bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Nonequilibrium Flow on the Structure of Turbulence Over River Dunes
Authors: Unsworth C. A. , Parsons D. R. , Hardy R. J. , Reesink A. J. H. , Best J. L. , Ashworth P. J. , Keevil G. M.
Published: August 2018

Most past experimental investigations of flow over river dunes have focused on conditions that match semiempirical flow‐depth scaling laws, yet such equilibrium conditions are of limited value because they rarely occur in natural channels. This paper quantifies the structure of mean and turbulent flow over fixed 2‐D laboratory dunes across a range of nonequilibrium conditions within the dune flow regime. The flow field was quantified using 2‐D particle imaging velocimetry for 12 conditions, including flows that are too deep, too shallow, too fast, or too slow for the size of the fixed dunes. The results demonstrate major departures in the patterns of the mean flow and structure of turbulence when compared to dunes formed under equilibrium flow conditions. The length of flow reattachment scales linearly with the ratio of mean depth‐averaged streamwise velocity to shear velocity at the dune crest (
), which provides a new predictive measure for flow reattachment length. Depth‐averaged vertical velocities at the dune crest (
) show a parabolic relationship with
, peaking at
~0.60 m/s, which matches the relationship of dune aspect ratio with transport stage present in mobile bed conditions. The spatial location of the turbulent wake was found to vary with flow depth and velocity, with lower
and greater flow depths causing the wake to rise toward the free surface. Deeper flows are likely to show less flow convergence over the crests of dunes due to reduced interaction of turbulence with the free surface, resulting in a reduction of transport stage.
Beyond Regime: A Stochastic Model of Floods, Bank Erosion, and Channel Migration
Authors: Davidson S. L. , Eaton B. C.
Published: August 2018

Equilibrium or regime models based on a single formative (channel‐forming) discharge have been instrumental in developing a quantitative understanding of river channel dynamics. However, alternative paradigms can be used to ask fundamentally different questions about river channel behavior. In this paper, we present the Stochastic Channel Simulator (STOCHASIM), a simple biogeomorphic model that models the interplay between erosion and vegetation encroachment through changes in channel geometry. Results for a range of flood distributions are compared to predictions from a similar model based upon a traditional regime approach. Flood variability strongly influences the mean channel geometry and channel stability; the regime model and the stochastic model predict the same channel width when flow variability is low but diverge as flow variability increases. The return period of the formative flow required to match the geometry generated by a traditional regime approach increases systematically, from about 2 years for flow regimes in humid regions to nearly 8 years for more variable flow regimes, like those typical of arid regions. While the traditional regime approach provides a reasonable simplification for streams with little variability in the flood distribution, stochastic modeling may provide more realistic estimates of channel size as flood variability increases (e.g., in arid streams or small watersheds). The success of STOCHASIM in replicating realistic patterns of erosion, as well as the historical contingency often observed in natural streams, suggests that adopting a stochastic dynamics paradigm could advance geomorphology, just as it has done in hydrology, ecology, and other natural sciences.
Honoring Earth and Space Scientists
Authors: Duncombe Jenessa
Published: August 2018

AGU members and others in the news.
Changes in Deep Water Oxygenation of the South China Sea Since the Last Glacial Period
Authors: Li Gang , Rashid Harunur , Zhong Lifeng , Xu Xing , Yan Wen , Chen Zhong
Published: August 2018

The Pacific meridional overturning circulation is thought to have a significant influence on global climate. However, the extent to which intermediate and deep circulations have changed in the Pacific Ocean since the Last Glacial Maximum (LGM) is not well known. At present, the South China Sea Deep Water (SCSDW) is fed by the upper Pacific Deep Water. Here we present new benthic foraminiferal δ13C and redox‐sensitive elemental data from a sediment core retrieved from the southern deep SCS to reconstruct the oxygenation history of the SCSDW since the LGM. Oxygenation records from the deep SCS and intermediate and deep waters in the Pacific Ocean demonstrate that the SCSDW deeper than 1,600 m has been sourced by the Pacific Deep Water since the LGM. Our data suggest that the well‐ventilated North Pacific Intermediate Water would not have influenced the SCSDW during cold stadials of the last deglacial period.
Large‐Scale Atmospheric Control on Non‐Gaussian Tails of Midlatitude Temperature Distributions
Authors: Linz Marianna , Chen Gang , Hu Zeyuan
Published: August 2018

Observed surface temperature distributions are non‐Gaussian, which has important implications for the likelihood of extreme events in a changing climate. We use a two‐dimensional advection‐diffusion model of temperature stirred by stochastically generated Rossby waves with a sustained background temperature gradient to explore non‐Gaussian temperature distributions. We examine how these distributions change with changes to thermal relaxation and eddy stirring. Weakening the background temperature gradient leads to decreased variance but no changes in other moments, while the eddy properties affect both the variance and skewness. A poleward movement of eddy stirring latitude leads to reduced skewness for most latitudes, implying a shift toward longer negative tails in temperature distributions, all else being equal. In contrast, the dependence of temperature skewness on eddy speed is a nuanced, nonlinear relationship.
On the Sensitivity of the Relationship Between Hadley Circulation Asymmetry and ENSO in CMIP5 Models
Authors: Guo Yi‐Peng , Tan Zhe‐Min
Published: August 2018

Recent study shows that the asymmetric component (AC) of Hadley circulation variability during late winter and early spring can be explained by the combined effect between background sea surface temperature (SST) and the SST anomalies associated with El Niño–Southern Oscillation (ENSO). But the sensitivity of AC‐ENSO relationship to background SST and ENSO properties is still unknown. Using 17 climate models from the Coupled Model Intercomparison Project phase 5, we investigated the sensitivity of the AC‐ENSO relationship to the background SST and three ENSO properties. Most of the Coupled Model Intercomparison Project phase 5 models capture the spatial structure of the AC and reproduce the AC‐ENSO relationship, but the AC‐ENSO relationship has large intermodel spread. The AC‐ENSO relationship is mostly sensitive to ENSO zonal extent. ENSO amplitude can also influence the AC‐ENSO relationship by affecting the zonal extent. However, ENSO meridional extent and background SST—above a certain threshold—have little influence on the AC‐ENSO relationship.
GaAs Spectrometer for Planetary Electron Spectroscopy
Authors: Lioliou G. , Butera S. , Zhao S. , Whitaker M. D. C. , Barnett A. M.
Published: August 2018

Work toward producing a radiation‐hard and high temperature tolerant direct detection electron spectrometer is reported. The motivation is to develop a low‐mass, low‐volume, low‐power, multimission capable instrument for future space science missions. The resultant prototype electron spectrometer employed a GaAs p+‐i‐n+ mesa photodiode (10 μm i layer thickness; 200 μm diameter) and a custom‐made charge‐sensitive preamplifier. The GaAs detector was initially electrically characterized as a function of temperature. The detector‐preamplifier assembly was then investigated for its utility in electron spectroscopy across the temperature range 100 to 20 °C using a laboratory 63Ni radioisotope β− particle source (end point energy = 66 keV). Monte Carlo simulations using the computer program CASINO were conducted and showed that the spectrometer had a quantum detection efficiency which increased with increasing electron energy up to 70 keV; a quantum detection efficiency of 73% was calculated. The accumulated 63Ni β− particle spectra together with CASINO simulations of the detected spectra showed that the GaAs based spectrometer could be used for counting electrons and measuring the energy deposited per electron in the detector's active region (i layer). The development of a GaAs electron spectrometer of this type may find use in future space missions to environments of intense radiation (such as at the surface of Europa for investigation of electron‐driven radiolysis of ice) and high temperature (such as at Mercury, and comets passing close to the Sun).
Mesoscale Plasma Convection Perturbations in the High‐Latitude Ionosphere
Authors: Chen Yun‐Ju , Heelis Roderick A.
Published: August 2018

An investigation of flow perturbations with spatial scale sizes between 100 and 500 km in the high‐latitude ionosphere is presented. These localized flow perturbations are deviations from the large‐scale background convection, expected to give us new insights into the magnetosphere‐ionosphere coupling process. Ion drift measurements from the Defense Meteorological Satellite Program F17 are utilized to identify these mesoscale flow perturbations. Our intent is to discover the properties of these perturbations in terms of perturbation flow speeds, location, scale size, and occurrence frequency as well as their dependence on the interplanetary magnetic field (IMF) and underlying large‐scale convection pattern. Observation suggests that flow perturbation locations strongly depend on the IMF orientation as does the occurrence frequency of the flow perturbations. For southward IMF, more flow perturbations occur in regions of sunward background flow than in regions of antisunward background flow. For flow perturbations with speeds over 300 m/s, an asymmetry in the preferred direction and scale size is seen for those embedded in sunward and antisunward background flows. Significantly less asymmetry is present for flow perturbations with speeds between 100 and 300 m/s. The flow perturbations exceeding 300 m/s are most likely closed locally with lower magnitude return flows or with adjacent flows across the convection reversal boundary and representing additional sources of frictional heating and momentum transfer to the thermosphere. The perturbation flow speed is almost independent of the scale size and underlying convection speed, but the largest speeds are preferentially seen at scale sizes between 200 and 300 km.
Fluid‐Assisted Deformation and Strain Localization in the Cooling Mantle Wedge of a Young Subduction Zone (Semail Ophiolite)
Authors: Prigent C. , Guillot S. , Agard P. , Ildefonse B.
Published: August 2018

This study reports on feedback mechanisms between fluid migration, ductile deformation, and strain localization processes in an incipiently forming mantle wedge: the basal banded unit of the Semail ophiolite. These peridotites were located right above the plate interface during intraoceanic subduction infancy that ultimately led to ophiolite obduction. During this stage, they were affected by coeval ductile deformation, forming (proto)mylonites at ~900–800 °C to ultramylonites at ~700 °C, and interaction with subduction fluids. From the petrological and microstructural study of these hydrated peridotites and their protolith (preserved lenses of porphyroclastic tectonites), we show that peridotite interaction with hydrous fluids triggered dissolution/precipitation processes. Dissolution of coarser grains and precipitation of new and smaller ones (mainly pyroxenes, spinel, and amphibole) resulted in a drastic grain size reduction, phase mixing and a switch from olivine dislocation to grain size sensitive creep in (proto)mylonites. Data also evidence a feedback process of fluid focusing in actively deforming shear zones. This rapid switch in olivine deformation mechanism, driven by subduction fluid‐peridotite interaction, triggered an intense weakening of the peridotites at ~900–800 °C and a transition from a mechanically decoupled to coupled plate interface (as witnessed by the detachment and underplating of a high‐temperature metamorphic sole to the base of the ophiolite). It also explains the intense strain localization (<1‐km‐thick shear zone) along this ductile portion of the plate interface. Considering that similar mechanisms take place in mature subduction zones, they may explain plate interface coupling at subarc depths in worldwide subduction zones.
O+Escape During the Extreme Space Weather Event of 4–10 September 2017
Authors: Schillings Audrey , Nilsson Hans , Slapak Rikard , Wintoft Peter , Yamauchi Masatoshi , Wik Magnus , Dandouras Iannis , Carr Chris M.
Published: August 2018

We have investigated the consequences of extreme space weather on ion outflow from the polar ionosphere by analyzing the solar storm that occurred early September 2017, causing a severe geomagnetic storm. Several X‐flares and coronal mass ejections were observed between 4 and 10 September. The first shock—likely associated with a coronal mass ejection—hit the Earth late on 6 September, produced a storm sudden commencement, and began the initial phase of the storm. It was followed by a second shock, approximately 24 hr later, that initiated the main phase and simultaneously the Dst index dropped to Dst = −142 nT and Kp index reached Kp = 8. Using COmposition DIstribution Function data on board Cluster satellite 4, we estimated the ionospheric O+outflow before and after the second shock. We found an enhancement in the polar cap by a factor of 3 for an unusually high ionospheric O+outflow (mapped to an ionospheric reference altitude) of 1013 m−2 s−1. We suggest that this high ionospheric O+outflow is due to a preheating of the ionosphere by the multiple X‐flares. Finally, we briefly discuss the space weather consequences on the magnetosphere as a whole and the enhanced O+outflow in connection with enhanced satellite drag.
Perturbed Input Ensemble Modeling With the Space Weather Modeling Framework
Authors: Morley S. K. , Welling D. T. , Woodroffe J. R.
Published: August 2018

To assess the effect of uncertainties in solar wind driving on the predictions from the operational configuration of the Space Weather Modeling Framework, we have developed a nonparametric method for generating multiple possible realizations of the solar wind just upstream of the bow shock, based on observations near the first Lagrangian point. We have applied this method to the solar wind inputs at the upstream boundary of Space Weather Modeling Framework and have simulated the geomagnetic storm of 5 April 2010. We ran a 40‐member ensemble for this event and have used this ensemble to quantify the uncertainty in the predicted Sym‐H index and ground magnetic disturbances due to the uncertainty in the upstream boundary conditions. Both the ensemble mean and the unperturbed simulation tend to underpredict the magnitude of Sym‐H in the quiet interval before the storm and overpredict in the storm itself, consistent with previous work. The ensemble mean is a more accurate predictor of Sym‐H, improving the mean absolute error by nearly 2 nT for this interval and displaying a smaller bias. We also examine the uncertainty in predicted maxima in ground magnetic disturbances. The confidence intervals are typically narrow during periods where the predicted dBH/dt is low. The confidence intervals are often much wider where the median prediction is for enhanced dBH/dt. The ensemble also allows us to identify intervals of activity that cannot be explained by uncertainty in the solar wind driver, driving further model improvements. This work demonstrates the feasibility and importance of ensemble modeling for space weather applications.
Exploring Controls on Rainfall‐Runoff Events: 2. Regional Patterns and Spatial Controls of Event Characteristics in Germany
Authors: Tarasova L. , Basso S. , Poncelet C. , Merz R.
Published: August 2018

This study unveils regional patterns of rainfall‐runoff event characteristics in Germany and identifies their spatial controls. Characteristics describing mean value, variability, and seasonality of event runoff coefficient, time scale, rise time, and of the occurrence of multiple‐peak events are derived for a set of 196,073 rainfall‐runoff events observed in 401 mesoscale German catchments. Multiobjective performances of various variable selection methods are used to identify hydrologically relevant variables from a comprehensive set of 115 descriptors of climate, topography, geomorphology, soil, land use, hydrogeology, and geology for every catchment. Results show that although event characteristics have relatively clear regional patterns due to the dominance of climatic controls at regional scale, subsurface properties (i.e., catchment storage) play a considerable role for the prediction of event runoff response. Compared to other tested variable selection methods, the application of a backward elimination procedure allows for the most accurate prediction of spatial patterns and regionalized values of event characteristics identifying soil depth, hydraulic permeability and frequency, size, and seasonality of wet spells as hydrologically relevant catchment descriptors. Climatic and hydrogeological descriptors outperform other generic groups of catchment descriptors. The hydrological interpretation of the emergent regional pattern of event characteristics, their variability, and seasonality provides insight on archetypical catchment behaviors and their controls.
Neurofilament light interaction with GluN1 modulates neurotransmission and schizophrenia-associated behaviors
Authors: Yuan Aidong , Veeranna  , Sershen Henry , Basavarajappa Balapal S. , Smiley John F. , Hashim Audrey , Bleiwas Cynthia , Berg Martin , Guifoyle David N. , Subbanna Shivakumar , Darji Sandipkumar , Kumar Asok , Rao Mala V. , Wilson Donald A. , Julien Jean-Pierre , Javitt Daniel C. , Nixon Ralph A.
Published: August 2018

Neurofilament (NFL) proteins have recently been found to play unique roles in synapses. NFL is known to interact with the GluN1 subunit of N-methyl-d-aspartic acid (NMDAR) and be reduced in schizophrenia though functional consequences are unknown. Here we investigated whether the interaction of NFL with GluN1 modulates synaptic transmission and schizophrenia-associated behaviors. The interaction of NFL with GluN1 was assessed by means of molecular, pharmacological, electrophysiological, magnetic resonance spectroscopy (MRS), and schizophrenia-associated behavior analyses. NFL deficits cause an NMDAR hypofunction phenotype including abnormal hippocampal function, as seen in schizophrenia. NFL−/− deletion in mice reduces dendritic spines and GluN1 protein levels, elevates ubiquitin-dependent turnover of GluN1 and hippocampal glutamate measured by MRS, and depresses hippocampal long-term potentiation. NMDAR-related behaviors are also impaired, including pup retrieval, spatial and social memory, prepulse inhibition, night-time activity, and response to NMDAR antagonist, whereas motor deficits are minimal. Importantly, partially lowering NFL in NFL+/− mice to levels seen regionally in schizophrenia, induced similar but milder NMDAR-related synaptic and behavioral deficits. Our findings support an emerging view that central nervous system neurofilament subunits including NFL in the present report, serve distinctive, critical roles in synapses relevant to neuropsychiatric diseases.
Correction to: MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy
Authors: Ren Wei-Wei , Li Dan-Dan , Chen Xiaolan , Li Xiao-Long , He Ya-Ping , Guo Le-Hang , Liu Lin-Na , Sun Li-Ping , Zhang Xiao-Ping
Published: August 2018

Following publication of the article, the authors reported that Huixiong Xu had left the department, and requested that the author list be amended accordingly.
A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers
Authors: Mosley Jonathan D. , Feng QiPing , Wells Quinn S. , Van Driest Sara L. , Shaffer Christian M. , Edwards Todd L. , Bastarache Lisa , Wei Wei-Qi , Davis Lea K. , McCarty Catherine A. , Thompson Will , Chute Christopher G. , Jarvik Gail P. , Gordon Adam S. , Palmer Melody R. , Crosslin David R. , Larson Eric B. , Carrell David S. , Kullo Iftikhar J. , Pacheco Jennifer A. , Peissig Peggy L. , Brilliant Murray H. , Linneman James G. , Namjou Bahram , Williams Marc S. , Ritchie Marylyn D. , Borthwick Kenneth M. , Verma Shefali S. , Karnes Jason H. , Weiss Scott T. , Wang Thomas J. , Stein C. Michael , Denny Josh C. , Roden Dan M.
Published: August 2018

Defining the full spectrum of human disease associated with a biomarker is necessary to advance the biomarker into clinical practice. We hypothesize that associating biomarker measurements with electronic health record (EHR) populations based on shared genetic architectures would establish the clinical epidemiology of the biomarker. We use Bayesian sparse linear mixed modeling to calculate SNP weightings for 53 biomarkers from the Atherosclerosis Risk in Communities study. We use the SNP weightings to computed predicted biomarker values in an EHR population and test associations with 1139 diagnoses. Here we report 116 associations meeting a Bonferroni level of significance. A false discovery rate (FDR)-based significance threshold reveals more known and undescribed associations across a broad range of biomarkers, including biometric measures, plasma proteins and metabolites, functional assays, and behaviors. We confirm an inverse association between LDL-cholesterol level and septicemia risk in an independent epidemiological cohort. This approach efficiently discovers biomarker-disease associations.
Interferon priming is essential for human CD34+ cell-derived plasmacytoid dendritic cell maturation and function
Authors: Laustsen A. , Bak R. O. , Krapp C. , Kjær L. , Egedahl J. H. , Petersen C. C. , Pillai S. , Tang H. Q. , Uldbjerg N. , Porteus M. , Roan N. R. , Nyegaard M. , Denton P. W. , Jakobsen M. R.
Published: August 2018

Plasmacytoid dendritic cells (pDC) are essential for immune competence. Here we show that pDC precursor differentiated from human CD34+ hematopoietic stem and progenitor cells (HSPC) has low surface expression of pDC markers, and has limited induction of type I interferon (IFN) and IL-6 upon TLR7 and TLR9 agonists treatment; by contrast, cGAS or RIG-I agonists-mediated activation is not altered. Importantly, after priming with type I and II IFN, these precursor pDCs attain a phenotype and functional activity similar to that of peripheral blood-derived pDCs. Data from CRISPR/Cas9-mediated genome editing of HSPCs further show that HSPC-pDCs with genetic modifications can be obtained, and that expression of the IFN-α receptor is essential for the optimal function, but dispensable for the differentiation, of HSPC-pDC percursor. Our results thus demonstrate the biological effects of IFNs for regulating pDC function, and provide the means of generating of gene-modified human pDCs.
Evidence of a turbulent ExB mixing avalanche mechanism of gas breakdown in strongly magnetized systems
Authors: Yoo Min-Gu , Lee Jeongwon , Kim Young-Gi , Kim Jayhyun , Maviglia Francesco , Sips Adrianus C. C. , Kim Hyun-Tae , Hahm Taik Soo , Hwang Yong-Seok , Lee Hae June , Na Yong-Su
Published: August 2018

Although gas breakdown phenomena have been intensively studied over 100 years, the breakdown mechanism in a strongly magnetized system, such as tokamak, has been still obscured due to complex electromagnetic topologies. There has been a widespread misconception that the conventional breakdown model of the unmagnetized system can be directly applied to the strongly magnetized system. However, we found clear evidence that existing theories cannot explain the experimental results. Here, we demonstrate the underlying mechanism of gas breakdown in tokamaks, a turbulent ExB mixing avalanche, which systematically considers multi-dimensional plasma dynamics in the complex electromagnetic topology. This mechanism clearly elucidates the experiments by identifying crucial roles of self-electric fields produced by space-charge that decrease the plasma density growth rate and cause a dominant transport via ExB drifts. A comprehensive understanding of plasma dynamics in complex electromagnetic topology provides general design strategy for robust breakdown scenarios in a tokamak fusion reactor.
Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution
Authors: Awakawa Takayoshi , Fujioka Takuma , Zhang Lihan , Hoshino Shotaro , Hu Zhijuan , Hashimoto Junko , Kozone Ikuko , Ikeda Haruo , Shin-Ya Kazuo , Liu Wen , Abe Ikuro
Published: August 2018

Reprogramming of the NRPS/PKS assembly line is an attractive method for the production of new bioactive molecules. However, it is usually hampered by the loss of intimate domain/module interactions required for the precise control of chain transfer and elongation reactions. In this study, we first establish heterologous expression systems of the unique antimycin-type cyclic depsipeptides: JBIR-06 (tri-lactone) and neoantimycin (tetra-lactone), and engineer their biosyntheses by taking advantage of bioinformatic analyses and evolutionary insights. As a result, we successfully accomplish three manipulations: (i) ring contraction of neoantimycin (from tetra-lactone to tri-lactone), (ii) ring expansion of JBIR-06 (from tri-lactone to tetra-lactone), and (iii) alkyl chain diversification of JBIR-06 by the incorporation of various alkylmalonyl-CoA extender units, to generate a set of unnatural derivatives in practical yields. This study presents a useful strategy for engineering NRPS-PKS module enzymes, based on nature’s diversification of the domain and module organizations.
Color-stable highly luminescent sky-blue perovskite light-emitting diodes
Authors: Xing Jun , Zhao Yongbiao , Askerka Mikhail , Quan Li Na , Gong Xiwen , Zhao Weijie , Zhao Jiaxin , Tan Hairen , Long Guankui , Gao Liang , Yang Zhenyu , Voznyy Oleksandr , Tang Jiang , Lu Zheng-Hong , Xiong Qihua , Sargent Edward H.
Published: August 2018

Perovskite light-emitting diodes (PeLEDs) have shown excellent performance in the green and near-infrared spectral regions, with high color purity, efficiency, and brightness. In order to shift the emission wavelength to the blue, compositional engineering (anion mixing) and quantum-confinement engineering (reduced-dimensionality) have been employed. Unfortunately, LED emission profiles shift with increasing driving voltages due to either phase separation or the coexistence of multiple crystal domains. Here we report color-stable sky-blue PeLEDs achieved by enhancing the phase monodispersity of quasi-2D perovskite thin films. We selected cation combinations that modulate the crystallization and layer thickness distribution of the domains. The perovskite films show a record photoluminescence quantum yield of 88% at 477 nm. The corresponding PeLEDs exhibit stable sky-blue emission under high operation voltages. A maximum luminance of 2480 cd m−2 at 490 nm is achieved, fully one order of magnitude higher than the previous record for quasi-2D blue PeLEDs.
Back to full interseismic plate locking decades after the giant 1960 Chile earthquake
Authors: Melnick Daniel , Li Shaoyang , Moreno Marcos , Cisternas Marco , Jara-Muñoz Julius , Wesson Robert , Nelson Alan , Báez Juan Carlos , Deng Zhiguo
Published: August 2018

Great megathrust earthquakes arise from the sudden release of energy accumulated during centuries of interseismic plate convergence. The moment deficit (energy available for future earthquakes) is commonly inferred by integrating the rate of interseismic plate locking over the time since the previous great earthquake. But accurate integration requires knowledge of how interseismic plate locking changes decades after earthquakes, measurements not available for most great earthquakes. Here we reconstruct the post-earthquake history of plate locking at Guafo Island, above the seismogenic zone of the giant 1960 (Mw = 9.5) Chile earthquake, through forward modeling of land-level changes inferred from aerial imagery (since 1974) and measured by GPS (since 1994). We find that interseismic locking increased to ~70% in the decade following the 1960 earthquake and then gradually to 100% by 2005. Our findings illustrate the transient evolution of plate locking in Chile, and suggest a similarly complex evolution elsewhere, with implications for the time- and magnitude-dependent probability of future events.
Restricted cell cycle is essential for clonal evolution and therapeutic resistance of pre-leukemic stem cells
Authors: Tremblay Cedric S. , Saw Jesslyn , Chiu Sung Kai , Wong Nicholas C. , Tsyganov Kirill , Ghotb Sarah , Graham Alison N. , Yan Feng , Guirguis Andrew A. , Sonderegger Stefan E. , Lee Nicole , Kalitsis Paul , Reynolds John , Ting Stephen B. , Powell David R. , Jane Stephen M. , Curtis David J.
Published: August 2018

Pre-leukemic stem cells (pre-LSCs) give rise to leukemic stem cells through acquisition of additional gene mutations and are an important source of relapse following chemotherapy. We postulated that cell-cycle kinetics of pre-LSCs may be an important determinant of clonal evolution and therapeutic resistance. Using a doxycycline-inducible H2B-GFP transgene in a mouse model of T-cell acute lymphoblastic leukemia to study cell cycle in vivo, we show that self-renewal, clonal evolution and therapeutic resistance are limited to a rare population of pre-LSCs with restricted cell cycle. We show that proliferative pre-LSCs are unable to return to a cell cycle-restricted state. Cell cycle-restricted pre-LSCs have activation of p53 and its downstream cell-cycle inhibitor p21. Furthermore, absence of p21 leads to proliferation of pre-LSCs, with clonal extinction through loss of asymmetric cell division and terminal differentiation. Thus, inducing proliferation of pre-LSCs represents a promising strategy to increase cure rates for acute leukemia.
Publisher Correction: Electrically driven three-dimensional solitary waves as director bullets in nematic liquid crystals
Authors: Li Bing-Xiang , Borshch Volodymyr , Xiao Rui-Lin , Paladugu Sathyanarayana , Turiv Taras , Shiyanovskii Sergij V. , Lavrentovich Oleg D.
Published: August 2018

The original version of this article contained an error in the description of Supplementary Movie 7, which incorrectly read ‘Collision resulting in annihilation of two solitons. U  = 45.1 V, f  = 600 Hz, T = 50 °C, d = 8.0 μm. The original movie is taken at the frame rate of 91 fps. The playback speed is 7 fps.’ The correct version reads ‘Death of a soliton at a dust particle. U = 65.6 V, f = 800 Hz, T = 50 °C, d = 7.7 µm. The original movie is taken at the frame rate of 92 fps. The playback speed is 7 fps.’ The HTML has been updated to include a corrected version of the ‘Description of Additional Supplementary Files’ file.
Publisher Correction: Pairwise library screen systematically interrogates Staphylococcus aureus Cas9 specificity in human cells
Authors: Tycko Josh , Barrera Luis A. , Huston Nicholas C. , Friedland Ari E. , Wu Xuebing , Gootenberg Jonathan S. , Abudayyeh Omar O. , Myer Vic E. , Wilson Christopher J. , Hsu Patrick D.
Published: August 2018

The original HTML version of this Article incorrectly listed an affiliation of Josh Tycko as ‘Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA’, instead of the correct ‘Present address: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA’. It also incorrectly listed an affiliation of this author as ‘Present address: Arrakis Therapeutics, 35 Gatehouse Dr., Waltham, MA, 02451, USA’.The original HTML version incorrectly listed an affiliation of Luis A. Barrera as ‘Present address: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06511, USA’, instead of the correct ‘Present address: Arrakis Therapeutics, 35 Gatehouse Dr., Waltham, MA 02451, USA’.Finally, the original HTML version incorrectly omitted an affiliation of Nicholas C. Huston: ‘Present address: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA’.This has been corrected in the HTML version of the Article. The PDF version was correct from the time of publication.
Publisher Correction: Differences in age-specific mortality between wild-caught and captive-born Asian elephants
Authors: Lahdenperä Mirkka , Mar Khyne U. , Courtiol Alexandre , Lummaa Virpi
Published: August 2018

The original version of this Article incorrectly cited as Ref. 45 the paper ‘Lynch, E. C., Lahdenperä, M., Mar, K. U. & Lummaa, V. The evolutionary significance of maternal kinship in a long-lived mammal. Philos. Trans. R. Soc. Lond. B (2018, in press)’ in the eighth sentence of the last paragraph of the Introduction, and the last sentence of the first paragraph of the ‘Study population’ section of the Methods. As this paper does not exist, this reference has been removed and all following citations have been renumbered as appropriate. This has been corrected in both the PDF and HTML versions of the Article.
Multidomain architecture of estrogen receptor reveals interfacial cross-talk between its DNA-binding and ligand-binding domains
Authors: Huang Wei , Peng Yi , Kiselar Janna , Zhao Xuan , Albaqami Aljawharah , Mendez Daniel , Chen Yinghua , Chakravarthy Srinivas , Gupta Sayan , Ralston Corie , Kao Hung-Ying , Chance Mark R. , Yang Sichun
Published: August 2018

Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in several other NRs, but for hERα, the detailed structural architecture of the complex is unknown. By utilizing integrated complementary techniques of small-angle X-ray scattering, hydroxyl radical protein footprinting and computational modeling, here we report an asymmetric L-shaped “boot” structure of the multidomain hERα and identify the specific sites on each domain at the domain interface involved in DBD–LBD interactions. We demonstrate the functional role of the proposed DBD–LBD domain interface through site-specific mutagenesis altering the hERα interfacial structure and allosteric signaling. The L-shaped structure of hERα is a distinctive DBD–LBD organization of NR complexes and more importantly, reveals a signaling mechanism mediated by inter-domain crosstalk that regulates this receptor’s allosteric function.
Author Correction: Long range electronic phase separation in CaFe3O5
Authors: Hong Ka. H. , Arevalo-Lopez Angel M. , Cumby James , Ritter Clemens , Attfield J. Paul
Published: August 2018

The original version of this Article contained an error in the third sentence of the legend of Fig. 2, which incorrectly read ‘The phase fractions of the charge ordered (CO) phase, obtained from synchrotron (X) and neutron (N) diffraction data are shown in the right-hand panel.’ The correct version states ‘charge averaged (CA)’ in place of ‘charge ordered (CO)’. This has been corrected in both the PDF and HTML versions of the Article.
Clampdown of inflammation in aging and anticancer therapies by limiting upregulation and activation of GPCR, CXCR4
Authors: Nair Raji R. , Madiwale Shreyas V. , Saini Deepak Kumar
Published: August 2018

One of the major pathological outcomes of DNA damage during aging or anticancer therapy is enhanced inflammation. However, the underlying signaling mechanism that drives this is not well understood. Here, we show that in response to DNA damage, ubiquitously expressed GPCR, CXCR4 is upregulated through the ATM kinase-HIF1α dependent DNA damage response (DDR) signaling, and enhances inflammatory response when activated by its ligand, chemokine CXCL12. A pharmacologically active compound screen revealed that this increased inflammation is dependent on reduction in cAMP levels achieved through activation of Gαi through CXCR4 receptor and PDE4A. Through in vivo analysis in mice where DNA damage was induced by irradiation, we validated that CXCR4 is induced systemically after DNA damage and inhibition of its activity or its induction blocked inflammation as well as tissue injury. We thus report a unique DNA damage-linked inflammatory cascade, which is mediated by expression level changes in a GPCR and can be targeted to counteract inflammation during anticancer therapies as well as aging.
The stability of educational achievement across school years is largely explained by genetic factors
Authors: Rimfeld Kaili , Malanchini Margherita , Krapohl Eva , Hannigan Laurie J. , Dale Philip S. , Plomin Robert
Published: August 2018

Little is known about the etiology of developmental change and continuity in educational achievement. Here, we study achievement from primary school to the end of compulsory education for 6000 twin pairs in the UK-representative Twins Early Development Study sample. Results showed that educational achievement is highly heritable across school years and across subjects studied at school (twin heritability ~60%; SNP heritability ~30%); achievement is highly stable (phenotypic correlations ~0.70 from ages 7 to 16). Twin analyses, applying simplex and common pathway models, showed that genetic factors accounted for most of this stability (70%), even after controlling for intelligence (60%). Shared environmental factors also contributed to the stability, while change was mostly accounted for by individual-specific environmental factors. Polygenic scores, derived from a genome-wide association analysis of adult years of education, also showed stable effects on school achievement. We conclude that the remarkable stability of achievement is largely driven genetically even after accounting for intelligence.
A deconvolutional Bayesian mixing model approach for river basin sediment source apportionment
Authors: Blake William H. , Boeckx Pascal , Stock Brian C. , Smith Hugh G. , Bodé Samuel , Upadhayay Hari R. , Gaspar Leticia , Goddard Rupert , Lennard Amy T. , Lizaga Ivan , Lobb David A. , Owens Philip N. , Petticrew Ellen L. , Kuzyk Zou Zou A. , Gari Bayu D. , Munishi Linus , Mtei Kelvin , Nebiyu Amsalu , Mabit Lionel , Navas Ana , Semmens Brice X.
Published: August 2018

Increasing complexity in human-environment interactions at multiple watershed scales presents major challenges to sediment source apportionment data acquisition and analysis. Herein, we present a step-change in the application of Bayesian mixing models: Deconvolutional-MixSIAR (D-MIXSIAR) to underpin sustainable management of soil and sediment. This new mixing model approach allows users to directly account for the ‘structural hierarchy’ of a river basin in terms of sub-watershed distribution. It works by deconvoluting apportionment data derived for multiple nodes along the stream-river network where sources are stratified by sub-watershed. Source and mixture samples were collected from two watersheds that represented (i) a longitudinal mixed agricultural watershed in the south west of England which had a distinct upper and lower zone related to topography and (ii) a distributed mixed agricultural and forested watershed in the mid-hills of Nepal with two distinct sub-watersheds. In the former, geochemical fingerprints were based upon weathering profiles and anthropogenic soil amendments. In the latter compound-specific stable isotope markers based on soil vegetation cover were applied. Mixing model posterior distributions of proportional sediment source contributions differed when sources were pooled across the watersheds (pooled-MixSIAR) compared to those where source terms were stratified by sub-watershed and the outputs deconvoluted (D-MixSIAR). In the first example, the stratified source data and the deconvolutional approach provided greater distinction between pasture and cultivated topsoil source signatures resulting in a different posterior distribution to non-deconvolutional model (conventional approaches over-estimated the contribution of cultivated land to downstream sediment by 2 to 5 times). In the second example, the deconvolutional model elucidated a large input of sediment delivered from a small tributary resulting in differences in the reported contribution of a discrete mixed forest source. Overall D-MixSIAR model posterior distributions had lower (by ca 25–50%) uncertainty and quicker model run times. In both cases, the structured, deconvoluted output cohered more closely with field observations and local knowledge underpinning the need for closer attention to hierarchy in source and mixture terms in river basin source apportionment. Soil erosion and siltation challenge the energy-food-water-environment nexus. This new tool for source apportionment offers wider application across complex environmental systems affected by natural and human-induced change and the lessons learned are relevant to source apportionment applications in other disciplines.
Subcontinental heat wave triggers terrestrial and marine, multi-taxa responses
Authors: Ruthrof Katinka X. , Breshears David D. , Fontaine Joseph B. , Froend Ray H. , Matusick George , Kala Jatin , Miller Ben P. , Mitchell Patrick J. , Wilson Shaun K. , van Keulen Mike , Enright Neal J. , Law Darin J. , Wernberg Thomas , Hardy Giles E. St. J.
Published: August 2018

Heat waves have profoundly impacted biota globally over the past decade, especially where their ecological impacts are rapid, diverse, and broad-scale. Although usually considered in isolation for either terrestrial or marine ecosystems, heat waves can straddle ecosystems of both types at subcontinental scales, potentially impacting larger areas and taxonomic breadth than previously envisioned. Using climatic and multi-species demographic data collected in Western Australia, we show that a massive heat wave event straddling terrestrial and maritime ecosystems triggered abrupt, synchronous, and multi-trophic ecological disruptions, including mortality, demographic shifts and altered species distributions. Tree die-off and coral bleaching occurred concurrently in response to the heat wave, and were accompanied by terrestrial plant mortality, seagrass and kelp loss, population crash of an endangered terrestrial bird species, plummeting breeding success in marine penguins, and outbreaks of terrestrial wood-boring insects. These multiple taxa and trophic-level impacts spanned >300,000 km2—comparable to the size of California—encompassing one terrestrial Global Biodiversity Hotspot and two marine World Heritage Areas. The subcontinental multi-taxa context documented here reveals that terrestrial and marine biotic responses to heat waves do not occur in isolation, implying that the extent of ecological vulnerability to projected increases in heat waves is underestimated.
Effects of Synchronous Electrode Pulses on Neural Recruitment During Multichannel Microstimulation
Authors: Hokanson James A. , Gaunt Robert A. , Weber Douglas J.
Published: August 2018

The recent proliferation of high-density microelectrode arrays has inspired several new applications of electrical microstimulation, including restoration of sensory functions in the visual, auditory, and somatosensory systems. In each case, the goal is to achieve precisely targeted activation of neurons, while patterning the location and timing of stimulation across the array to mimic naturalistic patterns of neural activity. However, when two or more electrodes deliver stimulation pulses at the same time, the electric fields created by each electrode interact. The effects of field interactions on neuronal recruitment depend on several factors, which have been studied extensively at the macro-scale but have been overlooked in the case of high density arrays. Here, we report that field interactions can significantly affect neural recruitment, even with low amplitude stimulation. We created a computational model of peripheral nerve axons to estimate stimulation parameters sufficient to generate neural recruitment during synchronous and asynchronous stimulation on two microelectrodes located within the peripheral nerve. Across a range of stimulus amplitudes, the model predicted that synchronous stimulation on adjacent electrodes (400 µm separation), would recruit 2–3 times more neurons than during asynchronous stimulation. Our results suggest that field interactions should not be ignored when designing multichannel microstimulation paradigms, even at threshold-level stimulus amplitudes.
Detection of antibiotics synthetized in microfluidic picolitre-droplets by various actinobacteria
Authors: Mahler Lisa , Wink Konstantin , Beulig R. Julia , Scherlach Kirstin , Tovar Miguel , Zang Emerson , Martin Karin , Hertweck Christian , Belder Detlev , Roth Martin
Published: August 2018

The natural bacterial diversity is regarded as a treasure trove for natural products. However, accessing complex cell mixtures derived from environmental samples in standardized high-throughput screenings is challenging. Here, we present a droplet-based microfluidic platform for ultrahigh-throughput screenings able to directly harness the diversity of entire microbial communities. This platform combines extensive cultivation protocols in aqueous droplets starting from single cells or spores with modular detection methods for produced antimicrobial compounds. After long-term incubation for bacterial cell propagation and metabolite production, we implemented a setup for mass spectrometric analysis relying on direct electrospray ionization and injection of single droplets. Even in the presence of dense biomass we show robust detection of streptomycin on the single droplet level. Furthermore, we developed an ultrahigh-throughput screening based on a functional whole-cell assay by picoinjecting reporter cells into droplets. Depending on the survival of reporter cells, droplets were selected for the isolation of producing bacteria, which we demonstrated for a microbial soil community. The established ultrahigh-throughput screening for producers of antibiotics in miniaturized bioreactors in which diverse cell mixtures can be screened on the single cell level is a promising approach to find novel antimicrobial scaffolds.