The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

Coding for High-Density Recording on a 1-D Granular Magnetic Medium

In terabit-density magnetic recording, several bits of data can be replaced by the values of their neighbors in the storage medium. As a result, errors in the medium are dependent on each other and also on the data written. We consider a simple 1-D combinatorial model of this medium. In our model, we assume a setting where binary data is sequentially written on the medium and a bit can erroneously change to the immediately preceding value. We derive several properties of codes that correct this type of errors, focusing on bounds on their cardinality. We also define a probabilistic finite-state channel model of the storage medium, and derive lower and upper estimates of its capacity. A lower bound is derived by evaluating the symmetric capacity of the channel, i.e., the maximum transmission rate under the assumption of the uniform input distribution of the channel. An upper bound is found by showing that the original channel is a stochastic degradation of another, related channel model whose capacity we can compute explicitly.

Continuous Recording of Retardation and Intensity of Echoes from the Ionosphere

Pulse retardation method of Breit and Tuve has been modified to record continuously the equivalent height as well as the intensity of reflections from the ionosphere. Synchronized pulses are transmitted, and the received ground pulse and the reflected pulses, after amplification and suitable distortion, are applied to the focusing cylinder of a cathode ray tube the horizontal deflecting plates of which are connected to a synchronized linear time base circuit. The pattern on the screen is composed of a bright straight line corresponding to the time base with dark gaps corresponding to the received pulses. The distance between the initial points of the gaps represents retardation while the widths of the gaps correspond to the intensity of the pulses. The pattern is photographed on a vertically moving film. One of the first few records taken at Bangalore on 4 megacycles is reproduced. It shows, among other things, that the less retarded component of magneto-ionic splitting from the F layer is present most of the time. Whenever the longer retardation component does occur, it has stronger intensity than the former. Towards the late evening hours, just before disappearing, when the F layer rises and exhibits magnetoionic splitting, the intensity of the less retarded component is extremely low compared with the other component.

Biological and materials properties of various cholesterol based systems

Liposomes composed of cationic lipids have become very popular gene delivery vehicles. A great deal of research is being pursued to make efficient vectors by varying their molecular architecture. Cholesterol being ubiquitous component in most of the animal cell membranes is increasingly being used as a hydrophobic segment of synthetic cationic lipids. In this review we describe various cholesterol based cationic lipids and focus on the effect of modifying various structural segments like linker and the head group of the cationic lipids on gene transfection efficiency with a special emphasis on the importance of ether linkage between cholesteryl backbone and the polar head group. Interaction of cationic cholesteryl lipids with dipalmitylphosphatidycholine membranes is also discussed here. Apart from cholesterol being an attractive scaffold in the drug/gene delivery vehicles, certain cholesteryl derivatives have also been shown to be attractive room temperature liquid-crystalline materials.

Injection-molded high-density polyethylene-hydroxyapatite-aluminum oxide hybrid composites for hard-tissue replacement: Mechanical, biological, and protein adsorption behavior

In this article, we report the mechanical and biocompatibility properties of injection-molded high-density polyethylene (HDPE) composites reinforced with 40 wt % ceramic filler [hydroxyapatite (HA) and/or Al2O3] and 2 wt % titanate as a coupling agent. The mechanical property measurements revealed that a combination of a maximum tensile strength of 18.7 MPa and a maximum tensile modulus of about 855 MPa could be achieved with the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites. For the same composite composition, the maximum compression strength was determined to be 71.6 MPa and the compression modulus was about 660 MPa. The fractrography study revealed the uniform distribution of ceramic fillers in the semicrystalline HDPE matrix. The cytocompatibility study with osteoblast-like SaOS2 cells confirmed extensive cell adhesion and proliferation on the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites. The cell viability analysis with the 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed a statistically significant difference between the injection-molded HDPE20 wt % HA20 wt % Al2O3 composites and sintered HA for various culture durations of upto 7 days. The difference in cytocompatibility properties among the biocomposites is explained in terms of the difference in the protein absorption behavior. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

From anomalies in neat liquid to structure, dynamics and function in the biological world

Water brings its remarkable thermodynamic and dynamic anomalies in the pure liquid state to biological world where water molecules face a multitude of additional interactions that frustrate its hydrogen bond network. Yet the water molecules participate and control enormous number of biological processes in manners which are yet to be understood at a molecular level. We discuss thermodynamics, structure, dynamics and properties of water around proteins and DNA, along with those in reverse micelles. We discuss the roles of water in enzyme kinetics, in drug-DNA intercalation and in kinetic-proof reading ( the theory of lack of errors in biosynthesis). We also discuss how water may play an important role in the natural selection of biomolecules. (C) 2011 Elsevier B. V. All rights reserved.

Synthesis, spectroscopic properties and biological evaluation of transition metal complexes of salicylhydrazone of anthranilhydrazide: X-ray crystal structure of copper complex

The transition metal complexes of salicylhydrazone of anthranilhydrazide (H2L) were synthesised. The structures of metal complexes were characterized by various spectroscopic [IR, NMR, UV-Vis, EPR], thermal and other physicochemical methods. The single-crystal X-ray diffraction study of [Cu(HL)Cl]center dot H2O reveal its orthorhombic system with space group P2(1)2(1)2 and Z=4. The copper center has a distorted square planar geometry with ONO and Cl as the donor atoms. The ligand and its metal chelates have been screened for their antimicrobial and anti-tubercular activities using serial dilution method. Metal complexes in general have exhibited better antibacterial and antifungal activity than the free ligand and in few cases better than the standard used. Among the bacterial strains used, the complexes are highly potent against Gram-positive strains compared to Gram-negative. Anti-tubercular activity exhibited by the Co(II) complex is comparable with the standard used. (C) 2011 Elsevier B. V. All rights reserved.

Mixed-ligand aroylhydrazone complexes of molybdenum: Synthesis, structure and biological activity

The reaction of the benzoylhydrazone of 2-hydroxybenzaldehyde (H2L) with MoO2(acac)(2)] proceeds smoothly in refluxing ethanol to afford an orange complex MoO2L(C2H5OH)] (1). The substrate binding capacity of 1 has been demonstrated by the formation and isolation of two mononuclear MoO2L(Q)] {where Q = imidazole (2a) and 1-methylimidazole (2b)} and one dinuclear (MoO2L)(2)(Q)] {Q = 4,4'-bipyridine (3)} mixed-ligand oxomolybdenum complex. All the complexes have been characterized by elemental analysis, magnetic and spectroscopic (IR, UV-Vis and NMR) measurements. The molecular structures of all the oxomolybdenum(VI) complexes (1, 2a, 2b and 3) have been determined by X-ray crystallography. In each complex, the dianionic planar ligand is coordinated to the metal centre via one enolate oxygen, one phenolate oxygen and an azomethine nitrogen atom. The complexes have been screened for their antibacterial activity against Escherichia coli, Bacillus and Pseudomonas aeruginosa. The minimum inhibitory concentration of these complexes and their antibacterial activity indicates that compounds 2a and 2b are potential lead molecules for drug designing. (C) 2012 Elsevier Ltd. All rights reserved.

Computational algorithms inspired by biological processes and evolution

In recent times computational algorithms inspired by biological processes and evolution are gaining much popularity for solving science and engineering problems. These algorithms are broadly classified into evolutionary computation and swarm intelligence algorithms, which are derived based on the analogy of natural evolution and biological activities. These include genetic algorithms, genetic programming, differential evolution, particle swarm optimization, ant colony optimization, artificial neural networks, etc. The algorithms being random-search techniques, use some heuristics to guide the search towards optimal solution and speed-up the convergence to obtain the global optimal solutions. The bio-inspired methods have several attractive features and advantages compared to conventional optimization solvers. They also facilitate the advantage of simulation and optimization environment simultaneously to solve hard-to-define (in simple expressions), real-world problems. These biologically inspired methods have provided novel ways of problem-solving for practical problems in traffic routing, networking, games, industry, robotics, economics, mechanical, chemical, electrical, civil, water resources and others fields. This article discusses the key features and development of bio-inspired computational algorithms, and their scope for application in science and engineering fields.

Analytical solutions for diffuse fluorescence spectroscopy/imaging in biological tissues. Part I: zero and extrapolated boundary conditions

The mathematical model for diffuse fluorescence spectroscopy/imaging is represented by coupled partial differential equations (PDEs), which describe the excitation and emission light propagation in soft biological tissues. The generic closed-form solutions for these coupled PDEs are derived in this work for the case of regular geometries using the Green's function approach using both zero and extrapolated boundary conditions. The specific solutions along with the typical data types, such as integrated intensity and the mean time of flight, for various regular geometries were also derived for both time-and frequency-domain cases. (C) 2013 Optical Society of America

Analytical solutions for diffuse fluorescence spectroscopy/imaging in biological tissues. Part II: comparison and validation

The analytical solutions for the coupled diffusion equations that are encountered in diffuse fluorescence spectroscopy/ imaging for regular geometries were compared with the well-established numerical models, which are based on the finite element method. Comparison among the analytical solutions obtained using zero boundary conditions and extrapolated boundary conditions (EBCs) was also performed. The results reveal that the analytical solutions are in close agreement with the numerical solutions, and solutions obtained using EBCs are more accurate in obtaining the mean time of flight data compared to their counterpart. The analytical solutions were also shown to be capable of providing bulk optical properties through a numerical experiment using a realistic breast model. (C) 2013 Optical Society of America

Mixed-ligand nickel(II) thiosemicarbazone complexes: Synthesis, characterization and biological evaluation

The syntheses and characterization of some new mixed-ligand nickel(II) complexes {Ni(L-1)(PPh3)] (1), Ni(L-1)(Py)] (2), Ni(L-2)(PPh3)]center dot DMSO (3), Ni(L-2)(Imz)] (4), Ni(L-3)(4-pic)] (5) and RNi(L-3))(2)(mu-4,4'-byp)]center dot 2DMSO (6)1 of three selected thiosemicarbazones the 4-(p-X-phenyl)thiosemicarbazones of salicylaldehyde) (H2L1-3) (A, Scheme 1) are described in the present study, differing in the inductive effect of the substituent X (X = F, Br and OCH3), in order to observe its influence, if any, on the redox potentials and biological activity of the complexes. All the synthesized ligands and the metal complexes were successfully characterized by elemental analysis, IR, UV-Vis, NMR spectroscopy and cyclic voltammetry. The molecular structures of four mononuclear (1-3 and 5) and one dinuclear (6) Ni(II) complex have been determined by X-ray crystallography. The complexes have been screened for their antibacterial activity against Escherichia coli and Bacillus. The minimum inhibitory concentrations of these complexes and their antibacterial activities indicate that compound 4 is the potential lead molecule for drug designing. (C) 2012 Elsevier Ltd. All rights reserved.

A study on the usefulness of Support Vector Machines for the realtime computational simulation of soft biological organs

Realistic and realtime computational simulation of soft biological organs (e.g., liver, kidney) is necessary when one tries to build a quality surgical simulator that can simulate surgical procedures involving these organs. Since the realistic simulation of these soft biological organs should account for both nonlinear material behavior and large deformation, achieving realistic simulations in realtime using continuum mechanics based numerical techniques necessitates the use of a supercomputer or a high end computer cluster which are costly. Hence there is a need to employ soft computing techniques like Support Vector Machines (SVMs) which can do function approximation, and hence could achieve physically realistic simulations in realtime by making use of just a desktop computer. Present work tries to simulate a pig liver in realtime. Liver is assumed to be homogeneous, isotropic, and hyperelastic. Hyperelastic material constants are taken from the literature. An SVM is employed to achieve realistic simulations in realtime, using just a desktop computer. The code for the SVM is obtained from [1]. The SVM is trained using the dataset generated by performing hyperelastic analyses on the liver geometry, using the commercial finite element software package ANSYS. The methodology followed in the present work closely follows the one followed in [2] except that [2] uses Artificial Neural Networks (ANNs) while the present work uses SVMs to achieve realistic simulations in realtime. Results indicate the speed and accuracy that is obtained by employing the SVM for the targeted realistic and realtime simulation of the liver.

Charge Injection through Nanocomposite Electrode in Microfluidic Channel for Electrical Lysis of Biological Cells

Several concepts have been developed in the recent years for nanomaterial based integrated MEMS platform in order to accelerate the process of biological sample preparation followed by selective screening and identification of target molecules. In this context, there exist several challenges which need to be addressed in the process of electrical lysis of biological cells. These are due to (i) low resource settings while achieving maximal lysis (ii) high throughput of target molecules to be detected (iii) automated extraction and purification of relevant molecules such as DNA and protein from extremely small volume of sample (iv) requirement of fast, accurate and yet scalable methods (v) multifunctionality toward process monitoring and (vi) downward compatibility with already existing diagnostic protocols. This paper reports on the optimization of electrical lysis process based on various different nanocomposite coated electrodes placed in a microfluidic channel. The nanocomposites are synthesized using different nanomaterials like Zinc nanorod dispersion in polymer. The efficiency of electrical lysis with various different electrode coatings has been experimentally verified in terms of DNA concentration, amplification and protein yield. The influence of the coating thickness on the injection current densities has been analyzed. We further correlate experimentally the current density vs. voltage relationship with the extent of bacterial cell lysis. A coupled multiphysics based simulation model is used to predict the cell trajectories and lysis efficiencies under various electrode boundary conditions as estimated from experimental results. Detailed in-situ fluorescence imaging and spectroscopy studies are performed to validate various hypotheses.