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1.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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2.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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3.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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4.
  • Megat, Salim, et al. (författare)
  • Integrative genetic analysis illuminates ALS heritability and identifies risk genes
  • 2023
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) has substantial heritability, in part shared with fronto-temporal dementia (FTD). We show that ALS heritability is enriched in splicing variants and in binding sites of 6 RNA-binding proteins including TDP-43 and FUS. A transcriptome wide association study (TWAS) identified 6 loci associated with ALS, including in NUP50 encoding for the nucleopore basket protein NUP50. Independently, rare variants in NUP50 were associated with ALS risk (P = 3.71.10−03; odds ratio = 3.29; 95%CI, 1.37 to 7.87) in a cohort of 9,390 ALS/FTD patients and 4,594 controls. Cells from one patient carrying a NUP50 frameshift mutation displayed a decreased level of NUP50. Loss of NUP50 leads to death of cultured neurons, and motor defects in Drosophila and zebrafish. Thus, our study identifies alterations in splicing in neurons as critical in ALS and provides genetic evidence linking nuclear pore defects to ALS.
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5.
  • Williamson, Alice, et al. (författare)
  • Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
  • Tidskriftsartikel (refereegranskat)abstract
    • Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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6.
  • Yang, Yi, et al. (författare)
  • High-contrast Polarimetry Observation of the T Tau Circumstellar Environment
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 861:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted high-contrast polarimetry observations of T Tau in the H-band, using the High Contrast Instrument for the Subaru Next Generation Adaptive Optics instrument mounted on the Subaru Telescope, revealing structures as near as 0 1 from the stars T Tau N and T Tau S. The whole T Tau system is found to be surrounded by nebulalike envelopes, and several outflow-related structures are detected in these envelopes. We analyzed the detailed polarization patterns of the circumstellar structures near each component of this triple young star system and determined constraints on the circumstellar disks and outflow structures. We suggest that the nearly face-on circumstellar disk of T Tau N is no larger than 0.''8, or 117 au, in the northwest, based on the existence of a hole in this direction, and no larger than 0.''27, or 40 au, in the south. A new structure, N5, extends to about 0.''42, or 59 au, southwest of the star, and is believed to be part of the disk. We suggest that T Tau S is surrounded by a highly inclined circumbinary disk with a radius of about 0.''3, or 44 au, with a position angle of about 30 degrees, that is misaligned with the orbit of the T Tau S binary. After analyzing the positions and polarization vector patterns of the outflow-related structures, we suggest that T Tau S should trigger the well-known E-W outflow, and is also likely to be responsible for a southwest precessing outflow coil and a possible south outflow.
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7.
  • Yang, Yi, et al. (författare)
  • NEAR-INFRARED IMAGING POLARIMETRY OF INNER REGION OF GG TAU A DISK
  • 2017
  • Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 153:1
  • Tidskriftsartikel (refereegranskat)abstract
    • By performing non-masked polarization imaging with Subaru/HiCIAO, polarized scattered light from the inner region of the disk around the GG Tau A system was successfully detected in the H band, with a spatial resolution of approximately 0 07, revealing the complicated inner disk structures around this young binary. This paper reports the observation of an arc-like structure to the north of GG Tau Ab, and part of a circumstellar structure that is noticeable around GG Tau Aa, extending to a distance of approximately 28 au from the primary star. The speckle noise around GG Tau Ab constrains its disk radius to < 13 au. Based on the size of the circumbinary ring and the circumstellar disk around GG Tau Aa, the semimajor axis of the binary's orbit is likely to be 62 au. A comparison of the present observations with previous Atacama Large Millimeter Array and near-infrared H-2 emission observations suggests that the north arc could be part of a large streamer flowing from the circumbinary ring to sustain the circumstellar disks. According to the previous studies, the circumstellar disk around GG Tau Aa has enough mass and can sustain itself for a duration sufficient for planet formation; thus, our study indicates that planets can form within close (separation. 100 au) young binary systems.
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8.
  • Andersen, Kasper Winther, et al. (författare)
  • Disentangling white-matter damage from physiological fibre orientation dispersion in multiple sclerosis
  • 2020
  • Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:2, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis leads to diffuse damage of the central nervous system, affecting also the normal-appearing white matter. Demyelination and axonal degeneration reduce regional fractional anisotropy in normal-appearing white matter, which can be routinely mapped with diffusion tensor imaging. However, the standard fractional anisotropy metric is also sensitive to physiological variations in orientation dispersion of white matter fibres. This complicates the detection of disease-related damage in large parts of cerebral white matter where microstructure physiologically displays a high degree of fibre dispersion. To resolve this ambiguity, we employed a novel tensor-valued encoding method for diffusion MRI, which yields a microscopic fractional anisotropy metric that is unaffected by regional variations in orientation dispersion. In 26 patients with relapsing-remitting multiple sclerosis, 14 patients with primary-progressive multiple sclerosis and 27 age-matched healthy controls, we compared standard fractional anisotropy mapping with the novel microscopic fractional anisotropy mapping method, focusing on normal-appearing white matter. Mean microscopic fractional anisotropy and standard fractional anisotropy of normal-appearing white matter were significantly reduced in both patient groups relative to healthy controls, but microscopic fractional anisotropy yielded a better reflection of disease-related white-matter alterations. The reduction in mean microscopic fractional anisotropy showed a significant positive linear relationship with physical disability, as reflected by the expanded disability status scale. Mean reduction of microscopic fractional anisotropy in normal-appearing white matter also scaled positively with individual cognitive dysfunction, as measured with the symbol digit modality test. Mean microscopic fractional anisotropy reduction in normal-appearing white matter also showed a positive relationship with total white-matter lesion load as well as lesion load in specific tract systems. None of these relationships between normal-appearing white-matter microstructure and clinical, cognitive or structural measures emerged when using mean fractional anisotropy. Together, the results provide converging evidence that microscopic fractional anisotropy mapping substantially advances the assessment of cerebral white matter in multiple sclerosis by disentangling microstructure damage from variations in physiological fibre orientation dispersion at the stage of data acquisition. Since tensor-valued encoding can be implemented in routine diffusion MRI, microscopic fractional anisotropy mapping bears considerable potential for the future assessment of disease progression in normal-appearing white matter in both relapsing-remitting and progressive forms of multiple sclerosis as well as other white-matter-related brain diseases.
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9.
  • Baum, Seth D., et al. (författare)
  • Long-term trajectories of human civilization
  • 2019
  • Ingår i: Foresight. - : Emerald Group Publishing Limited. - 1463-6689 .- 1465-9832. ; 21:11, s. 53-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This paper aims to formalize long-term trajectories of human civilization as a scientific and ethical field of study. The long-term trajectory of human civilization can be defined as the path that human civilization takes during the entire future time period in which human civilization could continue to exist. Design/methodology/approach: This paper focuses on four types of trajectories: status quo trajectories, in which human civilization persists in a state broadly similar to its current state into the distant future; catastrophe trajectories, in which one or more events cause significant harm to human civilization; technological transformation trajectories, in which radical technological breakthroughs put human civilization on a fundamentally different course; and astronomical trajectories, in which human civilization expands beyond its home planet and into the accessible portions of the cosmos. Findings: Status quo trajectories appear unlikely to persist into the distant future, especially in light of long-term astronomical processes. Several catastrophe, technological transformation and astronomical trajectories appear possible. Originality/value: Some current actions may be able to affect the long-term trajectory. Whether these actions should be pursued depends on a mix of empirical and ethical factors. For some ethical frameworks, these actions may be especially important to pursue.
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10.
  • Berne, Olivier, et al. (författare)
  • PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
  • 2022
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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11.
  • Bott, Lukas Thomas, et al. (författare)
  • Coulomb dissociation of O-16 into He-4 and C-12
  • 2023
  • Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
  • Konferensbidrag (refereegranskat)abstract
    • We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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13.
  • Chung, Sunjae, et al. (författare)
  • Direct Observation of Zhang-Li Torque Expansion of Magnetic Droplet Solitons
  • 2018
  • Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 120:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetic droplets are nontopological dynamical soli tons that can be nucleated in nanocontact based spin torque nano-oscillators (STNOs) with perpendicular magnetic anisotropy free layers. While theory predicts that the droplet should be of the same size as the nanocontact, its inherent drift instability has thwarted attempts at observing it directly using microscopy techniques. Here, we demonstrate highly stable magnetic droplets in all-perpendicular STNOs and present the first detailed droplet images using scanning transmission X-ray microscopy. In contrast to theoretical predictions, we find that the droplet diameter is about twice as large as the nanocontact. By extending the original droplet theory to properly account for the lateral current spread underneath the nanocontact, we show that the large discrepancy primarily arises from current-in-plane Zhang-Li torque adding an outward pressure on the droplet perimeter. Electrical measurements on droplets nucleated using a reversed current in the antiparallel state corroborate this picture.
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15.
  • de la Presilla, Roman José, et al. (författare)
  • Oscillating rolling element bearings : A review of tribotesting and analysis approaches
  • 2023
  • Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 188
  • Forskningsöversikt (refereegranskat)abstract
    • Rolling element bearings, when subjected to small oscillating movements or vibrations, run the risk of being damaged by mechanisms such as Standstill Marks and False Brinelling. Damages resulting from these phenomena can decrease bearing fatigue life and increase wear-induced friction torque. These failures do not correlate well with standard life estimation approaches. Experimental studies play a crucial role in gaining knowledge in this area. The review integrates knowledge from experiments ranging from single contacts to laboratory and full-scale bearings in wind power and aerospace applications. The generalization is achieved using a non-dimensional amplitude parameter that relates rolling element travel during an oscillation to the Hertzian contact size. The review encompasses testing methods, procedures, reporting practices, result scaling, and application-specific considerations.
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16.
  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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17.
  • Frampton, Matthew, et al. (författare)
  • Variation at 3p24.1 and 6q23.3 influences the risk of Hodgkin's lymphoma
  • 2013
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • In addition to HLA, recent genome-wide association studies (GWASs) of Hodgkin's lymphoma (HL) have identified susceptibility loci for HL at 2p16.1, 8q24.21 and 10p14. In this study, we perform a GWAS meta-analysis with published GWAS (totalling 1,465 cases and 6,417 controls of European background), and follow-up the most significant association signals in 2,024 cases and 1,853 controls. A combined analysis identifies new HL susceptibility loci mapping to 3p24.1 (rs3806624; P = 1.14 x 10(-12), odds ratio (OR) = 1.26) and 6q23.3 (rs7745098; P = 3.42 x 10(-9), OR = 1.21). rs3806624 localizes 5' to the EOMES (eomesodermin) gene within a p53 response element affecting p53 binding. rs7745098 maps intergenic to HBS1L and MYB, a region previously associated with haematopoiesis. These findings provide further insight into the genetic and biological basis of inherited susceptibility to HL.
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18.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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19.
  • Grillitsch, Markus, et al. (författare)
  • Knowledge Base Combinations and Innovation Performance in Swedish Regions
  • 2017
  • Ingår i: Economic Geography. - : Informa UK Limited. - 1944-8287 .- 0013-0095. ; 93:5, s. 458-479
  • Tidskriftsartikel (refereegranskat)abstract
    • The literature on geography of innovation suggests that innovation outcomes depend on a diversity of knowledge inputs, which can be captured with the differentiated knowledge base approach. While knowledge bases are distinct theoretical categories, existing studies stress that innovation often involves combinations of analytical, synthetic, and symbolic knowledge. It remains unclear, though, which combinations are most conducive to innovation at the level of the firm and how this is influenced by the knowledge bases available in the region. This article fills this gap by reviewing the conceptual arguments on how and why certain firm and regional knowledge base combinations relate to firm innovativeness and by investigating these relationships econometrically. The knowledge base is captured using detailed occupational data derived from linked employer–employee data sets merged at the firm level with information from Community Innovation Surveys in Sweden. The results indicate that analytical knowledge outweighs the importance of synthetic and symbolic knowledge and that, however, firms benefit most from being located in a region with a balanced mix of all three knowledge bases.
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20.
  • Gruber, Aurel, et al. (författare)
  • Interactive Sculpting of Digital Faces Using an Anatomical Modeling Paradigm
  • 2020
  • Ingår i: Computer Graphics Forum. - : Wiley. - 1467-8659 .- 0167-7055. ; 39:5, s. 93-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Digitally sculpting 3D human faces is a very challenging task. It typically requires either 1) highly-skilled artists using complex software packages for high quality results, or 2) highly-constrained simple interfaces for consumer-level avatar creation, such as in game engines. We propose a novel interactive method for the creation of digital faces that is simple and intuitive to use, even for novice users, while consistently producing plausible 3D face geometry, and allowing editing freedom beyond traditional video game avatar creation. At the core of our system lies a specialized anatomical local face model (ALM), which is constructed from a dataset of several hundred 3D face scans. User edits are propagated to constraints for an optimization of our data-driven ALM model, ensuring the resulting face remains plausible even for simple edits like clicking and dragging surface points. We show how several natural interaction methods can be implemented in our framework, including direct control of the surface, indirect control of semantic features like age, ethnicity, gender, and BMI, as well as indirect control through manipulating the underlying bony structures. The result is a simple new method for creating digital human faces, for artists and novice users alike. Our method is attractive for low-budget VFX and animation productions, and our anatomical modeling paradigm can complement traditional game engine avatar design packages.
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21.
  • Guerrieri, Davide, et al. (författare)
  • Acrylfentanyl: Another new psychoactive drug with fatal consequences
  • 2017
  • Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 277, s. E21-E29
  • Tidskriftsartikel (refereegranskat)abstract
    • The European Nordic Countries are the most exposed to opioid-related deaths. Between April and October 2016, a series of forty lethal intoxications occurred in Sweden, in which the presence of the synthetic opioid acrylfentanyl was determined to be the main - or a contributing - cause of death. In the reported cases, the blood concentration of acrylfentanyl - mostly detected in combination with other drugs - ranged from 0.01 ng/g to 5 ng/g; victims were predominantly males (34 males and 6 females), and their age varied between 18 and 53 years. We further describe five cases, representative of the different drug administration route (nasal spray, tablets) and intentions (accidental or voluntary intoxication). Moreover, we address nine cases of non-lethal intoxication, in single (8 cases) or polydrug scenario (1 case). We discuss the present characteristics of the Swedish drug market for fentanyl-analogs in general and acrylfentanyl in particular, reporting a structural difficulty to effectively counteracting the appearance of unscheduled substances due to the constant turnover of new molecules on the recreational drug market. (C) 2017 Published by Elsevier Ireland Ltd.
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22.
  • Guerrieri, Davide, et al. (författare)
  • Postmortem and Toxicological Findings in a Series of Furanylfentanyl-Related Deaths
  • 2017
  • Ingår i: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 41:3, s. 242-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the course of 4 months in 2015 and 2016, a cluster of seven fatal intoxications involving the opioid-analogue furanylfentanyl occurred in Sweden; toxicological analysis showed presence of furanylfentanyl either as the only drug or in combination with other illicit substances. Previous publications have only reported non-lethal furanylfentanyl intoxications. In the cases presented here, furanylfentanyl intoxication-alone or in combination with other drugs-was determined to be the cause of death by the responsible pathologist. All victims were young (24-37 years old) males, five of which had a well-documented history of drug abuse. Femoral blood concentration of furanylfentanyl ranged from 0.41 ng/g to 2.47 ng/g blood. Five cases presented a complex panel of drugs of abuse and prescription drugs. Moreover, in five cases the concurrent presence of pregabalin corroborates previous observations indicating pregabalin as a possible contributing factor in polydrug intoxications. We conclude that it is difficult to establish a specific lethal concentration of furanylfentanyl, due to incompletely known effects of possible pharmacokinetic and pharmacodynamic interactions with other drugs, as well as to the unknown degree of tolerance to opioids. We suggest that a full toxicological screening-to assess the possibility of drug interactions-together with segmental hair analysis regarding opioids-to estimate the level of opioid tolerance-be carried out to assist in the interpretation of cases involving synthetic opioids such as furanylfentanyl.
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23.
  • Herp, Simone, et al. (författare)
  • Mucispirillum schaedleri Antagonizes Salmonella Virulence to Protect Mice against Colitis
  • 2019
  • Ingår i: Cell Host and Microbe. - : Elsevier BV. - 1931-3128 .- 1934-6069. ; 25:5, s. 681-694.e8
  • Tidskriftsartikel (refereegranskat)abstract
    • The microbiota and the gastrointestinal mucus layer play a pivotal role in protection against non-typhoidal Salmonella enterica serovar Typhimurium (S. Tm) colitis. Here, we analyzed the course of Salmonella colitis in mice lacking a functional mucus layer in the gut. Unexpectedly, in contrast to mucus-proficient littermates, genetically deficient mice were protected against Salmonellainduced gut inflammation in the streptomycin colitis model. This correlated with microbiota alterations and enrichment of the bacterial phylum Deferribacteres. Using gnotobiotic mice associated with defined bacterial consortia, we causally linked Mucispirillum schaedleri, currently the sole known representative of Deferribacteres present in the mammalian microbiota, to host protection against S. Tm colitis. Inhibition by M. schaedleri involves interference with S. Tm invasion gene expression, partly by competing for anaerobic electron acceptors. In conclusion, this study establishes M. schaedleri, a core member of the murine gut microbiota, as a key antagonist of S. Tm virulence in the gut.
  •  
24.
  • Huber, Roman, et al. (författare)
  • Patent Foramen Ovale and Cryptogenic Strokes in the Stroke in Young Fabry Patients Study.
  • 2017
  • Ingår i: Stroke. - 1524-4628. ; 48:1, s. 30-35
  • Tidskriftsartikel (refereegranskat)abstract
    • A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO.We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0-). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns.PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P<0,001); subdivision of cryptogenic strokes revealed a PFO in 24% of 978 ASCO 3 patients (n.s. versus ASCO 1 and 2) and a higher prevalence of 36% in 750 ASCO 0 cases (P<0.001 versus ASCO 3 and versus ASCO 1 and 2). PFO was more commonly observed in ASCO 0- (n=271) than in ASCO 0+ patients (n=479; 48 versus 29%; P<0.001). There was no PFO-associated magnetic resonance imaging lesion pattern.Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.
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25.
  • Javaheri, Anahita, et al. (författare)
  • Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs
  • 2017
  • Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.
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26.
  • Johansson, Anna, et al. (författare)
  • A non-fatal intoxication and seven deaths involving the dissociative drug 3-MeO-PCP
  • 2017
  • Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 275, s. 76-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: 3-methoxyphencyclidine (3-MeO-PCP) appeared on the illicit drug market in 2011 and is an analogue of phencyclidine, which exhibits anesthetic, analgesic and hallucinogenic properties. In this paper, we report data from a non-fatal intoxication and seven deaths involving 3-MeO-PCP in Sweden during the period March 2014 until June 2016. Case descriptions: The non-fatal intoxication case, a 19-year-old male with drug problems and a medical history of depression, was found awake but tachycardic, hypertensive, tachypnoeic and catatonic at home. After being hospitalized, his condition worsened as he developed a fever and lactic acidosis concomitant with psychomotor agitation and hallucinations. After 22 h of intensive care, the patient had made a complete recovery. During his hospitalization, a total of four blood samples were collected at different time points. The seven autopsy cases, six males and one female, were all in their twenties to thirties with psychiatric problems and/or an ongoing drug abuse. Methods: 3-MeO-PCP was identified with liquid chromatography (LC)/time-of-flight technology and quantified using LC-tandem mass spectrometry. Results: In the clinical case, the concentration of 3-MeO-PCP was 0.14 mu g/g at admission, 0.08 mu g/g 2.5 h after admission, 0.06 mu g/g 5 h after admission and 0.04 mu g/g 17 h after admission. The half-life of 3-MeO-PCP was estimated to 11 h. In the autopsy cases, femoral blood concentrations ranged from 0.05 mu g/g to 0.38 mu g/g. 3-MeO-PCP was the sole finding in the case with the highest concentration and the cause of death was established as intoxication with 3-MeO-PCP. In the remaining six autopsy cases, other medications and drugs of abuse were present as well. Conclusion: Despite being scheduled in January 2015, 3-MeO-PCP continues to be abused in Sweden. Exposure to 3-MeO-PCP may cause severe adverse events and even death, especially if the user does not receive life-supporting treatment.
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27.
  • Josefsson, Martin, et al. (författare)
  • Liquid chromatography/tandem mass spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum and cerebrospinal fluid
  • 2010
  • Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 53:3, s. 576-582
  • Tidskriftsartikel (refereegranskat)abstract
    • A validated, accurate and sensitive LC-MS/MS method for determination of olanzapine and its metabolite N-desmethylolanzapine has been developed. The analytes were quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring Olanzapine and desmethylolanzapine were extracted from serum or cerebral spinal fluid samples, 200 mu l, with tert-butyl methyl ether using olanzapine-D3 as internal standard Calibrations for olanzapine and desmethylolanzapine were linear within the selected range of 0.2-30 ng/ml (6-96 nM) in cerebral spinal fluid and for olanzapine in plasma, in the range of 5-100 ng/ml (16-320 nM) The method was successfully used for the analysis of samples from patients treated with olanzapine in the dose range of 2.5-25 mg/day.
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28.
  • Krantz, David, et al. (författare)
  • IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity
  • 2020
  • Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 92:6
  • Tidskriftsartikel (refereegranskat)abstract
    • In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.
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29.
  • Kronstrand, Robert, et al. (författare)
  • A Cluster of Deaths Involving 5-(2-Aminopropyl)Indole(5-IT)
  • 2013
  • Ingår i: Journal of Analytical Toxicology. - : Oxford University Press (OUP): Policy F. - 0146-4760 .- 1945-2403. ; 37:8, s. 542-546
  • Tidskriftsartikel (refereegranskat)abstract
    • During 2012, the designer drug 5-(2-aminopropyl)indole emerged in Sweden, and became available at different web sites under the name 5-IT or 5-API. This compound is an indole derivative and a positional isomer of alpha-methyltryptamine. In this paper, we report the pathology and toxicology from 15 deaths involving 5-IT. Routine postmortem toxicology was performed in femoral blood, using a targeted screening for pharmaceuticals and drugs of abuse with liquid chromatography time-of-flight technology, and positive results were quantified using chromatographic techniques. For 5-IT, a new method was developed using ultra-high-performance liquid chromatography and tandem mass spectrometry. In 11 cases, intoxication was the cause of death. Two cases were signed out as causa ignota, and they were considered to be natural deaths. All determinations of 5-IT were performed in femoral blood and the concentrations ranged from 0.7 to 18.6 mg/g. Two cases had 5-IT as the only drug identified, while the others presented with other psychotropic drugs or medications in the blood as well. Shortly after this series of deaths, 5-IT was scheduled as a hazardous substance according to the regulation Certain Goods Dangerous to Health on 18 September 2012 prohibiting the handling and selling of the drug. Since then, no positive cases have been found.
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30.
  • Kronstrand, Robert, et al. (författare)
  • A Screening Method for 30 Drugs in Hair Using Ultrahigh-Performance Liquid Chromatography Time-of-Flight Mass Spectrometry
  • 2013
  • Ingår i: Therapeutic Drug Monitoring. - : Lippincott, Williams and Wilkins. - 0163-4356 .- 1536-3694. ; 35:3, s. 288-295
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The objectives of this study were to develop and to validate a qualitative screening method that met the new Society of Hair Testing (SoHT) guideline criteria for thresholds. less thanbrgreater than less thanbrgreater thanMethods: Extraction of 20 mg hair was performed by a previously validated procedure using overnight incubation in a mixture of methanol:acetonitrile:formiate buffer pH 3 (10:10:80). Analysis was performed on an Agilent 6540 quadrupole time-of-flight mass spectrometer in combination with an Agilent 1290 Infinity ultrahigh-performance liquid chromatography system. Separation was achieved with a 12-minute linear gradient chromatography on a high-strength silica T3 column at acidic conditions. An in-house database containing 30 compounds from the groups amphetamines, opiates, opioids, cocaine, benzodiazepines, and other sedatives including 6 deuterated internal standards was built by analyzing solutions from certified standards. Data were extracted using mass accuracy of +/- 10 ppm, retention time deviation of +/- 0.15 minutes, and area of andgt;= 30,000 counts. Identification was based on scoring of retention time, accurate mass measurement, and isotopic pattern. Validation included selectivity, repeatability of analyte area, and the scoring parameters at the proposed thresholds and a method comparison with the present liquid chromatography-mass spectrometry-mass spectrometry method using 50 authentic hair samples. A daily cutoff calibrator was used to identify positive samples. less thanbrgreater than less thanbrgreater thanResults: All cutoffs could be met with imprecisions of less than 5% for most parameters and analytes. Hair from drug-free subjects did not produce any positive results and the method comparison agreed in more than 90% of the cases. less thanbrgreater than less thanbrgreater thanConclusions: We conclude that the developed method meets the criteria of the new SoHT guidelines for screening cutoffs. Even though no thresholds have been suggested for benzodiazepines, we conclude that thresholds between 0.05 and 0.1 ng/mg should be sufficient to determine regular use of these substances.
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31.
  • Kronstrand, Robert, et al. (författare)
  • LC-QTOF-MS as a superior strategy to immunoassay for the comprehensive analysis of synthetic cannabinoids in urine
  • 2014
  • Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Verlag (Germany). - 1618-2642 .- 1618-2650. ; 406:15, s. 3599-3609
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to compare the performance of an immunoassay screening for synthetic cannabinoids with a newly developed confirmation method using liquid chromatography quadrupole time-of-flight mass spectrometry. The screening included metabolites from JWH-018, JWH-073, and AM-2201. The confirmation included metabolites from AM-2201, JWH-018, JWH-019, JWH-073, JWH-081, JWH-122, JWH-210, JWH-250, JWH-398, MAM-2201, RCS-4, and UR-144. The immunoassay was tested and found to have no cross-reactivity with UR-144 metabolites but considerable cross-reactivity with MAM-2201 and JWH-122 metabolites. Sensitivity and specificity for the immunoassay were evaluated with 87 authentic urine samples and found to be 87 % and 82 %, respectively. With a cutoff at 2 ng/ml, the confirmation showed 80 positive findings in 38 cases. The most common finding was JWH-122 5-OH-pentyl, followed by JWH-018 5-OH-pentyl. There were 9 findings of UR-144 metabolites and 3 of JWH-073 metabolites. In summary, the immunoassay performed well, presenting both high sensitivity and specificity for the synthetic cannabinoids present in the urine samples tested. The rapid exchange of one cannabinoid for another may pose problems for immunoassays as well as for confirmation methods. However, we consider time-of-flight mass spectrometry to be superior since new metabolites can be quickly included and identified.
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32.
  • Kronstrand, Robert, et al. (författare)
  • Quantitation of hexahydrocannabinol (HHC) and metabolites in blood from DUID cases
  • 2024
  • Ingår i: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403.
  • Tidskriftsartikel (refereegranskat)abstract
    • Hexahydrocannabinol (HHC) was first reported in the EU in May 2022. HHC has three chiral carbon atoms, but only (6aR,9R,10aR)-HHC (9R-HHC) and (6aR,9S,10aR)-HHC (9S-HHC) have been encountered in HHC products. The aim of this study was to develop and validate a method for the quantitative analysis of 9R-HHC, 9S-HHC, 11-OH-9R-HHC, 9R-HHC-COOH, 9S-HHC-COOH and 8-OH-9R-HHC. In addition, an objective was to investigate the immunochemical cross-reactivity. Blood samples from driving under the influence of drugs (DUID) cases screened positive for cannabis using enzyme-linked immunoadsorbent assay (ELISA) and confirmed negative for tetrahydrocannabinol (THC), 11-hydroxy-THC and THC-COOH were reanalyzed with a newly validated HHC method to investigate the presence of HHC and metabolites. The LC-MS-MS method was validated for matrix effects, lower limit of quantification (LLOQ), calibration model, precision, bias and autosampler stability. Cross-reactivity on an ELISA method was investigated separately for 9R-HHC-COOH and 9S-HHC-COOH at a concentration range between 5 and 200 ng/mL. The cross-reactivity was found to be 120% for 9R-HHC-COOH and 48% for 9S-HHC-COOH. In the LC-MS-MS method, 9R-HHC-COOH, 9S-HHC-COOH and 11-OH-9R-HHC showed matrix effects <25% at both concentrations, while 8-OH-9R-HHC, 9R-HHC and 9S-HHC matrix effects exceeded 25% at both concentrations but showed good precision (<10% for both inter and intra day) and low bias (<6%) in the further validation. The LLOQ was investigated and established at 0.2 ng/mL for all analytes except the carboxylated metabolites that had an LLOQ of 2.0 ng/mL. The upper LOQ was 20 and 200 ng/mL, respectively. Reanalysis of cases (n = 145) confirmed HHC and metabolites in 32 cases (22%). It was determined that the major metabolite in blood after administration of HHC was 9R-HHC-COOH followed by 11-OH-9R-HHC and that presumptive positive cases are caught by the routine ELISA screening for cannabis.
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33.
  • Kronstrand, Robert, et al. (författare)
  • Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry
  • 2018
  • Ingår i: Forensic Science International. - : ELSEVIER IRELAND LTD. - 0379-0738 .- 1872-6283. ; 283
  • Tidskriftsartikel (refereegranskat)abstract
    • Liquid chromatographic methods coupled to high resolution mass spectrometry are increasingly used to identify compounds in various matrices including hair but there are few recommendations regarding the parameters and their criteria to identify a compound. In this study we present a method for the identification and quantification of a range of drugs and discuss the parameters used to identify a compound with high resolution mass spectrometry. Drugs were extracted from hair by incubation in a buffer: solvent mixture at 37 degrees C during 18 h. Analysis was performed on a chromatographic system comprised of an Agilent 6550 QTOF coupled to a 1290 Infinity UHPLC system. High resolution accurate mass data were acquired in the All Ions mode and exported into Mass Hunter Quantitative software for quantitation and identification using qualifier fragment ions. Validation included selectivity, matrix effects, calibration range, within day and between day precision and accuracy. The analytes were 7-amino-flunitrazepam, 7-amino-clonazepam, 7-amino-nitrazepam, acetylmorphine, alimemazine, alprazolam, amphetamine, benzoylecgonine, buprenorphine, diazepam, ethylmorphine, fentanyl, hydroxyzine, ketobemidone, codeine, cocaine, MDMA, methadone, methamphetamine, morphine, oxycodone, promethazine, propiomazine, propoxyphene, tramadol, zaleplone, zolpidem, and zopiclone. As proof of concept, hair from 29 authentic post mortem cases were analysed. The calibration range was established between 0.05 ng/mg to 5.0 ng/mg for all analytes except fentanyl (0.02-2.0), buprenorphine (0.04-2.0), and ketobemidone (0.05-4.0) as well as for alimemazine, amphetamine, cocaine, methadone, and promethazine (0.10-5.0). For all analytes, the accuracy of the fortified pooled hair matrix was 84-108% at the low level and 89-106% at the high level. The within series precisions were between 1.4 and 6.7% and the between series precisions were between 1.4 and 10.1%. From the 29 autopsy cases, 121 positive findings were encountered from 23 of the analytes in concentrations similar to those previously published. We conclude that the developed method proved precise and accurate and that it had sufficient performance for the purpose of detecting regular use of drugs or treatment with prescription drugs. To identify a compound we recommend the use of ion ratios as a complement to instrument software "matching scores". (c) 2018 Elsevier B.V. All rights reserved.
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34.
  • Kronstrand, Robert, 1966-, et al. (författare)
  • Rilmazafone: A Designer Benzodiazepine Pro-Drug Involved in Fatal Intoxications
  • 2023
  • Ingår i: Journal of Analytical Toxicology. - : OXFORD UNIV PRESS INC. - 0146-4760 .- 1945-2403. ; 47:7, s. 640-643
  • Tidskriftsartikel (refereegranskat)abstract
    • Rilmazafone is a pro-drug that can be prescribed in Japan to treat insomnia. Rilmazafone metabolizes into active compounds by a ring closure resulting in a triazolo benzodiazepine structure similar to alprazolam. In mid-2022, the National Board of Forensic Medicine in Sweden were requested to investigate two separate deaths with the suspected use of pagoclone. Packages labeled "Pagoclone" were found at each scene that was suspected to contain rilmazafone based on website information. During screening by high resolution mass spectrometry, rilmazafone metabolites were presumptively identified. Due to the lack of reference material for the active metabolites, the metabolites were synthesized in house and quantification of the compounds identified in the two autopsy cases was prompted. In Case 1, femoral blood concentrations of 7.9, 65 and 170 ng/g of the metabolites rilmazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included the medications haloperidol, alimemazine, fluoxetine, olanzapine and acetaminophen. In Case 2, femoral blood concentrations of 1.7, 1.4 and 70 ng/g of rimazolam, N-desmethyl rilmazolam and di-desmethyl rilmazolam, respectively, were detected. Additional toxicological findings included loperamide, alimemazine and pregabalin. The intake of rilmazafone was determined as the cause of death in Case 1 and contributed in the Case 2.
  •  
35.
  • Kronstrand, Robert, et al. (författare)
  • Toxicological Findings of Synthetic Cannabinoids in Recreational Users
  • 2013
  • Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 37:8, s. 534-541
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, several synthetic cannabinoid compounds have become popular recreational drugs of abuse because of their psychoactive properties. This paper presents toxicological findings of synthetic cannabinoids in whole blood from some cases of severe intoxication including quantitative data from recreational users and a fatal intoxication. Samples were analyzed by liquid chromatography-tandem mass spectrometry in a scheduled multiple reaction mode after a basic liquid extraction. Twenty-nine synthetic cannabinoids were included in the method. In our data set of similar to 3000 cases, 28% were found positive for one or more synthetic cannabinoid(s). The most common finding was AM-2201. Most of the analytes had median concentrations of andlt;0.5 ng/g in agreement with other published data. The emerging drugs MAM-2201 (n = 151) and UR-144 (n = 181) had mean (median) concentrations of 1.04 (0.37) and 1.26 (0.34), respectively. The toxicity of the synthetic cannabinoids seems to be worse than that of natural cannabis, probably owing to the higher potency and perhaps also to the presence of several different cannabinoids in the smoked incense and the difficulties of proper dosing. The acute toxic effects may under certain circumstances contribute to death.
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36.
  • Kronstrand, Robert, et al. (författare)
  • Unintentional Fatal Intoxications with Mitragynine and O-Desmethyltramadol from the Herbal Blend Krypton
  • 2011
  • Ingår i: Journal of Analytical Toxicology. - Niles, IL, USA : Preston Publications Inc. - 0146-4760 .- 1945-2403. ; 35:4, s. 242-247
  • Tidskriftsartikel (refereegranskat)abstract
    • The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitragynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol, added. O-Desmethyltramadol is an active metabolite of tramadol, a commonly prescribed analgesic.We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. Neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 µg/g, and O-desmethyltramadol concentrations, determined by gas chromatography with nitrogen-specific detection, ranged from 0.4 to 4.3 µg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.
  •  
37.
  • Kronstrand, Robert, et al. (författare)
  • Unintentional fatal intoxications with mitragynine and O-Desmethyltramadol from the herbal blend krypton
  • 2011
  • Ingår i: Journal of Analytical Toxicology. - 0146-4760 .- 1945-2403. ; 35:4, s. 242-247
  • Tidskriftsartikel (refereegranskat)abstract
    • The leaves of Kratom, a medicinal plant in Southeast Asia, have been used as an herbal drug for a long time. At least one of the alkaloids present in Kratom, mitraynine, is a mu-receptor agonist. Both Kratom and an additional preparation called Krypton are available via the internet. It seems to consist of powdered Kratom leaves with another mu-receptor agonist, O-desmethyltramadol added. O-desmethyltramadol is an acitve metabolite of tramadol, a commonly prescribed analgesic. We present nine cases of intoxication, occurring in a period of less than one year, where both mitragynine and O-desmethyltramadol were detected in the postmortem blood samples. neither tramadol nor N-desmethyltramadol was present in these samples, which implies that the ingested drug was O-desmethyltramadol. The blood concentrations of mitragynine, determined by ultra-performance liquid chromatography-tandem mass spectrometry, ranged from 0.02 to 0.18 μg/g, and O-desmethyltramadol concentrations, determined by gas chromatogtraphy with nitrogen-specific detection, ranged from 0.4 to 4.3 μg/g. We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet websites.  
  •  
38.
  • Madrigal-Gonzalez, Jaime, et al. (författare)
  • Climate reverses directionality in the richness-abundance relationship across the World's main forest biomes
  • 2020
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • More tree species can increase the carbon storage capacity of forests (here referred to as the more species hypothesis) through increased tree productivity and tree abundance resulting from complementarity, but they can also be the consequence of increased tree abundance through increased available energy (more individuals hypothesis). To test these two contrasting hypotheses, we analyse the most plausible pathways in the richness-abundance relationship and its stability along global climatic gradients. We show that positive effect of species richness on tree abundance only prevails in eight of the twenty-three forest regions considered in this study. In the other forest regions, any benefit from having more species is just as likely (9 regions) or even less likely (6 regions) than the effects of having more individuals. We demonstrate that diversity effects prevail in the most productive environments, and abundance effects become dominant towards the most limiting conditions. These findings can contribute to refining cost-effective mitigation strategies based on fostering carbon storage through increased tree diversity. Specifically, in less productive environments, mitigation measures should promote abundance of locally adapted and stress tolerant tree species instead of increasing species richness. Correlations between tree species diversity and tree abundance are well established, but the direction of the relationship is unresolved. Here the authors use path models to estimate plausible causal pathways in the diversity-abundance relationship across 23 global forests regions, finding a lack of general support for a positive diversity-abundance relationship, which is prevalent in the most productive lands on Earth only
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39.
  • Maric, Selma, et al. (författare)
  • Time-resolved small-angle neutron scattering as a probe for the dynamics of lipid exchange between human lipoproteins and naturally derived membranes
  • 2019
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerosis is the main killer in the western world. Today's clinical markers include the total level of cholesterol and high-/low-density lipoproteins, which often fails to accurately predict the disease. The relationship between the lipid exchange capacity and lipoprotein structure should explain the extent by which they release or accept lipid cargo and should relate to the risk for developing atherosclerosis. Here, small-angle neutron scattering and tailored deuteration have been used to follow the molecular lipid exchange between human lipoprotein particles and cellular membrane mimics made of natural, "neutron invisible" phosphatidylcholines. We show that lipid exchange occurs via two different processes that include lipid transfer via collision and upon direct particle tethering to the membrane, and that high-density lipoprotein excels at exchanging the human-like unsaturated phosphatidylcholine. By mapping the specific lipid content and level of glycation/oxidation, the mode of action of specific lipoproteins can now be deciphered. This information can prove important for the development of improved diagnostic tools and in the treatment of atherosclerosis.
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40.
  • Martin, Roman, 1982, et al. (författare)
  • Regional Innovation Systems and Global Flows of Knowledge
  • 2018
  • Ingår i: New Avenues for Regional Innovation Systems - Theoretical Advances, Empirical Cases and Policy Lessons. - Cham : Springer. - 9783319716602 - 9783319716619 ; , s. 127-147
  • Bokkapitel (refereegranskat)abstract
    • The literature on regional innovation systems emphasizes the role of the region as locus for interactive learning and knowledge exchange, stressing the importance of (geographical) proximity for innovation. Even though the importance of extra-regional knowledge is widely acknowledged, there has been only little emphasis on the particular role and the nature of global knowledge flows. The aim of this chapter is to explore the differentiated nature of global knowledge flows in regional innovation systems. We provide an overview of the different ways firms can gain access to global knowledge sources. Identified knowledge sourcing channels include international R&D collaborations, foreign direct investments, personally embedded relationships, international mobility of skilled labour, virtual communities and online platforms, and the participation in temporary clusters such as fairs, exhibitions, and conferences. Depending on regional innovation system preconditions, firms use and combine different knowledge sourcing channels to access global knowledge. Firms in organisationally thick and diversified regional innovation systems have a geographical advantage in accessing knowledge globally, but even firms in peripheral areas can exchange knowledge worldwide, due to improved means of transport and communication at distance. Furthermore, not only multinational companies that are dominated by analytical or synthetic knowledge bases, but even small and medium sized enterprises in symbolic industries are often deeply involved in global knowledge sourcing activities. We illustrate our arguments with interview data collected among New Media firms in southern Sweden and in the Oslo Region in Norway.
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41.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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42.
  • Migliorini, Gabriele, et al. (författare)
  • Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype
  • 2013
  • Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 122:19, s. 3298-3307
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute lymphoblastic leukemia (ALL) is the major pediatric cancer diagnosed in economically developed countries with B-cell precursor (BCP)-ALL, accounting for approximately 70% of ALL. Recent genome-wide association studies (GWAS) have provided the first unambiguous evidence for common inherited susceptibility to BCP-ALL, identifying susceptibility loci at 7p12.2, 9p21.3, 10q21.2, and 14q11.2. To identify additional BCP-ALL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1658 cases and 4723 controls, with validation in 1449 cases and 1488 controls. Combined analysis identified novel loci mapping to 10p12.2 (rs10828317, odds ratio [OR] = 1.23; P = 2.30 x 10(-9)) and 10p14marked by rs3824662(OR = 1.31; P = 8.62 x 10(-12)). The single nucleotide polymorphism rs10828317 is responsible for the N215S polymorphism in exon 7 of PIP4K2A, and rs3824662 localizes to intron 3 of the transcription factor and putative tumor suppressor gene GATA3. The rs10828317 association was shown to be specifically associated with hyperdiploid ALL, whereas the rs3824662-associated risk was confined to nonhyperdiploid non-TEL-AML1 + ALL. The risk allele of rs3824662 was correlated with older age at diagnosis (P < .001) and significantly worse event-free survivorship (P < .0001). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to BCP-ALL and the influence of constitutional genotype on disease development.
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43.
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44.
  • Moeller, Steffen, et al. (författare)
  • Community-driven development for computational biology at Sprints, Hackathons and Codefests
  • 2014
  • Ingår i: BMC Bioinformatics. - 1471-2105. ; 15, s. S7-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Computational biology comprises a wide range of technologies and approaches. Multiple technologies can be combined to create more powerful workflows if the individuals contributing the data or providing tools for its interpretation can find mutual understanding and consensus. Much conversation and joint investigation are required in order to identify and implement the best approaches. Traditionally, scientific conferences feature talks presenting novel technologies or insights, followed up by informal discussions during coffee breaks. In multi-institution collaborations, in order to reach agreement on implementation details or to transfer deeper insights in a technology and practical skills, a representative of one group typically visits the other. However, this does not scale well when the number of technologies or research groups is large. Conferences have responded to this issue by introducing Birds-of-a-Feather (BoF) sessions, which offer an opportunity for individuals with common interests to intensify their interaction. However, parallel BoF sessions often make it hard for participants to join multiple BoFs and find common ground between the different technologies, and BoFs are generally too short to allow time for participants to program together. Results: This report summarises our experience with computational biology Codefests, Hackathons and Sprints, which are interactive developer meetings. They are structured to reduce the limitations of traditional scientific meetings described above by strengthening the interaction among peers and letting the participants determine the schedule and topics. These meetings are commonly run as loosely scheduled unconferences (self-organized identification of participants and topics for meetings) over at least two days, with early introductory talks to welcome and organize contributors, followed by intensive collaborative coding sessions. We summarise some prominent achievements of those meetings and describe differences in how these are organised, how their audience is addressed, and their outreach to their respective communities. Conclusions: Hackathons, Codefests and Sprints share a stimulating atmosphere that encourages participants to jointly brainstorm and tackle problems of shared interest in a self-driven proactive environment, as well as providing an opportunity for new participants to get involved in collaborative projects.
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45.
  • Moor, Kathrin, et al. (författare)
  • High-avidity IgA protects the intestine by enchaining growing bacteria
  • 2017
  • Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 544:7651, s. 498-
  • Tidskriftsartikel (refereegranskat)abstract
    • Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ('immune exclusion')(1-3). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.
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46.
  • Reiser, Mario, et al. (författare)
  • Resolving molecular diffusion and aggregation of antibody proteins with megahertz X-ray free-electron laser pulses
  • 2022
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray free-electron lasers (XFELs) with megahertz repetition rate can provide novel insights into structural dynamics of biological macromolecule solutions. However, very high dose rates can lead to beam-induced dynamics and structural changes due to radiation damage. Here, we probe the dynamics of dense antibody protein (Ig-PEG) solutions using megahertz X-ray photon correlation spectroscopy (MHz-XPCS) at the European XFEL. By varying the total dose and dose rate, we identify a regime for measuring the motion of proteins in their first coordination shell, quantify XFEL-induced effects such as driven motion, and map out the extent of agglomeration dynamics. The results indicate that for average dose rates below 1.06 kGy μs−1 in a time window up to 10 μs, it is possible to capture the protein dynamics before the onset of beam induced aggregation. We refer to this approach as correlation before aggregation and demonstrate that MHz-XPCS bridges an important spatio-temporal gap in measurement techniques for biological samples.
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47.
  • Roman, Markus, et al. (författare)
  • Liquid chromatography/time-of-flight mass spectrometry analysis of postmortem blood samples for targeted toxicological screening
  • 2013
  • Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Verlag (Germany). - 1618-2642 .- 1618-2650. ; 405:12, s. 4107-4125
  • Tidskriftsartikel (refereegranskat)abstract
    • A liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS) method for targeted toxicological screening in human postmortem blood samples from forensic autopsy cases has been developed, validated and compared with a previously used method using gas chromatography with nitrogen-phosphorus detection (GC-NPD). Separation was achieved within 12 min by high-resolution gradient chromatography. Ions were generated in positive and negative electrospray ionization mode and were detected in 2-GHz single mass spectrometry mode, m/z range 50-1,000. Before injection, 0.25 g blood was prepared by protein precipitation with 500 mu L of a mixture of acetonitrile and ethanol containing deuterated internal standards. An in-house database comprising 240 drugs and metabolites was built by analysing solutions from certified standards or other documented reference material available. Identification was based on scoring of retention time, accurate mass measurement and isotopic pattern. Validation was performed on spiked blood samples and authentic postmortem blood samples. The thresholds defined as minimum required performance levels were for most compounds in the range from 0.01 to 0.10 mu g/g. Typically, a mass error of less than 2 ppm and a precision of area measurements of less than 5 % coefficient of variation were achieved. Positive identification was confirmed at concentrations up to 500 mu g/g. Most compounds were determined in positive ionization mode, but for a limited number of compounds (fewer than 4 %) negative ionization was needed and a few early-eluted compounds could not be identified owing to substantial influence of interferences from the matrix and were thus not included in the screening. A robust and valid toxicological screening by LC-TOF-MS for postmortem blood samples, covering 50 % more compounds, and with higher precision and sensitivity than the previously used screening by GC-NPD was achieved.
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48.
  • Schmale, Julia, et al. (författare)
  • Collocated observations of cloud condensation nuclei, particle size distributions, and chemical composition
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Cloud condensation nuclei (CCN) number concentrations alongside with submicrometer particle number size distributions and particle chemical composition have been measured at atmospheric observatories of the Aerosols, Clouds, and Trace gases Research InfraStructure (ACTRIS) as well as other international sites over multiple years. Here, harmonized data records from 11 observatories are summarized, spanning 98,677 instrument hours for CCN data, 157,880 for particle number size distributions, and 70,817 for chemical composition data. The observatories represent nine different environments, e.g., Arctic, Atlantic, Pacific and Mediterranean maritime, boreal forest, or high alpine atmospheric conditions. This is a unique collection of aerosol particle properties most relevant for studying aerosol-cloud interactions which constitute the largest uncertainty in anthropogenic radiative forcing of the climate. The dataset is appropriate for comprehensive aerosol characterization (e.g., closure studies of CCN), model-measurement intercomparison and satellite retrieval method evaluation, among others. Data have been acquired and processed following international recommendations for quality assurance and have undergone multiple stages of quality assessment.
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49.
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50.
  • Scott, Robert A., et al. (författare)
  • An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans
  • 2017
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:11, s. 2888-2902
  • Tidskriftsartikel (refereegranskat)abstract
    • To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 x 10(-8)), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action-associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
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