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Sökning: WFRF:(Paulsen J)

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2.
  • Prusti, T., et al. (författare)
  • The Gaia mission
  • 2016
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
  • Tidskriftsartikel (refereegranskat)abstract
    • Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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3.
  • Cossarizza, A., et al. (författare)
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
  • 2019
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 49:10, s. 1457-1973
  • Tidskriftsartikel (refereegranskat)abstract
    • These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell types with helpful Tables detailing phenotypes in murine and human cells. The latest flow cytometry techniques and applications are also described, featuring examples of the data that can be generated and, importantly, how the data can be analysed. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid, all written and peer-reviewed by leading experts in the field, making this an essential research companion.
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4.
  • Wortman, J. R., et al. (författare)
  • The 2008 update of the Aspergillus nidulans genome annotation: A community effort
  • 2009
  • Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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6.
  • Lønborg, C., et al. (författare)
  • A global database of dissolved organic matter (DOM) concentration measurements in coastal waters (CoastDOM v1)
  • 2024
  • Ingår i: Earth System Science Data. - : Copernicus Publications. - 1866-3508 .- 1866-3516. ; 16:2, s. 1107-1119
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components ofbiogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOMv1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complementedby hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables(e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon andtotal alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However,most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the SouthernHemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC,20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequenceDOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focuson carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmolC L−1; median: 103 µmolC L−1) is13-fold higher than the average coastal DON concentration (13.6 ± 30.4 µmol N L−1; median: 8.0 µmol N L−1),which is itself 39-fold higher than the average coastal DOP concentration (0.34 ± 1.11 µmol P L−1; median:0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and willhelp facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing abaseline for modelling future changes in coastal waters. 
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7.
  • Gjestvang, D., et al. (författare)
  • Examination of how properties of a fissioning system impact isomeric yield ratios of the fragments
  • 2023
  • Ingår i: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 108:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The population of isomeric states in the prompt decay of fission fragments-so-called isomeric yield ratios (IYRs)-is known to be sensitive to the angular momentum J that the fragment emerged with, and may therefore contain valuable information on the mechanism behind the fission process. In this work, we investigate how changes in the fissioning system impact the measured IYRs of fission fragments to learn more about what parameters affect angular momentum generation. To enable this, a new technique for measuring IYRs is first demonstrated. It is based on the time of arrival of discrete gamma rays, and has the advantage that it enables the study of the IYR as a function of properties of the partner nucleus. This technique is used to extract the IYR of 134Te, strongly populated in actinide fission, from the three different fissioning systems: 232Th(n, f), 238U(n, f), at two different neutron energies, as well as 252Cf(sf). The impacts of changing the fissioning system, the compound nuclear excitation energy, the minimum J of the binary partner, and the number of neutrons emitted on the IYR of 134Te are determined. The decay code TALYS is used in combination with the fission simulation code FREYA to calculate the primary fragment angular momentum from the IYR. We find that the IYR of 134Te has a slope of 0.004 +/- 0.002 with increase in compound nucleus (CN) mass. When investigating the impact on the IYR of increased CN excitation energy, we find no change with an energy increase similar to the difference between thermal and fast fission. By varying the mass of the partner fragment emerging with 134Te, it is revealed that the IYR of 134Te is independent of the total amount of prompt neutrons emitted from the fragment pair. This indicates that neutrons carry minimal angular momentum away from the fission fragments. Comparisons with the FREYA+TALYS simulations reveal that the average angular momentum in 134Te following 238U(n, f) is 6.0 h over bar . This is not consistent with the value deduced from recent CGMF calculations. Finally, the IYR sensitivity to the angular momentum of the primary fragment is discussed. These results are not only important to help understanding the underlying mechanism in nuclear fission, but can also be used to constrain and benchmark fission models, and are relevant to the gamma -ray heating problem of reactors.
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9.
  • Djoussé, L, et al. (författare)
  • Interaction of normal and expanded CAG repeat sizes influences age at onset of Huntington disease.
  • 2003
  • Ingår i: American Journal of Medical Genetics. Part A. - : Wiley. - 1552-4825 .- 1552-4833. ; 119A:3, s. 279-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. Past studies have shown that the size of expanded CAG repeat is inversely associated with age at onset (AO) of HD. It is not known whether the normal Huntington allele size influences the relation between the expanded repeat and AO of HD. Data collected from two independent cohorts were used to test the hypothesis that the unexpanded CAG repeat interacts with the expanded CAG repeat to influence AO of HD. In the New England Huntington Disease Center Without Walls (NEHD) cohort of 221 HD affected persons and in the HD-MAPS cohort of 533 HD affected persons, we found evidence supporting an interaction between the expanded and unexpanded CAG repeat sizes which influences AO of HD (P = 0.08 and 0.07, respectively). The association was statistically significant when both cohorts were combined (P = 0.012). The estimated heritability of the AO residual was 0.56 after adjustment for normal and expanded repeats and their interaction. An analysis of tertiles of repeats sizes revealed that the effect of the normal allele is seen among persons with large HD repeat sizes (47-83). These findings suggest that an increase in the size of the normal repeat may mitigate the expression of the disease among HD affected persons with large expanded CAG repeats.
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10.
  • Li, Jian-Liang, et al. (författare)
  • A genome scan for modifiers of age at onset in Huntington disease : The HD MAPS study.
  • 2003
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 73:3, s. 682-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is caused by the expansion of a CAG repeat within the coding region of a novel gene on 4p16.3. Although the variation in age at onset is partly explained by the size of the expanded repeat, the unexplained variation in age at onset is strongly heritable (h2=0.56), which suggests that other genes modify the age at onset of HD. To identify these modifier loci, we performed a 10-cM density genomewide scan in 629 affected sibling pairs (295 pedigrees and 695 individuals), using ages at onset adjusted for the expanded and normal CAG repeat sizes. Because all those studied were HD affected, estimates of allele sharing identical by descent at and around the HD locus were adjusted by a positionally weighted method to correct for the increased allele sharing at 4p. Suggestive evidence for linkage was found at 4p16 (LOD=1.93), 6p21-23 (LOD=2.29), and 6q24-26 (LOD=2.28), which may be useful for investigation of genes that modify age at onset of HD.
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11.
  • Tulstrup, M., et al. (författare)
  • Effects of germ line DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia
  • 2020
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 136:10, s. 1161-1168
  • Tidskriftsartikel (refereegranskat)abstract
    • Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 x 10(-8)) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 x 10(-9)) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
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  • Pan, W. H., et al. (författare)
  • Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development
  • 2018
  • Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The interplay of epigenetic processes and the intestinal microbiota may play an important role in intestinal development and homeostasis. Previous studies have established that the microbiota regulates a large proportion of the intestinal epithelial transcriptome in the adult host, but microbial effects on DNA methylation and gene expression during early postnatal development are still poorly understood. Here, we sought to investigate the microbial effects on DNA methylation and the transcriptome of intestinal epithelial cells (IECs) during postnatal development. Methods: We collected IECs from the small intestine of each of five 1-, 4-and 12 to 16-week-old mice representing the infant, juvenile, and adult states, raised either in the presence or absence of a microbiota. The DNA methylation profile was determined using reduced representation bisulfite sequencing (RRBS) and the epithelial transcriptome by RNA sequencing using paired samples from each individual mouse to analyze the link between microbiota, gene expression, and DNA methylation. Results: We found that microbiota-dependent and -independent processes act together to shape the postnatal development of the transcriptome and DNA methylation signatures of IECs. The bacterial effect on the transcriptome increased over time, whereas most microbiota-dependent DNA methylation differences were detected already early after birth. Microbiota-responsive transcripts could be attributed to stage-specific cellular programs during postnatal development and regulated gene sets involved primarily immune pathways and metabolic processes. Integrated analysis of the methylome and transcriptome data identified 126 genomic loci at which coupled differential DNA methylation and RNA transcription were associated with the presence of intestinal microbiota. We validated a subset of differentially expressed and methylated genes in an independent mouse cohort, indicating the existence of microbiota-dependent " functional" methylation sites which may impact on long-term gene expression signatures in IECs. Conclusions: Our study represents the first genome-wide analysis of microbiota-mediated effects on maturation of DNA methylation signatures and the transcriptional program of IECs after birth. It indicates that the gut microbiota dynamically modulates large portions of the epithelial transcriptome during postnatal development, but targets only a subset of microbially responsive genes through their DNA methylation status.
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14.
  • Uter, W., et al. (författare)
  • The epidemic of methylisothiazolinone contact allergy in Europe : follow-up on changing exposures
  • 2020
  • Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 34:2, s. 333-339
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. Objective: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. Methods: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. Results: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. Conclusion: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.
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15.
  • Wichert, R., et al. (författare)
  • Mucus Detachment by Host Metalloprotease Meprin beta Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB
  • 2017
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 21:8, s. 2090-2103
  • Tidskriftsartikel (refereegranskat)abstract
    • The host metalloprotease meprin beta is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial over-growth. To gain access to the cleavage site in MUC2, meprin b must be proteolytically shed from epithelial cells. Hence, regulation of meprin b shedding and activation is important for physiological and pathophysiological conditions. Here, we demonstrate that meprin b activation and shedding are mutually exclusive events. Employing ex vivo small intestinal organoid and cell culture experiments, we found that ADAM-mediated shedding is restricted to the inactive pro-form of meprin beta and is completely inhibited upon its conversion to the active form at the cell surface. This strict regulation of meprin beta activity can be overridden by pathogens, as demonstrated for the bacterial protease Arg-gingipain (RgpB). This secreted cysteine protease potently converts membrane-bound meprin beta into its active form, impairing meprin beta shedding and its function as a mucus-detaching protease.
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16.
  • Bulone, Vincent, et al. (författare)
  • Characterisation of horse dander allergen glycoproteins using amino acid and glycan structure analyses - A mass spectrometric method for glycan chain analysis of glycoproteins separated by two-dimensional electrophoresis
  • 2000
  • Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 123:3, s. 220-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Separation of horse dander allergens using two-dimensional PAGE resulted in the identification of 16 proteins that react with allergic patient sera. A sensitive method has been developed for analysing the structures of the glycan chains of individual glycoprotein allergens transferred to blots following two-dimensional PAGE, and has allowed the structural identification of the glycan chains of the most abundant isoforms of Equ c 1, a glycosylated horse dander major allergen. The method involves separation of the allergens by two-dimensional PAGE, transfer to polyvinylidene difluoride membranes, release of the glycan chains using peptide N-glycosidase F, permethylation and mass spectrometric analysis of the derivatised glycans. The amino acid compositions of the 16 horse dander allergens separated by two-dimensional PAGE have been determined, allowing the identification of the various isoforms of Equ c 1. These results also confirmed that the two non-glycosylated major allergens, Equ c 2.0101 and Equ c 2.0102, belong to the lipocalin family, and support the idea that these two allergens are most probably isoforms of the same protein. The glycan structures identified using the mass spectrometric method are common biantennary and triantennary glycan chains. These carbohydrate moieties may have a role in the binding of IgE; however, it is more likely that the overall glycoprotein structure involving both the glycan and protein moieties, rather than the structure of the glycan chains alone, is responsible for eliciting allergic responses.
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18.
  • Djoussé, Luc, et al. (författare)
  • Evidence for a modifier of onset age in Huntington disease linked to the HD gene in 4p16.
  • 2004
  • Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 5:2, s. 109-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington disease (HD) is a neurodegenerative disorder caused by the abnormal expansion of CAG repeats in the HD gene on chromosome 4p16.3. A recent genome scan for genetic modifiers of age at onset of motor symptoms (AO) in HD suggests that one modifier may reside in the region close to the HD gene itself. We used data from 535 HD participants of the New England Huntington cohort and the HD MAPS cohort to assess whether AO was influenced by any of the three markers in the 4p16 region: MSX1 (Drosophila homeo box homologue 1, formerly known as homeo box 7, HOX7), Delta2642 (within the HD coding sequence), and BJ56 ( D4S127). Suggestive evidence for an association was seen between MSX1 alleles and AO, after adjustment for normal CAG repeat, expanded repeat, and their product term (model P value 0.079). Of the variance of AO that was not accounted for by HD and normal CAG repeats, 0.8% could be attributed to the MSX1 genotype. Individuals with MSX1 genotype 3/3 tended to have younger AO. No association was found between Delta2642 (P=0.44) and BJ56 (P=0.73) and AO. This study supports previous studies suggesting that there may be a significant genetic modifier for AO in HD in the 4p16 region. Furthermore, the modifier may be present on both HD and normal chromosomes bearing the 3 allele of the MSX1 marker.
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19.
  • Gonzalez, J. M., et al. (författare)
  • Genome analysis of the proteorhodopsin-containing marine bacterium Polaribacter sp. MED152 (Flavobacteria)
  • 2008
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 105:25, s. 8724-8729
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of marine cyanobacteria and proteobacteria genomes has provided a profound understanding of the life strategies of these organisms and their ecotype differentiation and metabolisms. However, a comparable analysis of the Bacteroidetes, the third major bacterioplankton group, is still lacking. In the present paper, we report on the genome of Polaribacter sp. strain MED152. On the one hand, MED152 contains a substantial number of genes for attachment to surfaces or particles, gliding motility, and polymer degradation. This agrees with the currently assumed life strategy of marine Bacteroidetes. On the other hand, it contains the proteorhoclopsin gene, together with a remarkable suite of genes to sense and respond to light, which may provide a survival advantage in the nutrient-poor sun-lit ocean surface when in search of fresh particles to colonize. Furthermore, an increase in CO2 fixation in the light suggests that the limited central metabolism is complemented by anaplerotic inorganic carbon fixation. This is mediated by a unique combination of membrane transporters and carboxylases. This suggests a dual life strategy that, if confirmed experimentally, would be notably different from what is known of the two other main bacterial groups (the autotrophic cyanobacteria and the heterotrophic proteobacteria) in the surface oceans. The Polaribacter genome provides insights into the physiological capabilities of proteorhodopsin-containing bacteria. The genome will serve as a model to study the cellular and molecular processes in bacteria that express proteorhoclopsin, their adaptation to the oceanic environment, and their role in carbon-cycling.
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23.
  • Sachdev, P.S., et al. (författare)
  • Diagnostic criteria for vascular cognitive disorders: A VASCOG statement
  • 2014
  • Ingår i: Alzheimer Disease and Associated Disorders. - 0893-0341. ; 28:3, s. 206-218
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:: Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. METHODS:: Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. RESULTS:: Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. CONCLUSIONS:: The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. © 2014 by Lippincott Williams and Wilkins.
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24.
  • Senise, R., et al. (författare)
  • Preface
  • 2020
  • Ingår i: World Review of Science, Technology and Sustainable Development. - : Inderscience Enterprises Ltd.. - 1741-2242 .- 1741-2234. ; 16:1, s. 1-3
  • Tidskriftsartikel (refereegranskat)
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25.
  • Thuvander, A., et al. (författare)
  • Levels of ochratoxin A in blood from Norwegian and Swedish blood donors and their possible correlation with food consumption
  • 2001
  • Ingår i: Food and Chemical Toxicology. - 0278-6915 .- 1873-6351. ; 39:12, s. 1145-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Blood levels of ochratoxin A were determined in 406 Scandinavian blood donors (206 from Oslo, Norway, and 200 from Visby on the island of Gotland, Sweden), using an HPLC method. In connection with the blood collection, the subjects were asked to fill in a food questionnaire to obtain individual dietary information relevant to ochratoxin A exposure. The mean plasma level of ochratoxin A was 0.18 ng/ml in Oslo and slightly higher, 0.21 ng/ml (P = 0.046) in Visby. There was no correlation between plasma levels of ochratoxin A and the estimated total dietary intake of ochratoxin A based on consumption data and levels in food (retrieved from the literature), neither was the plasma level of ochratoxin A correlated with the total amount of food consumed. However, consumption of several foods, including cereal products, wine, beer and pork, were to some minor degree related to high plasma levels of ochratoxin A. The strongest correlations (correlation coefficient r >0.4; P <0.001) were observed for women in relation to the consumption of beer or medium brown bread. Correlation analysis of combinations of two or more food categories did not result in any statistically significant correlation.
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26.
  • Aamodt, A. H., et al. (författare)
  • Blood neurofilament light concentration at admittance: a potential prognostic marker in COVID-19
  • 2021
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 268, s. 3574-3583
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To test the hypotheses that blood biomarkers for nervous system injury, serum concentrations of neurofilament light chain protein (NfL) and glial fibrillary acidic protein (GFAp) can serve as biomarkers for disease severity in COVID-19 patients. Methods Forty-seven inpatients with confirmed COVID-19 had blood samples drawn on admission for assessing serum biomarkers of CNS injury by Single molecule array (Simoa), NfL and GFAp. Concentrations of NfL and GFAp were analyzed in relation to symptoms, clinical signs, inflammatory biomarkers and clinical outcomes. We used multivariate linear models to test for differences in biomarker concentrations in the subgroups, accounting for confounding effects. Results In total, 21% (n = 10) of the patients were admitted to an intensive care unit, and the overall mortality rate was 13% (n = 6). Non-survivors had higher serum concentrations of NfL (p < 0.001) upon admission than patients who were discharged alive both in adjusted analyses (p = 2.6 x 10(-7)) and unadjusted analyses (p = 0.001). The concentrations of NfL in non-survivors increased over repeated measurements; whereas, the concentrations in survivors were stable. The GFAp concentration was also significantly higher in non-survivors than survivors (p = 0.02). Conclusion Increased concentrations of NfL and GFAp in COVID-19 patients on admission may indicate increased mortality risk. Measurement of blood biomarkers for nervous system injury can be useful to detect and monitor CNS injury in COVID-19.
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28.
  • Bjornsen, T., et al. (författare)
  • Frequent blood flow restricted training not to failure and to failure induces similar gains in myonuclei and muscle mass
  • 2021
  • Ingår i: Scandinavian Journal of Medicine & Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 31:7, s. 1420-1439
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to compare the effects of short-term high-frequency failure vs non-failure blood flow-restricted resistance exercise (BFRRE) on changes in satellite cells (SCs), myonuclei, muscle size, and strength. Seventeen untrained men performed four sets of BFRRE to failure (Failure) with one leg and not to failure (Non-failure; 30-15-15-15 repetitions) with the other leg using knee-extensions at 20% of one repetition maximum (1RM). Fourteen sessions were distributed over two 5-day blocks, separated by a 10-day rest period. Muscle samples obtained before, at mid-training, and 10-day post-intervention (Post10) were analyzed for muscle fiber area (MFA), myonuclei, and SC. Muscle size and echo intensity of m.rectus femoris (RF) and m.vastus lateralis (VL) were measured by ultrasonography, and knee extension strength with 1RM and maximal isometric contraction (MVC) up until Post24. Both protocols increased myonuclear numbers in type-1 (12%-17%) and type-2 fibers (20%-23%), and SC in type-1 (92%-134%) and type-2 fibers (23%-48%) at Post10 (p < 0.05). RF and VL size increased by 5%-10% in both legs at Post10 to Post24, whereas the MFA of type-1 fibers in Failure was decreased at Post10 (-10 +/- 16%; p = 0.02). Echo intensity increased by similar to 20% in both legs during Block1 (p < 0.001) and was similar to 8 to 11% below baseline at Post24 (p = 0.001-0.002). MVC and 1RM decreased by 5%-10% after Block1, but increased in both legs by 6%-11% at Post24 (p < 0.05). In conclusion, both short-term high-frequency failure and non-failure BFRRE induced increases in SCs, in myonuclei content, muscle size, and strength, concomitant with decreased echo intensity. Intriguingly, the responses were delayed and peaked 10-24 days after the training intervention. Our findings may shed light on the mechanisms involved in resistance exercise-induced overreaching and supercompensation.
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29.
  • Bjornsen, T., et al. (författare)
  • High-frequency blood flow-restricted resistance exercise results in acute and prolonged cellular stress more pronounced in type I than in type II fibers
  • 2021
  • Ingår i: Journal of Applied Physiology. - Rockville : American Physiological Society. - 8750-7587 .- 1522-1601. ; 131:2, s. 643-660
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocellular stress with high-frequency blood flow-restricted resistance exercise (BFRRE) was investigated by measures of heat shock protein (HSP) responses, glycogen content, and inflammatory markers. Thirteen participants [age: 24 +/- 2 yr (means +/- SD), 9 males] completed two 5-day blocks of seven BFRRE sessions, separated by 10 days. Four sets of unilateral knee extensions to failure at 20% of one-repetition maximum (1RM) were performed. Muscle samples obtained before, 1 h after the first session in the first and second block (acute 1 and acute 2), after three sessions (day 4), during the "rest week," and at 3 (post 3) and 10 days postintervention (post 10) were analyzed for HSP70, alpha beta-crystallin, glycogen [periodic acid-Schiff (PAS) staining], mRNAs, miRNAs, and CD68(+) (macrophages) and CD661D(+) (neutrophils) cell numbers. alpha beta-crystallin translocated from the cytosolic to the cytoskeletal fraction after acute 1 and acute 2 (P < 0.05) and immunostaining revealed larger responses in type I than in type II fibers (acute 1, 225 +/- 184% vs. 92 +/- 81%, respectively, P = 0.001). HSP70 was increased in the cytoskeletal fraction at day 4 and post 3, and immunostaining intensities were more elevated in type I than in type II fibers at day 4 (206 +/- 84% vs. 72 +/- 112%, respectively, P <0.001), during the rest week (98 +/- 66% vs. 42 +/- 79%, P < 0.001), and at post 3 (115 +/- 82% vs. 28 +/- 78%, P = 0.003). Glycogen content was reduced in both fiber types, but most pronounced in type I, which did not recover until the rest week (-15% to 29%, P <= 0.001). Intramuscular macrophage numbers were increased by similar to 65% postintervention, but no changes were observed in muscle neutrophils. We conclude that high-frequency BFRRE with sets performed till failure stresses both fiber types, with type I fibers being most affected. NEW & NOTEWORTHY BFRRE has been reported to preferentially stress type I muscle fibers, as evidenced by HSP responses. We extend these findings by showing that the HSP responses occur in both fiber types but more so in type I fibers and that they can still be induced after a short-term training period. Furthermore, the reductions in glycogen content of type I fibers after strenuous frequent BFRRE in unaccustomed subjects can be prolonged (>= 5 days), probably due to microdamage.
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30.
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31.
  • Folkesson, Mattias, 1972-, et al. (författare)
  • Immunohistochemical changes in the expression of HSP27 in exercised human vastus lateralis muscle
  • 2008
  • Ingår i: Acta Physiologica. - : Blackwell Publishing. - 1748-1708 .- 1748-1716. ; 194:3, s. 215-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: The role of HSP27 in the adaptive process of skeletal muscle to exercise, especially in humans, is not well understood. The objective of this study was to investigate immunohistochemical changes in HSP27 expression in human vastus lateralis muscle following resistance and endurance exercises.Methods: Two different exercise protocols were used: (1) one-leg ergometer cycling (EC, n = 6) consisting of two 30-min bouts at 40% and 75% of peak oxygen uptake, respectively, and (2) leg extension resistance exercise (RE, n = 9) including 10 sets of eight repetitions at a load corresponding to 70% of one maximal repetition (1RM). Immunohistochemistry using specific monoclonal antibodies was used to determine the location of HSP27 protein in muscle biopsies from human vastus lateralis.Results: Our results show that RE, but not EC, induced a significant appearance of scattered accumulations of HSP27 protein in muscle fibres from five of nine subjects. The number of fibres with accumulation of HSP27 in RE ranged from 0% to 32% with a mean of 6.3% of the total number of fibres.Conclusion: We conclude that this rapid HSP27 protein relocation after RE is an important player in the cellular remodelling of human muscle fibres in response to exercise involving high-force contractions, but not in response to endurance exercises.
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32.
  • Giblin, S. R., et al. (författare)
  • Pauling Entropy, Metastability, and Equilibrium in Dy2Ti2O7 Spin Ice
  • 2018
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 121:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Determining the fate of the Pauling entropy in the classical spin ice material Dy2Ti2O7 with respect to the third law of thermodynamics has become an important test case for understanding the existence and stability of ice-rule states in general. The standard model of spin ice-the dipolar spin ice model-predicts an ordering transition at T approximate to 0.15 K, but recent experiments by Pomaranski et al. suggest an entropy recovery over long timescales at temperatures as high as 0.5 K, much too high to be compatible with the theory. Using neutron scattering and specific heat measurements at low temperatures and with long timescales ( 0.35 K/10(6) s and 0.5 K/10(5) s, respectively) on several isotopically enriched samples, we find no evidence of a reduction of ice-rule correlations or spin entropy. High-resolution simulations of the neutron structure factor show that the spin correlations remain well described by the dipolar spin ice model at all temperatures. Furthermore, by careful consideration of hyperfine contributions, we conclude that the original entropy measurements of Ramirez et al. are, after all, essentially correct: The short-time relaxation method used in that study gives a reasonably accurate estimate of the equilibrium spin ice entropy due to a cancellation of contributions.
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33.
  • Kindeberg, Theodor, et al. (författare)
  • Porewater Carbonate Chemistry Dynamics in a Temperate and a Subtropical Seagrass System
  • 2020
  • Ingår i: Aquatic Geochemistry. - : Springer Science and Business Media LLC. - 1380-6165 .- 1573-1421.
  • Tidskriftsartikel (refereegranskat)abstract
    • Seagrass systems are integral components of both local and global carbon cycles and can substantially modify seawater biogeochemistry, which has ecological ramifications. However, the influence of seagrass on porewater biogeochemistry has not been fully described, and the exact role of this marine macrophyte and associated microbial communities in the modification of porewater chemistry remains equivocal. In the present study, carbonate chemistry in the water column and porewater was investigated over diel timescales in contrasting, tidally influenced seagrass systems in Southern California and Bermuda, including vegetated (Zostera marina) and unvegetated biomes (0–16 cm) in Mission Bay, San Diego, USA and a vegetated system (Thallasia testudinium) in Mangrove Bay, Ferry Reach, Bermuda. In Mission Bay, dissolved inorganic carbon (DIC) and total alkalinity (TA) exhibited strong increasing gradients with sediment depth. Vertical porewater profiles differed between the sites, with almost twice as high concentrations of DIC and TA observed in the vegetated compared to the unvegetated sediments. In Mangrove Bay, both the range and vertical profiles of porewater carbonate parameters such as DIC and TA were much lower and, in contrast to Mission Bay where no distinct temporal signal was observed, biogeochemical parameters followed the semi-diurnal tidal signal in the water column. The observed differences between the study sites most likely reflect a differential influence of biological (biomass, detritus and infauna) and physical processes (e.g., sediment permeability, residence time and mixing) on porewater carbonate chemistry in the different settings.
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34.
  • Landsverk, Ole J. B., et al. (författare)
  • Antibody-secreting plasma cells persist for decades in human intestine
  • 2017
  • Ingår i: Journal of Experimental Medicine. - NewYork, USA : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 214:2, s. 309-317
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.
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35.
  • Langbehn, D, et al. (författare)
  • A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length.
  • 2004
  • Ingår i: Clinical Genetics. - : Wiley. - 0009-9163 .- 1399-0004. ; 65:4, s. 267-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.
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36.
  • Ljungman, S., et al. (författare)
  • Factors associated with time to first dialysis-associated peritonitis episode: Data from the Peritonitis Prevention Study (PEPS)
  • 2023
  • Ingår i: Peritoneal Dialysis International. - 0896-8608. ; 43:3, s. 241-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Peritonitis remains a potentially serious complication of peritoneal dialysis (PD) treatment. It is therefore important to identify risk factors in order to reduce the incidence of peritonitis. The aim of the present analysis was to identify factors associated with time to first peritonitis episode. Methods: Incident PD patients from 57 centres in Europe participated in the prospective randomised controlled Peritonitis Prevention Study (PEPS) from 2010 to 2015. Peritonitis-free, self-care PD patients >= 18 years were randomised to a retraining or a control group and followed for 1-36 months after PD initiation. The association of biochemical, clinical and prescription data with time to first peritonitis episode was studied. Results: A first peritonitis episode was experienced by 33% (223/671) of participants. Univariable Cox proportional hazard regression showed a strong association between the time-updated number of PD bags connected per 24 h (PD bags/24 h) and time to first peritonitis episode (HR 1.35; 95% confidence interval (CI) 1.17-1.57), even after inclusion of PD modalities in the same model. Multivariable Cox regression revealed that the factors independently associated with time to first peritonitis episode included age (HR 1.16 per 10 years; 95% CI 1.05-1.28), PD bags/24 h (HR 1.32; 95% CI 1.13-1.54), serum albumin >35 g/L (HR 1.39; 95% CI 1.06-1.82) and body weight per 10 kg (HR 1.10; 95% CI 1.01-1.19). Conclusion: This study of incident PD patients indicates that older age, greater number of PD bags connected/24 h, higher body weight and hypoalbuminaemia are independently associated with a shorter time to first peritonitis episode.
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37.
  • Ljungman, Susanne, 1942, et al. (författare)
  • Retraining for prevention of peritonitis in peritoneal dialysis patients: A randomized controlled trial
  • 2020
  • Ingår i: Peritoneal Dialysis International. - : SAGE Publications. - 0896-8608 .- 1718-4304. ; 40:2, s. 141-152
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Peritonitis is more common in peritoneal dialysis (PD) patients nonadherent to the PD exchange protocol procedures than in compliant patients. We therefore investigated whether regular testing of PD knowledge with focus on infection prophylaxis could increase the time to first peritonitis (primary outcome) and reduce the peritonitis rate in new PD patients. Methods: This physician-initiated, open-label, parallel group trial took place at 57 centers in Sweden, Denmark, Norway, Finland, Estonia, Latvia, the Netherlands, and the United Kingdom from 2010 to 2015. New peritonitis-free PD patients were randomized using computer-generated numbers 1 month after the start of PD either to a control group (n = 331) treated according to center routines or to a retraining group (n = 340), which underwent testing of PD knowledge and skills at 1, 3, 6, 12, 18, 24, 30, and 36 months after PD start, followed by retraining if the goals were not achieved. Results: In all, 74% of the controls and 80% of the retraining patients discontinued the study. The groups did not differ significantly regarding cumulative incidence of first peritonitis adjusted for competing risks (kidney transplantation, transfer to hemodialysis and death; hazard ratio 0.84; 95% confidence interval (CI) 0.65-1.09) nor regarding peritonitis rate per patient year (relative risk 0.93; 95% CI 0.75-1.16). Conclusions: In this randomized controlled trial, we were unable to demonstrate that regular, targeted testing and retraining of new PD patients increased the time to first peritonitis or reduced the rate of peritonitis, as the study comprised patients with a low risk of peritonitis, was underpowered, open to type 1 statistical error, and contamination between groups.
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38.
  • Meaney, Paul M, 1960, et al. (författare)
  • Electrical Characterization of Glycerin: Water Mixtures: Implications for Use as a Coupling Medium in Microwave Tomography
  • 2017
  • Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 65:5, s. 1471-1478
  • Tidskriftsartikel (refereegranskat)abstract
    • We examine the broadband behavior of complex electrical properties of glycerin and water mixtures over the frequency range of 0.1-25.0 GHz, especially as they relate to using these liquids as coupling media for microwave tomographic imaging. Their combination is unique in that they are mutually miscible over the full range of concentrations, which allows them to be tailored to dielectric property matching for biological tissues. While the resultant mixture properties are partially driven by differences in the inherent low-frequency permittivity of each constituent, relaxation frequency shifts play a disproportionately larger role in increasing the permittivity dispersion while also dramatically increasing the effective conductivity over the frequency range of 1-3 GHz. For the full range of mixture ratios, the relaxation frequency shifts from 17.5 GHz for 0% glycerin to less than 0.1 GHz for 100% glycerin. Of particular interest is the fact that the conductivity stays above 1.0 S/m over the 1-3-GHz range for glycerin mixture ratios (70%-90% glycerin) we use for microwave breast tomography. The high level of attenuation is critical for suppressing unwanted multipath signals. This paper presents a full characterization of these liquids along with a discussion of their benefits and limitations in the context of microwave tomography.
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39.
  • Merok Paulsen, J., et al. (författare)
  • Superintendent leadership under shifting governance regimes
  • 2014
  • Ingår i: International Journal of Educational Management. - : Emerald Group Publishing Limited. - 0951-354X .- 1758-6518. ; 28:7, s. 813-822
  • Tidskriftsartikel (refereegranskat)abstract
    • PurposeThe purpose of this paper is to analyse the superintendent position, its relation to the local political system and the function as superior of principals in the school district in order to illuminate important district-level conditions for student learning. Influences from historical legacies and policy cultures are investigated by means of cross-country case analyses.Design/methodology/approachThis paper is based on data from national surveys of superintendent leadership in Sweden, Denmark, Finland and Norway.FindingsA key point is the observation of a mix-mode system of hard and soft governance. Municipalities, schools, teachers and pupils are – in different degrees across the Nordic countries – subjected to external evaluation and assessment by central control agencies, where the streams of reports, assessments and performance data are assembled. However, shifts in the governance systems are only modestly reflected in the self-reports on the superintendents’ role. Overall, superintendents in the cases express a self-preferred leadership style as professional learning facilitators who focus on pupil orientation, which positions the superintendent in “crossfires” between conflicting stakeholder demands.Research limitations/implicationsThe paper reinforces the importance of superintendent leadership in local school governance. It underscores the importance that superintendents facilitate learning conditions for school leaders, teachers and students, which we see as a promising path for further research.Originality/valueThe paper provides empirical evidence regarding superintendent leadership situated in local social and political contexts within the Nordic countries. The cross-country analysis illuminates how path-pendent historical legacies mediate current reform trends.
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40.
  • Nene, Vishvanath, et al. (författare)
  • Genome sequence of Aedes aegypti, a major arbovirus vector.
  • 2007
  • Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
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41.
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42.
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43.
  • Paulsen, B.D., et al. (författare)
  • Organic mixed ionic–electronic conductors
  • 2020
  • Ingår i: Nature Materials. - : Nature Publishing Group. - 1476-1122 .- 1476-4660. ; 19, s. 13-26
  • Forskningsöversikt (refereegranskat)abstract
    • Materials that efficiently transport and couple ionic and electronic charge are key to advancing a host of technological developments for next-generation bioelectronic, optoelectronic and energy storage devices. Here we highlight key progress in the design and study of organic mixed ionic–electronic conductors (OMIECs), a diverse family of soft synthetically tunable mixed conductors. Across applications, the same interrelated fundamental physical processes dictate OMIEC properties and determine device performance. Owing to ionic and electronic interactions and coupled transport properties, OMIECs demand special understanding beyond knowledge derived from the study of organic thin films and membranes meant to support either electronic or ionic processes only. We address seemingly conflicting views and terminology regarding charging processes in these materials, and highlight recent approaches that extend fundamental understanding and contribute to the advancement of materials. Further progress is predicated on multimodal and multi-scale approaches to overcome lingering barriers to OMIEC design and implementation.
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44.
  • Paulsen, B. S., et al. (författare)
  • Ectopic expression of RAD52 and dn53BP1 improves homology-directed repair during CRISPR-Cas9 genome editing
  • 2017
  • Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 1:11, s. 878-888
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene disruption by clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) is highly efficient and relies on the error-prone non-homologous end-joining pathway. Conversely, precise gene editing requires homology-directed repair (HDR), which occurs at a lower frequency than non-homologous end-joining in mammalian cells. Here, by testing whether manipulation of DNA repair factors improves HDR efficacy, we show that transient ectopic co-expression of RAD52 and a dominant-negative form of tumour protein p53-binding protein 1 (dn53BP1) synergize to enable efficient HDR using a single-stranded oligonucleotide DNA donor template at multiple loci in human cells, including patient-derived induced pluripotent stem cells. Co-expression of RAD52 and dn53BP1 improves multiplexed HDR-mediated editing, whereas expression of RAD52 alone enhances HDR with Cas9 nickase. Our data show that the frequency of non-homologous end-joining-mediated double-strand break repair in the presence of these two factors is not suppressed and suggest that dn53BP1 competitively antagonizes 53BP1 to augment HDR in combination with RAD52. Importantly, co-expression of RAD52 and dn53BP1 does not alter Cas9 off-target activity. These findings support the use of RAD52 and dn53BP1 co-expression to overcome bottlenecks that limit HDR in precision genome editing. © 2017 The Author(s).
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45.
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46.
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47.
  • Rank, Cecilie U., et al. (författare)
  • Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
  • 2020
  • Ingår i: Journal of Clinical Oncology. - Alexandria : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:2, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
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48.
  • Rypdal, K., et al. (författare)
  • Non-equilibrium quasi-stationary states in a magnetized plasma
  • 2003
  • Ingår i: Nonlinear processes in geophysics. - : Copernicus GmbH. - 1023-5809 .- 1607-7946. ; 10:02-jan, s. 139-149
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-equilibrium quasi-stationary states resulting from curvature driven interchange instabilities and driftwave instabilities in a low beta, weakly ionized, magnetized plasma are investigated in the context of laboratory experiments in a toroidal configuration. Analytic modelling, numerical simulations and experimental results are discussed with emphasis on identifying the unstable modes and understanding the physics of anomalous particle and energy fluxes and their linkage to self-organized pressure profiles.
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