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2.
  • Faatz, B., et al. (author)
  • Simultaneous operation of two soft x-ray free-electron lasers driven by one linear accelerator
  • 2016
  • In: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 18
  • Journal article (peer-reviewed)abstract
    • Extreme-ultraviolet to x-ray free-electron lasers (FELs) in operation for scientific applications are up to now single-user facilities. While most FELs generate around 100 photon pulses per second, FLASH at DESY can deliver almost two orders of magnitude more pulses in this time span due to its superconducting accelerator technology. This makes the facility a prime candidate to realize the next step in FELs-dividing the electron pulse trains into several FEL lines and delivering photon pulses to several users at the same time. Hence, FLASH has been extended with a second undulator line and self-amplified spontaneous emission (SASE) is demonstrated in both FELs simultaneously. FLASH can now deliver MHz pulse trains to two user experiments in parallel with individually selected photon beam characteristics. First results of the capabilities of this extension are shown with emphasis on independent variation of wavelength, repetition rate, and photon pulse length.
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3.
  • Patrignani, C., et al. (author)
  • REVIEW OF PARTICLE PHYSICS : Particle Data Group
  • 2016
  • In: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 40:10
  • Journal article (peer-reviewed)abstract
    • The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including new reviews on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available.
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4.
  • Guidoboni, G., et al. (author)
  • How to Reach a Thousand-Second in-Plane Polarization Lifetime with 0.97-GeV/c Deuterons in a Storage Ring
  • 2016
  • In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:5
  • Journal article (peer-reviewed)abstract
    • We observe a deuteron beam polarization lifetime near 1000 s in the horizontal plane of a magnetic storage ring (COSY). This long spin coherence time is maintained through a combination of beam bunching, electron cooling, sextupole field corrections, and the suppression of collective effects through beam current limits. This record lifetime is required for a storage ring search for an intrinsic electric dipole moment on the deuteron at a statistical sensitivity level approaching 10(-29) e cm.
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5.
  • Tiegs, Scott D., et al. (author)
  • Global patterns and drivers of ecosystem functioning in rivers and riparian zones
  • 2019
  • In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
  • Journal article (peer-reviewed)abstract
    • River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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6.
  • Adolph, C, et al. (author)
  • Measurement of the eta -> 3 pi(0) Dalitz plot distribution with the WASA detector at COSY
  • 2009
  • In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 677:1-2, s. 24-29
  • Journal article (peer-reviewed)abstract
    • In the first production run of the WASA experiment at COSY, the eta decay into three neutral pions was measured in proton-proton interactions at a proton beam kinetic energy of 1.4 GeV. The Dalitz plot of the three pious was Studied using 1.2 x 10(5) fully reconstructed events. and the quadratic slope parameter alpha was determined to be -0.027 +/- 0.008(stat) +/- 0.005(syst). The result is consistent with previous measurements and further corroborates the importance of pion-pion final state interactions. (C) 2009 Elsevier B.V. All rights reserved.
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  • Adlarson, Patrik, et al. (author)
  • Measurement of the eta -> pi(+)pi(-)pi(0) Dalitz plot distribution
  • 2014
  • In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 90:4, s. 045207-
  • Journal article (peer-reviewed)abstract
    • The Dalitz plot distribution of the eta -> pi(+)pi(-)pi(0) decay is determined by using a data sample of 1.2 x 10(7) eta mesons from the pd -> He-3 eta reaction at 1 GeV collected by the WASA detector at COSY.
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9.
  • Adlarson, Patrik, et al. (author)
  • Exclusive measurement of the eta -> pi(+) pi(-) gamma decay
  • 2012
  • In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 707:2, s. 243-249
  • Journal article (peer-reviewed)abstract
    • An exclusive measurement of the decay eta -> pi(+) pi(-) gamma has been performed at the WASA facility at COSY. The eta mesons were produced in the fusion reaction pd -> He-3 X at a proton beam momentum of 1.7 GeV/c. Efficiency corrected differential distributions have been extracted based on 13 960 +/- 140 events after background subtraction. The measured pion angular distribution is consistent with a relative p-wave of the two-pion system, whereas the measured photon energy spectrum was found at variance with the simplest gauge invariant matrix element of eta -> pi(+) pi(-) gamma. A parameterization of the data can be achieved by the additional inclusion of the empirical pion vector form factor multiplied by a first-order polynomial in the squared invariant mass of the pi(+) pi(-) system.
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10.
  • Chelban, V., et al. (author)
  • Neurofilament light levels predict clinical progression and death in multiple system atrophy
  • 2022
  • In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:12, s. 4398-4408
  • Journal article (peer-reviewed)abstract
    • In this large multiple system atrophy cohort, Chelban et al. show that plasma NfL correlates with clinical disease severity, progression and prognosis, and could help inform patient stratification and monitor treatment responses in future trials of putative disease-modifying agents. Disease-modifying treatments are currently being trialled in multiple system atrophy. Approaches based solely on clinical measures are challenged by heterogeneity of phenotype and pathogenic complexity. Neurofilament light chain protein has been explored as a reliable biomarker in several neurodegenerative disorders but data on multiple system atrophy have been limited. Therefore, neurofilament light chain is not yet routinely used as an outcome measure in multiple system atrophy. We aimed to comprehensively investigate the role and dynamics of neurofilament light chain in multiple system atrophy combined with cross-sectional and longitudinal clinical and imaging scales and for subject trial selection. In this cohort study, we recruited cross-sectional and longitudinal cases in a multicentre European set-up. Plasma and CSF neurofilament light chain concentrations were measured at baseline from 212 multiple system atrophy cases, annually for a mean period of 2 years in 44 multiple system atrophy patients in conjunction with clinical, neuropsychological and MRI brain assessments. Baseline neurofilament light chain characteristics were compared between groups. Cox regression was used to assess survival; receiver operating characteristic analysis to assess the ability of neurofilament light chain to distinguish between multiple system atrophy patients and healthy controls. Multivariate linear mixed-effects models were used to analyse longitudinal neurofilament light chain changes and correlated with clinical and imaging parameters. Polynomial models were used to determine the differential trajectories of neurofilament light chain in multiple system atrophy. We estimated sample sizes for trials aiming to decrease neurofilament light chain levels. We show that in multiple system atrophy, baseline plasma neurofilament light chain levels were better predictors of clinical progression, survival and degree of brain atrophy than the neurofilament light chain rate of change. Comparative analysis of multiple system atrophy progression over the course of disease, using plasma neurofilament light chain and clinical rating scales, indicated that neurofilament light chain levels rise as the motor symptoms progress, followed by deceleration in advanced stages. Sample size prediction suggested that significantly lower trial participant numbers would be needed to demonstrate treatment effects when incorporating plasma neurofilament light chain values into multiple system atrophy clinical trials in comparison to clinical measures alone. In conclusion, neurofilament light chain correlates with clinical disease severity, progression and prognosis in multiple system atrophy. Combined with clinical and imaging analysis, neurofilament light chain can inform patient stratification and serve as a reliable biomarker of treatment response in future multiple system atrophy trials of putative disease-modifying agents.
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11.
  • Gunton, L. M., et al. (author)
  • Annelids of the eastern Australian abyss collected by the 2017 RV 'Investigator' voyage
  • 2021
  • In: Zookeys. - : Pensoft Publishers. - 1313-2989 .- 1313-2970. ; :1020, s. 1-198
  • Journal article (peer-reviewed)abstract
    • In Australia, the deep-water (bathyal and abyssal) benthic invertebrate fauna is poorly known in comparison with that of shallow (subtidal and shelf) habitats. Benthic fauna from the deep eastern Australian margin was sampled systematically for the first time during 2017 RV 'Investigator' voyage 'Sampling the Abyss'. Box core, Brenke sledge, and beam trawl samples were collected at one-degree intervals from Tasmania, 42 degrees S, to southern Queensland, 24 degrees S, from 900 to 4800 m depth. Annelids collected were identified by taxonomic experts on individual families around the world. A complete list of all identified species is presented, accompanied with brief morphological diagnoses, taxonomic remarks, and colour images. A total of more than 6000 annelid specimens consisting of 50 families (47 Polychaeta, one Echiura, two Sipuncula) and 214 species were recovered. Twenty-seven species were given valid names, 45 were assigned the qualifier cf., 87 the qualifier sp., and 55 species were considered new to science. Geographical ranges of 16 morphospecies extended along the eastern Australian margin to the Great Australian Bight, South Australia; however, these ranges need to be confirmed with genetic data. This work providing critical baseline biodiversity data on an important group of benthic invertebrates from a virtually unknown region of the world's ocean will act as a springboard for future taxonomic and biogeographic studies in the area.
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  • Rothaug, J., et al. (author)
  • Patients' perception of postoperative pain management : Validation of the international pain outcomes (IPO) questionnaire
  • 2013
  • In: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 14:11, s. 1361-1370
  • Journal article (peer-reviewed)abstract
    • PAIN OUT is a European Commission-funded project aiming at improving postoperative pain management. It combines a registry that can be useful for quality improvement and research using treatment and patient-reported outcome measures. The core of the project is a patient questionnaire - the International Pain Outcomes questionnaire - that comprises key patient-level outcomes of postoperative pain management, including pain intensity, physical and emotional functional interference, side effects, and perceptions of care. Its psychometric quality after translation and adaptation to European patients is the subject of this validation study. The questionnaire was administered to 9,727 patients in 10 languages in 8 European countries and Israel. Construct validity was assessed using factor analysis. Discriminant validity assessment used Mann-Whitney U tests to detect mean group differences between 2 surgical disciplines. Internal consistency reliability was calculated as Cronbach's alpha. Factor analysis resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha at overall scale level was high (.86), and for the 3 subscales was low, moderate, or high (range,.53-.89). Significant mean group differences between general and orthopedic surgery patients confirmed discriminant validity. The psychometric quality of the International Pain Outcomes questionnaire can be regarded as satisfactory. Perspective The International Pain Outcomes questionnaire provides an instrument for postoperative pain assessment and improvement of quality of care, which demonstrated good psychometric quality when translated into a variety of languages in a large European and Israeli patient population. This measure provides the basis for the first comprehensive postoperative pain registry in Europe and other countries. © 2013 by the American Pain Society.
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  • Zaslansky, R., et al. (author)
  • PAIN OUT : An international acute pain registry supporting clinicians in decision making and in quality improvement activities
  • 2014
  • In: Journal of Evaluation In Clinical Practice. - : Wiley. - 1356-1294 .- 1365-2753. ; 20:6, s. 1090-1098
  • Journal article (peer-reviewed)abstract
    • Rationale, aims and objectives Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. Methods PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery. Results The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. Conclusion PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.
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  • Jujic, Amra, et al. (author)
  • Plasma Galectin-4 Levels Are Increased after Stroke in Mice and Humans
  • 2023
  • In: International Journal of Molecular Sciences. - 1661-6596 .- 1422-0067. ; 24:12
  • Journal article (peer-reviewed)abstract
    • Epidemiological studies have associated plasma galectin-4 (Gal-4) levels with prevalent and incident diabetes, and with an increased risk of coronary artery disease. To date, data regarding possible associations between plasma Gal-4 and stroke are lacking. Using linear and logistic regression analyses, we tested Gal-4 association with prevalent stroke in a population-based cohort. Additionally, in mice fed a high-fat diet (HFD), we investigated whether plasma Gal-4 increases in response to ischemic stroke. Plasma Gal-4 was higher in subjects with prevalent ischemic stroke, and was associated with prevalent ischemic stroke (odds ratio 1.52; 95% confidence interval 1.01-2.30; p = 0.048) adjusted for age, sex, and covariates of cardiometabolic health. Plasma Gal-4 increased after experimental stroke in both controls and HFD-fed mice. HFD exposure was devoid of impact on Gal-4 levels. This study demonstrates higher plasma Gal-4 levels in both experimental stroke and in humans that experienced ischemic stroke.
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  • Lill, Christina M., et al. (author)
  • The role of TREM2 R47H as a risk factor for Alzheimer's disease, frontotemporal lobar degeneration, amyotrophic lateral sclerosis, and Parkinson's disease
  • 2015
  • In: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:12, s. 1407-1416
  • Journal article (peer-reviewed)abstract
    • A rare variant in TREM2 (p.R47H, rs75932628) was recently reported to increase the risk of Alzheimer's disease (AD) and, subsequently, other neurodegenerative diseases, i.e. frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Here we comprehensively assessed TREM2 rs75932628 for association with these diseases in a total of 19,940 previously untyped subjects of European descent. These data were combined with those from 28 published data sets by meta-analysis. Furthermore, we tested whether rs75932628 shows association with amyloid beta (Ab42) and total-tau protein levels in the cerebrospinal fluid (CSF) of 828 individuals with AD or mild cognitive impairment. Our data show that rs75932628 is highly significantly associated with the risk of AD across 24,086 AD cases and 148,993 controls of European descent (odds ratio or OR = 2.71, P = 4.67 x 10(-25)). No consistent evidence for association was found between this marker and the risk of FTLD (OR = 2.24, P = .0113 across 2673 cases/9283 controls), PD (OR 5 1.36, P = .0767 across 8311 cases/79,938 controls) and ALS (OR 5 1.41, P = .198 across 5544 cases/7072 controls). Furthermore, carriers of the rs75932628 risk allele showed significantly increased levels of CSF-total-tau (P = .0110) but not Ab42 suggesting that TREM2's role in AD may involve tau dysfunction. (C) 2015 The Alzheimer's Association.
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  • Mandal, Pankaj K, et al. (author)
  • Efficient Ablation of Genes in Human Hematopoietic Stem and Effector Cells using CRISPR/Cas9.
  • 2014
  • In: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 15:5, s. 643-652
  • Journal article (peer-reviewed)abstract
    • Genome editing via CRISPR/Cas9 has rapidly become the tool of choice by virtue of its efficacy and ease of use. However, CRISPR/Cas9-mediated genome editing in clinically relevant human somatic cells remains untested. Here, we report CRISPR/Cas9 targeting of two clinically relevant genes, B2M and CCR5, in primary human CD4(+) T cells and CD34(+) hematopoietic stem and progenitor cells (HSPCs). Use of single RNA guides led to highly efficient mutagenesis in HSPCs but not in T cells. A dual guide approach improved gene deletion efficacy in both cell types. HSPCs that had undergone genome editing with CRISPR/Cas9 retained multilineage potential. We examined predicted on- and off-target mutations via target capture sequencing in HSPCs and observed low levels of off-target mutagenesis at only one site. These results demonstrate that CRISPR/Cas9 can efficiently ablate genes in HSPCs with minimal off-target mutagenesis, which could have broad applicability for hematopoietic cell-based therapy.
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  • Doerig, C, et al. (author)
  • Signalling in malaria parasites. The MALSIG consortium
  • 2009
  • In: Parasite. - : EDP Sciences. - 1252-607X .- 1776-1042. ; 16:3, s. 169-182
  • Journal article (peer-reviewed)abstract
    • Depending on their developmental stage in the life cycle, malaria parasites develop within or outside host cells, and in extremely diverse contexts such as the vertebrate liver and blood circulation, or the insect midgut and hemocoel. Cellular and molecular mechanisms enabling the parasite to sense and respond to the intra- and the extra-cellular environments are therefore key elements for the proliferation and transmission of Plasmodium, and therefore are, from a public health perspective, strategic targets in the fight against this deadly disease. The MALSIG consortium, which was initiated in February 2009, was designed with the primary objective to integrate research ongoing in Europe and India on i) the properties of Plasmodium signalling molecules, and ii) developmental processes occurring at various points of the parasite life cycle. On one hand, functional studies of individual genes and their products in Plasmodium falciparum (and in the technically more manageable rodent model Plasmodium berghei) are providing information on parasite protein kinases and phosphatases, and of the molecules governing cyclic nucleotide metabolism and calcium signalling. On the other hand, cellular and molecular studies are elucidating key steps of parasite development such as merozoite invasion and egress in blood and liver parasite stages, control of DNA replication in asexual and sexual development, membrane dynamics and trafficking, production of gametocytes in the vertebrate host and further parasite development in the mosquito. This article, which synthetically reviews such signalling molecules and cellular processes, aims to provide a glimpse of the global frame in which the activities of the MALSIG consortium will develop over the next three years.
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  • Durante, M., et al. (author)
  • All the fun of the FAIR: fundamental physics at the facility for antiproton and ion research
  • 2019
  • In: Physica Scripta. - : IOP Publishing. - 1402-4896 .- 0031-8949. ; 94:3
  • Research review (peer-reviewed)abstract
    • The Facility for Antiproton and Ion Research (FAIR) will be the accelerator-based flagship research facility in many basic sciences and their applications in Europe for the coming decades. FAIR will open up unprecedented research opportunities in hadron and nuclear physics, in atomic physics and nuclear astrophysics as well as in applied sciences like materials research, plasma physics and radiation biophysics with applications towards novel medical treatments and space science. FAIR is currently under construction as an international facility at the campus of the GSI Helmholtzzentrum for Heavy-Ion Research in Darmstadt, Germany. While the full science potential of FAIR can only be harvested once the new suite of accelerators and storage rings is completed and operational, some of the experimental detectors and instrumentation are already available and will be used starting in summer 2018 in a dedicated research program at GSI, exploiting also the significantly upgraded GSI accelerator chain. The current manuscript summarizes how FAIR will advance our knowledge in various research fields ranging from a deeper understanding of the fundamental interactions and symmetries in nature to a better understanding of the evolution of the Universe and the objects within.
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  • Gerold, Gisa, 1979-, et al. (author)
  • Quantitative Proteomics Identifies Serum Response Factor Binding Protein 1 as a Host Factor for Hepatitis C Virus Entry
  • 2015
  • In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 12:5, s. 864-878
  • Journal article (peer-reviewed)abstract
    • Hepatitis C virus (HCV) enters human hepatocytes through a multistep mechanism involving, among other host proteins, the virus receptor CD81. How CD81 governs HCV entry is poorly characterized, and CD81 protein interactions after virus binding remain elusive. We have developed a quantitative proteomics protocol to identify HCV-triggered CD81 interactions and found 26 dynamic binding partners. At least six of these proteins promote HCV infection, as indicated by RNAi. We further characterized serum response factor binding protein 1 (SRFBP1), which is recruited to CD81 during HCV uptake and supports HCV infection in hepatoma cells and primary human hepatocytes. SRFBP1 facilitates host cell penetration by all seven HCV genotypes, but not of vesicular stomatitis virus and human coronavirus. Thus, SRFBP1 is an HCV-specific, pan-genotypic host entry factor. These results demonstrate the use of quantitative proteomics to elucidate pathogen entry and underscore the importance of host protein-protein interactions during HCV invasion.
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  • Gierl, Christian, et al. (author)
  • Tuneable VCSEL aiming for the application in interconnects and short haul systems
  • 2011
  • In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819484963 ; 7959
  • Conference paper (other academic/artistic)abstract
    • Widely tunable vertical cavity surface emitting lasers (VCSEL) are of high interest for optical communications, gas spectroscopy and fiber-Bragg-grating measurements. In this paper we present tunable VCSEL operating at wavelength around 850 nm and 1550 nm with tuning ranges up to 20 nm and 76 nm respectively. The first versions of VCSEL operating at 1550 nm with 76 nm tuning range and an output power of 1.3mW were not designed for high speed modulation, but for applications where only stable continious tuning is essential (e.g. gas sensing). The next step was the design of non tunable VCSEL showing high speed modulation frequencies of 10 GHz with side mode supression ratios beyond 50 dB. The latest version of these devices show record output powers of 6.7mW at 20 °C and 3mW at 80 °C. The emphasis of our present and future work lies on the combination of both technologies. The tunable VCSEL operating in the 850 nm-region reaches a modulation bandwidth of 5.5GHz with an output power of 0.8mW.
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  • Han, W., et al. (author)
  • Dying transplanted neural stem cells mediate survival bystander effects in the injured brain
  • 2023
  • In: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 14:3
  • Journal article (peer-reviewed)abstract
    • Neural stem and progenitor cell (NSPC) transplants provide neuroprotection in models of acute brain injury, but the underlying mechanisms are not fully understood. Here, we provide evidence that caspase-dependent apoptotic cell death of NSPCs is required for sending survival signals to the injured brain. The secretome of dying NSPCs contains heat-stable proteins, which protect neurons against glutamate-induced toxicity and trophic factor withdrawal in vitro, and from ischemic brain damage in vivo. Our findings support a new concept suggesting a bystander effect of apoptotic NSPCs, which actively promote neuronal survival through the release of a protective "farewell" secretome. Similar protective effects by the secretome of apoptotic NSPC were also confirmed in human neural progenitor cells and neural stem cells but not in mouse embryonic fibroblasts (MEF) or human dopaminergic neurons, suggesting that the observed effects are cell type specific and exist for neural progenitor/stem cells across species.
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  • Lill, Christina M., et al. (author)
  • Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29 000 subjects
  • 2012
  • In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 49:9, s. 558-562
  • Journal article (peer-reviewed)abstract
    • Background Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently.Methods We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments.Results Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively).Conclusion Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
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  • Orce, J. N., et al. (author)
  • Reorientation-effect measurement of the (2+ 1 Eˆ22+ 1) matrix element in 10Be
  • 2012
  • In: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 86:4
  • Journal article (peer-reviewed)abstract
    • The highly-efficient and segmented TIGRESS gamma-ray spectrometer at TRIUMF has been used to perform a reorientation-effect Coulomb-excitation study of the 2(1)(+) state at 3.368 MeV in Be-10. This is the first Coulomb-excitation measurement that enables one to obtain information on diagonal matrix elements for such a high-lying first excited state from gamma-ray data. With the availability of accurate lifetime data, a value of -0.110 +/- 0.087 eb is determined for the diagonal matrix element, which assuming the rotor model, leads to a negative spectroscopic quadrupole moment of Q(S)(2(1)(+)) = -0.083 +/- 0.066 eb. This result is in agreement with both no-core shell-model calculations performed in this work with the CD-Bonn 2000 two-nucleon potential and large shell-model spaces, and Green's function Monte Carlo predictions with two-plus three-nucleon potentials.
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  • Davani, Hooman A., et al. (author)
  • Polarization investigation of a tunable high-speed short-wavelength bulk-micromachined MEMS-VCSEL
  • 2012
  • In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819489197 ; 8276, s. Art. no. 82760T-
  • Conference paper (peer-reviewed)abstract
    • We report the investigation of the state of polarization (SOP) of a tunable vertical-cavity surface-emitting laser (VCSEL) operating near 850 nm with a mode-hop free single-mode tuning range of about 12 nm and an amplitude modulation bandwidth of about 5 GHz. In addition, the effect of a sub-wavelength grating on the device and its influence on the polarization stability and polarization switching has been investigated. The VCSEL with an integrated sub-wavelength grating shows a stable SOP with a polarization mode suppression ratio (PMSR) more than 35 dB during the tuning.
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  • Davani, Hooman A., et al. (author)
  • Widely Electro Thermal Tunable Bulk-Micromachined MEMS-VCSEL Operating Around 850nm
  • 2011
  • In: Conference on Lasers and Electro-Optics/Pacific Rim, CLEOPR 2011; Sydney; Australia; 28 August 2011 through 1 September 2011. - 2162-2701. - 9780977565771 ; , s. 32-34
  • Conference paper (peer-reviewed)abstract
    • We present the highest reported continues tuning range of 37 nm and fastest electro thermal tuning speed of 700 Hz achieved with tunable vertical-cavity surface-emitting lasers (VCSEL) and semiconductor DBRs at 850 nm wavelength range.
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  • Davani, Hooman A., et al. (author)
  • Widely tunable high-speed bulk-micromachined short-wavelength MEMS-VCSEL
  • 2010
  • In: Semiconductor Laser Conference (ISLC), 2010 22nd IEEE International. - 0899-9406. - 9781424456833 ; , s. 9-10
  • Conference paper (peer-reviewed)abstract
    • We present the first results of a high-speed bulk-micromachined tunable vertical-cavity surface-emitting laser (VCSEL) operating near 850nm using a half-symmetric resonator with a movable curved microelectromechanical system (MEMS) membrane.
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  • Devos, David, et al. (author)
  • Trial of Deferiprone in Parkinson’s Disease
  • 2022
  • In: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
  • Journal article (peer-reviewed)abstract
    • BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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39.
  • Eklof, Bo G., et al. (author)
  • Revised CEAP classification for chronic verrous disorders
  • 2005
  • In: Phlebologie. - 0939-978X. ; 34:4, s. 220-225
  • Journal article (peer-reviewed)abstract
    • The CEAP classification for chronic venous disorders (CVD) was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995. Today most published clinical papers use all or portions of CEAP. Rather than have it stand as a static classification system, an ad hoc committee of the American Venous Forum, working with an international liaison committee, has recommended a number of practical changes, detailed in this consensus report. These include refinement of several definitions used in describing CVD; refinement of the C classes of CEAP, addition of the descriptor n (no venous abnormality identified); elaboration of the date of classification and level of investigation; and as a simpler alternative to the full (advanced) CEAP classification, introduction of a basic CEAP version. It is important to stress that CEAP is a descriptive classification, whereas venous severity scoring and quality of life scores are instruments for longitudinal research to assess outcomes.
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40.
  • Eklof, Bo G., et al. (author)
  • Revision of the CEAP classification for chronic venous disorders: Consensus statement
  • 2004
  • In: Journal of Vascular Surgery. - : Elsevier BV. - 1097-6809 .- 0741-5214. ; 40:6, s. 1248-1252
  • Journal article (peer-reviewed)abstract
    • The CEAP classification for chronic venous disorders (CVD) was developed in 1994 by an international ad hoc committee of the American Venous Forum, endorsed by the Society for Vascular Surgery, and incorporated into "Reporting Standards in Venous Disease" in 1995. Today most published clinical papers on CVD use all or portions of CEAP. Rather than have it stand as a static classification system, an ad hoc committee of the American Venous Forum, working with an international liaison committee, has recommended a number of practical changes, detailed in this consensus report. These include refinement of several definitions used in describing CVD; refinement of the C classes of CEAP; addition of the descriptor n (no venous abnormality identified); elaboration of the date of classification and level of investigation; and as a simpler alternative to the full (advanced) CEAP classification, introduction of a basic CEAP version. It is important to stress that CEAP is a descriptive classification, whereas venous severity scoring and quality of life scores are instruments for longitudinal research to assess outcomes.
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41.
  • Evers, AWM, et al. (author)
  • Implications of Placebo and Nocebo Effects for Clinical Practice: Expert Consensus
  • 2018
  • In: Psychotherapy and psychosomatics. - : S. Karger AG. - 1423-0348 .- 0033-3190. ; 87:4, s. 204-210
  • Journal article (peer-reviewed)abstract
    • <b><i>Background:</i></b> Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. <b><i>Methods:</i></b> A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. <b><i>Results:</i></b> There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. <b><i>Conclusions:</i></b> The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.
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42.
  • Gaget, Elie, et al. (author)
  • Benefits of protected areas for nonbreeding waterbirds adjusting their distributions under climate warming
  • 2021
  • In: Conservation Biology. - : Wiley. - 0888-8892 .- 1523-1739. ; 35:3, s. 834-845
  • Journal article (peer-reviewed)abstract
    • Climate warming is driving changes in species distributions and community composition. Many species have a so-called climatic debt, that is, shifts in range lag behind shifts in temperature isoclines. Inside protected areas (PAs), community changes in response to climate warming can be facilitated by greater colonization rates by warm-dwelling species, but also mitigated by lowering extirpation rates of cold-dwelling species. An evaluation of the relative importance of colonization-extirpation processes is important to inform conservation strategies that aim for both climate debt reduction and species conservation. We assessed the colonization-extirpation dynamics involved in community changes in response to climate inside and outside PAs. To do so, we used 25 years of occurrence data of nonbreeding waterbirds in the western Palearctic (97 species, 7071 sites, 39 countries, 1993–2017). We used a community temperature index (CTI) framework based on species thermal affinities to investigate species turnover induced by temperature increase. We determined whether thermal community adjustment was associated with colonization by warm-dwelling species or extirpation of cold-dwelling species by modeling change in standard deviation of the CTI (CTISD). Using linear mixed-effects models, we investigated whether communities in PAs had lower climatic debt and different patterns of community change than communities outside PAs. For CTI and CTISD combined, communities inside PAs had more species, higher colonization, lower extirpation, and lower climatic debt (16%) than communities outside PAs. Thus, our results suggest that PAs facilitate 2 independent processes that shape community dynamics and maintain biodiversity. The community adjustment was, however, not sufficiently fast to keep pace with the large temperature increases in the central and northeastern western Palearctic. Our results underline the potential of combining CTI and CTISD metrics to improve understanding of the colonization-extirpation patterns driven by climate warming.
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43.
  • Gan, M., et al. (author)
  • Calibration of indoor UWB sub-band divided ray tracing using multiobjective simulated annealing
  • 2014
  • In: 2014 IEEE International Conference on Communications, ICC 2014. - 9781479920037 ; , s. 4844-4849
  • Conference paper (peer-reviewed)abstract
    • Sub-band divided ray tracing (RT) has been widely used to reproduce as reliably as possible the ultra-wideband (UWB) radio wave propagation channel in realistic indoor environments. However, its accuracy is strictly limited by the available description of the environment. Moreover, its computational complexity scales with the number of selected subbands and the number of propagation paths. In the present work, our RT tool considers not only deterministic propagation paths but also diffuse scattering components. Based on a low-complexity sub-band divided RT implementation, we propose a calibration method for indoor UWB sub-band divided RT. The method estimates the optimal material parameters, including the dielectric parameters and the scattering parameters, using channel measurements and multiobjective simulated annealing (MOSA). This calibration can improve the accuracy of sub-band divided RT in terms of the power delay profile (PDP) and the root mean square (RMS) delay spread for all test locations including those not considered by the calibration. A measurement campaign is used to verify the calibration technique. © 2014 IEEE.
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44.
  • Gan, M., et al. (author)
  • Low-Complexity Sub-band Divided Ray Tracing for UWB Indoor Channels
  • 2014
  • In: IEEE Wireless Communications and Networking Conference, WCNC. - 1525-3511.
  • Conference paper (peer-reviewed)abstract
    • Ray tracing has been extensively used to simulateindoor channel characteristics. For an ultra-wideband system,the channel characteristics vary significantly over the entirebandwidth. To cope with this, sub-band divided RT has beenproposed by dividing the frequency of interest into multiplesubbands and superposing the RT results at the individual centerfrequency of each subband. Thus, the computational complexityis directly proportional to the number of subbands. In this paper,we propose a mathematical method to significantly reduce thecomputational complexity of the sub-band divided RT, making italmost independent of the number of subbands. It is important tonote that, based on our approach, not only the determination ofthe rays reaching a give location is made only once, but also theelectromagnetic calculation of the received signal is not neededto perform repeatedly. The accuracy of low-complexity sub-band divided RT algorithm is verified through a measurementcampaign.
  •  
45.
  • Grötsch, Marie Therese, et al. (author)
  • A Modified Progressive Supranuclear Palsy Rating Scale
  • 2021
  • In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 36:5, s. 1203-1215
  • Journal article (peer-reviewed)abstract
    • Background: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. Objective: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. Methods: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. Results: The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). Conclusions: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine.
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46.
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47.
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48.
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49.
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50.
  • Jujic, Amra, et al. (author)
  • Plasma S1P (Sphingosine-1-Phosphate) Links to Hypertension and Biomarkers of Inflammation and Cardiovascular Disease : Findings From a Translational Investigation
  • 2021
  • In: Hypertension. - 1524-4563. ; 78:1, s. 195-209
  • Journal article (peer-reviewed)abstract
    • S1P (Sphingosine-1-phosphate) is an important regulator of immune cell trafficking and vascular dysfunction contributing to the development and progression of overt hypertension. Although targeting S1P signaling revealed therapeutic potential in different experimental hypertension studies, validations of S1P-blood pressure (BP) associations in humans are lacking. In a translational approach, we explored the associations between plasma S1P and BP in a family based study cohort (MOS [Malmö Offspring Study]; N=1046) and in a longitudinally conducted murine hypertension cohort. In MOS, linear multivariate regression analyses showed that plasma S1P associates with increased systolic BP (β=1.06, P=0.015). Study subjects with systolic BP ≥140 mm Hg presented with significantly higher S1P plasma concentrations compared with subjects with BP <120 mm Hg independent of age and sex. The S1P-BP association was validated in a murine model where plasma S1P increased with systolic BP (r=0.7018, R2=0.4925; P<0.0001). In a subsample of MOS (N=444), proteomic profiling for markers of inflammation, metabolism, and cardiovascular disease using Proximity Extension Assays revealed multiple significant S1P associations, some of them with marked sex-specificity. In vitro and ex vivo validation of identified S1P associations disclosed augmented expression of different vascular dysfunction and inflammation markers in response to S1P. Our translational findings show a link between plasma S1P and systolic BP as well as several inflammation and cardiovascular disease markers and suggest S1P's biomarker potential. This encourages further studies to investigate its predictive capacity for hypertensive disease or the therapeutic potential of its signaling axis.
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