| 1. |
- Hibar, Derrek P., et al.
(author)
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Novel genetic loci associated with hippocampal volume
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Abbasi, Rasha, et al.
(author)
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IceCube search for neutrinos from GRB 221009A
- 2023
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In: Proceedings of 38th International Cosmic Ray Conference (ICRC 2023). - : Sissa Medialab Srl.
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Conference paper (peer-reviewed)abstract
- GRB 221009A is the brightest Gamma Ray Burst (GRB) ever observed. The observed extremelyhigh flux of high and very-high-energy photons provide a unique opportunity to probe the predictedneutrino counterpart to the electromagnetic emission. We have used a variety of methods to searchfor neutrinos in coincidence with the GRB over several time windows during the precursor, promptand afterglow phases of the GRB. MeV scale neutrinos are studied using photo-multiplier ratescalers which are normally used to search for galactic core-collapse supernovae neutrinos. GeVneutrinos are searched starting with DeepCore triggers. These events don’t have directionallocalization, but instead can indicate an excess in the rate of events. 10 GeV - 1 TeV and >TeVneutrinos are searched using traditional neutrino point source methods which take into accountthe direction and time of events with DeepCore and the entire IceCube detector respectively. The>TeV results include both a fast-response analysis conducted by IceCube in real-time with timewindows of T0 − 1 to T0 + 2 hours and T0 ± 1 day around the time of GRB 221009A, as well asan offline analysis with 3 new time windows up to a time window of T0 − 1 to T0 + 14 days, thelongest time period we consider. The combination of observations by IceCube covers 9 ordersof magnitude in neutrino energy, from MeV to PeV, placing upper limits across the range forpredicted neutrino emission.
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| 3. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 4. |
- Feng, Shaohong, et al.
(author)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Journal article (peer-reviewed)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 5. |
- Satizabal, Claudia L., et al.
(author)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Journal article (peer-reviewed)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Thompson, Paul M., et al.
(author)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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In: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Journal article (peer-reviewed)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 7. |
- Abazajian, Kevork, et al.
(author)
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CMB-S4 : Forecasting Constraints on Primordial Gravitational Waves
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 926:1
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Journal article (peer-reviewed)abstract
- CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL.
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| 8. |
- Ade, Peter, et al.
(author)
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The Simons Observatory : science goals and forecasts
- 2019
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In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
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Journal article (peer-reviewed)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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| 9. |
- Andersson, Erik P., 1984-, et al.
(author)
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Sex differences in performance and pacing strategies during a sprint time-trial in cross-country skiing
- 2018
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Conference paper (peer-reviewed)abstract
- INTRODUCTION: The aim of this study was to compare the pacing strategies, choice of sub-technique (i.e., gear) and overall performance between elite male and female cross-country (XC) skiers during a ski-skating sprint time-trial (TT) on snow.METHODS: Thirty-four elite XC skiers (20 males and 14 females: age, 23 ± 4 and 21 ± 3 yr; body mass, 76 ± 8 and 64 ± 5 kg; height, 183 ± 7 and 171 ± 5 cm; sprint FIS points, 86 ± 42 and 90 ± 54) performed a 1.6 km TT, which was 56% flat (or undulating), 21% uphill and 22% downhill. The sprint course was measured with a differential global navigation satellite system and divided into four flat, three uphill and two downhill sections. Race time was measured with the EMIT timing system (Emit AS, Oslo, Norway) and one 25-m uphill (4°) section was filmed continuously with a fixed camcorder (50 Hz). All skiers used a similar stone-grind and all skis were glide-waxed similarly. The air temperature was +1°C (fresh snow at ±0°C), relative humidity was 90% and the friction coefficient between ski and snow was estimated to 0.045 (i.e., very slow).RESULTS: Average speed during the TT was 25 ± 1 and 22 ± 1 km/h (TT time: 227 ± 11 and 254 ± 10 s) for males and females, respectively (P < 0.001, Cohen’s d effect size [ES] = 2.6). Average relative power output (PO) was estimated to 3.9 ± 0.3 and 3.3 ± 0.2 W/kg for males and females, respectively (P < 0.001, ES = 2.5). Average heart rate was 95 ± 2% and 96 ± 1% of maximum for males and females (P = 0.51), with a 2-min post-race blood lactate concentration of 10 ± 2 mmol/L for both sexes (P = 0.64). Within-athlete coefficient of variation in speed between sections was 20 ± 2% for males and 24 ± 1% for females (P < 0.001, ES = 2.6). Speeds on the flat, uphill and downhill sections were 26 ± 1, 19 ± 1 and 32 ± 1 km/h for males and 23 ± 1, 16 ± 1 and 30 ± 1 km/h for females (main effects for terrain, sex and interaction, all P < 0.01) corresponding to 9%, 16% and 8% slower speeds on flat, uphill and downhill terrain for females. Speeds relative to the average TT speed were 103 ± 1%, 77 ± 2% and 129 ± 4% for males and 105 ± 1%, 72 ± 2% and 133 ± 2% for females (main effects for terrain, sex and interaction, all P < 0.001). Relative PO on the flat, uphill and downhill sections were estimated to 4.0 ± 0.3, 4.9 ± 0.4 and 1.9 ± 0.2 W/kg for males and 3.5 ± 0.2, 4.0 ± 0.3 and 1.5 ± 0.2 W/kg for females (main effects for terrain, sex and interaction, all P < 0.001). The males were 20% faster than the females on the uphill video section (16 ± 1 versus 13 ± 1 km/h, P < 0.001, ES = 2.6), with 95% of the male skiers and 21% of the female skiers using gear 3 exclusively, and the remaining skiers using gear 2 exclusively or a combination of gears 2 and 3.CONCLUSION: The present results indicate an overall sex difference in sprint skiing performance of ~12% and reveal differences in terrain-specific pacing as well as gear choice between sexes with females showing a higher overall variation in speed and considerably slower uphill skiing.
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| 10. |
- Andersson, Erik, 1984-, et al.
(author)
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Sex differences in performance and pacing strategies during sprint skiing
- 2019
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In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 10
-
Journal article (peer-reviewed)abstract
- Purpose: This study aimed to compare performance and pacing strategies between elite male and female cross-country skiers during a sprint competition on snow using the skating technique.Methods: Twenty male and 14 female skiers completed an individual time-trial prolog (TT) and three head-to-head races (quarter, semi, and final) on the same 1,572-m course, which was divided into flat, uphill and downhill sections. Section-specific speeds, choice of sub-technique (i.e., gear), cycle characteristics, heart rate and post-race blood lactate concentration were monitored. Power output was estimated for the different sections during the TT, while metabolic demand was estimated for two uphill camera sections and the final 50-m flat camera section.Results: Average speed during the four races was ∼12.5% faster for males than females (P < 0.001), while speeds on the flat, uphill and downhill sections were ∼11, 18, and 9% faster for the males than females (all P< 0.001 for terrain, sex, and interaction). Differences in uphill TT speed between the sexes were associated with different sub-technique preferences, with males using a higher gear more frequently than females (P < 0.05). The estimated metabolic demand relative to maximal oxygen uptake (V˙" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max) was similar for both sexes during the two uphill camera sections (∼129% of V˙" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max) and for the final 50-m flat section (∼153% of V˙" role="presentation" style="box-sizing: border-box; display: inline; line-height: normal; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; padding: 0px; margin: 0px; position: relative; outline: 0px !important;">V˙V˙O2max). Relative power output during the TT was 18% higher for males compared to females (P < 0.001) and was highly variable along the course for both sexes (coefficient of variation [CV] between sections 4–9 was 53%), while the same variation in heart rate was low (CV was ∼3%). The head-to-head races were ∼2.4% faster than the TT for both sexes and most race winners (61%) were positioned first already after 30 m of the race. No sex differences were observed during any of the races for heart rate or blood lactate concentration.Conclusion: The average sex difference in sprint skiing performance was ∼12.5%, with varying differences for terrain-specific speeds. Moreover, females skied relatively slower uphill (at a lower gear) and thereby elicited more variation in their speed profiles compared to the males.
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