| 1. |
- Elhai, M, et al.
(author)
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Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study
- 2019
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987
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Journal article (peer-reviewed)abstract
- To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
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| 2. |
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| 3. |
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| 4. |
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| 5. |
- Vinko, S. M., et al.
(author)
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Electronic Structure of an XUV Photogenerated Solid-Density Aluminum Plasma
- 2010
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:22, s. 225001-
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Journal article (peer-reviewed)abstract
- By use of high intensity XUV radiation from the FLASH free-electron laser at DESY, we have created highly excited exotic states of matter in solid-density aluminum samples. The XUV intensity is sufficiently high to excite an inner-shell electron from a large fraction of the atoms in the focal region. We show that soft-x-ray emission spectroscopy measurements reveal the electronic temperature and density of this highly excited system immediately after the excitation pulse, with detailed calculations of the electronic structure, based on finite-temperature density functional theory, in good agreement with the experimental results.
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| 6. |
- Vinko, S. M., et al.
(author)
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Time-Resolved XUV Opacity Measurements of Warm Dense Aluminum
- 2020
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In: Physical Review Letters. - : American Physical Society. - 1079-7114 .- 0031-9007. ; 124:22
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Journal article (peer-reviewed)abstract
- The free-free opacity in plasmas is fundamental to our understanding of energy transport in stellar interiors and for inertial confinement fusion research. However, theoretical predictions in the challenging dense plasma regime are conflicting and there is a dearth of accurate experimental data to allow for direct model validation. Here we present time-resolved transmission measurements in solid-density Al heated by an XUV free-electron laser. We use a novel functional optimization approach to extract the temperature-dependent absorption coefficient directly from an oversampled pool of single-shot measurements, and find a pronounced enhancement of the opacity as the plasma is heated to temperatures of order of the Fermi energy. Plasma heating and opacity enhancement are observed on ultrafast timescales, within the duration of the femtosecond XUV pulse. We attribute further rises in the opacity on ps timescales to melt and the formation of warm dense matter.
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| 7. |
- Hajkova, V., et al.
(author)
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X-ray laser-induced ablation of lead compounds
- 2011
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In: DAMAGE TO VUV, EUV, AND X-RAY OPTICS III. - : SPIE.
-
Conference paper (peer-reviewed)abstract
- The recent commissioning of a X-ray free-electron laser triggered an extensive research in the area of X-ray ablation of high-Z, high-density materials. Such compounds should be used to shorten an effective attenuation length for obtaining clean ablation imprints required for the focused beam analysis. Compounds of lead (Z=82) represent the materials of first choice. In this contribution, single-shot ablation thresholds are reported for PbWO(4) and PbI(2) exposed to ultra-short pulses of extreme ultraviolet radiation and X-rays at FLASH and LCLS facilities, respectively. Interestingly, the threshold reaches only 0.11 J/cm(2) at 1.55 nm in lead tungstate although a value of 0.4 J/cm(2) is expected according to the wavelength dependence of an attenuation length and the threshold value determined in the XUV spectral region, i.e., 79 mJ/cm(2) at a FEL wavelength of 13.5 nm. Mechanisms of ablation processes are discussed to explain this discrepancy. Lead iodide shows at 1.55 nm significantly lower ablation threshold than tungstate although an attenuation length of the radiation is in both materials quite the same. Lower thermal and radiation stability of PbI(2) is responsible for this finding.
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| 8. |
- Hong, S. J., et al.
(author)
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TMEM106B and CPOX are genetic determinants of cerebrospinal fluid Alzheimer's disease biomarker levels
- 2021
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 17:10, s. 1628-1640
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Journal article (peer-reviewed)abstract
- Introduction Neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), and neurogranin (Ng) are biomarkers for Alzheimer's disease (AD) to monitor axonal damage, astroglial activation, and synaptic degeneration, respectively. Methods We performed genome-wide association studies (GWAS) using DNA and cerebrospinal fluid (CSF) samples from the EMIF-AD Multimodal Biomarker Discovery study for discovery, and the Alzheimer's Disease Neuroimaging Initiative study for validation analyses. GWAS were performed for all three CSF biomarkers using linear regression models adjusting for relevant covariates. Results We identify novel genome-wide significant associations between DNA variants in TMEM106B and CSF levels of NfL, and between CPOX and YKL-40. We confirm previous work suggesting that YKL-40 levels are associated with DNA variants in CHI3L1. Discussion Our study provides important new insights into the genetic architecture underlying interindividual variation in three AD-related CSF biomarkers. In particular, our data shed light on the sequence of events regarding the initiation and progression of neuropathological processes relevant in AD.
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| 9. |
- Bos, I., et al.
(author)
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Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum
- 2019
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:5, s. 644-654
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Journal article (peer-reviewed)abstract
- Introduction: We investigated relations between amyloid-beta (A beta) status, apolipoprotein E (APOE) e4, and cognition, with cerebrospinal fluid markers of neurogranin (Ng), neurofilament light (NFL), YKL-40, and total tau (T-tau). Methods: We included 770 individuals with normal cognition, mild cognitive impairment, and Alzheimer's disease (AD)-type dementia from the EMIF-AD Multimodal Biomarker Discovery study. We tested the association of Ng, NFL, YKL-40, and T-tau with A beta status (Ab beta- vs. A beta+), clinical diagnosis APOE epsilon 4 carriership, baseline cognition, and change in cognition. Results: Ng and T-tau distinguished between A beta+ from A beta- individuals in each clinical group, whereas NFL and YKL-40 were associated with A beta+ in nondemented individuals only. APOE epsilon 4 carriership did not influence NFL, Ng, and YKL-40 in A beta+ individuals. NFL was the best predictor of cognitive decline in A beta+ individuals across the cognitive spectrum. Discussion: Axonal degeneration, synaptic dysfunction, astroglial activation, and altered tau metabolism are involved already in preclinical AD. NFL may be a useful prognostic marker. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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| 10. |
- Boulo, S., et al.
(author)
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First amyloid β1-42 certified reference material for re-calibrating commercial immunoassays
- 2020
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In: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:11, s. 1493-1503
-
Journal article (peer-reviewed)abstract
- Introduction: Reference materials based on human cerebrospinal fluid were certified for the mass concentration of amyloid beta (Aβ)1-42 (Aβ42). They are intended to be used to calibrate diagnostic assays for Aβ42. Methods: The three certified reference materials (CRMs), ERM-DA480/IFCC, ERM-DA481/IFCC and ERM-DA482/IFCC, were prepared at three concentration levels and characterized using isotope dilution mass spectrometry methods. Roche, EUROIMMUN, and Fujirebio used the three CRMs to re-calibrate their immunoassays. Results: The certified Aβ42 mass concentrations in ERM-DA480/IFCC, ERM-DA481/IFCC, and ERM-DA482/IFCC are 0.45, 0.72, and 1.22μg/L, respectively, with expanded uncertainties (k=2) of 0.07, 0.11, and 0.18μg/L, respectively. Before re-calibration, a good correlation (Pearson's r>0.97), yet large biases, were observed between results from different commercial assays. After re-calibration the between-assay bias was reduced to<5%. Discussion: The Aβ42 CRMs can ensure the equivalence of results between methods and across platforms for the measurement of Aβ42. © 2020 the Alzheimer's Association
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| 11. |
- Friedman, James S., et al.
(author)
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Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa
- 2009
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 84:6, s. 792-800
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Journal article (peer-reviewed)abstract
- Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
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| 12. |
- Iwan, Bianca S, et al.
(author)
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TOF-OFF : A method for determining focal positions in tightly focused free-electron laser experiments by measurement of ejected ions
- 2011
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In: High Energy Density Physics. - : Elsevier BV. - 1574-1818. ; 7:4, s. 336-342
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Journal article (peer-reviewed)abstract
- Pulse intensities greater than 1017 Watt/cm2 were reached at the FLASH soft X-ray laser in Hamburg, Germany, using an off-axis parabolic mirror to focus 15 fs pulses of 5–70 μJ energy at 13.5 nm wavelength to a micron-sized spot. We describe the interaction of such pulses with niobium and vanadium targets and their deuterides. The beam produced craters in the solid targets, and we measured the kinetic energy of ions ejected from these craters. Ions with several keV kinetic energy were observed from craters approaching 5 μm in depth when the sample was at best focus. We also observed the onset of saturation in both ion acceleration and ablation with pulse intensities exceeding 1016 W/cm2, when the highest detected ion energies and the crater depths tend to saturate with increasing intensity. A general difficulty in working with micron and sub-micron focusing optics is finding the exact focus of the beam inside a vacuum chamber. Here we propose a direct method to measure the focal position to a resolution better than the Rayleigh length. The method is based on the correlation between the energies of ejected ions and the physical dimensions of the craters. We find that the focus position can be quickly determined from the ion time-of-flight (TOF) data as the target is scanned through the expected focal region. The method does not require external access to the sample or venting the vacuum chamber. Profile fitting employed to analyze the TOF data can extend resolution beyond the actual scanning step size.
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| 13. |
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| 14. |
- Nelson, A. J., et al.
(author)
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Soft x-ray free electron laser microfocus for exploring matter under extreme conditions
- 2009
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In: Optics Express. - 1094-4087. ; 17:20, s. 18271-18278
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Journal article (peer-reviewed)abstract
- We have focused a beam (BL3) of FLASH (Free-electron LASer in Hamburg: lambda = 13.5 nm, pulse length 15 fs, pulse energy 10-40 mu J, 5Hz) using a fine polished off-axis parabola having a focal length of 270 mm and coated with a Mo/Si multilayer with an initial reflectivity of 67% at 13.5 nm. The OAP was mounted and aligned with a picomotor controlled six-axis gimbal. Beam imprints on poly(methyl methacrylate) -PMMA were used to measure focus and the focused beam was used to create isochoric heating of various slab targets. Results show the focal spot has a diameter of <= 1 mu m. Observations were correlated with simulations of best focus to provide further relevant information.
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| 15. |
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| 16. |
- Andreasson, Jakob, et al.
(author)
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Saturated ablation in metal hydrides and acceleration of protons and deuterons to keV energies with a soft-x-ray laser
- 2011
-
In: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - 1539-3755 .- 1550-2376. ; 83:1, s. 016403-
-
Journal article (peer-reviewed)abstract
- Studies of materials under extreme conditions have relevance to a broad area of research, including planetary physics, fusion research, materials science, and structural biology with x-ray lasers. We study such extreme conditions and experimentally probe the interaction between ultrashort soft x-ray pulses and solid targets (metals and their deuterides) at the FLASH free-electron laser where power densities exceeding 1017 W/cm2 were reached. Time-of-flight ion spectrometry and crater analysis were used to characterize the interaction. The results show the onset of saturation in the ablation process at power densities above 1016 W/cm2. This effect can be linked to a transiently induced x-ray transparency in the solid by the femtosecond x-ray pulse at high power densities. The measured kinetic energies of protons and deuterons ejected from the surface reach several keV and concur with predictions from plasma-expansion models. Simulations of the interactions were performed with a nonlocal thermodynamic equilibrium code with radiation transfer. These calculations return critical depths similar to the observed crater depths and capture the transient surface transparency at higher power densities.
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| 17. |
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| 18. |
- Barty, A., et al.
(author)
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Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
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In: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
-
Journal article (peer-reviewed)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
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| 19. |
- Dicke, B., et al.
(author)
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Transferring the entatic-state principle to copper photochemistry
- 2018
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In: Nature Chemistry. - : NATURE PUBLISHING GROUP. - 1755-4330 .- 1755-4349. ; 10:3, s. 355-362
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Journal article (peer-reviewed)abstract
- The entatic state denotes a distorted coordination geometry of a complex from its typical arrangement that generates an improvement to its function. The entatic-state principle has been observed to apply to copper electron-transfer proteins and it results in a lowering of the reorganization energy of the electron-transfer process. It is thus crucial for a multitude of biochemical processes, but its importance to photoactive complexes is unexplored. Here we study a copper complex-with a specifically designed constraining ligand geometry-that exhibits metal-to-ligand charge-transfer state lifetimes that are very short. The guanidine-quinoline ligand used here acts on the bis(chelated) copper(I) centre, allowing only small structural changes after photoexcitation that result in very fast structural dynamics. The data were collected using a multimethod approach that featured time-resolved ultraviolet-visible, infrared and X-ray absorption and optical emission spectroscopy. Through supporting density functional calculations, we deliver a detailed picture of the structural dynamics in the picosecond-to-nanosecond time range.
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| 20. |
- Dicke, B., et al.
(author)
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Transferring the entatic-state principle to copper photochemistry
- 2018
-
In: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4349 .- 1755-4330. ; 10:3, s. 355-362
-
Journal article (peer-reviewed)abstract
- The entatic state denotes a distorted coordination geometry of a complex from its typical arrangement that generates an improvement to its function. The entatic-state principle has been observed to apply to copper electron-transfer proteins and it results in a lowering of the reorganization energy of the electron-transfer process. It is thus crucial for a multitude of biochemical processes, but its importance to photoactive complexes is unexplored. Here we study a copper complex-with a specifically designed constraining ligand geometry-that exhibits metal-to-ligand charge-transfer state lifetimes that are very short. The guanidine-quinoline ligand used here acts on the bis(chelated) copper(I) centre, allowing only small structural changes after photoexcitation that result in very fast structural dynamics. The data were collected using a multimethod approach that featured time-resolved ultraviolet-visible, infrared and X-ray absorption and optical emission spectroscopy. Through supporting density functional calculations, we deliver a detailed picture of the structural dynamics in the picosecond-to-nanosecond time range.
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| 21. |
- Karthik, K. R. G., et al.
(author)
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Physical and Electrical Properties of Single Zn2SnO4 Nanowires
- 2011
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In: Electrochemical and solid-state letters. - Pennington, NJ : Electrochemical Society. - 1099-0062 .- 1944-8775. ; 14:1, s. K5-K7
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Journal article (peer-reviewed)abstract
- Electrical characterizations of single Zn2SnO4 (ZTO) nanowire devices are presented. These include resistivity, mobility, and photosensing measurements. The resistivity and the mobility of the Zn2SnO4 nanowire were measured to be 5.6 cm and 0.2 cm2/Vs, respectively. These values were found to be strongly dependent on the amount of electron-donating defects and less dependent on the thickness of the nanowires. An increase in the resistivity when changing the ambient atmosphere is observed. This change is caused by defect states lying in the bandgap, as shown by photoluminescence. The results imply the potential of ZTO nanowires as phototransistors and other photosensitive devices. © 2010 The Electrochemical Society.
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| 22. |
- Mattsson, Niklas, 1979, et al.
(author)
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CSF biomarker variability in the Alzheimer's Association quality control program
- 2013
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In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 9:3, s. 251-261
-
Journal article (peer-reviewed)abstract
- Background The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Mölndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
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| 23. |
- Petkevicius, K., et al.
(author)
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TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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| 24. |
- Vaga, S., et al.
(author)
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Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
-
Journal article (peer-reviewed)abstract
- Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
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| 25. |
- Wohlfarth, C., et al.
(author)
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miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome
- 2017
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
-
Journal article (peer-reviewed)abstract
- Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3'UTR binding sites. The novel isoform HTR4b_2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.
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| 26. |
- Abadei, S., et al.
(author)
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DC field dependent properties of Na0.5 K0.5 NbO3/SiO2/Si structures at millimeter-wave frequencies
- 2001
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 78:13, s. 1900-1902
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Journal article (peer-reviewed)abstract
- Dielectric properties of laser-ablated 0.5-μm-thick c-axis epitaxial Na0.5K0.5NbO3 films on high-resistivity (7.7 Ω cm) silicon SiO2/Si substrate are studied experimentally at frequencies up to 40 GHz. For measurements, planar 0.5-μm-thick gold electrodes (interdigital and straight slot) are photolithography defined on the top surface of Na0.5K0.5NbO3 films. The slot width between the electrodes is 2 or 4 μm. 13% capacitance change at 40 V dc bias and Q factor more than 15 are observed at 40 GHz, which makes the structure useful for applications in electrically tunable millimeter-wave devices
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| 27. |
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| 28. |
- Andreasson, Joakim, 1973, et al.
(author)
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A molecule-based 1 : 2 digital demultiplexer
- 2007
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In: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 111:38, s. 14274-14278
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Journal article (peer-reviewed)abstract
- A trichromophoric molecule consisting of a porphyrin linked to both a dihydropyrene and a dihydroindolizine-type photochrome, in combination with a third harmonic generating crystal, functions as a 1:2 digital demultiplexer with photonic inputs and outputs. Each of the two photochromes may be cycled independently between two metastable forms, leading to four photoisomers, three of which are used in the demultiplexer. These isomers interact photochemically with the porphyrin in order to yield the demultiplexer function. With the address input (1064-nm light) turned off, one Output of the device (porphyrin fluorescence) tracks the state of the data input (532-nm light). When the address input is turned on, the second output (absorbance at 572 nm) tracks the state of the data input, while the first output remains off. The demultiplexer does not require chemical or electrical inputs, and can cycle through its operational sequences multiple times.
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| 29. |
- Andreasson, Joakim, 1973, et al.
(author)
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Molecular 2 : 1 digital multiplexer
- 2007
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In: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 46:6, s. 958-961
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Journal article (peer-reviewed)abstract
- (Chemical Equation Presented) Two into one: A porphyrin linked to two photochromic moieties performs as a 2:1 digital multiplexer (MUX). It takes heat and red light as the two inputs (in 1 and in 2), and a third switchable input (green light, sel) selects whether the output (porphyrin fluorescence) reports the state of in 1 or in 2. Each photochromic moiety may be independently photoisomerized to isomers that quench the porphyrin fluorescence. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
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| 30. |
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| 31. |
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| 32. |
- Andreasson, Ulf, 1968, et al.
(author)
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Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- 2023
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1245-1254
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Journal article (peer-reviewed)abstract
- Objectives Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.Methods Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.Results The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's rho >= 0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.Conclusions The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
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| 33. |
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| 34. |
- Appelgren, Patrik, et al.
(author)
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Modelling of a small helical magnetic flux compression generator
- 2007
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In: PPPS-2007 - Pulsed Power Plasma Science 2007. - 1424409144 - 9781424409143 ; , s. 1155-1158
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Conference paper (peer-reviewed)abstract
- Helical flux-compression generators convert the chemical energy bond in explosives into electric energy. This paper briefly presents a model of, implemented in Matlab-Simulink, and simulation results for such a device. The simulation results are compared to experimental data from two experiments with identical generators but with different seed currents, influencing the resistive losses and thus the current amplification. The model is used to analyse the performance of the generator.
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| 36. |
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| 37. |
- Bauer, S, et al.
(author)
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Phenotype in a Swedish family with X-linked retinitis pigmentosa caused by a novel splice defect in the RPGR gene
- 1998
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In: Investigative Ophthalmology & Visual Science. - 1552-5783. ; 39:12, s. 2470-2474
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Journal article (peer-reviewed)abstract
- PURPOSE: To assess the clinical phenotype in a Swedish family with X- linked retinitis pigmentosa (XLRP) resulting from a novel splice defect in the RPGR gene. METHODS: RPGR mutation analysis was performed in one family with XLRP, and several individuals from the family were examined clinically. RESULTS: The causative mutation in the family was demonstrated to be a single base-pair change at the splice donor site in intron 7 that resulted in skipping of the complete exon 7 in the mature RPGR transcript. The aberrant mRNA is predicted to produce an RPGR protein with an in-frame deletion of 53 amino acids, corresponding to an RCC1-homology repeat. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this splice mutation resulted in a comparatively less severe form of RP. CONCLUSIONS: Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward predictive diagnosis and should assist in the development of gene-based therapies in the future.
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| 38. |
- Cryan, J P, et al.
(author)
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Molecular frame Auger electron energy spectrum from N2
- 2012
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In: Journal of Physics B. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 45:5, s. 055601-
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Journal article (peer-reviewed)abstract
- Here we present the first angle-resolved, non-resonant (normal) Auger spectra for impulsively aligned nitrogen molecules. We have measured the angular pattern of Auger electron emission following K -shell photoionization by 1.1 keV photons from the Linac Coherent Light Source (LCLS). Using strong-field-induced molecular alignment to make molecular frame measurements is equally effective for both repulsive and quasi-bound final states. The capability to resolve Auger emission angular distributions in the molecular frame of reference provides a new tool for spectral assignments in congested Auger electron spectra that takes advantage of the symmetries of the final diction states. Based on our experimental results and theoretical predictions, we propose the assignment of the spectral features in the Auger electron spectrum.
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| 39. |
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| 40. |
- Eék, Niels, 1980, et al.
(author)
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Efficacy of an Internet-Based Community Reinforcement and Family Training Program to Increase Treatment Engagement for AUD and to Improve Psychiatric Health for CSOs: A Randomized Controlled Trial
- 2020
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In: Alcohol and alcoholism (Oxford, Oxfordshire). - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 55:2, s. 187-195
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Journal article (peer-reviewed)abstract
- AIMS: Community Reinforcement Approach and Family Training (CRAFT) is a support program for concerned significant others (CSOs) to identified persons (IPs) with alcohol use disorders, with the purpose of engaging IPs to treatment and to improve CSO functioning. The purpose of the present study was to investigate the efficacy of an internet-based version of CRAFT (iCRAFT). METHODS: Randomized controlled trial comparing iCRAFT with a wait-list (WL) condition with a nation-wide uptake in Sweden. A total of 94 CSOs to a treatment refusing IP, who described the IP according to DSM-IV criteria for alcohol dependence or abuse, were included in the study. iCRAFT consisted of five weekly administered therapist-guided modules with the following content: (a) improve CSOs' own mental health, (b) improve the CSOs skills in asking the IP to seek treatment, (c) positive communication skills training, (d) contingency management of IP drinking behavior. Main outcome measure was IPs initiative to seek treatment measured at 24weeks. Secondary outcomes were IP's daily alcohol consumption, CSOs mental health, quality of life and relational satisfaction. RESULTS: Of 94 participants, 15 CSOs reported IP treatment initiative during the study period. Of these, 10 belonged to the iCRAFT condition and five to the WL condition. The difference between conditions was nonsignificant, and the results were inconclusive. Participants in iCRAFT showed short-term improvements regarding depressive symptoms, quality of life and relational happiness. CONCLUSION: This study was unable to demonstrate substantial changes in the iCRAFT program regarding IP treatment seeking or CSO mental health. © The Author(s) 2020. Medical Council on Alcohol and Oxford University Press.
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| 41. |
- Engelmann, Petra, et al.
(author)
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Needs of multimorbid heart failure patients and their carers : a qualitative interview study and the creation of personas as a basis for a blended collaborative care intervention
- 2023
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In: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 10
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Journal article (peer-reviewed)abstract
- Introduction: Involving patients and carers in the development of blended collaborative care (BCC) interventions for multimorbid heart failure (HF) patients is recommended but rarely practised, and research on the patient perspective is scarce. The aim of this study is to investigate patients' and carers' care-related needs and preferences to better customize a novel international BCC intervention.Methods: A qualitative study design using framework analysis was employed. The study was performed in accordance with the EQUATOR standards for reporting qualitative research (SRQR). Patients aged at least 65 years with HF and at least two other physical diseases as well as their carers completed semistructured interviews in Germany, Italy, and Denmark. Based on these interviews, personas (prototype profiles of patients and carers) were created.Results: Data from interviews with 25 patients and 17 carers were analysed. Initially, seven country-specific personas were identified, which were iteratively narrowed down to a final set of 3 personas: (a) the one who needs and wants support, (b) the one who has accepted their situation with HF and reaches out when necessary, and (c) the one who feels neglected by the health care system. Carers identifying with the last persona showed high levels of psychological stress and a high need for support.Discussion: This is the first international qualitative study on patients' and carers' needs regarding a BCC intervention using the creation of personas. Across three European countries, data from interviews were used to develop three contrasting personas. Instead of providing "one size fits all" interventions, the results indicate that BCC interventions should offer different approaches based on the needs of individual patients and carers. The personas will serve as a basis for the development of a novel BCC intervention as part of the EU project ESCAPE (Evaluation of a patient-centred biopSychosocial blended collaborative CAre Pathway for the treatment of multimorbid Elderly patients).
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| 42. |
- Friedman, James S., et al.
(author)
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Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration
- 2006
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In: American Journal of Human Genetics. - 0002-9297. ; 79:6, s. 1059-1070
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Journal article (peer-reviewed)abstract
- The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing.
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| 43. |
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- He, J., et al.
(author)
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Switching of a photochromic molecule on gold electrodes: single-molecule measurements
- 2005
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In: Nanotechnology. - : IOP Publishing. - 1361-6528 .- 0957-4484. ; 16:6, s. 695-702
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Journal article (peer-reviewed)abstract
- We have studied the electronic changes caused by light-induced isomerization of a photochromic molecule between an open state (that absorbs in the UV to become closed) and a closed state (that absorbs in the visible to become open). Data obtained using a newly developed repetitive break junction method are interpreted in terms of single-molecule resistances of 526 +/- 90 M Omega in the open form and 4 +/- 1 M Omega in the closed form when the molecule is bound between two gold contacts via dithiol linkages. The corresponding ratio of open to closed resistance is in close agreement with the results of ab initio calculations, though the measured resistances are about half of the calculated values. Optical spectroscopy indicates that the photoisomerization occurs in both directions on small gold particles, evaporated thin gold films, and in the break junction experiments.
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| 48. |
- Hort, O., et al.
(author)
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High-flux source of coherent XUV pulses for user applications
- 2019
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In: Optics Express. - 1094-4087 .- 1094-4087. ; 27:6, s. 8871-8883
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Journal article (peer-reviewed)abstract
- We present experimental results obtained at a user-oriented XUV beamline implemented at the ELI Beamlines facility. The coherent XUV radiation is produced via high harmonic generation in gases in a loose focusing geometry. The heamline is designed to be driven by 1 kHz, 100 mJ, 20 Is pulses centered at a wavelength of 830 nm. Results such as XUV spectra, beam wavefront and pulse energy obtained during the heamline commissioning with a commercial 1 kHz, 5 mJ, 40 fs laser system are presented. A unique XUV spectrometer for source characterization designed to reach a very high sensitivity is described in detail, and we demonstrate a novel technique for single shot and every shot. XUV pulse energy measurement. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.
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| 49. |
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| 50. |
- Karlsson, D., et al.
(author)
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Inhibition of SGLT2 Preserves Function and Promotes Proliferation of Human Islets Cells In Vivo in Diabetic Mice
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:2
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Journal article (peer-reviewed)abstract
- Dapagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor used for the treatment of diabetes. This study examines the effects of dapagliflozin on human islets, focusing on alpha and beta cell composition in relation to function in vivo, following treatment of xeno-transplanted diabetic mice. Mouse beta cells were ablated by alloxan, and dapagliflozin was provided in the drinking water while controls received tap water. Body weight, food and water intake, plasma glucose, and human C-peptide levels were monitored, and intravenous arginine/glucose tolerance tests (IVarg GTT) were performed to evaluate islet function. The grafted human islets were isolated at termination and stained for insulin, glucagon, Ki67, caspase 3, and PDX-1 immunoreactivity in dual and triple combinations. In addition, human islets were treated in vitro with dapagliflozin at different glucose concentrations, followed by insulin and glucagon secretion measurements. SGLT2 inhibition increased the animal survival rate and reduced plasma glucose, accompanied by sustained human C-peptide levels and improved islet response to glucose/arginine. SGLT2 inhibition increased both alpha and beta cell proliferation (Ki67+glucagon+ and Ki67+insulin+) while apoptosis was reduced (caspase3+glucagon+ and caspase3+insulin+). Alpha cells were fewer following inhibition of SGLT2 with increased glucagon/PDX-1 double-positive cells, a marker of alpha to beta cell transdifferentiation. In vitro treatment of human islets with dapagliflozin had no apparent impact on islet function. In summary, SGLT2 inhibition supported human islet function in vivo in the hyperglycemic milieu and potentially promoted alpha to beta cell transdifferentiation, most likely through an indirect mechanism. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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