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Purpose: Ferroptosis is a form of cell death driven by iron-dependent lipid peroxidation. Intriguingly, KRAS-mutant cancers are particularly vulnerable to ferroptosis. Osthole is a natural coumarin extracted from Cnidium spp. and other Apiaceous plants. In the present study, we explored the antitumor potential of osthole in KRAS-mutant colorectal cancer (CRC) cells. Methods: Cell viability assay, EdU incorporation assay, flow cytometry, tumor xenograft model, western blot, immunochemistry staining, immunofluorescence, transcriptome RNA sequencing and quantitative reverse transcription-PCR were performed to evaluate the influence of osthole treatment on KRAS-mutant CRC cells. Results: We found that osthole treatment suppressed proliferation and tumor growth of KRAS-mutant CRC cell lines HCT116 and SW480. Moreover, osthole treatment increased ROS production and induced ferroptosis. Osthole treatment also promoted autophagy, but inhibition of autophagy by ATG7 knockdown or 3-MA showed no influence on osthole-induced ferroptosis. In comparison, osthole increased lysosomal activation, and co-treatment with lysosome inhibitor Baf-A1 attenuated osthole-induced ferroptosis. Besides, osthole treatment reduced the phosphorylation of AMPK, Akt and mTOR in HCT116 and SW480 cells, while restored AMPK signaling by AMPK agonist AICAR partially abrogated ferroptosis induced by osthole treatment. Finally, co-treatment with osthole increased the cytotoxicity of cetuximab in KRAS-mutant CRC cells in vitro and in vivo. Conclusion: Our results suggested that the natural product osthole exerted its anticancer effects in KRAS-mutant CRC cells via inducing ferroptosis, and this was partially through inhibiting AMPK/Akt/mTOR signaling. Our results may expand our current knowledge for the use of osthole as an anticancer agent. [ABSTRACT FROM AUTHOR]

Biomedical datasets are increasing in size, stored in many repositories, and face challenges in FAIRness (findability, accessibility, interoperability, reusability). As a Consortium of infectious disease researchers from 15 Centers, we aim to adopt open science practices to promote transparency, encourage reproducibility, and accelerate research advances through data reuse. To improve FAIRness of our datasets and computational tools, we evaluated metadata standards across established biomedical data repositories. The vast majority do not adhere to a single standard, such as Schema.org, which is widely-adopted by generalist repositories. Consequently, datasets in these repositories are not findable in aggregation projects like Google Dataset Search. We alleviated this gap by creating a reusable metadata schema based on Schema.org and catalogued nearly 400 datasets and computational tools we collected. The approach is easily reusable to create schemas interoperable with community standards, but customized to a particular context. Our approach enabled data discovery, increased the reusability of datasets from a large research consortium, and accelerated research. Lastly, we discuss ongoing challenges with FAIRness beyond discoverability. [ABSTRACT FROM AUTHOR]

A novel passive asymmetric quasi-zero stiffness vibration isolator (AQZS-VI) comprising two linear springs acting in parallel with one negative stiffness element (NSE) is proposed, of which the NSE is mainly constructed by the combination of cantilever plate spring and L-shaped lever (CPS-LSL). The static model of the isolator is deduced considering the geometrical nonlinearity of the NSE and the bending deformation of plate spring. The nonlinear stiffness properties of the CPS-LSL and the AQZS-VI, as well as the nonlinear damping properties of the AQZS-VI, are discussed. The absolute displacement transmissibility of the AQZS-VI under base displacement excitation is obtained using harmonic balance method, and the effects of different excitation amplitudes and damping factors on the vibration isolation performance are analyzed. Better than other quasi-zero stiffness vibration isolators (QZS-VI) whose NSEs do not provide supporting force at zero stiffness point, the NSE of the AQZS-VI provides more supporting force than the parallel connected linear springs, which is very beneficial for improving the bearing capacity of the isolator. Compared with a typical symmetric QZS-VI with same damping property, the AQZS-VI has longer stroke with low stiffness and lower peak value of displacement transmissibility. The prototype experiments indicate that the AQZS-VI outperforms the linear counterpart with much smaller starting frequency of vibration isolation and lower displacement transmissibility. The proposed AQZS-VI has great potential for applying in various engineering practices with superior vibration isolation performance. [ABSTRACT FROM AUTHOR]

Arctic absolute sea level variations were analyzed based on multi-mission satellite altimetry data and tide gauge observations for the period of 1993–2018. The range of linear absolute sea level trends were found −2.00 mm/a to 6.88 mm/a excluding the central Arctic, positive trend rates were predominantly located in shallow water and coastal areas, and negative rates were located in high-latitude areas and Baffin Bay. Satellite-derived results show that the average secular absolute sea level trend was (2.53±0.42) mm/a in the Arctic region. Large differences were presented between satellite-derived and tide gauge results, which are mainly due to low satellite data coverage, uncertainties in tidal height processing and vertical land movement (VLM). The VLM rates at 11 global navigation satellite system stations around the Arctic Ocean were analyzed, among which 6 stations were tide gauge co-located, the results indicate that the absolute sea level trends after VLM corrected were of the same magnitude as satellite altimetry results. Accurately calculating VLM is the primary uncertainty in interpreting tide gauge measurements such that differences between tide gauge and satellite altimetry data are attributable generally to VLM. [ABSTRACT FROM AUTHOR]

The folding wing, as a possible concept for designing morphing aircraft, has gained special attention. However, such a wing may encounter complex nonlinear aeroelastic effects with bilinear-hinge stiffnesses during the in-flight morphing process. This paper presents a novel parameterized nonlinear aeroelastic modeling methodology, based on the substructure synthesis of the folding wing with fictitious mass in hinge joints and piecewise-linear theory. The most attractive feature of the present methodology is that the nonlinear aeroelastic dynamics of the wing can be efficiently represented by piecewise, parameterized, linear subsystems using the parameterized fictitious mode method. To demonstrate the accuracy of the present method in representing the nonlinear dynamics of the morphing wing, a folding wing with bilinear stiffness in both fuselage-inboard and inboard-outboard hinges was selected as a numerical example. The numerical results demonstrate that the natural modes of each linear subsystem, as well as the limit-cycle oscillations of the folding wing at different folding angles, can be accurately predicted. In addition, a comparison between the time cost of the present parameterized method and the direct nonparameterized method was made. The comparison showed that the parameterized, nonlinear, aeroelastic modeling methodology provides an efficient way to analyze the nonlinear aeroelastic responses of a morphing wing with bilinear-hinge stiffness. [ABSTRACT FROM AUTHOR]

Purpose: This project aims to design a novel passive quasi-zero stiffness vibration isolator (QZS-VI) and analyze the static and dynamic mechanical properties of the QZS-VI. Methods: First, a novel combination of V-shaped lever, plate spring and cross-shaped structure (VL-PS-CS) vibration isolation platform is designed, and a nonlinear QZS-VI is built by parallel connecting VL-PS-CS and coil spring. Second, the static and dynamic modeling of QZS-VI are derived considering the geometrical nonlinearity of V-shaped lever and the large deflection of plate spring, and the average method is applied to obtain the displacement transmissibility. Third, the effects of different structural parameters (e.g., the lengths of long arm and short arm of V-shaped lever, the assembly angle between two arms, the thickness of plate spring) on the static mechanical and equivalent nonlinear friction properties of QZS-VI are thoroughly investigated. Finally, the vibration isolation performance of the designed QZS-VI is compared with another QZS-VI of buckled beam mechanism and traditional linear vibration isolator. Results: The QZS-VI with VL-PS-CS fully explores the nonlinear advantages of plate spring and V-shaped lever and can achieve excellent high static and low dynamic stiffness and nonlinear friction properties. The superior static mechanical properties and nonlinear friction of QZS-VI can be tuned with different structural parameters. The designed QZS-VI exhibits much smaller resonant frequency, lower peak value and more stability property at the peak frequency than other isolators due to its special nonlinear friction and stiffness properties. Conclusions: The designed QZS-VI is practical, novel and suitable for low-frequency vibration isolation. The innovative structure provides novel insights into the design of passive vibration isolators and has great potential for application in engineering practice. [ABSTRACT FROM AUTHOR]

In this study, to meet the need for accurate tidal prediction, the accuracy of global ocean tide models was assessed in the South China Sea (0°–26°N, 99°–121°E). Seven tide models, namely, DTU10, EOT11a, FES2014, GOT4.8, HAMTIDE12, OSU12 and TPXO8, were considered. The accuracy of eight major tidal constituents (i.e., Q1, O1, P1, K1, N2, M2, S2 and K2) were assessed for the shallow water and coastal areas based on the tidal constants derived from multi-mission satellite altimetry (TOPEX and Jason series) and tide gauge observations. The root mean square values of each constituent between satellite-derived tidal constants and tide models were found in the range of 0.72–1.90 cm in the deep ocean (depth>200 m) and 1.18–5.63 cm in shallow water area (depth<200 m). Large inter-model discrepancies were noted in the Strait of Malacca and the Taiwan Strait, which could be attributable to the complicated hydrodynamic systems and the paucity of high-quality satellite altimetry data. In coastal regions, an accuracy performance was investigated using tidal results from 37 tide gauge stations. The root sum square values were in the range of 9.35–19.11 cm, with the FES2014 model exhibiting slightly superior performance. [ABSTRACT FROM AUTHOR]

Gymnocypris namensis, the only commercial fish in Namtso Lake of Tibet in China, is rated as nearly threatened species in the Red List of China's Vertebrates. As one of the highest-altitude schizothorax fish in China, G. namensis has strong adaptability to the plateau harsh environment. Although being an indigenous economic fish with high value in research, the biological characterization, genetic diversity, and plateau adaptability of G. namensis are still unclear. Here, we used Pacific Biosciences single molecular real time long read sequencing technology to generate full-length transcripts of G. namensis. Sequences clustering analysis and error correction with Illumina-produced short reads to obtain 319,044 polished isoforms. After removing redundant reads, 125,396 non-redundant isoforms were obtained. Among all transcripts, 103,286 were annotated to public databases. Natural selection has acted on 42 genes for G. namensis, which were enriched on the functions of mismatch repair and Glutathione metabolism. Total 89,736 open reading frames, 95,947 microsatellites, and 21,360 long non-coding RNAs were identified across all transcripts. This is the first study of transcriptome in G. namensis by using PacBio Iso-seq. The acquisition of full-length transcript isoforms might accelerate the transcriptome research of G. namensis and provide basis for further research. [ABSTRACT FROM AUTHOR]

The focus of this study was first to determine the most suitable geophysical correction models for obtaining satellite-derived sea level height time series in the South China Sea (SCS; 0–26° N, 99° E–121 °E). Analysis of difference of the sea level anomaly standard deviation was conducted to assess the quality of the various correction models. The set of correction models was used to establish the continuous satellite-derived sea level height time series. Harmonic and response analysis methods were carried out for primary mission and interleaved mission along-track data, respectively, to extract the harmonic constants of eight major tidal constituents. We evaluated the quality of satellite-derived tidal constituents, which were derived from TOPEX/Poseidon, Jason-1, Jason-2, and Jason-3 over a 25-year period from February 1993 to January 2018, by a detailed comparison with values extracted from 27 tide gauge observations. The results showed that satellite-derived tidal constituents have high precision in most shallow water areas, but there are inevitably still some locations with large errors and poor predictability. [ABSTRACT FROM AUTHOR]

This paper investigated the quality of site-specific surface temperature and surface pressure data in the coastal regions of China, which were interpolated from the European Centre for Medium-Range Weather Forecast Interim reanalysis (ERA-Interim), Japanese 55-year Reanalysis Project (JRA-55), and the National Centers for Environmental Prediction Final (NCEP FNL) reanalysis surface meteorological datasets as well as from the new Global Pressure and Temperature (GPT2) model data. The measured temperature and pressure along with the collocated GPS data from 2014 were collected from 25 observation stations evenly located in the region. Compared with the actual meteorological observations, the performances of the interpolated data from three reanalysis datasets differ marginally, with the root mean square errors (RMSEs) of the interpolated surface temperature and pressure less than 2.4 K and 1.6 hPa, respectively; however, the RMSEs of the surface temperature and pressure interpolated from the GPT2 model were 3.0 K and 4.2 hPa, respectively. Data based on GPS PWV products that used the meteorological parameters interpolated from three reanalysis data were very close to those of meteorological observations, with biases within ± 0.4 mm and RMSEs below 0.5 mm in most areas, and the RMSE of PWV using the GPT2 model interpolation data was superior by 2 mm. The measurement of GPS PWV using the interpolated reanalysis meteorological data also compared well with radiosonde observations, with RMSE between them tending to increase with a decrease of the GPS station's latitude. However, the GPS PWV based on the interpolated data could not reflect the true change in water vapor during typhoon events. [ABSTRACT FROM AUTHOR]

A multi beam sonar survey is carried out in the continental slope of the Taixinan Basin to obtain submarine topographic and water column data. The data are processed to obtain water column images. Anomalous water column images, displaying plume characteristics, are found in gas hydrate enriched areas in the Taixinan Basin. This indicates the presence of natural gas resources in the Taixinan Basin. The multibeam sonar system is shown to provide an accurate and effective approach for detecting sub-sea gas hydrate. [ABSTRACT FROM AUTHOR]

To a multibeam echo sounder system (MBES), under water sound refraction plays an important role in depth measurement accuracy, and errors in sound velocity profile lead to inaccuracies in the measured depth (especially for outer beams). A method is developed to estimate the sound velocity profile based on the depth measured by vertical beam. Using this depth and other parameters, such as t (sound pulse propagation time), θ (beam inclination angle), etc. We can estimate a simple sound velocity profile with which the depth error has been reduced. This method has been tested with a real dataset acquired in the East China Sea. [ABSTRACT FROM AUTHOR]

Atherosclerosis is an inflammatory disease. Both innate and adaptive immunity are involved in lesion formation and development. A number of antigen candidates, such as oxidized low-density lipoprotein and heat shock protein, have been associated with the inflammation and immune reaction that is part of the atherosclerotic process. Because experimental models of some other inflammatory/autoimmune diseases can be improved by vaccination, it is of interest to investigate if vaccination can also be applied to prevent or retard atherosclerosis. Indeed, the modification of immune responses in animal models can greatly affect the development and progression of atherosclerosis. This review provides an overview of our current understanding of effects and proposed mechanisms of immunization on preventing atherosclerosis. [ABSTRACT FROM AUTHOR]

Studies the trace element characteristics in the diopsides of peridotite xenoliths at the Cenozoic Hannuoba basalts in northern China. Overall depletion and heterogeneity of the continental mantle beneath northern China Craton; Indicators of the partial melting of the xenoliths; Formation of xenoliths by mantle deformation.