Designs for generalized linear models with several variables and model uncertainty

Standard factorial designs sometimes may be inadequate for experiments that aim to estimate a generalized linear model, for example, for describing a binary response in terms of several variables. A method is proposed for finding exact designs for such experiments that uses a criterion allowing for uncertainty in the link function, the linear predictor, or the model parameters, together with a design search. Designs are assessed and compared by simulation of the distribution of efficiencies relative to locally optimal designs over a space of possible models. Exact designs are investigated for two applications, and their advantages over factorial and central composite designs are demonstrated.

Mixture models for detecting differentially expressed genes in microarrays

An important and common problem in microarray experiments is the detection of genes that are differentially expressed in a given number of classes. As this problem concerns the selection of significant genes from a large pool of candidate genes, it needs to be carried out within the framework of multiple hypothesis testing. In this paper, we focus on the use of mixture models to handle the multiplicity issue. With this approach, a measure of the local FDR (false discovery rate) is provided for each gene. An attractive feature of the mixture model approach is that it provides a framework for the estimation of the prior probability that a gene is not differentially expressed, and this probability can subsequently be used in forming a decision rule. The rule can also be formed to take the false negative rate into account. We apply this approach to a well-known publicly available data set on breast cancer, and discuss our findings with reference to other approaches.

Optimal crossover designs for logistic regression models in pharmacodynamics

Pharmacodynamics (PD) is the study of the biochemical and physiological effects of drugs. The construction of optimal designs for dose-ranging trials with multiple periods is considered in this paper, where the outcome of the trial (the effect of the drug) is considered to be a binary response: the success or failure of a drug to bring about a particular change in the subject after a given amount of time. The carryover effect of each dose from one period to the next is assumed to be proportional to the direct effect. It is shown for a logistic regression model that the efficiency of optimal parallel (single-period) or crossover (two-period) design is substantially greater than a balanced design. The optimal designs are also shown to be robust to misspecification of the value of the parameters. Finally, the parallel and crossover designs are combined to provide the experimenter with greater flexibility.

Public key cryptography and error correcting codes as Ising models

We employ the methods of statistical physics to study the performance of Gallager type error-correcting codes. In this approach, the transmitted codeword comprises Boolean sums of the original message bits selected by two randomly-constructed sparse matrices. We show that a broad range of these codes potentially saturate Shannon's bound but are limited due to the decoding dynamics used. Other codes show sub-optimal performance but are not restricted by the decoding dynamics. We show how these codes may also be employed as a practical public-key cryptosystem and are of competitive performance to modern cyptographical methods.

Learning curves for Gaussian processes models: fluctuations and universality

Based on a statistical mechanics approach, we develop a method for approximately computing average case learning curves and their sample fluctuations for Gaussian process regression models. We give examples for the Wiener process and show that universal relations (that are independent of the input distribution) between error measures can be derived.

Statistical physics of low density parity check error correcting codes

We study the performance of Low Density Parity Check (LDPC) error-correcting codes using the methods of statistical physics. LDPC codes are based on the generation of codewords using Boolean sums of the original message bits by employing two randomly-constructed sparse matrices. These codes can be mapped onto Ising spin models and studied using common methods of statistical physics. We examine various regular constructions and obtain insight into their theoretical and practical limitations. We also briefly report on results obtained for irregular code constructions, for codes with non-binary alphabet, and on how a finite system size effects the error probability.

Statistical mechanics of broadcast channels using low-density parity-check codes

We investigate the use of Gallager's low-density parity-check (LDPC) codes in a degraded broadcast channel, one of the fundamental models in network information theory. Combining linear codes is a standard technique in practical network communication schemes and is known to provide better performance than simple time sharing methods when algebraic codes are used. The statistical physics based analysis shows that the practical performance of the suggested method, achieved by employing the belief propagation algorithm, is superior to that of LDPC based time sharing codes while the best performance, when received transmissions are optimally decoded, is bounded by the time sharing limit.

CORD an object model supporting statistical summary information for management decision making

Information systems have developed to the stage that there is plenty of data available in most organisations but there are still major problems in turning that data into information for management decision making. This thesis argues that the link between decision support information and transaction processing data should be through a common object model which reflects the real world of the organisation and encompasses the artefacts of the information system. The CORD (Collections, Objects, Roles and Domains) model is developed which is richer in appropriate modelling abstractions than current Object Models. A flexible Object Prototyping tool based on a Semantic Data Storage Manager has been developed which enables a variety of models to be stored and experimented with. A statistical summary table model COST (Collections of Objects Statistical Table) has been developed within CORD and is shown to be adequate to meet the modelling needs of Decision Support and Executive Information Systems. The COST model is supported by a statistical table creator and editor COSTed which is also built on top of the Object Prototyper and uses the CORD model to manage its metadata.

Cost models for engineering services

This thesis describes the procedure and results from four years research undertaken through the IHD (Interdisciplinary Higher Degrees) Scheme at Aston University in Birmingham, sponsored by the SERC (Science and Engineering Research Council) and Monk Dunstone Associates, Chartered Quantity Surveyors. A stochastic networking technique VERT (Venture Evaluation and Review Technique) was used to model the pre-tender costs of public health, heating ventilating, air-conditioning, fire protection, lifts and electrical installations within office developments. The model enabled the quantity surveyor to analyse, manipulate and explore complex scenarios which previously had defied ready mathematical analysis. The process involved the examination of historical material costs, labour factors and design performance data. Components and installation types were defined and formatted. Data was updated and adjusted using mechanical and electrical pre-tender cost indices and location, selection of contractor, contract sum, height and site condition factors. Ranges of cost, time and performance data were represented by probability density functions and defined by constant, uniform, normal and beta distributions. These variables and a network of the interrelationships between services components provided the framework for analysis. The VERT program, in this particular study, relied upon Monte Carlo simulation to model the uncertainties associated with pre-tender estimates of all possible installations. The computer generated output in the form of relative and cumulative frequency distributions of current element and total services costs, critical path analyses and details of statistical parameters. From this data alternative design solutions were compared, the degree of risk associated with estimates was determined, heuristics were tested and redeveloped, and cost significant items were isolated for closer examination. The resultant models successfully combined cost, time and performance factors and provided the quantity surveyor with an appreciation of the cost ranges associated with the various engineering services design options.

High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization

Microfluidics has recently emerged as a new method of manufacturing liposomes, which allows for reproducible mixing in miliseconds on the nanoliter scale. Here we investigate microfluidics-based manufacturing of liposomes. The aim of these studies was to assess the parameters in a microfluidic process by varying the total flow rate (TFR) and the flow rate ratio (FRR) of the solvent and aqueous phases. Design of experiment and multivariate data analysis were used for increased process understanding and development of predictive and correlative models. High FRR lead to the bottom-up synthesis of liposomes, with a strong correlation with vesicle size, demonstrating the ability to in-process control liposomes size; the resulting liposome size correlated with the FRR in the microfluidics process, with liposomes of 50 nm being reproducibly manufactured. Furthermore, we demonstrate the potential of a high throughput manufacturing of liposomes using microfluidics with a four-fold increase in the volumetric flow rate, maintaining liposome characteristics. The efficacy of these liposomes was demonstrated in transfection studies and was modelled using predictive modeling. Mathematical modelling identified FRR as the key variable in the microfluidic process, with the highest impact on liposome size, polydispersity and transfection efficiency. This study demonstrates microfluidics as a robust and high-throughput method for the scalable and highly reproducible manufacture of size-controlled liposomes. Furthermore, the application of statistically based process control increases understanding and allows for the generation of a design-space for controlled particle characteristics.

Temporal and statistical properties of the ytterbium doped fiber laser

Recently, temporal and statistical properties of quasi-CW fiber lasers have attracted a great attention. In particular, properties of Raman fiber laser (RFLs) have been studied both numerically and experimentally [1,2]. Experimental investigation is more challengeable, as the full generation optical bandwidth (typically hundreds of GHz for RFLs) is much bigger than real-time bandwidth of oscilloscopes (up to 60GHz for the newest models). So experimentally measured time dynamics is highly bandwidth averaged and do not provide precise information about overall statistical properties. To overpass this, one can use the spectral filtering technique to study temporal and statistical properties within optical bandwidth comparable with measurement bandwidth [3] or indirect measurements [4]. Ytterbium-doped fiber lasers (YDFL) are more suitable for experimental investigation, as their generation spectrum usually 10 times narrower. Moreover, recently ultra-narrow-band generation has been demonstrated in YDFL [5] which provides in principle possibility to measure time dynamics and statistics in real time using conventional oscilloscopes. © 2013 IEEE.

UK social housing and housing market in England:a statistical review and trends

Around 80% of the 63 million people in the UK live in urban areas where demand for affordable housing is highest. Supply of new dwellings is a long way short of demand and with an average annual replacement rate of 0.5% more than 80% of the existing residential housing stock will still be in use by 2050. A high proportion of owner-occupiers, a weak private rental sector and lack of sustainable financing models render England’s housing market one of the least responsive in the developed world. As an exploratory research the purpose of this paper is to examine the provision of social housing in the United Kingdom with a particular focus on England, and to set out implications for housing associations delivering sustainable community development. The paper is based on an analysis of historical data series (Census data), current macro-economic data and population projections to 2033. The paper identifies a chronic undersupply of affordable housing in England which is likely to be exacerbated by demographic development, changes in household composition and reduced availability of finance to develop new homes. Based on the housing market trends analysed in this paper opportunities are identified for policy makers to remove barriers to the delivery of new affordable homes and for social housing providers to evolve their business models by taking a wider role in sustainable community development.

Toward prediction of class II mouse major histocompatibility complex peptide binding affinity:in silico bioinformatic evaluation using partial least squares, a robust multivariate statistical technique

The accurate identification of T-cell epitopes remains a principal goal of bioinformatics within immunology. As the immunogenicity of peptide epitopes is dependent on their binding to major histocompatibility complex (MHC) molecules, the prediction of binding affinity is a prerequisite to the reliable prediction of epitopes. The iterative self-consistent (ISC) partial-least-squares (PLS)-based additive method is a recently developed bioinformatic approach for predicting class II peptide−MHC binding affinity. The ISC−PLS method overcomes many of the conceptual difficulties inherent in the prediction of class II peptide−MHC affinity, such as the binding of a mixed population of peptide lengths due to the open-ended class II binding site. The method has applications in both the accurate prediction of class II epitopes and the manipulation of affinity for heteroclitic and competitor peptides. The method is applied here to six class II mouse alleles (I-Ab, I-Ad, I-Ak, I-As, I-Ed, and I-Ek) and included peptides up to 25 amino acids in length. A series of regression equations highlighting the quantitative contributions of individual amino acids at each peptide position was established. The initial model for each allele exhibited only moderate predictivity. Once the set of selected peptide subsequences had converged, the final models exhibited a satisfactory predictive power. Convergence was reached between the 4th and 17th iterations, and the leave-one-out cross-validation statistical terms - q2, SEP, and NC - ranged between 0.732 and 0.925, 0.418 and 0.816, and 1 and 6, respectively. The non-cross-validated statistical terms r2 and SEE ranged between 0.98 and 0.995 and 0.089 and 0.180, respectively. 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 freely available online (http://www.jenner.ac.uk/MHCPred).

Some Properties of Mittag-Leffler Functions and Matrix-Variate Analogues: A Statistical Perspective

Mathematical Subject Classification 2010:26A33, 33E99, 15A52, 62E15.