Identifying candidate subunit vaccines using an alignment-independent method based on principal amino acid properties

Subunit vaccine discovery is an accepted clinical priority. The empirical approach is time- and labor-consuming and can often end in failure. Rational information-driven approaches can overcome these limitations in a fast and efficient manner. However, informatics solutions require reliable algorithms for antigen identification. All known algorithms use sequence similarity to identify antigens. However, antigenicity may be encoded subtly in a sequence and may not be directly identifiable by sequence alignment. We propose a new alignment-independent method for antigen recognition based on the principal chemical properties of protein amino acid sequences. The method is tested by cross-validation on a training set of bacterial antigens and external validation on a test set of known antigens. The prediction accuracy is 83% for the cross-validation and 80% for the external test set. Our approach is accurate and robust, and provides a potent tool for the in silico discovery of medically relevant subunit vaccines.

Eye alignment:a novel approach

This thesis describes the design and development of an eye alignment/tracking system which allows self alignment of the eye’s optical axis with a measurement axis. Eye alignment is an area of research largely over-looked, yet it is a fundamental requirement in the acquisition of clinical data from the eye. New trends in the ophthalmic market, desiring portable hand-held apparatus, and the application of ophthalmic measurements in areas other than vision care have brought eye alignment under new scrutiny. Ophthalmic measurements taken in hand-held devices with out an clinician present requires alignment in an entirely new set of circumstances, requiring a novel solution. In order to solve this problem, the research has drawn upon eye tracking technology to monitor the eye, and a principle of self alignment to perform alignment correction. A handheld device naturally lends itself to the patient performing alignment, thus a technique has been designed to communicate raw eye tracking data to the user in a manner which allows the user to make the necessary corrections. The proposed technique is a novel methodology in which misalignment to the eye’s optical axis can be quantified, corrected and evaluated. The technique uses Purkinje Image tracking to monitor the eye’s movement as well as the orientation of the optical axis. The use of two sets of Purkinje Images allows quantification of the eye’s physical parameters needed for accurate Purkinje Image tracking, negating the need for prior anatomical data. An instrument employing the methodology was subsequently prototyped and validated, allowing a sample group to achieve self alignment of their optical axis with an imaging axis within 16.5-40.8 s, and with a rotational precision of 0.03-0.043°(95% confidence intervals). By encompassing all these factors the technique facilitates self alignment from an unaligned position on the visual axis to an aligned position on the optical axis. The consequence of this is that ophthalmic measurements, specifically pachymetric measurements, can be made in the absence of an optician, allowing the use of ophthalmic instrumentation and measurements in health professions other than vision care.

A statistical physics perspective on alignment-independent protein sequence comparison.

Motivation: Within bioinformatics, the textual alignment of amino acid sequences has long dominated the determination of similarity between proteins, with all that implies for shared structure, function, and evolutionary descent. Despite the relative success of modern-day sequence alignment algorithms, so-called alignment-free approaches offer a complementary means of determining and expressing similarity, with potential benefits in certain key applications, such as regression analysis of protein structure-function studies, where alignment-base similarity has performed poorly. Results: Here, we offer a fresh, statistical physics-based perspective focusing on the question of alignment-free comparison, in the process adapting results from “first passage probability distribution” to summarize statistics of ensemble averaged amino acid propensity values. In this paper, we introduce and elaborate this approach.

Weak form equation–based finite-element modeling of viscoelastic asphalt mixtures

The objective of this study is to demonstrate using weak form partial differential equation (PDE) method for a finite-element (FE) modeling of a new constitutive relation without the need of user subroutine programming. The viscoelastic asphalt mixtures were modeled by the weak form PDE-based FE method as the examples in the paper. A solid-like generalized Maxwell model was used to represent the deforming mechanism of a viscoelastic material, the constitutive relations of which were derived and implemented in the weak form PDE module of Comsol Multiphysics, a commercial FE program. The weak form PDE modeling of viscoelasticity was verified by comparing Comsol and Abaqus simulations, which employed the same loading configurations and material property inputs in virtual laboratory test simulations. Both produced identical results in terms of axial and radial strain responses. The weak form PDE modeling of viscoelasticity was further validated by comparing the weak form PDE predictions with real laboratory test results of six types of asphalt mixtures with two air void contents and three aging periods. The viscoelastic material properties such as the coefficients of a Prony series model for the relaxation modulus were obtained by converting from the master curves of dynamic modulus and phase angle. Strain responses of compressive creep tests at three temperatures and cyclic load tests were predicted using the weak form PDE modeling and found to be comparable with the measurements of the real laboratory tests. It was demonstrated that the weak form PDE-based FE modeling can serve as an efficient method to implement new constitutive models and can free engineers from user subroutine programming.

Soliton's eigenvalue based analysis on the generation mechanism of rogue wave phenomenon in optical fibers exhibiting weak third order dispersion

One of the extraordinary aspects of nonlinear wave evolution which has been observed as the spontaneous occurrence of astonishing and statistically extraordinary amplitude wave is called rogue wave. We show that the eigenvalues of the associated equation of nonlinear Schrödinger equation are almost constant in the vicinity of rogue wave and we validate that optical rogue waves are formed by the collision between quasi-solitons in anomalous dispersion fiber exhibiting weak third order dispersion.

Transitive state alignment for the quantum jensen-shannon kernel

Kernel methods provide a convenient way to apply a wide range of learning techniques to complex and structured data by shifting the representational problem from one of finding an embedding of the data to that of defining a positive semidefinite kernel. One problem with the most widely used kernels is that they neglect the locational information within the structures, resulting in less discrimination. Correspondence-based kernels, on the other hand, are in general more discriminating, at the cost of sacrificing positive-definiteness due to their inability to guarantee transitivity of the correspondences between multiple graphs. In this paper we generalize a recent structural kernel based on the Jensen-Shannon divergence between quantum walks over the structures by introducing a novel alignment step which rather than permuting the nodes of the structures, aligns the quantum states of their walks. This results in a novel kernel that maintains localization within the structures, but still guarantees positive definiteness. Experimental evaluation validates the effectiveness of the kernel for several structural classification tasks. © 2014 Springer-Verlag Berlin Heidelberg.

Between global ambitions and local change:how multi-level cooperation advances norm implementation in weak states

The purpose of this article is to investigate in which ways multi-level actor cooperation advances national and local implementation processes of human rights norms in weak-state contexts. Examining the cases of women’s rights in Bosnia and Herzegovina and children’s rights in Bangladesh, we comparatively point to some advantages and disadvantages cooperative relations between international organisations, national governments and local NGOs can entail. Whereas these multi-level actor constellations (MACs) usually initiate norm implementation processes reliably and compensate governmental deficits, they are not always sustainable in the long run. If international organisations withdraw support from temporary missions or policy projects, local NGOs are not able to perpetuate implementation activities if state capacities have not been strengthened by MACs. Our aim is to highlight functions of local agency within multi-level cooperation and to critically raise sustainability issues in human rights implementation to supplement norm research in International Relations.

Molecular alignment relaxation in polymer optical fibers for sensing applications

A systematic study of annealing behavior of drawn PMMA fibers was performed. Annealing dynamics were investigated under different environmental conditions by fiber longitudinal shrinkage monitoring. The shrinkage process was found to follow a stretched exponential decay function revealing the heterogeneous nature of the underlying molecular dynamics. The complex dependence of the fiber shrinkage on initial degree of molecular alignment in the fiber, annealing time and temperature was investigated and interpreted. Moreover, humidity was shown to have a profound effect on the annealing process, which was not recognized previously. Annealing was also shown to have considerable effect on the fiber mechanical properties associated with the relaxation of molecular alignment in the fiber. The consequences of fiber annealing for the climatic stability of certain polymer optical fiber-based sensors are discussed, emphasizing the importance of fiber controlled pre-annealing with respect to the foreseeable operating conditions.

Weak Langmuir optical turbulence in a fiber cavity

We study theoretically and numerically the dynamics of a passive optical fiber ring cavity pumped by a highly incoherent wave: an incoherently injected fiber laser. The theoretical analysis reveals that the turbulent dynamics of the cavity is dominated by the Raman effect. The forced-dissipative nature of the fiber cavity is responsible for a large diversity of turbulent behaviors: Aside from nonequilibrium statistical stationary states, we report the formation of a periodic pattern of spectral incoherent solitons, or the formation of different types of spectral singularities, e.g., dispersive shock waves and incoherent spectral collapse behaviors. We derive a mean-field kinetic equation that describes in detail the different turbulent regimes of the cavity and whose structure is formally analogous to the weak Langmuir turbulence kinetic equation in the presence of forcing and damping. A quantitative agreement is obtained between the simulations of the nonlinear Schrödinger equation with cavity boundary conditions and those of the mean-field kinetic equation and the corresponding singular integrodifferential reduction, without using adjustable parameters. We discuss the possible realization of a fiber cavity experimental setup in which the theoretical predictions can be observed and studied.