| 1. |
- Mullins, N., et al.
(author)
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Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
- 2021
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829
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Journal article (peer-reviewed)abstract
- Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
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| 2. |
- Aguilar, J. A., et al.
(author)
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Triboelectric backgrounds to radio-based polar ultra-high energy neutrino (UHEN) experiments
- 2023
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In: Astroparticle physics. - : Elsevier. - 0927-6505 .- 1873-2852. ; 145
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Journal article (peer-reviewed)abstract
- In the hopes of observing the highest-energy neutrinos (E> 1 EeV) populating the Universe, both past (RICE, AURA, ANITA) and current (RNO-G, ARIANNA, ARA and TAROGE-M) polar-sited experiments exploit the impulsive radio emission produced by neutrino interactions. In such experiments, rare single event candidates must be unambiguously identified above backgrounds. Background rejection strategies to date primarily target thermal noise fluctuations and also impulsive radio-frequency signals of anthropogenic origin. In this paper, we consider the possibility that 'fake' neutrino signals may also be generated naturally via the `triboelectric effect' This broadly describes any process in which force applied at a boundary layer results in displacement of surface charge, leading to the production of an electrostatic potential difference AV. Wind blowing over granular surfaces such as snow can induce such a potential difference, with subsequent coronal discharge. Discharges over timescales as short as nanoseconds can then lead to radio-frequency emissions at characteristic MHz-GHz frequencies. Using data from various past (RICE, AURA, SATRA, ANITA) and current (RNO G, ARIANNA and ARA) neutrino experiments, we find evidence for such backgrounds, which are generally characterized by: (a) a threshold wind velocity which likely depends on the experimental trigger criteria and layout; for the experiments considered herein, this value is typically O(10 m/s), (b) frequency spectra generally shifted to the low-end of the frequency regime to which current radio experiments are typically sensitive (100-200 MHz), (c) for the strongest background signals, an apparent preference for discharges from above-surface structures, although the presence of more isotropic, lower amplitude triboelectric discharges cannot be excluded.
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| 3. |
- Anker, A., et al.
(author)
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Developing new analysis tools for near surface radio-based neutrino detectors
- 2023
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In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :10
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Journal article (peer-reviewed)abstract
- The ARIANNA experiment is an Askaryan radio detector designed to measure high-energy neutrino induced cascades within the Antarctic ice. Ultra-high-energy neutrinos above 1016 eV have an extremely low flux, so experimental data captured at trigger level need to be classified correctly to retain as much neutrino signal as possible. We first describe two new physics-based neutrino selection methods, or "cuts", (the updown and dipole cut) that extend the previously published analysis to a specialized ARIANNA station with 8 antenna channels, which is double the number used in the prior analysis. For a standard trigger with a threshold signal to noise ratio at 4.4, the new cuts produce a neutrino efficiency of > 95% per station-year of operation, while rejecting 99.93% of the background (corresponding to 53 remaining experimental background events). When the new cuts are combined with a pre-viously developed cut using neutrino waveform templates, all background is removed at no change of efficiency. In addition, the neutrino efficiency is extrapolated to 1,000 station-years of operation, obtaining 91%. This work then introduces a new selection method (the deep learning cut) to augment the identification of neutrino events by using deep learning meth-ods and compares the efficiency to the physics-based analysis. The deep learning cut gives 99% signal efficiency per station-year of operation while rejecting 99.997% of the background (corresponding to 2 remaining experimental background events), which are subsequently re-moved by the waveform template cut at no significant change in efficiency. The results of the deep learning cut were verified using measured cosmic rays which shows that the simulations do not introduce artifacts with respect to experimental data. The paper demonstrates that the background rejection and signal efficiency of near surface antennas meets the require-ments of a large scale future array, as considered in baseline design of the radio component of IceCube-Gen2.
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| 4. |
- Anker, A., et al.
(author)
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Improving sensitivity of the ARIANNA detector by rejecting thermal noise with deep learning
- 2022
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In: Journal of Instrumentation. - : IOP Publishing. - 1748-0221. ; 17:3
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Journal article (peer-reviewed)abstract
- The ARIANNA experiment is an Askaryan detector designed to record radio signals induced by neutrino interactions in the Antarctic ice. Because of the low neutrino flux at high energies (E-nu > 10(16 )eV), the physics output is limited by statistics. Hence, an increase in sensitivity significantly improves the interpretation of data and offers the ability to probe new parameter spaces. The amplitudes of the trigger threshold are limited by the rate of triggering on unavoidable thermal noise fluctuations. We present a real-time thermal noise rejection algorithm that enables the trigger thresholds to be lowered, which increases the sensitivity to neutrinos by up to a factor of two (depending on energy) compared to the current ARIANNA capabilities. A deep learning discriminator, based on a Convolutional Neural Network (CNN), is implemented to identify and remove thermal events in real time. We describe a CNN trained on MC data that runs on the current ARIANNA microcomputer and retains 95% of the neutrino signal at a thermal noise rejection factor of 10(5), compared to a template matching procedure which reaches only 10(2) for the same signal efficiency. Then the results are verified in a lab measurement by feeding in generated neutrino-like signal pulses and thermal noise directly into the ARIANNA data acquisition system. Lastly, the same CNN is used to classify cosmic-rays events to make sure they are not rejected. The network classified 102 out of 104 cosmic-ray events as signal.
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| 5. |
- Anker, A., et al.
(author)
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Measuring the polarization reconstruction resolution of the ARIANNA neutrino detector with cosmic rays
- 2022
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :4
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Journal article (peer-reviewed)abstract
- The ARIANNA detector is designed to detect neutrinos with energies above 10(17) eV. Due to the similarities in generated radio signals, cosmic rays are often used as test beams for neutrino detectors. Some ARIANNA detector stations are equipped with antennas capable of detecting air showers. Since the radio emission properties of air showers are well understood, and the polarization of the radio signal can be predicted from the arrival direction, cosmic rays can be used as a proxy to assess the reconstruction capabilities of the ARIANNA neutrino detector. We report on dedicated efforts of reconstructing the polarization of cosmic-ray radio pulses. After correcting for difference in hardware, the two stations used in this study showed similar performance in terms of event rate and agreed with simulation. Subselecting high quality cosmic rays, the polarizations of these cosmic rays were reconstructed with a resolution of 2.5 degrees (68% containment), which agrees with the expected value obtained from simulation. A large fraction of this resolution originates from uncertainties in the predicted polarization because of the contribution of the subdominant Askaryan effect in addition to the dominant geomagnetic emission. Subselecting events with a zenith angle greater than 70 degrees removes most influence of the Askaryan emission, and, with limited statistics, we found the polarization uncertainty is reduced to 1.3 degrees (68% containment).
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| 6. |
- Arvidson, R. E., et al.
(author)
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Opportunity Mars Rover mission : Overview and selected results from Purgatory ripple to traverses to Endeavour crater
- 2011
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In: Journal of Geophysical Research. - Hoboken : Wiley-Blackwell. - 0148-0227 .- 2156-2202. ; 116, s. E00F15-
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Journal article (peer-reviewed)abstract
- Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.
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| 7. |
- Blokland, G. A. M., et al.
(author)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Journal article (peer-reviewed)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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| 8. |
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| 11. |
- Lumbers, R. T., et al.
(author)
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The genomics of heart failure: design and rationale of the HERMES consortium
- 2021
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In: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
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Journal article (peer-reviewed)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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| 12. |
- Postmus, I., et al.
(author)
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Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
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Journal article (peer-reviewed)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
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| 13. |
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| 14. |
- Sliz, E., et al.
(author)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 15. |
- Vaughan, A., et al.
(author)
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Regolith of the Crater Floor Units, Jezero Crater, Mars : Textures, Composition, and Implications for Provenance
- 2023
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In: Journal of Geophysical Research - Planets. - : John Wiley and Sons Inc. - 2169-9097 .- 2169-9100. ; 128:3
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Journal article (peer-reviewed)abstract
- A multi-instrument study of the regolith of Jezero crater floor units by the Perseverance rover has identified three types of regolith: fine-grained, coarse-grained, and mixed-type. Mastcam-Z, Wide Angle Topographic Sensor for Operations and eNgineering, and SuperCam Remote Micro Imager were used to characterize the regolith texture, particle size, and roundedness where possible. Mastcam-Z multispectral and SuperCam laser-induced breakdown spectroscopy data were used to constrain the composition of the regolith types. Fine-grained regolith is found surrounding bedrock and boulders, comprising bedforms, and accumulating on top of rocks in erosional depressions. Spectral and chemical data show it is compositionally consistent with pyroxene and a ferric-oxide phase. Coarse-grained regolith consists of 1–2 mm well-sorted gray grains that are found concentrated around the base of boulders and bedrock, and armoring bedforms. Its chemistry and spectra indicate it is olivine-bearing, and its spatial distribution and roundedness indicate it has been transported, likely by saltation-induced creep. Coarse grains share similarities with the olivine grains observed in the Séítah formation bedrock, making that unit a possible source for these grains. Mixed-type regolith contains fine- and coarse-grained regolith components and larger rock fragments. The rock fragments are texturally and spectrally similar to bedrock within the Máaz and Séítah formations, indicating origins by erosion from those units, although they could also be a lag deposit from erosion of an overlying unit. The fine- and coarse-grained types are compared to their counterparts at other landing sites to inform global, regional, and local inputs to regolith formation within Jezero crater. The regolith characterization presented here informs the regolith sampling efforts underway by Perseverance. © 2023. The Authors.
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