Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles

PEGylated gold nanoparticles are decorated with various amounts of human transferrin (Tf) to give a series of Tf-targeted particles with near-constant size and electrokinetic potential. The effects of Tf content on nanoparticle tumor targeting were investigated in mice bearing s.c. Neuro2A tumors. Quantitative biodistributions of the nanoparticles 24 h after i.v. tail-vein injections show that the nanoparticle accumulations in the tumors and other organs are independent of Tf. However, the nanoparticle localizations within a particular organ are influenced by the Tf content. In tumor tissue, the content of targeting ligands significantly influences the number of nanoparticles localized within the cancer cells. In liver tissue, high Tf content leads to small amounts of the nanoparticles residing in hepatocytes, whereas most nanoparticles remain in nonparenchymal cells. These results suggest that targeted nanoparticles can provide greater intracellular delivery of therapeutic agents to the cancer cells within solid tumors than their nontargeted analogs

Advances of the FRIB project

The Facility for Rare Isotope Beams (FRIB) Project has entered the phase of beam commissioning starting from the room-temperature front end and the superconducting linac segment of first 15 cryomodules. With the newly commissioned helium refrigeration system supplying 4.5K liquid helium to the quarter-wave resonators and solenoids, the FRIB accelerator team achieved the sectional key performance parameters as designed ahead of schedule accelerating heavy ion beams above 20MeV/u energy. Thus, FRIB accelerator becomes world's highest-energy heavy ion linear accelerator. We also validated machine protection and personnel protection systems that will be crucial to the next phase of commissioning. FRIB is on track towards a national user facility at the power frontier with a beam power two orders of magnitude higher than operating heavy-ion facilities. This paper summarizes the status of accelerator design, technology development, construction, commissioning as well as path to operations and upgrades

Identification of Substitute Thermophysical Properties of Gypsum Mould

Simplifications used in simulation program codes require the use of substitute parameters in the material databases (also called apparent or substitutive). On the one hand, they formally fit into the records used in the heat flow model, porosity, properties etc. and on the other hand they should be determined in conditions most similar to the real casting-mould system. The article presents results of a research on thermophysical parameters of gypsum mould used for precision casting moulds. Experiments were carried out on a cylindrical mould made of Plasticast gypsum, in which the heat source was a cylinder filled with liquid aluminium alloy of the temperature of 655°C. Energetic validation was carried out by using the NovaFlow&Solid ver. 6.3 simulation code. As a result of validation tests, substitute thermophysical parameters of gypsum were determined. For determined parameters, best-fit of solidification time from the experiment and simulation was obtained and the curves of gypsum mass heating were satisfactorily recreate

Cellular Automaton Finite Element Method Applied for Microstructure Prediction of Aluminium Casting Treated by Laser Beam

What is the limit of improvement the structure obtained directly from the liquid state, with possible heat treatment (supersaturation and aging)? This question was posed by casting engineers who put arbitrary requirements on reducing the DAS (Dendrite Arm Spacing) length to less than a dozen microns. The results of tests related to modification of the surface microstructure of AlSi7Mg alloy casting treated by laser beam and the rapid remelting and solidification of the superficial casting zone, were presented in the paper. The local properties of the surface treated with a laser beam concerns only a thickness ranging from a fraction to a single mm. These local properties should be considered in the aspect of application on surfaces of non-machined castings. Then the excellent surface layer properties can be used. The tests were carried out on the surface of the casting, the surface layer obtained in contact with the metal mould, after the initial machining (several mm), was treated by the laser beam. It turned out that the refinement of the microstructure measured with the DAS value is not available in a different way, i.e. directly by casting. The experimental-simulation validation using the Calcosoft CAFE (Cellular Automaton Finite Element) code was applied

Methodology of Comparative Validation of Selected Foundry Simulation Codes

The validation of each simulation code used in foundry domain requires individual approach due to its specificity. This validation can by elaborated on the basis of experimental results or in particular cases by comparison the simulation results from different codes. The article concerns the influence of grey cast iron density curve and different forms of solid fraction curve Fs=f(T) on the formation of shrinkage discontinuities. Solid fraction curves applying Newtonian Thermal Analysis (NTA) were estimated. The experimental and numerical simulation tests were performed on the castings, which were made with Derivative Thermal Analysis (DerTA) standard cups. The numerical tests were realized using NovaFlow&Solid (NF&S), ProCast and Vulcan codes. In this work, the coupled influence of both curves on the dynamics of the shrinkage-expansion phenomena and on shrinkage defects prognosis in grey cast iron castings has been revealed. The final evaluation of the simulation systems usefulness should be based on validation experiment, preceded by comparing the simulation results of available systems which are proposed in given technology

Examples of New Models Applied in Selected Simulation Systems with Respect to Database

The tolerance of damage rule progressively meets the approval in the design casting parts procedures. Therefore, there were appeared thenew challenges and expectations for permanent development of process virtualization in the mechanical engineering industry.Virtualization is increasingly developed on the stage of product design and materials technologies optimization. Increasing expectations of design and process engineers regarding the practical effectiveness of applied simulation systems with new proposed up-grades modules is observed. The purpose is to obtain simulation tools allowing the most possible realistic prognosis of the casting structure, including indication, with the highest possible probability, places in the casting that are endangered with the possibility of shrinkage– and gas porosity formation. This 3D map of discontinuities and structure transformed in local mechanical characteristics are used to calculate the local stresses and safety factors. The needs of tolerance of damage and new approach to evaluate the quality of such prognosis must be defined. These problems of validation of new models/modules used to predict the shrinkage– and gas porosity including the chosen structure parameters in the example of AlSi7 alloy are discussed in the paper

Methodology of Comparative Validation of Selected Foundry Simulation Codes

The validation of each simulation code used in foundry domain requires individual approach due to its specificity. This validation can by elaborated on the basis of experimental results or in particular cases by comparison the simulation results from different codes. The article concerns the influence of grey cast iron density curve and different forms of solid fraction curve Fs=f(T) on the formation of shrinkage discontinuities. Solid fraction curves applying Newtonian Thermal Analysis (NTA) were estimated. The experimental and numerical simulation tests were performed on the castings, which were made with Derivative Thermal Analysis (DerTA) standard cups. The numerical tests were realized using NovaFlow&Solid (NF&S), ProCast and Vulcan codes. In this work, the coupled influence of both curves on the dynamics of the shrinkage-expansion phenomena and on shrinkage defects prognosis in grey cast iron castings has been revealed. The final evaluation of the simulation systems usefulness should be based on validation experiment, preceded by comparing the simulation results of available systems which are proposed in given technology

Computer Simulation of Cast Iron Flow in Castability Trials

The paper includes validation studies of the flow module of the NovaFlow&Solid simulation code. Experiments of ductile iron and gray iron casting in a spiral test of castability were carried out. Casting experiments were then carried out in industrial conditions in the Ferrex Foundry in Poznań and the results are the castability spiral length and local cast iron rate during mould cavity pouring. Simulation tests using NovaFlow&Solid Control Volume code were made. The technological castability test was used to determine thermal-physical data through simplified inversion problem. Influence of physical parameters in the database of simulation code on the spiral length obtained as the result of simulation was analyzed. It was found that critical fraction of capillary flow CLF down has the biggest impact on cast iron castability in the simulation code. The simulations resulted in defining parameters of gray iron GJL 250 and ductile iron GJS-400-15. For the parameters set, the length of castability spiral in simulations was in accordance with casting experiments

Evaluation of the Cause and Consequences of Defects in Cast Metal-Ceramic Composite Foams

In this research, the quality of manufactured cast metal-ceramic foams (manufactured using blowing gas) was tested. The causes responsible for defect formation in the composite foams and their consequences were analyzed using the FMEA (Failure Mode and Effects Analysis) method, which is a useful tool for minimizing losses caused by low product quality. This method involves analytically determining correlations between the cause and consequences of potential product defects, and it takes into account the criticality factor (risk). The FMEA analysis showed that pore breaks were the most "critical defect" (with the highest number of effects on the product, the Risk Priority Number, affecting the quality of the composite foam). The second most critical defect was discontinuities in the foam frame structure. Destruction or damage to the foam structure (although very rare) deprived the composite foam of its primary function, which is to reinforce the product. The third most critical defect was non-uniform foam pore size