CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein

The CDKN2A gene encodes p16 (CDKN2A), a cell-cycle inhibitor protein which prevents inappropriate cell cycling and, hence, proliferation. Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM). We therefore sequenced exons 1alpha and 2 of CDKN2A using lymphocyte DNA isolated from index cases from 67 families with cancers at multiple sites, where the patterns of cancer did not resemble those attributable to known genes such as hMLH1, hMLH2, BRCA1, BRCA2, TP53 or other cancer susceptibility genes. We found one mutation, a mis-sense mutation resulting in a methionine to isoleucine change at codon 53 (M531) of exon 2. The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM. Other family members had been diagnosed with oral cancer (2 persons), bladder cancer (1 person) and possibly gall-bladder cancer. While this mutation has been reported in Australian and North American melanoma kindreds, we did not observe it in 618 chromosomes from Scottish and Canadian controls. Functional studies revealed that the CDKN2A variant carrying the M531 change was unable to bind effectively to CDK4, showing that this mutation is of pathological significance. Our results have confirmed that CDKN2A mutations are not limited to FAMMM kindreds but also demonstrate that multi-site cancer families without melanoma are very unlikely to contain CDKN2A mutations.

Computational approaches for modelling intrinsic noise and delays in genetic regulatory networks

This chapter focuses on the interactions and roles between delays and intrinsic noise effects within cellular pathways and regulatory networks. We address these aspects by focusing on genetic regulatory networks that share a common network motif, namely the negative feedback loop, leading to oscillatory gene expression and protein levels. In this context, we discuss computational simulation algorithms for addressing the interplay of delays and noise within the signaling pathways based on biological data. We address implementational issues associated with efficiency and robustness. In a molecular biology setting we present two case studies of temporal models for the Hes1 gene (Monk, 2003; Hirata et al., 2002), known to act as a molecular clock, and the Her1/Her7 regulatory system controlling the periodic somite segmentation in vertebrate embryos (Giudicelli and Lewis, 2004; Horikawa et al., 2006).

Closing the loop of design and analysis : Parametric modelling tools for early decision support

There is a growing need for parametric design software that communicates building performance feedback in early architectural exploration to support decision-making. This paper examines how the circuit of design and analysis process can be closed to provide active and concurrent feedback between architecture and services engineering domains. It presents the structure for an openly customisable design system that couples parametric modelling and energy analysis software to allow designers to assess the performance of early design iterations quickly. Finally, it discusses how user interactions with the system foster information exchanges that facilitate the sharing of design intelligence across disciplines.

Demonstration of closed-­loop airborne sense-­and-­avoid using machine vision

This paper describes a vision-based airborne collision avoidance system developed by the Australian Research Centre for Aerospace Automation (ARCAA) under its Dynamic Sense-and-Act (DSA) program. We outline the system architecture and the flight testing undertaken to validate the system performance under realistic collision course scenarios. The proposed system could be implemented in either manned or unmanned aircraft, and represents a step forward in the development of a “sense-and-avoid” capability equivalent to human “see-and-avoid”.

AtBAG7, an Arabidopsis Bcl-2-associated athanogene, resides in the endoplasmic reticulum and is involved in the unfolded protein response

The Bcl-2-associated athanogene (BAG) family is an evolutionarily conserved, multifunctional group of cochaperones that perform diverse cellular functions ranging from proliferation to growth arrest and cell death in yeast, in mammals, and, as recently observed, in plants. The Arabidopsis genome contains seven homologs of the BAG family, including four with domain organization similar to animal BAGs. In the present study we show that an Arabidopsis BAG, AtBAG7, is a uniquely localized endoplasmic reticulum (ER) BAG that is necessary for the proper maintenance of the unfolded protein response (UPR). AtBAG7was shown to interact directly in vivo with themolecular chaperone, AtBiP2, by bimolecular fluorescence complementation assays, and the interaction was confirmed by yeast two-hybrid assay. Treatment with an inducer of UPR, tunicamycin, resulted in accelerated cell death of AtBAG7-null mutants. Furthermore, AtBAG7 knockouts were sensitive to known ER stress stimuli, heat and cold. In these knockouts heat sensitivity was reverted successfully to the wild-type phenotype with the addition of the chemical chaperone, tauroursodexycholic acid (TUDCA). Real-time PCR of ER stress proteins indicated that the expression of the heat-shock protein, AtBiP3, is selectively up-regulated in AtBAG7-null mutants upon heat and cold stress. Our results reveal an unexpected diversity of the plant's BAG gene family and suggest that AtBAG7 is an essential component of the UPR during heat and cold tolerance, thus confirming the cytoprotective role of plant BAGs.

Closing the loop 21st century style : providing feedback on written assessment via MP3 recordings

Feedback on student performance, whether in the classroom or on written assignments, enables them to reflect on their understandings and restructure their thinking in order to develop more powerful ideas and capabilities. Research has identified a number of broad principles of good feedback practice. These include the provision of feedback that facilitates the development of reflection in learning; helps clarify what good performance is in terms of goals, criteria and expected standards; provides opportunities to close the gap between current and desired performance; delivers high quality information to students about their learning; and encourages positive motivational beliefs and self-esteem. However, high staff–student ratios and time pressures often result in a gulf between this ideal and reality. Whilst greater use of criteria referenced assessment has enabled an improvement in the extent of feedback being provided to students, this measure alone does not go far enough to satisfy the requirements of good feedback practice. Technology offers an effective and efficient means by which personalised feedback may be provided to students. This paper presents the findings of a trial of the use of the freely available Audacity program to provide individual feedback via MP3 recordings to final year Media Law students at the Queensland University of Technology on their written assignments. The trial has yielded wide acclaim by students as an effective means of explaining the exact reasons why they received the marks they were awarded, the things they did well and the areas needing improvement. It also showed that good feedback practice can be achieved without the burden of an increase in staff workload.

Loop closure detection on a suburban road network using a continuous appearance-based trajectory

This paper presents a novel technique for performing SLAM along a continuous trajectory of appearance. Derived from components of FastSLAM and FAB-MAP, the new system dubbed Continuous Appearance-based Trajectory SLAM (CAT-SLAM) augments appearancebased place recognition with particle-filter based ‘pose filtering’ within a probabilistic framework, without calculating global feature geometry or performing 3D map construction. For loop closure detection CAT-SLAM updates in constant time regardless of map size. We evaluate the effectiveness of CAT-SLAM on a 16km outdoor road network and determine its loop closure performance relative to FAB-MAP. CAT-SLAM recognizes 3 times the number of loop closures for the case where no false positives occur, demonstrating its potential use for robust loop closure detection in large environments.