| 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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| 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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