bluuebunny/crossref_metadata_2025 huggingface dataset:
Fourteenth Century England IX
Authors: Morgan Philip , Dryburgh Paul , Foley ine , Guyol Christopher , King Andy , Knowles Jessica , McVitty Amanda , Morgan David , Robinson David
Published: May 2022

The wide-ranging studies collected here reflect the latest concerns of and trends in fourteenth-century research, including work on politics, the law, religion, and chronicle writing. The lively (andcontroversial) debate around the death of Edward II, and the brief but eventful career of John of Eltham, earl of Cornwall, receive detailed treatment, as does the theory and implementation of both the law of treason in England and high status execution in Ireland. There is an investigation of the often overlooked, yet ever present, lesser parish clergy of pre-Black Death England, along with the notable connections between Roman remains and craft guild piety in fourteenth-century York. There are also chapters shedding new light on fourteenth-century chronicles: one examines the St Albans chronicle through the prism of chivalric culture, another analyses the importance of the Chester Annals of 1385-8 in the writing culture of the Midlands. Introduced with this volume is a new section on "Notes and Documents"; re-examined here is an often-cited letter from the reign of Richard II and the problematic, yet crucial, issue of its authorship and dating. James Bothwell is Lecturer in Later Medieval History at the University of Leicester; Gwilym Dodd is Associate Professor of Medieval History at the University of Nottingham  Contributors: Paul Dryburgh, ine Foley, Christopher Guyol, Andy King, Jessica Knowles, E. Amanda McVitty, D.A.L. Morgan, Philip Morgan, David Robinson.
China's Naval Operations in the South China Sea
Authors: Elleman Bruce
Published: May 2022

This book provides a history of the South China Sea conflict and lays out the stakes for each of the bordering states and China’s interaction with them - namely, Vietnam, the Philippines, Brunei, Malaysia, Taiwan, and Indonesia; it also examines the US government’s role in the region. China’s Naval Operations in the South China Sea is highly topical; it examines the evolving perception of the People’s Republic of China’s (PRC) of the South China Sea (SCS), and Beijing’s accompanying maritime strategy to claim the islands and waters, particularly in the context of the strategies of the neighbouring stake-holding nations. In addition to long-standing territorial disputes over the islands and waters of the SCS, China and the other littoral states - Vietnam, the Philippines, Brunei, Malaysia, Taiwan, and Indonesia - have growing and often mutually exclusive interests in the offshore energy reserves and fishing grounds. Many other countries outside of the region worry about the protection of sea lines of communication for military and commercial traffic, oil tankers in particular. These differences have been expressed in the increasing frequency and intensity of maritime incidents, involving both naval and civilian vessels, sometimes working in coordination against naval or civilian targets. Each chapter on the littoral states closely examines that state’s territorial claims to the islands and waters of the SCS, its primary economic and military interests in these areas, its views on the sovereignty disputes over the entire SCS, its strategy to achieve its objectives, and its views on the U.S. involvement in any and all of these issues.
The Call of Japan
Authors: Brinckmann Hans
Published: May 2022

Part personal memoir, part professional flashback, part socio-cultural commentary, The Call of Japan chronicles the author’s experiences during his forty years of living in Japan, from 1950 to 1974 as a ‘reluctant banker’, and from 2003 to the present as a writer. The Call of Japan comments extensively on the country’s economic, political and cultural realities during the crucial early years of post-war reconstruction as well as during more recent times.
Divergent Representation of Precipitation Recycling in the Amazon and the Congo in CMIP6 Models
Authors: Baker J. C. A. , Spracklen D. V.
Published: May 2022

Moisture evaporated from the land contributing to precipitation in a given area is known as precipitation recycling and needs to be accurately represented in climate models. The Amazon and Congo basins are reported to have the highest precipitation recycling rates globally, but model representation has not yet been assessed over these regions. We evaluated recycling over the Amazon and Congo in 45 Coupled Model Intercomparison Project Phase 6 models. Regional annual means from models and reanalyzes agreed well over both basins. Models captured seasonal variation in recycling over the Congo but there was a large‐scale underestimation of recycling during the Amazon dry‐to‐wet transition season relative to ERA5, caused by models underestimating Amazon evapotranspiration and overestimating incoming wind speed and associated water vapor imports. Both regions show robust declines in precipitation recycling over the next century under future climate‐change scenarios. Our results suggest models may underestimate impacts of deforestation on regional precipitation in the Amazon.
Coastal Downwelling Intensifies Landfalling Hurricanes
Authors: Gramer Lewis J. , Zhang Jun A. , Alaka Ghassan , Hazelton Andrew , Gopalakrishnan Sundararaman
Published: May 2022

This study demonstrates a link between coastal downwelling and tropical cyclone (TC) intensification. We show that coastal downwelling increases air‐sea enthalpy (heat, moisture) fluxes ahead of TCs as they approach land, creating conditions conducive to intensification even in the presence of typically inhibiting factors like strong vertical wind shear. The study uses a coupled TC model (HWRF‐B) and buoy observations to demonstrate that coastal downwelling developed as three TCs in 2020 approached land. Results show downwelling maintained warmer sea‐surface temperatures over the ocean shelf, enhancing air‐sea temperature/humidity contrasts. We found that in such cases resulting air‐sea enthalpy fluxes can replenish the boundary‐layer even when cool, dry air intrudes, as in sheared storms and storms approaching continental land‐masses. The resulting warm, moist air is advected into the TC inner core, enhancing convective development, thus providing energy for TC intensification. These results indicate coastal downwelling can be important in forecasting TC intensity change before landfall.
Southeastern Tibetan Plateau Growth Revealed by Inverse Analysis of Landscape Evolution Model
Authors: Yuan X. P. , Jiao R. , Dupont‐Nivet G. , Shen X.
Published: May 2022

The Cenozoic history of the Tibetan Plateau topography is critical for understanding the evolution of the Indian‐Eurasian collision, climate, and biodiversity. However, the long‐term growth and landscape evolution of the Tibetan Plateau remain ambiguous, it remains unclear if plateau uplift occurred soon after the India‐Asia collision in the Paleogene (∼50–25 Ma) or later in the Neogene (∼20–5 Ma). Here, we reproduce the uplift history of the southeastern Tibetan Plateau using a 2D landscape evolution model, which simultaneously solves fluvial erosion and sediment transport processes in the drainage basins of the Three Rivers region (Yangtze, Mekong, and Salween Rivers). Our model was optimized through a formal inverse analysis with 20,000 forward simulations, which aims to reconcile the transient states of the present‐day river profiles. The results, compared to existing paleoelevation and thermochronologic data, suggest initially low elevations (∼300–500 m) during the Paleogene, followed by a gradual southeastward propagation of topographic uplift of the plateau margin.
First Record of Oceanic Anoxic Event 1d at Southern High Latitudes: Sedimentary and Geochemical Evidence From International Ocean Discovery Program Expedition 369
Authors: Fan Qingchao , Xu Zhaokai , MacLeod Kenneth G. , Brumsack Hans‐Jürgen , Li Tiegang , Chang Fengming , Wan Shiming , Riquier Laurent , Fu Delong , Luan Zhendong , Duan Baichuan , Chen Hongjin , Wang Wei , Lim Dhongil
Published: May 2022

Oceanic anoxic event 1d (OAE 1d) has been well studied at northern low latitudes (i.e., in Tethys and the North Atlantic); however, the paleoenvironmental response to this event at high latitudes has not been documented and the triggering mechanism remains unknown. Here, we address both of these shortcomings by presenting the first detailed sedimentary and multi‐proxy geochemical record of the OAE 1d at southern high latitudes (60–62°S), obtained from sediments using Site U1513, IODP Expedition 369. Biostratigraphic and chemostratigraphic data support correlation of the interval studied with OAE 1d, and the sedimentary mercury proxy reveals that at least at Site U1513, OAE 1d is associated with the Central Kerguelen large igneous province volcanism. Furthermore, the significant increase in continental runoff and consequent terrigenous input from southwestern Australia in the southeastern proto‐India Ocean might have resulted in regionally weakened bottom‐water oxygenation and strengthened organic matter burial during OAE 1d.
Constraining the Earth's Dynamical Ellipticity From Ice Age Dynamics
Authors: Farhat Mohammad , Laskar Jacques , Boué Gwenaël
Published: May 2022

The dynamical ellipticity of a planet expresses the departure of its mass distribution from spherical symmetry. It enters as a parameter in the description of a planet's precession and nutation, as well as other rotational normal modes. In the case of the Earth, uncertainties in this quantity's history produce an uncertainty in the solutions for the past evolution of the Earth‐Moon system. Constraining this history has been a target of interdisciplinary efforts as it represents an astro‐geodetic parameter whose variation is shaped by geophysical processes, and whose imprints can be found in the geological signal. We revisit the classical problem of its variation during ice ages, where glacial cycles exerted a varying surface loading that had altered the shape of the geoid. In the framework of glacial isostatic adjustment, and with the help of a recent paleoclimatic proxy of ice volume, we present the evolution of the dynamical ellipticity over the Cenozoic ice ages. We map out the problem in full generality identifying major sensitivities to surface loading and internal variations in parameter space. This constrained evolution is aimed to be used in future astronomical computations of the orbital and insolation quantities of the Earth.
A Mechanistic Model for Mud Flocculation in Freshwater Rivers
Authors: Nghiem Justin A. , Fischer Woodward W. , Li Gen K. , Lamb Michael P.
Published: May 2022

The transport and deposition of mud in rivers are key processes in fluvial geomorphology and biogeochemical cycles. Recent work indicates that flocculation might regulate fluvial mud transport by increasing mud settling velocities, but we lack a calibrated mechanistic model for flocculation in freshwater rivers. Here, we developed and calibrated a semi‐empirical model for floc diameter and settling velocity in rivers. We compiled a global data set of river suspended sediment concentration‐depth profiles and inverted them for in situ settling velocity using the Rouse‐Vanoni equation. On average, clay and silt (diameters <39 μm) are flocculated with settling velocity of 1.8 mm s−1 and floc diameter of 130 μm. Among model variables, Kolmogorov microscale has the strongest positive correlation with floc diameter, supporting the idea that turbulent shear limits floc size. Sediment Al/Si (a mineralogy proxy) has the strongest negative correlation with floc diameter and settling velocity, indicating the importance of clay abundance and composition for flocculation. Floc settling velocity increases with greater mud and organic matter concentrations, consistent with flocculation driven by particle collisions and binding by organic matter which is often concentrated in mud. Relative charge density (a salinity proxy) correlates with smaller floc settling velocities, a finding that might reflect the primary particle size distribution and physical hosting of organic matter. The calibrated model explains river floc settling velocity data within a factor of about two. Results highlight that flocculation can impact the fate of mud and particulate organic carbon, holding implications for global biogeochemical cycles.
Sediment Residence Times in Large Rivers Quantified Using a Cosmogenic Nuclides Based Transport Model and Implications for Buffering of Continental Erosion Signals
Authors: Ben‐Israel Michal , Armon Moshe , ASTER Team  , Matmon Ari
Published: May 2022

The weathering of continental surfaces and the transport of sediments via rivers into the oceans is an integral part of the dynamic processes that shape the Earth's surface. To understand how tectonic and climatic forcings control regional rates of weathering, we must be able to identify their effects on sedimentary archives over geologic timescales. Cosmogenic nuclides are a valuable tool to study rates of surface processes and have long been applied in fluvial systems to quantify basin‐wide erosion rates. However, in large rivers, continual processes of erosion and deposition during sediment transport make it difficult to constrain how long sediments spend within the fluvial system. In this study, we examine the role of rivers in buffering erosional signals by constraining the timescales of fluvial transport in large rivers across the world. We apply a stochastic numerical model based on measurements of cosmogenic nuclides concentrations and calculate sediment residence times of 104–105 years in large rivers. These timescales are equal to or longer than climatic cycles, implying that changes to rates of erosion brought on by climatic variations are buffered during transport in large rivers and may not be recognizable in the sedimentary record.
Magnetostratigraphy of Abyssal Deposits in the Central Philippine Sea and Regional Sedimentary Dynamics During the Quaternary
Authors: Yi Liang , Hu Bangqi , Zhao Jingtao , Jiang Xingyu , Shu Yeqiang , Wang Xingxing , Guo Jianwei , Wang Feifei , Ding Xue , Liu Geng , Chen Weiwei , Li Yibing , Deng Chenglong
Published: May 2022

The Philippine Sea is a typical region of aeolian dust reposition and is located within the Western Pacific Warm Pool. Here, we use the paleomagnetic stratigraphy and the grain‐size distributions of Quaternary abyssal deposits in the Central Philippine Sea to investigate the factors controlling regional sedimentary and paleoenvironmental changes. Our principal results are as follows: (a) A reliable geochronologic framework for Quaternary sediments in the Central Philippine Sea is established. (b) An eastward expansion of the regional depocenter in the Middle Pleistocene is observed. (c) The mean grain size of the abyssal sediments is 7–8 µm, and there are only minor differences between the sites. Comparison of the geochronological framework with various paleoenvironmental events during the Mid‐Pleistocene Transition shows that sedimentary processes can be correlated to a major transition in global climate which affected regions from the Asian interior to the tropical Pacific, and that changes in aeolian sedimentation are likely the predominant factor responsible. A derived grain‐size proxy of the sedimentary dynamics and its comparison with various paleoenvironmental proxies show that the relative contributions are roughly estimated as 23%, 9%, and 68% for aeolian inputs, oceanic circulation, and the tropical Pacific zonal SST gradient, respectively, in the studied region. The relative importance of tropical processes in abyssal sedimentary dynamics highlights the possibility of the long‐term influence of (sub)mesoscale eddies in the upper ocean, via regional upwelling and unique submarine topography, on the deepest part (>5,000 m) of the Central Philippine Sea, from meteorological to geological timescales.
Reconstruction of Chemical Weathering Intensity and Asian Summer Monsoon Evolution in the Red River Basin Over the Past 36 kyr
Authors: Li Mingkun , Ouyang Tingping , Zhu Zhaoyu , Tian Chengjing , Peng Shasha , Zhong Hexian , Peng Xuechao , Qiu Yan
Published: May 2022

The Red River is located at the intersection of the Indian and East Asian monsoons. Understanding the evolution history of the monsoon in the Red River basin helps to comprehend the evolution of Asian Summer Monsoon. Herein, we present the high‐resolution major elements and Sr‐Nd isotopic ratios of the terrigenous sediment component for a well‐dated core retrieved from the northern South China Sea slope, aiming to identify the sediment provenance and reconstruct the silicate chemical weathering intensity since the past 36 kyr. The Red River was confirmed as the major sediment source through Sr‐Nd isotopic ratios. The silicate chemical weathering was affected by the rapid changes of sea level and monsoon, and thus it is difficult to indicate the regional paleoenvironment by the weathering degree. The principal component 1 composed of TFe2O3, Al2O3, K2O and MgO was shown to represent the fine‐grained sediment discharge, and employed as a proxy for the summer monsoon rainfall. Global cooling events/stages were identified through the proxies, including the Last Glacial Maximum, Heinrich events, Younger Dryas, and 8.2 ka, as well as the enhanced summer monsoon stages, including the Bølling/Allerød and early Holocene. Based on the comparison with the neighboring paleoclimate indicators, the region summer monsoon of the Red River basin was found to be governed by the Indian summer monsoon, and the summer insolation at low latitudes might be the primary forcing force on the orbital scale.
Domestic Groundwater Depletion Supports China's Full Supply Chains
Authors: Sun Siao , Tang Qiuhong , Konar Megan , Huang Zhongwei , Gleeson Tom , Ma Ting , Fang Chuanglin , Cai Ximing
Published: May 2022

Groundwater use underpins much economic production. The unsustainable use of groundwater threatens environmental flows in surface waters, sustainable development, and future food security. The connection between agricultural trade and groundwater depletion has been recently highlighted, but how groundwater depletion supports the production of industrial and tertiary goods, trade, and consumption remains less well understood. Here, we present the first analysis of groundwater use and depletion embedded in the complete supply chain of China (including primary, secondary, and tertiary products). We use a multiregion input‐output analysis coupled with the high‐resolution groundwater use modeling to track groundwater depletion from production to end consumer. Our modeling results show that groundwater depletion occurred primarily in water scarce North China for agricultural production, but the depleted resource was then incorporated throughout the supply chain and dispersed across Chinese and international consumers. ∼64 billion m3 yr−1 (±1 billion m3 yr−1) groundwater was depleted in China, in which more than a half was from Xinjiang, Hebei, Henan and Heilongjiang Provinces. Approximately 40% of the groundwater depletion can be traced to interprovincial transfer (21 billion m3 yr−1) and export (4.8 billion m3 yr−1). The hot spots for final consumption of groundwater depletion were major cities in both North and South China. Importantly, over 60% of the groundwater depletion was embodied in industrial and tertiary products for final consumption, highlighting the importance of tracing groundwater through the full economy. Groundwater depletion represents a long‐term risk to supply chains, and policy‐makers can use this understanding to sustainably manage groundwater and diversify supply chains.
Impacts of Heterogeneity on Aquifer Storage and Recovery in Saline Aquifers
Authors: Li Hongkai , Lu Chunhui , Werner Adrian D. , Irvine Dylan J. , Luo Jian
Published: May 2022

Aquifer storage and recovery (ASR) involves the injection, and later extraction, of freshwater into aquifers, which often contain saline groundwater. Mixing between the fresh injectant and native saltwater often leads to part of the injectant becoming unrecoverable, thereby impacting ASR performance. This study explores freshwater‐saltwater mixing within ASR operations arising from aquifer heterogeneity using Monte Carlo analysis of 2D‐axisymmetric, density‐dependent flow and transport models. Logarithmic hydraulic conductivity (lnK) distributions are generated using either two‐point statistics or higher‐order connectivity features. Results show that higher variance in lnK leads to stronger freshwater‐saltwater mixing, which lowers the recovery efficiency (RE; i.e., ratio of extracted to injected freshwater). On average, the lowest RE values were obtained from lnK fields with connected high‐K features, across all ASR cycles. In contrast, RE values from lnK fields with connected low‐K features were typically the highest, at least where buoyancy was considered. The impact of aquifer heterogeneity on RE reduces with subsequent ASR cycles. Buoyancy was a major factor in lowering RE regardless of the adopted heterogeneity model. Heterogeneity tended to mitigate the adverse impacts of buoyancy, leading to some heterogeneous cases having higher RE values than the corresponding homogeneous case. These results highlight the importance of understanding buoyancy effects and subsurface heterogeneity (including the connectivity of geological structures), and interrelationships thereof when assessing the feasibility of multi‐cycle ASR in heterogeneous saline aquifers.
Divergent Hydrological Responses to Forest Expansion in Dry and Wet Basins of China: Implications for Future Afforestation Planning
Authors: Xue Baolin , A Yinglan , Wang Guoqiang , Helman David , Sun Ge , Tao Shengli , Liu Tingxi , Yan Denghua , Zhao Tongtiegang , Zhang Hongbo , Chen Lihua , Sun Wenchao , Xiao Jingfeng
Published: May 2022

Afforestation to control soil erosion has been implemented throughout China over the past few decades. The long‐term hydrological effects, such as total water yield and baseflow, of this large‐scale anthropogenic activity remain unclear. Using six decades of hydrologic observations and remote sensing data, we explore the hydrological responses to forest expansion in four basins with contrasting climates across China. No significant change in runoff was found for the period 1970–2012 for the cold and dry Hailar River Basin in northeastern China. However, both forest expansion and reduced precipitation contributed to the runoff reduction after afforestation since the late 1990s. Similarly, afforestation and drying climate since the mid‐1990s induced a significant decrease in runoff for the Weihe River Basin in semi‐arid northwestern China. In contrast, the two wet basins in the humid southern China, Ganjiang River Basin and Dongjiang River Basin, showed insignificant changes in total runoff during their study periods. However, the baseflow in the winter dry seasons in these two watersheds significantly increased since the 1950s. Our results highlight the long‐term variable effects of forest expansion and local climatic variability on basin hydrology in different climatic regions. This study suggests that landuse change in the humid study watersheds did not cause dramatic change in river flow and that region‐specific afforestation policy should be considered to deal with forestation‐water quantity trade‐off. Conclusions from this study can help improve decision‐making for ecological restoration policies and water resource management in China and other countries where intensive afforestation efforts are taking place.
An Unprecedented View Inside a Hurricane
Authors: Foltz Gregory , Zhang Chidong , Meinig Christian , Zhang Jun , Zhang Dongxiao
Published: May 2022

To improve future tropical cyclone forecasts, researchers sent a remotely operated saildrone into the extreme winds and towering waves around the eye of a category 4 hurricane.
Climatic Influences on Summer Use of Winter Precipitation by Trees
Authors: Goldsmith Gregory R. , Allen Scott T. , Braun Sabine , Siegwolf Rolf T. W. , Kirchner James W.
Published: May 2022

Trees in seasonal climates may use water originating from both winter and summer precipitation. However, the seasonal origins of water used by trees have not been systematically studied. We used stable isotopes of water to compare the seasonal origins of water found in three common tree species across 24 Swiss forest sites sampled in two different years. Water from winter precipitation was observed in trees at most sites, even at the peak of summer, although the relative representation of seasonal sources differed by species. However, the representation of winter precipitation in trees decreased with site mean annual precipitation in both years; additionally, it was generally lower in the cooler and wetter year. Together, these relationships show that precipitation amount influenced the seasonal origin of water taken up by trees across both time and space. These results suggest higher turnover of the plant‐available soil‐water pool in wetter sites and wetter years.
Sand Transport on Titan: A Sticky Problem
Authors: Lorenz Ralph D.
Published: May 2022

Saltation modeling by Comola et al. (2022, https://doi.org/10.1029/2022GL097913) considering a higher interparticle cohesion suggests smaller sand size on Titan than previously assumed, with possibly frequent sand transport. These predictions are testable by the Dragonfly mission presently under development.
Loss of KDM4B impairs osteogenic differentiation of OMSCs and promotes oral bone aging
Authors: Deng Peng , Chang Insoon , Wang Jiongke , Badreldin Amr A. , Li Xiyao , Yu Bo , Wang Cun-Yu
Published: May 2022

Aging of craniofacial skeleton significantly impairs the repair and regeneration of trauma-induced bony defects, and complicates dental treatment outcomes. Age-related alveolar bone loss could be attributed to decreased progenitor pool through senescence, imbalance in bone metabolism and bone-fat ratio. Mesenchymal stem cells isolated from oral bones (OMSCs) have distinct lineage propensities and characteristics compared to MSCs from long bones, and are more suited for craniofacial regeneration. However, the effect of epigenetic modifications regulating OMSC differentiation and senescence in aging has not yet been investigated. In this study, we found that the histone demethylase KDM4B plays an essential role in regulating the osteogenesis of OMSCs and oral bone aging. Loss of KDM4B in OMSCs leads to inhibition of osteogenesis. Moreover, KDM4B loss promoted adipogenesis and OMSC senescence which further impairs bone-fat balance in the mandible. Together, our data suggest that KDM4B may underpin the molecular mechanisms of OMSC fate determination and alveolar bone homeostasis in skeletal aging, and present as a promising therapeutic target for addressing craniofacial skeletal defects associated with age-related deteriorations.
Physics and applications of Raman distributed optical fiber sensing
Authors: Li Jian , Zhang Mingjiang
Published: May 2022

Raman distributed optical fiber sensing has been demonstrated to be a mature and versatile scheme that presents great flexibility and effectivity for the distributed temperature measurement of a wide range of engineering applications over other established techniques. The past decades have witnessed its rapid development and extensive applicability ranging from scientific researches to industrial manufacturing. However, there are four theoretical or technical bottlenecks in traditional Raman distributed optical fiber sensing: (i) The difference in the Raman optical attenuation, a low signal-to-noise ratio (SNR) of the system and the fixed error of the Raman demodulation equation restrict the temperature measurement accuracy of the system. {ii) The sensing distance and spatial resolution cannot be reconciled. (iii) There is a contradiction between the SNR and measurement time of the system. (iv) Raman distributed optical fiber sensing cannot perform dual-parameter detection. Based on the above theoretical and technical bottlenecks, advances in performance enhancements and typical applications of Raman distributed optical fiber sensing are reviewed in this paper. Integration of this optical system technology with knowledge based, that is, demodulation technology etc. can further the performance and accuracy of these systems.
A biosensing system using a multiparameter nonlinear dynamic analysis of cardiomyocyte beating for drug-induced arrhythmia recognition
Authors: Wang Hao , Wu Yue , Zou Quchao , Yang Wenjian , Xu Zhongyuan , Dong Hao , Zhu Zhijing , Wang Depeng , Wang Tianxing , Hu Ning , Zhang Diming
Published: May 2022

Cardiovascular disease is the number one cause of death in humans. Therefore, cardiotoxicity is one of the most important adverse effects assessed by arrhythmia recognition in drug development. Recently, cell-based techniques developed for arrhythmia recognition primarily employ linear methods such as time-domain analysis that detect and compare individual waveforms and thus fall short in some applications that require automated and efficient arrhythmia recognition from large datasets. We carried out the first report to develop a biosensing system that integrated impedance measurement and multiparameter nonlinear dynamic algorithm (MNDA) analysis for drug-induced arrhythmia recognition and classification. The biosensing system cultured cardiomyocytes as physiologically relevant models, used interdigitated electrodes to detect the mechanical beating of the cardiomyocytes, and employed MNDA analysis to recognize drug-induced arrhythmia from the cardiomyocyte beating recording. The best performing MNDA parameter, approximate entropy, enabled the system to recognize the appearance of sertindole- and norepinephrine-induced arrhythmia in the recording. The MNDA reconstruction in phase space enabled the system to classify the different arrhythmias and quantify the severity of arrhythmia. This new biosensing system utilizing MNDA provides a promising and alternative method for drug-induced arrhythmia recognition and classification in cardiological and pharmaceutical applications.
Longitudinal trajectory of response to electroconvulsive therapy associated with transient immune response & white matter alteration post-stimulation
Authors: Andreou Blake , Reid Benjamin , Lyall Amanda E. , Cetin-Karayumak Suheyla , Kubicki Antoni , Espinoza Randall , Kruse Jennifer , Narr Katherine L. , Kubicki Marek
Published: May 2022

Research suggests electroconvulsive therapy (ECT) induces an acute neuroinflammatory response and changes in white matter (WM) structural connectivity. However, whether these processes are related, either to each other or to eventual treatment outcomes, has yet to be determined. We examined the relationship between levels of peripheral pro-inflammatory cytokines and diffusion imaging-indexed changes in WM microstructure in individuals with treatment-resistant depression (TRD) who underwent ECT. Forty-two patients were assessed at baseline, after their second ECT (T2), and after completion of ECT (T3). A Montgomery Åsberg Depression Rating Scale improvement of >50% post-ECT defined ECT-responders (n = 19) from non-responders (n = 23). Thirty-four controls were also examined. Tissue-specific fractional anisotropy (FAt) was estimated using diffusion imaging data and the Free-Water method in 17 WM tracts. Inflammatory panels were evaluated from peripheral blood. Cytokines were examined to characterize the association between potential ECT-induced changes in an inflammatory state and WM microstructure. Longitudinal trajectories of both measures were also examined separately for ECT-responders and non-responders. Patients exhibited elevated Interleukin-8 (IL-8) levels at baseline compared to controls. In patients, correlations between IL-8 and FAt changes from baseline to T2 were significant in the positive direction in the right superior longitudinal fasciculus (R-SLF) and right cingulum (R-CB) (psig = 0.003). In these tracts, linear mixed-effects models revealed that trajectories of IL-8 and FAt were significantly positively correlated across all time points in responders, but not non-responders (R-CB-p = .001; R-SLF-p = 0.008). Our results suggest that response to ECT in TRD may be mediated by IL-8 and WM microstructure.
Circular RNA circVAMP3 promotes aerobic glycolysis and proliferation by regulating LDHA in renal cell carcinoma
Authors: Li Jun , Zhang Qian , Guan Yupeng , Liao Dingzhun , Jiang Donggen , Xiong Haiyun , Zhan Hengji , Pang Jun
Published: May 2022

Metabolic dysfunction is seen in cancer cells where increased glycolysis provides energy for growth. Circular RNAs (circRNAs) are thought to assist in glucose metabolism and the switch to glycolysis. Through screening, we found that circVAMP3 was necessary for both glycolytic and proliferative activities in renal cell carcinoma (RCC). Furthermore, circVAMP3 expression was elevated in RCC patients in correspondence with TNM stage. Mechanistically, circVAMP3 was observed to interact directly with lactate dehydrogenase A (LDHA) and modulate its activity. The circVAMP3–LDHA interaction facilitated LDHA phosphorylation at tyrosine 10 (Y10) catalyzed by the upstream kinase fibroblast growth factor receptor type 1 (FGFR1). Therefore, this study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation through regulating the enzymatic activity of glycolytic enzyme, suggesting that circVAMP3 may represent an RCC biomarker and treatment target.
DNA hypermethylation modification promotes the development of hepatocellular carcinoma by depressing the tumor suppressor gene ZNF334
Authors: Sun Dapeng , Gan Xiaojie , Liu Lei , Yang Yuan , Ding Dongyang , Li Wen , Jiang Junyao , Ding Wenbin , Zhao Linghao , Hou Guojun , Yu Jian , Wang Jie , Yang Fu , Yuan Shengxian , Zhou Weiping
Published: May 2022

DNA methylation plays a pivotal role in the development and progression of tumors. However, studies focused on the dynamic changes of DNA methylation in the development of hepatocellular carcinoma (HCC) are rare. To systematically illustrate the dynamic DNA methylation alternation from premalignant to early-stage liver cancer with the same genetic background, this study enrolled 5 HBV-related patients preceded with liver cirrhosis, pathologically identified as early-stage HCC with dysplastic nodules. Liver fibrosis tissues, dysplastic nodules and early HCC tissues from these patients were used to measure DNA methylation. Here, we report significant differences in the DNA methylation spectrum among the three types of tissues. In the early stage of HCC, DNA hypermethylation of tumor suppressor genes is predominant. Additionally, DNA hypermethylation in the early stage of HCC changes the binding ability of transcription factor TP53 to the promoter of tumor suppressor gene ZNF334, and inhibits the expression of ZNF334 at the transcription level. Furthermore, through a series of in vivo and in vitro experiments, we have clarified the exacerbation effect of tumor suppressor gene ZNF334 deletion in the occurrence of HCC. Combined with clinical data, we found that the overall survival and relapse-free survival of patients with high ZNF334 expression are significantly longer. Thus, we partly elucidated a sequential alternation of DNA methylation modification during the occurrence of HCC, and clarified the biological function and regulatory mechanism of the tumor suppressor gene ZNF334, which is regulated by related DNA methylation sites. Our study provides a new target and clinical evidence for the early diagnosis and sheds light on the precise treatment of liver cancer.
Macrophage-mediated anti-tumor immunity against high-risk neuroblastoma
Authors: Tang Xao X. , Shimada Hiroyuki , Ikegaki Naohiko
Published: May 2022

Neuroblastoma is the most common extracranial childhood solid tumor. The majority of high-risk neuroblastoma is resistant/refractory to the current high intensity therapy. Neuroblastoma lacks classical HLA Class I expression and exhibits low mutation burden, allowing neuroblastoma cells to evade CD8+ T cell-mediated immunity. Neuroblastoma cells do not express PD-L1, and tumor-associated macrophages are the predominant PD-L1+ cells in the tumor. In this study, we performed gene expression profiling and survival analyses on large neuroblastoma datasets to address the prognostic effect of PD-L1 gene expression and the possible involvement of the SLAMF7 pathway in the anti-neuroblastoma immunity. High-level expression of PD-L1 was found significantly associated with better outcome of high-risk neuroblastoma patients; two populations of PD-1+ PD-L1+ macrophages could be present in high-risk tumors with PD-1/PD-L1 ratios, ≈1 and >1. Patients with the PD-1/PD-L1 ratio >1 tumor showed inferior survival. High-level co-expression of SLAMF7 and SH2D1B was significantly associated with better survival of the high-risk neuroblastoma patients. Together, this study supports the hypothesis that macrophages are important effector cells in the anti-high-risk neuroblastoma immunity, that PD-1 blockade therapy can be beneficial to the high-risk neuroblastoma subset with the PD-1/PD-L1 expression ratio >1, and that SLAMF7 is a new therapeutic target of high-risk neuroblastoma.
Inheritance through the cytoplasm
Authors: Camus M. Florencia , Alexander-Lawrie Bridie , Sharbrough Joel , Hurst Gregory D. D.
Published: May 2022

Most heritable information in eukaryotic cells is encoded in the nuclear genome, with inheritance patterns following classic Mendelian segregation. Genomes residing in the cytoplasm, however, prove to be a peculiar exception to this rule. Cytoplasmic genetic elements are generally maternally inherited, although there are several exceptions where these are paternally, biparentally or doubly-uniparentally inherited. In this review, we examine the diversity and peculiarities of cytoplasmically inherited genomes, and the broad evolutionary consequences that non-Mendelian inheritance brings. We first explore the origins of vertical transmission and uniparental inheritance, before detailing the vast diversity of cytoplasmic inheritance systems across Eukaryota. We then describe the evolution of genomic organisation across lineages, how this process has been shaped by interactions with the nuclear genome and population genetics dynamics. Finally, we discuss how both nuclear and cytoplasmic genomes have evolved to co-inhabit the same host cell via one of the longest symbiotic processes, and all the opportunities for intergenomic conflict that arise due to divergence in inheritance patterns. In sum, we cannot understand the evolution of eukaryotes without understanding hereditary symbiosis.
Petermann ice shelf may not recover after a future breakup
Authors: Åkesson Henning , Morlighem Mathieu , Nilsson Johan , Stranne Christian , Jakobsson Martin
Published: May 2022

Floating ice shelves buttress inland ice and curtail grounded-ice discharge. Climate warming causes melting and ultimately breakup of ice shelves, which could escalate ocean-bound ice discharge and thereby sea-level rise. Should ice shelves collapse, it is unclear whether they could recover, even if we meet the goals of the Paris Agreement. Here, we use a numerical ice-sheet model to determine if Petermann Ice Shelf in northwest Greenland can recover from a future breakup. Our experiments suggest that post-breakup recovery of confined ice shelves like Petermann’s is unlikely, unless iceberg calving is greatly reduced. Ice discharge from Petermann Glacier also remains up to 40% higher than today, even if the ocean cools below present-day temperatures. If this behaviour is not unique for Petermann, continued near-future ocean warming may push the ice shelves protecting Earth’s polar ice sheets into a new retreated high-discharge state which may be exceedingly difficult to recover from.
Colossal barocaloric effects with ultralow hysteresis in two-dimensional metal–halide perovskites
Authors: Seo Jinyoung , McGillicuddy Ryan D. , Slavney Adam H. , Zhang Selena , Ukani Rahil , Yakovenko Andrey A. , Zheng Shao-Liang , Mason Jarad A.
Published: May 2022

Pressure-induced thermal changes in solids—barocaloric effects—can be used to drive cooling cycles that offer a promising alternative to traditional vapor-compression technologies. Efficient barocaloric cooling requires materials that undergo reversible phase transitions with large entropy changes, high sensitivity to hydrostatic pressure, and minimal hysteresis, the combination of which has been challenging to achieve in existing barocaloric materials. Here, we report a new mechanism for achieving colossal barocaloric effects that leverages the large volume and conformational entropy changes of hydrocarbon order–disorder transitions within the organic bilayers of select two-dimensional metal–halide perovskites. Significantly, we show how the confined nature of these order–disorder phase transitions and the synthetic tunability of layered perovskites can be leveraged to reduce phase transition hysteresis through careful control over the inorganic–organic interface. The combination of ultralow hysteresis and high pressure sensitivity leads to colossal reversible isothermal entropy changes (>200 J kg−1 K−1) at record-low pressures (<300 bar).
Double-tap gene drive uses iterative genome targeting to help overcome resistance alleles
Authors: Bishop Alena L. , López Del Amo Víctor , Okamoto Emily M. , Bodai Zsolt , Komor Alexis C. , Gantz Valentino M.
Published: May 2022

Homing CRISPR gene drives could aid in curbing the spread of vector-borne diseases and controlling crop pest and invasive species populations due to an inheritance rate that surpasses Mendelian laws. However, this technology suffers from resistance alleles formed when the drive-induced DNA break is repaired by error-prone pathways, which creates mutations that disrupt the gRNA recognition sequence and prevent further gene-drive propagation. Here, we attempt to counteract this by encoding additional gRNAs that target the most commonly generated resistance alleles into the gene drive, allowing a second opportunity at gene-drive conversion. Our presented “double-tap” strategy improved drive efficiency by recycling resistance alleles. The double-tap drive also efficiently spreads in caged populations, outperforming the control drive. Overall, this double-tap strategy can be readily implemented in any CRISPR-based gene drive to improve performance, and similar approaches could benefit other systems suffering from low HDR frequencies, such as mammalian cells or mouse germline transformations.
Genetic and phylogenetic uncoupling of structure and function in human transmodal cortex
Authors: Valk Sofie L. , Xu Ting , Paquola Casey , Park Bo-yong , Bethlehem Richard A. I. , Vos de Wael Reinder , Royer Jessica , Masouleh Shahrzad Kharabian , Bayrak Şeyma , Kochunov Peter , Yeo B. T. Thomas , Margulies Daniel , Smallwood Jonathan , Eickhoff Simon B. , Bernhardt Boris C.
Published: May 2022

Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relative to humans. Meta-analysis suggested regions with the least genetic control (low heritable correspondence and different across primates) are linked to social-cognition and autobiographical memory. Our findings suggest that genetic and evolutionary uncoupling of structure and function in different transmodal systems may support the emergence of complex forms of cognition.
Redox-homogeneous, gel electrolyte-embedded high-mass-loading cathodes for high-energy lithium metal batteries
Authors: Kim Jung-Hui , Kim Ju-Myung , Cho Seok-Kyu , Kim Nag-Young , Lee Sang-Young
Published: May 2022

Lithium metal batteries have higher theoretical energy than their Li-ion counterparts, where graphite is used at the anode. However, one of the main stumbling blocks in developing practical Li metal batteries is the lack of cathodes with high-mass-loading capable of delivering highly reversible redox reactions. To overcome this issue, here we report an electrode structure that incorporates a UV-cured non-aqueous gel electrolyte and a cathode where the LiNi0.8Co0.1Mn0.1O2 active material is contained in an electron-conductive matrix produced via simultaneous electrospinning and electrospraying. This peculiar structure prevents the solvent-drying-triggered non-uniform distribution of electrode components and shortens the time for cell aging while improving the overall redox homogeneity. Moreover, the electron-conductive matrix eliminates the use of the metal current collector. When a cathode with a mass loading of 60 mg cm−2 is coupled with a 100 µm thick Li metal electrode using additional non-aqueous fluorinated electrolyte solution in lab-scale pouch cell configuration, a specific energy and energy density of 321 Wh kg−1 and 772 Wh L−1 (based on the total mass of the cell), respectively, can be delivered in the initial cycle at 0.1 C (i.e., 1.2 mA cm−2) and 25 °C.
Outpacing conventional nicotinamide hydrogenation catalysis by a strongly communicating heterodinuclear photocatalyst
Authors: Zedler Linda , Wintergerst Pascal , Mengele Alexander K. , Müller Carolin , Li Chunyu , Dietzek-Ivanšić Benjamin , Rau Sven
Published: May 2022

Unequivocal assignment of rate-limiting steps in supramolecular photocatalysts is of utmost importance to rationally optimize photocatalytic activity. By spectroscopic and catalytic analysis of a series of three structurally similar [(tbbpy)2Ru-BL-Rh(Cp*)Cl]3+ photocatalysts just differing in the central part (alkynyl, triazole or phenazine) of the bridging ligand (BL) we are able to derive design strategies for improved photocatalytic activity of this class of compounds (tbbpy = 4,4´-tert-butyl-2,2´-bipyridine, Cp* = pentamethylcyclopentadienyl). Most importantly, not the rate of the transfer of the first electron towards the RhIII center but rather the rate at which a two-fold reduced RhI species is generated can directly be correlated with the observed photocatalytic formation of NADH from NAD+. Interestingly, the complex which exhibits the fastest intramolecular electron transfer kinetics for the first electron is not the one that allows the fastest photocatalysis. With the photocatalytically most efficient alkynyl linked system, it is even possible to overcome the rate of thermal NADH formation by avoiding the rate-determining β-hydride elimination step. Moreover, for this photocatalyst loss of the alkynyl functionality under photocatalytic conditions is identified as an important deactivation pathway.