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.

Frequency response function based structural damage detection using artificial neural networks

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, few attempts have been made to explore the structure damage with frequency response functions (FRFs). This paper illustrates the damage identification and condition assessment of a beam structure using a new frequency response functions (FRFs) based damage index and Artificial Neural Networks (ANNs). In practice, usage of all available FRF data as an input to artificial neural networks makes the training and convergence impossible. Therefore one of the data reduction techniques Principal Component Analysis (PCA) is introduced in the algorithm. In the proposed procedure, a large set of FRFs are divided into sub-sets in order to find the damage indices for different frequency points of different damage scenarios. The basic idea of this method is to establish features of damaged structure using FRFs from different measurement points of different sub-sets of intact structure. Then using these features, damage indices of different damage cases of the structure are identified after reconstructing of available FRF data using PCA. The obtained damage indices corresponding to different damage locations and severities are introduced as input variable to developed artificial neural networks. Finally, the effectiveness of the proposed method is illustrated and validated by using the finite element modal of a beam structure. The illustrated results show that the PCA based damage index is suitable and effective for structural damage detection and condition assessment of building structures.

Towards testing the eclectic paradigm on multinational contracting: an approach to reviewing and analysing secondary data

In response to the need to leverage private finance and the lack of competition in some parts of the Australian public sector major infrastructure market, especially in very large economic infrastructure procured using Pubic Private Partnerships, the Australian Federal government has demonstrated its desire to attract new sources of in-bound foreign direct investment (FDI) into the Australian construction market. This paper aims to report on progress towards an investigation into the determinants of multinational contractors’ willingness to bid for Australian public sector major infrastructure projects and which is designed to give an improved understanding of matters surrounding FDI into the Australian construction sector. This research deploys Dunning’s eclectic theory for the first time in terms of in-bound FDI by multinational contractors and as head contractors bidding for Australian major infrastructure public sector projects. Elsewhere, the authors have developed Dunning’s principal hypothesis associated with his eclectic framework in order to suit the context of this research and to address a weakness arising in Dunning’s principal hypothesis that is based on a nominal approach to the factors in the eclectic framework and which fail to speak to the relative explanatory power of these factors. In this paper, an approach to reviewing and analysing secondary data, as part of the first stage investigation in this research, is developed and some illustrations given, vis-à-vis the selected sector (roads, bridges and tunnels) in Australia (as the host location) and using one of the selected home countries (Spain). In conclusion, some tentative thoughts are offered in anticipation of the completion of the first stage investigation - in terms of the extent to which this first stage based on secondary data only might suggest the relative importance of the factors in the eclectic framework. It is noted that more robust conclusions are expected following the future planned stages of the research and these stages including primary data are briefly outlined. Finally, and beyond theoretical contributions expected from the overall approach taken to developing and testing Dunning’s framework, other expected contributions concerning research method and practical implications are mentioned.

An analytical and experimental study of the vibration response of a clamped ribbed plate

An analytical solution is presented in this paper for the vibration response of a ribbed plate clamped on all its boundary edges by employing a travelling wave solution. A clamped ribbed plate test rig is also assembled in this study for the experimental investigation of the ribbed plate response and to provide verification results to the analytical solution. The dynamic characteristics and mode shapes of the ribbed plate are measured and compared to those obtained from the analytical solution and from finite element analysis (FEA). General good agreements are found between the results. Discrepancies between the computational and experimental results at low and high frequencies are also discussed. Explanations are offered in the study to disclose the mechanism causing the discrepancies. The dependency of the dynamic response of the ribbed plate on the distance between the excitation force and the rib is also investigated experimentally. It confirms the findings disclosed in a previous analytical study [T. R. Lin and J. Pan, A closed form solution for the dynamic response of finite ribbed plates. Journal of the Acoustical Society of America 119 (2006) 917-925] that the vibration response of a clamped ribbed plate due to a point force excitation is controlled by the plate stiffness when the source is more than a quarter plate bending wavelength away from the rib and from the plate boundary. The response is largely affected by the rib stiffness when the source location is less than a quarter bending wavelength away from the rib.

Shear in reinforced and unreinforced masonry : response, design and construction

This paper describes the vulnerability of masonry under shear; first the mechanisms of in-plane and out-of-plane shear performance of masonry are reviewed; both the unreinforced and lightly reinforced masonry wall systems are considered. Factors affecting the response of unreinforced and reinforced masonry to shear are described and the effect of the variability of those factors to the failure mode of masonry shear walls is also discussed. Some critique is provided on the existing design provisions in various masonry standards.

Intention, foresight and ending life : a response to "The Double Effect effect" by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope, (CQ 20(1))

In this paper I examine the recent arguments by Charles Foster, Jonathan Herring, Karen Melham and Tony Hope against the utility of the doctrine of double effect. One basis on which they reject the utility of the doctrine is their claim that it is notoriously difficult to apply what they identify as its 'core' component, namely, the distinction between intention and foresight. It is this contention that is the primarily focus of my article. I argue against this claim that the intention/foresight distinction remains a fundamental part of the law in those jurisdictions where intention remains an element of the offence of murder and that, accordingly, it is essential ro resolve the putative difficulties of applying the intention/foresight distinction so as to ensure the integrity of the law of murder. I argue that the main reasons advanced for the claim that the intention/foresight distinction is difficult to apply are ultimately unsustainable, and that the distinction is not as difficult to apply as the authors suggest.

Stop whining and make the best of it: a cross-national comparison of response to regional disadvantage in the wine industry

Our cross-national field study of wine entrepreneurship in the “wrong” places provides some redress to the focus of the “regional advantage” literature on places that have already won and on the firms that benefit from “clusters” and other centers of industry advantage. Regional “disadvantage” is at best a shadowy afterthought to this literature. By poking around in these shadows, we help to synthesize and extend the incipient yet burgeoning literature on entrepreneurial “resourcefulness” and we contribute to the developing body of insights and theory pertinent to the numerous but often ignored firms and startups that mostly need to worry about how they will compete at all now if they are ever to have of chance of “winning” in the future. The core of our findings suggests that understandable – though contested – processes of ingenuity underlie entrepreneurial responses to regional disadvantage. Because we study entrepreneurship that from many angles simply does not make sense, we are also able to proffer a novel perspective on entrepreneurial sensemaking.

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.

Response of partially grouted wider reinforced masonry walls to inplane cyclic shear

Partially grouted wider reinforced masonry wall, built predominantly using face shell bedded hollow concrete blocks, is an economical structural system and is popularly used in the cyclonic areas; its out-of-plane response to lateral loading is well understood, unfortunately its inplane shear behaviour is less well understood as to the effect of partial gouting in intervening the load paths within the wall. For rational analysis of the wall clarification is sought as to whether the wall acts as a composite of unreinforced panels and reinforced cores or as a continuum of masonry embedded with reinforced at wider spacing. This paper reports the results of four full scale walls tested under inplane cyclic shear loading to provide some insight into the effect of the grout cores in altering the load paths within the wall. The global lateral load - lateral deflection hysteric curves as well as local responses of some critical zones of the shear walls are presented.

Evaluation cortical bone elasticity in response to pulse power excitation using ultrasonic technique

This paper presents the ultrasonic velocity measurement method which investigates the possible effects of high voltage high frequency pulsed power on cortical bone material elasticity. Before applying a pulsed power signal on a live bone, it is essential to determine the safe parameters of pulsed power applied on bone non-destructively. Therefore, the possible changes in cortical bone material elasticity due to a specified pulsed power excitation have been investigated. A controllable positive buck-boost converter with adjustable output voltage and frequency has been used to generate high voltage pulses (500V magnitude at 10 KHz frequency). To determine bone elasticity, an ultrasonic velocity measurement has been conducted on two groups of control (unexposed to pulse power but in the same environmental condition) and cortical bone samples exposed to pulsed power. Young’s modulus of cortical bone samples have been determined and compared before and after applying the pulsed power signal. After applying the high voltage pulses, no significant variation in elastic property of cortical bone specimens was found compared to the control. The result shows that pulsed power with nominated parameters can be applied on cortical bone tissue without any considerable negative effect on elasticity of bone material.

A first stage test of Dunning's framework on multinational contracting into Australia : reviewing secondary data.

In response to the need to leverage private finance and the lack of competition in some parts of the Australian public sector infrastructure market, especially in the very large economic infrastructure sector procured using Pubic Private Partnerships, the Australian Federal government has demonstrated its desire to attract new sources of in-bound foreign direct investment (FDI). This paper aims to report on progress towards an investigation into the determinants of multinational contractors’ willingness to bid for Australian public sector major infrastructure projects. This research deploys Dunning’s eclectic theory for the first time in terms of in-bound FDI by multinational contractors into Australia. Elsewhere, the authors have developed Dunning’s principal hypothesis to suit the context of this research and to address a weakness arising in this hypothesis that is based on a nominal approach to the factors in Dunning's eclectic framework and which fails to speak to the relative explanatory power of these factors. In this paper, a first stage test of the authors' development of Dunning's hypothesis is presented by way of an initial review of secondary data vis-à-vis the selected sector (roads and bridges) in Australia (as the host location) and with respect to four selected home countries (China; Japan; Spain; and US). In doing so, the next stage in the research method concerning sampling and case studies is also further developed and described in this paper. In conclusion, the extent to which the initial review of secondary data suggests the relative importance of the factors in the eclectic framework is considered. It is noted that more robust conclusions are expected following the future planned stages of the research including primary data from the case studies and a global survey of the world’s largest contractors and which is briefly previewed. Finally, and beyond theoretical contributions expected from the overall approach taken to developing and testing Dunning’s framework, other expected contributions concerning research method and practical implications are mentioned.