| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 7. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 8. |
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| 9. |
- Su, Zhan, et al.
(författare)
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Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:10
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Tidskriftsartikel (refereegranskat)abstract
- Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (Pcombined=4.09×10(-9); odds ratio (OR)=1.21, 95% confidence interval (CI)=1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (Pcombined=2.74×10(-10); OR=1.14, 95% CI=1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
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| 10. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 11. |
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| 12. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 13. |
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| 14. |
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| 15. |
- Brizuela, F., et al.
(författare)
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Near-wavelength Resolution Extreme Ultraviolet Imaging With a Desktop-size Laser
- 2008
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Ingår i: 2008 CONFERENCE ON LASERS AND ELECTRO-OPTICS & QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE, VOLS 1-9. ; , s. 400-401
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Konferensbidrag (refereegranskat)abstract
- We have realized the first demonstration of imaging in the extreme ultraviolet (EUV) with near-wavelength spatial resolution, 54 nm, using a uniquely compact full-field microscope that can produce images with a single one nanosecond exposure.
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| 16. |
- Menoni, C. S., et al.
(författare)
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Advances in Nanoscale Resolution Soft X-Ray Laser Microscopy
- 2009
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Ingår i: X-RAY LASERS 2008, PROCEEDINGS. - : Springer Netherlands. - 9781402099236 ; , s. 341-347
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Konferensbidrag (refereegranskat)abstract
- We review our most recent results on table-top, nanometer-scale resolution, microscopy using compact soft x-ray lasers developed at Colorado State University. We have realized the first demonstration of wavelength-resolution microscopy in the soft x-ray spectral range. Images of carbon nanotubes, 50 nm in diameter, were obtained with a single similar to 1 ns duration laser pulse from a desk-top size capinary discharge 46.9 nm laser. We fully characterized the new microscope by measuring the modulation transfer function of the instrument for zone plate objectives with three different numerical apertures, demonstrating that 54 nm half-period structures can be resolved. The combination of near-wavelength spatial resolution with high temporal resolution imaging opens myriad opportunities for imaging nanoscale structures.
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| 17. |
- Menoni, C. S., et al.
(författare)
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Nanometer-scale imaging and ablation with Extreme Ultraviolet lasers
- 2007
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Ingår i: 2007 CONFERENCE ON LASERS & ELECTRO-OPTICS/QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2007), VOLS 1-5. - 9781424435906 ; , s. 1401-1402
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Konferensbidrag (refereegranskat)abstract
- The short wavelength and high brightness of compact extreme ultraviolet lasers is shown to enable the development of microscopes with spatial resolution of tens of nanometers and new types of nanoprobes.
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| 18. |
- Menoni, C. S., et al.
(författare)
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Nanoscale resolution microscopy and ablation with extreme ultraviolet lasers
- 2007
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Ingår i: 2007 IEEE LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2. - 9781424409242 ; , s. 488-489
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Konferensbidrag (refereegranskat)abstract
- We obtain a spatial resolution down to 38 run with full field imaging and laser-ablation systems that exploit the short wavelength and high brightness output from compact extreme ultraviolet lasers in combination with zone plate optics.
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| 19. |
- Rocca, J. J., et al.
(författare)
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Compact Soft X-ray Lasers for Imaging, Material Processing, and Characterization at the Nanoscale
- 2007
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Ingår i: 32nd IEEE/CPMT International Electronic Manufacturing Technology Symposium. - 9781424413355 ; , s. 72-73
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Konferensbidrag (refereegranskat)abstract
- As manufacturing of devices advances into the nanoscale, critical feature sizes have rapidly shrunk to below the wavelength of visible light. These advances in nanotechnology have created a need to develop better ways of accessing the nanoworld. The extreme ultraviolet (EUV)/ soft x-ray (SXR) region of the spectrum provides an opportunity to use coherent light at wavelengths that are 10- to 100-times shorter than visible light, at 1 to 100 nm. Given the diffraction limit in imaging resolution, these wavelengths allow us to "see" smaller features and "write" smaller patterns than would be possible with visible light. We have developed compact laser-pumped and discharge-pumped lasers operating at wavelengths of λ=13.2 nm [1] and λ=46.9 nm [2] respectively, and have used them in the demonstration of nanoscale full field imaging [3,4], nanopatterning [5], and nanoscale laser ablation [6]. The high brightness and short wavelength output from these lasers when combined with specialized EUV/SXR optics, offer unique opportunities for the implementation of table-top imaging, patterning and metrology tools with superior spatial resolution for applications in nanoscience and nanotechnology. Using these new compact short wavelength lasers we have built two microscopes, using λ=46.9 nm or λ=l 3.2 nm laser illumination. The compact λ=46.9 nm microscope (Fig. 1a and lb) condenses the light using a multilayer coated Schwarzschild mirror, and images the test object using a diffractive zone plate lens. The spatial resolution of this microscopes was assessed by imaging test samples consisting of dense line gratings of half-periods ranging from 200 down to 35 nm. Figure 2(a) and (b) show images of a 100 nm and 70 nm half-period gratings obtained with the λ =46.9 nm microscope. The lineout in the image of the 70 nm lines shows a modulation of ∼30% indicating that the features are fully resolved according to the Rayleigh criterion. By rearranging the optics, the λ=46.9 nm microscope can also image surfaces. An image of fully resolved dense metal lines, with half-period of 170 nm, patterned on the silicon wafer is shown in Figure 2 (c). The shorter wavelength λ= 3.2 nm microscope uses all zone plate optics to render images of transmissive test patterns with increased spatial resolution . An image of fully resolved 50 nm half-period dense lines acquired with a 20 seconds exposure is shown in Figure 2(d). From images like this one, the spatial resolution of the λ=13.2 nm table-top microscope was determined to be better than 38 nm [3]. The high coherence of these short wavelength lasers also allows for the printing of arrays of nanoscale features using interferometric lithography. We have demonstrated combined a λ=46.9 nm capillary discharge laser and a Lloyd's mirror to print arrays of cone-shaped nano-dots with ∼ 58 nm FWHM diameter (Fig 3a) [5]. The same arrangement was used to print arrays of nano-holes 120 nm FWHM and 100 nm in depth over areas in excess of 500 × 500 μm2 in different photoresists using exposure times as short as 80 s. Larger area patterns can be readily printed using precision translation stages and multiple exposures by overlay superposition. The ability to focus SXL laser light into near diffraction-limited spots also opens the possibility to develop new types of nanoprobes. We have demonstrated ablation of sub-100 nm diameter holes by directly focusing the output of a λ=46.9 nm laser onto a sample with a zone plate lens. Figure 3(b) shows an AFM image of a 82 nm diameter crater obtained ablating a 500 nm thick PMMA layer with a single laser shot. The holes were observed to have very clean walls and high reproducibility. We have recently added the capability to spectroscopically analyze the light emitted from the plasma created during the ablation, opening the possibility to develop analytic nanoprobles. All of these results illustrate the capabilities of compact short wavelength lasers for nanotechnology applications.
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| 20. |
- Brizuela, F., et al.
(författare)
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High resolution full-field imaging of nanostructures using compact extreme ultraviolet lasers
- 2009
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Ingår i: 9TH INTERNATIONAL CONFERENCE ON X-RAY MICROSCOPY. - : IOP Publishing.
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Konferensbidrag (refereegranskat)abstract
- Recent advances in the development of high peak brightness table-top extreme ultraviolet (EUV) and soft x-ray (SRX) lasers have opened new opportunities for the demonstration of compact full-field EUV/SXR microscopes capable of capturing images with short exposures down to a single laser shot. We demonstrate the practical application of table-top zone plate EUV microscopes that can image nanostructures with a spatial resolution of 54 nm and below and exposure times as short as 1.2 ns, the duration of a single laser shot.
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| 23. |
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| 25. |
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| 26. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
- Brewer, Courtney A., et al.
(författare)
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High spatial resolution full-field microscopy using a desktop-size soft x-ray laser
- 2007
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Ingår i: Proceedings of SPIE. - : SPIE.
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Konferensbidrag (refereegranskat)abstract
- Images with nanoscale resolution were obtained in both transmission and reflection modes using a full-field microscope that is illuminated by an extremely compact λ = 46.9 nm (hv = 26.4 eV) soft x-ray laser. The microscope was used to image the surface of partially processed silicon semiconductor chips containing periodic patterns of polysilicon and metal lines. To characterize the microscope, modulation transfer functions were experimentally built for three different objective zone plates, and images with near-wavelength resolution were obtained.
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| 31. |
- Brewer, Courtney A., et al.
(författare)
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Single-shot extreme ultraviolet laser imaging of nanostructures with wavelength resolution
- 2008
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Ingår i: Optics Letters. - : Optical Society of America. - 0146-9592 .- 1539-4794. ; 33:5, s. 518-520
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Tidskriftsartikel (refereegranskat)abstract
- We have demonstrated near-wavelength resolution microscopy in the extreme ultraviolet. Images of 50 nm diameter nanotubes were obtained with a single ~1 ns duration pulse from a desktop-size 46.9 nm laser. We measured the modulation transfer function of the microscope for three different numerical aperture zone plate objectives, demonstrating that 54 nm half-period structures can be resolved. The combination of near-wavelength spatial resolution and high temporal resolution opens myriad opportunities in imaging, such as the ability to directly investigate dynamics of nanoscale structures.
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| 32. |
- Brizuela, Fernando, et al.
(författare)
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Imaging at the Nanoscale With Practical Table-Top EUV Laser-Based Full-Field Microscopes
- 2012
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - 1077-260X. ; 18:1, s. 434-442
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Tidskriftsartikel (refereegranskat)abstract
- The demonstration of table-top high average power extreme-ultraviolet (EUV) lasers combined with the engineering of specialized optics has enabled the demonstration of full-field microscopes that have achieved tens of nanometer spatial resolution. This paper describes the geometry of the EUV microscopes tailored to specific imaging applications. The microscope illumination characteristics are assessed and an analysis on the microscope's spatial resolution is presented. Examples of the capabilities of these table-top EUV aerial microscopes for imaging nanostructures and surfaces are presented.
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| 33. |
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| 34. |
- Gosling, C. J., et al.
(författare)
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Known-groups and convergent validity of the theory of mind task battery in children with autism spectrum disorder
- 2023
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Ingår i: British Journal of Clinical Psychology. - 0144-6657. ; 62:2, s. 525-535
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesOne of the most promising Theory of Mind (ToM) tests developed for children with ASD is the Theory of Mind Task Battery (ToM-TB). Still, additional psychometric properties of this tool need to be assessed. The main objective of this preregistered study was to investigate the known-groups and convergent validities of the ToM-TB compared to a well-established test used to assess ToM in children with ASD (the Strange Stories Test; SST). MethodsA total of 68 school-aged children were recruited (34 children with ASD and 34 children with typical development). The groups were matched on sex and age, and on both receptive language abilities and overall cognitive functioning. ResultsRegarding the known-groups validity, we found group differences in the performance on the ToM-TB and SST. Additional analyses revealed that this result tended to be more robust for the ToM-TB than for the SST. Regarding convergent validity, we showed that the ToM-TB and SST correlated strongly, for children with ASD and children with typical development. In contrast, we found small correlations of these two tests with social competence in daily life. No evidence was found for greater known-groups or convergent validity of one test compared to the other. ConclusionOur data confirmed the relevance of the ToM-TB and the SST for the assessment of ToM in school-aged children. Future studies should continue to assess the psychometric qualities of various ToM tests to provide reliable information to best guide researchers and clinicians when choosing optimal neuropsychological tools.
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| 35. |
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| 38. |
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| 39. |
- Via, Allegra, et al.
(författare)
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Best practices in bioinformatics training for life scientists
- 2013
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 14:5, s. 528-537
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Tidskriftsartikel (refereegranskat)abstract
- The mountains of data thrusting from the new landscape of modern high-throughput biology are irrevocably changing biomedical research and creating a near-insatiable demand for training in data management and manipulation and data mining and analysis. Among life scientists, from clinicians to environmental researchers, a common theme is the need not just to use, and gain familiarity with, bioinformatics tools and resources but also to understand their underlying fundamental theoretical and practical concepts. Providing bioinformatics training to empower life scientists to handle and analyse their data efficiently, and progress their research, is a challenge across the globe. Delivering good training goes beyond traditional lectures and resource-centric demos, using interactivity, problem-solving exercises and cooperative learning to substantially enhance training quality and learning outcomes. In this context, this article discusses various pragmatic criteria for identifying training needs and learning objectives, for selecting suitable trainees and trainers, for developing and maintaining training skills and evaluating training quality. Adherence to these criteria may help not only to guide course organizers and trainers on the path towards bioinformatics training excellence but, importantly, also to improve the training experience for life scientists.
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| 40. |
- Yang, Y-W, et al.
(författare)
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Association and phase behaviour of statistical and block copolymers of ethylene oxide and butylene oxide in water
- 1997
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Ingår i: Polymer. - 0032-3861 .- 1873-2291. ; 38, s. 1659-1668
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Tidskriftsartikel (refereegranskat)abstract
- Three copolymers of ethylene oxide (EO) and 1,2-butylene oxide (BO) were prepared by anionic polymerization to have similiar molar masses (Mn ≈ 7000 g mol-1), molar mass distributions (Mw/Mn<1.1) and compositions (80mol% oxythylene) but different chain structures. A triblock copolymer was prepared by sequential copolymerization of EO followed by BO, and two statistical copolymers were prepared from mixed monomers, either to low (15%) or to high (93%) conversion. The disparity in reactivity ratios in the EO/BO copolymerization resulted in pronounced composition drift along the chains of the high conversion statistical copolymer, giving it the character of a block copolymer. This composition profile was checked by 13C n.m.r. spectroscopy. The association behaviour of the statistical copolymers in aqueous solution at 25°C was studied by dynamic and static light scattering. The low conversion statistical copolymer remained in its molecular state across the concentration range studied (up to 100 g dm-3), but the high conversion statistical copolymer associated into molecular clusters and micelles. Cloud point curves were determined for solutions of the three copolymers. The effect of associations on phase behaviour is discussed.
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