| 1. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 2. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 3. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 4. |
- Sønderby, Ida E., et al.
(författare)
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1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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| 5. |
- van der Meer, Dennis, et al.
(författare)
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Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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| 6. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 7. |
- Jacobs, Kevin B, et al.
(författare)
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Detectable clonal mosaicism and its relationship to aging and cancer.
- 2012
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Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:6, s. 651-658
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Tidskriftsartikel (refereegranskat)abstract
- In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
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| 8. |
- Sonderby, Ida E., et al.
(författare)
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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
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Tidskriftsartikel (refereegranskat)abstract
- Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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| 9. |
- Raymond, Christopher, et al.
(författare)
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Inclusive conservation and the Post-2020 Global Biodiversity Framework : Tensions and prospects
- 2022
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Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:3, s. 252-264
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Tidskriftsartikel (refereegranskat)abstract
- The draft Post-2020 Global Biodiversity Framework commits to achievement of equity and justice outcomes and represents a “relational turn” in how we understand inclusive conservation. Although “inclusivity” is drawn on as a means to engage diverse stakeholders, widening the framing of inclusivity can create new tensions with regard to how to manage protected areas. We first offer a set of tensions that emerge in the light of the relational turn in biodiversity conservation. Drawing on global case examples applying multiple methods of inclusive conservation, we then demonstrate that, by actively engaging in the interdependent phases of recognizing hybridity, enabling conditions for reflexivity and partnership building, tensions can not only be acknowledged but softened and, in some cases, reframed when managing for biodiversity, equity, and justice goals. The results can improve stakeholder engagement in protected area management, ultimately supporting better implementation of global biodiversity targets.
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| 10. |
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| 11. |
- Andersson Lassila, Andreas, et al.
(författare)
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Effects of different laser welding parameters on the joint quality for dissimilar material joints for battery applications
- 2024
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Ingår i: Optics and Laser Technology. - : Elsevier. - 0030-3992 .- 1879-2545. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- For battery pack assemblies, it is crucial that the laser welded cell-to-busbar joints demonstrate both high mechanical strength and minimal electrical resistance. The present study investigates the effect of different laser welding parameters, on the mechanical strength, electrical resistance, porosity formation and joint microstructure, for dissimilar material cell-to-busbar joints. Laser welding experiments are performed, on thin nickel-plated copper and steel plates. The plates are joined in an overlap configuration, using laser beam wobbling and power modulation. Both circular and sinusoidal laser beam wobbling are used as selected strategies to increase the interface width of the joints, where also a comparison is made between the two methods. The joint quality is evaluated using joint geometry analysis, shear strength tests, computed tomography scanning and electrical resistance measurements. The results show that circular laser beam wobbling gives a larger joint shear strength compared with sinusoidal laser beam wobbling. In addition, it is observed that both the total pore volume and material mixing are significantly increased with increasing laser power and wobbling frequency for circular laser beam wobbling. However, for the sinusoidal laser beam wobbling the wobbling frequency does not show a significant impact on the total pore volume.
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| 12. |
- Constance, B., et al.
(författare)
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Experimental Verification of the CLIC Two-Beam Acceleration Technology in CTF3
- 2013
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Ingår i: IPAC 2013: Proceedings of the 4th International Particle Accelerator Conference. - 9783954501229 ; , s. 1436-1438
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Konferensbidrag (refereegranskat)abstract
- The Compact Linear Collider international collaboration is pursuing an extensive R&D program towards a multi- TeV electron-positron collider. In particular, the development of two-beam acceleration technology is the focus of the CLIC test facility CTF3. In this paper we summarise the most recent results obtained at CTF3: The results of the studies on the drive beam generation are presented, the achieved two beam acceleration performance is reported and the measured breakdown rates and related observations are summarised. The stability of the deceleration process performed over 12 subsequent modules and a comparison of the obtained results with the theoretical expectations are discussed. We also outline the future experimental program.
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| 13. |
- Fazey, Ioan, et al.
(författare)
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Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
- 2020
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Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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| 14. |
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| 15. |
- Sarlus, Zmar, 1984-, et al.
(författare)
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Timing and origin of the host rocks to the Malmberget iron oxide-apatite deposit, Sweden
- 2020
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Ingår i: Precambrian Research. - : Elsevier. - 0301-9268 .- 1872-7433. ; 342
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Tidskriftsartikel (refereegranskat)abstract
- The northern Norrbotten region in Sweden hosts abundant iron-oxide apatite (IOA) deposits including Kiirunavaara, the type locality for Kiruna-type deposits, and Malmberget. Felsic and intermediate metavolcanic rocks hosting the Malmberget IOA deposit contain oscillatory zoned zircon which yield magmatic U-Pb SIMS ages of 1885±6 Ma and 1881±6 Ma, respectively. Metamorphic rims on zircon from these rocks yield 1797±7 Ma and 1775±6 Ma, respectively, and record the age of the latest Svecofennian regional metamorphic event in the Gällivare area, tentatively interpreted as regional contact metamorphism. Two granite dikes that cut the ore yield U-Pb zircon emplacement ages of 1790±6 Ma and 1791±7 Ma, respectively, overlapping with the metamorphic overgrowths, and set a lower age limit for ore formation in the Malmberget IOA deposit. Rocks hosting the Malmberget IOA deposit have an alkalic to alkali-calcic affinity with a geochemical signature that favors a continental-arc, transitional to extensional setting. These rocks are suggested to have been generated in a back-arc region, in response to subduction beneath the craton margin retreating to the SW or W. The obtained ages and geochemical signatures of these rocks coincide well with the regionally defined Kiirunavaara group rocks, hosting several other IOA deposits in northern Sweden.
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| 16. |
- Trujillo, F. J., et al.
(författare)
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Shrinkage Factor Analysis in the Dry Machining of UNS A92024 Alloy by FEM
- 2021
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Ingår i: 24th Innovative Manufacturing Engineering and Energy International Conference (IManEE 2020) 14<sup>th</sup>-15<sup>th</sup> December 2020, Athens, Greece. - : Institute of Physics (IOP).
-
Konferensbidrag (refereegranskat)abstract
- Chip evacuation becomes a relevant factor in the dry machining of aeronautical aluminium alloys, either when they are machined as isotropic material or hybridized with other materials. Chip morphology and geometry highly depend on cutting parameters. Several works can be found in the literature focusing on the analysis of chip morphology of aluminium alloys at high cutting speeds but there is a lack of studies that apply low cutting speeds. FEM simulation may be useful to reduce the experimental time and cost of this kind of analysis. Therefore, in this work, the influence of feed-rate on several chip geometrical parameters (height of peaks, height of valleys and shrinkage factor) of dry turned UNS A92024 alloy has been analysed by FEM simulation. Three different energy fracture modes have been tested as damage evolution criterion, in order to get the mode that better fit the experimental chip morphology. In general, the mixed mode was the fracture energy mode that best suited the chip morphology behaviour, within wider feed-rate range.
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| 17. |
- Amouzgar, Kaveh, 1980-, et al.
(författare)
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A framework for simulation-based multi-objective optimization and knowledge discovery of machining process
- 2018
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Ingår i: The International Journal of Advanced Manufacturing Technology. - : Springer Science and Business Media LLC. - 0268-3768 .- 1433-3015. ; 98:9-12, s. 2469-2486
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Tidskriftsartikel (refereegranskat)abstract
- The current study presents an effective framework for automated multi-objective optimization (MOO) of machining processes by using finite element (FE) simulations. The framework is demonstrated by optimizing a metal cutting process in turning AISI-1045, using an uncoated K10 tungsten carbide tool. The aim of the MOO is to minimize tool-chip interface temperature and tool wear depth, that are extracted from FE simulations, while maximizing the material removal rate. The effect of tool geometry parameters, i.e., clearance angle, rake angle, and cutting edge radius, and process parameters, i.e., cutting speed and feed rate on the objective functions are explored. Strength Pareto Evolutionary Algorithm (SPEA2) is adopted for the study. The framework integrates and connects several modules to completely automate the entire MOO process. The capability of performing the MOO in parallel is also enabled by adopting the framework. Basically, automation and parallel computing, accounts for the practicality of MOO by using FE simulations. The trade-off solutions obtained by MOO are presented. A knowledge discovery study is carried out on the trade-off solutions. The non-dominated solutions are analyzed using a recently proposed data mining technique to gain a deeper understanding of the turning process.
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| 18. |
- Amouzgar, Kaveh, 1980-, et al.
(författare)
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Metamodel based multi-objective optimization of a turning process by using finite element simulation
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This study investigates the advantages and potentials of the metamodelbased multi-objective optimization (MOO) of a turning operation through the application of finite element simulations and evolutionary algorithms to a metal cutting process. The objectives are minimizing the interface temperature and tool wear depth obtained from FE simulations using DEFORM2D software, and maximizing the material removal rate. Tool geometry and process parameters are considered as the input variables. Seven metamodelling methods are employed and evaluated, based on accuracy and suitability. Radial basis functions with a priori bias and Kriging are chosen to model tool–chip interface temperature and tool wear depth, respectively. The non-dominated solutions are found using the strength Pareto evolutionary algorithm SPEA2 and compared with the non-dominated front obtained from pure simulation-based MOO. The metamodel-based MOO method is not only advantageous in terms of reducing the computational time by 70%, but is also able to discover 31 new non-dominated solutions over simulation-based MOO.
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| 19. |
- Amouzgar, Kaveh, 1980-
(författare)
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Metamodel Based Multi-Objective Optimization with Finite-Element Applications
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- As a result of the increase in accessibility of computational resources and the increase of computer power during the last two decades, designers are able to create computer models to simulate the behavior of complex products. To address global competitiveness, companies are forced to optimize the design of their products and production processes. Optimizing the design and production very often need several runs of computationally expensive simulation models. Therefore, integrating metamodels, as an efficient and sufficiently accurate approximate of the simulation model, with optimization algorithms is necessary. Furthermore, in most of engineering problems, more than one objective function has to be optimized, leading to multi-objective optimization(MOO). However, the urge to employ metamodels in MOO, i.e., metamodel based MOO (MB-MOO), is more substantial.Radial basis functions (RBF) is one of the most popular metamodeling methods. In this thesis, a new approach to constructing RBF with the bias to beset a priori by using the normal equation is proposed. The performance of the suggested approach is compared to the classic RBF and four other well-known metamodeling methods, in terms of accuracy, efficiency and, most importantly, suitability for integration with MOO evolutionary algorithms. It has been found that the proposed approach is accurate in most of the test functions, and it was the fastest compared to other methods. Additionally, the new approach is the most suitable method for MB-MOO, when integrated with evolutionary algorithms. The proposed approach is integrated with the strength Pareto evolutionary algorithm (SPEA2) and applied to two real-world engineering problems: MB-MOO of the disk brake system of a heavy truck, and the metal cutting process in a turning operation. Thereafter, the Pareto-optimal fronts are obtained and the results are presented. The MB-MOO in both case studies has been found to be an efficient and effective method. To validate the results of the latter MB-MOO case study, a framework for automated finite element (FE) simulation based MOO (SB-MOO) of machining processes is developed and presented by applying it to the same metal cutting process in a turning operation. It has been proved that the framework is effective in achieving the MOO of machining processes based on actual FE simulations.
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| 20. |
- Andersson, Mattias, et al.
(författare)
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Polar codes for bidirectional broadcast channels with common and confidential messages
- 2012
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Ingår i: International Symposium on Wireless Communication Systems (ISWCS), 2012. - : IEEE conference proceedings. - 9781467307604 ; , s. 1014-1018
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Konferensbidrag (refereegranskat)abstract
- We consider the bidirectional broadcast channel with common and confidential messages. We show that polar codes achieve the capacity of binary input symmetrical bidirectional broadcast channels with confidential messages, if one node's channel is a degraded version of the other node's channel. We also find a new bound on the cardinality of the auxiliary random variable in this setup.
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| 21. |
- Andersson, Mattias, et al.
(författare)
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Polar Coding for Bidirectional Broadcast Channels with Common and Confidential Messages
- 2013
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Ingår i: IEEE Journal on Selected Areas in Communications. - 0733-8716 .- 1558-0008. ; 31:9, s. 1901-1908
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Tidskriftsartikel (refereegranskat)abstract
- The integration of multiple services such as the transmission of private, common, and confidential messages at the physical layer is becoming important for future wireless networks in order to increase spectral efficiency. In this paper, bidirectional relay networks are considered, in which a relay node establishes bidirectional communication between two other nodes using a decode-and-forward protocol. In the broadcast phase, the relay transmits additional common and confidential messages, which then requires the study of the bidirectional broadcast channel (BBC) with common and confidential messages. This channel generalizes the broadcast channel with receiver side information considered by Kramer and Shamai. Low complexity polar codes are constructed that achieve the capacity region of both the degraded symmetric BBC, and the BBC with common and confidential messages. The use of polar codes allows an intuitive interpretation of how to incorporate receiver side information and secrecy constraints as different sets of frozen bits at the different receivers for an optimal code design. In order to show that the constructed codes achieve capacity, a tighter bound on the cardinality of an auxiliary random variable used in the converse is found using a method by Salehi.
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| 22. |
- Andersson, Peder, et al.
(författare)
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Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm
- 2021
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers.MethodsWe performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients' background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1-2 whilst a poor outcome was defined as CPC 3-5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets.ResultsAUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p<0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions.ConclusionsIn this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance.
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| 23. |
- Andersson, R., et al.
(författare)
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Modeling of free fatty acid dynamics: insulin and nicotinic acid resistance under acute and chronic treatments
- 2017
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Ingår i: Journal of Pharmacokinetics and Pharmacodynamics. - : Springer Science and Business Media LLC. - 1573-8744 .- 1567-567X. ; 44:3, s. 203-222
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Tidskriftsartikel (refereegranskat)abstract
- Nicotinic acid (NiAc) is a potent inhibitor of adipose tissue lipolysis. Acute administration results in a rapid reduction of plasma free fatty acid (FFA) concentrations. Sustained NiAc exposure is associated with tolerance development (drug resistance) and complete adaptation (FFA returning to pretreatment levels). We conducted a meta-analysis on a rich pre-clinical data set of the NiAc-FFA interaction to establish the acute and chronic exposure-response relations from a macro perspective. The data were analyzed using a nonlinear mixed-effects framework. We also developed a new turnover model that describes the adaptation seen in plasma FFA concentrations in lean Sprague-Dawley and obese Zucker rats following acute and chronic NiAc exposure. The adaptive mechanisms within the system were described using integral control systems and dynamic efficacies in the traditional model. Insulin was incorporated in parallel with NiAc as the main endogenous co-variate of FFA dynamics. The model captured profound insulin resistance and complete drug resistance in obese rats. The efficacy of NiAc as an inhibitor of FFA release went from 1 to approximately 0 during sustained exposure in obese rats. The potency of NiAc as an inhibitor of insulin and of FFA release was estimated to be 0.338 and 0.436 , respectively, in obese rats. A range of dosing regimens was analyzed and predictions made for optimizing NiAc delivery to minimize FFA exposure. Given the exposure levels of the experiments, the importance of washout periods in-between NiAc infusions was illustrated. The washout periods should be 2 h longer than the infusions in order to optimize 24 h lowering of FFA in rats. However, the predicted concentration-response relationships suggests that higher AUC reductions might be attained at lower NiAc exposures.
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| 24. |
- Andersson, Stefan S., et al.
(författare)
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Apatite as a tracer of the source, chemistry and evolution of ore-forming fluids : The case of the Olserum-Djupedal REE-phosphate mineralisation, SE Sweden
- 2019
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Ingår i: Geochimica et Cosmochimica Acta. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0016-7037 .- 1872-9533. ; 255, s. 163-187
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Tidskriftsartikel (refereegranskat)abstract
- This study explores the suitability of apatite as a tracer of the source(s), chemistry, and evolution of ore-forming hydrothermal fluids. This is tested by analysing the halogen (F, Cl, Br, and I), stable Cl isotopic, and trace element compositions of fluorapatite from the regional-scale Olserum-Djupedal rare earth element (REE) phosphate mineralisation in SE Sweden, which is dominated by monazite-(Ce), xenotime-(Y), and fluorapatite. The primary hydrothermal fluid flow system is recorded in a sequence from proximal granite-hosted to distal metasediment-hosted fluorapatite. Along this sequence, primary fluorapatite shows a gradual increase of Cl and Br concentrations and in (Gd/Yb)N, a decrease of F and I concentrations, a decrease in δ37Cl values, in (La/Sm)N, and partly in (La/Yb)N and (Y/Ho)N. Local compositional differences of halogen and trace element concentrations have developed along rims and in domains adjacent to fractures of fluorapatite due to late-stage partial reaction with fracture fluids. These differences are insignificant compared to the larger deposit-scale zoning. This suggests that apatite can retain the primary record of the original ore-forming fluid despite later overprinting fluid events. The agreement between Br/Cl and I/Cl ratios of apatite and those of co-existing fluid inclusions at lower temperatures indicates that only a minor fractionation of Br from I occurs during apatite precipitation. The halogen ratios of apatite can thus be used as a first-order estimate for the composition of the ore-forming fluid. Taking the small fractionation factors for Cl isotopes between apatite and co-existing fluid at high temperatures into account, we propose that the Cl isotopic composition of apatite and the halogen ratios derived from the apatite composition can be used jointly to trace the source(s) of ore-forming fluids. By contrast, most trace elements incorporated in apatite are affected by the host rock environment and by fluid-mineral partitioning due to growth competition between co-crystallising minerals. Collectively, apatite is sensitive to changing fluid compositions, yet it is also able to record the character of primary ore-forming fluids. Thus, apatite is suitable for tracing the origin, chemistry, and evolution of fluids in hydrothermal ore-forming settings.
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| 25. |
- Andersson, Tobias, et al.
(författare)
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A machine vision system for estimation of size distributions by weight of limestone particles during ship loading
- 2012
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Ingår i: Minerals Engineering. - : Elsevier BV. - 0892-6875 .- 1872-9444. ; 25:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- The size distribution as a function of weight of particles is an important measure of product quality in the mining and aggregates industries. When using manual sampling and sieving, the weight of particles is readily available. However, when using a machine vision system, the particle size distributions are determined as a function of the number of particles. In this paper we first show that there can be a significant weight-transformation error when transforming from one type of size distribution to another. We also show how the problem can be overcome by training a classifier and scaling the results according to calibrated average weights of rocks. The performance of the algorithm is demonstrated with results of measurements of limestone particles on conveyor belts.
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| 26. |
- Andersson, Tobias, 1973-
(författare)
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Decision support tools for dynamic fleet management : applications in airline planning and ambulance logistics
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this work, decision support tools for dynamic fleet management problems are developed. The operational management tasks include dispatching, supervising and sometimes reconstructing the vehicle schedule. These tasks are often complex, while the time available to complete them is short. Therefore, decision support tools assisting the controller can be of great service.Two studies on dynamic fleet management problems are presented. The first concerns airline planning and the problem of how to handle schedule perturbations. The second study is within the field of ambulance logistics, with focus on operational ambulance control.For an airline, the flight perturbation problem arises when it is impossible to continue executing the original aircraft schedule, e.g. due to an aircraft breakdown. The flight controller then has to decide whether some flights have to be delayed or cancelled, or perhaps flights have to be reassigned to new aircraft. This is done in order to find an attainable, cost effective solution, where the airline can continue to serve the passengers. In this work, a decision support tool that can repair the aircraft schedule is suggested. The tool is based on a multicommodity network flow model with side constraints. A number of different solution strategies are suggested for the model, including heuristics based on column generation and meta heuristics utilizing path relinking. Computational tests show that several of the solution algorithms find near optimal solutions within a few seconds.Ambulance logistics comprises most aspects of managing an efficient ambulance health care. This involves both emergency medical services and patient transportations. Controlling a fleet of ambulances includes deciding which ambulance to dispatch to a call. The controller also has to ensure that most or all parts of the area of responsibility can be reached by an ambulance in a short time. This is referred to as maintaining an adequate level of preparedness in the area. In this work, a way of calculating the preparedness is presented. It is incorporated into a number of decision support tools, including a dispatch tool and a relocation tool. The dispatch tool can suggest which ambulance to assign to a new call. The relocation tool suggests a way of relocating the ambulances, i.e. sending them to new locations, to increase the level of preparedness in the area. A simulation tool is also developed and used to study the effect of dynamically relocating ambulances. Furthermore, it is used to test if new locations for the ambulance stations will affect the waiting periods for the patients. The results show that the decision support tools have a positive effect on the system performance.
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| 27. |
- Andrade, Pedro, et al.
(författare)
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Regulatory changes in pterin and carotenoid genes underlie balanced color polymorphisms in the wall lizard
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:12, s. 5633-5642
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Tidskriftsartikel (refereegranskat)abstract
- Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase (SPR)] and carotenoid [beta-carotene oxygenase 2 (BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.
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| 28. |
- Andrén, Oliver C. J., et al.
(författare)
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Antibiotic-Free Cationic Dendritic Hydrogels as Surgical-Site-Infection-Inhibiting Coatings
- 2019
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Ingår i: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659.
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Tidskriftsartikel (refereegranskat)abstract
- A non-toxic hydrolytically fast-degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two-component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear-dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2-bis(hydroxymethyl)propionic acid, and ii) a di-N-hydroxysuccinimide functional poly(ethylene glycol) cross-linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β-alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two-component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G' = 0.5-8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection.
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| 29. |
- Bermudo Gamboa, Carolina, et al.
(författare)
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Modeling of the fracture energy on the finite element simulation in Ti6Al4V alloy machining
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- One of the main problems that exists when working with Finite Element Methods (FEM) applied to machining processes is the lack of adequate experimental data for simulating the material properties. Moreover, for damage models based on fracture energy, the correct selection of the energy value is critical for the chip formation process. It is usually difficult to obtain the fracture energy values and requires complex tests. In this work, an analysis of the influence of this fracture energy on the cutting force and the chip generation process has been carried out for different sets of cutting parameters. The aim is to present an empirical relationship, that allows selecting the fracture energy based on the cutting force and cutting parameters. The work is based on a FEM model of an orthogonal turning process for Ti6Al4V alloy using Abaqus/Explicit and the fracture energy empirical relation. This work shows that it is necessary to adjust the fracture energy for each combination of cutting conditions, to be able to fit the experimental results. The cutting force and the chip geometry are analyzed, showing how the developed model adapts to the experimental results. It shows that as the cutting speed and the feed increase, the fracture energy value that best adapts to the model decreases. The evolution shows a more pronounced decrease related to the feed increment and high cutting speed.
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| 30. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 31. |
- Cordero, Gerardo A., et al.
(författare)
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Physiological plasticity in lizard embryos exposed to high-altitude hypoxia
- 2017
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Ingår i: JOURNAL OF EXPERIMENTAL ZOOLOGY PART A-ECOLOGICAL AND INTEGRATIVE PHYSIOLOGY. - : Wiley. - 2471-5646 .- 2471-5638. ; 327:7, s. 423-432
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Tidskriftsartikel (refereegranskat)abstract
- Coping with novel environments may be facilitated by plastic physiological responses that enable survival during environmentally sensitive life stages. We tested the capacity for embryos of the common wall lizard (Podarcis muralis) from low altitude to cope with low-oxygen partial pressure (hypoxia) in an alpine environment. Developing embryos subjected to hypoxic atmospheric conditions (15-16% O-2 sea-level equivalent) at 2,877m above sea level exhibited responses common to vertebrates acclimatized to or evolutionarily adapted to high altitude: suppressed metabolism, cardiac hypertrophy, and hyperventilation. These responses might have contributed to the unaltered incubation duration and hatching success relative to the ancestral, low-altitude, condition. Even so, hypoxia constrained egg energy utilization such that larger eggs produced hatchlings with relatively low mass. These findings highlight the role of physiological plasticity in maintaining fitness-relevant phenotypes in high-altitude environments, providing impetus to further explore altitudinal limits to ecological diversification in ectothermic vertebrates.
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| 32. |
- Logan, Leslie, 1992-, et al.
(författare)
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Energy Drive for the Kiruna Mining District Mineral System(s): Insights from U-Pb Zircon Geochronology
- 2022
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Ingår i: Minerals. - : MDPI. - 2075-163X. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- The Kiruna mining district, Sweden, known for the type locality of Kiruna-type iron oxide-apatite (IOA) deposits, also hosts several Cu-mineralized deposits including iron oxide-copper-gold (IOCG), exhalative stratiform Cu-(Fe-Zn), and structurally controlled to stratabound Cu +/- Au. However the relationship between the IOA and Cu-systems has not been contextualized within the regional tectonic evolution. A broader mineral systems approach is taken to assess the timing of energy drive(s) within a regional tectonic framework by conducting U-Pb zircon geochronology on intrusions from areas where Cu-mineralization is spatially proximal. Results unanimously yield U-Pb ages from the early Svecokarelian orogeny (ca. 1923-1867 Ma including age uncertainties), except one sample from the Archean basement (2698 +/- 3 Ma), indicating that a distinct thermal drive from magmatic activity was prominent for the early orogenic phase. A weighted average Pb-207/Pb-206 age of 1877 +/- 10 Ma of an iron-oxide-enriched gabbroic pluton overlaps in age with the Kiirunavaara IOA deposit and is suggested as a candidate for contributing mafic signatures to the IOA ore. The results leave the role of a late energy drive (and subsequent late Cu-mineralization and/or remobilization) ambiguous, despite evidence showing a late regional magmatic-style hydrothermal alteration is present in the district.
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| 33. |
- Oechtering, Tobias J., et al.
(författare)
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Arimoto-Blahut algorithm for the bidirectional broadcast channel with side information
- 2009
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Ingår i: 2009 IEEE Information Theory Workshop. - Taormina, Sicily. - 9781424449835 ; , s. 394-398
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Konferensbidrag (refereegranskat)abstract
- The bidirectional broadcast channel with random states known at the encoder denotes a broadcast channel with two receivers where each receiver knows the message intended for the other and the transmitter knows the channel state. For such a channel we derive an Arimoto-Blahut-like algorithm to compute the weighted-rate sum maxima. To this end we provide an equivalent characterization of the achievable rate region using Shannon's method of transmit strategies, which we use to show that the optimal coding does not gain from time-sharing. Finally, the trade-off of the input distribution and the impact of the random state is discussed in two examples.
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| 34. |
- Salomonsson, Kent E., et al.
(författare)
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Weighted Potential Methodology for Mixed Mode Cohesive Laws
- 2010
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Ingår i: Proceedings of the MECOM DEL BICENTENARIO, IX Argentinian Congress on Computational Mechanics. - : Asociación Argentina de Mecánica Comptacional. ; , s. 8355-8374
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Konferensbidrag (refereegranskat)abstract
- A weighted potential methodology is developed by utilizing pure mode I and mode II energy release rate experiments to determine the traction-separation relations for thin adhesive layers. The experimentally measured energy release rates act as boundary conditions for developing a weighted potential function. Thus, the tractions for any mixed mode loading can be established. Changes of mode mix during an experiment can also be captured by the law since every mixed mode variation is given by the potential function. Furthermore, by use of an inverse J-integral approach and damage type variables, the traction-separation relations for any mode mix can be approximated by use of pure mode experiments. Numerical simulations show the applicability of the methodology. The results indicate that the methodology is promising when simulating the constitutive behavior of adhesive layers.
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| 35. |
- Uller, Tobias, 1977, et al.
(författare)
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Female egg investment in relation to male sexual traits and the potential for transgenerational effects in sexual selection
- 2005
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Ingår i: Behavioral Ecology and Sociobiology. - : Springer Science and Business Media LLC. - 0340-5443 .- 1432-0762. ; 57:6, s. 584-590
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Tidskriftsartikel (refereegranskat)abstract
- Life-history theory predicts that individuals should increase their reproductive effort when the fitness return from reproduction is high. Females mated with high-quality males are therefore expected to have higher investment than females mated with low-quality males, which could bias estimates of paternal effects. Investigating the traits females use in their allocation decisions and the aspects of reproduction that are altered is essential for understanding how sexual selection is affected. We studied the potential for differential female allocation in a captive population of a precocial bird, the Chinese quail, Coturnix chinensis. Females paired with males with large sexual ornaments laid larger, but not more, eggs than females paired with males with small sexual ornaments. Furthermore, female egg mass was also significantly positively affected by male testis size, probably via some unknown effect of testis size on male phenotype. Testis size and ornament size were not correlated. Thus, both primary and secondary male sexual traits could be important components of female allocation decisions. Experimental manipulation of hormone levels during embryonic development showed that both male and female traits influencing female egg size were sensitive to early hormone exposure. Differences in prenatal hormone exposure as a result of maternal steroid allocation to eggs may explain some of the variation in reproductive success among individuals, with important implications for non-genetic transgenerational effects in sexual selection. © Springer-Verlag 2005.
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