Relative entropy rate based multiple hidden Markov Model Approximation

This paper proposes a novel relative entropy rate (RER) based approach for multiple HMM (MHMM) approximation of a class of discrete-time uncertain processes. Under different uncertainty assumptions, the model design problem is posed either as a min-max optimisation problem or stochastic minimisation problem on the RER between joint laws describing the state and output processes (rather than the more usual RER between output processes). A suitable filter is proposed for which performance results are established which bound conditional mean estimation performance and show that estimation performance improves as the RER is reduced. These filter consistency and convergence bounds are the first results characterising multiple HMM approximation performance and suggest that joint RER concepts provide a useful model selection criteria. The proposed model design process and MHMM filter are demonstrated on an important image processing dim-target detection problem.

Linkage and heritability analysis of migraine symptom groupings: A comparison of three different clustering methods on twin data

Migraine is a painful disorder for which the etiology remains obscure. Diagnosis is largely based on International Headache Society criteria. However, no feature occurs in all patients who meet these criteria, and no single symptom is required for diagnosis. Consequently, this definition may not accurately reflect the phenotypic heterogeneity or genetic basis of the disorder. Such phenotypic uncertainty is typical for complex genetic disorders and has encouraged interest in multivariate statistical methods for classifying disease phenotypes. We applied three popular statistical phenotyping methods—latent class analysis, grade of membership and grade of membership “fuzzy” clustering (Fanny)—to migraine symptom data, and compared heritability and genome-wide linkage results obtained using each approach. Our results demonstrate that different methodologies produce different clustering structures and non-negligible differences in subsequent analyses. We therefore urge caution in the use of any single approach and suggest that multiple phenotyping methods be used.

Statistical analysis and reduction of multiple access interference in MC-CDMA systems

Multicarrier code division multiple access (MC-CDMA) is a very promising candidate for the multiple access scheme in fourth generation wireless communi- cation systems. During asynchronous transmission, multiple access interference (MAI) is a major challenge for MC-CDMA systems and significantly affects their performance. The main objectives of this thesis are to analyze the MAI in asyn- chronous MC-CDMA, and to develop robust techniques to reduce the MAI effect. Focus is first on the statistical analysis of MAI in asynchronous MC-CDMA. A new statistical model of MAI is developed. In the new model, the derivation of MAI can be applied to different distributions of timing offset, and the MAI power is modelled as a Gamma distributed random variable. By applying the new statistical model of MAI, a new computer simulation model is proposed. This model is based on the modelling of a multiuser system as a single user system followed by an additive noise component representing the MAI, which enables the new simulation model to significantly reduce the computation load during computer simulations. MAI reduction using slow frequency hopping (SFH) technique is the topic of the second part of the thesis. Two subsystems are considered. The first sub- system involves subcarrier frequency hopping as a group, which is referred to as GSFH/MC-CDMA. In the second subsystem, the condition of group hopping is dropped, resulting in a more general system, namely individual subcarrier frequency hopping MC-CDMA (ISFH/MC-CDMA). This research found that with the introduction of SFH, both of GSFH/MC-CDMA and ISFH/MC-CDMA sys- tems generate less MAI power than the basic MC-CDMA system during asyn- chronous transmission. Because of this, both SFH systems are shown to outper- form MC-CDMA in terms of BER. This improvement, however, is at the expense of spectral widening. In the third part of this thesis, base station polarization diversity, as another MAI reduction technique, is introduced to asynchronous MC-CDMA. The com- bined system is referred to as Pol/MC-CDMA. In this part a new optimum com- bining technique namely maximal signal-to-MAI ratio combining (MSMAIRC) is proposed to combine the signals in two base station antennas. With the applica- tion of MSMAIRC and in the absents of additive white Gaussian noise (AWGN), the resulting signal-to-MAI ratio (SMAIR) is not only maximized but also in- dependent of cross polarization discrimination (XPD) and antenna angle. In the case when AWGN is present, the performance of MSMAIRC is still affected by the XPD and antenna angle, but to a much lesser degree than the traditional maximal ratio combining (MRC). Furthermore, this research found that the BER performance for Pol/MC-CDMA can be further improved by changing the angle between the two receiving antennas. Hence the optimum antenna angles for both MSMAIRC and MRC are derived and their effects on the BER performance are compared. With the derived optimum antenna angle, the Pol/MC-CDMA system is able to obtain the lowest BER for a given XPD.

Infrastructure Sustainability : Damage Assessment in Multiple-Girder Composite Bridges Using Vibration Characteristics

Assessing the structural health state of urban infrastructure is crucial in terms of infrastructure sustainability. This chapter uses dynamic computer simulation techniques to apply a procedure using vibration-based methods for damage assessment in multiple-girder composite bridges. In addition to changes in natural frequencies, this multi-criteria procedure incorporates two methods, namely, the modal flexibility and the modal strain energy method. Using the numerically simulated modal data obtained through finite element analysis software, algorithms based on modal flexibility and modal strain energy change, before and after damage, are obtained and used as the indices for the assessment of structural health state. The feasibility and capability of the approach is demonstrated through numerical studies of a proposed structure with six damage scenarios. It is concluded that the modal strain energy method is capable of application to multiple-girder composite bridges, as evidenced through the example treated in this chapter.

Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Reliability analysis and economic equipment replacement appraisal for substation and sub-transmission systems with explicit inclusion of non-repairable failures

The modern society has come to expect the electrical energy on demand, while many of the facilities in power systems are aging beyond repair and maintenance. The risk of failure is increasing with the aging equipments and can pose serious consequences for continuity of electricity supply. As the equipments used in high voltage power networks are very expensive, economically it may not be feasible to purchase and store spares in a warehouse for extended periods of time. On the other hand, there is normally a significant time before receiving equipment once it is ordered. This situation has created a considerable interest in the evaluation and application of probability methods for aging plant and provisions of spares in bulk supply networks, and can be of particular importance for substations. Quantitative adequacy assessment of substation and sub-transmission power systems is generally done using a contingency enumeration approach which includes the evaluation of contingencies, classification of the contingencies based on selected failure criteria. The problem is very complex because of the need to include detailed modelling and operation of substation and sub-transmission equipment using network flow evaluation and to consider multiple levels of component failures. In this thesis a new model associated with aging equipment is developed to combine the standard tools of random failures, as well as specific model for aging failures. This technique is applied in this thesis to include and examine the impact of aging equipments on system reliability of bulk supply loads and consumers in distribution network for defined range of planning years. The power system risk indices depend on many factors such as the actual physical network configuration and operation, aging conditions of the equipment, and the relevant constraints. The impact and importance of equipment reliability on power system risk indices in a network with aging facilities contains valuable information for utilities to better understand network performance and the weak links in the system. In this thesis, algorithms are developed to measure the contribution of individual equipment to the power system risk indices, as part of the novel risk analysis tool. A new cost worth approach was developed in this thesis that can make an early decision in planning for replacement activities concerning non-repairable aging components, in order to maintain a system reliability performance which economically is acceptable. The concepts, techniques and procedures developed in this thesis are illustrated numerically using published test systems. It is believed that the methods and approaches presented, substantially improve the accuracy of risk predictions by explicit consideration of the effect of equipment entering a period of increased risk of a non-repairable failure.

Multiple analysis of three common genetic alterations associated with thrombophilia

We have previously reported the use of a novel mini-sequencing protocol for detection of the factor V Leiden variant, the first nucleotide change (FNC) technology. This technology is based on a single nucleotide extension of a primer, which is hybridized immediately adjacent to the site of mutation. The extended nucleotide that carries a reporter molecule (fluorescein) has the power to discriminate the genotype at the site of mutation. More recently, the prothrombin 20210 and thermolabile methylene tetrahydrofolate reductase (MTHFR) 677 variants have been identified as possible risk factors associated with thrombophilia. This study describes the use of the FNC technology in a combined assay to detect factor V, prothrombin and MTHFR variants in a population of Australian blood donors, and describes the objective numerical methodology used to determine genotype cut-off values for each genetic variation. Using FNC to test 500 normal blood donors, the incidence of Factor V Leiden was 3.6% (all heterozygous), that of prothrombin 20210 was 2.8% (all heterozygous) and that of MTHFR was 10% (homozygous). The combined FNC technology offers a simple, rapid, automatable DNA-based test for the detection of these three important mutations that are associated with familial thrombophilia. (C) 2000 Lippincott Williams and Wilkins.

Evidence for CRHR1 in multiple sclerosis using supervised machine learning and meta-analysis in 12 566 individuals

The primary genetic risk factor in multiple sclerosis (MS) is the HLA-DRB1*1501 allele; however, much of the remaining genetic contribution to MS has yet to be elucidated. Several lines of evidence support a role for neuroendocrine system involvement in autoimmunity which may, in part, be genetically determined. Here, we comprehensively investigated variation within eight candidate hypothalamic-pituitary-adrenal (HPA) axis genes and susceptibility to MS. A total of 326 SNPs were investigated in a discovery dataset of 1343 MS cases and 1379 healthy controls of European ancestry using a multi-analytical strategy. Random Forests, a supervised machine-learning algorithm, identified eight intronic SNPs within the corticotrophin-releasing hormone receptor 1 or CRHR1 locus on 17q21.31 as important predictors of MS. On the basis of univariate analyses, six CRHR1 variants were associated with decreased risk for disease following a conservative correction for multiple tests. Independent replication was observed for CRHR1 in a large meta-analysis comprising 2624 MS cases and 7220 healthy controls of European ancestry. Results from a combined meta-analysis of all 3967 MS cases and 8599 controls provide strong evidence for the involvement of CRHR1 in MS. The strongest association was observed for rs242936 (OR = 0.82, 95% CI = 0.74-0.90, P = 9.7 × 10-5). Replicated CRHR1 variants appear to exist on a single associated haplotype. Further investigation of mechanisms involved in HPA axis regulation and response to stress in MS pathogenesis is warranted. © The Author 2010. Published by Oxford University Press. All rights reserved.

Analysis of multiple shared channel cooperative routing in OFDM based wireless networks

Diversity techniques have long been used to combat the channel fading in wireless communications systems. Recently cooperative communications has attracted lot of attention due to many benefits it offers. Thus cooperative routing protocols with diversity transmission can be developed to exploit the random nature of the wireless channels to improve the network efficiency by selecting multiple cooperative nodes to forward data. In this paper we analyze and evaluate the performance of a novel routing protocol with multiple cooperative nodes which share multiple channels. Multiple shared channels cooperative (MSCC) routing protocol achieves diversity advantage by using cooperative transmission. It unites clustering hierarchy with a bandwidth reuse scheme to mitigate the co-channel interference. Theoretical analysis of average packet reception rate and network throughput of the MSCC protocol are presented and compared with simulated results.

Handling incomplete data in survival analysis with multiple covariates

This paper studies the missing covariate problem which is often encountered in survival analysis. Three covariate imputation methods are employed in the study, and the effectiveness of each method is evaluated within the hazard prediction framework. Data from a typical engineering asset is used in the case study. Covariate values in some time steps are deliberately discarded to generate an incomplete covariate set. It is found that although the mean imputation method is simpler than others for solving missing covariate problems, the results calculated by it can differ largely from the real values of the missing covariates. This study also shows that in general, results obtained from the regression method are more accurate than those of the mean imputation method but at the cost of a higher computational expensive. Gaussian Mixture Model (GMM) method is found to be the most effective method within these three in terms of both computation efficiency and predication accuracy.

Effects of wireless sensor network uncertainties on output-only modal analysis employing merged data of multiple tests

The use of Wireless Sensor Networks (WSNs) for Structural Health Monitoring (SHM) has become a promising approach due to many advantages such as low cost, fast and flexible deployment. However, inherent technical issues such as data synchronization error and data loss have prevented these distinct systems from being extensively used. Recently, several SHM-oriented WSNs have been proposed and believed to be able to overcome a large number of technical uncertainties. Nevertheless, there is limited research verifying the applicability of those WSNs with respect to demanding SHM applications like modal analysis and damage identification. This paper first presents a brief review of the most inherent uncertainties of the SHM-oriented WSN platforms and then investigates their effects on outcomes and performance of the most robust Output-only Modal Analysis (OMA) techniques when employing merged data from multiple tests. The two OMA families selected for this investigation are Frequency Domain Decomposition (FDD) and Data-driven Stochastic Subspace Identification (SSI-data) due to the fact that they both have been widely applied in the past decade. Experimental accelerations collected by a wired sensory system on a large-scale laboratory bridge model are initially used as clean data before being contaminated by different data pollutants in sequential manner to simulate practical SHM-oriented WSN uncertainties. The results of this study show the robustness of FDD and the precautions needed for SSI-data family when dealing with SHM-WSN uncertainties. Finally, the use of the measurement channel projection for the time-domain OMA techniques and the preferred combination of the OMA techniques to cope with the SHM-WSN uncertainties is recommended.

Multi-criteria ranking and source apportionment of airborne particulate matter

Particulate matter research is essential because of the well known significant adverse effects of aerosol particles on human health and the environment. In particular, identification of the origin or sources of particulate matter emissions is of paramount importance in assisting efforts to control and reduce air pollution in the atmosphere. This thesis aims to: identify the sources of particulate matter; compare pollution conditions at urban, rural and roadside receptor sites; combine information about the sources with meteorological conditions at the sites to locate the emission sources; compare sources based on particle size or mass; and ultimately, provide the basis for control and reduction in particulate matter concentrations in the atmosphere. To achieve these objectives, data was obtained from assorted local and international receptor sites over long sampling periods. The samples were analysed using Ion Beam Analysis and Scanning Mobility Particle Sizer methods to measure the particle mass with chemical composition and the particle size distribution, respectively. Advanced data analysis techniques were employed to derive information from large, complex data sets. Multi-Criteria Decision Making (MCDM), a ranking method, drew on data variability to examine the overall trends, and provided the rank ordering of the sites and years that sampling was conducted. Coupled with the receptor model Positive Matrix Factorisation (PMF), the pollution emission sources were identified and meaningful information pertinent to the prioritisation of control and reduction strategies was obtained. This thesis is presented in the thesis by publication format. It includes four refereed papers which together demonstrate a novel combination of data analysis techniques that enabled particulate matter sources to be identified and sampling site/year ranked. The strength of this source identification process was corroborated when the analysis procedure was expanded to encompass multiple receptor sites. Initially applied to identify the contributing sources at roadside and suburban sites in Brisbane, the technique was subsequently applied to three receptor sites (roadside, urban and rural) located in Hong Kong. The comparable results from these international and national sites over several sampling periods indicated similarities in source contributions between receptor site-types, irrespective of global location and suggested the need to apply these methods to air pollution investigations worldwide. Furthermore, an investigation into particle size distribution data was conducted to deduce the sources of aerosol emissions based on particle size and elemental composition. Considering the adverse effects on human health caused by small-sized particles, knowledge of particle size distribution and their elemental composition provides a different perspective on the pollution problem. This thesis clearly illustrates that the application of an innovative combination of advanced data interpretation methods to identify particulate matter sources and rank sampling sites/years provides the basis for the prioritisation of future air pollution control measures. Moreover, this study contributes significantly to knowledge based on chemical composition of airborne particulate matter in Brisbane, Australia and on the identity and plausible locations of the contributing sources. Such novel source apportionment and ranking procedures are ultimately applicable to environmental investigations worldwide.

Ingenuity pathways analysis of urine metabonomics phenotypes toxicity of gentamicin in multiple organs

We introduce the use of Ingenuity Pathway Analysis to analyzing global metabonomics in order to characterize phenotypically biochemical perturbations and the potential mechanisms of the gentamicin-induced toxicity in multiple organs. A single dose of gentamicin was administered to Sprague Dawley rats (200 mg/kg, n = 6) and urine samples were collected at -24-0 h pre-dosage, 0-24, 24-48, 48-72 and 72-96 h post-dosage of gentamicin. The urine metabonomics analysis was performed by UPLC/MS, and the mass spectra signals of the detected metabolites were systematically deconvoluted and analyzed by pattern recognition analyses (Heatmap, PCA and PLS-DA), revealing a time-dependency of the biochemical perturbations induced by gentamicin toxicity. As result, the holistic metabolome change induced by gentamicin toxicity in the animal's organisms was characterized. Several metabolites involved in amino acid metabolism were identified in urine, and it was confirmed that gentamicin biochemical perturbations can be foreseen from these biomarkers. Notoriously, it was found that gentamicin induced toxicity in multiple organs system in the laboratory rats. The proof-of-knowledge based Ingenuity Pathway Analysis revealed gentamicin induced liver and heart toxicity, along with the previously known toxicity in kidney. The metabolites creatine, nicotinic acid, prostaglandin E2, and cholic acid were identified and validated as phenotypic biomarkers of gentamicin induced toxicity. Altogether, the significance of the use of metabonomics analyses in the assessment of drug toxicity is highlighted once more; furthermore, this work demonstrated the powerful predictive potential of the Ingenuity Pathway Analysis to study of drug toxicity and its valuable complementation for metabonomics based assessment of the drug toxicity.