Effects of CXCR4 Silencing by Sirna Engrafted Cotionized Dextran in Mouse Models of Colorectal Cancer and Liver Metastasis

Liver metastasis is the main cause of colorectal cancer related mortality. CXCR4 is necessary for the outgrowth of colon cancer micrometastasis. CXCR4 gene expression and serum total lactate dehydrogenase, creatine kinase and alkaline phosphatase levels are often increased in patients with colorectal cancer. RNA interference is a well recognized pathway involved in cellular defense against viral invasion and post transcriptional regulation. This technology has emerged as a promising new strategy for the study of functional genomics and drug target validation. It is currently being evaluated in clinical trials as a potential therapy for cancers. This study aims to evaluate the transfection efficiency of three biodegradable polymers as carriers for CXCR4 siRNAI, II to treat liver metastasis from colorectal cancer in vitro on mouse colon cancer cells (CT26.WT) and human colon cancer cells (HT29) and in vivo balb/c mice. In this study, dextran spermine, pullulan spermine and dextran hexamine were used as non-viral vectors for in vitro and in vivo CXCR4 siRNAs. Characterization of the morphology, size and stability of CXCR4 siRNAs cationized dextran were performed using transmission electron microscopy, particle sizer and zeta potential. CXCR4 expression in human colorectal cell line HT29 was measured by real-time reverse transcription PCR and immunocytochemistry. Cell proliferation assay, cell cycle analysis, acridine orange/propidium iodide staining and ultrastructural changes of cells using transmission electron microscopy were also studied as biological evaluations. Among three carriers studied, dextran spermine showed smallest size 99.25±4.3 nm with suitable zeta potential 34.15±1.55 mV. These findings were further supported by RT PCR that showed more silencing has been achieved by CXCR4 pool siRNA/dextran spermine in comparison to pullulan spermine and dextran hexamine. The percentage of viability for dextran spermine was higher than pullulan spermine and dextran-hexamine. Animal study demonstrated that inhibition of CXCR4 gene with CXCR4 siRNAI, II/dextran spermine was more efficient than naked CXCR4 siRNAI, II and also post treatment follow transfection of tumor cells more efficient than just transfection cells treatment with naked CXCR4 siRNAI, II or CXCR4 siRNAI, II/dextran spermine.CXCR4 expression was correlated with serum total lactate dehydrogenase, alkaline phosphatase and creatine kinase. These data show that CXCR4 expression lactate dehydrogenase, alkaline phosphatase and creatine kinase may be useful markers to predict liver metastasis in colorectal cancer. Dextran spermine demonstrated improved transfection efficiency in siRNA therapy

Modeling the effects of high strain rate loading on RC columns using Arbitrary Lagrangian Eulerian (ALE) technique

In recent years, many studies have been conducted by governmental and nongovernmental organizations across the world in an attempt to better understand the effect of explosive loads on buildings in order to better design against specific threats. This study is intended to contribute to increase the knowledge about how explosions affect reinforced concrete (RC) columns. In this study, a nonlinear model is developed to study the blast response of RC columns subjected to explosive loads. Numerical modeling of RC column under explosive load is presented using advanced finite element code LS DYNA. The obtained numerical model is validated with the experimental test and the results are in substantial agreement with the experimental data. ALE method for blast analysis is presented in the current research. The effects of scaled distance on the damage profile of RC columns are investigated. The results demonstrate that the level of damage increased with describing the scaled distance. Also the results shown duration for the blast loading, and hence the impulse, varies with charge masses at the specified scaled distance. Higher magnitude charge masses produced longer blast loading durations than lower magnitude charge masses. This means that at the same scaled distance, a charge mass of higher magnitude produced a higher impulse than the lower magnitude charge mass. The findings of this research represent the scaled distance is an important parameter that should be taken into account when analyzing the behavior of RC columns under explosive effects. The data collected from this research are being used to improve the knowledge of how structures will respond to a blast event, and improve finite element models for predicting the blast performance of concrete structures.Peer Reviewe

A study on examining interrelationships among customer satisfaction, loyalty, and switching intent in industrial food suppliers

Brand loyalty is one of the most important concepts in brand literature. Customer’s loyalty toward brand can increase firm’s share price. In addition, firms’ market share maintains close relationship with net profit and capital used return. Company efforts to motivate customers to switch from competitive brands to their own or to induce them to repurchase their own brands are very important in their marketing activities. Therefore, investigating customer variety-seeking orientation and level of involvement in decision-making plays essential role in explaining customers’ product selection activities. This study intends to examine interrelationships among customer satisfaction, loyalty, and switching intent in industrial food suppliers and verifies the moderating effect of customer variety-seeking orientation and purchase decision involvement. The findings indicate that, the impact of purchase involvement was lower than variety seeking and the satisfaction had the highest negative impact on switching intent of customers

Effect of different parameters on sonochemical synthesized nanocrystalline TiO2 particles

An ultrasonic-assisted method to directly prepare nanocrystalline TiO2 has been used. TiO2 was synthesized by the hydrolysis of Tetraisopropyl titanate (TIPT) in the presence of de-ionized water and ethanol under high-intensity ultrasonic irradiation (24 KHz, 300 W/cm2) at different conditions. The effect of water content, water-to-TIPT ratio, water-to-ethanol ratio and sonication time on the particle size of TiO2 has been investigated by using design of experiment (DOE). The water content, water-to-TIPT ratio, water-to-ethanol ratio and sonication time were varied in the range 100-150 ml, 50-75 v/v, 20-30 v/v and 3-4 hr, respectively. Particle size of TiO2 was characterized using particle size analyzer. The results of DOE show that water content has the greatest effect on the particle size of TiO2

Incorporating feature ranking and evolutionary methods for the classification of high-dimensional DNA microarray gene expression data

Background: DNA microarray gene expression classification poses a challenging task to the machine learning domain. Typically, the dimensionality of gene expression data sets could go from several thousands to over 10,000 genes. A potential solution to this issue is using feature selection to reduce the dimensionality. Aim The aim of this paper is to investigate how we can use feature quality information to improve the precision of microarray gene expression classification tasks. Method: We propose two evolutionary machine learning models based on the eXtended Classifier System (XCS) and a typical feature selection methodology. The first one, which we call FS-XCS, uses feature selection for feature reduction purposes. The second model is GRD-XCS, which uses feature ranking to bias the rule discovery process of XCS. Results: The results indicate that the use of feature selection/ranking methods is essential for tackling high-dimensional classification tasks, such as microarray gene expression classification. However, the results also suggest that using feature ranking to bias the rule discovery process performs significantly better than using the feature reduction method. In other words, using feature quality information to develop a smarter learning procedure is more efficient than reducing the feature set. Conclusion: Our findings have shown that extracting feature quality information can assist the learning process and improve classification accuracy. On the other hand, relying exclusively on the feature quality information might potentially decrease the classification performance (e.g., using feature reduction). Therefore, we recommend a hybrid approach that uses feature quality information to direct the learning process by highlighting the more informative features, but at the same time not restricting the learning process to explore other features

Heavy metal flocculation at Pirbazar River, Banadar Anzali, south west Caspian Sea

Heavy metal flocculation process was studied in the year 2002 in order to determine the interaction of water in Pirbazar River with Caspian Sea water. The effects of various salinity concentrations of Caspian Sea water were studied on determined heavy metals including Fe, Zn, Pb, Cu, Cd and Cr level of Pirbazar River using APHA method of extraction and measurement. The results illustrated that the level of heavy metal concentration in Pirbazar River were above standard limits and the extent of flocculation depended on both the salinity level and the heavy metal itself. The maximum flocculation for Cd and Cr were recorded at 7.65ppt, for Zn and Fe at 9.35ppt while for Pb and Cd were at 2.55ppt salinity. The order of flocculation with respect to percentage of original concentrations was found to be Zn > Fe > Cr> Cu > Cd> Pb