A Bayesian model predicts the response of axons to molecular gradients

Axon guidance by molecular gradients plays a crucial role in wiring up the nervous system. However, the mechanisms axons use to detect gradients are largely unknown. We first develop a Bayesian “ideal observer” analysis of gradient detection by axons, based on the hypothesis that a principal constraint on gradient detection is intrinsic receptor binding noise. Second, from this model, we derive an equation predicting how the degree of response of an axon to a gradient should vary with gradient steepness and absolute concentration. Third, we confirm this prediction quantitatively by performing the first systematic experimental analysis of how axonal response varies with both these quantities. These experiments demonstrate a degree of sensitivity much higher than previously reported for any chemotacting system. Together, these results reveal both the quantitative constraints that must be satisfied for effective axonal guidance and the computational principles that may be used by the underlying signal transduction pathways, and allow predictions for the degree of response of axons to gradients in a wide variety of in vivo and in vitro settings.

Stochastic analysis of the VEGF receptor response curve

Recently, an analysis of the response curve of the vascular endothelial growth factor (VEGF) receptor and its application to cancer therapy was described in [T. Alarcón, and K. Page, J. R. Soc. Lond. Interface 4, 283–304 (2007)]. The analysis is significantly extended here by demonstrating that an alternative computational strategy, namely the Krylov FSP algorithm for the direct solution of the chemical master equation, is feasible for the study of the receptor model. The new method allows us to further investigate the hypothesis of symmetry in the stochastic fluctuations of the response. Also, by augmenting the original model with a single reversible reaction we formulate a plausible mechanism capable of realizing a bimodal response, which is reported experimentally but which is not exhibited by the original model. The significance of these findings for mechanisms of tumour resistance to antiangiogenic therapy is discussed.

Understanding the diversity of non-specialised units within Australian property degrees

Building on the recommendations of the Bradley Review (2008), the Australian Federal government intends to promote a higher level of penetration of tertiary qualification across the broader Australian community which is anticipated to result in increased levels of standardisation across university degrees. In the field of property, tertiary academic programs are very closely aligned to the needs of a range of built environment professions and there are well developed synergies between the relevant professional bodies and the educational institutions. The strong nexus between the academic and the professional content is characterised by ongoing industry accreditation which nominates a range of outcomes which the academic programs must maintain across a range of specified metrics. Commonly, the accrediting bodies focus on standard of minimum requirements especially in the area of specialised subject areas where they require property graduates to demonstrate appropriate learning and attitudes. In addition to nominated content fields, in every undergraduate degree program there are also many other subjects which provide a richer experience for the students beyond the merely professional. This study focuses on the nonspecialised knowledge field which varies across the universities offering property degree courses as every university has the freedom to pursue its own policy for these non-specialised units. With universities being sensitive to their role of in the appropriate socialisation of new entrants, first year units have been used as a vehicle to support students’ transition into university education and the final year units seek to support students’ integration into the professional world. Consequentially, many property programs have to squeeze their property-specific units to accommodate more generic units for both first year and final year units and the resulting diversity is a feature of the current range of property degrees across Australia which this research will investigate. The matrix of knowledge fields nominated by the Australian Property Institute for accreditation of degrees accepted for Certified Practising Valuer (CPV) educational requirement and the complementary requirements of the other major accrediting body (RICS) are used to classify and compare similarities and differences across property degrees in the light of the streamlining anticipated from the Bradley Review.