| 1. |
- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 2. |
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| 3. |
- Bakken, TE, et al.
(author)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Journal article (peer-reviewed)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 4. |
- Gonzalez, C. A., et al.
(author)
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Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project
- 2012
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In: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 23:5, s. 1320-1324
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Journal article (peer-reviewed)abstract
- In epidemiological studies, Helicobacter pylori infection is usually detected by enzyme-linked immunosorbent assay (ELISA). However, infection can spontaneously clear from the mucosa during the progression of atrophy and could lead to substantial under-detection of infection and underestimation of its effect on gastric cancer (GC) risk. Antibodies detected by western blot are known to persist longer after the loss of the infection. In a nested case-control study from the Eurogast-EPIC cohort, including 88 noncardia GC cases and 338 controls, we assessed the association between noncardia GC and H. pylori infection comparing antibodies detected by western blot (HELICOBLOT2.1) to those detected by ELISA (Pyloriset EIA-GIII((R))). By immunoblot, 82 cases (93.2%) were H. pylori positive, 10 of these cases (11.4%) were negative by ELISA and only 6 cases (6.8%) were negative by both ELISA and immunoblot. Multivariable odds ratio (OR) for noncardia GC comparing immunoglobulin G positive versus negative by ELISA was 6.8 [95% confidence interval (CI) 3.0-15.1], and by immunoblot, the OR was 21.4 (95% CI 7.1-64.4). Using a western blot assay, nearly all noncardia GC were classified as H. pylori positive and the OR was more than threefold higher than the OR assessed by ELISA, supporting the hypothesis that H. pylori infection is a necessary condition for noncardia GC.
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| 5. |
- Tsilidis, K. K., et al.
(author)
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Oral contraceptives, reproductive history and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition
- 2010
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 103:11, s. 1755-1759
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Journal article (peer-reviewed)abstract
- BACKGROUND: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. METHODS: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. RESULTS: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83-1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74-0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. CONCLUSION: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. British Journal of Cancer (2010) 103, 1755-1759. doi:10.1038/sj.bjc.6605965 www.bjcancer.com Published online 2 November 2010 (C) 2010 Cancer Research UK
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| 6. |
- Tsilidis, K. K., et al.
(author)
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Oral contraceptive use and reproductive factors and risk of ovarian cancer in the European Prospective Investigation into Cancer and Nutrition
- 2011
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In: British Journal of Cancer. - London : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 105:9, s. 1436-1442
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. METHODS: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. RESULTS: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41-0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59-0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs <= 45 years: HR, 1.46; 95% CI, 1.06-1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. CONCLUSION: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors. British Journal of Cancer (2011) 105, 1436-1442. doi:10.1038/bjc.2011.371 www.bjcancer.com Published online 13 September 2011 (C) 2011 Cancer Research UK
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| 7. |
- Kyro, C., et al.
(author)
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ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
- 2013
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In: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 1207-1208
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Journal article (other academic/artistic)abstract
- Background and objectives: Few studies have investigatedthe association between whole-grain intake and colorectal cancer.Whole-grain products are one of the dietary items proneto measurement errors, making the use of objective measures,such as biomarkers, highly relevant. The objective of the studywas to investigate the association between biomarkers ofwhole-grain intake, alkylresorcinols, and colorectal cancer ina nested case-control study within the European ProspectiveInvestigation into Cancer and Nutrition (EPIC). Methods: We included 1372 first incident colorectal cancercases and 1372 individually matched controls and calculatedthe incidence rate ratios (IRR) for overall and sub-sites of colorectalcancer using conditional logistic regression adjusted forpotential confounders.Results: Plasma total alkylresorcinol concentrations werenot associated with risk of overall colorectal cancer, proximalcolon cancer or rectal cancer. However, high plasma total alkylresorcinolconcentrations were statistically significantly associatedwith lower incidence of cancer located in the distal (leftor descending) part of the colon. Adjusted IRR of distal coloncancer for highest versus lowest quartile of plasma alkylresorcinolwas 0.48 (95% confidence interval = 0.28 to 0.83). Furthermore,we observed an inverse association with colon cancerfor the Scandinavian part of the participants. Alkylresorcinolsmay be more appropriate as biomarkers in Middle Europe andScandinavia i.e. in areas where whole grains are regularly consumed.Conclusions: Whole-grain intake, assessed by alkylresorcinols,was associated with a lower incidence of distal coloncancer. Alkylresorcinols seem useful as objective biomarkersof whole-grain intake in populations where whole-grains are astaple part of the diet. Acknowledgements: This work was supportedby World Cancer Research Fund International (WCRF)and WCRF Netherlands (WCRF NL) (2011/436), and NordForsk(Centre of Excellence programme HELGA (070015)).
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| 8. |
- Aidas, Kestutis, et al.
(author)
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The Dalton quantum chemistry program system
- 2014
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In: WIREs Computational Molecular Science. - : Wiley. - 1759-0876 .- 1759-0884. ; 4:3, s. 269-284
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Journal article (peer-reviewed)abstract
- Dalton is a powerful general-purpose program system for the study of molecular electronic structure at the Hartree-Fock, Kohn-Sham, multiconfigurational self-consistent-field, MOller-Plesset, configuration-interaction, and coupled-cluster levels of theory. Apart from the total energy, a wide variety of molecular properties may be calculated using these electronic-structure models. Molecular gradients and Hessians are available for geometry optimizations, molecular dynamics, and vibrational studies, whereas magnetic resonance and optical activity can be studied in a gauge-origin-invariant manner. Frequency-dependent molecular properties can be calculated using linear, quadratic, and cubic response theory. A large number of singlet and triplet perturbation operators are available for the study of one-, two-, and three-photon processes. Environmental effects may be included using various dielectric-medium and quantum-mechanics/molecular-mechanics models. Large molecules may be studied using linear-scaling and massively parallel algorithms. Dalton is distributed at no cost from for a number of UNIX platforms.
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| 9. |
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| 10. |
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| 11. |
- Nygren, Arne, 1971, et al.
(author)
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A mega-cryptic species complex hidden among one of the most common annelids in the North East Atlantic
- 2018
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:6
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Journal article (peer-reviewed)abstract
- We investigate mitochondrial (COI, 16S rDNA) and nuclear (ITS2, 28S rDNA) genetic structure of North East Atlantic lineages of Terebellides, a genus of sedentary annelids mainly inhabiting continental shelf and slope sediments. We demonstrate the presence of more than 25 species of which only seven are formally described. Species boundaries are determined with molecular data using a broad range of analytical methods. Many of the new species are common and wide spread, and the majority of the species are found in sympatry with several other species in the complex. Being one of the most regularly encountered annelid taxa in the North East Atlantic, it is more likely to find an undescribed species of Terebellides than a described one.
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| 12. |
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| 13. |
- Smith, K.A., et al.
(author)
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Oxidation of atmospheric methane in Northern European soils, comparison with other ecosystems, and uncertainties in the global terrestrial sink
- 2000
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 6:7, s. 791-803
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Journal article (peer-reviewed)abstract
- This paper reports the range and statistical distribution of oxidation rates of atmospheric CH4 in soils found in Northern Europe in an international study, and compares them with published data for various other ecosystems. It reassesses the size, and the uncertainty in, the global terrestrial CH4 sink, and examines the effect of land-use change and other factors on the oxidation rate. Only soils with a very high water table were sources of CH4, all others were sinks. Oxidation rates varied from 1 to nearly 200 µg CH4 m-2 h-1, annual rates for sites measured for =1 y were 0.1-9.1 kg CH4 ha-1 y-1, with a log-normal distribution (log-mean ~ 1.6 kg CH4 ha-1 y-1). Conversion of natural soils to agriculture reduced oxidation rates by two-thirds - closely similar to results reported for other regions. N inputs also decreased oxidation rates. Full recovery of rates after these disturbances takes > 100 y. Soil bulk density, water content and gas diffusivity had major impacts on oxidation rates. Trends were similar to those derived from other published work. Increasing acidity reduced oxidation, partially but not wholly explained by poor diffusion through litter layers which did not themselves contribute to the oxidation. The effect of temperature was small, attributed to substrate limitation and low atmospheric concentration. Analysis of all available data for CH4 oxidation rates in situ showed similar log-normal distributions to those obtained for our results, with generally little difference between different natural ecosystems, or between short-and longer-term studies. The overall global terrestrial sink was estimated at 29 Tg CH4 y-1, close to the current IPCC assessment, but with a much wider uncertainty range (7 to > 100 Tg CH4 y-1). Little or no information is available for many major ecosystems, these should receive high priority in future research.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Schander, C, 1960, et al.
(author)
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The fauna of hydrothermal vents on the Mohn Ridge (North Atlantic)
- 2010
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In: Marine Biology Research. - 1745-1000. ; 6:2, s. 155-171
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Journal article (peer-reviewed)abstract
- The macrofauna of the newly discovered hydrothermal vent field on the Mohn Ridge at 71 degrees N was investigated. Samples were collected during the cruise BIODEEP 2006 using the ROV 'Bathysaurus'. A total of 180 species-level taxa were identified. The region contains very few vent-endemic species, but some species of Porifera, Crustacea and Mollusca may be vent-associated. Dense aggregations of motile non-vent species such as Heliometra glacialis and Gorgonocephalus eucnemis surrounded the vent area, but the area in general only held small numbers of sedentary animals. Calcareous sponges comprised an unusually high portion of the sponge species found and they constitute one of the first pioneers among the sessile invertebrates settling on these vents. Possible explanations for the structure of the fauna in the region are discussed.
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| 18. |
- Duell, Eric J, et al.
(author)
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Menstrual and reproductive factors, exogenous hormone use, and gastric cancer risk in a cohort of women from the European Prospective Investigation Into Cancer and Nutrition
- 2010
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 172:12, s. 1384-1393
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Journal article (peer-reviewed)abstract
- The worldwide incidence of gastric adenocarcinoma (GC) is lower in women than in men. Furthermore, cancer patients treated with estrogens have been reported to have a lower subsequent risk of GC. The authors conducted a prospective analysis of menstrual and reproductive factors, exogenous hormone use, and GC in 335,216 women from the European Prospective Investigation Into Cancer and Nutrition, a cohort study of individuals aged 35-70 years from 10 European countries. After a mean follow-up of 8.7 years (through 2004), 181 women for whom complete exposure data were available developed GC. Adjusted hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards models. All statistical tests were 2-sided. Women who had ovariectomy had a 79% increased risk of GC (based on 25 cases) compared with women who did not (hazard ratio = 1.79, 95% confidence interval: 1.15, 2.78). Total cumulative years of menstrual cycling was inversely associated with GC risk (fifth vs. first quintile: hazard ratio = 0.55, 95% confidence interval: 0.31, 0.98; P(trend) = 0.06). No other reproductive factors analyzed were associated with risk of GC. The results of this analysis provide some support for the hypothesis that endogenous ovarian sex hormones lower GC incidence in women.
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| 19. |
- Fritzsch, R., et al.
(author)
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Electromagnetic priming of ceramic foam filters (CFF) for liquid aluminum filtration
- 2016
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In: 142nd Annual Meeting and Exhibition, TMS 2013. - Cham : Springer International Publishing. ; , s. 973-979
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Conference paper (peer-reviewed)abstract
- Commercial Ceramic Foam Filters (CFF) of 30, 50 and 80 Pores Per Inch (PPI) have been primed, using magnetic field strengths of 0.06–0.2T, for periods of 1–10 minutes. The influence of time and field strength on the gas removal from the CFF structure, and the resulting improvements in filter productivity, are discussed. The obtained results are related to Finite Element Modeling (FEM) of the metal flow fields induced by the electromagnetic Lorentz forces. Higher filtration rates were obtained for 50 PPI magnetically primed, than for 30 PPI gravity primed filters. This suggests that electromagnetic priming offers an opportunity to use 50 PPI filters, with a higher overall filtration efficiency than 30 PPI filters, in existing cast house applications where the low productivity/high priming head of these filters would otherwise rule them out. Estimated filtration efficiency of different filter types are presented as functions of velocity and thickness.
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| 20. |
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| 21. |
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| 22. |
- Kennedy, M. W., et al.
(author)
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Analytical and fem modeling of aluminum billet induction heating with experimental verification
- 2016
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In: Light Metals 2012. - Cham : Springer International Publishing. ; , s. 269-275
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Book chapter (other academic/artistic)abstract
- Induction heating is commonly used in the re-heating of aluminum billets before forging or extrusion. Powerful finite element modeling (FEM) tools are available to assist in the design of such processes; however, such models should be validated by comparison with analytical solutions or experimental results to ensure accuracy. Induction heating experiments have been performed using a number of different coil designs and work piece dimensions at 50 Hz. Aluminum alloys with different electrical conductivities have been used, i.e. 6060 and A356. Process parameters such as: current, power, magnetic field, electrical conductivity, etc. have been measured with high precision instrumentation. Experimental data are presented and compared with equivalent 1D analytical and 2D axial symmetric FEM modeling results. The effect of frequency on the induction heating process is reviewed using the validated analytical and FEM models. Some recommendations are given with respect to appropriate modeling techniques, boundary conditions and numerical mesh sizes.
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| 23. |
- Kennedy, Mark W., et al.
(author)
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Analytical and FEM modeling of aluminum billet induction heating with experimental verification
- 2012
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In: Light Metals 2012. - Hoboken, NJ, USA : John Wiley & Sons. ; , s. 269-275
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Conference paper (peer-reviewed)abstract
- Induction heating is commonly used in the re-heating of aluminum billets before forging or extrusion. Powerful finite element modeling (FEM) tools are available to assist in the design of such processes; however, such models should be validated by comparison with analytical solutions or experimental results to ensure accuracy. Induction heating experiments have been performed using a number of different coil designs and work piece dimensions at 50 Hz. Aluminum alloys with different electrical conductivities have been used, i.e. 6060 and A356. Process parameters such as: current, power, magnetic field, electrical conductivity, etc. have been measured with high precision instrumentation. Experimental data are presented and compared with equivalent 1D analytical and 2D axial symmetric FEM modeling results. The effect of frequency on the induction heating process is reviewed using the validated analytical and FEM models. Some recommendations are given with respect to appropriate modeling techniques, boundary conditions and numerical mesh sizes.
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| 24. |
- Kennedy, Mark W., et al.
(author)
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Empirical Verification of a Short Coil Correction Factor
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Other publication (other academic/artistic)abstract
- The magnetic field produced in the air-gap by any particular 'short coil' at a fixed current, is affected by a highly complex interaction of the coil and work piece geometries and changes in frequency. A frequency modified semi-empirical short coil correction factor, based upon the formula published by Vaughan and Williamson in 1945, is presented and experimentally verified. This new equation is shown to predict the total system reactive power and the average magnetic flux at the surface of the work piece with typical differences of less than 2% at 50 Hz AC and to accurately predict work piece heating rates typically within 5% for aluminum billets at 50 Hz to 500 kHz AC. The work piece real and reactive powers, and total system reactive power are compared with both analytic and 2D axial symmetric FEM model solutions, as a function of operating frequencies from 50 Hz to 500 kHz. Measured flux density is compared to FEM and analytical predictions at 50 Hz.
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| 25. |
- Kennedy, M. W., et al.
(author)
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Review of classical design methods as applied to aluminum billet heating with induction coils
- 2011
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In: TMS Annual Meeting. - 9781617827389 ; , s. 707-722
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Conference paper (peer-reviewed)abstract
- In the present study classical induction design tools are applied to the problem of heating non-magnetic metal billets, using 50 Hz AC. As an example of great practical industrial interest, the induction heating of aluminum billets is addressed specifically. The predicted work piece power is compared with the measured work piece power for a long and a short coil, using well established methods, such as those of Burch and Davis, introduced in 1926/28, Dwight and Bagai in 1935, Baker in 1944/57, Vaughan and Williamson in 1945, and by Tudbury in 1960. A calculation methodology based on a combination of the available tools is also introduced and discussed. The method has proven to give an error of <10% of the actual work piece power. An equation for Tudbury's work piece shortness correction factor is disclosed for the first time.
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| 26. |
- Ruiz-Gomez, Maria de Lourdes, et al.
(author)
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Behavioral plasticity in rainbow trout (Oncorhynchus mykiss) with divergent coping styles : when doves become hawks
- 2008
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In: Hormones and Behavior. - : Elsevier BV. - 0018-506X .- 1095-6867. ; 54:4, s. 534-8
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Journal article (peer-reviewed)abstract
- Consistent and heritable individual differences in reaction to challenges, often referred to as stress coping styles, have been extensively documented in vertebrates. In fish, selection for divergent post-stress plasma cortisol levels in rainbow trout (Oncorhynchus mykiss) has yielded a low (LR) and a high responsive (HR) strain. A suite of behavioural traits is associated with this physiological difference, with LR (proactive) fish feeding more rapidly after transfer to a new environment and being socially dominant over HR (reactive) fish. Following transport from the UK to Norway, a switch in behavioural profile occurred in trout from the 3rd generation; HR fish regained feeding sooner than LR fish in a novel environment and became dominant in size-matched HR-LR pairs. One year after transport, HR fish still fed sooner, but no difference in social dominance was found. Among offspring of transported fish, no differences in feeding were observed, but as in pre-transported 3rd generation fish, HR fish lost fights for social dominance against size-matched LR opponents. Transported fish and their offspring retained their distinctive physiological profile throughout the study; HR fish showed consistently higher post-stress cortisol levels at all sampling points. Altered risk-taking and social dominance immediately after transport may be explained by the fact that HR fish lost more body mass during transport than did LR fish. These data demonstrate that some behavioural components of stress coping styles can be modified by experience, whereas behavioural plasticity is limited by genetic effects determining social position early in life story.
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