Molecular dynamics simulations of small molecule diffusion in hydrogels

Solute diffusion across polymer matrices is important in several technological applications such as controlled drug delivery, gel electrophoresis and gas separation. Our primary objective is to investigate the effect of size-exclusion on solute diffusion in polymer matrices with a focus on crosslinked hydrogel networks. The diffusion co-efficient of a solute in a hydrogel depends on the free-volume available as determined by the solute size and the polymer concentration. However, hydrogels have a highly disordered pore structure due to the random nature of the crosslinking techniques used in their preparation. The characterization of the free-volume of this pore structure by experimental techniques or mathematical modeling is not straightforward. Consequently, this precludes a direct testing of the correlation between diffusion and free-volume. In this thesis, we prepare simple, defect-free, end-crosslinked polymer networks via computer simulation. We choose a coarse-grained bead-spring representation for our polymer chains. In addition to crosslinked networks, we also prepare other host matrices: polymer solutions composed of flexible chains and fibrous matrices composed of interpenetrating rods. The free-volume available to a solute of a given size in these host matrices is characterized by calculating the so-called accessible volume fraction. Subsequently, the solute diffusion coefficients are computed by performing Molecular Dynamics (MD) simulations. Our general finding is that the solute diffusion coefficients in these host matrices correlate well with the accessible volume fraction, which collapses onto one single variable the twin effects of solute size and polymer concentration. In the case of a crosslinked network with a given crosslinking density, solute diffusivities are a unique function of the accessible volume fraction. We also conclude that the mobility of the chains in the polymer matrix has a significant effect on solute diffusion, even at high accessible volume fraction. We have also investigated the effect of attractive solute-polymer interactions on solute partitioning and diffusion in crosslinked networks. A solute with specific interactions diffuses faster than an inert solute of the same size. We attribute this to the active partitioning of solutes across the bottlenecks in the network that the solute encounters during diffusion.Ph.D., Chemical Engineering -- Drexel University, 200

PRODUCTION, CHARACTERIZATION AND PURIFICATION OF ALKALINE PROTEASE FROM ALCALIGENES sp., AND ITS APPLICATION IN DETERGENT INDUSTRY

Proteases are enzymes well known for their wide range industrial applications such as food, detergent, pharmaceutical etc. The aim of the present work was to study the production, purification and application of alkaline protease from the strain Alcaligenes sp. (MTCC 9730). Batch and fed batch fermentation were used as the production strategies. The optimum temperature and pH for the production of enzyme was found to be 55°C and pH 9 respectively. Ca2+ increased the activity, Cu2+ and Mg2+ mildly inhibited and by Zn2+ strongly inhibited the activity. The protease enzyme was purified using Ammonium sulphate precipitation and maximum activity of 60 U/ml was found at 70percent saturation. Alkaline protease is known to be an active ingredient of the commercial detergents. The enzyme was used to study its compatibility with other detergents and its ability to remove the protein stain. Keywords: Alkaline protease, Alcaligenes sp, fermentation, purification, detergent

FLAVONOIDS NUTRACEUTICALS IN PREVENTION AND TREATMENT OF CANCER: A REVIEW

The objective of the study was to discuss the preventive and treatment of cancer from flavonoids nutraceuticals from our daily dietary source. There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids through epidemiological studies. Numerous biological activities have been reported. Some clinical trials or meta-analyses have suggested positive associations between flavonoid intake and human health, Several findings have proven that dietary flavonoids to have anticancer properties. Flavonoids due to their nontoxicity in nature and vast, broad aspect of its benefits in biological activities have been intensively studied for their health benefits also added to its abundant availability in our daily diets, for example, green leaves, fruits, red wine, and tea vegetables

Utility of pulse-oximetry screening in newborns with nonductus-dependent cyanotic congenital heart defects: A reason to alarm?

Objectives : We aimed to compare the performance of pulse-oximetry screening in detecting nonductus-dependent cyanotic congenital heart defects (CCHDs). Methods : In a prospective cross-sectional study, we recorded post ductal saturation of neonates (<48 h old) born at a community hospital in northern India. Subsequently, all underwent clinical examination and echocardiogram by a trained cardiologist. A saturation <95% was considered a “failed” screen. Results : Ten neonates were identified to have nonductus-dependent CCHD on echocardiogram, five of whom had passed pulse-oximetry screen. This translated to a sensitivity of 50% (95% confidence interval [CI] 23.7%–76.3%) and a positive predictive value of 0.08 (95% CI 0.03–0.2), both of which were significantly less compared to that in ductus-dependent congenital heart defect. Conclusions : Up to half of the nonductus-dependent CCHD may be missed if screened only using pulse oximetry. Parents should not be reassured regarding the absence of CCHD only based on a “pass” in pulse-oximetry screening

Diphtheritic myocarditis: An unusual and reversible cause of heart failure

Diphtheria is a life-threatening infectious disease caused by Corynebacterium diphtheriae. Although the disease is seen infrequently in the postvaccination era, sporadic cases continue to occur. Cardiac involvement, in the form of myocarditis, is the most serious manifestation of diphtheria and is the most common cause of mortality in these patients. The features of diphtheritic myocarditis on cardiac magnetic resonance imaging (MRI) have not been reported previously. In this brief report, we describe the cardiac MRI and histopathologic features on endomyocardial biopsy of a patient with acute heart failure who was later diagnosed to be a case of diphtheritic myocarditis

Summary

In this work, we combined computational proteinprotein docking with computational and experimental mutagenesis to predict the structure of the complex formed by monoclonal antibody 806 (mAb 806) and the epidermal growth factor receptor (EGFR). We docked mAb 806, an antitumor antibody, to its epitope of EGFR residues 287–302. Potential mAb 806-EGFR orientations were generated, and computational mutagenesis was used to filter them according to their agreement with experimental mutagenesis data. Further computational mutagenesis suggested additional mutations, which were tested to arrive at a final structure that was most consistent with experimental mutagenesis data. We propose that this is the EGFR-mAb 806 structure, in which mAb 806 binds to an untethered form of the receptor, consistent with published experimental results. The steric hindrance created by the antibody near the EGFR dimer interface interferes with receptor dimerization, and we postulate this as the structural origin for the antitumor effect of mAb 806

BBD optimized antioxidants of Crotalaria candicans and its nanoconjugates, exert potent in vivo anti-biofilm effects against MRSA

Abstract Crotalaria genus is extensively dispersed in tropical and subtropical provinces, and it is found to harbor antioxidant flavonoids. Response surface methodology-based optimization was carried out for the purpose of efficient extraction involving a suitable solvent which can maximize the yield along with higher total phenolic content and total flavonoid content (TFC). Optimization conditions for extraction of C.candicans flavonoids (CCF) based on variables such as solvent, solid-solvent ratio and extraction temperature were evaluated. The optimized conditions were found as Solvent i.e., Aqueous-ethanol (53.42%), Solid-solvent ratio (1:15.83 w/v) and temperature (44.42 °C) and resulted to obtain the TFC as 176.23 mg QRET/g C. candicans extract with the yield 27.42 mg CCF/g (C. candicans dry weight). LC–MS analysis of CCF, revealed the presence of seven major flavonoids. The antioxidant flavonoids were further used to functionalize the zero-valent silver (ZVAgF) and copper (ZVCuF) nanoparticles. The ZVAgF and ZVCuF were investigated using UV–Vis spectrophotometry, FT-IR spectroscopy and X-ray diffractometry to confirm the presence of the zero valent metals and possible functional groups which capped the elemental metal. Further transmission electron microscopy, dynamic light scattering method and zeta-potential studies were done to understand their respective structural and morphological properties. The efficacy of the as-prepared ZVAgF/ZVCuF as antibiofilm agents on Methicillin-resistant Staphylococcus aureus (MRSA) with the mechanism studies have been explored. The MRSA-colony count from the infection zebrafish (in vivo) model, portrayed a reduction of > 1.9 fold for ZVCuF and > twofold for ZVAgF, with no alteration in liver morphology when treated with ZVAgF, implying that the nanoparticles were safe and biocompatible