Enabling three-dimensional real-space analysis of ionic colloidal crystallization.

Structures of molecular crystals are identified using scattering techniques because we cannot see inside them. Micrometre-sized colloidal particles enable the real-time observation of crystallization with optical microscopy, but in practice this is still hampered by a lack of 'X-ray vision'. Here we introduce a system of index-matched fluorescently labelled colloidal particles and demonstrate the robust formation of ionic crystals in aqueous solution, with structures that can be controlled by size ratio and salt concentration. Full three-dimensional coordinates of particles are distinguished through in situ confocal microscopy, and the crystal structures are identified via comparison of their simulated scattering pattern with known atomic arrangements. Finally, we leverage our ability to look inside colloidal crystals to observe the motion of defects and crystal melting in time and space and to reveal the origin of crystal twinning. Using this platform, the path to real-time analysis of ionic colloidal crystallization is now 'crystal clear'.

Self-assembly of lobed particles into amorphous and crystalline porous structures.

We report simulation studies on the self-assembly of hard-lobed particles (patchy particles where patches appear as lobes around a seed) of different shapes and show that various types of self-assembled morphologies can be achieved by tuning inter-lobe interactions. On self-assembly, the linear building blocks having two lobes around the seed formed rings, the trigonal planar building blocks formed cylindrical hollow tubes and two-dimensional sheets, and the square planar building blocks formed spherical clathrates. The tetrahedral, trigonal bipyramidal, and the octahedral-shaped particles formed compact porous crystalline structures which are constituted by either hexagonal close packed or face centered cubic lattices. The pore size distributions revealed that linear, trigonal planar, and square planar building blocks create highly porous self-assembled structures. Our results suggest that these self-assembled morphologies will potentially find applications in tissue engineering, host-guest chemistry, adsorption, and catalysis.

Self-assembly behavior of experimentally realizable lobed patchy particles.

We report simulation studies on the self-assembly behavior of five different types of lobed patchy particles of different shapes (snowman, dumbbell, trigonal planar, square planar, and tetrahedral). Inspired by an experimental method of synthesizing patchy particles (Wang et al., Nature, 2012, 491, 51-55), we control the lobe size indirectly by gradually varying the seed diameter and study its effect on self-assembled structures at different temperatures. Snowman shaped particles self-assemble only at a lower temperature and form two-dimensional sheets, elongated micelles, and spherical micelles, depending on the seed diameter. Each of the four other lobed particles self-assemble into four distinct morphologies (random aggregates, spherical aggregates, liquid droplets, and crystalline structures) for a given lobe size and temperature. We observed temperature-dependent transitions between two morphologies depending on the type of the lobed particle. The self-assembled structures formed by these four types of particles are porous. We show that their porosities can be tuned by controlling the lobe size and temperature.

Role of Entropy in Colloidal Self-Assembly.

Entropy plays a key role in the self-assembly of colloidal particles. Specifically, in the case of hard particles, which do not interact or overlap with each other during the process of self-assembly, the free energy is minimized due to an increase in the entropy of the system. Understanding the contribution of entropy and engineering it is increasingly becoming central to modern colloidal self-assembly research, because the entropy serves as a guide to design a wide variety of self-assembled structures for many technological and biomedical applications. In this work, we highlight the importance of entropy in different theoretical and experimental self-assembly studies. We discuss the role of shape entropy and depletion interactions in colloidal self-assembly. We also highlight the effect of entropy in the formation of open and closed crystalline structures, as well as describe recent advances in engineering entropy to achieve targeted self-assembled structures.

Development of chitosan based optimized edible coating for tomato (Solanum lycopersicum) and its characterization.

In the present work experiments were carried out to optimize coating formulation in central composite rotatable design varying chitosan and glycerol concentration from 0.5 to 3% (w/w) and 0 to 3% (w/w) respectively as two independent factors. Total color difference and respiration rate was selected for tomato parameters and water vapor permeability and percentage solubility was selected for coating parameters as response. Quadratic polynomial models generated was adequate to explain the effects of the chitosan and glycerol concentrations on response variables. Experimental validation confirmed the adequacy of the coating formulation for tomato optimized by response surface methodology with 2.15% chitosan and 0.50% glycerol. Characterization of the optimized coating was undertaken in scanning electron microscope, X-ray diffraction (XRD) and Fourier transform infra-red (FTIR) spectroscopy. Microstructure image revealed proper continuity, integrity and surface micro structure of the developed coating. XRD and FTIR spectra revealed the pattern of ideal chitosan based coatings and also unfolded various crystallographic, structural and molecular involvement and couplings in coating properties. XRD pattern reflected semicrystalline structure of chitosan based developed edible coating having crystal form-1 and crystal form-II. In addition to other expected ideal peaks, FTIR also confirmed the presence of water in the coating. Residual acetic acid (solvent for coating formulation) is also evident at around 1700 cm-1 of FTIR spectra, corresponding to carbonyl vibration of the carboxylic acid.

Study of sorption behavior, shelf life and colour kinetics of vacuum puffed honey powder at accelerated storage conditions.

In the study, the storage life of vacuum puffed honey powder at accelerated storage environment (90 % relative humidity and 36 °C) was computed by determining the sticky-point moisture content as the critical parameter of the honey powder. The value of monolayer moisture content in the GAB model was calculated to be 0.081 kg water/kg dry solids by fitting water activity and moisture sorption data. Shelf life of the honey powder was predicted to be 222 days when the powder was packaged in aluminum foil-laminated polyethylene pouches with permeability value of 5.427X10(-8) kg/m(2)//day/Pa. Actual shelf life of honey powder was experimentally determined as 189 days and analysis of mean relative percent derivation modulus (Rd) and root mean square (RMS) established the accuracy and acceptability of the technique for the prediction of shelf life of honey powder. Overall colour deviation pattern followed first order reaction kinetics with rate constant (k1) as 0.037 day(-1). This study revealed overall colour difference of 18.1 till the end of shelf life with drastic change during initial storage period.

Structure and dynamics of water inside endohedrally functionalized carbon nanotubes.

We have carried out classical molecular dynamics simulations on the formation of extended water chains inside single-walled carbon nanotubes (SWCNTs) in water in the presence of selected functional groups covalently attached to the inner wall of the tube. Analogues of polar amino acid sidechains have been chosen to carry out the endohedral functionalization of SWCNTs. Our results show a spontaneous and asymmetric filling of the nanotube with dynamical water chains in all the cases studied. The presence of Asp- and Glu-like sidechains is found to result in the formation of well-ordered water chains across the tube having the maximum number of water molecules being retained within the core with the largest residence times. The presence of methyl or methylene groups along the suspended chain is observed to disrupt the formation of water chains with higher length and/or longer residence times. The importance of hydrogen bonding in forming these water chains is assessed in terms of the relaxations of different hydrogen bond correlation functions. For a given dimension of the hydrophobic nanopore, we thus obtain a scale comparing the ability of carboxylic, alcohol, and imidazole groups in controlling the structure and dynamics of water in it. Our results also suggest that SWCNTs of varying lengths, endohedrally functionalized with Asp- and Glu-like sidechains, may be used as design templates in CNT-based water storage devices.

Temporal trends in severe malaria in Chittagong, Bangladesh.

BACKGROUND: Epidemiological data on malaria in Bangladesh are sparse, particularly on severe and fatal malaria. This hampers the allocation of healthcare provision in this resource-poor setting. Over 85% of the estimated 150,000-250,000 annual malaria cases in Bangladesh occur in Chittagong Division with 80% in the Chittagong Hill Tracts (CHT). Chittagong Medical College Hospital (CMCH) is the major tertiary referral hospital for severe malaria in Chittagong Division. METHODS: Malaria screening data from 22,785 inpatients in CMCH from 1999-2011 were analysed to investigate the patterns of referral, temporal trends and geographical distribution of severe malaria in Chittagong Division, Bangladesh. RESULTS: From 1999 till 2011, 2,394 malaria cases were admitted, of which 96% harboured Plasmodium falciparum and 4% Plasmodium vivax. Infection was commonest in males (67%) between 15 and 34 years of age. Seasonality of malaria incidence was marked with a single peak in P. falciparum transmission from June to August coinciding with peak rainfall, whereas P. vivax showed an additional peak in February-March possibly representing relapse infections. Since 2007 there has been a substantial decrease in the absolute number of admitted malaria cases. Case fatality in severe malaria was 18% from 2008-2011, remaining steady during this period.A travel history obtained in 226 malaria patients revealed only 33% had been to the CHT in the preceding three weeks. Of all admitted malaria patients, only 9% lived in the CHT, and none in the more remote malaria endemic regions near the Indian border. CONCLUSIONS: The overall decline in admitted malaria cases to CMCH suggests recent control measures are successful. However, there are no reliable data on the incidence of severe malaria in the CHT, the most endemic area of Bangladesh, and most of these patients do not reach tertiary health facilities. Improvement of early treatment and simple supportive care for severe malaria in remote areas and implementation of a referral system for cases requiring additional supportive care could be important contributors to further reducing malaria-attributable disease and death in Bangladesh.

Effect of acid concentration and treatment time on acid-alcohol modified jackfruit seed starch properties.

The properties of starch extracted from jackfruit (Artocarpus heterophyllus Lam.) seeds, collected from west Assam after acid-alcohol modification by short term treatment (ST) for 15-30min with concentrated hydrochloric acid and long term treatment (LT) for 1-15days with 1M hydrochloric acid, were investigated. Granule density, freeze thaw stability, solubility and light transmittance of the treated starches increased. A maximum decrease in the degree of polymerisation occurred in ST of 30min (2607.6). Jackfruit starch had 27.1±0.04% amylose content (db), which in ST initially decreased and then increased with the severity of treatment; in LT the effect was irregular. The pasting profile and granule morphology of the treated samples were severely modified. Native starch had the A-type crystalline pattern and crystalline structure increased on treatment. FTIR spectra revealed slight changes in bond stretching and bending. Colour measurement indicated that whiteness increased on treatment. Acid modified jackfruit seed starch can have applications in the food industry.

Reaction Coordinate and Thermodynamics of Base Flipping in RNA.

Base flipping is a key biophysical event involved in recognition of various ligands by ribonucleic acid (RNA) molecules. However, the mechanism of base flipping in RNA remains poorly understood, in part due to the lack of atomistic details on complex rearrangements in neighboring bases. In this work, we applied transition path sampling (TPS) methods to study base flipping in a double-stranded RNA (dsRNA) molecule that is known to interact with RNA-editing enzymes through this mechanism. We obtained an ensemble of 1000 transition trajectories to describe the base-flipping process. We used the likelihood maximization method to determine the refined reaction coordinate (RC) consisting of two collective variables (CVs), a distance and a dihedral angle between nucleotides that form stacking interactions with the flipping base. The free energy profile projected along the refined RC revealed three minima, two corresponding to the initial and final states and one for a metastable state. We suggest that the metastable state likely represents a wobbled conformation of nucleobases observed in NMR studies that is often characterized as the flipped state. The analyses of reactive trajectories further revealed that the base flipping is coupled to a global conformational change in a stem-loop of dsRNA.

Enhanced Porosity in Self-Assembled Morphologies Mediated by Charged Lobes on Patchy Particles.

Colloidal patchy particles are particles with anisotropic "patches" decorating their surfaces. Several properties of these patches including their size, number, location, and interactions provide control over self-assembly of patchy particles into structures with desired properties. We report on simulation studies of particles where patches take the form of lobes. Based on the number and locations of lobes, these particles have different shapes (trigonal planar, square planar, tetrahedral, trigonal bipyramidal, and octahedral). We investigated the effect of incorporating charges on the lobes in achieving porous self-assembled morphologies across a range of temperatures. We observed that an increase in the charge on the lobe resulted in lobed particles assembling over a wider range of temperatures. We also observed that the lobed particles with charges self-assembled into structures with enhanced porosity in comparison to lobed particles without charges.

Orthogonal order parameters to model the reaction coordinate of an enzyme catalyzed reaction.

The choice of suitable collective variables in formulating an optimal reaction coordinate is a challenging task for activated transitions between a pair of stable states especially when dealing with biochemical changes such as enzyme catalyzed reactions. A detailed benchmarking study is carried out on the choice of collective variables that can distinguish between the stable states unambiguously. We specifically address the issue if these variables may be directly used to model the optimal reaction coordinate, or if it would be better to use their orthogonalized counterparts. The proposed computational scheme is applied to the rate determining intramolecular proton transfer step in the enzyme human carbonic anhydrase II. The optimum reaction coordinate is determined with and without orthogonalization of the collective variables pertinent to a key conformational fluctuation and the actual proton transfer step at the active site of the enzyme. Suitability of the predicted reaction coordinates in different processes is examined in terms of the free energy profile projected along the reaction coordinate, the rate constant of transition and the underlying molecular mechanism of barrier crossing. Our results indicate that a better agreement with earlier simulation and experimental data is obtained when the orthogonalized collective variables are used to model the reaction coordinate.

Reaction Coordinate, Free Energy, and Rate of Intramolecular Proton Transfer in Human Carbonic Anhydrase II.

The role of structure and dynamics of an enzyme has been investigated at three different stages of its function including the chemical event it catalyzes. A one-pot computational method has been designed for each of these stages on the basis of classical and/or quantum mechanical-molecular mechanical molecular dynamics and transition path sampling simulations. For a pair of initial and final states A and B separated by a high free-energy barrier, using a two-stage selection process, several collective variables (CVs) are identified that can delineate A and B. However, these CVs are found to exhibit strong cross-coupling over the transition paths. A set of mutually orthogonal order parameters is then derived from these CVs and an optimal reaction coordinate, r, determined applying half-trajectory likelihood maximization along with a Bayesian information criterion. The transition paths are also used to project the multidimensional free energy surface and barrier crossing dynamics along r. The proposed scheme has been applied to the rate-determining intramolecular proton transfer reaction of the well-known enzyme human carbonic anhydrase II. The potential of mean force, F( r), in the absence of the chemical step is found to reproduce earlier results on the equilibrium population of two side-chain orientations of key residue His-64. Estimation of rate constants, k, from mean first passage times for the three different stages of catalysis shows that the rate-determining step of intramolecular proton transfer occurs with k ≃ 1.0 × 106 s-1, in close agreement with known experimental results.

Disease Severity and Effective Parasite Multiplication Rate in Falciparum Malaria.

Patients presenting with severe falciparum malaria in a Bangladeshi tertiary hospital had higher total parasite burden, estimated by parasitemia and plasma PfHRP2, than uncomplicated malaria patients despite shorter fever duration. This suggests that higher parasite multiplication rates (PMR) contribute to causing the higher biomass found in severe disease. Compared with patients without a history of previous malaria, patients with previous malaria carried a lower parasite biomass with similar fever duration at presentation, suggesting that host immunity reduces the PMR.

A comparative study of esmolol and dexmedetomidine on hemodynamic responses to carbon dioxide pneumoperitoneum during laparoscopic surgery.

BACKGROUND: Carbon dioxide pneumoperitoneum for laparoscopic surgery increases arterial pressures, heart rate (HR), and systemic vascular resistance. In this randomized, single-blind, placebo-controlled clinical study, we investigated and compared the efficacy of esmolol and dexmedetomidine to provide perioperative hemodynamic stability in patients undergoing laparoscopic cholecystectomy. METHODS: Sixty patients, of either sex undergoing elective laparoscopic cholecystectomy, were randomly allocated into three groups containing twenty patients each. Group E received bolus dose of 500 µg/kg intravenous (IV) esmolol before pneumoperitoneum followed by an infusion of 100 µg/kg/min. Group D received bolus dose of 1 µg/kg IV dexmedetomidine before pneumoperitoneum followed by infusion of 0.2 µg/kg/h. Group S (control) received saline 0.9%. RESULTS: Mean arterial pressure and HR in Group E and D were significantly less throughout the period of pneumoperitoneum in comparison to Group S. IV nitroglycerine was required in 45% (9 out of 20) patients in Group S to control intraoperative hypertension, and it was clinically significant in comparison to Group E and D. CONCLUSION: Both esmolol and dexmedetomidine attenuate the adverse hemodynamic response to pneumoperitoneum and provide hemodynamic stability during laparoscopic surgery.

Determination of the Reaction Coordinate for a Key Conformational Fluctuation in Human Carbonic Anhydrase II.

During the reversible hydration of carbon dioxide into bicarbonate by the enzyme human carbonic anhydrase II, the rate-determining step of proton transfer across the active site has been suggested to involve side chain rotation of the residue His-64 shuttling an excess proton in and out of the active site. In the present article, we have determined the reaction coordinate for this catalytically important conformational transition starting from a set of 32 order parameters (or candidate collective variables). Following the original work by Peters and Trout (J. Chem. Phys. 2006, 125, 054108), unbiased dynamical transition paths connecting the two major side chain conformations are harvested using an aimless shooting algorithm, and the reaction coordinate is determined using the method of forward-trajectory likelihood maximization. Several different models are tested involving a single order parameter or linear combinations of several of them chosen from the preselected set. An optimum reaction coordinate, identified using a Bayesian information criterion, is found to be a linear combination of 4 order parameters. This reaction coordinate is subsequently utilized to explore the associated free energy profile and diffusive barrier crossing dynamics. To the best of our knowledge, previous instances of this calculation include only alanine dipeptide and photoactive yellow protein (125 residues) in explicit water solvent. The present work is the first report of a quantitative determination of the reaction coordinate for conformational transition in a protein having as many as 259 residues in the presence of explicit water and sampled near the free energy barrier for about 1 µs.