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71.
The vortex flow characteristics of a sharp-edged delta wing with an apex strake was investigated through the visualization and particle image velocimetry (PIV) measurement of the wing-leeward flow region, and the wing-surface pressure measurement. The wing model was a flat-plate, and 65°-sweep cropped-delta wing with sharp leading edges. The apex strake was also a flat-plate wing with a cropped-delta shape of 65°/90° sweep, and it can change its incidence angle. The flow Reynolds number was 2.2 × 105 for the flow visualization and 8.2 × 105 for the PIV and wing-surface pressure measurements. The physics of the vortex flow in the wing-leeward flow region and the suction-pressure distribution on the wing upper-surface were interrelated and analyzed. The effect of a positive (negative) strake incidence-angle was the upward movement of the strake and wing vortices away from (downward movement of the strake and wing vortices toward) the wing-upper surface and the delayed (enhanced) coiling interaction between them. This change of vortex flow characteristics projected directly on the suction pressure distribution on the wing upper-surface.  相似文献   
72.
An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-144-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-144-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance.  相似文献   
73.
The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.Subject terms: Antibody therapy, Molecularly targeted therapy, Drug development  相似文献   
74.
Titanium nitride (TiN) - graphene (G) nanocomposites are promising for electrochemical charge storage where a high content of Ti species is desired. Herein, we propose an effective method for the preparation of TiN-G nanocomposites with a high concentration of Ti species. These nanocomposites can be successfully achieved through a further deposition of Ti on Ti-graphene oxide (GO) or a thermally exfoliated Ti-GO. Depending on the annealing condition employed (NH3 and N2), two types of TiN-G nanocomposites (NH3 annealing for TiN/G and TiN/G-TE, TE: thermal exfoliation) and a TiO2-G nanocomposite (N2 annealing for TiO2/G-TE) were prepared. These nanocomposites were then investigated for potential application as an electrochemical supercapacitor. Compare with TiO2/G-TE, the TiN-G nanocomposites both exhibited a higher specific capacitance, although one of these nanocomposites had a lower surface area than TiO2/G-TE. Among the nanocomposites prepared, TiN/G-TE delivered the best electrochemical performance. The relationship between the physical properties and the capacitive performance of the nanocomposites were systematically evaluated.  相似文献   
75.
Analytical and Bioanalytical Chemistry -  相似文献   
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78.
We study the structure of the complement of an F-bundle over a graph G when it can be expressed as an F-bundle over another graph G. In particular, we compute the characteristie polynomial of the complement of an F-bundle when its voltages lie in and abelian subgroup Г of Aut(F) which acts freely and transitively on the vertices of the fiber F Some applications to regular embeddings of graph bundles into Euclidean spaces are also discussed  相似文献   
79.
This paper presents a new discrete-time sliding mode controller to alleviate undesirable chattering in vibration control of a flexible beam structure. A smart beam featuring a piezoelectric film is devised and its governing equation of motion is derived. A discrete-time sliding mode controller which consists of discontinuous part and equivalent part is then designed by considering the separation principle. By doing this, undesirable chattering of the beam structure can be attenuated in the settled phase. The proposed controller is experimentally realized, and both transient and forced vibration control responses are evaluated in time domain.  相似文献   
80.
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