Modeling gene expression regulatory networks with the sparse vector autoregressive model

Abstract Background To understand the molecular mechanisms underlying important biological processes, a detailed description of the gene products networks involved is required. In order to define and understand such molecular networks, some statistical methods are proposed in the literature to estimate gene regulatory networks from time-series microarray data. However, several problems still need to be overcome. Firstly, information flow need to be inferred, in addition to the correlation between genes. Secondly, we usually try to identify large networks from a large number of genes (parameters) originating from a smaller number of microarray experiments (samples). Due to this situation, which is rather frequent in Bioinformatics, it is difficult to perform statistical tests using methods that model large gene-gene networks. In addition, most of the models are based on dimension reduction using clustering techniques, therefore, the resulting network is not a gene-gene network but a module-module network. Here, we present the Sparse Vector Autoregressive model as a solution to these problems. Results We have applied the Sparse Vector Autoregressive model to estimate gene regulatory networks based on gene expression profiles obtained from time-series microarray experiments. Through extensive simulations, by applying the SVAR method to artificial regulatory networks, we show that SVAR can infer true positive edges even under conditions in which the number of samples is smaller than the number of genes. Moreover, it is possible to control for false positives, a significant advantage when compared to other methods described in the literature, which are based on ranks or score functions. By applying SVAR to actual HeLa cell cycle gene expression data, we were able to identify well known transcription factor targets. Conclusion The proposed SVAR method is able to model gene regulatory networks in frequent situations in which the number of samples is lower than the number of genes, making it possible to naturally infer partial Granger causalities without any a priori information. In addition, we present a statistical test to control the false discovery rate, which was not previously possible using other gene regulatory network models.

Enabling Techniques and Algorithms for Integrated Communication and Navigation Satellite Systems

This thesis presents the outcomes of my Ph.D. course in telecommunications engineering. The focus of my research has been on Global Navigation Satellite Systems (GNSS) and in particular on the design of aiding schemes operating both at position and physical level and the evaluation of their feasibility and advantages. Assistance techniques at the position level are considered to enhance receiver availability in challenging scenarios where satellite visibility is limited. Novel positioning techniques relying on peer-to-peer interaction and exchange of information are thus introduced. More specifically two different techniques are proposed: the Pseudorange Sharing Algorithm (PSA), based on the exchange of GNSS data, that allows to obtain coarse positioning where the user has scarce satellite visibility, and the Hybrid approach, which also permits to improve the accuracy of the positioning solution. At the physical level, aiding schemes are investigated to improve the receiver’s ability to synchronize with satellite signals. An innovative code acquisition strategy for dual-band receivers, the Cross-Band Aiding (CBA) technique, is introduced to speed-up initial synchronization by exploiting the exchange of time references between the two bands. In addition vector configurations for code tracking are analyzed and their feedback generation process thoroughly investigated.

In vitro synthesis of the light-harvesting complex into artificial membrane systems

In green plants, the function of collecting solar energy for photosynthesis is fulfilled by a series of light-harvesting complexes (LHC). The light-harvesting chlorophyll a/b protein (LHCP) is synthesized in the cytosol as a precursor (pLHCP), then imported into chloroplasts and assembled into photosynthetic thylakoid membranes. Knowledge about the regulation of the transport processes of LHCP is rather limited. Closely mimicking the in vivo situation, cell-free protein expression system is employed in this dissertation to study the reconstitution of LHCP into artificial membranes. The approach starts merely from the genetic information of the protein, so the difficult and time-consuming procedures of protein expression and purification can be avoided. The LHCP encoding gene from Pisum sativum was cloned into a cell-free compatible vector system and the protein was expressed in wheat germ extracts. Vesicles or pigment-containing vesicles were prepared with either synthetic lipid or purified plant leaf lipid to mimic cell membranes. LHCP was synthesized in wheat germ extract systems with or without supplemented lipids. The addition of either synthetic or purified plant leaf lipid was found to be beneficial to the general productivity of the expression system. The lipid membrane insertion of the LHCP was investigated by radioactive labelling, protease digestion, and centrifugation assays. The LHCP is partially protected against protease digestion; however the protection is independent from the supplemented lipids.

Exclusive vector meson production in pp collisions at the COMPASS experiment

Produktionsmechanismen für Teilchenproduktion im mittleren Energiebereich wurden in Proton-Proton Kollisionen innerhalb der COMPASS-Kollaboration mit Hilfe des COMPASS-Spektrometers am SPS Beschleuniger am CERN untersucht. Die verschiedenen Produktionsmechanismen werden mittels Produktion der Vektormesonen omega und phi studiert und können die diffraktive Anregung des Strahlteilchens mit anschliessendem Zerfall der Resonanz, zentrale Produktion und den damit verwandten “Shake-off” Mechanismus enthalten. Die für diese Arbeit verwendeten Daten wurden in den Jahren 2008 und 2009 mit 190 GeV/c-Protonen aufgenommen, die auf ein Flüssigwasserstofftarget trafen. Das Target war von einem Rückstoßprotonendetektor umgeben, der ein integraler Bestandteil des neuentwickelten Hadrontriggersystems ist. Für dieses System wurden außerdem einige neue Detektoren gebaut. Die Leistungsfähigkeit des Rückstoßprotonendetektors und des Triggersystems wird untersucht und Effizienzen extrahiert. Außerdem wird sowohl eine Methode zur Rekonstruktion von Rückstoßprotonen als auch eine Methode zur Kalibration des Rückstoßprotonendetektors entwickelt und beschrieben. Die Produktion von omega-Mesonen wurde in der Reaktion pp -> p omega p, omega -> pi+pi-pi0 und die Produktion von phi-Mesonen in der Reaktion pp -> p phi p, phi -> K+K- bei einem Impulsübertrag zwischen 0.1 (GeV/c)^2 und 1 (GeV/c)^2 gemessen. Das Produktionsverhältnis s(pp -> p phi p)/s(pp -> p omega p) wird als Funktion des longitudinalen Impulsanteils xF bestimmt und mit der Vorhersage durch die Zweigregel verglichen. Es ergibt sich eine signifikante Verletzung der Zweigregel, die abhängig von xF ist. Die Verletzung wird in Verbindung zu resonanten Strukturen im pomega-Massenspektrum diskutiert. Die xF-Abhängigkeit verschwindet, wenn man die Region niedriger pomega- und pphi-Masse entfernt, die solche resonanten Strukturen aufweist. Zusätzlich wird die Spinausrichtung bzw. das Spindichtematrixelement rho00 für omega- und phi-Mesonen untersucht. Die Spinausrichtung wird im Helizitätssystemrnanalysiert, welches für eine Abgrenzung von resonanten, diffraktiven Anregungen geeignet ist. Außerdem wird die Spinausrichtung in einem Referenzsystem mit Bezug auf die Richtung des Impulsübertrags untersucht, mit dessen Hilfe zentrale Prozesse wie zentrale Produktion oder “shake-off” abgegrenzt werden. Auch hier wird eine Abhängigkeit von xF und der invarianten Masse des pomega-Systems beobachtet. Diese Abhängigkeit kann wieder auf die resonanten Strukturen in der Produktion von omega-Mesonen zurückgeführt werden. Die Ergebnisse werden abschließend im Hinblick auf die verschiedenen Produktionsmechanismen diskutiert.

A structural method for the design of fault tolerant distributed control systems

Distributed digital control systems provide alternatives to conventional, centralised digital control systems. Typically, a modern distributed control system will comprise a multi-processor or network of processors, a communications network, an associated set of sensors and actuators, and the systems and applications software. This thesis addresses the problem of how to design robust decentralised control systems, such as those used to control event-driven, real-time processes in time-critical environments. Emphasis is placed on studying the dynamical behaviour of a system and identifying ways of partitioning the system so that it may be controlled in a distributed manner. A structural partitioning technique is adopted which makes use of natural physical sub-processes in the system, which are then mapped into the software processes to control the system. However, communications are required between the processes because of the disjoint nature of the distributed (i.e. partitioned) state of the physical system. The structural partitioning technique, and recent developments in the theory of potential controllability and observability of a system, are the basis for the design of controllers. In particular, the method is used to derive a decentralised estimate of the state vector for a continuous-time system. The work is also extended to derive a distributed estimate for a discrete-time system. Emphasis is also given to the role of communications in the distributed control of processes and to the partitioning technique necessary to design distributed and decentralised systems with resilient structures. A method is presented for the systematic identification of necessary communications for distributed control. It is also shwon that the structural partitions can be used directly in the design of software fault tolerant concurrent controllers. In particular, the structural partition can be used to identify the boundary of the conversation which can be used to protect a specific part of the system. In addition, for certain classes of system, the partitions can be used to identify processes which may be dynamically reconfigured in the event of a fault. These methods should be of use in the design of robust distributed systems.

Subject identification via ECG fiducial-based systems:influence of the type of QT interval correction

Electrocardiography (ECG) has been recently proposed as biometric trait for identification purposes. Intra-individual variations of ECG might affect identification performance. These variations are mainly due to Heart Rate Variability (HRV). In particular, HRV causes changes in the QT intervals along the ECG waveforms. This work is aimed at analysing the influence of seven QT interval correction methods (based on population models) on the performance of ECG-fiducial-based identification systems. In addition, we have also considered the influence of training set size, classifier, classifier ensemble as well as the number of consecutive heartbeats in a majority voting scheme. The ECG signals used in this study were collected from thirty-nine subjects within the Physionet open access database. Public domain software was used for fiducial points detection. Results suggested that QT correction is indeed required to improve the performance. However, there is no clear choice among the seven explored approaches for QT correction (identification rate between 0.97 and 0.99). MultiLayer Perceptron and Support Vector Machine seemed to have better generalization capabilities, in terms of classification performance, with respect to Decision Tree-based classifiers. No such strong influence of the training-set size and the number of consecutive heartbeats has been observed on the majority voting scheme.

Passive solar systems for heating, daylighting and ventilation for rooms without an equator-facing facade

Spaces without northerly orientations have an impact on the ‘energy behaviour’ of a building. This paper outlines possible energy savings and better performance achieved by different zenithal solar passive strategies (skylights, roof monitors and clerestory roof windows) and element arrangements across the roof in zones of cold to temperate climates typical of the central and central-southern Argentina. Analyses were undertaken considering daylighting, thermal and ventilation performances of the different strategies. The results indicate that heating,ventilation and lighting loads in spaces without an equator-facing facade can be significantly reduced by implementing solar passive strategies. In the thermal aspect, the solar saving fraction reached for the different strategies were averaged 43.16% for clerestories, 41.4% for roof monitors and 38.86% for skylights for a glass area of 9% to the floor area. The results also indicate average illuminance levels above 500 lux for the different clerestory and monitor arrangements, uniformity ratios of 0.66–0.82 for the most distributed arrangements and day-lighting factors between 11.78 and 20.30% for clear sky conditions, depending on the strategy. In addition, minimum air changes rates of 4 were reached for the most extreme conditions.

Investigating relationships between relationship quality, customer loyalty and cooperation : an empirical study of convenience stores' franchise chain systems in Taiwan

Franchising has been widely accepted as an effective way to conduct and expand businesses. However, a franchise system is not a guarantee of success in the market. A successful franchise system should rely on a close and strong franchising relationship. Franchising is an important relationship management business. Franchising arrangements normally last for a number of years, so the franchisor and franchisee in the arrangement relationship are usually motivated to cooperate with each other. In addition, highly loyal franchisees may be obtained through a successful long-term franchising relationship. Over the last few decades, there has been a tremendous wave of interest in franchising relationships. However, little research has been conducted to determine the reasons for long-term franchising relationships. As a result, this study focuses on the important elements that might lead to a successful long-term franchising relationship. This study attempts to examine empirically three essential constructs (relationship quality, cooperation and customer loyalty), which might lead to successful long-term franchising relationships between franchisees and franchisors among the convenience stores in Taiwan. Mailed questionnaires were utilised to collect the research data. A total of 500 surveys were mailed randomly to the manager/supervisor of convenience stores’ franchisees among the four main franchisors (7-ELEVEN, Family, Hi-Life and OK) in Taiwan. The final sample size is 120, yielding a response rate of 24 per cent. The results show that relationship quality positively influences the cooperative relationships between franchisors and franchisees. Relationship quality is also positively correlated with franchisees’ loyalty. Additionally, the results indicate that the cooperative relationships between franchisors and franchisees are significantly associated with franchisees’ loyalty.

The problem of measurement indeterminacy in complex neurobiological movement systems

In the study of complex neurobiological movement systems, measurement indeterminacy has typically been overcome by imposing artificial modelling constraints to reduce the number of unknowns (e.g., reducing all muscle, bone and ligament forces crossing a joint to a single vector). However, this approach prevents human movement scientists from investigating more fully the role, functionality and ubiquity of coordinative structures or functional motor synergies. Advancements in measurement methods and analysis techniques are required if the contribution of individual component parts or degrees of freedom of these task-specific structural units is to be established, thereby effectively solving the indeterminacy problem by reducing the number of unknowns. A further benefit of establishing more of the unknowns is that human movement scientists will be able to gain greater insight into ubiquitous processes of physical self-organising that underpin the formation of coordinative structures and the confluence of organismic, environmental and task constraints that determine the exact morphology of these special-purpose devices.

Integrated Diagnosis and Prognosis Model for High Pressure LNG Pump

In condition-based maintenance (CBM), effective diagnostics and prognostics are essential tools for maintenance engineers to identify imminent fault and to predict the remaining useful life before the components finally fail. This enables remedial actions to be taken in advance and reschedules production if necessary. This paper presents a technique for accurate assessment of the remnant life of machines based on historical failure knowledge embedded in the closed loop diagnostic and prognostic system. The technique uses the Support Vector Machine (SVM) classifier for both fault diagnosis and evaluation of health stages of machine degradation. To validate the feasibility of the proposed model, the five different level data of typical four faults from High Pressure Liquefied Natural Gas (HP-LNG) pumps were used for multi-class fault diagnosis. In addition, two sets of impeller-rub data were analysed and employed to predict the remnant life of pump based on estimation of health state. The results obtained were very encouraging and showed that the proposed prognosis system has the potential to be used as an estimation tool for machine remnant life prediction in real life industrial applications.

A Numerical Solution Using an Adaptively Preconditioned Lanczos Method for a Class of Linear Systems Related with the Fractional Poisson Equation

This study considers the solution of a class of linear systems related with the fractional Poisson equation (FPE) (−∇2)α/2φ=g(x,y) with nonhomogeneous boundary conditions on a bounded domain. A numerical approximation to FPE is derived using a matrix representation of the Laplacian to generate a linear system of equations with its matrix A raised to the fractional power α/2. The solution of the linear system then requires the action of the matrix function f(A)=A−α/2 on a vector b. For large, sparse, and symmetric positive definite matrices, the Lanczos approximation generates f(A)b≈β0Vmf(Tm)e1. This method works well when both the analytic grade of A with respect to b and the residual for the linear system are sufficiently small. Memory constraints often require restarting the Lanczos decomposition; however this is not straightforward in the context of matrix function approximation. In this paper, we use the idea of thick-restart and adaptive preconditioning for solving linear systems to improve convergence of the Lanczos approximation. We give an error bound for the new method and illustrate its role in solving FPE. Numerical results are provided to gauge the performance of the proposed method relative to exact analytic solutions.

A role mining inspired approach to representing user behaviour in ERP systems

Despite all attempts to prevent fraud, it continues to be a major threat to industry and government. Traditionally, organizations have focused on fraud prevention rather than detection, to combat fraud. In this paper we present a role mining inspired approach to represent user behaviour in Enterprise Resource Planning (ERP) systems, primarily aimed at detecting opportunities to commit fraud or potentially suspicious activities. We have adapted an approach which uses set theory to create transaction profiles based on analysis of user activity records. Based on these transaction profiles, we propose a set of (1) anomaly types to detect potentially suspicious user behaviour and (2) scenarios to identify inadequate segregation of duties in an ERP environment. In addition, we present two algorithms to construct a directed acyclic graph to represent relationships between transaction profiles. Experiments were conducted using a real dataset obtained from a teaching environment and a demonstration dataset, both using SAP R/3, presently the most predominant ERP system. The results of this empirical research demonstrate the effectiveness of the proposed approach.

Evaluating information systems

The book within which this chapter appears is published as a research reference book (not a coursework textbook) on Management Information Systems (MIS) for seniors or graduate students in Chinese universities. It is hoped that this chapter, along with the others, will be helpful to MIS scholars and PhD/Masters research students in China who seek understanding of several central Information Systems (IS) research topics and related issues. The subject of this chapter - ‘Evaluating Information Systems’ - is broad, and cannot be addressed in its entirety in any depth within a single book chapter. The chapter proceeds from the truism that organizations have limited resources and those resources need to be invested in a way that provides greatest benefit to the organization. IT expenditure represents a substantial portion of any organization’s investment budget and IT related innovations have broad organizational impacts. Evaluation of the impact of this major investment is essential to justify this expenditure both pre- and post-investment. Evaluation is also important to prioritize possible improvements. The chapter (and most of the literature reviewed herein) admittedly assumes a blackbox view of IS/IT1, emphasizing measures of its consequences (e.g. for organizational performance or the economy) or perceptions of its quality from a user perspective. This reflects the MIS emphasis – a ‘management’ emphasis rather than a software engineering emphasis2, where a software engineering emphasis might be on the technical characteristics and technical performance. Though a black-box approach limits diagnostic specificity of findings from a technical perspective, it offers many benefits. In addition to superior management information, these benefits may include economy of measurement and comparability of findings (e.g. see Part 4 on Benchmarking IS). The chapter does not purport to be a comprehensive treatment of the relevant literature. It does, however, reflect many of the more influential works, and a representative range of important writings in the area. The author has been somewhat opportunistic in Part 2, employing a single journal – The Journal of Strategic Information Systems – to derive a classification of literature in the broader domain. Nonetheless, the arguments for this approach are believed to be sound, and the value from this exercise real. The chapter drills down from the general to the specific. It commences with a highlevel overview of the general topic area. This is achieved in 2 parts: - Part 1 addressing existing research in the more comprehensive IS research outlets (e.g. MISQ, JAIS, ISR, JMIS, ICIS), and Part 2 addressing existing research in a key specialist outlet (i.e. Journal of Strategic Information Systems). Subsequently, in Part 3, the chapter narrows to focus on the sub-topic ‘Information Systems Success Measurement’; then drilling deeper to become even more focused in Part 4 on ‘Benchmarking Information Systems’. In other words, the chapter drills down from Parts 1&2 Value of IS, to Part 3 Measuring Information Systems Success, to Part 4 Benchmarking IS. While the commencing Parts (1&2) are by definition broadly relevant to the chapter topic, the subsequent, more focused Parts (3 and 4) admittedly reflect the author’s more specific interests. Thus, the three chapter foci – value of IS, measuring IS success, and benchmarking IS - are not mutually exclusive, but, rather, each subsequent focus is in most respects a sub-set of the former. Parts 1&2, ‘the Value of IS’, take a broad view, with much emphasis on ‘the business Value of IS’, or the relationship between information technology and organizational performance. Part 3, ‘Information System Success Measurement’, focuses more specifically on measures and constructs employed in empirical research into the drivers of IS success (ISS). (DeLone and McLean 1992) inventoried and rationalized disparate prior measures of ISS into 6 constructs – System Quality, Information Quality, Individual Impact, Organizational Impact, Satisfaction and Use (later suggesting a 7th construct – Service Quality (DeLone and McLean 2003)). These 6 constructs have been used extensively, individually or in some combination, as the dependent variable in research seeking to better understand the important antecedents or drivers of IS Success. Part 3 reviews this body of work. Part 4, ‘Benchmarking Information Systems’, drills deeper again, focusing more specifically on a measure of the IS that can be used as a ‘benchmark’3. This section consolidates and extends the work of the author and his colleagues4 to derive a robust, validated IS-Impact measurement model for benchmarking contemporary Information Systems (IS). Though IS-Impact, like ISS, has potential value in empirical, causal research, its design and validation has emphasized its role and value as a comparator; a measure that is simple, robust and generalizable and which yields results that are as far as possible comparable across time, across stakeholders, and across differing systems and systems contexts.