- Abelev, Betty, et al.
(författare)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
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Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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| 4. |
- Cederholm, Jan, et al.
(författare)
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Blood pressure and risk of cardiovascular diseases in type 2 diabetes : further findings from the Swedish National Diabetes Register (NDR-BP II)
- 2012
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 30:10, s. 2020-2030
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Estimate risks of coronary heart disease (CHD), stroke and cardiovascular disease (CVD) with updated mean systolic (SBP) and diastolic (DBP) blood pressure in an observational study of patients with type 2 diabetes. Methods: Thirty-five thousand and forty-one patients treated with antihypertensive drugs, and 18 512 untreated patients, aged 30-75 years, without previous heart failure, followed for 6 years until 2009. Results: In treated patients, nonlinear splines for 6-year risk of fatal/nonfatal CHD, stroke and CVD by BP as a continuous variable showed a progressive increase with higher SBP from 140 mmHg and higher, and with DBP from 80 mmHg, with a J-shaped risk curve at lowest SBP levels, but not obviously at lowest DBP levels. Analysing intervals of SBP with 130-134 mmHg as reference at Cox regression, adjusted hazard ratios (HR) for fatal/nonfatal CHD, stroke and CVD with at least 140 mmHg were 1.22 [95% confidence interval (CI): 1.08-1.39], 1,43 (1.18-1.72), 1.26 (1.13-1.41), all P<0.001. HR with 115-129 and 135-139 mmHg were nonsignificant, whereas increased with 100-114 mmHg, 1.96 (P<0.001), 1.75 (P=0.02), 2.08 (P < 0.001), respectively. With DBP 75-79 mmHg as reference, adjusted HR for fatal/nonfatal CHD, stroke and CVD with DBP 80-84 mmHg were 1.42 (1.26-1.59), 1.46 (1.24-1.72), 1.39 (1.26-1.53), all P< 0.001. Corresponding HR with DBP at least 85 mmHg were 1.70 (1.50-1.92), 2.35 (1.99-2.77), 1..87 (1.69-2.07), all P < 0.001. Corresponding HR with DBP 60-69 and 70-74 mmHg were nonsignificant. The picture was similar in 7059 patients with previous CVD and in untreated patients. Conclusion: BP around 130-135/75-79 mmHg showed lower risks of cardiovascular diseases in patients with type 2 diabetes.
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| 5. |
- de Jong, Sarah, et al.
(författare)
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Effect of rare coding variants in the CFI gene on Factor I expression levels
- 2020
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 29:14, s. 2313-2324
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Tidskriftsartikel (refereegranskat)abstract
- Factor I (FI) is one of the main inhibitors of complement activity, and numerous rare coding variants have been reported in patients with age-related macular degeneration, atypical hemolytic uremic syndrome and C3 glomerulopathy. Since many of these variants are of unknown clinical significance, this study aimed to determine the effect of rare coding variants in the complement factor I (CFI) gene on FI expression. We measured FI levels in plasma samples of carriers of rare coding variants and in vitro in the supernatants of epithelial cells expressing recombinant FI. FI levels were measured in 177 plasma samples of 155 individuals, carrying 24 different rare coding variants in CFI. In carriers of the variants p.Gly119Arg, p.Leu131Arg, p.Gly188Ala and c.772G>A (r.685_773del), significantly reduced FI plasma levels were detected. Furthermore, recombinant FI expression levels were determined for 126 rare coding variants. Of these variants 68 (54%) resulted in significantly reduced FI expression in supernatant compared to wildtype (WT). The recombinant protein expression levels correlated significantly with the FI level in plasma of carriers of CFI variants. In this study, we performed the most comprehensive FI expression level analysis of rare coding variants in CFI to date. More than half of CFI variants lead to reduced FI expression, which might impair complement regulation in vivo. Our study will aid the interpretation of rare coding CFI variants identified in clinical practice, which is in particular important in light of patient inclusion in ongoing clinical trials for CFI gene supplementation in AMD.
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| 6. |
- de Jong, Sarah, et al.
(författare)
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Functional Analysis of Variants in Complement Factor I Identified in Age-Related Macular Degeneration and Atypical Hemolytic Uremic Syndrome
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Complement factor I (FI) is a central inhibitor of the complement system, and impaired FI function increases complement activation, contributing to diseases such as age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (aHUS). Genetic variation in complement factor I (CFI) has been identified in both AMD and aHUS, with more than half of these variants leading to reduced FI secretion levels. For many of the variants with normal FI secretion, however, functional implications are not yet known. Here we studied 11 rare missense variants, with FI secretion levels comparable to wildtype, but a predicted damaging effects based on the Combined Annotation Dependent Depletion (CADD) score. Three variants (p.Pro50Ala, p.Arg339Gln, and p.Ser570Thr) were analyzed in plasma and serum samples of carriers affected by AMD. All 11 variants (nine for the first time in this study) were recombinantly expressed and the ability to degrade C3b was studied with the C3b degradation assay. The amount of degradation was determined by measuring the degradation product iC3b with ELISA. Eight of 11 (73%) mutant proteins (p.Pro50Ala, p.Arg339Gln, p.Ile340Thr, p.Gly342Glu, p.Gly349Arg, p.Arg474Gln, p.Gly487Cys, and p.Gly512Ser) showed significantly impaired C3b degradation, and were therefore classified as likely pathogenic. Our data indicate that genetic variants in CFI with a CADD score >20 are likely to affect FI function, and that monitoring iC3b in a degradation assay is a useful tool to establish the pathogenicity of CFI variants in functional studies.
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| 7. |
- Geerlings, Maartje J., et al.
(författare)
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The functional effect of rare variants in complement genes on C3b degradation in patients with age-related macular degeneration
- 2017
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Ingår i: JAMA Ophthalmology. - : American Medical Association (AMA). - 2168-6165. ; 135:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE In age-related macular degeneration (AMD), rare variants in the complement system have been described, but their functional consequences remain largely unexplored. OBJECTIVES To identify new rare variants in complement genes and determine the functional effect of identified variants on complement levels and complement regulation in serum samples from carriers and noncarriers. DESIGN, SETTING, AND PARTICIPANTS This study evaluated affected (n = 114) and unaffected (n = 60) members of 22 families with AMD and a case-control cohort consisting of 1831 unrelated patients with AMD and 1367 control individuals from the European Genetic Database from March 29, 2006, to April 26, 2013, in Nijmegen, the Netherlands, and Cologne, Germany. Exome sequencing data of families were filtered for rare variants in the complement factor H (CFH), complement factor I (CFI), complement C9 (C9), and complement C3 (C3) genes. The case-control cohort was genotyped with allele-specific assays. Serum samples were obtained from carriers of identified variants (n = 177) and age-matched noncarriers (n = 157). Serum concentrations of factor H (FH), factor I (FI), C9, and C3 were measured, and C3b degradation ability was determined. MAIN OUTCOMES AND MEASURES Association of rare variants in the CFH, CFI, C9, and C3 genes with AMD, serum levels of corresponding proteins, and C3b degradation ability of CFH and CFI variant carriers. RESULTS The 1831 unrelated patients with AMD had a mean (SD) age of 75.0 (9.4) years, and 60.5%were female. The 1367 unrelated control participants had a mean (SD) age of 70.4 (7.0), and 58.7%were female. All individuals were of European descent. Rare variants in CFH, CFI, C9, and C3 contributed to an increased risk of developing AMD (odds ratio, 2.04; 95%CI, 1.47-2.82; P < .001). CFI carriers had decreased median FI serum levels (18.2 μg/mL in Gly119Arg carriers and 16.2 μg/mL in Leu131Arg carriers vs 27.2 and 30.4 μg/mL in noncarrier cases and controls, respectively; both P < .001). Elevated C9 levels were observed in Pro167Ser carriers (10.7 μg/mL vs 6.6 and 6.1 μg/mL in noncarrier cases and controls, respectively; P < .001). The median FH serum levels were 299.4 μg/mL for CFH Arg175Gln and 266.3 μg/mL for CFH Ser193Leu carriers vs 302.4 and 283.0 μg/mL for noncarrier cases and controls, respectively. The median C3 serum levels were 943.2 μg/mL for C3 Arg161Trp and 946.7 μg/mL for C3 Lys155Gln carriers vs 874.0 and 946.7 μg/mL for noncarrier cases and controls, respectively. The FH and FI levels correlated with C3b degradation in noncarriers (R2 = 0.35 and R2 = 0.31, respectively; both P < .001). CONCLUSIONS AND RELEVANCE Reduced serum levels were associated with C3b degradation in carriers of CFI but not CFH variants, suggesting that CFH variants affect functional activity of FH rather than serum levels. Carriers of CFH (Arg175Gln and Ser193Leu) and CFI (Gly119Arg and Leu131Arg) variants have an impaired ability to regulate complement activation and may benefit more from complement-inhibiting therapy than patients with AMD in general.
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| 8. |
- Hall-Wilton, Richard, et al.
(författare)
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Detectors for the European Spallation Source
- 2012
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Ingår i: 2012 IEEE Nuclear Science Symposium and Medical Imaging Conference Record (NSS/MIC). - 1082-3654. ; , s. 4283-4289
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Konferensbidrag (refereegranskat)abstract
- The European Spallation Source (ESS) in Lund, Sweden will become the world's leading neutron source for the study of materials by 2025. First neutrons will be produced in 2019. It will be a long pulse source, with an average beam power of 5 MW delivered to the target station. The pulse length will be 2.86 ms and the repetition rate 14 Hz. The ESS is presently in a design update phase, which ends in February 2013 with a Technical Design Report (TDR). Construction will subsequently start with the goal of bringing the first seven instruments into operation in 2019 at the same time as the source. The full baseline suite of 22 instruments will be brought online by 2025. These instruments present numerous challenges for detector technology in the absence of the availability of Helium-3, which is the default choice for detectors for instruments built until today. Additionally a new generation of source requires a new generation of detector technologies to fully exploit the opportunities that this source provides. This contribution presents briefly the current status of the ESS, and outlines the timeline to completion. The number of instruments and the framework for the decisions on which instruments should be built are shown. For a conjectured full instrument suite, which has been chosen for demonstration purposes for the TDR, a snapshot of the current expected detector requirements is presented. An outline as to how some of these requirements might be tackled is shown. Given that the delivery of the ESS TDR is only a few months away, this contribution reflects strongly the content of the TDR.
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| 9. |
- Jensen, Kim Steen, et al.
(författare)
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FoxO3A promotes metabolic adaptation to hypoxia by antagonizing Myc function
- 2011
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Ingår i: EMBO Journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 30:22, s. 4554-4570
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Tidskriftsartikel (refereegranskat)abstract
- Exposure of metazoan organisms to hypoxia engages a metabolic switch orchestrated by the hypoxia-inducible factor 1 (HIF-1). HIF-1 mediates induction of glycolysis and active repression of mitochondrial respiration that reduces oxygen consumption and inhibits the production of potentially harmful reactive oxygen species (ROS). Here, we show that FoxO3A is activated in hypoxia downstream of HIF-1 and mediates the hypoxic repression of a set of nuclear-encoded mitochondrial genes. FoxO3A is required for hypoxic suppression of mitochondrial mass, oxygen consumption, and ROS production and promotes cell survival in hypoxia. FoxO3A is recruited to the promoters of nuclear-encoded mitochondrial genes where it directly antagonizes c-Myc function via a mechanism that does not require binding to the consensus FoxO recognition element. Furthermore, we show that FoxO3A is activated in human hypoxic tumour tissue in vivo and that FoxO3A shor-thairpin RNA (shRNA)-expressing xenograft tumours are decreased in size and metabolically changed. Our findings define a novel mechanism by which FoxO3A promotes metabolic adaptation and stress resistance in hypoxia. The EMBO Journal (2011) 30, 4554-4570. doi:10.1038/emboj.2011.323; Published online 13 September 2011
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| 10. |
- Jonsson, Stefan, et al.
(författare)
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Identification of sequence variants influencing immunoglobulin levels
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
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