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- Ade, Peter, et al.
(författare)
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The Simons Observatory : science goals and forecasts
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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- Couch, Fergus J., et al.
(författare)
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AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
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Tidskriftsartikel (refereegranskat)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
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- Gerbino, Martina, et al.
(författare)
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Impact of neutrino properties on the estimation of inflationary parameters from current and future observations
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 95:4
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Tidskriftsartikel (refereegranskat)abstract
- We study the impact of assumptions about neutrino properties on the estimation of inflationary parameters from cosmological data, with a specific focus on the allowed contours in the n(s)/r plane, where n(s) is the scalar spectral index and r is the tensor-to-scalar ratio. We study the following neutrino properties: (i) the total neutrino mass M-i = Sigma(i)m(i) (where the index i = 1, 2, 3 runs over the three neutrino mass eigenstates); (ii) the number of relativistic degrees of freedom N-eff at the time of recombination; and (iii) the neutrino hierarchy. Whereas previous literature assumed three degenerate neutrino masses or two massless neutrino species (approximations that clearly do not match neutrino oscillation data), we study the cases of normal and inverted hierarchy. Our basic result is that these three neutrino properties induce < 1 sigma shift of the probability contours in the n(s)/r plane with both current or upcoming data. We find that the choice of neutrino hierarchy (normal, inverted, or degenerate) has a negligible impact. However, the minimal cutoff on the total neutrino mass M-v,M-min = 0 that accompanies previous works using the degenerate hierarchy does introduce biases in the n(s)/r plane and should be replaced by M-v,M-min = 0.059 eV as required by oscillation data. Using current cosmic microwave background (CMB) data from Planck and Bicep/Keck, marginalizing over the total neutrino mass M-v and over r can lead to a shift in the mean value of ns of similar to 0.3 sigma toward lower values. However, once baryon acoustic oscillation measurements are included, the standard contours in the n(s)/r plane are basically reproduced. Larger shifts of the contours in the n(s)/r plane (up to 0.8 sigma) arise for nonstandard values of N-eff. We also provide forecasts for the future CMB experiments Cosmic Origins Explorer (COrE, satellite) and Stage-IV (ground-based) and show that the incomplete knowledge of neutrino properties, taken into account by a marginalization over M-v, could induce a shift of similar to 0.4 sigma toward lower values in the determination of ns (or a similar to 0.8 sigma shift if one marginalizes over N-eff). Comparison to specific inflationary models is shown. Imperfect knowledge of neutrino properties must be taken into account properly, given the desired precision in determining whether or not inflationary models match the future data.
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- Giusarma, Elena, et al.
(författare)
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Improvement of cosmological neutrino mass bounds
- 2016
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Ingår i: Physical Review D. - 2470-0010. ; 94:8
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Tidskriftsartikel (refereegranskat)abstract
- The most recent measurements of the temperature and low-multipole polarization anisotropies of the cosmic microwave background from the Planck satellite, when combined with galaxy clustering data from the Baryon Oscillation Spectroscopic Survey in the form of the full shape of the power spectrum, and with baryon acoustic oscillation measurements, provide a 95% confidence level (C.L.) upper bound on the sum of the three active neutrinos Sigma m(nu) < 0.183 eV, among the tightest neutrino mass bounds in the literature, to date, when the same data sets are taken into account. This very same data combination is able to set, at similar to 70% C.L., an upper limit on Sigma m(nu) of 0.0968 eV, a value that approximately corresponds to the minimal mass expected in the inverted neutrino mass hierarchy scenario. If high-multipole polarization data from Planck is also considered, the 95% C.L. upper bound is tightened to Sigma m(nu) < 0.176 eV. Further improvements are obtained by considering recent measurements of the Hubble parameter. These limits are obtained assuming a specific nondegenerate neutrino mass spectrum; they slightly worsen when considering other degenerate neutrino mass schemes. Low-redshift quantities, such as the Hubble constant or the reionization optical depth, play a very important role when setting the neutrino mass constraints. We also comment on the eventual shifts in the cosmological bounds on Sigma m(nu) when possible variations in the former two quantities are addressed.
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- Giusarma, Elena, et al.
(författare)
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Scale-dependent galaxy bias, CMB lensing-galaxy cross-correlation, and neutrino masses
- 2018
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 98:12
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Tidskriftsartikel (refereegranskat)abstract
- One of the most powerful cosmological data sets when it comes to constraining neutrino masses is represented by galaxy power spectrum measurements, P-gg(k). The constraining power of P-gg(k) is however severely limited by uncertainties in the modeling of the scale-dependent galaxy bias b(k). In this work we present a new proof-of-principle for a method to constrain b(k) by using the cross-correlation between the cosmic microwave background (CMB) lensing signal and galaxy maps (C-l(kappa g)) using a simple but theoretically well-motivated parametrization for b(k). We apply the method using C-l(kappa g) measured by cross-correlating Planck lensing maps and the Baryon Oscillation Spectroscopic Survey (BOSS) Data Release 11 (DR11) CMASS galaxy sample, and P-gg(k) measured from the BOSS DR12 CMASS sample. We detect a nonzero scale-dependence at moderate significance, which suggests that a proper modeling of b(k) is necessary in order to reduce the impact of nonlinearities and minimize the corresponding systematics. The accomplished increase in constraining power of P-gg(k) is demonstrated by determining a 95% confidence level upper bound on the sum of the three active neutrino masses M-nu of M-nu < 0.19 eV. This limit represents a significant improvement over previous bounds with comparable data sets. Our method will prove especially powerful and important as future large-scale structure surveys will overlap more significantly with the CMB lensing kernel providing a large cross-correlation signal.
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- Gloster, Tracey M., et al.
(författare)
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Characterization and three-dimensional structures of two distinct bacterial xyloglucanases from families GH5 and GH12
- 2007
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:26, s. 19177-19189
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Tidskriftsartikel (refereegranskat)abstract
- The plant cell wall is a complex material in which the cellulose microfibrils are embedded within a mesh of other polysaccharides, some of which are loosely termed hemicellulose. One such hemicellulose is xyloglucan, which displays a beta-1,4-linked D-glucose backbone substituted with xylose, galactose, and occasionally fucose moieties. Both xyloglucan and the enzymes responsible for its modification and degradation are finding increasing prominence, reflecting both the drive for enzymatic biomass conversion, their role in detergent applications, and the utility of modified xyloglucans for cellulose fiber modification. Here we present the enzymatic characterization and three-dimensional structures in ligand free and xyloglucan- oligosaccharide complexed forms of two distinct xyloglucanases from glycoside hydrolase families GH5 and GH12. The enzymes, Paenibacillus pabuli XG5 and Bacillus licheniformis XG12, both display open active center grooves grafted upon their respective (beta/alpha)(8) and beta-jelly roll folds, in which the side chain decorations of xyloglucan may be accommodated. For the beta-jelly roll enzyme topology of GH12, binding of xylosyl and pendant galactosyl moieties is tolerated, but the enzymeis similarly competent in the degradation of unbranched glucans. In the case of the (beta/alpha)(8) GH5 enzyme, kinetically productive interactions are made with both xylose and galactose substituents, as reflected in both a high specific activity on xyloglucan and the kinetics of a series of aryl glycosides. The differential strategies for the accommodation of the side chains of xyloglucan presumably facilitate the action of these microbial hydrolases in milieus where diverse and differently substituted substrates may be encountered.
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- Jones, Geraint H., et al.
(författare)
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The Comet Interceptor Mission
- 2024
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Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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- Kirchhoff, Tomas, et al.
(författare)
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Breast cancer risk and 6q22.33 : combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
- 2012
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Ingår i: PLOS ONE. - : Public library of science. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
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- Martrat, Griselda, et al.
(författare)
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Exploring the link between MORF4L1 and risk of breast cancer
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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- Osorio, Ana, et al.
(författare)
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DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.
- 2014
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7×10-3) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8×10-3). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
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- Vagnozzi, Sunny, et al.
(författare)
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Unveiling nu secrets with cosmological data : Neutrino masses and mass hierarchy
- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:12
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Tidskriftsartikel (refereegranskat)abstract
- Using some of the latest cosmological data sets publicly available, we derive the strongest bounds in the literature on the sum of the three active neutrino masses, M-nu, within the assumption of a background flat Lambda CDM cosmology. In the most conservative scheme, combining Planck cosmic microwave background temperature anisotropies and baryon acoustic oscillations (BAO) data, as well as the up-to-date constraint on the optical depth to reionization (tau), the tightest 95% confidence level upper bound we find is M-nu < 0.151 eV. The addition of Planck high-l polarization data, which, however, might still be contaminated by systematics, further tightens the bound to M-nu < 0.118 eV. A proper model comparison treatment shows that the two aforementioned combinations disfavor the inverted hierarchy at similar to 64% C.L. and similar to 71% C.L., respectively. In addition, we compare the constraining power of measurements of the full- shape galaxy power spectrum versus the BAO signature, from the BOSS survey. Even though the latest BOSS full-shape measurements cover a larger volume and benefit from smaller error bars compared to previous similar measurements, the analysis method commonly adopted results in their constraining power still being less powerful than that of the extracted BAO signal. Our work uses only cosmological data; imposing the constraint M-nu > 0.06 eV from oscillations data would raise the quoted upper bounds by O(0.1 sigma) and would not affect our conclusions.
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- Vigorito, Elena, et al.
(författare)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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