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Search Results: 1 - 10 of 329 matches for " Muralidharan Muthu "
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The Crystal Structures of Dystrophin and Utrophin Spectrin Repeats: Implications for Domain Boundaries
Muralidharan Muthu, Kylie A. Richardson, Andrew J. Sutherland-Smith
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0040066
Abstract: Dystrophin and utrophin link the F-actin cytoskeleton to the cell membrane via an associated glycoprotein complex. This functionality results from their domain organization having an N-terminal actin-binding domain followed by multiple spectrin-repeat domains and then C-terminal protein-binding motifs. Therapeutic strategies to replace defective dystrophin with utrophin in patients with Duchenne muscular dystrophy require full-characterization of both these proteins to assess their degree of structural and functional equivalence. Here the high resolution structures of the first spectrin repeats (N-terminal repeat 1) from both dystrophin and utrophin have been determined by x-ray crystallography. The repeat structures both display a three-helix bundle fold very similar to one another and to homologous domains from spectrin, α-actinin and plectin. The utrophin and dystrophin repeat structures reveal the relationship between the structural domain and the canonical spectrin repeat domain sequence motif, showing the compact structural domain of spectrin repeat one to be extended at the C-terminus relative to its previously defined sequence repeat. These structures explain previous in vitro biochemical studies in which extending dystrophin spectrin repeat domain length leads to increased protein stability. Furthermore we show that the first dystrophin and utrophin spectrin repeats have no affinity for F-actin in the absence of other domains.
Guidelines Based Software Engineering for Developing Software Components  [PDF]
Muthu Ramachandran
Journal of Software Engineering and Applications (JSEA) , 2012, DOI: 10.4236/jsea.2012.51001
Abstract: Software guidelines have been with us in many forms within Software Engineering community such as knowledge, experiences, domain expertise, laws, software design principles, rules, design heuristics, hypothesis, experimental results, programming rules, best practices, observations, skills, algorithms have played major role in software development. This paper presents a new discipline known as Guidelines Based Software Engineering where the aim is to learn from well-known best practices and documenting newly developed and successful best practices as a knowledge based (could be part of the overall KM strategies) when developing software systems across the life cycle. Thereby it allows reuse of knowledge and experiences.
Simple Estimation of Bosentan in Tablet Formulation by RP-HPLC  [PDF]
Selvadurai Muralidharan, Jaya Raja Kumar
American Journal of Analytical Chemistry (AJAC) , 2012, DOI: 10.4236/ajac.2012.311095
Abstract: A simple, precise, and accurate method is developed and validated for the analysis of Bosentan tablet formulation. The method has shown adequate separation of the ingredients from Tablets. Separation was achieved on a C18 column using a mobile phase consisting of acetonitrile: 10 Mm ammonium acetate (pH 4.5) buffer (70:30, v/v) at a flow rate of 1.0 ml/min and UV detection at 265 nm. This new method is validated as per the ICH, which includes accuracy, precision, selectivity, linearity and range, robustness and ruggedness. The current method demonstrates good linearity over the range of 5 - 70 ng/ml of bosentan with r2 of 0.999. The average recovery of the method is 98.6%. The degree of reproducibility of the results obtained as an outcome of small deliberate variations in the method parameters and by changing analytical operator has proven that this method is robust and rugged.
Firefly Algorithm in Determining Maximum Load Utilization Point and Its Enhancement through Optimal Placement of FACTS Device  [PDF]
S. Rajasekaran, Dr. S. Muralidharan
Circuits and Systems (CS) , 2016, DOI: 10.4236/cs.2016.710262
Abstract: In a Power System, load is the most uncertain and extremely time varying unit. Hence it is important to determine the system’s supreme acceptable loadability limit called maximum loadabilitypoint to accommodate the sudden variation of load demand. Nowadays the enhancement of themaximum loadability point is essential to meet the rapid growth of load demand by improvising the system’s load utilization capacity. Flexible AC Transmission system devices (FACTS) with their speed and flexibility will play a key role in enhancing the controllability and power transfer capability of the system. Considering the theme of FACTS devices in the loadability limit enhancement,in this paper maximum loadability limit determination and itsenhancement are prepared with the help of swarm intelligence based meta-heuristic Firefly Algorithm(FFA) by finding the optimal loading factor for each load and optimally placing the SVC (Shunt Compensation) and TCSC (SeriesCompensation) FACTS devices in the system. To illuminate the effectiveness of FACTS devices inthe loadability enhancement, the line contingency scenario is also concernedin the study. The study of FACTS based maximum system load utilization acceptability point determination is demonstrated with the help of modified IEEE 30 bus, IEEE 57 Bus and IEEE 118 Bus test systems. The results of FACTS devices involvement in determining the maximum loading point enhance the load
Improved Quantification of Glomerular Filtration Rate and Differential Renal Function of Ectopic Kidneys in a Dual Head Gamma Camera  [PDF]
Gopal Sonai Muthu, Sujata Mitra
Open Journal of Medical Imaging (OJMI) , 2014, DOI: 10.4236/ojmi.2014.41003
Abstract: Introduction: Tc-99m Di-ethylene Tri-amine Penta Acetic Acid (DTPA) renogram is an accepted method to measure Glomerular Filtration Rate (GFR) of the kidneys. The depth and position of ectopic kidneys may vary. This may lead to variation in tissue attenuation and error in the computed GFR and Differential Renal Function (DRF) of each kidney. Objective: The present study was undertaken in patients with ectopic kidneys to improve the accuracy of GFR and DRF calculation in a renogram with single injection of Tc-99m DTPA on a dual head gamma camera. Materials and Method: The study was conducted on 55 patients with ectopic kidneys. Images were acquired on a dual head gamma camera simultaneously in anterior and posterior views. Both anterior and posterior image datasets were used to compute the GFR of the ectopic kidney by Gates method. Depth correction of the ectopic kidney was done using the lateral view image. Total GFR was calculated as the sum of the anterior dataset ectopic kidney GFR and the posterior dataset normal kidney GFR. DRF was calculated again, by using the anterior dataset GFR of the ectopic kidney and posterior dataset for normal kidneys. The total GFR calculated by our method was compared to the patient’s eGFR (based on serum creatinine, age and sex). Result: The GFR calculated by anterior data set in the ectopic kidney was significantly higher than that calculated by posterior dataset (p < 0.001). Similarly, the differential GFR of the ectopic kidney was higher when the anterior dataset was used (p
Reactive oxygen species—Control and management using amphiphilic biosynthetic hydrogels for cardiac applications  [PDF]
Gnanaprakasam Thankam Finosh, Muthu Jayabalan
Advances in Bioscience and Biotechnology (ABB) , 2013, DOI: 10.4236/abb.2013.412150

The reactive oxygen species (ROS) originated from endogenous and exogenous sources play a dominant role in the initiation and propagation of several diseases. It is therefore an urgent need to explore substances capable of encountering the ROS and resist the damage caused by ROS. The present paper deals with various aspects of generation and implications of ROS in the management of myocardial infarction. The use of biosynthetic amphiphilic biodegradable hydrogels in the control and management of ROS in myocardial infarction was studied using a biosynthetic hydrogel (PA-PEGDA) comprising poly(propylene fumarate)-co-alginate copolymer cross-linked with calcium and polyethylene glycol diacrylate (PEGDA). The effect of ROS on the cell growth was studied using H2O2 as model ROS molecule. The present hydrogel resists the penetration of ROS in the cell which was evident from the live/dead assay, increased intra cellular GSH levels when compared with the H2O2 treated positive and curcumin treated negative control cells. The Comet assay reveals genomic integrity of the cells exposed to the present hydrogel. The hydrogel is a promising injectable material for the management of myocardial infarction and ischemia. 

Pharmacokinetic-Pharmacodynamic Model of Newly Developed Dexibuprofen Sustained Release Formulations
Selvadurai Muralidharan
ISRN Pharmaceutics , 2012, DOI: 10.5402/2012/451481
Pharmacokinetic-Pharmacodynamic Model of Newly Developed Dexibuprofen Sustained Release Formulations
Selvadurai Muralidharan
ISRN Pharmaceutics , 2012, DOI: 10.5402/2012/451481
Abstract: Pharmacokinetic-pharmacodynamic (PK-PD) modeling has emerged as a major tool in clinical pharmacology to optimize drug use by designing rational dosage forms and dosage regimes. Quantitative representation of the dose-concentration-response relationship should provide information for the prediction of the level of response to a certain level of drug dose. This paper describes the experimental details of the preformulation study, tablet manufacture, optimization, and bioanalytical methods for the estimation of dexibuprofen in human plasma. The hydrophilic matrix was prepared with xanthen gum with additives Avicel PH 102. The effect of the concentration of the polymer and different filler, on the in vitro drug release, was studied. Various pharmacokinetic parameters including AUC0–t, AUC0–∞, , , , and elimination rate constant ( ) were determined from the plasma concentration of both formulations of test (dexibuprofen 300?mg) and reference (dexibuprofen 300?mg tablets). The merits of PK-PD in the development of dosage forms and how PK-PD model development necessitates the development of new drugs and bio analytical method development and validation are discussed. The objectives of the present study, namely, to develop and validate the methods to estimate the selected drugs in the biological fluids by HPLC, the development of in vitro dissolution methods, and PK-PD model development have been described. 1. Introduction Dexibuprofen, S(+)-ibuprofen, is a pharmacologically active form and is more potent than ibuprofen, which has equal quantities of R(?)- and S(+)-enantiomers [1]. Ibuprofen is an NSAID and is widely used to reduce pain, fever, and inflammation. This drug inhibits cyclooxygenases and activates peroxisome proliferators-activated receptors; both of these actions result in reduced inflammation [2–4]. Pharmacokinetic-pharmacodynamic (PK-PD) modeling is a scientific tool to help developers selecte a rational dosage regimen for confirmatory clinical testing. PK/PD modeling can be executed using various approaches, such as direct versus indirect response models and parametric versus nonparametric models. PK/PD concepts can be applied to the individual dose optimization. The limits of PK/PD approaches include the development of appropriate models, the validity of surrogate endpoints, and the acceptance of these models in a regulatory environment. PK-PD modeling allows the estimation of PK-PD parameters and the prediction of these derived, clinically relevant parameters as well. PK-PD simulations allow the assessment of the descriptive parameters as
An empirical Bayes mixture method for effect size and false discovery rate estimation
Omkar Muralidharan
Statistics , 2010, DOI: 10.1214/09-AOAS276
Abstract: Many statistical problems involve data from thousands of parallel cases. Each case has some associated effect size, and most cases will have no effect. It is often important to estimate the effect size and the local or tail-area false discovery rate for each case. Most current methods do this separately, and most are designed for normal data. This paper uses an empirical Bayes mixture model approach to estimate both quantities together for exponential family data. The proposed method yields simple, interpretable models that can still be used nonparametrically. It can also estimate an empirical null and incorporate it fully into the model. The method outperforms existing effect size and false discovery rate estimation procedures in normal data simulations; it nearly acheives the Bayes error for effect size estimation. The method is implemented in an R package (mixfdr), freely available from CRAN.
Nanoparticles based on PLGA and its co-polymer: An overview
Muthu M
Asian Journal of Pharmaceutics , 2009,
Abstract: Poly (D, L-lactide-co-glycolide) (PLGA) is approved by the Food and Drug Administration for drug delivery use. The polymeric nanoparticles based on PLGA and its co-polymer are designed for controlled and targeted drug delivery. Also, PLGA and its co-polymer are important in designing nanoparticles with desired characteristics such as biocompatibility, biodegradation, particle size, surface properties, drug release and targetability. This review focuses on the polymer literature, methods for preparation of nanoparticles and recent studies on the nanoparticles based on PLGA and its co-polymer for the conventional and targeted delivery of drugs by various routes.
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