| 1. |
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| 2. |
- 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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| 3. |
- Fomalont, E. B., et al.
(författare)
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THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
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Tidskriftsartikel (refereegranskat)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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| 4. |
- Kang, E. Y., et al.
(författare)
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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study
- 2023
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 129:5, s. 697-713
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclin E1 (CCNE1) is a potential predictive marker and therapeutic target in tubo-ovarian high-grade serous carcinoma (HGSC). Smaller studies have revealed unfavorable associations for CCNE1 amplification and CCNE1 overexpression with survival, but to date no large-scale, histotype-specific validation has been performed. The hypothesis was that high-level amplification of CCNE1 and CCNE1 overexpression, as well as a combination of the two, are linked to shorter overall survival in HGSC. Methods: Within the Ovarian Tumor Tissue Analysis consortium, amplification status and protein level in 3029 HGSC cases and mRNA expression in 2419 samples were investigated. Results: High-level amplification (>8 copies by chromogenic in situ hybridization) was found in 8.6% of HGSC and overexpression (>60% with at least 5% demonstrating strong intensity by immunohistochemistry) was found in 22.4%. CCNE1 high-level amplification and overexpression both were linked to shorter overall survival in multivariate survival analysis adjusted for age and stage, with hazard stratification by study (hazard ratio [HR], 1.26; 95% CI, 1.08-1.47, p = .034, and HR, 1.18; 95% CI, 1.05-1.32, p = .015, respectively). This was also true for cases with combined high-level amplification/overexpression (HR, 1.26; 95% CI, 1.09-1.47, p = .033). CCNE1 mRNA expression was not associated with overall survival (HR, 1.00 per 1-SD increase; 95% CI, 0.94-1.06; p = .58). CCNE1 high-level amplification is mutually exclusive with the presence of germline BRCA1/2 pathogenic variants and shows an inverse association to RB1 loss. Conclusion: This study provides large-scale validation that CCNE1 high-level amplification is associated with shorter survival, supporting its utility as a prognostic biomarker in HGSC.
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| 5. |
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| 6. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 7. |
- Pelsers, M. M. A. L., et al.
(författare)
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Skeletal muscle fatty acid transporter protein expression in type 2 diabetes patients compared with overweight, sedentary men and age-matched, endurance-trained cyclists
- 2007
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Ingår i: Acta Physiologica. - Chichester : Wiley-Blackwell. - 1748-1708 .- 1748-1716. ; 190:3, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Membrane fatty acid transporters can modulate the balance between fatty acid uptake and subsequent storage and/or oxidation in muscle tissue. As such, skeletal muscle fatty acid transporter protein expression could play an important role in the etiology of insulin resistance and/or type 2 diabetes.METHODS: In the present study, fatty acid translocase (FAT/CD36), plasma membrane-bound fatty acid-binding protein (FABPpm) and fatty acid transport protein 1 (FATP1) mRNA and protein expression were assessed in muscle tissue obtained from 10 sedentary, overweight type 2 diabetes patients (60 +/- 2 years), 10 sedentary, weight-matched normoglycemic controls (60 +/- 2 years) and 10 age-matched, endurance trained cyclists (57 +/- 1 years).RESULTS: Both FAT/CD36 and FATP1 mRNA and protein expression did not differ between groups. In contrast, FABPpm mRNA and protein expression were approx. 30-40% higher in the trained men compared with the diabetes patients (P < 0.01) and sedentary controls (P < 0.05).CONCLUSIONS: Skeletal muscle FAT/CD36, FABPpm and FATP1 mRNA and protein expression are not up- or downregulated in a sedentary and/or insulin resistant state. In contrast, FABPpm expression is upregulated in the endurance trained state and likely instrumental to allow greater fatty acid oxidation rates. © 2007 The Authors.
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| 8. |
- Popat, S, et al.
(författare)
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Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.
- 2002
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Ingår i: Annals of human genetics. - 0003-4800 .- 1469-1809. ; 66:Pt 2, s. 125-37
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Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.
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| 9. |
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| 10. |
- Correa, J., et al.
(författare)
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On the Charge Collection Efficiency of the PERCIVAL Detector
- 2016
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Ingår i: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- The PERCIVAL soft X-ray imager is being developed by DESY, RAL, Elettra, DLS, and PAL to address the challenges at high brilliance Light Sources such as new-generation Synchrotrons and Free Electron Lasers. Typical requirements for detector systems at these sources are high frame rates, large dynamic range, single-photon counting capability with low probability of false positives, high quantum efficiency, and (multi)-mega-pixel arrangements. PERCIVAL is a monolithic active pixel sensor, based on CMOS technology. It is designed for the soft X-ray regime and, therefore, it is post-processed in order to achieve high quantum efficiency in its primary energy range (250 eV to 1 keV) . This work will report on the latest experimental results on charge collection efficiency obtained for multiple back-side-illuminated test sensors during two campaigns, at the P04 beam-line at PETRA III, and the CiPo beam-line at Elettra, spanning most of the primary energy range as well as testing the performance for photon-energies below 250 eV . In addition, XPS surface analysis was used to cross-check the obtained results.
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| 11. |
- Jarvis, M.J., et al.
(författare)
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The discovery of a z = 0.7092 OH megamaser with the MIGHTEE survey
- 2024
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Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 529:4, s. 3484-3494
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery of the most distant OH megamaser (OHM) to be observed in the main lines, using data from the MeerKAT International Giga-Hertz Tiered Extragalactic Exploration (MIGHTEE) survey. At a newly measured redshift of z = 0.7092, the system has strong emission in both the 1665 MHz (L ≈ 2500 L-) and 1667 MHz (L ≈ 4.5 × 104 L-) transitions, with both narrow and broad components. We interpret the broad line as a high-velocity-dispersion component of the 1667 MHz transition, with velocity v ∼330 km s-1 with respect to the systemic velocity. The host galaxy has a stellar mass of M = 2.95 × 1010 M- and a star formation rate of SFR = 371 M- yr-1, placing it ∼1.5 dex above the main sequence for star-forming galaxies at this redshift, and can be classified as an ultraluminous infrared galaxy. Alongside the optical imaging data, which exhibit evidence for a tidal tail, this suggests that the OHM arises from a system that is currently undergoing a merger, which is stimulating star formation and providing the necessary conditions for pumping the OH molecule to saturation. The OHM is likely to be lensed, with a magnification factor of ∼2.5, and perhaps more if the maser emitting region is compact and suitably offset relative to the centroid of its host galaxy's optical light. This discovery demonstrates that spectral line mapping with the new generation of radio interferometers may provide important information on the cosmic merger history of galaxies.
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| 12. |
- Jewell, Jessica, 1982, et al.
(författare)
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Reply to: Why fossil fuel producer subsidies matter
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 578:7793, s. E5-E7
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Khromova, A., et al.
(författare)
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Report on recent results of the PERCIVAL soft X-ray imager
- 2016
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Ingår i: Journal of Instrumentation. - : IOP. - 1748-0221. ; 11:November
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Tidskriftsartikel (refereegranskat)abstract
- The PERCIVAL (Pixelated Energy Resolving CMOS Imager, Versatile And Large) soft X-ray 2D imaging detector is based on stitched, wafer-scale sensors possessing a thick epi-layer, which together with back-thinning and back-side illumination yields elevated quantum efficiency in the photon energy range of 125–1000 eV. Main application fields of PERCIVAL are foreseen in photon science with FELs and synchrotron radiation. This requires high dynamic range up to 105 ph @ 250 eV paired with single photon sensitivity with high confidence at moderate frame rates in the range of 10–120 Hz. These figures imply the availability of dynamic gain switching on a pixel-by-pixel basis and a highly parallel, low noise analog and digital readout, which has been realized in the PERCIVAL sensor layout. Different aspects of the detector performance have been assessed using prototype sensors with different pixel and ADC types. This work will report on the recent test results performed on the newest chip prototypes with the improved pixel and ADC architecture. For the target frame rates in the 10–120 Hz range an average noise floor of 14e− has been determined, indicating the ability of detecting single photons with energies above 250 eV. Owing to the successfully implemented adaptive 3-stage multiple-gain switching, the integrated charge level exceeds 4 centerdot 106 e− or 57000 X-ray photons at 250 eV per frame at 120 Hz. For all gains the noise level remains below the Poisson limit also in high-flux conditions. Additionally, a short overview over the updates on an oncoming 2 Mpixel (P2M) detector system (expected at the end of 2016) will be reported.
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| 14. |
- Löken, Line Sofie, 1977, et al.
(författare)
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Contribution of dorsal horn CGRP-expressing interneurons to mechanical sensitivity
- 2021
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Ingår i: Elife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Primary sensory neurons are generally considered the only source of dorsal horn calcitonin gene-related peptide (CGRP), a neuropeptide critical to the transmission of pain messages. Using a tamoxifen-inducible CalcaCreER transgenic mouse, here we identified a distinct population of CGRP-expressing excitatory interneurons in lamina III of the spinal cord dorsal horn and trigeminal nucleus caudalis. These interneurons have spine-laden, dorsally directed, dendrites, and ventrally directed axons. As under resting conditions, CGRP interneurons are under tonic inhibitory control, neither innocuous nor noxious stimulation provoked significant Fos expression in these neurons. However, synchronous, electrical non-nociceptive Ab primary afferent stimulation of dorsal roots depolarized the CGRP interneurons, consistent with their receipt of a VGLUT1 innervation. On the other hand, chemogenetic activation of the neurons produced a mechanical hypersensitivity in response to von Frey stimulation, whereas their caspase-mediated ablation led to mechanical hyposensitivity. Finally, after partial peripheral nerve injury, innocuous stimulation (brush) induced significant Fos expression in the CGRP interneurons. These findings suggest that CGRP interneurons become hyperexcitable and contribute either to ascending circuits originating in deep dorsal horn or to the reflex circuits in baseline conditions, but not in the setting of nerve injury.
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| 15. |
- Marras, Alessandro, et al.
(författare)
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Characterization of the Percival detector with soft X-rays
- 2021
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Ingår i: Journal of Synchrotron Radiation. - 0909-0495 .- 1600-5775. ; 28, s. 131-145
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Tidskriftsartikel (refereegranskat)abstract
- In this paper the back-side-illuminated Percival 2-Megapixel (P2M) detector is presented, along with its characterization by means of optical and X-ray photons. For the first time, the response of the system to soft X-rays (250 eV to 1 keV) is presented. The main performance parameters of the first detector are measured, assessing the capabilities in terms of noise, dynamic range and single-photon discrimination capability. Present limitations and coming improvements are discussed.
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| 16. |
- Popat, S, et al.
(författare)
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Genome screening of coeliac disease.
- 2001
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Ingår i: Journal of Medical Genetics. - 0022-2593 .- 1468-6244. ; 39, s. 328-331
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Tidskriftsartikel (refereegranskat)
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| 17. |
- Popat, S, et al.
(författare)
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Genome screening of coeliac disease
- 2002
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 39:5, s. 328-331
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Tidskriftsartikel (refereegranskat)
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| 18. |
- Popat, S, et al.
(författare)
-
Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease
- 2002
-
Ingår i: Annals of Human Genetics. - : Wiley. - 1469-1809 .- 0003-4800. ; 66:2, s. 125-137
-
Tidskriftsartikel (refereegranskat)abstract
- Susceptibility to coeliae disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined Our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliae disease by linkage and association analyses. However. the findings did not attain formal statistical significance (p=0.004 and 0.039. respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (910 families) : p values. 0.0001 and 0.0014 at D2S2214. respectively. and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.
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| 19. |
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