Prediction of transcriptional regulatory interactions in bacteria : a comparative genomics approach

Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.

A constraint to improve the reliability of stereo matching using the rank transform

The rank transform is a non-parametric technique which has been recently proposed for the stereo matching problem. The motivation behind its application to the matching problem is its invariance to certain types of image distortion and noise, as well as its amenability to real-time implementation. This paper derives an analytic expression for the process of matching using the rank transform, and then goes on to derive one constraint which must be satisfied for a correct match. This has been dubbed the rank order constraint or simply the rank constraint. Experimental work has shown that this constraint is capable of resolving ambiguous matches, thereby improving matching reliability. This constraint was incorporated into a new algorithm for matching using the rank transform. This modified algorithm resulted in an increased proportion of correct matches, for all test imagery used.

Quantitative evaluation of matching methods and validity measures for stereo vision

The authors present a qualitative and quantitative comparison of various similarity measures that form the kernel of common area-based stereo-matching systems. The authors compare classical difference and correlation measures as well as nonparametric measures based on the rank and census transforms for a number of outdoor images. For robotic applications, important considerations include robustness to image defects such as intensity variation and noise, the number of false matches, and computational complexity. In the absence of ground truth data, the authors compare the matching techniques based on the percentage of matches that pass the left-right consistency test. The authors also evaluate the discriminatory power of several match validity measures that are reported in the literature for eliminating false matches and for estimating match confidence. For guidance applications, it is essential to have and estimate of confidence in the three-dimensional points generated by stereo vision. Finally, a new validity measure, the rank constraint, is introduced that is capable of resolving ambiguous matches for rank transform-based matching.

Influence of inflow turbulence in shock-wave/turbulent-boundary-layer interaction computations

The influence of inflow turbulence on the results of Favre–Reynolds-averaged Navier–Stokes computations of supersonic oblique-shock-wave/turbulent-boundary-layer interactions (shock-wave Mach-number MSW ∼2.9), using seven-equation Reynolds-stress model turbulence closures, is studied. The generation of inflow conditions (and the initialization of the flowfield) for mean flow, Reynolds stresses, and turbulence length scale, based on semi-analytic grid-independent boundary-layer profiles, is described in detail. Particular emphasis is given to freestream turbulence intensity and length scale. The influence of external-flow turbulence intensity is studied in detail both for flat-plate boundary-layer flow and for a compression-ramp interaction with large separation. It is concluded that the Reynolds-stress model correctly reproduces the effects of external flow turbulence.

Thinking Critically in the Land of Princesses and Giants : The Affordances and Challenges of Critical Approaches in the Early Years

During the last four decades, educators have created a range of critical literacy approaches for different contexts, including compulsory schooling (Luke & Woods, 2009) and second language education (Luke & Dooley, 2011). Despite inspirational examples of critical work with young students (e.g., O’Brien, 1994; Vasquez, 1994), Comber (2012) laments the persistent myth that critical literacy is not viable in the early years. Assumptions about childhood innocence and the priorities of the back-to-basics movement seem to limit the possibilities for early years literacy teaching and learning. Yet, teachers of young students need not face an either/or choice between the basic and critical dimensions of literacy. Systematic ways of treating literacy in all its complexity exist. We argue that the integrative imperative is especially important in schools that are under pressure to improve technical literacy outcomes. In this chapter, we document how critical literacy was addressed in a fairytales unit taught to 4.5 - 5.5 year olds in a high diversity, high poverty Australian school. We analyze the affordances and challenges of different approaches to critical literacy, concluding they are complementary rather than competing sources of possibility. Furthermore, we make the case for turning familiar classroom activities to critical ends.

The product of text and 'Other' statements : discourse analysis and the critical use of Foucault

Much has been written on Michel Foucault’s reluctance to clearly delineate a research method, particularly with respect to genealogy (Harwood 2000; Meadmore, Hatcher, & McWilliam 2000; Tamboukou 1999). Foucault (1994, p. 288) himself disliked prescription stating, “I take care not to dictate how things should be” and wrote provocatively to disrupt equilibrium and certainty, so that “all those who speak for others or to others” no longer know what to do. It is doubtful, however, that Foucault ever intended for researchers to be stricken by that malaise to the point of being unwilling to make an intellectual commitment to methodological possibilities. Taking criticism of “Foucauldian” discourse analysis as a convenient point of departure to discuss the objectives of poststructural analyses of language, this paper develops what might be called a discursive analytic; a methodological plan to approach the analysis of discourses through the location of statements that function with constitutive effects.

Enhancing security of linux-based android devices

Our daily lives become more and more dependent upon smartphones due to their increased capabilities. Smartphones are used in various ways from payment systems to assisting the lives of elderly or disabled people. Security threats for these devices become increasingly dangerous since there is still a lack of proper security tools for protection. Android emerges as an open smartphone platform which allows modification even on operating system level. Therefore, third-party developers have the opportunity to develop kernel-based low-level security tools which is not normal for smartphone platforms. Android quickly gained its popularity among smartphone developers and even beyond since it bases on Java on top of "open" Linux in comparison to former proprietary platforms which have very restrictive SDKs and corresponding APIs. Symbian OS for example, holding the greatest market share among all smartphone OSs, was closing critical APIs to common developers and introduced application certification. This was done since this OS was the main target for smartphone malwares in the past. In fact, more than 290 malwares designed for Symbian OS appeared from July 2004 to July 2008. Android, in turn, promises to be completely open source. Together with the Linux-based smartphone OS OpenMoko, open smartphone platforms may attract malware writers for creating malicious applications endangering the critical smartphone applications and owners� privacy. In this work, we present our current results in analyzing the security of Android smartphones with a focus on its Linux side. Our results are not limited to Android, they are also applicable to Linux-based smartphones such as OpenMoko Neo FreeRunner. Our contribution in this work is three-fold. First, we analyze android framework and the Linux-kernel to check security functionalities. We survey wellaccepted security mechanisms and tools which can increase device security. We provide descriptions on how to adopt these security tools on Android kernel, and provide their overhead analysis in terms of resource usage. As open smartphones are released and may increase their market share similar to Symbian, they may attract attention of malware writers. Therefore, our second contribution focuses on malware detection techniques at the kernel level. We test applicability of existing signature and intrusion detection methods in Android environment. We focus on monitoring events on the kernel; that is, identifying critical kernel, log file, file system and network activity events, and devising efficient mechanisms to monitor them in a resource limited environment. Our third contribution involves initial results of our malware detection mechanism basing on static function call analysis. We identified approximately 105 Executable and Linking Format (ELF) executables installed to the Linux side of Android. We perform a statistical analysis on the function calls used by these applications. The results of the analysis can be compared to newly installed applications for detecting significant differences. Additionally, certain function calls indicate malicious activity. Therefore, we present a simple decision tree for deciding the suspiciousness of the corresponding application. Our results present a first step towards detecting malicious applications on Android-based devices.

Design and modeling of collaboration architecture for security

Threats against computer networks evolve very fast and require more and more complex measures. We argue that teams respectively groups with a common purpose for intrusion detection and prevention improve the measures against rapid propagating attacks similar to the concept of teams solving complex tasks known from field of work sociology. Collaboration in this sense is not easy task especially for heterarchical environments. We propose CIMD (collaborative intrusion and malware detection) as a security overlay framework to enable cooperative intrusion detection approaches. Objectives and associated interests are used to create detection groups for exchange of security-related data. In this work, we contribute a tree-oriented data model for device representation in the scope of security. We introduce an algorithm for the formation of detection groups, show realization strategies for the system and conduct vulnerability analysis. We evaluate the benefit of CIMD by simulation and probabilistic analysis.

Dimensions of short break destination attractiveness : a comparison of cognitive, affective and conative perceptions

Although there has been exponential growth in the number of studies of destination image appearing in the tourism literature, few have addressed the role of affective perceptions. This paper analyses the market positions held by a competitive set of destinations, through a comparison of cognitive, affective and conative perceptions. Cognitive perceptions were measured by trialling a factor analytic adaptation of importance-performance analysis. Affective perceptions were measured using an affective response grid. The alignment of the results from these techniques identified leadership positions held by two quite different destinations on two quite different dimensions of short break destination attractiveness.

Starter packs : a good start to therapy?

Samples of drugs are often given to doctors by pharmaceutical representatives as part of a marketing strategy. Despite the well described advantages of drug samples, little has been published on the potential adverse outcomes. A series of consumer calls to the Adverse Medicine Events Line has highlighted concerns regarding the quality use of medicines associated with drug samples. The most commonly reported problems were drug samples being supplied to patients with inadequate information regarding dosage, administration, storage and possible adverse effects. In addition, some patients were given excessive quantities of a drug. To reduce such adverse outcomes, the drug industry, health professionals and consumers should be aware of the potential problems associated with starter packs.

Goodbye TAIS and thanks for all the information

The Therapeutic Advice and Information Service was funded by the National Prescribing Service to provide a national drug information service for health professionals working in the community. For ten years the service achieved high levels of client satisfaction, and reached its contracted target of 6000 enquiries about medicines per year, however the service ceased on 30 June 2010.

An Android application sandbox system for suspicious software detection

Smartphones are steadily gaining popularity, creating new application areas as their capabilities increase in terms of computational power, sensors and communication. Emerging new features of mobile devices give opportunity to new threats. Android is one of the newer operating systems targeting smartphones. While being based on a Linux kernel, Android has unique properties and specific limitations due to its mobile nature. This makes it harder to detect and react upon malware attacks if using conventional techniques. In this paper, we propose an Android Application Sandbox (AASandbox) which is able to perform both static and dynamic analysis on Android programs to automatically detect suspicious applications. Static analysis scans the software for malicious patterns without installing it. Dynamic analysis executes the application in a fully isolated environment, i.e. sandbox, which intervenes and logs low-level interactions with the system for further analysis. Both the sandbox and the detection algorithms can be deployed in the cloud, providing a fast and distributed detection of suspicious software in a mobile software store akin to Google's Android Market. Additionally, AASandbox might be used to improve the efficiency of classical anti-virus applications available for the Android operating system.

Developing and benchmarking native Linux applications on Android

Smartphones get increasingly popular where more and more smartphone platforms emerge. Special attention was gained by the open source platform Android which was presented by the Open Handset Alliance (OHA) hosting members like Google, Motorola, and HTC. Android uses a Linux kernel and a stripped-down userland with a custom Java VM set on top. The resulting system joins the advantages of both environments, while third-parties are intended to develop only Java applications at the moment. In this work, we present the benefit of using native applications in Android. Android includes a fully functional Linux, and using it for heavy computational tasks when developing applications can bring in substantional performance increase. We present how to develop native applications and software components, as well as how to let Linux applications and components communicate with Java programs. Additionally, we present performance measurements of native and Java applications executing identical tasks. The results show that native C applications can be up to 30 times as fast as an identical algorithm running in Dalvik VM. Java applications can become a speed-up of up to 10 times if utilizing JNI.

Monitoring android for collaborative anomaly detection : a first architectural draft

Our daily lives become more and more dependent upon smartphones due to their increased capabilities. Smartphones are used in various ways, e.g. for payment systems or assisting the lives of elderly or disabled people. Security threats for these devices become more and more dangerous since there is still a lack of proper security tools for protection. Android emerges as an open smartphone platform which allows modification even on operating system level and where third-party developers first time have the opportunity to develop kernel-based low-level security tools. Android quickly gained its popularity among smartphone developers and even beyond since it bases on Java on top of "open" Linux in comparison to former proprietary platforms which have very restrictive SDKs and corresponding APIs. Symbian OS, holding the greatest market share among all smartphone OSs, was even closing critical APIs to common developers and introduced application certification. This was done since this OS was the main target for smartphone malwares in the past. In fact, more than 290 malwares designed for Symbian OS appeared from July 2004 to July 2008. Android, in turn, promises to be completely open source. Together with the Linux-based smartphone OS OpenMoko, open smartphone platforms may attract malware writers for creating malicious applications endangering the critical smartphone applications and owners privacy. Since signature-based approaches mainly detect known malwares, anomaly-based approaches can be a valuable addition to these systems. They base on mathematical algorithms processing data that describe the state of a certain device. For gaining this data, a monitoring client is needed that has to extract usable information (features) from the monitored system. Our approach follows a dual system for analyzing these features. On the one hand, functionality for on-device light-weight detection is provided. But since most algorithms are resource exhaustive, remote feature analysis is provided on the other hand. Having this dual system enables event-based detection that can react to the current detection need. In our ongoing research we aim to investigates the feasibility of light-weight on-device detection for certain occasions. On other occasions, whenever significant changes are detected on the device, the system can trigger remote detection with heavy-weight algorithms for better detection results. In the absence of the server respectively as a supplementary approach, we also consider a collaborative scenario. Here, mobile devices sharing a common objective are enabled by a collaboration module to share information, such as intrusion detection data and results. This is based on an ad-hoc network mode that can be provided by a WiFi or Bluetooth adapter nearly every smartphone possesses.

An entry mode decision-making model for the international expansion of construction enterprises

Purpose – The purpose of this paper is to provide a new type of entry mode decision-making model for construction enterprises involved in international business. Design/methodology/approach – A hybrid method combining analytic hierarchy process (AHP) with preference ranking organization method for enrichment evaluations (PROMETHEE) is used to aid entry mode decisions. The AHP is used to decompose the entry mode problem into several dimensions and determine the weight of each criterion. In addition, PROMETHEE method is used to rank candidate entry modes and carry out sensitivity analyses. Findings – The proposed decision-making method is demonstrated to be a suitable approach to resolve the entry mode selection decision problem. Practical implications – The research provides practitioners with a more systematic decision framework and a more precise decision method. Originality/value – The paper sheds light on the further development of entry strategies for international construction markets. It not only introduces a new decision-making model for entry mode decision making, but also provides a conceptual framework with five determinants for a construction company entry mode selection based on the unique properties of the construction industry.