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Cellular uptake of several viruses and polybasic macromolecules requires the expression of cell-surface heparan sulfate proteoglycan (HSPG) through as yet ill defined mechanisms. We unexpectedly found that among several cell-surface-binding single chain variable fragment (scFv) anti-HS antibody (aHS) clones, only one, AO4B08, efficiently translocated macromolecular cargo to intracellular vesicles through induction of HSPG endocytosis. Interestingly, AO4B08-induced PG internalization was strictly dependent on HS 2-O-sulfation and appeared independent of intact N-sulfation. A04B08 and human immunodeficiency virus (HIV)-Tat, i.e. a well known cell-penetrating peptide, were shown to compete for the internalizing PG population. To obtain a more detailed characterization of this pathway, we have developed a procedure for the isolation of endocytic vesicles by conjugating AO4B08 with superparamagnetic nanoparticles. [35S]sulfate-labeled HSPG was found to accumulate in isolated, AO4B08-containing vesicles, providing the first biochemical evidence for intact HSPG co-internalization with its ligand. Further analysis revealed the existence of both syndecan, i.e. a transmembrane HSPG, and glycosyl-phosphatidyl-inositol-anchored glypican in purified vesicles. Importantly, internalized syndecan and glypican were found to colocalize in AO4B08-containing vesicles. Our data establish HSPGs as true internalizing receptors of macromolecular cargo and indicate that the sorting of cell-surface HSPG to endocytic vesicles is determined by a specific HS epitope that can be carried by both syndecan and glypican core protein. [ABSTRACT FROM AUTHOR]

In order to reveal the influence of breathing-type straight cracks on the motion characteristics and stability of a turbine rotor-bearing-seal system. The study examines the motion characteristic of a cracked rotor system under different loads with different crack depths, the coupled thermal and dynamic loads. The research derives motion differential equations for the cracked system, considering nonlinear dynamic properties such as nonlinear stiffness and damping. The equations incorporate the nonlinear steam flow excited force obtained from numerical simulations. The resulting motion equations are solved using the Runge-Kutta method, and the accuracy of the investigation of nonlinear dynamic characteristics is validated through experimental comparisons. Based on these findings, the motion characteristics and stability of the cracked rotor system under different conditions are analyzed. The results indicate that the motion characteristics of the rotor are progressively altered by the crack depth, and at a certain depth, the motion deviates from the established pattern. The influence of cracks on rotor stability is predominantly notable in the 34–58% THA region and under high load conditions. Moreover, the chaotic characteristics of rotor motion is more significant after applied the coupled thermal and dynamic loads, and the stability of the 34–58% THA region is significantly worse. • The MATLAB power-series fitting method is utilized to express the excitation force function accurately. • Improves the motion differential equations of the system and the accuracy of the equation is verified by experiments. • This study focuses on analyzing the motion characteristics of cracked turbine rotors under different loads. • This research takes into account the impact of thermal and dynamic loads during actual operation. [ABSTRACT FROM AUTHOR]

• An apparatus for in-situ measurement of interfacial separation is designed. • Evolutions of separations are recorded for flattening rough metallic samples. • Variations of the average separations in loading–unloading circles are discussed. • A piecewise power-law dependence of interfacial stiffness on loads is observed. The direct measurement of interfacial separation between rough solids is hitherto one of the most challenging tasks in contact mechanics. This paper develops an optical interferometric technique for in-situ measuring interfacial separation with nanoscale precision. For the contact of metallic samples, the evolutions of interfacial separation and stiffness with load are measured. In the loading process, the dependence of interfacial stiffness on load can be described by a power law with the exponent smaller than unity at low loads and larger than unity at large loads. Similar relations have been found for unloading but interrupted with a linear relation at intermediate loads. These characteristics are significantly different from those known for rough elastic solids, and provide new insights in tribology. [ABSTRACT FROM AUTHOR]

Abstract: Giant magnetostrictive SmFe2/Fe exchange-coupled multilayers were fabricated by ion beam sputtering deposition on glass substrates. The effects of SmFe2/Fe exchange coupling action and vacuum annealing on soft-magnetic property and static-dynamic magnetostrictive characteristics of SmFe2/Fe multilayers were investigated. The results showed that the soft-magnetic, static–dynamic magnetostrictive characteristics were greatly improved by SmFe2/Fe exchange coupling action and proper vacuum annealing treatment temperature. Compared with that of SmFe2 single film, the coercivity in the direction of easy magnetization axis for SmFe2/Fe exchange-coupled multilayers exhibited a greater decrease. Better soft-magnetic properties were achieved (H c =2.54kA/m, M s =120.38emu/g, and M r /M s =0.21) after vacuum annealing at certain temperature. The magnetostrictive coefficient for SmFe2/Fe exchange-coupled multilayers was about 135ppm at 16kA/m magnetic field. At first order resonant frequency (99.2Hz), the amplitude peak–peak value for the as-deposited SmFe2/Fe exchange-coupled multilayers was 46μm. After the vacuum annealing treatment at 250°C, the amplitude peak–peak value increased to 650μm. [Copyright &y& Elsevier]

Abstract: Considerable researches have been done about integrin ανβ6 and carcinomas, but little information has been shown about the relationship between integrin ανβ6 and apoptosis. In this study, we investigated the apoptosis and its related signal pathways to integrin αvβ6 in colon cancer cells. After we blocked the function of integrin αvβ6 in HT29 cells used the monoclonal antibody, the apoptotic cells increased markedly. Meanwhile, cytochrome C released from mitochondria into cytosol, Bcl-2 decreased while Bax increased significantly, and Fas and Fas-ligand had no change. The activities of caspase-3 and caspase-9 increased, while caspase-8 remained no change. Moreover, the expression of phosphorylated extracellular signal-related kinase (P-ERK) decreased. We confirmed that integrin αvβ6 acted as an important role in inhibiting apoptosis in colon cancer cells, and the signaling involved the mitochondrial pathway. [Copyright &y& Elsevier]

Purpose: HAb18G/CD147 is a hepatocellular carcinoma (HCC)-associated antigen. We developed iodine (131I) metuximab injection (Licartin), a novel 131I-labeled HAb18G/CD147-specific monoclonal antibody F(ab’)2 fragment, and evaluated its safety, pharmacokinetics, and clinical efficacy on HCC in Phase I/II trials. Methods and Materials: In a Phase I trial, 28 patients were randomly assigned to receive the injection in 9.25-, 18.5-, 27.75-, or 37-MBq/kg doses by hepatic artery infusion. In a multicenter Phase II trial, 106 patients received the injection (27.75 MBq/kg) on Day 1 of a 28-day cycle. Response rate and survival rate were the endpoints. Results: No life-threatening toxic effects were found. The safe dosage was 27.75 MBq/kg. The blood clearance fitted a biphasic model, and its half-life was 90.56–63.93 h. In the Phase II trial, the injection was found to be targeted and concentrated to tumor tissues. Of the 73 patients completing two cycles, 6 (8.22%) had a partial response, 14 (19.18%) minor response, and 43 (58.90%) stable disease. The 21-month survival rate was 44.54%. The survival rate of progression-free patients was significantly higher than that of patients with progressive disease after either one or two cycles (p < 0.0001 or p = 0.0019). Conclusion: Iodine (131I) metuximab injection is safe and active for HCC patients. [Copyright &y& Elsevier]

Solid particle erosion (SPE) in governing stage is one of the concerns for large capacity steam turbine. Based on Euler-Lagrange method and Finnie erosion model, the influence of valve governing mode on SPE and efficiency of governing stage were numerically investigated. Results show that the erosion rate density of different circumferential nozzles changes greatly, and the erosion rate density of the most serious erosion nozzle is about 4 × 103 times that of the lightest erosion nozzle. The max erosion rate density of nozzle under sequential valve governing mode (SEVGM) is higher than that under single valve governing mode (SIVGM), in which the particle impact velocity plays a decisive role. With the increase of roughness, the governing stage efficiency decreases under two types of valve governing modes. Moreover, the governing stage efficiency under SEVGM decreases more obviously than that under SIVGM. • Steam-particle flow characteristics in governing stage of steam turbine is simulated. • Erosion of different circumferential nozzles is different greatly. • Erosion of nozzle deteriorates rapidly under sequential valve governing mode. • Particle impact velocity changes greatly under different valve governing modes. • Governing stage efficiency is more sensitive to roughness under sequential valve governing mode. [ABSTRACT FROM AUTHOR]