Novel evolutionary models and applications to sequence alignment problems

In this paper, we present a novel graph-theoretical approach for representing a wide variety of sequence analysis problems within a single model. The model allows incorporation of the operations “insertion”, “deletion”, and “substitution”, and various parameters such as relative distances and weights. Conceptually, we refer the problem as the minimum weight common mutated sequence (MWCMS) problem. The MWCMS model has many applications including multiple sequence alignment problem, the phylogenetic analysis, the DNA sequencing problem, and sequence comparison problem, which encompass a core set of very difficult problems in computational biology. Thus the model presented in this paper lays out a mathematical modeling framework that allows one to investigate theoretical and computational issues, and to forge new advances for these distinct, but related problems. Through the introduction of supernodes, and the multi-layer supergraph, we proved that MWCMS is -complete. Furthermore, it was shown that a conflict graph derived from the multi-layer supergraph has the property that a solution to the associated node-packing problem of the conflict graph corresponds to a solution of the MWCMS problem. In this case, we proved that when the number of input sequences is a constant, MWCMS is polynomial-time solvable. We also demonstrated that some well-known combinatorial problems can be viewed as special cases of the MWCMS problem. In particular, we presented theoretical results implied by the MWCMS theory for the minimum weight supersequence problem, the minimum weight superstring problem, and the longest common subsequence problem. Two integer programming formulations were presented and a simple yet elegant decomposition heuristic was introduced. The integer programming instances have proven to be computationally intensive. Consequently, research involving simultaneous column and row generation and parallel computing will be explored. The heuristic algorithm, introduced herein for multiple sequence alignment, overcomes the order-dependent drawbacks of many of the existing algorithms, and is capable of returning good sequence alignments within reasonable computational time. It is able to return the optimal alignment for multiple sequences of length less than 1500 base pairs within 30 minutes. Its algorithmic decomposition nature lends itself naturally for parallel distributed computing, and we continue to explore its flexibility and scalability in a massive parallel environment.     

Synthesis and characterization of Bi-doped zirconia for solid electrolyte

(100-x)ZrO₂(x)Bi₂O₃ (x = 5, 10, 15) system has been synthesized by solid-state reaction technique. Tetragonal Bi_7.38Zr_0.62O_12.31 phase has formed in all the samples after sintering at 850 °C for 24 h. Apart from this, ZrO₂ and Bi₂O₃ are also identified as minority phases. The volume fraction of Bi_7.38Zr_0.62O_12.31 phase increases with increasing concentration of Bi₂O₃. The AC conductivity plots exhibit phase transition at 570 °C and 460 °C for x = 10 and x = 15 samples, respectively. The maximum conductivity is observed (1.60 mS/cm) in x = 15 sample. These results are correlated and supported with microstructural and thermal analysis.     

Interacting branching process as a simple model of innovation

We describe innovation in terms of a generalized branching process. Each new invention pairs with any existing one to produce a number of offspring, which is Poisson distributed with mean p. Existing inventions die with probability p/τ at each generation. In contrast with mean field results, no phase transition occurs; the chance for survival is finite for all p > 0. For τ = ∞, surviving processes exhibit a bottleneck before exploding superexponentially-a growth consistent with a law of accelerating returns. This behavior persists for finite τ. We analyze, in detail, the asymptotic behavior as p→0.     

A higher order uniformly convergent method for singularly perturbed parabolic turning point problems

In this article, we study numerical approximation for a class of singularly perturbed parabolic (SPP) convection-diffusion turning point problems. The considered SPP problem exhibits a parabolic boundary layer in the neighborhood of one of the sides of the domain. Some a priori bounds are given on the exact solution and its derivatives, which are necessary for the error analysis. A numerical scheme comprising of implicit finite difference method for time discretization on a uniform mesh and a hybrid scheme for spatial discretization on a generalized Shishkin mesh is proposed. Then Richardson extrapolation method is applied to increase the order of convergence in time direction. The resulting scheme has second-order convergence up to a logarithmic factor in space and second-order convergence in time. Numerical experiments are conducted to demonstrate the theoretical results and the comparative study is done with the existing schemes in literature to show better accuracy of the proposed schemes.     

Control of defect concentrations within a semiconductor through adsorption

The technologically useful properties of a crystalline solid depend upon the concentration of defects it contains. Here we show that defect concentrations as deep as 0.5 microm within a semiconductor can be profoundly influenced by gas adsorption. Self-diffusion rates within silicon show that nitrogen atoms adsorbed at less than 1% of a monolayer lead to defect concentrations that vary controllably over several orders of magnitude. The results show that previous measurements of diffusion and defect thermodynamics in semiconductors may have suffered from neglect of adsorption effects.     

A new family of Schröder's method and its variants based on power means for multiple roots of nonlinear equations

In this article, we derive one-parameter family of Schröder's method based on Gupta et al.'s (K.C. Gupta, V. Kanwar, and S. Kumar, A family of ellipse methods for solving non-linear equations, Int. J. Math. Educ. Sci. Technol. 40 (2009), pp. 571–575) family of ellipse methods for the solution of nonlinear equations. Further, we introduce new families of Schröder-type methods for multiple roots with cubic convergence. Proposed families are derived from modified Newton's method for multiple roots and one-parameter family of Schröder's method. Numerical examples are also provided to show that these new methods are competitive to other known methods for multiple roots.     

Pyrazole‐4‐carboxylic Acids from Vanadium‐catalyzed Chemical Transformation of Pyrazole‐4‐carbaldehydes

The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole‐4‐aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H₂O₂ as an oxidant is described. The catalytic technology was successfully applied to a range of various 4‐formylpyrazoles, and plausible mechanism is also discussed.     

Diversified Synthetic Strategies for Pyrroloindoles: An Overview

In current scenario, heterocyclic compounds' role in medicinal chemistry has been tremendously increased as they possess wide number of pharmacological activities. One of the common heterocycles include indole skeleton with well‐established biological significance in field of medicinal chemistry. Fusion of indole nucleus with pyrrole heterocycle constitutes pyrroloindole scaffold, which further modifies the existing properties of indole alone. Pyrroloindole is a privileged scaffold found in various types of bioactive entities including natural compounds and exhibits wide variety of pharmacological activities like muscle relaxant, antifungal, antitumor, and antibiotic. Therefore, it is considered as attractive template for drug discovery. From several years, numbers of synthetic strategies have been reported for the synthesis of pyrroloindole and its derivatives, including also natural compounds such as amauromine, yuremamine, and chimonanthines. Here, in this review, we have tried to compile various synthetic strategies of pyrroloindole and its derivatives.     

New lignan glycosides from Cissus quadrangularis stems

Phytochemical investigation of Cissus quadrangularis stems led to the isolation of one new phenolic glycoside (1) and two new lignan glycosides (7 &; 8) along with twelve known compounds (2–6 &; 9–15). Their chemical structures were determined on the basis of extensive spectroscopic analysis using 1D, 2D NMR, and mass spectrometric analysis. Among the known compounds, 4–6, 9 and 12 were isolated for the first time from the genus Cissus whereas compounds 10, 11 and 13 for the first time from this plant.     

Design and Synthesis of Imidazole and Triazole Pyrazoles as Mycobacterium Tuberculosis CYP121A1 Inhibitors

The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (K_D). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert-butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, K_D 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 ų, topological polar surface area <40 Ų.