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2.
  • Bouyoucef, S E, et al. (författare)
  • Poster Session 2 : Monday 4 May 2015, 08
  • 2015
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
  • Tidskriftsartikel (refereegranskat)
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3.
  • Abbasi, R., et al. (författare)
  • Measurement of the atmospheric neutrino energy spectrum from 100 GeV to 400 TeV with IceCube
  • 2011
  • Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 83:1, s. 012001-
  • Tidskriftsartikel (refereegranskat)abstract
    • A measurement of the atmospheric muon neutrino energy spectrum from 100 GeV to 400 TeV was performed using a data sample of about 18 000 up-going atmospheric muon neutrino events in IceCube. Boosted decision trees were used for event selection to reject misreconstructed atmospheric muons and obtain a sample of up-going muon neutrino events. Background contamination in the final event sample is less than 1%. This is the first measurement of atmospheric neutrinos up to 400 TeV, and is fundamental to understanding the impact of this neutrino background on astrophysical neutrino observations with IceCube. The measured spectrum is consistent with predictions for the atmospheric nu(mu) + (nu) over bar (mu) flux.
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4.
  • Abbasi, R., et al. (författare)
  • Limits on a muon flux from Kaluza-Klein dark matter annihilations in the Sun from the IceCube 22-string detector
  • 2010
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 81:5, s. 057101-
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for muon neutrinos from Kaluza-Klein dark matter annihilations in the Sun has been performed with the 22-string configuration of the IceCube neutrino detector using data collected in 104.3 days of live time in 2007. No excess over the expected atmospheric background has been observed. Upper limits have been obtained on the annihilation rate of captured lightest Kaluza-Klein particle (LKP) WIMPs in the Sun and converted to limits on the LKP-proton cross sections for LKP masses in the range 250-3000 GeV. These results are the most stringent limits to date on LKP annihilation in the Sun.
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5.
  • Abbasi, R., et al. (författare)
  • Search for point sources of high energy neutrinos with final data from AMANDA-II
  • 2009
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 062001-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a search for point sources of high energy neutrinos using 3.8 yr of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the northern sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E(-2) neutrino fluxes from points in the northern sky, with an average upper limit of E(2)Phi(nu mu)+nu(tau)<= 5.2x10(-11) TeV cm(-2) s(-1) on the sum of nu(mu) and nu(tau) fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.
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  • Abbasi, R., et al. (författare)
  • Calibration and characterization of the IceCube photomultiplier tube
  • 2010
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 618:1-3, s. 139-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Over 5000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-in. diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts. (C) 2010 Elsevier B.V. All rights reserved.
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7.
  • Abbasi, R., et al. (författare)
  • Measurement of acoustic attenuation in South Pole ice
  • 2011
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:6, s. 382-393
  • Tidskriftsartikel (refereegranskat)abstract
    • Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient alpha = 3.20 +/- 0.57 km(-1) between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for lambda equivalent to 1/alpha of similar to 300 m with 20% uncertainty. No significant depth or frequency dependence has been found.
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  • Abbasi, R., et al. (författare)
  • Search for relativistic magnetic monopoles with the AMANDA-II neutrino telescope
  • 2010
  • Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 69:3-4, s. 361-378
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the search for Cherenkov signatures from relativistic magnetic monopoles in data taken with the AMANDA-II detector, a neutrino telescope deployed in the Antarctic ice cap at the Geographic South Pole. The non-observation of a monopole signal in data collected during the year 2000 improves present experimental limits on the flux of relativistic magnetic monopoles: Our flux limit varies between 3.8x10(-17) cm(-2) s(-1) sr(-1) (for monopoles moving at the vacuum speed of light) and 8.8x10(-16) cm(-2) s(-1) sr(-1) (for monopoles moving at a speed beta=v/c=0.76, just above the Cherenkov threshold in ice). These limits apply to monopoles that are energetic enough to penetrate the Earth and enter the detector from below the horizon. The limit obtained for monopoles reaching the detector from above the horizon is less stringent by roughly an order of magnitude, due to the much larger background from down-going atmospheric muons. This looser limit is however valid for a larger class of magnetic monopoles, since the monopoles are not required to pass through the Earth.
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  • Abbasi, R., et al. (författare)
  • The energy spectrum of atmospheric neutrinos between 2 and 200 TeV with the AMANDA-II detector
  • 2010
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:1, s. 48-58
  • Tidskriftsartikel (refereegranskat)abstract
    • The muon and anti-muon neutrino energy spectrum is determined from 2000-2003 AMANDA telescope data using regularised unfolding. This is the first measurement of atmospheric neutrinos in the energy range 2-200 TeV. The result is compared to different atmospheric neutrino models and it is compatible with the atmospheric neutrinos from pion and kaon decays. No significant contribution from charm had-ron decays or extraterrestrial neutrinos is detected. The capabilities to improve the measurement of the neutrino spectrum with the successor experiment IceCube are discussed.
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10.
  • Abbasi, R., et al. (författare)
  • Measurement of sound speed vs. depth in South Pole ice for neutrino astronomy
  • 2010
  • Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 33:5-6, s. 277-286
  • Tidskriftsartikel (refereegranskat)abstract
    • We have measured the speed of both pressure waves and shear waves as a function of depth between 80 and 500 m depth in South Pole ice with better than 1% precision. The measurements were made using the South Pole Acoustic Test Setup (SPATS), an array of transmitters and sensors deployed in the ice at the South Pole in order to measure the acoustic properties relevant to acoustic detection of astrophysical neutrinos. The transmitters and sensors use piezoceramics operating at similar to 5-25 kHz. Between 200 m and 500 m depth, the measured profile is consistent with zero variation of the sound speed with depth, resulting in zero refraction, for both pressure and shear waves. We also performed a complementary study featuring an explosive signal propagating vertically from 50 to 2250 m depth, from which we determined a value for the pressure wave speed consistent with that determined for shallower depths, higher frequencies, and horizontal propagation with the SPATS sensors. The sound speed profile presented here can be used to achieve good acoustic source position and emission time reconstruction in general, and neutrino direction and energy reconstruction in particular. The reconstructed quantities could also help separate neutrino signals from background. (C) 2010 Elsevier B.V. All rights reserved.
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  • Abbasi, R., et al. (författare)
  • SEARCH FOR HIGH-ENERGY MUON NEUTRINOS FROM THE "NAKED-EYE" GRB 080319B WITH THE IceCube NEUTRINO TELESCOPE
  • 2009
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 701:2, s. 1721-1731
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a search with the IceCube detector for high-energy muon neutrinos from GRB 080319B, one of the brightest gamma-ray bursts (GRBs) ever observed. The fireball model predicts that a mean of 0.1 events should be detected by IceCube for a bulk Lorentz boost of the jet of 300. In both the direct on-time window of 66 s and an extended window of about 300 s around the GRB, no excess was found above background. The 90% CL upper limit on the number of track-like events from the GRB is 2.7, corresponding to a muon neutrino fluence limit of 9.5 x 10(-3) erg cm(-2) in the energy range between 120 TeV and 2.2 PeV, which contains 90% of the expected events.
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  • Achterberg, A., et al. (författare)
  • Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
  • 2007
  • Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:4, s. 042008-
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E-2 Phi(90%C.L.)< 7.4x10(-8) GeV cm(-2) s(-1) sr(-1) is placed on the diffuse flux of muon neutrinos with a Phi proportional to E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Phi proportional to E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Phi proportional to E-2.
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13.
  • Abbasi, R, et al. (författare)
  • Extending the Search for Neutrino Point Sources with IceCube above the Horizon
  • 2009
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:22, s. 221102-
  • Tidskriftsartikel (refereegranskat)abstract
    • Point source searches with the IceCube neutrino telescope have been restricted to one hemisphere, due to the exclusive selection of upward going events as a way of rejecting the atmospheric muon background. We show that the region above the horizon can be included by suppressing the background through energy-sensitive cuts. This improves the sensitivity above PeV energies, previously not accessible for declinations of more than a few degrees below the horizon due to the absorption of neutrinos in Earth. We present results based on data collected with 22 strings of IceCube, extending its field of view and energy reach for point source searches. No significant excess above the atmospheric background is observed in a sky scan and in tests of source candidates. Upper limits are reported, which for the first time cover point sources in the southern sky up to EeV energies.
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  • Nieminen, M. S., et al. (författare)
  • Repetitive use of levosimendan for treatment of chronic advanced heart failure : Clinical evidence, practical considerations, and perspectives: An expert panel consensus
  • 2014
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 174:2, s. 360-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. Methods and results: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. Conclusions: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made. (C) 2014 The Authors. Published by Elsevier Ireland Ltd.
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  • Kuokkanen, S, et al. (författare)
  • A putative vulnerability locus to multiple clerosis maps to 5p14-p12 in a region syntenic to the murine locus Eae2
  • 1996
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 13:4, s. 477-480
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by multifocal damage of myelin in the central nervous system (CNS). The prevalence of this putative autoimmune disease is 0.1% in individuals of northern European origin. Family, adoption and twin studies implicate genetic factors in the aetiology. MS is widely speculated to be a multifactorial disorder with a complex mode of inheritance. Despite many studies of candidate genes, only an association with HLA-DR2-DQ6 has been generally detected, and the number of susceptibility genes remains unknown. The chronic variant of experimental allergic encephalomyelitis (EAE), a T-cell mediated autoimmune disease in rodents, represents a relevant animal model for MS given the chronic relapsing disease course and inflammatory changes of CNS observed in these demyelinating disorders. Susceptibility to EAE is also influenced by the major histocompatibility complex (MHC). Human syntenic regions to murine loci predisposing to EAE were tested as candidate regions for genetic susceptibility of MS. Three chromosomal regions (1p22-q23, 5p14-p12 and Xq13.2-q22) were screened in 21 Finnish multiplex MS families most originating from a high risk region in western Finland. Several markers yielded positive lod scores on 5p14-p12, syntenic to the murine locus Eae2. Our data provide evidence for a predisposing locus for MS on 5p14-p12.
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  • Millischer, V., et al. (författare)
  • Improving lithium dose prediction using population pharmacokinetics and pharmacogenomics: a cohort genome-wide association study in Sweden
  • 2022
  • Ingår i: Lancet Psychiatry. - 2215-0374. ; 9:6, s. 447-457
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lithium is the most effective treatment for bipolar disorder, resulting in strong suicide prevention effects. The therapeutic range of lithium, however, is narrow and treatment initiation requires individual titration to address inter-individual variability. We aimed to improve lithium dose prediction using clinical and genomic data. Methods We performed a population pharmacokinetic study followed by a genome-wide association study (GWAS), including two clinical Swedish cohorts. Participants in cohort 1 were from specialised outpatient clinics at Huddinge Hospital, in Stockholm, Sweden, and participants in cohort 2 were identified using the Swedish National Quality Registry for Bipolar disorder (BipolaR). Patients who received a lithium dose corresponding to at least one tablet of lithium sulphate (6 mmol) per day and had clinically relevant plasma concentrations of lithium were included in the study. Data on age, sex, bodyweight, height, creatinine concentration, estimated glomerular filtration rate (eGFR), lithium preparation, number of tablets of lithium per day, serum lithium concentration, and medications affecting kidney function (C09 antihypertensives, C03 [except C03D] sodium-retaining diuretics, and non-steroidal anti-inflammatory drugs) were obtained retrospectively for several timepoints when possible from electronic health records, BipolaR, and the Swedish prescription registry. The median time between timepoints was 1.07 years for cohort 1 and 1.09 years for cohort 2. The primary outcome of interest was the natural logarithm of total body clearance for lithium (CLLi) associated with the clinical variables. The residual effects after accounting for age and sex, representing the individual-level effects (CLLi,age/sex), were used as the dependent variable in a GWAS. Findings 2357 patients who were administered lithium (1423 women [60.4%] and 934 men [39.6%]; mean age 53.6 years [range 17-89], mainly of European descent) were included and 5627 data points were obtained. Age (variance explained [R-2]: R-cohort1(2)=0.41 and R-cohort2(2)=0.31; both p<0.0001), sex (R-cohort1(2)=0.0063 [p=0.045] and R-cohort2(2)=0.026 [p<0.0001]), eGFR (R-cohort1(2)=0.38 and R-cohort2(2)=0.0; both p<0.0001), comedication with diuretics (R-cohort1(2)=0.0058 [p=0.014] and R-cohort2(2)=0.0026 [p<0.0001]), and agents acting on the renin-aldosterone-angiotensin system (R-cohort1(2)=0.028 and R-cohort2(2)=0.015; both p<0.0001) were clinical predictors of CLLi. Notably, an association between CLLi and serum lithium was observed, with a lower CLLi being associated with higher serum lithium (R-cohort1(2)=0.13 and R-cohort2(2)=0.15; both p<0.0001). In a GWAS of CLLi,age/sex, one locus was associated with a change in CLLi (rs583503; beta=-0.053 [95% CI -0.071 to -0.034]; p<0.00000005). We also found enrichment of the associations with genes expressed in the medulla (p=0.0014, corrected FDR=0.04) and cortex of the kidney (p=0.0015, corrected FDR=0.04), as well as associations with polygenic risk scores for eGFR (p value threshold: 0.05, p=0.01), body-mass index (p value threshold: 0.05, p=0.00025), and blood urea nitrogen (p value threshold: 0.001, p=0.00043). The model based on six clinical predictors explained 61.4% of the variance in CLLi in cohort 1 and 49.8% in cohort 2. Adding genetic markers did not lead to major improvement of the models: within the subsample of genotyped individuals, the variance explained only increased from 59.32% to 59.36% in cohort 1 and from 49.21% to 50.03% in cohort 2 when including rs583503 and the four first principal components. Interpretation Our model predictors could be used clinically to better guide lithium dosage, shortening the time to reach therapeutic concentrations, thus improving care. Identification of the first genomic locus and PRS to be associated with CLLi introduces the opportunity of individualised medicine in lithium treatment. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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  • Brindefalk, B., et al. (författare)
  • Bacterial composition in Swedish raw drinking water reveals three major interacting ubiquitous metacommunities
  • 2022
  • Ingår i: Microbiologyopen. - : Wiley. - 2045-8827. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Surface raw water used as a source for drinking water production is a critical resource, sensitive to contamination. We conducted a study on Swedish raw water sources, aiming to identify mutually co-occurring metacommunities of bacteria, and environmental factors driving such patterns. Methods The water sources were different regarding nutrient composition, water quality, and climate characteristics, and displayed various degrees of anthropogenic impact. Water inlet samples were collected at six drinking water treatment plants over 3 years, totaling 230 samples. The bacterial communities of DNA sequenced samples (n = 175), obtained by 16S metabarcoding, were analyzed using a joint model for taxa abundance. Results Two major groups of well-defined metacommunities of microorganisms were identified, in addition to a third, less distinct, and taxonomically more diverse group. These three metacommunities showed various associations to the measured environmental data. Predictions for the well-defined metacommunities revealed differing sets of favored metabolic pathways and life strategies. In one community, taxa with methanogenic metabolism were common, while a second community was dominated by taxa with carbohydrate and lipid-focused metabolism. Conclusion The identification of ubiquitous persistent co-occurring bacterial metacommunities in freshwater habitats could potentially facilitate microbial source tracking analysis of contamination issues in freshwater sources.
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31.
  • Buttle, David J, et al. (författare)
  • Interactions of papaya proteinase IV with inhibitors
  • 1990
  • Ingår i: FEBS Letters. - 1873-3468. ; 262:1, s. 58-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Papaya proteinase IV (PPIV) is not inhibited by chicken cystatin, or human cystatins A or C, unlike most other proteinases of the papain superfamily. The enzyme inactivates chicken cystatin and human cystatin C by limited proteolysis of the glycyl bond previously shown to be involved in the inhibitory inactivity of the cystatins, but has no action on cystatin A. Contamination of commercial crystalline papain with PPIV accounts for the limited proteolysis of cystatins by ‘papain’ reported previously. PPIV is slowly bound by human α2-macroglobulin. The enzyme is irreversibly inactivated by E-64, and by peptidyl diazomethanes containing glycine in P1 and a hydrophobic side-chain in P2. The reaction of PPIV with iodoacetate is extremely slow. PPIV is inhibited by peptide aldehydes despite the presence of bulky sidechains in P1, suggesting that these reversible inhibitors do not bind as substrate analogues.
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  • Hu, J., et al. (författare)
  • The effects of chemotherapeutic drugs on human monocyte-derived dendritic cell differentiation and antigen presentation
  • 2013
  • Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 172:3, s. 490-499
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies indicate that chemotherapeutic agents may increase the anti-tumoral immune response. Based on the pivotal role of dendritic cells (DCs) in host tumour-specific immune responses, we investigated the effect of commonly used chemotherapeutic drugs dexamethasone, doxorubicin, cisplatin and irinotecan and glucocorticoids on monocyte-derived DCs (moDCs). Dexamethasone displayed the strongest inhibitory effect on DC differentiation. The effect of cisplatin and irinotecan was moderate, while only weak effects were noticed for doxorubicin. Surprisingly, when the functional consequence of chemotherapy-treated CD14+ monocytes and their capacity to activate CD4+ T responders cells were investigated, cisplatin-treated monocytes gave rise to increased T cell proliferation. However, dexamethasone, doxorubicin and irinotecan-pretreated monocytes did not stimulate any increased T cell proliferation. Further investigation of this observation revealed that cisplatin treatment during DC differentiation up-regulated significantly the interferon (IFN)- transcript. By contrast, no effect was evident on the expression of interleukin (IL)-1, tumour necrosis factor (TNF)-, IL-6 or IFN- transcripts. Blocking IFN- attenuated the cisplatin-enhanced T cell proliferation significantly. In conclusion, cisplatin treatment enhanced the immune stimulatory ability of human monocytes, a mechanism mediated mainly by the increased production of IFN-.
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  • Nyblom, Anna Maria, 1975, et al. (författare)
  • Exceptional overproduction of a functional human membrane protein
  • 2007
  • Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928 .- 1096-0279. ; 56:1, s. 110-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Eukaryotic-especially human-membrane protein overproduction remains a major challenge in biochemistry. Heterologously overproduced and purified proteins provide a starting point for further biochemical, biophysical and structural studies, and the lack of sufficient quantities of functional membrane proteins is frequently a bottleneck hindering this. Here, we report exceptionally high production levels of a correctly folded and crystallisable recombinant human integral membrane protein in its active form; human aquaporin 1 (hAQP1) has been heterologously produced in the membranes of the methylotrophic yeast Pichia pastoris. After solubilisation and a two step purification procedure, at least 90 mg hAQP1 per liter of culture is obtained. Water channel activity of this purified hAQP was verified by reconstitution into proteoliposomes and performing stopped-flow vesicle shrinkage measurements. Mass spectrometry confirmed the identity of hAQPI in crude membrane preparations, and also from purified protein reconstituted into proteoliposomes. Furthermore, crystallisation screens yielded diffraction quality crystals of untagged recombinant hAQP1. This study illustrates the power of the yeast P. pastoris as a host to produce exceptionally high yields of a functionally active, human integral membrane protein for subsequent functional and structural characterization. (c) 2007 Elsevier Inc. All rights reserved.
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44.
  • Olofsson, Mona, et al. (författare)
  • A description of characteristics of very elderly patients newly diagnosed with heart failure : a retrospective population-based cohort study in Sweden
  • 2017
  • Ingår i: European Journal of Heart Failure. - : European Society of Cardiology. - 1388-9842 .- 1879-0844. ; 19:S1, s. 362-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Over a quarter of patients with heart failure (HF) in Sweden are very elderly (defined as aged ≥85 years). Evidence on the demographic and clinical characteristics of these patients, and on the diagnostic procedures they receive in clinical practice, is scarce.Methods: Patients with HF were identified via electronic medical records from primary and/or secondary care in Västerbotten, linked via unique identifiers to data from the National Patient Register and Swedish Prescribed Drug Register. Local echocardiography data were used to identify patients with HF with preserved (HFpEF, ≥50%) and reduced (HFrEF, <50%) ejection fraction. Patients aged ≥18 years with ≥2 diagnoses of HF between 01/01/2010 and 31/03/2015 and an ICD-10 diagnostic code of I50 (inclusive of all granular codes), I42.0, I42.6, I42.7, I42.9, I110, I130 or I132 in any position were included. The date of the first diagnosis was the index date. ICD-10 codes were also used to identify comorbidities. A 10-year look-back period was used to exclude prevalent HF cases. Patient characteristics were assessed at index, except comorbidities (in the 5 years before index) and pre-diagnosis comedications (in the first year before index).Results: In total, 8702 patients with HF were identified; 27.7% were aged ≥85 years. Compared with patients <85 years, more patients ≥85 years were female (60.2% vs 40.6%) and fewer were overweight (BMI >25 kg/m2, 42.3% vs 63.5%). In both groups, HF was more commonly diagnosed in secondary than in primary care, but patients ≥85 years were more often diagnosed in primary care than those <85 years (31.2% vs 20.9%). Fewer patients ≥85 years than those <85 years received an echocardiogram at diagnosis (19.3% vs 42.9%); of those who did, more patients ≥85 years than <85 years had HFpEF (46.8% vs 33.4%). Patients ≥85 years had a comorbidity burden similar to those <85 years (mean number of comorbidities/patient, 2.4 vs 2.3); prevalence of atrial fibrillation (32.0% vs 30.4%), hypertension (53.2% vs 53.0%) and ischaemic heart disease (20.5% vs 22.5%) were also similar in both age groups. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and systolic blood pressure (BP) increased with age, and diastolic BP and estimated glomerular filtration rate decreased. Potassium and sodium levels did not differ between age groups (Table). The most common pre-diagnosis comedications were ?-blockers, antithrombotic agents and diuretics; ?-blockers were less frequently prescribed in patients ≥85 years (59.6% vs 64.4%), and antithrombotic agents and diuretics were more frequently prescribed in those ≥85 years (antithrombotic agents, 57.0% vs 54.3%; diuretics, 50.1% vs 43.1%).Conclusions: Very elderly patients with HF in Sweden are clinically different from younger patients, with a higher prevalence of HFpEF and higher NT-proBNP levels (as expected). Most importantly, very elderly patients seldom receive an echocardiogram at diagnosis.
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  • Ormo, J., et al. (författare)
  • The geology of the Malingen structure: A probable doublet to the Lockne marine-target impact crater, central Sweden
  • 2014
  • Ingår i: Meteoritics & Planetary Science. - : Wiley. - 1086-9379. ; 49:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • The Malingen structure is an approximately 700m wide, rimmed, sediment-filled, circular depression in Precambrian crystalline basement approximately 16.2km from the concentric, marine-target Lockne crater (inner, basement crater diameter approximately 7.5km, total diameter in sedimentary strata approximately 13.5km). We present here results from geologic mapping, a 148.8m deep core drilling from the center of the structure, detailed biostratigraphic dating of the structure's formation and its age correlation with Lockne, chemostratigraphy of the sedimentary infill, and indication for shock metamorphism in quartz from breccias below the crater infill. The drill core reveals, from bottom to the top, approximately 33m of basement rocks with increased fracturing upward, approximately 10m of polymict crystalline breccia with shock features, approximately 97m of slumped Cambrian mudstone, approximately 4.7m of a normally graded, polymict sedimentary breccia that in its uppermost part grades into sandstone and siltstone (cf. resurge deposits), and approximately 1.6m of secular sediments. The combined data set shows that the Malingen structure formed in conjunction with the Lockne crater in the same marine setting. The shape and depth of the basement crater and the cored sequence of crystalline breccias with shocked quartz, slumped sediments, and resurge deposits support an impact origin. The stratigraphic and geographic relationship with Lockne suggests the Lockne and Malingen craters to be the first described doublet impact structure by a binary asteroid into a marine-target setting.
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  • Purhonen, J., et al. (författare)
  • A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1/(p.S78G) mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cyb(p.D254N)), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1/(p.S78G) tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc(1) complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.
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