bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico Simulations and Functional Cell Studies Evidence Similar Potency and Distinct Binding of Pacific and Caribbean Ciguatoxins
Authors: Raposo-García Sandra , Castro David , Lence Emilio , Estévez Pablo , Leão José Manuel , González-Bello Concepción , Gago-Martínez Ana , Louzao M. Carmen , Vale Carmen , Botana Luis M.
Published: October 2022

Ciguatoxins (CTX) cause ciguatera poisoning, which is the most common reported human food poisoning related to natural marine toxins. Pacific ciguatoxins are the most abundant and studied CTX analogues; however, the growing distribution of Caribbean analogues and the limited data available on their biological effects make necessary to re-evaluate their relative potency. For decades, the guidelines established by regulatory agencies have assumed that the potency of the Caribbean CTXs were tenfold lower than the Pacific CTXs. We present here an integrated study involving Neuro-2a cells (the method used worldwide to test ciguatoxins), electrophysiological assays, and in silico simulations that evidence the similar cytotoxicity of Caribbean and Pacific ciguatoxins and their asymmetry binding within sodium channels. The binding mode of the toxins was first explored by molecular docking using the GOLD program and the resulting binary complexes were further studied by Molecular Dynamics simulation studies using the molecular mechanics force field AMBER. The simulation studies explain their distinct impact on the activation potential of the channel as experimentally observed and provide a detailed picture of the effects caused by these toxins on an atomic scale.

Graphical Abstract
Three-dimensional b-value and Fractal Dimension Mapping of the Uttarakhand Himalayan Region
Authors: Mandal Prantik , Srinagesh D. , Suresh G. , Naresh B. , Singh Dhiraj Kumar , Swathi K. , Devi Arti , Raghavan R. Vijaya , Shekar M. , Saha Satish , Vengala P.K. , Gupta A.K.
Published: October 2022

The 3-D distributions of b-value of the frequency-magnitude distribution and fractal correlation dimension (D2) of seismically active Uttarakhand Himalayan seismic zone is presented. For this study, a catalogue of 525 local earthquakes was used (ML1.0-5.5) during 2017-2020. The de-clustered catalog is found to be complete above ML=2.6. The b-value is estimated to be 0.82±0.06 by maximum likelihood method. The modelled b- and D2 estimates in the study area range from 0.35 to 1.524 and 0.29 to 1.71, respectively. The present study reveals a negative b-D2 relationship (i.e. D2=-0.008b + 1.536, with a correlation coefficient of 0.9892) with week clustering. The modeling detects two zones (viz., A, and B) of high D2 and low b-values within the MCT zone, which are defined as high hazard zones (HHZ) while zone C (in the SE part of the MCT zone) with high D2 and high b-values is detected as an intermediate hazard zone. Also, three zones (D, E and F) with low D2 and low b-values are identified as low hazard zones (LHZ), which are located away from the MCT zone. The A and B high hazard zones can accumulate high levels of tectonic stress and pose risks for generating large earthquakes in the future. But, IHZ-C represents intermediate hazard level that can generate M≥5 events in future. The mapped A and B zones are inferred to be most hazardous in the region, which correlate well with recognized seismogeneic nodes capable of M6.5+ earthquakes in the region as suggested by the geomorphological zoning using pattern recognition.
Reliability Analysis for Liquefaction Risk Assessment for the City of Patna, India using Hybrid Computational Modeling
Authors: Ghani Sufyan , Sunita Kumari
Published: October 2022

In the present study, the first-order reliability method (FORM) is applied to evaluate the failure of soil deposits during seismic excitation for the city of Patna, India. Patna is emerging as one of the metro cities and the rapid infrastructure development in the city with high pace construction of road and metro services along with several smart city projects have led to immense growth in civil engineering structures. Therefore, liquefaction assessment of Patna is an important subject due to the geographical and seismic location of the city. A detailed comparative study has been performed between first-order second moment (FOSM) and advanced first-order second-moment (AFOSM) reliability methods to determine the most suitable method to evaluate the potential risk of liquefaction for Patna city. Reliability index (β) values obtained from AFOSM analysis are in true accordance with the deterministic approach and therefore can be considered as an appropriate tool for reliability analysis for this city. The analysis establishes that the city of Patna exhibits high possibilities of liquefaction failure during high-intensity earthquakes i.e. Mw = 6.5. Also, a concept of a predictive computational model developed by the hybridization of ANN and GWO algorithms to determine β value using geotechnical and seismic parameters has been proposed. The high precision and error-free performance of the ANN-GWO model provides a powerful computational tool to assist the prediction of β. The results of the study could be used to comprehend the potential risk against liquefaction and provide a novel and insightful concept of risk assessment for safe and economic construction practices.
Fine Grained Braided River Sedimentation in Brahmaputra River, Majuli, Assam, India
Authors: Saikia Suman , Laskar Jayanta Jivan
Published: October 2022

The Brahmaputra River in Assam exhibits a typical braided pattern and is characterized by a sediment load comprising of sand and mud. The river contains channel-bars of varied types and dimensions and embraces the world’s largest river island – Majuli, which at present is under the effect of severe bank-erosion along its southern margin. The objective of this study is to examine the characteristics of fluvial sedimentation prevailing along the southern margin of the Majuli landmass. Both channel as well as bank sediments were analyzed to understand the mechanism of transportation, depositional process and hydrodynamic behavior. Both channel and bank sediments consist of very fine to medium sand with subordinate amount of silt and mud. Majority of the sediments exhibit well to very well sorting and positive skewness. The Probability curves of grain size distribution indicate transportation of sediments dominantly by saltation mode with minor amount by suspension and surface-creep mode. CM plot suggest transportation by graded suspension (saltation) with subordinate rolling and uniform suspension process by means of tractive current. The internal stratifications are dominated by planar cross stratifications followed by horizontal stratifications, trough cross stratifications, ripple laminated layers and massive sand. The bank sediments in few locations exhibit a general fining upward sequence which ends up with the deposition of a mud layer.The lithofacies sequences of the study area show prevalence of both lower as well as upper flow regime energy conditions indicating fluctuations of energy conditions during their respective sedimentation.
Study on the Hydrogeochemical Processes Regulating the Groundwater Chemistry in the Southeast Rajasthan
Authors: Meena Parmeshwar Lal
Published: October 2022

The current study is focused on evaluation of hydrogeochemical aspects of groundwater for analysis of groundwater chemistry and quality assessment in the south east Rajasthan (India). A total of 50 groundwater samples were collected and analyzed for the assessment of major cations and anions, total dissolved solid (TDS), electrical conductance (EC), total hardness (TH) and total alkalinity (TA), and the results were compared with the WHO standards of drinking water. The results have demonstrated that the groundwater is alkaline in nature and in most of the groundwater samples the quantity of TH, TDS, EC, TA and NO3- is exceeded to the WHO standards. Additionally, alkali metal ions are mainly contributed from the dissolution of halite and silicate weathering processes, whereas the alkaline earth metal ions from the carbonate dissolution and silicate weathering processes. The saturation indices (SI) values show that the groundwater in the study area is oversaturated in terms of dolomite, calcite and argonite while undersaturated in gypsum. Hydrogeochemically the groundwater is Ca.Mg-HCO3, Ca.Mg-Cl and Ca.Mg-SO4 types. Moreover, it is mixed type with reference to cations and anions. The ionic plots, molar ionic ratios, CAI, SI and Gibb’s diagram have revealed that the chemical weathering of rock minerals, reverse ion exchange and anthropogenic activities are the key processes, regulating the chemical composition of ground water in the study area.
Multithematic Geoscience Data Integration for Identification of Mineral Potential Areas in Parts of Central Indian Precambrian Craton
Authors: Singh Ajit , Dash Debasmita , Kumar Rajesh , Sarkar Niroj Kumar
Published: October 2022

The paper highlights the results of multi-thematic geoscience data integration involving geological, geophysical, geochemical and remote sensing data sets, for an area of 4000 Sq. Km in parts of Precambrian Bastar craton, Chhattisgarh. The present team has been able to identify two discrete mineral potential areas for base metal sulphides, Sn, W and REE in sheared and altered felsic volcanics in Kotra-Bhansula area and for gold in propylitically altered meta basalts in Bhursatola-Khampura area. The dataset utilized during collation and integration includes (i) high resolution aeromagnetic data (ii) 1:50000 geological data covering litho-structural and mineralisation attributes (iii) 1:50 k geochemical data for 61 elements (iv) multispectral ASTER satellite data and its derivative alteration maps. Thematic data and derivative maps were studied and interpreted for evaluation of concerned parameters for estimating their role in mineralisation. The data integration has been implemented in three steps beginning with GIS based spatial modelling using Fuzzy logic method resulting into production of mineral favourability map, followed by detailed field evaluation and characterization of the identified mineral favourability areas. Eventual identification of potential areas was based on synthesis of modelling output, field outcome and laboratory results of analyses carried out on critical samples collected from mineral favourability areas. The identified two mineral potential areas are recommended for further detailed exploration for gold, base metal, Sn, W and REE through surface and sub-surface probing.
Escaping the Impossibility of Fairness: From Formal to Substantive Algorithmic Fairness
Authors: Green Ben
Published: October 2022

Efforts to promote equitable public policy with algorithms appear to be fundamentally constrained by the “impossibility of fairness” (an incompatibility between mathematical definitions of fairness). This technical limitation raises a central question about algorithmic fairness: How can computer scientists and policymakers support equitable policy reforms with algorithms? In this article, I argue that promoting justice with algorithms requires reforming the methodology of algorithmic fairness. First, I diagnose the problems of the current methodology for algorithmic fairness, which I call “formal algorithmic fairness.” Because formal algorithmic fairness restricts analysis to isolated decision-making procedures, it leads to the impossibility of fairness and to models that exacerbate oppression despite appearing “fair.” Second, I draw on theories of substantive equality from law and philosophy to propose an alternative methodology, which I call “substantive algorithmic fairness.” Because substantive algorithmic fairness takes a more expansive scope of analysis, it enables an escape from the impossibility of fairness and provides a rigorous guide for alleviating injustice with algorithms. In sum, substantive algorithmic fairness presents a new direction for algorithmic fairness: away from formal mathematical models of “fair” decision-making and toward substantive evaluations of whether and how algorithms can promote justice in practice.
Deep learned vectors’ formation using auto-correlation, scaling, and derivations with CNN for complex and huge image retrieval
Authors: Naeem Ahmad , Anees Tayyaba , Ahmed Khawaja Tehseen , Naqvi Rizwan Ali , Ahmad Shabir , Whangbo Taegkeun
Published: October 2022

Deep learning for image retrieval has been used in this era, but image retrieval with the highest accuracy is the biggest challenge, which still lacks auto-correlation for feature extraction and description. In this paper, a novel deep learning technique for achieving highly accurate results for image retrieval is proposed, which implements a convolutional neural network with auto-correlation, gradient computation, scaling, filter, and localization coupled with state-of-the-art content-based image retrieval methods. For this purpose, novel image features are fused with signatures produced by the VGG-16. In the initial step, images from rectangular neighboring key points are auto-correlated. The image smoothing is achieved by computing intensities according to the local gradient. The result of Gaussian approximation with the lowest scale and suppression is adjusted by the by-box filter with the standard deviation adjusted to the lowest scale. The parameterized images are smoothed at different scales at various levels to achieve high accuracy. The principal component analysis has been used to reduce feature vectors and combine them with the VGG features. These features are integrated with the spatial color coordinates to represent color channels. This experimentation has been performed on Cifar-100, Cifar-10, Tropical fruits, 17 Flowers, Oxford, and Corel-1000 datasets. This study has achieved an extraordinary result for the Cifar-10 and Cifar-100 datasets. Similarly, the results of the study have shown efficient results for texture datasets of 17 Flowers and Tropical fruits. Moreover, when compared to state-of-the-art approaches, this research produced outstanding results for the Corel-1000 dataset.
How corporate social responsibility mediates the relationship between corporate reputation and enterprise risk management: evidence from Spain
Authors: Pérez-Cornejo Clara , de Quevedo-Puente Esther
Published: October 2022

Enterprise risk management (ERM) systems lessen the probability of risks harming a firm’s reputation for a number of reasons. First, a high-quality ERM system makes it less likely a firm will suffer a risk-based reputational crisis. Second, ERM systems help companies to behave more responsibly towards all stakeholders, thereby ensuring firms meet stakeholders’ expectations. Third, when a crisis stemming from an uncontrollable risk occurs, a high-quality ERM system helps to reduce the negative impact on reputation because stakeholders will not attribute guilt to a firm which has acted responsibly in its risk management. In this research, we explore the link between corporate reputation and ERM systems together with the role played by corporate social responsibility (CSR) performance as a mediator. Our results support the notion that ERM system quality enhances CSR performance as well as corporate reputation. The results also confirm that ERM systems have a positive impact on corporate reputation via the mediating effect of CSR performance. Companies should therefore use risk management policies to bolster both their CSR and their reputation.
Experimental Study of Inorganic Foundry Sand Binders for Mold and Cast Quality
Authors: Anwar Nurul , Jalava Kalle , Orkas Juhani
Published: October 2022

The interest in inorganic foundry binders has been rising steadily in recent times due to their favorable environmental characteristics. This paper compares the mold quality and cast quality attained with different inorganic binders. Three different types of sand and five different inorganic binders were used for the mold quality study. Of the inorganic binders, there was liquid sodium silicate used in different hardening methods, a geopolymer binder, and also solid sodium silicate. The mold quality was assessed through bending strength, residual bending strength, tensile strength, and loss on ignition measurement. A total of 12 castings were made using molds of different binders and sand materials. The cast quality was then assessed by tracking changes in dimension and the surface quality of final castings. Inorganic binders performed well in terms of mold strength and very well in terms of loss on ignition but there is room for improvement in the surface quality of the castings attained.
Improving quantum genetic optimization through granular computing
Authors: Acampora Giovanni , Vitiello Autilia
Published: October 2022

Quantum computers promise to revolutionize the world of computing thanks to some features of quantum mechanics that can enable massive parallelism in computation. This benefit may be particularly relevant in the design of evolutionary algorithms, where the quantum paradigm could support the exploration of multiple regions of the search space in a concurrent way. Although some efforts in this research field are ongoing, the potential of quantum computing is not yet fully expressed due to the limited number of qubits of current quantum processors. This limitation is even more acute when one wants to deal with continuous optimization problems, where the search space is potentially infinite. The goal of this paper is to address this limitation by introducing a hybrid and granular approach to quantum algorithm design, specifically designed for genetic optimization. This approach is defined as hybrid, because it uses a digital computer to evaluate fitness functions, and a quantum processor to evolve the genetic population; moreover, it uses granular computing to hierarchically reduce the size of the search space of a problem, so that good near-optimal solutions can be identified even on small quantum computers. As shown in the experiments, where IBM Q family processors are used, the usage of a granular computation scheme statistically enhances the performance of the state-of-the-art evolutionary algorithm implemented on quantum computers, when it is run to optimize well-known benchmark continuous functions.
Drivers of Late Miocene Tropical Sea Surface Cooling: A New Perspective From the Equatorial Indian Ocean
Authors: Martinot Claire , Bolton Clara T. , Sarr Anta‐Clarisse , Donnadieu Yannick , Garcia Marta , Gray Emmeline , Tachikawa Kazuyo
Published: October 2022

During the late Miocene, global cooling occurred alongside the establishment of near‐modern terrestrial and marine ecosystems. Significant (3°C–5°C) sea surface cooling from 7.5 to 5.5 Ma is recorded by proxies at midlatitudes to high latitudes, yet the magnitude of tropical cooling and the role of atmospheric carbon dioxide (pCO2) in driving this trend are debated. Here, we present a new orbital‐resolution sea surface temperature (SST) record spanning the late Miocene to earliest Pliocene (9–5 Ma) from the eastern equatorial Indian Ocean (International Ocean Discovery Program Site U1443) based on Mg/Ca ratios measured in tests of the planktic foraminifer Trilobatus trilobus. Our SST record reveals a 3.2°C decrease from 7.4 to 5.8 Ma, significantly increasing previous estimates of late Miocene tropical cooling. Analysis of orbital‐scale variability shows that before the onset of cooling, SST variations were dominated by precession‐band (19–23 kyr) variability, whereas tropical temperature became highly sensitive to obliquity (41 kyr) after 7.5 Ma, suggesting an increase in high‐latitude forcing. We compare a revised global SST database with new paleoclimate model simulations and show that a pCO2 decrease from 560 to 300 ppm, in the range suggested by pCO2 proxy records, could explain most of the late Miocene sea surface cooling observed at Site U1443. Using our new Site U1443 record as representative of tropical SST evolution, estimated meridional SST gradients suggest a much more modest increase over the late Miocene than previously suggested, in agreement with modeled meridional SST gradients.
Device Made for the Moon May Aid in Carbon Sequestration on Earth
Authors: Morris Bill
Published: October 2022

A pocket-sized device intended for use on the Moon could soon play a key role in Japan’s ambitious plans to sequester carbon dioxide.
Significant Seasonal N2O Dynamics Revealed by Multi‐Year Observations in the Northern South China Sea
Authors: Wan Xianhui S. , Lin Hua , Ward Bess B. , Kao Shuh‐Ji , Dai Minhan
Published: October 2022

The coastal ocean and marginal sea play a disproportionally important role in the release of nitrous oxide (N2O) into the atmosphere. The spatial and temporal distribution of N2O in these important source regions remains highly uncertain due to the scarcity of N2O measurements. Here we present a large data set of N2O concentrations and fluxes obtained from 10 cruises covering four seasons in the Northern South China Sea (NSCS). The study area is overall a net source of atmospheric N2O with an annual flux of 1.9 ± 1.2 × 108, 0.8 ± 0.5 × 108 and 1.2 ± 0.7 × 108 mol N2O yr−1 in the shelf, slope and basin regions, respectively. In terms of global warming potentials, the N2O emissions offset 27.8% of the CO2 sink on the shelf, and are equivalent to 3.5 and 0.2‐fold of the CO2 emission in the slope and basin of the NSCS. On the seasonal time scale, N2O flux was significantly higher in autumn and winter than in the warm seasons. The spatial variability was contrastingly less pronounced. The seasonality of N2O distribution in the shelf region was modulated by the riverine discharge, while intrusion of the Kuroshio Current exerted profound control on N2O distribution in the open waters of the NSCS. The variable relationships between N2O excess, apparent oxygen utilization, and nitrate in the shelf, NSCS basin and the Luzon Strait indicated a regional difference in N2O cycling pathways along with the impact of water mass mixing. Our study establishes a robust baseline to understand N2O distribution and flux in the NSCS.
Regional‐Scale Lithospheric Recycling on Venus Via Peel‐Back Delamination
Authors: Adams A. C. , Stegman D. R. , Smrekar S. E. , Tackley P. J.
Published: October 2022

We currently have a limited understanding of the tectonic framework that governs Venus. Schubert and Sandwell (1995, https://doi.org/10.1006/icar.1995.1150) identified over 10,000 km of possible subduction sites at both coronae and chasmata rift zones. Previous numerical and experimental studies have shown the viability of regional‐scale lithospheric recycling via plume‐lithosphere interactions at coronae, yet little work has been done to study the possibility of resurfacing initiated at Venusian rift zones. We created 2D numerical models to test if and how regional‐scale resurfacing could be initiated at a lateral lithospheric discontinuity. We observed several instances of peel‐back delamination—a form of lithospheric recycling in which the dense lithospheric mantle decouples and peels away from the weak, initially 30 km‐thick crust, leaving behind a hot, thinned layer of crust at the surface. Delamination initiation is driven by the negative buoyancy of the lithospheric mantle and is resisted by the coupling of the plate across the Moho, the significant positive buoyancy of the crust arising from a range of crustal densities, and the viscous strength of the plate. Initial plate bending promotes yielding and weakening in the crust, which is crucial to allow decoupling of the crust and lithospheric mantle. When there is sufficient excess negative buoyancy in the lithospheric mantle, both positively and negatively buoyant plates may undergo delamination. Following a delamination event, the emplacement of hot, buoyant asthenosphere beneath the crust may have consequences for regional‐scale volcanism and local tectonic deformation on Venus within the context of the regional equilibrium resurfacing hypothesis.
Probing the Upper End of Intracontinental Earthquake Magnitude: A Prehistoric Example From the Dzhungarian and Lepsy Faults of Kazakhstan
Authors: Tsai C.‐H. , Abdrakhmatov K. , Mukambayev A. , Elliott A. J. , Elliott J. R. , Grützner C. , Rhodes E. J. , Ivester A. H. , Walker R. T. , Wilkinson R.
Published: October 2022

The study of surface ruptures is key to understanding the earthquake occurrence of faults especially in the absence of historical events. We present a detailed analysis of geomorphic displacements along the Dzhungarian Fault, which straddles the border of China and Kazakhstan. We use digital elevation models derived from structure‐from‐motion analysis of Pléiades satellite imagery and drone imagery from specific field sites to measure surface offsets. We provide direct age constraints from alluvial terraces displaced by faulting and indirect dating from morphological analysis of the scarps. We find that the southern 250 km of the fault likely ruptured in a single event in the last 4,000 years, with displacements of 10–15 m, and potentially up to 20 m at one site. We infer that this Dzhungarian rupture is likely linked with a previously identified paleo‐earthquake rupture on the Lepsy Fault through a system of splays in the intervening highlands. Though there are remaining uncertainties regarding consistency in age constraints between the two fault ruptures, most of the sites along the two faults are consistent with a most recent event 2,000–4,000 years ago. Rupture on the Dzhungarian Fault alone is likely to have exceeded Mw 8, and the combined Lepsy‐Dzhungarian rupture scenario may have been up to Mw 8.4. Despite being at the upper end of known or inferred continental earthquake magnitudes, our proposed scenario combining the 375 km of the Dzhungarian and Lepsy ruptures yields a slip‐to‐length ratio consistent with global averages and so do other historical intracontinental earthquakes in Central Asia.
Placing Another Piece of the Tethyan Puzzle: The First Paleozoic Paleomagnetic Data From the South Qiangtang Block and Its Paleogeographic Implications
Authors: Wei Bitian , Cheng Xin , Domeier Mathew , Jiang Nan , Wu Yiying , Zhang Weijie , Wu Ke , Wang Baofeng , Xu Pengxiang , Xing Longyun , Zhang Dongmeng , Li Teng , Deng Xiaohong , Liu Feifan , Zhou Yanan , Wu Hanning
Published: October 2022

The origin and drift history of the South Qiangtang block (SQB) is critical to understanding the internal dimensions and kinematics of the late Paleozoic to early Mesozoic Tethyan realm and the subsequent evolution of the Qinghai‐Tibet Plateau, but so far no paleomagnetic data constrain the SQB in Paleozoic time. Here we present a paleomagnetic study of the middle Permian volcanic and sedimentary rocks from the SQB. Well‐defined high‐temperature components of magnetization were isolated from 6 sites of tuffaceous sandstone and 9 sites of basalt, but their directional populations are distinct. On the basis of a conglomerate test and comparisons with younger paleomagnetic data, we argue the basalts preserve a primary magnetization, whereas the sandstones may have been remagnetized during the Triassic. The magnetic directions from the basalt indicate that the SQB was located at a latitude of 22.3 ± 5.8°S during the middle Permian. Together with existing paleomagnetic data from other Tethyan continental blocks, this new constraint reveals that during the middle Permian the Neo‐Tethys Ocean spanned ∼10–20° of latitude and the Paleo‐Tethys Ocean spanned ∼50°, but also that the latter was a composite ocean system which included at least two important branches. In further considering the geological records of the SQB, we propose the block rifted from the northern margin of Gondwana during opening of the Neo‐Tethys in early Permian time, and then drifted rapidly northward until ultimately colliding with the North Qiangtang block and the southern margin of Laurasia during final closure of the Paleo‐Tethys in the Triassic.
Tension of plus-end tracking protein Clip170 confers directionality and aggressiveness during breast cancer migration
Authors: Hu Yunfeng , Xie Qiu , Wu Xiang , Liu Weizhen , Li DongFang , Li Chen , Zhao WangXing , Chen LinLin , Zheng Zihui , Li GuangMing , Guo Jun
Published: October 2022

The microtubule (MT) plus-end binding protein Clip170 is associated closely with breast cancer invasion and migration. In this study, Clip170 tension observed by a newly designed cpstFRET tension probe was suggested to be positive related to breast cancer aggressiveness, which could be regulated by α-tubulin detyrosination-induced MT disassembly. Clip170 phosphorylation induced by Ribosomal protein S6 kinase (RSK) could also increase its tension and promote the conversion of a discrete comet-like Clip-170 distribution into a spotty pattern during cancer metastasis. Heightened Clip170 tension was correlated with the formation of cortactin-associated filopodia and lamellipodia, and then promoted invasion and metastasis both in vitro and in vivo. Meanwhile, Clip170 tension enhanced at the leading edge in directional migration, accompanying with IQGAP1 subcellular distribution variation. Our work indicates that the malignancy and directionality during breast cancer migration depend on the magnitude and polarization of Clip170 tension, and we suggest Clip170 tension as a new potential drug target for breast cancer therapy.
PLEKHH2 binds β-arrestin1 through its FERM domain, activates FAK/PI3K/AKT phosphorylation, and promotes the malignant phenotype of non-small cell lung cancer
Authors: Wang Rui , Wang Si , Li Zhen , Luo Yuan , Zhao Yue , Han Qiang , Rong Xue-Zhu , Guo Yao-Xing , Liu Yang
Published: October 2022

PLEKHH2 is an important FERM domain containing-protein. However, the role of PLEKHH2 in human solid tumors has not been reported yet. We report that PLEKHH2 showed enhanced cytoplasmic expression in non-small cell lung cancer (NSCLC). Its overexpression was positively correlated with high TNM stage, low differentiation, lymphatic node metastasis, and poor prognosis. In A549 and H1299 cells, high expression of PLEKHH2 significantly promoted cell proliferation, migration, invasion, and increased the expression of proliferation- and invasion-related proteins. It also enhanced the phosphorylation of FAK and promoted the activity of the PI3K/AKT pathway. Immunofluorescence and co-immunoprecipitation analyses were performed to elucidate the molecular mechanism underlying PLEKHH2-mediated regulation of proliferation and invasion in lung cancer cells. Upon transfection of full length PLEKHH2 or its FERM domain, we observed enhanced binding of PLEKHH2 to β-arrestin1, whereas FAK- β-arrestin1 binding was diminished and this led to an increase in FAK phosphorylation. PLEKHH2-mutant plasmids without the FERM domain could not effectively promote its binding to β-arrestin1, activation of FAK phosphorylation, PI3K/AKT activation, or the malignant phenotype. Our findings suggested that PLEKHH2 is an important oncogene in NSCLC. PLEKHH2 binding to β-arrestin1 through the FERM domain competitively inhibits β-arrestin1 binding to FAK, which causes the dissociation of FAK from the FAK-β-arrestin1 complex. Furthermore, the dissociation of FAK promotes its autophosphorylation, activates the PI3K/AKT signaling pathway, and subsequently promotes lung cancer cell proliferation, migration, and invasion. These results provide evidence for the potential use of PLEKHH2 inhibition as an anticancer therapy.
Mitochondrial event as an ultimate step in ferroptosis
Authors: Oh Soo-Jin , Ikeda Masataka , Ide Tomomi , Hur Kyu Yeon , Lee Myung-Shik
Published: October 2022

In ferroptosis, the roles of mitochondria have been controversial. To explore the role of mitochondrial events in ferroptosis, we employed mitochondrial DNA-depleted ρ0 cells that are resistant to cell death due to enhanced expression of antioxidant enzymes. Expression of mitochondrial-type GPx4 (mGPx4) but no other forms of GPx4 was increased in SK-Hep1 ρ0 cells. Likely due to high mGPx4 expression, SK-Hep1 ρ0 cells were resistant to ferroptosis by erastin inhibiting xCT channel. In contrast, SK-Hep1 ρ0 cells were susceptible to cell death by a high concentration of RSL3 imposing ferroptosis by GPx4 inhibition. Accumulation of cellular ROS and oxidized lipids was observed in erastin- or RSL3-treated SK-Hep1 ρ+ cells but not in erastin-treated SK-Hep1 ρ0 cells. Mitochondrial ROS and mitochondrial peroxidized lipids accumulated in SK-Hep1 ρ+ cells not only by RSL3 but also by erastin acting on xCT on the plasma membrane. Mitochondrial ROS quenching inhibited SK-Hep1 ρ+ cell death by erastin or a high dose of RSL3, suggesting a critical role of mitochondrial ROS in ferroptosis. Ferroptosis by erastin or RSL3 was inhibited by a more than 20-fold lower concentration of MitoQ, a mitochondrial ROS quencher, compared to DecylQ, a non-targeting counterpart. Ferroptosis of SK-Hep1 ρ+ cells by erastin or RSL3 was markedly inhibited by a VDAC inhibitor, accompanied by significantly reduced accumulation of mitochondria ROS, total peroxidized lipids, and mitochondrial peroxidized lipids, strongly supporting the role of mitochondrial events in ferroptotic death and that of VDAC in mitochondrial steps of ferroptosis induced by erastin or RSL3. SK-Hep1 ρ+ cell ferroptosis by sorafenib was also suppressed by mitochondrial ROS quenchers, accompanied by abrogation of sorafenib-induced mitochondrial ROS and mitochondrial peroxidized lipid accumulation. These results suggest that SK-Hep1 ρ0 cells are resistant to ferroptosis due to upregulation of mGPx4 expression and mitochondrial events could be the ultimate step in determining final cell fate.
Arginase: shedding light on the mechanisms and opportunities in cardiovascular diseases
Authors: Li Zhuozhuo , Wang Liwei , Ren Yuanyuan , Huang Yaoyao , Liu Wenxuan , Lv Ziwei , Qian Lu , Yu Yi , Xiong Yuyan
Published: October 2022

Arginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.
Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK
Authors: Ge Chenxu , Tan Jun , Dai Xianling , Kuang Qin , Zhong Shaoyu , Lai Lili , Yi Chao , Sun Yan , Luo Jing , Zhang Chufeng , Zhu Liancai , Wang Bochu , Xu Minxuan
Published: October 2022

Nonalcoholic steatohepatitis (NASH), a common clinical disease, is becoming a leading cause of hepatocellular carcinoma (HCC). Dual specificity phosphatase 22 (DUSP22, also known as JKAP or JSP-1) expressed in numerous tissues plays essential biological functions in immune responses and tumor growth. However, the effects of DUSP22 on NASH still remain unknown. Here, we find a significant decrease of DUSP22 expression in human and murine fatty liver, which is mediated by reactive oxygen species (ROS) generation. Hepatic-specific DUSP22 deletion particularly exacerbates lipid deposition, inflammatory response and fibrosis in liver, facilitating NASH and non-alcoholic fatty liver disease (NAFLD)-associated HCC progression. In contrast, transgenic over-expression, lentivirus or adeno-associated virus (AAV)-mediated DUSP22 gene therapy substantially inhibit NASH-related phenotypes and HCC development in mice. We provide mechanistic evidence that DUSP22 directly interacts with focal adhesion kinase (FAK) and restrains its phosphorylation at Tyr397 (Y397) and Y576 + Y577 residues, subsequently prohibiting downstream activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB) cascades. The binding of DUSP22 to FAK and the dephosphorylation of FAK are indispensable for DUSP22-meliorated NASH progression. Collectively, our findings identify DUSP22 as a key suppressor of NASH-HCC, and underscore the DUSP22-FAK axis as a promising therapeutic target for treatment of the disease.
Spatial structure of city population growth
Authors: Reia Sandro M. , Rao P. Suresh C. , Barthelemy Marc , Ukkusuri Satish V.
Published: October 2022

We show here that population growth, resolved at the county level, is spatially heterogeneous both among and within the U.S. metropolitan statistical areas. Our analysis of data for over 3,100 U.S. counties reveals that annual population flows, resulting from domestic migration during the 2015–2019 period, are much larger than natural demographic growth, and are primarily responsible for this heterogeneous growth. More precisely, we show that intra-city flows are generally along a negative population density gradient, while inter-city flows are concentrated in high-density core areas. Intra-city flows are anisotropic and generally directed towards external counties of cities, driving asymmetrical urban sprawl. Such domestic migration dynamics are also responsible for tempering local population shocks by redistributing inflows within a given city. This spill-over effect leads to a smoother population dynamics at the county level, in contrast to that observed at the city level. Understanding the spatial structure of domestic migration flows is a key ingredient for analyzing their drivers and consequences, thus representing a crucial knowledge for urban policy makers and planners.
Photoredox-catalyzed C–C bond cleavage of cyclopropanes for the formation of C(sp3)–heteroatom bonds
Authors: Ge Liang , Zhang Chi , Pan Chengkai , Wang Ding-Xing , Liu Dong-Ying , Li Zhi-Qiang , Shen Pingkang , Tian Lifang , Feng Chao
Published: October 2022

Sterically congested C–O and C–N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)–heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C–C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.
Enhanced metanephric specification to functional proximal tubule enables toxicity screening and infectious disease modelling in kidney organoids
Authors: Vanslambrouck Jessica M. , Wilson Sean B. , Tan Ker Sin , Groenewegen Ella , Rudraraju Rajeev , Neil Jessica , Lawlor Kynan T. , Mah Sophia , Scurr Michelle , Howden Sara E. , Subbarao Kanta , Little Melissa H.
Published: October 2022

While pluripotent stem cell-derived kidney organoids are now being used to model renal disease, the proximal nephron remains immature with limited evidence for key functional solute channels. This may reflect early mispatterning of the nephrogenic mesenchyme and/or insufficient maturation. Here we show that enhanced specification to metanephric nephron progenitors results in elongated and radially aligned proximalised nephrons with distinct S1 - S3 proximal tubule cell types. Such PT-enhanced organoids possess improved albumin and organic cation uptake, appropriate KIM-1 upregulation in response to cisplatin, and improved expression of SARS-CoV-2 entry factors resulting in increased viral replication. The striking proximo-distal orientation of nephrons resulted from localized WNT antagonism originating from the organoid stromal core. PT-enhanced organoids represent an improved model to study inherited and acquired proximal tubular disease as well as drug and viral responses.
Metamaterial-enabled asymmetric negative refraction of GHz mechanical waves
Authors: Zanotto Simone , Biasiol Giorgio , Santos Paulo V. , Pitanti Alessandro
Published: October 2022

Wave refraction at an interface between different materials is a basic yet fundamental phenomenon, transversal to several scientific realms – electromagnetism, gas and fluid acoustics, solid mechanics, and possibly also matter waves. Under specific circumstances, mostly enabled by structuration below the wavelength scale, i.e., through the metamaterial approach, waves undergo negative refraction, eventually enabling superlensing and transformation optics. However, presently known negative refraction systems are symmetric, in that they cannot distinguish between positive and negative angles of incidence. Exploiting a metamaterial with an asymmetric unit cell, we demonstrate that the aforementioned symmetry can be broken, ultimately relying on the specific shape of the Bloch mode isofrequency curves. Our study specialized upon a mechanical metamaterial operating at GHz frequency, which is by itself a building block for advanced technologies such as chip-scale hybrid optomechanical and electromechanical devices. However, the phenomenon is based on general wave theory concepts, and it applies to any frequency and time scale for any kind of linear waves, provided that a suitable shaping of the isofrequency contours is implemented.
Controllable DNA hybridization by host–guest complexation-mediated ligand invasion
Authors: Xiao Lin , Wang Liang-Liang , Wu Chao-Qun , Li Han , Zhang Qiu-Long , Wang Yang , Xu Liang
Published: October 2022

Dynamic regulation of nucleic acid hybridization is fundamental for switchable nanostructures and controllable functionalities of nucleic acids in both material developments and biological regulations. In this work, we report a ligand-invasion pathway to regulate DNA hybridization based on host–guest interactions. We propose a concept of recognition handle as the ligand binding site to disrupt Watson–Crick base pairs and induce the direct dissociation of DNA duplex structures. Taking cucurbit[7]uril as the invading ligand and its guest molecules that are integrated into the nucleobase as recognition handles, we successfully achieve orthogonal and reversible manipulation of DNA duplex dissociation and recovery. Moreover, we further apply this approach of ligand-controlled nucleic acid hybridization for functional regulations of both the RNA-cleaving DNAzyme in test tubes and the antisense oligonucleotide in living cells. This ligand-invasion strategy establishes a general pathway toward dynamic control of nucleic acid structures and functionalities by supramolecular interactions.
Importance of structural hinderance in performance–stability equilibrium of organic photovoltaics
Authors: Fan Baobing , Gao Wei , Wu Xuanhao , Xia Xinxin , Wu Yue , Lin Francis R. , Fan Qunping , Lu Xinhui , Li Wen Jung , Ma Wei , Jen Alex K.-Y.
Published: October 2022

Power conversion efficiency and long-term stability are two critical metrics for evaluating the commercial potential of organic photovoltaics. Although the field has witnessed a rapid progress of efficiency towards 19%, the intrinsic trade-off between efficiency and stability is still a challenging issue for bulk-heterojunction cells due to the very delicate crystallization dynamics of organic species. Herein, we developed a class of non-fullerene acceptors with varied side groups as an alternative to aliphatic chains. Among them, the acceptors with conjugated side groups show larger side-group torsion and more twisted backbone, however, they can deliver an efficiency as high as 18.3% in xylene-processed cells, which is among the highest values reported for non-halogenated solvent processed cells. Meanwhile, decent thermal/photo stability is realized for these acceptors containing conjugated side groups. Through the investigation of the geometry–performance–stability relationship, we highlight the importance of side-group steric hinderance of acceptors in achieving combined high-performance, stable, and eco-friendly organic photovoltaics.
A public database of thermoelectric materials and system-identified material representation for data-driven discovery
Authors: Na Gyoung S. , Chang Hyunju
Published: October 2022

Thermoelectric materials have received much attention as energy harvesting devices and power generators. However, discovering novel high-performance thermoelectric materials is challenging due to the structural diversity and complexity of the thermoelectric materials containing alloys and dopants. For the efficient data-driven discovery of novel thermoelectric materials, we constructed a public dataset that contains experimentally synthesized thermoelectric materials and their experimental thermoelectric properties. For the collected dataset, we were able to construct prediction models that achieved R2-scores greater than 0.9 in the regression problems to predict the experimentally measured thermoelectric properties from the chemical compositions of the materials. Furthermore, we devised a material descriptor for the chemical compositions of the materials to improve the extrapolation capabilities of machine learning methods. Based on transfer learning with the proposed material descriptor, we significantly improved the R2-score from 0.13 to 0.71 in predicting experimental ZTs of the materials from completely unexplored material groups.
Breaking the vicious circle—the Asthma Referral Identifier (ReferID) tool
Authors: Beekman Maarten , Hales Julie , Al-Ahmad Mona , del Olmo Ricardo , Tan Tze Lee
Published: October 2022

Asthma is associated with a significant burden of disease, especially for patients with severe or uncontrolled asthma. Many patients with severe asthma still receive treatment in primary care settings and despite the availability of effective options, inadequate asthma treatment remains a concern, particularly the use of systemic corticosteroids to treat exacerbations and severe asthma. Around the world, many patients are stuck in a vicious circle of misdiagnosis, undertreatment, and poor understanding of disease severity and management. In this manuscript, we describe the development of The Asthma Referral Identifier (ReferID) tool, a simple, 4-item questionnaire that healthcare providers can use to help identify patients with uncontrolled and/or potentially severe asthma. ReferID was developed specifically for use in primary care clinics in low- and middle-income countries and other clinics, where the optimisation of asthma assessments and treatment recommended for countries with well-established healthcare systems, are not possible. ReferID was developed through an informal collaborative process involving international asthma experts as well as general practitioners, nurses, and specialists throughout the Asia Pacific, Latin America and Middle East regions, in conjunction with current evidence and treatment guidelines. In collaboration with local and regional partners around the world, the developers have adapted ReferID and translated it into 21 languages, and implementation is ongoing in 30 countries. ReferID has the potential to help break the vicious circle, improving disease outcomes and health-related quality of life for patients with asthma.