NrichD database: sequence databases enriched with computationally designed protein-like sequences aid in remote homology detection

NrichD ( ext-link-type=''uri'' xlink:href=''http://proline.biochem.iisc.ernet.in/NRICHD/'' xlink:type=''simple''>http://proline.biochem.iisc.ernet.in/NRICHD/)< /named-content> is a database of computationally designed protein-like sequences, augmented into natural sequence databases that can perform hops in protein sequence space to assist in the detection of remote relationships. Establishing protein relationships in the absence of structural evidence or natural `intermediately related sequences' is a challenging task. Recently, we have demonstrated that the computational design of artificial intermediary sequences/linkers is an effective approach to fill naturally occurring voids in protein sequence space. Through a large-scale assessment we have demonstrated that such sequences can be plugged into commonly employed search databases to improve the performance of routinely used sequence search methods in detecting remote relationships. Since it is anticipated that such data sets will be employed to establish protein relationships, two databases that have already captured these relationships at the structural and functional domain level, namely, the SCOP database and the Pfam database, have been `enriched' with these artificial intermediary sequences. NrichD database currently contains 3 611 010 artificial sequences that have been generated between 27 882 pairs of families from 374 SCOP folds. The data sets are freely available for download. Additional features include the design of artificial sequences between any two protein families of interest to the user.

Water-responsive carbon nanotubes for selective detection of toxic gases

Ammonia plays an important role in our daily lives and hence its quantitative and qualitative sensing has become necessary. Bulk structure of carbon nanotubes (CNTs) has been employed to detect the gas concentration of 10 ppm. Hydrophobic CNTs were turned to hydrophilic via the application of a ramp electric field that allowed confinement of a controlled amount of water inside CNT microstructure. These samples were then also used to detect different gases. A comparative study has been performed for sensing three reducing gases, namely, ammonia, sulphur-di-oxide, and hydrogen sulphide to elaborate the selectivity of the sensor. A considerable structural bending in the bulk CNT was observed on evaporation of the confined water, which can be accounted to the zipping of individual nanotubes. However, the rate of the stress induced on these bulk microstructures increased on the exposure of ammonia due to the change in the surface tension of the confined solvent. A prototype of an alarm system has been developed to illustrate sensing concept, wherein the generated stress in the bulk CNT induces a reversible loss in electrical contact that changes the equivalent resistance of the electrical circuit upon exposure to the gas. (C) 2015 AIP Publishing LLC.

Detection of G-Quadruplex DNA Using Primer Extension as a Tool

DNA sequence and structure play a key role in imparting fragility to different regions of the genome. Recent studies have shown that non-B DNA structures play a key role in causing genomic instability, apart from their physiological roles at telomeres and promoters. Structures such as G-quadruplexes, cruciforms, and triplexes have been implicated in making DNA susceptible to breakage, resulting in genomic rearrangements. Hence, techniques that aid in the easy identification of such non-B DNA motifs will prove to be very useful in determining factors responsible for genomic instability. In this study, we provide evidence for the use of primer extension as a sensitive and specific tool to detect such altered DNA structures. We have used the G-quadruplex motif, recently characterized at the BCL2 major breakpoint region as a proof of principle to demonstrate the advantages of the technique. Our results show that pause sites corresponding to the non-B DNA are specific, since they are absent when the G-quadruplex motif is mutated and their positions change in tandem with that of the primers. The efficiency of primer extension pause sites varied according to the concentration of monovalant cations tested, which support G-quadruplex formation. Overall, our results demonstrate that primer extension is a strong in vitro tool to detect non-B DNA structures such as G-quadruplex on a plasmid DNA, which can be further adapted to identify non-B DNA structures, even at the genomic level.

Analyzing the kinetic response of tin oxide-carbon and tin oxide-CNT composites gas sensors for alcohols detection

Tin oxide nanoparticles are synthesized using solution combustion technique and tin oxide - carbon composite thick films are fabricated with amorphous carbon as well as carbon nanotubes (CNTs). The x-ray diffraction, Raman spectroscopy and porosity measurements show that the as-synthesized nanoparticles are having rutile phase with average crystallite size similar to 7 nm and similar to 95 m(2)/g surface area. The difference between morphologies of the carbon doped and CNT doped SnO2 thick films, are characterized using scanning electron microscopy and transmission electron microscopy. The adsorption-desorption kinetics and transient response curves are analyzed using Langmuir isotherm curve fittings and modeled using power law of semiconductor gas sensors. (C) 2015 Author(s).

Electron-Rich Triphenylamine-Based Sensors for Picric Acid Detection

This paper demonstrates the role of solvent in selectivity and sensitivity of a series of electron-rich compounds for the detection of trace amounts of picric acid. Two new electron-rich fluorescent esters (6, 7) containing a triphenylamine backbone as well as their analogous carboxylic acids (8, 9) have been synthesized and characterized. Fluorescent triphenylamine coupled with an ethynyl moiety constitutes p-electron-rich selective and sensitive probes for electron-deficient picric acid (PA). In solution, the high sensitivity of all the sensors toward PA can be attributed to a combined effect of the ground-state charge-transfer complex formation and resonance energy transfer between the sensor and analyte. The acids 8 and 9 also showed enhanced sensitivity for nitroaromatics in the solid state, and their enhanced sensitivity could be attributed to exciton migration due to close proximity of the neighboring acid molecules, as evident from the X-ray diffraction study. The compounds were found to be quite sensitive for the detection of trace amount of nitroaromatics in solution, solid, and contact mode.

Synthesis of cadmium oxide and carbon nanotube based nanocomposites and their use as a sensing interface for xanthine detection

Xanthine oxidase (XOD) extracted from bovine milk was immobilized covalently via N-ethyl-N'-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxy succinimide (NHS) chemistry onto cadmium oxide nanoparticles (CdO)/carboxylated multiwalled carbon nanotube (c-MWCNT) composite film electrodeposited on the surface of an Au electrode. The nanocomposite modified Au electrode was characterized by Fourier transform infrared (FTIR), cyclic voltammetry (CV), scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) before and after immobilization of XOD. Under optimal operation conditions (25 degrees C, + 0.2 V vs. Ag/AgCl, sodium phosphate buffer, pH 7.5), the following characteristics are attributed to the biosensor: linearity of response up to xanthine concentrations of 120 mu M, detection limit of 0.05 mu M (S/N = 3) and a response time of at most 4 s. After being used 100 times over a period of 120 days, only 50% loss of the initial activity of the biosensor was evaluated when stored at 4 degrees C. The fabricated biosensor was successfully employed for the determination of xanthine in fish meat.

Postsynthetic Exterior Decoration of an Organic Cage by Copper(I)-Catalysed A(3)-Coupling and Detection of Nitroaromatics

A new synthetic protocol based on one-pot, copper(I)-catalysed multicomponent reaction of formaldehyde, secondary amine and terminal alkyne has been employed to postsynthetically modify a self-assembled nanoscopic organic cage. By employing this synthetic strategy, three new cages appended with phenyl-, xylyl-and naphthyl-acetylene moieties have been synthesised. The resulting modified cages were characterised by using a range of spectroscopic techniques. The synthesised cages were fluorescent and thus one of them was tested to explore the potential use of such compounds as chemosensors for the detection of nitroaromatics. Experimental findings suggest a high selective quenching of initial fluorescence intensity in the presence of nitroaromatic compounds. Furthermore, it has been observed that among the various nitroaromatics tested, nitrophenolic compounds have better quenching ability.

Polyfunctional Lewis Acids: Intriguing Solid-State Structure and Selective Detection and Discrimination of Nitroaromatic Explosives

Synthesis and crystal structures of three porphyrin-based polyfunctional Lewis acids 1-3 are reported. Intermolecular HgClHgCl (linear and -type) interactions in the solid state of the peripherally ArHgCl-decorated compound 3 lead to a fascinating 3D supramolecular architecture. Compound3 shows a selective fluorescence quenching response to picric acid and discriminates other nitroaromatic-based explosives. For the first time, an electron-deficient polyfunctional Lewis acid is shown to be useful for the selective detection and discrimination of nitroaromatic explosives. The Stern-Volmer quenching constant and detection limits of compound3 for picric acid are the best among the reported small-molecular receptors for nitroaromatic explosives. The electronic structure, Lewis acidity, and selective sensing characteristics of 3 are well corroborated by DFT calculations.

Coherent (photon) vs incoherent (current) detection of multidimensional optical signals from single molecules in open junctions

The nonlinear optical response of a current-carrying single molecule coupled to two metal leads and driven by a sequence of impulsive optical pulses with controllable phases and time delays is calculated. Coherent (stimulated, heterodyne) detection of photons and incoherent detection of the optically induced current are compared. Using a diagrammatic Liouville space superoperator formalism, the signals are recast in terms of molecular correlation functions which are then expanded in the many-body molecular states. Two dimensional signals in benzene-1,4-dithiol molecule show cross peaks involving charged states. The correlation between optical and charge current signal is also observed. (C) 2015 AIP Publishing LLC.

A New Algorithm for Nonparametric Sequential Detection

We consider nonparametric sequential hypothesis testing problem when the distribution under the null hypothesis is fully known but the alternate hypothesis corresponds to a general family of distributions. We propose a simple algorithm to address the problem. Its performance is analysed and asymptotic properties are proved. The simulated and analysed performance of the algorithm is compared with an earlier algorithm addressing the same problem with similar assumptions. Finally, we provide a justification for our model motivated by a Cognitive Radio scenario and modify the algorithm for optimizing performance when information about the prior probabilities of occurrence of the two hypotheses is available.

Detection of a quantum particle on a lattice under repeated projective measurements

We consider a quantum particle, moving on a lattice with a tight-binding Hamiltonian, which is subjected to measurements to detect its arrival at a particular chosen set of sites. The projective measurements are made at regular time intervals tau, and we consider the evolution of the wave function until the time a detection occurs. We study the probabilities of its first detection at some time and, conversely, the probability of it not being detected (i.e., surviving) up to that time. We propose a general perturbative approach for understanding the dynamics which maps the evolution operator, which consists of unitary transformations followed by projections, to one described by a non-Hermitian Hamiltonian. For some examples of a particle moving on one-and two-dimensional lattices with one or more detection sites, we use this approach to find exact expressions for the survival probability and find excellent agreement with direct numerical results. A mean-field model with hopping between all pairs of sites and detection at one site is solved exactly. For the one-and two-dimensional systems, the survival probability is shown to have a power-law decay with time, where the power depends on the initial position of the particle. Finally, we show an interesting and nontrivial connection between the dynamics of the particle in our model and the evolution of a particle under a non-Hermitian Hamiltonian with a large absorbing potential at some sites.

Robust Whisper Activity Detection Using Long-Term Log Energy Variation of Sub-Band Signal

The goal in the whisper activity detection (WAD) is to find the whispered speech segments in a given noisy recording of whispered speech. Since whispering lacks the periodic glottal excitation, it resembles an unvoiced speech. This noise-like nature of the whispered speech makes WAD a more challenging task compared to a typical voice activity detection (VAD) problem. In this paper, we propose a feature based on the long term variation of the logarithm of the short-time sub-band signal energy for WAD. We also propose an automatic sub-band selection algorithm to maximally discriminate noisy whisper from noise. Experiments with eight noise types in four different signal-to-noise ratio (SNR) conditions show that, for most of the noises, the performance of the proposed WAD scheme is significantly better than that of the existing VAD schemes and whisper detection schemes when used for WAD.

Boron and Nitrogen Co-doped Carbon Nanoparticles as Photoluminescent Probes for Selective and Sensitive Detection of Picric Acid

Here, we report the synthesis of boron and nitrogen Co-doped carbon nanoparticles (BN-CNPs) by a hydrothermal method using sucrose, boric acid, and urea as the precursors. The BN-CNPs show excellent photoluminescence with a quantum yield of similar to 14.2% in aqueous solution and can be used as photoluminescent probes for selective and sensitive detection of picric acid (PA). PA quenches the photoluminescence signal remarkably, while other explosives cause a little quenching confirming the high selectivity of BN-CNPs. The sensitivity toward PA sensing is high at pH 7 and increases with temperature. The detection limit as well as the sensitivity are shown to improve by adding NaCl to the PA. The low detection limit can be as low as 10 nM at room temperature and pH 7, which indicates the BN-CNPs are superior as compared to other luminescent probes reported in the literature.

De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods

Background: In the post-genomic era where sequences are being determined at a rapid rate, we are highly reliant on computational methods for their tentative biochemical characterization. The Pfam database currently contains 3,786 families corresponding to ``Domains of Unknown Function'' (DUF) or ``Uncharacterized Protein Family'' (UPF), of which 3,087 families have no reported three-dimensional structure, constituting almost one-fourth of the known protein families in search for both structure and function. Results: We applied a `computational structural genomics' approach using five state-of-the-art remote similarity detection methods to detect the relationship between uncharacterized DUFs and domain families of known structures. The association with a structural domain family could serve as a start point in elucidating the function of a DUF. Amongst these five methods, searches in SCOP-NrichD database have been applied for the first time. Predictions were classified into high, medium and low-confidence based on the consensus of results from various approaches and also annotated with enzyme and Gene ontology terms. 614 uncharacterized DUFs could be associated with a known structural domain, of which high confidence predictions, involving at least four methods, were made for 54 families. These structure-function relationships for the 614 DUF families can be accessed on-line at http://proline.biochem.iisc.ernet.in/RHD_DUFS/. For potential enzymes in this set, we assessed their compatibility with the associated fold and performed detailed structural and functional annotation by examining alignments and extent of conservation of functional residues. Detailed discussion is provided for interesting assignments for DUF3050, DUF1636, DUF1572, DUF2092 and DUF659. Conclusions: This study provides insights into the structure and potential function for nearly 20 % of the DUFs. Use of different computational approaches enables us to reliably recognize distant relationships, especially when they converge to a common assignment because the methods are often complementary. We observe that while pointers to the structural domain can offer the right clues to the function of a protein, recognition of its precise functional role is still `non-trivial' with many DUF domains conserving only some of the critical residues. It is not clear whether these are functional vestiges or instances involving alternate substrates and interacting partners. Reviewers: This article was reviewed by Drs Eugene Koonin, Frank Eisenhaber and Srikrishna Subramanian.

Damage quantification under sliding and seizure condition using first-of-a-kind fretting machine

In a practical situation, it is difficult to model exact contact conditions clue to challenges involved in the estimation of contact forces, and relative displacements between the contacting bodies. Sliding and seizure conditions were simulated on first-of-a-kind displacement controlled system. Self-mated stainless steels have been investigated in detail. Categorization of contact conditions prevailing at the contact interface has been carried out based on the variation of coefficient of friction with number of cycles, and three-dimensional fretting loops. Surface and subsurface micro-cracks have been observed, and their characteristic shows strong dependence on loading conditions. Existence of shear bands in the subsurface region has been observed for high strain and low strain rate loading conditions. Studies also include the influence of initial surface roughness on the damage under two extreme contact conditions. (C) 2013 Elsevier B.V. All rights reserved.