On-line learning in neural networks

On-line learning is one of the most powerful and commonly used techniques for training large layered networks and has been used successfully in many real-world applications. Traditional analytical methods have been recently complemented by ones from statistical physics and Bayesian statistics. This powerful combination of analytical methods provides more insight and deeper understanding of existing algorithms and leads to novel and principled proposals for their improvement. This book presents a coherent picture of the state-of-the-art in the theoretical analysis of on-line learning. An introduction relates the subject to other developments in neural networks and explains the overall picture. Surveys by leading experts in the field combine new and established material and enable non-experts to learn more about the techniques and methods used. This book, the first in the area, provides a comprehensive view of the subject and will be welcomed by mathematicians, scientists and engineers, whether in industry or academia.

Statistical mechanics analysis of LDPC coding in MIMO Gaussian channels

Using analytical methods of statistical mechanics, we analyse the typical behaviour of a multiple-input multiple-output (MIMO) Gaussian channel with binary inputs under low-density parity-check (LDPC) network coding and joint decoding. The saddle point equations for the replica symmetric solution are found in particular realizations of this channel, including a small and large number of transmitters and receivers. In particular, we examine the cases of a single transmitter, a single receiver and symmetric and asymmetric interference. Both dynamical and thermodynamical transitions from the ferromagnetic solution of perfect decoding to a non-ferromagnetic solution are identified for the cases considered, marking the practical and theoretical limits of the system under the current coding scheme. Numerical results are provided, showing the typical level of improvement/deterioration achieved with respect to the single transmitter/receiver result, for the various cases. © 2007 IOP Publishing Ltd.

Biochemical markers and contact lens wear

The project objective was to develop a reliable selection procedure to match contact lens materials with individual wearers by the identification of a biochemical marker for assessment of in-eye performance of contact lenses. There is a need for such a procedure as one of the main reasons for contact lens wearers ceasing wearing contact lenses is poor end of day comfort i.e. the lenses become intolerable to the wearer as the day progresses. The selection of an optimal material for individual wearers has the potential benefit to reduce drop Qut, hence increasing the overall contact lens population, and to improve contact lens comfort for established wearers. Using novel analytical methods and statistical techniques, we were able to investigate the interactions between the composition of the tear film and of the biofilm deposited on the contact lenses and contact lens performance. The investigations were limited to studying the lipid components of the tear film; the lipid layer, which plays a key role in preventing evaporation and stabilising the tear film, has been reported to be significantly thinner and of different mixing characteristics during contact lens wear. Different lipid families were found to influence symptomatology, in vivo tear film structure and stability as well as ocular integrity. Whereas the symptomatology was affected by both the tear film lipid composition and the nature of the lipid deposition, the structure of the tear film and its stability were mainly influenced by the tear film lipid composition. The ocular integrity also appeared to be influenced by the nature of the lipid deposition. Potential markers within the lipid species have been identified and could be applied as follows: When required in order to identify a problematic wearer or to match the contact lens material to the contact lens wearer, tear samples collected by the clinician could be dispatched to an analytical laboratory where lipid analysis could be carried out by HPLC. A colorimetric kit based on the lipid markers could also be developed and used by clinician directly in the practice; such a kit would involve tear sampling and classification according to the colour into "Problem", "Border line" and "Good" contact lens wearers groups. A test kit would also have wider scope for marketing in other areas such as general dry-eye pathology.

An examination of the appropriateness of the contemporary strategic management models for the Greek small manufacturing enterprises

The starting point of the project was the observation that strategic management is absent in small businesses. The first objective of the project was to examine the reasons causing this situation in Greece, the second one, to examine the appropriateness of the contemporary models of strategic planning for the Greek S.M.E.s, and the third to examine the appropriateness of the alternative approaches to strategic management for the Greek S.M.E.s. The term appropriateness includes (a) the ability of managers to use the models and (b) the ability of the models to assist the managers. The results of the research indicate that none of the two above conditions exists, hence, it is suggested that the contemporary models of strategic management are inappropriate for the Greek S.M.E.s. Many previous research projects on the topic suggest that since the strategic decision making process in S.M.E.s is informal, the whole process is absent or ineffective. Current trends in S.M.E.s' strategic management do not consider the informality of the strategic decision making process as a kind of managerial illness, but as a managerial characteristic. The use of sophisticated data collection and analytical methods does not indicate successful strategic decisions, but it indicates the method large firms use to manage their strategy. According to the literature review, the S.M.E.s' managers avoid the use of the contemporary models of strategic management, because they do not have the knowledge, the resources or the time. Another thesis, expressed by some firms' specialists, suggests that small firms are different from large ones, hence their practice of strategic management should not follow the large firm's prototypes.

Chemical synthesis of isotopically labelled (M+4) purine nucleosides and their incorporation into DNA oligomers

Development of accurate and sensitive analytical methods to measure the level of biomarkers, such as 8-oxo-guanine or its corresponding nucleoside, 8-oxo-2’-deoxyguanosine, has become imperative in the study of DNA oxidative damage in vivo. Of the most promising techniques, HPLC-MS/MS, has many attractive advantages. Like any method that employs the MS technique, its accuracy depends on the use of multiply, isotopically-labelled internal standards. This project is aimed at making available such internal standards. The first task was to synthesise the multiply, isotopically-labelled bases (M+4) guanine and (M+4) 8-oxo-guanine. Synthetic routes for both (M+4) guanine and (M+4) 8-oxo-guanine were designed and validated using the unlabelled compounds. The reaction conditions were also optimized during the “dry runs”. The amination of the 4-hydroxy-2,6-dichloropyrimidine, appeared to be very sensitive to the purity of the commercial [15]N benzylamine reagent. Having failed, after several attempts, to obtain the pure reagent from commercial suppliers, [15]N benzylamine was successfully synthesised in our laboratory and used in the first synthesis of (M+4) guanine. Although (M+4) bases can be, and indeed have been used as internal standards in the quantitative analysis of oxidative damage, they can not account for the errors that may occur during the early sample preparation stages. Therefore, internal standards in the form of nucleosides and DNA oligomers are more desirable. After evaluating a number of methods, an enzymatic transglycolization technique was adopted for the transfer of the labelled bases to give their corresponding nucleosides. Both (M+4) 2-deoxyguanosine and (M+4) 8-oxo-2’-deoxyguanosine can be purified on micro scale by HPLC. The challenge came from the purification of larger scale (>50 mg) synthesis of nucleosides. A gel filtration method was successfully developed, which resulted in excellent separation of (M+4) 2’-deoxyguanosine from the incubation mixture. The (M+4) 2’-deoxyguanosine was then fully protected in three steps and successfully incorporated, by solid supported synthesis, into a DNA oligomer containing 18 residues. Thus, synthesis of 8-oxo-deoxyguanosine on a bigger scale for its future incorporation into DNA oligomers is now a possibility resulting from this thesis work. We believe that these internal standards can be used to develop procedures that can make the measurement of oxidative DNA damage more accurate and sensitive.

A soft-computing-based method for the automatic discovery of fuzzy rules in databases:uses for academic research and management support in marketing

The study here highlights the potential that analytical methods based on Knowledge Discovery in Databases (KDD) methodologies have to aid both the resolution of unstructured marketing/business problems and the process of scholarly knowledge discovery. The authors present and discuss the application of KDD in these situations prior to the presentation of an analytical method based on fuzzy logic and evolutionary algorithms, developed to analyze marketing databases and uncover relationships among variables. A detailed implementation on a pre-existing data set illustrates the method. © 2012 Published by Elsevier Inc.

The influence of marketing factors and substance characteristics on pharmaceutical sales in a state-controlled prescriptions pharmaceuticals market

The present dissertation investigates the influence of brand as well as substance-related marketing attributes on prescription pharmaceutical sales within a state-controlled market. For this purpose, a systematic literature review was conducted in the first instance, during which knowledge about the most relevant research within this field was gathered. Consequently, over 538 publications were reviewed and indicated as being potentially relevant, leading to an eventual count of 98 core publications. However, most of these studies had been conducted in the mainly unrestricted US market. These findings were then summarised and statistically evaluated. In a second step, based on the literature review, a qualitative study, containing focus and Delphi groups, was then performed. The participants in these studies were involved in pharmaceutical marketing within a state-controlled prescriptions pharmaceuticals market. Consequently, the findings were slightly different to those derived by the systematic literature review. Based on this second step, seven hypotheses were proposed. In the third step, these hypotheses were tested, using collected data and a secondary market dataset provided by a market research institute. A statistical analysis was then performed, applying descriptive as well as multiple regression analytical methods. The evaluation of the results resulted in a conceptual model of physician targeting, leading to several theoretical, methodological and managerial implications.

Analysis of a full-memory multidestination ARQ protocol over broadcast links

Based on an assumption that a steady state exists in the full-memory multidestination automatic repeat request (ARQ) scheme, we propose a novel analytical method called steady-state function method (SSFM), to evaluate the performance of the scheme with any size of receiver buffer. For a wide range of system parameters, SSFM has higher accuracy on throughput estimation as compared to the conventional analytical methods.

Oxidiative lipidomics coming of age:advances in analysis of oxidized phospholipids in physiology and pathology

Significance: Oxidized phospholipids are now well-recognized as markers of biological oxidative stress and bioactive molecules with both pro-inflammatory and anti-inflammatory effects. While analytical methods continue to be developed for studies of generic lipid oxidation, mass spectrometry (MS) has underpinned the advances in knowledge of specific oxidized phospholipids by allowing their identification and characterization, and is responsible for the expansion of oxidative lipidomics. Recent Advances: Studies of oxidized phospholipids in biological samples, both from animal models and clinical samples, have been facilitated by the recent improvements in MS, especially targeted routines that depend on the fragmentation pattern of the parent molecular ion and improved resolution and mass accuracy. MS can be used to identify selectively individual compounds or groups of compounds with common features, which greatly improves the sensitivity and specificity of detection. Application of these methods have enabled important advances in understanding the mechanisms of inflammatory diseases such as atherosclerosis, steatohepatitis, leprosy and cystic fibrosis, and offer potential for developing biomarkers of molecular aspects of the diseases. Critical Issues and Future Directions: The future in this field will depend on development of improved MS technologies, such as ion mobility, novel enrichment methods and databases and software for data analysis, owing to the very large amount of data generated in these experiments. Imaging of oxidized phospholipids in tissue MS is an additional exciting direction emerging that can be expected to advance understanding of physiology and disease.

The extracellular surface of the GLP-1 receptor is a molecular trigger for biased agonism

Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists.