Computational Techniques for Haplotype Inference and for Local Alignment Significance

This thesis which consists of an introduction and four peer-reviewed original publications studies the problems of haplotype inference (haplotyping) and local alignment significance. The problems studied here belong to the broad area of bioinformatics and computational biology. The presented solutions are computationally fast and accurate, which makes them practical in high-throughput sequence data analysis. Haplotype inference is a computational problem where the goal is to estimate haplotypes from a sample of genotypes as accurately as possible. This problem is important as the direct measurement of haplotypes is difficult, whereas the genotypes are easier to quantify. Haplotypes are the key-players when studying for example the genetic causes of diseases. In this thesis, three methods are presented for the haplotype inference problem referred to as HaploParser, HIT, and BACH. HaploParser is based on a combinatorial mosaic model and hierarchical parsing that together mimic recombinations and point-mutations in a biologically plausible way. In this mosaic model, the current population is assumed to be evolved from a small founder population. Thus, the haplotypes of the current population are recombinations of the (implicit) founder haplotypes with some point--mutations. HIT (Haplotype Inference Technique) uses a hidden Markov model for haplotypes and efficient algorithms are presented to learn this model from genotype data. The model structure of HIT is analogous to the mosaic model of HaploParser with founder haplotypes. Therefore, it can be seen as a probabilistic model of recombinations and point-mutations. BACH (Bayesian Context-based Haplotyping) utilizes a context tree weighting algorithm to efficiently sum over all variable-length Markov chains to evaluate the posterior probability of a haplotype configuration. Algorithms are presented that find haplotype configurations with high posterior probability. BACH is the most accurate method presented in this thesis and has comparable performance to the best available software for haplotype inference. Local alignment significance is a computational problem where one is interested in whether the local similarities in two sequences are due to the fact that the sequences are related or just by chance. Similarity of sequences is measured by their best local alignment score and from that, a p-value is computed. This p-value is the probability of picking two sequences from the null model that have as good or better best local alignment score. Local alignment significance is used routinely for example in homology searches. In this thesis, a general framework is sketched that allows one to compute a tight upper bound for the p-value of a local pairwise alignment score. Unlike the previous methods, the presented framework is not affeced by so-called edge-effects and can handle gaps (deletions and insertions) without troublesome sampling and curve fitting.

Charge transfer complexes of crown ethers with neutral organic gyama-acceptor, 2-dicyanoethylene 1,3-indane dione

The interaction of benzo-15-crown-5, dibenzo-18-crown-6 and dibenzo-24-crown-8 with 2-dicyanoethylene 1,3-indane dione in CH2Cl2 has been described in terms of the formation of 1 : 1 molecular complexes. The magnitude of association constants and thermodynamic parameters indicate cooperative interactions of oxygens with the acceptors. The 1H and 13C NMR spectra of the complexes show that gyama-gyama interactions are a major source of ground state stabilization in these complexes.

Isoaccepting Lysine Transfer Ribonucleic Acid Species of Pseudomonas Aeruginosa

Pseudomonas aeruginosa tRNA was treated with iodine, CNBr and N-ethylmaleimide,three thionucleotide-specific reagents. Reaction with iodine resulted in extensive loss of acceptor activity by lysine tRNA, glutamic acid tRNA, glutamine tRNA, serine tRNA and tyrosine tRNA. CNBr treatment resulted in high loss of acceptor ability by lysine tRNA, glutamic acid tRNA and glutamine tRNA. Only the acceptor ability of tyrosine tRNA was inhibited up to 66% by N-ethylmaleimide treatment, a reagent specific for 4-thiouridine. By the combined use of benzoylated DEAE-cellulose and DEAESephadex columns, lysine tRNA of Ps. aeruginosa was resolved into two isoaccepting species, a major, tRNAL'y and a minor, tRNA'Ys. Co-chromatography of 14C-labelled tRNALYS and 3H-labelled tRNALy, on benzoylated DEAE-cellulose at pH4.5 gave two distinct, non-superimposable profiles for the two activity peaks, suggesting that they were separate species. The acceptor activity of these two species was inhibited by about 95% by iodine and CNBr. Both the species showed equal response to codons AAA and AAG and also for poly(A) and poly(A1,Gl) suggesting that the anticodon of these species was UUU. Chemical modification of these two species by iodine did not inhibit the coding response. The two species of lysine of Ps. aeruginosa are truly redundant in that they are indistinguishable either by chemical modification or by their coding response.

Harmonic Analysis of Advanced Bus-Clamping PWM Techniques

Special switching sequences can be employed in space-vector-based generation of pulsewidth-modulated (PWM) waveforms for voltage-source inverters. These sequences involve switching a phase twice, switching the second phase once, and clamping the third phase in a subcycle. Advanced bus-clamping PWM (ABCPWM) techniques have been proposed recently that employ such switching sequences. This letter studies the spectral properties of the waveforms produced by these PWM techniques. Further, analytical closed-form expressions are derived for the total rms harmonic distortion due to these techniques. It is shown that the ABCPWM techniques lead to lower distortion than conventional space vector PWM and discontinuous PWM at higher modulation indexes. The findings are validated on a 2.2-kW constant $V/f$ induction motor drive and also on a 100-kW motor drive.

Charge transfer in Chevrel phases

Chemical shifts of Mo K-absorption edge and Mo core level binding energies in Ax Mo6 Ch8 (Ch = S, Se, Te) Chevrel phases show clear evidence for charge transfer from the A element to the Mo6 cluster. The chemical shifts vary linearly with the intercluster Mo-Mo distance as well as the rhombohedral parameter.

Superhydrophobic fabrics for oil-water separation based on the metal organic charge transfer complex CuTCNAQ

This work reports on the fabrication of a superhydrophobic nylon textile based on the organic charge transfer complex CuTCNAQ (TCNAQ = 11,11,12,12-tetracyanoanthraquinodimethane). The nylon fabric that is metallized with copper undergoes a spontaneous chemical reaction with TCNAQ dissolved in acetonitrile to form nanorods of CuTCNAQ that are intertwined over the entire surface of the fabric. This creates the necessary micro and nanoscale roughness that is required for the Cassie-Baxter state thereby achieving a superhydrophobic/superoleophilic surface without the need for a fluorinated surface. The material is characterised with SEM, FT-IR and XPS spectroscopy and investigated for its ability to separate oil and water in two modes, namely under gravity and as an absorbent. It is found that the fabric can separate dichloromethane, olive oil and crude oil from water and in fact reduce the water content of the oil during the separation process. The fabric is reusable and tolerant to conditions such as seawater, hydrochloric acid and extensive time periods on the shelf. Given that CuTCNAQ is a copper based semiconductor may also open up the possibility of other applications in areas such as photocatalysis and antibacterial applications.

Feature selection and the concept of immediate neighborhood in the context of clustering techniques

The concept of feature selection in a nonparametric unsupervised learning environment is practically undeveloped because no true measure for the effectiveness of a feature exists in such an environment. The lack of a feature selection phase preceding the clustering process seriously affects the reliability of such learning. New concepts such as significant features, level of significance of features, and immediate neighborhood are introduced which result in meeting implicitly the need for feature slection in the context of clustering techniques.

Mass transfer with surface reaction in arrays of cylinders at low reynolds and high peclet numbers

Creeping flow hydrodynamics combined with diffusion boundary layer equation are solved in conjunction with free-surface cell model to obtain a solution of the problem of convective transfer with surface reaction for flow parallel to an array of cylindrical pellets at high Peclet numbers and under fast and intermediate kinetics regimes. Expressions are derived for surface concentration, boundary layer thickness, mass flux and Sherwood number in terms of Damkoehler number, Peclet number and void fraction of the array. The theoretical results are evaluated numerically.

Application of the Conjugate Gradient Method to a Problem on Minimum Time Orbit Transfer

This correspondence considers the problem of optimally controlling the thrust steering angle of an ion-propelled spaceship so as to effect a minimum time coplanar orbit transfer from the mean orbital distance of Earth to mean Martian and Venusian orbital distances. This problem has been modelled as a free terminal time-optimal control problem with unbounded control variable and with state variable equality constraints at the final time. The problem has been solved by the penalty function approach, using the conjugate gradient algorithm. In general, the optimal solution shows a significant departure from earlier work. In particular, the optimal control in the case of Earth-Mars orbit transfer, during the initial phase of the spaceship's flight, is found to be negative, resulting in the motion of the spaceship within the Earth's orbit for a significant fraction of the total optimized orbit transfer time. Such a feature exhibited by the optimal solution has not been reported at all by earlier investigators of this problem.

Separation of sulfur-containing components of transfer ribonucleic acid on Bio-Gel P-2 and Sephadex G-10 columns

S-Labeled nucleosides of E. coli tRNA and some of the derivatives of thionucleosides were separated on Bio-Gel P-2 and Sephadex G-10 columns employing buffers of low salt concentration and high pH.

Review of continuum, finite element and hybrid techniques in the analysis of stress concentrations in structures

When a uniform flow of any nature is interrupted, the readjustment of the flow results in concentrations and rare-factions, so that the peak value of the flow parameter will be higher than that which an elementary computation would suggest. When stress flow in a structure is interrupted, there are stress concentrations. These are generally localized and often large, in relation to the values indicated by simple equilibrium calculations. With the advent of the industrial revolution, dynamic and repeated loading of materials had become commonplace in engine parts and fast moving vehicles of locomotion. This led to serious fatigue failures arising from stress concentrations. Also, many metal forming processes, fabrication techniques and weak-link type safety systems benefit substantially from the intelligent use or avoidance, as appropriate, of stress concentrations. As a result, in the last 80 years, the study and and evaluation of stress concentrations has been a primary objective in the study of solid mechanics. Exact mathematical analysis of stress concentrations in finite bodies presents considerable difficulty for all but a few problems of infinite fields, concentric annuli and the like, treated under the presumption of small deformation, linear elasticity. A whole series of techniques have been developed to deal with different classes of shapes and domains, causes and sources of concentration, material behaviour, phenomenological formulation, etc. These include real and complex functions, conformal mapping, transform techniques, integral equations, finite differences and relaxation, and, more recently, the finite element methods. With the advent of large high speed computers, development of finite element concepts and a good understanding of functional analysis, it is now, in principle, possible to obtain with economy satisfactory solutions to a whole range of concentration problems by intelligently combining theory and computer application. An example is the hybridization of continuum concepts with computer based finite element formulations. This new situation also makes possible a more direct approach to the problem of design which is the primary purpose of most engineering analyses. The trend would appear to be clear: the computer will shape the theory, analysis and design.

Laminar compressible boundary layers with vectored mass transfer

The paper studies the influence of vectored suction or injection on the flow and heat transfer at the stagnation point of a two-dimensional body (a cylinder) and an axisymmetric body (a sphere) with allowance for the effects of variable gas properties. The analysis is based on the boundary-layer equations in dimensionless form for the steady compressible fluid with variable properties in the stagnation region of a two-dimensional or an axisymmetric body with tangential and normal surface mass transfer under similarity requirements. It is shown that the variation of the density-viscosity product across the boundary layer has a strong effect on the skin friction and heat transfer. This gives rise to a point of inflection which can be removed by suction and by increasing the wall temperature. The skin friction and heat transfer are significantly affected by the pressure gradient parameter.