Effective Tumor Targeting by EphA2-Agonist-Biotin-Streptavidin Conjugates

We recently reported on a potent synthetic agent, 135H11, that selectively targets the receptor tyrosine kinase, EphA2. While 135H11 possesses a relatively high binding affinity for the ligand-binding domain of EphA2 (Kd~130 nM), receptor activation in the cell required the synthesis of dimeric versions of such agent (namely 135H12). This was expected given that the natural ephrin ligands also need to be dimerized or clustered to elicit agonistic activity in cell. In the present report we investigated whether the agonistic activity of 135H11 could be enhanced by biotin conjugation followed by complex formation with streptavidin. Therefore, we measured the agonistic EphA2 activity of 135H11-biotin (147B5) at various agent/streptavidin ratios, side by side with 135H12, and a scrambled version of 147B5 in pancreatic- and breast-cancer cell lines. The (147B5)n-streptavidin complexes (when n = 2, 3, 4, but not when n = 1) induced a strong receptor degradation effect in both cell lines compared to 135H12 or the (scrambled-147B5)4-streptavidin complex as a control, indicating that multimerization of the targeting agent resulted in an increased ability to cause receptor clustering and internalization. Subsequently, we prepared an Alexa-Fluor-streptavidin conjugate to demonstrate that (147B5)4-AF-streptavidin, but not the scrambled equivalent complex, concentrates in pancreatic and breast cancers in orthotopic nude-mouse models. Hence, we conclude that these novel targeting agents, with proper derivatization with imaging reagents or chemotherapy, can be used as diagnostics, and/or to deliver chemotherapy selectively to EphA2-expressing tumors.

Free vibration analysis of embedded and co-cured perforated damping sandwich composite beam

The free vibration behaviors of the embedded and co-cured perforated damping sandwich composite (ECPDSC) in which the holes are filled with resin are investigated. The displacement field of laminated structure and the equivalent elastic parameters of the heterogeneous damping layer are presented by the combination of the first order shear deformation theory with homogenization method. The dynamic equations of the structure are derived on basis of the equivalent complex modulus theory, and the theoretical results are verified by experimental platform. The relationships of damping area ratio and the thickness of damping layer as well as the elastic modulus of viscoelastic material with the dynamic properties of ECPDSC are theoretically explored further. Results indicate that the modal frequency decreases slowly when the damping area ratio is relatively small, the modal frequency decreases rapidly when the damping area ratio is relatively large, and the trend of loss factor is just opposite. This investigation will lay a foundation for the design and manufacture of composite components with light weight, large damping as well as high stiffness.

Analytical model of high-frequency energy flow response for a beam with free layer damping

Energy flow analysis (EFA) is developed to predict the vibrational energy density of beam structures with both full free layer damping (FFLD) and partial free layer damping (PFLD) treatments in the high frequency range. Both equivalent flexural stiffness and structural damping loss factor of a beam with free layer damping are obtained using the equivalent complex stiffness method. Then the energy density governing equation considering high damping effect is derived for a beam with FFLD treatment. Following obtainment of the energy transfer coefficients at both ends of free damping layer, the energy density within a beam with PFLD treatment is evaluated by solving the presented energy governing equation. To verify the proposed formulation, numerical simulations are performed for the pinned-pinned beams with FFLD and PFLD treatments. The EFA results are compared with the exact solutions from wave analysis at various frequencies, and good correlations are observed between the developed EFA results and the exact solutions.

The Optical Properties of Aerosols at the Summit of Mount Tai in May and June and the Retrieval of the Complex Refractive Index

To study the optical properties of background atmospheric aerosols in East China, we carried out observations of the physical, chemical and optical properties of atmospheric aerosols at the summit of Mount Tai (Mt. Tai, 1533.7 m above sea level) from 13 May to 25 June 2017. The results show that the average scattering coefficient ( σ sca , 550 ) at 550 nm of the aerosols at the summit of Mt. Tai is 40.3 Mm−1, and the average absorption coefficient ( σ abs , 550 ) at 550 nm is 16.0 Mm−1. The complex refractive index of aerosols is a key parameter for aerosol retrieval and modeling. There are few studies on the equivalent complex refractive index of aerosol in the Taishan area. We calculated the aerosol equivalent complex refractive index using the observed aerosol scattering coefficients, absorption coefficients and particle size distribution data, providing more data support for future modeling in this region. The real part (n) of the complex refractive index at 550 nm of aerosol ranges from 1.31 to 1.98 (mostly under 1.50), with an average value of 1.38, while the imaginary part (k) ranges from 0.014 to 0.251 (less than 0.10 for over 95% samples), with an average value of 0.040. The analysis of the n and k of the aerosol average complex refractive index shows that the scattering properties of the aerosols at the summit of Mt. Tai are relatively weak and the absorption properties are relatively strong when compared with those of other kinds of aerosols. The k of the aerosol complex refractive index at the summit of Mt. Tai has strong correlations with the wind speed, temperature, as revealed by the correlation analysis.

Analysis of Engine Support Bracket for Frequency and Stress Optimization

In this paper we present new step by step approach for analysis of engine bracket. As we know all engine shocks are supported by engine brackets for heavier engines. Being a critical Component engine bracket must be analyzed properly as it forms a link between stiff chassis and vibrating engine. Complex design of engine bracket demands for proper step by step analysis as it is equivalent complex component as engine, cooling system, transmission system, battery, turbo etc. This present work focuses on the investigation of engine supporting bracket by using ANSYS. This current article accounts for review of the work that has been previously done on engine supporting bracket. This paper will result in suggesting the best suitable material for such complex material and best suitable geometrical options for in depth analysis. In initial stage of analysis three usual industrial materials are taken into account and suggesting best suitable material for industrial applications in all aspects.

Potential sources of bioactive compounds and antioxidants from 7 Brazilian native fruits

Background: Brazil is considered a country with the highest biological biodiversity in the world and exploring this underutilized food source could diversify food production and reduce nutritional problems. Objective: This study aimed to determine the antioxidant capacity and the bioactive compounds of seven native fruits from Brazil. Method: The samples were obtained from different cities of Brazil after confirmation of the botanical species. Carotenoids and anthocyanins were exhaustively extracted and injected into high-performance liquid chromatography. The antioxidant capacity was determined by the capture of the free radical ABTS. Vitamin A activity was calculated based on retinol activity equivalent. Complex B and C vitamins were determined by high-performance liquid chromatography. Result: The main carotenoid for all species was β-carotene, and Jaracatiá showed the highest amount of β-cryptoxanthin, zeaxanthin, α- and β-carotene. Açaí Juçara and the Butiás stood out among fruits analyzed with the highest antioxidant capacity (trolox equivalent). Concerning the anthocyanins, in the Açaí Juçara were identified the compounds Cyanidin 3-glucoside and Cyanidin 3-rutinoside. The values of all the compounds vary according to the harvest location. Jaracatiá is distinguished by the high vitamin A, C, B2, and B6 content, as well the Butiás (Praia and Serra), for B1, B2, B5 and B7. Vitamin B3 was only detected in Fisális fruits and Açaí showed higher content of B5. Conclusion: Fruits included in this study had considerable amounts of bioactive compounds, vitamins and antioxidant capacity showing that they can contribute to the improvement of the population diet.