| 1. |
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| 2. |
- Niemi, MEK, et al.
(författare)
-
- 2021
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swepub:Mat__t
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| 3. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 4. |
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| 5. |
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 14. |
- Adcox, K, et al.
(författare)
-
PHENIX detector overview
- 2003
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 15. |
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| 16. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 17. |
- Lumbers, R. T., et al.
(författare)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Tidskriftsartikel (refereegranskat)abstract
- Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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| 18. |
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| 19. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 20. |
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| 21. |
- Blain, H., et al.
(författare)
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A comprehensive fracture prevention strategy in older adults : the European union geriatric medicine society (EUGMS) statement
- 2016
-
Ingår i: European Geriatric Medicine. - : Elsevier. - 1878-7649 .- 1878-7657. ; 7:6, s. 519-525
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Tidskriftsartikel (refereegranskat)abstract
- Prevention of fragility fractures in older people has become a public health priority, although the most appropriate and cost-effective strategy remains unclear. In the present statement, the Interest group on falls and fracture prevention of the European union geriatric medicine society (EUGMS), in collaboration with the International association of gerontology and geriatrics for the European region (IAGG-ER), the European union of medical specialists (EUMS), the Fragility fracture network (FFN), the International osteoporosis foundation (IOF) - European society for clinical and economic aspects of osteoporosis and osteoarthritis (ECCEO), outlines its views on the main points in the current debate in relation to the primary and secondary prevention of falls, the diagnosis and treatment of bone fragility, and the place of combined falls and fracture liaison services for fracture prevention in older people.
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| 22. |
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| 23. |
- Adcox, K, et al.
(författare)
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Centrality dependence of the high (PT) charged hadron suppression in Au+Au collisions at root s(NN)=130 GeV
- 2003
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 561:1-2, s. 82-92
-
Tidskriftsartikel (refereegranskat)abstract
- PHENIX has measured the centrality dependence of charged hadron p(T) spectra from Au +An collisions at root(s)NN = 130 GeV The truncated mean p(T) decreases with centrality for p(T) > 2 GeV/c, indicating an apparent reduction of the contribution from hard scattering to high p(T) hadrdn production. For central collisions the yield at high p(T) is shown to be suppressed compared to binary nucleon-nucleon collision scaling of p + p, data. This suppression is monotonically increasing with centrality, but most of the change occurs below 30% centrality, i.e., for collisions with less than similar to140 participating nucleons. The observed p(T) and centrality dependence is consistent with the particle production predicted by models including hard scattering and subsequent energy loss of the scattered partons in the dense matter created in the collisions. (C) 2003 Published by Elsevier Science B.V.
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| 24. |
- Adcox, K, et al.
(författare)
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Event-by-event fluctuations in mean p(T) and mean E(T) in root s(NN)=130 GeVAu+Au collisions
- 2002
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:2
-
Tidskriftsartikel (refereegranskat)abstract
- Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at roots(NN)=130 GeV at the Relativistic Heavy-Ion Collider. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of nonstatistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant nonrandom fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p(T) or e(T) spectra, we exclude a region of fluctuations in roots(NN)=130 GeV Au+Au collisions.
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| 25. |
- Adcox, K, et al.
(författare)
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Flow Measurements via Two-Particle Azimuthal Correlations in Au+Au Collisions at sqrt[sNN]=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 89
-
Tidskriftsartikel (refereegranskat)abstract
- Two-particle azimuthal correlation functions are presented for charged hadrons produced in Au+Au collisions at the Relativistic Heavy Ion Collider (sqrt[sNN]=130 GeV). The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values (v2) show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone ε, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low pT. A breakdown of this ε scaling is observed for charged hadrons with pT >1.0 GeV/c.
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| 26. |
- Adcox, K, et al.
(författare)
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Measurement of Lambda and (Lambda)over-bar particles in Au plus Au collisions at root s(NN)=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 89:9
-
Tidskriftsartikel (refereegranskat)abstract
- We present results on the measurement of Lambda and (&ULambda;) over bar production in Au+Au collisions at roots(NN)=130 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider. The transverse momentum spectra were measured for minimum bias and for the 5% most central events. The (&ULambda;) over bar/Lambda ratios are constant as a function of p(T) and the number of participants. The measured net Lambda density is significantly larger than predicted by models based on hadronic strings (e.g., HIJING) but in approximate agreement with models which include the gluon-junction mechanism.
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| 27. |
- Adcox, K, et al.
(författare)
-
Measurement of single electrons and implications for charm production in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 88:19
-
Tidskriftsartikel (refereegranskat)abstract
- Transverse momentum spectra of electrons from Au+Au collisions at roots(NN) = 130 GeV have been measured at midrapidity by the PHENIX experiment at the Relativistic Heavy Ion Collider. The spectra show an excess above the background from photon conversions and light hadron decays. The electron signal is consistent with that expected from semileptonic decays of charm. The yield of the electron signal dN(e)/dy for p(T) > 0.8 GeV/c is 0.025 +/- 0.004(stat) +/- 0.010( syst) in central collisions, and the corresponding charm cross section is 380 +/- 60(stat) +/- 200(syst ) mub per binary nucleon-nucleon collision.
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| 28. |
- Adcox, K, et al.
(författare)
-
Net charge fluctuations in Au+Au interactions root s(NN)=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 89
-
Tidskriftsartikel (refereegranskat)abstract
- Data from Au+ Au interactions at s(NN)=130 GeV, obtained with the PHENIX detector at the Relativistic Heavy-Ion Collider, are used to investigate local net charge fluctuations among particles produced near midrapidity. According to recent suggestions, such fluctuations may carry information from the quark-gluon plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.
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| 29. |
- Adcox, K, et al.
(författare)
-
Suppression of hadrons with large transverse momentum in central Au+Au collisions at root s(NN)=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 88:2
-
Tidskriftsartikel (refereegranskat)abstract
- Transverse momentum spectra for charged hadrons and for neutral pions in the range 1 Gev/c < P-T < 5 GeV/c have been measured by the PHENIX experiment at RHIC in Au + Au collisions at rootS(NN) = 130 GeV. At high p(T) the spectra from peripheral nuclear collisions are consistent with scaling the spectra from p + p collisions by the average number of binary nucleon-nucleon collisions. The spectra from central collisions are significantly suppressed when compared to the binary-scaled p + p expectation, and also when compared to similarly binary-scaled peripheral collisions, indicating a novel nuclear-medium effect in central nuclear collisions at RHIC energies.
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| 30. |
- Adcox, K, et al.
(författare)
-
Transverse-mass dependence of two-pion correlations in Au+Au collisions at root(NN)-N-S=130 GeV
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114. ; 88:19
-
Tidskriftsartikel (refereegranskat)abstract
- Two-pion correlations in roots(NN) = 130 GeV Au+Au collisions at RHIC have been measured over a broad range of pair transverse momentum k(T) by the PHENIX experiment at RHIC. The k(T) dependent transverse radii are similar to results from heavy-ion collisions at roots(NN) = 4.1 , 4.9, and 17.3 GeV, whereas the longitudinal radius increases monotonically with beam energy. The ratio of the outwards to sidewards transverse radii (R-out/R-side) is consistent with unity and independent of k(T) .
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| 31. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 32. |
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| 33. |
- Leisawitz, David, et al.
(författare)
-
The origins space telescope
- 2019
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11115
-
Konferensbidrag (refereegranskat)abstract
- The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of Herschel, the largest telescope flown in space to date. After a 3 1/2 year study, the Origins Science and Technology Definition Team will recommend to the Decadal Survey a concept for Origins with a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (MISC-T) will measure the spectra of transiting exoplanets in the 2.8-20 μm wavelength range and offer unprecedented sensitivity, enabling definitive biosignature detections. The Far-IR Imager Polarimeter (FIP) will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer (OSS) will cover wavelengths from 25-588 μm, make wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The telescope has a Spitzer-like architecture and requires very few deployments after launch. The cryo-thermal system design leverages JWST technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural backgroundlimited sensitivity.
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| 34. |
- Ryu, Y. -H., et al.
(författare)
-
OGLE-2016-BLG-1190Lb : The First Spitzer Bulge Planet Lies Near the Planet/Brown-dwarf Boundary
- 2018
-
Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 155:1
-
Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of OGLE-2016-BLG-1190Lb, which is likely to be the first Spitzer microlensing planet in the Galactic bulge/ bar, an assignation that can be confirmed by two epochs of high-resolution imaging of the combined source-lens baseline object. The planet's mass, M-p = 13.4 +/- 0.9 M-J, places it right at the deuteriumburning limit, i. e., the conventional boundary between planets and brown dwarfs. Its existence raises the question of whether such objects are really planets (formed within the disks of their hosts) or failed stars (lowmass objects formed by gas fragmentation). This question may ultimately be addressed by comparing disk and bulge/bar planets, which is a goal of the Spitzer microlens program. The host is a G dwarf, M-host = 0.89. +/- 0.07 M-circle dot, and the planet has a semimajor axis a similar to 2.0 au. We use Kepler K2 Campaign 9 microlensing data to break the lens-mass degeneracy that generically impacts parallax solutions from Earth-Spitzer observations alone, which is the first successful application of this approach. The microlensing data, derived primarily from near-continuous, ultradense survey observations from OGLE, MOA, and three KMTNet telescopes, contain more orbital information than for any previous microlensing planet, but not quite enough to accurately specify the full orbit. However, these data do permit the first rigorous test of microlensing orbital-motion measurements, which are typically derived from data taken over < 1% of an orbital period.
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| 35. |
- Flannick, Jason, et al.
(författare)
-
Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 36. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 37. |
- Leisawitz, David, et al.
(författare)
-
Origins Space Telescope: Baseline mission concept
- 2021
-
Ingår i: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural background-limited sensitivity.
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| 38. |
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| 39. |
- Adler, SS, et al.
(författare)
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PHENIX on-line systems
- 2003
-
Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 560-592
-
Tidskriftsartikel (refereegranskat)abstract
- The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 40. |
- Curigliano, G, et al.
(författare)
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De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
- 2017
-
Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 28:8, s. 1700-1712
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Tidskriftsartikel (refereegranskat)abstract
- The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.
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| 41. |
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| 42. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 43. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 44. |
- Leisawitz, David, et al.
(författare)
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The Origins Space Telescope: Mission concept overview
- 2018
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Konferensbidrag (refereegranskat)abstract
- Downloading of the abstract is permitted for personal use only. The Origins Space Telescope (OST) will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did the universe evolve in response to its changing ingredients? How common are life-bearing planets? To accomplish its scientific objectives, OST will operate at mid- and far-infrared wavelengths and offer superlative sensitivity and new spectroscopic capabilities. The OST study team will present a scientifically compelling, executable mission concept to the 2020 Decadal Survey in Astrophysics. To understand the concept solution space, our team studied two alternative mission concepts. We report on the study approach and describe both of these concepts, give the rationale for major design decisions, and briefly describe the mission-enabling technology.
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| 45. |
- Manning, Alisa, et al.
(författare)
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A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Han, C., et al.
(författare)
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OGLE-2017-BLG-0329L : A Microlensing Binary Characterized with Dramatically Enhanced Precision Using Data from Space-based Observations
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 859:2
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Tidskriftsartikel (refereegranskat)abstract
- Mass measurements of gravitational microlenses require one to determine the microlens parallax pE, but precise pE measurement, in many cases, is hampered due to the subtlety of the microlens-parallax signal combined with the difficulty of distinguishing the signal from those induced by other higher-order effects. In this work, we present the analysis of the binary-lens event OGLE-2017-BLG-0329, for which pi(E) is measured with a dramatically improved precision using additional data from space-based Spitzer observations. We find that while the parallax model based on the ground-based data cannot be distinguished from a zero-pi(E) model at the 2 sigma level, the addition of the Spitzer data enables us to identify two classes of solutions, each composed of a pair of solutions according to the well-known ecliptic degeneracy. It is found that the space-based data reduce the measurement uncertainties of the north and east components of the microlens-parallax vector pE by factors similar to 18 and similar to 4, respectively. With the measured microlens parallax combined with the angular Einstein radius measured from the resolved caustic crossings, we find that the lens is composed of a binary with component masses of either (M-1, M-2) similar to (1.1, 0.8) M-circle dot or similar to(0.4, 0.3) M-circle dot according to the two solution classes. The first solution is significantly favored but the second cannot be securely ruled out based on the microlensing data alone. However, the degeneracy can be resolved from adaptive optics observations taken similar to 10 years after the event.
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| 50. |
- Hirao, Yuki, et al.
(författare)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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