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Sökning: WFRF:(Kraus Stefan)

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1.
  • 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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2.
  • 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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3.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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4.
  • Abdalla, H., et al. (författare)
  • Gamma-ray blazar spectra with HESS II mono analysis : The case of PKS2155-304 and PG1553+113
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 600
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The addition of a 28 m Cherenkov telescope (CT5) to the H.E.S.S. array extended the experiment's sensitivity to lower energies. The lowest energy threshold is obtained using monoscopic analysis of data taken with CT5, providing access to gamma-ray energies below 100 GeV for small zenith angle observations. Such an extension of the instrument's energy range is particularly beneficial for studies of active galactic nuclei with soft spectra, as expected for those at a redshift >= 0.5. The high-frequency peaked BL Lac objects PKS 2155-304 (z = 0.116) and PG 1553 + 113 (0.43 < z < 0.58) are among the brightest objects in the gamma-ray sky, both showing clear signatures of gamma-ray absorption at E > 100 GeV interpreted as being due to interactions with the extragalactic background light (EBL). Aims. The aims of this work are twofold: to demonstrate the monoscopic analysis of CT5 data with a low energy threshold, and to obtain accurate measurements of the spectral energy distributions (SED) of PKS 2155-304 and PG 1553 + 113 near their SED peaks at energies approximate to 100 GeV. Methods. Multiple observational campaigns of PKS 2155 304 and PG 1553 + 113 were conducted during 2013 and 2014 using the full H.E.S.S. II instrument (CT1-5). A monoscopic analysis of the data taken with the new CT5 telescope was developed along with an investigation into the systematic uncertainties on the spectral parameters which are derived from this analysis. Results. Using the data from CT5, the energy spectra of PKS 2155 304 and PG 1553 + 113 were reconstructed down to conservative threshold energies of 80 GeV for PKS 2155 304, which transits near zenith, and 110 GeV for the more northern PG 1553 + 113. The measured spectra, well fitted in both cases by a log-parabola spectral model ( with a 5.0 similar to statistical preference for non-zero curvature for PKS 2155 304 and 4.5 sigma for PG 1553+113), were found consistent with spectra derived from contemporaneous Fermi-LAT data, indicating a sharp break in the observed spectra of both sources at E approximate to 100 GeV. When corrected for EBL absorption, the intrinsic H.E.S.S. II mono and Fermi-LAT spectrum of PKS 2155 304 was found to show significant curvature. For PG 1553+113, however, no significant detection of curvature in the intrinsic spectrum could be found within statistical and systematic uncertainties.
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5.
  • Addolorato, Giovanni, et al. (författare)
  • Hormones and drinking behaviour: new findings on ghrelin, insulin, leptin and volume-regulating hormones. An ESBRA Symposium report.
  • 2009
  • Ingår i: Drug and alcohol review. - : Wiley. - 1465-3362 .- 0959-5236. ; 28:2, s. 160-5
  • Tidskriftsartikel (refereegranskat)abstract
    • There is growing evidence for a role of appetite-related peptides and volume-regulating hormones in alcoholism. In particular, recent evidence has suggested that hormones, such as ghrelin, insulin and leptin and volume-regulating hormones, could play a role in alcohol-seeking behaviour. The goal of this review is to discuss the results of recent preclinical and clinical investigations on this topic. The findings indicate that neuroendocrinological mechanisms are potentially involved in the neurobiology of alcohol craving. Accordingly, research on this topic could lead to possible development of new therapeutic approaches in the treatment of patients with alcohol problems.
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6.
  • Colomb-Delsuc, Mathieu, et al. (författare)
  • Assessment of the percentage of full recombinant adeno-associated virus particles in a gene therapy drug using CryoTEM
  • 2022
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:6
  • Tidskriftsartikel (refereegranskat)abstract
    • In spite of continuous development of gene therapy vectors with thousands of drug candidates in clinical drug trials there are only a small number approved on the market today stressing the need to have characterization methods to assist in the validation of the drug development process. The level of packaging of the vector capsids appears to play a critical role in immunogenicity, hence an objective quantitative method assessing the content of particles containing a genome is an essential quality measurement. As transmission electron microscopy (TEM) allows direct visualization of the particles present in a specimen, it naturally seems as the most intuitive method of choice for characterizing recombinant adeno-associated virus (rAAV) particle packaging. Negative stain TEM (nsTEM) is an established characterization method for analysing the packaging of viral vectors. It has however shown limitations in terms of reliability. To overcome this drawback, we propose an analytical method based on CryoTEM that unambiguously and robustly determines the percentage of filled particles in an rAAV sample. In addition, we show that at a fixed number of vector particles the portion of filled particles correlates well with the potency of the drug. The method has been validated according to the ICH Q2 (R1) guidelines and the components investigated during the validation are presented in this study. The reliability of nsTEM as a method for the assessment of filled particles is also investigated along with a discussion about the origin of the observed variability of this method.
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7.
  • Ebersole, Charles R., et al. (författare)
  • Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
  • 2020
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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8.
  • Emery, Carolyn A, et al. (författare)
  • Establishing outcome measures in early knee osteoarthritis
  • 2019
  • Ingår i: Nature Reviews Rheumatology. - : Springer Science and Business Media LLC. - 1759-4804 .- 1759-4790. ; 15:7, s. 438-448
  • Forskningsöversikt (refereegranskat)abstract
    • The classification and monitoring of individuals with early knee osteoarthritis (OA) are important considerations for the design and evaluation of therapeutic interventions and require the identification of appropriate outcome measures. Potential outcome domains to assess for early OA include patient-reported outcomes (such as pain, function and quality of life), features of clinical examination (such as joint line tenderness and crepitus), objective measures of physical function, levels of physical activity, features of imaging modalities (such as of magnetic resonance imaging) and biochemical markers in body fluid. Patient characteristics such as adiposity and biomechanics of the knee could also have relevance to the assessment of early OA. Importantly, research is needed to enable the selection of outcome measures that are feasible, reliable and validated in individuals at risk of knee OA or with early knee OA. In this Perspectives article, potential outcome measures for early symptomatic knee OA are discussed, including those measures that could be of use in clinical practice and/or the research setting.
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9.
  • Fu, Jinglin, et al. (författare)
  • Survey of bidirectional transmittance distribution function measurement facilities by multilateral scale comparisons
  • 2024
  • Ingår i: Metrologia. - : Institute of Physics. - 0026-1394 .- 1681-7575. ; 61:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In recent years, a growing demand for the capability of performing accurate measurements of the bidirectional transmittance distribution function (BTDF) has been observed in industry, research and development, and aerospace applications. However, there exists no calibration and measurement capabilities-entry for BTDF in the database of the Bureau International des Poids et Mesures and to date no BTDF comparison has been conducted between different national metrology institutes (NMIs) or designated institutes (DIs). As a first step to a possible future key comparison and to test the existing capabilities of determining this measurand, two interlaboratory comparisons were performed. In comparison one, five samples of three different types of optical transmissive diffusers were measured by five NMIs and one DI. By specific sample choice, the focus for this study lay more on orientation-dependent scatter properties. In comparison two, where one NMI, one DI, one university, and three industrial partners investigated their measurement capabilities, the dependence on the orientation was not assessed, but two additional samples of the same material and different thickness were measured. Results of the two comparisons are presented, giving a good overview of existing experimental solutions, and showing specific sample-related problems to be solved for improved future BTDF measurements.
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10.
  • Gardner, Tyler, et al. (författare)
  • Precision Orbit of delta Delphini and Prospects for Astrometric Detection of Exoplanets
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 855:1, s. 1-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Combining visual and spectroscopic orbits of binary stars leads to a determination of the full 3D orbit, individual masses, and distance to the system. We present a full analysis of the evolved binary system delta Delphini using astrometric data from the MIRC and PAVO instruments on the CHARA long-baseline interferometer, 97 new spectra from the Fairborn Observatory, and 87 unpublished spectra from the Lick Observatory. We determine the full set of orbital elements for delta Del, along with masses of 1.78 +/- 0.07 M-circle dot and 1.62 +/- 0.07 M-circle dot for each component, and a distance of 63.61 +/- 0.89 pc. These results are important in two contexts: for testing stellar evolution models and for defining the detection capabilities for future planet searches. We find that the evolutionary state of this system is puzzling, as our measured flux ratios, radii, and masses imply a similar to 200 Myr age difference between the components, using standard stellar evolution models. Possible explanations for this age discrepancy include mass transfer scenarios with a now-ejected tertiary companion. For individual measurements taken over a span of two years, we achieve <10 mu as precision on the differential position with 10 minute observations. The high precision of our astrometric orbit suggests that exoplanet detection capabilities are within reach of MIRC at CHARA. We compute exoplanet detection limits around delta Del and conclude that, if this precision is extended to wider systems, we should be able to detect most exoplanets >2M(J) on orbits >0.75 au around individual components of hot binary stars via differential astrometry.
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11.
  • Golightly, Yvonne M., et al. (författare)
  • Association of Traumatic Knee Injury With Radiographic Evidence of Knee Osteoarthritis in Military Officers
  • 2023
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 75:8, s. 1744-1751
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The association between knee injury and knee osteoarthritis (OA) is understudied relative to its importance, particularly in younger populations. This study was undertaken to examine the association of knee injury with radiographic features of knee OA in military officers, who have a physically demanding profession and high rates of knee injury. Methods: Participants were recruited in 2015–2017 from an existing program that enrolled 6,452 military officers during 2004–2009. Officers with a history of knee ligament or meniscal injuries (n = 117 via medical record review) were compared to officers with no history of knee injury (n = 143). Bilateral posteroanterior knee radiographs were obtained using a standardized fixed-flexion positioning frame. All images were read for Kellgren/Lawrence (K/L) grade, osteophyte (OST), and joint space narrowing (JSN) scores. Data were analyzed using linear-risk regression models with generalized estimating equations. Results: Injured and noninjured participants were similar (mean age 28 years, mean body mass index 25 kg/m2, ~40% female). The mean time from first knee injury to imaging among injured participants was 9.2 years. Compared with noninjured knees, greater prevalence of radiographic OA (K/L grade ≥ 2), OST (grade ≥ 1), and JSN (grade ≥ 1) was observed among injured knees, with prevalence differences of +16% (95% confidence interval [95% CI] 10%, 22%), +29% (95% CI 20%, 38%), and + 17% (95% CI 10%, 24%), respectively. Approximately 1 in 6 officers with prior knee injury progressed to radiographic OA by age 30 years. Conclusion: At the midpoint of a projected 20-year military career, officers with a history of traumatic knee injury have a markedly increased prevalence of knee radiographic OA compared to officers without injury.
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12.
  • Huttmann, Felix, et al. (författare)
  • Europium Cyclooctatetraene Nanowire Carpets : A Low-Dimensional, Organometallic, and Ferromagnetic Insulator
  • 2019
  • Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 10:5, s. 911-917
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate the magnetic and electronic properties of europium cyclooctatetraene (EuCot) nanowires by means of low-temperature X-ray magnetic circular dichroism (XMCD) and scanning tunneling microscopy (STM) and spectroscopy (STS). The EuCot nanowires are prepared in situ on a graphene surface. STS measurements identify EuCot as an insulator with a minority band gap of 2.3 eV. By means of Eu M5,4 edge XMCD, orbital and spin magnetic moments of (-0.1 ± 0.3)μB and (+7.0 ± 0.6)μB, respectively, were determined. Field-dependent measurements of the XMCD signal at the Eu M5 edge show hysteresis for grazing X-ray incidence at 5 K, thus confirming EuCot as a ferromagnetic material. Our density functional theory calculations reproduce the experimentally observed minority band gap. Modeling the experimental results theoretically, we find that the effective interatomic exchange interaction between Eu atoms is on the order of millielectronvolts, that magnetocrystalline anisotropy energy is roughly half as big, and that dipolar energy is approximately ten times lower.
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13.
  • Hörmann, Ulrich, et al. (författare)
  • Voc from a Morphology Point of View : the Influence of Molecular Orientation on the Open Circuit Voltage of Organic Planar Heterojunction Solar Cells
  • 2014
  • Ingår i: Journal of physical chemistry C. - : American Chemical Society (ACS). - 1932-7455 .- 1932-7447. ; 118:46, s. 26462-26470
  • Tidskriftsartikel (refereegranskat)abstract
    • The film morphology and device performance of planar heterojunctionsolar cells based on the molecular donor material α-sexithiophene (6T) are investigated.Planar heterojunctions of 6T with two different acceptor molecules, the C60 fullerene anddiindenoperylene (DIP), have been prepared. The growth temperature of the 6T bottomlayer has been varied between room temperature and 100 °C for each acceptor. By meansof X-ray diffraction and X-ray absorption, we show that the crystallinity and the molecularorientation of 6T is influenced by the preparation conditions and that the 6T filmtemplates the growth of the subsequent acceptor layer. These structural changes areaccompanied by changes in the characteristic parameters of the correspondingphotovoltaic cells. This is most prominently observed as a shift of the open circuitvoltage (Voc): In the case of 6T/C60 heterojunctions, Voc decreases from 0.4 to 0.3 V,approximately, if the growth temperature of 6T is increased from room temperature to 100°C. By contrast, Voc increases from about 1.2 V to almost 1.4 V in the case of 6T/DIP solarcells under the same conditions. We attribute these changes upon substrate heating toincreased recombination in the C60 case while an orientation dependent intermolecular coupling seems to change the origin of the photovoltaic gap in the DIP case.
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14.
  • Jax, Elinor, et al. (författare)
  • Health monitoring in birds using bio-loggers and whole blood transcriptomics
  • 2021
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Monitoring and early detection of emerging infectious diseases in wild animals is of crucial global importance, yet reliable ways to measure immune status and responses are lacking for animals in the wild. Here we assess the usefulness of bio-loggers for detecting disease outbreaks in free-living birds and confirm detailed responses using leukocyte composition and large-scale transcriptomics. We simulated natural infections by viral and bacterial pathogens in captive mallards (Anas platyrhynchos), an important natural vector for avian influenza virus. We show that body temperature, heart rate and leukocyte composition change reliably during an acute phase immune response. Using genome-wide gene expression profiling of whole blood across time points we confirm that immunostimulants activate pathogen-specific gene regulatory networks. By reporting immune response related changes in physiological and behavioural traits that can be studied in free-ranging populations, we provide baseline information with importance to the global monitoring of zoonotic diseases.
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15.
  • Kraus, B, et al. (författare)
  • Quantum memory for nonstationary light fields based on controlled reversible inhomogeneous broadening
  • 2006
  • Ingår i: Physical Review A (Atomic, Molecular and Optical Physics). - 1050-2947. ; 73:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We propose a method for efficient storage and recall of arbitrary nonstationary light fields, such as, for instance, single photon time-bin qubits or intense fields, in optically dense atomic ensembles. Our approach to quantum memory is based on controlled, reversible, inhomogeneous broadening and relies on a hidden time-reversal symmetry of the optical Bloch equations describing the propagation of the light field. We briefly discuss experimental realizations of our proposal.
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16.
  • Kraus, Stefan, et al. (författare)
  • Planet Formation Imager (PFI) : Science vision and key requirements
  • 2016
  • Ingår i: Optical and Infrared Interferometry and Imaging V. - : SPIE. - 9781510601932 ; 9907
  • Konferensbidrag (refereegranskat)abstract
    • The Planet Formation Imager (PFI) project aims to provide a strong scientific vision for ground-based optical astronomy beyond the upcoming generation of Extremely Large Telescopes. We make the case that a breakthrough in angular resolution imaging capabilities is required in order to unravel the processes involved in planet formation. PFI will be optimised to provide a complete census of the protoplanet population at all stellocentric radii and over the age range from 0.1 to ∼100 Myr. Within this age period, planetary systems undergo dramatic changes and the final architecture of planetary systems is determined. Our goal is to study the planetary birth on the natural spatial scale where the material is assembled, which is the "Hill Sphere" of the forming planet, and to characterise the protoplanetary cores by measuring their masses and physical properties. Our science working group has investigated the observational characteristics of these young protoplanets as well as the migration mechanisms that might alter the system architecture. We simulated the imprints that the planets leave in the disk and study how PFI could revolutionise areas ranging from exoplanet to extragalactic science. In this contribution we outline the key science drivers of PFI and discuss the requirements that will guide the technology choices, the site selection, and potential science/technology tradeoffs.
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17.
  • Kraus, V. B., et al. (författare)
  • Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis
  • 2011
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:5, s. 515-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. Methods: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). Results: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. Conclusions: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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18.
  • Kraus, V B, et al. (författare)
  • Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use.
  • 2015
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 23:8, s. 1233-1241
  • Forskningsöversikt (refereegranskat)abstract
    • Osteoarthritis (OA) is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for OA that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of OA Development) and ROAP (Risk of OA Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages - REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools.
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19.
  • Kraus, V B, et al. (författare)
  • OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.
  • 2015
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 23:5, s. 686-697
  • Forskningsöversikt (refereegranskat)abstract
    • The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification.
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20.
  • Luetkemeier, Robert, et al. (författare)
  • A Qualitative Exploration of Conflicts in Human-Wildlife Interactions in Namibia's Kunene Region
  • 2023
  • Ingår i: Diversity. - : MDPI AG. - 1424-2818. ; 15:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Wildlife numbers are declining globally due to anthropogenic pressures. In Namibia, however, wildlife populations increased with policy instruments that allow private ownership and incentivize their sustainable use. Antithetically, this resulted in increased resource competition between humans and wildlife and triggered conflicts among various stakeholder groups. This paper summarizes the results of a qualitative exploration of conflicts in wildlife management in Namibia’s Kunene Region, adjacent to Etosha National Park. We conducted a workshop and expert interviews with stakeholders from relevant sectors. Our qualitative research sheds light on societal conflicts over wildlife that originate from diverging interests, livelihood strategies, moral values, knowledge holders, personal relations and views on institutional procedures. We frame our insights into conflicting human–wildlife interactions with theoretical concepts of social-ecological systems, ecosystem services and ecosystem disservices and open the floor for quantitative assessments. Overall, our results may present a suitable way of understanding biodiversity conflicts in a theoretical way.
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21.
  • Mobasheri, Ali, et al. (författare)
  • Osteoarthritis Research Society International (OARSI) : Past, present and future
  • 2021
  • Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:2
  • Forskningsöversikt (refereegranskat)abstract
    • We provide a detailed account of the origin and establishment of the Osteoarthritis Research Society International (OARSI) and celebrate its history from inception to the current day. We discuss the mission, vision and strategic objectives of OARSI and how these have developed and evolved over the last 3 decades. We celebrate the achievements of the society as we approach its 30th birthday, honor the entire presidential line and respectfully pay tribute to the past presidents who are no longer with us. We reflect on the strong foundations of our society, OARSI's efforts to disseminate understanding of the health, disability and economic burdens of osteoarthritis (OA) to policymakers, and the exciting initiatives to make the society inclusive and international. We thank our corporate and industrial sponsors, who have supported us over many years, without whom our annual congresses would not have been possible. We celebrate our longstanding strategic partnership with our publisher, Elsevier, and the successful launch of our new journal Osteoarthritis and Cartilage Open, the most significant new development in our dissemination toolbox. For the first time in the history of the organization, our annual congress was cancelled in April 2020 and the 2021 meeting will be virtual. Despite the numerous challenges posed by the ongoing COVID-19 pandemic and the need to adapt quickly to a rapidly changing landscape, we must remain optimistic about the future. We will take advantage of new exciting opportunities to advance our mission and vision to enhance the quality of life of persons with OA.
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22.
  • Ohta, Yurina, et al. (författare)
  • Extreme asymmetry in the polarized disk of V1247 Orionis
  • 2016
  • Ingår i: Nippon Tenmon Gakkai obun kenkyu hokoku. - : Oxford University Press (OUP). - 0004-6264. ; 68:4
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first near-infrared scattered-light detection of the transitional disk around V1247 Ori, which was obtained using high-resolution polarimetric differential imaging observations with Subaru/HiCIAO. Our imaging in the H band reveals the disk morphology at separations of similar to 0.'' 14-0.'' 86 (54-330 au) from the central star. The polarized intensity image shows a remarkable arc-like structure toward the southeast of the star, whereas the fainter northwest region does not exhibit any notable features. The shape of the arm is consistent with an arc of 0.'' 28 +/- 0.'' 09 in radius (108 au from the star), although the possibility of a spiral arm with a small pitch angle cannot be excluded. V1247 Ori features an exceptionally large azimuthal contrast in scattered, polarized light; the radial peak of the southeastern arc is about three times brighter than the northwestern disk measured at the same distance from the star. Combined with the previous indication of an inhomogeneous density distribution in the gap at less than or similar to 46 au, the notable asymmetry in the outer disk suggests the presence of unseen companions and/or planet-forming processes ongoing in the arc.
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23.
  • Quanz, Sascha P., et al. (författare)
  • Atmospheric characterization of terrestrial exoplanets in the mid-infrared : biosignatures, habitability, and diversity
  • 2022
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 54:2-3, s. 1197-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • Exoplanet science is one of the most thriving fields of modern astrophysics. A major goal is the atmospheric characterization of dozens of small, terrestrial exoplanets in order to search for signatures in their atmospheres that indicate biological activity, assess their ability to provide conditions for life as we know it, and investigate their expected atmospheric diversity. None of the currently adopted projects or missions, from ground or in space, can address these goals. In this White Paper, submitted to ESA in response to the Voyage 2050 Call, we argue that a large space-based mission designed to detect and investigate thermal emission spectra of terrestrial exoplanets in the mid-infrared wavelength range provides unique scientific potential to address these goals and surpasses the capabilities of other approaches. While NASA might be focusing on large missions that aim to detect terrestrial planets in reflected light, ESA has the opportunity to take leadership and spearhead the development of a large mid-infrared exoplanet mission within the scope of the “Voyage 2050” long-term plan establishing Europe at the forefront of exoplanet science for decades to come. Given the ambitious science goals of such a mission, additional international partners might be interested in participating and contributing to a roadmap that, in the long run, leads to a successful implementation. A new, dedicated development program funded by ESA to help reduce development and implementation cost and further push some of the required key technologies would be a first important step in this direction. Ultimately, a large mid-infrared exoplanet imaging mission will be needed to help answer one of humankind’s most fundamental questions: “How unique is our Earth?” 
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24.
  • Schmidt, Stefan, et al. (författare)
  • Identification of sawflies and horntails (Hymenoptera, ‘Symphyta’) through DNA barcodes: successes and caveats
  • 2017
  • Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 17, s. 670-685
  • Tidskriftsartikel (refereegranskat)abstract
    • The ‘Symphyta’ is a paraphyletic assemblage at the base of the order Hymenoptera, comprising 14 families and about 8750 species. All have phytophagous larvae, except for the Orussidae, which are parasitoids. This study presents and evaluates the results of DNA barcoding of approximately 5360 specimens of ‘Symphyta’, mainly adults, and 4362 sequences covering 1037 species were deemed of suitable quality for inclusion in the analysis. All extant families are represented, except for the Anaxyelidae. The majority of species and specimens are from Europe, but approximately 38% of the species and 13% of the specimens are of non-European origin. The utility of barcoding for species identification and taxonomy of ‘Symphyta’ is discussed on the basis of examples from each of the included families. A significant level of cryptic species diversity was apparent in many groups. Other attractive applications include the identification of immature stages without the need to rear them, community analyses based on metabarcoding of bulk samples and association of the sexes of adults.
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25.
  • Speakman, John R., et al. (författare)
  • Total daily energy expenditure has declined over the past three decades due to declining basal expenditure, not reduced activity expenditure
  • 2023
  • Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 579-588
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Obesity is caused by a prolonged positive energy balance(1,2). Whether reduced energy expenditure stemming from reduced activity levels contributes is debated(3,4). Here we show that in both sexes, total energy expenditure (TEE) adjusted for body composition and age declined since the late 1980s, while adjusted activity energy expenditure increased over time. We use the International Atomic Energy Agency Doubly Labelled Water database on energy expenditure of adults in the United States and Europe (n = 4,799) to explore patterns in total (TEE: n = 4,799), basal (BEE: n = 1,432) and physical activity energy expenditure (n = 1,432) over time. In males, adjusted BEE decreased significantly, but in females this did not reach significance. A larger dataset of basal metabolic rate (equivalent to BEE) measurements of 9,912 adults across 163 studies spanning 100 years replicates the decline in BEE in both sexes. We conclude that increasing obesity in the United States/Europe has probably not been fuelled by reduced physical activity leading to lowered TEE. We identify here a decline in adjusted BEE as a previously unrecognized factor.
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26.
  • Stitziel, Nathan O., et al. (författare)
  • Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
  • 2016
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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27.
  • Webb, Thomas R., et al. (författare)
  • Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
  • 2017
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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