Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of ...interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bioengineering models in conjunction with molecular cell biology tools, we found that fluid shear (2 dyn/cm(2)) markedly upregulates matrix metalloproteinase 12 (MMP-12) expression and its activity in human chondrosarcoma cells. MMP-12 expression is induced in human chondrocytes during malignant transformation. However, the signaling pathway regulating MMP-12 expression and its potential role in human chondrosarcoma cell invasion and metastasis have yet to be delineated. We discovered that fluid shear stress induces the synthesis of insulin growth factor-2 (IGF-2) and vascular endothelial growth factor (VEGF) B and D, which in turn transactivate MMP-12 via PI3-K, p38 and JNK signaling pathways. IGF-2-, VEGF-B- or VEGF-D-stimulated chondrosarcoma cells display markedly higher migratory and invasive potentials in vitro, which are blocked by inhibiting MMP-12, PI3-K, p38 or JNK activity. Moreover, recombinant human MMP-12 or MMP-12 overexpression can potentiate chondrosarcoma cell invasion in vitro and the lung colonization in vivo. By reconstructing and delineating the signaling pathway regulating MMP-12 activation, potential therapeutic strategies that interfere with chondrosarcoma cell invasion may be identified.
The local atomic structures of amorphous Ge-Sb-Te phase-change materials have yet to be clarified and the rapid crystal-amorphous phase change resulting in distinct optical contrast is not well ...understood. We report the direct observation of local atomic structures in amorphous Ge_{2}Sb_{2}Te_{5} using "local" reverse Monte Carlo modeling dedicated to an angstrom-beam electron diffraction analysis. The results corroborated the existence of local structures with rocksalt crystal-like topology that were greatly distorted compared to the crystal symmetry. This distortion resulted in the breaking of ideal octahedral atomic environments, thereby forming local disordered structures that basically satisfied the overall amorphous structure factor. The crystal-like distorted octahedral structures could be the main building blocks in the formation of the overall amorphous structure of Ge-Sb-Te.
Despite the fact that phase-change materials are widely used for data storage, no consensus exists on the unique mechanism of their ultrafast phase change and its accompanied large and rapid optical ...change. By using the pump-probe observation method combining a femtosecond optical laser and an x-ray free-electron laser, we substantiate experimentally that, in both GeTe and Ge_{2}Sb_{2}Te_{5} crystals, rattling motion of mainly Ge atoms takes place with keeping the off-center position just after femtosecond-optical-laser irradiation, which eventually leads to a higher symmetry or disordered state. This very initial rattling motion in the undistorted lattice can be related to instantaneous optical change due to the loss of resonant bonding that characterizes GeTe-based phase change materials. Based on the amorphous structure derived by first-principles molecular dynamics simulation, we infer a plausible ultrafast amorphization mechanism via nonmelting.
Being a key feature of a glassy state, low temperature relaxation has important implications on the mechanical behavior of glasses; however, the mechanism of low temperature relaxation is still an ...open issue, which has been debated for decades. By systematically investigating the influences of cooling rate and pressure on low temperature relaxation in the Zr50Cu50 metallic glasses, it is found that even though pressure does induce pronounced local structural change, the low temperature-relaxation behavior of the metallic glass is affected mainly by cooling rate, not by pressure. According to the atomic displacement and connection mode analysis, we further demonstrate that the low temperature relaxation is dominated by the dispersion degree of fast dynamic atoms rather than the most probable atomic nonaffine displacement. Our finding provides the direct atomic-level evidence that the intrinsic heterogeneity is the key factor that determines the low temperature-relaxation behavior of the metallic glasses.
Amorphous solids lack long-range order. Therefore identifying structural defects -- akin to dislocations in crystalline solids -- that carry plastic flow in these systems remains a daunting ...challenge. By comparing many different structural indicators in computational models of glasses, under a variety of conditions we carefully assess which of these indicators are able to robustly identify the structural defects responsible for plastic flow in amorphous solids. We further demonstrate that the density of defects changes as a function of material preparation and strain in a manner that is highly correlated with the macroscopic material response. Our work represents an important step towards predicting how and when an amorphous solid will fail from its microscopic structure.
The interleukin-13 receptor alpha2 (IL-13Rα2) is a cancer-associated receptor overexpressed in human glioblastoma multiforme (GBM). This receptor is undetectable in normal brain which makes it a ...highly suitable target for diagnostic and therapeutic purposes. However, the pathological role of this receptor in GBM remains to be established. Here we report that IL-13Rα2 alone induces invasiveness of human GBM cells without affecting their proliferation. In contrast, in the presence of the mutant EGFR (EGFRvIII), IL-13Rα2 promotes GBM cell proliferation in vitro and in vivo. Mechanistically, the cytoplasmic domain of IL-13Rα2 specifically binds to EGFRvIII, and this binding upregulates the tyrosine kinase activity of EGFRvIII and activates the RAS/RAF/MEK/ERK and STAT3 pathways. Our findings support the "To Go or To Grow" hypothesis whereby IL-13Rα2 serves as a molecular switch from invasion to proliferation, and suggest that targeting both receptors with STAT3 signaling inhibitor might be a therapeutic approach for the treatment of GBM.
We report a hybrid atomic packing scheme comprised of a covalent-bond-mediated "stereochemical" structure and a densely packed icosahedron in a bulk metallic glass Pd40Ni40P20. The coexistence of two ...atomic packing models can simultaneously satisfy the criteria for both the charge saturation of the metalloid element and the densest atomic packing of the metallic elements. The hybrid packing scheme uncovers the structural origins of the excellent glass forming ability of Pd40Ni40P20 and has important implications in understanding the bulk metallic glass formation of metal-metalloid alloys.
Although the Cu1.8S compound consisting of cheap and earth-abundant elements has been reported to be a potential candidate of thermoelectric material, its thermoelectric performance is not very high. ...In this work, a fast doping strategy is offered to introduce both point defects and nanostructures into thermoelectric materials to improve the performance. Ball-milled Cu1.8S powders were mixed with different amounts of In2S3 powders and were then sintered into bulk samples by the spark plasma sintering (SPS) technique. During the SPS process, In2S3 was doped into the Cu1.8S matrix at 723 K for 10 min, and the fast doping process results in point defects and nanostructures of the Cu1.8S bulk sample including nanopores and those with an included second phase. On the one hand, In doping increased the effective mass of charge carriers in Cu1.8S and improved the Seebeck coefficient, whereas on the other hand, the nanostructures reduced thermal conductivity significantly. The phase structure and microstructure of Cu1.8S bulks are highly dependent on the In2S3 content. Density functional theory calculations revealed that Cu1.8S has an intrinsically low lattice thermal conductivity because of low-frequency localized vibrations from the Cu ionic migration and Cu vacancies. As a result, Cu1.8S+3 wt% In2S3 bulk sample achieved a ZT value of ∼1.4 at 773 K compared with that of 0.45 at 773 K for the pristine Cu1.8S sample; this value is the highest ZT value in sulfide thermoelectric materials at this temperature. The fast doping strategy demonstrated in this work can also be applied for reducing thermal conductivity and improving ZT values of other thermoelectric systems.
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•The nanostructured Cu1.8S bulk sample with excellent thermoelectric properties was obtained by a fast doping strategy.•The nanostructure of nanopores with an inside second phase was observed.•The formation mechanism of the nanostructure was discussed in detail.•The nanostructures contribute to a high ZT value of 1.4 at 773 K for the Cu1.8S bulk sample, which is the highest ZT value for sulfides.
The problem of tracking control for a class of uncertain time-delay non-linear system with state constraint is addressed. To prevent constraint violation, the tangent barrier Lyapunov function (TBLF) ...is firstly used for time-delay nonlinear system. By ensuring boundedness of the TBLF in the closed loop, besides those limits are not transgressed, the authors also tackle scenarios wherein parametric uncertainties and time delays are presented. Asymptotically tracking stable in the sense of uniformly ultimate boundedness is achieved without violation of the constraint. Finally, the performance of the proposed control has been illustrated through a chaotic system. PUBLICATION ABSTRACT
A relevant problem in computer vision is how to detect and track moving objects from video sequences efficiently. Some algorithms require manual calibration in terms of specification of parameters or ...some hypotheses. A novel method is developed to extract moving objects through multi-scale wavelet transform across background subtraction. The optimal selection of threshold is automatically determined which does not require any complex supervised training or manual calibration. The proposed approach is efficient in detecting moving objects with low contrast against the background and the detection is less affected by the presence of moving objects in the scene. The developed method combines region connectivity with chromatic consistency to overcome the aperture problem. Ghosts are removed by the proposed background update function, which efficiently prevents undesired corruption of background model and does not consider adaptation coefficient. The mentioned approach is scene-independent and the capacity to extract moving object and suppress cast shadow is high. The developed algorithm is flexible and computationally cost-effective. Experiments show that the proposed approach is robust and efficient in segmenting foreground and suppressing shadow by comparison.
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