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Ideal leading and nominee compounds with inhibiting effects on KRAS G12C were selected from the ZINC database, laying a cornerstone for the progress of anticancer drugs. A variety of computational virtual screening methods were utilized to screen possible inhibitors of KRAS G12C. LibDock was utilized to estimate 17 930 compounds and the top 20 were nominated for additional study, which was absorption, distribution, metabolism, and excretion and harmfulness prediction. Molecule docking was employed to prove the binding connection between certain ligands and KRAS G12C. Natural novel compounds ZINC000012494057 and ZINC000003789195 were selected to bind stably with KRAS G12C. In addition, they had lower scores in Ames mutagenicity, rodent carcinogenicity, cytochrome P450 2D6(CYP2D6) tolerance, and non-developmental toxicity potential. Molecular dynamic simulations demonstrate that the combination of ZINC000012494057 and ZINC000003789195 with KRAS G12C has more favorable potential energy, which provides conditions for their stable existence in the natural environment. Natural compounds ZINC000012494057 and ZINC000003789195 were identified as KRAS G12C potential inhibitors. These two compounds have been verified to have enormous importance for the progress of anticancer medicines.

To reveal the landslide mechanism of the loess slope induced by rainfall, we carried out a series of tests for loess under different permeability durations, and studied the influences of rainfall on the permeability coefficient, the soil water characteristic curve, the components, the microstructure, and the shear strength of the loess. Test results show that the total dissolved solids, the sand particles, and the clay particles will decrease, but the silt particles will increase with the permeability duration, it changes the soil original structure and influences the soil water characteristic curve of the loess. And more than 68% permeability coefficients will loss after permeability test. The infiltrated rainwater will increase the effective saturation of the soil, and the shear strength of the soil will decrease with the increasing of effective saturation. The shear strength further decreases with the infiltration time (or rainfall duration). The landslide will initial once the shear strength reduces to the geostatic stress of the soil slope. The shear strength loss of the soils induced by rainfall should be considered during slope stability analysis. This study can help to understand the initiation of loess landslide induced by rainfall.

Particle packing is widely applied in organic pollutant adsorption, catalytic reaction, biomass combustion, nuclear cooling, and other scenarios. Due to the complexity of the shape, the studies on the void fraction of the cylindrical particles are not as thorough as the spherical particles. This study investigated the influence of the filling rate, material properties and sphericity on the void fraction of cylinders through experiments and simulation. DEM (discrete element method) was validated by the internal structures of the packing obtained by CT (computed tomography). Based on the logarithmic correlation between the void fraction and filling rate, an ingenious framework for predicting the void fraction of cylindrical particles was presented with two intermediate coefficients. By correlating the coefficients with the material property and sphericity, a novel void-fraction prediction model was established with R-squared of 0.996. The mechanism of void fraction under random loose packing for cylinders was eventually found in this study.

The mechanism and origins of site-selectivity of Rh2(S-tfpttl)4-catalyzed C(sp3)–H bond aminations were studied using density functional theory (DFT) calculations. The synergistic combination of the dirhodium complex Rh2(S-tfpttl)4 with tert-butylphenol sulfamate TBPhsNH2 composes a pocket that can access both tertiary and benzylic C–H bonds. The nonactivated tertiary C–H bond was selectively aminated in the presence of an electronically activated benzylic C–H bond. Both singlet and triplet energy surfaces were investigated in this study. The computational results suggest that the triplet stepwise pathway is more favorable than the singlet concerted pathway. In the hydrogen atom abstraction by Rh–nitrene species, which is the rate- and site-selectivity-determining step, there is an attractive π–π stacking interaction between the phenyl group of the substrate and the phthalimido group of the ligand in the tertiary C–H activation transition structure. By contrast, such attractive interaction is absent in the benzylic C–H amination transition structure. Therefore, the DFT computational results clearly demonstrate how the synergistic combination of the dirhodium complex with sulfamate overrides the intrinsic preference for benzylic C–H amination to achieve the amination of the nonactivated tertiary C–H bond.

With the development of location-based services and smart terminals, skyline query technique has been used widely in intelligent transportation systems. In skyline queries, the areas and keywords queried by users have a great impact on the quality of the query results and users may only be interested in the closer results of the skyline query. However, current approaches for the continuous skyline query limit the area of the skyline query to a specific area in the road network, which leads to that many useful query results cannot be retrieved. To this end, an innovative continuous skyline query approach in city range is proposed in this paper, where a multi-scale area divisions of the urban road network are provided to find the optimize query scale and area. In our approach, first, the dominant area of each intersection node in the road network is established based on the Voronoi. Then, all Points of Interest (POIs) are divided into the dominant area of each intersection node. After that, the intersection node aggregation algorithm (INAA), link remolding algorithm (LMA) and link fitting algorithm (LFA) are proposed to reduce the number of intersection nodes in the road network, so as to increase the dominant area of the remaining intersection nodes and the number of POIs in these nodes. Finally, a better query scale by considering the efficiency and quality of the query is given through the studies.

Previous studies have shown a significant increase in monoclonal gammopathy (MG) prevalence in patients with human immunodeficiency virus (HIV). HIV and MG both can cause renal injury and have attracted increasing nephrologists' attention. To date, there has been a lack of relevant studies on the renal pathology of HIV combined with MG. Here, we report a case of a newly diagnosed HIV patient with co-morbid MG and subsequent or concurrent massive proteinuria whose renal biopsy showed minimal change disease (MCD). After a period of administration of highly active antiretroviral therapy (HAART), HIV viral RNA was undetectable in plasma, along with complete remission of the nephropathy. However, there was no significant effect on MG.

Diffusion magnetic resonance imaging (dMRI) datasets are susceptible to several confounding factors related to data quality, which is especially true in studies involving young children. With the recent trend of large-scale multicenter studies, it is more critical to be aware of the varied impacts of data quality on measures of interest. Here, we investigated data quality and its effect on different diffusion measures using a multicenter dataset. dMRI data were obtained from 691 participants (5-17 years of age) from six different centers. Six data quality metrics-contrast to noise ratio, outlier slices, and motion (absolute, relative, translation, and rotational)-and four diffusion measures-fractional anisotropy, mean diffusivity, tract density, and length-were computed for each of 36 major fiber tracts for all participants. The results indicated that four out of six data quality metrics (all except absolute and translation motion) differed significantly between centers. Associations between these data quality metrics and the diffusion measures differed significantly across the tracts and centers. Moreover, these effects remained significant after applying recently proposed harmonization algorithms that purport to remove unwanted between-site variation in diffusion data. These results demonstrate the widespread impact of dMRI data quality on diffusion measures. These tracts and measures have been routinely associated with individual differences as well as group-wide differences between neurotypical populations and individuals with neurological or developmental disorders. Accordingly, for analyses of individual differences or group effects (particularly in multisite dataset), we encourage the inclusion of data quality metrics in dMRI analysis.

The age of Yunnanosaurus youngi, a non-sauropod basal sauropodomorph, was reported as the Middle Jurassic. However, no basal sauropodomorphs have been reported worldwide in the Middle Jurassic prev...

Alpha linolenic acid (ALA) is an essential polyunsaturated fatty acids that can improve human health. Rapeseed is the second largest oil crop in the world but the ALA content in its seed fatty acids is only about 10%. Two rapeseed germplasms YH25005 and R8Q10 with high content (up to 21%) ALA were developed by intervarietal crossing. They were used as the maternal parent (P1) when crossed with a low ALA parent SW (P2) to produce the seeds of the F1 hybrid, F2, and backcrosses to P1 (BCP1) and P2 (BCP2). A multigeneration joint segregation analysis was conducted to determine major gene ​+ ​polygene effects of the content of three major unsaturated fatty acids including oleic (OA), linoleic (LA) and ALA. The results showed that, although some genes favorable to ALA accumulation were not allelic in R8Q10 and YH25005, all the inheritances of OA, LA and ALA in YH25005 ​× ​SW and R8Q10 ​× ​SW followed a genetic model of ‘two pairs of additive major genes ​+ ​additive-dominant polygenes’. It is suggested that the contents of OA, LA and ALA are closely related and the major genes in the parent SW containing loss-of-function mutations in FAD2 and FAD3 loci had strong effect to reduce ALA and elevate OA. However, total genetic effect of the polygenes was greater than that of the two major genes, especial on ALA content. It indicated that it is necessary to employ a larger F2 population to find the plant that accumulate enough minor-effect polygenes for high ALA content. The results are useful for high ALA rapeseed breeding and future work of gene mapping.

Urban rail transit stations are the key nodes of urban rail transit network. Identifying and analyzing land use characteristics around urban rail transit stations can significantly contribute to urban rail transportation operation and management. Therefore, a visualization method of land use characteristics around urban rail transit stations based on POI is proposed in this paper. In the proposed method, first, the Voronoi diagram is used to determine coverage of urban rail transit stations and each POI is put in a coverage area based on their physical location. Then, topic-oriented hierarchical POIs of each urban rail transit station are extracted based on skyline idea. Finally, the land use characteristics around an urban rail transit station are visualized based on the extracted hierarchical POIs. We carried out two case studies and a quality evaluation. By using realistic data from Beijing rail transit in order to validate the method proposed in this paper. Results show that our method can clarify various situations of land use of urban rail transit stations and may provide support for the application of transportation model technology.

Over the past few years, atmospheric Inductively Coupled Plasma (ICP) has aroused extensive attention in optical fabrication field since its chemical etching-based processing mode does not mechanically damage work-pieces. However, commercial Fassel-type torch are commonly employed in processing, and the high temperature plasma jet generated by commercial Fassel-type torch will cause thermal damage to optical elements. In this paper, an ICP jet torch is developed for optical fabrication, capable of maintaining plasma jet under a low power of 156 W. By reducing the minimum maintenance power of plasma jet, the processing temperature is down-regulated to 112 °C. To explain the low maintenance power principle in this research, the effect of radial confinement and axial pushing-off on the plasma are analyzed by simulation and experiment processes. Moreover, the effect of these two phenomena on the maintenance power is analyzed experimentally. Subsequently, the experiments are performed to verify the processing temperature, removal efficiency and removal stability of the torch. As revealed from the experimental results, the proposed torch exhibits the stability of footprint up to 97.5%.

Multi-agent technologies have been widely applied to many applications, such as in e-markets, cloud computing, service-oriented environments, etc. In real applications, service-oriented environments are open and dynamic, where loosely coupled agents interact to consume and provide services. How to accurately evaluate the potential performance (i.e., QoS) of service providers on the service requested by a service consumer in such open and dynamic environments is a challenging issue in both theory and practice. In this paper, an innovative approach is proposed to evaluate the QoS of service providers in service-oriented environments. The proposed approach first borrows the reference report mechanism from the certified reputation model, so as to efficiently collect reference reports (i.e., historical performance) of service providers in open and dynamic environments. Then, a tensor-based QoS model is proposed to construct multi-dimensional relationships between QoS evaluation factors and the QoS values of service providers based on the collected reference reports. The QoS evaluation factors include the type of services, the performance of service providers, the subjectivity of service consumers, the time slot of reference reports. Finally, a CANDECOMP/PARAFAC decomposition and gradient descent-based mechanism is used to evaluate the QoS values of service providers through completing the missing entry values in the constructed tensor. The uniform random simulation experiments indicate that the proposed approach can achieve efficient and accurate QoS evaluation in service-oriented environments with only limited collected reference reports, especially when some service providers do not have reference reports.

Based on deterministic chemical etching, atmospheric pressure plasma processing (APPP) with a high material removal rate and spatial machining resolution, is a promising computer-controlled optical surfacing (CCOS) technique for freeform surface generation. However, the time-variant removal characteristics of APPP induce nonlinearity in the CCOS process, which requires more consideration in the dwell-time calculation. In this paper, the nonlinear dwell-time algorithm based on the concept of controlling volumetric removal is studied. The freeform surface generation by controlling volumetric removal is modeled to provide the theoretical basis for the algorithm. The applicability of the algorithm in freeform generation by APPP with time-varying characteristics is explored through numerical simulations. Finally, a freeform surface is successfully created based on the algorithm and relevant analysis results, which validates the applicability of the algorithm in freeform generation using time-variant tool influence functions.

Uniaxial models are commonly used to describe the change in magnitude of in-situ principal stresses around depleted reservoirs. The accuracy of these models is assessed in this paper through a reservoir-scale analytical solution for the stresses induced by depleting a disk-shaped reservoir embedded within an infinite elastic model of the subsurface. The Hankel-Fourier transform expressions of axisymmetric Green’s functions for a ring-shaped eigenstrain in an infinite elastic medium are used to develop the solution. This solution is validated against numerical simulation results of COMSOL®. The solution is next used to obtain the safest deviation survey, as well as the corresponding drilling margins of infill wellbores that are drilled in the general vicinity of depleted reservoirs. Inside and outside of a reservoir subjected to different faulting regimes are considered for the wellbore-scale stress analysis. Results indicate that despite their common use, the uniaxial models may return significantly erroneous predictions of the in-situ stress state in depleted reservoirs. In particular, the in-situ stress changes are found to strongly depend on the geological azimuth and radial distance from the reservoir center point. Consequently, the uniaxial models may fall short in accurate prediction of the shear or tensile failure gradients of infill wells. These errors would be more substantial for wells that are closer to the reservoir flanks.

In the present paper, some new exact solutions of the (3+1)-dimensional sinh-Gorden equation are displayed. First, based on the Lie point symmetry, basic infinitesimal generators given; also, and the Lie algebra and commutative relations are shown. Second, some exact solutions are obtained using the F-expansion method, and a great many Jacobian-elliptic function solutions are presented. Finally, other forms of solutions are derived using the traveling wave transform.

Void fraction of cylindrical particles greatly influences heat and mass transfer and resistance characteristics involved in the processes. The effect of the filling rate of cylindrical particles on the void fraction of the random loose packing (RLP) was studied through the experiments. Then, the discrete element method (DEM) was used to reproduce the RLP process of the cylindrical particles, and the effect of the filling rate on the void fraction of the packing was revealed by the internal packing structure. The following conclusions can be drawn: the void fraction increased with the logarithm of the filling rate and did not change after reaching the maximum value; a void fraction prediction model of cylindrical particles, considering filling rate, was established; a larger filling rate would cause the particles to interact to form “bridge” structures, forming larger particle inclination angles and resulting in a larger void fraction of the packing.

Traffic flow prediction plays an important role in intelligent transportation applications, such as traffic control, navigation, path planning, etc., which are closely related to people’s daily life. In the last twenty years, many traffic flow prediction approaches have been proposed. However, some of these approaches use the regression based mechanisms, which cannot achieve accurate short-term traffic flow predication. While, other approaches use the neural network based mechanisms, which cannot work well with limited amount of training data. To this end, a light weight tensor-based traffic flow prediction approach is proposed, which can achieve efficient and accurate short-term traffic flow prediction with continuous traffic flow data in a limited period of time. In the proposed approach, first, a tensor-based traffic flow model is proposed to establish the multi-dimensional relationships for traffic flow values in continuous time intervals. Then, a CANDECOMP/PARAFAC decomposition based algorithm is employed to complete the missing values in the constructed tensor. Finally, the completed tensor can be directly used to achieve efficient and accurate traffic flow prediction. The experiments on the real dataset indicate that the proposed approach outperforms many current approaches on traffic flow prediction with limited amount of traffic flow data.