bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent Hydrological Consequences of Hurricane Maria in Puerto Rico
Authors: Miller P. W. , Kumar A. , Mote T. L. , Moraes F. D. S. , Mishra D. R.
Published: January 2019

In September 2017, Hurricane Maria severely defoliated Puerto Rico's landscape, coinciding with a series of persistent hydrological consequences involving the atmospheric, terrestrial, and marine components of the water cycle. During the defoliated period, the atmosphere's thermodynamic structure more strongly explained daily cloud activity (R2PRE = 0.02; R2POST = 0.40) and precipitation (R2PRE = 0.19; R2POST = 0.33) than before landfall, indicating that post‐Maria land‐atmosphere interactions were comparatively muted, with similar precipitation patterns also found following Hurricanes Hugo (1989) and Georges (1998). Meanwhile, modeled post‐Maria runoff exceeded statistical expectations given the magnitude of contemporaneous precipitation. Enhanced runoff also coincided with greater sediment loads in nearshore waters, increasing sediment content greater than twofold. This study offers a holistic narrative of hydrospheric disturbance and recovery, whereby the instantaneous, large‐scale removal of vegetation is accompanied by hydrologic changes “upstream” in the atmosphere and “downstream” in rivers and estuaries.
Modulations of Saturn's UV Auroral Oval Location by Planetary Period Oscillations
Authors: Bader A. , Badman S.V. , Kinrade J. , Cowley S.W.H. , Provan G. , Pryor W.
Published: January 2019

It is well known that Saturn's magnetospheric dynamics are greatly influenced by the so‐called planetary period oscillations (PPOs). Based on Cassini Ultraviolet Imaging Spectrograph (UVIS) imagery, it has been shown previously that the UV auroral intensity is clearly modulated in phase with rotating field‐aligned current (FAC) systems associated with the PPOs. Here we expand upon this investigation by using the same data set to examine the PPO‐induced spatial modulation of the main auroral oval. We present a robust algorithm used for determining the location of the main emission in Cassini‐UVIS images. The location markers obtained are then used to calculate the statistical location of the auroral oval and its periodic displacement due to the PPO FACs and the related ionospheric flows. We find that the largest equatorward displacement of the main arc lags behind the PPO‐dependent statistical brightening of the UV aurora by roughly 45–90° in both hemispheres and is not colocated with it as the present model based on magnetometer observations suggests. We furthermore find the center of the auroral oval by fitting circles to the main emission and analyze its elliptic motion as the entire oval is displaced in phase with the PPO phases. It is demonstrated that the periodic displacements of both the auroral oval arc and its center are larger when the two PPO systems rotate in relative antiphase than when they are in phase, clearly indicating that interhemispheric PPO FAC closure modulates not only the intensity but also the location of the main UV auroral emission.
Global‐Scale ULF Waves Associated With SSC Accelerate Magnetospheric Ultrarelativistic Electrons
Authors: Hao Y. X. , Zong Q.‐G. , Zhou X.‐Z. , Rankin R. , Chen X. R. , Liu Y. , Fu S. Y. , Baker D. N. , Spence H. E. , Blake J. B. , Reeves G. D. , Claudepierre S. G.
Published: January 2019

We study electron behavior in the outer radiation belts during the 16 July 2017 storm sudden commencement (SSC), in which prompt intensification of ultrarelativistic electron fluxes was observed at around L = 4.8 by Van Allen Probe B immediately after an interplanetary shock. The electron fluxes in multiple energy channels show clear oscillations in the Pc5 frequency range, although the oscillation characteristics are quite different in different energy channels. At energies above ∼1 MeV, the oscillation periods were very close to the electron drift period, which resembles an energy spectrogram evolution expected for an energetic particle injection event and its drift echoes. At lower energies, however, the oscillation periods hardly depended on the energy: They were very close to the ultralow frequency (ULF) wave period derived from electric field measurements (about 250 s according to wavelet analysis). These complex signatures are consistent with the picture of drift resonance between electrons and short‐lived ULF waves with low azimuthal wave numbers. Good agreement between the observations and numerical simulations confirms that shock‐induced global‐scale ULF waves can efficiently accelerate outer belt ultrarelativistic electrons up to 3.4 MeV over a time scale shorter than 1 hr.
The Hall Electric Field in Earth's Magnetotail Thin Current Sheet
Authors: Lu San , Artemyev A. V. , Angelopoulos V. , Lin Y. , Zhang X.‐J. , Liu J. , Avanov L. A. , Giles B. L. , Russell C. T. , Strangeway R. J.
Published: January 2019

One of the most important properties of Earth's magnetotail thin current sheet (TCS) is that its current is predominantly contributed by magnetized electrons. The Hall electric field, normal to the TCS and generated by charge separation, is critical to the generation of this electron current as well as a dawn‐dusk asymmetry of the magnetotail, such as duskside preference of magnetic reconnection and related structures and phenomena. However, systematic investigation of the Hall electric field has so far been lacking. Utilizing observations of TCS by Magnetospheric Multiscale and Time History of Events and Macroscale Interactions during Substorm spacecraft, we study the properties of this field. Our results, from various, complementary methods, show that the Hall electric field Ez (in the geocentric solar magnetospheric, coordinate system) or En (normal to the TCS plane) can be clearly observed to point toward the center of the current sheet. The typical magnitude of this electric field is several tenths of 1 mV/m. Statistics of Magnetospheric Multiscale magnetotail TCS crossings show that the Hall electric field is stronger on the duskside, indicating a stronger Hall effect there, which confirms predictions from global‐scale hybrid and particle‐in‐cell simulations.
The Permeability of Volcanic Mixtures—Implications for Pyroclastic Currents
Authors: Breard Eric C. P. , Jones Jim R. , Fullard Luke , Lube Gert , Davies Clive , Dufek Josef
Published: January 2019

Geophysical fluid‐granular flows, such as pyroclastic currents and debris flows, owe much of their runout and hazard behavior to the occurrence and time‐variant decay of a flow‐internal fluid pore pressure. However, modeling the effects of fluid pore pressure to forecast hazards is challenging because a unified method in Earth Sciences to quantitatively determine the permeability of these natural mixtures is currently missing. Here we combine experiments on fluidization and defluidization of pyroclastic materials, eolian sediments, and glass beads mixtures with numerical multiphase simulations to compare previous attempts to compute the permeability of complex natural particle‐fluid mixtures. In analogy to particle‐engineering studies on simple gas‐particle mixtures, we demonstrate that the effective length‐scale in the characterization of the fluid‐particle interaction of complex natural mixtures is the product of the Sauter mean diameter and the particle sphericity. Its use in the Kozeny‐Carman equation allows accurate prediction of mixture permeability, and we suggest the routine calculation of the Sauter mean from grain size distributions of the deposits of geophysical mass flows in Earth Sciences. We also show, through defluidization experiments, that the duration of gas retention in natural mixtures is well described when using the Sauter mean as the effective particle size. Further, we show through multiphase simulations that initial bed expansion extends the pore pressure diffusion timescale up to nine times. These results can be applied to small‐to‐large volume dense pyroclastic currents where the ranges of Sauter mean diameter predict gas retention for long duration and to debris flows and snow avalanches.
Constitutive Law for Earthquake Production Based on Rate‐and‐State Friction: Theory and Application of Interacting Sources
Authors: Heimisson Elías R.
Published: January 2019

The constitutive relationship of Dieterich (1994, https://doi.org/10.1029/93JB02581) for earthquake production has been applied widely to earthquake triggering. The Dieterich theory achieves mathematical simplicity and thus lends itself to practical applications through a number of simplifying assumptions. Perhaps the most suspect and criticized assumption is that seismic sources do not interact. Here I provide an extension of the constitutive framework, using the modified formulation of Heimisson and Segall (2018, https://doi.org/10.1029/2018JB015656) which accounts for source interactions. Moreover, I explore ways to account for earthquake magnitudes and highlight potential directions for future research. I identify conditions under which the constitutive relationship with interactions reduces to the noninteracting Dieterich theory, revealing that an interacting population may be modeled as an equivalent noninteracting population. This result may partly explain the success of the Dieterich theory in spite of assuming no interactions. These special conditions reveal that if the magnitude distribution (e.g., the b value) is altered by a stress perturbation, then the Dieterich model may either underpredict or overpredict the seismicity rate. Furthermore, the interaction model grants insight into the physical interpretation of the background seismicity rate, which is frequently considered to be a declustered rate. However, the results suggest that interactions do not change the total cumulative number of events over a long time span (t ≫ ta). Finally, I apply the interaction theory to fault slip models, aftershock diffusion, and secondary triggering as illustrative examples.
Assimilating INSAT‐3D Thermal Infrared Window Imager Observation With the Particle Filter: A Case Study for Vardah Cyclone
Authors: Kumar Prashant , Shukla Munn V.
Published: January 2019

A big challenge in the satellite data assimilation is the effective use of InfraRed (IR) window channel radiances in the high‐resolution weather model. A hybrid data‐assimilation method is used in this study for very severe cyclonic storm “Vardah,” in which three‐dimensional variational method is used to assimilate control observations, and particle filter method is used to assimilate Indian geostationary satellite INSAT‐3D data. In the context of imperfect weather model, various particles (or ensembles) are prepared with different combinations of model physics. To implement particle filter, INSAT‐3D thermal IR window channel 1 (TIR‐1; center wavelength 11 μm) measured brightness temperature (BT) and cloud mask product are used to assign appropriate weights to different particles to reduce model uncertainties. This step is followed by resampling step in which new particles are generated from high weight particles using stochastic kinetic‐energy backscatter scheme method and dynamical variables are perturbed into the model physics. Results suggest that simulated TIR‐1 BT analysis and forecasts from WPF (with INSAT‐3D data using particle filter experiments) are closer to INSAT‐3D measured TIR‐1 BT in comparison to WCNT (without INSAT‐3D data using particle filter) experiments. Furthermore, approximately 10% to 50% improvements are found in mean track error forecasts in WPF experiments. An improvement of ~10% is noticed in cyclone center position in analysis. Prediction of storm intensity is also improved after assimilation. Results also suggest that vertical structure of WPF simulated humidity, temperature, wind speed, and surface pressure is improved over WCNT runs.
Progradation Rates Measured at Modern River Outlets: A First‐Order Constraint on the Pace of Deltaic Deposition
Authors: Aadland Tore , Helland‐Hansen William
Published: January 2019

We present a compilation of modern shoreline progradation rates measured close to river outlets entering deltaic coastlines, and we discuss how these observations relate to the overall evolution of both modern and ancient deltaic coastlines. We analyzed Landsat‐derived satellite images to identify plan view changes in the subaerial morphology of 331 modern deltaic coastlines. Our rate compilation (km2/year) had a lognormal distribution with parameters μ = −1.85 and σ2 = 1.01. We found that the rate data could be predicted to within an order of magnitude by an empirically derived power law using only fluvial water discharge and suspended sediment load as input parameters (
). We justified this river‐centric model of our progradation rates by assuming that delta progradation rates measured close to river outlets were more reflective of fluvial processes than of basinal processes, and preliminary tests supported this assumption. Our rate compilation and empirical model could provide useful constraints to guide stratigraphic analysis of ancient source‐to‐sink systems and to build analog and numerical models.
Simulated Greenland Surface Mass Balance in the GISS ModelE2 GCM: Role of the Ice Sheet Surface
Authors: Alexander P. M. , LeGrande A. N. , Fischer E. , Tedesco M. , Fettweis X. , Kelley M. , Nowicki S. M. J. , Schmidt G. A.
Published: January 2019

The rate of growth or retreat of the Greenland and Antarctic ice sheets remains a highly uncertain component of future sea level change. Here we examine the simulation of Greenland ice sheet surface mass balance (GrIS SMB) in a development branch of the ModelE2 version of the NASA Goddard Institute for Space Studies (GISS) general circulation model (GCM). GCMs are often limited in their ability to represent SMB compared with polar region regional climate models. We compare ModelE2‐simulated GrIS SMB for present‐day (1996–2005) simulations with fixed ocean conditions, at a spatial resolution of 2° latitude by 2.5° longitude (~200 km), with SMB simulated by the Modèle Atmosphérique Régionale (MAR) regional climate model (1996–2005 at a 25‐km resolution). ModelE2 SMB agrees well with MAR SMB on the whole, but there are distinct spatial patterns of differences and large differences in some SMB components. The impacts of changes to the ModelE2 surface are tested, including a subgrid‐scale representation of SMB with surface elevation classes. This has a minimal effect on ice sheet‐wide SMB but corrects local biases. Replacing fixed surface albedo with satellite‐derived values and an age‐dependent scheme has a larger impact, increasing simulated melt by 60%–100%. We also find that lower surface albedo can enhance the effects of elevation classes. Reducing ModelE2 surface roughness length to values closer to MAR reduces sublimation by ~50%. Further work is required to account for meltwater refreezing in ModelE2 and to understand how differences in atmospheric processes and model resolution influence simulated SMB.
Improved Spatiotemporal Representativeness and Bias Reduction of Satellite‐Based Evapotranspiration Retrievals via Use of In Situ Meteorology and Constrained Canopy Surface Resistance
Authors: Sullivan Ryan C. , Cook David R. , Ghate Virendra P. , Kotamarthi V. Rao , Feng Yan
Published: January 2019

Evapotranspiration (ET) is a key component of the atmospheric and terrestrial water and energy budgets. Satellite‐based vegetation index approaches have used remotely sensed vegetation and reanalysis meteorological properties with surface energy balance models to estimate global ET (MOD16 ET). We reconstructed satellite retrievals using in situ meteorology (Argonne‐ET) and evaluated them using a dense network of surface turbulent heat flux measurements. Argonne‐ET resolves spatial heterogeneity of ET across the U.S. Southern Great Plains that is not well characterized by MOD16; MOD16 ET exhibits spatial autocorrelation (Moran's I significantly >0 in May–Aug.), whereas in situ and Argonne‐ET exhibit characteristics of a random spatial process (Moran's I not significantly different from 0). The skill in resolving ET temporal variability is not significantly different between MOD16 and Argonne‐ET (correlation coefficient = 0.75 and 0.72, respectively). However, the root‐mean‐square errors were significantly lower for Argonne‐ET (36 W/m2) than MOD16 (43 W/m2), and MOD16 exhibits substantial bias in annual ET relative to in situ measurements (−38%). This is attributed to overestimation in the dry canopy surface resistance (rs) parameterization. Using rs constrained to the range of typical measured values, Argonne‐ET substantially reduces the bias in the annual ET (+1%). The improved ET estimates are critical for regional water budget analyses. The methodology presented herein also demonstrates the ability to retrieve high temporally resolved (30 min; cf. 8‐day MOD16) ET that can be used for development of processed‐based diagnostics of model biases and to elucidate avenues to improve ET model parameterizations.
One‐ to 10‐Day Forecasts of Ionospheric Total Electron Content Using a Statistical Model
Authors: Lean J. L.
Published: January 2019

A new, rapid, nonassimilative technique is demonstrated for forecasting the ionosphere's vertical total electron content (TEC) on time scales longer than 1 day. The approach uses a statistical model constructed by regressing solar extreme ultraviolet irradiance and seasonal, diurnal, and geomagnetic predictors at multiple lags against the 2‐hourly International Global Navigation Satellite Systems Service observations, with a formulation that accounts for solar modulation of the seasonal oscillations and solar and seasonal modulation of the diurnal oscillations. Solar irradiance inputs to the statistical model are forecast at successive 2‐hr intervals from 1999 to 2015 using an autoregressive model of irradiance variations during the prior 100 days. As the forecast time increment increases from 1 to 10 days, the average over the globe of the mean absolute error of TEC observations and the forecasts increases from 2.5 to 3.2 TECU (total electron content unit, 1 TECU = 1016 el/m2); the root‐mean‐square error increases from 3.7 to 4.8 TECU. Averaged over the equatorial ionization anomaly region (30°S–30°N) the mean absolute error of the forecasts increases from 3.2 to 4.3 TECU and the root‐mean‐square error increases from 4.6 to 6.4 TECU. The skill of the TEC forecasts at time increments of 3, 5, and 8 days ahead exceeds persistence by 9%, 13%, and 15% and climatology by 9%, 12%, and 10%, respectively. Forecast skill is higher in April than in July. Long‐range, multiyear forecasts from 2018 to 2030 are demonstrated based on current expectations that solar activity in cycle 25 will be comparable to that in cycle 24.
Using phenome-wide association to investigate the function of a schizophrenia risk locus at SLC39A8
Authors: McCoy Thomas H. , Pellegrini Amelia M. , Perlis Roy H.
Published: January 2019

While nearly all common genomic variants associated with schizophrenia have no known function, one corresponds to a missense variant associated with change in efficiency of a metal ion transporter, ZIP8, coded by SLC39A8. This variant has been linked to a range of phenotypes and is believed to be under recent selection pressure, but its impact on health is poorly understood. We sought to understand phenotypic implications of this variant in a large genomic biobank using an unbiased phenome-wide approach. Specifically, we generated 50 topics based on diagnostic codes using latent Dirichlet allocation, and examined them for association with the risk variant. Then, any significant topics were further characterized by examining association with individual diagnostic codes contributing to the topic. Among 50 topics, 1 was associated at an experiment-wide significance threshold (beta = 0.003, uncorrected p = 0.00049), comprising predominantly brain-related codes, including intracranial hemorrhage, cerebrovascular disease, and delirium/dementia. These results suggest that a functional variant previously associated with schizophrenia risk also increases liability to cerebrovascular disease. They further illustrate the utility of a topic-based approach to phenome-wide association.
Towards maximized volumetric capacity via pore-coordinated design for large-volume-change lithium-ion battery anodes
Authors: Ma Jiyoung , Sung Jaekyung , Hong Jaehyung , Chae Sujong , Kim Namhyung , Choi Seong-Hyeon , Nam Gyutae , Son Yoonkook , Kim Sung Youb , Ko Minseong , Cho Jaephil
Published: January 2019

To achieve the urgent requirement for high volumetric energy density in lithium-ion batteries, alloy-based anodes have been spotlighted as next-generation alternatives. Nonetheless, for the veritable accomplishment with regards to high-energy demand, alloy-based anodes must be evaluated considering several crucial factors that determine volumetric capacity. In particular, the electrode swelling upon cycling must be contemplated if these anodes are to replace conventional graphite anodes in terms of volumetric capacity. Herein, we propose macropore-coordinated graphite-silicon composite by incorporating simulation and mathematical calculation of numerical values from experimental data. This unique structure exhibits minimized electrode swelling comparable to conventional graphite under industrial electrode fabrication conditions. Consequently, this hybrid anode, even with high specific capacity (527 mAh g−1) and initial coulombic efficiency (93%) in half-cell, achieves higher volumetric capacity (493.9 mAh cm−3) and energy density (1825.7 Wh L−1) than conventional graphite (361.4 mAh cm−3 and 1376.3 Wh L−1) after 100 cycles in the full-cell configuration.
Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms
Authors: Jones Samuel E. , Lane Jacqueline M. , Wood Andrew R. , van Hees Vincent T. , Tyrrell Jessica , Beaumont Robin N. , Jeffries Aaron R. , Dashti Hassan S. , Hillsdon Melvyn , Ruth Katherine S. , Tuke Marcus A. , Yaghootkar Hanieh , Sharp Seth A. , Jie Yingjie , Thompson William D. , Harrison Jamie W. , Dawes Amy , Byrne Enda M. , Tiemeier Henning , Allebrandt Karla V. , Bowden Jack , Ray David W. , Freathy Rachel M. , Murray Anna , Mazzotti Diego R. , Gehrman Philip R. , Lawlor Debbie A. , Frayling Timothy M. , Rutter Martin K. , Hinds David A. , Saxena Richa , Weedon Michael N.
Published: January 2019

Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 individuals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of individuals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.
Indirect tail states formation by thermal-induced polar fluctuations in halide perovskites
Authors: Wu Bo , Yuan Haifeng , Xu Qiang , Steele Julian A. , Giovanni David , Puech Pascal , Fu Jianhui , Ng Yan Fong , Jamaludin Nur Fadilah , Solanki Ankur , Mhaisalkar Subodh , Mathews Nripan , Roeffaers Maarten B. J. , Grätzel Michael , Hofkens Johan , Sum Tze Chien
Published: January 2019

Halide perovskites possess enormous potential for various optoelectronic applications. Presently, a clear understanding of the interplay between the lattice and electronic effects is still elusive. Specifically, the weakly absorbing tail states and dual emission from perovskites are not satisfactorily described by existing theories based on the Urbach tail and reabsorption effect. Herein, through temperature-dependent and time-resolved spectroscopy on metal halide perovskite single crystals with organic or inorganic A-site cations, we confirm the existence of indirect tail states below the direct transition edge to arise from a dynamical Rashba splitting effect, caused by the PbBr6 octahedral thermal polar distortions at elevated temperatures. This dynamic effect is distinct from the static Rashba splitting effect, caused by non-spherical A-site cations or surface induced lattice distortions. Our findings shed fresh perspectives on the electronic-lattice relations paramount for the design and optimization of emergent perovskites, revealing broad implications for light harvesting/photo-detection and light emission/lasing applications.
Frustrated supercritical collapse in tunable charge arrays on graphene
Authors: Lu Jiong , Tsai Hsin-Zon , Tatan Alpin N. , Wickenburg Sebastian , Omrani Arash A. , Wong Dillon , Riss Alexander , Piatti Erik , Watanabe Kenji , Taniguchi Takashi , Zettl Alex , Pereira Vitor M. , Crommie Michael F.
Published: January 2019

The photon-like behavior of electrons in graphene causes unusual confinement properties that depend strongly on the geometry and strength of the surrounding potential. We report bottom-up synthesis of atomically-precise one-dimensional (1D) arrays of point charges on graphene that allow exploration of a new type of supercritical confinement of graphene carriers. The arrays were synthesized by arranging F4TCNQ molecules into a 1D lattice on back-gated graphene, allowing precise tuning of both the molecular charge and the array periodicity. While dilute arrays of ionized F4TCNQ molecules are seen to behave like isolated subcritical charges, dense arrays show emergent supercriticality. In contrast to compact supercritical clusters, these extended arrays display both supercritical and subcritical characteristics and belong to a new physical regime termed “frustrated supercritical collapse”. Here carriers in the far-field are attracted by a supercritical charge distribution, but their fall to the center is frustrated by subcritical potentials in the near-field, similar to trapping of light by a dense cluster of stars in general relativity.
Porous supraparticle assembly through self-lubricating evaporating colloidal ouzo drops
Authors: Tan Huanshu , Wooh Sanghyuk , Butt Hans-Jürgen , Zhang Xuehua , Lohse Detlef
Published: January 2019

The assembly of colloidal particles from evaporating suspension drops is seen as a versatile route for the fabrication of supraparticles for various applications. However, drop contact line pining leads to uncontrolled shapes of the emerging supraparticles, hindering this technique. Here we report how the pinning problem can be overcome by self-lubrication. The colloidal particles are dispersed in ternary drops (water, ethanol, and anise-oil). As the ethanol evaporates, oil microdroplets form (‘ouzo effect’). The oil microdroplets coalesce and form an oil ring at the contact line, levitating the evaporating colloidal drop (‘self-lubrication’). Then the water evaporates, leaving behind a porous supraparticle, which easily detaches from the surface. The dispersed oil microdroplets act as templates, leading to multi-scale, fractal-like structures inside the supraparticle. Employing this method, we could produce a large number of supraparticles with tunable shapes and high porosity on hydrophobic surfaces.
Integrative analysis with expanded DNA methylation data reveals common key regulators and pathways in cancers
Authors: Fan Shicai , Tang Jianxiong , Li Nan , Zhao Ying , Ai Rizi , Zhang Kai , Wang Mengchi , Du Wei , Wang Wei
Published: February 2019

The integration of genomic and DNA methylation data has been demonstrated as a powerful strategy in understanding cancer mechanisms and identifying therapeutic targets. The TCGA consortium has mapped DNA methylation in thousands of cancer samples using Illumina Infinium Human Methylation 450 K BeadChip (Illumina 450 K array) that only covers about 1.5% of CpGs in the human genome. Therefore, increasing the coverage of the DNA methylome would significantly leverage the usage of the TCGA data. Here, we present a new model called EAGLING that can expand the Illumina 450 K array data 18 times to cover about 30% of the CpGs in the human genome. We applied it to analyze 13 cancers in TCGA. By integrating the expanded methylation, gene expression, and somatic mutation data, we identified the genes showing differential patterns in each of the 13 cancers. Many of the triple-evidenced genes identified in majority of the cancers are biomarkers or potential biomarkers. Pan-cancer analysis also revealed the pathways in which the triple-evidenced genes are enriched, which include well known ones as well as new ones, such as axonal guidance signaling pathway and pathways related to inflammatory processing or inflammation response. Triple-evidenced genes, particularly TNXB, RRM2, CELSR3, SLC16A3, FANCI, MMP9, MMP11, SIK1, and TRIM59 showed superior predictive power in both tumor diagnosis and prognosis. These results have demonstrated that the integrative analysis using the expanded methylation data is powerful in identifying critical genes/pathways that may serve as new therapeutic targets.
Basic clinical features do not predict dopamine transporter binding in idiopathic REM behavior disorder
Authors: Chahine L. M. , Iranzo A. , Fernández-Arcos A. , Simuni T. , Seedorff N. , Caspell-Garcia C. , Amara A. W. , Comella C. , Högl B. , Hamilton J. , Marek K. , Mayer G. , Mollenhauer B. , Postuma R. , Tolosa E. , Trenkwalder C. , Videnovic A. , Oertel W. ,   the PPMI Sleep Working Group, Kumar B. , James L. , Nomikos G. , Cedarbaum J. , Yang M. , Brys M. , Irzhevesky V. , Schmidt K. , Jennings N. , Reith A. , Tattersall D. , Sanchez M. , Daegele N. , Min C. , Malkani R. , Peterschmitt J. , Sardi P. , Bozzi S. , Fischer T. , Evans R. , Kiyasova V. , Simen A. , Siderowf A.
Published: January 2019

REM sleep behavior disorder (RBD) is strongly associated with development of Parkinson’s Disease and other α-synuclein-related disorders. Dopamine transporter (DAT) binding deficit predicts conversion to α-synuclein-related disorders in individuals with RBD. In turn, identifying which individuals with RBD have the highest likelihood of having abnormal DAT binding would be useful. The objective of this analysis was to examine if there are basic clinical predictors of DAT deficit in RBD. Participants referred for inclusion in the RBD cohort of the Parkinson Progression Markers Initiative were included. Assessments at the screening visit including DAT SPECT imaging, physical examination, cognitive function screen, and questionnaire-based non-motor assessment. The group with DAT binding deficit (n = 49) was compared to those without (n = 26). There were no significant differences in demographic or clinical features between the two groups. When recruiting RBD cohorts enriched for high risk of neurodegenerative disorders, our data support the need for objective biomarker assessments.
Structure, function, and inhibition of drug reactivating human gut microbial β-glucuronidases
Authors: Biernat Kristen A. , Pellock Samuel J. , Bhatt Aadra P. , Bivins Marissa M. , Walton William G. , Tran Bich Ngoc T. , Wei Lianjie , Snider Michael C. , Cesmat Andrew P. , Tripathy Ashutosh , Erie Dorothy A. , Redinbo Matthew R.
Published: January 2019

Bacterial β-glucuronidase (GUS) enzymes cause drug toxicity by reversing Phase II glucuronidation in the gastrointestinal tract. While many human gut microbial GUS enzymes have been examined with model glucuronide substrates like p-nitrophenol-β-D-glucuronide (pNPG), the GUS orthologs that are most efficient at processing drug-glucuronides remain unclear. Here we present the crystal structures of GUS enzymes from human gut commensals Lactobacillus rhamnosus, Ruminococcus gnavus, and Faecalibacterium prausnitzii that possess an active site loop (Loop 1; L1) analogous to that found in E. coli GUS, which processes drug substrates. We also resolve the structure of the No Loop GUS from Bacteroides dorei. We then compare the pNPG and diclofenac glucuronide processing abilities of a panel of twelve structurally diverse GUS proteins, and find that the new L1 GUS enzymes presented here process small glucuronide substrates inefficiently compared to previously characterized L1 GUS enzymes like E. coli GUS. We further demonstrate that our GUS inhibitors, which are effective against some L1 enzymes, are not potent towards all. Our findings pinpoint active site structural features necessary for the processing of drug-glucuronide substrates and the inhibition of such processing.
Biochemical and Proteomic Characterization of Recombinant Human α/β Hydrolase Domain 6
Authors: Shields Christina Miyabe , Zvonok Nikolai , Zvonok Alexander , Makriyannis Alexandros
Published: January 2019

Human alpha/beta hydrolase domain 6 (hABHD6) is an enzyme that hydrolyzes 2-arachidonoylglycerol (2-AG), a potent agonist at both cannabinoid CB1 and CB2 receptors. In vivo modulation of ABHD6 expression has been shown to have potential therapeutic applications, making the enzyme a promising drug target. However, the lack of structural information on hABHD6 limits the discovery and design of selective inhibitors. We have performed E. coli expression, purification and activity profiling screening of different hABHD6 constructs and identified a truncated variant without N-terminal transmembrane (TM) domain, hΔ29-3-ABHD6, as the most promising protein for further characterization. The elimination of the TM domain did not affect 2-AG or fluorogenic arachidonoyl, 7-hydroxy-6-methoxy-4-methylcoumarin ester (AHMMCE) substrates hydrolysis, suggesting that the TM is not essential for enzyme catalytic activity. The hΔ29-3-ABHD6 variant was purified in a single step using Immobilized Metal Affinity Chromatography (IMAC), in-solution trypsin digested, and proteomically characterized by Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). The N-terminal peptide without methionine was identified indicating on a post-translational modification of the recombinant protein. The mechanism of inhibition of hABHD6 with AM6701 and WWL70 covalent probes was elucidated based on MS analysis of trypsin digested hABHD6 following the Ligand Assisted Protein Structure (LAPS) approach. We identified the carbamylated peptides containing catalytic serine (Ser148) suggesting a selective carbamylation of the enzyme by AM6701 or WWL70 and confirming an essential role of this residue in catalysis. The ability to produce substantial quantities of functional, pure hABHD6 will aid in the downstream structural characterization, and development of potent, selective inhibitors.
Large-scale experiments into the tsunamigenic potential of different iceberg calving mechanisms
Authors: Heller Valentin , Chen Fan , Brühl Markus , Gabl Roman , Chen Xuexue , Wolters Guido , Fuchs Helge
Published: January 2019

Mass balance analysis of ice sheets is a key component to understand the effects of global warming. A significant component of ice sheet and shelf mass balance is iceberg calving, which can generate large tsunamis endangering human beings and coastal infrastructure. Such iceberg-tsunamis have reached amplitudes of 50 m and destroyed harbours. Calving icebergs interact with the surrounding water through different mechanisms and we investigate five; A: capsizing, B: gravity-dominated fall, C: buoyancy-dominated fall, D: gravity-dominated overturning and E: buoyancy-dominated overturning. Gravity-dominated icebergs essentially fall into the water body whereas buoyancy-dominated icebergs rise to the water surface. We find with unique large-scale laboratory experiments that iceberg-tsunami heights from gravity-dominated mechanisms (B and D) are roughly an order of magnitude larger than from A, C and E. A theoretical model for released iceberg energy supports this finding and the measured wave periods upscaled to Greenlandic outlet glaciers agree with field observations. Whilst existing empirical equations for landslide-tsunamis establish estimates of an upper envelope of the maximum iceberg-tsunami heights, they fail to capture the physics of most iceberg-tsunami mechanisms.
Rationally designed bimetallic Au@Pt nanoparticles for glucose oxidation
Authors: Shim Kyubin , Lee Won-Chul , Heo Yoon-Uk , Shahabuddin Mohammed , Park Min-Sik , Hossain Md Shahriar A. , Kim Jung Ho
Published: January 2019

Bimetallic nanoparticles (NPs) have aroused interest in various fields because of their synergetic and unique properties. Among those nanoparticles, we strategically approached and synthesized Au@Pt NPs via the sonochemical method with different molar ratios (e.g. 3:7, 5:5, and 7:3) of Au to Pt precursors. The particle structure was confirmed to be core-shell, and the size was estimated to be 60, 52, and 47 nm, respectively, for 3:7, 5:5, and 7:3 ratios of Au to Pt. The detailed structure and crystallinity of as-prepared Au@Pt NPs were further studied by scanning electron microscopy, transmission electron microscopy with element mapping, and X-ray diffraction. It should be noted that thickness of the dendritic Pt shell in the core-shell structure can be easily tuned by controlling the molar ratio of Au to Pt. To explore the possibility of this material as glucose sensor, we confirmed the detection of glucose using amperometry. Two dynamic ranges in a calibration plot were displayed at 0.5–50.0 µM and 0.05–10.0 mM, and their detection limit as glucose sensor was determined to be 319.8 (±5.4) nM.
Exon junction complex components Y14 and Mago still play a role in budding yeast
Authors: Boisramé Anita , Devillers Hugo , Onésime Djamila , Brunel François , Pouch Juliette , Piot Mathieu , Neuvéglise Cécile
Published: January 2019

Since their divergence from Pezizomycotina, the mRNA metabolism of budding yeasts have undergone regressive evolution. With the dramatic loss of introns, a number of quality control mechanisms have been simplified or lost during evolution, such as the exon junction complex (EJC). We report the identification of the core EJC components, Mago, Y14, and eIF4A3, in at least seven Saccharomycotina species, including Yarrowia lipolytica. Peripheral factors that join EJC, either to mediate its assembly (Ibp160 or Cwc22), or trigger downstream processes, are present in the same species, forming an evolutionary package. Co-immunoprecipitation studies in Y. lipolytica showed that Mago and Y14 have retained the capacity to form heterodimers, which successively bind to the peripheral factors Upf3, Aly/REF, and Pym. Phenotypes and RNA-Seq analysis of EJC mutants showed evidence of Y14 and Mago involvement in mRNA metabolism. Differences in unspliced mRNA levels suggest that Y14 binding either interferes with pre-mRNA splicing or retains mRNA in the nucleus before their export and translation. These findings indicate that yeast could be a relevant model for understanding EJC function.
Cerebellar Gray Matter Volume, Executive Function, and Insomnia: Gender Differences in Adolescents
Authors: Jung Kyu-In , Park Min-Hyeon , Park Bumhee , Kim Shin-Young , Kim Yae On , Kim Bung-Nyun , Park Subin , Song Chan-Hee
Published: January 2019

The cerebellum is an important region responsible for adolescent cognitive function and sleep, and their correlation is expected to show different patterns depending on age and gender. We examined the regional cerebellar gray matter volume (GMV), executive function (EF) and insomnia symptoms to identify their correlation and gender differences in adolescents. Data for a total of 55 subjects’ (M = 31, F = 24, 14.80 ± 1.39 years old) were analyzed. The correlations between cerebellar regional GMV and Wisconsin card sorting test (WCST) subcategories showed that EF was better with larger GMV both in males and females. Far more overall correlations with cerebellar regions were observed in boys, with corresponding correlation strength being higher, and differences in localization were also observed in contrast to girls. Larger cerebellar GMV corresponded to better EF in adolescents. Insomnia did not influence the correlations between cerebellar regional GMV and EF, but more severe insomnia in boys correlated to smaller GMV in the right flocculonodular lobe. These results might implicate that the adolescent cerebellum is involved differently in EF dependent on gender.
Infant dietary patterns and early childhood caries in a multi-ethnic Asian cohort
Authors: Hu Shijia , Sim Yu Fan , Toh Jia Ying , Saw Seang Mei , Godfrey Keith M. , Chong Yap-Seng , Yap Fabian , Lee Yung Seng , Shek Lynette Pei-Chi , Tan Kok Hian , Chong Mary Foong-Fong , Hsu Chin-Ying Stephen
Published: January 2019

Dental caries, although preventable, remains one of the most prevalent chronic disease worldwide. Most studies focused on the relationship between sugar intake and caries. However, examining multidimensional dietary patterns is becoming increasingly important. Here, we examined the relationship between dietary patterns from ages 6 to 12 months and early childhood caries (ECC) at age 2 to 3-years. Infant dietary data was collected from caregivers and dietary pattern trajectories from 6 to 12 months derived. Oral examinations were carried out by trained calibrated dentists at ages 2 and 3 years. Associations between dietary pattern and ECC were estimated using generalized estimating equation. We found a 3.9 fold lower prevalence of decayed surfaces among children with high Guidelines dietary pattern scores at 6-months (IRR 0.26; CI [0.12–0.53]; p-value < 0.001) and 100% reduction of decayed surfaces with increased intakes of Guidelines dietary pattern foods from 6 to 12-month (IRR 2.4 × 10−4; CI [4.2 × 10−7–0.13]; p-value = 0.01). Suggesting that following the Guideline dietary pattern, which corresponds most closely to current World Health Organization weaning guidelines, at 6 months and an increase in pattern score between 6 and 12 months were protective against ECC development compared to Predominantly breastmilk, Easy-to-prepare foods and Noodles (in soup) and seafood dietary patterns.
Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation
Authors: Hsieh Cheng-Fang , Liu Ching-Kuan , Lee Ching-Tien , Yu Liang-En , Wang Jiz-Yuh
Published: January 2019

Diabetes mellitus is associated with an increased risk of Alzheimer’s dementia and cognitive decline. The cause of neurodegeneration in chronic diabetic patients remains unclear. Changes in brain microglial activity due to glycemic fluctuations may be an etiological factor. Here, we examined the impact of acute ambient glucose fluctuations on BV-2 microglial activity. Biochemical parameters were assayed and showed that the shift from normal glucose (NG; 5.5 mM) to high glucose (HG; 25 mM) promoted cell growth and induced oxidative/inflammatory stress and microglial activation, as evidenced by increased MTT reduction, elevated pro-inflammatory factor secretion (i.e., TNF-α and oxygen free radicals), and upregulated expression of stress/inflammatory proteins (i.e., HSP70, HO-1, iNOS, and COX-2). Also, LPS-induced inflammation was enlarged by an NG-to-HG shift. In contrast, the HG-to-NG shift trapped microglia in a state of metabolic stress, which led to apoptosis and autophagy, as evidenced by decreased Bcl-2 and increased cleaved caspase-3, TUNEL staining, and LC3B-II expression. These stress episodes were primarily mediated through MAPKs, PI3K/Akt, and NF-κB cascades. Our study demonstrates that acute glucose fluctuation forms the stress that alters microglial activity (e.g., inflammatory activation or self-degradation), representing a novel pathogenic mechanism for the continued deterioration of neurological function in diabetic patients.
Neu-medullocytes, sialidase-positive B cells in the thymus, express autoimmune regulator (AIRE)
Authors: Kijimoto-Ochiai Shigeko , Kamimura Keiko , Koda Toshiaki
Published: January 2019

Neu-medullocytes, which were previously identified and named by our group, are sialidase (neuraminidase)-positive B cells that express immunoglobulin and Mac-1 in the mouse thymus. Recently, B cells that migrated into the thymus were reported to express autoimmune regulator (AIRE) and to contribute to self-tolerance. We sought to determine whether Neu-medullocytes also express AIRE. We obtained positive results by triple staining Neu-medullocytes forin situsialidase activity, anti-AIRE, and either anti-IgG or anti-IgM antibodies and observing the staining with confocal microscopy. Additional molecules including CD5, IgM, major histocompatibility complex (MHC) Class II, and neuraminidase 1 (NEU1) were found in sialidase-positive cells independently. The real-time PCR results suggest that the primary sialidase in AIRE-positive cells is neuraminidase 2 (NEU2). Furthermore, some of the AIRE-positive medullary thymic epithelial cells also clearly showed sialidase activity when a triple staining of sialidase activity, anti-AIRE, andUlex europaeusagglutinin-1 (UEA-1) was performed. Neu-medullocytes may presentAire-dependent antigens for negative selection. We discuss the negative selection steps in consideration of sialidases and sialic acids.
SLIME: robust, high-speed 3D microvascular mapping
Authors: Liu Yehe , Broberg Meredith C. G. , Watanabe Michiko , Rollins Andrew M. , Jenkins Michael W.
Published: January 2019

Three dimensional (3D) microvascular imaging of cubic millimeter to centimeter size volumes often requires much time and expensive instruments. By combining optical clearing with a novel scatter-based optical coherence tomography (OCT) contrast agent, we have greatly extended OCT imaging depth in excised tissues while maintaining a simple and low cost approach that does not require in-depth OCT knowledge. The new method enables fast 3D microvascular mapping in large tissue volumes, providing a promising tool for investigating organ level microvascular abnormalities in large cohorts.
Involvement of the Red Nucleus in the Compensation of Parkinsonism may Explain why Primates can develop Stable Parkinson’s Disease
Authors: Philippens Ingrid H. C. H. M. , Wubben Jacqueline A. , Franke Sigrid K. , Hofman Sam , Langermans Jan A. M.
Published: January 2019

Neurological compensatory mechanisms help our brain to adjust to neurodegeneration as in Parkinson’s disease. It is suggested that the compensation of the damaged striato-thalamo-cortical circuit is focused on the intact thalamo-rubro-cerebellar pathway as seen during presymptomatic Parkinson, paradoxical movement and sensorimotor rhythm (SMR). Indeed, the size of the red nucleus, connecting the cerebellum with the cerebral cortex, is larger in Parkinson’s disease patients suggesting an increased activation of this brain area. Therefore, the red nucleus was examined in MPTP-induced parkinsonian marmoset monkeys during the presymptomatic stage and after SMR activation by neurofeedback training. We found a reverse significant correlation between the early expression of parkinsonian signs and the size of the parvocellular part of the red nucleus, which is predominantly present in human and non-human primates. In quadrupedal animals it consists mainly of the magnocellular part. Furthermore, SMR activation, that mitigated parkinsonian signs, further increased the size of the red nucleus in the marmoset monkey. This plasticity of the brain helps to compensate for dysfunctional movement control and can be a promising target for compensatory treatment with neurofeedback technology, vibrotactile stimulation or DBS in order to improve the quality of life for Parkinson’s disease patients.