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| 4. |
- Kesteloot, N., et al.
(author)
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Deformation and mixing of coexisting shapes in neutron-deficient polonium isotopes
- 2015
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:5
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Journal article (peer-reviewed)abstract
- Coulomb-excitation experiments are performed with postaccelerated beams of neutron-deficient Po-196,Po-198,Po-200,Po-202 isotopes at the REX-ISOLDE facility. A set of matrix elements, coupling the low-lying states in these isotopes, is extracted. In the two heaviest isotopes, Po-196,Po-198, the transitional and diagonal matrix elements of the 2(1)(+) state are determined. In Po-196,Po-198 multistep Coulomb excitation is observed, populating the 4(1)(+), 0(2)(+), and 2(2)(+) states. The experimental results are compared to the results from the measurement of mean-square charge radii in polonium isotopes, confirming the onset of deformation from Po-196 onwards. Three model descriptions are used to compare to the data. Calculations with the beyond-mean-field model, the interacting boson model, and the general Bohr Hamiltonian model show partial agreement with the experimental data. Finally, calculations with a phenomenological two-level mixing model hint at the mixing of a spherical structure with a weakly deformed rotational structure.
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| 5. |
- Wallin, Anders, 1950, et al.
(author)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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In: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Journal article (peer-reviewed)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 6. |
- Al-Khalili, L, et al.
(author)
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MEF2 activation in differentiated primary human skeletal muscle cultures requires coordinated involvement of parallel pathways
- 2004
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In: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 286:6, s. C1410-C1416
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Journal article (peer-reviewed)abstract
- The myocyte enhancer factor (MEF)2 transcription factor is important for development of differentiated skeletal muscle. We investigated the regulation of MEF2 DNA binding in differentiated primary human skeletal muscle cells and isolated rat skeletal muscle after exposure to various stimuli. MEF2 DNA binding activity in nonstimulated (basal) muscle cultures was almost undetectable. Exposure of cells for 20 min to 120 nM insulin, 0.1 and 1.0 mM hydrogen peroxide, osmotic stress (400 mM mannitol), or 1.0 mM 5-aminoimidazole-4-carboxamide-1-β- d-ribofuranoside (AICAR) led to a profound increase in MEF2 DNA binding. To study signaling pathways mediating MEF2 activity, we preincubated human skeletal muscle cell cultures or isolated rat epitrochlearis muscles with inhibitors of p38 mitogen-activated protein kinase (MAPK) (10 μM SB-203580), MEK1 (50 μM PD-98059), PKC (1 and 10 μM GF109203X), phosphatidylinositol (PI) 3-kinase (10 μM LY-294002), or AMP-activated protein kinase (AMPK; 20 μM compound C). All stimuli resulted primarily in activation of MEF2D DNA binding. Exposure of cells to osmotic or oxidative stress increased MEF2 DNA binding via pathways that were completely blocked by MAPK inhibitors and partially blocked by inhibitors of PKC, PI 3-kinase, and AMPK. In epitrochlearis muscle, MAPK inhibitors blocked contraction but not AICAR-mediated MEF2 DNA binding. Thus activation of MEF2 in skeletal muscle is regulated via parallel intracellular signaling pathways in response to insulin, cellular stress, or activation of AMPK.
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| 7. |
- Andreasen, N, et al.
(author)
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Prevalence and incidence of clinically diagnosed memory impairments in a geographically defined general population in Sweden. The Piteå Dementia Project
- 1999
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In: Neuroepidemiology. - : S. Karger AG. - 0251-5350 .- 1423-0208. ; 18:3, s. 144-155
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Journal article (peer-reviewed)abstract
- In the Piteå River Valley all persons with memory impairment that interferes with normal life are referred to one hospital department for clinical workup and diagnosis. 619 patients were assessed in the department during the years 1990–1995. Of these, 36.9% had Alzheimer’s disease (AD), 30.4% had vascular dementia (VaD), 3.0% had a mixed AD/VaD, 3.2% had frontotemporal dementia and 5.3% had other forms of dementia. Another 7% had memory impairment but no dementia. The overall mean annual incidence rate of clinically relevant dementia was 295/100,000 persons at risk and the mean prevalence rate was 755/100,000 persons. For persons 65 years and older the incidence and prevalence rates were 840 and 2,150/100,000 persons, respectively. This means that annually, approximately 300 persons/100,000 population over the age of 40 need medical attention or social services.
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| 9. |
- Araujo, Rafael B., et al.
(author)
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Assessing the electrochemical properties of polypyridine and polythiophene for prospective applications in sustainable organic batteries
- 2017
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 19:4, s. 3307-3314
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Journal article (peer-reviewed)abstract
- Conducting polymers are being considered promising candidates for sustainable organic batteries mainly due to their fast electron transport properties and high recyclability. In this work, the key properties of polythiophene and polypyridine have been assessed through a combined theoretical and experimental study focusing on such applications. A theoretical protocol has been developed to calculate redox potentials in solution within the framework of the density functional theory and using continuous solvation models. Here, the evolution of the electrochemical properties of solvated oligomers as a function of the length of the chain is analyzed and then the polymer properties are estimated via linear regressions using ordinary least square. The predicted values were verified against our electrochemical experiments. This protocol can now be employed to screen a large database of compounds in order to identify organic electrodes with superior properties.
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| 10. |
- Araujo, Rafael B., et al.
(author)
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Designing strategies to tune reduction potential of organic molecules for sustainable high capacity battery application
- 2017
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In: Journal of Materials Chemistry A. - : Royal Society of Chemistry. - 2050-7488 .- 2050-7496. ; 5:9, s. 4430-4454
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Journal article (peer-reviewed)abstract
- Organic compounds evolve as a promising alternative to currently used inorganic materials in rechargeable batteries due to their low-cost, environmental friendliness and flexibility. One of the strategies to reach acceptable energy densities and to deal with the high solubility of known organic compounds is to combine small redox active molecules, acting as capacity carrying centres, with conducting polymers. Following this strategy, it is important to achieve redox matching between the chosen molecule and the polymer backbone. Here, a synergetic approach combining theory and experiment has been employed to investigate this strategy. The framework of the density functional theory connected with the reaction field method has been applied to predict the formal potential of 137 molecules and identify promising candidates for the referent application. The effects of including different ring types, e.g. fused rings or bonded rings, heteroatoms, and pi bonds, as well as carboxyl groups on the formal potential, have been rationalized. Finally, we have identified a number of molecules with acceptable theoretical capacities that show redox matching with thiophene-based conducting polymers which, hence, are suggested as pendent groups for the development of conducting redox polymer based electrode materials.
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| 11. |
- Arulkumaran, S., et al.
(author)
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Enhancement of both direct-current and microwave characteristics of AlGaN/GaN high-electron-mobility transistors by furnace annealing
- 2006
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In: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 88:2
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Journal article (peer-reviewed)abstract
- The enhancement of both direct-current (dc) and microwave characteristics of AlGaN/GaN high-electron-mobility transistors (HEMTs) were demonstrated by conventional furnace annealing at 400 degrees C for 5 min. Due to the improvement in Ni/Au Schottky contact properties by furnace annealing, about 17%, 34%, 23%, and 25% of enhancements in maximum drain current density, maximum extrinsic transconductance (g(m max)), cutoff frequency and maximum oscillation frequency were observed, respectively. A positive threshold voltage shift and the increase in g(m max) can also be correlated to the improved Schottky parameters such as ideality factor and barrier height. The annealed devices exhibited low reverse gate-leakage-current by more than three orders of magnitude and low drain-leakage-current by two orders of magnitude. Correspondingly, the devices exhibited 55% of higher breakdown voltage after annealing. The furnace annealing is an effective and viable means to enhance both dc and microwave characteristics of AlGaN/GaN HEMTs.
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| 13. |
- Deisenhammer, F, et al.
(author)
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Prediction of natalizumab anti-drug antibodies persistency
- 2019
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In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 25:3, s. 392-398
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Journal article (peer-reviewed)abstract
- Anti-drug antibodies (ADA) against natalizumab develop early during treatment. ADA persistency is defined by two consecutive positive results as performed by the current qualitative ELISA assay (positive/negative). Very little is known about the magnitude of the natalizumab ADA response and persistency. Design/methods: We developed a highly sensitive natalizumab ADA titration assay on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We included 43 patients with a positive ELISA-ADA result within 6 months of treatment initiation (baseline) of whom a follow-up serum sample was available 12–30 months after treatment start. MSD-ADA titres and drug levels were measured. Results: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA persistency. Reversion to ADA negativity occurred in 10 patients with mean drug levels of 10.8 μg/mL. The median trough drug level in ADA-positive samples was 0 µg/mL. PK levels and ADA titres correlated strongly negatively ( r = −0.67). Conclusion: High baseline natalizumab ADA titres accurately predict persistency. Despite continuous treatment, the majority of patients with persistent ADA had no detectable drug levels indicating loss of efficacy in line with phase 3 study results.
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| 16. |
- Healy, C, et al.
(author)
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Supporting timing analysis by automatic bounding of loop iterations
- 2000
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In: REAL-TIME SYSTEMS. - : KLUWER ACADEMIC PUBL. - 0922-6443. ; 18:2-3, s. 129-156
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Journal article (peer-reviewed)abstract
- Static timing analyzers, which are used to analyze real-time systems, need to know the minimum and maximum number of iterations associated with each loop in a real-time program so accurate timing predictions can be obtained. This paper describes three com
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| 17. |
- Karadenizli, A., et al.
(author)
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Genomic analyses of Francisella tularensis strains confirm disease transmission from drinking water sources, Turkey, 2008, 2009 and 2012
- 2015
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In: Eurosurveillance. - 1025-496X .- 1560-7917. ; 20:21
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Journal article (peer-reviewed)abstract
- Waterborne epidemics of tularaemia caused by Francisella tularensis are increasingly reported in Turkey. We have used whole genome sequencing to investigate if F. tularensis isolated from patients could be traced back to drinking water sources. Tonsil swabs from 33 patients diagnosed with oropharyngeal tularaemia in three outbreaks and 140 water specimens were analysed. F. tularensis subsp. holarctica was confirmed by microagglutination and PCR in 12 patients and five water specimens. Genomic analysis of three pairs of patient and water isolates from outbreaks in Sivas, Corum, and Kocaeli showed the isolates to belong to two new clusters of the F. tularensis B. 12 genetic clade. The clusters were defined by 19 and 15 single nucleotide polymorphisms (SNPs) in a multiple alignment based on 507 F. tularensis genomes. One synonymous SNP was chosen as a new canonical SNP (canSNP) for each cluster for future use in diagnostic assays. No SNP was identified between the genomes from the patient-water pair of isolates from Kocaeli, one SNP between the pair of isolates from Sivas, whereas the pair from Corum differed at seven SNPs. These results illustrate the power of whole genome sequencing for tracing F. tularensis patient isolates back to their environmental source.
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| 18. |
- Malm, C, et al.
(author)
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Effects of eccentric exercise on the immune system in men
- 1999
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In: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 86:2, s. 461-468
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Journal article (peer-reviewed)abstract
- The effects of eccentric exercise on changes in numbers of circulating leukocytes, cell activation, cell adhesion, and cellular memory function were investigated in 12 men, aged 22–35 yr. The immunologic effects of postexercise epidermal treatment with monochromatic, infrared light were also evaluated. Blood was drawn before and 6, 24, and 48 h after exercise for phenotyping and analysis of creatine kinase activity. There was an increase in leukocyte, monocyte, and neutrophil number, no change in the number of basophils, eosinophils, B cells, and T cells, and a decrease in natural killer cell number postexercise. Some markers of lymphocyte and monocyte activation remained unchanged or decreased, whereas the expression of adhesion molecules 62L and 11b increased on monocytes. It is concluded that eccentric exercise induced decreased activation, and increased cell adhesion capacity, of monocytes. Altered trafficking of cells between lymphoid tissue and blood, selective apoptosis, or attachment/detachment from the endothelial wall can explain the observed phenotypic changes. Treatment with monochromatic, infrared light did not significantly affect any of the investigated variables. Correlations between immunologic and physiological parameters indicate a role of the immune system in adaptation to physical exercise.
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| 31. |
- Sjodin, M., et al.
(author)
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Proton-coupled electron transfer from tyrosine in a tyrosine-ruthenium-tris-bipyridine complex : Comparison with Tyrosine(z) oxidation in photosystem II
- 2000
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 122:16, s. 3932-3936
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Journal article (peer-reviewed)abstract
- The pH- and the temperature dependence of the rate constant for electron transfer from tyrosine to ruthenium in Ru(II)(bpy)(2)(4-Me-4'CONH-L-tyrosine etyl ester-2,2'-bpy) 2PF(6) was investigated using flash photolysis. At a pH below the tyrosine pK(a) approximate to 10 the rate constant increased monotonically with pH. This increase was consistent with a concerted electron transfer/deprotonation mechanism. Also indicative of a concerted reaction was the unusually high reorganization energy, 2 eV, extracted from temperature-dependent measurements. Deprotonation of the tyrosine group, at pH > pK(a), resulted in a 100-fold increase in rate constant due to a decreased reorganization energy, lambda = 0.9 eV. Also, the rate constant became independent of pH, In Mn-depleted photosystem II a similar pH dependence has been found for electron transfer from tyrosine(Z) (Tyr(Z)) to the oxidized primary donor P680(+). On the basis of the kinetic similarities we propose that the mechanisms in the two systems are the same, that is, the electron transfer occurs as a concerted proton-coupled electron-transfer reaction, and at pH < 7 the Tyr(Z) proton is released directly to the bulk water.
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| 32. |
- Sjodin, M., et al.
(author)
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The mechanism for proton-coupled electron transfer from tyrosine in a model complex and comparisons with Y-z oxidation in photosystem II
- 2002
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In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 357:1426, s. 1471-1478
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Journal article (peer-reviewed)abstract
- In the water-oxidizing reactions of photosystem II (PSII), a tyrosine residue plays a key part as an intermediate electron-transfer reactant between the primary donor chlorophylls (the pigment P-680) and the water-oxidizing Mn cluster. The tyrosine is deprotonated upon oxidation, and the coupling between the proton reaction and electron transfer is of great mechanistic importance for the understanding of the water-oxidation mechanism. Within a programme on artificial photosynthesis, we have made and studied the proton-coupled tyrosine oxidation in a model system and been able to draw mechanistic conclusions that we use to interpret the analogous reactions in PSII.
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| 33. |
- Sjodin, M., et al.
(author)
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Tuning proton coupled electron transfer from tyrosine : A competition between concerted and step-wise mechanisms
- 2004
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 6:20, s. 4851-4858
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Journal article (peer-reviewed)abstract
- The intra-molecular, proton-coupled electron transfer from a tyrosine residue to covalently linked tris-bipyridine ruthenium(III) complexes in aqueous solution (Ru-III-TyrOH --> Ru-II-TyrO(.) + H+) is studied in two complexes. The Ru-III-TyrOH state is generated by laser flash-induced photo-oxidation in the presence of the electron acceptor methyl viologen. The reaction is shown to follow either a concerted electron transfer-deprotonation (CEP) mechanism or a step-wise mechanism with electron transfer followed by deprotonation (ETPT). The CEP is characterised by a pH-dependent rate constant, a large reorganisation energy (lambda = 1.4 eV at pH = 7) and a significant kinetic isotope effect: k(H)/k(D) = 1.5-3. We can explain the pH-dependence and the high lambda by the pH-dependent DeltaGdegrees' for proton release to bulk water, and by the additional reorganisation energy associated with the proton transfer coordinate (both internal and solvent), respectively. In the calculation of lambda from the temperature dependent rate constant, correction is made for the large entropy increase of the reaction (TDeltaS(rxn) approximate to0.41 eV at pH = 7 and T = 298 K). The step-wise ETPT mechanism on the other hand shows a pH-independent rate, a lower reorganisation energy and no kinetic isotope effect. We propose that our complexes can be used as models to understand proton-coupled electron transfer in radical proteins. We show that the mechanism can be switched between CEP and ETPT by tuning the reaction pH and the electrochemical potential of the Ru-III/II oxidant. With a low driving force for the overall reaction the energy conservative CEP mechanism may dominate, in spite of the higher reorganisation energy as compared to ETPT.
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| 34. |
- Toft, A., et al.
(author)
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Endo-lysosomal protein concentrations in CSF from patients with frontotemporal dementia caused by CHMP2B mutation
- 2023
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In: Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring. - : Wiley. - 2352-8729. ; 15:1
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Journal article (peer-reviewed)abstract
- IntroductionIncreasing evidence implicates proteostatic dysfunction as an early event in the development of frontotemporal dementia (FTD). This study aimed to explore potential cerebrospinal fluid (CSF) biomarkers associated with the proteolytic systems in genetic FTD caused by CHMP2B mutation. MethodsCombining solid-phase extraction and parallel reaction monitoring mass spectrometry, a panel of 47 peptides derived from 20 proteins was analyzed in CSF from 31 members of the Danish CHMP2B-FTD family. ResultsCompared with family controls, mutation carriers had significantly higher levels of complement C9, lysozyme and transcobalamin II, and lower levels of ubiquitin, cathepsin B, and amyloid precursor protein. DiscussionLower CSF ubiquitin concentrations in CHMP2B mutation carriers indicate that ubiquitin levels relate to the specific disease pathology, rather than all-cause neurodegeneration. Increased lysozyme and complement proteins may indicate innate immune activation. Altered levels of amyloid precursor protein and cathepsins have previously been associated with impaired lysosomal proteolysis in FTD. HighlightsCSF markers of proteostasis were explored in CHMP2B-mediated frontotemporal dementia (FTD).31 members of the Danish CHMP2B-FTD family were included.We used solid-phase extraction and parallel reaction monitoring mass spectrometry.Six protein levels were significantly altered in CHMP2B-FTD compared with controls.Lower CSF ubiquitin levels in patients suggest association with disease mechanisms.
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| 36. |
- Zhou, L. Y., et al.
(author)
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A transition of atmospheric emissions of particles and gases from on-road heavy-duty trucks
- 2020
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:3, s. 1701-1722
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Journal article (peer-reviewed)abstract
- The transition, in extent and characteristics, of atmospheric emissions caused by the modernization of the heavy-duty on-road fleet was studied utilizing roadside measurements. Emissions of particle number (PN), particle mass (PM), black carbon (BC), nitrogen oxides (NOx), carbon monoxide (CO), hydrocarbon (HC), particle size distributions, and particle volatility were measured from 556 individual heavy-duty trucks (HDTs). Substantial reductions in PM, BC, NOx, CO, and to a lesser extent PN were observed from Euro III to Euro VI HDTs by 99 %, 98 %, 93 %, and 57% for the average emission factors of PM, BC, NOx, and CO, respectively. Despite significant total reductions in NOx emissions, the fraction of NO2 in the NOx emissions increased continuously from Euro IV to Euro VI HDTs. Larger data scattering was evident for PN emissions in comparison to solid particle number (SPN) for Euro VI HDTs, indicating a highly variable fraction of volatile particle components. Particle size distributions of Euro III to enhanced environmentally friendly vehicle (EEV) HDTs were bimodal, whereas those of Euro VI HDTs were nucleation mode dominated. High emitters disproportionately contributed to a large fraction of the total emissions with the highest-emitting 10% of HDTs in each pollutant category being responsible for 65% of total PM, 70% of total PN, and 44% of total NOx emissions. Euro VI HDTs, which accounted for 53% of total kilometres driven by Swedish HDTs, were estimated to only contribute to 2 %, 6 %, 12 %, and 47% of PM, BC, NOx, and PN emissions, respectively. A shift to a fleet dominated by Euro VI HDTs would promote a transition of atmospheric emissions towards low PM, BC, NOx, and CO levels. Nonetheless, reducing PN, SPN, and NO2 emissions from Euro VI HDTs is still important to improve air quality in urban environments.
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