One of the crucial regulators of embryonic patterning and tissue development is the Hedgehog‐glioma (Hh‐Gli) signalling pathway; its uncontrolled activation has been implicated in different types of cancer in adult tissues. Primary cilium is one of the important factors required for the activation of Hh signalling, as it brings the critical components together for key protein–protein interactions required for Hh pathway regulation. Most of the synthetic and natural small molecule modulators of the pathway primarily antagonise Smoothened (Smo) or other effectors like Hh ligand or Gli. Here, we report a previously described Hh antagonist, with a pyrimidine–indole hybrid (PIH) core structure, as an inhibitor of ciliogenesis. The compound is unique in its mode of action, as it shows perturbation of microtubule dynamics in both cell‐based assays and in vivo systems (zebrafish embryos). Further studies revealed that the probable targets are α‐tubulin and its acetylated form, found in the cytoplasm and primary cilia. PIH also showed axonal defasiculation in developing zebrafish embryos. We thus propose that PIH antagonises Hh signalling by repressing cilia biogenesis and disassembling α‐tubulin from its stabilised form. 相似文献
Floods are common and recurring natural hazards which damages is the destruction for society. Several regions of the world with different climatic conditions face the challenge of floods in different magnitudes. Here we estimate flood susceptibility based on Analytical neural network (ANN), Deep learning neural network (DLNN) and Deep boost (DB) algorithm approach. We also attempt to estimate the future rainfall scenario, using the General circulation model (GCM) with its ensemble. The Representative concentration pathway (RCP) scenario is employed for estimating the future rainfall in more an authentic way. The validation of all models was done with considering different indices and the results show that the DB model is most optimal as compared to the other models. According to the DB model, the spatial coverage of very low, low, moderate, high and very high flood prone region is 68.20%, 9.48%, 5.64%, 7.34% and 9.33% respectively. The approach and results in this research would be beneficial to take the decision in managing this natural hazard in a more efficient way.
Pattern Analysis and Applications - Decomposition and representation of electrical circuit drawings to a suitable vector form has widespread applications related to data compression, storage,... 相似文献
This paper considers the problem of simulating the humidity distributions of a grain storage system. The distributions are described by partial differential equations (PDE). It is quite difficult to obtain the humidity profiles from the PDE model. Hence, a discretization method is applied to obtain an equivalent ordinary differential equation model. However, after applying the discretization technique, the cost of solving the system increases as the size increases to a few thousands. It may be noted that after discretization, the degree of freedom of the system remain the same while the order increases. The large dynamic model is reduced using a proper orthogonal decomposition based technique and an equivalent model but of much reduced size is obtained. A controller based on optimal control theory is designed to obtain an input such that the output humidity reaches a desired profile and also its stability is analyzed. Numerical results are presented to show the validity of the reduced model and possible further extensions are identified. 相似文献
Organoselective membrane was prepared from ethylene propylene diene monomer (EPDM) rubber. Crosslinked EPDM rubber was filled with 2, 4 and 6 wt% N330 carbon black filler to produce three different filled membranes designated as EPDMCV2, EPDMCV4 and EPDMCV6, respectively. These filled rubber membranes were used for pervaporative recovery of low concentration of pyridine from water. These filled membranes were characterized by crosslink density, SEM, XRD and mechanical properties. Sorption thermodynamics were discussed. Partial permeability, intrinsic membrane selectivity and diffusion coefficients of solvents were also determined. The filled membranes showed much higher pyridine selectivity than most of the membranes reported for similar system. 相似文献