| 1. |
- Walker, Anthony P, et al.
(författare)
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Horizon 2020 EuPRAXIA design study
- 2017
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 874:1
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Tidskriftsartikel (refereegranskat)abstract
- The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.
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| 2. |
- Clifford, B. L., et al.
(författare)
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FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:8
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Tidskriftsartikel (refereegranskat)abstract
- FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono-and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
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| 3. |
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| 4. |
- Pirozhkov, A. S., et al.
(författare)
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Diagnostic of laser contrast using target reflectivity
- 2009
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 94:24
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Tidskriftsartikel (refereegranskat)abstract
- Using three different laser systems, we demonstrate a convenient and simple plasma based diagnostic of the contrast of high-power short-pulse lasers. The technique is based on measuring the specular reflectivity from a solid target. The reflectivity remains high even at relativistic intensities above 10(19) W/cm(2) in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops with increasing intensities in the case of systems with insufficient contrast due to beam breakup and increased absorption caused by preplasma.
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| 5. |
- Schneider, K. M., et al.
(författare)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 6. |
- Faldon, M. E, et al.
(författare)
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Studies of time-resolved harmonic generation in intense laser fields in xenon
- 1992
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Ingår i: Journal of the Optical Society of America B: Optical Physics. - 0740-3224. ; 9:11, s. 2094-2099
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Tidskriftsartikel (refereegranskat)abstract
- We report preliminary experimental and computational studies of the temporal evolution of the harmonics, generated in xenon, by 50-ps pulses from a Nd: YLF laser, amplified in Nd: glass amplifiers, and focused to produce intensities in the range 1013--5 {\texttimes} 1013 W cm{\textminus}2. Measurements were made of the temporal profiles of the seventh- and ninth-order harmonics using a specially modified VUV streak camera with better than 7-ps temporal resolution. These results were compared with predictions of a numerical model that included the effects of neutral atom depletion and photoelectron dispersion in the calculation of the harmonic output as a function of time.
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| 7. |
- Giuffrida, L., et al.
(författare)
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Nano and micro structured targets to modulate the spatial profile of laser driven proton beams
- 2017
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 12:3, s. article no C03040 -
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Tidskriftsartikel (refereegranskat)abstract
- Nano and micro structured thin (μ m-scale) foils were designed, fabricated and irradiated with the high intensity laser system operating at LLC (Lund Laser Centre, Sweden) in order to systematically study and improve the main proton beam parameters. Nano-spheres deposited on the front (laser irradiated) surface of a flat Mylar foil enabled a small enhancement of the maximum energy and number of the accelerated protons. Nano-spheres on the rear side allowed to modify the proton beam spatial profile. In particular, with nanospheres deposited on the rear of the target, the proton beam spatial homogeneity was clearly enhanced. Silicon nitride thin foils having micro grating structures (with different step dimensions) on the rear surface were also used as targets to influence the divergence of the proton beam and drastically change its shape through a sort of stretching effect. The target fabrication process used for the different target types is described, and representative experimental results are shown and discussed along with supporting 3D particle-in-cell simulations. © 2017 IOP Publishing Ltd and Sissa Medialab srl.
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| 8. |
- Mörtzell Henriksson, Monica, et al.
(författare)
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Adverse events in apheresis : an update of the WAA registry data
- 2016
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Ingår i: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 54:1, s. 2-15
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Forskningsöversikt (refereegranskat)abstract
- Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.
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| 9. |
- Ovadia, C., et al.
(författare)
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Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher’s exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19. © 2020, The Author(s).
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| 10. |
- Xu, M. H., et al.
(författare)
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Enhancement of ion generation in femtosecond ultraintense laser-foil interactions by defocusing
- 2012
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 100:8
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Tidskriftsartikel (refereegranskat)abstract
- A simple method to enhance ion generation with femtosecond ultraintense lasers is demonstrated experimentally by defocusing laser beams on target surface. When the laser is optimally defocused, we find that the population of medium and low energy protons from ultra-thin foils is increased significantly while the proton cutoff energy is almost unchanged. In this way, the total proton yield can be enhanced by more than 1 order, even though the peak laser intensity drops. The depression of the amplified spontaneous emission (ASE) effect and the population increase of moderate-energy electrons are believed to be the main reasons for the effective enhancement. (C) 2012 American Institute of Physics. [doi:10.1063/1.3688027]
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| 11. |
- Birch, J., et al.
(författare)
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Structural characterization of precious-mean quasiperiodic Mo/V single-crystal superlattices grown by dual-target magnetron sputtering
- 1990
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Ingår i: Physical Review B. - 1098-0121. ; 41:15, s. 10398-10407
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Tidskriftsartikel (refereegranskat)abstract
- A class of quasiperiodic superlattice structures, which can be generated by the concurrent inflation rule A→AmB and B→A (where m=positive integer), has been studied both theoretically and experimentally. Given that the ratios between the thicknesses of the two superlattice building blocks, A and B, are chosen to be γ(m)=[m+(m2+4)1/2]/2 (known as the ‘‘precious means’’), then the x-ray- and electron-diffraction peak positions are analytically found to be located at the wave vectors q=2πΛ−1r[γ(m)]k, where r and k are integers and Λ is an average superlattice wavelength. The analytically obtained results have been compared to experimental results from single-crystalline Mo/V superlattice structures, generated with m=1, 2, and 3. The superlattices were grown by dual-target dc-magnetron sputtering on MgO(001) substrates kept at 700 °C. X-ray diffraction (XRD) and selected-area electron diffraction (SAED) showed that the analytical model mentioned above predicts the peak positions of the experimental XRD and SAED spectra with a very high accuracy. Furthermore, numerical calculations of the diffraction intensities based on a kinematical model of diffraction showed good agreement with the experimental data for all three cases. In addition to a direct verification of the quasiperiodic modulation, both conventional and high-resolution cross-sectional transmission electron microscopy (XTEM) showed that the superlattices are of high crystalline quality with sharp interfaces. Based on lattice resolution images, the width of the interfaces was determined to be less than two (002) lattice-plane spacings (≊0.31 nm).
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| 12. |
- Brenner, C. M., et al.
(författare)
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Dependence of laser accelerated protons on laser energy following the interaction of defocused, intense laser pulses with ultra-thin targets
- 2011
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Ingår i: Laser and Particle Beams. - 0263-0346. ; 29:3, s. 345-351
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Tidskriftsartikel (refereegranskat)abstract
- The scaling of the flux and maximum energy of laser-driven sheath-accelerated protons has been investigated as a function of laser pulse energy in the range of 15-380 mJ at intensities of 10(16)-10(18) W/cm(2). The pulse duration and target thickness were fixed at 40 fs and 25 nm, respectively, while the laser focal spot size and drive energy were varied. Our results indicate that while the maximum proton energy is dependent on the laser energy and laser spot diameter, the proton flux is primarily related to the laser pulse energy under the conditions studied here. Our measurements show that increasing the laser energy by an order of magnitude results in a more than 500-fold increase in the observed proton flux. Whereas, an order of magnitude increase in the laser intensity generated by decreasing the laser focal spot size, at constant laser energy, gives rise to less than a tenfold increase in observed proton flux.
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| 13. |
- Descamps, D, et al.
(författare)
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Extreme ultraviolet interferometry measurements with high-order harmonics
- 2000
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Ingår i: Optics Letters. - 0146-9592. ; 25:2, s. 135-137
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that high-order harmonics generated by short, intense laser pulses in gases provide an interesting radiation source for extreme ultraviolet interferometry, since they are tunable, coherent, of short pulse duration, and simple to manipulate. Harmonics from the 9th to the 15th are used to measure the thickness of an aluminum layer. The 11th harmonic is used to determine the spatial distribution of the electron density of a plasma produced by a 300-ps laser. Electronic densities higher than 2-10(20) electrons/cm(3) are measured. (C) 2000 Optical Society of America. OCIS codes: 190.0190, 190.4160, 190.7110, 120.3180, 140.7240, 350.4500.
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| 14. |
- Desforges, F. G., et al.
(författare)
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Analysis of Electron Injection in Laser Wakefield Acceleration Using Betatron Emission in Capillary Tubes
- 2015
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Ingår i: Laser Acceleration of Electrons, Protons, and Ions III; and Medical Applications of Laser-Generated Beams of Particles III. - : SPIE. - 1996-756X .- 0277-786X. ; 9514, s. 95140-95140
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Konferensbidrag (refereegranskat)abstract
- The dynamics of ionization-induced electron injection in the high density (similar to 1.2 x 10(19)cm(-3)) regime of Laser Wakefield Acceleration (LWFA) was investigated by analyzing betatron X-ray emission inside dielectric capillary tubes. A comparative study of the electron and betatron X-ray properties was performed for both self-injection and ionization-induced injection. Direct experimental evidence of early onset of ionization-induced injection into the plasma wave was obtained by mapping the X-ray emission zone inside the plasma. Particle-In-Cell (PIC) simulations showed that the early onset of ionization-induced injection, due to its lower trapping threshold, suppresses self-injection of electrons. An increase of X-ray fluence by at least a factor of two was observed in the case of ionization-induced injection due to an increased trapped charge compared to self-injection mechanism.
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| 15. |
- Desforges, F. G., et al.
(författare)
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Dynamics of ionization-induced electron injection in the high density regime of laser wakefield acceleration
- 2014
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Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- The dynamics of ionization-induced electron injection in high density (similar to 1.2 x 10(19) cm(-3)) regime of laser wakefield acceleration is investigated by analyzing the betatron X-ray emission. In such high density operation, the laser normalized vector potential exceeds the injection-thresholds of both ionization-injection and self-injection due to self-focusing. In this regime, direct experimental evidence of early on-set of ionization-induced injection into the plasma wave is given by mapping the X-ray emission zone inside the plasma. Particle-In-Cell simulations show that this early on-set of ionization-induced injection, due to its lower trapping threshold, suppresses the trapping of self-injected electrons. A comparative study of the electron and X-ray properties is performed for both self-injection and ionization-induced injection. An increase of X-ray fluence by at least a factor of two is observed in the case of ionization-induced injection due to increased trapped charge compared to self-injection mechanism. (C) 2014 AIP Publishing LLC.
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| 16. |
- Einbeigi, Z., et al.
(författare)
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A founder mutation of the BRCA1 gene in Western Sweden associated with a high incidence of breast and ovarian cancer
- 2001
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 37:15, s. 1904-1909
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe and characterise a founder mutation of the BRCA1 gene in western Sweden. Of 62 families screened for BRCA mutations, 24 had BRCA1 mutations and two had BRCA2 mutations. Tumours that occurred in family members were histologically reviewed and mutational status was analysed using archival paraffin-embedded tissues. The same BRCA1 mutation, 3171ins5, was found in 16 families who were clustered along the western coast of Sweden. Mutation analysis revealed a maternal linkage in 13 families and a paternal linkage in 3. There was complete agreement between mutation analysis results obtained from blood and archival tissues. The penetrance of breast or ovarian cancer by age 70 years was estimated to be between 59 and 93%. There were no differences in survivals between breast or ovarian cancer patients with the mutation and age-matched controls. Thus, a predominant BRCA1 gene founder mutation associated with a high risk of breast and ovarian cancer has been identified and found to occur in a restricted geographical area, thereby allowing timely and cost-effective mutation screening using blood samples or archival histological material.
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| 17. |
- Giuffrida, L., et al.
(författare)
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Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets
- 2017
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Ingår i: Physical Review Accelerators and Beams. - 2469-9888. ; 20:8, s. 081301-
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Tidskriftsartikel (refereegranskat)abstract
- Nanostructured and microstructured thin foils have been fabricated and used experimentally as targets to manipulate the spatial profile of proton bunches accelerated through the interaction with high intensity laser pulses (6 x 1019 W/cm(2)). Monolayers of polystyrene nanospheres were placed on the rear surfaces of thin plastic targets to improve the spatial homogeneity of the accelerated proton beams. Moreover, thin targets with grating structures of various configurations on their rear sides were used tomodify the proton beam divergence. Experimental results are presented, discussed, and supported by 3D particle-in-cell numerical simulations.
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| 18. |
- Green, J. S., et al.
(författare)
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Enhanced proton flux in the MeV range by defocused laser irradiation
- 2010
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Ingår i: New Journal of Physics. - : IOP Publishing. - 1367-2630. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Thin Al foils (50 nm and 6 mu m) were irradiated at intensities of up to 2x10(19) W cm(-2) using high contrast (10(8)) laser pulses. Ion emission from the rear of the targets was measured using a scintillator-based Thomson parabola and beam sampling 'footprint' monitor. The variation of the ion spectra and beam profile with focal spot size was systematically studied. The results show that while the maximum proton energy is achieved around tight focus for both target thicknesses, as the spot size increases the ion flux at lower energies is seen to peak at significantly increased spot sizes. Measurements of the proton footprint, however, show that the off-axis proton flux is highest at tight focus, indicating that a previously identified proton deflection mechanism may alter the on-axis spectrum. One-dimensional particle-in-cell modelling of the experiment supports our hypothesis that the observed change in spectra with focal spot size is due to the competition of two effects: decrease in laser intensity and an increase in proton emission area.
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| 19. |
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| 20. |
- Hewett, D., et al.
(författare)
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Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map
- 2002
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 0888-7543. ; 79:3, s. 305-14
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.
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| 21. |
- Hof, Tineke, et al.
(författare)
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Multilevel Intervention Mapping with sleepiness in focus
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Driver fatigue is an important risk factor in traffic safety and an issue for both private and professional drivers. This report provides an analysis of risk factors related to fatigue-related road accidents, and describes intervention goals at multiple levels in order to reduce sleepy driving among drivers. Private drivers who are on their way to or from their holiday were assigned as the specific target group.
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| 22. |
- Holmgren, G, et al.
(författare)
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Linkage of G8 (D4S10) in two Swedish families with Huntington's disease.
- 1987
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Ingår i: Clinical Genetics. - 0009-9163 .- 1399-0004. ; 32:5, s. 289-94
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Tidskriftsartikel (refereegranskat)abstract
- Two Swedish families with Huntington's disease (HD) have been investigated for linkage with G8 (D4S10). In one family from northern Sweden (Family 1) 48 family members were examined, and in another family from the southwestern part of Sweden (Family 2) 14 family members were examined. The lod scores were 1.531 for Family 1 and 2.057 for Family 2, and the combined lod score was 3.59. The HD gene was segregating with the haplotype C in Family 1 and with haplotype A in Family 2. The predictive value of the test was obvious. Before the testing with the G8 probe, 84.2% of the family members in Family 1 had a theoretical risk of 25% or 50% of having the HD gene. After the testing with the G8 probe, only 23.7% of the family members remained at the same risk, and it could also be certified that 63.2% had no or little risk of having the HD gene. Only one asymptomatic person was predicted to have HD.
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| 23. |
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| 24. |
- Knoppers, B.M., et al.
(författare)
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Ethic's issues in stem cell research
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 312:5772, s. 366-367
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 25. |
- Liao, Lijun, et al.
(författare)
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Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis.
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:8, s. 1477-92
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Tidskriftsartikel (refereegranskat)abstract
- There is a striking association between human cholestatic liver disease (CLD) and inflammatory bowel disease. However, the functional implications for intestinal microbiota and inflammasome-mediated innate immune response in CLD remain elusive. Here we investigated the functional role of gut-liver crosstalk for CLD in the murine Mdr2 knockout (Mdr2-/-) model resembling human primary sclerosing cholangitis (PSC).Male Mdr2-/-, Mdr2-/- crossed with hepatocyte-specific deletion of caspase-8 (Mdr2-/- /Casp8∆hepa) and wild-type (WT) control mice were housed for 8 or 52weeks, respectively, to characterise the impact of Mdr2 deletion on liver and gut including bile acid and microbiota profiling. To block caspase activation, a pan-caspase inhibitor (IDN-7314) was administered. Finally, the functional role of Mdr2-/- -associated intestinal dysbiosis was studied by microbiota transfer experiments.Mdr2-/- mice displayed an unfavourable intestinal microbiota signature and pronounced NLRP3 inflammasome activation within the gut-liver axis. Intestinal dysbiosis in Mdr2-/- mice prompted intestinal barrier dysfunction and increased bacterial translocation amplifying the hepatic NLRP3-mediated innate immune response. Transfer of Mdr2-/- microbiota into healthy WT control mice induced significant liver injury in recipient mice, highlighting the causal role of intestinal dysbiosis for disease progression. Strikingly, IDN-7314 dampened inflammasome activation, ameliorated liver injury, reversed serum bile acid profile and cholestasis-associated microbiota signature.MDR2-associated cholestasis triggers intestinal dysbiosis. In turn, translocation of endotoxin into the portal vein and subsequent NLRP3 inflammasome activation contribute to higher liver injury. This process does not essentially depend on caspase-8 in hepatocytes, but can be blocked by IDN-7314.
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| 26. |
- Lopez, Rodrigo, et al.
(författare)
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Amplitude and phase control of attosecond light pulses
- 2005
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Ingår i: Physical Review Letters. - 1079-7114. ; 94:3
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation, compression, and delivery on target of ultrashort extreme-ultraviolet light pulses using external amplitude and phase control. Broadband harmonic radiation is first generated by focusing an infrared laser with a carefully chosen intensity into a gas cell containing argon atoms. The emitted light then goes through a hard aperture and a thin aluminum filter that selects a 30-eV bandwidth around a 30-eV photon energy and synchronizes all of the components, thereby enabling the formation of a train of almost Fourier-transform-limited single-cycle 170 attosecond pulses. Our experiment demonstrates a practical method for synthesizing and controlling attosecond waveforms.
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| 27. |
- Merdji, H., et al.
(författare)
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Coherence properties of high-order harmonics : Application to high-density laser-plasma diagnostic
- 2000
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Ingår i: Laser and Particle Beams. - 0263-0346. ; 18:3, s. 495-502
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Tidskriftsartikel (refereegranskat)abstract
- We present two interferometry schemes in the extreme ultraviolet, based on either the wave-front division of a unique harmonic beam (1st scheme) or two spatially separated, phase-locked harmonic sources (2nd scheme). In the first scheme using a Fresnel bimirror interferometer, we measure the degree of spatial coherence of the 13 th harmonic generated in xenon, as a function of different parameters. A high degree of coherence, larger than 0.5, is found for the best conditions in almost the full section of the beam. Then, we demonstrate that the second scheme can be used for interferometry measurements with an ultrahigh time resolution. The 11th harmonic is used to study the spatial variation of the electron density of a laser-produced plasma. Electronic densities higher than 2.10 20 cm -3 are measured.
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| 28. |
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| 29. |
- Robroek, Suzan J W, et al.
(författare)
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Influence of obesity and physical workload on disability benefits among construction workers followed up for 37 years
- 2017
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Ingår i: Journal of Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1076-2752 .- 1536-5948 .- 1351-0711 .- 1470-7926. ; 74:9, s. 621-627
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The objectives of this study are to investigate the relation between obesity and labour force exit via diagnosis-specific disability benefits, and whether physical workload modifies this association.METHODS: A longitudinal analysis was performed among 3 28 743 Swedish construction workers in the age of 15-65 years. Body weight and height were measured at a health examination and enriched with register information on disability benefits up to 37 years later. Diagnoses of disability benefits were categorised into cardiovascular diseases (CVDs), musculoskeletal diseases (MSDs), mental disorders and others. A job exposure matrix, based on self-reported lifting of heavy loads and working in bent forward or twisted position, was applied as a measure of physical workload. Cox proportional hazards regression analyses were performed, and the relative excess risk due to interaction (RERI) between obesity and physical workload was calculated.RESULTS: Obese construction workers were at increased risk of receiving disability benefits (HR 1.70, 95% CI 1.65 to 2.76), mainly through CVD (HR 2.30) and MSD (HR 1.71). Construction workers with a high physical workload were also more likely to receive a disability benefit (HR 2.28, 95% CI 2.21 to 2.34), particularly via MSD (HR 3.02). Obesity in combination with a higher physical workload increased the risk of disability benefits (RERI 0.28) more than the sum of the risks of obesity and higher physical workload, particularly for MSD (RERI 0.44).CONCLUSIONS: Obesity and a high physical workload are risk factors for disability benefit. Furthermore, these factors are synergistic risk factors for labour force exit via disability benefit through MSD. Comprehensive programmes that target health promotion to prevent obesity and ergonomic interventions to reduce physical workload are important to facilitate sustained employment.
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| 30. |
- Scheffle, M., et al.
(författare)
-
Low cost large area panel processing of MCM-D substrates and packages
- 2001
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Ingår i: Proceedings of IPACK’01. ; , s. -8
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Konferensbidrag (refereegranskat)abstract
- The paper describes the results of the EU research project LAP that had the target to develop and to demonstrate a low-cost high-density substrate manufacturing technology for 1st-level die assemblies. The cost target of 1€€/in2 had to be obtained by increasing toady’s 4x4in2 panel sizes to panels upto 24x24in2. The results focus on RF characterization (integrated antennas up to 83GHz, inductors up a Q value of 50), novel packaging strategies (integration of substrate and package), and cost achievements (approaching the cost target). The technology capabilities have been demonstrated with a 9:4 satellite switch operating up to 2.4GHz and readout electronics for physics experiments.
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| 31. |
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| 32. |
- Starczewski, Tomas, et al.
(författare)
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Time-resolved Harmonic-generation In An Ionizing Gas
- 1994
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Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 27:14, s. 3291-3301
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Tidskriftsartikel (refereegranskat)abstract
- We report on a time-resolved study of the fifth harmonic generated in xenon by 140 ps pulses from a Nd:YAG laser in the 10(13) W cm-2 intensity regime. Absolute timing between the driving laser pulse and the harmonic pulse could be determined by means of reference harmonics generated in non-linear crystals and a single common streak camera. Above a certain laser intensity the centre of the observed harmonic pulse was shifted earlier in time relative to the laser pulse. We found the intensity dependence of this shift to be approximately linear within the intensity range used which is consistent with the results of numerical simulations taking the ionization and dispersion of the xenon gas into account.
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| 33. |
- Strandvik, Birgitta, 1938, et al.
(författare)
-
Spectrum of mutations in the CFTR gene of patients with classical and atypical forms of cystic fibrosis from southwestern Sweden: identification of 12 novel mutations.
- 2001
-
Ingår i: Genetic testing. - : Mary Ann Liebert Inc. - 1090-6576 .- 1557-7473. ; 5:3, s. 235-42
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is caused by mutations in the CFTR gene. The spectrum of CFTR mutations varies between populations and depends on different factors, such as ethnic background and geographical location. The extensive CFTR mutation screening of 129 patients with classical or atypical CF from the south-western region of Sweden revealed the presence of 37 CFTR mutations, including 12 novel alleles. The overall mutation detection rate in this study population was 92%, the highest among all tested regions in Sweden. Eight mutations with a frequency above 1% (DeltaF508, 394delTT, R117C, 3659delC, E60X, 1112delT, R764X, and 621 + 1G --> T) accounted for 78% of CF chromosomes and have been recommended for inclusion in the CFTR mutation screening panel for molecular diagnosis of CF in this region. The multiple occurrence of specific CFTR alleles less common than the predominant DeltaF508 mutation (394delTT, R117C, 3659delC) allowed for genotype-phenotype comparisons and revealed consistent relationships between these mutations and disease severity.
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| 34. |
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| 35. |
- Al-Dury, Samer, et al.
(författare)
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Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Pruritus is a common complication of cholestatic liver diseases. Inhibition of the ileal bile acid transporter (IBAT/ASBT) may emerge as treatment option. Our aim was to assess tolerability and effect on pruritus of the selective IBAT inhibitor A4250 in patients with primary biliary cholangitis (PBC). Ten patients with PBC and bile acid sequestrant treatment of cholestatic pruritus were after a two-week wash out of the bile acid sequestrant treated with either 0.75 mg (n = 4) or 1.5 mg (n = 5) of A4250 for four weeks. Patients' pruritus was assessed by Visual Analogue Scale (VAS), 5-D itch scale and the pruritus module of the PBC40 questionnaire. Plasma bile acids and 7 alpha-hydroxy-4-cholesten-3-one were measured by UPLC-MS/MS, plasma fibroblast growth factor 19 by ELISA, and serum autotaxin activity by homemade assay. All nine patients exposed to A4250 reported a remarkable improvement in pruritus, until none or mild according to 5-D itch, VAS and PBC40 pruritus. Five patients finished the study prematurely due to abdominal pain (5/5) and diarrhoea (4/5). The high incidence of probably bile acid malabsorption-related diarrhoea and abdominal pain in the bile acid sequestrant pre-treated population indicates that the start dose of A4250 may have been too high for adult patients.
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| 36. |
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| 37. |
- Amundsen, S. S., et al.
(författare)
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Genetic analysis of the CD28/CTLA4/ICOS (CELIAC3) region in coeliac disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 64:5, s. 593-9
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Tidskriftsartikel (refereegranskat)abstract
- In order to extend our previous findings of genetic linkage to the CD28/CTLA4/ICOS region on chromosome 2q33 (CELIAC3) in coeliac disease (CD), we have investigated 22 genetic markers in 325 Norwegian/Swedish multiplex and simplex CD families. We found both linkage and association with several markers, primarily in the multiplex material. We observed strong linkage disequilibrium (LD) between SNPs (Single Nucleotide Polymorphisms) within an LD block delimited by MH30 and D2S72. A haplotype of this region marked by the alleles -1147*T: + 49*A:CT60*G:CT61*A was significantly associated with CD, suggesting that one or more polymorphisms of this haplotype, possibly -1147*T, are involved in CD susceptibility. The CT60 SNP, a polymorphism found to be most strongly associated with some other immune-mediated diseases, was not associated with CD, as this SNP was part of both associated and non-associated haplotypes. Moreover, our results suggest that CELIAC3 harbours several independent loci contributing to CD susceptibility.
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| 38. |
- An, W. W., et al.
(författare)
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Synthesis and surface characteristics of CeTbO3+delta induced by femtosecond laser irradiation
- 2007
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Ingår i: Applied Surface Science. - : Elsevier BV. - 1873-5584 .- 0169-4332. ; 253:8, s. 3884-3887
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Tidskriftsartikel (refereegranskat)abstract
- This work describes the use of focused, high-intensity light from a Ti: sapphire laser that generates femtosecond pulses to irradiate mixture of CeO2 and Tb4O7 under ambient conditions. The prepared samples were investigated by means of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM). XRD and XPS measurement results demonstrated that solid solution CeTbO3+delta with cubic fluorite structure has been synthesized on the irradiated target surface. SEM micrographs showed that the ultra-short laser irradiation resulted in the formation of foamy structure and spherical particles with size varying from about 30 to 200 nm. The formation mechanism has been discussed in detail. (c) 2006 Elsevier B.V. All rights reserved.
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| 39. |
- Andreasson, Björn, et al.
(författare)
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The measurement of venous haematocrit in patients with polycythaemia vera.
- 1999
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Ingår i: Journal of internal medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 246:3, s. 293-7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In clinical practice, patients with polycythaemia vera (PV) are monitored by measurement of venous packed cell volume (PCV). However, whereas treatment recommendations are still based upon studies in which the results were obtained with the centrifuged microhaematocrit, currently in most instances automated blood cell counters are used to calculate PCV. In a group of patients with polycythaemia we therefore compared the results obtained by the microhaematocrit method with PCV calculated by haematology analysers. DESIGN: The study was carried out on a prospective basis. Duplicate venous blood samples were collected. The centrifuged microhaemotocrit was obtained by using an IEC Micro-MB Centrifuge. Depending on different routine methods used in the participating hospitals, the blood cell counter PCV was calculated using Coulter STKS, Bayer Technicon H2 or H3. SETTING: Patients were included from four Swedish university hospitals: Akademiska (Uppsala), Huddinge and Karolinska (Stockholm) and Sahlgrenska (Göteborg). SUBJECTS: Seventy-four patients with PV and 10 patients with secondary polycythaemia were included and a total of 150 duplicate blood samples were analysed from these subjects. RESULTS: In the 150 measurements the mean blood cell counter calculated PCV was 0.448 +/- 0.037; the mean for centrifuged microhaematocrit was 0.467 +/- 0. 037 and the difference between means was highly significant (P = 6.8 x 10-25). The means for centrifuged haematocrit and calculated PCV differed significantly in the groups of PV patients treated with phlebotomy only, hydroxyurea or radiophosphorous (P < 0.0001, respectively). In PV patients treated with alpha-interferon and in patients with secondary polycythaemia the difference in means did not reach statistical significance (P = 0.07 and P = 0.13, respectively). The groups of patients with MCV <80 fL and >/=80 fL both presented significant differences between means for calculated PCV and centrifuged haematocrit. CONCLUSIONS: If PV patients are monitored with blood cell counter calculated PCV it appears that the therapeutic goal should be to maintain the calculated PCV below 0.43, provided the local differences in calculated PCV and centrifuged haematocrit are of the same magnitude as in this study.
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| 40. |
- Arm, Maria, et al.
(författare)
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How Does the European Recovery Target for Construction & Demolition Waste Affect Resource Management?
- 2017
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Ingår i: Waste and Biomass Valorization. - : Springer Netherlands. - 1877-2641 .- 1877-265X. ; 8:5, s. 1491-1504
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Tidskriftsartikel (refereegranskat)abstract
- The revised EU Waste Framework Directive (WFD) includes a 70 % target for recovery of construction and demolition (C&D) waste. In order to study the potential change in the resource management of the main C&D waste fractions, as a consequence of fulfilling the WFD target, a Nordic project (ENCORT-CDW) has been performed. Waste fractions studied included asphalt, concrete, bricks, track ballast, gypsum-based construction materials and wood. Recovery scenarios were identified and estimations were made regarding expected savings of primary materials, impact on transport, and pollution and emissions. For wood waste, the main differences between re-use, material recycling and energy recovery were evaluated in a carbon footprint screening based on life cycle assessment methodology. The study concluded that the EU recovery target does not ensure a resource efficient and environmentally sustainable waste recovery in its present form since: It is very sensitive to how the legal definitions of waste and recovery are interpreted in the Member States. This means that certain construction material cycles might not count in the implementation reports while other, less efficient and environmentally safe, recovery processes of the same material will count. It is weight-based and consequently favours large and heavy waste streams. The result is that smaller flows with equal or larger resource efficiency and environmental benefit will be insignificant for reaching the target. It does not distinguish between the various recovery processes, meaning that resource efficient and environmentally safe recovery cannot be given priority. Improved knowledge on C&D waste generation and handling, as well as on content and emissions of dangerous substances, is required to achieve a sustainable recovery.
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| 41. |
- Audet, T. L., et al.
(författare)
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Investigation of ionization-induced electron injection in a wakefield driven by laser inside a gas cell
- 2016
-
Ingår i: Physics of Plasmas. - : AIP Publishing. - 1070-664X .- 1089-7674. ; 23:2
-
Tidskriftsartikel (refereegranskat)abstract
- Ionization-induced electron injection was investigated experimentally by focusing a driving laser pulse with a maximum normalized potential of 1.2 at different positions along the plasma density profile inside a gas cell, filled with a gas mixture composed of 99%H2+1%N2. Changing the laser focus position relative to the gas cell entrance controls the accelerated electron bunch properties, such as the spectrum width, maximum energy, and accelerated charge. Simulations performed using the 3D particle-in-cell code WARP with a realistic density profile give results that are in good agreement with the experimental ones. The interest of this regime for optimizing the bunch charge in a selected energy window is discussed.
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| 42. |
- Baghdasaryan, A., et al.
(författare)
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Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis
- 2016
-
Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278. ; 64:3, s. 674-681
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Approximately 95% of bile acids (BAs) excreted into bile are reabsorbed in the gut and circulate back to the liver for further biliary secretion. Therefore, pharmacological inhibition of the ileal apical sodium-dependent BA transporter (ASBT/SLC10A2) may protect against BA-mediated cholestatic liver and bile duct injury. Methods: Eight week old Mdr2(-/-) (Abcb4(-/-)) mice (model of cholestatic liver injury and sclerosing cholangitis) received either a diet supplemented with A4250 (0.01% w/w) - a highly potent and selective ASBT inhibitor - or a chow diet. Liver injury was assessed biochemically and histologically after 4 weeks of A4250 treatment. Expression profiles of genes involved in BA homeostasis, inflammation and fibrosis were assessed via RT-PCR from liver and ileum homogenates. Intestinal inflammation was assessed by RNA expression profiling and immunohistochemistry. Bile flow and composition, as well as biliary and fecal BA profiles were analyzed after 1 week of ASBT inhibitor feeding. Results: A4250 improved sclerosing cholangitis in Mdr2(-/-) mice and significantly reduced serum alanine aminotransferase, alkaline phosphatase and BAs levels, hepatic expression of proinflammatory (Tnf-alpha, Vcam1, Mcp-1) and pro-fibrogenic (Col1a1, Col1a2) genes and bile duct proliferation (mRNA and immunohistochemistry for cytokeratin 19 (CK19)). Furthermore, A4250 significantly reduced bile flow and biliary BA output, which correlated with reduced Bsep transcription, while Ntcp and Cyp7a1 were induced. Importantly A4250 significantly reduced biliary BA secretion but preserved HCO3- and biliary phospholipid secretion resulting in an increased HCO3-/BA and PL/BA ratio. In addition, A4250 profoundly increased fecal BA excretion without causing diarrhea and altered BA pool composition, resulting in diminished concentrations of primary BAs tauro-beta-muricholic acid and taurocholic acid. Conclusions: Pharmacological ASBT inhibition attenuates cholestatic liver and bile duct injury by reducing biliary BA concentrations in mice. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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| 43. |
- Barker, Dean, 1977, et al.
(författare)
-
Pedagogical narrative: Working with technology as student teachers
- 2016
-
Ingår i: Pedagogical Cases: Digital Technologies in Youth Physical Activity, Physical Education & Sport. - London : Routledge.
-
Bokkapitel (refereegranskat)abstract
- The objective of this chapter is to provide an illustration of how digital technologies are being experienced/utilised/problematised by physical educators. This chapter introduces two Physical Education Teacher Education (PETE) students working at the University of Gothenburg and focuses on course work conducted by those students within their program. The students received an assignment to choose a particular digital technology, develop their own competence with that technology, and then demonstrate to peers how the technology can be used to facilitate learning related to the Swedish physical education curriculum for upper secondary school. A narrative of their experiences and reflections, developed through written reflections as well as informal conversations with the lead author, is presented in the first section. Three theoretical accounts of the practitioners’ narrative are then put forward. A Deweyan perspective draws attention to the ways that students and their situations are continually transformed in transaction and how digital technologies become implicated in this process. A Foucaultian perspective focuses on the regulating and controlling aspects of technology and highlights the need for care when using digital technologies. An applied Information Technology perspective highlights the ways in which digital technologies may become part of the social practices of physical education. After introducing these perspectives, a broader pedagogical account is offered in which connections between the three perspectives and current physical education scholarship is made. These connections concern: (1) meaning making; (2) student agency and possibilities for student decision making; (3) the effects of technology on lesson content; and (4) students’ digital competence. The chapter is concluded with reflections from the two PETE students.
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| 44. |
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| 45. |
- Bergman, Jan, et al.
(författare)
-
Synthesis of indolocarbazole quinones; potent aryl hydrocarbon receptor ligands
- 2002
-
Ingår i: Tetrahedron. - 0040-4020 .- 1464-5416. ; 58:7, s. 1443-1452
-
Tidskriftsartikel (refereegranskat)abstract
- Syntheses of indolo[2,3-b]carbazole-6,12-dione and the isomeric indolo[3,2-b]carbazole-6,12-dione, an extremely efficient inducer of the aryl hydrocarbon (Ah) receptor are described. Initial oxidation of the parent indolo[3,2-b]carbazole followed by several different ring-closing strategies produced the latter compound. Entries into syntheses of unsymmetrical 6,12-disubstituted indolo[2,3-b]carbazoles are also described.
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| 46. |
- Borgstrom, S, et al.
(författare)
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Time-resolved x-ray spectroscopy of optical-field-ionized plasmas
- 1995
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Ingår i: Laser and Particle Beams. - 0263-0346. ; 13:4, s. 459-468
-
Tidskriftsartikel (refereegranskat)abstract
- The time-dependent soft X-ray emission of helium and nitrogen plasmas generated by optical-field ionization is reported. The experiments were carried out by focusing pulses of the high-power Ti:sapphire laser of the Lund Institute of Technology (lambda = 796 nm, pulse duration 150 fs, pulse energy 150 mJ) to a 50-mu m diameter spot close to a nozzle, using He and N-2 as target gases. The emission on He+, N4+, and N3+ resonance lines was recorded by means of a flat-field grating spectrometer coupled to an X-ray streak camera. A pronounced difference in the temporal shape of the emission of the Lyman-alpha line of hydrogen-like helium and of the 2p-3d resonance lines of lithium-like and beryllium-like nitrogen was observed. The helium line exhibited an initial spike followed by a slow revival of the emission, whereas the nitrogen lines showed a slow decay after a fast initial rise. These observations are explained with the help of simulations.
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| 47. |
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| 48. |
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| 49. |
- Carlsson, J, et al.
(författare)
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Time-resolved Studies of Light-propagation In Paper
- 1995
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Ingår i: Applied Optics. - 2155-3165. ; 34:9, s. 1528-1535
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Tidskriftsartikel (refereegranskat)abstract
- A method for time-resolved recording of light scattering in thin, highly scattering media is described. Subpicosecond pulses from a high-power Ti:sapphire laser are used, and single-shot recordings of the scattered light are made with a fast streak camera. The method is applied to the study of light scattering in paper, and a 1-ps resolution is demonstrated. The dependence of the light scattering on the basis of weight and density of the paper has been studied. A white-light continuum generated from the high-power pulses by the use of self phase modulation in water is used to study the wavelength dependence of the scattering process. A model for the propagation of light in paper has been developed and used in Monte Carlo simulations. The experimental results are used for testing this model, and absorption and scattering parameters are determined from that comparison.
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| 50. |
- Clarke, R. J., et al.
(författare)
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Detection of short lived radioisotopes as a fast diagnostic for intense laser-solid interactions
- 2006
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 89:14
-
Tidskriftsartikel (refereegranskat)abstract
- As a diagnostic of high-intensity laser interactions (> 10(19) W cm(-2)), the detection of radioactive isotopes is regularly used for the characterization of proton, neutron, ion, and photon beams. This involves sample removal from the interaction chamber and time consuming post shot analysis using NaI coincidence counting or Ge detectors. This letter describes the use of in situ detectors to measure laser-driven (p,n) reactions in Al-27 as an almost real-time diagnostic for proton acceleration. The produced Si-27 isotope decays with a 4.16 s half-life by the predominantly beta+ emission, producing a strong 511 keV annihilation peak. (c) 2006 American Institute of Physics.
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