Inhibition of growth and metastasis of triple-negative breast cancer targeted by Traditional Chinese Medicine Tubeimu in orthotopic mice models

Objective： Triple-negative breast cancer（TNBC） is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu（TBM）, the rhizome of Bolbostemma paniculatum（Maxim.） Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu（ETBM） on TNBC orthotopic mouse models and cell lines.Methods： We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line. Digital gene expression sequencing was performed and Kyoto Encyclopedia of Genes and Genomes（KEGG） analysis applied to explore the pathways influenced by ETBM.Moreover, quantitative real-time polymerase chain reactions（q RT-PCR） and Western blot were delivered to confirm the gene expression changes.Results： ETBM exhibited noticeable control on tumor metastasis and growth of TNBC tumors with no obvious toxicity. In compliance with this, it also showed inhibition of cell migration and invasion in vitro. Its impact on the changed biological behavior in TNBC may be a result of decreased expression of integrin β1（ITGβ1）, integrin β8（ITGβ8） and Rho GTPase activating protein 5（ARHGAP5）, which disabled the focal adhesion pathway and caused change in cell morphology.Conclusions： This study reveals that ETBM has anti-metastatic effects on MDA-MB-231-GFP tumor and may lead to a new therapeutic agent for the integrative treatment of highly invasive TNBC.

3-D multi-parameter type traveltime tomography in a spherical coordinate frame: comparison of double and triple class simultaneous inversions

It is now common practice to perform simultaneous traveltime inversion for the velocity field and the reflector geometry in reflection/refraction tomography, or the velocity field and the hypocenter locations in regional earthquake tomography, but seldom are all three classes of model parameters updated simultaneously. This is mainly due to the trade-off between the different types of model parameters and the lack of different seismic phases to constrain the model parameters. Using a spherical-coordinate ray tracing algorithm for first and later（primary reflected） arrival tracing algorithm in combination with a popular linearized inversion solver, it is possible to simultaneously recover the three classes of model parameters in regional or global tomographic studies. In this paper we incorporate the multistage irregular shortest-path ray tracing algorithm（in a spherical coordinate system） with a subspace inversion solver to formulate a simultaneous inversion algorithm for triple model parameters updating using direct and later arrival time information.Comparison tests for two sets of data（noise free and added noise） indicate that the new triple-class parameter inversion algorithm is capable of obtaining nearly the same results as the double-class parameter inversion scheme. Furthermore,the proposed multi-parameter type inversion method is not sensitive to a modest level of picking error in the traveltime data, and also performs well with a relatively large uncertainty in earthquake hypocentral locations. This shows it to be a feasible and promising approach in regional or global tomographic applications.

Ensemble Cloud Model Application in Simulating the Catastrophic Heavy Rainfall Event

An attempt has been made in the present research to simulate a deadly flash-flood event over the City of Skopje,Macedonia on 6 August 2016.A cloud model ensemble forecast method is developed to simulate a super-cell storm’s initiation and evolutionary features.Sounding data are generated using an ensemble approach,that utilizes a triple-nested WRF model.A three-dimensional(3-D)convective cloud model(CCM)with a very fine horizontal grid resolution of 250-m is initialized,using the initial representative sounding data,derived from the WRF 1-km forecast outputs.CCM is configured and run with an open lateral boundary conditions LBC,allowing explicit simulation of convective scale processes.This preliminary study showed that the ensemble approach has some advantages in the generation of the initial data and the model initialization.The applied method minimizes the uncertainties and provides a more qualitative-quantitative assessment of super-cell storm initiation,cell structure,evolutionary properties,and intensity.A high-resolution 3-D run is capable to resolve detailed aspects of convection,including high-intensity convective precipitation.The results are significant not only from the aspect of the cloud model’s ability to provide a qualitative-quantitative assessment of intense precipitation but also for a deeper understanding of the essence of storm development,its vortex dynamics,and the meaning of micro-physical processes for the production and release of large amounts of precipitation that were the cause of the catastrophic flood in an urban area.After a series of experiments and verification,such a system could be a reliable tool in weather services for very short-range forecasting(now-casting)and early warning of weather disasters.

Triple Medium Physical Model of Post Fracturing High-Rank Coal Reservoir in Southern Qinshui Basin

In this paper, influences on the reservoir permeability, the reservoir architecture and the fluid flow pattern caused by hydraulic fracturing are analyzed. Based on the structure and production fluid flow model of post fracturing high-rank coal reservoir, Warren-Root Model is improved. A new physical model that is more suitable for post fracturing high-rank coal reservoir is established. The results show that the width, the flow conductivity and the permeability of hydraulic fractures are much larger than natural fractures in coal bed reservoir. Hydraulic fracture changes the flow pattern of gas and flow channel to wellbore, thus should be treated as an independent medium. Warrant-Root Model has some limitations and can’t give a comprehensive interpretation of seepage mechanism in post fracturing high-rank coal reservoir. Modified Warrant-Root Model simplifies coal bed reservoir to an ideal system with hydraulic fracture, orthogonal macroscopic fracture and cuboid matrix. Hydraulic fracture is double wing, vertical and symmetric to wellbore. Coal bed reservoir is divided into cuboids by hydraulic fracture and further by macroscopic fractures. Flow behaviors in coal bed reservoir are simplified to three step flows of gas and two step flows of water. The swap mode of methane between coal matrix and macroscopic fractures is pseudo steady fluid channeling. The flow behaviors of methane to wellbore no longer follow Darcy’s Law and are mainly affected by inertia force. The flow pattern of water follows Darcy’s Law. The new physical model is more suitable for post fracturing high-rank coal reservoir.