| 1. |
- Acharya, B. S., et al.
(författare)
-
Introducing the CTA concept
- 2013
-
Ingår i: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 43, s. 3-18
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The Cherenkov Telescope Array (CTA) is a new observatory for very high-energy (VHE) gamma rays. CTA has ambitions science goals, for which it is necessary to achieve full-sky coverage, to improve the sensitivity by about an order of magnitude, to span about four decades of energy, from a few tens of GeV to above 100 TeV with enhanced angular and energy resolutions over existing VHE gamma-ray observatories. An international collaboration has formed with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America. In 2010 the CTA Consortium completed a Design Study and started a three-year Preparatory Phase which leads to production readiness of CTA in 2014. In this paper we introduce the science goals and the concept of CTA, and provide an overview of the project. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Abdalla, E., et al.
(författare)
-
Cosmology intertwined : A review of the particle physics, astrophysics, and cosmology associated with the cosmological tensions and anomalies
- 2022
-
Ingår i: Journal of High Energy Astrophysics. - : Elsevier BV. - 2214-4048 .- 2214-4056. ; 34, s. 49-211
-
Tidskriftsartikel (refereegranskat)abstract
- The standard Λ Cold Dark Matter (ΛCDM) cosmological model provides a good description of a wide range of astrophysical and cosmological data. However, there are a few big open questions that make the standard model look like an approximation to a more realistic scenario yet to be found. In this paper, we list a few important goals that need to be addressed in the next decade, taking into account the current discordances between the different cosmological probes, such as the disagreement in the value of the Hubble constant H0, the σ8–S8 tension, and other less statistically significant anomalies. While these discordances can still be in part the result of systematic errors, their persistence after several years of accurate analysis strongly hints at cracks in the standard cosmological scenario and the necessity for new physics or generalisations beyond the standard model. In this paper, we focus on the 5.0σ tension between the Planck CMB estimate of the Hubble constant H0 and the SH0ES collaboration measurements. After showing the H0 evaluations made from different teams using different methods and geometric calibrations, we list a few interesting new physics models that could alleviate this tension and discuss how the next decade's experiments will be crucial. Moreover, we focus on the tension of the Planck CMB data with weak lensing measurements and redshift surveys, about the value of the matter energy density Ωm, and the amplitude or rate of the growth of structure (σ8,fσ8). We list a few interesting models proposed for alleviating this tension, and we discuss the importance of trying to fit a full array of data with a single model and not just one parameter at a time. Additionally, we present a wide range of other less discussed anomalies at a statistical significance level lower than the H0–S8 tensions which may also constitute hints towards new physics, and we discuss possible generic theoretical approaches that can collectively explain the non-standard nature of these signals. Finally, we give an overview of upgraded experiments and next-generation space missions and facilities on Earth that will be of crucial importance to address all these open questions.
|
|
| 3. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
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.
|
|
| 4. |
- Marouli, Eirini, et al.
(författare)
-
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.
|
|
| 5. |
- Menden, MP, et al.
(författare)
-
Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
-
Tidskriftsartikel (refereegranskat)abstract
- The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
|
|
| 6. |
- Clark, Andrew G., et al.
(författare)
-
Evolution of genes and genomes on the Drosophila phylogeny
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
|
|
| 7. |
- Amiri, M., et al.
(författare)
-
Periodic activity from a fast radio burst source
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582:7812, s. 351-355
-
Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are bright, millisecond-duration radio transients originating from sources at extragalactic distances1, the origin of which is unknown. Some FRB sources emit repeat bursts, ruling out cataclysmic origins for those events2–4. Despite searches for periodicity in repeat burst arrival times on timescales from milliseconds to many days2,5–7, these bursts have hitherto been observed to appear sporadically and—although clustered8—without a regular pattern. Here we report observations of a 16.35 ± 0.15 day periodicity (or possibly a higher-frequency alias of that periodicity) from the repeating FRB 180916.J0158+65 detected by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst Project4,9. In 38 bursts recorded from 16 September 2018 to 4 February 2020 utc, we find that all bursts arrive in a five-day phase window, and 50 per cent of the bursts arrive in a 0.6-day phase window. Our results suggest a mechanism for periodic modulation either of the burst emission itself or through external amplification or absorption, and disfavour models invoking purely sporadic processes.
|
|
| 8. |
- Koul, R., et al.
(författare)
-
The TACTIC atmospheric Cherenkov imaging telescope
- 2007
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 578:3, s. 548-564
-
Tidskriftsartikel (refereegranskat)abstract
- The TACTIC (TeV Atomospheric Cherenkov Telescope with Imaging Camera) γγ-ray telescope, equipped with a light collector of area ∼9.5m2 and a medium resolution imaging camera of 349 pixels, has been in operation at Mt. Abu, India, since 2001. This paper describes the main features of its various subsystems and its overall performance with regard to (a) tracking accuracy of its two-axes drive system, (b) spot size of the light collector, (c) back-end signal processing electronics and topological trigger generation scheme, (d) data acquisition and control system and (e) relative and absolute gain calibration methodology. Using a trigger field-of-view of 11×1111×11 pixels (∼3.4∘×3.4∘)(∼3.4∘×3.4∘), the telescope records a cosmic ray event rate of ∼2.5Hz at a typical zenith angle of 15∘15∘. Monte Carlo simulation results are also presented in the paper for comparing the expected performance of the telescope with actual observational results. The consistent detection of a steady signal from the Crab Nebula above ∼1.2TeV energy, at a sensitivity level of ∼5.0σ∼5.0σ in ∼25h, alongwith excellent matching of its energy spectrum with that obtained by other groups, reassures that the performance of the TACTIC telescope is quite stable and reliable. Furthermore, encouraged by the detection of strong γγ-ray signals from Mrk 501 (during 1997 and 2006 observations) and Mrk 421 (during 2001 and 2005–2006 observations), we believe that there is considerable scope for the TACTIC telescope to monitor similar TeV γγ-ray emission activity from other active galactic nuclei on a long-term basis.
|
|
| 9. |
- Tickoo, A. K., et al.
(författare)
-
A generalized ray-tracing procedure for an atmospheric Cherenkov imaging telescope and optical characteristics of the TACTIC light collector
- 2005
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 539:1-2, s. 177-190
-
Tidskriftsartikel (refereegranskat)abstract
- A generalized ray-tracing procedure has been developed, which facilitates the design of a multimirror-based light collector used in atmospheric Cherenkov telescopes. This procedure has been employed to study the optical characteristics of the 3.5 m diameter light collector of the TACTIC Imaging telescope. Comparison of the measured point-spread function of the light collector with the simulated performance of ideal Davies–Cotton and paraboloid designs has been made to determine an optimum arrangement of the 34 spherical mirror facets used in the telescope to obtain the best possible point-spread function. A description of the ray-tracing subroutine used for processing CORSIKA-generated Cherenkov data, required for carrying out Monte-Carlo simulation studies, is also discussed in the paper.
|
|
| 10. |
- Marsh, J. C., et al.
(författare)
-
Identification of triaxial strongly deformed bands in Hf-164
- 2013
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 88:4
-
Tidskriftsartikel (refereegranskat)abstract
- Two new rotational bands of distinct character have been identified in Hf-164. They are suggested to correspond to the long-anticipated triaxial strongly deformed (TSD) bands predicted by theoretical studies. The bands have been linked to known states, and the level spins and energies could be determined. The bands are also substantially stronger in intensity and are located at lower spins than the previously observed TSD bands in Hf-168, hereby making Hf-164 the best even-even system so far for the study of TSD structures in the A similar to 160 mass region. Cranking calculations based on the modified-oscillator model suggest that the bands are associated with four-quasiparticle configurations that involve high-j intruder (i(13/2))(2) proton orbitals.
|
|
