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Sökning: WFRF:(Reinert T.)

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2.
  • Dyrskjot, L., et al. (författare)
  • Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR
  • 2012
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 107:8, s. 1392-1398
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio = 7.4 (95% confidence interval: 3.4-15.9), P < 0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.
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3.
  • Horio, M., et al. (författare)
  • Oxide Fermi liquid universality revealed by electron spectroscopy
  • 2020
  • Ingår i: Physical Review B. - 2469-9969 .- 2469-9950. ; 102:24
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a combined soft x-ray and high-resolution vacuum-ultraviolet angle-resolved photoemission spectroscopy study of the electron-overdoped cuprate Pr1.3-xLa0.7CexCuO4 (PLCCO). Demonstration of its highly two-dimensional band structure enabled precise determination of the in-plane self-energy dominated by electron-electron scattering. Through analysis of this self-energy and the Fermi liquid cut-off energy scale, we find-in contrast to hole-doped cuprates-a momentum isotropic and comparatively weak electron correlation in PLCCO. Yet, the self-energies extracted from multiple oxide systems combine to demonstrate a logarithmic divergent relation between the quasiparticle scattering rate and mass. This constitutes a spectroscopic version of the Kadowaki-Woods relation with an important merit-the demonstration of Fermi liquid quasiparticle lifetime and mass being set by a single energy scale.
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4.
  • Bodda, C., et al. (författare)
  • HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection
  • 2020
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 217:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus (HSV) is the main cause of viral encephalitis in the Western world, and the type I interferon (IFN) system is important for antiviral control in the brain. Here, we have compared Ifnb induction in mixed murine brain cell cultures by a panel of HSV1 mutants, each devoid of one mechanism to counteract the IFN-stimulating cGAS-STING pathway. We found that a mutant lacking the deubiquitinase (DUB) activity of the VP1-2 protein induced particularly strong expression of Ifnb and IFN-stimulated genes. HSV1 ΔDUB also induced elevated IFN expression in murine and human microglia and exhibited reduced viral replication in the brain. This was associated with increased ubiquitination of STING and elevated phosphorylation of STING, TBK1, and IRF3. VP1-2 associated directly with STING, leading to its deubiquitination. Recruitment of VP1-2 to STING was dependent on K150 of STING, which was ubiquitinated by TRIM32. Thus, the DUB activity of HSV1 VP1-2 is a major viral immune-evasion mechanism in the brain. © 2020 Bodda et al.
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5.
  • Islam, Fhokrul, et al. (författare)
  • Systematics of electronic and magnetic properties in the transition metal doped Sb2Te3 quantum anomalous Hall platform
  • 2018
  • Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 97:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The quantum anomalous Hall effect (QAHE) has recently been reported to emerge in magnetically doped topological insulators. Although its general phenomenology is well established, the microscopic origin is far from being properly understood and controlled. Here, we report on a detailed and systematic investigation of transition metal (TM) doped Sb2Te3. By combining density functional theory calculations with complementary experimental techniques, i.e., scanning tunneling microscopy, resonant photoemission, and x-raymagnetic circular dichroism, we provide a complete spectroscopic characterization of both electronic and magnetic properties. Our results reveal that the TM dopants not only affect the magnetic state of the host material, but also significantly alter the electronic structure by generating impurity-derived energy bands. Our findings demonstrate the existence of a delicate interplay between electronic and magnetic properties in TM doped topological insulators. In particular, we find that the fate of the topological surface states critically depends on the specific character of the TM impurity: while V-and Fe-doped Sb2Te3 display resonant impurity states in the vicinity of the Dirac point, Cr and Mn impurities leave the energy gap unaffected. The single-ion magnetic anisotropy energy and easy axis, which control the magnetic gap opening and its stability, are also found to be strongly TM impurity dependent and can vary from in plane to out of plane depending on the impurity and its distance from the surface. Overall, our results provide general guidelines for the realization of a robust QAHE in TM doped Sb2Te3 in the ferromagnetic state.
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6.
  • Lekki, J., et al. (författare)
  • On the follicular pathway of percutaneous uptake of nanoparticles: Ion microscopy and autoradiography studies
  • 2007
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 260:1, s. 174-177
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on the visualization of the penetration of sunscreen formulations containing TiO2 nanoparticles (about 20 nm primary particle size) into hair follicles of both human and porcine skin using the complementary methods of ion microscopy (PIXE, RBS, STIM) and autoradiography. Particles were found as deep as approx. 400 pin in the follicle, obviously introduced mechanically rather than by a diffusive process. No particles were observed in vital tissue nor in sebaceous glands. (c) 2007 Elsevier B.V. All rights reserved.
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  • Nilsson, Charlotta, et al. (författare)
  • The new target chamber at LIPSION: The new translation stage and goniometer and the new irradiation platform for single cell experiments
  • 2007
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. ; 260:1, s. 71-76
  • Tidskriftsartikel (refereegranskat)abstract
    • A new target chamber as well as a new 7-axes translation stage with goniometer will shortly be implemented at the LIPSION nanoprobe in Leipzig. This new stage should enable linear motion as well as rotary motion with high precision, positioning accuracy and repeatability. These different features have been investigated online as well as offline, with encouraging results. Along with the new equipment, new software is also being developed, to provide stage control running over network. These software developments, including a graphical user interface, will also be described. As part of the new target chamber, a new external beam facility and irradiation platform for single ion experiments on single living cells is being assembled. A detailed description of the new cell irradiation platform, including beam extraction, new cell dishes, and cell recognition aspects will be given. It will be shown that the possibility of offline cell recognition, possibly using a differential interference contrast microscope, is an option.
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  • Bentmann, H., et al. (författare)
  • Strong Linear Dichroism in Spin-Polarized Photoemission from Spin-Orbit-Coupled Surface States
  • 2017
  • Ingår i: Physical Review Letters. - 0031-9007. ; 119:10
  • Tidskriftsartikel (refereegranskat)abstract
    • A comprehensive understanding of spin-polarized photoemission is crucial for accessing the electronic structure of spin-orbit coupled materials. Yet, the impact of the final state in the photoemission process on the photoelectron spin has been difficult to assess in these systems. We present experiments for the spin-orbit split states in a Bi-Ag surface alloy showing that the alteration of the final state with energy may cause a complete reversal of the photoelectron spin polarization. We explain the effect on the basis of ab initio one-step photoemission theory and describe how it originates from linear dichroism in the angular distribution of photoelectrons. Our analysis shows that the modulated photoelectron spin polarization reflects the intrinsic spin density of the surface state being sampled differently depending on the final state, and it indicates linear dichroism as a natural probe of spin-orbit coupling at surfaces.
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11.
  • Iversen, M. B., et al. (författare)
  • An innate antiviral pathway acting before interferons at epithelial surfaces
  • 2016
  • Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 17:2, s. 150-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Mucosal surfaces are exposed to environmental substances and represent a major portal of entry for microorganisms. The innate immune system is responsible for early defense against infections and it is believed that the interferons (IFNs) constitute the first line of defense against viruses. Here we identify an innate antiviral pathway that works at epithelial surfaces before the IFNs. The pathway is activated independently of known innate sensors of viral infections through a mechanism dependent on viral O-linked glycans, which induce CXCR3 chemokines and stimulate antiviral activity in a manner dependent on neutrophils. This study therefore identifies a previously unknown layer of antiviral defense that exerts its action on epithelial surfaces before the classical IFN response is operative.
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12.
  • Jacquet, J M, et al. (författare)
  • Safety and immunogenicity of a combined DTPa-IPV vaccine administered as a booster from 4 years of age : a review
  • 2006
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 24:13, s. 2440-2448
  • Tidskriftsartikel (refereegranskat)abstract
    • A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed compared to 5.5% of DTPw-primed children. Large swelling involving the entire upper arm (extending to involve the elbow joint) was reported for up to 1.2% of DTPa-primed subjects, which is consistent with literature reports for other DTPa vaccines.
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13.
  • Karlsen, Reinert Huseby, et al. (författare)
  • A post audit and inverse modeling in reactive transport : 50 years of artificial recharge in the Amsterdam Water Supply Dunes
  • 2012
  • Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 454, s. 7-25
  • Tidskriftsartikel (refereegranskat)abstract
    • This article describes the post audit and inverse modeling of a 1-D forward reactive transport model. The model simulates the changes in water quality following artificial recharge of pre-treated water from the river Rhine in the Amsterdam Water Supply Dunes using the PHREEQC-2 numerical code. One observation dataset is used for model calibration, and another dataset for validation of model predictions. The total simulation time of the model is 50 years, from 1957 10 2007, with recharge composition varying on a monthly basis and the post audit is performed 26 years after the former model simulation period. The post audit revealed that the original model could reasonably predict conservative transport and kinetic redox reactions (oxygen and nitrate reduction coupled to the oxidation of soil organic carbon), but showed discrepancies in the simulation of cation exchange. Conceptualizations of the former model were inadequate to accurately simulate water quality changes controlled by cation exchange, especially concerning the breakthrough of potassium and magnesium fronts. Changes in conceptualization and model design, including the addition of five flow paths, to a total of six, and the use of parameter estimation software (PEST), resulted in a better model to measurement fit and system representation. No unique parameter set could be found for the model, primarily due to high parameter correlations, and an assessment of the predictive error was made using a calibration constrained Monte-Carlo method, and evaluated against field observations. The predictive error was found to be low for Na+ and Ca2+, except for greater travel times, while the K+ and Mg2+ error was restricted to the exchange fronts at some of the flow paths. Optimized cation exchange coefficients were relatively high, especially for potassium, but still within the observed range in literature. The exchange coefficient for potassium agrees with strong fixation on illite, a main clay mineral in the area. Optimized CEC values were systematically lower than clay and organic matter contents indicated, possibly reflecting preferential flow of groundwater through the more permeable but less reactive aquifer parts. Whereas the artificial recharge initially acted as an intrusion of relatively saline water triggering Na+ for Ca2+ exchange, further increasing total hardness of the recharged water, the gradual long-term reduction in salinity of the river Rhine since the mid 1970s has shifted to an intrusion of fresher water causing Ca2+ for Na+ exchange. As a result, seasonal and longer term reversal of the initial cation exchange processes was observed adding to the general long-term reduction in total hardness of the recharged Rhine water.
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14.
  • Karlsen, Reinert, 1983-, et al. (författare)
  • The role of landscape properties, storage and evapotranspiration on variability in streamflow recessions in a boreal catchment
  • 2019
  • Ingår i: Journal of Hydrology. - : ELSEVIER SCIENCE BV. - 0022-1694 .- 1879-2707. ; 570, s. 315-328
  • Tidskriftsartikel (refereegranskat)abstract
    • Streamflow recession analysis provides valuable insights into catchment functioning that can be related to runoff generation, storage retention and baseflow dynamics. As an integrated characteristic, recession analysis is particularly useful in catchment comparison studies to help explain drivers of spatial and temporal variability in hydrological behavior. Here, five years of hourly streamflow data from 14, partly nested, catchments within a 68 km(2) boreal forest landscape in Northern Sweden were used to explore spatiotemporal variation in hydrological processes through recession analysis. The aim of this study was to better understand spatial variation in runoff generation and storage-discharge dynamics across the landscape, as well as the relation to landscape properties. Due to high collinearity between variables, partial least square regression was used to quantify the associations between recession characteristics and catchment properties, as well as to identify key variables controlling recession behavior. We analyzed recession characteristics using both an aggregated approach including all recession data and individual recession events. The analyses based on individual recession events, indicated that catchment topography, quantified by indices such as mean slope or elevation above the stream network, is a primary control on the recession behavior during relatively high flows, whereas catchment area gains importance when flows are relatively low. The proportion of sediment and deep soils also controlled recession behavior. Furthermore, we found that recession characteristics are influenced by both evapotranspiration (ET) and proxies of antecedent catchment storage, but that the patterns were different depending on catchment properties. ET was less influential in catchments with deeper soils and larger catchment area. Shifts in recession rates were primarily related to variation in storage, with faster streamflow recessions occurring during periods with low storage. The results demonstrate the influence of catchment properties on recession behavior, and we found great value in analyzing individual recession events for an increased understanding of spatial and temporal recession characteristics. When recession properties were lumped together, the relationships to catchment characteristics were obscured. This indicates the value of more detailed analyses, at least under the strongly seasonal hydroclimatic conditions of this site.
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  • Sullivan, Nathaniel A.T., et al. (författare)
  • Differences in analysis and treatment of upper airway obstruction in Robin sequence across different countries in Europe
  • 2023
  • Ingår i: European Journal of Pediatrics. - : Springer Verlag. - 0340-6199 .- 1432-1076. ; 182:3, s. 1271-1280
  • Tidskriftsartikel (refereegranskat)abstract
    • The goal of this study was to explore the availability of diagnostic and treatment options for managing upper airway obstruction (UAO) in infants with Robin Sequence (RS) in Europe. Countries were divided in lower- (LHECs, i.e., PPP per capita < $4000) and higher-health expenditure countries (HHECs, i.e., PPP per capita ≥ $4000). An online survey was sent to European healthcare professionals who treat RS. The survey was designed to determine the availability of diagnostic tools such as arterial blood gas analysis (ABG), pulse oximetry, CO2 analysis, polysomnography (PSG), and sleep questionnaires, as well as to identify the used treatment options in a specific center. Responses were received from professionals of 85 centers, originating from 31 different countries. It was equally challenging to provide care for infants with RS in both LHECs and HHECs (3.67/10 versus 2.65/10, p = 0.45). Furthermore, in the LHECs, there was less access to ABG (85% versus 98%, p = 0.03), CO2 analysis (45% versus 70%, p = 0.03), and PSG (54% versus 93%, p < 0.01). There were no significant differences in the accessibility concerning pulse oximetry, sleep questionnaires, home saturation monitoring, nasopharyngeal tubes, Tuebingen plates, and mandibular distraction. Conclusion: This study demonstrates a large difference in available care for infants with RS throughout Europe. LHECs have less access to diagnostic tools in RS when compared to HHECs. There is, however, no difference in the availability of treatment modalities between LHECs and HHECs.What is Known:• Patients with Robin sequence (RS) require complex and multidisciplinary care. They can present with moderate to severe upper airway obstruction (UAO). There exists a large variety in the use of diagnostics for both UAO treatmentindications and evaluations. In most cases, conservative management of UAO in RS is sufficient. Patients with UAO that persist despite conservative management ultimately need surgical intervention. To determine which intervention is best suitable for theindividual RS patient, the level of UAO needs to be determined through diagnostic testing.• There is a substantial variation among institutions across Europe for both diagnostics and treatment options in UAO. A standardized, internationally accepted protocol for the assessment and management of UAO in RS could guide healthcare professionals in the timing of assessment and indications to prevent escalation of UAO. Creating such a protocol might be a challenge, as there are large financial differences between countries in Europe (e.g., health expenditure per capita in purchasing power parity in international dollars ranges from $600 to over $8500).What is New:• There is a substantial variation in the availability of objective diagnostic tools between European countries. Arterial blood gas analysis, CO2 analysis and polysomnography are not equally accessible for lower-healthcare expenditure countries (LHECs) compared to higher-healthcare expenditure countries (HHECs). These differences are not only limited to availability; there is also a difference in quality of these diagnostic tools. Surprisingly, there is no difference in access to treatment tools between LHECs and HHECs.• There is national heterogeneity in access to tools for diagnosis and treatment of RS, which suggests centralization of health care, showing that specialized care is only available in tertiary centers. By centralization of care for RS infants, diagnostics and treatment can be optimized in the best possible way to create a uniform European protocol and ultimately equal care across Europe. Learning what is necessary for adequate monitoring could lead to better allocation of resources, which is especially important in a low-resource setting.
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18.
  • Teutschbein, Claudia, 1985-, et al. (författare)
  • Simulating streamflow in ungauged basins under a changing climate : The importance of landscape characteristics
  • 2018
  • Ingår i: Journal of Hydrology. - : Elsevier. - 0022-1694 .- 1879-2707. ; 561, s. 160-178
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we explored how landscape characteristics such as topography, geology, soils and land cover influence the way catchments respond to changing climate conditions. Based on an ensemble of 15 regional climate models bias-corrected with a distribution-mapping approach, present and future streamflow in 14 neighboring and rather similar catchments in Northern Sweden was simulated with the HBV model. We established functional relationships between a range of landscape characteristics and projected changes in streamflow signatures. These were then used to analyze hydrological consequences of physical perturbations in a hypothetically ungauged basin in a climate change context. Our analysis showed a strong connection between the forest cover extent and the sensitivity of different components of a catchment's hydrological regime to changing climate conditions. This emphasizes the need to redefine forestry goals and practices in advance of climate change-related risks and uncertainties.
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