Quantitative neuropathology:data collection and statistical analysis

The use of quantitative methods has become increasingly important in the study of neuropathology and especially in neurodegenerative disease. Disorders such as Alzheimer's disease (AD) and the frontotemporal dementias (FTD) are characterized by the formation of discrete, microscopic, pathological lesions which play an important role in pathological diagnosis. This chapter reviews the advantages and limitations of the different methods of quantifying pathological lesions in histological sections including estimates of density, frequency, coverage, and the use of semi-quantitative scores. The sampling strategies by which these quantitative measures can be obtained from histological sections, including plot or quadrat sampling, transect sampling, and point-quarter sampling, are described. In addition, data analysis methods commonly used to analysis quantitative data in neuropathology, including analysis of variance (ANOVA), polynomial curve fitting, multiple regression, classification trees, and principal components analysis (PCA), are discussed. These methods are illustrated with reference to quantitative studies of a variety of neurodegenerative disorders.

Relaxation procedures for an iterative MFS algorithm for the stable reconstruction of elastic fields from Cauchy data in two-dimensional isotropic linear elasticity

We investigate two numerical procedures for the Cauchy problem in linear elasticity, involving the relaxation of either the given boundary displacements (Dirichlet data) or the prescribed boundary tractions (Neumann data) on the over-specified boundary, in the alternating iterative algorithm of Kozlov et al. (1991). The two mixed direct (well-posed) problems associated with each iteration are solved using the method of fundamental solutions (MFS), in conjunction with the Tikhonov regularization method, while the optimal value of the regularization parameter is chosen via the generalized cross-validation (GCV) criterion. An efficient regularizing stopping criterion which ceases the iterative procedure at the point where the accumulation of noise becomes dominant and the errors in predicting the exact solutions increase, is also presented. The MFS-based iterative algorithms with relaxation are tested for Cauchy problems for isotropic linear elastic materials in various geometries to confirm the numerical convergence, stability, accuracy and computational efficiency of the proposed method.

Fast reconstruction of harmonic functions from Cauchy data using integral equation techniques

We consider the problem of stable determination of a harmonic function from knowledge of the solution and its normal derivative on a part of the boundary of the (bounded) solution domain. The alternating method is a procedure to generate an approximation to the harmonic function from such Cauchy data and we investigate a numerical implementation of this procedure based on Fredholm integral equations and Nyström discretization schemes, which makes it possible to perform a large number of iterations (millions) with minor computational cost (seconds) and high accuracy. Moreover, the original problem is rewritten as a fixed point equation on the boundary, and various other direct regularization techniques are discussed to solve that equation. We also discuss how knowledge of the smoothness of the data can be used to further improve the accuracy. Numerical examples are presented showing that accurate approximations of both the solution and its normal derivative can be obtained with much less computational time than in previous works.

Aggregating preference ranking with fuzzy Data Envelopment Analysis

Selecting the best alternative in a group decision making is a subject of many recent studies. The most popular method proposed for ranking the alternatives is based on the distance of each alternative to the ideal alternative. The ideal alternative may never exist; hence the ranking results are biased to the ideal point. The main aim in this study is to calculate a fuzzy ideal point that is more realistic to the crisp ideal point. On the other hand, recently Data Envelopment Analysis (DEA) is used to find the optimum weights for ranking the alternatives. This paper proposes a four stage approach based on DEA in the Fuzzy environment to aggregate preference rankings. An application of preferential voting system shows how the new model can be applied to rank a set of alternatives. Other two examples indicate the priority of the proposed method compared to the some other suggested methods.

PIP-DB:the protein isoelectric point database

A protein's isoelectric point or pI corresponds to the solution pH at which its net surface charge is zero. Since the early days of solution biochemistry, the pI has been recorded and reported, and thus literature reports of pI abound. The Protein Isoelectric Point database (PIP-DB) has collected and collated these data to provide an increasingly comprehensive database for comparison and benchmarking purposes. A web application has been developed to warehouse this database and provide public access to this unique resource. PIP-DB is a web-enabled SQL database with an HTML GUI front-end. PIP-DB is fully searchable across a range of properties.

Advances in characterisation, calibration and data processing speed of optical coherence tomography systems

This thesis describes advances in the characterisation, calibration and data processing of optical coherence tomography (OCT) systems. Femtosecond (fs) laser inscription was used for producing OCT-phantoms. Transparent materials are generally inert to infra-red radiations, but with fs lasers material modification occurs via non-linear processes when the highly focused light source interacts with the materials. This modification is confined to the focal volume and is highly reproducible. In order to select the best inscription parameters, combination of different inscription parameters were tested, using three fs laser systems, with different operating properties, on a variety of materials. This facilitated the understanding of the key characteristics of the produced structures with the aim of producing viable OCT-phantoms. Finally, OCT-phantoms were successfully designed and fabricated in fused silica. The use of these phantoms to characterise many properties (resolution, distortion, sensitivity decay, scan linearity) of an OCT system was demonstrated. Quantitative methods were developed to support the characterisation of an OCT system collecting images from phantoms and also to improve the quality of the OCT images. Characterisation methods include the measurement of the spatially variant resolution (point spread function (PSF) and modulation transfer function (MTF)), sensitivity and distortion. Processing of OCT data is a computer intensive process. Standard central processing unit (CPU) based processing might take several minutes to a few hours to process acquired data, thus data processing is a significant bottleneck. An alternative choice is to use expensive hardware-based processing such as field programmable gate arrays (FPGAs). However, recently graphics processing unit (GPU) based data processing methods have been developed to minimize this data processing and rendering time. These processing techniques include standard-processing methods which includes a set of algorithms to process the raw data (interference) obtained by the detector and generate A-scans. The work presented here describes accelerated data processing and post processing techniques for OCT systems. The GPU based processing developed, during the PhD, was later implemented into a custom built Fourier domain optical coherence tomography (FD-OCT) system. This system currently processes and renders data in real time. Processing throughput of this system is currently limited by the camera capture rate. OCTphantoms have been heavily used for the qualitative characterization and adjustment/ fine tuning of the operating conditions of OCT system. Currently, investigations are under way to characterize OCT systems using our phantoms. The work presented in this thesis demonstrate several novel techniques of fabricating OCT-phantoms and accelerating OCT data processing using GPUs. In the process of developing phantoms and quantitative methods, a thorough understanding and practical knowledge of OCT and fs laser processing systems was developed. This understanding leads to several novel pieces of research that are not only relevant to OCT but have broader importance. For example, extensive understanding of the properties of fs inscribed structures will be useful in other photonic application such as making of phase mask, wave guides and microfluidic channels. Acceleration of data processing with GPUs is also useful in other fields.

Optimum bias point in broadband subcarrier multiplexing with optical IQ modulators

This paper develops a theoretical analysis of the tradeoff between carrier suppression and nonlinearities induced by optical IQ modulators in direct-detection subcarrier multiplexing systems. The tradeoff is obtained by examining the influence of the bias conditions of the modulator on the transmitted single side band signal. The frequency components in the electric field and the associated photocurrent at the output of the IQ modulator are derived mathematically. For any frequency plan, the optimum bias point can be identified by calculating the sensitivity gain for every subchannel. A setup composed of subcarriers located at multiples of the data rate ensures that the effects of intermodulation distortion are studied in the most suitable conditions. Experimental tests with up to five QPSK electrical subchannels are performed to verify the mathematical model and validate the predicted gains in sensitivity.

Data Flow Analysis and the Linear Programming Model

* The research is supported partly by INTAS: 04-77-7173 project, http://www.intas.be

Topographic visual analytics of multibeam dynamic SONAR data

This paper considers the problem of low-dimensional visualisation of very high dimensional information sources for the purpose of situation awareness in the maritime environment. In response to the requirement for human decision support aids to reduce information overload (and specifically, data amenable to inter-point relative similarity measures) appropriate to the below-water maritime domain, we are investigating a preliminary prototype topographic visualisation model. The focus of the current paper is on the mathematical problem of exploiting a relative dissimilarity representation of signals in a visual informatics mapping model, driven by real-world sonar systems. A realistic noise model is explored and incorporated into non-linear and topographic visualisation algorithms building on the approach of [9]. Concepts are illustrated using a real world dataset of 32 hydrophones monitoring a shallow-water environment in which targets are present and dynamic.

Application of Two-Phase Regression to Geotechnical Data

2000 Mathematics Subject Classification: 62F10, 62J05, 62P30

Accurate estimation of isoelectric point of protein and peptide based on amino acid sequences

Motivation: In any macromolecular polyprotic system - for example protein, DNA or RNA - the isoelectric point - commonly referred to as the pI - can be defined as the point of singularity in a titration curve, corresponding to the solution pH value at which the net overall surface charge - and thus the electrophoretic mobility - of the ampholyte sums to zero. Different modern analytical biochemistry and proteomics methods depend on the isoelectric point as a principal feature for protein and peptide characterization. Protein separation by isoelectric point is a critical part of 2-D gel electrophoresis, a key precursor of proteomics, where discrete spots can be digested in-gel, and proteins subsequently identified by analytical mass spectrometry. Peptide fractionation according to their pI is also widely used in current proteomics sample preparation procedures previous to the LC-MS/MS analysis. Therefore accurate theoretical prediction of pI would expedite such analysis. While such pI calculation is widely used, it remains largely untested, motivating our efforts to benchmark pI prediction methods. Results: Using data from the database PIP-DB and one publically available dataset as our reference gold standard, we have undertaken the benchmarking of pI calculation methods. We find that methods vary in their accuracy and are highly sensitive to the choice of basis set. The machine-learning algorithms, especially the SVM-based algorithm, showed a superior performance when studying peptide mixtures. In general, learning-based pI prediction methods (such as Cofactor, SVM and Branca) require a large training dataset and their resulting performance will strongly depend of the quality of that data. In contrast with Iterative methods, machine-learning algorithms have the advantage of being able to add new features to improve the accuracy of prediction. Contact: yperez@ebi.ac.uk Availability and Implementation: The software and data are freely available at https://github.com/ypriverol/pIR. Supplementary information: Supplementary data are available at Bioinformatics online.

Semantic distributed database management with applications to the Internet dissemination of environmental data

The research presented in this dissertation is comprised of several parts which jointly attain the goal of Semantic Distributed Database Management with Applications to Internet Dissemination of Environmental Data. ^ Part of the research into more effective and efficient data management has been pursued through enhancements to the Semantic Binary Object-Oriented database (Sem-ODB) such as more effective load balancing techniques for the database engine, and the use of Sem-ODB as a tool for integrating structured and unstructured heterogeneous data sources. Another part of the research in data management has pursued methods for optimizing queries in distributed databases through the intelligent use of network bandwidth; this has applications in networks that provide varying levels of Quality of Service or throughput. ^ The application of the Semantic Binary database model as a tool for relational database modeling has also been pursued. This has resulted in database applications that are used by researchers at the Everglades National Park to store environmental data and to remotely-sensed imagery. ^ The areas of research described above have contributed to the creation TerraFly, which provides for the dissemination of geospatial data via the Internet. TerraFly research presented herein ranges from the development of TerraFly's back-end database and interfaces, through the features that are presented to the public (such as the ability to provide autopilot scripts and on-demand data about a point), to applications of TerraFly in the areas of hazard mitigation, recreation, and aviation. ^

A framework for automatic feature extraction from airborne light detection and ranging data

Recent advances in airborne Light Detection and Ranging (LIDAR) technology allow rapid and inexpensive measurements of topography over large areas. Airborne LIDAR systems usually return a 3-dimensional cloud of point measurements from reflective objects scanned by the laser beneath the flight path. This technology is becoming a primary method for extracting information of different kinds of geometrical objects, such as high-resolution digital terrain models (DTMs), buildings and trees, etc. In the past decade, LIDAR gets more and more interest from researchers in the field of remote sensing and GIS. Compared to the traditional data sources, such as aerial photography and satellite images, LIDAR measurements are not influenced by sun shadow and relief displacement. However, voluminous data pose a new challenge for automated extraction the geometrical information from LIDAR measurements because many raster image processing techniques cannot be directly applied to irregularly spaced LIDAR points. ^ In this dissertation, a framework is proposed to filter out information about different kinds of geometrical objects, such as terrain and buildings from LIDAR automatically. They are essential to numerous applications such as flood modeling, landslide prediction and hurricane animation. The framework consists of several intuitive algorithms. Firstly, a progressive morphological filter was developed to detect non-ground LIDAR measurements. By gradually increasing the window size and elevation difference threshold of the filter, the measurements of vehicles, vegetation, and buildings are removed, while ground data are preserved. Then, building measurements are identified from no-ground measurements using a region growing algorithm based on the plane-fitting technique. Raw footprints for segmented building measurements are derived by connecting boundary points and are further simplified and adjusted by several proposed operations to remove noise, which is caused by irregularly spaced LIDAR measurements. To reconstruct 3D building models, the raw 2D topology of each building is first extracted and then further adjusted. Since the adjusting operations for simple building models do not work well on 2D topology, 2D snake algorithm is proposed to adjust 2D topology. The 2D snake algorithm consists of newly defined energy functions for topology adjusting and a linear algorithm to find the minimal energy value of 2D snake problems. Data sets from urbanized areas including large institutional, commercial, and small residential buildings were employed to test the proposed framework. The results demonstrated that the proposed framework achieves a very good performance. ^

Rigid and non-rigid point-based medical image registration

The primary goal of this dissertation is to develop point-based rigid and non-rigid image registration methods that have better accuracy than existing methods. We first present point-based PoIRe, which provides the framework for point-based global rigid registrations. It allows a choice of different search strategies including (a) branch-and-bound, (b) probabilistic hill-climbing, and (c) a novel hybrid method that takes advantage of the best characteristics of the other two methods. We use a robust similarity measure that is insensitive to noise, which is often introduced during feature extraction. We show the robustness of PoIRe using it to register images obtained with an electronic portal imaging device (EPID), which have large amounts of scatter and low contrast. To evaluate PoIRe we used (a) simulated images and (b) images with fiducial markers; PoIRe was extensively tested with 2D EPID images and images generated by 3D Computer Tomography (CT) and Magnetic Resonance (MR) images. PoIRe was also evaluated using benchmark data sets from the blind retrospective evaluation project (RIRE). We show that PoIRe is better than existing methods such as Iterative Closest Point (ICP) and methods based on mutual information. We also present a novel point-based local non-rigid shape registration algorithm. We extend the robust similarity measure used in PoIRe to non-rigid registrations adapting it to a free form deformation (FFD) model and making it robust to local minima, which is a drawback common to existing non-rigid point-based methods. For non-rigid registrations we show that it performs better than existing methods and that is less sensitive to starting conditions. We test our non-rigid registration method using available benchmark data sets for shape registration. Finally, we also explore the extraction of features invariant to changes in perspective and illumination, and explore how they can help improve the accuracy of multi-modal registration. For multimodal registration of EPID-DRR images we present a method based on a local descriptor defined by a vector of complex responses to a circular Gabor filter.

A generalized adaptive mathematical morphological filter for LIDAR data

Airborne Light Detection and Ranging (LIDAR) technology has become the primary method to derive high-resolution Digital Terrain Models (DTMs), which are essential for studying Earth's surface processes, such as flooding and landslides. The critical step in generating a DTM is to separate ground and non-ground measurements in a voluminous point LIDAR dataset, using a filter, because the DTM is created by interpolating ground points. As one of widely used filtering methods, the progressive morphological (PM) filter has the advantages of classifying the LIDAR data at the point level, a linear computational complexity, and preserving the geometric shapes of terrain features. The filter works well in an urban setting with a gentle slope and a mixture of vegetation and buildings. However, the PM filter often removes ground measurements incorrectly at the topographic high area, along with large sizes of non-ground objects, because it uses a constant threshold slope, resulting in "cut-off" errors. A novel cluster analysis method was developed in this study and incorporated into the PM filter to prevent the removal of the ground measurements at topographic highs. Furthermore, to obtain the optimal filtering results for an area with undulating terrain, a trend analysis method was developed to adaptively estimate the slope-related thresholds of the PM filter based on changes of topographic slopes and the characteristics of non-terrain objects. The comparison of the PM and generalized adaptive PM (GAPM) filters for selected study areas indicates that the GAPM filter preserves the most "cut-off" points removed incorrectly by the PM filter. The application of the GAPM filter to seven ISPRS benchmark datasets shows that the GAPM filter reduces the filtering error by 20% on average, compared with the method used by the popular commercial software TerraScan. The combination of the cluster method, adaptive trend analysis, and the PM filter allows users without much experience in processing LIDAR data to effectively and efficiently identify ground measurements for the complex terrains in a large LIDAR data set. The GAPM filter is highly automatic and requires little human input. Therefore, it can significantly reduce the effort of manually processing voluminous LIDAR measurements.