Computational Model for Predicting Effective siRNA Sequences Using Whole Stacking Energy (% G) for Gene Silencing

The small interfering RNA (siRNA) alters the regulatory role of mRNA during gene expression by translational inhibition. Recent studies show that upregulation of mRNA because serious diseases like cancer. So designing effective siRNA with good knockdown effects plays an important role in gene silencing. Various siRNA design tools had been developed earlier. In this work, we are trying to analyze the existing good scoring second generation siRNA predicting tools and to optimize the efficiency of siRNA prediction by designing a computational model using Artificial Neural Network and whole stacking energy (%G), which may help in gene silencing and drug design in cancer therapy. Our model is trained and tested against a large data set of siRNA sequences. Validation of our results is done by finding correlation coefficient of experimental versus observed inhibition efficacy of siRNA. We achieved a correlation coefficient of 0.727 in our previous computational model and we could improve the correlation coefficient up to 0.753 when the threshold of whole tacking energy is greater than or equal to -32.5 kcal/mol.

Improved Wavelet Neural Networks for Early Cancer Diagnosis Using Clustering Algorithms

Wavelet neural networks (WNNs) have emerged as a vital alternative to the vastly studied multilayer perceptrons (MLPs) since its first implementation. In this paper, we applied various clustering algorithms, namely, K-means (KM), Fuzzy C-means (FCM), symmetry-based K-means (SBKM), symmetry-based Fuzzy C-means (SBFCM) and modified point symmetry-based K-means (MPKM) clustering algorithms in choosing the translation parameter of a WNN. These modified WNNs are further applied to the heterogeneous cancer classification using benchmark microarray data and were compared against the conventional WNN with random initialization method. Experimental results showed that a WNN classifier with the MPKM algorithm is more precise than the conventional WNN as well as the WNNs with other clustering algorithms.

Endometrial Cancer Recognition via EEG Dependent upon 14-3-3 Protein Leading to an Ontological Diagnosis

The purpose of my research proposal is to demonstrate that there is a relationship between EEG and endometrial cancer. The above relationship is based on an Aristotelian Syllogism; since it is known that the 14-3-3 protein is related to the electrical activity of the brain via control of the flow of Na+ and K+ ions and since it is also known that many types of cancer are associated with 14-3-3 protein, it is possible that there is a relationship between EEG and cancer. This research will be carried out by well-defined diagnostic indicators, obtained via the EEG, using signal processing procedures and pattern recognition tools such as neural networks in order to recognize the endometrial cancer type. The current research shall compare the findings from EEG and hysteroscopy performed on women of a wide age range. Moreover, this practice could be expanded to other types of cancer. The implementation of this methodology will be completed with the creation of an ontology. This ontology shall define the concepts existing in this research-s domain and the relationships between them. It will represent the types of relationships between hysteroscopy and EEG findings.

Risk Monitoring through Traceability Information Model

This paper shows a traceability framework for supply risk monitoring, beginning with the identification, analysis, and evaluation of the supply chain risk and focusing on the supply operations of the Health Care Institutions with oncology services in Bogota, Colombia. It includes a brief presentation of the state of the art of the Supply Chain Risk Management and traceability systems in logistics operations, and it concludes with the methodology to integrate the SCRM model with the traceability system.

Novel Hybrid Method for Gene Selection and Cancer Prediction

Microarray data profiles gene expression on a whole genome scale, therefore, it provides a good way to study associations between gene expression and occurrence or progression of cancer. More and more researchers realized that microarray data is helpful to predict cancer sample. However, the high dimension of gene expressions is much larger than the sample size, which makes this task very difficult. Therefore, how to identify the significant genes causing cancer becomes emergency and also a hot and hard research topic. Many feature selection algorithms have been proposed in the past focusing on improving cancer predictive accuracy at the expense of ignoring the correlations between the features. In this work, a novel framework (named by SGS) is presented for stable gene selection and efficient cancer prediction . The proposed framework first performs clustering algorithm to find the gene groups where genes in each group have higher correlation coefficient, and then selects the significant genes in each group with Bayesian Lasso and important gene groups with group Lasso, and finally builds prediction model based on the shrinkage gene space with efficient classification algorithm (such as, SVM, 1NN, Regression and etc.). Experiment results on real world data show that the proposed framework often outperforms the existing feature selection and prediction methods, say SAM, IG and Lasso-type prediction model.

A Functional Beverage: Lemonade

Fruits and vegetables are the essentials of a healthy diet, mainly because of their antioxidant properties contributing to disease blockage especially for some certain types of cancer. Being a favourite fruit, citrus are produced for economic and commercial purposes worldwide. Particularly, lemon fruit (Citrus limon L.), has an important place in export products of Turkey. Lemon has a great importance on human nutrition with regard to being a source of nutrients, flavonoids, vitamin C and minerals. It is used for food flavouring and pickling and also processed for lemonade. By processing citrus into fruit juices, consumption may increase and also become easier. Like many fruits and vegetables lemons are cheap and abundant during harvesting period, while they are quite expensive in other seasons. Lemon juice and concentrate production allows consumers to get benefits from lemon fruit in any time of the year. Lemonade is getting in to the focus of consumers’ attention preferring non-carbonated drinks. The demand of healthy, convenient functional foods affects consumer trends through innovative products. For this reason, lemonade could be enriched with different natural herb extracts such as ginger (Zingiber officinale), linden (Tilia cordata), and mint (Mentha piperita).

An Immunosensor for Bladder Cancer Screening

Nuclear matrix protein 22 (NMP22) is a FDA approved biomarker for bladder cancer. The objective of this study is to develop a simple NMP22 immumosensor (NMP22-IMS) for accurate measurement of NMP22. The NMP22-IMS was constructed with NMP22 antibody immobilized on screen-printed carbon electrodes. The construction procedures and antibody immobilization are simple. Results showed that the NMP22-IMS has an excellent (r2³0.95) response range (20 – 100 ng/mL). In conclusion, a simple and reliable NMP22-IMS was developed, capable of precisely determining urine NMP22 level.

Extraction of Symbolic Rules from Artificial Neural Networks

Although backpropagation ANNs generally predict better than decision trees do for pattern classification problems, they are often regarded as black boxes, i.e., their predictions cannot be explained as those of decision trees. In many applications, it is desirable to extract knowledge from trained ANNs for the users to gain a better understanding of how the networks solve the problems. A new rule extraction algorithm, called rule extraction from artificial neural networks (REANN) is proposed and implemented to extract symbolic rules from ANNs. A standard three-layer feedforward ANN is the basis of the algorithm. A four-phase training algorithm is proposed for backpropagation learning. Explicitness of the extracted rules is supported by comparing them to the symbolic rules generated by other methods. Extracted rules are comparable with other methods in terms of number of rules, average number of conditions for a rule, and predictive accuracy. Extensive experimental studies on several benchmarks classification problems, such as breast cancer, iris, diabetes, and season classification problems, demonstrate the effectiveness of the proposed approach with good generalization ability.

Screening and Evaluation of in vivo and in vitro Generated Insulin Plant (Vernonia divergens) for Antimicrobial and Anticancer Activities

Vernonia divergens Benth., commonly known as “Insulin Plant” (Fam: Asteraceae) is a potent sugar killer. Locally the leaves of the plant, boiled in water are successfully administered to a large number of diabetic patients. The present study evaluates the putative anti-diabetic ingredients, isolated from the in vivo and in vitro grown plantlets of V. divergens for their antimicrobial and anticancer activities. Sterilized explants of nodal segments were cultured on MS (Musashige and Skoog, 1962) medium in presence of different combinations of hormones. Multiple shoots along with bunch of roots were regenerated at 1mg l-1 BAP and 0.5 mg l-1 NAA. Micro-plantlets were separated and sub-cultured on the double strength (2X) of the above combination of hormones leading to increased length of roots and shoots. These plantlets were successfully transferred to soil and survived well in nature. The ethanol extract of plantlets from both in vivo & in vitro sources were prepared in soxhlet extractor and then concentrated to dryness under reduced pressure in rotary evaporator. Thus obtainedconcentrated extracts showed significant inhibitory activity against gram negative bacteria like Escherichia coli and Pseudomonas aeruginosa but no inhibition was found against gram positive bacteria. Further, these ethanol extracts were screened for in vitro percentage cytotoxicity at different time periods (24 h, 48 h and 72 h) of different dilutions. The in vivo plant extract inhibited the growth of EAC mouse cell lines in the range of 65, 66, 78, and 88% at 100, 50, 25 & 12.5μg mL-1 but at 72 h of treatment. In case of the extract of in vitro origin, the inhibition was found against EAC cell lines even at 48h. During spectrophotometric scanning, the extracts exhibited different maxima (ʎ) - four peaks in in vitro extracts as against single in in vivo preparation suggesting the possible change in the nature of ingredients during micropropagation through tissue culture techniques.

Improved Technique of Non-viral Gene Delivery into Cancer Cells

Liposomal magnetofection is a simple, highly efficient technology for cell transfection, demonstrating better outcome than a number of other common gene delivery methods. However, aggregate complexes distribution over the cell surface is non-uniform due to the gradient of the permanent magnetic field. The aim of this study was to estimate the efficiency of liposomal magnetofection for prostate carcinoma PC3 cell line using newly designed device, “DynaFECTOR", ensuring magnetofection in a dynamic gradient magnetic field. Liposomal magnetofection in a dynamic gradient magnetic field demonstrated the highest transfection efficiency for PC3 cells – it increased for 21% in comparison with liposomal magnetofection and for 42% in comparison with lipofection alone. The optimal incubation time under dynamic magnetic field for PC3 cell line was 5 minutes and the optimal rotation frequency of magnets – 5 rpm. The new approach also revealed lower cytotoxic effect to cells than liposomal magnetofection.

Advanced Image Analysis Tools Development for the Early Stage Bronchial Cancer Detection

Autofluorescence (AF) bronchoscopy is an established method to detect dysplasia and carcinoma in situ (CIS). For this reason the “Sotiria" Hospital uses the Karl Storz D-light system. However, in early tumor stages the visualization is not that obvious. With the help of a PC, we analyzed the color images we captured by developing certain tools in Matlab®. We used statistical methods based on texture analysis, signal processing methods based on Gabor models and conversion algorithms between devicedependent color spaces. Our belief is that we reduced the error made by the naked eye. The tools we implemented improve the quality of patients' life.

The Cytotoxic Effect of PM 701 and its Fractions on Cell Proliferation of Breast Cancer Cells, McF7

Breast cancer is the most common malignancy in the world among women. Many therapies have been designed to treat this disease. Mamectomy, chemotherapy and radiotherapy are still the main therapies of breast cancer. However, the results were unsatisfactory and still far from the ideal treatment. PM 701is a natural product, has anticancer activity. The bioactive fraction PMF and subfraction PMFK had been isolated from PM701. PM 701 and its fractions were proved to have a cytotoxic properties against different cancer cell lines. This article is directed for the further examination of lyophilized PM701 and its active fractions on the growth of breast cancer cells (MCF-7). PM 701, PMF or PMFK were adding to the cultural medium, where MCF-7 is incubated. PM 701, PMF or PMFK were able to inhibit significantly the proliferation of MCF-7 cells, Moreover these new agents were proved to induce apoptosis of the breast cancer cells; through its direct effect on the nuclei.

Development of a 3D Mathematical Model for a Doxorubicin Controlled Release System using Pluronic Gel for Breast Cancer Treatment

Female breast cancer is the second in frequency after cervical cancer. Surgery is the most common treatment for breast cancer, followed by chemotherapy as a treatment of choice. Although effective, it causes serious side effects. Controlled-release drug delivery is an alternative method to improve the efficacy and safety of the treatment. It can release the dosage of drug between the minimum effect concentration (MEC) and minimum toxic concentration (MTC) within tumor tissue and reduce the damage of normal tissue and the side effect. Because an in vivo experiment of this system can be time-consuming and labor-intensive, a mathematical model is desired to study the effects of important parameters before the experiments are performed. Here, we describe a 3D mathematical model to predict the release of doxorubicin from pluronic gel to treat human breast cancer. This model can, ultimately, be used to effectively design the in vivo experiments.

Artificial Intelligence Support for Interferon Treatment Decision in Chronic Hepatitis B

Chronic hepatitis B can evolve to cirrhosis and liver cancer. Interferon is the only effective treatment, for carefully selected patients, but it is very expensive. Some of the selection criteria are based on liver biopsy, an invasive, costly and painful medical procedure. Therefore, developing efficient non-invasive selection systems, could be in the patients benefit and also save money. We investigated the possibility to create intelligent systems to assist the Interferon therapeutical decision, mainly by predicting with acceptable accuracy the results of the biopsy. We used a knowledge discovery in integrated medical data - imaging, clinical, and laboratory data. The resulted intelligent systems, tested on 500 patients with chronic hepatitis B, based on C5.0 decision trees and boosting, predict with 100% accuracy the results of the liver biopsy. Also, by integrating the other patients selection criteria, they offer a non-invasive support for the correct Interferon therapeutic decision. To our best knowledge, these decision systems outperformed all similar systems published in the literature, and offer a realistic opportunity to replace liver biopsy in this medical context.

Molecular Dynamics and Circular Dichroism Studies on Aurein 1.2 and Retro Analog

Aurein 1.2 is a 13-residue amphipathic peptide with antibacterial and anticancer activity. Aurein1.2 and its retro analog were synthesized to study the activity of the peptides in relation to their structure. The antibacterial test result showed the retro-analog is inactive. The secondary structural analysis by CD spectra indicated that both of the peptides at TFE/Water adopt alpha-helical conformation. MD simulation was performed on aurein 1.2 and retro-analog in water and TFE in order to analyse the factors that are involved in the activity difference between retro and the native peptide. The simulation results are discussed and validated in the light of experimental data from the CD experiment. Both of the peptides showed a relatively similar pattern for their hydrophobicity, hydrophilicity, solvent accessible surfaces, and solvent accessible hydrophobic surfaces. However, they showed different in directions of dipole moment of peptides. Also, Our results further indicate that the reversion of the amino acid sequence affects flexibility .The data also showed that factors causing structural rigidity may decrease the activity. Consequently, our finding suggests that in the case of sequence-reversed peptide strategy, one has to pay attention to the role of amino acid sequence order in making flexibility and role of dipole moment direction in peptide activity. KeywordsAntimicrobial peptides, retro, molecular dynamic, circular dichroism.

Topical Delivery of Thymidine Dinucleotide to Induce p53 Generation in the Skin by Elastic Liposome

Transcription factor p53 has a powerful tumor suppressing function that is associated with many cancers. However, p53 of the molecular weight was higher make the limitation across to skin or cell membrane. Thymidine dinucleotide (pTT), an oligonucleotide, can activate the p53 transcription factor. pTT is a hydrophilic and negative charge oligonucleotide, which delivery in to cell membrane need an appropriate carrier. The aim of this study was to improve the bioavailability of the nucleotide fragment, thymidine dinucleotide (pTT), using elasic liposome carriers to deliver the drug into the skin. The study demonstrate that dioleoylphosphocholine (DOPC) incorporated with sodium cholate at molar ratio 1:1 can archived the particle size about 220 nm. This elastic liposome could penetration through skin from stratum corneum to whole epidermis by confocal laser scanning microscopy (CLSM). Moreover, we observed the the slight increase in generation of p53 by western blot.

5-Aminolevulinic Acid-Loaded Gel, Sponge Collagen to Enhance the Delivery Ability to Skin

Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for treating superficial cancer, especially for skin or oral cancer. ALA, a precursor of the photosensitizer protoporphyrin IX (PpIX), is present as zwitterions and hydrophilic property which make the low permeability through the cell membrane. Collagen is a traditional carrier; its molecular composed various amino acids which bear positive charge and negative charge. In order to utilize the ion-pairs with ALA and collagen, the study employed various pH values adjusting the net charge. The aim of this study was to compare a series collagen form, including solution, gel and sponge to investigate the topical delivery behavior of ALA. The in vivo confocal laser scanning microscopy (CLSM) study demonstrated that PpIX generation ability was different pattern after apply for 6 h. Gel type could generate high PpIX, and archived more deep of skin depth.

A Study of Liver Checkup in Patients with Hepatitis C in the Region of Batna

Hepatitis C is an infectious disease transmitted by blood and due to hepatitis C virus (HCV), which attacks the liver. The infection is characterized by liver inflammation (hepatitis) that is often asymptomatic but can progress to chronic hepatitis and later cirrhosis and liver cancer. Our problem tends to highlight on the one hand the prevalence of infectious disease in the population of the region of Batna and on other hand the biological characteristics of this disease by a screening and a specific diagnosis based on serological tests, liver checkup (measurement of haematological and biochemical parameters). The results showed: The serology of hepatitis C establishes the diagnosis of infection with hepatitis C. In this study and with the serological test, 24 cases of the disease of hepatitis C were found in 1000 suspected cases (7 cases with normal transaminases and 17 cases with elevated transaminases). The prevalence of this disease in this study population was 2.4%. The presence of hepatitis C disrupts liver function including the onset of cytolysis, cholestasis, jaundice, thrombocytopenia, and coagulation disorders.

Lung Nodule Detection in CT Scans

In this paper we describe a computer-aided diagnosis (CAD) system for automated detection of pulmonary nodules in computed-tomography (CT) images. After extracting the pulmonary parenchyma using a combination of image processing techniques, a region growing method is applied to detect nodules based on 3D geometric features. We applied the CAD system to CT scans collected in a screening program for lung cancer detection. Each scan consists of a sequence of about 300 slices stored in DICOM (Digital Imaging and Communications in Medicine) format. All malignant nodules were detected and a low false-positive detection rate was achieved.

Colorectal Cancer Screening by a CEACAM-6 Immunosensor

The biomarker for colorectal cancer (CRC) is CEACAM-6 antigen (C6AG). Therefore, this study aims to develop a novel, simple and low-cost CEACAM-6 antigen immumosensor (C6AG-IMS), based on electrical impedance measurement, for precise determination of C6AG. A low-cost screen-printed graphite electrode was constructed and used as the sensor, with CEACAM-6 antibody (C6AB) immobilized on it. The procedures of sensor fabrication and antibody immobilization are simple and low-cost. Measurement of the electrical impedance at a definite frequency ranges (0.43 – 1.26 MHz) showed that the C6AG-IMS has an excellent linear (r2>0.9) response range (8.125 – 65 pg/mL), covering the normal physiological and pathological ranges of blood C6AG levels. Also, the C6AG-IMS has excellent reliability and validity, with the intraclass correlation coefficient being 0.97. In conclusion, a novel, simple, low-cost and reliable C6AG-IMS was designed and developed, being able to accurately determine blood C6AG levels in the range of pathological and normal physiological regions. The C6AG-IMS can provide a point-of-care and immediate screening results to the user at home.