bluuebunny/crossref_metadata_2025 huggingface dataset:
Fully Controlled 6 Meters per Pixel Mosaic of Mars's South Polar Region
Authors: Robbins Stuart J. , Kirchoff Michelle R. , Hoover Rachael H.
Published: September 2020

The Mars Reconnaissance Orbiter (MRO) spacecraft has been in operation around Mars since March 2006. The Context Camera (CTX), aboard MRO, has returned over 110,000 images of Mars at ≈5–6 m/px, providing nearly global coverage. Based on our work, reconstruction of MRO's orbit and camera pointing from ground tracking are offset from the Mars global coordinate system, with the 95th percentile of test points offset by ≈850 m, corresponding to ≈150 CTX pixels. While the original level of accuracy is potentially useful for some applications, providing relative control (image‐to‐image) and absolute or full control (image‐to‐ground reference) greatly improves the utility of the data. As a proof‐of‐concept, we have fully controlled all usable images of Mars Chart 30, Mare Australe, which is poleward of 65°S. This represents 4.7% of Mars's surface area and comprises 9,652 images (≈8% of the CTX catalog as of PDS release #48). The control was produced through a mixture of automated code and manual adjustment and validation, and mosaics were produced with manual input to provide a useful product with the best, most consistent images on top. The data—mosaics and updated SPICE kernels—are available to the community through NASA's Planetary Data System (PDS) Imaging and Cartography Annex. The workflow developed for this product is applicable to the remainder of Mars and other planetary bodies.
Diagenesis of Vera Rubin Ridge, Gale Crater, Mars, From Mastcam Multispectral Images
Authors: Horgan Briony H. N. , Johnson Jeffrey R. , Fraeman Abigail A. , Rice Melissa S. , Seeger Christina , Bell James F. , Bennett Kristen A. , Cloutis Edward A. , Edgar Lauren A. , Frydenvang Jens , Grotzinger John P. , L'Haridon Jonas , Jacob Samantha R. , Mangold Nicolas , Rampe Elizabeth B. , Rivera‐Hernandez Frances , Sun Vivian Z. , Thompson Lucy M. , Wellington Danika
Published: September 2020

Images from the Mars Science Laboratory (MSL) mission of lacustrine sedimentary rocks of Vera Rubin ridge on “Mt. Sharp” in Gale crater, Mars, have shown stark color variations from red to purple to gray. These color differences crosscut stratigraphy and are likely due to diagenetic alteration of the sediments after deposition. However, the chemistry and timing of these fluid interactions is unclear. Determining how diagenetic processes may have modified chemical and mineralogical signatures of ancient Martian environments is critical for understanding the past habitability of Mars and achieving the goals of the MSL mission. Here we use visible/near‐infrared spectra from Mastcam and ChemCam to determine the mineralogical origins of color variations in the ridge. Color variations are consistent with changes in spectral properties related to the crystallinity, grain size, and texture of hematite. Coarse‐grained gray hematite spectrally dominates in the gray patches and is present in the purple areas, while nanophase and fine‐grained red crystalline hematite are present and spectrally dominate in the red and purple areas. We hypothesize that these differences were caused by grain‐size coarsening of hematite by diagenetic fluids, as observed in terrestrial analogs. In this model, early primary reddening by oxidizing fluids near the surface was followed during or after burial by bleaching to form the gray patches, possibly with limited secondary reddening after exhumation. Diagenetic alteration may have diminished the preservation of biosignatures and changed the composition of the sediments, making it more difficult to interpret how conditions evolved in the paleolake over time.
Temporal Changes of Near‐Surface Air Temperature in Poland for 1781–2016 and in Tbilisi (Georgia) for 1881–2016
Authors: Modzelewska R. , Alania M. V. , Kapanadze N. I. , Khelaia E. I.
Published: September 2020

Analyses of near‐surface air temperature T in Poland for 1781–2016 and in Tbilisi (Georgia) for 1881–2016 have been carried out. We show that the centenary warming effect in Poland and in Tbilisi has almost the same peculiarities. An average centenary warming effect ΔT = (1.08 ± 0.29)°C is observed in Poland and in Tbilisi for 1881–2016. A warming effect is larger in winter season (ΔT = ~1.15°C) than in other seasons (average warming effect for these seasons ΔT = ~0.95°C). We show that a centenary warming is mainly related to the change of solar activity (estimated by sunspot number [SSN] and total solar irradiance [TSI]), particularly, a time interval about ~70 years (1890–1960), when correlation coefficients between 11‐year smoothed SSN and T, and TSI and T are high, r = 0.66 ± 0.07 and r = 0.73 ± 0.07 for Poland and r = 0.82 ± 0.05 and r = 0.90 ± 0.05 for Tbilisi, respectively; in this period solar activity contributes decisively in the global warming. We show that a global warming effect equals zero based on the temperature T data in Poland for period 1781–1880, when human activities were relatively less than in 1881–2016. We recognize a few feeble ~20 ± 3 years of disturbances in the temperature changes for period 1885–1980, most likely related with the fluctuations of solar magnetic cycles. We distinguish the fluctuations of ~7–8 years in Poland's T data, possibly connected with local effects of the North Atlantic Oscillation.
Depth Estimation of Potential Field Sources by Using Improved Chebyshev‐Padé Downward Continuation in Wave Number Domain
Authors: Yuan Yuan , Zhou Wenna , Zhang Xiangyu , Wu Guochao , Tang Shuiliang , Dai Weiming
Published: September 2020

Studies of downward continuation mainly focused on improving the stability more than depth calculation. Stable downward continuation is a promising technique for estimating the depth of sources. In this study, based on the filter curve in wave number domain, a new depth estimation method was developed using the Chebyshev‐Padé downward continuation method. First, the filter curves of Tikhonov regularized method and the Chebyshev‐Padé downward continuation method in wave number domain were compared. We concluded the reason that the Tikhonov regularized method can be used to obtain the depth information is that the filter curve converges to zero. Therefore, to use the Chebyshev‐Padé downward continuation method for calculating the depth, a simple low‐pass filter based on upward continuation was used to improve it in the wave number domain, making the filter curve of the new improved method converge to zero. Similar to the Tikhonov regularized method, our new method can obtain the depth information when calculating downward continuation data from the original level to an expected maximum depth level. To verify the effectivity, different synthetic models were used to test our method, indicating that the new method can achieve a more reasonable depth compared to the Tikhonov regularized method. Finally, the new method was applied to real magnetic data collected using unmanned aerial vehicle aeromagnetic surveys to test on a big car in Southeastern Zhejiang, China. The calculated depth matches with its actual depth. These results show that the new method is a useful depth estimation tool for potential field sources.
Tropical Cyclones Suppress Rainfall in Their Wakes
Authors: Kornei Katherine
Published: September 2020

Passing storms dredge up colder ocean water, curbing evaporation and decreasing cloud coverage and rainfall for weeks, satellite data reveal.
Miocene Subsidence and Surface Uplift of Southernmost Tibet Induced by Indian Subduction Dynamics
Authors: Shen T. , Wang G. , Replumaz A. , Husson L. , Webb A. A. G. , Bernet M. , Leloup P. H. , Zhang P. , Mahéo G. , Zhang K.
Published: September 2020

The Indus‐Yarlung suture of southernmost Tibet marks the initial collisional zone, the ongoing India‐Asia collision, and yet more than ~30 million years after the onset of collision, a thick detrital sedimentary unit was deposited just north of the suture: the Kailas Formation. The mechanism permitting subsidence of the deep intracontinental Kailas basin in a compressional tectonic regime remains uncertain. We present new apatite (16–11 Ma) and zircon (24–19 Ma) fission track (AFT and ZFT) ages from the Gangdese batholith just north of the Kailas basin. ZFT analysis of modern‐river sand from the northern Gangdese magmatic arc indicates an exhumation at 27.3 ± 1.3 Ma. Thermal modeling indicates that the batholith experienced reheating between 28 and 20 Ma, coeval with deposition in the Kailas basin (between 26 and 21 Ma), followed by overall rapid cooling between 20 and 17 Ma. We interpret this thermal history as a phase of regional Oligocene‐Miocene sedimentary burial followed by exhumation. By modeling mantle dynamics in the geodynamic framework of the India‐Asia collision, we show that transient dynamic topography over the relative southward folding of the Indian slab is consistent with burial and exhumation of the Gangdese magmatic arc during Oligocene‐Miocene time. The northward migration of the Indian continent relative to its own stati onary slab created a wave of dynamic topography that caused subsidence in the overriding plate north of the Himalaya, followed by a phase of surface uplift since ~27 Ma of the northern Gangdese magmatic arc. During latest Oligocene‐early Miocene time, the dynamic deflection center was in the Kailas area, and it progressively relocated southward to its present position at the Ganges basin.
The Impact of Life on Climate Stabilization Over Different Timescales
Authors: Höning Dennis
Published: September 2020

Surface life has been argued to be crucial in keeping a planet habitable in the long term. Biologically enhanced weathering compensates for increasing solar luminosity, and temperature‐dependent plant productivity weakens climate perturbations. Furthermore, a reduced calcification rate of marine organisms provides a negative feedback to rising atmospheric CO2. Here, I present a model of the long‐term carbon cycle including biological enhancement of weathering and marine calcification. Climate oscillations of periods from thousands to millions of years arise from a simple model of mountain uplift and erosion. I systematically study the influence of the biologically driven feedbacks on damping these oscillations. For oscillations of periods <2 Myr, the marine calcification feedback yields surface temperature amplitudes that are approximately 1/3 lower compared to a model that ignores this feedback. Abiotic oceans, however, would not necessarily imply a less stable climate on short timescales, due to a higher pH and thereby a higher buffer capacity. On longer timescales, the higher ocean pH would reduce climate stability, since the seafloor weathering feedback would work less efficiently. Biological enhancement of weathering helps stabilizing the climate against oscillations of periods >0.5 Myr. These findings are sensitive to the ratio of land to oceans, however. Furthermore, the mantle carbon degassing rate plays a role, since the temperature dependence of biological primary productivity may be smaller at higher temperatures. Altogether, life can be argued to stabilize the climate on timescales longer than some 100 kyr, while details depend on the geological state of the planet.
Proton Properties in Mercury's Magnetotail: A Statistical Study
Authors: Zhao J.‐T. , Zong Q.‐G. , Slavin J. A. , Sun W.‐J. , Zhou X.‐Z. , Yue C. , Raines J. M. , Ip W.‐H.
Published: September 2020

This study investigates the properties of protons in the magnetotail plasma sheet of Mercury. By superposing 5‐year measurements from the MESSENGER spacecraft, we obtain the average energy spectrum of protons in the plasma sheet, which can be fitted nicely by the Gaussian‐Kappa model. The proton density, pressure, and energy spectral index κ are found to be higher on the dawnside than on the duskside. The proton temperature shows a clearly outward radial gradient. The field‐aligned density profile indicates that the protons in the outer plasma sheet move adiabatically. The pitch angle distribution reveals the reflected fluxes to be always less than the incident fluxes and indicates the loss of protons due to their impact on the planetary surface.
Glacier Loss Impacts Riverine Organic Carbon Transport to the Ocean
Authors: Hood Eran , Fellman Jason B. , Spencer Robert G. M.
Published: September 2020

Lateral transport of organic carbon (OC) to the coastal ocean is an important component of the global carbon cycle because rivers transport, mineralize, and bury significant amounts of OC. Glaciers drive water and sediment export from many high‐elevation and high‐latitude ecosystems, yet their role in watershed OC balances is poorly understood, particularly with regard to particulate OC. Here, we evaluate seasonal water, sediment, and comprehensive OC budgets, including both dissolved and particulate forms, for three watersheds in southeast Alaska that vary in glacier coverage. We show that glacier loss will shift the dominant size fraction of riverine OC from particulate toward dissolved and potentially alter the provenance of particulate OC. Glacier coverage also controls whether OC export is source (C stock) or transport (runoff) limited at the watershed scale. These findings provide insight into the future trajectory of riverine OC export in glacierized regions.
Magnetosphere: From Plasma Observations to Reconnection Theory
Authors: Vasyliūnas Vytenis M.
Published: September 2020

I outline the development of my scientific work from graduate school to about the mid‐1980s (plus some mention of related later work), in particular the transition from instrument testing to data analysis to abstruse theory, and the origin of some of my key papers.
Is Coulomb Stress the Best Choice for Aftershock Forecasting?
Authors: Sharma Shubham , Hainzl Sebastian , Zöeller Gert , Holschneider Matthias
Published: September 2020

The Coulomb failure stress (CFS) criterion is the most commonly used method for predicting spatial distributions of aftershocks following large earthquakes. However, large uncertainties are always associated with the calculation of Coulomb stress change. The uncertainties mainly arise due to nonunique slip inversions and unknown receiver faults; especially for the latter, results are highly dependent on the choice of the assumed receiver mechanism. Based on binary tests (aftershocks yes/no), recent studies suggest that alternative stress quantities, a distance‐slip probabilistic model as well as deep neural network (DNN) approaches, all are superior to CFS with predefined receiver mechanism. To challenge this conclusion, which might have large implications, we use 289 slip inversions from SRCMOD database to calculate more realistic CFS values for a layered half‐space and variable receiver mechanisms. We also analyze the effect of the magnitude cutoff, grid size variation, and aftershock duration to verify the use of receiver operating characteristic (ROC) analysis for the ranking of stress metrics. The observations suggest that introducing a layered half‐space does not improve the stress maps and ROC curves. However, results significantly improve for larger aftershocks and shorter time periods but without changing the ranking. We also go beyond binary testing and apply alternative statistics to test the ability to estimate aftershock numbers, which confirm that simple stress metrics perform better than the classic Coulomb failure stress calculations and are also better than the distance‐slip probabilistic model.
Simulation of Topography Effects on Rockfall‐Generated Seismic Signals: Application to Piton de la Fournaise Volcano
Authors: Kuehnert J. , Mangeney A. , Capdeville Y. , Métaxian J. P. , Bonilla L. F. , Stutzmann E. , Chaljub E. , Boissier P. , Brunet C. , Kowalski P. , Lauret F. , Hibert C.
Published: September 2020

Seismic waves generated by rockfalls contain valuable information on the properties of these events. However, as rockfalls mainly occur in mountainous regions, the generated seismic waves can be affected by strong surface topography variations. We present a methodology for investigating the influence of topography using a Spectral‐Element‐based simulation of 3‐D wave propagation in various geological media. This methodology is applied here to Dolomieu crater on the Piton de la Fournaise volcano, Reunion Island, but it can be used for other sites, taking into account local topography and medium properties. The complexity of wave fields generated by single‐point forces is analyzed for different velocity models and topographies. Ground‐motion amplification is studied relative to flat reference models, showing that Peak Ground Velocity (PGV) and total kinetic energy can be amplified by factors of up to 10 and 20, respectively. Simulations with Dolomieu‐like crater shapes suggest that curvature variations are more influential than depth variations. Topographic effects on seismic signals from rockfalls at Dolomieu crater are revealed by interstation spectral ratios. Results suggest that propagation along the topography rather than source direction dominates the spectral ratios and that resulting radiation patterns can be neglected. The seismic signature of single rockfall impacts is studied. Using Hertz contact theory, impact force and duration are estimated and then used to scale simulations, achieving order‐of‐magnitude agreement with observed signal amplitudes and frequency thresholds. Our study shows that combining Hertz theory with high‐frequency seismic wave simulations on real topography improves the quantitative analysis of rockfall seismic signals.
Thermoelastic Dispersion and Attenuation of P and SV Wave Scattering by Aligned Fluid‐Saturated Cracks of Finite Thickness in an Isothermal Elastic Medium
Authors: Wei Jia , Fu Li‐Yun , Han Tongcheng , Carcione José M.
Published: September 2020

P and SV wave scattering by thermally constrained saturated cracks couples elastic deformation with temperature. We estimate the scattering attenuation and velocity dispersion by aligned fluid‐saturated cracks with finite thickness, which are sparsely and randomly embedded in an isothermal and isotropic elastic medium. By incorporating thermoelastic effects into the representation theorem with the non‐interaction Foldy approximation, we formulate the dispersion and attenuation of P and SV waves induced by displacement discontinuities across aligned cracks constrained by a thermoelastic boundary condition. The frequency‐dependent response as a function of temperature is calculated for various P and SV wave incidence angles. The resulting scattering attenuation and dispersion are compared with those of the conventional aligned‐crack model. The examples show that the dissipation increases with increasing temperature, but the scattering is inhibited at a given temperature. The P wave shows a strong sensitivity to temperature along the direction normal to the cracks, whereas the SV wave has an opposite behavior. This theory has the potential to assess the distribution of temperature from seismic attributes.
Structure and Density of H2O‐Rich Mg2SiO4 Melts at High Pressure From Ab Initio Simulations
Authors: Yuan Liang , Steinle‐Neumann Gerd , Suzuki Akio
Published: September 2020

Water has a strong effect on silicate melt properties, yet its dissolution mechanism in depolymerized melts, typical for mantle composition, remains poorly understood. Here we report results of first‐principles molecular dynamics simulations for hydrous Mg2SiO4 melts with 6, 16, and 27 wt% H2O at pressure and temperature conditions relevant to the upper mantle and mantle transition zone. The results show that hydrogen bonds not only to the network‐forming cation Si but also to Mg which—nevertheless—remains the most important network modifier. There is no evidence to support the hypothesis based on experimental data that water may cause an increase in melt polymerization for ultramafic magmas; the ratio of non‐bridging oxygen per Si increases with the addition of the oxygen from H2O. The partial molar volume of water is independent on concentration in our simulations which allows us to examine the density of hydrous melt systematically. The critical water content—at which melts are neutrally buoyant compared to the surrounding mantle—is ~4 wt% H2O for a pyrolite composition, much lower than the high water content (>10 wt%) observed in petrological experiments and estimated thermodynamically for low‐degree partial melts formed in the vicinity of the mantle transition zone.
Seasonal Physical Fronts and Associated Biogeochemical‐Ecological Effects off the Jiangsu Shoal in the Western Yellow Sea, China
Authors: Wei Qinsheng , Fu Mingzhu , Sun Junchuan , Yao Qingzhen , Wang Baodong , Liu Xuehai , Yu Zhigang
Published: September 2020

The Jiangsu Shoal and its adjacent area in the western Yellow Sea (YS) have become hotspots of ecological disasters in China and have attracted considerable attention. Based on remote sensing and field observations in this region, we investigated the physical fronts and their seasonal variations and clarified the spatiotemporal patterns of physical‐biogeochemical factors as well as their interactions and synergies. The results show that pronounced physical fronts were present in the study area. Specifically, arc‐ and “S”‐shaped thermal fronts existed off the shoal in summer and winter, respectively. The saline front largely expanded southeastward in spring, autumn, and winter, while it expanded northeastward in summer. The turbidity over the shoal was high year‐round, and a marked turbidity front was formed between the nearshore water and the offshore seawater. The seasonal patterns and variations of the physical fronts significantly influenced material transport. During cold seasons, the frontal system was responsible for the significant turbid water plume expanding in a southeastern direction from the Jiangsu Coast. In summer, the arc‐shaped thermal front confined the turbid water within the shoal. The expansion of excess dissolved inorganic nitrogen was consistent with the saline front, and the vertical transport of nutrients by upwelling occurred off the shoal in summer. Due to favorable conditions, the frontal region off the shoal is prone to high chlorophyll a (Chl‐a) and may act as oases in either summer or winter. A conceptual diagram is assembled to provide an overview of physical‐biogeochemical‐ecological interactions off the Jiangsu Shoal in the western YS.
Investigation of the Variability of Near‐Surface Temperature Anomaly and Its Causes Over the Tibetan Plateau
Authors: Liu Ye , Xue Yongkang , Li Qian , Lettenmaier Dennis , Zhao Ping
Published: September 2020

Recent research has reported the great influence of springtime land surface temperature (LST) and subsurface temperature (SUBT) over the Tibetan Plateau (TP) on downstream region summer precipitation, indicating the potential application of LST/SUBT on subseasonal to seasonal (S2S) prediction. In this study, we employed both observational data and offline model simulation to explore the memory of surface and subsurface variables and assess the driving effects of snow/albedo and SUBT on the LST anomaly. Our composite analysis based on observation shows that the anomalous LST in the TP can sustain for seasons and is accompanied by persistent SUBT as well as snow and associated surface albedo anomalies. A multilayer frozen soil model reproduces the observed LST anomaly and shows surface albedo and middle‐layer SUBT have 1–3 months memory, indicating the degree of persistence or dissipation of anomaly through time with more extended memory during spring. With simulated middle‐layer SUBT as a predictor, the linear regression model produces
of 0.44 and 0.26 for 1‐ and 2‐month LST prediction, respectively. The predictability is higher during the spring. Our results also show February snowfall, May snowmelt, and aero in snow exert substantial impacts on springtime LST through snow albedo feedback. The long memory of SUBT allows it to preserve the surface thermal anomaly and release it gradually in the following months to seasons. Meanwhile, the sensitivity study indicates that the soil properties and soil column depth predominate SUBT memory, which suggests the key processes to improve LST/SUBT then downstream S2S prediction.
Diurnal Climatology of Planetary Boundary Layer Height Over the Contiguous United States Derived From AMDAR and Reanalysis Data
Authors: Zhang Yuanjie , Sun Kang , Gao Zhiqiu , Pan Zaitao , Shook Michael A. , Li Dan
Published: September 2020

The diurnal variation of the planetary boundary layer height (PBLH) over the contiguous United States (CONUS) is examined using Aircraft Meteorological Data Reports (AMDAR) at 54 major airports and the ERA5 reanalysis product. The bulk Richardson number method is used to derive the PBLH at hourly scales from the AMDAR profiles. It is found that the estimated PBLH is sensitive to the value of the critical bulk Richardson number and to the consideration of the surface friction effect, especially under stable and near‐neutral conditions. Parameters constrained by field campaign observations are finally selected to estimate the PBLH. The results reveal that the diurnal climatology of PBLH exhibits seasonal and spatial variations, with greater diurnal variations in spring and summer and in the western regions. It is demonstrated that the traditional twice‐daily radiosonde data may roughly capture the diurnal amplitude of PBLH in the western but not the eastern CONUS. Compared to the AMDAR data, the ERA5 reanalysis product overestimates the daytime PBLH throughout the CONUS by 18–41% and shows an earlier peak time by 1–2 hr in the western regions and a later peak time by 1 hr in the eastern regions.
COnstraining ORographic Drag Effects (COORDE): A Model Comparison of Resolved and Parametrized Orographic Drag
Authors: van Niekerk Annelize , Sandu Irina , Zadra Ayrton , Bazile Eric , Kanehama Takafumi , Köhler Martin , Koo Myung‐Seo , Choi Hyun‐Joo , Kuroki Yukihiro , Toy Michael D. , Vosper Simon B. , Yudin Valery
Published: September 2020

The parametrization of orographic drag processes is a major source of circulation uncertainty in models. The COnstraining ORographic Drag Effects (COORDE) project makes a coordinated effort to narrow this uncertainty by bringing together the modeling community to: explore the variety of orographic drag parametrizations employed in current operational models; assess the resolution sensitivity of resolved and parametrized orographic drag across models; and to validate the parametrized orographic drag in low‐resolution simulations using explicitly resolved orographic drag from high‐resolution simulations. Eleven models from eight major modeling centers are used to estimate resolved orographic drag from high‐resolution (km‐scale) simulations and parametrized orographic drag from low‐resolution simulations, typically used for seasonal forecasting (∼40 km) and climate projections (∼100 km). In most models, at both seasonal and climate resolutions, the total (resolved plus parametrized) orographic gravity wave drag over land is shown to be underestimated by a considerable amount (up to 50%) over the Northern and Southern Hemisphere and by more than 60% over the Middle East region, with respect to the resolved gravity wave drag estimated from km‐scale simulations. The km‐scale simulations also provide evidence that the parametrized surface stress and the parametrized low‐level orographic drag throughout the troposphere are overestimated in most models over the Middle East region, particularly at climate resolutions. Through this process‐based evaluation, COORDE provides model developers new valuable information on the current representation of orographic drag at seasonal and climate resolutions and the vertical partitioning of orographic low‐level and gravity wave drag.
Correction: The Smart Life Stay (SLS) program: effects of a lifestyle intervention program in combination with health tourism and health guidance for type 2 diabetes
Authors: Matsushita Madoka , Muramoto Akiko , Nomura Eri , Eguchi Yukari , Kato Ayako , Sano Yoshiko , Kabayama Mai , Arakawa Masashi , Oguma Yuko , Yabe Daisuke , Matsunaga Masaaki , Yatsuya Hiroshi , Arima Hiroshi , Tsushita Kazuyo
Published: September 2020

Following publication, the authors asked to add the following institution to the affiliations of author Madoka Matsushita: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine Both the PDF and HTML versions of the Article have been updated accordingly.
Sarcoma stratification by combined pH2AX and MAP17 (PDZK1IP1) levels for a better outcome on doxorubicin plus olaparib treatment
Authors: Perez Marco , García-Heredia José Manuel , Felipe-Abrio Blanca , Muñoz-Galván Sandra , Martín-Broto Javier , Carnero Amancio
Published: September 2020

Sarcomas constitute a rare heterogeneous group of tumors, including a wide variety of histological subtypes. Despite advances in our understanding of the pathophysiology of the disease, first-line sarcoma treatment options are still limited and new treatment approaches are needed. Histone H2AX phosphorylation is a sensitive marker for double strand breaks and has recently emerged as biomarker of DNA damage for new drug development. In this study, we explored the role of H2AX phosphorylation at Ser139 alone or in combination with MAP17 protein, an inducer of DNA damage through ROS increase, as prognostic biomarkers in sarcoma tumors. Next, we proposed doxorubicin and olaparib combination as potential therapeutic strategies against sarcomas displaying high level of both markers. We evaluate retrospectively the levels of pH2AX (Ser139) and MAP17 in a cohort of 69 patients with different sarcoma types and its relationship with clinical and pathological features. We found that the levels of pH2AX and MAP17 were related to clinical features and poor survival. Next, we pursued PARP1 inhibition with olaparib to potentiate the antitumor effect of DNA damaging effect of the DNA damaging agent doxorubicin to achieve an optimal synergy in sarcoma. We demonstrated that the combination of olaparib and doxorubicin was synergistic in vitro, inhibiting cell proliferation and enhancing pH2AX intranuclear accumulation, as a result of DNA damage. The synergism was corroborated in patient-derived xenografts (PDX) where the combination was effective in tumors with high levels of pH2AX and MAP17, suggesting that both biomarkers might potentially identify patients who better benefit from this combined therapy.
Recent advances in the development of protein–protein interactions modulators: mechanisms and clinical trials
Authors: Lu Haiying , Zhou Qiaodan , He Jun , Jiang Zhongliang , Peng Cheng , Tong Rongsheng , Shi Jianyou
Published: September 2020

Protein–protein interactions (PPIs) have pivotal roles in life processes. The studies showed that aberrant PPIs are associated with various diseases, including cancer, infectious diseases, and neurodegenerative diseases. Therefore, targeting PPIs is a direction in treating diseases and an essential strategy for the development of new drugs. In the past few decades, the modulation of PPIs has been recognized as one of the most challenging drug discovery tasks. In recent years, some PPIs modulators have entered clinical studies, some of which been approved for marketing, indicating that the modulators targeting PPIs have broad prospects. Here, we summarize the recent advances in PPIs modulators, including small molecules, peptides, and antibodies, hoping to provide some guidance to the design of novel drugs targeting PPIs in the future.
Evaluation of a novel fixed-space maintainer made of light-cured acrylic resin: an in vitro study
Authors: Souror Yasser R. , Maaly Tayseer , Khawandanah Mohammed Sameer
Published: September 2020

To evaluate a fixed-space maintainer made of light-cure acrylic resin (LCAR) for its flexural and shear bond strength using different bonding systems to the enamel. 45 extracted primary teeth were selected. They were randomly divided into three equal groups (n = 15) along with the type of adhesive system (Tetric Flow, Transbond XT, and Fuji Ortho LC) used for bonding (LCAR) to the tooth surface. Surfaces were treated; LCAR was attached to the treated surfaces using a split Teflon mold. For flexural strength testing, ten bars of LCAR were made using another Teflon-split mold. Shear bond strength and mean flexural strength values were evaluated by a universal testing machine. The highest values of bond strength were recorded for Transbond XT, followed by Tetric Flow, while the lowest values were for Fuji Ortho LC. Various groups had a significant difference as investigated by ANOVA. ARI scores showed no significant difference in debond sites. Mean value and standard deviation of flexural strength for LCAR were 82.83  ± 5.2. LCAR has superior mechanical properties and could be an alternative to currently-in-use space maintainer though in vivo and in vitro trials are needed to progress the ultimate design of LCAR.
Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-κB pathway
Authors: Chen Junxiong , Yang Xiangling , Liu Ruixian , Wen Chuangyu , Wang Huihui , Huang Lanlan , Li Weiqian , Zhu Zefeng , Zhu Yonglin , Liu Huanliang
Published: September 2020

Circular RNAs (circRNAs) are a newly discovered type of biological molecule that belongs to the noncoding RNA family. Abundant evidence has shown that circRNAs are involved in the progression of various cancers. However, the particular functions of circRNAs in colorectal cancer (CRC) remain elusive. In this study, we investigated the differentially expressed circRNAs in three pairs of cancer tissue and adjacent normal tissue of CRC. We revealed that circGLIS2 expression was higher in CRC tissue and cell lines. Gain-and-loss function assays showed that circGLIS2 was involved in the regulation of cell migration. Moreover, overexpressing circGLIS2 in CRC cells activated the NF-κB pathway and induced pro-inflammatory chemokine production, which evoked tumor-associated inflammation through recruiting leukocytes. In turn, when the cancer cells were exposed to the supernatant of circGLIS2 overexpressed cancer cells, they were endowed with the ability of migration and chemokines production. Furthermore, the rescue assay confirmed that circGLIS2 activated NF-κB signaling and promoted cell migration by sponging miR-671. Overall, our study reveals that circGLIS2, acting as a potential oncogene, maintains the abnormal activation state of the NF-κB signaling pathway via the miR-671 sponge mechanism in CRC cells. This study provides a scientific basis for targeting circGLIS2 in colorectal cancer interventions.
Together we stand, apart we fall: how cell-to-cell contact/interplay provides resistance to ferroptosis
Authors: Vucetic Milica , Daher Boutaina , Cassim Shamir , Meira Willian , Pouyssegur Jacques
Published: September 2020

Contextualisation of the new type of cell death called “ferroptosis” opened a completely new avenue for the development of anti-cancer therapies. Cumulative fundamental research dating back to the mid-20th century, crowned by the extraordinary work of the group led by Dr. Stockwell from Columbia University in 2012, finally got its candidature to be applied in the clinical settings. Although the potential for clinical importance is undoubtedly growing every day, as showed by the increasing number of papers dealing with ferroptosis and its applications, long experience of cancer research and treatment taught us that caution is still necessary. The plasticity of the tumour cells, particularly acute, along with its involvement in the resistance mechanisms, that have been seen, to greater or lesser extent, for almost all currently used therapies, represents the biggest fascinations in biomedical research field and also the biggest challenge to achieving cures in cancer patients. Accordingly, the main features of fundamental research have to be vigilance and anticipation. In this review, we tried to summarize the literature data, accumulated in the past couple of years, which point out the pitfalls in which “ferroptosis inducers” can fall if used prematurely in the clinical settings, but at the same time can provide a great advantage in the exhausting battle with cancer resistance. This is the first comprehensive review focusing on the effects of the cell-to-cell contact/interplay in the development of resistance to ferroptosis, while the contribution of cell-born factors has been summarized previously so here we just listed them.
Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway
Authors: Bildik Gamze , Akin Nazli , Esmaeilian Yashar , Hela Francesko , Yildiz Ceren Sultan , Iltumur Ece , İncir Said , Karahuseyinoglu Sercin , Yakin Kayhan , Oktem Ozgur
Published: September 2020

Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.
Transcriptomic profiling of human cardiac cells predicts protein kinase inhibitor-associated cardiotoxicity
Authors: van Hasselt J. G. Coen , Rahman Rayees , Hansen Jens , Stern Alan , Shim Jaehee V. , Xiong Yuguang , Pickard Amanda , Jayaraman Gomathi , Hu Bin , Mahajan Milind , Gallo James M. , Goldfarb Joseph , Sobie Eric A. , Birtwistle Marc R. , Schlessinger Avner , Azeloglu Evren U. , Iyengar Ravi
Published: September 2020

Kinase inhibitors (KIs) represent an important class of anti-cancer drugs. Although cardiotoxicity is a serious adverse event associated with several KIs, the reasons remain poorly understood, and its prediction remains challenging. We obtain transcriptional profiles of human heart-derived primary cardiomyocyte like cell lines treated with a panel of 26 FDA-approved KIs and classify their effects on subcellular pathways and processes. Individual cardiotoxicity patient reports for these KIs, obtained from the FDA Adverse Event Reporting System, are used to compute relative risk scores. These are then combined with the cell line-derived transcriptomic datasets through elastic net regression analysis to identify a gene signature that can predict risk of cardiotoxicity. We also identify relationships between cardiotoxicity risk and structural/binding profiles of individual KIs. We conclude that acute transcriptomic changes in cell-based assays combined with drug substructures are predictive of KI-induced cardiotoxicity risk, and that they can be informative for future drug discovery.
Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma
Authors: Tseng Hsiang-chi , Xiong Wei , Badeti Saiaditya , Yang Yan , Ma Minh , Liu Ting , Ramos Carlos A. , Dotti Gianpietro , Fritzky Luke , Jiang Jie-gen , Yi Qing , Guarrera James , Zong Wei-Xing , Liu Chen , Liu Dongfang
Published: September 2020

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.
Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics
Authors: Yu Jinhua , Deng Yinhui , Liu Tongtong , Zhou Jin , Jia Xiaohong , Xiao Tianlei , Zhou Shichong , Li Jiawei , Guo Yi , Wang Yuanyuan , Zhou Jianqiao , Chang Cai
Published: September 2020

Non-invasive assessment of the risk of lymph node metastasis (LNM) in patients with papillary thyroid carcinoma (PTC) is of great value for the treatment option selection. The purpose of this paper is to develop a transfer learning radiomics (TLR) model for preoperative prediction of LNM in PTC patients in a multicenter, cross-machine, multi-operator scenario. Here we report the TLR model produces a stable LNM prediction. In the experiments of cross-validation and independent testing of the main cohort according to diagnostic time, machine, and operator, the TLR achieves an average area under the curve (AUC) of 0.90. In the other two independent cohorts, TLR also achieves 0.93 AUC, and this performance is statistically better than the other three methods according to Delong test. Decision curve analysis also proves that the TLR model brings more benefit to PTC patients than other methods.
Probing magnetism in atomically thin semiconducting PtSe2
Authors: Avsar Ahmet , Cheon Cheol-Yeon , Pizzochero Michele , Tripathi Mukesh , Ciarrocchi Alberto , Yazyev Oleg V. , Kis Andras
Published: September 2020

Atomic-scale disorder in two-dimensional transition metal dichalcogenides is often accompanied by local magnetic moments, which can conceivably induce long-range magnetic ordering into intrinsically non-magnetic materials. Here, we demonstrate the signature of long-range magnetic orderings in defective mono- and bi-layer semiconducting PtSe2 by performing magnetoresistance measurements under both lateral and vertical measurement configurations. As the material is thinned down from bi- to mono-layer thickness, we observe a ferromagnetic-to-antiferromagnetic crossover, a behavior which is opposite to the one observed in the prototypical 2D magnet CrI3. Our first-principles calculations, supported by aberration-corrected transmission electron microscopy imaging of point defects, associate this transition to the interplay between the defect-induced magnetism and the interlayer interactions in PtSe2. Furthermore, we show that graphene can be effectively used to probe the magnetization of adjacent semiconducting PtSe2. Our findings in an ultimately scaled monolayer system lay the foundation for atom-by-atom engineering of magnetism in otherwise non-magnetic 2D materials.
Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development
Authors: Ambati Jayakrishna , Magagnoli Joseph , Leung Hannah , Wang Shao-bin , Andrews Chris A. , Fu Dongxu , Pandey Akshat , Sahu Srabani , Narendran Siddharth , Hirahara Shuichiro , Fukuda Shinichi , Sun Jian , Pandya Lekha , Ambati Meenakshi , Pereira Felipe , Varshney Akhil , Cummings Tammy , Hardin James W. , Edun Babatunde , Bennett Charles L. , Ambati Kameshwari , Fowler Benjamin J. , Kerur Nagaraj , Röver Christian , Leitinger Norbert , Werner Brian C. , Stein Joshua D. , Sutton S. Scott , Gelfand Bradley D.
Published: September 2020

Innate immune signaling through the NLRP3 inflammasome is activated by multiple diabetes-related stressors, but whether targeting the inflammasome is beneficial for diabetes is still unclear. Nucleoside reverse-transcriptase inhibitors (NRTI), drugs approved to treat HIV-1 and hepatitis B infections, also block inflammasome activation. Here, we show, by analyzing five health insurance databases, that the adjusted risk of incident diabetes is 33% lower in patients with NRTI exposure among 128,861 patients with HIV-1 or hepatitis B (adjusted hazard ratio for NRTI exposure, 0.673; 95% confidence interval, 0.638 to 0.710; P < 0.0001; 95% prediction interval, 0.618 to 0.734). Meanwhile, an NRTI, lamivudine, improves insulin sensitivity and reduces inflammasome activation in diabetic and insulin resistance-induced human cells, as well as in mice fed with high-fat chow; mechanistically, inflammasome-activating short interspersed nuclear element (SINE) transcripts are elevated, whereas SINE-catabolizing DICER1 is reduced, in diabetic cells and mice. These data suggest the possibility of repurposing an approved class of drugs for prevention of diabetes.
Understanding electrochemical switchability of perovskite-type exsolution catalysts
Authors: Opitz Alexander K. , Nenning Andreas , Vonk Vedran , Volkov Sergey , Bertram Florian , Summerer Harald , Schwarz Sabine , Steiger-Thirsfeld Andreas , Bernardi Johannes , Stierle Andreas , Fleig Jürgen
Published: September 2020

Exsolution of metal nanoparticles from perovskite-type oxides is a very promising approach to obtain catalysts with superior properties. One particularly interesting property of exsolution catalysts is the possibility of electrochemical switching between different activity states. In this work, synchrotron-based in-situ X-ray diffraction experiments on electrochemically polarized La0.6Sr0.4FeO3-δthin film electrodes are performed, in order to simultaneously obtain insights into the phase composition and the catalytic activity of the electrode surface. This shows that reversible electrochemical switching between a high and low activity state is accompanied by a phase change of exsolved particles between metallic α-­Fe and Fe-oxides. Reintegration of iron into the perovskite lattice is thus not required for obtaining a switchable catalyst, making this process especially interesting for intermediate temperature applications. These measurements also reveal how metallic particles on La0.6Sr0.4FeO3-δelectrodes affect the H2oxidation and H2O splitting mechanism and why the particle size plays a minor role.