Inclusion of Enclosed Hydration Effects in the Binding Free Energy Estimation of Dopamine D3 Receptor Complexes

Confined hydration and conformational flexibility are some of the challenges encountered for the rational design of selective antagonists of G-protein coupled receptors. We present a set of C3-substituted (-)-stepholidine derivatives as potent binders of the dopamine D3 receptor. The compounds are characterized biochemically, as well as by computer modeling using a novel molecular dynamics-based alchemical binding free energy approach which incorporates the effect of the displacement of enclosed water molecules from the binding site. The free energy of displacement of specific hydration sites is obtained using the Hydration Site Analysis method with explicit solvation. This work underscores the critical role of confined hydration and conformational reorganization in the molecular recognition mechanism of dopamine receptors and illustrates the potential of binding free energy models to represent these key phenomena.Comment: This is the first report of using enclosed hydration in estimating binding free energies of protein-ligand complexes using implicit solvatio

Discrimination Prevention with Privacy Preservation in Data Mining

Discrimination is a crucial issue while considering the legality and morality of data mining. People never like to be distinguished on basis of their caste, gender, nationality, etc. specifically while making decisions with consideration of this attributes, like offering them a job, property, loan, and so forth. Also when a data is released for analysis, there are chances that personal data may be misused for different reasons. Therefore, many companies and institutions are trying to bridge the gap between mining and sharing user data so that their services are improved and user privacy is ensured. We are trying to adapt an approach which will publish the discrimination free data such that probability of learning sensitive value of individual will be reduced. Concept of Slicing is used for preserving privacy. Slicing is better approach of privacy publishing in comparison with other approaches like generalization and bucketization, as it preserves correlation between attributes and it prevents attribute disclosure. The input to the system is discriminated dataset and output will be the sliced data that helps to preserve privacy

Functionalization of carbon nanotubes using phenosafranin

The functionalization of carbon nanotubes by using phenosafranin was discussed. The self-assembly of phenosafranin (PSF) to multiwalled carbon nanotube (MWNT) was shown by using spectroscopic analysis and atomic force microscopy (AFM) phase imaging studies. It was observed that the shift in absorption spectra was associated with charge transfer of valence electrons from PSF to electron accepting sites on the MWNT. The Raman-active disorder modes were used to fingerprint PSF attachment to MWNT via defect states. A molecular topographic visual confirmation of PSF attached to the MWNT was obtained by using AFM phase imaging

APPLICATION OF NANOTECHNOLOGY FOR TARGETED DELIVERY OF ANTIBACTERIAL ENZYMES AND FOR ENZYME-BASED COATINGS ON MEDICAL DEVICES AND IMPLANTS

The frequency of S. aureus infection and subsequent biofilm formation associated with vascular catheterization has been increasing in recent years and often begins as a local colonization at the site of the catheter insertion. Antimicrobial enzymes and peptides, which are effective against a broad range of pathogens and low rates of resistance, have attracted attention as promising alternative candidates in treatment of infections caused by antibiotic resistant bacteria. The use of nanoparticles as carriers for enzymes, in addition to their size, charge, high surface area per volume etc. offers targeted delivery of enzymes to pathogenic bacteria. We proposed to use nanoparticles as surfaces for targeted delivery of antibacterial enzymes and as `surrogate\u27 surface coatings on indwelling central venous catheters (CVCs) to inhibit bacterial colonization and subsequent biofilm formation. It was shown that nanoparticle charge can be used to enhance delivery and increase bactericidal activity of an antimicrobial enzyme, lysozyme. In the case of bacterial lysis assay with a Gram-positive bacterium Micrococcus lysodeikticus, activity of lysozyme conjugated to positively charged nanoparticles was approximately twice as high as that of free lysozyme. This was believed to occur through charge-directed targeting of enzyme-nanoparticle conjugates to negatively charged bacterial cell walls through enhanced electrostatic interactions. In a clinically more relevant model, we studied antimicrobial activity of lysostaphin against S. aureus for both lysostaphin-coated and lysostaphin-antibody coated nanoparticle conjugates at different enzyme: antibody: nanoparticle ratios. At the highest antibody loading, bacterial lysis rates for antibody-lysostaphin-coated samples were significantly higher than for plain lysostaphin-coated samples and free enzyme due to multiple-ligand directed targeting of antibody molecules to bacterial cell walls (p\u3c0.05). We also performed in vitro experiments to evaluate the inhibition of bacterial colonies adhering to a surface. Bacterial infections by S. aureus strains are among the most common postoperative complications in surgical hernia repair with synthetic polymer meshes. Colony counting data from the broth count (model for bacteria in wound fluid) and wash count (model for colonized bacteria) for the enzyme-coated samples showed significantly decreased number of colony forming units (CFU) when compared to uncoated samples (p\u3c 0.05). A pilot in vivo study showed a dose-dependent anti-S. aureus efficacy of lysostaphin-coated meshes in a rat model. Finally, we observed that that coating of nanoparticles overall did not significantly improve binding yield, leaching, durability and antibiofilm activity of enzymes adsorbed on catheter segments (p\u3e0.05). Alternatives to coating catheter surfaces using covalent chemistry through functional groups on nanoparticles either directly or through appropriate crosslinkers could result in significantly higher enzyme loadings, better stability and long term durability for future applications. The approach developed here is universal and can potentially be used for treatment of other medical device-associated infections. Moreover, use of antibacterial enzyme-NP conjugates can eventually be expanded for intravenous administration, which will further broaden its range of application

Register Allocation for Accurate Garbage Collection of C++

Register Allocation for Accurate Garbage Collection of C++ S. Satishkumar* M.S. Creative Component Accurate garbage collection of C++ requires that every memory location and every register be known to contain either a pointer or a non-pointer. In order to minimize the run-time overhead of tagging memory locations and registers, techniques for partitioning memory and registers into separate classes dedicated independently to the representation of pointers and non-pointers respectively have been developed. This paper describes the implementation and performance of a specially designed register allocator for the GNU g++ compiler. * Portions of this paper were excerpted from Code Generation to Support Efficient Accurate Garbage Collection of C++ on Stock Hardware , a paper currently being prepared for publication by Kelvin Nilsen, Ravichandran Ganesan, Satish Guggilla, Satish Kumar, and Kannan Narasimha

Implementation of Koha Integrated Library Management System (ILMS) In Acharya & BM Reddy College 0f Pharmacy Library & Information Center: A Study

This study appraised the implementation of Koha software in Acharya Pharmacy Library & Information Center to automate its library operations by using Koha open-source software Integrated Library Management System (ILMS). The Koha is a widely used library software. It has provisions for all library operations. The library automation enabled the library staff to manage library resources efficiently, including Acquisitions, cataloguing, patron profiles, serial control and inventory management. With Koha web OPAC now, users can easily search for the books and other materials available in the library, track their circulation history, renew books, reserve books and send online requisitions. The web-based interface of Koha allows for remote access to the system, enabling users to access resources from anywhere and anytime, 24/7. The koha has also provided the library staff with advanced report capabilities. Enabling them to generate detailed reports on circulation, inventory, Periodicals, overdue, patron activity etc. Overall, The implementation of Koha Library software has enabled ABMRCP Library & Information Center to improve its library services, providing better access to information and resources for its users/patrons

A method for the reconstruction of unknown non-monotonic growth functions in the chemostat

We propose an adaptive control law that allows one to identify unstable steady states of the open-loop system in the single-species chemostat model without the knowledge of the growth function. We then show how one can use this control law to trace out (reconstruct) the whole graph of the growth function. The process of tracing out the graph can be performed either continuously or step-wise. We present and compare both approaches. Even in the case of two species in competition, which is not directly accessible with our approach due to lack of controllability, feedback control improves identifiability of the non-dominant growth rate.Comment: expansion of ideas from proceedings paper (17 pages, 8 figures), proceedings paper is version v

Acute Decline in Renal Function, Inflammation, and Cardiovascular Risk after an Acute Coronary Syndrome

Background and objectives: Chronic kidney disease is associated with a higher risk of cardiovascular outcomes. The prognostic significance of worsening renal function has also been shown in various cohorts of cardiac disease; however, the predictors of worsening renal function and the contribution of inflammation remains to be established. Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants. Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3). Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease

Simplified Space Vector Pulse Width Modulation based on Switching Schemes with Reduced Switching Frequency and Harmonics for Five Level Cascaded H-Bridge Inverter

This paper presents a simplified control strategy of spacevector pulse width modulation technique with a three segment switching sequence and seven segment switching sequence for high power applications of multilevel inverters. In the proposed method, the inverter switching sequences are optimized for minimization of device switching frequency and improvement of harmonic spectrum by using the three most desired switching states and one suitable redundant state for each space vector. The proposed three-segment sequence is compared with conventional seven-segment sequence for five level Cascaded H-Bridge inverter with various values of switching frequencies including very low frequency. The output spectrum of the proposed sequence design shows the reduction of device switching frequency, current and line voltage THD, thereby minimizing the filter size requirement of the inverter, employed in industrial applications, where sinusoidal output voltage is required

Glimpses Of Modern India In Gita Mehta’s ‘Snakes And Ladders

Gita Mehta, in her fiction and non-fiction, has dealt with the paradox of the old and the new as a significant component of Indian culture. Scholars tend to believe that the twin factors of tradition and modernity are not antithetical to each other, as some earlier thinkers used to consider. They always co- exist, drawing regularly from each other and work together for the progression of society. Taking into consideration the observations of the scholars on the aspects of tradition, modernity, modernization and westernization, the present article is an effort to study Gita Mehta’s attempt to explore the dual strands of the Indian ritualistic past and its modern rationalistic present, their interaction and their impact on the Indian culture. For this study, Mehta’s non-fiction Snakes and Ladders: Glimpses of Modern India is being taken into consideration