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51.	Chasman, Daniel I., et al. (författare) Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function 2012 Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:24, s. 5329-5343 Tidskriftsartikel (refereegranskat)abstract In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.
52.	Chávez de Paz, Luis, 1974, et al. (författare) Response to alkaline stress by root canal bacteria in biofilms. : Viability and mechanisms of response to alkaline stress by selected root canal bacteria. 2007 Ingår i: International endodontic journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 40:5, s. 344-55 Tidskriftsartikel (refereegranskat)abstract AIM: To determine whether bacteria isolated from infected root canals survive alkaline shifts better in biofilms than in planktonic cultures. METHODOLOGY: Clinical isolates of Enterococcus faecalis, Lactobacillus paracasei, Olsenella uli, Streptococcus anginosus, S. gordonii, S. oralis and Fusobacterium nucleatum in biofilm and planktonic cultures were stressed at pH 10.5 for 4 h, and cell viability determined using the fluorescent staining LIVE/DEAD BacLight bacterial viability kit. In addition, proteins released into extracellular culture fluids were identified by Western blotting. RESULTS: Enterococcus faecalis, L. paracasei, O. uli and S. gordonii survived in high numbers in both planktonic cultures and in biofilms after alkaline challenge. S. anginosus, S. oralis and F. nucleatum showed increased viability in biofilms compared with planktonic cultures. Alkaline exposure caused all planktonic cultures to aggregate into clusters and resulted in a greater extrusion of cellular proteins compared with cells in biofilms. Increased levels of DnaK, HPr and fructose-1,6-bisphosphate aldolase were observed in culture fluids, especially amongst streptococci. CONCLUSIONS: In general, bacteria isolated from infected roots canals resisted alkaline stress better in biofilms than in planktonic cultures, however, planktonic cells appeared to use aggregation and the extracellular transport of specific proteins as survival mechanisms.
53.	Chávez de Paz, Luis, 1974, et al. (författare) Streptococci from root canals in teeth with apical periodontitis receiving endodontic treatment. 2005 Ingår i: Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. - : Elsevier BV. - 1528-395X .- 1079-2104. ; 100:2, s. 232-41 Tidskriftsartikel (refereegranskat)abstract OBJECTIVES: The object of this study was to investigate the diversity among streptococcal species isolated from root canals in conjunction with endodontic therapy and to characterize their production of extracellular proteins. STUDY DESIGN: Consecutive root canal samples (RCS) taken as bacteriological controls during root canal treatment of teeth with apical periodontitis were analyzed in a total of 100 clinical cases. Bacteria were isolated and classified by selective media and gas liquid chromatography. Streptococcal strains were identified by carbohydrate fermentation, hydrolysis of aesculin/arginine, and production of enzymes. Releases of extracellular proteins by streptococci and Enterococcus spp in fluid culture media were examined with SDS-PAGE and 2-dimension gel electrophoresis (2 DE). Extracellular proteins produced were quantified and qualitatively analyzed. Specific proteins were targeted with Western immunoblot assays. Comparisons were made with type strains. RESULTS: Of a total of 241 bacterial strains recovered in the first samples submitted, Streptococcus gordonii, S anginosus, and S oralis were the most frequently isolated streptococci. In 49 of 89 resubmitted samples showing bacterial growth, S gordonii and S oralis still predominated among streptococci. Other common bacterial isolates were Enterococcus spp, Lactobacillus paracasei, and Olsenella uli. Quantitative and qualitative differences in extracellular protein production were observed among clinical isolates and laboratory streptococcal strains. In similar conditions for growth, S intermedius, S anginosus, S oralis, and S gordonii were strong producers of extracellular proteins (>3.0 microg/mL), while Enterococcus spp and S mutans were weak. Whole cell protein extracts showed a different profile from that of extracellular proteins. The chaperone protein DnaK was recognized to be produced extracellularly by S gordonii, S oralis, S anginosus, and S parasanguis. CONCLUSIONS: Being strong producers of extracellular proteins and by virtue of common presence in teeth undergoing endodontic therapy, S gordonii, S anginosus, and S oralis may be of pathogenic significance in posttreatment apical periodontitis.
54.	Christopoulos, Arthur, et al. (författare) THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. 2021 Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1 Forskningsöversikt (refereegranskat)abstract The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
55.	de la Hoz, P., et al. (författare) Unpolarized states and hidden polarization 2014 Ingår i: Physical Review A. Atomic, Molecular, and Optical Physics. - 1050-2947 .- 1094-1622. ; 90:4, s. 043826- Tidskriftsartikel (refereegranskat)abstract We capitalize on a multipolar expansion of the polarization density matrix, in which multipoles appear as successive moments of the Stokes variables. When all the multipoles up to a given order K vanish, we can properly say that the state is Kth-order unpolarized, as it lacks of polarization information to that order. First-order unpolarized states coincide with the corresponding classical ones, whereas unpolarized to any order tally with the quantum notion of fully invariant states. In between these two extreme cases, there is a rich variety of situations that are explored here. The existence of hidden polarization emerges in a natural way in this context.
56.	Di Angelantonio, Emanuele, et al. (författare) Association of Cardiometabolic Multimorbidity With Mortality : The Emerging Risk Factors Collaboration 2015 Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 314:1, s. 52-60 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.
57.	Docherty, Anna R, et al. (författare) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. 2023 Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738 Tidskriftsartikel (refereegranskat)abstract Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
58.	Doncheva, Atanaska, I, et al. (författare) Serglycin Is Involved in Adipose Tissue Inflammation in Obesity 2022 Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 208:1, s. 121-132 Tidskriftsartikel (refereegranskat)abstract Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn(+/+) and Srgn(-/-) mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn(+/+) and Srgn(-/-) mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn(-/)- mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn(-/-) compared with Srgn(+/+) mice. Further, Srgn(-/-) mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.
59.	Du Rietz, G. Einar, et al. (författare) Zur Kenntnis der Vegetation des Sees Tåkern 1939 Bok (övrigt vetenskapligt/konstnärligt)
60.	E Johnsen, H, et al. (författare) Priming with r-metHuSCF and filgrastim or chemotherapy and filgrastim in patients with malignant lymphomas: a randomized phase II pilot study of mobilization and engraftment 2011 Ingår i: BONE MARROW TRANSPLANTATION. - : Nature Publishing Group. - 0268-3369 .- 1476-5365. ; 46:1, s. 44-51 Tidskriftsartikel (refereegranskat)abstract SCF has been shown to synergize with G-CSF to mobilize CD34(+) PBPCs. In this study we report results from this combination after a phase II trial of 32 patients with malignant lymphoma randomized to receive recombinant methionyl human SCF (ancestim, r-metHuSCF) in combination with recombinant methionyl human G-CSF (filgrastim, r-metHuG-CSF) (experimental arm A) or routine chemotherapy plus filgrastim (conventional arm B). The primary objective was to evaluate the side effects and toxicity during priming and mobilization. The secondary objectives were efficacy by the level of blood-circulating PBPCs, the number of harvest days and the time to three-lineage engraftment after autografting. First, during priming 5 patients had 8 serious events, 4 in each arm. A summary of all adverse events revealed 30 (94%) patients suffering from 132 events of all grading. Second, neutropenia and thrombocytopenia was documented in arm B. Third, 9/14 (64%) patients in arm A reached the target of 5 million CD34(+) cells/kg body weight (bw) compared with 13/15 (87%) in arm B. The results represent the first randomized trial of growth factor plus chemotherapy priming and indicate that a formal phase III trial very unlikely may challenge chemotherapy plus r-metHuG-CSF priming in candidates for high-dose therapy.
61.	Eicher, John D., et al. (författare) Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals 2016 Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 40-55 Tidskriftsartikel (refereegranskat)abstract Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
62.	Ekberg, O., et al. (författare) Effect of Barium Sulfate Contrast Medium on Rheology and Sensory Texture Attributes in a Model Food 2009 Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 50:2, s. 131-138 Tidskriftsartikel (refereegranskat)abstract Background: The swallowing process can be visualized using videoradiography, by mixing food with contrast medium, e.g., barium sulfate (BaSO4), making it radiopaque. The sensory properties of foods may be affected by adding this medium. Purpose: To evaluate if and to what extent sensory and rheological characteristics of mango puree were altered by adding barium sulfate to the food. Material and Methods: This study evaluated four food samples based on mango puree, with no or added barium sulfate contrast medium (0%, 12.5%, 25.0%, and 37.5%), by a radiographic method, and measured sensory texture properties and rheological characteristics. The sensory evaluation was performed by an external trained panel using quantitative descriptive analysis. The ease of swallowing the foods was also evaluated. Results: The sensory texture properties of mango puree were significantly affected by the added barium in all evaluated attributes, as was the perception of particles. Moreover, ease of swallowing was significantly higher in the sample without added contrast medium. All samples decreased in extensional viscosity with increasing extension rate, i.e., all samples were tension thinning. Shear viscosity was not as dependent on the concentration of BaSO4 as extensional viscosity. Conclusion: Addition of barium sulfate to a model food of mango puree has a major impact on perceived sensory texture attributes as well as on rheological parameters.
63.	Estrada, Karol, et al. (författare) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. 2012 Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501 Tidskriftsartikel (refereegranskat)abstract Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
64.	Ganguly, Koustav, et al. (författare) Computational modeling of lung deposition of inhaled particles in chronic obstructive pulmonary disease (COPD) patients : identification of gaps in knowledge and data 2019 Ingår i: Critical reviews in toxicology. - : TAYLOR & FRANCIS LTD. - 1040-8444 .- 1547-6898. ; 49:2, s. 160-173 Forskningsöversikt (refereegranskat)abstract Computational modeling together with experimental data are essential to assess the risk for particulate matter mediated lung toxicity and to predict the efficacy, safety and fate of aerosolized drug molecules used in inhalation therapy. In silico models are widely used to understand the deposition, distribution, and clearance of inhaled particles and aerosols in the human lung. Exacerbations of chronic obstructive pulmonary disease (COPD) have been reported due to increased particulate matter related air pollution episodes. Considering the profound functional, anatomical and structural changes occurring in COPD lungs, the relevance of the existing in silico models for mimicking diseased lungs warrants reevaluation. Currently available computational modeling tools were developed for the healthy adult (male) lung. Here, we analyze the major alterations occurring in the airway structure, anatomy and pulmonary function in the COPD lung, as compared to the healthy lung. We also scrutinize the various physiological and particle characteristics that influence particle deposition, distribution and clearance in the lung. The aim of this review is to evaluate the availability of the fundamental knowledge and data required for modeling particle deposition in a COPD lung departing from the existing healthy lung models. The extent to which COPD pathophysiology may affect aerosol deposition depends on the relative contribution of several factors such as altered lung structure and function, bronchoconstriction, emphysema, loss of elastic recoil, altered breathing pattern and altered liquid volumes that warrant consideration while developing physiologically relevant in silico models.
65.	Gaulton, Kyle J, et al. (författare) Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci. 2015 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415 Tidskriftsartikel (refereegranskat)abstract We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
66.	Gesheva, Kostadinka, et al. (författare) Optical, structural and electrochromic properties of sputter deposited W-Mo oxide thin films 2016 Ingår i: INERA CONFERENCE. - : Institute of Physics Publishing (IOPP). Konferensbidrag (refereegranskat)abstract Thin metal oxide films were investigated by a series of characterization techniques including impedance spectroscopy, spectroscopic ellipsometry, Raman spectroscopy, and Atomic Force Microscopy. Thin film deposition by reactive DC magnetron sputtering was performed at the Ångström Laboratory. W and Mo targets (5 cm diameter) and various oxygen gas flows were employed to prepare samples with different properties, whereas the gas pressure was kept constant at about 30 mTorr. The substrates were 5×5 cm2 plates of unheated glass pre-coated with ITO having a resistance of 40 ohm/sq. Film thicknesses were around 300nm as determined by surface profilometry. Newly acquired equipment was used to study optical spectra, optoelectronic properties, and film structure. Films of WO3 and of mixed W–Mo oxide with three compositions showed coloring and bleaching under the application of a small voltage. Cyclic voltammograms were recorded with a scan rate of 5 mV s–1. Ellipsometric data for the optical constants show dependence on the amount of MoOx in the chemical composition. Single MoOx film, and the mixed one with only 8% MoOx have the highest value of refractive index, and similar dispersion in the visible spectral range. Raman spectra displayed strong lines at wavenumbers between 780 cm–1 and 950 cm–1 related to stretching vibrations of WO3, and MoO3. AFM gave evidence for domains of different composition in mixed W-Mo oxide films.
67.	Gevorkyana, A.S., et al. (författare) Novel algorithm for simulation of 3D quantum reactive atom-diatom scattering 2010 Ingår i: Procedia Computer Science. - : Elsevier BV. - 1877-0509. ; 1:1, s. 1195-1201 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract A new approach is described to the evaluation of the quantum scattering S-matrix in 3D atom-diatom reactive collision. The theory is developed in terms of natural collision coordinates where the coordinate reaction fulfills the same role as a time in a time-dependent scattering formulation. Having written the full wavefunction of the particles system in the coupled-channel representation we have proved that the 3D multi-channel scattering problem can be reduced to the inelastic single-arrangement problem which is described by system of ordinary dierential equations (ODE) of second order. The system of coupled-channel second order ODEs exactly is reduced to the system of integro-dierential equations (IDE) of first order which is solved with the initial conditions. The problem of Koshi for the system of IDEs is proposed to be solved by the method of Runge-Kutta of fourth order. The detailed algorithm for parallel simulation of initial 3D scattering problem is proposed. In result of simulation of IDEs the full wavefunction and all S-matrix elements of reactive transitions and state-to-state cross section are obtained simultaneously without other extra calculations.
68.	Geyer, H., et al. (författare) Development Of An Mf Patient Reported Outcome (Pro) Tool For Fda Qualification : Comprehensive Literature Search And Physician Cognitive Debriefing Results 2016 Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 101, s. 564-564 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
69.	Geyer, H., et al. (författare) Gender Differences and MPN Symptom Burden : An Analysis by the MPN Quality of Life International Study Group (MPN-QOL ISG) 2014 Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 99, s. 396-397 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
70.	Geyer, H., et al. (författare) Impact Of Splenomegaly On Mpn Symptoms And Association With Clinical Features : An Analysis By The Mpn Quality Of Life International Study Group 2016 Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 101, s. 555-555 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
71.	Geyer, H., et al. (författare) PRIMARY MYELOFIBROSIS, POST-ET AND POST-PV MYELOFIBROSIS HAVE DISTINCT CLINICAL PROFILES AND SYMPTOMATIC BURDENS : AN ANALYSIS BY THE MPN QUALITY OF LIFE INTERNATIONAL STUDY GROUP (MPN-QOL ISG) 2015 Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 100, s. 261-262 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
72.	Gordon, C., et al. (författare) EULAR points to consider for conducting clinical trials in systemic lupus erythematosus 2009 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 68:4, s. 470-476 Tidskriftsartikel (refereegranskat)abstract Objective: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. Designing a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. Methods: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. Results: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. Conclusions: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.
73.	Granqvist, C.-G., et al. (författare) Recent advances in electrochromics for smart windows applications 1998 Ingår i: Solar Energy. - 0038-092X .- 1471-1257. ; 63:4, s. 199-216 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Electrochromic smart windows are able to vary their throughput of radiant energy by low-voltage electrical pulses. This function is caused by reversible shuttling of electrons and charge balancing ions between an electrochromic thin film and a transparent counter electrode. The ion transport takes place via a solid electrolyte. Charge transport is evoked by a voltage applied between transparent electrical conductors surrounding the electrochromic film/electrolyte/counter electrode stack. This review summarizes recent progress concerning: (i) calculated optical properties of crystalline WO3, (ii) electrochromic properties of heavily disordered W oxide and oxyfluoride films produced by reactive magnetron bias sputtering, (iii) novel transparent reactively sputter-deposited Zr-Ce oxide counter electrodes and (iv) a new proton-conducting antimonic-acid-based polymer electrolyte. Special in depth presentations are given on elastic light scattering from W-oxide-based films and of electronic band structure effects affecting opto-chronopotentiometry data in Zr-Ce oxide. The review also contains some new device data for an electrochromic smart window capable of very high optical transmittance.Electrochromic smart windows are able to vary their throughput of radiant energy by low-voltage electrical pulses. This function is caused by reversible shuttling of electrons and charge balancing ions between an electrochromic thin film and a transparent counter electrode. The ion transport takes place via a solid electrolyte. Charge transport is evoked by a voltage applied between transparent electrical conductors surrounding the electrochromic film/electrolyte/counter electrode stack. This review summarizes recent progress concerning: (i) calculated optical properties of crystalline WO3, (ii) electrochromic properties of heavily disordered W oxide and oxyfluoride films produced by reactive magnetron bias sputtering, (iii) novel transparent reactively sputter-deposited Zr-Ce oxide counter electrodes and (iv) a new proton-conducting antimonic-acid-based polymer electrolyte. Special in depth presentations are given on elastic light scattering from W-oxide-based films and of electronic band structure effects affecting opto-chronopotentiometry data in Zr-Ce oxide. The review also contains some new device data for an electrochromic smart window capable of very high optical transmittance.
74.	Guerova, G., et al. (författare) Advanced Global Navigation Satellite Systems Tropospheric Products for Monitoring Severe Weather Events and Climate (GNSS4SWEC) 2013 Ingår i: 4th International Colloquium Scientific and Fundamental Aspects of the Galileo Programme. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Global Navigation Satellite Systems (GNSS) have revolutionised positioning, navigation, and timing, becominga common part of our everyday life. Aside from these well-known civilian and commercial applications, GNSS is now an established atmospheric observing system which can accurately sense water vapour, the most abundant greenhouse gas, accounting for 60-70 % of atmospheric warming. Water vapour is under-sampled in the current meteorological and climate observing systems, obtaining and exploiting more high-quality humidity observations is essential to weather forecasting and climate monitoring. The European COST Action ES1206 ”Advanced Global Navigation Satellite Systems tropospheric products for monitoring severe weather eventsand climate (GNSS4SWEC)” will address new and improvedcapabilities from concurrent developments in both the GNSS and the meteorological communities. For the first time, the synergy of the three GNSS systems (GPS, GLONASS and Galileo) will be used to develop new, advanced tropospheric products, exploiting the full potential of multi-GNSS water vapour estimates on a wide range of temporal and spatial scales, from real-time monitoring and forecasting of severe weather, to climate research. In addition, the COST Action ES1206 will promote the use of meteorological data in GNSS positioning, navigation, and timing services and it will stimulate knowledge transfer and data sharing throughout Europe.
75.	Guerova, G., et al. (författare) Review of the state of the art and future prospects of the ground-based GNSS meteorology in Europe 2016 Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:11, s. 5385-5406 Forskningsöversikt (refereegranskat)abstract Global navigation satellite systems (GNSSs) have revolutionised positioning, navigation, and timing, becoming a common part of our everyday life. Aside from these well-known civilian and commercial applications, GNSS is now an established atmospheric observing system, which can accurately sense water vapour, the most abundant greenhouse gas, accounting for 60-70% of atmospheric warming. In Europe, the application of GNSS in meteorology started roughly two decades ago, and today it is a well-established field in both research and operation. This review covers the state of the art in GNSS meteorology in Europe. The advances in GNSS processing for derivation of tropospheric products, application of GNSS tropospheric products in operational weather prediction and application of GNSS tropospheric products for climate monitoring are discussed. The GNSS processing techniques and tropospheric products are reviewed. A summary of the use of the products for validation and impact studies with operational numerical weather prediction (NWP) models as well as very short weather prediction (nowcasting) case studies is given. Climate research with GNSSs is an emerging field of research, but the studies so far have been limited to comparison with climate models and derivation of trends. More than 15 years of GNSS meteorology in Europe has already achieved outstanding cooperation between the atmospheric and geodetic communities. It is now feasible to develop next-generation GNSS tropospheric products and applications that can enhance the quality of weather forecasts and climate monitoring. This work is carried out within COST Action ES1206 advanced global navigation satellite systems tropospheric products for monitoring severe weather events and climate (GNSS4SWEC, http://gnss4swec.knmi.nl).
76.	Gugliotta, L., et al. (författare) Treatment Of Essential Thrombocythaemia In Europe : An Observational Study Of 3649 High-Risk Patients In Exels 2015 Ingår i: Haematologica. - St Orsola Malpighi Hosp, Dept Hematol, L&A Seragnoli, Bologna, Italy. Univ Bari, Hematol Transplantat, Bari, Italy. Osped Maggiore della Carita, Novara, Italy. IRCCS Casa Sollievo Sofferenza, Div Ematol, San Giovanni Rotondo, FG, Italy. Arcispedale S Maria Nuova, Reggio Emilia, Italy. Hop St Louis, APHP, Ctr Invest Clin, Paris, France. Hosp del Mar IMIM, Dept Hematol, Barcelona, Spain. Johannes Wesling Med Ctr, Hematol & Oncol, Minden, Germany. Guys & St Thomas NHS Fdn Trust, Dept Haematol, London, England. Shire Pharmaceut, Global Biometr, Wayne, NJ USA. Shire Int GmbH, Res & Dev, Zug, Switzerland. Uppsala Univ, Dept Haematol, Uppsala, Sweden.. - 0390-6078 .- 1592-8721. ; 38, s. 216-216 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
77.	Halme, P., et al. (författare) Challenges of ecological restoration : Lessons from forests in northern Europe 2013 Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207 .- 1873-2917. ; 167, s. 248-256 Forskningsöversikt (refereegranskat)abstract The alarming rate of ecosystem degradation has raised the need for ecological restoration throughout different biomes and continents. North European forests may appear as one of the least vulnerable ecosystems from a global perspective, since forest cover is not rapidly decreasing and many ecosystem services remain at high level. However, extensive areas of northern forests are heavily exploited and have lost a major part of their biodiversity value. There is a strong requirement to restore these areas towards a more natural condition in order to meet the targets of the Convention on Biological Diversity. Several northern countries are now taking up this challenge by restoring forest biodiversity with increasing intensity. The ecology and biodiversity of boreal forests are relatively well understood making them a good model for restoration activities in many other forest ecosystems. Here we introduce northern forests as an ecosystem, discuss the historical and recent human impact and provide a brief status report on the ecological restoration projects and research already conducted there. Based on this discussion, we argue that before any restoration actions commence, the ecology of the target ecosystem should be established with the need for restoration carefully assessed and the outcome properly monitored. Finally, we identify the most important challenges that need to be solved in order to carry out efficient restoration with powerful and long-term positive impacts on biodiversity: coping with unpredictability, maintaining connectivity in time and space, assessment of functionality, management of conflicting interests and social restrictions and ensuring adequate funding. © 2013 Elsevier Ltd.
78.	Hanbouch, L., et al. (författare) Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic A beta Peptides 2022 Ingår i: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 59, s. 7056-7073 Tidskriftsartikel (refereegranskat)abstract Excess brain cholesterol is strongly implicated in the pathogenesis of Alzheimer's disease (AD). Here we evaluated how the presence of a cholesterol-binding site (CBS) in the transmembrane and juxtamembrane regions of the amyloid precursor protein (APP) regulates its processing. We generated nine point mutations in the APP gene, changing the charge and/or hydrophobicity of the amino-acids which were previously shown as part of the CBS. Most mutations triggered a reduction of amyloid-beta peptides A beta 40 and A beta 42 secretion from transiently transfected HEK293T cells. Only the mutations at position 28 of A beta in the APP sequence resulted in a concomitant significant increase in the production of shorter A beta peptides. Mass spectrometry (MS) confirmed the predominance of A beta x-33 and A beta x-34 with the APP(K28A) mutant. The enzymatic activity of alpha-, beta-, and gamma-secretases remained unchanged in cells expressing all mutants. Similarly, subcellular localization of the mutants in early endosomes did not differ from the APP(WT) protein. A transient increase of plasma membrane cholesterol enhanced the production of A beta 40 and A beta 42 by APP(WT), an effect absent in APP(K28A) mutant. Finally, WT but not CBS mutant A beta derived peptides bound to cholesterol-rich exosomes. Collectively, the present data revealed a major role of juxtamembrane amino acids of the APP CBS in modulating the production of toxic A beta species. More generally, they underpin the role of cholesterol in the pathophysiology of AD.
79.	Hanly, J G, et al. (författare) Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis 2008 Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:3, s. 843-853 Tidskriftsartikel (refereegranskat)abstract Objective. To examine, in an inception cohort of systemic lupus erythematosus (SLE) patients, the association between neuropsychiatric (NP) events and anti-ribosomal P (anti-P), antiphospholipid (lupus anticoagulant [LAC], anticardiolipin), anti-beta 2-glycoprotein I, and anti-NR2 glutamate receptor antibodies. Methods. NP events were identified using the American College of Rheumatology case definitions and clustered into central/peripheral and diffuse/focal events. Attribution of NP events to SLE was determined using decision rules of differing stringency. Autoantibodies were measured without knowledge of NP events or their attribution. Results. Four hundred twelve patients were studied (87.4% female; mean +/- SD age 34.9 +/- 13.5 years, mean +/- SD disease duration 5.0 +/- 4.2 months). There were 214 NP events in 133 patients (32.3%). The proportion of NP events attributed to SLE varied from 15% to 36%. There was no association between autoantibodies and NP events overall. However, the frequency of anti-P antibodies in patients with central NP events attributed to SLE was 4 of 20 (20%), versus 3 of 107 (2.8%) in patients with other NP events and 24 of 279 (8.6%) in those with no NP events (P = 0.04). Among patients with diffuse NP events, 3 of 11 had anti-P antibodies (27%), compared with 4 of 111 patients with other NP events (3.6%) and 24 of 279 of those with no NP events (8.6%) (P 0.02). Specific clinical-serologic associations were found between anti-P and psychosis attributed to SLE (P = 0.02) and between LAC and cerebrovascular disease attributed to SLE (P = 0.038). There was no significant association between other autoantibodies and NP events. Conclusion. Clinically distinct NP events attributed to SLE and occurring around the time of diagnosis were found to be associated with anti-P antibodies and LAC. This Suggests that there are different autoimmune pathogenetic mechanisms, although low sensitivity limits the clinical application of testing for these antibodies.
80.	Hanly, John G., et al. (författare) Headache in Systemic Lupus Erythematosus Results From a Prospective, International Inception Cohort Study 2013 Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 65:11, s. 2887-2897 Tidskriftsartikel (refereegranskat)abstract ObjectiveTo examine the frequency and characteristics of headaches and their association with global disease activity and health-related quality of life (HRQOL) in patients with systemic lupus erythematosus (SLE). MethodsA disease inception cohort was assessed annually for headache (5 types) and 18 other neuropsychiatric (NP) events. Global disease activity scores (SLE Disease Activity Index 2000 [SLEDAI-2K]), damage scores (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI]), and Short Form 36 (SF-36) mental and physical component summary scores were collected. Time to first headache and associations with SF-36 scores were analyzed using Cox proportional hazards and linear regression models with generalized estimating equations. ResultsAmong the 1,732 SLE patients enrolled, 89.3% were female and 48.3% were white. The mean SD age was 34.6 +/- 13.4 years, duration of disease was 5.6 +/- 5.2 months, and length of followup was 3.8 +/- 3.1 years. At enrollment, 17.8% of patients had headache (migraine [60.7%], tension [38.6%], intractable nonspecific [7.1%], cluster [2.6%], and intracranial hypertension [1.0%]). The prevalence of headache increased to 58% after 10 years. Only 1.5% of patients had lupus headache, as identified in the SLEDAI-2K. In addition, headache was associated with other NP events attributed to either SLE or non-SLE causes. There was no association of headache with SLEDAI-2K scores (without the lupus headache variable), SDI scores, use of corticosteroids, use of antimalarials, use of immunosuppressive medications, or specific autoantibodies. SF-36 mental component scores were lower in patients with headache compared with those without headache (mean +/- SD 42.5 +/- 12.2 versus 47.8 +/- 11.3; P < 0.001), and similar differences in physical component scores were seen (38.0 +/- 11.0 in those with headache versus 42.6 +/- 11.4 in those without headache; P < 0.001). In 56.1% of patients, the headaches resolved over followup. ConclusionHeadache is frequent in SLE, but overall, it is not associated with global disease activity or specific autoantibodies. Although headaches are associated with a lower HRQOL, the majority of headaches resolve over time, independent of lupus-specific therapies.
81.	Hanly, J. G., et al. (författare) Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus - An international inception cohort study 2007 Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 56:1, s. 265-273 Tidskriftsartikel (refereegranskat)abstract Objective. To describe the prevalence, characteristics, attribution, and clinical significance of neuropsychiatric (NP) events in an international inception cohort of systemic lupus erythematosus (SLE) patients. Methods. The study was conducted by the Systemic Lupus International Collaborating Clinics (SLICC). Patients were enrolled within 15 months of fulfilling the American College of Rheumatology (ACR) SLE classification criteria. All NP events within a predefined enrollment window were identified using the ACR case definitions of 19 NP syndromes. Decision rules were derived to determine the proportion of NP disease attributable to SLE. Clinical significance was determined using the Short Form 36 (SF-36) Health Survey and the SLICC/ACR Damage Index (SDI). Results. A total of 572 patients (88% female) were recruited, with a mean +/- SD age of 35 +/- 14 years. The mean +/- SD disease duration was 5.2 +/- 4.2 months. Within the enrollment window, 158 of 572 patients (28%) had at least 1 NP event. In total, there were 242 NP events that encompassed 15 of 19 NP syndromes. The proportion of NP events attributed to SLE varied from 19% to 38% using alternate attribution models and occurred in 6.1-11.7% of patients. Those with NP events, regardless of attribution, had lower scores on the SF-36 and higher SDI scores compared with patients with no NP events. Conclusion. Twenty-eight percent of SLE patients experienced at least 1 NP event around the time of diagnosis of SLE, of which only a minority were attributed to SLE. Regardless of attribution, the occurrence of NP events was associated with reduced quality of life and increased organ damage.
82.	Hanly, J. G., et al. (författare) Short-term outcome of neuropsychiatric events in systemic lupus erythematosus upon enrollment into an international inception cohort study 2008 Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 59:5, s. 721-729 Tidskriftsartikel (refereegranskat)abstract Objective. To determine the short-term outcome of neuropsychiatric (NP) events upon enrollment into an international inception cohort of patients with systemic lupus erythematosus (SLE). Methods. The study was performed by the Systemic Lupus International Collaborating Clinics. Patients were enrolled within 15 months of SLE diagnosis and NP events were characterized using the American College of Rheumatology case definitions. Decision rules were derived to identify NP events attributable to SLE. Physician outcome scores of NP events and patient-derived mental component summary (MCS) and physical component summary (PCS) scores of the Short Form 36 were recorded. Results. There were 890 patients (88.7% female) with a mean +/- SD age of 33.8 +/- 13.4 years and mean disease duration of 5.3 +/- 4.2 months. Within the enrollment window, 271 (33.5%) of 890 patients had at least 1 NP event encompassing 15 NP syndromes. NP events attributed to SLE varied from 16.5% to 33.9% using alternate attribution models and occurred in 6.0-11.5% of patients. Outcome scores for NP events attributed to SLE were significantly better than for NP events due to non-SLE causes. Higher global disease activity was associated with worse outcomes. MCS scores were lower in patients with NP events, regardless of attribution, and were also lower in patients with diffuse and central NP events. There was a significant association between physician outcome scores and patient MCS scores only for NP events attributed to SLE. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events. Conclusion. In SLE patients, the short-term outcome of NP events is determined by both the characteristics and attribution of the events.
83.	Hanly, John G, et al. (författare) The frequency and outcome of lupus nephritis: results from an international inception cohort study. 2015 Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 55:2, s. 252-262 Tidskriftsartikel (refereegranskat)abstract To determine nephritis outcomes in a prospective multi-ethnic/racial SLE inception cohort.
84.	Hardarson, Johann P. P., et al. (författare) Appraisals of Social Trauma and Their Role in the Development of Post-Traumatic Stress Disorder and Social Anxiety Disorder 2023 Ingår i: Behavioral Sciences. - : MDPI. - 2076-328X. ; 13:7 Tidskriftsartikel (refereegranskat)abstract Cognitive theories of post-traumatic stress disorder (PTSD) feature appraisal of trauma as a critical factor in the development and maintenance of the disorder. Here we explored appraisals of social trauma (severe rejection or humiliation). Participants were outpatients with social anxiety disorder (SAD) and clinically significant PTSD symptoms (PTSS) after social trauma (n = 15); two clinical control groups of either SAD (n = 32) or obsessive-compulsive disorder (OCD; n = 13); and a control group with no diagnoses (n = 38). Measures included a clinical interview to assess social trauma and related open-ended appraisals and the Posttraumatic Cognitions Inventory (PTCI). Raters blind to group assignment performed content analyses of appraisals. Results showed that the PTSS group scored significantly higher than either clinical group on the PTCI SELF subscale. Only the SELF subscale predicted a diagnosis of both PTSS and SAD. All but one PTSS participant reported primarily negative beliefs about their social trauma, and the most common categories were flawed self and others are critical or cruel. Post-traumatic appraisals implicated in the course of PTSD are significant in how individuals respond to social trauma, with negative self-cognitions linked to both PTSS and SAD.
85.	Helgadottir, Anna, et al. (författare) The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm 2008 Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224 Tidskriftsartikel (refereegranskat)abstract Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
86.	Henriksson, Gunnar, et al. (författare) A critical review of cellobiose dehydrogenases 2000 Ingår i: Journal of Biotechnology. - : ELSEVIER SCIENCE BV. - 0168-1656 .- 1873-4863. ; 78:2, s. 93-113 Forskningsöversikt (refereegranskat)abstract Cellobiose dehydrogenase (CDH) is an extracellular enzyme produced by various wood-degrading fungi. It oxidizes soluble cellodextrins, mannodextrins and lactose efficiently to their corresponding lactones by a ping-pong mechanism using a wide spectrum of electron accepters including quinones, phenoxyradicals, Fe3+, Cu2+ and tiiodide ion. Monosaccharides, maltose and molecular oxygen are:poop substrates. CDH that adsorbs strongly and specifically to cellulose carries two prosthetic groups; namely, an FAD and a heme in two different domains that can be separated after limited proteolysis. The FAD-containing fragment carries all known catalytic and cellulose binding properties. One-electron accepters, like ferricyanide, cytochrome c and phenoxy radicals, are, however, reduced more slowly by the FAD-fragment than by the intact enzyme, suggesting that the function of the heme group is to facilitate one-electron transfer. Non-heme forms of CDH have been found in the culture filtrate of some fungi (probably due to the action of fungal proteases) and were for a long time believed to represent a separate enzyme (cellobiose:quinone oxidoreductase, CBQ). The amino acid sequence of CDH has been determined and no significant homology with other proteins was detected for the heme domain. The FAD-domain sequence belongs to the GMC oxidoreductase family that includes, among others, Aspergillus niger glucose oxidase. The homology is most distinct in regions that correspond to the FAD-binding domain in glucose oxidase. A cellulose-binding domain of the fungal type is present in CDH from Myceliophtore thermophila (Sporotrichum thermophile), but in others an internal sequence rich in aromatic amino acid residues has been suggested to be responsible for the cellulose binding. The biological function of CDH is not fully understood, but recent results support a hydroxyl radical-generating mechanism whereby the radical can degrade and modify cellulose, hemicellulose and lignin. CDH has found technical use in highly selective amperometric biosensors and several other applications have been suggested.
87.	Henriksson, Gunnar, et al. (författare) Is cellobiose dehydrogenase from Phanerochaete chrysosporium a lignin degrading enzyme? 2000 Ingår i: Biochimica et Biophysica Acta - Protein Structure and Molecular Enzymology. - 0167-4838 .- 1879-2588. ; 1480:02-jan, s. 83-91 Tidskriftsartikel (refereegranskat)abstract Cellobiose dehydrogenase (CDH) is an extracellular redox enzyme of ping-pong type, i.e. it has separate oxidative and reductive half reactions. Several wood degrading fungi produce CDH, but the biological function of the enzyme is not known with certainty. It can, however, indirectly generate hydroxyl radicals by reducing Fe3+ to Fe2+ and O-2 to H2O2. Hydroxyl radicals are then generated by a Fenton type reaction and they can react with various wood compounds, including lignin. In this work we study the effect of CDH on a non-phenolic lignin model compound (3,4-dimethoxyphenyl glycol). The results indicate that CDH can affect lignins in three important ways. (1) It breaks beta-ethers; (2) it demethoxylates aromatic structures in lignins; (3) it introduces hydroxyl groups in non-phenolic lignins. The gamma-irradiated model compound gave a similar pattern of products as the CDH treated model compound? when the samples were analyzed by HPLC, suggesting that hydroxyl radicals are the active component of the CDH system.
88.	Hilden, L., et al. (författare) Do the extracellular enzymes cellobiose dehydrogenase and manganese peroxidase form a pathway in lignin biodegradation? 2000 Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 477:02-jan, s. 79-83 Tidskriftsartikel (refereegranskat)abstract The extracellular enzyme manganese peroxidase is believed to degrade lignin by a hydrogen peroxide-dependent oxidation of Mn(II) to the reactive species Mn(III) that attacks the lignin, However, Mn(III) is not able to directly oxidise the non-phenolic lignin structures that predominate in native lignin, We show here that pretreatment of a non-phenolic lignin model compound with another extracellular fungal enzyme, cellobiose dehydrogenase, allows the manganese peroxidase system to oxidise this molecule. The mechanism behind this effect is demethoxylation and/or hydroxylation, i.e. conversion of a nonphenolic structure to a phenolic one, mediated by hydroxyl radicals generated by cellobiose dehydrogenase, This suggests that cellobiose dehydrogenase and manganese peroxidase may act in an extracellular pathway in fungal lignin biodegradation, Analytical techniques used in this paper are reverse-phase high-pressure liquid chromatography, gas chromatography connected to mass spectroscopy and UV-visible spectroscopy.
89.	Hossain, M., et al. (författare) Potentiality of intermediate depth aquifer as a source of arsenic and manganese safe tubewells in Bangladesh 2012 Ingår i: Understanding the Geological and Medical Interface of Arsenic, As 2012 - 4th International Congress: Arsenic in the Environment. - : Taylor & Francis Group. - 9780415637633 ; , s. 71-73 Konferensbidrag (refereegranskat)abstract Shallow tubewells excepting those installed in red/off-white sediments are mostly contaminated with high arsenic. Social survey conducted in 96 villages of Matlab, a worse-affected area of Bangladesh, reveals that only 18% of tubewells provide As-safe water. In such a condition, high Manganese in many wells is found to be an additional problem. Based on monitoring in depth-specific piezometers, drinking water wells were installed in intermediate depth aquifer around 120 m. Ninety percent of the wells installed in light grey medium sand, had arsenic concentrations below the Bangladesh standard of 50 ÎŒg/L and manganese was within the previous WHO guideline (0.4 mg/L). Availability of similar sand over this depth range could be targeted by local drillers to tap safe water at a reasonable cost. Replication trials and periodical monitoring are emphasized for validation and sustainability.
90.	Hossain, Mohammad, et al. (författare) Strategic approach for up-scaling safe water access considering hydrogeological suitability and social mapping in Matlab, southeastern Bangladesh 2013 Konferensbidrag (refereegranskat)abstract In recent years, there has been a significant progress in understanding the source and mobilization process, sediment-water interactions, and distributions of arsenic in groundwater environment in Bangladesh. However, the impacts of arsenic mitigation are still very limited. A social survey conducted during 2009-2011 in 96 villages in Matlab revealed that only 18% of total tubewells provide As-safe water. The safe water access also varied between 0 and 90 percent in the region due to lack of knowledge about the local geology and unplanned tubewell development. SASMIT, an initiative of KTH-International Groundwater Arsenic Research Group has developed a method for safe tubewell installation considering hydrogeological suitability, safe water access and other relevant social and demographic information into account.Piezometers installed at 15 locations over an area of 410 km2, using local boring techniques allowed to delineate the hydrostratigraphy, characterize the aquifers in terms of sediment characteristics, water chemistry and hydraulic head distribution, which ultimately led to the identification of the suitable aquifers for tapping safe water. The piezometer locations with safe drinking water quality were then targeted for safe well installation based on the determination of safe buffer distances in a cluster of a few villages (mouzas). Social mapping of all the villages within the mauzas were done using GIS to evaluate the availability of safe water options for a cluster of households (bari). For safe well installations, priority was given to regions with safe water access, greater number of beneficiaries especially in poor households, and easy access to the site from a cluster of households. Through this approach, it was thus possible to make 95% of the newly installed wells As-safe thus scaled up the safe water access upto 40% in some mauzas. Thus the as a strategy to improve safe water access, the SASMIT study recommends investigating the hydrogeological suitability through installation of few piezometers with a minimum effort and based on the results the implementation plan can be made using GIS based social mappings for relatively uniform distribution and to maximize the safe water access.
91.	Hultquist, Gunnar B., et al. (författare) Detection of hydrogen in corrosion of copper in pure water 2008 Ingår i: Int. Corros. Congr.: Corros. Control Serv. Soc.. - 9781615674251 ; , s. 2378-2386 Konferensbidrag (refereegranskat)abstract Copper is generally assumed to be immune to corrosion by water itself. However, this is not supported by any scientific experimental evidence. Corrosion results from 15 years of exposure are presented here. A transition from O 2-consuming to H 2-evolving copper corrosion is concluded, which implies that copper can corrode by water itself. The complex corrosion product contains hydrogen. We have also measured a hydrogen uptake in the copper metal as a result of metallic copper corrosion by water which implies a sample thickness dependence on hydrogen uptake. The results are described in terms of autoionisation of water which offers an explanation why copper corrosion can take place in pure O 2-free water.
92.	Ippolito, A., et al. (författare) Autoantibodies in systemic lupus erythematosus: comparison of historical and current assessment of seropositivity 2011 Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 20:3, s. 250-255 Tidskriftsartikel (refereegranskat)abstract Systemic lupus erythematosus (SLE) is characterized by multiple autoantibodies and complement activation. Recent studies have suggested that anti-nuclear antibody (ANA) positivity may disappear over time in some SLE patients. Anti-double-stranded DNA (dsDNA) antibody titers and complement levels may vary with time and immunosuppressive treatment, while the behavior of anti-extractable nuclear antigen (ENA) over time is less well understood. This study sought to determine the correlation between historical autoantibody tests and current testing in patients with SLE. Three hundred and two SLE patients from the ACR Reclassification of SLE (AROSE) database with both historical and current laboratory data were selected for analysis. The historical laboratory data were compared with the current autoantibody tests done at the reference laboratory and tested for agreement using percent agreement and Kappa statistic. Serologic tests included ANA, anti-dsDNA, anti-Smith, anti-ribonucleoprotein (RNP), anti-Ro, anti-La, rheumatoid factor (RF), C3 and C4. Among those historically negative for immunologic markers, a current assessment of the markers by the reference laboratory generally yielded a low percentage of additional positives (3-13%). However, 6/11 (55%) of those historically negative for ANA were positive by the reference laboratory, and the reference laboratory test also identified 20% more patients with anti-RNP and 18% more with RF. Among those historically positive for immunologic markers, the reference laboratory results were generally positive on the same laboratory test (range 57% to 97%). However, among those with a history of low C3 or C4, the current reference laboratory results indicated low C3 or C4 a low percentage of the time (18% and 39%, respectively). ANA positivity remained positive over time, in contrast to previous studies. Anti-Ro, La, RNP, Smith and anti-dsDNA antibodies had substantial agreement over time, while complement had less agreement. This variation could partially be explained by variability of the historical assays, which were done by local laboratories over varying periods of time. Variation in the results for complement, however, is more likely to be explained by response to treatment. These findings deserve consideration in the context of diagnosis and enrolment in clinical trials. Lupus (2011) 20, 250-255.
93.	Isenberg, D. A., et al. (författare) An assessment of disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and the flare version of SELENA 2011 Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:1, s. 54-59 Tidskriftsartikel (refereegranskat)abstract Aims To compare the British Isles Lupus Assessment Group (BILAG) 2004, the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) flare index (SFI) and physician's global assessment (PGA) in assessing flares of disease activity in patients with systemic lupus erythematosus (SLE). Methods Sixteen patients with active SLE were assessed by a panel of 16 rheumatologists. The order in which the patients were seen was randomised using a 4x4 Latin square design. Each patient's flare status was determined at each assessment using the BILAG 2004 activity index; the SFI and a PGA. A group of five specialists designated each patient into severe, moderate, mild or no flare categories. Results The rate of complete agreement (95% CI) of the four individual examining physicians for any flare versus no flare was 81% (55% to 94%), 75% (49% to 90%) and 75% (49% to 90%) for the BILAG 2004 index, SELENA flare instrument and PGA, respectively. The overall agreement between flare defined by BILAG 2004 and the SFI was 81% and when type of flare was considered was 52%. Intraclass correlation coefficients (95% CI), as a measure of internal reliability, were 0.54 (0.32 to 0.78) for BILAG 2004 flare compared with 0.21 (0.08 to 0.48) for SELENA flare and 0.18 (0.06 to 0.45) for PGA. Severe flare was associated with good agreement between the indices but mild/moderate flare was much less consistent. Conclusions The assessment of flare in patients with SLE is challenging. No flare and severe flare are identifiable but further work is needed to optimise the accurate 'capture' of mild and moderate flares.
94.	Ivanov, Alexander G, et al. (författare) Acclimation to temperature and irradiance modulates PSII charge recombination. 2006 Ingår i: FEBS Letters. - : Wiley. - 0014-5793. ; 580:11, s. 2797-802 Tidskriftsartikel (refereegranskat)abstract Acclimation of wild type and the chlorina F2 mutant of barley to either high light or low temperature results in a 2- to 3-fold increase in non-photochemical quenching which occurred independently of either energy-dependent quenching (qE), xanthophyll cycle-mediated antenna quenching or state transitions. Results of in vivo thermoluminescence measurements used to address this conundrum indicated that excitation pressure regulates the temperature gap for Click to view the MathML source and Click to view the MathML source charge recombinations within photosystem II reaction centers. This is discussed in terms of photoprotection through non-radiative charge recombination.
95.	Ivanov, A G, et al. (författare) Photosynthetic electron transport adjustments in overwintering Scots pine (Pinus sylvestris L.) 2001 Ingår i: Planta. - 0032-0935 .- 1432-2048. ; 213:4, s. 575-585 Tidskriftsartikel (refereegranskat)abstract As shown before [C. Ottander et al. (1995) Planta 197:176-183], there is a severe inhibition of the photosystem (PS) II photochemical efficiency of Scots pine (Pinus sylvestris L.) during the winter. In contrast, the in vivo PSI photochemistry is less inhibited during winter as shown by in vivo measurements of DeltaA(820)/Delta (820) (P700(+)). There was also an enhanced cyclic electron transfer around PSI in winter-stressed needles as indicated by 4-fold faster reduction kinetics of P700(+). The differential functional stability of PSII and PSI was accompanied by a 3.7-fold higher intersystem electron pool size, and a 5-fold increase in the stromal electron pool available for P700(+) reduction. There was also a strong reduction of the QB band in the thermoluminescence glow curve and markedly slower Q-A re-oxidation in needles of winter pine, indicating an inhibition of electron transfer between QA and QB. The data presented indicate that the plastoquinone pool is largely reduced in winter pine, and that this reduced state is likely to be of metabolic rather than photochemical origin. The retention of PSI photochemistry, and the suggested metabolic reduction of the plastoquinone pool in winter stressed needles of Scots pine are discussed in terms of the need for enhanced photoprotection of the needles during the winter and the role of metabolically supplied energy for the recovery of photosynthesis from winter stress in evergreens.
96.	Jadersten, M., et al. (författare) Targeting SAMHD1 with hydroxyurea in first-line cytarabine-based therapy of newly diagnosed acute myeloid leukaemia: Results from the HEAT-AML trial 2022 Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 292:6, s. 925-940 Tidskriftsartikel (refereegranskat)abstract Background Treatment of newly diagnosed acute myeloid leukaemia (AML) is based on combination chemotherapy with cytarabine (ara-C) and anthracyclines. Five-year overall survival is below 30%, which has partly been attributed to cytarabine resistance. Preclinical data suggest that the addition of hydroxyurea potentiates cytarabine efficacy by increasing ara-C triphosphate (ara-CTP) levels through targeted inhibition of SAMHD1. Objectives In this phase 1 trial, we evaluated the feasibility, safety and efficacy of the addition of hydroxyurea to standard chemotherapy with cytarabine/daunorubicin in newly diagnosed AML patients. Methods Nine patients were enrolled and received at least two courses of ara-C (1 g/m(2)/2 h b.i.d. d1-5, i.e., a total of 10 g/m(2) per course), hydroxyurea (1-2 g d1-5) and daunorubicin (60 mg/m(2) d1-3). The primary endpoint was safety; secondary endpoints were complete remission rate and measurable residual disease (MRD). Additionally, pharmacokinetic studies of ara-CTP and ex vivo drug sensitivity assays were performed. Results The most common grade 3-4 toxicity was febrile neutropenia (100%). No unexpected toxicities were observed. Pharmacokinetic analyses showed a significant increase in median ara-CTP levels (1.5-fold; p = 0.04) in patients receiving doses of 1 g hydroxyurea. Ex vivo, diagnostic leukaemic bone marrow blasts from study patients were significantly sensitised to ara-C by a median factor of 2.1 (p = 0.0047). All nine patients (100%) achieved complete remission, and all eight (100%) with validated MRD measurements (flow cytometry or real-time quantitative polymerase chain reaction [RT-qPCR]) had an MRD level <0.1% after two cycles of chemotherapy. Treatment was well-tolerated, and median time to neutrophil recovery >1.0 x 10(9)/L and to platelet recovery >50 x 10(9)/L after the start of cycle 1 was 19 days and 22 days, respectively. Six of nine patients underwent allogeneic haematopoietic stem-cell transplantation (allo-HSCT). With a median follow-up of 18.0 (range 14.9-20.5) months, one patient with adverse risk not fit for HSCT experienced a relapse after 11.9 months but is now in second complete remission. Conclusion Targeted inhibition of SAMHD1 by the addition of hydroxyurea to conventional AML therapy is safe and appears efficacious within the limitations of the small phase 1 patient cohort. These results need to be corroborated in a larger study.
97.	Jarbo, Caroline, et al. (författare) Detailed assessment of chromosome 22 aberrations in sporadic pheochromocytoma using array-CGH. 2006 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 118:5, s. 1159-64 Tidskriftsartikel (refereegranskat)abstract Pheochromocytoma is a predominantly sporadic neuroendocrine tumor derived from the adrenal medulla. Previous low resolution LOH and metaphase-CGH studies reported the loss of chromosomes 1p, 3q, 17p and 22q at various frequencies. However, the molecular mechanism(s) behind development of sporadic pheochromocytoma remains largely unknown. We have applied high-resolution tiling-path microarray-CGH with the primary aim to characterize copy number imbalances affecting chromosome 22 in 66 sporadic pheochromocytomas. We detected copy number alterations on 22q at a frequency of 44%. The predominant finding was monosomy 22 (30%), followed by terminal deletions in 8 samples (12%) and a single interstitial deletion. We further applied a chromosome 1 tiling-path array in 7 tumors with terminal deletions of 22q and found deletions of 1p in all cases. Our overall results suggest that at least 2 distinct regions on both 22q and 1p are important in the tumorigenesis of sporadic pheochromocytoma. A large proportion of pheochromocytomas also displayed indications of cellular heterogeneity. Our study is to our knowledge the first array-CGH study of sporadic pheochromocytoma. Future analysis of this tumor type should preferably be performed in the context of the entire human genome using genome-wide array-CGH, which is a superior methodological approach. Supplemental material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.htm
98.	Johansson, Fredrik, et al. (författare) Effects of albuterol enantiomers on in vitro bronchial reactivity 1996 Ingår i: Clinical reviews in allergy and immunology. - 1080-0549 .- 1559-0267. ; 14:1, s. 57-64 Tidskriftsartikel (refereegranskat)
99.	Jonsson, Bengt Gunnar, 1963-, et al. (författare) Skogspolitiken hotar biologiska mångfalden 2008 Ingår i: Dagens nyheter (DN debatt). - 1101-2447. Tidskriftsartikel (populärvet., debatt m.m.)
100.	Lapointe, Catherine, et al. (författare) Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model 2023 Ingår i: Journal of the American Heart Association. - : Wolters Kluwer. - 2047-9980. ; 12:4 Tidskriftsartikel (refereegranskat)abstract Background: Deep vein thrombosis (DVT) is the primary cause of pulmonary embolism and the third most life-threatening cardiovascular disease in North America. Post-DVT anticoagulants, such as warfarin, heparin, and direct oral anticoagulants, reduce the incidence of subsequent venous thrombi. However, all currently used anticoagulants affect bleeding time at various degrees, and there is therefore a need for improved therapeutic regimens in DVT. It has recently been shown that mast cells play a crucial role in a DVT murine model. The underlying mechanism involved in the prothrombotic properties of mast cells, however, has yet to be identified.Methods and Results: C57BL/6 mice and mouse mast cell protease-4 (mMCP-4) genetically depleted mice (mMCP-4 knockout) were used in 2 mouse models of DVT, partial ligation (stenosis) and ferric chloride-endothelial injury model of the inferior vena cava. Thrombus formation and impact of genetically repressed or pharmacologically (specific inhibitor TY-51469) inhibited mMCP-4 were evaluated by morphometric measurements of thrombi immunochemistry (mouse and human DVT), color Doppler ultrasound, bleeding times, and enzymatic activity assays ex vivo. Recombinant chymases, mMCP-4 (mouse) and CMA-1 (human), were used to characterize the interaction with murine and human plasmin, respectively, by mass spectrometry and enzymatic activity assays. Inhibiting mast cell-generated mMCP-4, genetically or pharmacologically, resolves and prevents venous thrombus formation in both DVT models. Inferior vena cava blood flow obstruction was observed in the stenosis model after 6 hours of ligation, in control- but not in TY-51469-treated mice. In addition, chymase inhibition had no impact on bleeding times of healthy or DVT mice. Furthermore, endogenous chymase limits plasmin activity in thrombi ex vivo. Recombinant mouse or human chymase degrades/inactivates purified plasmin in vitro. Finally, mast cell-containing immunoreactive chymase was identified in human DVT.Conclusions: This study identified a major role for mMCP-4, a granule-localized protease of chymase type, in DVT formation. These findings support a novel pharmacological strategy to resolve or prevent DVT without affecting the coagulation cascade through the inhibition of chymase activity.

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