The genotype-phenotype relationship in multicellular pattern-generating models - the neglected role of pattern descriptors

Background: A deep understanding of what causes the phenotypic variation arising from biological patterning processes, cannot be claimed before we are able to recreate this variation by mathematical models capable of generating genotype-phenotype maps in a causally cohesive way. However, the concept of pattern in a multicellular context implies that what matters is not the state of every single cell, but certain emergent qualities of the total cell aggregate. Thus, in order to set up a genotype-phenotype map in such a spatiotemporal pattern setting one is actually forced to establish new pattern descriptors and derive their relations to parameters of the original model. A pattern descriptor is a variable that describes and quantifies a certain qualitative feature of the pattern, for example the degree to which certain macroscopic structures are present. There is today no general procedure for how to relate a set of patterns and their characteristic features to the functional relationships, parameter values and initial values of an original pattern-generating model. Here we present a new, generic approach for explorative analysis of complex patterning models which focuses on the essential pattern features and their relations to the model parameters. The approach is illustrated on an existing model for Delta-Notch lateral inhibition over a two-dimensional lattice. Results: By combining computer simulations according to a succession of statistical experimental designs, computer graphics, automatic image analysis, human sensory descriptive analysis and multivariate data modelling, we derive a pattern descriptor model of those macroscopic, emergent aspects of the patterns that we consider of interest. The pattern descriptor model relates the values of the new, dedicated pattern descriptors to the parameter values of the original model, for example by predicting the parameter values leading to particular patterns, and provides insights that would have been hard to obtain by traditional methods. Conclusion: The results suggest that our approach may qualify as a general procedure for how to discover and relate relevant features and characteristics of emergent patterns to the functional relationships, parameter values and initial values of an underlying pattern-generating mathematical model

Trick or Heat? Manipulating Critical Temperature-Based Control Systems Using Rectification Attacks

Temperature sensing and control systems are widely used in the closed-loop control of critical processes such as maintaining the thermal stability of patients, or in alarm systems for detecting temperature-related hazards. However, the security of these systems has yet to be completely explored, leaving potential attack surfaces that can be exploited to take control over critical systems. In this paper we investigate the reliability of temperature-based control systems from a security and safety perspective. We show how unexpected consequences and safety risks can be induced by physical-level attacks on analog temperature sensing components. For instance, we demonstrate that an adversary could remotely manipulate the temperature sensor measurements of an infant incubator to cause potential safety issues, without tampering with the victim system or triggering automatic temperature alarms. This attack exploits the unintended rectification effect that can be induced in operational and instrumentation amplifiers to control the sensor output, tricking the internal control loop of the victim system to heat up or cool down. Furthermore, we show how the exploit of this hardware-level vulnerability could affect different classes of analog sensors that share similar signal conditioning processes. Our experimental results indicate that conventional defenses commonly deployed in these systems are not sufficient to mitigate the threat, so we propose a prototype design of a low-cost anomaly detector for critical applications to ensure the integrity of temperature sensor signals.Comment: Accepted at the ACM Conference on Computer and Communications Security (CCS), 201

Susceptibility, diffusion and relaxation contrast in NMR microscopy at high resolution : a thesis presented in partial fulfilment of the requirement for the degree of Master of Science in physics at Massey University

An integrated approach to the functional NMR imaging of plant tissue at moderately-high transverse resolution (23 µm) was undertaken. Attention was paid to all the possible commonly-known influences, such as sources of nuclear spin relaxation or of artefacts, relevant to the final image intensity of the different tissues. While it was not clear at the outset which influences might prove to be significant, two phenomena in particular, susceptibility inhomogeneity and correlated diffusion effects, were selected for detailed investigation using simple model systems constructed from small glass tubes and rods combined with aqueous solutions, before continuing on to more complex plant samples. Simulated images compared well with the experimental results in these studies. Preliminary images of a stem of an intact Stachys sylvatica L. plant showed that the apparent T₂ relaxation time is much less (an order of magnitude) than the T₁ relaxation time in all tissues. A range of diagnostic pulse sequences was then carried out on this and similar stems in order to reveal the signatures for different models of T₂ relaxation which might explain this fact (assuming that the water protons imaged fall within the extreme-narrowed region of Bloembergen, Purcell and Pound theory). It was found that measures were necessary to avoid the complicating factor of attenuation due to diffusion in the applied read gradient, specifically the use of Carr-Purcell-Meiboom-Gill (CPMG) refocusing pulses. Susceptibility inhomogeneity seemed important in sensitive gradient echo images, but further experiments at different B₀ strengths revealed that it (and chemical shift exchange) does not contribute significantly to the spin echo image contrast. The Brownstein-Tarr model of relaxation at boundaries and surfaces (without local field offsets) was also considered as a possibility, but was ruled out for at least some of the tissues (those which display a CPMG pulse-spacing dependence). Another alternative explanation is short-range dipole interactions between water protons and protons of more slowly-moving molecules, which should be abundant in the particular cells which escape the other hypotheses, but it is difficult to confirm this within the scope of the pulse sequences used here. More progress might be possible with proper multicomponent T₂ analysis and improved knowledge of subcellular structure of our particular tissues

Texture dependence of motion sensing and free flight behavior in blowflies

Lindemann JP, Egelhaaf M. Texture dependence of motion sensing and free flight behavior in blowflies. Frontiers in Behavioral Neuroscience. 2013;6:92.Many flying insects exhibit an active flight and gaze strategy: purely translational flight segments alternate with quick turns called saccades. To generate such a saccadic flight pattern, the animals decide the timing, direction, and amplitude of the next saccade during the previous translatory intersaccadic interval. The information underlying these decisions is assumed to be extracted from the retinal image displacements (optic flow), which scale with the distance to objects during the intersaccadic flight phases. In an earlier study we proposed a saccade-generation mechanism based on the responses of large-field motion-sensitive neurons. In closed-loop simulations we achieved collision avoidance behavior in a limited set of environments but observed collisions in others. Here we show by open-loop simulations that the cause of this observation is the known texture-dependence of elementary motion detection in flies, reflected also in the responses of large-field neurons as used in our model. We verified by electrophysiological experiments that this result is not an artifact of the sensory model. Already subtle changes in the texture may lead to qualitative differences in the responses of both our model cells and their biological counterparts in the fly's brain. Nonetheless, free flight behavior of blowflies is only moderately affected by such texture changes. This divergent texture dependence of motion-sensitive neurons and behavioral performance suggests either mechanisms that compensate for the texture dependence of the visual motion pathway at the level of the circuits generating the saccadic turn decisions or the involvement of a hypothetical parallel pathway in saccadic control that provides the information for collision avoidance independent of the textural properties of the environment