Toward the prediction of class I and II mouse major histocompatibility complex-peptide-binding affinity:in silico bioinformatic step-by-step guide using quantitative structure-activity relationships

Quantitative structure-activity relationship (QSAR) analysis is a cornerstone of modern informatics. Predictive computational models of peptide-major histocompatibility complex (MHC)-binding affinity based on QSAR technology have now become important components of modern computational immunovaccinology. Historically, such approaches have been built around semiqualitative, classification methods, but these are now giving way to quantitative regression methods. We review three methods--a 2D-QSAR additive-partial least squares (PLS) and a 3D-QSAR comparative molecular similarity index analysis (CoMSIA) method--which can identify the sequence dependence of peptide-binding specificity for various class I MHC alleles from the reported binding affinities (IC50) of peptide sets. The third method is an iterative self-consistent (ISC) PLS-based additive method, which is a recently developed extension to the additive method for the affinity prediction of class II peptides. The QSAR methods presented here have established themselves as immunoinformatic techniques complementary to existing methodology, useful in the quantitative prediction of binding affinity: current methods for the in silico identification of T-cell epitopes (which form the basis of many vaccines, diagnostics, and reagents) rely on the accurate computational prediction of peptide-MHC affinity. We have reviewed various human and mouse class I and class II allele models. Studied alleles comprise HLA-A*0101, HLA-A*0201, HLA-A*0202, HLA-A*0203, HLA-A*0206, HLA-A*0301, HLA-A*1101, HLA-A*3101, HLA-A*6801, HLA-A*6802, HLA-B*3501, H2-K(k), H2-K(b), H2-D(b) HLA-DRB1*0101, HLA-DRB1*0401, HLA-DRB1*0701, I-A(b), I-A(d), I-A(k), I-A(S), I-E(d), and I-E(k). In this chapter we show a step-by-step guide into predicting the reliability and the resulting models to represent an advance on existing methods. The peptides used in this study are available from the AntiJen database (http://www.jenner.ac.uk/AntiJen). The PLS method is available commercially in the SYBYL molecular modeling software package. The resulting models, which can be used for accurate T-cell epitope prediction, will be made are freely available online at the URL http://www.jenner.ac.uk/MHCPred.

A predictor of membrane class:discriminating α-helical and β-barrel membrane proteins from non-membranous proteins

Accurate protein structure prediction remains an active objective of research in bioinformatics. Membrane proteins comprise approximately 20% of most genomes. They are, however, poorly tractable targets of experimental structure determination. Their analysis using bioinformatics thus makes an important contribution to their on-going study. Using a method based on Bayesian Networks, which provides a flexible and powerful framework for statistical inference, we have addressed the alignment-free discrimination of membrane from non-membrane proteins. The method successfully identifies prokaryotic and eukaryotic α-helical membrane proteins at 94.4% accuracy, β-barrel proteins at 72.4% accuracy, and distinguishes assorted non-membranous proteins with 85.9% accuracy. The method here is an important potential advance in the computational analysis of membrane protein structure. It represents a useful tool for the characterisation of membrane proteins with a wide variety of potential applications.

Enhanced Raman amplifier flatness with nonlinear broadening over non-standard transmission fibre

Nonlinear CW pump broadening over non-standard transmission fibre is used for the first time to achieve improved gain flatness in a single-pump broadband Raman amplifier. As an illustration of the benefits that can be obtained from this approach, a threefold increase in the bandwidth for 0.1 dB gain variation is reported when the broadened pump is used to produce 9.2 dB on-off gain over 25 km LEAF fibre. © 2005 Elsevier B.V. All rights reserved.

Multi-class subcellular location prediction for bacterial proteins

Two algorithms, based onBayesian Networks (BNs), for bacterial subcellular location prediction, are explored in this paper: one predicts all locations for Gram+ bacteria and the other all locations for Gram- bacteria. Methods were evaluated using different numbers of residues (from the N-terminal 10 residues to the whole sequence) and residue representation (amino acid-composition, percentage amino acid-composition or normalised amino acid-composition). The accuracy of the best resulting BN was compared to PSORTB. The accuracy of this multi-location BN was roughly comparable to PSORTB; the difference in predictions is low, often less than 2%. The BN method thus represents both an important new avenue of methodological development for subcellular location prediction and a potentially value new tool of true utilitarian value for candidate subunit vaccine selection.

Phase synchronization of a two-channel phase-sensitive amplifier based on optical injection-locking of InP quantum-dash mode-locked lasers

A synchronization scheme for a two-channel phase sensitive amplifier is implemented based on the injection-locking of single InP quantum-dash mode-locked laser. Error free performance with penalty <1 dB is demonstrated for both channels. © 2011 Optical Society of America.

Minimising total energy requirements in amplified links by optimising amplifier spacing

We investigate the energy optimization (minimization) for amplified links. We show that using the using a well-established analytic nonlinear signal-to-noise ratio noise model that for a simple amplifier model there are very clear, fiber independent, amplifier gains which minimize the total energy requirement. With a generalized amplifier model we establish the spacing for the optimum power per bit as well as the nonlinear limited optimum power. An amplifier spacing corresponding to 13 dB gain is shown to be a suitable compromise for practical amplifiers operating at the optimum nonlinear power. © 2014 Optical Society of America.

Enhanced Raman amplifier gain performance with HNLF broadening

Nonlinear CW pump broadening over non-standard transmission fiber is used for the first time to achieve superior gain variation performance in a single-pump broadband Raman amplifier. A threefold increase in the bandwidth for 0.1 dB gain variation is reported.

Optimization of gain and SNR in bi-directionally pumped dispersion compensating amplifier modules

In this paper, we present an analysis and optimisation of the performance of bi-directionally pumped dispersion compensation modules acting as simultaneous Raman amplifiers, with optimal configurations for operation with different fibers commercially available. The ratio between forward and backward pump powers for minimum noise influence is obtained in each case, with improvements in the SNR of up to 8 dB when compared to a purely backward-pumped case.

Improved WDM performance of a fibre optical parametric amplifier using Raman-assisted pumping

We experimentally demonstrate a Raman-Assisted Fibre Optical Parametric Amplifier (RA-FOPA) with 20dB net gain using wavelength division multiplexed signals. We report amplification of 10×58Gb/s 100GHz-spaced QPSK signals and show that by appropriate tuning of the parametric pump power and frequency, gain improvement of up to 5dB can be achieved for the RA-FOPA compared with combined individual contributions from the parametric and Raman pumps. We compare the RAFOPA with an equivalent-gain conventional FOPA and find that four-wave mixing crosstalk is substantially reduced by up to 5.8 ± 0.4dB using the RA-FOPA. Worst-case performance penalty of the RA-FOPA is found to be only 1.0 ± 0.2dB over all measured OSNRs, frequencies and input powers, making it an attractive proposal for future communications systems.

Towards the in silico identification of class II restricted T-cell epitopes:a partial least squares iterative self-consistent algorithm for affinity prediction

Motivation: The immunogenicity of peptides depends on their ability to bind to MHC molecules. MHC binding affinity prediction methods can save significant amounts of experimental work. The class II MHC binding site is open at both ends, making epitope prediction difficult because of the multiple binding ability of long peptides. Results: An iterative self-consistent partial least squares (PLS)-based additive method was applied to a set of 66 pep- tides no longer than 16 amino acids, binding to DRB1*0401. A regression equation containing the quantitative contributions of the amino acids at each of the nine positions was generated. Its predictability was tested using two external test sets which gave r pred =0.593 and r pred=0.655, respectively. Furthermore, it was benchmarked using 25 known T-cell epitopes restricted by DRB1*0401 and we compared our results with four other online predictive methods. The additive method showed the best result finding 24 of the 25 T-cell epitopes. Availability: Peptides used in the study are available from http://www.jenner.ac.uk/JenPep. The PLS method is available commercially in the SYBYL molecular modelling software package. The final model for affinity prediction of peptides binding to DRB1*0401 molecule is available at http://www.jenner.ac.uk/MHCPred. Models developed for DRB1*0101 and DRB1*0701 also are available in MHC- Pred

Applications of the Owa-Srivastava Operator to the Class of K-Uniformly Convex Functions

2000 Mathematics Subject Classification: Primary 30C45, 26A33; Secondary 33C15

MPGN – An Approach for Discovering Class Association Rules

his article presents some of the results of the Ph.D. thesis Class Association Rule Mining Using MultiDimensional Numbered Information Spaces by Iliya Mitov (Institute of Mathematics and Informatics, BAS), successfully defended at Hasselt University, Faculty of Science on 15 November 2011 in Belgium

On the approximation by convolution operators in homogeneous Banach spaces on R^d

AMS Subject Classification 2010: 41A25, 41A35, 41A40, 41A63, 41A65, 42A38, 42A85, 42B10, 42B20

Generalized D-Symmetric Operators I

2000 Mathematics Subject Classification: Primary: 47B47, 47B10; secondary 47A30.