| 1. |
- Acharya, B. S., et al.
(författare)
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Introducing the CTA concept
- 2013
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Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Abazov, V. M., et al.
(författare)
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The upgraded DO detector
- 2006
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 565:2, s. 463-537
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Tidskriftsartikel (refereegranskat)abstract
- The DO experiment enjoyed a very successful data-collection run at the Fermilab Tevatron collider between 1992 and 1996. Since then, the detector has been upgraded to take advantage of improvements to the Tevatron and to enhance its physics capabilities. We describe the new elements of the detector, including the silicon microstrip tracker, central fiber tracker, solenoidal magnet, preshower detectors, forward muon detector, and forward proton detector. The uranium/liquid -argon calorimeters and central muon detector, remaining from Run 1, are discussed briefly. We also present the associated electronics, triggering, and data acquisition systems, along with the design and implementation of software specific to DO.
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| 3. |
- Actis, M., et al.
(författare)
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Design concepts for the Cherenkov Telescope Array CTA : an advanced facility for ground-based high-energy gamma-ray astronomy
- 2011
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Ingår i: Experimental astronomy. - : Springer. - 0922-6435 .- 1572-9508. ; 32:3, s. 193-316
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Dahl-Jensen, D., et al.
(författare)
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Eemian interglacial reconstructed from a Greenland folded ice core
- 2013
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7433, s. 489-494
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Tidskriftsartikel (refereegranskat)abstract
- Efforts to extract a Greenland ice core with a complete record of the Eemian interglacial (130,000 to 115,000 years ago) have until now been unsuccessful. The response of the Greenland ice sheet to the warmer-than-present climate of the Eemian has thus remained unclear. Here we present the new North Greenland Eemian Ice Drilling ('NEEM') ice core and show only a modest ice-sheet response to the strong warming in the early Eemian. We reconstructed the Eemian record from folded ice using globally homogeneous parameters known from dated Greenland and Antarctic ice-core records. On the basis of water stable isotopes, NEEM surface temperatures after the onset of the Eemian (126,000 years ago) peaked at 8 +/- 4 degrees Celsius above the mean of the past millennium, followed by a gradual cooling that was probably driven by the decreasing summer insolation. Between 128,000 and 122,000 years ago, the thickness of the northwest Greenland ice sheet decreased by 400 +/- 250 metres, reaching surface elevations 122,000 years ago of 130 +/- 300 metres lower than the present. Extensive surface melt occurred at the NEEM site during the Eemian, a phenomenon witnessed when melt layers formed again at NEEM during the exceptional heat of July 2012. With additional warming, surface melt might become more common in the future.
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| 8. |
- Cirasuolo, M., et al.
(författare)
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MOONS: the Multi-Object Optical and Near-infrared Spectrograph for the VLT
- 2014
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Ingår i: Ground-based and Airborne Instrumentation for Astronomy V. - : SPIE. - 1996-756X .- 0277-786X. ; 9147, s. 91470-91470
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Konferensbidrag (refereegranskat)abstract
- MOONS (the Multi-Object Optical and Near-infrared Spectrograph) has been selected by ESO as a third-generation instrument for the Very Large Telescope (VLT). The light grasp of the large collecting area offered by the VLT (8.2m diameter), combined with the large multiplex and wavelength coverage (optical to near-IR: 0.8 -1.8 mu m) of MOONS will provide the European astronomical community with a powerful, unique instrument able to pioneer a wide range of Galactic, extragalactic and cosmological studies, and it will provide crucial follow-up for major facilities such as Gaia, VISTA, Euclid and LSST. MOONS has the observational power needed to unveil galaxy formation and evolution over the entire history of the Universe, from stars in our Milky Way, through the redshift desert, and up to the epoch of very first galaxies and reionization of the Universe at redshifts of z > 8-9, just a few million years after the Big Bang. From five years of observations MOONS will provide high-quality spectra for > 3M stars in our Galaxy and the Local Group, and for 1-2M galaxies at z > 1 (for an SDSS-like survey), promising to revolutionize our understanding of the Universe. The baseline design consists of similar to 1000 fibres, deployable over a field-of-view of similar to 500 arcmin(2), the largest patrol field offered by the Nasmyth focus at the VLT. The total wavelength coverage is 0.8 -1.8 mu m with two spectral resolving powers: in the medium-resolution mode (R similar to 4,000-6,000) the entire wavelength range is observed simultaneously, while the high-resolution mode will cover three selected sub-regions simultaneously: one region with R similar to 8,000 near the Ca II triplet to measure stellar radial velocities, and two regions at R similar to 20,000 (one in each of the J- and H-bands), for precision measurements of chemical abundances.
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| 9. |
- Beaumont, Robin N, et al.
(författare)
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Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth.
- 2023
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Ingår i: Nature genetics. - 1546-1718 .- 1061-4036. ; 55:11, s. 1807-19
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Tidskriftsartikel (refereegranskat)abstract
- A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n=65,405), maternal (n=61,228) and paternal (n=52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.
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| 10. |
- López-Puertas, M., et al.
(författare)
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Non-local thermodynamic equilibrium limb radiances for the mipas instrument on Envisat-1
- 1998
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - 0022-4073 .- 1879-1352. ; 59:3-5, s. 377-403
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Tidskriftsartikel (refereegranskat)abstract
- An evaluation of the effects that the assumption of local thermodynamic equilibrium (LTE) has on the retrieval of pressure, temperature and the five primary target gases (O3, H2O, CH4, N2O, and HNO3) from spectra to be taken by Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) on the Envisat-1 platform has been conducted. For doing so, non-LTE and LTE limb radiances in the spectral range of 680–2275 cm−1 (4.15–14.6 μm) with a resolution of 0.05 cm−1 at tangent heights from 10 to 70 km have been computed. These calculations included the most updated non-LTE populations of a large number of vibrational levels of the CO2, O3, H2O, CH4, N2O and HNO3 molecules which cause the most prominent atmospheric infrared emissions. A discussion of the most important non-LTE effects on the limb radiances as well as on the retrievals of pressure-temperature and volume mixing ratios of O3, H2O, CH4, N2O, and HNO3 is presented, together with the most important non-LTE issues that could be studied with the future coming of MIPAS data.
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| 11. |
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| 12. |
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| 13. |
- Manuilova, R.O., et al.
(författare)
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Modelling of non-LTE limb spectra of i.r. ozone bands for the MIPAS space experiment
- 1998
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Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - 0022-4073 .- 1879-1352. ; 59:3-5, s. 405-422
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Tidskriftsartikel (refereegranskat)abstract
- A new model for calculating the populations of the ozone vibrational states under non-LTE (Local Thermodynamic Equilibrium) conditions is presented. In the model, 23 vibrational levels of the O3 molecule, as well as three vibrational levels of the O2 molecule and two vibrational levels of the N2 molecule, are considered. The radiative transfer at the break-down of LTE was treated explicitly for 150 000 ro-vibrational transitions. The populations obtained were used to calculate limb radiances in various spectral regions of the 4.8 and 9.6 μm bands. Test retrievals of O3 vertical volume mixing ratio (VMR) profiles with a radiance model disregarding non-LTE were performed in order to assess the potential impact of non-LTE effects on the retrieval of the O3 abundances from MIPAS (Michelson Interferometer for Passive Atmospheric Sounding) measurements.
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| 14. |
- Pilgaard, K., et al.
(författare)
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The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men
- 2009
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:7, s. 1298-1307
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Tidskriftsartikel (refereegranskat)abstract
- We studied the physiological, metabolic and hormonal mechanisms underlying the elevated risk of type 2 diabetes in carriers of TCF7L2 gene. We undertook genotyping of 81 healthy young Danish men for rs7903146 of TCF7L2 and carried out various beta cell tests including: 24 h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic and peripheral insulin action. Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p < 0.05) and reduced insulin secretion relative to glucose during a mixed meal test (beta index: p < 0.003), but not during an IVGTT. This was further supported by reduced late-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p < 0.02) suggesting altered alpha cell function. Elevated hepatic glucose production and reduced insulinotropic effect of incretin hormones contribute to an increased risk of type 2 diabetes in carriers of the rs7903146 risk T allele of TCF7L2.
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| 15. |
- Schüpbach, S., et al.
(författare)
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Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.
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| 16. |
- Tison, J.-L., et al.
(författare)
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Retrieving the paleoclimatic signal from the deeper part of the EPICA Dome C ice core
- 2015
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 9:4, s. 1633-1648
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Tidskriftsartikel (refereegranskat)abstract
- An important share of paleoclimatic information is buried within the lowermost layers of deep ice cores. Because improving our records further back in time is one of the main challenges in the near future, it is essential to judge how deep these records remain unaltered, since the proximity of the bedrock is likely to interfere both with the recorded temporal sequence and the ice properties. In this paper, we present a multiparametric study (delta D-delta O-18(ice), delta O-18(atm), total air content, CO2, CH4, N2O, dust, high-resolution chemistry, ice texture) of the bottom 60 m of the EPICA (European Project for Ice Coring in Antarctica) Dome C ice core from central Antarctica. These bottom layers were subdivided into two distinct facies: the lower 12 m showing visible solid inclusions (basal dispersed ice facies) and the upper 48 m, which we will refer to as the basal clean ice facies. Some of the data are consistent with a pristine paleoclimatic signal, others show clear anomalies It is demonstrated that neither large-scale bottom refreezing of subglacial water, nor mixing (be it internal or with a local basal end term from a previous/initial ice sheet configuration) can explain the observed bottom-ice properties. We focus on the high-resolution chemical profiles and on the available remote sensing data on the subglacial topography of the site to propose a mechanism by which relative stretching of the bottom-ice sheet layers is made possible, due to the progressively confining effect of subglacial valley sides. This stress field change, combined with bottom-ice temperature close to the pressure melting point, induces accelerated migration recrystallization, which results in spatial chemical sorting of the impurities, depending on their state (dissolved vs. solid) and if they are involved or not in salt formation. This chemical sorting effect is responsible for the progressive build-up of the visible solid aggregates that therefore mainly originate from within, and not from incorporation processes of debris from the ice sheet's substrate. We further discuss how the proposed mechanism is compatible with the other ice properties described. We conclude that the paleoclimatic signal is only marginally affected in terms of global ice properties at the bottom of EPICA Dome C, but that the timescale was considerably distorted by mechanical stretching of MIS20 due to the increasing influence of the subglacial topography, a process that might have started well above the bottom ice. A clear paleoclimatic signal can therefore not be inferred from the deeper part of the EPICA Dome C ice core. Our work suggests that the existence of a flat monotonic ice bedrock interface, extending for several times the ice thickness, would be a crucial factor in choosing a future oldest ice drilling location in Antarctica.
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| 17. |
- Yusuf, D, et al.
(författare)
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The transcription factor encyclopedia
- 2012
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906. ; 13:3, s. R24-
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Tidskriftsartikel (refereegranskat)
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| 18. |
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| 19. |
- Hedström, Anna Karin, et al.
(författare)
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The interaction between smoking and HLA genes in multiple sclerosis : replication and refinement
- 2017
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 23:1, s. 37-37
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Tidskriftsartikel (refereegranskat)abstract
- Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case-control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States). A pooled analysis was performed for replication of previous observations (7190 cases, 8876 controls). Refined detailed analyses were carried out by combining the genetically similar populations from the Nordic studies (6265 cases, 8401 controls). In both the pooled analyses and in the combined Nordic material, interactions were observed between HLA-DRB*15 and absence of HLA-A*02 and between smoking and each of the genetic risk factors. Two way interactions were observed between each combination of the three variables, invariant over categories of the third. Further, there was also a three way interaction between the risk factors. The difference in MS risk between the extremes was considerable; smokers carrying HLA-DRB1*15 and lacking HLA-A*02 had a 13-fold increased risk compared with never smokers without these genetic risk factors (OR 12.7, 95% CI 10.8-14.9). The risk of MS associated with HLA genotypes is strongly influenced by smoking status and vice versa. Since the function of HLA molecules is to present peptide antigens to T cells, the demonstrated interactions strongly suggest that smoking alters MS risk through actions on adaptive immunity.
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| 20. |
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| 21. |
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| 22. |
- Tillett, W, et al.
(författare)
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DYNAMICS OF NAIL PSORIASIS WITH GUSELKUMAB TREATMENT AND WITHDRAWAL IN ASSOCIATION WITH SKIN RESPONSE AND PATIENT-REPORTED OUTCOMES: A POST HOC ANALYSIS OF THE VOYAGE 2 PHASE 3 TRIAL
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 830-830
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Nail psoriasis can be difficult to treat, affects ~50% of patients with psoriasis and can involve the nail matrix (pitting, leukonychia) and/or nail bed (onycholysis, splinter haemorrhages). Evidence suggests nail psoriasis may be associated with risk of developing psoriatic arthritis, in particular distal interphalangeal joint erosion.1–3 Data to Week (Wk) 24 from VOYAGE 1 and 2, two Phase 3 clinical trials, indicate that the anti-interleukin-23 monoclonal antibody guselkumab (GUS) is more effective than placebo and as effective as adalimumab in treating nail psoriasis.4 Furthermore, GUS is also associated with maintained Psoriasis Area and Severity Index (PASI) following treatment withdrawal in VOYAGE 2; however, nail response is not as well understood in this context.5ObjectivesThis VOYAGE 2 post hoc analysis evaluated nail response and its association with skin response and patient-reported outcomes (PROs) in two groups, one experiencing GUS withdrawal and the other receiving continuous GUS.MethodsPatients had moderate-to-severe plaque psoriasis and nail psoriasis, were initially randomised to GUS, and achieved PASI 90 at Wk 28. Patients were then re-randomised to placebo (GUS withdrawal) or GUS every 8 wks (GUS continuation). Nail Psoriasis Severity Index (NAPSI; grading the most affected nail), fingernail Physician’s Global Assessment (f-PGA), PASI and Dermatology Life Quality Index (DLQI) are reported as observed at Wk 0, 16, 24 and 48.ResultsAmong 209 patients, NAPSI, f-PGA, PASI and DLQI showed similar trends in both groups until Wk 24. All endpoints improved from baseline; and at Wk 24, patients in the GUS withdrawal and GUS continuation groups achieved a mean NAPSI of 1.7 and 1.8 (nail matrix 1.0 and 1.0; nail bed 0.7 and 0.8); f-PGA 0.9 and 0.9; PASI 0.6 and 0.6; and DLQI 2.2 and 2.3, respectively (Table 1). Nail changes continued to follow skin trends through Wk 48 (Figure 1); with GUS withdrawal, worsening of PASI and DLQI was proportionally greater than that of NAPSI and f-PGA; with GUS continuation, PASI and DLQI remained fairly stable, and NAPSI and f-PGA continued to improve. Nails were numerically slower to respond to GUS initiation and withdrawal than skin, with a more pronounced delay for nail matrix vs nail bed. In patients who sustained a PASI 90 response at Wk 48, despite GUS withdrawal, a high level of nail response was also maintained.Table 1.NAPSI, f-PGA, PASI and DLQI through Wk 48 in GUS withdrawal and GUS continuation groupsWk 0Wk 16Wk 24Wk 28Wk 48GUS withdrawal*GUSRPlacebon97969696NAPSI5.0 (2.1)2.5 (1.9)1.7 (1.9)1.9 (2.1)Nail matrix2.7 (1.3)1.5 (1.3)1.0 (1.2)0.9 (1.3)Nail bed2.2 (1.2)0.9 (1.0)0.7 (1.0)1.0 (1.1)n98979797f-PGA2.5 (0.8)1.3 (0.9)0.9 (0.8)1.1 (1.0)n101101100100PASI23.1 (9.0)1.3 (2.7)0.6 (1.4)5.2 (6.1)n101101100100DLQI14.5 (6.1)2.8 (4.1)2.2 (3.6)7.0 (7.4)GUS continuationGUSRGUSn108106107105NAPSI4.4 (1.8)2.4 (2.2)1.8 (2.0)1.2 (1.6)Nail matrix2.5 (1.2)†1.4 (1.3)1.0 (1.2)0.7 (1.0)Nail bed1.9 (1.2)1.0 (1.1)0.8 (1.0)0.5 (0.8)n108106107105f-PGA2.4 (0.9)1.1 (0.9)0.9 (0.9)0.7 (0.8)n108108108106PASI22.6 (8.8)1.2 (2.1)0.6 (1.1)1.3 (3.5)n107108108104DLQI14.3 (6.4)2.9 (4.2)2.3 (4.0)1.8 (3.4)Data are mean (standard deviation). *n=10 reinitiated GUS upon loss of 50% of Wk 28 PASI 90(at n=1 Wk 36, n=2 Wk 40, n=7 Wk 44); †n=107; R, re-randomisation of PASI 90 responders.ConclusionGUS treatment through Wk 48 improved nail psoriasis, skin psoriasis and PROs. When GUS was withdrawn, loss of response was slower in nails vs skin. These findings support that nail outcomes follow skin outcome trends with GUS treatment and that nail outcomes should contribute to evaluation of treatment efficacy and disease progression.2,3,6References[1]Robert B. Dermatology 2010; 221 Suppl 1: 1–5;[2]Antony A et al. J Rheumatol 2019; 46: 1097–102.[3]Wilson F et al. Arthritis Rheum 2009; 61: 233–39;[4]Foley P et al. JAMA Dermatol 2018; 154: 676–83;[5]Conrad C et al. AAD 2021. P26573.[6]Conrad C et al. Dermatol Ther 2022; 12: 233–41.AcknowledgementsThis analysis was funded by Janssen and medical writing support was provided by OPEN Health Medical Communications.Disclosure of InterestsWilliam Tillett Speakers bureau: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant of: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Grant/research support from: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Alexander Egeberg Speakers bureau: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and JanssenPharmaceuticals, Consultant of: AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and JanssenPharmaceuticals, Grant/research support from: Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, Enikö Sonkoly Speakers bureau: AbbVie, Eli Lilly, UCB, Janssen, Novartis, Sanofi and LEO Pharma, Grant/research support from: Pfizer, Patricia Gorecki Employee of: Janssen, Anna Tjärnlund Employee of: Janssen, Jozefien Buyze Employee of: Janssen, Sven Wegner Employee of: Janssen, Dennis McGonagle Speakers bureau: Abbvie, BMS, Celgene, Janssen, Novartis, Lilly, UCB, Grant/research support from: Abbvie, BMS, Celgene, Janssen, Novartis, Lilly, UCB
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| 23. |
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| 24. |
- Avdeichikov, Vladimir, et al.
(författare)
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Systematics in the light response of BGO, CsI(T1) and GSO(Ce) scintillators to charged particles
- 2002
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 484:1-3, s. 251-258
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Tidskriftsartikel (refereegranskat)abstract
- The light response of a BGO crystal has been measured for particles Z = 1-8, A = 1-16 in the energy range similar to2-60 A MeV. The reaction products are identified by a DeltaE(Si) - E(Sci/PD) telescope, The position of the jump in the value of the signal from the PD at the punch-through points is used to calibrate both the DeltaE(Si) and E(Sci/PD) scales in MeV. The dependence of the light output on the energy E, ion atomic number Z and mass A is parameterized by the power law relation, L(Z, A, E) = a(1)((Z, A))E(a2(Z, A)). The parameters a(1) and a(2) have a smooth dependence on Z for all three crystals. The mass dependence of a(1), a(2) is deduced as a simple analytical expression, The systematics of these parameters is presented for BGO, CsI(Tl) and GSO(Ce) scintillators as a function of Z, A. Calculations of the response function, based on the Murray-Mayer model provide an excellent description of the shape of L(Z, A, E) versus E dependence, but show some deviations in the individual ion normalization constant for the BGO and GSO(Ce) scintillators. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 25. |
- Erhardt, Tobias, et al.
(författare)
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High-resolution aerosol concentration data from the Greenland NorthGRIP and NEEM deep ice cores
- 2022
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Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 14:3, s. 1215-1231
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Tidskriftsartikel (refereegranskat)abstract
- Records of chemical impurities from ice cores enable us to reconstruct the past deposition of aerosols onto polar ice sheets and alpine glaciers. Through this they allow us to gain insight into changes of the source, transport and deposition processes that ultimately determine the deposition flux at the coring location. However, the low concentrations of the aerosol species in the ice and the resulting high risk of contamination pose a formidable analytical challenge, especially if long, continuous and highly resolved records are needed. Continuous flow analysis, CFA, the continuous melting, decontamination and analysis of ice-core samples has mostly overcome this issue and has quickly become the de facto standard to obtain high-resolution aerosol records from ice cores after its inception at the University of Bern in the mid-1990s.Here, we present continuous records of calcium (Ca2+), sodium (Na+), ammonium (NH+4), nitrate (NO-3) and electrolytic conductivity at 1 mm depth resolution from the NGRIP (North Greenland Ice Core Project) and NEEM (North Greenland Eemian Ice Drilling) ice cores produced by the Bern Continuous Flow Analysis group in the years 2000 to 2011 (Erhardt et al., 2021). Both of the records were previously used in a number of studies but were never published in full 1 mm resolution. Alongside the 1 mm datasets we provide decadal averages, a detailed description of the methods, relevant references, an assessment of the quality of the data and its usable resolution. Along the way we will also give some historical context on the development of the Bern CFA system.
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| 26. |
- Eyerich, K, et al.
(författare)
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IL-23 blockade with guselkumab potentially modifies psoriasis pathogenesis: rationale and study protocol of a phase 3b, randomised, double-blind, multicentre study in participants with moderate-to-severe plaque-type psoriasis (GUIDE)
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:9, s. e049822-
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Tidskriftsartikel (refereegranskat)abstract
- Guselkumab is an interleukin (IL)-23 pathway blocker with proven efficacy in patients with moderate-to-severe plaque psoriasis. Early intervention with guselkumab may result in changes to the clinical disease course versus later intervention.Methods and analysisHere we present the rationale and design of a phase 3b, randomised, double-blind, multicentre study (GUIDE), comparing treatment effects of guselkumab in patients with short (≤2 years) or longer (>2 years) duration of plaque-type psoriasis, measured from first appearance of psoriatic plaques. Participants achieving skin clearance (Psoriasis Area and Severity Index (PASI)=0) by week 20 and maintaining complete clearance at week 28 visit (‘super-responders’ (SRe)) will be randomised to continue approved maintenance dosing every 8 weeks (q8w) versus an investigational maintenance dosing interval of 16 weeks (q16w) until week 68. Primary endpoint: proportion of participants in the q8w vs q16w arms with absolute PASI <3 at week 68. Participants with PASI <3 at week 68 will be withdrawn from guselkumab treatment for up to 48 weeks. Participants not achieving SRe criteria (non-SRe) will remain in the study with q8w guselkumab dosing through week 68. Additional to serum samples obtained from all patients, skin biopsies and whole-blood samples will be taken from SRe and non-SRe participants at various time points in optional substudies. Analyses include: genetics; immunophenotyping (fluorescence-activated cell sorting); gene and protein expression profiling; immunohistology. By merging clinical endpoints with mechanistic findings, this study aims to elucidate how IL-23 blockade with guselkumab can modify the disease course by altering molecular and cellular drivers that cause relapse after treatment withdrawal, particularly among SRe.Ethics and disseminationApproval obtained from ethics committee Medical Council Hamburg, Germany (PVN5925). GUIDE is compliant with the Declaration of Helsinki.Trial registration numberRegistered at ClinicalTrials.gov (NCT03818035). All primary endpoint results (prespecified analyses) will be submitted to peer-reviewed, international journals within 18 months after primary completion date.
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| 27. |
- Fischer, Hubertus, et al.
(författare)
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Reconstruction of millennial changes in dust emission, transport and regional sea ice coverage using the deep EPICA ice cores from the Atlantic and Indian Ocean sector of Antarctica
- 2007
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X. ; 260, s. 340-354
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Tidskriftsartikel (refereegranskat)abstract
- Continuous sea salt and mineral dust aerosol records have been studied on the two EPICA (European Project for Ice Coring inAntarctica) deep ice cores. The joint use of these records from opposite sides of the East Antarctic plateau allows for an estimate ofchanges in dust transport and emission intensity as well as for the identification of regional differences in the sea salt aerosolsource. The mineral dust flux records at both sites show a strong coherency over the last 150 kyr related to dust emission changes inthe glacial Patagonian dust source with three times higher dust fluxes in the Atlantic compared to the Indian Ocean sector of theSouthern Ocean (SO). Using a simple conceptual transport model this indicates that transport can explain only 40% of theatmospheric dust concentration changes in Antarctica, while factor 5–10 changes occurred. Accordingly, the main cause for the strong glacial dust flux changes in Antarctica must lie in environmental changes in Patagonia. Dust emissions, hence environmentalconditions in Patagonia, were very similar during the last two glacials and interglacials, respectively, despite 2–4 °C warmertemperatures recorded in Antarctica during the penultimate interglacial than today. 2–3 times higher sea salt fluxes found in bothice cores in the glacial compared to the Holocene are difficult to reconcile with a largely unchanged transport intensity and thedistant open ocean source. The substantial glacial enhancements in sea salt aerosol fluxes can be readily explained assuming sea iceformation as the main sea salt aerosol source with a significantly larger expansion of (summer) sea ice in the Weddell Sea than inthe Indian Ocean sector. During the penultimate interglacial, our sea salt records point to a 50% reduction of winter sea icecoverage compared to the Holocene both in the Indian and Atlantic Ocean sector of the SO. However, from 20 to 80 ka beforepresent sea salt fluxes show only very subdued millennial changes despite pronounced temperature fluctuations, likely due to thelarge distance of the sea ice salt source to our drill sites.
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| 28. |
- Gstrein, Chiara, et al.
(författare)
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Solvatochromism of dye-labeled dendronized polymers of generation numbers 1–4: comparison to dendrimers
- 2016
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Ingår i: Chemical Science. - 2041-6539. ; :7, s. 4644-4652
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Tidskriftsartikel (refereegranskat)abstract
- Two series of dendronized polymers (DPs) of generations g = 1–4 with different levels of dendritic substitution (low and high) and a solvatochromic probe at g = 1 level are used to study their swelling behavior in a collection of solvents largely differing in polarity as indicated by the Kamlet–Taft parameters. This is done by measuring the UV-Vis spectra of all samples in all solvents and determining the longest wavelength absorptions (λmax). The λmax values fall into a range defined by the extreme situations, when the solvatochromic probe is either fully surrounded by solvent or completely shielded against it. The former situation is achieved in a model compound and the latter situation is believed to be reached when in a poor solvent the dendritic shell around the backbone is fully collapsed. We observe that solvent penetration into the interior of the DPs decreases with increasing g and does so faster for the more highly dendritically substituted series than for the less highly substituted one. Interestingly, the swelling of the more highly substituted DP series already at the g = 4 level has decreased to approximately 20% of that at the g = 1 level which supports an earlier proposal that high g DPs can be viewed as nano-sized molecular objects. Furthermore, when comparing these two DP series with a g = 1–6 series of dendrimers investigated by Fréchet et al. it becomes evident that even the less substituted series of DPs is much less responsive to solvent changes as assessed by the solvatochromic probe than the dendrimers, suggesting the branches around the (polymeric) core in DPs to be more densely packed compared to those in dendrimers, thus, establishing a key difference between these two dendritic macromolecules.
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| 29. |
- Hindy, George, et al.
(författare)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 30. |
- Kamber, Umut, et al.
(författare)
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Self-induced spin glass state in elemental and crystalline neodymium
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 368:6494
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Tidskriftsartikel (refereegranskat)abstract
- Spin glasses are a highly complex magnetic state of matter intricately linked to spin frustration and structural disorder. They exhibit no long-range order and exude aging phenomena, distinguishing them from quantum spin liquids. We report a previously unknown type of spin glass state, the spin-Q glass, observable in bulk-like crystalline metallic neodymium thick films. Using spin-polarized scanning tunneling microscopy combined with ab initio calculations and atomistic spin-dynamics simulations, we visualized the variations in atomic-scale noncolinear order and its response to magnetic field and temperature. We quantified the aging phenomena relating the glassiness to crystalline symmetry and the energy landscape. This result not only resolves the long-standing debate of the magnetism of neodymium, but also suggests that glassiness may arise in other magnetic solids lacking extrinsic disorder.
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| 31. |
- Kunz, Anne, et al.
(författare)
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Intermolecular London Dispersion Interactions of Azobenzene Switches for Tuning Molecular Solar Thermal Energy Storage Systems
- 2019
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Ingår i: ChemPlusChem. - : Wiley. - 2192-6506. ; 84:8, s. 1145-1148
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Tidskriftsartikel (refereegranskat)abstract
- The performance of molecular solar thermal energy storage systems (MOST) depends amongst others on the amount of energy stored. Azobenzenes have been investigated as high-potential materials for MOST applications. In the present study it could be shown that intermolecular attractive London dispersion interactions stabilize the (E)-isomer in bisazobenzene that is linked by different alkyl bridges. Differential scanning calorimetry (DSC) measurements revealed, that this interaction leads to an increased storage energy per azo-unit of more than 3 kcal/mol compared to the parent azobenzene. The origin of this effect has been supported by computation as well as X-ray analysis. In the solid state structure attractive London dispersion interactions between the C−H of the alkyl bridge and the π-system of the azobenzene could be clearly assigned. This concept will be highly useful in designing more effective MOST systems in the future.
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| 32. |
- Ling, Charlotte, et al.
(författare)
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Impact of the peroxisome proliferator activated receptor-gamma coactivator-1 beta (PGC-1 beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1 beta expression and fibre type composition in human skeletal muscle
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:8, s. 1615-1620
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Peroxisome proliferator activated receptor-gamma coactivator-lp (PGC-1 beta, also known as PPARGCIB) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1 beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1 beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1 beta expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods The PGC-1 beta Ala203Pro polymerphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1 beta expression, in vivo metabolism and markers for fibre type composition. Results Insulin-stimulated non-oxidative glucose metabolism (NOGM; p=0.025) and glycolytic flux rate (GF; p=0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1 beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1 beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p <= 0.001), there was no significant age-related decline in PGC-1 beta expression in carriers of the 203Pro allele (p >= 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1 beta expression. Finally, PGC-1 beta expression correlated positively with markers for oxidative fibres in human muscle. Conclusions/interpretation This study suggests that young carriers of a PGC-1 beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1 beta expression in muscle.
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| 33. |
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| 34. |
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| 35. |
- Passos, Vania, et al.
(författare)
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Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons
- 2024
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Ingår i: Journal of Medical Virology. - : John Wiley & Sons. - 0146-6615 .- 1096-9071. ; 96:2
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory coronavirus 2 (SARS-CoV-2) causes neurological disease in the peripheral and central nervous system (PNS and CNS, respectively) of some patients. It is not clear whether SARS-CoV-2 infection or the subsequent immune response are the key factors that cause neurological disease. Here, we addressed this question by infecting human induced pluripotent stem cell-derived CNS and PNS neurons with SARS-CoV-2. SARS-CoV-2 infected a low number of CNS neurons and did not elicit a robust innate immune response. On the contrary, SARS-CoV-2 infected a higher number of PNS neurons. This resulted in expression of interferon (IFN) λ1, several IFN-stimulated genes and proinflammatory cytokines. The PNS neurons also displayed alterations characteristic of neuronal damage, as increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and α-synuclein, and lower levels of cytoskeletal proteins. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neuronal damage, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. Our results provide a basis to study coronavirus disease 2019 (COVID-19) related neuronal pathology and to test future preventive or therapeutic strategies.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Schlueter, A. Dieter, et al.
(författare)
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Dendronized Polymers: Molecular Objects between Conventional Linear Polymers and Colloidal Particles
- 2014
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Ingår i: ACS Macro Letters. - : American Chemical Society (ACS). - 2161-1653. ; 3:10, s. 991-998
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Tidskriftsartikel (refereegranskat)abstract
- The term molecular object (MO) is introduced to describe single, shape persistent macromolecules that retain their form and mesoscopic dimensions irrespective of solvent quality and adsorption onto a surface. The concept is illustrated with results concerning homologous series of dendronized polymers (DP). In particular, we discuss imaging experiments quantifying deformation upon adsorption, defect characterization, and atomistic molecular dynamics simulations of DP structure. We argue that MOs such as high generation DP, with their large dimensions and high internal density, provide an opportunity to address fundamental questions regarding the onset of bulk-like behavior in single molecules. Illustrative examples of such questions concern the smallest MO exhibiting a glass transition, glassy behavior or a constant bulk density. The characteristics of DP MO are highlighted by comparison to polymer beads, polymeric micelles, globular proteins, and carbon nanotubes. We discuss future research directions and speculate on possibilities involving multiarmed and toroid DP and the effect of DP on friction and rheology, as well as their utilization for nanoconstruction.
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| 40. |
- Teleki, A, et al.
(författare)
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Flame-coating of titania particles with silica
- 2005
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Ingår i: Journal of Materials Research. - Swiss Fed Inst Technol, Particle Technol Lab, Inst Proc Engn, Dept Mech & Proc Engn, CH-8092 Zurich, Switzerland. Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inorgan Chem Lab, CH-8093 Zurich, Switzerland.. - 0884-2914 .- 2044-5326. ; 20:5, s. 1336-1347
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Tidskriftsartikel (refereegranskat)abstract
- Silica/titania composite particles were prepared by co-oxidation of titanium-tetra-isopropoxide and hexamethyldisiloxane in a co-flow diffusion flame reactor. The influence of precursor composition on product powder characteristics was studied by x-ray diffraction, nitrogen adsorption, electron microscopy, elemental mapping, and energy-dispersive x-ray analysis. The flame temperature was measured by Fourier transform infrared spectroscopy. The evolution of composite particle morphology from ramified agglomerates to spot- or fully coated particles was investigated by thermophoretic sampling and transmission/scanning electron microscopy. At 40-60 wt% TiO2, particles with segregated regions of silica and titania were formed, while at 80 wt% TiO2 rough silica coatings were obtained. Rapid flame-quenching with a critical flow nozzle at 5 cm above the burner nearly halved the product particle size, changed its crystallinity from pure anatase to mostly rutile and resulted in smooth silica coatings on particles containing 80 wt% TiO2.
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| 41. |
- Verlhac, Benjamin, et al.
(författare)
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Thermally induced magnetic order from glassiness in elemental neodymium
- 2022
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Ingår i: Nature Physics. - : Nature Portfolio. - 1745-2473 .- 1745-2481. ; 18:8, s. 905-911
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Tidskriftsartikel (refereegranskat)abstract
- At finite temperatures, fluctuations invariably introduce disorder and are responsible for ultimately destroying ordered phases. Here we present an unusual magnetic transition in elemental neodymium where, with increasing temperature, long-range multiply periodic 'multi-Q' magnetic order emerges from a self-induced spin glass. Using temperature-dependent spin-polarized scanning tunnelling microscopy, we characterize the local order of a previously reported spin glass phase, and quantify the emergence of long-range multi-Q order with increasing temperature. We develop two analysis tools that allow us to determine the glass transition temperature from measurements of the spatially dependent magnetization. We compare these observations with atomistic spin dynamics simulations, which reproduce the qualitative observation of a phase transition from a low-temperature spin glass phase to an intermediate ordered multi-Q phase. These simulations trace the origin of the unexpected high-temperature order in weakened frustration driven by temperature-dependent sublattice correlations. These findings constitute an example of order from disorder, and provide a platform to study the rich magnetization dynamics of a self-induced spin glass.Thermal fluctuations associated with higher temperatures normally destroy long-range order, but in some circumstances they can stabilize new ordered phases. This 'order by disorder' phenomenon has now been observed in the magnetic phases of neodymium.
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| 42. |
- Wang, Zhihang, 1989, et al.
(författare)
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Storing energy with molecular photoisomers
- 2021
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Ingår i: Joule. - : Elsevier BV. - 2542-4351. ; 5:12, s. 3116-3136
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Forskningsöversikt (refereegranskat)abstract
- Some molecular photoisomers can be isomerized to a metastable high-energy state by exposure to light. These molecules can then be thermally or catalytically converted back to their initial state, releasing heat in the process. Such a reversible photochemical process has been considered for developing molecular solar thermal (MOST) systems. In this review, we introduce the concept, criteria, and state-of-the-art of MOST systems, with an emphasis on the three most promising molecular systems: norbornadiene/quadricyclane, E/Z-azobenzene, and dihydroazulene/vinylheptafulvene. After discussing the fundamental working principles, we focus on molecular design strategies for improving solar energy storage performance, remaining challenges, and potential focus areas. Finally, we summarize the current molecular incorporation into functional devices and conclude with a perspective on challenges and future directions.
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| 43. |
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| 44. |
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| 45. |
- Wolff, E. W., et al.
(författare)
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Changes in environment over the last 800,000 years from chemical analysis of the EPICA Dome C ice core
- 2010
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 29:1-2, s. 285-295
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Tidskriftsartikel (refereegranskat)abstract
- The EPICA ice core from Dome C extends 3259 m in depth, and encompasses 800 ka of datable and sequential ice. Numerous chemical species have been measured along the length of the cores. Here we concentrate on interpreting the main low-resolution patterns of major ions. We extend the published record for non-sea-salt calcium, sea-salt sodium and non-sea-salt sulfate flux to 800 ka. The non-sea-salt calcium record confirms that terrestrial dust originating from South America closely mirrored Antarctic climate, both at orbital and millennial timescales. A major cause of the main trends is most likely climate in southern South America, which could be sensitive to subtle changes in atmospheric circulation. Sea-salt sodium also follows temperature, but With a threshold at low temperature. We re-examine the use of sodium as a sea ice proxy, concluding that it is probably reflecting extent, with high salt concentrations reflecting larger ice extents. With this interpretation, the sodium flux record indicates low ice extent operating as an amplifier in warm interglacials. Non-sea-salt sulfate flux is almost constant along the core, confirming the lack of change in marine productivity (for sulfur-producing organisms) in the areas of the Southern Ocean contributing to the flux at Dome C. For the first time we also present long records of reversible species such as nitrate and chloride, and show that the pattern of post-depositional losses described for shallower ice is maintained in older ice. It appears possible to use these concentrations to constrain snow accumulation rates in interglacial ice at this site, and the results suggest a possible correction to accumulation rates in one early interglacial. Taken together the chemistry records offer a number of constraints on the way the Earth system combined to give the major climate fluctuations of the late Quaternary period.
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