Dynamic Bayesian network inferencing for non-homogeneous complex systems

Dynamic Bayesian Networks (DBNs) provide a versatile platform for predicting and analysing the behaviour of complex systems. As such, they are well suited to the prediction of complex ecosystem population trajectories under anthropogenic disturbances such as the dredging of marine seagrass ecosystems. However, DBNs assume a homogeneous Markov chain whereas a key characteristics of complex ecosystems is the presence of feedback loops, path dependencies and regime changes whereby the behaviour of the system can vary based on past states. This paper develops a method based on the small world structure of complex systems networks to modularise a non-homogeneous DBN and enable the computation of posterior marginal probabilities given evidence in forwards inference. It also provides an approach for an approximate solution for backwards inference as convergence is not guaranteed for a path dependent system. When applied to the seagrass dredging problem, the incorporation of path dependency can implement conditional absorption and allows release from the zero state in line with environmental and ecological observations. As dredging has a marked global impact on seagrass and other marine ecosystems of high environmental and economic value, using such a complex systems model to develop practical ways to meet the needs of conservation and industry through enhancing resistance and/or recovery is of paramount importance.

An upstream open reading frame is essential for feedback regulation of ascorbate biosynthesis in arabidopsis

Ascorbate (vitamin C) is an essential antioxidant and enzyme cofactor in both plants and animals. Ascorbate concentration is tightly regulated in plants, partly to respond to stress. Here, we demonstrate that ascorbate concentrations are determined via the posttranscriptional repression of GDP-l-galactose phosphorylase (GGP), a major control enzyme in the ascorbate biosynthesis pathway. This regulation requires a cis-acting upstream open reading frame (uORF) that represses the translation of the downstream GGP open reading frame under high ascorbate concentration. Disruption of this uORF stops the ascorbate feedback regulation of translation and results in increased ascorbate concentrations in leaves. The uORF is predicted to initiate at a noncanonical codon (ACG rather than AUG) and encode a 60- to 65-residue peptide. Analysis of ribosome protection data from Arabidopsis thaliana showed colocation of high levels of ribosomes with both the uORF and the main coding sequence of GGP. Together, our data indicate that the noncanonical uORF is translated and encodes a peptide that functions in the ascorbate inhibition of translation. This posttranslational regulation of ascorbate is likely an ancient mechanism of control as the uORF is conserved in GGP genes from mosses to angiosperms.

Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.

Proteomics science & society : the role of knowledge translation in moving towards clinical applications

Background: Outside the mass-spectrometer, proteomics research does not take place in a vacuum. It is affected by policies on funding and research infrastructure. Proteomics research both impacts and is impacted by potential clinical applications. It provides new techniques & clinically relevant findings, but the possibilities for such innovations (and thus the perception of the potential for the field by funders) are also impacted by regulatory practices and the readiness of the health sector to incorporate proteomics-related tools & findings. Key to this process is how knowledge is translated. Methods: We present preliminary results from a multi-year social science project, funded by the Canadian Institutes of Health Research, on the processes and motivations for knowledge translation in the health sciences. The proteomics case within this wider study uses qualitative methods to examine the interplay between proteomics science and regulatory and policy makers regarding clinical applications of proteomics. Results: Adopting an interactive format to encourage conference attendees’ feedback, our poster focuses on deficits in effective knowledge translation strategies from the laboratory to policy, clinical, & regulatory arenas. An analysis of the interviews conducted to date suggests five significant choke points: the changing priorities of funding agencies; the complexity of proteomics research; the organisation of proteomics research; the relationship of proteomics to genomics and other omics sciences; and conflict over the appropriate role of standardisation. Conclusion: We suggest that engagement with aspects of knowledge translation, such as those mentioned above, is crucially important for the eventual clinical application ofproteomics science on any meaningful scale.

The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts

Heparan sulfate proteoglycans cooperate with basic fibroblast growth factor (bFGF/FGF2) signaling to control osteoblast growth and differentiation, as well as metabolic functions of osteoblasts. FGF2 signaling modulates the expression and activity of Runt-related transcription factor 2 (Runx2/Cbfa1), a key regulator of osteoblast proliferation and maturation. Here, we have characterized novel Runx2 target genes in osteoprogenitors under conditions that promote growth arrest while not yet permitting sustained phenotypic maturation. Runx2 enhances expression of genes related to proteoglycan-mediated signaling, including FGF receptors (e.g., FGFR2 and FGFR3) and proteoglycans (e.g., syndecans [Sdc1, Sdc2, Sdc3], glypicans [Gpc1], versican [Vcan]). Runx2 increases expression of the glycosyltransferase Exostosin-1 (Ext1) and heparanase, as well as alters the relative expression of N-linked sulfotransferases (Ndst1 = Ndst2 > Ndst3) and enzymes mediating O-linked sulfation of heparan sulfate (Hs2st > Hs6st) or chondroitin sulfate (Cs4st > Cs6st). Runx2 cooperates with FGF2 to induce expression of Sdc4 and the sulfatase Galns, but Runx2 and FGF2 suppress Gpc6, thus suggesting intricate Runx2 and FGF2 dependent changes in proteoglycan utilization. One functional consequence of Runx2 mediated modulations in proteoglycan-related gene expression is a change in the responsiveness of bone markers to FGF2 stimulation. Runx2 and FGF2 synergistically enhance osteopontin expression (>100 fold), while FGF2 blocks Runx2 induction of alkaline phosphatase. Our data suggest that Runx2 and the FGF/proteoglycan axis may form an extracellular matrix (ECM)-related regulatory feed-back loop that controls osteoblast proliferation and execution of the osteogenic program.

The effect of feedback from pupil to teacher on assessment for leaning and visible learning: An ethnographic case study in a community school in England and the outcome in a state high school in Queensland, Australia

This study shows that there is positive regulatory effect of feedback from pupils to teachers on Assessment for Learning (AfL), classroom proactiveness, and on visible and progressive learning but not on behaviour. This research finding further articulates feedback from pupil to teacher as a paradigm shift from the classical paradigm of feedback from teacher to pupil. Here, the emphasis is geared towards pupils understanding of objectives built from previous knowledge. These are then feedback onto the teachers by the pupils in the form of discrete loops of cues and questions, where they are with their learning. This therefore enables them to move to the next level of understanding, and thus acquired independence, which in turn is reflected by their success in both formative and summative assessments. This study therefore shows that when feedback from pupil to teacher is used in combination with teacher to pupil feedback, AfL is ameliorated and hence, visible and accelerated learning occurs in a gender, nor subject non-dependent manner.

Mini-Orb : A personal indoor climate preference feedback interface

The control of environmental factors in open-office environments, such as lighting and temperature is becoming increasingly automated. This development means that office inhabitants are losing the ability to manually adjust environmental conditions according to their needs. In this paper we describe the design, use and evaluation of MiniOrb, a system that employs ambient and tangible interaction mechanisms to allow inhabitants of office environments to maintain awareness of environmental factors, report on their own subjectively perceived office comfort levels and see how these compare to group average preferences. The system is complemented by a mobile application, which enables users to see and set the same sensor values and preferences, but using a screen-based interface. We give an account of the system’s design and outline the results of an in-situ trial and user study. Our results show that devices that combine ambient and tangible interaction approaches are well suited to the task of recording indoor climate preferences and afford a rich set of possible interactions that can complement those enabled by more conventional screen-based interfaces.

Automated Feedback for 'Fill in the Gap' Programming Exercises

Timely feedback is a vital component in the learning process. It is especially important for beginner students in Information Technology since many have not yet formed an effective internal model of a computer that they can use to construct viable knowledge. Research has shown that learning efficiency is increased if immediate feedback is provided for students. Automatic analysis of student programs has the potential to provide immediate feedback for students and to assist teaching staff in the marking process. This paper describes a “fill in the gap” programming analysis framework which tests students’ solutions and gives feedback on their correctness, detects logic errors and provides hints on how to fix these errors. Currently, the framework is being used with the Environment for Learning to Programming (ELP) system at Queensland University of Technology (QUT); however, the framework can be integrated into any existing online learning environment or programming Integrated Development Environment (IDE)

Program Annotations: Feedback for Students Learning to Program

This paper presents a novel program annotation mechanism which enables students to obtain feedback from tutors on their programs in a far simpler and more efficient way than is possible with, for example, email. A common scenario with beginning students is to email tutors with copies of their malfunctioning programs. Unfortunately the emailed program often bears little resemblance to the program the student has been trying to make work; often it is incomplete, a different version and corrupted. We propose an annotation mechanism enabling students to simply and easily annotate their programs with comments asking for help. Similarly our mechanism enables tutors to view students’ programs and to reply to their comments in a simple and structured fashion. This means students can get frequent and timely feedback on their programs; tutors can provide such feedback efficiently, and hence students’ learning is greatly improved.