Journal of Computational Medicine The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. An Object-Oriented Framework for Versatile Finite Element Based Simulations of Neurostimulation Tue, 09 Feb 2016 08:54:51 +0000 Computational simulations of transcranial electrical stimulation (TES) are commonly utilized by the neurostimulation community, and while vastly different TES application areas can be investigated, the mathematical equations and physiological characteristics that govern this research are identical. The goal of this work was to develop a robust software framework for TES that efficiently supports the spectrum of computational simulations routinely utilized by the TES community and in addition easily extends to support alternative neurostimulation research objectives. Using well-established object-oriented software engineering techniques, we have designed a software framework based upon the physical and computational aspects of TES. The framework’s versatility is demonstrated with a set of diverse neurostimulation simulations that (i) reinforce the importance of using anisotropic tissue conductivities, (ii) demonstrate the enhanced precision of high-definition stimulation electrodes, and (iii) highlight the benefits of utilizing multigrid solution algorithms. Our approaches result in a framework that facilitates rapid prototyping of real-world, customized TES administrations and supports virtually any clinical, biomedical, or computational aspect of this treatment. Software reuse and maintainability are optimized, and in addition, the same code can be effortlessly augmented to provide support for alternative neurostimulation research endeavors. Edward T. Dougherty and James C. Turner Copyright © 2016 Edward T. Dougherty and James C. Turner. All rights reserved. Musculoskeletal Simulation for Assessment of Effect of Movement-Based Structure-Modifying Treatment Strategies Sun, 27 Dec 2015 08:10:24 +0000 The better understanding of the complex mechanism between neural motor control and its resulting joint kinematics and muscle forces allows a better elucidation of the mechanisms behind body growth, aging progression, and disease development. This study aimed at investigating the impact of movement-based structure-modifying treatment strategies on joint kinematics, muscle forces, and muscle synergies of the gait with instrumented implant. A patient-specific musculoskeletal model was used to quantitatively assess the deviations of joint and muscle behaviors between the normal gait and 4 gait modifications (bouncy, medial thrust, midcrouch, and mtp (i.e., gait with forefoot strike)). Moreover, muscle synergy analysis was performed using EMG-based nonnegative matrix factorization. Large variation of 19 degrees and 190 N was found for knee flexion/extension and lower limb muscle forces, respectively. EMG-based muscle synergy analysis revealed that the activation levels of the vastus lateralis and tibialis anterior are dominant for the midcrouch gait. In addition, an important contribution of semimembranosus to the medial thrust and midcrouch gaits was also observed. In fact, such useful information could allow a better understanding of the joint function and muscle synergy strategies leading to deeper knowledge of joint and muscle mechanisms related to neural voluntary motor commands. Tien Tuan Dao Copyright © 2015 Tien Tuan Dao. All rights reserved. A Hertzian Integrated Contact Model of the Total Knee Replacement Implant for the Estimation of Joint Contact Forces Tue, 13 Oct 2015 06:08:13 +0000 The prediction of lower limb muscle and contact forces may provide useful knowledge to assist the clinicians in the diagnosis as well as in the development of appropriate treatment for musculoskeletal disorders. Research studies have commonly estimated joint contact forces using model-based muscle force estimation due to the lack of a reliable contact model and material properties. The objective of this present study was to develop a Hertzian integrated contact model. Then, in vivo elastic properties of the Total Knee Replacement (TKR) implant were identified using in vivo contact forces leading to providing reliable material properties for modeling purposes. First, a patient specific rigid musculoskeletal model was built. Second, a STL-based implant model was designed to compute the contact area evolutions during gait motions. Finally, a Hertzian integrated contact model was defined for the in vivo identification of elastic properties (Young’s modulus and Poisson coefficient) of the instrumented TKR implant. Our study showed a potential use of a new approach to predict the contact forces without knowledge of muscle forces. Thus, the outcomes may lead to accurate and reliable prediction of human joint contact forces for new case study. Tien Tuan Dao and Philippe Pouletaut Copyright © 2015 Tien Tuan Dao and Philippe Pouletaut. All rights reserved. Computational Simulation of Tumor Surgical Resection Coupled with the Immune System Response to Neoplastic Cells Wed, 31 Dec 2014 00:10:13 +0000 Numerous mathematical and computational models have arisen to study and predict the effects of diverse therapies against cancer (e.g., chemotherapy, immunotherapy, and even therapies under research with oncolytic viruses) but, unfortunately, few efforts have been directed towards development of tumor resection models, the first therapy against cancer. The model hereby presented was stated upon fundamental assumptions to produce a predictor of the clinical outcomes of patients undergoing a tumor resection. It uses ordinary differential equations validated for predicting the immune system response and the tumor growth in oncologic patients. This model could be further extended to a personalized prognosis predictor and tools for improving therapeutic strategies. J. Jesús Naveja, Flavio F. Contreras-Torres, Andrés Rodríguez-Galván, and Erick Martínez-Lorán Copyright © 2014 J. Jesús Naveja et al. All rights reserved. Genetic Algorithm Based Approach in Attribute Weighting for a Medical Data Set Wed, 03 Sep 2014 06:48:09 +0000 Genetic algorithms have been utilized in many complex optimization and simulation tasks because of their powerful search method. In this research we studied whether the classification performance of the attribute weighted methods based on the nearest neighbour search can be improved when using the genetic algorithm in the evolution of attribute weighting. The attribute weights in the starting population were based on the weights set by the application area experts and machine learning methods instead of random weight setting. The genetic algorithm improved the total classification accuracy and the median true positive rate of the attribute weighted k-nearest neighbour method using neighbour’s class-based attribute weighting. With other methods, the changes after genetic algorithm were moderate. Kirsi Varpa, Kati Iltanen, and Martti Juhola Copyright © 2014 Kirsi Varpa et al. All rights reserved. On the Role of Optimal Counseling and Antiviral Therapy on Controlling HCV among Intravenous Drug Misusers Wed, 25 Jun 2014 06:44:38 +0000 Hepatitis C virus (HCV) remains a major health challenge despite the availability of highly effective antiviral drugs. Prior studies suggest that many physicians are reluctant to treat intravenous drug misusers due to low levels of treatment adherence associated with intravenous drug misusers. HCV treatment guidelines and recommendations stipulate that HCV patients in treatment should abstain from intravenous drug misuse activities in order to reduce the likelihood of treatment failure, drug resistance, reinfection, superinfection, or mixed infection. In this paper, a mathematical model for exploring the transmission dynamics of HCV among intravenous drug misusers is proposed. The model incorporates essential characteristics of intravenous drug misusers such as relapse and nonadherence to treatment guidelines. With the aid of optimal control theory we assess the effects of time dependent HCV screening and treatment. Results from this study provide a framework for designing the appropriate strategies on controlling the long-term dynamics of HCV among intravenous drug users. Steady Mushayabasa Copyright © 2014 Steady Mushayabasa. All rights reserved. Mathematical Modeling of the Expert System Predicting the Severity of Acute Pancreatitis Mon, 09 Jun 2014 15:02:53 +0000 The method of building the hyperplane which separates the convex hulls in the Euclidean space is proposed. The algorithm of prediction of the presence of severity in patients based on this method is developed and applied in practice to predict the presence of severity in patients with acute pancreatitis. Maria A. Ivanchuk, Vitalij V. Maksimyuk, and Igor V. Malyk Copyright © 2014 Maria A. Ivanchuk et al. All rights reserved. 2D-QSAR Study of Indolylpyrimidines Derivative as Antibacterial against Pseudomonas aeruginosa and Staphylococcus aureus: A Comparative Approach Thu, 05 Jun 2014 07:31:15 +0000 A set of 15 indolylpyrimidine derivatives with their antibacterial activities in terms of minimum inhibitory concentration against the gram-negative bacteria Pseudomonas aeruginosa and gram-positive Staphylococcus aureus were selected for 2D quantitative structure activity relationship (QSAR) analysis. QSAR was performed using a combination of various descriptors such as steric, electronic and topological. Stepwise regression method was used to derive the most significant QSAR equation for predicting the inhibitory activity of this class of molecules. The best QSAR model was further validated by a leave one out technique as well as by the random trials. A high correlation between experimental and predicted inhibitory values was observed. A comparative picture of behavior of indolylpyrimidines against both of the microorganisms is discussed. Prasanna A. Datar Copyright © 2014 Prasanna A. Datar. All rights reserved. Combined 3D QSAR Based Virtual Screening and Molecular Docking Study of Some Selected PDK-1 Kinase Inhibitors Sun, 01 Jun 2014 09:13:37 +0000 Phosphoinositide-dependent kinase-1 (PDK-1) is an important therapeutic target for the treatment of cancer. In order to identify the important chemical features of PDK-1 inhibitors, a 3D QSAR pharmacophore model was developed based on 21 available PDK-1 inhibitors. The best pharmacophore model (Hypo1) exhibits all the important chemical features required for PDK-1 inhibitors. The correlation coefficient, root mean square deviation (RMSD), and cost difference were 0.96906, 1.0719, and 168.13, respectively, suggesting a good predictive ability of the model (Hypo1) among all the ten pharmacophore models that were analyzed. The best pharmacophore model (Hypo1) was further validated by Fisher’s randomization method (95%), test set method , and the decoy set with the goodness of fit (0.73). Further, this validated pharmacophore model Hypo1 was used as a 3D query to screen the molecules from databases like NCI database and Maybridge. The resultant hit compounds were subsequently subjected to filtration by Lipinski’s rule of five as well as the ADMET study. Docking study was done to refine the retrieved hits and as a result to reduce the rate of false positive. Best hits will further be subjected to in vitro study in future. Shalini Singh and Pradeep Srivastava Copyright © 2014 Shalini Singh and Pradeep Srivastava. All rights reserved. Reducing the Inconsistency between Doppler and Invasive Measurements of the Severity of Aortic Stenosis Using Aortic Valve Coefficient: A Retrospective Study on Humans Wed, 28 May 2014 11:48:44 +0000 Background. It is not uncommon to observe inconsistencies in the diagnostic parameters derived from Doppler and catheterization measurements for assessing the severity of aortic stenosis (AS) which can result in suboptimal clinical decisions. In this pilot study, we investigate the possibility of improving the concordance between Doppler and catheter assessment of AS severity using the functional diagnostic parameter called aortic valve coefficient (AVC), defined as the ratio of the transvalvular pressure drop to the proximal dynamic pressure. Method and Results. AVC was calculated using diagnostic parameters obtained from retrospective chart reviews. AVC values were calculated independently from cardiac catheterization () and Doppler measurements (). An improved significant correlation was observed between Doppler and catheter derived AVC (, ) when compared to the correlation between Doppler and catheter measurements of mean pressure gradient (, ) and aortic valve area (, ). The correlation between Doppler and catheter derived AVC exhibited a marginal improvement over the correlation between Doppler and catheter derived aortic valve resistance (, ). Conclusion. AVC is a refined clinical parameter that can improve the concordance between the noninvasive and invasive measures of the severity of aortic stenosis. Anup K. Paul, Rupak K. Banerjee, Arumugam Narayanan, Mohamed A. Effat, and Jason J. Paquin Copyright © 2014 Anup K. Paul et al. All rights reserved. Context-Based Separation of Cell Clusters for the Automatic Biocompatibility Testing of Implant Materials Thu, 20 Mar 2014 12:19:20 +0000 This paper presents a new method to separate cells on microscopic surfaces joined together in cell clusters into individual cells. Important features of this method are that the remaining object geometry is preserved and few contour points are required for finding joints between neighboring cells. There are alternative methods such as morphological operations or the watershed transformation based on the inverse distance transformation but they have certain disadvantages compared to the method presented in this paper. The discussed method contains knowledge-based components in form of a decision function and exchangeable rules to avoid unwanted separations. S. Buhl, B. Neumann, and S. C. Schäfer Copyright © 2014 S. Buhl et al. All rights reserved. Modeling Requirements for Computer Simulation of Cerebral Aneurysm Sun, 16 Feb 2014 15:27:05 +0000 Background. In order to reduce the mortality risk of aneurysm rupture, a timely diagnosis and treatment are vital. There are different reasons for aneurysm, such as hypertension, arteriosclerosis, and heredity. An efficient and cost-effective method to study the generation, development, and rupture of aneurysm and also analysis of treatment methods can accelerate progress. The Computational Fluid Dynamics is a well-known tool to simulate various phenomena. A reliable virtual modeling in biology depends on our knowledge about variety of characteristics, that is, biological features, structural properties, and flow conditions. Objective. Because of the vast research about the related subjects, an organized review is required. The aim of current review article is classification of the required foundations for a reliable virtual modeling of cerebral aneurysm, especially in the Circle of Willis. S. R. Ghodsi, V. Esfahanian, and S. M. Ghodsi Copyright © 2014 S. R. Ghodsi et al. All rights reserved. Transmission Dynamics of Hepatitis C with Control Strategies Thu, 13 Feb 2014 12:24:04 +0000 We present a rigorous mathematical analysis of a deterministic model, for the transmission dynamics of hepatitis C, using a standard incidence function. The infected population is divided into three distinct compartments featuring two distinct infection stages (acute and chronic) along with an isolation compartment. It is shown that for basic reproduction number , the disease-free equilibrium is locally and globally asymptotically stable. The model also has an endemic equilibrium for . Uncertainty and sensitivity analyses are carried out to identify and study the impact of critical parameters on . In addition, we have presented the numerical simulations to investigate the influence of different important parameters on . Since we have a locally stable endemic equilibrium, optimal control is applied to the deterministic model to reduce the total infected population. Two different optimal control strategies (vaccination and isolation) are designed to control the disease and reduce the infected population. Pontryagin’s Maximum Principle is used to characterize the optimal controls in terms of an optimality system which is solved numerically. Numerical results for the optimal controls are compared against the constant controls and their effectiveness is discussed. Adnan Khan, Sultan Sial, and Mudassar Imran Copyright © 2014 Adnan Khan et al. All rights reserved. Validation of Shape Context Based Image Registration Method Using Digital Image Correlation Measurement on a Rat Stomach Mon, 06 Jan 2014 16:33:07 +0000 Recently we developed analysis for 3D visceral organ deformation by combining the shape context (SC) method with a full-field strain (strain distribution on a whole 3D surface) analysis for calculating distension-induced rat stomach deformation. The surface deformation detected by the SC method needs to be further verified by using a feature tracking measurement. Hence, the aim of this study was to verify the SC method-based calculation by using digital image correlation (DIC) measurement on a rat stomach. The rat stomach exposed to distension pressures 0.0, 0.2, 0.4, and 0.6 kPa were studied using both 3D DIC system and SC-based image registration calculation. Three different surface sample counts between the reference and the target surfaces were used to gauge the effect of the surface sample counts on the calculation. Each pair of the surface points between the DIC measured target surface and the SC calculated correspondence surface was compared. Compared with DIC measurement, the SC calculated surface had errors from 5% to 23% at pressures from 0.2 to 0.6 kPa with different surface sample counts between the reference surface and the target surface. This indicates good qualitative and quantitative agreement on the surfaces with small dissimilarity and small sample count difference between the reference surface and the target surface. In conclusion, this is the first study to validate the 3D SC-based image registration method by using unique tracking features measurement. The developed method can be used in the future for analysing scientific and clinical data of visceral organ geometry and biomechanical properties in health and disease. Donghua Liao, Peng Wang, Jingbo Zhao, and Hans Gregersen Copyright © 2014 Donghua Liao et al. All rights reserved. Use of SSA and MCSSA in the Analysis of Cardiac RR Time Series Tue, 24 Dec 2013 10:51:08 +0000 A new preprocessing procedure in the analysis of cardiac RR interval time series is described. It uses the singular spectrum analysis (SSA) and the Monte Carlo SSA (MCSSA) test. A novel feature of this preprocessing procedure is the ability to identify the noise component present in the series with a given probability and to separate the time series into a trend, signal, and noise. The MCSSA test involves testing whether the modes obtained from SSA can be generated by a noise process leading to separation of the noise modes from the signal. The procedure described here does not discard or modify any sample in the record but merely separates the time series into a trend, signal, and noise, allowing for further analysis of these components. The procedure is not limited to the length of the record and could be applied to nonstationary data. The basis functions used in SSA are data adaptive in that they are not chosen a priori but instead are dependent on the data set used, increasing flexibility to the analysis. The procedure is illustrated using the RR interval time series of a healthy, congestive heart failure, and atrial fibrillation subject. R. A. Thuraisingham Copyright © 2013 R. A. Thuraisingham. All rights reserved. Molecular Docking Assessment of Efficacy of Different Clinically Used Arsenic Chelator Drugs Sun, 15 Dec 2013 14:46:54 +0000 Arsenic contamination of ground water has become a global problem affecting specially, south-east Asian countries like Bangladesh and eastern parts of India. It also affects South America and some parts of the US. Different organs of the physiological system are affected due to contamination of inorganic arsenic in water. Animal studies with different chelators are not very conclusive as far as the multi/differential organ effect(s) of arsenic is concerned. Our docking study establishes the molecular rationale of blood test for early detection of arsenic toxicity; as arsenic has a high affinity to albumin, a plasma protein and actin, a structural protein of all cells including Red Blood Cells. This study also shows that there is a little possibility of male reproductive organs toxicity by different forms of inorganic arsenic; however, female reproductive system is very much susceptible to sodium-arsenite. Through comparative analysis regarding the chelating effectiveness among the available arsenic chelator drugs, meso-2,3 dimercaptosuccinic acid (DMSA) and in some cases lipoic acid is the most preferred choice of drug for removing of arsenic deposits. This computational method actually reinforces the clinical finding regarding DMSA as the most preferred drug in removal of arsenic deposits from majority of the human tissues. Durjoy Majumder and Sayan Mukherjee Copyright © 2013 Durjoy Majumder and Sayan Mukherjee. All rights reserved. Mathematical Modeling of Melanoma Cell Migration with an Elastic Continuum Model for the Evaluation of the Influence of Tumor Necrosis Factor-Alpha on Migration Wed, 25 Sep 2013 14:45:38 +0000 An elastic continuum mathematical model was implemented to study collective C8161 melanoma cell migration during a “scratch wound” assay, in control and under the influence of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-α). The model has four constants: force that results from lamellipod formation (F), adhesion constant between cells and extracellular matrix (ECM) (b), cell layer elasticity modulus (k), and growth rate (ρ). A nonlinear regression routine was used to obtain the parameters of the model with data from an experiment made with C8161 melanoma cells, with and without TNF-α. Coefficient of determination for both situations was and , respectively. The parameters values obtained were similar to the ones found in the literature. However, the adhesion constant value decreased with the introduction of TNF-α, which is not in accordance with expected since the presence of TNF-α is associated with an increased expression of integrins that would promote an enhanced adhesion among cells. The model was used in a study relating to the adhesion constant and cell migration, and the results suggested that cell migration decreases with higher adhesion, which is also not in accordance with expected. These differences would not occur if it was considered that TNF-α increases the elasticity modulus of the cell layer. Julia Vianna Gallinaro, Claudia Mirian de Godoy Marques, Fernando Mendes de Azevedo, and Daniela Ota Hisayasu Suzuki Copyright © 2013 Julia Vianna Gallinaro et al. All rights reserved. Structure-Based Virtual Screening and Molecular Dynamic Simulation Studies to Identify Novel Cytochrome bc1 Inhibitors as Antimalarial Agents Sat, 24 Aug 2013 09:02:38 +0000 Cytochrome bc1 (EC, bc1) is an essential component of the cellular respiratory chain, which catalyzes electron transfer from quinol to cytochrome c and concomitantly the translocation of protons across the membrane. It has been identified as a promising target in malaria parasites. The structure-based pharmacophore modelling and molecular dynamic simulation approach have been employed to identify novel inhibitors of cytochrome bc1. The best structure-based pharmacophore hypothesis (Hypo1) consists of one hydrogen bond acceptor (HBA), one general hydrophobic (HY), and two hydrophobic aromatic features (HYAr). Further, hydrogen interactions and hydrophobic interactions of known potent inhibitors with cytochrome bc1 were compared with Hypo1, which showed that the Hypo1 has good predictive ability. The validated Hypo1 was used to screen the chemical databases. The hits obtained were subsequently subjected to the molecular docking analysis to identify false-positive hits. Moreover, the molecular docking results were further validated by molecular dynamics simulations. Binding-free energy analysis using MM-GBSA method reveals that the van der Waals interactions and the electrostatic energy provide the basis for favorable absolute free energy of the complex. The five virtual hits were identified as possible candidates for the designing of potent cytochrome bc1 inhibitors. Rahul P. Gangwal, Gaurao V. Dhoke, Mangesh V. Damre, Kanchan Khandelwal, and Abhay T. Sangamwar Copyright © 2013 Rahul P. Gangwal et al. All rights reserved. LASSO-ing Potential Nuclear Receptor Agonists and Antagonists: A New Computational Method for Database Screening Mon, 24 Jun 2013 09:52:03 +0000 Nuclear receptors (NRs) are important biological macromolecular transcription factors that are implicated in multiple biological pathways and may interact with other xenobiotics that are endocrine disruptors present in the environment. Examples of important NRs include the androgen receptor (AR), estrogen receptors (ER), and the pregnane X receptor (PXR). In this study we have utilized the Ligand Activity by Surface Similarity Order (LASSO) method, a ligand-based virtual screening strategy to derive structural (surface/shape) molecular features used to generate predictive models of biomolecular activity for AR, ER, and PXR. For PXR, twenty-five models were built using between 8 to 128 agonists and tested using 3000, 8000, and 24,000 drug-like decoys including PXR inactive compounds . Preliminary studies with AR and ER using LASSO suggested the utility of this approach with 2-fold enrichment factors at 20%. We found that models with 64–128 PXR actives provided enrichment factors of 10-fold (10% actives in the top 1% of compounds screened). The LASSO models for AR and ER have been deployed and are freely available online, and they represent a ligand-based prediction method for putative NR activity of compounds in this database. Sean Ekins, Michael-R. Goldsmith, Aniko Simon, Zsolt Zsoldos, Orr Ravitz, and Antony J. Williams Copyright © 2013 Sean Ekins et al. All rights reserved. QSAR Investigation on Quinolizidinyl Derivatives in Alzheimer’s Disease Tue, 30 Apr 2013 08:48:33 +0000 Sets of quinolizidinyl derivatives of bi- and tri-cyclic (hetero) aromatic systems were studied as selective inhibitors. On the pattern, quantitative structure-activity relationship (QSAR) study has been done on quinolizidinyl derivatives as potent inhibitors of acetylcholinesterase in alzheimer’s disease (AD). Multiple linear regression (MLR), partial least squares (PLSs), principal component regression (PCR), and least absolute shrinkage and selection operator (LASSO) were used to create QSAR models. Geometry optimization of compounds was carried out by B3LYP method employing 6–31 G basis set. HyperChem, Gaussian 98 W, and Dragon software programs were used for geometry optimization of the molecules and calculation of the quantum chemical descriptors. Finally, Unscrambler program was used for the analysis of data. In the present study, the root mean square error of the calibration and R2 using MLR method were obtained as 0.1434 and 0.95, respectively. Also, the R and R2 values were obtained as 0.79, 0.62 from stepwise MLR model. The R2 and mean square values using LASSO method were obtained as 0.766 and 3.226, respectively. The root mean square error of the calibration and R2 using PLS method were obtained as 0.3726 and 0.62, respectively. According to the obtained results, it was found that MLR model is the most favorable method in comparison with other statistical methods and is suitable for use in QSAR models. Ghasem Ghasemi, Sattar Arshadi, Alireza Nemati Rashtehroodi, Mahyar Nirouei, Shahab Shariati, and Zinab Rastgoo Copyright © 2013 Ghasem Ghasemi et al. All rights reserved. SAR and Computer-Aided Drug Design Approaches in the Discovery of Peroxisome Proliferator-Activated Receptor γ Activators: A Perspective Thu, 04 Apr 2013 17:14:13 +0000 Activators of PPARγ, Troglitazone (TGZ), Rosiglitazone (RGZ), and Pioglitazone (PGZ) were introduced for treatment of Type 2 diabetes, but TGZ and RGZ have been withdrawn from the market along with other promising leads due cardiovascular side effects and hepatotoxicity. However, the continuously improving understanding of the structure/function of PPARγ and its interactions with potential ligands maintain the importance of PPARγ as an antidiabetic target. Extensive structure activity relationship (SAR) studies have thus been performed on a variety of structural scaffolds by various research groups. Computer-aided drug discovery (CADD) approaches have also played a vital role in the search and optimization of potential lead compounds. This paper focuses on these approaches adopted for the discovery of PPARγ ligands for the treatment of Type 2 diabetes. Key concepts employed during the discovery phase, classification based on agonistic character, applications of various QSAR, pharmacophore mapping, virtual screening, molecular docking, and molecular dynamics studies are highlighted. Molecular level analysis of the dynamic nature of ligand-receptor interaction is presented for the future design of ligands with better potency and safety profiles. Recently identified mechanism of inhibition of phosphorylation of PPARγ at SER273 by ligands is reviewed as a new strategy to identify novel drug candidates. Vaibhav A. Dixit and Prasad V. Bharatam Copyright © 2013 Vaibhav A. Dixit and Prasad V. Bharatam. All rights reserved. Molecular Docking Study on the Interaction of Riboflavin (Vitamin ) and Cyanocobalamin (Vitamin ) Coenzymes Sun, 31 Mar 2013 13:49:22 +0000 Cobalamins are the largest and structurally complex cofactors found in biological systems and have attracted considerable attention due to their participation in the metabolic reactions taking place in humans, animals, and microorganisms. Riboflavin (vitamin B2) is a micronutrient and is the precursor of coenzymes, FMN and FAD, required for a wide variety of cellular processes with a key role in energy-based metabolic reactions. As coenzymes of both vitamins are the part of enzyme systems, the possibility of their mutual interaction in the body cannot be overruled. A molecular docking study was conducted on riboflavin molecule with B12 coenzymes present in the enzymes glutamate mutase, diol dehydratase, and methionine synthase by using ArgusLab 4.0.1 software to understand the possible mode of interaction between these vitamins. The results from ArgusLab showed the best binding affinity of riboflavin with the enzyme glutamate mutase for which the calculated least binding energy has been found to be −7.13 kcal/mol. The results indicate a significant inhibitory effect of riboflavin on the catalysis of B12-dependent enzymes. This information can be utilized to design potent therapeutic drugs having structural similarity to that of riboflavin. Ambreen Hafeez, Zafar Saied Saify, Afshan Naz, Farzana Yasmin, and Naheed Akhtar Copyright © 2013 Ambreen Hafeez et al. All rights reserved. Automatic Segmentation of Medical Images Using Fuzzy c-Means and the Genetic Algorithm Sun, 03 Feb 2013 08:55:35 +0000 Magnetic resonance imaging (MRI) segmentation is a complex issue. This paper proposes a new method for estimating the right number of segments and automatic segmentation of human normal and abnormal MR brain images. The purpose of automatic diagnosis of the segments is to find the number of divided image areas of an image according to its entropy and with correctly diagnose of the segment of an image also increased the precision of segmentation. Regarding the fact that guessing the number of image segments and the center of segments automatically requires algorithm test many states in order to solve this problem and to have a high accuracy, we used a combination of the genetic algorithm and the fuzzy c-means (FCM) method. In this method, it has been tried to change the FCM method as a fitness function for combination of it in genetic algorithm to do the image segmentation more accurately. Our experiment shows that the proposed method has a significant improvement in the accuracy of image segmentation in comparison to similar methods. Omid Jamshidi and Abdol Hamid Pilevar Copyright © 2013 Omid Jamshidi and Abdol Hamid Pilevar. All rights reserved.