Tryptophan-water interaction in Monellin:Hydration patterns from molecular dynamics simulations

Femtosecond spectroscopy carried out earlier on Monellin and some other systems has given insights into the hydration dynamics of the proteins. In the present work, molecular dynamics simulations have been performed on Monellin to study the hydration dynamics. A method has been described to follow up the molecular events of the protein–water interactions in detail. The time constants of the survival correlation function match well with the reported experimental values. This validates the procedure, adapted here for Monellin, to investigate the hydration dynamics in general.

Structural Annotation of Mycobacterium tuberculosis Proteome

Of the similar to 4000 ORFs identified through the genome sequence of Mycobacterium tuberculosis (TB) H37Rv, experimentally determined structures are available for 312. Since knowledge of protein structures is essential to obtain a high-resolution understanding of the underlying biology, we seek to obtain a structural annotation for the genome, using computational methods. Structural models were obtained and validated for similar to 2877 ORFs, covering similar to 70% of the genome. Functional annotation of each protein was based on fold-based functional assignments and a novel binding site based ligand association. New algorithms for binding site detection and genome scale binding site comparison at the structural level, recently reported from the laboratory, were utilized. Besides these, the annotation covers detection of various sequence and sub-structural motifs and quaternary structure predictions based on the corresponding templates. The study provides an opportunity to obtain a global perspective of the fold distribution in the genome. The annotation indicates that cellular metabolism can be achieved with only 219 folds. New insights about the folds that predominate in the genome, as well as the fold-combinations that make up multi-domain proteins are also obtained. 1728 binding pockets have been associated with ligands through binding site identification and sub-structure similarity analyses. The resource (http://proline.physics.iisc.ernet.in/Tbstructuralannotation), being one of the first to be based on structure-derived functional annotations at a genome scale, is expected to be useful for better understanding of TB and for application in drug discovery. The reported annotation pipeline is fairly generic and can be applied to other genomes as well.

Implementation of a phase array diffuse optical tomographic imager

Diffuse optical tomography (DOT) using near-infrared (NIR) light is a promising tool for noninvasive imaging of deep tissue. This technique is capable of quantitative reconstructions of absorption coefficient inhomogeneities of tissue. The motivation for reconstructing the optical property variation is that it, and, in particular, the absorption coefficient variation, can be used to diagnose different metabolic and disease states of tissue. In DOT, like any other medical imaging modality, the aim is to produce a reconstruction with good spatial resolution and accuracy from noisy measurements. We study the performance of a phase array system for detection of optical inhomogeneities in tissue. The light transport through a tissue is diffusive in nature and can be modeled using diffusion equation if the optical parameters of the inhomogeneity are close to the optical properties of the background. The amplitude cancellation method that uses dual out-of-phase sources (phase array) can detect and locate small objects in turbid medium. The inverse problem is solved using model based iterative image reconstruction. Diffusion equation is solved using finite element method for providing the forward model for photon transport. The solution of the forward problem is used for computing the Jacobian and the simultaneous equation is solved using conjugate gradient search. The simulation studies have been carried out and the results show that a phase array system can resolve inhomogeneities with sizes of 5 mm when the absorption coefficient of the inhomogeneity is twice that of the background tissue. To validate this result, a prototype model for performing a dual-source system has been developed. Experiments are carried out by inserting an inhomogeneity of high optical absorption coefficient in an otherwise homogeneous phantom while keeping the scattering coefficient same. The high frequency (100 MHz) modulated dual out-of-phase laser source light is propagated through the phantom. The interference of these sources creates an amplitude null and a phase shift of 180° along a plane between the two sources with a homogeneous object. A solid resin phantom with inhomogeneities simulating the tumor is used in our experiment. The amplitude and phase changes are found to be disturbed by the presence of the inhomogeneity in the object. The experimental data (amplitude and the phase measured at the detector) are used for reconstruction. The results show that the method is able to detect multiple inhomogeneities with sizes of 4 mm. The localization error for a 5 mm inhomogeneity is found to be approximately 1 mm.

Diffuse optical tomographic imager using a single light source

Near-infrared diffuse optical tomography (DOT) technique has the capability of providing good quantitative reconstruction of tissue absorption and scattering properties with additional inputs such as input and output modulation depths and correction for the photon leakage. We have calculated the two-dimensional (2D) input modulation depth from three-dimensional (3D) diffusion to model the 2D diffusion of photons. The photon leakage when light traverses from phantom to the fiber tip is estimated using a solid angle model. The experiments are carried for single (5 and 6 mm) as well as multiple inhomogeneities (6 and 8 mm) with higher absorption coefficient in a homogeneous phantom. Diffusion equation for photon transport is solved using finite element method and Jacobian is modeled for reconstructing the optical parameters. We study the development and performance of DOT system using modulated single light source and multiple detectors. The dual source methods are reported to have better reconstruction capabilities to resolve and localize single as well as multiple inhomogeneities because of its superior noise rejection capability. However, an experimental setup with dual sources is much more difficult to implement because of adjustment of two out of phase identical light probes symmetrically on either side of the detector during scanning time. Our work shows that with a relatively simpler system with a single source, the results are better in terms of resolution and localization. The experiments are carried out with 5 and 6 mm inhomogeneities separately and 6 and 8 mm inhomogeneities both together with absorption coefficient almost three times as that of the background. The results show that our experimental single source system with additional inputs such as 2D input/output modulation depth and air fiber interface correction is capable of detecting 5 and 6 mm inhomogeneities separately and can identify the size difference of multiple inhomogeneities such as 6 and 8 mm. The localization error is zero. The recovered absorption coefficient is 93% of inhomogeneity that we have embedded in experimental phantom.

Federated Search Service for OAI-compliant, Open-Access Repositories in India

Many of the research institutions and universities across the world are facilitating open-access (OA) to their intellectual outputs through their respective OA institutional repositories (IRs) or through the centralized subject-based repositories. The registry of open access repositories (ROAR) lists more than 2850 such repositories across the world. The awareness about the benefits of OA to scholarly literature and OA publishing is picking up in India, too. As per the ROAR statistics, to date, there are more than 90 OA repositories in the country. India is doing particularly well in publishing open-access journals (OAJ). As per the directory of open-access journals (DOAJ), to date, India with 390 OAJs, is ranked 5th in the world in terms of numbers of OAJs being published. Much of the research done in India is reported in the journals published from India. These journals have limited readership and many of them are not being indexed by Web of Science, Scopus or other leading international abstracting and indexing databases. Consequently, research done in the country gets hidden not only from the fellow countrymen, but also from the international community. This situation can be easily overcome if all the researchers facilitate OA to their publications. One of the easiest ways to facilitate OA to scientific literature is through the institutional repositories. If every research institution and university in India set up an open-access IR and ensure that copies of the final accepted versions of all the research publications are uploaded in the IRs, then the research done in India will get far better visibility. The federation of metadata from all the distributed, interoperable OA repositories in the country will serve as a window to the research done across the country. Federation of metadata from the distributed OAI-compliant repositories can be easily achieved by setting up harvesting software like the PKP Harvester. In this paper, we share our experience in setting up a prototype metadata harvesting service using the PKP harvesting software for the OAI-compliant repositories in India.

Structural and dielectric characteristics of Bi2O3-TiO2-SrB4O7 glasses

Glasses of the composition 0.20 Bi2O3 - 0.30 TiO2 - 0.50 SrB4O7 and 0.30 Bi2O3 - 0.45 TiO2 - 0.25 SrB4O7 have been fabricated by conventional glass processing technique. These glasses have been characterized using X-ray powder diffraction (XRD), differential thermal analysis (DTA) and high resolution transmission electron microscopy (HRTEM). The frequency response of the dielectric constant and the loss tangent of these glasses has been studied. The formation of the crystalline bismuth titanate, Bi4Ti3O12 (BiT) phase in the heat treated samples has been confirmed by XRD and HRTEM studies. The measured ET Of the glass-ceramics are found to be in good agreement with those predicted by the logarithmic mixture rule. Optical second harmonic generation (SHG) at 1064 nm has been observed in the heat treated samples and is attributed to the formation of crystalline Bi4Ti3O12 (BiT) phase in the SrB4O7 (SBO) matrix.

Practical fully three-dimensional reconstruction algorithms for diffuse optical tomography

We have developed an efficient fully three-dimensional (3D) reconstruction algorithm for diffuse optical tomography (DOT). The 3D DOT, a severely ill-posed problem, is tackled through a pseudodynamic (PD) approach wherein an ordinary differential equation representing the evolution of the solution on pseudotime is integrated that bypasses an explicit inversion of the associated, ill-conditioned system matrix. One of the most computationally expensive parts of the iterative DOT algorithm, the reevaluation of the Jacobian in each of the iterations, is avoided by using the adjoint-Broyden update formula to provide low rank updates to the Jacobian. In addition, wherever feasible, we have also made the algorithm efficient by integrating along the quadratic path provided by the perturbation equation containing the Hessian. These algorithms are then proven by reconstruction, using simulated and experimental data and verifying the PD results with those from the popular Gauss-Newton scheme. The major findings of this work are as follows: (i) the PD reconstructions are comparatively artifact free, providing superior absorption coefficient maps in terms of quantitative accuracy and contrast recovery; (ii) the scaling of computation time with the dimension of the measurement set is much less steep with the Jacobian update formula in place than without it; and (iii) an increase in the data dimension, even though it renders the reconstruction problem less ill conditioned and thus provides relatively artifact-free reconstructions, does not necessarily provide better contrast property recovery. For the latter, one should also take care to uniformly distribute the measurement points, avoiding regions close to the source so that the relative strength of the derivatives for measurements away from the source does not become insignificant. (c) 2012 Optical Society of America

Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative `Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed `3interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

Flux density calibration in diffuse optical tomographic systems

The solution of the forward equation that models the transport of light through a highly scattering tissue material in diffuse optical tomography (DOT) using the finite element method gives flux density (Phi) at the nodal points of the mesh. The experimentally measured flux (U-measured) on the boundary over a finite surface area in a DOT system has to be corrected to account for the system transfer functions (R) of various building blocks of the measurement system. We present two methods to compensate for the perturbations caused by R and estimate true flux density (Phi) from U-measured(cal). In the first approach, the measurement data with a homogeneous phantom (U-measured(homo)) is used to calibrate the measurement system. The second scheme estimates the homogeneous phantom measurement using only the measurement from a heterogeneous phantom, thereby eliminating the necessity of a homogeneous phantom. This is done by statistically averaging the data (U-measured(hetero)) and redistributing it to the corresponding detector positions. The experiments carried out on tissue mimicking phantom with single and multiple inhomogeneities, human hand, and a pork tissue phantom demonstrate the robustness of the approach. (C) 2013 Society of Photo-Optical Instrumentation Engineers (SPIE) DOI: 10.1117/1.JBO.18.2.026023]

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation I as augmentation therapeutic strategy approaches in muscular dystrophy

Backgrond: Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods: In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results: The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

A borane-bithiophene-BODIPY triad: intriguing tricolor emission and selective fluorescence response towards fluoride ions

The structure and photophysical properties of a new triad (borane-bithiophene-BODIPY) 1 have been investigated. Triad 1 exhibits unprecedented tricolour emission when excited at the borane centred high energy absorption band and also acts as a selective fluorescent and colorimetric sensor for fluoride ions with ratiometric response. The experimental results are supported by computational studies.

Correlated Conductance Fluctuations Close to the Berezinskii-Kosterlitz-Thouless Transition in Ultrathin NbN Films

We probe the presence of long-range correlations in phase fluctuations by analyzing the higher-order spectrum of resistance fluctuations in ultrathin NbN superconducting films. The non-Gaussian component of resistance fluctuations is found to be sensitive to film thickness close to the transition, which allows us to distinguish between mean field and Berezinskii-Kosterlitz-Thouless (BKT) type superconducting transitions. The extent of non-Gaussianity was found to be bounded by the BKT and mean field transition temperatures and depends strongly on the roughness and structural inhomogeneity of the superconducting films. Our experiment outlines a novel fluctuation-based kinetic probe in detecting the nature of superconductivity in disordered low-dimensional materials.

Projection Error Propagation-based Regularization (PEPR) method for resistivity reconstruction in Electrical Impedance Tomography (EIT)

A novel Projection Error Propagation-based Regularization (PEPR) method is proposed to improve the image quality in Electrical Impedance Tomography (EIT). PEPR method defines the regularization parameter as a function of the projection error developed by difference between experimental measurements and calculated data. The regularization parameter in the reconstruction algorithm gets modified automatically according to the noise level in measured data and ill-posedness of the Hessian matrix. Resistivity imaging of practical phantoms in a Model Based Iterative Image Reconstruction (MoBIIR) algorithm as well as with Electrical Impedance Diffuse Optical Reconstruction Software (EIDORS) with PEPR. The effect of PEPR method is also studied with phantoms with different configurations and with different current injection methods. All the resistivity images reconstructed with PEPR method are compared with the single step regularization (STR) and Modified Levenberg Regularization (LMR) techniques. The results show that, the PEPR technique reduces the projection error and solution error in each iterations both for simulated and experimental data in both the algorithms and improves the reconstructed images with better contrast to noise ratio (CNR), percentage of contrast recovery (PCR), coefficient of contrast (COC) and diametric resistivity profile (DRP). (C) 2013 Elsevier Ltd. All rights reserved.

Going beyond Red with a Tri- and Tetracoordinate Boron Conjugate: Intriguing Near-IR Optical Properties and Applications in Anion Sensing

The design and synthesis of a new tri- and tetracoordinate boron conjugate is reported. The conjugate shows broad near-IR emission (similar to 625-850 nm) and is found to be a selective colorimetric and ratiometric sensor for fluoride ions.

Studies on an improved indigenous pressure wave generator and its testing with a pulse tube cooler

Earlier version of an indigenously developed Pressure Wave Generator (PWG) could not develop the necessary pressure ratio to satisfactorily operate a pulse tube cooler, largely due to high blow by losses in the piston cylinder seal gap and due to a few design deficiencies. Effect of different parameters like seal gap, piston diameter, piston stroke, moving mass and the piston back volume on the performance is studied analytically. Modifications were done to the PWG based on analysis and the performance is experimentally measured. A significant improvement in PWG performance is seen as a result of the modifications. The improved PWG is tested with the same pulse tube cooler but with different inertance tube configurations. A no load temperature of 130 K is achieved with an inertance tube configuration designed using Sage software. The delivered PV power is estimated to be 28.4 W which can produce a refrigeration of about 1 W at 80 K.