bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate‐vegetation interaction and amplification of Australian dust variability
Authors: Evans Stuart , Ginoux Paul , Malyshev Sergey , Shevliakova Elena
Published: November 2016

Observations show that Australian dust activity varies by a factor of 4 on decadal timescales. General circulation models, however, typically fail to simulate this variability. Here we introduce a new dust parameterization into the NOAA/Geophysical Fluid Dynamics Laboratory climate model CM3 that represents land surface processes controlling dust sources including soil water and ice, snow cover, vegetation characteristics, and land type. In an additional novel step, we couple this new dust parameterization to the dynamic vegetation model LM3. In Australia, the new parameterization amplifies the magnitude and timescale of dust variability and better simulates the El Niño–Southern Oscillation‐dust relationship by more than doubling its strength. We attribute these improvements primarily to the slow response time of vegetation to precipitation anomalies and show that vegetation changes account for approximately 50% of enhanced dust emission during El Niño events. The amplified dust leads to radiative forcing over Australia greater than −1 and −20 W/m2 at top of atmosphere and surface, respectively.
Using GPS radio occultations to infer the water vapor feedback
Authors: Vergados Panagiotis , Mannucci Anthony J. , Ao Chi O. , Fetzer Eric J.
Published: November 2016

The air refractive index at L‐band frequencies depends on the air's water vapor content and density. Exploiting this relationship, we derive for the first time a theoretical model to infer the specific humidity response to surface temperature variations, dq/dTs, given knowledge of how the air refractive index and temperature vary with surface temperature. We validate this model by using 1.2–1.6 GHz Global Positioning System Radio Occultation (GPS RO) observations from 2007 to 2010 at 250 hPa, where the water vapor feedback on surface warming is strongest. The dq/dTs estimation from GPS RO observations shows excellent agreement with previously published results and the responses estimated by using the Atmospheric Infrared Sounder and the NASA's Modern‐Era Retrospective Analysis for Research and Applications data sets. Because of their high sensitivity to fractional changes in water vapor, current and future GPS RO observations show great promise in monitoring climate feedback and their trends.
Individual particle morphology, coatings, and impurities of black carbon aerosols in Antarctic ice and tropical rainfall
Authors: Ellis Aja , Edwards Ross , Saunders Martin , Chakrabarty Rajan K. , Subramanian R. , Timms Nicholas E. , van Riessen Arie , Smith Andrew M. , Lambrinidis Dionisia , Nunes Laurie J. , Vallelonga Paul , Goodwin Ian D. , Moy Andrew D. , Curran Mark A. J. , van Ommen Tas D.
Published: November 2016

Black carbon (BC) aerosols are a large source of climate warming, impact atmospheric chemistry, and are implicated in large‐scale changes in atmospheric circulation. Inventories of BC emissions suggest significant changes in the global BC aerosol distribution due to human activity. However, little is known regarding BC's atmospheric distribution or aged particle characteristics before the twentieth century. Here we investigate the prevalence and structural properties of BC particles in Antarctic ice cores from 1759, 1838, and 1930 Common Era (C.E.) using transmission electron microscopy and energy‐dispersive X‐ray spectroscopy. The study revealed an unexpected diversity in particle morphology, insoluble coatings, and association with metals. In addition to conventionally occurring BC aggregates, we observed single BC monomers, complex aggregates with internally, and externally mixed metal and mineral impurities, tar balls, and organonitrogen coatings. The results of the study show BC particles in the remote Antarctic atmosphere exhibit complexity that is unaccounted for in atmospheric models of BC.
Temperature dependence of the zeta potential in intact natural carbonates
Authors: Al Mahrouqi Dawoud , Vinogradov Jan , Jackson Matthew D.
Published: November 2016

The zeta potential is a measure of the electrical charge on mineral surfaces and is an important control on subsurface geophysical monitoring, adsorption of polar species in aquifers, and rock wettability. We report the first measurements of zeta potential in intact, water‐saturated, natural carbonate samples at temperatures up to 120°C. The zeta potential is negative and decreases in magnitude with increasing temperature at low ionic strength (0.01 M NaCl, comparable to potable water) but is independent of temperature at high ionic strength (0.5 M NaCl, comparable to seawater). The equilibrium calcium concentration resulting from carbonate dissolution also increases with increasing temperature at low ionic strength but is independent of temperature at high ionic strength. The temperature dependence of the zeta potential is correlated with the temperature dependence of the equilibrium calcium concentration and shows a Nernstian linear relationship. Our findings are applicable to many subsurface carbonate rocks at elevated temperature.
A global view of atmospheric ice particle complexity
Authors: Schmitt Carl G. , Heymsfield Andrew J. , Connolly Paul , Järvinen Emma , Schnaiter Martin
Published: November 2016

Atmospheric ice particles exist in a variety of shapes and sizes. Single hexagonal crystals like common hexagonal plates and columns are possible, but more frequently, atmospheric ice particles are much more complex. Ice particle shapes have a substantial impact on many atmospheric processes through fall speed, affecting cloud lifetime, to radiative properties, affecting energy balance to name a few. This publication builds on earlier work where a technique was demonstrated to separate single crystals and aggregates of crystals using particle imagery data from aircraft field campaigns. Here data from 10 field programs have been analyzed and ice particle complexity parameterized by cloud temperature for arctic, midlatitude (summer and frontal), and tropical cloud systems. Results show that the transition from simple to complex particles can be as small as 80 µm or as large as 400 µm depending on conditions. All regimes show trends of decreasing transition size with decreasing temperature.
New discoveries from MESSENGER and insights into Mercury's exosphere
Authors: Vervack R. J. , Killen R. M. , McClintock W. E. , Merkel A. W. , Burger M. H. , Cassidy T. A. , Sarantos M.
Published: November 2016

For most of the orbital phase of the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) mission, a regular search for weakly emitting or less abundant species in Mercury's exosphere resulted in nondetections. However, during the final Earth year of the mission, emission from multiple lines of manganese, aluminum, and ionized calcium was detected. These observations validate the detection of a single line of ionized calcium during the third MESSENGER Mercury flyby, provide definitive confirmation for weak aluminum detections in ground‐based observations, and represent the discovery of manganese in Mercury's exosphere. These detections occurred over a limited range of predawn local times and Mercury true anomaly angles (0°–70°), and each has a distinct spatial distribution. Equally interesting is the absence of detectable emission from oxygen at limits well below the levels reported for Mariner 10.
Midlatitude atmospheric responses to Arctic sensible heat flux anomalies in Community Climate Model, Version 4
Authors: Mills Catrin M. , Cassano John J. , Cassano Elizabeth N.
Published: November 2016

Possible linkages between Arctic sea ice loss and midlatitude weather are strongly debated in the literature. We analyze a coupled model simulation to assess the possibility of Arctic ice variability forcing a midlatitude response, ensuring consistency between atmosphere, ocean, and ice components. We work with weekly running mean daily sensible heat fluxes with the self‐organizing map technique to identify Arctic sensible heat flux anomaly patterns and the associated atmospheric response, without the need of metrics to define the Arctic forcing or measure the midlatitude response. We find that low‐level warm anomalies during autumn can build planetary wave patterns that propagate downstream into the midlatitudes, creating robust surface cold anomalies in the eastern United States.
Drift paths of ions composing multiple‐nose spectral structures near the inner edge of the plasma sheet
Authors: Ferradas C. P. , Zhang J.‐C. , Spence H. E. , Kistler L. M. , Larsen B. A. , Reeves G. , Skoug R. , Funsten H.
Published: November 2016

We present a case study of the H+, He+, and O+ multiple‐nose structures observed by the Helium, Oxygen, Proton, and Electron instrument on board Van Allen Probe A over one complete orbit on 28 September 2013. Nose structures are observed near the inner edge of the plasma sheet and constitute the signatures of ion drift in the highly dynamic environment of the inner magnetosphere. We find that the multiple noses are intrinsically associated with variations in the solar wind. Backward ion drift path tracings show new details of the drift trajectories of these ions; i.e., multiple noses are formed by ions with a short drift time from the assumed source location to the inner region and whose trajectories (1) encircle the Earth different number of times or (2) encircle the Earth equal number of times but with different drift time, before reaching the observation site.
Synoptic and quantitative attributions of the extreme precipitation leading to the August 2016 Louisiana flood
Authors: Wang S.‐Y. Simon , Zhao Lin , Gillies Robert R.
Published: November 2016

The catastrophic August 2016 flood in the U.S. state of Louisiana was a result of intense precipitation produced by a slow‐moving tropical low‐pressure system interacting with an eastward traveling baroclinic trough to the north. While tropical‐midlatitude interactions of this nature are rare, they are not unprecedented. Analyses presented point toward the tendency for more and perhaps stronger upper level troughs propagating out of the western U.S. in summer; these then have an increasing potential to cross paths with low‐pressure systems that form around the Gulf Coast. Combined with the projected increase in precipitable water, resulting precipitation magnitude would increase. Large‐ensemble modeling indicates that the prospect of future tropical‐midlatitude interactions is a scenario that Louisiana will face in the future, while regional simulations estimate that the climate warming since 1985 may have increased the event precipitation (11–14 August 2016) on the order of 20%, all of which allude to a conceivable forecast of nonhurricane‐related, warm season extreme precipitation in the Gulf Coast states.
Lithospheric structure beneath the northern Central Andean Plateau from the joint inversion of ambient noise and earthquake‐generated surface waves
Authors: Ward Kevin M. , Zandt George , Beck Susan L. , Wagner Lara S. , Tavera Hernando
Published: November 2016

The Central Andean Plateau (CAP), as defined by elevations in excess of 3 km, extends over 1800 km along the active South American Cordilleran margin making it the second largest active orogenic plateau on Earth. The uplift history of this high Plateau, with an average elevation around 4 km above sea level, remains uncertain as paleoelevation studies along the CAP suggest a complex, nonuniform uplift history. As part of the Central Andean Uplift and the Geodynamics of High Topography (CAUGHT) project, we image the S wave velocity structure of the crust and upper mantle using surface waves measured from ambient noise and teleseismic earthquakes to investigate the upper mantle component of plateau uplift. We observe three main features in our S wave velocity model including (1) a positive velocity perturbation associated with the subducting Nazca slab; (2) a negative velocity perturbation below the sub‐Andean crust that we interpret as anisotropic Brazilian cratonic lithosphere; and (3) a high‐velocity feature in the mantle above the slab that extends along the length of the Altiplano from the base of the Moho to a depth of ~120 km. A strong spatial correlation exists between the lateral extent of this high‐velocity feature and the relatively lower elevations of the Altiplano basin suggesting a potential relationship. Determining if this high‐velocity feature represents a small lithospheric root or foundering of orogenic lithosphere requires more integration of observations, but either interpretation implies a strong geodynamic connection with the uppermost mantle and the current topography of the northern CAP.
Pulsed growth of the West Qinling at ~30 Ma in northeastern Tibet: Evidence from Lanzhou Basin magnetostratigraphy and provenance
Authors: Wang Weitao , Zhang Peizhen , Liu Caicai , Zheng Dewen , Yu Jingxing , Zheng Wenjun , Wang Yizhou , Zhang Huiping , Chen Xiuyan
Published: November 2016

The development of Cenozoic basins in the northeast margin of the Tibetan Plateau is central to understanding the dynamics of plateau growth. Here we present a magnetostratigraphy from the Lanzhou Basin, dating the terrestrial deposits from the Eocene (~47 Ma) to the middle Miocene (~15 Ma). The stratigraphic observation, palocurrent, and sediment provenance analysis suggest that the Lanzhou Basin (subbasin of the Longzhong Basin) probably initiated as a topographically enclosed depression during Eocene to early Oligocene (~47–30 Ma). We suspect that right‐lateral transtensional deformation inherited from the Cretaceous may result in formation of the Lanzhou Basin at the Eocene. Subsequently, changes in paleocurrent, sandstone and conglomerate compositions and detrital zircon provenance reflect the pulsed growth of the West Qinling at ~30 Ma, which triggered not only the formation of new flexural subsidence to the north of the West Qinling, but also renewed subsidence of Lanzhou Basin into the broad foreland basin system. We compare this growth history with major NE Tibet deformation and suggest that it may result from northeastward extrusion of the Tibetan Plateau due to the onset of Altyn Tagh Fault activity at Oligocene.
Distinct effects of obesity and puberty on risk and age at onset of pediatric MS
Authors: Chitnis Tanuja , Graves Jennifer , Weinstock‐Guttman Bianca , Belman Anita , Olsen Cody , Misra Madhusmita , Aaen Gregory , Benson Leslie , Candee Meghan , Gorman Mark , Greenberg Benjamin , Krupp Lauren , Lotze Timothy , Mar Soe , Ness Jayne , Rose John , Rubin Jennifer , Schreiner Teri , Tillema Jan , Waldman Amy , Rodriguez Moses , Casper Charlie , Waubant Emmanuelle ,   the U.S. Network of Pediatric MS Centers
Published: November 2016

Objective

The aim of this study was to examine the relative contributions of body mass index (BMI) and pubertal measures for risk and age of onset of pediatric MS.

Methods

Case–control study of 254 (63% female) MS cases (onset<18 years of age) and 420 (49% female) controls conducted at 14 U.S. Pediatric MS Centers. Sex‐ and age‐stratified BMI percentiles were calculated using CDC growth charts from height and weight measured at enrollment for controls, and within 1 year of onset for MS cases. Sex‐stratified associations between MS risk and age at symptom onset with both BMI and pubertal factors were estimated controlling for race and ethnicity.

Results

Only 11% of girls and 15% of boys were prepubertal (Tanner stage I) at MS onset. 80% of girls had onset of MS after menarche. BMI percentiles were higher in MS cases versus controls (girls: P < 0.001; boys: P = 0.018). BMI was associated with odds of MS in multivariate models in postpubertal girls (OR = 1.60, 95% confidence interval [CI]: 1.12, 2.27, P = 0.009) and boys (OR = 1.43, 95% CI: 1.08, 1.88, P = 0.011). In girls with MS onset after menarche, higher BMI was associated with younger age at first symptoms (P = 0.031). Younger menarche was associated with stronger effects of BMI through mediation and interaction analysis. In pubertal/postpubertal boys, 89% of whom were obese/overweight, earlier sexual maturity was associated with earlier onset of MS (P < 0.001).

Interpretation

Higher BMI in early adolescence is a risk factor for MS in girls and boys. Earlier age at sexual maturity contributes to earlier age at MS onset, particularly in association with obesity.
Investigation of the effect of magnetic field on mass transfer parameters of CO2 absorption using Fe3O4‐water nanofluid
Authors: Karimi Darvanjooghi Mohammad Hossein , Pahlevaninezhad Maedeh , Abdollahi Ali , Davoodi Seyyed Mohammadreza
Published: November 2016

In this study, the enhancement of physical absorption of carbon dioxide by Fe3O4‐water nanofluid under the influence of AC and DC magnetic fields was investigated. Furthermore, a gas‐liquid mass transfer model for single bubble systems was applied to predict mass transfer parameters. The coated Fe3O4 nanoparticles were prepared using co‐percipitation method. The results from characterization indicated that the nanoparticles surfaces were covered with hydroxyl groups and nanoparticles diameter were 10–13 nm. The findings showed that the mass transfer rate and solubility of carbon dioxide in magnetic nanofluid increased with an increase in the magnetic field strength. Results indicated that the enhancement of carbon dioxide solubility and average molar flux gas into liquid phase, particularly in the case of AC magnetic field. Moreover, results demonstrated that mass diffusivity of CO2 in nanofluid and renewal surface factor increased when the intensity of the field increased and consequently diffusion layer thickness decreased. © 2016 American Institute of Chemical Engineers AIChE J, 63: 2176–2186, 2017
Urinary metabolomics of complete Freund's adjuvant‐induced hyperalgesia in rats
Authors: Liu Yang , Chen Hui , Lu Jun , Jiang Youshui , Yang Rui , Gao Songyan , Dong Xin , Chen Wei
Published: November 2016

The aim of this study was to demonstrate the differences of metabolomics changes in a hyperalgesia model and find potent biomarkers of hyperalgesia. Seven rats were placed in metabolic cages. An emulsion containing 500 μg of Complete Freund's adjuvant (CFA) was used to induce hyperalgesia. Urine samples were collected prior to the injection of CFA and on post‐injection days 1, 3 and 7. Ultraperformance liquid chromatography, coupled with quadrupole‐time‐of‐flight mass spectrometry (UHPLC‐Q‐TOF/MS), was used for a quantitative analysis of urinary metabolic changes in the CFA‐induced hyperalgesia model. Differences between the metabolic profiles of the rats in the four groups were analyzed using partial least squares discriminant analysis. Thirty‐four potential urine metabolite biomarkers were identified, which changed in a trend similar to the pain threshold. These potential biomarkers were involved in 11 metabolic pathways, as follows: alanine, aspartate, and glutamate metabolism; ascorbate and aldarate metabolism; glycerolipid metabolism; glycerophospholipid metabolism; histidine metabolism; phenylalanine metabolism; sphingolipid metabolism; tryptophan metabolism; tyrosine metabolism; valine, leucine and isoleucine biosynthesis; and vitamin B6 metabolism. These results may improve our understanding of hyperalgesia and provide a basis for the clinical diagnosis of hyperalgesia.
Long‐term results of definitive concurrent chemoradiotherapy using paclitaxel plus oxaliplatin in unresectable locally advanced esophageal cancer: a prospective phase II trial
Authors: Song Tao , Zhang Xuebang , Fang Min , Zhao Ruping , Wu Shixiu
Published: November 2016

This prospective study aimed at assessing the efficiency and safety of concurrent chemoradiotherapy (CCRT) using paclitaxel (PTX) plus oxaliplatin (OHP) in unresectable locally advanced esophageal cancer patients. Between January 2006 and December 2010, 34 patients with unresectable locally advanced esophageal cancer were enrolled in this study. Radiotherapy was delivered with a daily fraction of 2.0 Gy to a total dose of 60 Gy over 6 weeks. Concurrent PTX (135 mg/m², d1) and OHP (130 mg/m², d1) were administered on Day 1 and Day 29 of radiotherapy. Of these patients, 76.5% completed the treatment course with a response rate of 73.5%, including eight (23.5%) patients with complete response and 17 (50.0%) patients with partial response. The median overall survival (OS) time was 23.7 months (range: 4.0–65.5 months) with 1‐, 3‐ and 5‐year OS rates were 64.3%, 36.6% and 25.8%, respectively. The median progression‐free survival (PFS) time was 21.2 months with 1‐, 3‐ and 5‐year PFS rates were 63.8%, 30.9% and 20.4%, respectively, During the CCRT course, the main grade 3 or greater acute toxicities were leukopenia (38.2%), esophagitis (14.7%), and dysphagia (11.8%), with late toxicity being infrequent. Although this study did not meet its primary endpoint, the application of CCRT with PTX and OHP in unresectable locally advanced esophageal carcinoma yielded satisfactory clinical outcomes and manageable toxicities.
Rap1A promotes ovarian cancer metastasis via activation of ERK/p38 and notch signaling
Authors: Lu Lili , Wang Jingshu , Wu Yougen , Wan Ping , Yang Gong
Published: November 2016

As one of the Ras‐associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal‐regulated kinase (ERK), p38 mitogen‐activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial‐mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9. However, the pretreatment of Rap1A‐overexpressing cells with the Notch inhibitor DAPT or ERK inhibitor (U0126) inhibited the up‐regulated expression of those molecules. These findings provide the first evidence linking Rap1A with ovarian cancer development through the ERK/p38 and Notch signaling pathways, indicating that Rap1A may be used as a novel diagnostic marker or a therapeutic target for ovarian cancer.
Nitrogen‐Doped Hierarchical Porous Carbons Derived from Sodium Alginate as Efficient Oxygen Reduction Reaction Electrocatalysts
Authors: Xuan Cuijuan , Wu Zexing , Lei Wen , Wang Jie , Guo Junpo , Wang Deli
Published: November 2016

The exploration of earth‐abundant and low‐cost eco‐friendly materials with an excellent electrocatalytic performance is crucial for sustainable energy development. In this work, 3 D N‐doped hierarchical porous carbon (NC) materials with an interconnected mesoporous/macroporous structure have been synthesized by the simple single‐step pyrolysis of naturally available sodium alginate in the presence of urea. The systematic investigation of the pyrolysis temperature on the performance in the oxygen reduction reaction in 0.1 m KOH solution indicates that the catalyst obtained at 900 °C (NC‐900) exhibits the best catalytic performance because of the high degree of graphitization and the unique hierarchical porous structure. Furthermore, NC‐900 exhibits an excellent durability and a remarkable resistance to methanol poisoning compared to Pt/C in alkaline solution. This work highlights the significance and potential of biomass‐derived hierarchical porous carbon materials for applications in energy conversion devices.
Estimation of Flat‐topped Gaussian distribution with application in system identification
Authors: Tan Ruomu , Huang Biao , Li Zukui
Published: November 2016

Uniformly distributed uncertainty exists in industrial process; additive error introduced by quantization is an example. To be able to handle additive uniform and Gaussian measurement uncertainty simultaneously in system identification, the Flat‐topped Gaussian distribution is considered in this paper as an alternative to the Gaussian distribution. To incorporate this type of uncertainty in the maximum likelihood estimation framework, the explicit form of its density function is of necessity. This work proposes an approach for obtaining both the functional structure and corresponding parameter estimation of Flat‐topped Gaussian distribution by a moment fitting strategy. The performance of the proposed approximation function is verified by comparison to the Flat‐topped Gaussian distributed random variable with different Gaussian and uniform components. Results of numerical simulations and industrial applications in system identification are presented to verify the effectiveness of the Flat‐topped Gaussian distribution for noise distribution in handling additional uniform uncertainty.
Anticoagulation Endpoints With Clinical Implementation of Warfarin Pharmacogenetic Dosing in a Real‐World Setting: A Proposal for a New Pharmacogenetic Dosing Approach
Authors: Arwood MJ , Deng J , Drozda K , Pugach O , Nutescu EA , Schmidt S , Duarte JD , Cavallari LH
Published: November 2016

Achieving therapeutic anticoagulation efficiently with warfarin is important to reduce thrombotic and bleeding risks and is influenced by genotype. Utilizing data from a diverse population of 257 patients who received VKORC1 and CYP2C9 genotype‐guided warfarin dosing, we aimed to examine genotype‐associated differences in anticoagulation endpoints and derive a novel pharmacogenetic nomogram to more optimally dose warfarin. We observed significant differences across patients with 0, 1, or ≥2 reduced‐function VKORC1 or CYP2C9 alleles, respectively, in time to achieve therapeutic international normalized ratio (INR) (7.8 ± 5.8, 7.2 ± 4.7, and 5.4 ± 4.6 days, P = 0.0004) and mean percentage of time in therapeutic range in the first 28 days (22.2, 27.8, and 32.2%, P = 0.0127) with use of existing pharmacogenetic algorithms. These data suggest that more aggressive dosing is necessary for patients with 0 to 1 VKORC1/CYP2C9 variants to more efficiently achieve therapeutic anticoagulation. Herein, we provide a novel kinetic/pharmacodynamic‐derived dosing nomogram optimized for a heterogeneous patient population.
Does selective logging stress tropical forest invertebrates? Using fat stores to examine sublethal responses in dung beetles
Authors: França Filipe , Barlow Jos , Araújo Bárbara , Louzada Julio
Published: November 2016

The increased global demand for tropical timber has driven vast expanses of tropical forests to be selectively logged worldwide. While logging impacts on wildlife are predicted to change species distribution and abundance, the underlying physiological responses are poorly understood. Although there is a growing consensus that selective logging impacts on natural populations start with individual stress‐induced sublethal responses, this literature is dominated by investigations conducted with vertebrates from temperate zones. Moreover, the sublethal effects of human‐induced forest disturbance on tropical invertebrates have never been examined. To help address this knowledge gap, we examined the body fat content and relative abundance of three dung beetle species (Coleoptera: Scarabaeinae) with minimum abundance of 40 individuals within each examined treatment level. These were sampled across 34 plots in a before‐after control‐impact design (BACI) in a timber concession area of the Brazilian Amazon. For the first time, we present evidence of logging‐induced physiological stress responses in tropical invertebrates. Selective logging increased the individual levels of fat storage and reduced the relative abundance of two dung beetle species. Given this qualitative similarity, we support the measurement of body fat content as reliable biomarker to assess stress‐induced sublethal effects on dung beetles. Understanding how environmental modification impacts the wildlife has never been more important. Our novel approach provides new insights into the mechanisms through which forest disturbances impose population‐level impacts on tropical invertebrates.
Identifying multispecies synchrony in response to environmental covariates
Authors: Swallow Ben , King Ruth , Buckland Stephen T. , Toms Mike P.
Published: November 2016

The importance of multispecies models for understanding complex ecological processes and interactions is beginning to be realized. Recent developments, such as those by Lahoz‐Monfort et al. (2011), have enabled synchrony in demographic parameters across multiple species to be explored. Species in a similar environment would be expected to be subject to similar exogenous factors, although their response to each of these factors may be quite different. The ability to group species together according to how they respond to a particular measured covariate may be of particular interest to ecologists. We fit a multispecies model to two sets of similar species of garden bird monitored under the British Trust for Ornithology's Garden Bird Feeding Survey. Posterior model probabilities were estimated using the reversible jump algorithm to compare posterior support for competing models with different species sharing different subsets of regression coefficients. There was frequently good agreement between species with small asynchronous random‐effect components and those with posterior support for models with shared regression coefficients; however, this was not always the case. When groups of species were less correlated, greater uncertainty was found in whether regression coefficients should be shared or not. The methods outlined in this study can test additional hypotheses about the similarities or synchrony across multiple species that share the same environment. Through the use of posterior model probabilities, estimated using the reversible jump algorithm, we can detect multispecies responses in relation to measured covariates across any combination of species and covariates under consideration. The method can account for synchrony across species in relation to measured covariates, as well as unexplained variation accounted for using random effects. For more flexible, multiparameter distributions, the support for species‐specific parameters can also be measured.
Extreme flood‐driven fluvial bank erosion and sediment loads: direct process measurements using integrated Mobile Laser Scanning (MLS) and hydro‐acoustic techniques
Authors: Leyland Julian , Hackney Christopher R. , Darby Stephen E. , Parsons Daniel R. , Best James L. , Nicholas Andrew P. , Aalto Rolf , Lague Dimitri
Published: November 2016

This methods paper details the first attempt at monitoring bank erosion, flow and suspended sediment at a site during flooding on the Mekong River induced by the passage of tropical cyclones. We deployed integrated mobile laser scanning (MLS) and multibeam echo sounding (MBES), alongside acoustic Doppler current profiling (aDcp), to directly measure changes in river bank and bed at high (~0.05 m) spatial resolution, in conjunction with measurements of flow and suspended sediment dynamics. We outline the methodological steps used to collect and process this complex point cloud data, and detail the procedures used to process and calibrate the aDcp flow and sediment flux data. A comparison with conventional remote sensing methods of estimating bank erosion, using aerial images and Landsat imagery, reveals that traditional techniques are error prone at the high temporal resolutions required to quantify the patterns and volumes of bank erosion induced by the passage of individual flood events. Our analysis reveals the importance of cyclone‐driven flood events in causing high rates of erosion and suspended sediment transport, with a c. twofold increase in bank erosion volumes and a fourfold increase in suspended sediment volumes in the cyclone‐affected wet season. Copyright © 2016 John Wiley & Sons, Ltd.
Low‐level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment
Authors: Kim Jung Hee , Sinn Dong Hyun , Kang Wonseok , Gwak Geum‐Youn , Paik Yong‐Han , Choi Moon Seok , Lee Joon Hyeok , Koh Kwang Cheol , Paik Seung Woon
Published: November 2016

The long‐term clinical impact of low‐level viremia (LLV; <2,000 IU/mL) is not well understood. As a result, it is unclear whether the development of LLV during entecavir monotherapy requires a change in therapy. A retrospective cohort of 875 treatment‐naive chronic hepatitis B virus (HBV) monoinfected patients (mean age 47.7 years, male = 564 [65.5%], cirrhosis = 443 [50.6%]) who received entecavir monotherapy were analyzed for the development of hepatocellular carcinoma (HCC). The HCC risk was compared between patients who maintained virological response (MVR), defined by persistently undetectable HBV DNA (<12 IU/mL), and patients who experienced LLV, defined by either persistent or intermittent episodes of <2,000 IU/mL detectable HBV DNA. During a median 4.5 years of follow‐up (range 1.0‐8.7 years), HCC was diagnosed in 85 patients (9.7%). HCC developed more frequently in patients who experienced LLV than MVR (14.3% versus 7.5% at 5 years, P = 0.015). The hazard ratio comparing those with LLV to MVR was 1.98 (95% confidence interval = 1.28‐3.06, P = 0.002, adjusted for age, sex, hepatitis B e antigen, baseline HBV DNA levels, and cirrhosis). Among patients with cirrhosis, those with LLV exhibited a significantly higher HCC risk than those with MVR (HCC incidence rate at 5 years 23.4% versus 10.3%, adjusted hazard ratio = 2.20, 95% confidence interval 1.34‐3.60; P = 0.002). However, for patients without cirrhosis, there was no significant difference in the HCC risk between LLV and MVR. Conclusion: LLV observed during entecavir monotherapy was associated with a higher risk of HCC, especially for those with cirrhosis, indicating that LLV during potent antiviral therapy is consequential. (Hepatology 2017;66:335–343).
The hepatic “matrisome” responds dynamically to injury: Characterization of transitional changes to the extracellular matrix in mice
Authors: Massey Veronica L. , Dolin Christine E. , Poole Lauren G. , Hudson Shanice V. , Siow Deanna L. , Brock Guy N. , Merchant Michael L. , Wilkey Daniel W. , Arteel Gavin E.
Published: November 2016

The extracellular matrix (ECM) consists of diverse components that work bidirectionally with surrounding cells to create a responsive microenvironment. In some contexts (e.g., hepatic fibrosis), changes to the ECM are well recognized and understood. However, it is becoming increasingly accepted that the hepatic ECM proteome (i.e., matrisome) responds dynamically to stress well before fibrosis. The term “transitional tissue remodeling” describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these changes in ECM may contribute to early disease initiation and/or progression. The nature and magnitude of these changes to the ECM in liver injury are poorly understood. The goals of this work were to validate analysis of the ECM proteome and compare the impact of 6 weeks of ethanol diet and/or acute lipopolysaccharide (LPS). Liver sections were processed in a series of increasingly rigorous extraction buffers to separate proteins by solubility. Extracted proteins were identified using liquid chromatography/tandem mass spectrometry (LC‐MS/MS). Both ethanol and LPS dramatically increased the number of matrisome proteins ∼25%. The enhancement of LPS‐induced liver damage by ethanol preexposure was associated with unique protein changes. Conclusion: An extraction method to enrich the hepatic ECM was characterized. The results demonstrate that the hepatic matrisome responds dynamically to both acute (LPS) and chronic (ethanol) stresses, long before more‐dramatic fibrotic changes to the liver occur. The changes to the mastrisome may contribute, at least in part, to the pathological responses to these stresses. It is also interesting that several ECM proteins responded similarly to both stresses, suggesting a common mechanism in both models. Nevertheless, there were responses that were unique to the individual and combined exposures. (Hepatology 2017;65:969‐982).
The unfolded protein response mediates fibrogenesis and collagen I secretion through regulating TANGO1 in mice
Authors: Maiers Jessica L. , Kostallari Enis , Mushref Malek , deAssuncao Thiago M. , Li Haiyang , Jalan‐Sakrikar Nidhi , Huebert Robert C. , Cao Sheng , Malhi Harmeet , Shah Vijay H.
Published: November 2016

Fibrogenesis encompasses the deposition of matrix proteins, such as collagen I, by hepatic stellate cells (HSCs) that culminates in cirrhosis. Fibrogenic signals drive transcription of procollagen I, which enters the endoplasmic reticulum (ER), is trafficked through the secretory pathway, and released to generate extracellular matrix. Alternatively, disruption of procollagen I ER export could activate the unfolded protein response (UPR) and drive HSC apoptosis. Using a small interfering RNA screen, we identified Transport and Golgi organization 1 (TANGO1) as a potential participant in collagen I secretion. We investigated the role of TANGO1 in procollagen I secretion in HSCs and liver fibrogenesis. Depletion of TANGO1 in HSCs blocked collagen I secretion without affecting other matrix proteins. Disruption of secretion led to procollagen I retention within the ER, induction of the UPR, and HSC apoptosis. In wild‐type (WT) HSCs, both TANGO1 and the UPR were induced by transforming growth factor β (TGFβ). As the UPR up‐regulates proteins involved in secretion, we studied whether TANGO1 was a target of the UPR. We found that UPR signaling is responsible for up‐regulating TANGO1 in response to TGFβ, and this mechanism is mediated by the transcription factor X‐box binding protein 1 (XBP1). In vivo, murine and human cirrhotic tissue displayed increased TANGO1 messenger RNA levels. Finally, TANGO1+/– mice displayed less hepatic fibrosis compared to WT mice in two separate murine models: CCl4 and bile duct ligation. Conclusion: Loss of TANGO1 leads to procollagen I retention in the ER, which promotes UPR‐mediated HSC apoptosis. TANGO1 regulation during HSC activation occurs through a UPR‐dependent mechanism that requires the transcription factor, XBP1. Finally, TANGO1 is critical for fibrogenesis through mediating HSC homeostasis. The work reveals a unique role for TANGO1 and the UPR in facilitating collagen I secretion and fibrogenesis. (Hepatology 2017;65:983‐998).
Reduction in liver transplant wait‐listing in the era of direct‐acting antiviral therapy
Authors: Flemming Jennifer A. , Kim W. Ray , Brosgart Carol L. , Terrault Norah A.
Published: November 2016

Direct‐acting antiviral (DAA) therapy, recently approved for patients with decompensated cirrhosis (DC) secondary to hepatitis C virus (HCV), is associated with improved hepatic function. We analyzed trends in liver transplant (LT) wait‐listing (WL) to explore potential impact of effective medical therapy on WL registration. This is a cohort study using the Scientific Registry of Transplant Recipients database from 2003 to 2015. A total of 47,591 adults wait‐listed for LT from HCV, hepatitis B virus (HBV), and nonalcoholic steatohepatitis (NASH) were identified. LT indication was defined as DC if the Model for End‐Stage Liver Disease (MELD) at WL was ≥15 or hepatocellular carcinoma (HCC). Era of listing was divided into interferon (IFN; 2003‐2010), protease inhibitor (PI; 2011‐2013), and direct‐acting antiviral (DAA; 2014‐2015). Annual standardized incidence rates of WL were analyzed using Poisson regression. Adjusted incidences of LT WL for DC in HCV patients decreased by 5% in the PI era (P = 0.004) and 32% in the DAA era (P < 0.001) compared to the IFN era. Listing for DC in HBV also decreased in the PI (–17%; P = 0.002) and DAA eras (–24%; P < 0.001). Conversely, WL for DC in NASH increased by 41% in the PI era (P < 0.001) and 81% in the DAA era (P < 0.001). WL for HCC in both the HCV and NASH populations increased in both the PI and DAA eras (P < 0.001 for all) whereas HCC WL in HBV remained stable (P > 0.05 for all). Conclusion: The rate of LT WL for HCV complicated by DC has decreased by over 30% in the era of DAA therapy. Further reductions in WL are anticipated with increased testing, linkage to care, and access to DAA therapy. (Hepatology 2017;65:804‐812).
Loss of the transforming growth factor‐β effector β2‐Spectrin promotes genomic instability
Authors: Chen Jian , Shukla Vivek , Farci Patrizia , Andricovich Jaclyn , Jogunoori Wilma , Kwong Lawrence N. , Katz Lior H. , Shetty Kirti , Rashid Asif , Su Xiaoping , White Jon , Li Lei , Wang Alan Yaoqi , Blechacz Boris , Raju Gottumukkala S. , Davila Marta , Nguyen Bao‐Ngoc , Stroehlein John R. , Chen Junjie , Kim Sang Soo , Levin Heather , Machida Keigo , Tsukamoto Hidekazu , Michaely Peter , Tzatsos Alexandros , Mishra Bibhuti , Amdur Richard , Mishra Lopa
Published: November 2016

Exposure to genotoxins such as ethanol‐derived acetaldehyde leads to DNA damage and liver injury and promotes the development of cancer. We report here a major role for the transforming growth factor β/mothers against decapentaplegic homolog 3 adaptor β2‐Spectrin (β2SP, gene Sptbn1) in maintaining genomic stability following alcohol‐induced DNA damage. β2SP supports DNA repair through β2SP‐dependent activation of Fanconi anemia complementation group D2 (Fancd2), a core component of the Fanconi anemia complex. Loss of β2SP leads to decreased Fancd2 levels and sensitizes β2SP mutants to DNA damage by ethanol treatment, leading to phenotypes that closely resemble those observed in animals lacking both aldehyde dehydrogenase 2 and Fancd2 and resemble human fetal alcohol syndrome. Sptbn1‐deficient cells are hypersensitive to DNA crosslinking agents and have defective DNA double‐strand break repair that is rescued by ectopic Fancd2 expression. Moreover, Fancd2 transcription in response to DNA damage/transforming growth factor β stimulation is regulated by the β2SP/mothers against decapentaplegic homolog 3 complex. Conclusion: Dysfunctional transforming growth factor β/β2SP signaling impacts the processing of genotoxic metabolites by altering the Fanconi anemia DNA repair pathway. (Hepatology 2017;65:678‐693)
Prostaglandin E2 promotes hepatic bile acid synthesis by an E prostanoid receptor 3‐mediated hepatocyte nuclear receptor 4α/cholesterol 7α‐hydroxylase pathway in mice
Authors: Yan Shuai , Tang Juan , Zhang Yuyao , Wang Yuanyang , Zuo Shengkai , Shen Yujun , Zhang Qianqian , Chen Di , Yu Yu , Wang Kai , Duan Sheng‐Zhong , Yu Ying
Published: November 2016

Prostaglandin E2 (PGE2) is an important lipid mediator of inflammation. However, whether and how PGE2 regulates hepatic cholesterol metabolism remains unknown. We found that expression of the PGE2 receptor, E prostanoid receptor 3 (EP3) expression is remarkably increased in hepatocytes in response to hyperlipidemic stress. Hepatocyte‐specific deletion of EP3 receptor (EP3

hep–/–
) results in hypercholesterolemia and augments diet‐induced atherosclerosis in low‐density lipoprotein receptor knockout (Ldlr

–/–
) mice. Cholesterol 7α‐hydroxylase (CYP7A1) is down‐regulated in livers of EP3hep–/–Ldlr−/−
mice, leading to suppressed hepatic bile acid (BA) biosynthesis. Mechanistically, hepatic‐EP3 deficiency suppresses CYP7A1 expression by elevating protein kinase A (PKA)‐dependent Ser143 phosphorylation of hepatocyte nuclear receptor 4α (HNF4α). Disruption of the PKA‐HNF4α interaction and BA sequestration rescue impaired BA excretion and ameliorated atherosclerosis in EP3hep–/–Ldlr−/−
mice. Conclusion: Our results demonstrated an unexpected role of proinflammatory mediator PGE2 in improving hepatic cholesterol metabolism through activation of the EP3‐mediated PKA/HNF4α/CYP7A1 pathway, indicating that inhibition of this pathway may be a novel therapeutic strategy for dyslipidemia and atherosclerosis. (Hepatology 2017;65:999‐1014)
EGFR gene copy number predicts response to anti‐EGFR treatment in RAS wild type and RAS/BRAF/PIK3CA wild type metastatic colorectal cancer
Authors: Ålgars Annika , Sundström Jari , Lintunen Minnamaija , Jokilehto Terhi , Kytölä Soili , Kaare Milja , Vainionpää Reetta , Orpana Arto , Österlund Pia , Ristimäki Ari , Carpen Olli , Ristamäki Raija
Published: November 2016

Anti‐EGFR antibodies are used for the treatment of RAS wild type metastatic colorectal cancer. We previously showed that EGFR gene copy number (GCN) predicts response to anti‐EGFR therapy in KRAS exon 2 wild type metastatic colorectal cancer. The aim of our study was to analyse the predictive role of EGFR GCN in RAS/BRAF/PIK3CA wild type metastatic colorectal cancer. The material included 102 patients with KRAS exon 2 wild type metastatic colorectal cancer treated with anti‐EGFR ± cytotoxic therapy. Next generation sequencing was used for KRAS, NRAS, BRAF and PIK3CA gene mutation analyses. EGFR GCN was analysed by EGFR immunohistochemistry guided automated silver in situ hybridisation. Increased EGFR GCN (≥4.0) predicted a better response and prolonged progression free survival in anti‐EGFR treated RAS/BRAF/PIK3CA wild type patients (Log‐rank test, p = 0.0004). In contrast, survival of RAS/BRAF/PIK3CA wild type, EGFR GCN below 4.0 patients did not differ from patients with mutant RAS, BRAF or PIK3CA. Our study indicates that EGFR GCN predicts anti‐EGFR treatment efficacy in patients with RAS/BRAF/PIK3CA wt metastatic CRC. Tumours with EGFR GCN below 4.0 appear to be as refractory to anti‐EGFR treatment as tumours with mutation in any of the RAS/RAF/PIK3CA pathway genes.
Genetic variants of JNK and p38α pathways and risk of non‐small cell lung cancer in an Eastern Chinese population
Authors: Jia Ming , Zhu Meiling , Zhou Fei , Wang Mengyun , Sun Menghong , Yang Yajun , Wang Xiaofeng , Wang Jiucun , Jin Li , Xiang Jiaqing , Zhang Yawei , Chang Jianhua , Wei Qingyi
Published: November 2016

The JNK and p38α pathways play an important role in carcinogenesis. Therefore, we hypothesize that single nucleotide polymorphisms (SNPs) of genes involved in these pathways are associated with risk of lung cancer. We first selected and genotyped 11 independent SNPs of the JNK and p38α pathway‐related genes in a discovery set of 1,002 non‐small cell lung cancer (NSCLC) cases and 1,025 cancer‐free controls of Eastern Chinese. Then, we validated those significant SNPs in a replication set of 1,333 NSCLC cases and 1,339 cancer‐free controls of Eastern Chinese. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to identify interactions between significant SNPs and other covariates. In both discovery and replication as well as their pooled analysis, carriers of GADD45G rs8252T variant genotypes had a significantly lower risk of NSCLC (adjusted OR = 0.81 and 0.79, 95% CI = 0.72–0.92 and 0.64–0.99 and p = 0.001 and 0.040 for dominant and recessive genetic models, respectively) and carriers of MAP2K7 rs3679T variant genotypes had an increased risk of NSCLC (adjusted OR = 1.19 and 1.29, 95% CI = 1.05–1.34 and 1.09–1.54 and p = 0.005 and 0.004 for dominant and recessive genetic models, respectively). Furthermore, rs8252 variant CT/TT carriers showed significantly higher levels of GADD45G mRNA expression than CC carriers in the target tissues. We observed some evidence of interactions between rs8252 genotypes and sex in NSCLC risk. These results indicate that GADD45G rs8252 and MAP2K7 rs3679 SNPs may be susceptibility biomarkers for NSCLC in Eastern Chinese populations.