Simulation of transport and extravasation of nanoparticles in tumors which exhibit enhanced permeability and retention effect

Determining the factors that influence the delivery of sub-micron particles to tumors and understanding the relative importance of each of these factors is fundamental to the optimization of the particle delivery process. In this paper, a model that combines random walk with the pressure driven movement of nanoparticles in a tumor vasculature is presented. Nanoparticle movement in a cylindrical tube with dimensions similar to the tumor's blood capillary with a single pore is simulated. Nanoparticle velocities are calculated as a pressure driven flow over imposed to Brownian motion. The number and percentage of nanoparticles leaving the blood vessel through a single pore is obtained as a function of pore size, nanoparticle size and concentration, interstitial pressure, and blood pressure. The model presented here is able to determine the importance of these controllable parameters and thus it can be used to understand the process and predict the best conditions for nanoparticle-based treatment. The results indicate that the nanoparticle delivery gradually increases with pore size and decreases with nanoparticle size for tumors with high interstitial fluid pressure (in this work we found this behavior for head and neck carcinoma and for metastatic melanoma with interstitial pressures of 18 mmHg and 19 mmHg, respectively). For tumors with lower interstitial fluid pressure (rectal carcinoma with 15.3 mmHg) however, delivery is observed to have little sensitivity to particle size for almost the entire nanoparticle size range. Though an increase in nanoparticle concentration increases the number of nanoparticles being delivered, the efficiency of the delivery (percentage of nanoparticles delivered) is found to remain closely unaffected.     

Genotoxicity testing of extracts from aflatoxin-contaminated peanut meal, following chemical decontamination

One of the most important concerns in the decontamination of aflatoxin-containing feed commodities is the safety of the products for food-producing animals and for human consumption of products derived from these animals. A new method, based on the use of florisil and C18 solid phase extraction columns, was developed for the preparation of extracts from decontaminated peanut meal, which allowed testing with in vitro genotoxicity assays without interference of the residual aflatoxin B₁. Recovery of degradation products in the extracts was evaluated by the use of radiolabelled \[¹⁴C]-aflatoxin B₁ (AFB₁) added to naturallycontaminated peanut meal (3.5mg AFB₁/kg). The meal was treated by a small-scale version of an industrial decontamination process based on ammoniation. Following decontamination, more than 90% of the label could not be extracted from the meal. AFB₁ accounted for about 10% of the radiolabel present in the extractable fraction, indicating a total AFB reduction of more than 99%. Decontamination of the meal by a number of other small- and industrial-scale ammonia-based processes resulted in similar efficiencies. Application of the extraction procedure resulted in AFB₁-rich and AFB₁-poor fractions, the latter containing half of the extractable decontamination products but less than 1% of the residual AFB₁. Testing in the Salmonella /microsome mutagenicity assay (TA 100, with S9-mix) of the original crude extracts and AFB1 rich fractions prepared from non-treated and decontaminated meal, showed the positive results expected from the AFB₁ contents as determined by HPLC analysis. Analysis and testing of the AFB₁-poor fractions showed that the various decontamination processes not only resulted in a successful degradation of AFB₁ but also did not produce other potent mutagenic compounds. Slight positive results obtained with these extracts were similar for the untreated and treated meals and may be due to unknown compounds originally present in the meal. Results obtained with an unscheduled DNA synthesis (UDS) and Comet assay with rat hepatocytes supported this conclusion. Positive results obtained with the micronucleus assay, using immortalized mouse hepatocytes (GKB), did not clearly reflect the mycotoxin levels and require further examination. It is concluded that the newly developed extraction procedure yields highly reproducible fractions and hence is very suitable for examining the possible formation of less potent degradation products of aflatoxins in short-term genotoxicity tests.     

Fabrication and evaluation of solid-oxide fuel cell anodes employing reaction-sintered yttria-stabilized zirconia

This paper reports on the fabrication and performance of solid-oxide fuel cell (SOFC) anodes utilizing yttria reaction-sintered zirconia (YRSZ). Through the reaction-sintering process, the technical-grade YSZ commonly used in the Ni-YSZ anode cermet is replaced with lower-cost ZrO₂ and Y₂O₃ materials. When sintered in the presence of nickel oxide, ZrO₂ and Y₂O₃ form cubic-phase YSZ at temperatures characteristic of SOFC processing (1400-1550 °C). Reaction sintering enables the formation of YSZ during cell fabrication, reducing SOFC anode raw-materials cost and the number of SOFC-fabrication processes. This paper reports the results of a broad range of characterization and performance measurements to evaluate the YRSZ material, including (1) crystal structure, (2) morphology, (3) pore-size distribution, (4) electronic resistivity, (5) fracture strength, (6) gas transport and catalytic activity, and (7) electrochemical performance. Material properties and performance are found to be comparable to or better than equivalent materials fabricated by conventional processes.     

Contact-impact by the pinball algorithm with penalty and Lagrangian methods

Contact-impact algorithms, which are sometimes called slideline algorithms, are a computationally time-consuming part of many explicit simulations of non-linear problems because they involve many branches, so they are not amenable to vectorization, which is essential for speed on supercomputers. The pinball algorithm is a simplified slideline algorithm which is readily vectorized. Its major idea is to embed pinballs in surface elements and to enforce the impenetrability condition only to pinballs. It can be implemented in either a Lagrange multiplier or penalty method. It is shown that, in any Lagrange multiplier method, no iterations are needed to define the contact surface. Examples of solutions and running times are given.     

Second harmonic generation from LB superlattices containing two active components

Second harmonic generation has been observed from Langmuir-Blodgett multilayer arrays containing two active components. Both materials were based on long chain donor-acceptor dye compounds, but were designed with the donor-acceptor groups in opposite senses with respect to the hydrocarbon chain. Preliminary results indicate a significant enhancement of the second-order polarisability for this type of supermolecular array.     

Cancer cell necrosis by autoschizis: Synergism of antitumor activity of vitamin C: Vitamin K3 on human bladder carcinoma T24 cells

Scanning and transmission electron microscopy and fluorescence light microscopy were employed to characterize the cytotoxic effects of vitamin C (VitC), vitamin K₃ (VitK₃) or a VitC:VK₃ combination on a human bladder carcinoma cell line (T24) following 1-h and 2-h vitamin treatment. T24 cells exposed to VitC alone exhibited membranous damage (blebs and endoplasmic extrusions, elongated microvilli). VitK₃-treated cells displayed greater membrane damage and enucleation than those treated with VitC as well as cytoplasmic defects characteristic of cytoskeletal damage. VitC:VitK₃-treated cells showed exaggerated membrane damage and an enucleation process in which the perikarya separate from the main cytoplasmic cell body by self-excision. Self-excisions continued for perikarya which contained an intact nucleus surrounded by damaged organelles. After further excisions of cytoplasm, the nuclei exhibited nucleolar segregation and chromatin decondensation followed by nuclear karryorhexis and karyolysis. This process of cell death induced by oxidative stress was named autoschizis because it showed both apoptotic and necrotic morphologic characteristics.     

Bizarre imagery: The misremembered mnemonic.

Conducted 2 experiments with 56 undergraduates to measure the effects of bizarre imagery and image interaction on the brief and long-term memory of word pairs. Ss in Exp I performed an incidental learning task and were administered free- and cued-recall tests either 5 min or 1 wk after the task. Ss in Exp II received more intensive training in the learning task and completed 2 cued-recall tests in the same session and another cued-recall test 1 wk later. In both experiments, bizarre imagery did not improve memory more than plausible, interactive imagery. The degree of interaction in the image was a strong determinant of cued-recall performance at both retention intervals. Most Ss in Exp II believed that they had remembered more bizarre than plausible pairs, even though this was clearly not the case. Possible reasons for the acceptance of the notion that bizarre imagery improves memory are discussed. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)