Multivalent ligand presentation as a central concept to study intricate carbohydrate-protein interactions

Studying the weak binding affinities between carbohydrates and proteins has been a central theme in sustained efforts to uncover intricate details of this class of biomolecular interaction. The amphiphilic nature of most carbohydrates, the competing nature of the surrounding water molecules to a given protein receptor site and the receptor binding site characteristics led to the realization that carbohydrates are required to exert favorable interactions, primarily through clustering of the ligands. The clustering of sugar ligands has been augmented using many different innovative molecular scaffolds. The synthesis of clustered ligands also facilitates fine-tuning of the spatial and topological proximities between the ligands, so as to allow the identification of optimal molecular features for significant binding affinity enhancements. The kinetic and thermodynamic parameters have been delineated in many instances, thereby allowing an ability to correlate the multivalent presentation and the observed ligand-receptor interaction profiles. This critical review presents various multivalent ligands, synthetic and semisynthetic, and mechanisms by which the weak binding affinities are overcome, and the ligand-receptor complexation leads to significantly enhanced binding affinities (157 references).

A formal synthesis of the perhydrogephyrotoxin

A short but uneventful formal synthesis of perhydrogephyrotoxin 3 from readily available tricyclo[5.2.1.0(2,6)]decane derivative 8 via the intermediacy of the cis-hydroindanone 13 is reported. This work constitutes further demonstration of the carbocycle-heterocycle equivalency theme in the synthesis of alkaloids.

Dimorphism and structural modulation in quinoxaline

The Z' = 1 and Z' = 5 structures of quinoxaline are compared. The nature of the intermolecular interactions in the Z' = 5 structure is studied by means of variable-temperature single-crystal X-ray diffraction. The C-H center dot center dot center dot N and pi ... pi it interactions in these structures are of a stabilizing nature. The high Z' structure has the better interactions, whereas the low Z' structure has the better stability. This trade-off is a recurrent theme in molecular crystals and is a manifestation of the distinction between thermodynamically and kinetically favoured crystal forms.

Orientational relaxation in dipolar systems: How much do we understand the role of correlations

Dipolar systems, both liquids and solids, constitute a class of naturally abundant systems that are important in all branches of natural science. The study of orientational relaxation provides a powerful method to understand the microscopic properties of these systems and, fortunately, there are many experimental tools to study orientational relaxation in the condensed phases. However, even after many years of intense research, our understanding of orientational relaxation in dipolar systems has remained largely imperfect. A major hurdle towards achieving a comprehensive understanding is the long range and complex nature of dipolar interactions which also made reliable theoretical study extremely difficult. These difficulties have led to the development of continuum model based theories, which although they provide simple, elegant expressions for quantities of interest, are mostly unsatisfactory as they totally neglect the molecularity of inter-molecular interactions. The situation has improved in recent years because of renewed studies, led by computer simulations. In this review, we shall address some of the recent advances, with emphasis on the work done in our laboratory at Bangalore. The reasons for the failure of the continuum model, as revealed by the recent Brownian dynamics simulations of the dipolar lattice, are discussed. The main reason is that the continuum model predicts too fast a decay of the torque-torque correlation function. On the other hand, a perturbative calculation, based on Zwanzig's projection operator technique, provides a fairly satisfactory description of the single particle orientational dynamics for not too strongly polar dipolar systems. A recently developed molecular hydrodynamic theory that properly includes the effects of intermolecular orientational pair correlations provides an even better description of the single-particle orientational dynamics. We also discuss the rank dependence of the dielectric friction. The other topics reviewed here includes dielectric relaxation and solvation dynamics, as they are intimately connected with orientational relaxation. Recent molecular dynamics simulations of the dipolar lattice are also discussed. The main theme of the present review is to understand the effects of intermolecular interactions on orientational relaxation. The presence of strong orientational pair correlation leads to a strong coupling between the single particle and the collective dynamics. This coupling can lead to rich dynamical properties, some of which are detailed here, while a major part remains yet unexplored.

Thiol/disulphide exchange reaction: A key regulatory process in biological systems

Cysteine residues in proteins serve many important functions such as stabilizing and maintaining the three-dimensional conformation of many proteins(1), in enzyme catalysis, as a residue undergoing post-translational 2 and in the formation of DNA-binding modification domain of a class of transcriptional activators(3), It is also involved in biological redox coupling(4) and xenobiotic metabolism(5). Disulphide bonds formed by xenobiotic metabolism oxidation of cysteine residues have been used as a probe to study the structure/function relationships of proteins, Introducing novel disulphide bonds in proteins to increase their thermal stability and, therefore, the shelf life is an important goal of protein engineering(6,7), In addition, the thiol group of cysteine residue participates in a reaction termed as thiol/disulphide exchange reaction, the biological significance of this reaction being the theme of this review.

Synergy between the N-terminal and C-terminal domains of Mycobacterium tuberculosis HupB is essential for high-affinity binding, DNA supercoiling and inhibition of RecA-promoted strand exchange

The occurrence of DNA architectural proteins containing two functional domains derived from two different architectural proteins is an interesting emerging research theme in the field of nucleoid structure and function. Mycobacterium tuberculosis HupB, unlike Escherichia coli HU, is a two-domain protein that, in the N-terminal region, shows broad sequence homology with bacterial HU. The long C-terminal extension, on the other hand, contains seven PAKK/KAAK motifs, which are characteristic of the histone H1/H5 family of proteins. In this article, we describe several aspects of HupB function, in comparison with its truncated derivatives lacking either the C-terminus or N-terminus. We found that HupB binds a variety of DNA repair and replication intermediates with K(d) values in the nanomolar range. By contrast, the N-terminal fragment of M. tuberculosis HupB (HupB(MtbN)) showed diminished DNA-binding activity, with K(d) values in the micromolar range, and the C-terminal domain was completely devoid of DNA-binding activity. Unlike HupB(MtbN), HupB was able to constrain DNA in negative supercoils and introduce negative superhelical turns into relaxed DNA. Similarly, HupB exerted a robust inhibitory effect on DNA strand exchange promoted by cognate and noncognate RecA proteins, whereas HupB(MtbN), even at a 50-fold molar excess, had no inhibitory effect. Considered together, these results suggest that synergy between the N-terminal and C-terminal domains of HupB is essential for its DNA-binding ability, and to modulate the topological features of DNA, which has implications for processes such as DNA compaction, gene regulation, homologous recombination, and DNA repair.

Seismic Microzonation of Bangalore - Preliminary Maps

This paper presents an overview of the seismic microzonation and the grade/level based study along with methods used for estimating hazard. The principles of seismic microzonation along with some current practices are discussed. Summary of seismic microzonation experiments carried out in India is presented. A detailed work of seismic microzonation of Bangalore has been presented as a case study. In this case study, a seismotectonic map for microzonation area has been developed covering 350 km radius around Bangalore, India using seismicity and seismotectonic parameters of the region. For seismic microzonation Bangalore Mahanagar Palike (BMP) area of 220 km2 has been selected as the study area. Seismic hazard analysis has been carried out using deterministic as well as probabilistic approaches. Synthetic ground motion at 653 locations, recurrence relation and peak ground acceleration maps at rock level have been generated. A detailed site characterization has been carried out using borehole with standard penetration test (SPT) ―N‖ values and geophysical data. The base map and 3-dimensional sub surface borehole model has been generated for study area using geographical information system (GIS). Multichannel analysis of surface wave (MASW)method has been used to generate one-dimensional shear wave velocity profile at 58 locations and two- dimensional profile at 20 locations. These shear wave velocities are used to estimate equivalent shear wave velocity in the study area at every 5m intervals up to a depth of 30m. Because of wider variation in the rock depth, equivalent shear for the soil overburden thickness alone has been estimated and mapped using ArcGIS 9.2. Based on equivalent shear wave velocity of soil overburden thickness, the study area is classified as ―site class D‖. Site response study has been carried out using geotechnical properties and synthetic ground motions with program SHAKE2000.The soil in the study area is classified as soil with moderate amplification potential. Site response results obtained using standard penetration test (SPT) ―N‖ values and shear wave velocity are compared, it is found that the results based on shear wave velocity is lower than the results based on SPT ―N‖ values. Further, predominant frequency of soil column has been estimated based on ambient noise survey measurements using instruments of L4-3D short period sensors equipped with Reftek 24 bit digital acquisition systems. Predominant frequency obtained from site response study is compared with ambient noise survey. In general, predominant frequencies in the study area vary from 3Hz to 12Hz. Due to flat terrain in the study area, the induced effect of land slide possibility is considered to be remote. However, induced effect of liquefaction hazard has been estimated and mapped. Finally, by integrating the above hazard parameters two hazard index maps have been developed using Analytic Hierarchy Process (AHP) on GIS platform. One map is based on deterministic hazard analysis and other map is based on probabilistic hazard analysis. Finally, a general guideline is proposed by bringing out the advantages and disadvantages of different approaches.

An Overview of Homogenization

Homogenization of partial differential equations is relatively a new area and has tremendous applications in various branches of engineering sciences like: material science,porous media, study of vibrations of thin structures, composite materials to name a few. Though the material scientists and others had reasonable idea about the homogenization process, it was lacking a good mathematical theory till early seventies. The first proper mathematical procedure was developed in the seventies and later in the last 30 years or so it has flourished in various ways both application wise and mathematically. This is not a full survey article and on the other hand we will not be concentrating on a specialized problem. Indeed, we do indicate certain specialized problems of our interest without much details and that is not the main theme of the article. I plan to give an introductory presentation with the aim of catering to a wider audience. We go through few examples to understand homogenization procedure in a general perspective together with applications. We also present various mathematical techniques available and if possible some details about some of the techniques. A possible definition of homogenization would be that it is a process of understanding a heterogeneous (in-homogeneous) media, where the heterogeneties are at the microscopic level, like in composite materials, by a homogeneous media. In other words, one would like to obtain a homogeneous description of a highly oscillating in-homogeneous media. We also present other generalizations to non linear problems, porous media and so on. Finally, we will like to see a closely related issue of optimal bounds which itself is an independent area of research.

Session 6 grouting and deep mixing: New concept and applications

The theme of the session is the New Concept and Applications both for the grouting and deep mixing technologies. Nineteen papers were submitted to this session, and those covered a variety of topics; 1) New concepts and development, 2) Refinement of techniques, and 3) analysis and applications. Eight papers out of them were presented orally.

What is really real?

There has been substantial public debate recently on a host of issues such as climate change, genetically modified crops and nuclear power; a common theme running through these issues involves science and public policy. This note will be based broadly on three interlinked themes: growth of specialization in science, significant commercial interests pushing science and technology, and a checkered track record of the promises made and the broken-reality.

Heat shock protein 90 from neglected protozoan parasites

Significant advances have been made in our understanding of heat shock protein 90 (Hsp90) in terms of its structure, biochemical characteristics, post-translational modifications, interactomes, regulation and functions. In addition to yeast as a model several new systems have now been examined including flies, worms, plants as well as mammalian cells. This review discusses themes emerging out of studies reported on Hsp90 from infectious disease causing protozoa. A common theme of sensing and responding to host cell microenvironment emerges out of analysis of Hsp90 in Malaria, Trypanosmiasis as well as Leishmaniasis. In addition to their functional roles, the potential of Hsp90 from these infectious disease causing organisms to serve as drug targets and the current status of this drug development endeavor are discussed. Finally, a unique and the only known example of a split Hsp90 gene from another disease causing protozoan Giardia lamblia and its evolutionary significance are discussed. Clearly studies on Hsp90 from protozoan parasites promise to reveal important new paradigms in Hsp90 biology while exploring its potential as an anti-infective drug target. This article is part of a Special Issue entitled: Heat Shock Protein 90 (HSP90). (C) 2011 Elsevier B.V. All rights reserved.

Interference Alignment in Regenerating Codes for Distributed Storage: Necessity and Code Constructions

Regenerating codes are a class of recently developed codes for distributed storage that, like Reed-Solomon codes, permit data recovery from any arbitrary of nodes. However regenerating codes possess in addition, the ability to repair a failed node by connecting to any arbitrary nodes and downloading an amount of data that is typically far less than the size of the data file. This amount of download is termed the repair bandwidth. Minimum storage regenerating (MSR) codes are a subclass of regenerating codes that require the least amount of network storage; every such code is a maximum distance separable (MDS) code. Further, when a replacement node stores data identical to that in the failed node, the repair is termed as exact. The four principal results of the paper are (a) the explicit construction of a class of MDS codes for d = n - 1 >= 2k - 1 termed the MISER code, that achieves the cut-set bound on the repair bandwidth for the exact repair of systematic nodes, (b) proof of the necessity of interference alignment in exact-repair MSR codes, (c) a proof showing the impossibility of constructing linear, exact-repair MSR codes for d < 2k - 3 in the absence of symbol extension, and (d) the construction, also explicit, of high-rate MSR codes for d = k+1. Interference alignment (IA) is a theme that runs throughout the paper: the MISER code is built on the principles of IA and IA is also a crucial component to the nonexistence proof for d < 2k - 3. To the best of our knowledge, the constructions presented in this paper are the first explicit constructions of regenerating codes that achieve the cut-set bound.

Soil stabilization with waste materials based binder

This paper describes a laboratory trial to study the effectiveness of a waste-based binder to stabilize expansive soils. The proposed binders viz., Fly ash and/or Ground granulated Blast furnace slag (GGBS) were mixed with the expansive soil along with a small amount of lime to increase soil pH and enable pozzolanic reactions. The geotechnical characteristics of the various combinations of samples were investigated through the compaction tests, unconfined compression tests etc. It was found that the addition of GGBS with and without fly ash and lime has significant influence on the geotechnical characteristics of the soil.

Clay mineral liner system for leachates containing organic contaminants

A conventional liner with a good performance against inorganic contaminants with a minimal hydraulic conductivity does not usually perform well for retention/removal of leachates containing organic contaminants. Organic modification of clay can render the naturally organophobic clay tobe organophilic. Incorporation of modified organo clay along with unmodified inorganic clay in liner systems can overcome the inherent incompatibility of conventional liners to organic contaminants and can increase organic sorption. The performance of commercially available organo clay and natural bentonite and mixtures of them in different pore fluids has been studied. It is found that the properties of mixtures improve with increase in organically modified clay particularly in non aqueous fluids from the considerations of liner application.

Realistic minimum desorption temperatures and compressor sizing for activated carbon + HFC 134a adsorption coolers

A low thermal diffusivity of adsorption beds induces a large thermal gradient across cylindrical adsorbers used in adsorption cooling cycles. This reduces the concentration difference across which a thermal compressor operates. Slow adsorption kinetics in conjunction with the void volume effect further diminishes throughputs from those adsorption thermal compressors. The problem can be partially alleviated by increasing the desorption temperatures. The theme of this paper is the determination the minimum desorption temperature required for a given set of evaporating/condensing temperatures for an activated carbon + HFC 134a adsorption cooler. The calculation scheme is validated from experimental data. Results from a parametric analysis covering a range of evaporating/condensing/desorption temperatures are presented. It is found that the overall uptake efficiency and Carnot COP characterize these bounds. A design methodology for adsorber sizing is evolved. (c) 2012 Elsevier Ltd. All rights reserved.