| 1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Abreu, P., et al.
(författare)
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Measurement of the gluon fragmentation function and a comparison of the scaling violation in gluon and quark jets
- 2000
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 13:4, s. 573-589
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Tidskriftsartikel (refereegranskat)abstract
- The fragmentation functions of quarks and gluons are measured in various three-jet topologies in Z decays from the full data set collected with the DELPHI detector at the Z resonance between 1992 and 995. The results at different values of transverse momentum-like scales are compared. A parameterization of the quark and gluon fragmentation functions at a fixed reference scale is given. The quark and gluon fragmentation functions show the predicted pattern of scaling violations. The scaling violation for quark jets as a function of a transverse momentum-like scale is in a good agreement with that observed in lower energy e+e- annihilation experiments. For gluon jets it appears to be significantly stronger. The scale dependences of the gluon and quark fragmentation functions agree with the prediction of the DGLAP evolution equations from which the colour factor ratio CA/CF is measured to be: CA/CF = 2.26 ± 0.09stat. ± 0.06sys. ± 0.12clus.,scale..
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| 3. |
- Abreu, P., et al.
(författare)
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Study of dimuon production in photon-photon collisions and measurement of QED photon structure functions at LEP
- 2001
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 19:1, s. 15-28
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Tidskriftsartikel (refereegranskat)abstract
- Muon pair production in the process e+e- → e+e- μ+μ- is studied using the data taken at LEP1 (√s ≃ mz) with the DELPHI detector during the years 1992-1995. The corresponding integrated luminosity is 138.5 pb-1. The QED predictions have been tested over the whole Q2 range accessible at LEP1 (from several GeV2/c4 to several hundred GeV2/c4) by comparing experimental distributions with distributions resulting from Monte Carlo simulations using various generators. Selected events are used to extract the leptonic photon structure function Fγ 2. Azimuthal correlations are used to obtain information on additional structure functions, Fγ A and Fγ B, which originate from interference terms of the scattering amplitudes. The measured ratios Fγ A/Fγ 2 and FγB/Fγ 2 are significantly different from zero and consistent with QED predictions.
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| 4. |
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| 5. |
- Malmgren, B., et al.
(författare)
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Guidelines for the management of traumatic dental injuries: 3. Injuries in the primary dentition
- 2018
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Ingår i: Pediatric Dentistry. - 0164-1263. ; 40:6, s. 432-440
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic injuries to the primary dentition present special problems and the management is often different as compared with the permanent dentition. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialities were included in the task group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care for management of primary teeth injuries. The IADT cannot and does not guarantee favorable outcomes from strict adherence to the guidelines, but believe that their application can maximize the chances of a positive outcome. Copyright © 2012, International Association of Dental Traumatology, www.iadt-dentaltrauma.org.
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| 6. |
- Malmgren, B., et al.
(författare)
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International Association of Dental Traumatology guidelines for the management of traumatic dental injuries: 3. Injuries in the primary dentition
- 2012
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Ingår i: Dental Traumatology. - : Wiley. - 1600-4469. ; 28:3, s. 174-182
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Tidskriftsartikel (refereegranskat)abstract
- Traumatic injuries to the primary dentition present special problems and the management is often different as compared with the permanent dentition. The International Association of Dental Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialities were included in the task group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care for management of primary teeth injuries. The IADT cannot and does not guarantee favorable outcomes from strict adherence to the guidelines, but believe that their application can maximize the chances of a positive outcome.
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| 7. |
- Martens, L., et al.
(författare)
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Electromagnetic field calculations used for exposure experiments on small animals in TEM-cells
- 1993
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Ingår i: Bioelectrochemistry and Bioenergetics. - : Elsevier BV. - 0302-4598. ; 30:C, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional electromagnetic calculations for loaded transverse electromagnetic (TEM) transmission cells are presented. Based on those calculations a prediction of the perturbation of the standard uniform field in the TEM-cell, due to the scattering by inhomogeneous structures placed inside the cell cavity, is given. The influence of the dimensions of a lossy structure and its position in the TEM-cell on its absorption of the electromagnetic fields is presented. Knowing the perturbation of the uniform field is important for good interpretation of the biological experimental results.
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| 8. |
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| 9. |
- Belyaev, I Y, et al.
(författare)
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915 MHz microwaves and 50 Hz magnetic field affect chromatin conformation and 53BP1 foci in human lymphocytes from hypersensitive and healthy persons
- 2005
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Ingår i: Bioelectromagnetics. - : Wiley. - 0197-8462 .- 1521-186X. ; 26:3, s. 173-184
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Tidskriftsartikel (refereegranskat)abstract
- We used exposure to microwaves from a global system for mobile communication (GSM) mobile phone (915 MHz, specific absorption rate (SAR) 37 mW/kg) and power frequency magnetic field (50 Hz, 15 mu T peak value) to investigate the response of lymphocytes from healthy subjects and from persons reporting hypersensitivity to electromagnetic field (EMF). The hypersensitive and healthy donors were matched by gender and age and the data were analyzed blind to treatment condition. The changes in chromatin conformation were measured with the method of anomalous viscosity time dependencies (AVTD). 53BP1 protein, which has been shown to colocalize in foci with DNA double strand breaks (DSBs), was analyzed by immunostaining in situ. Exposure at room temperature to either 915 MHz or 50 Hz resulted in significant condensation of chromatin, shown as AVTD changes, which was similar to the effect of heat shock at 41 degrees C. No significant differences in responses between normal and hypersensitive subjects were detected. Neither 915 MHz nor 50 Hz exposure induced 53BP1 foci. On the contrary, a distinct decrease in background level of 53BP1 signaling was observed upon these exposures as well as after heat shock treatments. This decrease correlated with the AVTD data and may indicate decrease in accessibility of 53BP1 to antibodies because of stress-induced chromatin condensation. Apoptosis was determined by morphological changes and by apoptotic fragmentation of DNA as analyzed by pulsed-field gel electrophoresis (PFGE). No apoptosis was induced by exposure to 50 Hz and 915 MHz microwaves. In conclusion, 50 Hz magnetic field and 915 MHz microwaves under specified conditions of exposure induced comparable responses in lymphocytes from healthy and hypersensitive donors that were similar but not identical to stress response induced by heat shock.
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| 10. |
- Benoit, D D, et al.
(författare)
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Outcome in patients perceived as receiving excessive care across different ethical climates: a prospective study in 68 intensive care units in Europe and the USA.
- 2018
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Ingår i: Intensive care medicine. - 1432-1238. ; 44:7, s. 1039-1049
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Tidskriftsartikel (refereegranskat)abstract
- Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown.In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis.Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0-1.00) and 85.9% (75.4-92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20-2.92) or receiving a written TLD (HR 2.32, CI 1.11-4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former.Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.
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| 11. |
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| 12. |
- Brockstedt, Sara, et al.
(författare)
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Vertical field MR imaging of upper thorax and spine in small children. Evaluation of a new surface coil
- 1993
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Ingår i: Acta Radiologica. - 1600-0455. ; 34:6, s. 549-553
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Tidskriftsartikel (refereegranskat)abstract
- To improve image quality in a vertical field MR imaging unit, operating at low field strength (0.3 T), we have designed a half-elliptical coil for use in the upper thoracic region of small children. Our intention was also to shorten the examination time, which until now has been long, because several scans with different coils have been necessary to cover the thoracic region. The experimental coil is designed so that a child's shoulders fit into the central region. The coil consists of 2 serially connected cable-loops, mounted on a foam rubber vest. The coil performance was tested in a phantom and improvements relative to standard coils were demonstrated in in vivo studies. The results indicate that by using the half-elliptical coil, the signal-to-noise (S/N) ratio can be improved by a factor of 2 to 3 in the thoracic region of a child.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Helsmoortel, Celine, et al.
(författare)
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A SWI/SNF-related autism syndrome caused by de novo mutations in ADNP
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:4, s. 380-
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Tidskriftsartikel (refereegranskat)abstract
- Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests or activities(1), a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile- X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in nextgeneration sequencing, for the large majority of cases no molecular diagnosis can be established(2-7). Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/ SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD- associated genes known to date.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Olsson, D., et al.
(författare)
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Commissioning status of the chopper system for the Max IV injector
- 2016
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Ingår i: Proceedings of the 28th Linear Accelerator Conference, LINAC 2016. - 9783954501694 ; , s. 468-471
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Konferensbidrag (refereegranskat)abstract
- The MAX IV facility in Lund, Sweden consists of two storage rings for production of synchrotron radiation, and a short-pulse-facility (SPF). The two rings are designed for 3 GeV and 1.5 GeV, respectively, where the initial beam commissioning of the former has recently been completed, and commissioning of the latter was started in September 2016. Both rings will be operating with top-up injections delivered by a full-energy injector. In order to reduce losses of high-energy electrons along the injector and in the rings during injection, only electrons that are within a time structure where they can be accumulated in the ring buckets are accelerated. Electrons outside this time structure are dumped before they reach the first LINAC structure by a chopper system. The performance of the chopper system during commissioning of the 3 GeV ring is presented in this paper.
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| 23. |
- Robinson-Cohen, C., et al.
(författare)
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Genetic Variants Associated with Circulating Fibroblast Growth Factor 23
- 2018
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 29:10, s. 2583-2592
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Tidskriftsartikel (refereegranskat)abstract
- Background Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences. Methods We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR. Results We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level. Conclusions Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.
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| 24. |
- Ruiz-Solani, N., et al.
(författare)
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Arabidopsis metacaspase MC1 localizes in stress granules, clears protein aggregates, and delays senescence
- 2023
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Ingår i: Plant Cell. - 1040-4651. ; 35:9, s. 3325-3344
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Tidskriftsartikel (refereegranskat)abstract
- The Arabidopsis metacaspase MC1 is recruited to stress granules upon proteotoxic stress, participates in clearance of pathological protein aggregates, and delays senescence. Stress granules (SGs) are highly conserved cytoplasmic condensates that assemble in response to stress and contribute to maintaining protein homeostasis. These membraneless organelles are dynamic, disassembling once the stress is no longer present. Persistence of SGs due to mutations or chronic stress has been often related to age-dependent protein-misfolding diseases in animals. Here, we find that the metacaspase MC1 is dynamically recruited into SGs upon proteotoxic stress in Arabidopsis (Arabidopsis thaliana). Two predicted disordered regions, the prodomain and the 360 loop, mediate MC1 recruitment to and release from SGs. Importantly, we show that MC1 has the capacity to clear toxic protein aggregates in vivo and in vitro, acting as a disaggregase. Finally, we demonstrate that overexpressing MC1 delays senescence and this phenotype is dependent on the presence of the 360 loop and an intact catalytic domain. Together, our data indicate that MC1 regulates senescence through its recruitment into SGs and this function could potentially be linked to its remarkable protein aggregate-clearing activity.
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| 25. |
- Wrobel, L., et al.
(författare)
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Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome. Here we find that compounds that activate the D1 ATPase activity of VCP/p97 fulfill these requirements. Such effects are seen with small molecule VCP activators like SMER28, which activate autophagosome biogenesis by enhancing interactions of PI3K complex components to increase PI(3)P production, and also accelerate VCP-dependent proteasomal clearance of such substrates. Thus, this mode of VCP activation may be a very attractive target for many neurodegenerative diseases. Several neurodegenerative diseases are characterized by the aggregation of cytoplasmic proteins. Here, the authors demonstrate that the small molecule SMER28 activates VCP, which enhances both autophagic and proteasomal clearance of aggregate-prone proteins.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Andersson-Roswall, L, et al.
(författare)
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Verbal memory decline and adverse effects on cognition in adult patients with pharmacoresistant partial epilepsy: A longitudinal controlled study of 36 patients
- 2004
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Ingår i: Epilepsy & Behavior. ; 5:5, s. 677-686
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to delineate possible longitudinal cognitive changes in adult patients with a long history of pharmacoresistant partial epilepsy. Thirty-six patients and thirty healthy controls were investigated at baseline. A reassessment was conducted, with median test intervals of 4.8 years for the patients and 3.1 years for controls. A standardized battery was used for assessment of general cognitive level and memory. At baseline, patients performed at a significantly lower level on general cognition, immediate recall of pairs of associated words, and retention of learned words and visuospatial stimuli, compared with controls. Analyses of change over time in the patients disclosed significant verbal memory decline in retention of pairs of associated words. Group comparisons of change over time revealed adverse effects in the performance aspect of general cognition on the patients. Also, group comparisons indicated impaired performance across time for the patients in retention of pairs of associated words and retention of visuospatial stimuli. The adverse effect on memory and general cognition in this patient group over the period was clear-cut when compared with the longitudinal changes in an adequate control group.
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| 33. |
- Arnbjörnsson, E., et al.
(författare)
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Computed Tomography and Magnetic Resonance Tomography Findings in Children Operated for Anal Atresia
- 1990
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Ingår i: European Journal of Pediatric Surgery. - : Georg Thieme Verlag KG. - 0939-7248 .- 1439-359X. ; 45:3, s. 178-181
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Tidskriftsartikel (refereegranskat)abstract
- Computerised tomography and magnetic resonance tomography were performed in nine faecally incontinent patients more than eight years after rectoplasty for high imperforate anus. No statistically significant correlation was found between function, i. e. degree of faecal incontinence, and anatomical findings. Thus, in spite of a detailed demonstration of the post-operative anatomy, the information does not seem to be directly applicable in indicating a way to reoperate for faecal incontinence in this group of patients.
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| 34. |
- Bartosch, P., et al.
(författare)
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In community-dwelling women frailty is associated with imminent risk of osteoporotic fractures
- 2021
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 32:9, s. 1735-1744
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Tidskriftsartikel (refereegranskat)abstract
- Summary: Frailty reflects an accelerated health decline. Frailty is a consequence of fracture and contributes to fracture. Greater frailty was associated with higher fracture risk. Frail women were at immediate risk (within 24 months) of a hip or major fracture. Fracture prevention could be improved by considering frailty status. Introduction: Frailty encompasses the functional decline in multiple systems, particularly the musculoskeletal system. Frailty can be a consequence of and contribute to fracture, leading to a cycle of further fractures and greater frailty. This study investigates this association, specifically time frames for risk, associated fracture types, and how grade of frailty affects risk. Methods: The study is performed in the OPRA cohort of 1044, 75-year-old women. A frailty index was created at baseline and 5 and 10 years. Women were categorized as frail or nonfrail and in quartiles (Q1 least frail; Q4 most frail). Fracture risk was assessed over short (1 and 2 years) and long terms (5 and 10 years). Fracture risk was defined for any fracture, major osteoporotic fractures (MOFs), and hip and vertebral fracture, using models including bone mineral density (BMD) and death as a competing risk. Results: For women aged 75, frailty was associated with higher risk of fracture within 2 years (Hip SHRadj. 3.16 (1.34–7.47)) and MOF (2 years SHRadj. 1.88 (1.12–3.16)). The increased risk continued for up to 5 years (Hip SHRadj. 2.02 (1.07–3.82)); (MOF SHRadj. 1.43 (0.99–2.05)). Grade of frailty was associated with increased 10-year probability of fracture (p = 0.03). Frailty predicted fracture independently of BMD. For women aged 80, frailty was similarly associated with fracture. Conclusion: Frail elderly women are at immediate risk of fracture, regardless of bone density and continue to be at risk over subsequent years compared to identically aged nonfrail women. Incorporating regular frailty assessment into fracture management could improve identification of women at high fracture risk.
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| 35. |
- Bocchetta, Carlo, et al.
(författare)
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Project Status of the Polish Synchrotron Radiation Facility Solaris
- 2011
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Ingår i: Proceedings of IPAC2011. - 9789290833666 ; , s. 3014-3016
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Abstract in Undetermined The Polish synchrotron radiation facility Solaris is being built at the Jagiellonian University in Krakow. The project is based on an identical copy of the 1.5 GeV storage ring being concurrently built for the MAX IV project in Lund, Sweden. A general description of the facility is given together with a status of activities. Unique features associated with Solaris are outlined, such as infrastructure, the injector and operational characteristics.
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| 36. |
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| 37. |
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| 38. |
- Cross, J. H., et al.
(författare)
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Epilepsy surgery for children and adolescents: evidence-based but underused
- 2022
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Ingår i: Lancet Child & Adolescent Health. - : Elsevier BV. - 2352-4642. ; 6:7, s. 484-494
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Forskningsöversikt (refereegranskat)abstract
- Paediatric epilepsy surgery is an increasingly used evidence-based management option with low risks for complications. Developments in neuroimaging techniques and other advanced diagnostics have widened the spectrum of children who could benefit from the procedure, and surgery is now considered a standard management approach for epilepsy. Available data indicate that early surgery improves outcomes. Despite these considerable advances, epilepsy surgery in children is still underused. In this Review, we summarise the indications, patient selection, principles of presurgical investigations, optimal timing, and types of epilepsy surgery. We also examine comprehensive outcomes after surgery, including seizure outcomes, complications, cognition, neurodevelopment, vocational outcome, and health-related quality of life of children and their parents. Successful epilepsy surgery could lead to improvement in all these areas. Children should, therefore, be referred early for evaluation in an appropriately competent centre.
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| 39. |
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| 40. |
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| 41. |
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| 42. |
- Egund, L., et al.
(författare)
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Longitudinal Measurements of FGF23, Sarcopenia, Frailty and Fracture in Older Community Dwelling Women
- 2023
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Ingår i: Journal of Frailty and Aging. - : SERDI. - 2260-1341 .- 2273-4309. ; 12, s. 166-174
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Tidskriftsartikel (refereegranskat)abstract
- Background: FGF23 has been associated with frailty and functional performance in older individuals, but the association to sarcopenia is unknown. Objectives: To investigate the association between FGF23, frailty, sarcopenia and fractures in older community dwelling women. Design: Prospective longitudinal cohort study. Setting: Malmö, Sweden. Participants: 995 75-year-old women, followed prospectively for ten years, with re-investigations after five (n=667) and ten (n=324) years. Measurements: C-terminal levels of FGF23 were measured and a frailty index of ‘deficits in health’ created. Sarcopenia was defined by low muscle mass and strength and “probable sarcopenia” by low muscle mass only. Incident fractures were continuously registered for 10-years. Based on tertiles of FGF23, odds ratio for frailty, sarcopenia and probable sarcopenia was investigated using logistic regression models adjusted for: eGFR, PTH, calcium, vitamin D and phosphate. Fracture-free survival during 10-year follow-up was depicted using Kaplan Meier curves. Results: While fracture-free survival did not differ between tertiles, women in the highest tertile of FGF23 had lower muscle strength and gait speed, and higher proportion with impaired mobility at baseline. At age 75, these women had higher odds of also being frail (ORadj 1.6 (95% CI 1.1–2.4)) and suffering from probable sarcopenia (ORadj 1.8 (95% CI 1.1–3.1)), but not sarcopenia. At follow-up the association between FGF23 and probable sarcopenia was not evident. While the association with frailty was attenuated at age 80 after adjustment (ORadj 1.6 (95% CI 1.0–2.5)), women in the highest tertile had higher odds of being frail at age 85 (ORadj 3.4 (95% CI 1.7–6.6)). Conclusions: FGF23 may be a promising clinical marker for muscle strength, functional performance, and frailty in older women, but not for future fragility fractures. Whether FGF23 is also associated with sarcopenia requires further investigation.
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| 43. |
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| 44. |
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| 45. |
- Giorgetti, Melania, et al.
(författare)
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New generation ENaC inhibitors detach cystic fibrosis airway mucus bundles via sodium/hydrogen exchanger inhibition
- 2021
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999. ; 904
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis (CF) is a recessive inherited disease caused by mutations affecting anion transport by the epithelial ion channel cystic fibrosis transmembrane conductance regulator (CFTR). The disease is characterized by mucus accumulation in the airways and intestine, but the major cause of mortality in CF is airway mucus accumulation, leading to bacterial colonization, inflammation and respiratory failure. Several drug targets are under evaluation to alleviate airway mucus obstruction in CF and one of these targets is the epithelial sodium channel ENaC. To explore effects of ENaC inhibitors on mucus properties, we used two model systems to investigate mucus characteristics, mucus attachment in mouse ileum and mucus bundle transport in piglet airways. We quantified mucus attachment in explants from CFTR null (CF) mice and tracheobronchial explants from newborn CFTR null (CF) piglets to evaluate effects of ENaC or sodium/hydrogen exchanger (NHE) inhibitors on mucus attachment. ENaC inhibitors detached mucus in the CF mouse ileum, although the ileum lacks ENaC expression. This effect was mimicked by two NHE inhibitors. Airway mucus bundles were immobile in untreated newborn CF piglets but were detached by the therapeutic drug candidate AZD5634 (patent WO, 2015140527). These results suggest that the ENaC inhibitor AZD5634 causes detachment of CF mucus in the ileum and airway via NHE inhibition and that drug design should focus on NHE instead of ENaC inhibition.
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- Hill, Sandra Malmgren, 1987, et al.
(författare)
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VCP/p97 regulates Beclin-1-dependent autophagy initiation
- 2021
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 17, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is an essential cellular process that removes harmful protein species, and autophagy upregulation may be able to protect against neurodegeneration and various pathogens. Here, we have identified the essential protein VCP/p97 (VCP, valosin-containing protein) as a novel regulator of autophagosome biogenesis, where VCP regulates autophagy induction in two ways, both dependent on Beclin-1. Utilizing small-molecule inhibitors of VCP ATPase activity, we show that VCP stabilizes Beclin-1 levels by promoting the deubiquitinase activity of ataxin-3 towards Beclin-1. VCP also regulates the assembly and activity of the Beclin-1-containing phosphatidylinositol-3-kinase (PI3K) complex I, thus regulating the production of PI(3)P, a key signaling lipid responsible for the recruitment of downstream autophagy factors. A decreased level of VCP, or inhibition of its ATPase activity, impairs starvation-induced production of PI(3)P and limits downstream recruitment of WIPI2, ATG16L and LC3, thereby decreasing autophagosome formation, illustrating an important role for VCP in early autophagy initiation.
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