A versatile and reliable two-component system for tissue-specific gene induction in Arabidopsis

Developmental progression and differentiation of distinct cell types depend on the regulation of gene expression in space and time. Tools that allow spatial and temporal control of gene expression are crucial for the accurate elucidation of gene function. Most systems to manipulate gene expression allow control of only one factor, space or time, and currently available systems that control both temporal and spatial expression of genes have their limitations. We have developed a versatile two-component system that overcomes these limitations, providing reliable, conditional gene activation in restricted tissues or cell types. This system allows conditional tissue-specific ectopic gene expression and provides a tool for conditional cell type- or tissue-specific complementation of mutants. The chimeric transcription factor XVE, in conjunction with Gateway recombination cloning technology, was used to generate a tractable system that can efficiently and faithfully activate target genes in a variety of cell types. Six promoters/enhancers, each with different tissue specificities (including vascular tissue, trichomes, root, and reproductive cell types), were used in activation constructs to generate different expression patterns of XVE. Conditional transactivation of reporter genes was achieved in a predictable, tissue-specific pattern of expression, following the insertion of the activator or the responder T-DNA in a wide variety of positions in the genome. Expression patterns were faithfully replicated in independent transgenic plant lines. Results demonstrate that we can also induce mutant phenotypes using conditional ectopic gene expression. One of these mutant phenotypes could not have been identified using noninducible ectopic gene expression approaches.

Bayesian spatiotemporal analysis of socio-ecologic drivers of Ross River Virus transmission in Queensland, Australia

This study aims to examine the impact of socio-ecologic factors on the transmission of Ross River virus (RRV) infection and to identify areas prone to social and ecologic-driven epidemics in Queensland, Australia. We used a Bayesian spatiotemporal conditional autoregressive model to quantify the relationship between monthly variation of RRV incidence and socio-ecologic factors and to determine spatiotemporal patterns. Our results show that the average increase in monthly RRV incidence was 2.4% (95% credible interval (CrI): 0.1–4.5%) and 2.0% (95% CrI: 1.6–2.3%) for a 1°C increase in monthly average maximum temperature and a 10 mm increase in monthly average rainfall, respectively. A significant spatiotemporal variation and interactive effect between temperature and rainfall on RRV incidence were found. No association between Socio-economic Index for Areas (SEIFA) and RRV was observed. The transmission of RRV in Queensland, Australia appeared to be primarily driven by ecologic variables rather than social factors.

Improving the performance of model-order selection criteria by partial-model selection search

The traditional searching method for model-order selection in linear regression is a nested full-parameters-set searching procedure over the desired orders, which we call full-model order selection. On the other hand, a method for model-selection searches for the best sub-model within each order. In this paper, we propose using the model-selection searching method for model-order selection, which we call partial-model order selection. We show by simulations that the proposed searching method gives better accuracies than the traditional one, especially for low signal-to-noise ratios over a wide range of model-order selection criteria (both information theoretic based and bootstrap-based). Also, we show that for some models the performance of the bootstrap-based criterion improves significantly by using the proposed partial-model selection searching method. Index Terms— Model order estimation, model selection, information theoretic criteria, bootstrap 1. INTRODUCTION Several model-order selection criteria can be applied to find the optimal order. Some of the more commonly used information theoretic-based procedures include Akaike’s information criterion (AIC) [1], corrected Akaike (AICc) [2], minimum description length (MDL) [3], normalized maximum likelihood (NML) [4], Hannan-Quinn criterion (HQC) [5], conditional model-order estimation (CME) [6], and the efficient detection criterion (EDC) [7]. From a practical point of view, it is difficult to decide which model order selection criterion to use. Many of them perform reasonably well when the signal-to-noise ratio (SNR) is high. The discrepancies in their performance, however, become more evident when the SNR is low. In those situations, the performance of the given technique is not only determined by the model structure (say a polynomial trend versus a Fourier series) but, more importantly, by the relative values of the parameters within the model. This makes the comparison between the model-order selection algorithms difficult as within the same model with a given order one could find an example for which one of the methods performs favourably well or fails [6, 8]. Our aim is to improve the performance of the model order selection criteria in cases where the SNR is low by considering a model-selection searching procedure that takes into account not only the full-model order search but also a partial model order search within the given model order. Understandably, the improvement in the performance of the model order estimation is at the expense of additional computational complexity.

Hierarchical Bayesian models for estimating the extent of plant pest invasions

Plant biosecurity requires statistical tools to interpret field surveillance data in order to manage pest incursions that threaten crop production and trade. Ultimately, management decisions need to be based on the probability that an area is infested or free of a pest. Current informal approaches to delimiting pest extent rely upon expert ecological interpretation of presence / absence data over space and time. Hierarchical Bayesian models provide a cohesive statistical framework that can formally integrate the available information on both pest ecology and data. The overarching method involves constructing an observation model for the surveillance data, conditional on the hidden extent of the pest and uncertain detection sensitivity. The extent of the pest is then modelled as a dynamic invasion process that includes uncertainty in ecological parameters. Modelling approaches to assimilate this information are explored through case studies on spiralling whitefly, Aleurodicus dispersus and red banded mango caterpillar, Deanolis sublimbalis. Markov chain Monte Carlo simulation is used to estimate the probable extent of pests, given the observation and process model conditioned by surveillance data. Statistical methods, based on time-to-event models, are developed to apply hierarchical Bayesian models to early detection programs and to demonstrate area freedom from pests. The value of early detection surveillance programs is demonstrated through an application to interpret surveillance data for exotic plant pests with uncertain spread rates. The model suggests that typical early detection programs provide a moderate reduction in the probability of an area being infested but a dramatic reduction in the expected area of incursions at a given time. Estimates of spiralling whitefly extent are examined at local, district and state-wide scales. The local model estimates the rate of natural spread and the influence of host architecture, host suitability and inspector efficiency. These parameter estimates can support the development of robust surveillance programs. Hierarchical Bayesian models for the human-mediated spread of spiralling whitefly are developed for the colonisation of discrete cells connected by a modified gravity model. By estimating dispersal parameters, the model can be used to predict the extent of the pest over time. An extended model predicts the climate restricted distribution of the pest in Queensland. These novel human-mediated movement models are well suited to demonstrating area freedom at coarse spatio-temporal scales. At finer scales, and in the presence of ecological complexity, exploratory models are developed to investigate the capacity for surveillance information to estimate the extent of red banded mango caterpillar. It is apparent that excessive uncertainty about observation and ecological parameters can impose limits on inference at the scales required for effective management of response programs. The thesis contributes novel statistical approaches to estimating the extent of pests and develops applications to assist decision-making across a range of plant biosecurity surveillance activities. Hierarchical Bayesian modelling is demonstrated as both a useful analytical tool for estimating pest extent and a natural investigative paradigm for developing and focussing biosecurity programs.

A framework for reasoning about inherent parallelism in modern object-oriented languages

With the emergence of multi-core processors into the mainstream, parallel programming is no longer the specialized domain it once was. There is a growing need for systems to allow programmers to more easily reason about data dependencies and inherent parallelism in general purpose programs. Many of these programs are written in popular imperative programming languages like Java and C]. In this thesis I present a system for reasoning about side-effects of evaluation in an abstract and composable manner that is suitable for use by both programmers and automated tools such as compilers. The goal of developing such a system is to both facilitate the automatic exploitation of the inherent parallelism present in imperative programs and to allow programmers to reason about dependencies which may be limiting the parallelism available for exploitation in their applications. Previous work on languages and type systems for parallel computing has tended to focus on providing the programmer with tools to facilitate the manual parallelization of programs; programmers must decide when and where it is safe to employ parallelism without the assistance of the compiler or other automated tools. None of the existing systems combine abstraction and composition with parallelization and correctness checking to produce a framework which helps both programmers and automated tools to reason about inherent parallelism. In this work I present a system for abstractly reasoning about side-effects and data dependencies in modern, imperative, object-oriented languages using a type and effect system based on ideas from Ownership Types. I have developed sufficient conditions for the safe, automated detection and exploitation of a number task, data and loop parallelism patterns in terms of ownership relationships. To validate my work, I have applied my ideas to the C] version 3.0 language to produce a language extension called Zal. I have implemented a compiler for the Zal language as an extension of the GPC] research compiler as a proof of concept of my system. I have used it to parallelize a number of real-world applications to demonstrate the feasibility of my proposed approach. In addition to this empirical validation, I present an argument for the correctness of the type system and language semantics I have proposed as well as sketches of proofs for the correctness of the sufficient conditions for parallelization proposed.

Impact of traffic oscillations on freeway crash occurrences

Traffic oscillations are typical features of congested traffic flow that are characterized by recurring decelerations followed by accelerations (stop-and-go driving). The negative environmental impacts of these oscillations are widely accepted, but their impact on traffic safety has been debated. This paper describes the impact of freeway traffic oscillations on traffic safety. This study employs a matched case-control design using high-resolution traffic and crash data from a freeway segment. Traffic conditions prior to each crash were taken as cases, while traffic conditions during the same periods on days without crashes were taken as controls. These were also matched by presence of congestion, geometry and weather. A total of 82 cases and about 80,000 candidate controls were extracted from more than three years of data from 2004 to 2007. Conditional logistic regression models were developed based on the case-control samples. To verify consistency in the results, 20 different sets of controls were randomly extracted from the candidate pool for varying control-case ratios. The results reveal that the standard deviation of speed (thus, oscillations) is a significant variable, with an average odds ratio of about 1.08. This implies that the likelihood of a (rear-end) crash increases by about 8% with an additional unit increase in the standard deviation of speed. The average traffic states prior to crashes were less significant than the speed variations in congestion.

Land Sales Act 1984: The time limit for an application for exemption

The decision of Wilson J in Wan and Ors v NPD Property Development Pty Ltd [2004] QSC 232 also concerned the operation of the Land Sales Act 1984 (Qld) (‘the Act’). As previously noted, s 8(1) of the Act provides that a proposed allotment of freehold land might be sold only in certain circumstances. An agreement made in contravention of s 8(1) is void. Section 19 allows a purchaser (and others) to apply for an exemption from any of the provisions of Pt 2. By s 19(6), notwithstanding s 8, a person may agree to sell a proposed allotment if the instrument that binds a person to purchase the proposed allotment is conditional upon the grant of an exemption. By s 19(7) an application for exemption must be made ‘within 30 days after the event that marks the entry of a purchaser upon the purchase of the proposed allotment.’

Diversification and value-at-risk

A pervasive and puzzling feature of banks’ Value-at-Risk (VaR) is its abnormally high level, which leads to excessive regulatory capital. A possible explanation for the tendency of commercial banks to overstate their VaR is that they incompletely account for the diversification effect among broad risk categories (e.g., equity, interest rate, commodity, credit spread, and foreign exchange). By underestimating the diversification effect, bank’s proprietary VaR models produce overly prudent market risk assessments. In this paper, we examine empirically the validity of this hypothesis using actual VaR data from major US commercial banks. In contrast to the VaR diversification hypothesis, we find that US banks show no sign of systematic underestimation of the diversification effect. In particular, diversification effects used by banks is very close to (and quite often larger than) our empirical diversification estimates. A direct implication of this finding is that individual VaRs for each broad risk category, just like aggregate VaRs, are biased risk assessments.

Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Classification with a reject option using a hinge loss

We consider the problem of binary classification where the classifier can, for a particular cost, choose not to classify an observation. Just as in the conventional classification problem, minimization of the sample average of the cost is a difficult optimization problem. As an alternative, we propose the optimization of a certain convex loss function φ, analogous to the hinge loss used in support vector machines (SVMs). Its convexity ensures that the sample average of this surrogate loss can be efficiently minimized. We study its statistical properties. We show that minimizing the expected surrogate loss—the φ-risk—also minimizes the risk. We also study the rate at which the φ-risk approaches its minimum value. We show that fast rates are possible when the conditional probability P(Y=1|X) is unlikely to be close to certain critical values.