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1.
  • Karlsson, Bengt, et al. (författare)
  • Thyroid dysfunction in Down's syndrome : relation to age and thyroid autoimmunity
  • 1998
  • Ingår i: Archives of Disease in Childhood. - 0003-9888 .- 1468-2044. ; 79:3, s. 242-245
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The prevalence of thyroid disease is increased in Down's syndrome. Most available data come from cross sectional studies. AIMS: To study longitudinally thyroid function in patients with Down's syndrome in Uppsala county (85 patients) up to the age of 25 years. METHODS: Observational study based on yearly follow up in a children's clinic. Thyroid function tests were performed at each visit to the clinic. RESULTS: Hypothyroidism was found in 30 and hyperthyroidism was found in two of the 85 patients. No sex difference was seen. Half of the patients with hypothyroidism acquired the condition before the age of 8 years, but only one of them displayed thyroid autoantibodies at diagnosis. Most patients who developed hypothyroidism after this age had thyroid autoantibodies. In the prepubertal patients with hypothyroidism, growth velocity was lower during the year before the start of thyroxine treatment than during the year after treatment began; it was also lower than that of sex and age matched euthyroidic children with Down's syndrome. CONCLUSION: Thyroid dysfunction in patients with Down's syndrome is common in childhood. Consequently, annual screening is important. Autoimmune thyroid disease is uncommon in young children with Down's syndrome but is common after 8 years of age.
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2.
  • Pulit, S. L., et al. (författare)
  • Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
  • 2018
  • Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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3.
  • Singh, B. P., et al. (författare)
  • Experimental access to Transition Distribution Amplitudes with the PANDA experiment at FAIR
  • 2015
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 51:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Baryon-to-meson Transition Distribution Amplitudes (TDAs) encoding valuable new information on hadron structure appear as building blocks in the collinear factorized description for several types of hard exclusive reactions. In this paper, we address the possibility of accessing nucleon-to-pion (pi N) TDAs from (p) over barp -> e(+)e(-)pi(0) reaction with the future PANDA detector at the FAIR facility. At high center-of-mass energy and high invariant mass squared of the lepton pair q(2), the amplitude of the signal channel (p) over barp -> e(+)e(-)pi(0) admits a QCD factorized description in terms of pi N TDAs and nucleon Distribution Amplitudes (DAs) in the forward aid backward kinematic regimes. Assuming the validity of this factorized description, we perform feasibility studies for measuring (p) over barp -> e(+)e(-)pi(0) with the PANDA detector. Detailed simulations on signal reconstruction efficiency as well as on rejection of the most severe background channel, i.e. (p) over barp -> pi(+)pi(-)pi(0) were performed for the center-of-mass energy squared s = 5 GeV2 and s = 10 GeV2, in the kinematic regions 3.0 < q(2) < 4.3 GeV2 and 5 < q(2) < 9 GeV2, respectively, with a neutral pion scattered in the forward or backward cone vertical bar cos theta(pi 0)vertical bar > 0.5 in the proton-antiproton center-of-mass frame. Results of the simulation show that the particle identification capabilities of the PANDA detector will allow to achieve a background rejection factor of 5 . 10(7) (1 . 10(7)) at low (high) q(2) for s = 5 GeV2, and of 1 . 10(8) (6 . 10(6)) at low (high) q(2) for s = 10 GeV2, while keeping the signal reconstruction efficiency at around 40%. At both energies, a clean lepton signal can be reconstructed with the expected statistics corresponding to 2 of integrated luminosity. The cross sections obtained from the simulations are used to show that a test of QCD collinear factorization can be done at the lowest order by measuring scaling laws and angular distributions. The future measurement of the signal channel cross section with PANDA will provide a new test of the perturbative QCD description of a novel class of hard exclusive reactions and will open the possibility of experimentally accessing pi N TDAs.
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4.
  • Strakova, A., et al. (författare)
  • Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for 'selfish' traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby 'selfish' positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells.
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5.
  • 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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6.
  • Aamodt, K., et al. (författare)
  • Alignment of the ALICE Inner Tracking System with cosmic-ray tracks
  • 2010
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 5
  • Konferensbidrag (refereegranskat)abstract
    • ALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 mu m in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10(5) charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.
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7.
  • Aamodt, K., et al. (författare)
  • Charged-particle multiplicity measurement in proton-proton collisions at root s=0.9 and 2.36 TeV with ALICE at LHC
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:1-2, s. 89-108
  • Tidskriftsartikel (refereegranskat)abstract
    • Charged-particle production was studied in proton-proton collisions collected at the LHC with the ALICE detector at centre-of-mass energies 0.9 TeV and 2.36 TeV in the pseudorapidity range vertical bar eta vertical bar < 1.4. In the central region (vertical bar eta vertical bar < 0.5), at 0.9 TeV, we measure charged-particle pseudo-rapidity density dN(ch)/d eta = 3.02 +/- 0.01(stat.)(-0.05)(+0.08)(syst.) for inelastic interactions, and dN(ch)/d eta = 3.58 +/- 0.01 (stat.)(-0.12)(+0.12)(syst.) for non-single-diffractive interactions. At 2.36 TeV, we find dN(ch)/d eta = 3.77 +/- 0.01(stat.)(-0.12)(+0.25)(syst.) for inelastic, and dN(ch)/d eta = 4.43 +/- 0.01(stat.)(-0.12)(+0.17)(syst.) for non-single-diffractive collisions. The relative increase in charged-particle multiplicity from the lower to higher energy is 24.7% +/- 0.5%(stat.)(-2.8)(+5.7)%(syst.) for inelastic and 23.7% +/- 0.5%(stat.)(-1.1)(+4.6)%(syst.) for non-single-diffractive interactions. This increase is consistent with that reported by the CMS collaboration for non-single-diffractive events and larger than that found by a number of commonly used models. The multiplicity distribution was measured in different pseudorapidity intervals and studied in terms of KNO variables at both energies. The results are compared to proton-antiproton data and to model predictions.
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8.
  • Aamodt, K., et al. (författare)
  • Charged-particle multiplicity measurement in proton-proton collisions at root s=7 TeV with ALICE at LHC
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 68:3-4, s. 345-354
  • Tidskriftsartikel (refereegranskat)abstract
    • The pseudorapidity density and multiplicity distribution of charged particles produced in proton-proton collisions at the LHC, at a centre-of-mass energy root s = 7 TeV, were measured in the central pseudorapidity region vertical bar eta vertical bar < 1. Comparisons are made with previous measurements at root s = 0.9 TeV and 2.36 TeV. At root s = 7 TeV, for events with at least one charged particle in |eta vertical bar| < 1, we obtain dN(ch)/d eta = 6.01 +/- 0.01(stat.)(-0.12)(+0.20) (syst.). This corresponds to an increase of 57.6%+/-0.4%(stat.)(-1.8%)(+3.6) (syst.) relative to collisions at 0.9 TeV, significantly higher than calculations from commonly used models. The multiplicity distribution at 7 TeV is described fairly well by the negative binomial distribution.
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9.
  • Aamodt, K., et al. (författare)
  • First proton-proton collisions at the LHC as observed with the ALICE detector: measurement of the charged-particle pseudorapidity density at root s=900 GeV
  • 2010
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 65:1-2, s. 111-125
  • Tidskriftsartikel (refereegranskat)abstract
    • On 23rd November 2009, during the early commissioning of the CERN Large Hadron Collider (LHC), two counter-rotating proton bunches were circulated for the first time concurrently in the machine, at the LHC injection energy of 450 GeV per beam. Although the proton intensity was very low, with only one pilot bunch per beam, and no systematic attempt was made to optimize the collision optics, all LHC experiments reported a number of collision candidates. In the ALICE experiment, the collision region was centred very well in both the longitudinal and transverse directions and 284 events were recorded in coincidence with the two passing proton bunches. The events were immediately reconstructed and analyzed both online and offline. We have used these events to measure the pseudorapidity density of charged primary particles in the central region. In the range vertical bar eta vertical bar < 0.5, we obtain dN(ch)/d eta = 3.10 +/- 0.13(stat.) +/- 0.22(syst.) for all inelastic interactions, and dN(ch)/d eta = 3.51 +/- 0.15(stat.) +/- 0.25(syst.) for nonsingle diffractive interactions. These results are consistent with previous measurements in proton-antiproton interactions at the same centre-of-mass energy at the CERN Sp<(p)over bar>S collider. They also illustrate the excellent functioning and rapid progress of the LHC accelerator, and of both the hardware and software of the ALICE experiment, in this early start-up phase.
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10.
  • Aamodt, K., et al. (författare)
  • Midrapidity Antiproton-to-Proton Ratio in pp Collisons root s=0.9 and 7 TeV Measured by the ALICE Experiment
  • 2010
  • Ingår i: Physical Review Letters. - 1079-7114. ; 105:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The ratio of the yields of antiprotons to protons in pp collisions has been measured by the ALICE experiment at root s = 0.9 and 7 TeV during the initial running periods of the Large Hadron Collider. The measurement covers the transverse momentum interval 0.45 < p(t) < 1.05 GeV/c and rapidity vertical bar y vertical bar < 0.5. The ratio is measured to be R-vertical bar y vertical bar<0.5 = 0.957 +/- 0.006(stat) +/- 0.0014(syst) at 0.9 Tev and R-vertical bar y vertical bar<0.5 = 0.991 +/- 0.005 +/- 0.014(syst) at 7 TeV and it is independent of both rapidity and transverse momentum. The results are consistent with the conventional model of baryon-number transport and set stringent limits on any additional contributions to baryon-number transfer over very large rapidity intervals in pp collisions.
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11.
  • Aamodt, K., et al. (författare)
  • Production of pions, kaons and protons in pp collisions at root s=900 GeV with ALICE at the LHC
  • 2011
  • Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 71:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The production of pi(+), pi(-), K+, K-, p, and (p) over bar at mid-rapidity has been measured in proton-proton collisions at root s = 900 GeV with the ALICE detector. Particle identification is performed using the specific energy loss in the inner tracking silicon detector and the time projection chamber. In addition, time-of-flight information is used to identify hadrons at higher momenta. Finally, the distinctive kink topology of the weak decay of charged kaons is used for an alternative measurement of the kaon transverse momentum (p(t)) spectra. Since these various particle identification tools give the best separation capabilities over different momentum ranges, the results are combined to extract spectra from p(t) = 100 MeV/c to 2.5 GeV/c. The measured spectra are further compared with QCD-inspired models which yield a poor description. The total yields and the mean pt are compared with previous measurements, and the trends as a function of collision energy are discussed.
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12.
  • Aamodt, K., et al. (författare)
  • Transverse momentum spectra of charged particles in proton-proton collisions at root s=900 GeV with ALICE at the LHC
  • 2010
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 693:2, s. 53-68
  • Tidskriftsartikel (refereegranskat)abstract
    • The inclusive charged particle transverse momentum distribution is measured in proton-proton collisions at root s = 900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (vertical bar eta vertical bar < 0.8) over the transverse momentum range 0.15 < p(T) < 10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for vertical bar eta vertical bar < 0.8 is < p(T)>(INEL) = 0.483 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c and < p(T)>(NSD) = 0.489 +/- 0.001 (stat.) +/- 0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger < p(T)> than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET. (C) 2010 Published by Elsevier B.V.
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13.
  • Aamodt, K., et al. (författare)
  • Two-pion Bose-Einstein correlations in pp collisions at root s=900 GeV
  • 2010
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 82:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the measurement of two-pion correlation functions from pp collisions at root s = 900 GeV performed by the ALICE experiment at the Large Hadron Collider. Our analysis shows an increase of the Hanbury Brown-Twiss radius with increasing event multiplicity, in line with other measurements done in particle- and nuclear collisions. Conversely, the strong decrease of the radius with increasing transverse momentum, as observed at the Relativistic Heavy Ion Collider and at Tevatron, is not manifest in our data.
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14.
  • Ala-Laurinaho, J., et al. (författare)
  • TUMESA - MEMS tuneable metamaterials for smart wireless applications
  • 2012
  • Ingår i: European Microwave Week 2012: "Space for Microwaves", EuMW 2012, Conference Proceedings - 7th European Microwave Integrated Circuits Conference, EuMIC 2012. - : IEEE. - 9782874870286 ; , s. 95-98
  • Konferensbidrag (refereegranskat)abstract
    • This paper describes the main results of the EU FP7 project TUMESA - MEMS tuneable metamaterials for smart wireless applications. In this project, we studied several reconfigurable antenna approaches that combine the new technology of MEMS with the new concept of artificial electromagnetic materials and surfaces (metamaterials and metasurfaces) for realisation of millimetre wave phase shifters and beam-steering devices. MEMS technology allows to miniaturise electronic components, reduce their cost in batch production, and effectively compete with semiconductor and ferroelectric based technologies in terms of losses at millimetre wavelengths. Novel tuneable materials and components proposed in this project perform as smart beam steering devices. Fabricated with MEMS technology in batch and on a single chip, proposed tuneable devices allow substituting of larger and more complex sub-system of, e.g., a radar sensor. This substitution provides a dramatic cost reduction on a system level.
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15.
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16.
  • Collaboration, The PANDA, et al. (författare)
  • Feasibility studies of time-like proton electromagnetic form factors at PANDA at FAIR
  • 2016
  • Ingår i: European Physical Journal A. - : Springer Publishing Company. - 1434-6001 .- 1434-601X. ; 52:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Simulation results for future measurements of electromagnetic proton form factors at P ¯ ANDA (FAIR) within the PandaRoot software framework are reported. The statistical precision with which the proton form factors can be determined is estimated. The signal channel p¯ p→ e+e- is studied on the basis of two different but consistent procedures. The suppression of the main background channel, i.e.p¯ p→ π+π-, is studied. Furthermore, the background versus signal efficiency, statistical and systematical uncertainties on the extracted proton form factors are evaluated using two different procedures. The results are consistent with those of a previous simulation study using an older, simplified framework. However, a slightly better precision is achieved in the PandaRoot study in a large range of momentum transfer, assuming the nominal beam conditions and detector performance.
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17.
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18.
  • Edelstam, Greta, et al. (författare)
  • New reference values for routine blood samples and human neutrophilic lipocalin during third-trimester pregnancy
  • 2001
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 61:8, s. 583-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.
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19.
  • Edwards, John S. A., et al. (författare)
  • Preface
  • 2003
  • Ingår i: Culinary arts and sciences IV. - Bournemouth : Worshipful Company of Cooks Research Centre at Bournemouth University, UK. - 1858991390 ; , s. i-i
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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20.
  • Edwards, John S. A., et al. (författare)
  • The Five Aspects Meal Model
  • 2008
  • Ingår i: Journal of Foodservice. - Oxford : Wiley-Blackwell. - 1748-0140. ; 19:1, s. 4-12
  • Forskningsöversikt (refereegranskat)abstract
    • Eating and eating out involve a number of additional factors over and above the consumption of food. This paper briefly reviews the research undertaken on these factors, and identifies models to categorise and describe them. In particular, it presents and justifies the Five Aspects Meal Model (FAMM), which forms the basic structure for teaching at the Department of Restaurant and Culinary Art at Örebro University. This also formed the theoretical framework for the First International PhD Conference held at Örebro University in June 2007.
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21.
  • Edwards, John S.A., et al. (författare)
  • The room and atmosphere as aspects of the meal : a review
  • 2008
  • Ingår i: Journal of foodservice. - Oxford : Blackwell Publishing. - 1748-0140. ; 19:1, s. 22-34
  • Forskningsöversikt (refereegranskat)abstract
    • The consumption of food takes place within what can loosely be termed ‘the room’, although in reality, this could be a variety of settings, both indoors and outside. Aspects and features within that room contribute towards and make up the atmosphere, something that is relatively easy to appreciate but rather more difficult to quantify and describe. This review considers selected aspects under the headings of interior variables, background music and noise,and odour; layout and design variables, table layout and seating; and human variables, density and crowding, and social facilitation, which contribute towards the room's atmosphere. It is important to recognise and appreciate that other attributes, of similar if not equal or more importance, also exist.
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22.
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23.
  • Erni, W., et al. (författare)
  • Technical design report for the PANDA (AntiProton Annihilations at Darmstadt) Straw Tube Tracker
  • 2013
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 49:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This document describes the technical layout and the expected performance of the Straw Tube Tracker (STT), the main tracking detector of the PANDA target spectrometer. The STT encloses a Micro-Vertex-Detector (MVD) for the inner tracking and is followed in beam direction by a set of GEM stations. The tasks of the STT are the measurement of the particle momentum from the reconstructed trajectory and the measurement of the specific energy loss for a particle identification. Dedicated simulations with full analysis studies of certain proton-antiproton reactions, identified as being benchmark tests for the whole PANDA scientific program, have been performed to test the STT layout and performance. The results are presented, and the time lines to construct the STT are described.
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24.
  • Fakhardji, Wissam, et al. (författare)
  • Collision-induced absorption in Ar–Kr gas mixtures : A molecular dynamics study with new potential and dipole data
  • 2019
  • Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 151:14
  • Tidskriftsartikel (refereegranskat)abstract
    • We have implemented a scheme for classical molecular dynamics simulations of collision-induced absorption. The program has been applied to a gas mixture of argon (Ar) and krypton (Kr). The simulations are compared with accurate quantum dynamical calculations. The comparisons of the absorption coefficients show that classical molecular dynamics is correct within 10% for photon wave numbers up to 220 cm−1 at a temperature of 200 K for this system. At higher temperatures, the agreement is even better. Molecular dynamics accounts for many-body interactions, which, for example, give rise to continuous dimer formation and destruction in the gas. In this way, the method has an advantage compared with bimolecular classical (trajectory) treatments. The calculations are carried out with a new empirical Ar–Kr pair potential. This has been obtained through extensive analysis of experimental thermophysical and transport properties. We also present a new high level ab initio Ar–Kr potential curve for comparison, as well as ab initio interaction-induced dipole curves computed with different methods. In addition, the Ar–Kr polarizability and hyperpolarizability are reported. A comparison of the computed absorption spectra with an experiment taken at 300 K shows satisfactory agreement although a difference in absolute magnitude of 10%–15% persists. This discrepancy we attribute mainly to experimental uncertainty.
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25.
  • Fakhardji, Wissam, et al. (författare)
  • Contribution from dimers to the collision-induced absorption spectra in an Ar–Kr gas mixture
  • 2019
  • Ingår i: 24th International Conference on Spectral Lines Shapes 17-22 June 2018, Dublin, Ireland. - : Institute of Physics (IOP).
  • Konferensbidrag (refereegranskat)abstract
    • We have developed an empirical Barker, Fisher and Watts (BFW) interatomic potential for the Ar–Kr pair along with a dipole moment computed from first principles using Møller–Plesset perturbation theory to second order (MP2). Using these results, we performed molecular dynamics calculations to compute the Ar–Kr collision induced absorption (CIA) spectrum at different temperatures. By comparing them to other calculations using a two body interaction treated with quantum mechanics, we have shown that the difference is due to the dimer's contribution which grows in importance as the temperature is lowered.
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26.
  • Fakhardji, Wissam, et al. (författare)
  • Molecular dynamics calculations of collision-induced absorption in a gas mixture of neon and krypton
  • 2020
  • Ingår i: Journal of Chemical Physics. - : American Institute of Physics (AIP). - 0021-9606 .- 1089-7690. ; 152:23
  • Tidskriftsartikel (refereegranskat)abstract
    • We continue the development of the in-house molecular dynamics software package SpaCIAL and test it for the computation of the collision-induced absorption coefficients for a neon (Ne) and krypton (Kr) gas mixture. An apodization procedure for the dipole autocorrelation function is implemented and tested. We also carry out a statistical study of the convergence rate with respect to ensemble size. The resulting absorption coefficients show a good accordance with quantum mechanical results. Comparison with laboratory measurements shows agreement within 10%–20% at T = 295 K. At T = 480 K, a larger difference of 40%–80% is observed, which can presumably be explained by experimental uncertainties. For the study, an empirical (Barker, Fisher, and Watts) interaction-potential [Mol. Phys. 21, 657 (1971)] for Ne–Kr has been developed. Ab initio {coupled cluster with singles and doubles (triples) [CCSD(T)]} potentials for Ne–Ne, Kr–Kr, and Ne–Kr have been computed, as well as the CCSD(T) interaction-induced Ne–Kr dipole moment curve.
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27.
  • Franceschini, N., et al. (författare)
  • GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
  • 2018
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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28.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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29.
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30.
  • Gustafsson, Magnus, 1969-, et al. (författare)
  • Collision-induced absorption in Ar-Xe: a comparative study of empirical and ab initio interaction potentials and electric dipole moments
  • 2022
  • Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 292
  • Tidskriftsartikel (refereegranskat)abstract
    • Empirical Barker-Fisher-Watts and modified Tang-Toennies potential energy curves are obtained through fit to experimental vibrational transition energies for argon–argon, xenon–xenon, and argon–xenon pairs. The potentials are tested against experimental thermophysical and transport properties, and agreement is observed. Also, an interaction-induced electric dipole moment curve for the argon–xenon pair is determined through a fit to experimental spectral moments for collision-induced absorption. The argon–xenon potentials and dipole are tested in a complete quantum dynamical calculation of the collision-induced absorption profiles, which can be compared with a laboratory measurement. This provides further analysis of the accuracy of the empirical argon–xenon data, as calculations of absorption profiles are highly sensitive to the input of molecular data.
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31.
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32.
  • Isaksson, H. S., et al. (författare)
  • Whole genome microarray expression analysis in blood identifies pathways linked to signs and symptoms of a patient with hypercalprotectinaemia and hyperzincaemia
  • 2018
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 191:2, s. 240-251
  • Tidskriftsartikel (refereegranskat)abstract
    • A child, 2 years with the hypercalprotectinaemia with hyperzincaemia' clinical syndrome, presented with atypical symptoms and signs, notably persistent fever of approximately 38 degrees C, thrombocythaemia of >700x10(9)/l and a predominance of persistent intestinal symptoms. In an effort to find a cure by identifying the dysregulated pathways we analysed whole-genome mRNA expression by the Affymetrix HG U133 Plus 20 array in blood on three occasions 3-5 months apart. Major up-regulation was demonstrated for the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway including, in particular, CD177, S100A8, S100A9 and S100A12, accounting for the thrombocytosis; a large number of interleukins, their receptors and activators, accounting for the febrile apathic state; and the high mobility group box 1 (HMBG1) gene, possibly accounting for part of the intestinal symptoms. These results show that gene expression array technology may assist the clinician in the diagnostic work-up of individual patients with suspected syndromal states of unknown origin, and the expression data can guide the selection of optimal treatment directed at the identified target pathways.
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33.
  • Jemth, Ann-Sofie, et al. (författare)
  • MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP
  • 2018
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 46:20, s. 10888-10904
  • Tidskriftsartikel (refereegranskat)abstract
    • Nucleotides in the free pool are more susceptible to nonenzymatic methylation than those protected in the DNA double helix. Methylated nucleotides like O6-methyl-dGTP can be mutagenic and toxic if incorporated into DNA. Removal of methylated nucleotides from the nucleotide pool may therefore be important to maintain genome integrity. We show that MutT homologue 1 (MTH1) efficiently catalyzes the hydrolysis of O6-methyl-dGTP with a catalytic efficiency similar to that for 8-oxo-dGTP. O6-methyl-dGTP activity is exclusive to MTH1 among human NUDIX proteins and conserved through evolution but not found in bacterial MutT. We present a high resolution crystal structure of human and zebrafish MTH1 in complex with O6-methyl-dGMP. By microinjecting fertilized zebrafish eggs with O6-methyl-dGTP and inhibiting MTH1 we demonstrate that survival is dependent on active MTH1 in vivo. O6-methyl-dG levels are higher in DNA extracted from zebrafish embryos microinjected with O6-methyl-dGTP and inhibition of O6-methylguanine-DNA methyl transferase (MGMT) increases the toxicity of O6-methyl-dGTP demonstrating that O6-methyl-dGTP is incorporated into DNA. MTH1 deficiency sensitizes human cells to the alkylating agent Temozolomide, a sensitization that is more pronounced upon MGMT inhibition. These results expand the cellular MTH1 function and suggests MTH1 also is important for removal of methylated nucleotides from the nucleotide pool.
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34.
  • Karlsson, B, et al. (författare)
  • Thyroid dysfunction in Down's syndrome : relation to age and thyroid autoimmunity
  • 1998
  • Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 79:3, s. 242-245
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The prevalence of thyroid disease is increased in Down's syndrome. Most available data come from cross sectional studies. AIMS: To study longitudinally thyroid function in patients with Down's syndrome in Uppsala county (85 patients) up to the age of 25 years. METHODS: Observational study based on yearly follow up in a children's clinic. Thyroid function tests were performed at each visit to the clinic. RESULTS: Hypothyroidism was found in 30 and hyperthyroidism was found in two of the 85 patients. No sex difference was seen. Half of the patients with hypothyroidism acquired the condition before the age of 8 years, but only one of them displayed thyroid autoantibodies at diagnosis. Most patients who developed hypothyroidism after this age had thyroid autoantibodies. In the prepubertal patients with hypothyroidism, growth velocity was lower during the year before the start of thyroxine treatment than during the year after treatment began; it was also lower than that of sex and age matched euthyroidic children with Down's syndrome. CONCLUSION: Thyroid dysfunction in patients with Down's syndrome is common in childhood. Consequently, annual screening is important. Autoimmune thyroid disease is uncommon in young children with Down's syndrome but is common after 8 years of age.
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35.
  • Liu, C, et al. (författare)
  • A DNA methylation biomarker of alcohol consumption.
  • 2018
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
  • Tidskriftsartikel (refereegranskat)abstract
    • The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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36.
  • Nilsson, K O, et al. (författare)
  • Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.
  • 1996
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 81, s. 635-
  • Tidskriftsartikel (refereegranskat)abstract
    • The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.
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37.
  • Olahova, M., et al. (författare)
  • POLRMT mutations impair mitochondrial transcription causing neurological disease
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • While >300 disease-causing variants have been identified in the mitochondrial DNA (mtDNA) polymerase gamma, no mitochondrial phenotypes have been associated with POLRMT, the RNA polymerase responsible for transcription of the mitochondrial genome. Here, we characterise the clinical and molecular nature of POLRMT variants in eight individuals from seven unrelated families. Patients present with global developmental delay, hypotonia, short stature, and speech/intellectual disability in childhood; one subject displayed an indolent progressive external ophthalmoplegia phenotype. Massive parallel sequencing of all subjects identifies recessive and dominant variants in the POLRMT gene. Patient fibroblasts have a defect in mitochondrial mRNA synthesis, but no mtDNA deletions or copy number abnormalities. The in vitro characterisation of the recombinant POLRMT mutants reveals variable, but deleterious effects on mitochondrial transcription. Together, our in vivo and in vitro functional studies of POLRMT variants establish defective mitochondrial transcription as an important disease mechanism. POLRMT is key for transcription of the mitochondrial genome, yet has not been implicated in mitochondrial disease to date. Here, the authors identify mutations in POLRMT in individuals with mitochondrial disease-related phenotypes and characterise underlying defects in mitochondrial transcription.
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38.
  • Ramdas, S., et al. (författare)
  • A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
  • 2022
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
  • Tidskriftsartikel (refereegranskat)abstract
    • A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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39.
  • Singh, B., et al. (författare)
  • Feasibility study for the measurement of pi N transition distribution amplitudes at (P)over-barANDA in (P)over-barp -> J/psi pi(0)
  • 2017
  • Ingår i: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 95:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The exclusive charmonium production process in (P) over barp annihilation with an associated pi 0 meson (p) over barp -> J/psi pi(0) is studied in the framework of QCD collinear factorization. The feasibility of measuring this reaction through the J/psi -> e(+) e(-) decay channel with the AntiProton ANnihilation at DArmstadt ((P) over bar ANDA) experiment is investigated. Simulations on signal reconstruction efficiency as well as the background rejection from various sources including the (P) over barp -> pi(+)pi(-)pi(0) and (p) over barp -> J/psi pi(0)pi(0) reactions are performed with PANDAROOT, the simulation and analysis software framework of the (P) over bar ANDA experiment. It is shown that the measurement can be done at (P) over bar ANDA with significant constraining power under the assumption of an integrated luminosity attainable in four to five months of data taking at the maximum design luminosity.
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40.
  • Singh, B., et al. (författare)
  • Study of doubly strange systems using stored antiprotons
  • 2016
  • Ingår i: Nuclear Physics A. - : Elsevier. - 0375-9474 .- 1873-1554. ; 954, s. 323-340
  • Tidskriftsartikel (refereegranskat)abstract
    • Bound nuclear systems with two units of strangeness are still poorly known despite their importance for many strong interaction phenomena. Stored antiprotons beams in the GeV range represent an unparalleled factory for various hyperon-antihyperon pairs. Their outstanding large production probability in antiproton collisions will open the floodgates for a series of new studies of systems which contain two or even more units of strangeness at the PANDA experiment at FAIR. For the first time, high resolution gamma-spectroscopy of doubly strange Lambda Lambda-hypernuclei will be performed, thus complementing measurements of ground state decays of Lambda Lambda-hypernuclei at J-PARC or possible decays of particle unstable hypernuclei in heavy ion reactions. High resolution spectroscopy of multistrange Xi(-) -atoms will be feasible and even the production of Omega(-) -atoms will be within reach. The latter might open the door to the vertical bar S vertical bar = 3 world in strangeness nuclear physics, by the study of the hadronic Omega(-) -nucleus interaction. For the first time it will be possible to study the behavior of Xi(+) in nuclear systems under well controlled conditions.
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41.
  • Torkildsen, J. V., et al. (författare)
  • App-Based Morphological Training Produces Lasting Effects on Word Knowledge in Primary School Children: A Randomized Controlled Trial
  • 2022
  • Ingår i: Journal of Educational Psychology. - : American Psychological Association (APA). - 0022-0663 .- 1939-2176. ; 114:4, s. 833-854
  • Tidskriftsartikel (refereegranskat)abstract
    • Morphemes, the smallest meaning-bearing units of language, recur in many words. Therefore, morphological knowledge can facilitate the comprehension of novel words. This study tested the effectiveness of a morphological training program on children's learning and retention of exposed words and morphologically related unexposed words compared with an active control condition. Norwegian second graders (N = 717) unselected for ability were individually randomized to either a morphological (n = 366) or a mathematical training program (n = 351). Both programs lasted for 8 weeks and were delivered as self-contained apps in a classroom setting. The morphological training built on the principle that frequency of target elements together with variation of nontarget elements can support implicit learning. Treatment-blind examiners assessed participants' meaning-based knowledge (word comprehension and definitions) and code-based knowledge (word reading fluency and spelling) at pretraining, immediately post training, and at follow-up 6 months later. An intention-to-treat analysis showed lasting effects of the morphological training on meaning-based knowledge of exposed words (posttest: d = .37; follow-up: d = .31) and unexposed words containing trained morphemes (posttest: d = .27; follow-up: d = .27) and code-based knowledge of exposed words (posttest: d = .22; follow-up: d = .13). For code-based knowledge of unexposed words, there were significant training effects at the posttest (d = .12) but not follow-up (d = .05). There were no significant effects on a far-transfer measure of general vocabulary. These results demonstrate that a brief morphological training program can produce lasting and educationally meaningful gains in students' word knowledge. Educational Impact and Implications Statement Words can consist of several meaningful parts, or morphemes, such as -ist in guitarist and re- in reuse. Understanding common morphemes helps children infer the meanings of new words. In this study, we tested the effects of working with an educational application (app) focusing on morphemes. Children completed app exercises such as sorting words or pictures according to their meaning, combining morphemes to build words, or identifying the correct word or morpheme to fit a sentence or picture context. We found that the app was effective in improving Norwegian second graders' ability to explain, understand, read, and spell words, including words which were not shown in the app, but which contained trained morphemes. The brief low-cost training produced long-term effects with a minimal burden on teachers.
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42.
  • Widerström, E G, et al. (författare)
  • Relations between experimentally induced tooth pain threshold changes, psychometrics and clinical pain relief following TENS. A retrospective study in patients with long-lasting pain.
  • 1992
  • Ingår i: Pain. - 0304-3959. ; 51:3, s. 281-7
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study investigates the relationships between clinical pain relief, physiological and psychological parameters. Out of 50 patients with long-lasting musculoskeletal neck- and shoulder-pain treated with transcutaneous electrical nerve stimulation (TENS), 21 were selected and classified as responders (n = 13) or non-responders (n = 8). Tooth pain thresholds (PT) were measured before and after an experimental TENS treatment and the relative change in PT following the stimulation was calculated. Three psychometric self-inventories were administered: Zung Depression Scale, Spielberger's Trait Anxiety Scale and the Multidimensional Health Locus of Control Scale. Responders (R) and non-responders (NR) differed significantly from each other in the PT measurements as well as on the psychometric scales. NR exhibited higher levels of anxiety and depression, a more pronounced powerful other orientation and no change or a decrease in PT following TENS compared to R. These findings indicate relationships and interactions between physiological and psychological factors in patients with long-lasting pain.
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43.
  • Williams, Cecilia, 1969-, et al. (författare)
  • A genome-wide study of the repressive effects of estrogen receptor beta on estrogen receptor alpha signaling in breast cancer cells.
  • 2008
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 27:7, s. 1019-1032
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptional effects of estrogen result from its activation of two estrogen receptor (ER) isoforms; ERalpha that drives proliferation and ERbeta that is antiproliferative. Expression of ERbeta in xenograft tumors from the T47D breast cancer cell line reduces tumor growth and angiogenesis. If ERbeta can halt tumor growth, its introduction into cancers may be a novel therapeutic approach to the treatment of estrogen-responsive cancers. To assess the complete impact of ERbeta on transcription, we have made a full transcriptome analysis of ERalpha- and ERbeta-mediated gene regulation in T47D cell line with Tet-Off regulated ERbeta expression. Of the 35 000 genes and transcripts analysed, 4.1% (1434) were altered by ERalpha activation. Tet withdrawal and subsequent ERbeta expression inhibited the ERalpha regulation of 998 genes and, in addition, altered expression of 152 non-ERalpha-regulated genes. ERalpha-induced and ERbeta-repressed genes were involved in proliferation, steroid/xenobiotic metabolism and ion transport. The ERbeta repressive effect was further confirmed by proliferation assays, where ERbeta was shown to completely oppose the ERalpha-E2 induced proliferation. Additional analysis of ERbeta with a mutated DNA-binding domain revealed that this mutant, at least for a quantity of genes, antagonizes ERalpha even more strongly than ERbeta wt. From an examination of the genes regulated by ERalpha and ERbeta, we suggest that introduction of ERbeta may be an alternative therapeutic approach to the treatment of certain cancers.
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