Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with ‘bursts’ in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated. These include whether eve transcription is simply OFF or ON, with a single ON rate, or whether it proceeds by a more complex mechanism, with multiple ON rates. We find that both mechanisms can produce long (multi-minute) RNA bursts, but that the short-time (minute-to-minute) statistics of the data is indicative of eve being transcribed with at least two distinct ON rates, consistent with data on the joint activation of eve by Bicoid and Hunchback. We also predict distinct statistical signatures for cases in which eve is repressed (e.g. along the edges of the stripe) vs. cases in which activation is reduced (e.g. by mutagenesis of transcription factor binding sites). Fundamental developmental processes such as gene transcription are intrinsically noisy; our approach presents a new way to quantify and analyze time series data during developmental patterning in order to understand regulatory mechanisms and how they propagate noise and impact embryonic robustness., Peer-reviewed article, Published. Received: November 21, 2016; Accepted: April 8, 2017; Published: April 24, 2017.
Most building materials are porous, composed of solid matrix and pores. The time varying indoor and outdoor climatic conditions result heat, air and moisture (HAM) transfer across building enclosures. In this paper, a transient model that solves the coupled heat, air and moisture transfer through multilayered porous media is developed and benchmarked using internationally published analytical, numerical and experimental test cases. The good agreements obtained with the respective test cases suggest that the model can be used to assess the hygrothermal performance of building envelope components as well as to simulate the dynamic moisture absorption and release of moisture buffering materials., Peer reviewed article, Published. Received 26 February 2009, Revised 30 September 2009, Accepted 1 October 2009, Available online 13 April 2010.
Douglas-fir heartwood thermomechanical pulp was treated with laccase enzymes at 25 and 50°C with and without added oxygen. The treated pulps were cleached with hudrogen peroxide at increasing alkali charges. Laccase treatments without added oxygen increased bleached brightness by 1.5-2.5 pts ISO, and decreased hydrogen peroxide consumption by 15-20%. The enzyme treatments were not enhanced when supplemented with oxygen. When the effectiveness of four different laccase enzymes was compared for the treatment of Douglas-fir heartwood thermomechanical pulp, there were no significant differences found in the performance among the enzymes. Possible explanations for the observed results are given., Peer-reviewed article, Published.
Belief revision is concerned with incorporating new information into a pre-existing set of beliefs. When the new information comes from another agent, we must first determine if that agent should be trusted. In this paper, we define trust as a pre-processing step before revision. We emphasize that trust in an agent is often restricted to a particular domain of expertise. We demonstrate that this form of trust can be captured by associating a state partition with each agent, then relativizing all reports to this partition before revising. We position the resulting family of trust-sensitive revision operators within the class of selective revision operators of Ferme and Hansson, and we prove a representation result that characterizes the class of trust-sensitive revision operators in terms of a set of postulates. We also show that trust-sensitive revision is manipulable, in the sense that agents can sometimes have incentive to pass on misleading information., Article, Published.
Proceedings of the Twenty-Fourth International Joint Conference on Artificial Intelligence in Buenos Aires, Argentina, 25–31 July 2015. Belief revision is concerned with incorporating new information into a pre-existing set of beliefs. When the new information comes from another agent, we must first determine if that agent should be trusted. In this paper, we define trust as a pre-processing step before revision. We emphasize that trust in an agent is often restricted to a particular domain of expertise. We demonstrate that this form of trust can be captured by associating a state partition with each agent, then relativizing all reports to this partition before revising. We position the resulting family of trust-sensitive revision operators within the class of selective revision operators of Ferme and Hansson, and we examine its properties. In particular, we show how trust-sensitive revision is manipulable, in the sense that agents can sometimes have incentive to pass on misleading information. When multiple reporting agents are involved, we use a distance function over states to represent differing degrees of trust; this ensures that the most trusted reports will be believed., Conference paper, Published.
This paper presents an analysis of a phenomenon known as "The Relative Age" effect. When assessing the innate ability (or talent) of individual children who are grouped into age cohorts, systematic errors occur due to differences in biological maturity. A structural model of a multi-period progression through levels (or grades) that employs screening and selection is developed. Through a series of simulations, impact of the relative age on the of selection process is analyzed., Thesis, Draft published.
As the world urbanizes, the role of cities in determining sustainability outcomes grows in importance. Cities are the dominant form of human habitat, and most of the world's resources are either directly or indirectly consumed in cities. Sustainable city analysis and management requires understanding the demands a city places on a wider geographical area and its ecological resource base. We present a detailed, integrated urban metabolism of residential consumption and ecological footprint analysis of the Vancouver metropolitan region for the year 2006. Our overall goal is to demonstrate the application of a bottom-up ecological footprint analysis using an urban metabolism framework at a metropolitan, regional scale. Our specific objectives are: a) to quantify energy and material consumption using locally generated data and b) to relate these data to global ecological carrying capacity. Although water is the largest material flow through Metro Vancouver (424,860,000 m3), it has the smallest ecological footprint (23,100 gha). Food (2,636,850 tonnes) contributes the largest component to the ecological footprint (4,514,400 gha) which includes crop and grazing land as well as carbon sinks required to sequester emissions from food production and distribution. Transportation fuels (3,339,000 m3) associated with motor vehicle operation and passenger air travel comprises the second largest material flow through the region and the largest source of carbon dioxide emissions (7,577,000 tonnes). Transportation also accounts for the second largest component of the EF (2,323,200 gha). Buildings account for the largest electricity flow (17,515,150 MWh) and constitute the third largest component of the EF (1,779,240 gha). Consumables (2,400,000 tonnes) comprise the fourth largest component of the EF (1,414,440 gha). Metro Vancouver's total Ecological Footprint in 2006 was 10,071,670 gha, an area approximately 36 times larger than the region itself. The EFA reveals that cropland and carbon sinks (forested land required to sequester carbon dioxide emissions) account for 90% of Metro Vancouver's overall demand for biocapacity. The per capita ecological footprint is 4.76 gha, nearly three times the per capita global supply of biocapacity. Note that this value excludes national government services that operate outside the region and could account for up to an additional 2 gha/ca., Peer-reviewed article, Published. Received 23 December 2011; Revised 25 February 2013; Accepted 5 March 2013; Available online 19 April 2013.
Proceedings of 12th International Heat Transfer Conference: 18 August 2002, Grenoble, France. Using numerical modelling to simulate and predict the hygrothermal (i.e., combined thermal and moisture)performance of building envelopes is very recent. Key questions include: how to model accurately coupled heat-air and capillary moisture transports in building envelope components; a satisfactory definition of a set of representative environmental boundary conditions to be used for long-term hygrothermal calculations; how to characterize the moisture- and temperature-dependent properties; the effect of aging and cyclic environmental conditions on porous building materials; and how to develop sound criteria to predict the moisture durability of building envelope components. This paper presents the findings of a research project involving detailed hygrothermal modelling. The heat, air and moisture results demonstrated that the in-house model could be adapted successfully for high-rise building calculations. The findings also show how the long-term hygrothermal performance of typical wall systems can be assessed using numerical modelling. A short description of an advanced in-house heat, air and moisture model, hygIRC, is also presented., Conference paper, Published. A version of this document is published in: 12th International Heat Transfer Conference, Grenoble, France, Sept. 18, 2002, pp. 165-170.
This chapter surveys recent developments in simulating the evolution of GRNs in developmental biology. Over the past two decades, computational biologists have developed a number of approaches to study how developmental GRNs evolve. This has led to a number of breakthroughs in understanding the mechanisms of how species maintain their body plans, and how they evolve or speciate in response to environmental perturbations. EA uses the general evolutionary processes of repeated mutation, reproduction and selection in optimization problems. The progress in computational biology described here has deepened and refined understanding of the biological principles underlying these processes. Our aim is for this chapter to provide some inspiration to computer scientists in EA to incorporate new biologically inspired techniques. We feel this offers a large potential for improving EA efficiency. In turn, computational biology could greatly benefit from EA research, for instance in multi-objective optimization, coding of multiscale problems, and efficiencies in solution techniques. Following a brief survey of the major trends in the computational biology approaches, we discuss the refinements these have made to understanding evolutionary mechanisms. In particular, we discuss the factors affecting GRN evolvability and robustness; the effect different genetic alteration mechanisms (e.g. types of mutation) have on evolutionary speed and robustness; the role of network growth; modelling co-evolution; modelling multi-factor control of gene expression; and applying these techniques to the evolution of GRNs controlling spatially-dependent gene expression (underlying embryonic tissue differentiation). We finish with a brief summary of how these might be incorporated into and improve EA searches., Book chapter, Published.
This paper surveys modeling approaches for studying the evolution of gene regulatory networks (GRNs). Modeling of the design or ‘wiring’ of GRNs has become increasingly common in developmental and medical biology, as a means of quantifying gene–gene interactions, the response to perturbations, and the overall dynamic motifs of networks. Drawing from developments in GRN ‘design’ modeling, a number of groups are now using simulations to study how GRNs evolve, both for comparative genomics and to uncover general principles of evolutionary processes. Such work can generally be termed evolution in silico. Complementary to these biologically-focused approaches, a now well-established field of computer science is Evolutionary Computations (ECs), in which highly efficient optimization techniques are inspired from evolutionary principles. In surveying biological simulation approaches, we discuss the considerations that must be taken with respect to: (a) the precision and completeness of the data (e.g. are the simulations for very close matches to anatomical data, or are they for more general exploration of evolutionary principles); (b) the level of detail to model (we proceed from ‘coarse-grained’ evolution of simple gene-gene interactions to ‘fine-grained’ evolution at the DNA sequence level); (c) to what degree is it important to include the genome’s cellular context; and (d) the efficiency of computation. With respect to the latter, we argue that developments in computer science EC offer the means to perform more complete simulation searches, and will lead to more comprehensive biological predictions., Peer-reviewed article, Published.
Proceedings of the Sixth Workshop on Nonmonotonic Reasoning, Action, and Change (NRAC-05), Edinburgh, Scotland, 2005. We use ranking functions to reason about belief change following an alternating sequence of actions and observations. At each instant, an agent assigns a plausibility value to every action and every state; the most plausible world histories are obtained by minimizing the sum of these values. Since plausibility is given a quantitative rank, an agent is able to compare the plausibility of actions and observations. This allows action occurrences to be postulated or refuted in response to new observations. We demonstrate that our formalism is a generalization of our previous work on the interaction of revision and update., Conference paper, Published.