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Sökning: WFRF:(Moritz Per)

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1.
  • Sundqvist, Bertil, et al. (författare)
  • Physical properties of pressure polymerized C60
  • 1996
  • Ingår i: Fullerenes: Recent Advances in the Chemistry and Physics of Fullerenes and Related Materials, volume 3. - Pennington, NJ : The Electrochemical Society. - 1566771625 ; , s. 1014-1028
  • Konferensbidrag (refereegranskat)abstract
    • We present in this paper an overview of the physical properties of the high pressure polymerized C60 phase commonly known as "soft fcc". This phase has been studied by several methods over wide ranges in temperature T and/or pressure, p. We present here experimental information about the specific heat capacity, the thermal expansion coefficient, the lattice structure, and the thermal conductivity, and we also show results obtained by NMR and Raman spectroscopy. All data presented agree with the accepted model that the individual molecules in this phase are covalently bound to form linear molecular chains. In particular, the NMR data show clearly the presence of covalent bonds, and the Raman data exhibit several new lines at very low energies connected with chain vibrations. Thermal conductivity data obtained during polymerization show both the time dependence of the process and that polymerization occurs at lower p and T than observed previously for this phase.
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3.
  • Abdellah, Tebani, et al. (författare)
  • Integration of molecular profiles in a longitudinal wellness profiling cohort.
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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6.
  • Barucca, G., et al. (författare)
  • Study of excited Ξ baryons with the P¯ ANDA detector
  • 2021
  • Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The study of baryon excitation spectra provides insight into the inner structure of baryons. So far, most of the world-wide efforts have been directed towards N∗ and Δ spectroscopy. Nevertheless, the study of the double and triple strange baryon spectrum provides independent information to the N∗ and Δ spectra. The future antiproton experiment P¯ANDA will provide direct access to final states containing a Ξ¯ Ξ pair, for which production cross sections up to μb are expected in p¯p reactions. With a luminosity of L= 10 31 cm- 2 s- 1 in the first phase of the experiment, the expected cross sections correspond to a production rate of ∼106events/day. With a nearly 4 π detector acceptance, P¯ANDA will thus be a hyperon factory. In this study, reactions of the type p¯p → Ξ¯ +Ξ∗ - as well as p¯p → Ξ¯ ∗ +Ξ- with various decay modes are investigated. For the exclusive reconstruction of the signal events a full decay tree fit is used, resulting in reconstruction efficiencies between 3 and 5%. This allows high statistics data to be collected within a few weeks of data taking.
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7.
  • Barucca, G., et al. (författare)
  • The potential of Λ and Ξ- studies with PANDA at FAIR
  • 2021
  • Ingår i: European Physical Journal A. - : Springer Nature. - 1434-6001 .- 1434-601X. ; 57:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The antiproton experiment PANDA at FAIR is designed to bring hadron physics to a new level in terms of scope, precision and accuracy. In this work, its unique capability for studies of hyperons is outlined. We discuss ground-state hyperons as diagnostic tools to study non-perturbative aspects of the strong interaction, and fundamental symmetries. New simulation studies have been carried out for two benchmark hyperon-antihyperon production channels: p¯ p→ Λ¯ Λ and p¯ p→ Ξ¯ +Ξ-. The results, presented in detail in this paper, show that hyperon-antihyperon pairs from these reactions can be exclusively reconstructed with high efficiency and very low background contamination. In addition, the polarisation and spin correlations have been studied, exploiting the weak, self-analysing decay of hyperons and antihyperons. Two independent approaches to the finite efficiency have been applied and evaluated: one standard multidimensional efficiency correction approach, and one efficiency independent approach. The applicability of the latter was thoroughly evaluated for all channels, beam momenta and observables. The standard method yields good results in all cases, and shows that spin observables can be studied with high precision and accuracy already in the first phase of data taking with PANDA.
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8.
  • Bäckström, Daniel, 1973- (författare)
  • Managing and Exploring Large Data Sets Generated by Liquid Separation - Mass Spectrometry
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A trend in natural science and especially in analytical chemistry is the increasing need for analysis of a large number of complex samples with low analyte concentrations. Biological samples (urine, blood, plasma, cerebral spinal fluid, tissue etc.) are often suitable for analysis with liquid separation mass spectrometry (LS-MS), resulting in two-way data tables (time vs. m/z). Such biological 'fingerprints' taken for all samples in a study correspond to a large amount of data. Detailed characterization requires a high sampling rate in combination with high mass resolution and wide mass range, which presents a challenge in data handling and exploration. This thesis describes methods for managing and exploring large data sets made up of such detailed 'fingerprints' (represented as data matrices). The methods were implemented as scripts and functions in Matlab, a wide-spread environment for matrix manipulations. A single-file structure to hold the imported data facilitated both easy access and fast manipulation. Routines for baseline removal and noise reduction were intended to reduce the amount of data without loosing relevant information. A tool for visualizing and exploring single runs was also included. When comparing two or more 'fingerprints' they usually have to be aligned due to unintended shifts in analyte positions in time and m/z. A PCA-like multivariate method proved to be less sensitive to such shifts, and an ANOVA implementation made it easier to find systematic differences within the data sets. The above strategies and methods were applied to complex samples such as plasma, protein digests, and urine. The field of application included urine profiling (paracetamole intake; beverage effects), peptide mapping (different digestion protocols) and search for potential biomarkers (appendicitis diagnosis) . The influence of the experimental factors was visualized by PCA score plots as well as clustering diagrams (dendrograms).
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9.
  • Capo, Eric, et al. (författare)
  • Oxygen-deficient water zones in the Baltic Sea promote uncharacterized Hg methylating microorganisms in underlying sediments
  • 2022
  • Ingår i: Limnology and Oceanography. - : Wiley. - 1939-5590 .- 0024-3590. ; 67:1, s. 135-146
  • Tidskriftsartikel (refereegranskat)abstract
    • Human-induced expansion of oxygen-deficient zones can have dramatic impacts on marine systems and its resident biota. One example is the formation of the potent neurotoxic methylmercury (MeHg) that is mediated by microbial methylation of inorganic divalent Hg (HgII) under oxygen-deficient conditions. A negative consequence of the expansion of oxygen-deficient zones could be an increase in MeHg production due to shifts in microbial communities in favor of microorganisms methylating Hg. There is, however, limited knowledge about Hg-methylating microbes, i.e., those carrying hgc genes critical for mediating the process, from marine sediments. Here, we aim to study the presence of hgc genes and transcripts in metagenomes and metatranscriptomes from four surface sediments with contrasting concentrations of oxygen and sulfide in the Baltic Sea. We show that potential Hg methylators differed among sediments depending on redox conditions. Sediments with an oxygenated surface featured hgc-like genes and transcripts predominantly associated with uncultured Desulfobacterota (OalgD group) and Desulfobacterales (including Desulfobacula sp.) while sediments with a hypoxic-anoxic surface included hgc-carrying Verrucomicrobia, unclassified Desulfobacterales, Desulfatiglandales, and uncharacterized microbes. Our data suggest that the expansion of oxygen-deficient zones in marine systems may lead to a compositional change of Hg-methylating microbial groups in the sediments, where Hg methylators whose metabolism and biology have not yet been characterized will be promoted and expand.
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10.
  • Chrobok, Daria, et al. (författare)
  • Dissecting the Metabolic Role of Mitochondria during Developmental Leaf Senescence
  • 2016
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 172:4, s. 2132-2153
  • Tidskriftsartikel (refereegranskat)abstract
    • The functions of mitochondria during leaf senescence, a type of programmed cell death aimed at the massive retrieval of nutrients from the senescing organ to the rest of the plant, remain elusive. Here, combining experimental and analytical approaches, we showed that mitochondrial integrity in Arabidopsis (Arabidopsis thaliana) is conserved until the latest stages of leaf senescence, while their number drops by 30%. Adenylate phosphorylation state assays and mitochondrial respiratory measurements indicated that the leaf energy status also is maintained during this time period. Furthermore, after establishing a curated list of genes coding for products targeted to mitochondria, we analyzed in isolation their transcript profiles, focusing on several key mitochondrial functions, such as the tricarboxylic acid cycle, mitochondrial electron transfer chain, iron-sulfur cluster biosynthesis, transporters, as well as catabolic pathways. In tandem with a metabolomic approach, our data indicated that mitochondrial metabolism was reorganized to support the selective catabolism of both amino acids and fatty acids. Such adjustments would ensure the replenishment of alpha-ketoglutarate and glutamate, which provide the carbon backbones for nitrogen remobilization. Glutamate, being the substrate of the strongly up-regulated cytosolic glutamine synthase, is likely to become a metabolically limiting factor in the latest stages of developmental leaf senescence. Finally, an evolutionary age analysis revealed that, while branched-chain amino acid and proline catabolism are very old mitochondrial functions particularly enriched at the latest stages of leaf senescence, auxin metabolism appears to be rather newly acquired. In summation, our work shows that, during developmental leaf senescence, mitochondria orchestrate catabolic processes by becoming increasingly central energy and metabolic hubs.
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11.
  • 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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12.
  • Franzén, Gunilla, et al. (författare)
  • National implementation commission for Eurocode 7 for joint development of geotechnical engineering practice
  • 2022
  • Ingår i: Proceedings of 20th International Conference on Soil Mechanics and Geotechnical Engineering. - St Ives. ; , s. 4759-4764
  • Konferensbidrag (refereegranskat)abstract
    • The objective of this paper is to describe how upcoming design code revisions can be used to facilitate a national joint development of geotechnical engineering practice. The paper describes the Swedish experience with establishing a national implementation commission for the second generation of Eurocode 7. The purpose is to inspire others to take similar initiatives when new design codes and standards are introduced. The paper covers how stakeholders from all parts of the Swedish geotechnical construction industry established the implementation commission IEG 2.0 as a non-profit organization and how obstacles were solved. This includes financing and establishing an efficient work process to analyze the many upcoming changes to the Eurocode clauses. This in fact being the second Swedish implementation commission for Eurocode 7, the paper concludes that this procedure of working together in the industry is a great success, facilitating an increased competence among Swedish geotechnical engineers and therefore also increased competitiveness of the Swedish geotechnical construction industry.
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13.
  • Furukawa, Toshi A., et al. (författare)
  • Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
  • 2021
  • Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
  • Forskningsöversikt (refereegranskat)abstract
    • Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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14.
  • Hertz, Hans M., et al. (författare)
  • Laboratory x-ray micro imaging : Sources, optics, systems and applications
  • 2009
  • Ingår i: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 186
  • Tidskriftsartikel (refereegranskat)abstract
    • We summarize the recent progress in laboratory-scale soft and hard x-ray micro imaging in Stockholm. Our soft x-ray work is based on liquid-jet laser-plasma sources which are combined with diffractive and multilayer optics to form laboratory x-ray microscopes. In the hard x-ray regime the imaging is based on a liquid-metal-jet electron-impact source which provides the necessary coherence to allow phase-contrast imaging with high fidelity.
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15.
  • Hunold, Oliver, et al. (författare)
  • Correlative theoretical and experimental investigation of the formation of AIYB(14) and competing phases
  • 2016
  • Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 119:8
  • Tidskriftsartikel (refereegranskat)abstract
    • The phase formation in the boron-rich section of the Al-Y-B system has been explored by a correlative theoretical and experimental research approach. The structure of coatings deposited via high power pulsed magnetron sputtering from a compound target was studied using elastic recoil detection analysis, electron energy loss spectroscopy spectrum imaging, as well as X-ray and electron diffraction data. The formation of AlYB14 together with the (Y,Al)B-6 impurity phase, containing 1.8 at. % less B than AlYB14, was observed at a growth temperature of 800 degrees C and hence 600 degrees C below the bulk synthesis temperature. Based on quantum mechanical calculations, we infer that minute compositional variations within the film may be responsible for the formation of both icosahedrally bonded AlYB14 and cubic (Y,Al)B-6 phases. These findings are relevant for synthesis attempts of all boron rich icosahedrally bonded compounds with the space group: Imma that form ternary phases at similar compositions.
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16.
  • Jönsson, Daniel, et al. (författare)
  • Gingival tissue transcriptomes in experimental gingivitis.
  • 2011
  • Ingår i: Journal of clinical periodontology. - : John Wiley & Sons. - 1600-051X .- 0303-6979. ; 38:7, s. 599-611
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated the sequential gene expression in the gingiva during the induction and resolution of experimental gingivitis.
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17.
  • Kalman, Janos L, et al. (författare)
  • Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
  • 2019
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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18.
  • Karyotaki, Eirini, et al. (författare)
  • Do guided internet-based interventions result in clinically relevant changes for patients with depression? : An individual participant data meta-analysis
  • 2018
  • Ingår i: Clinical Psychology Review. - : Elsevier. - 0272-7358 .- 1873-7811. ; 63, s. 80-92
  • Forskningsöversikt (refereegranskat)abstract
    • Little is known about clinically relevant changes in guided Internet-based interventions for depression. Moreover, methodological and power limitations preclude the identification of patients' groups that may benefit more from these interventions. This study aimed to investigate response rates, remission rates, and their moderators in randomized controlled trials (RCTs) comparing the effect of guided Internet-based interventions for adult depression to control groups using an individual patient data meta-analysis approach. Literature searches in PubMed, Embase, PsycINFO and Cochrane Library resulted in 13,384 abstracts from database inception to January 1, 2016. Twenty-four RCTs (4889 participants) comparing a guided Internet-based intervention with a control group contributed data to the analysis. Missing data were multiply imputed. To examine treatment outcome on response and remission, mixed-effects models with participants nested within studies were used. Response and remission rates were calculated using the Reliable Change Index. The intervention group obtained significantly higher response rates (OR = 2.49, 95% CI 2.17-2.85) and remission rates compared to controls (OR = 2.41, 95% CI 2.07-2.79). The moderator analysis indicated that older participants (OR = 1.01) and native-born participants (1.66) were more likely to respond to treatment compared to younger participants and ethnic minorities respectively. Age (OR = 1.01) and ethnicity (1.73) also moderated the effects of treatment on remission.Moreover, adults with more severe depressive symptoms at baseline were more likely to remit after receiving intemet-based treatment (OR = 1.19). Guided Internet-based interventions lead to substantial positive treatment effects on treatment response and remission at post-treatment. Thus, such interventions may complement existing services for depression and potentially reduce the gap between the need and provision of evidence-based treatments.
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19.
  • Karyotaki, Eirini, et al. (författare)
  • Internet-Based Cognitive Behavioral Therapy for Depression : A Systematic Review and Individual Patient Data Network Meta-analysis
  • 2021
  • Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:4, s. 361-371
  • Forskningsöversikt (refereegranskat)abstract
    • IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them.OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information.DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019.STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization.DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression.MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire-9 (PHQ-9) scores.RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9.CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
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20.
  • Karyotaki, E., et al. (författare)
  • Predictors of treatment dropout in self-guided web-based interventions for depression: an individual patient data meta-analysis
  • 2015
  • Ingår i: Psychological Medicine. - : CAMBRIDGE UNIV PRESS. - 0033-2917 .- 1469-8978. ; 45:13, s. 2717-2726
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. It is well known that web-based interventions can be effective treatments for depression. However, dropout rates in web-based interventions are typically high, especially in self-guided web-based interventions. Rigorous empirical evidence regarding factors influencing dropout in self-guided web-based interventions is lacking due to small study sample sizes. In this paper we examined predictors of dropout in an individual patient data meta-analysis to gain a better understanding of who may benefit from these interventions. Method. A comprehensive literature search for all randomized controlled trials (RCTs) of psychotherapy for adults with depression from 2006 to January 2013 was conducted. Next, we approached authors to collect the primary data of the selected studies. Predictors of dropout, such as socio-demographic, clinical, and intervention characteristics were examined. Results. Data from 2705 participants across ten RCTs of self-guided web-based interventions for depression were analysed. The multivariate analysis indicated that male gender [relative risk (RR) 1.08], lower educational level (primary education, RR 1.26) and co-morbid anxiety symptoms (RR 1.18) significantly increased the risk of dropping out, while for every additional 4 years of age, the risk of dropping out significantly decreased (RR 0.94). Conclusions. Dropout can be predicted by several variables and is not randomly distributed. This knowledge may inform tailoring of online self-help interventions to prevent dropout in identified groups at risk.
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21.
  • Keller, Annika, et al. (författare)
  • Mutations in the gene encoding PDGF-B cause brain calcifications in humans and mice
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:9, s. 1077-
  • Tidskriftsartikel (refereegranskat)abstract
    • Calcifications in the basal ganglia are a common incidental finding and are sometimes inherited as an autosomal dominant trait ( idiopathic basal ganglia calcification (IBGC)). Recently, mutations in the PDGFRB gene coding for the platelet-derived growth factor receptor beta (PDGF-R beta) were linked to IBGC. Here we identify six families of different ancestry with nonsense and missense mutations in the gene encoding PDGF-B, the main ligand for PDGF-R beta. We also show that mice carrying hypomorphic Pdgfb alleles develop brain calcifications that show age-related expansion. The occurrence of these calcium depositions depends on the loss of endothelial PDGF-B and correlates with the degree of pericyte and blood-brain barrier deficiency. Thus, our data present a clear link between Pdgfb mutations and brain calcifications in mice, as well as between PDGFB mutations and IBGC in humans.
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22.
  • Kramer, John Vincent, 1990- (författare)
  • Essays on Macroeconomics, Monetary Policy and Mobility
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The Cyclicality of Earnings Growth Along the Distribution - Causes and ConsequencesEarnings growth is more procyclical at the bottom of the income distribution than at the top. Using high-quality administrative data from Germany, I show that the heterogeneity is chiefly driven by transitions between employment and non-employment, specifically job-finding. I build a heterogeneous agent business cycle model that can rationalize these empirical findings. Agents in the model endogenously choose where to search for work in a labor market that features directed search. The model reproduces the heterogeneous procyclicality of earnings growth, as well as the contribution of job-finding, along the income distribution. I use this model to evaluate two policies aimed at reducing business cycle risk: countercyclical hiring subsidies and Universal Basic Income (UBI). The first policy proposal increases welfare relative to the baseline economy. Implementing UBI decreases the volatility of aggregate consumption but decreases welfare overall.Monetary Policy and Liquidity Constraints: Evidence from the Euro AreaWe quantify the relationship between the response of output to monetary policy shocks and the share of liquidity constrained households. We do so in the context of the euro area using a Local Projections Instrumental Variables estimation. We construct an instrument for changes in interest rates from changes in overnight indexed swap rates in a narrow time window around ECB announcements. Monetary policy shocks have heterogeneous effects on output across countries. Using micro data, we show that the elasticity of output to monetary policy is larger in countries that have a larger fraction of households that are liquidity constrained.The Curious Incidence of Monetary Policy Across the Income DistributionWe use high-frequency administrative data from Germany to study the effects of monetary policy on incomes and employment prospects across the earnings distribution. Earnings growth at the bottom of the distribution is substantially more elastic to policy shocks. The unequal incidence is driven by differences in employment risk across the distribution - lower-earning households experience higher employment risk in response to contractionary shocks. Our empirical estimates imply significant amplification of the aggregate consumption response to shocks to future consumption and interest rates.It Runs in the Family: Occupational Choice and the Allocation of TalentChildren frequently grow up to work in the same jobs as their parents. Using unique data on worker skills and personality traits, and administrative data on the labor market outcomes of Swedish men, we study occupational choice and its impact on the allocation of talent. We document that sons are disproportionately more likely to follow into the same occupation as their fathers, across all levels of skills and earnings. We estimate a general equilibrium Roy model with costly occupational choice and heterogeneous entry barriers depending on parental background. We find that these entry barriers lead to substantial misallocation. Equalizing entry costs across workers leads occupational following to fall by half. However, this reallocation of workers increases intergenerational mobility and aggregate income only modestly, because sons move to occupations that are similar to those of their fathers in income and skill requirements. Our findings are consistent with intergenerational persistence in occupations and incomes reflecting transmission of skills and sorting on comparative advantage.
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23.
  • Larsson, Per-Ola, et al. (författare)
  • A Framework for Nonlinear Model-Predictive Control Using Object-Oriented Modeling with a Case Study in Power Plant Start-Up
  • 2013
  • Ingår i: IEEE Conference on Computer Aided Control System Design (CACSD), 2013. - 9781479915644 ; , s. 346-351
  • Konferensbidrag (refereegranskat)abstract
    • In this paper, nonlinear model predictive control (NMPC) is applied to the start-up of a combined-cycle power plant. An object-oriented first-principle model library expressed in the high-level language Modelica has been written for the plant and used to set up the simulation and optimization models. The NMPC optimization problems are both encoded, using a high-level notation, and solved in the open-source framework JModelica.org. The results demonstrate the effectiveness of the framework and its high-level description. It bridges the gap between an intuitive physical modeling format and state of the art numerical optimization algorithms. Promising closed-loop control results are shown for plant start-up when the NMPC model contains parametric errors and the simulation model, corresponding to the real plant, is subject to disturbances.
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24.
  • Law, Simon R., et al. (författare)
  • Darkened leaves use different metabolic strategies for senescence and survival
  • 2018
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 177:1, s. 132-150
  • Tidskriftsartikel (refereegranskat)abstract
    • In plants, an individually darkened leaf initiates senescence much more rapidly than a leaf from a whole darkened plant. Combining transcriptomic and metabolomic approaches in Arabidopsis (Arabidopsis thaliana), we present an overview of the metabolic strategies that are employed in response to different darkening treatments. Under darkened plant conditions, the perception of carbon starvation drove a profound metabolic readjustment in which branched-chain amino acids and potentially monosaccharides released from cell wall loosening became important substrates for maintaining minimal ATP production. Concomitantly, the increased accumulation of amino acids with a high nitrogen-carbon ratio may provide a safety mechanism for the storage of metabolically derived cytotoxic ammonium and a pool of nitrogen for use upon returning to typical growth conditions. Conversely, in individually darkened leaf, the metabolic profiling that followed our 13C-enrichment assays revealed a temporal and differential exchange of metabolites, including sugars and amino acids, between the darkened leaf and the rest of the plant. This active transport could be the basis for a progressive metabolic shift in the substrates fueling mitochondrial activities, which are central to the catabolic reactions facilitating the retrieval of nutrients from the senescing leaf. We propose a model illustrating the specific metabolic strategies employed by leaves in response to these two darkening treatments, which support either rapid senescence or a strong capacity for survival.
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25.
  • Liebsch, Daniela, et al. (författare)
  • Metabolic control of arginine and ornithine levels paces the progression of leaf senescence
  • 2022
  • Ingår i: Plant Physiology. - : Oxford University Press. - 0032-0889 .- 1532-2548. ; 189:4, s. 1943-1960
  • Tidskriftsartikel (refereegranskat)abstract
    • Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts—likely due to the lack of induction of amino acids (AAs) transport—can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival.
  •  
26.
  • Liljeqvist, Moritz Lindquist, et al. (författare)
  • Neutrophil Elastase-Derived Fibrin Degradation Products Indicate Presence of Abdominal Aortic Aneurysms and Correlate with Intraluminal Thrombus Volume
  • 2018
  • Ingår i: Thrombosis and Haemostasis. - : Schattauer GmbH Verlag für Medizin und Naturwissenschaften. - 0340-6245 .- 2567-689X. ; 118:2, s. 329-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The intraluminal thrombi (ILT) of abdominal aortic aneurysms (AAA) contain neutrophils, which can secrete elastase. We evaluated whether plasma neutrophil elastase-derived cross-linked fibrin degradation products (E-XDP) could reveal the presence, size and mechanical stress of AAAs and its ILTs. Methods E-XDP and D-dimer were measured in plasma from 37 male patients with AAA and 42 male controls. The ILT volumes of the AAAs and any coexisting aneurysms could be measured in 29 patients and finite element analysis was performed to estimate mechanical stress of the ILT. E-XDP, neutrophil elastase and neutrophil marker CD66acd were evaluated in aortic tissue with immunohistochemistry (IHC). The association between ILT volume and E-XDP was validated in a separate cohort (n = 51). Results E-XDP levels were elevated in patients with AAA compared with controls (p = 5.8e-13), indicated AAA with 98% sensitivity, 86% specificity and increased with presence of coexisting aneurysms. The association between AAA and increased E-XDP was independent of smoking, comorbidities and medication. E-XDP correlated with volume of all ILTs (r = 0.76, p = 4.5e-06), mean ILTstress (r = 0.46, p = 0.013) and the volume of the AAA-associated ILT (r = 0.64, p = 0.00017). E-XDP correlated stronger with ILT volume compared with D-dimer (r = 0.76 vs. r = 0.64, p = 0.018). The correlation between E-XDP and ILT volume was validated in the separate cohort (r = 0.53, p = 7.6e-05). IHC revealed E-XDP expression in the ILT, spatially related to neutrophil elastase and neutrophils. Conclusion E-XDP is a marker of the presence of AAA and coexisting aneurysms as well as the volume and mechanical stress of the ILT.
  •  
27.
  • Linden, Pernilla, et al. (författare)
  • Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling
  • 2016
  • Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 67:10, s. 3123-3135
  • Tidskriftsartikel (refereegranskat)abstract
    • Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a 13CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1. The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and 13C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions.
  •  
28.
  • Moritz, Per, 1961- (författare)
  • Fjällfolk : livsformer och kulturprocesser i Tärna socken under 1800- och 1900-talen
  • 1990
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this study is to investigate life forms and the dynamics of cultural processes in the parish of Tärna, Västerbotten. The material is an investigation of the life stories of two families, which have been investigated from an overall scientific aspect. The aim has been to examine the exploitation of resources by individuals and cognitive structures within the framework of ecological adaption. These aspects have been illuminated by the use of comprehensive source materials. Estate inventories have revealed different object categories which were associated with the exploitation of natural resources. Church registers, judgement books, tape recordings from folklore archives and the author's own interview material described life stories in a Saami mountain family and a settler family. It turned out that people in the mountains had supported themselves on a combination of stock-raising, hunting and fishing. Comprehensive socialized knowledge of the environment and its resources was a decisive factor for ecological adaption and survival. The settler family had a solid knowledge of various handicrafts. The Saami in Tärna have settled down at an early stage and abandoned their former nomadism. The Saamish family investigated had a strong sense of family identity and their living story-telling tradition strengthened their identity and became a uniting factor. At the end of the 19th century and the beginning of the 20th century innovations began to emerge in the mountain parish, which often came to revolutionize the whole life pattern. The process of cultural change in Tärna in the 20th century has been dramatic. It has included the development of technology, modernization and changing exploitation of resources. Through the investigation of the life stories of the two families a clear picture has emerged of the exploitation of resources and of values, i.e. the total life pattern.
  •  
29.
  • Peery, M Zachariah, et al. (författare)
  • Genetic analyses of historic and modern marbled murrelets suggest decoupling of migration and gene flow after habitat fragmentation.
  • 2010
  • Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 277:1682, s. 697-706
  • Tidskriftsartikel (refereegranskat)abstract
    • The dispersal of individuals among fragmented populations is generally thought to prevent genetic and demographic isolation, and ultimately reduce extinction risk. In this study, we show that a century of reduction in coastal old-growth forests, as well as a number of other environmental factors, has probably resulted in the genetic divergence of marbled murrelets (Brachyramphus marmoratus) in central California, despite the fact that 7 per cent of modern-sampled murrelets in this population were classified as migrants using genetic assignment tests. Genetic differentiation appears to persist because individuals dispersing from northern populations contributed relatively few young to the central California population, as indicated by the fact that migrants were much less likely to be members of parent-offspring pairs than residents (10.5% versus 45.4%). Moreover, a recent 1.4 per cent annual increase in the proportion of migrants in central California, without appreciable reproduction, may have masked an underlying decline in the resident population without resulting in demographic rescue. Our results emphasize the need to understand the behaviour of migrants and the extent to which they contribute offspring in order to determine whether dispersal results in gene flow and prevents declines in resident populations.
  •  
30.
  • Renberg, Linda, et al. (författare)
  • A metabolomic approach to study major metabolite changes during acclimation to limiting CO2 in chlamydomonas reinhardtii
  • 2010
  • Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 154:1, s. 187-196
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high-and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.
  •  
31.
  • Rubio, Carlos A., et al. (författare)
  • Assessing the Size of Polyp Phantoms in Tandem Colonoscopies
  • 2009
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:5, s. 1539-1545
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The size of colorectal neoplastic polyps is important for their clinical management. Materials and Methods: The size of 12 polyp phantoms was assessed in tandem colonoscopies carried out by 7 endoscopists differing in years of clinical endoscopical experience. The endoscopists measured, with (n=5) or without (n=2) the aid of open forceps, the largest diameter of 12 polyp phantoms. Measurements in two independent trials were compared with the gold standard-size assessed at The Department Of Production Engineering, The Royal Institute of Technology. Results: In tandem trials, 99.4% (167/168) of the measurements underscored the gold standard size. In the 1st trial, the size in all 84 measurements was underestimated by -40% (range -34% to -45%) and in the 2nd trial the size in 83 of the 84 measurements was underestimated by -34% (range -24% to -42%). Neither the age of the participant, nor the years of experience with clinical endoscopy improved the results obtained. The participants significantly underestimated larger devices (>= 20 mm) whereas the smallest "polyps" were also underestimated, but with a lower degree of inaccuracy. The absolute difference between the golden standard size and the mean of all measurements performed on each polyp in 167 out of 168 measurements followed a regular downward trend. The volume of the devices was one of the confounding factors in size assessment. When compared to the gold standard size, the larger the "polyp" size, the higher the degree of underestimation. This may be crucial considering that the risk for colorectal adenomas to shelter an invasive growth is 46%, for adenomas measuring >= 2 cm, a limit accepted as a guideline worldwide for the management of patients with large colorectal polyps. Conclusion: Considering the clinical implications of the results obtained, the possibility of developing a method that would allow the assessment of the true size of polyps in clinical colonoscopy, is being explored.
  •  
32.
  • Suur, Bianca E., et al. (författare)
  • Therapeutic potential of the Proprotein Convertase Subtilisin/Kexin family in vascular disease
  • 2022
  • Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.
  •  
33.
  • Warmbrunn, Moritz V., et al. (författare)
  • Oral histidine affects gut microbiota and MAIT cells improving glycemic control in type 2 diabetes patients
  • 2024
  • Ingår i: GUT MICROBES. - 1949-0976 .- 1949-0984. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Amino acids, metabolized by host cells as well as commensal gut bacteria, have signaling effects on host metabolism. Oral supplementation of the essential amino acid histidine has been shown to exert metabolic benefits. To investigate whether dietary histidine aids glycemic control, we performed a case-controlled parallel clinical intervention study in participants with type 2 diabetes (T2D) and healthy controls. Participants received oral histidine for seven weeks. After 2 weeks of histidine supplementation, the microbiome was depleted by antibiotics to determine the microbial contribution to histidine metabolism. We assessed glycemic control, immunophenotyping of peripheral blood mononucelar cells (PBMC), DNA methylation of PBMCs and fecal gut microbiota composition. Histidine improves several markers of glycemic control, including postprandial glucose levels with a concordant increase in the proportion of MAIT cells after two weeks of histidine supplementation. The increase in MAIT cells was associated with changes in gut microbial pathways such as riboflavin biosynthesis and epigenetic changes in the amino acid transporter SLC7A5. Associations between the microbiome and MAIT cells were replicated in the MetaCardis cohort. We propose a conceptual framework for how oral histidine may affect MAIT cells via altered gut microbiota composition and SLC7A5 expression in MAIT cells directly and thereby influencing glycemic control. Future studies should focus on the role of flavin biosynthesis intermediates and SLC7A5 modulation in MAIT cells to modulate glycemic control.
  •  
34.
  • Åkesson, Per, et al. (författare)
  • IdeS, a highly specific immunoglobulin G (IgG)-cleaving enzyme from Streptococcus pyogenes, is inhibited by specific IgG antibodies generated during infection
  • 2006
  • Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 74:1, s. 497-503
  • Tidskriftsartikel (refereegranskat)abstract
    • IdeS, a recently discovered cysteine proteinase secreted by the important human pathogen Streptococcus pyogenes, interferes with phagocytic killing by specifically cleaving the heavy chain of immunoglobulin G. The fact that the enzyme targets one of the key molecules of the adapted immune response raised the question of whether an antibody response against IdeS could inhibit, i.e., neutralize, enzyme activity. Paired acute- and convalescent-phase serum samples from patients with pharyngotonsillitis (n = 10), bacteremia (n = 7), and erysipelas (n = 4) were analyzed. Antibodies with the ability to neutralize IdeS enzymatic activity were already found in two-thirds of acute-phase sera. However, patients who seroconverted to IdeS, in particular patients with pharyngotonsillitis and erysipelas, developed specific antibodies during convalescence with an increased capability to efficiently neutralize the enzymatic activity of IdeS. Also, the presence of neutralizing antibodies decreased the ability of IdeS to mediate bacterial survival in human immune blood. In patients with bacteremia, several acute-phase sera contained neutralizing antibodies, but no correlation was found to severity or outcome of invasive infections. Still, the fact that the human immune response targets the enzymatic activity of IdeS supports the view that the enzyme plays an important role during streptococcal infection.
  •  
35.
  • Aad, G., et al. (författare)
  • 2015
  • Ingår i: Physical Review D. Particles and fields. - : American Physics Society. - 0556-2821 .- 1089-4918. ; 92:11
  • Tidskriftsartikel (refereegranskat)
  •  
36.
  • Aad, G., et al. (författare)
  • 2015
  • Ingår i: Journal of High Energy Physics. - : Springer. - 1029-8479 .- 1126-6708. ; :12
  • Tidskriftsartikel (refereegranskat)
  •  
37.
  • Aad, G., et al. (författare)
  • 2016
  • Ingår i: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 93:1
  • Tidskriftsartikel (refereegranskat)
  •  
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