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- Delacroix, Christian, et al.
(författare)
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Laboratory demonstration of a mid-infrared AGPM vector vortex coronagraph
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 553, s. A98-
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Tidskriftsartikel (refereegranskat)abstract
- Context. Coronagraphy is a powerful technique to achieve high contrast imaging, hence to image faint companions around bright targets. Various concepts have been used in the visible and near-infrared regimes, while coronagraphic applications in the mid-infrared nowadays remain largely unexplored. Vector vortex phase masks based on concentric subwavelength gratings show great promise for such applications.Aims. We aim at producing and validating the first high-performance broadband focal plane phase mask coronagraphs for applications in the mid-infrared regime, and in particular the L band with a fractional bandwidth of ~16% (3.5–4.1 μm).Methods. Based on rigorous coupled wave analysis, we designed an annular groove phase mask (AGPM) producing a vortex effect in the L band, and etched it onto a series of diamond substrates. The grating parameters were measured by means of scanning electron microscopy. The resulting components were then tested on a mid-infrared coronagraphic test bench.Results. A broadband raw null depth of 2 × 10-3 was obtained for our best L-band AGPM after only a few iterations between design and manufacturing. This corresponds to a raw contrast of about 6 × 10-5 (10.5 mag) at 2λ/D. This result is fully in line with our projections based on rigorous coupled wave analysis modelling, using the measured grating parameters. The sensitivity to tilt and focus has also been evaluated.Conclusions. After years of technological developments, mid-infrared vector vortex coronagraphs have finally become a reality and live up to our expectations. Based on their measured performance, our L-band AGPMs are now ready to open a new parameter space in exoplanet imaging at major ground-based observatories.
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- Escott-Price, Valentina, et al.
(författare)
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Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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- Moeller, Steffen, et al.
(författare)
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Community-driven development for computational biology at Sprints, Hackathons and Codefests
- 2014
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Ingår i: BMC Bioinformatics. - 1471-2105. ; 15, s. S7-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Computational biology comprises a wide range of technologies and approaches. Multiple technologies can be combined to create more powerful workflows if the individuals contributing the data or providing tools for its interpretation can find mutual understanding and consensus. Much conversation and joint investigation are required in order to identify and implement the best approaches. Traditionally, scientific conferences feature talks presenting novel technologies or insights, followed up by informal discussions during coffee breaks. In multi-institution collaborations, in order to reach agreement on implementation details or to transfer deeper insights in a technology and practical skills, a representative of one group typically visits the other. However, this does not scale well when the number of technologies or research groups is large. Conferences have responded to this issue by introducing Birds-of-a-Feather (BoF) sessions, which offer an opportunity for individuals with common interests to intensify their interaction. However, parallel BoF sessions often make it hard for participants to join multiple BoFs and find common ground between the different technologies, and BoFs are generally too short to allow time for participants to program together. Results: This report summarises our experience with computational biology Codefests, Hackathons and Sprints, which are interactive developer meetings. They are structured to reduce the limitations of traditional scientific meetings described above by strengthening the interaction among peers and letting the participants determine the schedule and topics. These meetings are commonly run as loosely scheduled unconferences (self-organized identification of participants and topics for meetings) over at least two days, with early introductory talks to welcome and organize contributors, followed by intensive collaborative coding sessions. We summarise some prominent achievements of those meetings and describe differences in how these are organised, how their audience is addressed, and their outreach to their respective communities. Conclusions: Hackathons, Codefests and Sprints share a stimulating atmosphere that encourages participants to jointly brainstorm and tackle problems of shared interest in a self-driven proactive environment, as well as providing an opportunity for new participants to get involved in collaborative projects.
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- Psoma, Sotiria D., et al.
(författare)
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A novel enzyme entrapment in SU-8 microfabricated films for glucose micro-biosensors
- 2010
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Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 26:4, s. 1582-1587
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Tidskriftsartikel (refereegranskat)abstract
- The present work investigates the utilisation of the widely used SU-8 photoresist as an immobilisation matrix for glucose oxidase (GOx) for the development of glucose micro-biosensors. The strong advantage of the proposed approach is the simultaneous enzyme entrapment during the microfabrication process within a single step, which is of high importance for the simplification of the BioMEMS procedures. Successful encapsulation of the enzyme GOx in "customised" SU-8 microfabricated structures was achieved through optimisation of the one-step microfabrication process. Although the process involved contact with organic solvents, UV-light exposure, heating for pre- and post-bake and enzyme entrapment in a hard and rigid epoxy resin matrix, the enzyme retained its activity after encapsulation in SU-8. Measurements of the immobilised enzymes activity inside the SU-8 matrix were carried out using amperometric detection of hydrogen peroxide in a 3-electrode setup. Films without enzyme showed negligible variation in current upon the addition of glucose, as opposed to films with encapsulated enzyme which showed a very clear increase in current. Experiments using films of increased thickness or enzyme concentration, showed a higher response, thus proving that the enzyme remained active not only on the films surface, but also inside the matrix as well. The proposed enzyme immobilisation in SU-8 films opens up new possibilities for combining BioMEMS with biosensors and organic electronics.
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- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
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Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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- 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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- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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