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

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

Forest Carbon Stock in Woody Plants of Ades Forest, Western Hararghe Zone of Ethiopia and its Variation along Environmental Factors: Implication for Climate Change Mitigation

Forests play an important role in the global carbon cycle. They are not only having a significant impact on climate change, but also influence it. Through their destruction, forests can be serious sources of greenhouse gases and through their sustainable management they can be important sinks of the same gases. The study was accompanied to estimate the carbon stock and its variation along environmental gradient. The general objective of this study is to determine the carbon sequestration potential of Ades forest and indicating its contribution to climate change mitigation. Sample plots were laid along line transects based on altitudinal variation of the study area. A randomly sampling plot (10 m x 20 m) in each site was established. The procedures were based on data collection and analysis of carbon accumulating in different carbon pools. The forest was arranged in classes based on different criteria in order to use appropriate methods for estimation of forest biomass. The mean total carbon stock density of Ades forest was found to be 585.40ton/ha which is ranged about 97.54to5919.52 ton/ha, of which 259.17 ton/ha, 52.20 ton/ha, 2.34 ton /ha and 271.69 ton/ ha comprised by above the ground biomass, below the ground biomass, litter carbon and soil organic carbon respectively. Altitude, aspect and slop gradients are such a factors that affect the carbon stock potential in above ground biomass, below ground biomass, litter biomass and soil organic carbon. The middle altitudinal zone of the study site had better carbon stock potential than the rest classes due to the presence of high DBH class of individuals’ and suitable environmental condition whereas the carbon stock of AGC, BGC.LC and SOC showed an increasing trend with increasing slop. The total carbon stock value have direct relationship with altitude and slope, it increases with increasing slope and altitude. The amount of total carbon stock was higher on the southern aspect as compared to other aspects. The current study shows that carbon stock value of Ades forest was highly affected by environmental factors such as altitude, slope and aspects, but aspect was the only factor that showed significance difference in carbon stocks of the forest and this condition concluded that the forest should be conserved and managed for further carbon reservoirs. Keywords: Ades forest, biomass, carbon stock, environmental factors, global climate chang

Marketing of Library Products and Services: A theoretical analysis

The creation of libraries and information centres reflects the realization that marketing of information products and services is a crucial component of administration, particularly for readers\u27 expected levels of satisfaction. Taking this into consideration, the study outlines all the procedures and tactics that may be used when selling information products and services. Additionally, it looks into the intent, viability, and actual application of Web 2.0 in the marketing and promotion of library resources and services. The idea of marketing does not come to mind when we think of library operations. But because of the literature\u27s explosive expansion and the widespread use of information technology, marketing has become a crucial instrument for promoting library services and goods. An institution set up to provide services is a library

Carbon Sock of Gambella National Park: Implication for Climate Change Mitigation

Recent attempts to mitigate global climatic change have brought forestry based carbon sequestration into sharp focus due to its potential to absorb CO2 from the atmosphere. Although a number of studies have been done on carbon stock estimation, the National Park carbon stock has not been properly addressed. This paper was conducted to estimate the carbon stock in forest of the Gambella National Park with 76 plots in the categories of riverine and terrestrial forest. The total mean carbon stock in forest part of the National Park was 394.85±24.34ton/ha. The carbon stocks in each pool exhibited distinct patterns between the forest Stratum (riverine and terrestrial). The total carbon stock in the riverine forest and forest land/wood land was 454.51±26.01ton/ha and 324.89±17.25 ton/ha respectively. The results of LULCC analysis indicated that the forest and woodland decreasing at an average rate of 120,470.6ha. This study concluded that despite the rapid decline in the forest land and woodland coverage, the existing forest/wood land has a huge potential sequestration of carbon for mitigation of climate change. Keywords: Carbon sequestration, Land use and land cover change, Gambella National Park, Terrestrial forest, Riverine forest.

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