Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases MUTYH and hOGG1 in Colorectal Cancer Patients

Oxidative stress, oxidative DNA damage and resulting mutations play a role in colorectal carcinogenesis. Impaired equilibrium between DNA damage formation, antioxidant status, and DNA repair capacity is responsible for the accumulation of genetic mutations and genomic instability. The lesion-specific DNA glycosylases, e.g., hOGG1 and MUTYH, initiate the repair of oxidative DNA damage. Hereditary syndromes (MUTYH-associated polyposis, NTHL1-associated tumor syndrome) with germline mutations causing a loss-of-function in base excision repair glycosylases, serve as straight forward evidence on the role of oxidative DNA damage and its repair. Altered or inhibited function of above glycosylases result in an accumulation of oxidative DNA damage and contribute to the adenoma-adenocarcinoma transition. Oxidative DNA damage, unless repaired, often gives rise G:C > T:A mutations in tumor suppressor genes and proto-oncogenes with subsequent occurrence of chromosomal copy-neutral loss of heterozygosity. For instance, G>T transversions in position c.34 of a KRAS gene serves as a pre-screening tool for MUTYH-associated polyposis diagnosis. Since sporadic colorectal cancer represents more complex and heterogenous disease, the situation is more complicated. In the present study we focused on the roles of base excision repair glycosylases (hOGG1, MUTYH) in colorectal cancer patients by investigating tumor and adjacent mucosa tissues. Although we found downregulation of both glycosylases and significantly lower expression of hOGG1 in tumor tissues, accompanied with G>T mutations in KRAS gene, oxidative DNA damage and its repair cannot solely explain the onset of sporadic colorectal cancer. In this respect, other factors (especially microenvironment) per se or in combination with oxidative DNA damage warrant further attention. Base excision repair characteristics determined in colorectal cancer tissues and their association with disease prognosis have been discussed as well.     

Fractional-order adaptive backstepping control of a class of uncertain systems with external disturbances

Fractional control schemes are powerful tools for fulfilling robust tracking performance of different systems. This paper is the pioneering one in developing a fractional-order adaptive backstepping controller (FOABC) for a general class of integer-order and fractional-order (FO) systems. Model uncertainties and external disturbances can perturb system response and the controller is designed such that it can suppress the performance degradation caused by these factors. Moreover, rigorous mathematical analyses are carried out based on fractional Lyapunov theorems to ensure stability of the controlled systems. To justify the claims, worked-out examples including integer-order and FO systems are simulated. Good tracking performance of the proposed controller as well as robustness against uncertainties and insensitivity to external disturbances make it a good candidate for a broad range of systems. The results of implementing the proposed controller on different systems are compared with some newly proposed control approaches which highlight the outperformance of the FOABC.     

Experimental and numerical investigation of bridge pier scour estimation using ANFIS and teaching–learning-based optimization methods

Studies have shown that the major cause of the bridge failures is the local scour around the pier foundations or their abutments. The local scour around the bridge pier is occurred by changing the flow pattern and creating secondary vortices in the front and rear of the bridge piers. Until now, many researchers have proposed empirical equations to estimate the bridge pier scour based on laboratory and field datasets. However, scale impact, laboratory simplification, natural complexity of rivers and the personal judgement are among the main causes of inaccuracy in the empirical equations. Therefore, due to the deficiencies and disadvantages of existing equations and the complex nature of the local scour phenomenon, in this study, the adaptive network-based fuzzy inference system (ANFIS) and teaching–learning-based optimization (TLBO) method were combined and used. The parameters of the ANFIS were optimized by using TLBO optimization method. To develop the model and validate its performance, two datasets were used including laboratory dataset that consisted of experimental results from the current study and previous ones and the field dataset. In total, 27 scaled experiments of different types of pier groups with different cross sections and side slopes were carried out. To evaluate the model ability in prediction of scour depth, results were compared to the standard ANFIS and empirical equations using evaluation functions including Hec-18, Froehlich and Laursen and Toch equations. The results showed that adding TLBO to the standard ANFIS was efficient and can increase the model capability and reliability. Proposed model achieved better results than Laursen and Toch equation which had the best results among empirical relationships. For instance, proposed model in comparison with the Laursen and Toch equation, based on the RMSE function, yielded 50.4% and 71.8% better results in laboratory and field datasets, respectively.

     

Monodisperse Gold Nanoparticles: A Review on Synthesis and Their Application in Modern Medicine

Gold nanoparticles (AuNPs) are becoming increasingly popular as drug carriers due to their unique properties such as size tenability, multivalency, low toxicity and biocompatibility. AuNPs have physical features that distinguish them from bulk materials, small molecules and other nanoscale particles. Their unique combination of characteristics is just now being fully realized in various biomedical applications. In this review, we focus on the research accomplishments and new opportunities in this field, and we describe the rising developments in the use of monodisperse AuNPs for diagnostic and therapeutic applications. This study addresses the key principles and the most recent published data, focusing on monodisperse AuNP synthesis, surface modifications, and future theranostic applications. Moving forward, we also consider the possible development of functionalized monodisperse AuNPs for theranostic applications based on these efforts. We anticipate that as research advances, flexible AuNPs will become a crucial platform for medical applications.     

A metadata model for collaborative experiments and simulations in earthquake engineering

Research projects in earthquake engineering yield a very large amount of complex data from experiments and computer simulations. Understanding and exchanging these complicated and voluminous data sets prompted the development of metadata models that document the processes of data generation, and facilitate the collaboration and exchange of information between researchers. The present metadata model was designed to document and exchange a large number of large data files in earthquake engineering, but is applicable to other fields of engineering and science. The model was conceived based on a series of former data models, which were unduly complicated and limited to few types of experiments. Simpler than its predecessors, the present metadata model applies to all kinds of earthquake engineering experiments. It was developed in the object-oriented framework using Protégé. Its applications are illustrated with examples from centrifuge experiments.     

Evaluation of the Role of p53 Tumour Suppressor Posttranslational Modifications and TTC5 Cofactor in Lung Cancer

Mutations in the p53 tumor suppressor are found in over 50% of cancers. p53 function is controlled through posttranslational modifications and cofactor interactions. In this study, we investigated the posttranslationally modified p53, including p53 acetylated at lysine 382 (K382), p53 phosphorylated at serine 46 (S46), and the p53 cofactor TTC5/STRAP (Tetratricopeptide repeat domain 5/ Stress-responsive activator of p300-TTC5) proteins in lung cancer. Immunohistochemical (IHC) analysis of lung cancer tissues from 250 patients was carried out and the results were correlated with clinicopathological features. Significant associations between total or modified p53 with a higher grade of the tumour and shorter overall survival (OS) probability were detected, suggesting that mutant and/or modified p53 acts as an oncoprotein in these patients. Acetylated at K382 p53 was predominantly nuclear in some samples and cytoplasmic in others. The localization of the K382 acetylated p53 was significantly associated with the gender and grade of the disease. The TTC5 protein levels were significantly associated with the grade, tumor size, and node involvement in a complex manner. SIRT1 expression was evaluated in 50 lung cancer patients and significant positive correlation was found with p53 S46 intensity, whereas negative TTC5 staining was associated with SIRT1 expression. Furthermore, p53 protein levels showed positive association with poor OS, whereas TTC5 protein levels showed positive association with better OS outcome. Overall, our results indicate that an analysis of p53 modified versions together with TTC5 expression, upon testing on a larger sample size of patients, could serve as useful prognostic factors or drug targets for lung cancer treatment.     

Spectrophotometric and chemometric studies on the simultaneous determination of two benzodiazepines in human plasma

A numerical simple, accurate and precise method based on spectrophotometric data coupled with multivariate calibration methods, PLS and MLR, combined with GA was developed for the simultaneous determination of two benzodiazepines, Clobazam and Flurazepam. A data set of absorption spectra obtained from a calibration set of mixtures containing the compounds was used to build GA-PLS and GA-MLR models. The models were tested using a dataset constructed from the compound synthetic solutions. The better model was also applied to plasma samples. The proposed method requires no preliminary separation steps and can be used for these drugs analysis in quality control laboratories.     

Effects of Kenaf core on properties of poly(lactic acid) bio‐composite

In this study, biodegradable poly(lactic acid) (PLA)/Kenaf core composites with different amount of Kenaf core were prepared using screw extrusion. The Structure, thermal stability, mechanical properties, and biodegradation of bio‐composites are evaluated. FTIR result shows the possible interaction between the Ken core and PLA matrix. The FESEM result showed that Kenaf core was uniformly disperse in PLA matrix. Tensile and flexural strength of PLA was improved Up to the 30%vol of kenaf core content. Young's modulus and hardness properties were improved by adding kenaf core into PLA matrix. Bio‐composite density has been decreased by adding more kenaf core and water absorption of the compound was increased linear. High Kenaf core content was also found to increase the rate of biodegradability of PLA/kenaf core. It can be proven by exposure of the samples to the environment and weight loss in soil burial analysis. POLYM. COMPOS., 35:1220–1227, 2014. © 2013 Society of Plastics Engineers