Dynamics of Barrierless and Activated Chemical Reactions in a Dispersive Medium within the Fractional Diffusion Equation Approach

Barrierless chemical reactions have often been modeled as a Brownian motion on a one-dimensional harmonic potential energy surface with a position-dependent reaction sink or window located near the minimum of the surface. This simple (but highly successful) description leads to a nonexponential survival probability only at small to intermediate times but exponential decay in the long-time limit. However, in several reactive events involving proteins and glasses, the reactions are found to exhibit a strongly nonexponential (power law) decay kinetics even in the long time. In order to address such reactions, here, we introduce a model of barrierless chemical reaction where the motion along the reaction coordinate sustains dispersive diffusion. A complete analytical solution of the model can be obtained only in the frequency domain, but an asymptotic solution is obtained in the limit of long time. In this case, the asymptotic long-time decay of the survival probability is a power law of the Mittag−Leffler functional form. When the barrier height is increased, the decay of the survival probability still remains nonexponential, in contrast to the ordinary Brownian motion case where the rate is given by the Smoluchowski limit of the well-known Kramers' expression. Interestingly, the reaction under dispersive diffusion is shown to exhibit strong dependence on the initial state of the system, thus predicting a strong dependence on the excitation wavelength for photoisomerization reactions in a dispersive medium. The theory also predicts a fractional viscosity dependence of the rate, which is often observed in the reactions occurring in complex environments.

Three-dimensional structure of heat shock protein 90 from Plasmodium falciparum: molecular modelling approach to rational drug design against malaria

We have recently implicated heat shock protein 90 from Plasmodium falciparum (PfHsp90) as a potential drug target against malaria. Using inhibitors specific to the nucleotide binding domain of Hsp90, we have shown potent growth inhibitory effects on development of malarial parasite in human erythrocytes. To gain better understanding of the vital role played by PfHsp90 in parasite growth, we have modeled its three dimensional structure using recently described full length structure of yeast Hsp90. Sequence similarity found between PfHsp90 and yeast Hsp90 allowed us to model the core structure with high confidence. The superimposition of the predicted structure with that of the template yeast Hsp90 structure reveals an RMSD of 3.31 angstrom. The N-terminal and middle domains showed the least RMSD (1.76 angstrom) while the more divergent C-terminus showed a greater RMSD (2.84 angstrom) with respect to the template. The structure shows overall conservation of domains involved in nucleotide binding, ATPase activity, co-chaperone binding as well as inter-subunit interactions. Important co-chaperones known to modulate Hsp90 function in other eukaryotes are conserved in malarial parasite as well. An acidic stretch of amino acids found in the linker region, which is uniquely extended in PfHsp90 could not be modeled in this structure suggesting a flexible conformation. Our results provide a basis to compare the overall structure and functional pathways dependent on PfHsp90 in malarial parasite. Further analysis of differences found between human and parasite Hsp90 may make it possible to design inhibitors targeted specifically against malaria.

Electronic structure and bonding of beta-rhombohedral boron using cluster fragment approach

Theoretical studies using density functional theory are carried out to understand the electronic structure and bonding and electronic properties of elemental beta-rhombohedral boron. The calculated band structure of ideal beta-rhombohedral boron (B-105) shows valence electron deficiency and depicts metallic behavior. This is in contrast to the experimental result that it is a semiconductor. To understand this ambiguity we discuss the electronic structure and bonding of this allotrope with cluster fragment approach using our recently proposed mno rule. This helps us to comprehend in greater detail the structure of B-105 and materials which are closely related to beta-rhombohedral boron. The molecular structures B12H12-2, B28H21+1, BeB27H21, LiB27H21-1, CB27H21+2, B57H36+3, Be3B54H36, and Li2CB54H36, and corresponding solids Li8Be3B102 and Li10CB102 are arrived at using these ideas and studied using first principles density functional theory calculations.

Hexagonally ordered arrays of metallic nanodots from thin films of functional block copolymers

We demonstrate a new and simple route to fabricate highly dense arrays of hexagonally close packed inorganic nanodots using functional diblock copolymer (PS-b-P4VP) thin films. The deposition of pre-synthesized inorganic nanoparticles selectively into the P4VP domains of PS-b-P4VP thin films, followed by removal of the polymer, led to highly ordered metallic patterns identical to the order of the starting thin film. Examples of Au, Pt and Pd nanodot arrays are presented. The affinity of the different metal nanoparticles towards P4VP chains is also understood by extending this approach to PS-b-P4VP micellar thin films. The procedure used here is simple, eco-friendly, and compatible with the existing silicon-based technology. Also the method could be applied to various other block copolymer morphologies for generating 1-dimensional (1D) and 2-dimensional (2D) structures. (c) 2010 Elsevier Ltd. All rights reserved.

Real-Time PCR : A Molecular Approach to Investigate the Role of Intestinal Microbiota in the Pathophysiology of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a common multifactorial functional intestinal disorder, the pathogenesis of which is not completely understood. Increasing scientific evidence suggests that microbes are involved in the onset and maintenance of IBS symptoms. The microbiota of the human gastrointestinal (GI) tract constitutes a massive and complex ecosystem consisting mainly of obligate anaerobic microorganisms making the use of culture-based methods demanding and prone to misinterpretation. To overcome these drawbacks, an extensive panel of species- and group-specific assays for an accurate quantification of bacteria from fecal samples with real-time PCR was developed, optimized, and validated. As a result, the target bacteria were detectable at a minimum concentration range of approximately 10 000 bacterial genomes per gram of fecal sample, which corresponds to the sensitivity to detect 0.000001% subpopulations of the total fecal microbiota. The real-time PCR panel covering both commensal and pathogenic microorganisms was assessed to compare the intestinal microbiota of patients suffering from IBS with a healthy control group devoid of GI symptoms. Both the IBS and control groups showed considerable individual variation in gut microbiota composition. Sorting of the IBS patients according to the symptom subtypes (diarrhea, constipation, and alternating predominant type) revealed that lower amounts of Lactobacillus spp. were present in the samples of diarrhea predominant IBS patients, whereas constipation predominant IBS patients carried increased amounts of Veillonella spp. In the screening of intestinal pathogens, 17% of IBS samples tested positive for Staphylococcus aureus, whereas no positive cases were discovered among healthy controls. Furthermore, the methodology was applied to monitor the effects of a multispecies probiotic supplementation on GI microbiota of IBS sufferers. In the placebo-controlled double-blind probiotic intervention trial of IBS patients, each supplemented probiotic strain was detected in fecal samples. Intestinal microbiota remained stable during the trial, except for Bifidobacterium spp., which increased in the placebo group and decreased in the probiotic group. The combination of assays developed and applied in this thesis has an overall coverage of 300-400 known bacterial species, along with the number of yet unknown phylotypes. Hence, it provides good means for studying the intestinal microbiota, irrespective of the intestinal condition and health status. In particular, it allows screening and identification of microbes putatively associated with IBS. The alterations in the gut microbiota discovered here support the hypothesis that microbes are likely to contribute to the pathophysiology of IBS. The central question is whether the microbiota changes described represent the cause for, rather than the effect of, disturbed gut physiology. Therefore, more studies are needed to determine the role and importance of individual microbial species or groups in IBS. In addition, it is essential that the microbial alterations observed in this study will be confirmed using a larger set of IBS samples of different subtypes, preferably from various geographical locations.

Functional Surfaces for Microfluidics in Proteomic Analysis

Microchips for use in biomolecular analysis show a lot of promise for medical diagnostics and biomedical basic research. Among the potential advantages are more sensitive and faster analyses as well as reduced cost and sample consumption. Due to scaling laws, the surface are to volume ratios of microfluidic chips is very high. Because of this, tailoring the surface properties and surface functionalization are very important technical issues for microchip development. This thesis studies two different types of functional surfaces, surfaces for open surface capillary microfluidics and surfaces for surface assisted laser desorption ionization mass spectrometry, and combinations thereof. Open surface capillary microfluidics can be used to transport and control liquid samples on easily accessible open surfaces simply based on surface forces, without any connections to pumps or electrical power sources. Capillary filling of open partially wetting grooves is shown to be possible with certain geometries, aspect ratios and contact angles, and a theoretical model is developed to identify complete channel filling domains, as well as partial filling domains. On the other hand, partially wetting surfaces with triangular microstructures can be used for achieving directional wetting, where the water droplets do not spread isotropically, but instead only spread to a predetermined sector. Furthermore, by patterning completely wetting and superhydrophobic areas on the same surface, complex droplet shapes are achieved, as the water stretches to make contact with the wetting surface, but does not enter into the superhydrophobic domains. Surfaces for surface assisted laser desorption ionization mass spectrometry are developed by applying various active thin film coatings on multiple substrates, in order to separate surface and bulk effects. Clear differences are observed between both surface and substrate layers. The best performance surfaces consisted of amorphous silicon coating and an inorganic-organic hybrid substrate, with nanopillars and nanopores. These surfaces are used for matrix-free ionization of drugs, peptides and proteins, and for some analytes, the detection limits were in the high attomoles. Microfluidics and laser desorption ionization surfaces are combined on a functionalized drying platforms, where the surface is used to control the shape of the deposited analyte droplet, and the shape of the initial analyte droplet affects the dried droplet solute deposition pattern. The deposited droplets can then directly detected by mass spectrometry. Utilizing this approach, results of analyte concentration, splitting and separation are demonstrated.

A functional style of programming with CSP-like communication mechanisms

This paper introduces CSP-like communication mechanisms into Backus’ Functional Programming (FP) systems extended by nondeterministic constructs. Several new functionals are used to describe nondeterminism and communication in programs. The functionals union and restriction are introduced into FP systems to develop a simple algebra of programs with nondeterminism. The behaviour of other functionals proposed in this paper are characterized by the properties of union and restriction. The axiomatic semantics of communication constructs are presented. Examples show that it is possible to reason about a communicating program by first transforming it into a non-communicating program by using the axioms of communication, and then reasoning about the resulting non-communicating version of the program. It is also shown that communicating programs can be developed from non-communicating programs given as specifications by using a transformational approach.

A knowledge-based approach to pattern generation

Pattern Cognition is looked at from the functional view point. The need for knowledge in synthesizing such patterns is explained and various aspects of knowledge-based pattern generation are highlighted. This approach to the generation of patterns is detailed with a concrete example.

Network approach for capturing ligand-induced subtle global changes in protein structures

Ligand-induced conformational changes in proteins are of immense functional relevance. It is a major challenge to elucidate the network of amino acids that are responsible for the percolation of ligand-induced conformational changes to distal regions in the protein from a global perspective. Functionally important subtle conformational changes (at the level of side-chain noncovalent interactions) upon ligand binding or as a result of environmental variations are also elusive in conventional studies such as those using root-mean-square deviations (r.m.s.d.s). In this article, the network representation of protein structures and their analyses provides an efficient tool to capture these variations (both drastic and subtle) in atomistic detail in a global milieu. A generalized graph theoretical metric, using network parameters such as cliques and/or communities, is used to determine similarities or differences between structures in a rigorous manner. The ligand-induced global rewiring in the protein structures is also quantified in terms of network parameters. Thus, a judicious use of graph theory in the context of protein structures can provide meaningful insights into global structural reorganizations upon perturbation and can also be helpful for rigorous structural comparison. Data sets for the present study include high-resolution crystal structures of serine proteases from the S1A family and are probed to quantify the ligand-induced subtle structural variations.

Hybrid systems through natural product leads: An approach towards new molecular entities

Hybrid systems are constructs of different molecular entities, natural or unnatural, to generate functional molecules in which the characteristics of various components are modulated, amplified or give rise to entirely new properties. These hybrids can be designed from carefully selected components either through domain intergration of key structural/functional features or via straightforward covalent linkages. Some of the recently reported hybrid systems based on steroid, carbohydrate, C-60-fullerene platforms, amongst others, mainly crafted with the object of enhancement of the therapeutical spectrum, will be discussed.

Smooth DMS-FEM: A new approach to solving nearly incompressible nonlinear elasto-static problems

The DMS-FEM, which enables functional approximations with C(1) or still higher inter-element continuity within an FEM-based meshing of the domain, has recently been proposed by Sunilkumar and Roy [39,40]. Through numerical explorations on linear elasto-static problems, the method was found to have conspicuously superior convergence characteristics as well as higher numerical stability against locking. These observations motivate the present study, which aims at extending and exploring the DMS-FEM to (geometrically) nonlinear elasto-static problems of interest in solid mechanics and assessing its numerical performance vis-a-vis the FEM. In particular, the DMS-FEM is shown to vastly outperform the FEM (presently implemented through the commercial software ANSYS (R)) as the former requires fewer linearization and load steps to achieve convergence. In addition, in the context of nearly incompressible nonlinear systems prone to volumetric locking and with no special numerical artefacts (e.g. stabilized or mixed weak forms) employed to arrest locking, the DMS-FEM is shown to approach the incompressibility limit much more closely and with significantly fewer iterations than the FEM. The numerical findings are suggestive of the important role that higher order (uniform) continuity of the approximated field variables play in overcoming volumetric locking and the great promise that the method holds for a range of other numerically ill-conditioned problems of interest in computational structural mechanics. (C) 2011 Elsevier Ltd. All rights reserved.

Study of molecular structure and vibrational spectra of poly (beta,-1-malic acid) PMLA] using DFT approach

Poly (beta-L-malic acid) (PMLA) is a biodegradable polymer and it has various important applications in the biomedical field. In the present work the structural and spectral characteristics of PMLA have been studied by methods of infrared. Raman spectroscopy and quantum chemistry. Electrostatic potential surface, optimized geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by density functional theory (DFT) using oligomeric approach employing B3LYP with complete relaxation in the potential energy surface using 6-311++G (d, p) basis set. Based on results, we have discussed the correlation between the vibrational modes and the structure of the PMLA. A complete analysis of the experimental infrared and Raman spectra has been reported on the basis of wavenumber of the vibrational bands and potential energy distribution. The calculated HOMO and LUMO energies shows that charge transfer occur within the molecule. The calculated infrared and the Raman spectra of the polymer based on DFT calculations show reasonable agreement with the experimental results. (c) 2012 Elsevier Ltd. All rights reserved.

Self-Assembly and Catalytic Activity of Metal Nanoparticles Immobilized in Polymer Membrane Prepared via Layer-by-Layer Approach

Densely packed nanoparticles distributed in a stable and robust thin film is a highly preferred system for utilizing the various applications of nanoparticles. Here, we report covalent bond mediated layer-by-layer (LbL) self-assembled thin films of nanoparticles embedded in polymer membrane. Polymer with complementary functional group is utilized for fabrication of thin film via covalent bonding. UV-visible spectroscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to monitor the growth of LbL thin film. Subsequently, the composite thin film is used for catalysis of an organic electron transfer reaction of p-nitrophenol to p-aminophenol by sodium borohydride. The catalytic activity of these composite films is assayed multiple times, proving its applicability as a catalyst. The kinetic data obtained by monitoring reduction of p-nitrophenol suggest that the reaction rates are directly related to the sizes of the nanoparticle and porosity of the membrane.

Smoothed functional and Quasi-Newton algorithms for routing in multi-stage queueing network with constraints

We consider the problem of optimal routing in a multi-stage network of queues with constraints on queue lengths. We develop three algorithms for probabilistic routing for this problem using only the total end-to-end delays. These algorithms use the smoothed functional (SF) approach to optimize the routing probabilities. In our model all the queues are assumed to have constraints on the average queue length. We also propose a novel quasi-Newton based SF algorithm. Policies like Join Shortest Queue or Least Work Left work only for unconstrained routing. Besides assuming knowledge of the queue length at all the queues. If the only information available is the expected end-to-end delay as with our case such policies cannot be used. We also give simulation results showing the performance of the SF algorithms for this problem.

A Bottom-Up Approach toward Fabrication of Ultrathin PbS Sheets

Two-dimensional (2D) sheets are currently in the spotlight of nanotechnology owing to high-performance device fabrication possibilities. Building a free-standing quantum sheet with controlled morphology is challenging when large planar geometry and ultranarrow thickness are simultaneously concerned. Coalescence of nanowires into large single-crystalline sheet is a promising approach leading to large, molecularly thick 2D sheets with controlled planar morphology. Here we report on a bottom-up approach to fabricate high-quality ultrathin 2D single crystalline sheets with well-defined rectangular morphology via collective coalescence of PbS nanowires. The ultrathin sheets are strictly rectangular with 1.8 nm thickness, 200-250 nm width, and 3-20 mu m length. The sheets show high electrical conductivity at room and cryogenic temperatures upon device fabrication. Density functional theory (DFT) calculations reveal that a single row of delocalized orbitals of a nanowire is gradually converted into several parallel conduction channels upon sheet formation, which enable superior in-plane carrier conduction.