River delta plains (deltas) are susceptible to subsidence producing undesirable environmental impact and affecting dense population. The City of Shanghai, located in the easternmost of Yangtze Delta ...in China, is one of the most developed regions in China that experiences the greatest land subsidence. Excessive groundwater withdrawal is thought to be the primary cause of the land subsidence, but rapid urbanization and economic development, mass construction of skyscrapers, metro lines and highways are also contributing factors. In this paper, a spatial–temporal analysis of the land subsidence in Shanghai was performed with the help of the Small Baseline Subset Interferometric Synthetic Aperture Radar. Twenty
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-band ALOS PALSAR images acquired during 2007–2010 were used to produce a linear deformation rate map and to derive time series of ground deformation. The results show homogeneous subsidence within the research area, but exceptionally rapid subsidence around skyscrapers, along metro lines, elevated roads and highways was also observed. Because groundwater exploitation and rapid urbanization responsible for much of the subsidence in the Shanghai region are expected to continue, future subsidence monitoring is warranted.
The functional annotation of livestock genomes is crucial for understanding the molecular mechanisms that underpin complex traits of economic importance, adaptive evolution and comparative genomics. ...Here, we provide the most comprehensive catalogue to date of regulatory elements in the pig (Sus scrofa) by integrating 223 epigenomic and transcriptomic data sets, representing 14 biologically important tissues. We systematically describe the dynamic epigenetic landscape across tissues by functionally annotating 15 different chromatin states and defining their tissue-specific regulatory activities. We demonstrate that genomic variants associated with complex traits and adaptive evolution in pig are significantly enriched in active promoters and enhancers. Furthermore, we reveal distinct tissue-specific regulatory selection between Asian and European pig domestication processes. Compared with human and mouse epigenomes, we show that porcine regulatory elements are more conserved in DNA sequence, under both rapid and slow evolution, than those under neutral evolution across pig, mouse, and human. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating 47 human genome-wide association studies, we demonstrate that, depending on the traits, mouse or pig might be more appropriate biomedical models for different complex traits and diseases.
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•The surface deformation in the western KFTB from 2015 to 2017 is derived based on the SBAS-InSAR method.•Most namakiers show distinguishable and heterogeneous surface ...displacement.•The surface deformation is mainly concentrated in the Qiulitage structural belt, where tectonic activity is active.•The subsurface structure and topography are the principal factors that control the namakier surface deformation.
The Kuqa foreland fold-thrust belt is one of the key areas for gas exploration and a rare region with allochthonous salt outcrops well-preserved. In this study, twenty-eight Sentinel-1A Synthetic Aperture Radar (SAR) images acquired from 2015 to 2017 were utilized to detect and map the surface deformation in the western Kuqa fold-thrust belt (KFTB) based on the Small Baseline Subset (SBAS) Interferometric Synthetic Aperture Radar (InSAR) method. Spatial-temporal statistics analysis and comparison in different structural belts and geomorphology were made based on the inversion results. The results show that the spatial distribution characteristics of the surface deformation detected in subaerial salt structures are highly consistent with the previous studies, but the deformation rate in Daxiagu and Awate namakier increased to 25–35 mm/a. It indicates that the KFTB is still undergoing continuous north–south compression and shortening, which drives the underground salt to keep moving. Combined with the sufficient salt supply, increased activity of subaerial namakier and enhanced surface process in recent years, a variety of spatial–temporal surface deformation patterns are observed in the western KFTB. These varieties are attributed to the differences in structure and geomorphology in different belts, which can provide vital clues for exploring the roles of tectonics and surface processes in the spatial–temporal evolution of surface morphology in active tectonic regions.
The Kuqa fold–thrust belt (KFTB) has a complex thrust-system geometry and comprises basement-involved thrusts, décollement thrusts, triangle zones, strike-slip faults, transpressional faults, and ...pop-up structures. These structures, combined with the effects of Paleogene salt tectonics and Paleozoic basement uplift form a complex structural zone trending E–W. Interpretation and comprehensive analysis of recent high-quality seismic data, field observations, boreholes, and gravity data covering the KFTB has been performed to understand the characteristics and mechanisms of the deformation styles along strike. Regional sections, fold–thrust system maps of the surface and the sub-salt layer, salt and basement structure distribution maps have been created, and a comprehensive analysis of thrust systems performed. The results indicate that the thrust-fold system in Paleogene salt range can be divided into five segments from east to west: the Kela-3, Keshen, Dabei, Bozi, and Awate segments. In the easternmost and westernmost parts of the Paleogene salt range, strike-slip faulting and basement-involved thrusting are the dominant deformation styles, as basement uplift and the limits of the Cenozoic evaporite deposit are the main controls on deformation. Salt-core detachment fold–thrust systems coincide with areas of salt tectonics, and pop-up, imbricate, and duplex structures are associated with the main thrust faults in the sub-salt layer. Distribution maps of thrust systems, basement structures, and salt tectonics show that Paleozoic basement uplift controlled the Paleozoic foreland basin morphology and the distribution of Cenozoic salt in the KFTB, and thus had a strong influence on the segmented structural deformation and evolution of the fold–thrust belt. Three types of transfer zone are identified, based on the characteristics of the salt layer and basement uplift, and the effects of these zones on the fault systems are evaluated. Basement uplift and the boundary of the salt deposit generated strike-slip faults in the sub-salt layer and supra-salt layers at the basin boundary (Model A). When changes in the basement occurred within the salt basin, strike-slip faults controlled the deformation styles in the sub-salt layer and shear-zone dominated in the supra-salt layer (Model B). A homogeneous basement and discontinues salt layer formed different accommodation zones in the sub- and supra-salt layers (Model C). In the sub-salt layer the thrusts form imbricate structures on the basal décollement, whereas the supra-salt layer shows overlapping, discontinuous faults and folds with kinds of salt tectonics, and has greater structural variation than the sub-salt layer.
•Various deformation styles in supra-salt layer and sub-salt layer in different structural segments of fold-thrust belt using 2D/3D seismic data, field data, satellite imagine and gravity data.•3 transfer models were built for salt bearing fold-thrust belt controlled by basement uplift and intermedia salt layer.•Interaction of intermedia salt décollement and basement uplift in fold-thrust belt.
Ephemeral subaerial salt diapirs are gravitationally unstable and vulnerable to climate and tectonic activity due to the rheology and incompressibility of rock salt. Quantifying the kinematics of ...subaerial salt and clarifying the role of tectonics, surface processes, and climate in reshaping the surface salt morphology provides an invaluable opportunity to explore the interactions between Earth’s spheres on a much shorter timescale. With diverse exposed salt diapirs and potential motions, the Kuqa fold‐thrust belt (KFTB), NW China, represents an optimum natural laboratory to understand subaerial salt kinematics. Here, we integrated ascending and descending geometries of Sentinel‐1 synthetic aperture radar images with optical remote sensing data, seismic profiles, digital elevation models, and meteorological records to explore the potential correlation between subaerial salt motions and geomorphic, tectonic, and climatic factors. Using the interferometric synthetic aperture radar technique, we observed a maximum of 25 mm/yr in vertical and 40 mm/yr in horizontal surface salt deformation in the KFTB from 2014 to 2020. Our findings demonstrate a gravity spreading dominant system, where topography exerts a primary control on the surface displacement patterns of salt structures, while weather variables influence deformation mainly by softening salt and facilitating gravity‐driven salt flow.
Plain Language Summary
Investigating tectonic‐climate‐surface interactions is crucial for understanding the solid Earth’s evolution, but it still faces an array of challenges due to the varying timescales of different processes. Surface salt bodies possess distinctive viscous fluid rheology that bridges portions of the gap between rock and ice, providing a unique natural laboratory to study the interactions between Earth's different spheres. Here we rely on remote sensing technology and multidisciplinary data sets to investigate the kinematics and dynamics of surface salt bodies in the western Kuqa fold‐thrust belt, NW China. The monitoring reveals a variety of deformations across surface salt bodies controlled by the coupling of geomorphic, tectonic, and climatic factors. Topography has a first‐order control on the salt deformation pattern, regional and local structures determine underground salt replenishment, and weather variables influence deformation mainly by affecting the water content of salt and subsequently increasing gravity‐driven salt flow. These findings will advance our knowledge of the subaerial salt behavior and how different systems interact across the Earth’s surface in reshaping salt morphology.
Key Points
The subaerial salt structures show nonuniform deformation controlled by the coupling of geomorphology, tectonics, and climate
Topography exerts a primary control on surface salt motion, while regional and local tectonics drive underground salt replenishment
Weather influences subaerial salt motion primarily by affecting the water content of salt rather than by dissolution/erosion
Induction of compensatory mechanisms and ERK reactivation has limited the effectiveness of Raf and MEK inhibitors in RAS-mutant cancers. We determined that direct pharmacologic inhibition of ERK ...suppressed the growth of a subset of KRAS-mutant pancreatic cancer cell lines and that concurrent phosphatidylinositol 3-kinase (PI3K) inhibition caused synergistic cell death. Additional combinations that enhanced ERK inhibitor action were also identified. Unexpectedly, long-term treatment of sensitive cell lines caused senescence, mediated in part by MYC degradation and p16 reactivation. Enhanced basal PI3K-AKT-mTOR signaling was associated with de novo resistance to ERK inhibitor, as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-function screen. Our findings reveal distinct consequences of inhibiting this kinase cascade at the level of ERK.
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•Bimodal action: differential consequences of short-versus long-term ERK inhibition•ERK inhibitor sensitivity is associated with MYC degradation in vitro and in vivo•PI3K-AKT-mTOR signaling drives basal resistance to ERK inhibitor treatment•Resistance mechanisms are complex and display significant inter-tumor heterogeneity
Hayes et al. report an ERK inhibition-mediated growth suppression mechanism involving MYC degradation that is associated with the induction of a senescence-like phenotype in KRAS-mutant pancreatic cancer cells. Inhibitor combinations that enhance the effect of ERK inhibitor are also identified.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare, aggressive ovarian cancer in young women that is universally driven by loss of the SWI/SNF ATPase subunits SMARCA4 and ...SMARCA2. A great need exists for effective targeted therapies for SCCOHT.
To identify underlying therapeutic vulnerabilities in SCCOHT, we conducted high-throughput siRNA and drug screens. Complementary proteomics approaches profiled kinases inhibited by ponatinib. Ponatinib was tested for efficacy in two patient-derived xenograft (PDX) models and one cell-line xenograft model of SCCOHT.
The receptor tyrosine kinase (RTK) family was enriched in siRNA screen hits, with FGFRs and PDGFRs being overlapping hits between drug and siRNA screens. Of multiple potent drug classes in SCCOHT cell lines, RTK inhibitors were only one of two classes with selectivity in SCCOHT relative to three SWI/SNF wild-type ovarian cancer cell lines. We further identified ponatinib as the most effective clinically approved RTK inhibitor. Reexpression of SMARCA4 was shown to confer a 1.7-fold increase in resistance to ponatinib. Subsequent proteomic assessment of ponatinib target modulation in SCCOHT cell models confirmed inhibition of nine known ponatinib target kinases alongside 77 noncanonical ponatinib targets in SCCOHT. Finally, ponatinib delayed tumor doubling time 4-fold in SCCOHT-1 xenografts while reducing final tumor volumes in SCCOHT PDX models by 58.6% and 42.5%.
Ponatinib is an effective agent for
-mutant SCCOHT in both
and
preclinical models through its inhibition of multiple kinases. Clinical investigation of this FDA-approved oncology drug in SCCOHT is warranted.
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•The fault-related folds and step-type thrust faults are predominant features of the Xu-Huai thrust-and-fold belt.•Two geological cross-sections were used for structural balancing and ...restoration.•A shortening rate of 43–46% was obtained from the restoration of two balanced cross-sections.•The Xu-Huai belt was derived from the Early Mesozoic crustal underthrusting of the SE margin of NCB beneath the SCB.
The Xu-Huai thrust-and-fold belt, located in the southeastern margin of the North China Block, consists mainly of thrust and folded pre-Mesozoic strata. Its geodynamic evolution and tectonic setting are topics of long debate. This paper provides new evidence from geological mapping, structural analysis, and making balance cross-sections, with restoration of cross-sections. Results suggest that this belt was subjected to two-phase deformation, including an early-phase regional-scale NW-ward thrust and fold, and a late-phase extension followed by the emplacement of dioritic, monzodioritic porphyrites dated at 131–135Ma and locally strike-slip shearing. According to the mapping, field observations and drill-hole data, three structural units were distinguished, namely, (1) the pre-Neoproterozoic crystalline basement in the eastern segment, (2) the nappe unit or the thrust-and-fold zone in the central segment, which is composed of Neoproterozoic to Ordovician carbonate rocks and Carboniferous-Permian coal-bearing rocks, about 2600m thick, and (3) the western frontal zone. A major decollement fault has also been identified in the base of the nappe unit, on which dozen-meter to km-scale thrust-and-fold bodies were commonly developed. All pre-Mesozoic depositional sequences were involved into a widespread thrust and fold event. Six uncompetent-rock layers with biostratigraphic ages (Nanjing University, 1996) have been recognized, and each uncompetent-rock layer occurred mainly in the top of the footwall, playing an important role in the development of the Xu-Huai thrust-and-fold belt. Geometry of the major decollement fault suggests that the nappe unit of this belt was rooted in its eastern side, near the Tan-Lu Fault Zone. Two geological cross-sections were chosen for structural balancing and restoration. From the balanced cross-sections, ramp-flat and imbricated faults as well as fault-related folds were identified. A shortening of 20.6–29.6km was obtained from restoration of balanced sections, corresponding to a shortening rate of 43.6–46.4%. This shortening deformation was likely related to the SE-ward intracontinental underthrust of the North China Block beneath the South China Block during the Mesozoic.
In recent years, using clustering technology to realize equipment security warning is a research hotspot in the field of data mining applications. However, due to the lack of data fusion mechanism ...and prior knowledge guidance, the performance of most existing methods is limited when applied to complex equipment such as elevator. In this paper, a novel Tensorial Multi-view Subspace Clustering with Side constraints is proposed for elevator security warning, which first introduces tensorial multi-view subspace learning to achieve data fusion based on high-order correlation. Second, the prior knowledge is formalized as side constraints between samples through adaptive graph learning, where certain elevators are forced to have similar or dissimilar operation status. Third, a unified model combining tensorial multi-view subspace learning and adaptive graph learning is constructed to eliminate the instability caused by phased learning. Furthermore, an efficient optimization algorithm is designed to solve this model. Extensive experiments on several benchmark datasets demonstrate the superiority of our method, and the experimental results on real elevator status datasets demonstrate that our method accurately identifies the operating status of each elevator equipment.
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