1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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2. |
- Andersson, Malte, 1941, et al.
(författare)
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”Minskande befolkning är inte problemet”
- 2020
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Ingår i: Dagens Nyheter. ; :1 augusti, DN-debatt
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Nätverket Population Matters Sweden: En uppmärksammad studie i The Lancet pekar mot en lägre befolkningsökning i världen än tidigare prognoser. Men en miljard människor till är fortfarande långt över vad jorden klarar. Befolkningstrenden måste snarare vända neråt, och det kräver åtgärder för att stärka kvinnors rättigheter världen över.
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3. |
- Bergman, Olle, 1978, et al.
(författare)
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Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease?
- 2009
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:3, s. 333-8
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Tidskriftsartikel (refereegranskat)abstract
- The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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4. |
- de Frias, Cindy M., et al.
(författare)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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6. |
- Eriksson, Anders, et al.
(författare)
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Accuracy of death certificates of cardiovascular disease in a community intervention in Sweden.
- 2013
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 41:8, s. 883-889
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim was to investigate the possibility to evaluate the mortality pattern in a community intervention programme against cardiovascular disease by official death certificates.Methods: For all deceased in the intervention area (Norsjö), the accuracy of the official death certificates were compared with matched controls in the rest of Västerbotten. The official causes of death were compared with new certificates, based on the last clinical record, issued by three of the authors, and coded by one of the authors, all four accordingly blinded.Results: The degree of agreement between the official underlying causes of death in "cardiovascular disease" (CVD) and the re-evaluated certificates was not found to differ between Norsjö and the rest of Västerbotten. The agreement was 87% and 88% at chapter level, respectively, but only 55% and 55% at 4-digit level, respectively. The reclassification resulted in a 1% decrease of "cardiovascular deaths" in both Norsjö and the rest of Västerbotten.Conclusions: The disagreements in the reclassification of cause of death were equal but large in both directions. The official death certificates should be used with caution to evaluate CVD in small community intervention programmes, and restricted to the chapter level and total populations.
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9. |
- Eriksson, Jan W., et al.
(författare)
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Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
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Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-1037
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P
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10. |
- Eriksson, Olof, et al.
(författare)
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Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas
- 2014
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:3, s. 460-465
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Tidskriftsartikel (refereegranskat)abstract
- Serotonergic biosynthesis in the endocrine pancreas, of which the islets of Langerhans is the major constituent, has been implicated in insulin release and β cell proliferation. In this study, we investigated the feasibility of quantitative noninvasive imaging of the serotonergic metabolism in the pancreas using the PET tracer (11)C-5-hydroxy-l-tryptophan ((11)C-5-HTP).METHODS: Uptake of (11)C-5-HTP, and its specificity for key enzymes in the serotonergic metabolic pathway, was assessed in vitro (INS-1 and PANC1 cells and human islet and exocrine preparations) and in vivo (nonhuman primates and healthy and diabetic rats).RESULTS: In vitro tracer uptake in endocrine cells (INS-1 and human islets), but not PANC1 and exocrine cells, was mediated specifically by intracellular conversion into serotonin. Pancreatic uptake of (11)C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts (11)C-5-HTP to (11)C-serotonin and increased after inhibition of monoamine oxidase-A, the main enzyme responsible for serotonin degradation. Uptake in the rat pancreas was similarly modulated by inhibition of monoamine oxidase-A and was reduced in animals with induced diabetes.CONCLUSION: The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.
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11. |
- Eriksson, Olof, et al.
(författare)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Tidskriftsartikel (refereegranskat)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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13. |
- Klaric, Lucija, et al.
(författare)
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Mendelian randomisation identifies alternative splicing of the FAS death receptor as a mediator of severe COVID-19.
- 2021
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory. ; , s. 1-28
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Severe COVID-19 is characterised by immunopathology and epithelial injury. Proteomic studies have identified circulating proteins that are biomarkers of severe COVID-19, but cannot distinguish correlation from causation. To address this, we performed Mendelian randomisation (MR) to identify proteins that mediate severe COVID-19. Using protein quantitative trait loci (pQTL) data from the SCALLOP consortium, involving meta-analysis of up to 26,494 individuals, and COVID-19 genome-wide association data from the Host Genetics Initiative, we performed MR for 157 COVID-19 severity protein biomarkers. We identified significant MR results for five proteins: FAS, TNFRSF10A, CCL2, EPHB4 and LGALS9. Further evaluation of these candidates using sensitivity analyses and colocalization testing provided strong evidence to implicate the apoptosis-associated cytokine receptor FAS as a causal mediator of severe COVID-19. This effect was specific to severe disease. Using RNA-seq data from 4,778 individuals, we demonstrate that the pQTL at the FAS locus results from genetically influenced alternate splicing causing skipping of exon 6. We show that the risk allele for very severe COVID-19 increases the proportion of transcripts lacking exon 6, and thereby increases soluble FAS. Soluble FAS acts as a decoy receptor for FAS-ligand, inhibiting apoptosis induced through membrane-bound FAS. In summary, we demonstrate a novel genetic mechanism that contributes to risk of severe of COVID-19, highlighting a pathway that may be a promising therapeutic target.
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16. |
- Shia-Hui, Peng, 1967, et al.
(författare)
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CAA analysis of a wing section with flap side-edges based on hybrid RANS-LES computation
- 2015
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Ingår i: 21st AIAA/CEAS Aeroacoustics Conference, AIAA Aviation. - Reston, Virginia : American Institute of Aeronautics and Astronautics. - 9781624103674
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Konferensbidrag (refereegranskat)abstract
- Based on hybrid RANS-LES computation of the turbulent flow around a double-flapped wing section, CAA (Computational Aero-Acoustics) analysis was conducted using the Curle, the Kirchhoff and the FW-H acoustic analogy methods. The focus was placed on the flow-induced noise due to the flap side-edges (FSE). It was shown that the FSE has triggered extensive unsteady vortex motions and being the most potent noise-generating source with significant pressure fluctuations on the side-edge surface. In the CAA analysis, two integral surfaces, defined by the iso-surface of vorticity magnitude, were verified when using the Kirchhoff and the FW-H methods. The Kirchhoff method is more sensitive to the location of the integral surface. The analysis using the Curle method indicates that the pressure fluctuations on the surface of the main wing and the first flap have made similar contributions to the far-field noise level, while the second flap contributes slightly less. The Kirchhoff and FW-H methods have predicted overall higher noise levels comparing to the Curle method. In the comparison, the result obtained with a stochastic method based on a RANS solution was also involved. The result has clearly demonstrated that, to capture the most potential noise generation in the presence of flap side edges, turbulence-resolving simulations should be incorporated in hybrid CFD/CAA analysis.
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17. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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18. |
- Vimaleswaran, Karani S, et al.
(författare)
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Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study.
- 2014
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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595 .- 2213-8587. ; 2:9, s. 719-29
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Tidskriftsartikel (refereegranskat)abstract
- Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.
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21. |
- Aardal-Eriksson, Elisabeth, et al.
(författare)
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Pre-trauma Salivary Cortisol Levels and General Health Ratings in Relation to Post-trauma Changes in Cortisol and Psychological Distress after UN-service in Bosnia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The psychobiology of post-traumatic distress is known to some extent, however the pre-trauma psychobiology is not. The aims of the present study were to relate pre- and post-trauma salivary cortisol levels and general health to post-traumatic distress in a Swedish UN-battalion in Bosnia.Methods: Salivary 8 AM and I 0 PM cortisol levels and "General Health Questionnaire" ratings were collected from 145 subjects before the six months' mission, at return and two and six months after mission. During follow-up, the ratings were extended by the "Impact of Events Scale" (IES) and "Post Traumatic Symptom Scale".Results: Low pre-trauma morning and evening salivary cortisol levels were statistically significantly related to high scores in all rating scales six months after mission and to increasing IES scores during follow-up. Low morning and high evening post-trauma salivary cortisol levels were related to high ratings of psychological distress six months after missionConclusions: Pre-trauma salivary cortisol levels seem to be related to posttrauma psychological distress, however not to the extent that salivary cortisol levels in a simple way could be used for predictive screening.
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23. |
- Aardal-Eriksson, Elisabeth, et al.
(författare)
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Salivary cortisol, posttraumatic stress symptoms, and general health in the acute phase and during 9-month follow-up
- 2001
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 50:12, s. 986-993
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Tidskriftsartikel (refereegranskat)abstract
- Background: Because traumatic events are unpredictable, there are few studies of psychobiological states immediately following such events. Our study aimed to determine the relation of salivary cortisol to psychologic distress immediately after a traumatic event and then during follow-up.Methods: Measurement of morning and evening salivary cortisol and ratings of psychologic distress (using the Impact of Events Scale [IES], the Post Traumatic Symptom Scale, and the General Health Questionnaire) were performed with 31 United Nations soldiers at three time points—5 days and 2 and 9 months—following a mine accident in Lebanon.Results: Five days after the accident, 15 subjects reported substantial posttraumatic distress according to the IES, as well as significantly lower morning and higher evening cortisol levels compared with the low-impact group. Within 9 months, the posttraumatic distress of the high-impact group was reduced, accompanied by an increase in morning and a decrease in evening cortisol levels. There were significant relationships between evening cortisol and all rating scales at the first and third time points.Conclusions: Subclinical posttraumatic stress following an adverse event can be measured biologically via salivary cortisol levels soon after the event.
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24. |
- Aardal-Eriksson, Elisabeth, et al.
(författare)
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Twelve Months Follow-up of Salivary Cortisol in Relation to Psychological Distress and General Health in Swedish UN-personnel after Severe Combat Exposure during Six Months Mission in Bosnia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Our group has presented evidence of relationships between salivary cortisol levels and psychological distress before, during and after trauma-related stress. The aim of the present study was to confirm the part of evidence of relationships between salivary cortisol and posttraumatic distress and their change over time.Methods: Salivary cortisol levels at 8 AM and 10 PM and self-ratings were collected from 106 subjects six and twelve months after a six months UNmission in Bosnia. The rating instruments were the "Impact of Event Scale" (IES), the "Post Traumatic Symptom Scale" and the "General Health Questionnaire".Results: Significant statistical interactions were found between changes in mean cortisol levels and IES scores over time. Decreasing evening cortisol levels over time were significantly related to decreasing IES scores and vice versa. Morning cortisol levels showed negative, and evening cortisol positive correlations with all rating scores.Conclusions: The evidence from previous studies on trauma related stress, that salivary cortisol is related to the development of posttraumatic stress reactions, the morning cortisol in reverse (negative) direction to that (positive) of evening cortisol, were confirmed.
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25. |
- Aare, Sudhakar, et al.
(författare)
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Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
- 2011
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 43:24, s. 1334-1350
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Tidskriftsartikel (refereegranskat)abstract
- Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.
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26. |
- Aare, Sudhakar, et al.
(författare)
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The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
- 2012
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 44:18, s. 865-877
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Tidskriftsartikel (refereegranskat)abstract
- Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.
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27. |
- Ahmed, Istaq, 1972, et al.
(författare)
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Structural study and proton conductivity in Yb-doped BaZrO3
- 2007
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Ingår i: Solid State Ionics. - 0167-2738. ; 178:(7-10), s. 515-520
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Tidskriftsartikel (refereegranskat)abstract
- Traditional solid state sintering has been used to prepare the perovskite BaZr0.9Yb0.1O3-delta. Analysis of X-ray powder diffraction data shows that an increase of the unit cell parameter, a, was observed compared to undoped BaZrO3. Rietveld analysis of room temperature neutron powder diffraction data confirmed cubic symmetry (space group Pm-3m). Dynamic thermogravimetric analysis (TGA) indicates that the hydration process occurs below 200 degrees C. The strong O-H stretch band, 2500-3500 cm(-1), in the infrared absorbance spectrum clearly manifests the presence of protons in the hydrated material. Proton conductivity was investigated on hydrated and as-prepared samples under dry and wet atmospheres, respectively. Keywords: X-ray diffraction; neutron diffraction; Rietveld refinement; proton conductor; perovskite
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28. |
- Ahmed, Istaq, 1972, et al.
(författare)
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Synthesis and structural characterization of perovskite type proton conducting BaZr1-xInxO3-delta (0.0 <= x <= 0.75)
- 2006
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Ingår i: Solid State Ionics. - : Elsevier BV. - 0167-2738 .- 1872-7689. ; 177:17-18, s. 1395-1403
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Tidskriftsartikel (refereegranskat)abstract
- Solid state sintering has been used to prepare the cubic perovskite structured compounds BaZr1-xInxO3-delta (0.0 <= x <= 0.75). Analysis of X-ray powder diffraction (XRPD) data reveals that the unit cell parameter, a, increases linearly with an increased Indium concentration. XRPD data was also used to demonstrate the completion of sample hydration, which was reached when the materials showed a set of single-phase Bragg-peaks. Dynamic thermogravimetric analysis (TGA) data showed that approx. 89% of the total number of available oxygen vacancies can be filled in BaZr1-xInxO3-delta for x=0.50, and that the maximum water uptake occurs below 300 degrees C. Rietveld analysis of the room temperature neutron powder diffraction (NPD) data confirmed the average cubic symmetry (space group Pm-3m), and an expansion of the unit cell parameter after the hydration reaction. The strong O-H stretch band, 2500-3500 cm(-1), in the infrared absorbance spectrum clearly manifests the presence of protons in the hydrated material. Proton conductivity of hydrated BaZr1-xInxO3-delta, x=0.75 was investigated during heating and cooling cycles under dry argon atmosphere. The total conductivity during the heating cycle was nearly two orders of magnitude greater than that of cooling cycle at 300 degrees C, whilst these values were similar at higher temperatures i.e. T > 600 degrees C.
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30. |
- Andersson, Niklas, 1976, et al.
(författare)
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A Study of Mach 0.75 Jets and Their Radiated Sound Using Large-Eddy Simulation
- 2004
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Ingår i: AIAA 2004-3024, proc. of 10th AIAA/CEAS Aeroacoustics Conference, May 10-12, 2004.
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Konferensbidrag (refereegranskat)abstract
- Large-Eddy Simulations (LES) of a compressible nozzle/jet configuration have been carried out. Two jets were simulated, an isothermal jet and a jet with a higher temperature than the quiescent surrounding air. The Mach number was in both cases 0.75 and the jet Reynolds number was 50,000. Sound pressure levels in far-field observer locations were evaluated using Kirchhoff surface integration. The Favre filtered Navier-Stokes equations were solved using a finite volume method solver with a low-dissipation third-order upwind scheme for the convective fluxes, a second-order centered difference approach for the viscous fluxes and a three-stage second-order Runge-Kutta technique in time. The computational domain was discretized using a block structured boundary fitted mesh with approximately 3,000,000 cells. The calculations were performed on a parallel computer, using message-passing interface (MPI). A compressible form of Smagorinsky's subgrid scale model was used for computation of the subgrid scale stresses. Absorbing boundary conditions based on characteristic variables were adopted for all free boundaries. Velocity components specified at the entrainment boundaries were estimated from corresponding Reynolds Averaged Navier-Stokes (RANS) calculations, which enable the use of a rather narrow domain. This, furthermore, ensures that the correct amount of fluid is entrained into the domain. Two-point space-time correlations were obtained for locations in the shear layer center, from which length and time scales of turbulence structures were evaluated. Predicted near-field flow statistics and far-field sound pressure levels (SPL) are both in good agreement with experiments. Predicted (SPL) are for all observers locations, where evaluated, within a 3.0 [dB] deviation from measured levels and for most locations within a 1.0 [dB] deviation. Experimental data used for validation were provided by Laboratoire dEtude Aeròdynamiques, Poitiers, France.
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31. |
- Andersson, Niklas, 1976, et al.
(författare)
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Effects of Inflow Conditions and Subgrid Model on LES for Turbulent Jets
- 2005
-
Ingår i: AIAA 2005-2925, proc. of 11th AIAA/CEAS Aeroacoustics Conference, May 23-25, 2005, Monterey, California.
-
Konferensbidrag (refereegranskat)abstract
- The turbulent mixing process prescribing the spreading rate of the jet and the length of the potential core region is influenced by a number of factors. Using large-eddy simulation (LES), the four factors that are believed to be the most important in this respect are: subgrid-scale properties, the accuracy of the numerical scheme, the entrainment boundary conditions, and the inflow conditions. In a previously performed study of a subsonic (Mach 0.75) jet, the turbulence mixing was found to be too efficient and hence the length of the potential core region was underpredicted. In that study indications were found of that the overpredicted mixing was due to the inflow conditions. For a model nozzle, capturing the initial turbulent shear flow might not be of that great importance for accurate prediction of radiated sound since most of these effects will appear in the high-frequency range. When dealing with real engine geometries, however, it becomes quite important. Moreover, methods for industrial use have to cope with complex geometries and high temperature and velocity ratios making the ability to capture the initial flow physics even more important. In the present work LES has been used for the same Mach 0.75 jet. The acoustic field is extracted to the far field using Kirchhoff surface integration. The effects of inflow conditions, Reynolds number, and subgrid-scale model on flowfield and acoustic signature are investigated.The Favre-filtered Navier-Stokes equations were solved using a finite-volume method solver with a low-dissipation third-order upwind scheme for the convective fluxes, a second-order centered difference approach for the viscous fluxes and a three-stage second-order Runge-Kutta technique in time. The computational domain was discretized using a block-structured boundary-fitted mesh with approximately 3,000,000 cells. The calculations were performed on a parallel computer, using message-passing interface (MPI). A compressible form of Smagorinsky's subgrid-scale model was used to compute the subgrid-scale stresses. Absorbing boundary conditions based on characteristic variables were adopted for all free boundaries.
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32. |
- Andersson, Niklas, 1976, et al.
(författare)
-
Investigation of an Isothermal Mach 0.75 Jet and its Radiated sound Using Large-Eddy Simulation and Kirchhoff Surface Integration
- 2005
-
Ingår i: International Journal of Heat and Fluid Flow. ; 26, s. 393-410
-
Tidskriftsartikel (refereegranskat)abstract
- A large-eddy simulation (LES) of a compressible nozzle/jet configuration has been carried out. An isothermal Mach 0.75 jet was simulated. The Reynolds number based on the jet velocity at the nozzle exit plane and the nozzle diameter was 50,000. The Favre filtered Navier-Stokes equations were solved using a finite volume method solver with a low-dissipation third-order upwind scheme for the convective fluxes, a second-order centered difference approach for the viscous fluxes and a three-stage second-order Runge-Kutta time marching technique. A compressible form of Smagorinsky's subgrid scale model was used for computation of the subgrid scale stresses. The computational domain was discretized using a block structured boundary fitted mesh with approximately 3,000,000 cells. The calculations were performed on a parallel computer, using message-passing interface (MPI). Absorbing boundary conditions based on characteristic variables were adopted for all free boundaries. Velocity components specified at the entrainment boundaries were estimated from a corresponding Reynolds Averaged Navier-Stokes (RANS) calculation, which enabled the use of a rather narrow domain. In order to diminish disturbances caused by the outlet boundary, a buffer layer was added at the domain outlet. Kirchhoff surface integration using instantaneous pressure data from the LES was utilized to obtain far-field sound pressure levels in a number of observer locations. The predicted sound pressure levels were for all observer locations within a 3dB deviation from the measured levels and for most observer locations within a 1dB deviation. Aerodynamic results and predicted sound pressure levels are both in good agreement with experiments. Experimental data were provided by Laboratoire dEtude Aeròdynamiques, Poiters, France.
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33. |
- Andersson, Niklas, 1976, et al.
(författare)
-
Large-Eddy Simulation of a Mach 0.75 Jet
- 2003
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Ingår i: AIAA 2003-3312, proc. of 9th AIAA/CEAS Aeroacoustic Conference, May 12-14, 2003.
-
Konferensbidrag (refereegranskat)abstract
- A large-eddy simulation (LES) of a compressible nozzle/jet configuration has been carried out. A cold Mach 0.75 jet was simulated. The Reynolds number based on the jet velocity at the nozzle exit plane and the nozzle diameter was 50,000. The Favre filtered Navier-Stokes equations were solved using a finite volume method with a low dissipative third order upwind scheme for the convective fluxes, a second order centered difference approach for the viscous fluxes and a three-stage second order Runge-Kutta time marching technique. A compressible form of Smagorinsky's sub-grid scale model was used for computation of the sub-grid scale stresses. The calculations were performed using a block structured boundary fitted mesh with approximately 3,000,000 cells. The calculations have been performed on a parallel computer, using message-passing interface (MPI). Absorbing boundary conditions based on characteristic variables were adopted for all free boundaries. Velocity components specified at the entrainment boundaries were estimated from a corresponding Reynolds Averaged Navier-Stokes (RANS) calculation. In order to diminish disturbances caused by the outlet boundary a buffer layer was added at the domain outlet. Kirchhoff surface integration has been utilized to obtain far-field sound pressure levels in a number of observer locations using instantaneous pressure from the LES. Aerodynamic results and predicted sound pressure levels are both in good agreement with experiments. Experimental data were provided by Laboratoire dEtude Aeròdynamiques, Poiters, France.
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34. |
- Andersson, Niklas, 1976, et al.
(författare)
-
Large-Eddy Simulation of Subsonic Turbulent Jets and Their Radiated Sound
- 2005
-
Ingår i: AIAA Journal. ; 43:9, s. 1899-1912
-
Tidskriftsartikel (refereegranskat)abstract
- Large-Eddy Simulations (LES) of a compressible nozzle/jet configuration have been carried out. Two jets were simulated, an isothermal jet and a jet with a higher temperature than the quiescent surrounding air. The Mach number was in both cases 0.75 and the jet Reynolds number was 50,000. Sound pressure levels in far-field observer locations were evaluated using Kirchhoff surface integration. The Favre filtered Navier-Stokes equations were solved using a finite volume method solver with a low-dissipation third-order upwind scheme for the convective fluxes, a second-order centered difference approach for the viscous fluxes and a three-stage second-order Runge-Kutta technique in time. The computational domain was discretized using a block structured boundary fitted mesh with approximately 3,000,000 cells. The calculations were performed on a parallel computer, using message-passing interface (MPI). A compressible form of Smagorinsky's subgrid scale model was used for computation of the subgrid scale stresses. Absorbing boundary conditions based on characteristic variables were adopted for all free boundaries. Velocity components specified at the entrainment boundaries were estimated from corresponding Reynolds Averaged Navier-Stokes (RANS) calculations, which enable the use of a rather narrow domain. This, furthermore, ensures that the correct amount of fluid is entrained into the domain. Two-point space-time correlations were obtained for locations in the shear layer center, from which length and time scales of turbulence structures were evaluated. Predicted near-field flow statistics and far-field sound pressure levels (SPL) are both in good agreement with experiments. Predicted (SPL) are for all observers locations, where evaluated, within a 3.0 [dB] deviation from measured levels and for most locations within a 1.0 [dB] deviation. Experimental data used for validation were provided by Laboratoire dEtude Aeròdynamiques, Poiters, France.
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35. |
- Andersson, Niklas, 1976, et al.
(författare)
-
LES Prediction of Flow and Acoustic Field of a Coaxial Jet
- 2005
-
Ingår i: AIAA 2005-2884, proc. of 11th AIAA/CEAS Aeroacoustics Conference, May 23-25, 2005, Monterey, California.
-
Konferensbidrag (refereegranskat)abstract
- A compressible high-subsonic coaxial jet has been simulated using large-eddy simulation (LES). The acoustic field was extended to the far field using Kirchhoff surface integration. The jet Mach number based on the local speed of sound is approximately 0.9 for both the primary and secondary stream. The static temperature in the primary stream is three times that of the secondary stream. In order to resolve the acoustic field, it is desirable to have a computational domain with a rather large radial extent and a mesh that is relatively fine even in the far-field regions. Furthermore, the mesh should be as equidistant as possible so as to minimize the introduction of numerical errors. In order to keep the number of cells down, the computational domain was divided into three regions: a well resolved near-wall LES region, a medium-resolution LES region optimized for propagation of acoustic waves, and a coarse LES region. Over the interfaces between these regions, the number of cells is increased by factor two in each direction. Special treatment of the interfaces between the regions is utilized in order to minimize undesirable numerical errors. The radial extent of the computational domain increases downstream such that the flow in the outer boundary region can be assumed to be irrotational and axisymmetric. Hence, the flow outside the three-dimensional computational domain can be represented by a less expensive two-dimensional axisymmetric calculation. The interface between the full 3D LES region and the 2D region is based on azimuthally averaged quantities and acts as an absorbing boundary condition. The Favre-filtered Navier-Stokes equations were solved using a finite-volume method solver with a low-dissipation third-order upwind scheme for the convective fluxes, a second-order centered difference approach for the viscous fluxes and a three-stage second-order Runge-Kutta technique in time. The computational domain was discretized using a block-structured boundary-fitted mesh with approximately 20,000,000 nodes. The calculations were performed on a parallel computer, using message-passing interface (MPI). A compressible form of Smagorinsky's subgrid-scale model was used to compute the subgrid-scale stresses.
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36. |
- Andersson, Per H., et al.
(författare)
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Theoretical study of structural and electronic properties of VHx
- 1998
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 58:9, s. 5230-5235
-
Tidskriftsartikel (refereegranskat)abstract
- We have calculated the change in the electronic structure and the distortion of the lattice in vanadium upon hydrogenation from first principles using the full-potential linear muffin-tin-orbital method and the linear augmented plane-wave method in the local-density approximation. The calculated hydrogen induced volume expansions agree with experiment and the change in the c/a ratio is also in good agreement with observations where such are available for single phase VHx. Among several changes in the electronic structure, we note a hybridization of the d band of vanadium with the hydrogen 1s band. We also observe an antiferromagnetically ordered moment at V/Vexp=1.08. The possibility of producing magnetic V by means of hydrogenation in combination with epitaxial growth is suggested.
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37. |
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38. |
- Andersson, Per, et al.
(författare)
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Modelling and Architecture Examples of Model Based Engine Control
- 1999
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Konferensbidrag (refereegranskat)abstract
- Environmental regulations and drivability issues are driving forces in the development of control systems for automotive engines. Precise control of the air and fuel is fundamental for achieving the goals. Furthermore, the architecture for the controller plays a central role in how the goals are achieved.A comparison is made between two conventional controller structures and a model based structure. The performance of the different control structures is evaluated on a simulation model. To point out the differences the evaluation is concentrated to transient conditions where a step in throttle angle is used as input to the system. In addition, connections between controllers and the engine model is discussed.
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39. |
- Andersson, Åke, et al.
(författare)
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Status of the new injector for MAX-lab
- 2002
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Ingår i: 8th European Particle Accelerator Conference. ; , s. 772-774
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Konferensbidrag (refereegranskat)abstract
- The new injector for MAX-lab is built around two 125 MeV linacs [B. Anderberg, (2000)] equipped with SLED cavities [Z.D. Farkas, (1974)]. The electron beam is recirculated once to reach 500 MeV. A 2.3 MeV thermionic RF gun [B. Anderberg, (2000)] injects into the system. The RF-gun is put into operation and commissioning of the first linac is proceeding. Results from the thermionic RF-gun operation, linac commissioning and first beam operations are presented.
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40. |
- Andreasson, Jakob, 1975, et al.
(författare)
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Electron-phonon interactions in perovskites containing Fe and Cr studied by Raman scattering using oxygen-isotope and cation substitution
- 2008
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X .- 2469-9950 .- 2469-9969. ; 78:23, s. 235103-
-
Tidskriftsartikel (refereegranskat)abstract
- We use temperature-dependent inelastic light scattering to study the origin of the strong multiphonon scattering of a local oxygen breathing mode present in the mixed B-site orthorhombic (space group Pnma) perovskite LaFe0.5Cr0.5O3 but absent in isostructural LaFeO3 and LaCrO3. It is seen that the multiphonon scattering is critically sensitive to the presence of both Fe and Cr ions on the B site. These results support our interpretation that the multiphonon scattering is activated by local electron-phonon interactions according to the Franck-Condon picture following an Fe-Cr charge transfer. Further, O-18 substitution is performed on the x=0, 0.04, and 0.5 compounds and clearly shows that all modes appearing above the first-order phonon-scattering region in these compounds originate from higher-order oxygen stretching vibrations. In particular this is the case for the strong second-order scattering dominating the scattering response in LaFeO3. Accordingly we propose that these modes are generated by infrared-active longitudinal optical (IR LO) two-phonon and combination scattering activated by Frohlich interaction. For x=0.02 and 0.04 the characteristic IR LO two-phonon and Franck-Condon multiphonon-scattering profiles mix. We also study the influence of isovalent cation substitution and Sr doping in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) and La1-ySryFe0.5Cr0.5O3-delta (y=0, 0.16, and 0.5) on the strong electron-phonon coupling present in LaFe0.5Cr0.5O3. The Franck-Condon effect in LaFe0.5Cr0.5O3, is not significantly affected by isovalent A-site substitution, despite the increasing orthorhombic distortion associated with decreasing A-site ionic radii. On the contrary, aliovalent Sr doping causes a rapid decrease in the Franck-Condon scattering. This shows that the strong electron-phonon coupling in these compounds is highly sensitive to local lattice and electronic decoherence but insensitive to global lattice distortions. Finally, a preliminary assignment of the A(g) and B-2g phonon modes in AFe(0.5)Cr(0.5)O(3) (A=La, Nd, and Gd) is made based on the present observations and published results for LaCrO3 and AMnO(3). The modes associated with oxygen octahedral tilt and bending vibrations are heavily influenced by the magnitude of the orthorhombic distortion.
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41. |
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42. |
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43. |
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44. |
- Aronsson, Martin, et al.
(författare)
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The programming language GCLA: A definitional approach to logic programming
- 1989. - 1
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- We present a logic programming language, GCLA (Generalized horn Clause LAnguage), that is based on a generalization of Prolog. This generalization is unusual in that it takes a quite different view of the meaning of a logic program--a "definitional" view rather than the traditional logical view. GCLA has a number of noteworthy properties, for instance hypothetical and non-monotonic reasoning. This makes implementation of reasoning in knowledge-based systems more direct in GCLA than in Prolog. GCLA is also general enough to incorporate functional programming as a special case. GCLA and its syntax and semantics are described. The use of various language constructs are illustrated with several examples.
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45. |
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46. |
- Athanasiu, L., et al.
(författare)
-
A genetic association study of CSMD1 and CSMD2 with cognitive function
- 2017
-
Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 61, s. 209-216
-
Tidskriftsartikel (refereegranskat)abstract
- The complement cascade plays a role in synaptic pruning and synaptic plasticity, which seem to be involved in cognitive functions and psychiatric disorders. Genetic variants in the closely related CSMD1 and CSMD2 genes, which are implicated in complement regulation, are associated with schizophrenia. Since patients with schizophrenia often show cognitive impairments, we tested whether variants in CSMD1 and CSMD2 are also associated with cognitive functions per se. We took a discovery-replication approach, using well-characterized Scandinavian cohorts. A total of 1637 SNPs in CSMD1 and 206 SNPs in CSMD2 were tested for association with cognitive functions in the NCNG sample (Norwegian Cognitive NeuroGenetics; n = 670). Replication testing of SNPs with p-value < 0.001 (7 in CSMD1 and 3 in CSMD2) was carried out in the TOP sample (Thematically Organized Psychosis; n =1025) and the BETULA sample (Betula Longitudinal Study on aging, memory and dementia; n = 1742). Finally, we conducted a meta-analysis of these SNPs using all three samples. The previously identified schizophrenia marker in CSMD1 (SNP rs10503253) was also included. The strongest association was observed between the CSMDI SNP rs2740931 and performance in immediate episodic memory (p-value = 5 Chi 10(-6), minor allele A, MAF 0.48-0.49, negative direction of effect). This association reached the study-wide significance level (p <= 1.2 Chi 10(-5)). SNP rs10503253 was not significantly associated with cognitive functions in our samples. In conclusion, we studied n = 3437 individuals and found evidence that a variant in CSMD1 is associated with cognitive function. Additional studies of larger samples with cognitive phenotypes will be needed to further clarify the role of CSMD1 in cognitive phenotypes in health and disease. (C) 2016 The Authors. Published by Elsevier Inc.
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47. |
- Backeström, A., et al.
(författare)
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Glucose metabolism and cognitive dysfunction
- 2010
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Ingår i: Abstracts of the EASD, Stockholm 2010. - : Springer Science and Business Media LLC. ; , s. S292-S292
-
Konferensbidrag (refereegranskat)abstract
- Background and aims: The association between type 2 diabetes and different forms of cognitive impairment is well established. The mechanism behind the association is however still unrevealed. We have recently reported that raised blood glucose levels were associated to impairment in episodic memory, the memory function first affected in the progress to dementia. However, patients with type 2 diabetes have not only elevated levels of blood glucose, but also increased levels of insulin because of insulin resistance. It has been suggested that insulin itself might have a negative effect on cognitive function and memory. Diabetes is associated with a long standing hyperglycaemia but also with hypertension and hyperlipideima, leading to micro and macro vascular disease. Thus, our aim was to study whether insulin affects episodic memory independently of glucose in a nondiabetic adult population. Materials and methods: We linked and matched two large population based data sets in Sweden, the Betula study and the Västerbotten Intervention Program. We identified 364 (F/M 207/157, mean age 50.5 ±8.0 years) nondiabetic subjects, free from dementia, who had participated in the two surveys within six months. The memory test included testing of episodic memory. We transformed the results using the mean values and standard deviation from the youngest age group to compute a composite z-score (subjects’ value minus mean score in the 40-year-old group divided by SD). Fasting plasma insulin (FPI) and glucose (FPG) were analyzed with standard methods. Results: Women had higher levels of episodic memory (mean z-score -0.06, SD 0.54) compared to men (mean z-score -0.36, SD 0.51, p<0.001). Given the sex difference in the outcome variable we stratified for sex. In a univariate linear regression both FPG (B -0.274, SE 0.068, Beta -0.271, p<0.001) and FPI (B -0.389, SE 0.131, Beta -0.204, p=0.003) were significantly associated with episodic memory in women but not in men. FPG, but not FPI, remained significantly associated with episodic memory after adjustment for hypertension, total P-cholesterol, bodymass index, educational level, depression, smoking and cardiovascular disease ( FPG: B -0.218, SE 0.070, Beta -0.220, p=0.002; FPI: B -0.232, SE 0.149, Beta -0.127, p=n.s.), when FPG and FPI were analyzed separately. Entering both FPG and FPI into the regression model did not attenuate the association between FPG and episodic memory (FPG: B -0.204, SE 0.071, Beta -0.206, p=0.005). Conclusion: We conclude that an increase in plasma glucose, but not plasma insulin, is associated with impairment in episodic memory in women. This could be explained by a negative effect on the hippocampus caused by raised plasma glucose levels.
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48. |
- Banduseela, Varuna C., et al.
(författare)
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Gene expression and muscle fiber function in a porcine ICU model
- 2009
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 39:3, s. 141-159
-
Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to 1) the poorly understood intricate cellular and molecular networks and 2) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a 5-day period. Among the differentially regulated transcripts, extracellular matrix, energy metabolism, sarcomeric and LIM protein mRNA levels were downregulated, while ubiquitin proteasome system, cathepsins, oxidative stress responsive genes and heat shock proteins (HSP) mRNAs were upregulated. Despite 5 days of immobilization and mechanical ventilation single muscle fiber cross-sectional areas as well as the maximum force generating capacity at the single muscle fiber level were preserved. It is proposed that HSP induction in skeletal muscle is an inherent, primary, but temporary protective mechanism against protein degradation. To our knowledge, this is the first study that isolates the effect of immobilization and mechanical ventilation in an ICU condition from various other cofactors.
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49. |
- Banduseela, Varuna, et al.
(författare)
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Impaired autophagy, chaperone expression, and protein synthesis in response to critical illness interventions in porcine skeletal muscle
- 2013
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:12, s. 477-486
-
Tidskriftsartikel (refereegranskat)abstract
- Critical illness myopathy (CIM) is characterized by a preferential loss of the motor protein myosin, muscle wasting, and impaired muscle function in critically ill intensive care unit (ICU) patients. CIM is associated with severe morbidity and mortality and has a significant negative socioeconomic effect. Neuromuscular blocking agents, corticosteroids, sepsis, mechanical ventilation, and immobilization have been implicated as important risk factors, but the causal relationship between CIM and the risk factors has not been established. A porcine ICU model has been used to determine the immediate molecular and cellular cascades that may contribute to the pathogenesis prior to myosin loss and extensive muscle wasting. Expression profiles have been compared between pigs exposed to the ICU interventions, i.e., mechanically ventilated, sedated, and immobilized for 5 days, with pigs exposed to critical illness interventions, i.e., neuromuscular blocking agents, corticosteroids, and induced sepsis in addition to the ICU interventions for 5 days. Impaired autophagy as well as impaired chaperone expression and protein synthesis were observed in the skeletal muscle in response to critical illness interventions. A novel finding in this study is impaired core autophagy machinery in response to critical illness interventions, which when in concert with downregulated chaperone expression and protein synthesis may collectively affect the proteostasis in skeletal muscle and may exacerbate the disease progression in CIM.
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50. |
- Bergman, Olle, 1978, et al.
(författare)
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Preliminary evidence that polymorphisms in dopamine-related transcription factors LMX1A, LMX1B and PITX3 are associated with schizophrenia
- 2010
-
Ingår i: Progress in Neuro-psychopharmacology and Biological Psychiatry. - : Elsevier. - 0278-5846 .- 1878-4216. ; 34:6, s. 1094-1097
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Tidskriftsartikel (refereegranskat)abstract
- The early development of dopaminergic pathways has been attributed importance for the aetiology of schizophrenia. Several transcription factors are involved in the survival and maturation of dopamine neurons, including LMX1A, LMX1B and PITX3. The possibility that polymorphisms in these genes may influence the development and/or the maintenance of dopaminergic neurons prompted us to investigate if five single nucleotide polymorphisms (SNPs) previously linked to Parkinson's disease are associated with this disorder. Preliminary evidence that genetic variation in LMX1A (rs6668493, rs4657411), LMX1B (rs10987386) and PITX3 (rs4919621) may increase the risk of developing schizophrenia is presented.
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