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  • Agui, A, et al. (author)
  • Direct observation of interface effects of thin AlAs(100) layers buried in GaAs
  • 2000
  • In: APPLIED SURFACE SCIENCE. - : ELSEVIER SCIENCE BV. - 0169-4332. ; 166:1-4, s. 309-312
  • Journal article (peer-reviewed)abstract
    • A study of the electronic structure of ultrathin AlAs layers buried in GaAs(100) and their interfaces is presented. Al L-2,L-3 soft-X-ray-emission (SXE) spectra from the AlAs layers were measured. The spectra show distinct thickness-dependent features, wh
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  • ANDERSSON, CBM, et al. (author)
  • SPUTTERED AND ANNEALED INAS(111)OVER-BAR - AN UNRECONSTRUCTED SURFACE
  • 1994
  • In: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 307, s. 885-889
  • Journal article (peer-reviewed)abstract
    • The electronic structure of the InAs(111BAR)1 X 1 surface has been investigated by angle resolved photoelectron spectroscopy along the symmetry lines GAMMAKBAR, GAMMAMBAR, and GAMMAMBAR of the surface Brillouin zone. The bulk valence band structure was calculated using a combination of the linear augmented plane-wave method and the relativistic augmented plane-wave method. We have projected the theoretical bulk band structure onto the surface Brillouin zone to separate surface states from surface resonances. Two surface related structures, S1 and S2, have been observed and their E(i)(k(parallel-to)) dispersions are established. Both S1 and S2 show the symmetry of the 1 X 1 surface Brillouin zone, which is consistent with the observed 1 X 1 LEED pattern. We identify S1 as the As-derived dangling bond state, and S2 is associated with the backbonds connecting the As atoms in the surface layer with the underlying In layer.
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  • Andersson, JLR, et al. (author)
  • Regional cerebral blood flow and oxygen metabolism during migraine with and without aura
  • 1997
  • In: CEPHALALGIA. - : SCANDINAVIAN UNIVERSITY PRESS. - 0333-1024. ; 17:5, s. 570-579
  • Journal article (other academic/artistic)abstract
    • Eleven cases of migraine with and without aura were investigated with positron emission tomography (PET). Regional cerebral blood flow (rCBF), oxygen metabolism (rCMRO(2)) and oxygen extraction (rOER) were measured during baseline (n = 11), aura (n = 6),
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  • Andersson, PO, et al. (author)
  • From a local and closed to an international and virtual library: a case report
  • 1997
  • In: ELECTRONIC LIBRARY. - : Emerald. - 0264-0473. ; 15:6, s. 475-484
  • Journal article (other academic/artistic)abstract
    • One of the main challenges faced by libraries is to present their services and holdings to patrons in a truly professional and user‐friendly way. The standard library software available does not usually adapt to new technology as quickly as library users and staff would like. However, such limitations need not be accepted. By thinking in terms of small‐scale, incremental development and by using general computer software, an ambitious library can create a technologically up‐to‐date information browsing instrument even though finances and resources are limited. This paper describes the strategic and technological steps involved in such a process.
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9.
  • Andersson, SK, et al. (author)
  • Infrared properties of beta-sialon as a function of composition
  • 1998
  • In: OPTICAL MATERIALS. - : ELSEVIER SCIENCE BV. - 0925-3467. ; 10:1, s. 85-93
  • Journal article (peer-reviewed)abstract
    • The infrared properties of beta-sialons, Si6-zAlzOzN8-z, prepared by hot, isostatic pressing for nine z-values, as well as a corresponding set of samples containing 1 wt% of yttria have been studied. The samples all have densities over 99% of their theore
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10.
  • Andersson, Staffan, et al. (author)
  • Twenty-four-hour electrocardiography in a healthy elderly population
  • 1988
  • In: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 34:3, s. 139-144
  • Journal article (peer-reviewed)abstract
    • Twenty-four hour electrocardiography was performed in fifteen 73-year-old and seventeen 82-year-old subjects without known cardiovascular disease. They were selected from a representative population of elderly people. All subjects showed supraventricular premature beats. Supraventricular tachycardia was seen in 63%. Eighty-four percent showed ventricular premature beats (VPBs), and more than two VPB configuration types were seen in 23% of the subjects. Episodes of intermittent atrial flutter and fibrillation, higher-degree atrioventricular blocks and ventricular tachycardia were absent or rare.
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  • Dahl, F, et al. (author)
  • Imaging single DNA molecules for high precision NIPT
  • 2018
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 4549-
  • Journal article (peer-reviewed)abstract
    • Cell-free DNA analysis is becoming adopted for first line aneuploidy screening, however for most healthcare programs, cost and workflow complexity is limiting adoption of the test. We report a novel cost effective method, the Vanadis NIPT assay, designed for high precision digitally-enabled measurement of chromosomal aneuploidies in maternal plasma. Reducing NIPT assay complexity is achieved by using novel molecular probe technology that specifically label target chromosomes combined with a new readout format using a nanofilter to enrich single molecules for imaging and counting without DNA amplification, microarrays or sequencing. The primary objective of this study was to assess the Vanadis NIPT assay with respect to analytical precision and clinical feasibility. Analysis of reference DNA samples indicate that samples which are challenging to analyze with low fetal-fraction can be readily detected with a limit of detection determined at <2% fetal-fraction. In total of 286 clinical samples were analysed and 30 out of 30 pregnancies affected by trisomy 21 were classified correctly. This method has the potential to make cost effective NIPT more widely available with more women benefiting from superior detection and false positive rates.
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  • Fatsis-Kavalopoulos, Nikos, et al. (author)
  • CombiANT : Antibiotic interaction testing made easy
  • 2020
  • In: PLoS biology. - : PUBLIC LIBRARY SCIENCE. - 1544-9173 .- 1545-7885. ; 18:9
  • Journal article (peer-reviewed)abstract
    • Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens,Escherichia coli,Pseudomonas aeruginosa, andStaphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12E.coliurinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.
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  • Gudmundsdottir, Jonina S., et al. (author)
  • The chemotherapeutic drug methotrexate selects for antibiotic resistance
  • 2021
  • In: EBioMedicine. - : Elsevier. - 2352-3964. ; 74
  • Journal article (peer-reviewed)abstract
    • Background: Understanding drivers of antibiotic resistance evolution is fundamental for designing optimal treatment strategies and interventions to reduce the spread of antibiotic resistance. Various cytotoxic drugs used in cancer chemotherapy have antibacterial properties, but how bacterial populations are affected by these selective pressures is unknown. Here we test the hypothesis that the widely used cytotoxic drug methotrexate affects the evolution and selection of antibiotic resistance.Methods: First, we determined methotrexate susceptibility (IC90) and selective abilities in a collection of Escherichia coli and Klebsiella pneumoniae strains with and without pre-existing trimethoprim resistance determinants. We constructed fluorescently labelled pairs of E. coli MG1655 differing only in trimethoprim resistance determinants and determined the minimum selective concentrations of methotrexate using flow-cytometry. We further used an experimental evolution approach to investigate the effects of methotrexate on de novo trimethoprim resistance evolution.Findings: We show that methotrexate can select for acquired trimethoprim resistance determinants located on the chromosome or a plasmid. Additionally, methotrexate co-selects for genetically linked resistance determinants when present together with trimethoprim resistance on a multi-drug resistance plasmid. These selective effects occur at concentrations 40- to >320-fold below the methotrexate minimal inhibitory concentration.Interpretation: Our results strongly suggest a selective role of methotrexate for virtually any antibiotic resistance determinant when present together with trimethoprim resistance on a multi-drug resistance plasmid. The presented results may have significant implications for patient groups strongly depending on effective antibiotic treatment.
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  • Hjort, Karin, et al. (author)
  • Antibiotic Minimal Selective Concentrations and Fitness Costs during Biofilm and Planktonic Growth
  • 2022
  • In: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 13:3
  • Journal article (peer-reviewed)abstract
    • The use and misuse of antibiotics have resulted in the selection of difficult-to-treat resistant bacteria. Two key parameters that influence the selection of resistant bacteria are the minimal selective concentration (MSC) and the fitness cost of resistance, both of which have been measured during planktonic growth in several studies. However, bacterial growth most often occurs in biofilms, and it is unclear if and how these parameters differ under these two growth conditions. To address this knowledge gap, we compared a selection of several types of antibiotic-resistant Escherichia coli mutants during planktonic and biofilm growth to determine the fitness costs and MSCs. Biofilm-forming Escherichia coli strains are commonly found in catheter-associated and recurrent urinary tract infections. Isogenic strains of a biofilm-forming E. coli strain, differing only in the resistance mechanisms and the fluorescent markers, were constructed, and susceptible and resistant bacteria were grown in head-to-head competitions at various concentrations of antibiotics under planktonic and biofilm conditions. Mutants with resistance to five different antibiotics were studied. The results show that during both planktonic and biofilm growth, selection for the resistant mutants occurred for all antibiotics at sub-MICs far below the MIC of the antibiotic. Even though differences were seen, the MSC values and the fitness costs did not differ systematically between planktonic and biofilm growth, implying that despite the different growth modes, the basic selection parameters are similar. These findings highlight the risk that resistant mutants may, similarly to planktonic growth, also be selected at sub-MICs of antibiotics in biofilms.IMPORTANCE Our understanding of how and where antibiotic resistance is selected in response to antibiotic exposure is still limited, and this is particularly true for selective processes when bacteria are growing in biofilms, arguably the most significant mode of growth of bacteria in human and animal infections as well as in other settings. In this study, we compared how different types of resistant E. coli strains were selected in response to antibiotic exposure during planktonic and biofilm growth. Determination of the minimal selective concentrations (MSCs) and fitness costs of resistance showed that they were comparable under these two different conditions, even though some differences were observed. Importantly, the MSCs were far below the MICs for all mutants under both planktonic and biofilm growth, emphasizing the significance of low antibiotic concentrations in driving the emergence and enrichment of resistant bacteria. Our understanding of how and where antibiotic resistance is selected in response to antibiotic exposure is still limited, and this is particularly true for selective processes when bacteria are growing in biofilms, arguably the most significant mode of growth of bacteria in human and animal infections as well as in other settings. In this study, we compared how different types of resistant E. coli strains were selected in response to antibiotic exposure during planktonic and biofilm growth.
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  • Larsson, PO, et al. (author)
  • Complete oxidation of CO, ethanol, and ethyl acetate over copper oxide supported on titania and ceria modified titania
  • 1998
  • In: Journal of Catalysis. - : Elsevier BV. - 1090-2694 .- 0021-9517. ; 179:1, s. 72-89
  • Journal article (peer-reviewed)abstract
    • Titania and titania modified with 3 and 12 mu mol Ce/m(2) surface area of the titania were prepared and were used as supports for copper oxide. Preparations with 3 and 12 mu mol CuOx/m(2) surface area of the support were tested for the combustion of CO, ethyl acetate, and ethanol. The results show that the Ce-doped titania surface is good as support for CuOx and that the cerium not only enhances the activity of the copper species, but also stabilises the surface area of the TiO2 support in the presence of copper oxide. Additions of Al, K, and La are also found to stabilise the TiO2 support but, compared with Ce, these elements do not to the same extent enhance the activity of the copper species. Acetaldehyde is observed to be an intermediate in the combustion of both ethanol and ethyl acetate over Cu-Ce-Ti-O catalysts. Since acetaldehyde is more harmful than any of the reactants and also is photochemically active, it is in applications important to assure that the combustion is complete. Cu-Ce-Ti-O catalysts show good performance not only for feeds without water vapour, but also for humid feeds. Although the concentrations of intermediates are affected by the addition of water, there is little effect on the temperature required for obtaining complete conversion to carbon dioxide and water. Characterisation with XRD, FT-Raman, TPR, and XPS indicates that the dispersed copper species are in the form of patches or a bidimensional layer which interacts with the surface of the support. When the content of cerium and copper is low, other types of dispersed copper species are present, which possibly are monomers or dimers. The copper species are predominantly Cu2+ species. (C) 1998 Academic Press
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  • Larsson, PO, et al. (author)
  • Oxides of copper, ceria promoted copper, manganese and copper manganese on Al2O3 for the combustion of CO, ethyl acetate and ethanol
  • 2000
  • In: Applied Catalysis B: Environmental. - 0926-3373. ; 24:3-4, s. 175-192
  • Journal article (peer-reviewed)abstract
    • Combustion of CO, ethyl acetate and ethanol was studied over CuOx/Al2O3, CuOx-CeO2/Al2O3, CuMn2O4/Al2O3 and Mn2O3/Al2O3 catalysts. It was found that modification of the alumina with ceria before subsequent copper oxide deposition increases the activity for combustion of CO substantially, but the effect of ceria was small on the combustion of ethyl acetate and ethanol, The activity increases with the CuOx loading until crystalline CuO particles are formed, which contribute little to the total active surface, The CuOx-CeO2/Al2O3 catalyst is more active than the CuMn2O4/Al2O3 catalyst for the oxidation of CO but the CuMn2O4/Al2O3 catalyst is more active for the combustion of ethyl acetate and ethanol. Thermal ageing and water vapour in the feed caused a modest decrease in activity and did not affect the CuOx-CeO2/Al2O3 and CuMn2O4/Al2O3 catalysts differently. In addition, no difference in intermediates formed over the two catalysts was observed. Characterisation with XRD, FT-Raman and TPR indicates that the copper oxide is present as a copper aluminate surface phase on alumina at low loading. At high loading, bulk CuO crystallites are present as well. Modification of the alumina with ceria before the copper oxide deposition gives well dispersed copper oxide species and bulk CuO crystallites associated to the ceria, in addition to the two copper oxide species on the bare alumina. The distribution of copper species depends on the ceria and copper oxide loading. The alumina supported copper manganese oxide and manganese oxide catalysts consist mainly of crystalline CuMn2O4 and Mn2O3, respectively, on Al2O3 (C) 2000 Elsevier Science B.V. All rights reserved.
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  • Larsson, PO, et al. (author)
  • Supported metal oxides for catalytic combustion of CO and VOCs emissions: Preparation of titania overlayers on a macroporous support
  • 1997
  • In: Catalysis Today. - 0920-5861. ; 35:1-2, s. 137-144
  • Journal article (peer-reviewed)abstract
    • TiO2 (anatase), SiO2 and gamma-Al2O3 were used as supports for Co-, Cu-, Fe- and Mn-oxide with a loading of active phase corresponding to one theoretical layer. The catalysts were tested for the combustion of CO and toluene, and the best combinations with active phase and support were submitted to a deactivation test in a waste gas incinerator for 50 days. The catalyst screening showed that CuOx/TiO2 was the most promising system. To design a catalyst with good activity and transport properties, a macroporous substrate was coated with TiO2 for use as a support for Cu-oxide, Titania overlayers were prepared by precipitation from oxychloride, tetrachloride and alkoxide, and stabilisation with ZrO2 and SiO2 was tried. The results show that precipitation from oxychloride gives the best properties and that addition of ZrO2 gives enhanced activity to the catalyst, while SiO2 addition produces increased stability.
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  • Lehmann, S, et al. (author)
  • Targeting p53 in vivo : a first-in-man study with the p53-targeting compound APR-246 in refractory hematologic malignancies and prostate cancer
  • 2012
  • In: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 30:29, s. 3633-3639
  • Journal article (peer-reviewed)abstract
    • PURPOSE: APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246.PATIENTS AND METHODS: APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg.RESULTS: MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response.CONCLUSION: We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.
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  • Lundin, Erik, et al. (author)
  • Experimental Determination and Prediction of the Fitness Effects of Random Point Mutations in the Biosynthetic Enzyme HisA
  • 2018
  • In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 35:3, s. 704-718
  • Journal article (peer-reviewed)abstract
    • The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the L-histidine biosynthesis pathway of Salmonella enterica. For the full set of mutants, the distribution was bimodal with many apparently neutral mutations and many lethal mutations. For a subset of 81 single, nonsynonymous mutants most mutations appeared neutral at high expression levels, whereas at low expression levels only a few mutations were neutral. Furthermore, we examined how the magnitude of the observed fitness effects was correlated to several measures of biophysical properties and phylogenetic conservation.We conclude that for HisA: (i) The effect of mutations can be masked by high expression levels, such that mutations that are deleterious to the function of the protein can still be neutral with regard to organism fitness if the protein is expressed at a sufficiently high level; (ii) the shape of the fitness distribution is dependent on the extent to which the protein is rate-limiting for growth; (iii) negative epistatic interactions, on an average, amplified the combined effect of nonsynonymous mutations; and (iv) no single sequence-based predictor could confidently predict the fitness effects of mutations in HisA, but a combination of multiple predictors could predict the effect with a SD of 0.04 resulting in 80% of the mutations predicted within 12% of their observed selection coefficients.
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  • Puértolas-Balint, Fabiola, et al. (author)
  • Mutations that increase expression of the EmrAB-TolC efflux pump confer increased resistance to nitroxoline in Escherichia coli
  • 2020
  • In: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 75:2, s. 300-308
  • Journal article (peer-reviewed)abstract
    • ObjectivesTo determine the mechanism of resistance to the antibiotic nitroxoline in Escherichia coli.MethodsSpontaneous nitroxoline-resistant mutants were selected at different concentrations of nitroxoline. WGS and strain reconstruction were used to define the genetic basis for the resistance. The mechanistic basis of resistance was determined by quantitative PCR (qPCR) and by overexpression of target genes. Fitness costs of the resistance mutations and cross-resistance to other antibiotics were also determined.ResultsMutations in the transcriptional repressor emrR conferred low-level resistance to nitroxoline [nitroxoline MIC (MICNOX)=16 mg/L] by increasing the expression of the emrA and emrB genes of the EmrAB-TolC efflux pump. These resistant mutants showed no fitness reduction and displayed cross-resistance to nalidixic acid. Second-step mutants with higher-level resistance (MICNOX=32–64 mg/L) had mutations in the emrR gene, together with either a 50 kb amplification, a mutation in the gene marA, or an IS upstream of the lon gene. The latter mutations resulted in higher-level nitroxoline resistance due to increased expression of the tolC gene, which was confirmed by overexpressing tolC from an inducible plasmid in a low-level resistance mutant. Furthermore, the emrR mutations conferred a small increase in resistance to nitrofurantoin only when combined with an nfsAB double-knockout mutation. However, nitrofurantoin-resistant nfsAB mutants showed no cross-resistance to nitroxoline.ConclusionsMutations in different genes causing increased expression of the EmrAB-TolC pump lead to an increased resistance to nitroxoline. The structurally similar antibiotics nitroxoline and nitrofurantoin appear to have different modes of action and resistance mechanisms.
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  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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  • Skårman, Björn, et al. (author)
  • Carbon monoxide oxidation on copper oxide thin films supported on corrugated cerium dioxide {111} and {001} surfaces
  • 1999
  • In: Journal of Catalysis. - : Elsevier BV. - 1090-2694 .- 0021-9517. ; 181:1, s. 6-15
  • Journal article (peer-reviewed)abstract
    • Thin films of CeO2 with and without a thin layer of copper oxide were prepared by rf magnetron sputtering on surfaces of alpha-Al2O3 (sapphire) substrates. Careful characterisation of the surfaces was performed down to the atomic level using high-resolution electron-microscopy, atomic force microscopy, and X-ray photoelectron spectroscopy. Surprisingly, the as-deposited, corrugated ceria surfaces, nominally (001), consist exclusively of {111}-type lattice planes, but, upon annealing at 800 degrees C, a well-defined portion of (001) surfaces are formed. Oxidation of carbon monoxide to carbon dioxide was studied, having the prepared films in a stirred batch reactor. A batch reactor was chosen so that the conversion over the small sample surface area (ca 10(-4) m(2)) could be monitored as a function of the reaction time. The activity of copper oxide on annealed ceria surfaces is markedly higher than on nonannealed surfaces, indicating a favourable synergetic effect between the ceria (001) surface and the copper oxide phase. (C) 1999 Academic Press.
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  • Soder, B, et al. (author)
  • Unique database study linking gingival inflammation and smoking in carcinogenesis
  • 2015
  • In: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 370:1661, s. 20140041-
  • Journal article (peer-reviewed)abstract
    • We investigated statistical association between gingival inflammation and cancer in a group of patients followed up for 26 years with the hypothesis that gingival inflammation affects carcinogenesis. Altogether, 1676 30- to 40-year-old subjects from Stockholm were clinically examined in 1985. In 2011, we compared the baseline oral examination and follow-up data with cancer diagnoses sourced from the Swedish national hospital register databases. Of 1676 individuals, 89 (55 women, 34 men) had got cancer by the year 2011. Women were found to be at higher risk for cancer than men. Smoking (expressed in pack-years) had been more prevalent in the cancer group than in those with no cancer diagnosis. Gingival index, marker of gingival inflammation, was higher in the cancer group than in subjects with no cancer. There were no significant differences between the groups regarding age, education, dental plaque and calculus index scores, or in the number of missing teeth. In multiple logistic regression analysis with cancer as the dependent variable and several independent variables, pack-years of smoking appeared to be a principal independent predictor with odds ratio (OR) 1.32 while gingival inflammation showed OR 1.29. Hence, our present findings showed that together with smoking, gingival inflammation indeed associated with the incidence of cancer in this cohort.
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  • Svegmark, K, et al. (author)
  • Comparison of potato amylopectin starches and potato starches - influence of year and variety
  • 2002
  • In: Carbohydrate Polymers. - 0144-8617. ; 47:4, s. 331-340
  • Journal article (peer-reviewed)abstract
    • Starches from three potato varieties and their respective transformants producing amylopectin starch were studied over a period of 3 years. The gelatinisation, swelling and dispersion properties were studied using differential scanning calorimetry (DSC), X-ray diffraction, swelling capacity measurements and a Brabender Viscograph. The potato amylopectin starches (PAP) exhibited higher endothermic temperatures as well as higher enthalpies than the normal potato starches (NPS). PAP samples gave rise to an exceptionally sharp viscosity peak during gelatinisation and a relatively low increase in viscosity on cooling. Swelling capacity measurements showed that PAP granules swelled more rapidly, and that the dispersion of the swollen granules occurred at a lower temperature (85 degreesC). Analysis of variance (ANOVA) also revealed that the year influenced the DSC results, and that both year and variety affect some of the Brabender parameters. Furthermore, the PAP and NPS samples were subjected to heat-moisture treatment at three different moisture levels, and the Brabender viscosity properties were studied. (C) 2002 Elsevier Science Ltd. All rights reserved.
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  • Tang, Po-Cheng, et al. (author)
  • A Microfluidic Chip for Studies of the Dynamics of Antibiotic Resistance Selection in Bacterial Biofilms
  • 2022
  • In: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 12
  • Journal article (peer-reviewed)abstract
    • Biofilms are arguably the most important mode of growth of bacteria, but how antibiotic resistance emerges and is selected in biofilms remains poorly understood. Several models to study evolution of antibiotic resistance have been developed, however, their usability varies depending on the nature of the biological question. Here, we developed and validated a microfluidic chip (Brimor) for studying the dynamics of enrichment of antibiotic-resistant bacteria in biofilms using real-time monitoring with confocal microscopy. In situ extracellular cellulose staining and physical disruption of the biomass confirmed Escherichia coli growth as biofilms in the chip. We showed that seven generations of growth occur in 16 h when biofilms were established in the growth chambers of Brimor, and that bacterial death and growth rates could be estimated under these conditions using a plasmid with a conditional replication origin. Additionally, competition experiments between antibiotic-susceptible and -resistant bacteria at sub-inhibitory concentrations demonstrated that the antibiotic ciprofloxacin selected for antibiotic resistance in bacterial biofilms at concentrations 17-fold below the minimal inhibitory concentration of susceptible planktonic bacteria. Overall, the microfluidic chip is easy to use and a relevant model for studying the dynamics of selection of antibiotic resistance in bacterial biofilms and we anticipate that the Brimor chip will facilitate basic research in this area.
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49.
  • Tang, Po-Cheng (author)
  • Antibiotic interactions and selection for resistance in biofilms
  • 2023
  • Doctoral thesis (other academic/artistic)abstract
    • The challenges posed by antibiotic-resistant bacteria in treating infections, particularly those associated with biofilms, require a deeper understanding of this lifestyle and its connection to resistance selection. Additionally, gaining insights into drug interactions is crucial for enhancing combination treatment efficacy and mitigating resistance development. This thesis is divided into these two main themes, each consisting of individual papers with specific objectives and aims that tackle these two themes.The first introduces a proof-of-concept microfluidic chip named Brimor, which demonstrates the selection of ciprofloxacin-resistant mutants in Escherichia coli biofilms at concentrations below the minimum inhibitory concentration (sub-MIC). Brimor exhibits potential applications beyond antibiotics and bacteria.The second explores the emergence of resistance in both planktonic and biofilm lifestyles. Using the FlexiPeg model and uropathogenic E. coli, the fitness cost and minimal selective concentrations were assessed for five antibiotics and six resistance-conferring mutations during biofilm and planktonic growth. This analysis revealed resistance development in both lifestyles at sub-MIC.Furthermore, an assay called CombiANT® was developed and validated with three major pathogens, enabling simple quantification and subsequent categorization of antibiotic interactions. This assay demonstrated comparable performance to the gold-standard checkerboard and time-kill assays. CombiANT® also shows potential for applications beyond antibiotics and bacteria.Isolate-specific interaction profiling was emphasized as crucial among five important Gram-negative pathogens for achieving precise and effective combination therapy. Interactions of clinically used antibiotic combinations varied significantly between and within susceptible species, with additive and antagonistic interactions being the most common. Only a small percentage exhibited clinically relevant synergy.The mutations associated with synergy and loss of synergy for the tetracycline and spectinomycin combination in E. coli was elucidated. Genetic changes associated with efflux regulation and metabolic pathways were identified as factors contributing to the loss of synergy in mutants. The bioavailability model was the prevailing mechanism of action accounting for synergy and loss of synergy for the combination.In summary, the papers presented in this thesis provide valuable insights on antibiotic resistance selection in biofilms, antibiotic interactions, and the development of innovative tools for studying biofilms and combination therapies. Further understanding of these factors is necessary for applying these findings in clinical settings and to optimize combination strategies for effective personalized therapy and antibiotic stewardship.
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50.
  • Tang, Po-Cheng, et al. (author)
  • Low conservation of antibiotic interactions between and within Gram-negative bacterial species
  • In: PLoS biology. - 1544-9173 .- 1545-7885.
  • Journal article (other academic/artistic)abstract
    • Treatments with antibiotic combinations are becoming increasingly important even though the supposed clinical benefits of combinations are in many cases unclear. Here, we systematically examined how several clinically used antibiotics interact and affect the antimicrobial efficacy against five especially problematic Gram-negative pathogens. A total of 232 bacterial isolates were tested against different pairwise antibiotic combinations spanning five classes, and the ability of all combinations in inhibiting growth was quantified. Descriptive statistics, PCA and Spearman’s rank correlation matrix were used to determine correlations between the different combinations on interaction outcome. Several important conclusions can be drawn from the 696 examined interactions. Firstly, within a species the interactions are often isolate-specific for a given antibiotic combination and can range from antagonistic to synergistic. Secondly, interactions may vary extensively between different Gram- negative species. Thirdly, additive and antagonistic interactions are the most common observed across species and antibiotics, with 99.7 % of all isolate and antibiotic combinations belonging to either of these two types and with only 0.3 % showing synergy. These findings suggest that to achieve the highest precision and efficacy of combination therapy, isolate-specific interaction profiling ought to be routinely performed, in particular to avoid using drug combinations that show antagonistic interaction and an expected associated reduction in efficacy, but also to discover rare and potentially valuable synergistic interactions. 
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