| 1. |
- Khorsand Vakilzadeh, Majid, 1984, et al.
(författare)
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Sequential gauss-newton MCMC algorithm for high-dimensional bayesian model updating
- 2017
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Ingår i: Conference Proceedings of the Society for Experimental Mechanics Series. - Cham : Springer International Publishing. - 2191-5644 .- 2191-5652. ; 3 Part F2, s. 303-314
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Konferensbidrag (refereegranskat)abstract
- Bayesian model updating provides a rigorous framework to account for uncertainty induced by lack of knowledge about engineering systems in their respective mathematical models through updates of the joint probability density function (PDF), the so-called posterior PDF, of the unknown model parameters. The Markov chain Monte Carlo (MCMC) methods are currently the most popular approaches for generating samples from the posterior PDF. However, these methods often found wanting when sampling from difficult distributions (e.g., high-dimensional PDFs, PDFs with flat manifolds, multimodal PDFs, and very peaked PDFs). This paper introduces a new multi-level sampling approach for Bayesian model updating, called Sequential Gauss-Newton algorithm, which is inspired by the Transitional Markov chain Monte Carlo (TMCMC) algorithm. The Sequential Gauss-Newton algorithm improves two aspects of TMCMC to make an efficient and effective MCMC algorithm for drawing samples from difficult posterior PDFs. First, the statistical efficiency of the algorithm is enhanced by use of the systematic resampling scheme. Second, a new MCMC algorithm, called Gauss-Newton MCMC algorithm, is proposed which is essentially an M-H algorithm with a Gaussian proposal PDF tailored to the posterior PDF using the gradient and Hessian information of the negative log posterior. The effectiveness of the proposed algorithm for solving the Bayesian model updating problem is illustrated using three examples with irregularly shaped posterior PDFs.
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| 2. |
- Rosqvist, Fredrik, 1985-, et al.
(författare)
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Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
- 2019
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
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| 3. |
- Andersson, Mats X., 1977, et al.
(författare)
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Involvement of the Electrophilic Isothiocyanate Sulforaphane in Arabidopsis Local Defense Responses
- 2015
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Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 167:1
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Tidskriftsartikel (refereegranskat)abstract
- Plants defend themselves against microbial pathogens through a range of highly sophisticated and integrated molecular systems. Recognition of pathogen-secreted effector proteins often triggers the hypersensitive response (HR), a complex multicellular defense reaction where programmed cell death of cells surrounding the primary site of infection is a prominent feature. Even though the HR was described almost a century ago, cell-to-cell factors acting at the local level generating the full defense reaction have remained obscure. In this study, we sought to identify diffusible molecules produced during the HR that could induce cell death in naive tissue. We found that 4-methylsulfinylbutyl isothiocyanate (sulforaphane) is released by Arabidopsis (Arabidopsis thaliana) leaf tissue undergoing the HR and that this compound induces cell death as well as primes defense in naive tissue. Two different mutants impaired in the pathogen-induced accumulation of sulforaphane displayed attenuated programmed cell death upon bacterial and oomycete effector recognition as well as decreased resistance to several isolates of the plant pathogen Hyaloperonospora arabidopsidis. Treatment with sulforaphane provided protection against a virulent H. arabidopsidis isolate. Glucosinolate breakdown products are recognized as antifeeding compounds toward insects and recently also as intracellular signaling and bacteriostatic molecules in Arabidopsis. The data presented here indicate that these compounds also trigger local defense responses in Arabidopsis tissue.
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| 4. |
- Buvall, Lisa, 1976, et al.
(författare)
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Orellanine specifically targets renal clear cell carcinoma
- 2017
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:53, s. 91085-91098
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells. Orellanine would thus target both primary and metastatic ccRCC in vitro and in vivo. We found that orellanine induces dose-dependent cell death in proximal tubular cells and in all ccRCC cells tested, both primary and cell lines, with no toxicity detected in control cells. The toxic action of orellanine involve decreased protein synthesis, disrupted cell metabolism and induction of apoptosis. In nude rats carrying human ccRCC xenografts, brief orellanine treatment eliminated more than 90% of viable tumor mass compared to control rats. This identifies orellanine as a potential treatment concept for ccRCC patients on dialysis, due to its unique selective toxicity towards ccRCC.
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| 5. |
- Carlsson, Sigrid, 1982, et al.
(författare)
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Population-based study of long-term functional outcomes after prostate cancer treatment
- 2016
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Ingår i: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 117:6B, s. E36-E45
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate long-term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median follow-up of 12 years (IQR 11-13).PATIENTS AND METHODS: In this nationwide, population-based study, we identified from the National Prostate Cancer Register, Sweden, 6,003 men diagnosed with localized prostate cancer (clinical local stage T1-2, any Gleason score, prostate specific antigen < 20 ng/mL, NX or N0, MX or M0) between 1997 and 2002 who were ≤70 years at diagnosis. 1,000 prostate cancer-free controls were selected, matched for age and county of residence. Functional outcomes were evaluated with a validated self-reported questionnaire.RESULTS: Responses were obtained from 3,937/6,003 cases (66%) and 459/1,000 (46%) controls. Twelve years post diagnosis, at a median age of 75 years, the proportion of cases with adverse symptoms was 87% for erectile dysfunction or sexually inactive, 20% for urinary incontinence and 14% for bowel disturbances. The corresponding proportions for controls were 62%, 6% and 7%, respectively. Men with prostate cancer, except those on surveillance, had an increased risk of erectile dysfunction, compared to control men. Radical prostatectomy was associated with increased risk of urinary incontinence (odds ratio; OR 2.29 [95% CI 1.83-2.86] and radiotherapy increased the risk of bowel dysfunction (OR 2.46 [95% CI 1.73-3.49]) compared to control men. Multi-modal treatment, in particular including androgen deprivation therapy (ADT), was associated with the highest risk of adverse effects; for instance radical prostatectomy followed by radiotherapy and ADT was associated with an OR of 3.74 [95 CI 1.76-7.95] for erectile dysfunction and OR 3.22 [95% CI 1.93-5.37] for urinary incontinence.CONCLUSION: The proportion of men who suffer long-term impact on functional outcomes after prostate cancer treatment was substantial.
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| 6. |
- Corcoll, Natàlia, 1981, et al.
(författare)
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Linking pesticide pollution with periphyton quality in agricultural streams: a fatty-acids approach
- 2018
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Ingår i: SETAC Europe 28th Annual Meeting 13−17 May 2018 | Rome, Italy. Abstract Book.. - 2309-8031.
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Konferensbidrag (refereegranskat)abstract
- Although the environmental risks associated with pesticide pollution in agricultural streams are quite well documented, little is know about its potential effects on periphyton quality. Periphyton provides many of the essential polyunsaturated fatty acids (PUFA) that are needed for organisms at higher trophic levels in river food webs. This study aims to assess the effects of pesticide mixtures on periphyton quality in situ. Three streams (Höje å, Skivarpsån and M42) located in the agriculturally dominated region of Skåne (SE Sweden) were sampled in September and October 2016. The effects of pesticide pollution were assessed by passive field sampling coupled with laboratory ecotoxicity tests, by mixture toxicity modelling to predict which chemical stressors were potentially driving the toxicity, and by examining the fatty acid profiles, pigment content and algal diversity of periphyton communities. Results from water chemical analyses clearly showed higher levels of nutrients and pesticide pollution in Skivarpsån and M42 than in Höje å. Ecotoxicity tests using the passive sampler extracts demonstrated that the pesticide mixtures ocurring at Skivarpsån and M42 were toxic for periphyton communities from Höje å, causing an inhibition of the photosynthetic activity up to 63% and 53%, respectively. Cluster and principal component analyses based on pigments content, algal diversity and fatty acid profiles, clearly separated the periphyton from the three river sites studied. Algal biomass from periphyton of pesticide polluted streams (Skivarpsån and M42) was higher than in Höje å. The nutritive quality of the periphyton differed among streams, and fatty acids considered high-quality such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also more abundant in pesticide polluted streams (Skivarpsån and M42). Overal, even though results from the lab show that the mixture of pesticides pollution in the studied streams might be toxic for periphyton (i.e. inhibiting the photosynthetic activity), being herbicides the driving chemical stressors. Results from the field, indicate that when the levels of pesticide pollution are low and co-occur with high levels of nutrients pollution, nutrients migh mask pesticides effects on periphyton quantity and quality because compensatory effects from nutrients
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| 7. |
- Herdean, Andrei, 1984, et al.
(författare)
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A voltage-dependent chloride channel fine-tunes photosynthesis in plants
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7:artikel nr 11654
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Tidskriftsartikel (refereegranskat)abstract
- n natural habitats, plants frequently experience rapid changes in the intensity of sunlight. To cope with these changes and maximize growth, plants adjust photosynthetic light utilization in electron transport and photoprotective mechanisms. This involves a proton motive force (PMF) across the thylakoid membrane, postulated to be affected by unknown anion (Cl−) channels. Here we report that a bestrophin-like protein from Arabidopsis thaliana functions as a voltage-dependent Cl− channel in electrophysiological experiments. AtVCCN1 localizes to the thylakoid membrane, and fine-tunes PMF by anion influx into the lumen during illumination, adjusting electron transport and the photoprotective mechanisms. The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Our results reveal that AtVCCN1, a member of a conserved anion channel family, acts as an early component in the rapid adjustment of photosynthesis in variable light environments.
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| 8. |
- Häggström, Ida, 1982-, et al.
(författare)
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A Monte Carlo study of the dependence of early frame sampling on uncertainty and bias in pharmacokinetic parameters from dynamic PET
- 2015
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Ingår i: Journal of Nuclear Medicine Technology. - : Society of Nuclear Medicine. - 0091-4916 .- 1535-5675. ; 43:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- Compartmental modeling of dynamic PET data enables quantifi- cation of tracer kinetics in vivo, through the calculated model parameters. In this study, we aimed to investigate the effect of early frame sampling and reconstruction method on pharmacokinetic parameters obtained from a 2-tissue model, in terms of bias and uncertainty (SD). Methods: The GATE Monte Carlo software was used to simulate 2 · 15 dynamic 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) brain PET studies, typical in terms of noise level and kinetic parameters. The data were reconstructed by both 3- dimensional (3D) filtered backprojection with reprojection (3DRP) and 3D ordered-subset expectation maximization (OSEM) into 6 dynamic image sets with different early frame durations of 1, 2, 4, 6, 10, and 15 s. Bias and SD were evaluated for fitted parameter estimates, calculated from regions of interest. Results: The 2-tissue-model parameter estimates K1, k2, and fraction of arterial blood in tissue depended on early frame sampling, and a sampling of 6–15 s generally minimized bias and SD. The shortest sampling of 1 s yielded a 25% and 42% larger bias than the other schemes, for 3DRP and OSEM, respectively, and a parameter uncertainty that was 10%–70% higher. The schemes from 4 to 15 s were generally not significantly different in regards to bias and SD. Typically, the reconstruction method 3DRP yielded less framesampling dependence and less uncertain results, compared with OSEM, but was on average more biased. Conclusion: Of the 6 sampling schemes investigated in this study, an early frame duration of 6–15 s generally kept both bias and uncertainty to a minimum, for both 3DRP and OSEM reconstructions. Veryshort frames of 1 s should be avoided because they typically resulted in the largest parameter bias and uncertainty. Furthermore, 3DRP may be p
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| 9. |
- Johansson, Anders, 1982, et al.
(författare)
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A method for improving test rig performance using passive components
- 2015
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Ingår i: Mechanical Systems and Signal Processing. - : Elsevier BV. - 0888-3270 .- 1096-1216. ; 52-53:1, s. 614-627
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Tidskriftsartikel (refereegranskat)abstract
- The time waveform replication (TWR) algorithm is presently used in industry for calculating the actuation force needed to replicate a certain reference sensor output in a test rig. Power and force rate limitations restrict the feasible range of that actuation force. If the input force distribution of the reference test cannot be replicated in the test rig, the required test rig input force magnitudes may be large or the replication properties poor due to lack of controllability. To circumvent this, a theory of passive components to improve replication and limit the input force demands of dynamic test rigs is developed. The theory fits within the framework of the TWR algorithm.
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| 10. |
- Johansson, Karin S L, et al.
(författare)
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Molecular basis of variation in stomatal responsiveness to elevated CO2
- 2015
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Ingår i: Agriculture and Climate Change - Adapting Crops to Increased Uncertainty. 15-17 February 2015, Amsterdam, the Netherlands. Procedia Environmental Sciences. - : Elsevier. - 1878-0296.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Stomata are small pores in the surface of plant leaves, balancing the uptake of CO2 against the loss of water vapour. As drought stress is projected to increase in many parts of the world, an improved understanding of how plants regulate their stomata in response to environmental stimuli may have important implications for securing food production in a future climate. The stomata of most plants respond to elevated CO2 concentration by partial closing, but the magnitude of this response shows a large variation among species and ecotypes. Plants that substantially decrease stomatal conductance under elevated CO2 reduce their water consumption and increase their water-use efficiency. However, the genetic basis for inter- and intraspecific variation in responsiveness is poorly understood, as are the mechanisms for sensing and responding to CO2. In the current study, we have measured the short-term stomatal response to elevated CO2 in a population of Arabidopsis thaliana recombinant inbred lines (RILs) originating from a cross between two parental genotypes showing a large difference in stomatal responsiveness. Hence, this RIL population showed a broad range in stomatal responsiveness, ranging from a 10% to a 60% reduction of stomatal conductance following an increase in CO2 concentration from 400 to 800 ppm. Using quantitative trait locus (QTL) mapping we have identified two genetic loci involved in the stomatal response to elevated CO2. Potential candidate genes regulating the stomatal response will be discussed.
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