A solvent-free matrix application method for matrix-assisted laser desorption/ionization imaging of small molecules

Matrix application continues to be a critical step in sample preparation for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). Imaging of small molecules such as drugs and metabolites is particularly problematic because the commonly used washing steps to remove salts are usually omitted as they may also remove the analyte, and analyte spreading is more likely with conventional wet matrix application methods. We have developed a method which uses the application of matrix as a dry, finely divided powder, here referred to as dry matrix application, for the imaging of drug compounds. This appears to offer a complementary method to wet matrix application for the MALDI-MSI of small molecules, with the alternative matrix application techniques producing different ion profiles, and allows the visualization of compounds not observed using wet matrix application methods. We demonstrate its value in imaging clozapine from rat kidney and 4-bromophenyl-1,4-diazabicyclo(3.2.2)nonane-4-carboxylic acid from rat brain. In addition, exposure of the dry matrix coated sample to a saturated moist atmosphere appears to enhance the visualization of a different set of molecules.

Method for characterisation of weakly guiding waveguides by measuring mode field diameter

In this paper, we described an efficient theoretical approach to determine the integral characteristics such as Mode Field Diameter (MFD) and V-parameter of the Weakly guiding waveguides. To test the described method we measured MFD for the commercially available step index single mode fibre with known parameters. The results of these measurements are presented for two different wavelengths. It is worth noting that the developed approach implies infinite cladding, thus care should be taken to avoid influence of finiteness of cladding when MFD compares to cladding diamete.

Analysis of β-amyloid (Aβ) deposition in the temporal lobe in Alzheimer's disease using Fourier (spectral) analysis

To determine the spatial pattern of ß-amyloid (Aß) deposition throughout the temporal lobe in Alzheimer's disease (AD). Methods: Sections of the complete temporal lobe from six cases of sporadic AD were immunolabelled with antibody against Aß. Fourier (spectral) analysis was used to identify sinusoidal patterns in the fluctuation of Aß deposition in a direction parallel to the pia mater or alveus. Results: Significant sinusoidal fluctuations in density were evident in 81/99 (82%) analyses. In 64% of analyses, two frequency components were present with density peaks of Aß deposits repeating every 500–1000 µm and at distances greater than 1000 µm. In 25% of analyses, three or more frequency components were present. The estimated period or wavelength (number of sample units to complete one full cycle) of the first and second frequency components did not vary significantly between gyri of the temporal lobe, but there was evidence that the fluctuations of the classic deposits had longer periods than the diffuse and primitive deposits. Conclusions: (i) Aß deposits exhibit complex sinusoidal fluctuations in density in the temporal lobe in AD; (ii) fluctuations in Aß deposition may reflect the formation of Aß deposits in relation to the modular and vascular structure of the cortex; and (iii) Fourier analysis may be a useful statistical method for studying the patterns of Aß deposition both in AD and in transgenic models of disease.

Parallel implementation of image segmentation algorithms on a network of transputers

Image segmentation is one of the most computationally intensive operations in image processing and computer vision. This is because a large volume of data is involved and many different features have to be extracted from the image data. This thesis is concerned with the investigation of practical issues related to the implementation of several classes of image segmentation algorithms on parallel architectures. The Transputer is used as the basic building block of hardware architectures and Occam is used as the programming language. The segmentation methods chosen for implementation are convolution, for edge-based segmentation; the Split and Merge algorithm for segmenting non-textured regions; and the Granlund method for segmentation of textured images. Three different convolution methods have been implemented. The direct method of convolution, carried out in the spatial domain, uses the array architecture. The other two methods, based on convolution in the frequency domain, require the use of the two-dimensional Fourier transform. Parallel implementations of two different Fast Fourier Transform algorithms have been developed, incorporating original solutions. For the Row-Column method the array architecture has been adopted, and for the Vector-Radix method, the pyramid architecture. The texture segmentation algorithm, for which a system-level design is given, demonstrates a further application of the Vector-Radix Fourier transform. A novel concurrent version of the quad-tree based Split and Merge algorithm has been implemented on the pyramid architecture. The performance of the developed parallel implementations is analysed. Many of the obtained speed-up and efficiency measures show values close to their respective theoretical maxima. Where appropriate comparisons are drawn between different implementations. The thesis concludes with comments on general issues related to the use of the Transputer system as a development tool for image processing applications; and on the issues related to the engineering of concurrent image processing applications.

Femtosecond laser inscribed superstructure fibre gratings

We demonstrate the development of femtosecond laser inscribed superstructure fiber gratings (fsSFG) in silica optical fibre. We utilise a single step process, to inscribe low loss and polarisation independent, sampled gratings in optical fibres using the point by point femtosecond laser inscription method. Our approach results in a controlled modulated index change with complete suppression of any overlapping LPG structure leading to highly symmetric superstructure spectra, with the grating reflection well within the Fourier design limit. We also solve Maxwell's equations and calculate the back reflection spectrum using the bidirectional beam propagation method (BiBPM). Experimental results validate our numerical analysis and the estimation of inscription parameters such as ac index modulation, wavelength and the relative peak strength. We also explore how changes in the grating's period influence the reflection spectrum.

An alternating boundary integral based method for a Cauchy problem for the Laplace equation in a quadrant

We study the Cauchy problem for the Laplace equation in a quadrant (quarter-plane) containing a bounded inclusion. Given the values of the solution and its derivative on the edges of the quadrant the solution is reconstructed on the boundary of the inclusion. This is achieved using an alternating iterative method where at each iteration step mixed boundary value problems are being solved. A numerical method is also proposed and investigated for the direct mixed problems reducing these to integral equations over the inclusion. Numerical examples verify the efficiency of the proposed scheme.

An alternating boundary integral based method for a Cauchy problem for the Laplace equation in semi-infinite regions

We consider a Cauchy problem for the Laplace equation in a two-dimensional semi-infinite region with a bounded inclusion, i.e. the region is the intersection between a half-plane and the exterior of a bounded closed curve contained in the half-plane. The Cauchy data are given on the unbounded part of the boundary of the region and the aim is to construct the solution on the boundary of the inclusion. In 1989, Kozlov and Maz'ya [10] proposed an alternating iterative method for solving Cauchy problems for general strongly elliptic and formally self-adjoint systems in bounded domains. We extend their approach to our setting and in each iteration step mixed boundary value problems for the Laplace equation in the semi-infinite region are solved. Well-posedness of these mixed problems are investigated and convergence of the alternating procedure is examined. For the numerical implementation an efficient boundary integral equation method is proposed, based on the indirect variant of the boundary integral equation approach. The mixed problems are reduced to integral equations over the (bounded) boundary of the inclusion. Numerical examples are included showing the feasibility of the proposed method.

An iterative method based on boundary integrals for elliptic Cauchy problems in semi-infinite domains

In this study, we investigate the problem of reconstruction of a stationary temperature field from given temperature and heat flux on a part of the boundary of a semi-infinite region containing an inclusion. This situation can be modelled as a Cauchy problem for the Laplace operator and it is an ill-posed problem in the sense of Hadamard. We propose and investigate a Landweber-Fridman type iterative method, which preserve the (stationary) heat operator, for the stable reconstruction of the temperature field on the boundary of the inclusion. In each iteration step, mixed boundary value problems for the Laplace operator are solved in the semi-infinite region. Well-posedness of these problems is investigated and convergence of the procedures is discussed. For the numerical implementation of these mixed problems an efficient boundary integral method is proposed which is based on the indirect variant of the boundary integral approach. Using this approach the mixed problems are reduced to integral equations over the (bounded) boundary of the inclusion. Numerical examples are included showing that stable and accurate reconstructions of the temperature field on the boundary of the inclusion can be obtained also in the case of noisy data. These results are compared with those obtained with the alternating iterative method.

Recovering boundary data in planar heat conduction using boundary integral equation method

We consider a Cauchy problem for the heat equation, where the temperature field is to be reconstructed from the temperature and heat flux given on a part of the boundary of the solution domain. We employ a Landweber type method proposed in [2], where a sequence of mixed well-posed problems are solved at each iteration step to obtain a stable approximation to the original Cauchy problem. We develop an efficient boundary integral equation method for the numerical solution of these mixed problems, based on the method of Rothe. Numerical examples are presented both with exact and noisy data, showing the efficiency and stability of the proposed procedure and approximations.

Simultaneous ultrafast optical pulse train bursts generation and shaping based on Fourier series developments using superimposed fiber Bragg gratings

We propose an all-fiber method for the generation of ultrafast shaped pulse train bursts from a single pulse based on Fourier Series Developments (FDSs). The implementation of the FSD based filter only requires the use of a very simple non apodized Superimposed Fiber Bragg Grating (S-FBG) for the generation of the Shaped Output Pulse Train Burst (SOPTB). In this approach, the shape, the period and the temporal length of the generated SOPTB have no dependency on the input pulse rate.

Method for characterisation of weakly guiding waveguides by measuring mode field diameter

In this paper, we described an efficient theoretical approach to determine the integral characteristics such as Mode Field Diameter (MFD) and V-parameter of the Weakly guiding waveguides. To test the described method we measured MFD for the commercially available step index single mode fibre with known parameters. The results of these measurements are presented for two different wavelengths. It is worth noting that the developed approach implies infinite cladding, thus care should be taken to avoid influence of finiteness of cladding when MFD compares to cladding diamete.

A variational method for identifying a spacewise-dependent heat source

The inverse problem of determining a spacewise-dependent heat source for the parabolic heat equation using the usual conditions of the direct problem and information from one supplementary temperature measurement at a given instant of time is studied. This spacewise-dependent temperature measurement ensures that this inverse problem has a unique solution, but the solution is unstable and hence the problem is ill-posed. We propose a variational conjugate gradient-type iterative algorithm for the stable reconstruction of the heat source based on a sequence of well-posed direct problems for the parabolic heat equation which are solved at each iteration step using the boundary element method. The instability is overcome by stopping the iterative procedure at the first iteration for which the discrepancy principle is satisfied. Numerical results are presented which have the input measured data perturbed by increasing amounts of random noise. The numerical results show that the proposed procedure yields stable and accurate numerical approximations after only a few iterations.

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 new method for respiratory-volume monitoring based on long-period fibre gratings

Respiratory-volume monitoring is an indispensable part of mechanical ventilation. Here we present a new method of the respiratory-volume measurement based on a single fibre-optical long-period sensor of bending and the correlation between torso curvature and lung volume. Unlike the commonly used air-flow based measurement methods the proposed sensor is drift-free and immune to air-leaks. In the paper, we explain the working principle of sensors, a two-step calibration-test measurement procedure and present results that establish a linear correlation between the change in the local thorax curvature and the change of the lung volume. We also discuss the advantages and limitations of these sensors with respect to the current standards. © 2013 IEEE.

An iterative method for a Cauchy problem for the heat equation

An iterative method for reconstruction of the solution to a parabolic initial boundary value problem of second order from Cauchy data is presented. The data are given on a part of the boundary. At each iteration step, a series of well-posed mixed boundary value problems are solved for the parabolic operator and its adjoint. The convergence proof of this method in a weighted L2-space is included.