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| 5. |
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- 2019
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Journal article (peer-reviewed)
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| 6. |
- Adam, A, et al.
(author)
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Abstracts from Hydrocephalus 2016.
- 2017
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In: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 14:Suppl 1
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Journal article (peer-reviewed)
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| 7. |
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| 8. |
- Kirk, A., et al.
(author)
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Overview of recent physics results from MAST
- 2017
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 57:10
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Journal article (peer-reviewed)abstract
- New results from MAST are presented that focus on validating models in order to extrapolate to future devices. Measurements during start-up experiments have shown how the bulk ion temperature rise scales with the square of the reconnecting field. During the current ramp-up, models are not able to correctly predict the current diffusion. Experiments have been performed looking at edge and core turbulence. At the edge, detailed studies have revealed how filament characteristics are responsible for determining the near and far scrape off layer density profiles. In the core the intrinsic rotation and electron scale turbulence have been measured. The role that the fast ion gradient has on redistributing fast ions through fishbone modes has led to a redesign of the neutral beam injector on MAST Upgrade. In H-mode the turbulence at the pedestal top has been shown to be consistent with being due to electron temperature gradient modes. A reconnection process appears to occur during edge localized modes (ELMs) and the number of filaments released determines the power profile at the divertor. Resonant magnetic perturbations can mitigate ELMs provided the edge peeling response is maximised and the core kink response minimised. The mitigation of intrinsic error fields with toroidal mode number n > 1 has been shown to be important for plasma performance.
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| 9. |
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| 10. |
- Wang, Li-San, et al.
(author)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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In: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Journal article (peer-reviewed)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 11. |
- Chapman, I. T., et al.
(author)
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Overview of MAST results
- 2015
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 55:10
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Journal article (peer-reviewed)abstract
- The Mega Ampere Spherical Tokamak (MAST) programme is strongly focused on addressing key physics issues in preparation for operation of ITER as well as providing solutions for DEMO design choices. In this regard, MAST has provided key results in understanding and optimizing H-mode confinement, operating with smaller edge localized modes (ELMs), predicting and handling plasma exhaust and tailoring auxiliary current drive. In all cases, the high-resolution diagnostic capability on MAST is complemented by sophisticated numerical modelling to facilitate a deeper understanding. Mitigation of ELMs with resonant magnetic perturbations (RMPs) with toroidal mode number n(RMP) = 2, 3, 4, 6 has been demonstrated: at high and low collisionality; for the first ELM following the transition to high confinement operation; during the current ramp-up; and with rotating n(RMP) = 3 RMPs. n(RMP) = 4, 6 fields cause less rotation braking whilst the power to access H-mode is less with n(RMP) = 4 than n(RMP) = 3, 6. Refuelling with gas or pellets gives plasmas with mitigated ELMs and reduced peak heat flux at the same time as achieving good confinement. A synergy exists between pellet fuelling and RMPs, since mitigated ELMs remove fewer particles. Inter-ELM instabilities observed with Doppler backscattering are consistent with gyrokinetic simulations of micro-tearing modes in the pedestal. Meanwhile, ELM precursors have been strikingly observed with beam emission spectroscopy (BES) measurements. A scan in beta at the L-H transition shows that pedestal height scales strongly with core pressure. Gyro-Bohm normalized turbulent ion heat flux (as estimated from the BES data) is observed to decrease with increasing tilt of the turbulent eddies. Fast ion redistribution by energetic particle modes depends on density, and access to a quiescent domain with 'classical' fast ion transport is found above a critical density. Highly efficient electron Bernstein wave current drive (1 A W-1) has been achieved in solenoid-free start-up. A new proton detector has characterized escaping fusion products. Langmuir probes and a high-speed camera suggest filaments play a role in particle transport in the private flux region whilst coherence imaging has measured scrape-off layer (SOL) flows. BOUT++ simulations show that fluxes due to filaments are strongly dependent on resistivity and magnetic geometry of the SOL, with higher radial fluxes at higher resistivity. Finally, MAST Upgrade is due to begin operation in 2016 to support ITER preparation and importantly to operate with a Super-X divertor to test extended leg concepts for particle and power exhaust.
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| 12. |
- Harrison, J.R., et al.
(author)
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Overview of new MAST physics in anticipation of first results from MAST Upgrade
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Research review (peer-reviewed)abstract
- The mega amp spherical tokamak (MAST) was a low aspect ratio device (R/a = 0.85/0.65 ∼ 1.3) with similar poloidal cross-section to other medium-size tokamaks. The physics programme concentrates on addressing key physics issues for the operation of ITER, design of DEMO and future spherical tokamaks by utilising high resolution diagnostic measurements closely coupled with theory and modelling to significantly advance our understanding. An empirical scaling of the energy confinement time that favours higher power, lower collisionality devices is consistent with gyrokinetic modelling of electron scale turbulence. Measurements of ion scale turbulence with beam emission spectroscopy and gyrokinetic modelling in up-down symmetric plasmas find that the symmetry of the turbulence is broken by flow shear. Near the non-linear stability threshold, flow shear tilts the density fluctuation correlation function and skews the fluctuation amplitude distribution. Results from fast particle physics studies include the observation that sawteeth are found to redistribute passing and trapped fast particles injected from neutral beam injectors in equal measure, suggesting that resonances between the m = 1 perturbation and the fast ion orbits may be playing a dominant role in the fast ion transport. Measured D-D fusion products from a neutron camera and a charged fusion product detector are 40% lower than predictions from TRANSP/NUBEAM, highlighting possible deficiencies in the guiding centre approximation. Modelling of fast ion losses in the presence of resonant magnetic perturbations (RMPs) can reproduce trends observed in experiments when the plasma response and charge-exchange losses are accounted for. Measurements with a neutral particle analyser during merging-compression start-up indicate the acceleration of ions and electrons. Transport at the plasma edge has been improved through reciprocating probe measurements that have characterised a geodesic acoustic mode at the edge of an ohmic L-mode plasma and particle-in-cell modelling has improved the interpretation of plasma potential estimates from ball-pen probes. The application of RMPs leads to a reduction in particle confinement in L-mode and H-mode and an increase in the core ionization source. The ejection of secondary filaments following type-I ELMs correlates with interactions with surfaces near the X-point. Simulations of the interaction between pairs of filaments in the scrape-off layer suggest this results in modest changes to their velocity, and in most cases can be treated as moving independently. A stochastic model of scrape-off layer profile formation based on the superposition of non-interacting filaments is in good agreement with measured time-average profiles. Transport in the divertor has been improved through fast camera imaging, indicating the presence of a quiescent region devoid of filament near the X-point, extending from the separatrix to ψ n ∼ 1.02. Simulations of turbulent transport in the divertor show that the angle between the divertor leg on the curvature vector strongly influences transport into the private flux region via the interchange mechanism. Coherence imaging measurements show counter-streaming flows of impurities due to gas puffing increasing the pressure on field lines where the gas is ionised. MAST Upgrade is based on the original MAST device, with substantially improved capabilities to operate with a Super-X divertor to test extended divertor leg concepts. SOLPS-ITER modelling predicts the detachment threshold will be reduced by more than a factor of 2, in terms of upstream density, in the Super-X compared with a conventional configuration and that the radiation front movement is passively stabilised before it reaches the X-point. 1D fluid modelling reveals the key role of momentum and power loss mechanisms in governing detachment onset and evolution. Analytic modelling indicates that long legs placed at large major radius, or equivalently low at the target compared with the X-point are more amenable to external control. With MAST Upgrade experiments expected in 2019, a thorough characterisation of the sources of the intrinsic error field has been carried out and a mitigation strategy developed.
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| 13. |
- Agha, R. A., et al.
(author)
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The SCARE 2018 statement: Updating consensus Surgical CAse REport (SCARE) guidelines
- 2018
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In: International Journal of Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 1743-9191. ; 60, s. 132-136
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Journal article (peer-reviewed)abstract
- Introduction: The SCARE Guidelines were published in 2016 to provide a structure for reporting surgical case reports. Since their publication, SCARE guidelines have been widely endorsed by authors, journal editors, and reviewers, and have helped to improve reporting transparency of case reports across a range of surgical specialties. In order to encourage further progress in reporting quality, the SCARE guidelines must themselves be kept up to date. We completed a Delphi consensus exercise to update the SCARE guidelines. Methods: A Delphi consensus exercise was undertaken. All members of the previous Delphi group were invited to participate, in addition to researchers who have previously studied case reports, and editors from the International Journal of Surgery Case Reports. The expert group was sent an online questionnaire where they were asked to rate their agreement with proposed changes to each of the 24 items. Results: 56 people agreed to participate and 45 (80%) invitees completed the survey which put forward modifications to the original guideline. The collated responses resulted in modifications. There was high agreement amongst the expert group. Conclusion: A modified and improved SCARE checklist is presented, after a Delphi consensus exercise was completed. The SCARE 2018 Statement: Updating Consensus Surgical CAse REport (SCARE) Guidelines. © 2018
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| 14. |
- Nicolas, Aude, et al.
(author)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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In: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Journal article (peer-reviewed)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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| 15. |
- Athan, E., et al.
(author)
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Influence of vancomycin minimum inhibitory concentration on the outcome of methicillin-susceptible Staphylococcus aureus left-sided infective endocarditis treated with antistaphylococcal β-lactam antibiotics: a prospective cohort study by the International Collaboration on Endocarditis
- 2017
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 23, s. 544-549
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Journal article (peer-reviewed)abstract
- © 2017 European Society of Clinical Microbiology and Infectious Diseases Objectives Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire.
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| 16. |
- Doriese, W B, et al.
(author)
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A practical superconducting-microcalorimeter X-ray spectrometer for beamline and laboratory science
- 2017
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In: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 88:5
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Journal article (peer-reviewed)abstract
- We describe a series of microcalorimeter X-ray spectrometers designed for a broad suite of measurement applications. The chief advantage of this type of spectrometer is that it can be orders of magnitude more efficient at collecting X-rays than more traditional high-resolution spectrometers that rely on wavelength-dispersive techniques. This advantage is most useful in applications that are traditionally photon-starved and/or involve radiation-sensitive samples. Each energy-dispersive spectrometer is built around an array of several hundred transition-edge sensors (TESs). TESs are superconducting thin films that are biased into their superconducting-to-normal-metal transitions. The spectrometers share a common readout architecture and many design elements, such as a compact, 65 mK detector package, 8-column time-division-multiplexed superconducting quantum-interference device readout, and a liquid-cryogen-free cryogenic system that is a two-stage adiabatic-demagnetization refrigerator backed by a pulse-tube cryocooler. We have adapted this flexible architecture to mate to a variety of sample chambers and measurement systems that encompass a range of observing geometries. There are two different types of TES pixels employed. The first, designed for X-ray energies below 10 keV, has a best demonstrated energy resolution of 2.1 eV (full-width-at-half-maximum or FWHM) at 5.9 keV. The second, designed for X-ray energies below 2 keV, has a best demonstrated resolution of 1.0 eV (FWHM) at 500 eV. Our team has now deployed seven of these X-ray spectrometers to a variety of light sources, accelerator facilities, and laboratory-scale experiments; these seven spectrometers have already performed measurements related to their applications. Another five of these spectrometers will come online in the near future. We have applied our TES spectrometers to the following measurement applications: synchrotron-based absorption and emission spectroscopy and energy-resolved scattering; accelerator-based spectroscopy of hadronic atoms and particle-induced-emission spectroscopy; laboratory-based time-resolved absorption and emission spectroscopy with a tabletop, broadband source; and laboratory-based metrology of X-ray-emission lines. Here, we discuss the design, construction, and operation of our TES spectrometers and show first-light measurements from the various systems. Finally, because X-ray-TES technology continues to mature, we discuss improvements to array size, energy resolution, and counting speed that we anticipate in our next generation of TES-X-ray spectrometers and beyond.
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| 17. |
- Jones, Gregory T., et al.
(author)
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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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In: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Journal article (peer-reviewed)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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| 18. |
- Leisawitz, David, et al.
(author)
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The origins space telescope
- 2019
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 11115
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Conference paper (peer-reviewed)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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| 19. |
- Leisawitz, David, et al.
(author)
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The Origins Space Telescope: Mission concept overview
- 2018
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In: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Conference paper (peer-reviewed)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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| 20. |
- 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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| 21. |
- Ridgers, C. P., et al.
(author)
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Signatures of quantum effects on radiation reaction in laser-electron-beam collisions
- 2017
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In: Journal of Plasma Physics. - : Cambridge University Press (CUP). - 0022-3778 .- 1469-7807. ; 83:5
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Journal article (peer-reviewed)abstract
- Two signatures of quantum effects on radiation reaction in the collision of a similar to GeV electron beam with a high intensity (>3 x 10(20) W cm(-2)) laser pulse have been considered. We show that the decrease in the average energy of the electron beam may be used to measure the Gaunt factor g for synchrotron emission. We derive an equation for the evolution of the variance in the energy of the electron beam in the quantum regime, i.e. quantum efficiency parameter eta (sic) 1. We show that the evolution of the variance may be used as a direct measure of the quantum stochasticity of the radiation reaction and determine the parameter regime where this is observable. For example, stochastic emission results in a 25 % increase in the standard deviation of the energy spectrum of a GeV electron beam, 1 fs after it collides with a laser pulse of intensity 10(21) W cm(-2). This effect should therefore be measurable using current high-intensity laser systems.
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| 22. |
- Andersen, J. L., et al.
(author)
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Pleistocene Evolution of a Scandinavian Plateau Landscape
- 2018
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In: Journal of Geophysical Research - Earth Surface. - 2169-9003 .- 2169-9011. ; 123:12, s. 3370-3387
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Journal article (peer-reviewed)abstract
- The origins and Pleistocene evolution of plateau landscapes along passive continental margins of the North Atlantic have been debated for more than a century. A key question in this debate concerns whether glacial and periglacial surface processes have substantially eroded plateau areas during late Cenozoic climatic cooling or whether the plateaus have mainly been protected from erosion by cold-based and largely nonerosive ice sheets. Here we investigate the Pleistocene evolution of a prominent plateau landscape in Reinheimen National Park, southern Norway. We estimate erosion rates across the plateau via inverse modeling of 141 new cosmogenic Be-10 and Al-26 measurements in regolith profiles and bedrock. We combine these results with sedimentological analyses of the regolith. In the vicinity of Reinheimen's regolith-covered summits, the combination of uniformly slow erosion (<10m/Myr) and near-parabolic slope geometry suggests long-term equilibrium with the presently active periglacial mass-wasting processes. Outside summit areas, erosion is faster (up to >50m/Myr), possibly due to episodic glacial erosion. Despite some indications of chemical alteration, such as grusic saprolite and small amounts of secondary minerals, the fine regolith comprises low clay/silt ratios and is dominated by primary minerals with no sign of dissolution. Together with our modeled erosion rates, this indicates that the regolith cover formed, and continues to develop, during the cold climate of the Late Pleistocene. Plain Language Summary Plateaus dissected by steep-sided valleys and fjords are common landscape elements within the mountains bordering the North Atlantic. Most of these plateaus have likely experienced millions of years of near-freezing temperatures and were repeatedly covered by ice sheets during recent glacial periods. Yet the imprint of cold-climate erosion processes on the plateau landscape evolution remains poorly understood. Here we investigate the Pleistocene evolution of an extensive Scandinavian plateau landscape in Reinheimen National Park, southern Norway. We measure cosmogenic nuclides within the surficial layers of rock and sediment on the plateau. The concentration of these cosmogenic nuclides reflects the erosion of the plateau landscape and thereby the impact of recent cold-climate surface processes. We find that erosion has influenced the plateaus within the latest glacial cycles. In the vicinity of the highest, sediment-clad summits, the plateau shape is determined by processes related to freezing and thawing of rocks and sediment, while the influence of erosion by glaciers and streams increases further downslope.
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| 23. |
- Cao, Yi, et al.
(author)
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A strong ultraviolet pulse from a newborn type Ia supernova
- 2015
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 521:7552, s. 328-
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Journal article (peer-reviewed)abstract
- Type Ia supernovae(1) are destructive explosions of carbon-oxygen white dwarfs(2,3). Although they are used empirically to measure cosmological distances(4-6), the nature of their progenitors remains mysterious(3). One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion(3,7,8). Here we report observations with the Swift Space Telescope of strong but declining ultraviolet emission from a type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star(9), and therefore provides evidence that some type Ia supernovae arise from the single degenerate channel.
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| 24. |
- Cao, Yi, et al.
(author)
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ABSENCE OF FAST-MOVING IRON IN AN INTERMEDIATE TYPE Ia SUPERNOVA BETWEEN NORMAL AND SUPER-CHANDRASEKHAR
- 2016
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In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:2
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Journal article (peer-reviewed)abstract
- In this paper, we report observations of a peculiar SN Ia iPTF13asv (a.k.a., SN2013cv) from the onset of the explosion to months after its peak. The early-phase spectra of iPTF13asv show an absence of iron absorption, indicating that synthesized iron elements are confined to low-velocity regions of the ejecta, which, in turn, implies a stratified ejecta structure along the line of sight. Our analysis of iPTF13asv's light curves and spectra shows that it is an intermediate case between normal and super-Chandrasekhar events. On the one hand, its light curve shape (B-band Delta m(15)=1.03 +/- 0.01) and overall spectral features resemble those of normal SNe Ia. On the other hand, its large peak optical and UV luminosity (M-B = -19.84 mag, M-uvm2 = -15.5 mag) and its low but almost constant Si II velocities of about 10,000 km s (1) are similar to those in super-Chandrasekhar events, and its persistent carbon signatures in the spectra are weaker than those seen commonly in super-Chandrasekhar events. We estimate a Ni-56 mass of 0.81(-0.18)(+0.10) M-circle dot and a total ejecta mass of 1.59(-0.12)(+0.45) M-circle dot. The large ejecta mass of iPTF13asv and its stratified ejecta structure together seemingly favor a double-degenerate origin.
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| 25. |
- Foote, Andrew D., et al.
(author)
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Killer whale genomes reveal a complex history of recurrent admixture and vicariance
- 2019
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In: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 28:14, s. 3427-3444
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Journal article (peer-reviewed)abstract
- Reconstruction of the demographic and evolutionary history of populations assuming a consensus tree-like relationship can mask more complex scenarios, which are prevalent in nature. An emerging genomic toolset, which has been most comprehensively harnessed in the reconstruction of human evolutionary history, enables molecular ecologists to elucidate complex population histories. Killer whales have limited extrinsic barriers to dispersal and have radiated globally, and are therefore a good candidate model for the application of such tools. Here, we analyse a global data set of killer whale genomes in a rare attempt to elucidate global population structure in a nonhuman species. We identify a pattern of genetic homogenisation at lower latitudes and the greatest differentiation at high latitudes, even between currently sympatric lineages. The processes underlying the major axis of structure include high drift at the edge of species' range, likely associated with founder effects and allelic surfing during postglacial range expansion. Divergence between Antarctic and non-Antarctic lineages is further driven by ancestry segments with up to fourfold older coalescence time than the genome-wide average; relicts of a previous vicariance during an earlier glacial cycle. Our study further underpins that episodic gene flow is ubiquitous in natural populations, and can occur across great distances and after substantial periods of isolation between populations. Thus, understanding the evolutionary history of a species requires comprehensive geographic sampling and genome-wide data to sample the variation in ancestry within individuals.
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| 26. |
- Johansson, Mattias, et al.
(author)
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The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study
- 2019
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In: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:1
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Journal article (peer-reviewed)abstract
- Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation.Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
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| 27. |
- Scelo, Ghislaine, et al.
(author)
-
Genome-wide association study identifies multiple risk loci for renal cell carcinoma.
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.
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| 28. |
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| 29. |
- Conradson, Steven D., et al.
(author)
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Closure of the Mott gap and formation of a superthermal metal in the Frohlich-type nonequilibrium polaron Bose-Einstein condensate in UO2+x
- 2017
-
In: Physical Review B. - 2469-9950 .- 2469-9969. ; 96:12
-
Journal article (peer-reviewed)abstract
- Mixed valence O-doped UO2+x. and photoexcited UO2 containing transitory U3+ and U5+ host a coherent polaronic quantum phase (CPQP) that exhibits the characteristics of a Frohlich-type, nonequilibrium, phononcoupled Bose-Einstein condensate whose stability and coherence are amplified by collective, anharmonic motions of atoms and charges. Complementary to the available, detailed, real space information from scattering and EXAFS, an outstanding question is the electronic structure. Mapping the Mott gap in UO2, U4O9, and U3O7 with O XAS and NIXS and UM5 RIXS shows that O doping raises the peak of the U5f states of the valence band by similar to 0.4 eV relative to a calculated value of 0.25 eV. However, it lowers the edge of the conduction band by 1.5 eV vs the calculated 0.6 eV, a difference much larger than the experimental error. This 1.9 eV reduction in the gap width constitutes most of the 2-2.2 eV gap measured by optical absorption. In addition, the XAS spectra show a tail that will intersect the occupied U5f states and give a continuous density-of-states that increases rapidly above its constricted intersection. Femtosecond-resolved photoemission measurements of UO2, coincident with the excitation pulse with 4.7 eV excitation, show the unoccupied U5f states of UO2 and no hot electrons. 3.1 eV excitation, however, complements the O-doping results by giving a continuous population of electrons for several eV above the Fermi level. The CPQP in photoexcited UO2 therefore fulfills the criteria for a nonequilibrium condensate. The electron distributions resulting from both excitations persist for 5-10 ps, indicating that they are the final state that therefore forms without passing through the initial continuous distribution of nonthermal electrons observed for other materials. Three exceptional findings are: (1) the direct formation of both of these long lived (> 3-10 ps) excited states without the short lived nonthermal intermediate; (2) the superthermal metallic state is as or more stable than typical photoinduced metallic phases; and (3) the absence of hot electrons accompanying the insulating UO2 excited state. This heterogeneous, nonequilibrium, Frohlich BEC stabilized by a Fano-Feshbach resonance therefore continues to exhibit unique properties.
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| 30. |
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| 31. |
- De, Kishalay, et al.
(author)
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iPTF 16hgs : A Double-peaked Ca-rich Gap Transient in a Metal-poor, Star-forming Dwarf Galaxy
- 2018
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 866:1
-
Journal article (peer-reviewed)abstract
- Calcium-rich gap transients represent an intriguing new class of faint and fast-evolving supernovae that exhibit strong [Ca II] emission in their nebular phase spectra. In this paper, we present the discovery and follow-up observations of a faint and fast-evolving transient, iPTF 16hgs, that exhibited a double-peaked light curve. Exhibiting a Type Ib spectrum in the photospheric phase and an early transition to a [Ca II] dominated nebular phase, iPTF 16hgs shows properties consistent with the class of Ca-rich gap transients, with two important exceptions. First, while the second peak of the light curve is similar to other Ca-rich gap transients, the first blue and fast-fading peak (declining over approximate to 2 days) is unique to this source. Second, we find that iPTF 16hgs occurred in the outskirts (projected offset of approximate to 6 kpc approximate to 1.9 R-eff) of a low-metallicity (approximate to 0.4 Z(circle dot)), star-forming, dwarf spiral galaxy. Deep limits from late-time radio observations suggest a low-density environment for the source. If iPTF 16hgs shares explosion physics with the class of Ca-rich gap transients, the first peak can be explained by the presence of 0.01 M-circle dot of Ni-56 in the outer layers the ejecta, reminiscent of some models of He-shell detonations on WDs. However, if iPTF 16hgs is physically unrelated to the class, the first peak is consistent with shock cooling emission (of an envelope with a mass of approximate to 0.08 M-circle dot and radius of approximate to 13 R-circle dot) in a core-collapse explosion of a highly stripped massive star in a close binary system.
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| 32. |
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| 33. |
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| 34. |
- Foote, Andrew D., et al.
(author)
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Genome-culture coevolution promotes rapid divergence of killer whale ecotypes
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- Analysing population genomic data from killer whale ecotypes, which we estimate have globally radiated within less than 250,000 years, we show that genetic structuring including the segregation of potentially functional alleles is associated with socially inherited ecological niche. Reconstruction of ancestral demographic history revealed bottlenecks during founder events, likely promoting ecological divergence and genetic drift resulting in a wide range of genome-wide differentiation between pairs of allopatric and sympatric ecotypes. Functional enrichment analyses provided evidence for regional genomic divergence associated with habitat, dietary preferences and post-zygotic reproductive isolation. Our findings are consistent with expansion of small founder groups into novel niches by an initial plastic behavioural response, perpetuated by social learning imposing an altered natural selection regime. The study constitutes an important step towards an understanding of the complex interaction between demographic history, culture, ecological adaptation and evolution at the genomic level.
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| 35. |
- Hollund, H. I., et al.
(author)
-
Pick the Right Pocket. Sub-sampling of Bone Sections to Investigate Diagenesis and DNA Preservation
- 2017
-
In: International journal of osteoarchaeology. - : WILEY. - 1047-482X .- 1099-1212. ; 27:3, s. 365-374
-
Journal article (peer-reviewed)abstract
- Many archaeological bones display a heterogeneous degradation pattern. Highly degraded bones could contain pockets of well-preserved bone, harbouring good quality DNA. This dichotomy may explain why the relationships between global bone preservation parameters such as histological integrity, bone mineral crystallinity or collagen yield, and bulk DNA preservation/amplification success rate have been found to be at best, weak to moderate. In this pilot study, we explore whether or not a more localised approach will highlight a stronger relationship between diagenetic parameters and DNA preservation. This study includes a detailed histological characterisation of bone diagenesis in sub-areas of three bone samples. Regions of the same bone, which displayed differential degrees of preservation or type of diagenesis were sampled for further analysis and both genetic (small scale Illumina MiSeq sequencing) and chemical (Fourier-transform infrared spectrometric analysis) analyses were performed. The aim was to investigate how bone diagenetic processes relate to DNA preservation at a higher resolution than in previous studies. This is key in order to improve DNA analytical success rates. The expected relationship between bone and DNA preservation (retrieved endogenous DNA) was observed and the results corroborate previous work that DNA preservation is linked to the integrity of bone collagen and mineral. The results further suggest that non-biological diagenetic alterations such as etching and the presence of mineral infiltrations and inclusions have a negative effect on DNA preservation/extraction. Copyright (C) 2016 John Wiley & Sons, Ltd.
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| 36. |
- Hosseinzadeh, Griffin, et al.
(author)
-
Type Ibn Supernovae Show Photometric Homogeneity and Spectral Diversity at Maximum Light
- 2017
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 836:2
-
Journal article (peer-reviewed)abstract
- Type Ibn supernovae (SNe) are a small yet intriguing class of explosions whose spectra are characterized by low-velocity helium emission lines with little to no evidence for hydrogen. The prevailing theory has been that these are the core-collapse explosions of very massive stars embedded in helium-rich circumstellar material (CSM). We report optical observations of six new SNe Ibn: PTF11rfh, PTF12ldy, iPTF14aki, iPTF15ul, SN 2015G, and iPTF15akq. This brings the sample size of such objects in the literature to 22. We also report new data, including a near-infrared spectrum, on the Type Ibn SN 2015U. In order to characterize the class as a whole, we analyze the photometric and spectroscopic properties of the full Type Ibn sample. We find that, despite the expectation that CSM interaction would generate a heterogeneous set of light curves, as seen in SNe IIn, most Type Ibn light curves are quite similar in shape, declining at rates around 0.1 mag day(-1) during the first month after maximum light, with a few significant exceptions. Early spectra of SNe Ibn come in at least two varieties, one that shows narrow P Cygni lines and another dominated by broader emission lines, both around maximum light, which may be an indication of differences in the state of the progenitor system at the time of explosion. Alternatively, the spectral diversity could arise from viewing-angle effects or merely from a lack of early spectroscopic coverage. Together, the relative light curve homogeneity and narrow spectral features suggest that the CSM consists of a spatially confined shell of helium surrounded by a less dense extended wind.
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| 37. |
- Huss, M., et al.
(author)
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Toward mountains without permanent snow and ice
- 2017
-
In: Earth's Future. - 2328-4277. ; 5:5, s. 418-435
-
Research review (peer-reviewed)abstract
- The cryosphere in mountain regions is rapidly declining, a trend that is expected to accelerate over the next several decades due to anthropogenic climate change. A cascade of effects will result, extending from mountains to lowlands with associated impacts on human livelihood, economy, and ecosystems. With rising air temperatures and increased radiative forcing, glaciers will become smaller and, in some cases, disappear, the area of frozen ground will diminish, the ratio of snow to rainfall will decrease, and the timing and magnitude of both maximum and minimum streamflow will change. These changes will affect erosion rates, sediment, and nutrient flux, and the biogeochemistry of rivers and proglacial lakes, all of which influence water quality, aquatic habitat, and biotic communities. Changes in the length of the growing season will allow low-elevation plants and animals to expand their ranges upward. Slope failures due to thawing alpine permafrost, and outburst floods from glacier-and moraine-dammed lakes will threaten downstream populations.Societies even well beyond the mountains depend on meltwater from glaciers and snow for drinking water supplies, irrigation, mining, hydropower, agriculture, and recreation. Here, we review and, where possible, quantify the impacts of anticipated climate change on the alpine cryosphere, hydrosphere, and biosphere, and consider the implications for adaptation to a future of mountains without permanent snow and ice.
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| 38. |
- Kenna, Kevin P., et al.
(author)
-
NEK1 variants confer susceptibility to amyotrophic lateral sclerosis
- 2016
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1037-1042
-
Journal article (peer-reviewed)abstract
- To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261 His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261 His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology.
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| 39. |
- Lopes, Renato D., et al.
(author)
-
Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy
- 2017
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In: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 129:22, s. 2980-2987
-
Journal article (peer-reviewed)abstract
- We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received >= 1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3%). Apixaban resulted in significantly less ICH (0.33% per year), regardless of type and location, than warfarin (0.80% per year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th percentiles) time from most recent international normalized ratio (INR) to ICH was 13 days (6, 21 days). Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale score at discharge was >= 4 in 55.7% of patients, and the overall mortality rate at 30 days was 43.3% with no difference between apixaban- and warfarin-treated patients. ICH occurred at a rate of 0.80% per year with warfarin regardless of INR control and at a rate of 0.33% per year with apixaban and was associated with high short-termmorbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients of older age. This trial was registered at www.clinicaltrials.gov as #NCT00412984.
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| 40. |
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| 41. |
- O’Neil, Galen C., et al.
(author)
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Ultrafast Time-Resolved X-ray Absorption Spectroscopy of Ferrioxalate Photolysis with a Laser Plasma X-ray Source and Microcalorimeter Array
- 2017
-
In: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 8:5, s. 1099-1104
-
Journal article (peer-reviewed)abstract
- The detailed pathways of photoactivity on ultrafast time scales are a topic of contemporary interest. Using a tabletop apparatus based on a laser plasma X-ray source and an array of cryogenic microcalorimeter X-ray detectors, we measured a transient X-ray absorption spectrum during the ferrioxalate photoreduction reaction. With these high-efficiency detectors, we observe the Fe K edge move to lower energies and the amplitude of the extended X-ray absorption fine structure reduce, consistent with a photoreduction mechanism in which electron transfer precedes disassociation. These results are compared to previously published transient X-ray absorption measurements on the same reaction and found to be consistent with the results from Ogi et al. and inconsistent with the results of Chen et al. (Ogi, Y.; et al. Struct. Dyn. 2015, 2, 034901; Chen, J.; Zhang, H.; Tomov, I. V.; Ding, X.; Rentzepis, P. M. Chem. Phys. Lett. 2007, 437, 50-55). We provide quantitative limits on the Fe-O bond length change. Finally, we review potential improvements to our measurement technique, highlighting the future potential of tabletop X-ray science using microcalorimeter sensors.
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| 42. |
- Over, Bjorn, et al.
(author)
-
Structural and conformational determinants of macrocycle cell permeability
- 2016
-
In: Nature Chemical Biology. - New York : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 12:12, s. 1065-1074
-
Journal article (peer-reviewed)abstract
- Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 nonpeptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.
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| 43. |
- Perley, Daniel A., et al.
(author)
-
The fast, luminous ultraviolet transient AT2018cow : extreme supernova, or disruption of a star by an intermediate-mass black hole?
- 2019
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:1, s. 1031-1049
-
Journal article (peer-reviewed)abstract
- Wide-field optical surveys have begun to uncover large samples of fast (t(rise) less than or similar to 5 d), luminous (M-peak < 18), blue transients. While commonly attributed to the breakout of a supernova shock into a dense wind, the great distances to the transients of this class found so far have hampered detailed investigation of their properties. We present photometry and spectroscopy from a comprehensive worldwide campaign to observe AT 2018cow (ATLAS 18qqn), the first fast-luminous optical transient to be found in real time at low redshift. Our first spectra (<2 days after discovery) are entirely featureless. A very broad absorption feature suggestive of near-relativistic velocities develops between 3 and 8 days, then disappears. Broad emission features of H and He develop after >10 days. The spectrum remains extremely hot throughout its evolution, and the photospheric radius contracts with time (receding below R < 10 (14) cm after 1 month). This behaviour does not match that of any known supernova, although a relativistic jet within a fallback supernova could explain some of the observed features. Alternatively, the transient could originate from the disruption of a star by an intermediate-mass black hole, although this would require long-lasting emission of highly super-Eddington thermal radiation. In either case, AT 2018cow suggests that the population of fast luminous transients represents a new class of astrophysical event. Intensive follow-up of this event in its late phases, and of any future events found at comparable distance, will be essential to better constrain their origins.
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| 44. |
- Rubin, Adam, et al.
(author)
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TYPE II SUPERNOVA ENERGETICS AND COMPARISON OF LIGHT CURVES TO SHOCK-COOLING MODELS
- 2016
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 820:1
-
Journal article (peer-reviewed)abstract
- During the first few days after explosion, Type II supernovae (SNe) are dominated by relatively simple physics. Theoretical predictions regarding early-time SN light curves in the ultraviolet (UV) and optical bands are thus quite robust. We present, for the first time, a sample of 57 R-band SN II light curves that are well-monitored during their rise, with > 5 detections during the first 10 days after discovery, and a well-constrained time of explosion to within 1-3 days. We show that the energy per unit mass (E/M) can be deduced to roughly a factor of five by comparing early-time optical data to the 2011 model of Rabinak & Waxman, while the progenitor radius cannot be determined based on R-band data alone. We find that SN II explosion energies span a range of E/M = (0.2-20) x 10(51) erg/(10 M-circle dot), and have a mean energy per unit mass of < E/M > = 0.85 x 10(51) erg/(10 M-circle dot), corrected for Malmquist bias. Assuming a small spread in progenitor masses, this indicates a large intrinsic diversity in explosion energy. Moreover, E/M is positively correlated with the amount of Ni-56 produced in the explosion, as predicted by some recent models of core-collapse SNe. We further present several empirical correlations. The peak magnitude is correlated with the decline rate (Delta m(15)), the decline rate is weakly correlated with the rise time, and the rise time is not significantly correlated with the peak magnitude. Faster declining SNe are more luminous and have longer rise times. This limits the possible power sources for such events.
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| 45. |
- van Rheenen, Wouter, et al.
(author)
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Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis
- 2016
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:9, s. 1043-1048
-
Journal article (peer-reviewed)abstract
- To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577 cases and 23,475 controls, combined with 2,579 cases and 2,767 controls in an independent replication cohort, we fine-mapped a new risk locus on chromosome 21 and identified C21orf2 as a gene associated with ALS risk. In addition, we identified MOBP and SCFD1 as new associated risk loci. We established evidence of ALS being a complex genetic trait with a polygenic architecture. Furthermore, we estimated the SNP-based heritability at 8.5%, with a distinct and important role for low-frequency variants (frequency 1-10%). This study motivates the interrogation of larger samples with full genome coverage to identify rare causal variants that underpin ALS risk.
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| 46. |
- Vreeswijk, Paul M., et al.
(author)
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ON THE EARLY-TIME EXCESS EMISSION IN HYDROGEN-POOR SUPERLUMINOUS SUPERNOVAE
- 2017
-
In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 835:1
-
Journal article (peer-reviewed)abstract
- We present the light curves of the hydrogen-poor superluminous supernovae (SLSNe I) PTF 12dam and iPTF 13dcc, discovered by the (intermediate) Palomar Transient Factory. Both show excess emission at early times and a slowly declining light curve at late times. The early bump in PTF 12dam is very similar in duration (similar to 10 days) and brightness relative to the main peak (2-3 mag fainter) compared to that observed in other SLSNe I. In contrast, the long-duration (>30 days) early excess emission in iPTF 13dcc, whose brightness competes with that of the main peak, appears to be of a different nature. We construct bolometric light curves for both targets, and fit a variety of light-curve models to both the early bump and main peak in an attempt to understand the nature of these explosions. Even though the slope of the late-time decline in the light curves of both SLSNe is suggestively close to that expected from the radioactive decay of Ni-56 and Co-56, the amount of nickel required to power the full light curves is too large considering the estimated ejecta mass. The magnetar model including an increasing escape fraction provides a reasonable description of the PTF 12dam observations. However, neither the basic nor the double-peaked magnetar model is capable of reproducing the light curve of iPTF 13dcc. A model combining a shock breakout in an extended envelope with late-time magnetar energy injection provides a reasonable fit to the iPTF 13dcc observations. Finally, we find that the light curves of both PTF 12dam and iPTF 13dcc can be adequately fit with the model involving interaction with the circumstellar medium.
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| 47. |
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| 48. |
- Amidon, Gregory E., et al.
(author)
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Fifty-Eight Years and Counting : High-Impact Publishing in Computational Pharmaceutical Sciences and Mechanism-Based Modeling
- 2019
-
In: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 108:1, s. 2-7
-
Journal article (peer-reviewed)abstract
- With this issue of the Journal of Pharmaceutical Sciences, we celebrate the nearly 6 decades of contributions to mechanistic-based modeling and computational pharmaceutical sciences. Along with its predecessor, The Journal of the American Pharmaceutical Association: Scientific Edition first published in 1911, JPharmSci has been a leader in the advancement of pharmaceutical sciences beginning with its inaugural edition in 1961. As one of the first scientific journals focusing on pharmaceutical sciences, JPharmSci has established a reputation for publishing high-quality research articles using computational methods and mechanism-based modeling. The journal’s publication record is remarkable. With over 15,000 articles, 3000 notes, and more than 650 reviews from industry, academia, and regulatory agencies around the world, JPharmSci has truly been the leader in advancing pharmaceutical sciences.
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| 49. |
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| 50. |
- Collett-Solberg, Paulo F., et al.
(author)
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Diagnosis, Genetics, and Therapy of Short Stature in Children : A Growth Hormone Research Society International Perspective
- 2019
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In: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 92:1, s. 1-14
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Journal article (peer-reviewed)abstract
- The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
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