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Träfflista för sökning "WFRF:(Hellström S) "

Sökning: WFRF:(Hellström S)

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1.
  • Adam, A, et al. (författare)
  • Abstracts from Hydrocephalus 2016.
  • 2017
  • Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
  • Tidskriftsartikel (refereegranskat)
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2.
  • Lalkovski, S., et al. (författare)
  • Core-coupled states and split proton-neutron quasiparticle multiplets in Ag122-126
  • 2013
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:3, s. 034308-
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutron-rich silver isotopes were populated in the fragmentation of a Xe-136 beam and the relativistic fission of U-238. The fragments were mass analyzed with the GSI Fragment Separator and subsequently implanted into a passive stopper. Isomeric transitions were detected by 105 high-purity germanium detectors. Eight isomeric states were observed in Ag122-126 nuclei. The level schemes of Ag-122,Ag-123,Ag-125 were revised and extended with isomeric transitions being observed for the first time. The excited states in the odd-mass silver isotopes are interpreted as core-coupled states. The isomeric states in the even-mass silver isotopes are discussed in the framework of the proton-neutron split multiplets. The results of shell-model calculations, performed for the most neutron-rich silver nuclei are compared to the experimental data.
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3.
  • Caceres, L., et al. (författare)
  • Spherical proton-neutron structure of isomeric states in Cd-128
  • 2009
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 79:1, s. 011301-
  • Tidskriftsartikel (refereegranskat)abstract
    • The gamma-ray decay of isomeric states in the even-even nucleus Cd-128 has been observed. The nucleus of interest was produced both by the fragmentation of Xe-136 and the fission of U-238 primary beams. The level scheme was unambiguously constructed based on.. coincidence relations in conjunction with detailed lifetime analysis employed for the first time on this nucleus. Large-scale shell-model calculations, without consideration of excitations across the N = 82 shell closure, were performed and provide a consistent description of the experimental level scheme. The structure of the isomeric states and their decays exhibit coexistence of proton, neutron, and strongly mixed configurations due to p. interaction in overlapping orbitals for both proton and neutron holes.
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4.
  • Gorska, M., et al. (författare)
  • Evolution of the N=82 Shell Gap below 132Sn Inferred from Core Excited States in 131In
  • 2009
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 672:4-5, s. 313-316
  • Tidskriftsartikel (refereegranskat)abstract
    • The gamma-ray decay of ail excited state in In-131, the one proton hole neighbor of the doubly magic (132)sn has been measured. A high-spin, core-excited isomer with T-1/2 = 630(60) us was identified following production by both relativistic fragmentation of a Xe-136 beam and fission Of a U-238 beam. This state deexcites by a single gamma-ray branch of 3782(2) keV from which direct evidence for the size of the N = 82 shell gal) is inferred. The results are discussed in comparison to a shell-model Calculation including configurations across the closed shells at N = 82 and Z = 50. (C) 2009 Elsevier B.V. All rights reserved.
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5.
  • Doornenbal, P., et al. (författare)
  • RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
  • 2007
  • Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
  • Konferensbidrag (refereegranskat)abstract
    • The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
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6.
  • Fu, Z., et al. (författare)
  • Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice
  • 2018
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:5, s. 974-985
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinal neuronal abnormalities occur before vascular changes in diabetic retinopathy. Accumulating experimental evidence suggests that neurons control vascular pathology in diabetic and other neovascular retinal diseases. Therefore, normalizing neuronal activity in diabetes may prevent vascular pathology. We investigated whether fibroblast growth factor 21 (FGF21) prevented retinal neuronal dysfunction in insulindeficient diabetic mice. We found that in diabetic neural retina, photoreceptor rather than inner retinal function was most affected and administration of the long-acting FGF21 analog PF-05231023 restored the retinal neuronal functional deficits detected by electroretinography. PF-05231023 administration protected against diabetes-induced disorganization of photoreceptor segments seen in retinal cross section with immunohistochemistry and attenuated the reduction in the thickness of photoreceptor segments measured by optical coherence tomography. PF-05231023, independent of its downstream metabolic modulator adiponectin, reduced inflammatory marker interleukin-1β (IL-1β) mRNA levels. PF-05231023 activated the AKT-nuclear factor erythroid 2-related factor 2 pathway and reduced IL-1β expression in stressed photoreceptors. PF-05231023 administration did not change retinal expression of vascular endothelial growth factor A, suggesting a novel therapeutic approach for the prevention of early diabetic retinopathy by protecting photoreceptor function in diabetes.
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7.
  • Naqvi, F., et al. (författare)
  • Isomer spectroscopy of (127)Cd
  • 2010
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 82:3, s. 034323-
  • Tidskriftsartikel (refereegranskat)abstract
    • The spin and configurational structure of excited states of (127)Cd, the two-proton and three-neutron hole neighbor of (132)Sn, has been studied. An isomeric state with a half-life of 17.5(3) mu s was populated in the fragmentation of a (136)Xe beam on a (9)Be target at a beam energy of 750 MeV/u. Time distributions of the delayed gamma transitions and gamma gamma coincidence relations were exploited to construct a decay scheme. The observed yrast (19/2)(+) isomer is proposed to have dominant configurations of nu(h(11/2)(-3))pi(g(9/2)(-1), p(1/2)(-1)), nu(h(11/2)(-2)d(3/2)(-1))pi(g(9/2)(-2)), and nu(h(11/2)(-2), s(1/2)(-1))pi(g(9/2)(-2)) and to decay by two competing stretched M2 and E3 transitions. Experimental results are compared with the isotone (129)Sn. The new information provides input for the proton-neutron interaction and the evolution of neutron hole energies in nuclei around the doubly magic (132)Sn core.
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8.
  • Pietri, S., et al. (författare)
  • First observation of the decay of a 15(-) seniority v=4 isomer in Sn-128
  • 2011
  • Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 83:4, s. 044328-
  • Tidskriftsartikel (refereegranskat)abstract
    • Isomeric states in the semimagic Sn128-130 isotopes were populated in the fragmentation of a Xe-136 beam on a Be-9 target at an energy of 750 A.MeV. The decay of an isomeric state in Sn-128 at an excitation energy of 4098 keV has been observed. Its half live has been determined to be T-1/2 = 220(30) ns from the time distributions of the delayed gamma rays emitted in its decay. gamma gamma coincidence relations were analyzed in order to establish the decay pattern of the newly established state toward the known (7(-)) and (10(+)) isomers at excitation energies of 2092 and 2492 keV, respectively. Based on a comparison with results of state-of-the-art shell-model calculations the new isomeric state is proposed to have the nu h(11/2)(-3)d(3/2)(-1) configuration with the four neutron holes in Sn-132 maximally aligned to a total spin of I-pi = 15(-).
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9.
  • Podolyak, Zs., et al. (författare)
  • Isomeric Decay Studies Around 204Pt and 148Tb
  • 2007
  • Ingår i: The European Physical Journal. Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 150, s. 165-168
  • Tidskriftsartikel (refereegranskat)abstract
    • Relativistic energy projectile fragmentation of Pb-208 has been used to produce a range of exotic nuclei. The nuclei of interest were studied by detecting delayed gamma rays following the decay of isomeric states. Experimental information on the excited states of the neutron-rich N = 126 nucleus, Pt-204, following internal decay of two isomeric states, was obtained for the first time. In addition, decays from the previously reported isomeric I=27h and I=(49/2)h states in Tb-148 and Gd-147, respectively, have been observed. These isomeric decays represent the highest spin discrete states observed to date following a projectile fragmentation reaction, and opens further the possibility of doing 'high-spin physics' using this technique.
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10.
  • Regan, P. H., et al. (författare)
  • First Results from the Stopped RISING Campaign at GSI: The Mapping of Isomeric Decays in Highly Exotic Nuclei
  • 2007
  • Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 899, s. 19-22
  • Konferensbidrag (refereegranskat)abstract
    • The first results from the Stopped Beam RISING experimental campaign performed at the GSI laboratory in Darmstadt, Germany, are presented. RISING (Rare ISotope INvestigations at GSI) constitutes a major new experimental program in European nuclear structure physics research aimed at using relativistic‐energy, projectile‐fragmentation reactions to study nuclei with exotic proton‐to‐neutron ratios. This paper introduces the physics aims of the Stopped RISING collaboration and presents some technical details and initial results from experiments using the RISING array to study decays from metastable nuclear states in both proton and neutron‐rich nuclei.
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11.
  • Rudolph, Dirk, et al. (författare)
  • Exciting Isomers from the First Stopped-beam RISING Campaign
  • 2007
  • Ingår i: The European Physical Journal. Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 150, s. 173-176
  • Tidskriftsartikel (refereegranskat)abstract
    • First results are reported from a major new initiative of experiments, which focus on nuclear structure studies at extreme isospin values by means of isomer spectroscopy. The experiments represent the first part of the so-called stopped-beam campaign within the Rare ISotope INvestigations at GSI (RISING) project. Time-correlated gamma decays from individually identified nuclear species have been measured, allowing the clean identification of isomeric decays in a wide range of exotic nuclei both at the proton drip-line and in heavy, neutron-rich systems. An overview of the experimental technique will be given, together with the performance of the new germanium detector array and future research plans for the collaboration.
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12.
  • Fu, Z. J., et al. (författare)
  • Dyslipidemia in retinal metabolic disorders
  • 2019
  • Ingår i: Embo Molecular Medicine. - : EMBO. - 1757-4676 .- 1757-4684. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • The light-sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid-rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.
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13.
  • Gong, Y., et al. (författare)
  • Cytochrome P450 Oxidase 2C Inhibition Adds to-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization
  • 2016
  • Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 36:9, s. 1919-1927
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of -3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but -3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of -3 LCPUFA on neovascular eye diseases. Approach and Results The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of -3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and -3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of -3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a -3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C -3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected -3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. Conclusions Inhibition of CYP2C activity adds to the protective effects of -3 LCPUFA on pathological retinal neovascularization and CNV.
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14.
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16.
  • Ocke, M. C., et al. (författare)
  • Energy intake and sources of energy intake in the European Prospective Investigation into Cancer and Nutrition
  • 2009
  • Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 63:4s, s. 3-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To describe energy intake and its macronutrient and food sources among 27 regions in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: Between 1995 and 2000, 36 034 subjects aged 35-74 years were administered a standardized 24-h dietary recall. Intakes of macronutrients (g/day) and energy (kcal/day) were estimated using standardized national nutrient databases. Mean intakes were weighted by season and day of the week and were adjusted for age, height and weight, after stratification by gender. Extreme low- and high-energy reporters were identified using Goldberg's cutoff points (ratio of energy intake and estimated basal metabolic rate <0.88 or >2.72), and their effects on macronutrient and energy intakes were studied. Results: Low-energy reporting was more prevalent in women than in men. The exclusion of extreme-energy reporters substantially lowered the EPIC-wide range in mean energy intake from 2196-2877 to 2309-2866 kcal among men. For women, these ranges were 1659-2070 and 1873-2108 kcal. There was no north-south gradient in energy intake or in the prevalence of low-energy reporting. In most centres, cereals and cereal products were the largest contributors to energy intake. The food groups meat, dairy products and fats and oils were also important energy sources. In many centres, the highest mean energy intakes were observed on Saturdays. Conclusions: These data highlight and quantify the variations and similarities in energy intake and sources of energy intake among 10 European countries. The prevalence of low-energy reporting indicates that the study of energy intake is hampered by the problem of underreporting. European Journal of Clinical Nutrition (2009) 63, S3-S15; doi: 10.1038/ejcn.2009.72
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17.
  • Fu, Z. J., et al. (författare)
  • FGF21 Administration Suppresses Retinal and Choroidal Neovascularization in Mice
  • 2017
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 18:7, s. 1606-1613
  • Tidskriftsartikel (refereegranskat)abstract
    • Pathological neovascularization, a leading cause of blindness, is seen in retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration. Using a mouse model of hypoxia-driven retinal neovascularization, wefind that fibroblast growth factor 21 (FGF21) administration suppresses, and FGF21 deficiency worsens, retinal neovessel growth. The protective effect of FGF21 against neovessel growth was abolished in adiponectin (APN)-deficient mice. FGF21 administration also decreased neovascular lesions in two models of neovascular age-related macular degeneration: very-low-density lipoprotein-receptor-deficient mice with retinal angiomatous proliferation and laser-induced choroidal neovascularization. FGF21 inhibited tumor necrosis alpha (TNF-alpha) expression but did not alter Vegfa expression in neovascular eyes. These data suggest that FGF21 may be a therapeutic target for pathologic vessel growth in patients with neovascular eye diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration.
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18.
  • Fu, Z. J., et al. (författare)
  • Targeting Neurovascular Interaction in Retinal Disorders
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 21:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The tightly structured neural retina has a unique vascular network comprised of three interconnected plexuses in the inner retina (and choroid for outer retina), which provide oxygen and nutrients to neurons to maintain normal function. Clinical and experimental evidence suggests that neuronal metabolic needs control both normal retinal vascular development and pathological aberrant vascular growth. Particularly, photoreceptors, with the highest density of mitochondria in the body, regulate retinal vascular development by modulating angiogenic and inflammatory factors. Photoreceptor metabolic dysfunction, oxidative stress, and inflammation may cause adaptive but ultimately pathological retinal vascular responses, leading to blindness. Here we focus on the factors involved in neurovascular interactions, which are potential therapeutic targets to decrease energy demand and/or to increase energy production for neovascular retinal disorders.
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19.
  • Ramos Santesmases, David, et al. (författare)
  • Optical concentration in fully delineated mid-wave infrared T2SL detectors arrays
  • 2023
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 123:18
  • Tidskriftsartikel (refereegranskat)abstract
    • The dependence of quantum efficiency (QE) on fill factor and pixel pitch is studied theoretically and experimentally in fully delineated type-II superlattice (T2SL) detectors. Theoretically, a 2-dimensional simulation model is used to compute the absorption in the array geometry, which shows an insensitivity of the optical response to the fill factor. This is a result of the photodiode array (PDA) geometry concentrating the light in the pixel area. QE measurements on PDAs with varying pixel pitch (from 225 to 10 μm) and fill factors (from 98% to 64%) confirm this independence of the QE on the fill factor and results in a 50% increase in the photocurrent density in 10 μm pitch PDAs compared to 225 μm pitch PDAs. Furthermore, measurements of the dark current density vs pixel size revealed an absence of surface leakage in these PDAs, which, combined with the increased photocurrent density results in an improved signal-to-noise ratio when reducing the pitch in these T2SL detectors. Finally, this result resolves the QE-modulation transfer function trade-off, as the electrical isolation of the pixel is carried out without impacting the QE of the array.
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20.
  • Ramos Santesmases, David, et al. (författare)
  • Simulation and Characterization of the Modulation Transfer Function in Fully Delineated Type-II Superlattices Infrared Detectors
  • 2024
  • Ingår i: IEEE Transactions on Electron Devices. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9383 .- 1557-9646. ; 71:4, s. 2459-2464
  • Tidskriftsartikel (refereegranskat)abstract
    • The modulation transfer function (MTF) in fully delineated 15 μ m pitch type-II superlattice (T2SL) mid-wave infrared (IR) detectors is studied theoretically and experimentally. Theoretically, a 2-D model to simulate the spot scan (SS) profile is presented and used to compute the MTF as a function of the wavelength and the array geometry (pitch size, trench width). The dependence of the detector trench on the MTF is also evaluated experimentally by the edge spread function (ESF) method according to the ISO12233 standard. The experimental results show an excellent agreement with the theoretical model, reporting an MTF of 0.61 and 0.60 at the Nyquist frequency for 1 and 2 μ m trench, respectively. With the simulation model, the effect of the increased optical crosstalk for smaller pixel pitch is discussed as a function of the trench width (0.5, 1, and 2 μ m) and incidence angle up to ± 30 ∘ . Simulation results show MTF values at the Nyquist frequency between 0.61–0.62, 0.58–0.60, and 0.55–0.57 with an average degradation of 1%, 2%, and 7% at an angle of ± 30 ∘ compared to normal incidence for the 10, 7.5, and 5 μ m pitch, respectively.
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21.
  • Tomita, Y., et al. (författare)
  • Free fatty acid receptor 4 activation protects against choroidal neovascularization in mice
  • 2020
  • Ingår i: Angiogenesis. - : Springer Science and Business Media LLC. - 0969-6970 .- 1573-7209. ; 23, s. 385-394
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine whether free fatty acid receptor 4 (FFAR4) activation can protect against choroidal neovascularization (CNV), which is a common cause of blindness, and to elucidate the mechanism underlying the inhibition, we used the mouse model of laser-induced CNV to mimic angiogenic aspects of age-related macular degeneration (AMD). Laser-induced CNV was compared between groups treated with an FFAR4 agonist or vehicle, and between FFAR4 wild-type (Ffar4+/+) and knock out (Ffar4−/−) mice on a C57BL/6J/6N background. The ex vivo choroid-sprouting assay, including primary retinal pigment epithelium (RPE) and choroid, without retina was used to investigate whether FFAR4 affects choroidal angiogenesis. Western blotting for pNF-ĸB/NF-ĸB and qRT-PCR for Il-6, Il-1β, Tnf-α, Vegf, and Nf-ĸb were used to examine the influence of FFAR4 on inflammation, known to influence CNV. RPE isolated from Ffar4+/+ and Ffar4−/− mice were used to assess RPE contribution to inflammation. The FFAR4 agonist suppressed laser-induced CNV in C57BL/6J mice, and CNV increased in Ffar4−/− compared to Ffar4+/+ mice. We showed that the FFAR4 agonist acted through the FFAR4 receptor. The FFAR4 agonist suppressed mRNA expression of inflammation markers (Il-6, Il-1β) via the NF-ĸB pathway in the retina, choroid, RPE complex. The FFAR4 agonist suppressed neovascularization in the choroid-sprouting ex vivo assay and FFAR4 deficiency exacerbated sprouting. Inflammation markers were increased in primary RPE cells of Ffar4−/− mice compared with Ffar4+/+ RPE. In this mouse model, the FFAR4 agonist suppressed CNV, suggesting FFAR4 to be a new molecular target to reduce pathological angiogenesis in CNV. © 2020, Springer Nature B.V.
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22.
  • Wang, Y. T., et al. (författare)
  • Regional gastrointestinal transit and pH studied in 215 healthy volunteers using the wireless motility capsule : influence of age, gender, study country and testing protocol
  • 2015
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 42:6, s. 761-772
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe wireless motility capsule (WMC) offers the ability to investigate luminal gastrointestinal (GI) physiology in a minimally invasive manner. AimTo investigate the effect of testing protocol, gender, age and study country on regional GI transit times and associated pH values using the WMC. MethodsRegional GI transit times and pH values were determined in 215 healthy volunteers from USA and Sweden studied using the WMC over a 6.5-year period. The effects of test protocol, gender, age and study country were examined. ResultsFor GI transit times, testing protocol was associated with differences in gastric emptying time (GET; shorter with protocol 2 (motility capsule ingested immediately after meal) vs. protocol 1 (motility capsule immediately before): median difference: 52min, P=0.0063) and colonic transit time (CTT; longer with protocol 2: median 140min, P=0.0189), but had no overall effect on whole gut transit time. Females had longer GET (by median 17min, P=0.0307), and also longer CTT by (104min, P=0.0285) and whole gut transit time by (263min, P=0.0077). Increasing age was associated with shorter small bowel transit time (P=0.002), and study country also influenced small bowel and CTTs. Whole gut and CTTs showed clustering of data at values separated by 24h, suggesting that describing these measures as continuous variables is invalid. Testing protocol, gender and study country also significantly influenced pH values. ConclusionsRegional GI transit times and pH values, delineated using the wireless motility capsule (WMC), vary based on testing protocol, gender, age and country. Standardisation of testing is crucial for cross-referencing in clinical practice and future research.
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25.
  • Boström, Hans, et al. (författare)
  • PDGF-A signaling is a critical event in lung alveolar myofibroblast development and alveogenesis.
  • 1996
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 85:6, s. 863-73
  • Tidskriftsartikel (refereegranskat)abstract
    • A mouse platelet-derived growth factor A chain (PDGF-A) null allele is shown to be homozygous lethal, with two distinct restriction points, one prenatally before E10 and one postnatally. Postnatally surviving PDGF-A-deficient mice develop lung emphysema secondary to the failure of alveolar septation. This is apparently caused by the loss of alveolar myofibroblasts and associated elastin fiber deposits. PDGF alpha receptor-positive cells in the lung having the location of putative alveolar myofibroblast progenitors were specifically absent in PDGF-A null mutants. We conclude that PDGF-A is crucial for alveolar myofibroblast ontogeny. We have previously shown that PDGF-B is required in the ontogeny of kidney mesangial cells. The PDGFs therefore appear to regulate the generation of specific populations of myofibroblasts during mammalian development. The two PDGF null phenotypes also reveal analogous morphogenetic functions for myofibroblast-type cells in lung and kidney organogenesis.
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26.
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27.
  • Fu, Z. J., et al. (författare)
  • Adiponectin Mediates Dietary Omega-3 Long-Chain Polyunsaturated Fatty Acid Protection Against Choroidal Neovascularization in Mice
  • 2017
  • Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 0146-0404 .- 1552-5783. ; 58:10, s. 3862-3870
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Neovascular age-related macular degeneration (AMD) is a major cause of legal blindness in the elderly. Diets with omega3-long-chain-polyunsaturated-fatty-acid (omega 3-LCPUFA) correlate with a decreased risk of AMD. Dietary omega 3-LCPUFA versus omega 6-LCPUFA inhibits mouse ocular neovascularization, but the underlying mechanism needs further exploration. The aim of this study was to investigate if adiponectin (APN) mediated x omega 3-LCPUFA suppression of neovessels in AMD. METHODS. The mouse laser-induced choroidal neovascularization (CNV) model was used to mimic some of the inflammatory aspect of AMD. CNV was compared between wild-type (WT) and Apn(-/-) mice fed either otherwise matched diets with 2% x3 or 2% omega 6-LCPUFAs. Vldlr(-/-) mice were used to mimic some of the metabolic aspects of AMD. Choroid assay ex vivo and human retinal microvascular endothelial cell (HRMEC) proliferation assay in vitro was used to investigate the APN pathway in angiogenesis. Western blot for p-AMPK alpha/AMPK alpha and qPCR for Apn, Mmps, and IL-10 were used to define mechanism. RESULTS. omega 3-LCPUFA intake suppressed laser-induced CNV in WT mice; suppression was abolished with APN deficiency. omega 3-LCPUFA, mediated by APN, decreased mouse Mmps expression. APN deficiency decreased AMPK alpha phosphorylation in vivo and exacerbated choroid-sprouting ex vivo. APN pathway activation inhibited HRMEC proliferation and decreased Mmps. In Vldlr(-/-) mice, omega 3-LCPUFA increased retinal AdipoR1 and inhibited NV. omega 3-LCPUFA decreased IL-10 but did not affect Mmps in Vldlr(-/-) retinas. CONCLUSIONS. APN in part mediated omega 3-LCPUFA inhibition of neovascularization in two mouse models of AMD. Modulating the APN pathway in conjunction with a omega 3-LCPUFA-enriched-diet may augment the beneficial effects of omega 3-LCPUFA in AMD patients.
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28.
  • Fu, Z. J., et al. (författare)
  • Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration
  • 2021
  • Ingår i: Iscience. - : Elsevier BV. - 2589-0042. ; 24:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The group of retinal degenerations, retinitis pigmentosa (RP), comprises more than 150 genetic abnormalities affecting photoreceptors. Finding degenerative pathways common to all genetic abnormalities may allow general treatment such as neuroprotection. Neuroprotection may include enhancing the function of cells that directly support photoreceptors, retinal pigment epithelial cells, and Muller glia. Treatment with fibroblast growth factor 21 (FGF21), a neuro-protectant, from postnatal week 4-10, during rod and cone loss in P23H mice (an RP model) with retinal degeneration, preserved photoreceptor function and normalized Muller glial cell morphology. Single-cell transcriptomics of retinal cells showed that FGF21 receptor Fgfr1 was specifically expressed in Muller glia/astrocytes. Of all retinal cells, FGF21 predominantly affected genes in Muller glia/astrocytes with increased expression of axon development and synapse formation pathway genes. Therefore, enhancing retinal glial axon and synapse formation with neurons may preserve retinal function in RP and may suggest a general therapeutic approach for retinal degenerative diseases.
  •  
29.
  • Gong, Y., et al. (författare)
  • Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis
  • 2016
  • Ingår i: Ebiomedicine. - : Elsevier BV. - 2352-3964. ; 13, s. 201-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)alpha agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP) 2C with higher affinity than to PPAR alpha. CYP2C metabolizes omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). While omega-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both omega-3 and omega-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C omega-3 LCPUFA (and omega-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPAR alpha-/-mice and augmented omega-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic.-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPAR alpha. Fenofibrate augmented the overall protective effects of omega-3 LCPUFAs on neovascular eye diseases. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://reativecommons.org/licenses/by-nc-nd/4.0/).
  •  
30.
  • Holgersson, G., et al. (författare)
  • Molecular profiling using tissue microarrays as a tool to identify predictive biomarkers in laryngeal cancer treated with radiotherapy
  • 2010
  • Ingår i: Cancer Genomics & Proteomics. - 1109-6535 .- 1790-6245. ; 7:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To explore the usefulness of the expression of five potential cancer biomarkers in predicting outcome in patients with laryngeal cancer. Materials and Methods: In the present study, the Swedish National Cancer Registry databases were used to identify patients with laryngeal cancer diagnosed during the years 1978-2004 in the Uppsala-Örebro region and treated with radiotherapy. The expression of Ki-67, MutS homolog 2, (MSH2), p53, B-cell CLL/lymphoma 2 (Bcl-2) and cyclin D1 in the cancer cells was assessed immunohistochemically using tissue microarrays (TMAs) and its predictve value on survival and relapse was analyzed using Cox regression models. Results: A total of 39 patients were included in the present study. Nuclear MSH2 staining was statistically significantly correlated to Ki-67 expression (p=0.022). However, univariate and multivariate Cox analyses showed no statistically significant association between the expression of the investigated biomarkers and overall survival or relapse. Conclusion: The present exploratory study does not show any significant predictive value of the biomarkers examined with respect to survival or relapse. However, with larger patient cohorts, we believe that protein profiling using TMAs and immunohistochemistry is a feasible strategy for prognostic and predictive biomarker screening in laryngeal cancer.
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31.
  • Kim, Y. E., et al. (författare)
  • Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB
  • 2017
  • Ingår i: Neuropharmacology. - : Elsevier BV. - 0028-3908. ; 117, s. 21-32
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroinflammation is significant in the pathogenesis and development of Alzheimer's disease (AD). Previously, we showed lipopolysaccharide (LPS)-induced neuroinflammation caused memory impairment. We investigated the possible preventive effects of punicalagin (PUN), a component of pomegranate, on memory deficiency caused by LPS, along with the fundamental mechanisms. LPS-treated cultured astrocytes and microglial BV -2 cells were investigated for anti-neuroinflammatory effects of PUN. PUN (1.5 mu g/kg) ameliorates LPS (250 mu g/kg daily 7 times) -induced memory impairment as well as prevents the LPS-induced expression of inflammatory proteins. In in vitro study, we also found that PUN (1 mu g/ml) inhibited the LPS-(10, 20 and 50 mu M) induced expression of iNOS and Cox -2 as well as the production of ROS, NO, TNF-alpha and IL-1 beta(PUN also suppress activation of NF-kappa B via inhibition of I kappa B degradation as well as p50 and p65 translocation into the nucleus in LPS treated mouse brain and cultured astrocytes and microglial BV -2 cells. Consistent with the inhibitory effect on neuro inflammation, PUN inhibited LPS-induced A beta(1-42) generation through down-regulation of APP and BACE1 expression in in vivo and in vitro study. Moreover, PUN directly binds to NF-kappa B subunit p50 evidenced by a docking model and pull down assay. These results suggest that PUN inhibits LPS-induced memory impairment via anti-inflammatory and anti-amylogenic mechanisms through inhibition of NF-kappa B activation. (C) 2017 Elsevier Ltd. All rights reserved.
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32.
  • Kontio, T., et al. (författare)
  • Early neurophysiology and MRI in predicting neurological outcome at 9-10 years after birth asphyxia
  • 2013
  • Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 124:6, s. 1089-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To assess whether early somatosensory evoked potentials (SEP) predict long-term neurodevelopmental outcome in normothermic, full-term infants with mild to moderate neonatal encephalopathy (NE), and to compare their predictive value to already available amplitude integrated EEG (aEEG) and magnetic resonance imaging (MRI). Methods: Fifty-six infants with post-asphyxia NE were prospectively recruited, and their SEP, aEEG and MRI data were acquired during the first five days. Follow-up continued to 9-10 years for assessment of neuromotor and neurocognitive development. We analysed SEP latency (N1 component), normality of aEEG background pattern, as well as patterns of injury on the neonatal MRI. Neurological outcome measures at 9-10 years included conventional MRI, Movement-ABC and the WISC-III NL. Results: A SEP latency <50 ms during the first five days was associated with a normal neuromotor outcome (p < 0.03), and a prolonged day 3 latency was associated with lower childhood IQ (p = 0.02). The presence of multiple seizures in aEEG, as well as a moderate or severe injury on the neonatal MRI was associated with a poor neuromotor score (p = 0.03 and p < 0.01, respectively). Combination of multiple techniques improved prediction of long-term outcome compared to single modality. Conclusion: Early SEPs provide information that is comparable to the already available aEEG and MRI paradigms in the prediction of long-term outcome of full-term infants with mild to moderate neonatal encephalopathy. Significance: The present results call for further studies using early SEP to aid early assessment of infants treated with hypothermia.
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33.
  • Naska, A, et al. (författare)
  • Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.
  • 2011
  • Ingår i: International Journal of Obesity. - : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 35:3, s. 416-426
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants. METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders. RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (β=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (β=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake. CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.
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34.
  • O'Neill, A.G., et al. (författare)
  • Strained silicon technology
  • 2007
  • Ingår i: ICSICT-2006. - 1424401615 - 9781424401611 ; , s. 104-107
  • Konferensbidrag (refereegranskat)abstract
    • Following a brief review of strained silicon technology options, this paper presents results and analysis of strained Si n-channel MOSFETs fabricated on thin SiGe virtual substrates. Significant improvements in electrical performance are demonstrated compared with Si control devices. The impact of SiGe device self-heating is compared for strained Si MOSFETs fabricated on thin and thick virtual substrates. The work demonstrates that by using high quality thin virtual substrates the compromised performance enhancements commonly observed in short gate length MOSFETs and high bias conditions due to self-heating in conventional thick virtual substrate devices are eradicated.
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35.
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36.
  • Rudolph, Dirk, et al. (författare)
  • Isospin Symmetry and Proton Decay: Identification of the 10+ Isomer in 54Ni
  • 2008
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The gamma decays from an isomeric 10+ state at 6457 keV in the nucleus 54Ni have been identified using the GSI fragment separator in conjunction with the RISING Ge-detector array. The state is interpreted as the isobaric analog of the 6527-keV 10+ isomer in 54Fe. The results are discussed in terms of isospin-dependent shell-model calculations. Clear evidence is presented for a discrete l = 5 proton decay branch into the first excited 9/2- state of the daughter 53Co. This decay is the first of its kind observed following projectile fragmentation reactions.
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37.
  • Sánchez Van Kammen, Mayte, et al. (författare)
  • Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia
  • 2021
  • Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
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38.
  • Scutelnic, Adrian, et al. (författare)
  • Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.
  • 2022
  • Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
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39.
  • Tomita, Y., et al. (författare)
  • Long-acting FGF21 inhibits retinal vascular leakage in in vivo and in vitro models
  • 2020
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 21:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current study was to investigate the impact of long-acting fibroblast growth factor 21 (FGF21) on retinal vascular leakage utilizing machine learning and to clarify the mechanism underlying the protection. To assess the effect on retinal vascular leakage, C57BL/6J mice were pre-treated with long-acting FGF21 analog or vehicle (Phosphate Buffered Saline; PBS) intraperitoneally (i.p.) before induction of retinal vascular leakage with intravitreal injection of mouse (m) vascular endothelial growth factor 164 (VEGF164) or PBS control. Five hours after mVEGF164 injection, we retro-orbitally injected Fluorescein isothiocyanate (FITC) -dextran and quantified fluorescence intensity as a readout of vascular leakage, using the Image Analysis Module with a machine learning algorithm. In FGF21- or vehicle-treated primary human retinal microvascular endothelial cells (HRMECs), cell permeability was induced with human (h) VEGF165 and evaluated using FITC-dextran and trans-endothelial electrical resistance (TEER). Western blots for tight junction markers were performed. Retinal vascular leakage in vivo was reduced in the FGF21 versus vehicle- treated mice. In HRMECs in vitro, FGF21 versus vehicle prevented hVEGF-induced increase in cell permeability, identified with FITC-dextran. FGF21 significantly preserved TEER compared to hVEGF. Taken together, FGF21 regulates permeability through tight junctions; in particular, FGF21 increases Claudin-1 protein levels in hVEGF-induced HRMECs. Long-acting FGF21 may help reduce retinal vascular leakage in retinal disorders and machine learning assessment can help to standardize vascular leakage quantification. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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40.
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41.
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42.
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43.
  • Becker, F, et al. (författare)
  • Status of the RISING Project at GSI
  • 2005
  • Ingår i: European Physical Journal A. Hadrons and Nuclei. - : Springer Science and Business Media LLC. - 1434-6001. ; 25:Suppl 1, s. 719-722
  • Tidskriftsartikel (refereegranskat)abstract
    • The FRS-RISING set-up at GSI uses secondary radioactive beams at relativistic energies for nuclear structure studies. At GSI the fragmentation or fission of stable primary beams up to U-238 provide secondary beams with sufficient intensity to perform gamma-ray spectroscopy. The RISING set-up is described and results of the first RISING campaign are presented. New experimental methods at relativistic energies are being investigated. Future experiments focus on state-of-the art nuclear structure physics covering exotic nuclei all over the nuclear chart.
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44.
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45.
  • Cakir, B., et al. (författare)
  • Thrombocytopenia is associated with severe retinopathy of prematurity
  • 2018
  • Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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46.
  • Connor, K. M., et al. (författare)
  • Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis
  • 2007
  • Ingår i: Nat Med. - 1078-8956.
  • Tidskriftsartikel (refereegranskat)abstract
    • Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy.
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47.
  • Edholm, T, et al. (författare)
  • The incretin hormones GIP and GLP-1 in diabetic rats : effects on insulin secretion and small bowel motility
  • 2009
  • Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:3, s. 313-321
  • Tidskriftsartikel (refereegranskat)abstract
    • Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L−1) or GLP-1 (10 nmol L−1) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1–400 pmol kg−1 min−1) or GLP-1 (0.1–20 pmol kg−1 min−1). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6–16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.
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48.
  • Ejskjaer, N, et al. (författare)
  • Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis
  • 2009
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 29:11, s. 1179-1187
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: TZP-101 is a synthetic, selective ghrelin agonist in development for gastroparesis. AIM: To assess safety and effects of TZP-101 in diabetes patients with symptomatic gastroparesis. METHODS: Adults with type 1 or type 2 diabetes mellitus received placebo and TZP-101 (80, 160, 320 or 600 microg/kg) infusions in a cross-over manner following a radiolabelled meal. Blood glucose levels were stabilized using a hyperinsulinemic-euglycemic clamp. Primary endpoints were gastric half emptying and latency times. Secondary measures included assessment of gastroparesis symptoms and endocrine responses. RESULTS: Ten patients with type 1 (n = 7) or 2 (n = 3) diabetes, moderate-to-severe gastroparesis symptoms and > or =29% retention 4 h after a radiolabelled solid meal were enrolled. TZP-101 produced significant reductions in solid meal half-emptying (20%, P = 0.043) and latency (34%, P = 0.037) times vs. placebo. Reductions in overall postmeal symptom intensity (24%) and postprandial fullness (37%) following TZP-101 infusion were not statistically significant. Most adverse events were mild and self-limiting and there were no identifiable differences in numbers or types of adverse events between TZP-101 and placebo. CONCLUSIONS: This proof-of-concept study demonstrates that the ghrelin agonist TZP-101 is well-tolerated in diabetes patients with moderate-to-severe chronic gastroparesis and shows statistically significant improvements in gastric emptying.
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49.
  • Farmer, A. D., et al. (författare)
  • Regional gastrointestinal contractility parameters using the wireless motility capsule : inter-observer reproducibility and influence of age, gender and study country
  • 2018
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 47:3, s. 391-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. Aims: To describe normative values for motility/contractility parameters across age, gender and testing centres.Methods:Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators.Results:Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.412 vs 122 +/- 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic log(e) motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times.Conclusions: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.
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50.
  • Fluckiger, S., et al. (författare)
  • [The early postnatal weight gain as a predictor of retinopathy of prematurity] : Der frühe postnatale Gewichtsverlauf als Prädiktor einer Frühgeborenenretinopathie
  • 2011
  • Ingår i: Klinische Monatsblätter für Augenheilkunde. - 1439-3999. ; 228:4, s. 306-10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Premature infants are often stressed by the current retinopathy of prematurity (ROP) screening procedure. Additionally, only < 10 % of the screened infants will develop a ROP stadium requiring laser therapy. Therefore the present screening strategy is unsatisfactory. Furthermore, the current guidelines do not take into account postnatal factors. A new method considering postnatal factors is the weight, insulin-like growth factor, neonatal ROP (WINROP) algorithm. This approach is based on the early postnatal weight gain. The aim of this study was to assign the WINROP-algorithm to a preterm population in Switzerland and to analyze its ability for prediction. PATIENTS AND METHODS: In this retrospective study, all preterm infants with a gestational age (GA) < 32 weeks and/or a birth weight (BW)
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