| 1. |
- Bécoulet, A., et al.
(författare)
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Science and technology research and development in support to ITER and the Broader Approach at CEA
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10
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Tidskriftsartikel (refereegranskat)abstract
- In parallel to the direct contribution to the procurement phase of ITER and Broader Approach, CEA has initiated research & development programmes, accompanied by experiments together with a significant modelling effort, aimed at ensuring robust operation, plasma performance, as well as mitigating the risks of the procurement phase. This overview reports the latest progress in both fusion science and technology including many areas, namely the mitigation of superconducting magnet quenches, disruption-generated runaway electrons, edge-localized modes (ELMs), the development of imaging surveillance, and heating and current drive systems for steady-state operation. The WEST (W Environment for Steady-state Tokamaks) project, turning Tore Supra into an actively cooled W-divertor platform open to the ITER partners and industries, is presented.
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| 8. |
- Wiegell, S. R., et al.
(författare)
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A randomized, multicentre study of directed daylight exposure times of 11/2 vs. 21/2 h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp
- 2011
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 164:5, s. 1083-1090
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Tidskriftsartikel (refereegranskat)abstract
- Background Vascular endothelial growth factor (VEGF)-A, placenta growth factor (PlGF) and their corresponding membrane receptors are involved in autocrine and paracrine regulation of melanoma growth and metastasis. Besides the membrane receptors, a soluble form of the VEGF receptor (VEGFR)-1 (sVEGFR-1) has been identified, that behaves both as a decoy receptor, sequestering VEGF-A and PlGF, and as an extracellular matrix (ECM) molecule, promoting endothelial cell adhesion and migration through the interaction with alpha 5 beta 1 integrin. Objectives To analyse whether sVEGFR-1 plays a role during melanoma progression. Methods sVEGFR-1 expression was evaluated in a panel of 36 melanoma cell lines and 11 primary human melanocyte cultures by quantitative real-time polymerase chain reaction analysis and in specimens of primary or metastatic melanoma lesions from 23 patients by immunohistochemical analysis. Results sVEGFR-1 expression was highly upregulated in melanoma cell lines with respect to human melanocytes. Interestingly, cell lines obtained from cutaneous metastases showed a significant reduction of sVEGFR-1 expression, as compared with cell lines derived from primary tumours. These results were confirmed by immunohistochemical analysis of sections from primary skin melanomas and the corresponding cutaneous metastases, suggesting that modulation of sVEGFR-1 expression influences ECM invasion by melanoma cells and metastasis localization. Moreover, we provide evidence that adhesion of melanoma cells to sVEGFR-1 is favoured by the activation of a VEGF-A/VEGFR-2 autocrine loop. Conclusions Our data strongly suggest that sVEGFR-1 plays a role in melanoma progression and that low sVEGFR-1/VEGF-A and sVEGFR-1/transmembrane VEGFR-1 ratios might predict a poor outcome in patients with melanoma.
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| 9. |
- Wiegell, S. R., et al.
(författare)
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Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp : a randomized multicentre study
- 2012
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 166:6, s. 1327-1332
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Tidskriftsartikel (refereegranskat)abstract
- Background Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight-mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)-PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field-cancerized treatment area. Objectives In a randomized multicentre study to evaluate efficacy of daylight-mediated PDT for different severity grades of AKs. Methods One hundred and forty-five patients with a total of 2768 AKs (severity grades I-III) of the face and scalp were randomized to either 1 1/2 or 2 1/2 h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist-borne dosimeter. Results No difference in lesion response was found between the 1 1/2 and 2 1/2 h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75.9%) than in grade II (61.2%) and grade III (49.1%) lesions (P < 0.0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow-up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3.5 J cm(-2). Conclusions Daylight-mediated PDT of moderate to thick AKs was less effective than daylight-mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight-mediated PDT.
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| 10. |
- Ingelsson, Erik, et al.
(författare)
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Detailed Physiologic Characterization Reveals Diverse Mechanisms for Novel Genetic Loci Regulating Glucose and Insulin Metabolism in Humans
- 2010
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Ingår i: Diabetes. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Konferensbidrag (refereegranskat)abstract
- OBJECTIVE-Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS-We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS-The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS-Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes. Diabetes 59:1266-1275, 2010
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| 11. |
- Ingelsson, Erik, et al.
(författare)
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Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans
- 2010
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 59:5, s. 1266-1275
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Recent genome-wide association studies have revealed loci associated with glucose and insulin-related traits. We aimed to characterize 19 such loci using detailed measures of insulin processing, secretion, and sensitivity to help elucidate their role in regulation of glucose control, insulin secretion and/or action. RESEARCH DESIGN AND METHODS We investigated associations of loci identified by the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) with circulating proinsulin, measures of insulin secretion and sensitivity from oral glucose tolerance tests (OGTTs), euglycemic clamps, insulin suppression tests, or frequently sampled intravenous glucose tolerance tests in nondiabetic humans (n = 29,084). RESULTS The glucose-raising allele in MADD was associated with abnormal insulin processing (a dramatic effect on higher proinsulin levels, but no association with insulinogenic index) at extremely persuasive levels of statistical significance (P = 2.1 x 10(-71)). Defects in insulin processing and insulin secretion were seen in glucose-raising allele carriers at TCF7L2, SCL30A8, GIPR, and C2CD4B. Abnormalities in early insulin secretion were suggested in glucose-raising allele carriers at MTNR1B, GCK, FADS1, DGKB, and PROX1 (lower insulinogenic index; no association with proinsulin or insulin sensitivity). Two loci previously associated with fasting insulin (GCKR and IGF1) were associated with OGTT-derived insulin sensitivity indices in a consistent direction. CONCLUSIONS Genetic loci identified through their effect on hyperglycemia and/or hyperinsulinemia demonstrate considerable heterogeneity in associations with measures of insulin processing, secretion, and sensitivity. Our findings emphasize the importance of detailed physiological characterization of such loci for improved understanding of pathways associated with alterations in glucose homeostasis and eventually type 2 diabetes.
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| 13. |
- Hoppe, Torborg, et al.
(författare)
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X-linked recessive ichthyosis : an impaired barrier function evokes limited gene responses before and after moisturizing treatments
- 2012
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 0007-0963 .- 1365-2133. ; 167:3, s. 514-522
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Tidskriftsartikel (refereegranskat)abstract
- Background X-linked recessive ichthyosis (XLRI) is due to deletions or inactivating mutations in the steroid sulfatase (STS) gene. This results in an accumulation of cholesterol sulphate affecting the packing of intercorneocyte lipids. XLRI is characterized by dry, scaly skin and increased skin barrier permeability; patients are often dependent on daily use of moisturizers.Objectives To examine the biophysical and molecular changes in the skin of patients with XLRI compared with healthy volunteers, and to analyse the effects of moisturizers on the patients' barrier function.Methods Patients with XLRI (n = 14) and healthy controls (n = 14) were included in the study. Skin dryness score, transepidermal water loss (TEWL) and skin surface pH were monitored at baseline, and punch biopsies were obtained for mRNA expression profiles determined by oligonucleotide arrays. Measurements were repeated in the patients with XLRI after a 4-week treatment with three different moisturizers on the volar forearms. Results Patients with XLRI showed, compared with healthy controls, increased dryness and TEWL, equal skin pH and altered expression of 27 genes. There were no signs of activation of inflammation or repair pathways. Five selected genes were significantly altered also on quantitative polymerase chain reaction analysis. Treatment with the moisturizers showed similar effects: they improved skin dryness but had no effect on TEWL, pH or expression of selected genes.Conclusions Despite a dysfunctional skin barrier, the limited number of genes altered in XLRI skin suggests that no inflammatory or repair mechanisms are triggered. Treatment with moisturizers does not have any major impact on the skin barrier properties of patients with XLRI.
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| 14. |
- Hoseiny, Seyyed Mohammad Hamed, 1980, et al.
(författare)
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The effect of the martensitic packet size on the machinability of modified AISI P20 prehardened mold steel
- 2012
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Ingår i: Journal of Materials Science. - : Springer Science and Business Media LLC. - 0022-2461 .- 1573-4803. ; 47:8, s. 3613-3620
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Tidskriftsartikel (refereegranskat)abstract
- The effect of martensitic packet size on the machinability of prehardened mold steel at a hardness of similar to 40 HRC (typical hardness for prehardened mold steels) was studied in terms of cutting force and tool life. The machinability tests were performed in end milling using coated, cemented carbide tools at three different cutting speeds. The results showed that an increase in the martensite packet size led to higher cutting force and shorter tool life. The increase in cutting force was related to the increase of work hardening. The work material with a coarser martensite packet size showed a higher amount of work hardening that can explain the higher cutting force. The longer tool life in the workpieces with finer structure was correlated to smaller amplitude of the variation in cutting force.
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| 15. |
- Menesini, E., et al.
(författare)
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Cyberbullying Definition Among Adolescents: A Comparison Across Six European Countries
- 2012
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Ingår i: Cyberpsychology Behavior and Social Networking. - : Mary Ann Liebert Inc. - 2152-2715 .- 2152-2723. ; 15:9, s. 455-463
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Tidskriftsartikel (refereegranskat)abstract
- Several criteria have been proposed for defining cyberbullying to young people, but no studies have proved their relevance. There are also variations across different countries in the meaning and the definition of this behavior. We systematically investigated the role of five definitional criteria for cyberbullying, in six European countries. These criteria (intentionality, imbalance of power, repetition, anonymity, and public vs. private) were combined through a set of 32 scenarios, covering a range of four types of behaviors (written-verbal, visual, exclusion, and impersonation). For each scenario, participants were asked whether it was cyberbullying or not. A randomized version of the questionnaire was shown to 295 Italian, 610 Spanish, 365 German, 320 Sweden, 336 Estonian, and 331 French adolescents aged 11-17 years. Results from multidimensional scaling across country and type of behavior suggested a clear first dimension characterized by imbalance of power and a clear second dimension characterized by intentionality and, at a lower level, by anonymity. In terms of differences across types of behaviors, descriptive frequencies showed a more ambiguous role for exclusion as a form of cyberbullying, but general support was given to the relevance of the two dimensions across all the types of behavior. In terms of country differences, French participants more often perceived the scenarios as cyberbullying as compared with those in other countries, but general support was found for the relevance of the two dimensions across countries.
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| 16. |
- Perisic, L., et al.
(författare)
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Profiling of atherosclerotic lesions by gene and tissue microarrays reveals pcsk6 as a novel protease in unstable carotid atherosclerosis
- 2013
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 33:10, s. 2432-2443
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - : Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions. APPROACH AND RESULTS - : Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 (P<0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 (P<0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle α-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA. CONCLUSIONS - : Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.
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| 17. |
- Rydén, Lars, et al.
(författare)
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ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:39, s. 3035-3087
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Tidskriftsartikel (refereegranskat)abstract
- This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
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| 18. |
- Troch, Peter A., et al.
(författare)
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The importance of hydraulic groundwater theory in catchment hydrology : The legacy of Wilfried Brutsaert and Jean-Yves Parlange
- 2013
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Ingår i: Water resources research. - : American Geophysical Union (AGU). - 0043-1397 .- 1944-7973. ; 49:9, s. 5099-5116
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Forskningsöversikt (refereegranskat)abstract
- Based on a literature overview, this paper summarizes the impact and legacy of the contributions of Wilfried Brutsaert and Jean-Yves Parlange (Cornell University) with respect to the current state-of-the-art understanding in hydraulic groundwater theory. Forming the basis of many applications in catchment hydrology, ranging from drought flow analysis to surface water-groundwater interactions, hydraulic groundwater theory simplifies the description of water flow in unconfined riparian and perched aquifers through assumptions attributed to Dupuit and Forchheimer. Boussinesq (1877) derived a general equation to study flow dynamics of unconfined aquifers in uniformly sloping hillslopes, resulting in a remarkably accurate and applicable family of results, though often challenging to solve due to its nonlinear form. Under certain conditions, the Boussinesq equation can be solved analytically allowing compact representation of soil and geomorphological controls on unconfined aquifer storage and release dynamics. The Boussinesq equation has been extended to account for flow divergence/convergence as well as for nonuniform bedrock slope (concave/convex). The extended Boussinesq equation has been favorably compared to numerical solutions of the three-dimensional Richards equation, confirming its validity under certain geometric conditions. Analytical solutions of the linearized original and extended Boussinesq equations led to the formulation of similarity indices for baseflow recession analysis, including scaling rules, to predict the moments of baseflow response. Validation of theoretical recession parameters on real-world streamflow data is complicated due to limited measurement accuracy, changing boundary conditions, and the strong coupling between the saturated aquifer with the overlying unsaturated zone. However, recent advances are shown to have mitigated several of these issues. The extended Boussinesq equation has been successfully applied to represent baseflow dynamics in catchment-scale hydrological models, and it is currently considered to represent lateral redistribution of groundwater in land surface schemes applied in global circulation models. From the review, it is clear that Wilfried Brutsaert and Jean-Yves Parlange stimulated a body of research that has led to several fundamental discoveries and practical applications with important contributions in hydrological modeling.
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| 19. |
- Wallström, Sofia, 1988, et al.
(författare)
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CO rotational line emission from a dense knot in Cassiopeia A: Evidence for active post-reverse-shock chemistry
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 558:L2
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Tidskriftsartikel (refereegranskat)abstract
- We report a Herschel detection of high-J rotational CO lines from a dense knot in the supernova remnant Cas A. Based on a combined analysis of these rotational lines and previously observed ro-vibrational CO lines, we find the gas to be warm (two components at ~400 and 2000 K) and dense (1e6−7 cm-3), with a CO column density of ~5e17 cm-2. This, along with the broad line widths (~400 km/s), suggests that the CO emission originates in the post-shock region of the reverse shock. As the passage of the reverse shock dissociates any existing molecules, the CO has most likely reformed in the past several years in the post-shock gas. The CO cooling time is similar to the CO formation time, therefore we discuss possible heating sources (UV photons from the shock front, X-rays, electron conduction) that may maintain the high column density of warm CO.
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| 20. |
- Winge, Mårten C G, et al.
(författare)
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Filaggrin genotype determines functional and molecular alterations in skin of patients with atopic dermatitis and ichthyosis vulgaris
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Several common genetic and environmental disease mechanisms are important for the pathophysiology behind atopic dermatitis (AD). Filaggrin (FLG) loss-of-function is of great significance for barrier impairment in AD and ichthyosis vulgaris (IV), which is commonly associated with AD. The molecular background is, however, complex and various clusters of genes are altered, including inflammatory and epidermal-differentiation genes.OBJECTIVE:The objective was to study whether the functional and molecular alterations in AD and IV skin depend directly on FLG loss-of-function, and whether FLG genotype determines the type of downstream molecular pathway affected.METHODS AND FINDINGS:Patients with AD/IV (n = 43) and controls (n = 15) were recruited from two Swedish outpatient clinics and a Swedish AD family material with known FLG genotype. They were clinically examined and their medical history recorded using a standardized questionnaire. Blood samples and punch biopsies were taken and trans-epidermal water loss (TEWL) and skin pH was assessed with standard techniques. In addition to FLG genotyping, the STS gene was analyzed to exclude X-linked recessive ichthyosis (XLI). Microarrays and quantitative real-time PCR were used to compare differences in gene expression depending on FLG genotype. Several different signalling pathways were altered depending on FLG genotype in patients suffering from AD or AD/IV. Disease severity, TEWL and pH follow FLG deficiency in the skin; and the number of altered genes and pathways are correlated to FLG mRNA expression.CONCLUSIONS:We emphasize further the role of FLG in skin-barrier integrity and the complex compensatory activation of signalling pathways. This involves inflammation, epidermal differentiation, lipid metabolism, cell signalling and adhesion in response to FLG-dependent skin-barrier dysfunction.
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