Blurred edges look faint, and faint edges look sharp:The effect of a gradient threshold in a multi-scale edge coding model

A multi-scale model of edge coding based on normalized Gaussian derivative filters successfully predicts perceived scale (blur) for a wide variety of edge profiles [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in press). From filters to features: Scale-space analysis of edge and blur coding in human vision. Journal of Vision]. Our model spatially differentiates the luminance profile, half-wave rectifies the 1st derivative, and then differentiates twice more, to give the 3rd derivative of all regions with a positive gradient. This process is implemented by a set of Gaussian derivative filters with a range of scales. Peaks in the inverted normalized 3rd derivative across space and scale indicate the positions and scales of the edges. The edge contrast can be estimated from the height of the peak. The model provides a veridical estimate of the scale and contrast of edges that have a Gaussian integral profile. Therefore, since scale and contrast are independent stimulus parameters, the model predicts that the perceived value of either of these parameters should be unaffected by changes in the other. This prediction was found to be incorrect: reducing the contrast of an edge made it look sharper, and increasing its scale led to a decrease in the perceived contrast. Our model can account for these effects when the simple half-wave rectifier after the 1st derivative is replaced by a smoothed threshold function described by two parameters. For each subject, one pair of parameters provided a satisfactory fit to the data from all the experiments presented here and in the accompanying paper [May, K. A. & Georgeson, M. A. (2007). Added luminance ramp alters perceived edge blur and contrast: A critical test for derivative-based models of edge coding. Vision Research, 47, 1721-1731]. Thus, when we allow for the visual system's insensitivity to very shallow luminance gradients, our multi-scale model can be extended to edge coding over a wide range of contrasts and blurs. © 2007 Elsevier Ltd. All rights reserved.

Mach edges: a key role for 3rd derivative filters in spatial vision

Edges are key points of information in visual scenes. One important class of models supposes that edges correspond to the steepest parts of the luminance profile, implying that they can be found as peaks and troughs in the response of a gradient (first-derivative) filter, or as zero-crossings (ZCs) in the second-derivative. A variety of multi-scale models are based on this idea. We tested this approach by devising a stimulus that has no local peaks of gradient and no ZCs, at any scale. Our stimulus profile is analogous to the classic Mach-band stimulus, but it is the local luminance gradient (not the absolute luminance) that increases as a linear ramp between two plateaux. The luminance profile is a smoothed triangle wave and is obtained by integrating the gradient profile. Subjects used a cursor to mark the position and polarity of perceived edges. For all the ramp-widths tested, observers marked edges at or close to the corner points in the gradient profile, even though these were not gradient maxima. These new Mach edges correspond to peaks and troughs in the third-derivative. They are analogous to Mach bands - light and dark bars are seen where there are no luminance peaks but there are peaks in the second derivative. Here, peaks in the third derivative were seen as light-to-dark edges, troughs as dark-to-light edges. Thus Mach edges are inconsistent with many standard edge detectors, but are nicely predicted by a new model that uses a (nonlinear) third-derivative operator to find edge points.

Perceiving edge contrast

We have shown previously that a template model for edge perception successfully predicts perceived blur for a variety of edge profiles (Georgeson, 2001 Journal of Vision 1 438a; Barbieri-Hesse and Georgeson, 2002 Perception 31 Supplement, 54). This study concerns the perceived contrast of edges. Our model spatially differentiates the luminance profile, half-wave rectifies this first derivative, and then differentiates again to create the edge's 'signature'. The spatial scale of the signature is evaluated by filtering it with a set of Gaussian derivative operators. This process finds the correlation between the signature and each operator kernel at each position. These kernels therefore act as templates, and the position and scale of the best-fitting template indicate the position and blur of the edge. Our previous finding, that reducing edge contrast reduces perceived blur, can be explained by replacing the half-wave rectifier with a smooth, biased rectifier function (May and Georgeson, 2003 Perception 32 388; May and Georgeson, 2003 Perception 32 Supplement, 46). With the half-wave rectifier, the peak template response R to a Gaussian edge with contrast C and scale s is given by: R=Cp-1/4s-3/2. Hence, edge contrast can be estimated from response magnitude and blur: C=Rp1/4s3/2. Use of this equation with the modified rectifier predicts that perceived contrast will decrease with increasing blur, particularly at low contrasts. Contrast-matching experiments supported this prediction. In addition, the model correctly predicts the perceived contrast of Gaussian edges modified either by spatial truncation or by the addition of a ramp.

Perceiving edge blur: Gaussian-derivative filtering and a rectifying nonlinearity

We studied the visual mechanisms that encode edge blur in images. Our previous work suggested that the visual system spatially differentiates the luminance profile twice to create the `signature' of the edge, and then evaluates the spatial scale of this signature profile by applying Gaussian derivative templates of different sizes. The scale of the best-fitting template indicates the blur of the edge. In blur-matching experiments, a staircase procedure was used to adjust the blur of a comparison edge (40% contrast, 0.3 s duration) until it appeared to match the blur of test edges at different contrasts (5% - 40%) and blurs (6 - 32 min of arc). Results showed that lower-contrast edges looked progressively sharper. We also added a linear luminance gradient to blurred test edges. When the added gradient was of opposite polarity to the edge gradient, it made the edge look progressively sharper. Both effects can be explained quantitatively by the action of a half-wave rectifying nonlinearity that sits between the first and second (linear) differentiating stages. This rectifier was introduced to account for a range of other effects on perceived blur (Barbieri-Hesse and Georgeson, 2002 Perception 31 Supplement, 54), but it readily predicts the influence of the negative ramp. The effect of contrast arises because the rectifier has a threshold: it not only suppresses negative values but also small positive values. At low contrasts, more of the gradient profile falls below threshold and its effective spatial scale shrinks in size, leading to perceived sharpening.

Perceiving edge blur: linear filtering and a rectifying nonlinearity

We studied the visual mechanisms that encode edge blur in images. Our previous work suggested that the visual system spatially differentiates the luminance profile twice to create the 'signature' of the edge, and then evaluates the spatial scale of this signature profile by applying Gaussian derivative templates of different sizes. The scale of the best-fitting template indicates the blur of the edge. In blur-matching experiments, a staircase procedure was used to adjust the blur of a comparison edge (40% contrast, 0.3 s duration) until it appeared to match the blur of test edges at different contrasts (5% - 40%) and blurs (6 - 32 min of arc). Results showed that lower-contrast edges looked progressively sharper.We also added a linear luminance gradient to blurred test edges. When the added gradient was of opposite polarity to the edge gradient, it made the edge look progressively sharper. Both effects can be explained quantitatively by the action of a half-wave rectifying nonlinearity that sits between the first and second (linear) differentiating stages. This rectifier was introduced to account for a range of other effects on perceived blur (Barbieri-Hesse and Georgeson, 2002 Perception 31 Supplement, 54), but it readily predicts the influence of the negative ramp. The effect of contrast arises because the rectifier has a threshold: it not only suppresses negative values but also small positive values. At low contrasts, more of the gradient profile falls below threshold and its effective spatial scale shrinks in size, leading to perceived sharpening.

Modulating receptor function through RAMPs:can they represent drug targets in themselves?

G protein-coupled receptors (GPCRs) are successfully exploited as drug targets. As our understanding of how distinct GPCR subtypes can be generated expands, so do possibilities for therapeutic intervention via these receptors. Receptor activity-modifying proteins (RAMPs) are excellent examples of proteins that enhance diversity in. GPCR function. They facilitate the creation of binding pockets, controlling the pharmacology of some GPCRs. Moreover, they have the ability to regulate cell-surface trafficking, internalisation and signalling of GPCRs, creating novel opportunities for drug discovery. RAMPs could be directly targeted by drugs, or advantage could be taken of unique RAMP/GPCR interfaces for generating highly selective ligands.

Structure-function analysis of RAMP1 by Alanine Mutagenesis

Receptor activity modifying protein 1 (RAMP1) is an integral component of several receptors including the calcitonin gene-related peptide (CGRP) receptor. It forms a complex with the calcitonin receptor-like receptor (CLR) and is required for receptor trafficking and ligand binding. The N-terminus of RAMP1 comprises three helices. The current study investigated regions of RAMP1 important for CGRP or CLR interactions by alanine mutagenesis. Modeling suggested the second and third helices were important in protein-protein interactions. Most of the conserved residues in the N-terminus (M48, W56, Y66, P85, N66, H97, F101, D113, P114, P115), together with a further 13 residues spread throughout three helices of RAMP1, were mutated to alanine and coexpressed with CLR in Cos 7 cells. None of the mutations significantly reduced RAMP expression. Of the nine mutants from helix 1, only M48A had any effect, producing a modest reduction in trafficking of CLR to the cell surface. In helix 2 Y66A almost completely abolished CLR trafficking; L69A and T73A reduced the potency of CGRP to produce cAMP. In helix 3, H97A abolished CLR trafficking; P85A, N86A, and F101A had caused modest reductions in CLR trafficking and also reduced the potency of CGRP on cAMP production. F93A caused a modest reduction in CLR trafficking alone and L94A increased cAMP production. The data are consistent with a CLR recognition site particularly involving Y66 and H97, with lesser roles for adjacent residues in helix 3. L69 and T73 may contribute to a CGRP recognition site in helix 2 also involving nearby residues.

RAMPs and the modulation of G-protein coupled receptors

Receptor activity modifying proteins (RAMPs) are a family of three proteins that can interact with G-protein coupled receptors (GPCRs) to create new receptors and also alter the signalling and trafficing of existing receptors. There are frequently changes in RAMP expression in cardiovascular disease RAMPs represent important drug targets.

Mach Bands: multi-scale spatial filtering and co-operative coding of edges and bars

Perception of Mach bands may be explained by spatial filtering ('lateral inhibition') that can be approximated by 2nd derivative computation, and several alternative models have been proposed. To distinguish between them, we used a novel set of ‘generalised Gaussian’ images, in which the sharp ramp-plateau junction of the Mach ramp was replaced by smoother transitions. The images ranged from a slightly blurred Mach ramp to a Gaussian edge and beyond, and also included a sine-wave edge. The probability of seeing Mach Bands increased with the (relative) sharpness of the junction, but was largely independent of absolute spatial scale. These data did not fit the predictions of MIRAGE, nor 2nd derivative computation at a single fine scale. In experiment 2, observers used a cursor to mark features on the same set of images. Data on perceived position of Mach bands did not support the local energy model. Perceived width of Mach bands was poorly explained by a single-scale edge detection model, despite its previous success with Mach edges (Wallis & Georgeson, 2009, Vision Research, 49, 1886-1893). A more successful model used separate (odd and even) scale-space filtering for edges and bars, local peak detection to find candidate features, and the MAX operator to compare odd- and even-filter response maps (Georgeson, VSS 2006, Journal of Vision 6(6), 191a). Mach bands are seen when there is a local peak in the even-filter (bar) response map, AND that peak value exceeds corresponding responses in the odd-filter (edge) maps.

The acceptability of alcohol fuels for automobile engines

The aim of this project was to carry out an investigastion into suitable alternatives to gasoline for use in modern automobiles. The fuel would provide the western world with a means of extending the natural gasoline resources and the third world a way of cutting down their dependence on the oil producing countries for their energy supply. Alcohols, namely methanol and ethanol, provide this solution. They can be used as gasoline extenders or as fuels on their own.In order to fulfil the aims of the project a literature study was carried out to investigate methods and costs of producing these fuels. An experimental programme was then set up in which the performance of the alcohols was studied on a conventional engine. The engine used for this purpose was the Fiat 127 930cc four cylinder engine. This engine was used because of its popularity in the European countries. The Weber fixed jet carburettor, since it was designed to be used with gasoline, was adapted so that the alcohol fuels and the blends could be used in the most efficient way. This was mainly to take account of the lower heat content of the alcohols. The adaptation of the carburettor was in the form of enlarging the main metering jet. Allowances for the alcohol's lower specfic gravity were made during fuel metering.Owing to the low front end volatility of methanol and ethanol, it was expected that `start up' problems would occur. An experimental programme was set up to determine the temperature range for a minimum required percentage `take off' that would ease start-up since it was determined that a `take off' of about 5% v/v liquid in the vapour phase would be sufficient for starting. Additions such as iso-pentane and n-pentane were used to improve the front end volatility. This proved to be successful.The lower heat content of the alcohol fuels also meant that a greater charge of fuel would be required. This was seen to pose further problems with fuel distribution from the carburettor to the individual cylinders on a multicylinder engine. Since it was not possible to modify the existing manifold on the Fiat 127 engine, experimental tests on manifold geometry were carried out using the Ricardo E6 single cylinder variable compression engine. Results from these tests showed that the length, shape and cross-sectional area of the manifold play an important part in the distribution of the fuel entering the cylinder, ie. vapour phase, vapour/small liquid droplet/liquid film phase, vapour/large liquid droplet/liquid film phase etc.The solvent properties of the alcohols and their greater electrical conductivity suggested that the materials used on the engine would be prone to chemical attack. In order to determine the type and rate of chemical attack, an experimental programme was set up whereby carburettor and other components were immersed in the alcohols and in blends of alcohol with gasoline. The test fuels were aerated and in some instances kept at temperatures ranging from 50oC to 90oC. Results from these tests suggest that not all materials used in the conventional engine are equally suitable for use with alcohols and alcohol/gasoline blends. Aluminium for instance was severely attacked by methanol causing pitting and pin-holing in the surface.In general this whole experimental programme gave valuable information on the acceptability of substitute fuels. While the long term effects of alcohol use merit further study, it is clear that methanol and ethanol will be increasingly used in place of gasoline.

Influencing water consumption at South Staffordshire Water PLC : a disaggregated behavioural analysis of contributory factors

This research identifies factors which influence the consumption of potable water supplied to customers' property. A complete spectrum of the customer base is examined including household, commercial and industrial properties. The research considers information from around the world, particularly demand management and tariff related projects from North America. A device termed the Flow Moderator was developed and proven, with extensive trials, to conserve water at a rate equivalent to 40 litres/property/day whilst maintaining standards-of-service considerably in excess of Regulatory requirements. A detailed appraisal of the Moderator underlines the costs and benefits available to the industry through deliberate application of even mild demand management. More radically the concept of a charging policy utilising the Moderator is developed and appraised. Advantages include the lower costs of conventional fixed-price charging systems coupled with the conservation and equitability aspects associated with metering. Explanatory models were developed linking consumption to a range of variables demonstrated that households served by a communal water service-pipe (known in the UK as a shared supply) are subject to associated restrictions equivalent to -180 litres/property/day. The research confirmed that occupancy levels were a significant predictive element for household, commercial and industrial customers. The occurrence of on-property leakage was also demonstrated to be a significant factor recorded as an event which offers considerable scope for demand management in its own right.

Functional characterization of two human receptor activity-modifying protein 3 variants

Adrenomedullin (AM) and amylin are involved in angiogenesis/lymphangiogenesis and glucose homeostasis/food intake, respectively. They activate receptor activity-modifying protein (RAMP)/G protein-coupled receptor (GPCR) complexes. RAMP3 with the calcitonin receptor-like receptor (CLR) forms the AM(2) receptor, whereas when paired with the calcitonin receptor AMY(3) receptors are formed. RAMP3 interacts with other GPCRs although the consequences of these interactions are poorly understood. Therefore, variations in the RAMP3 sequence, such as single nucleotide polymorphisms or mutations could be relevant to human health. Variants of RAMP3 have been identified. In particular, analysis of AK222469 (Homo sapiens mRNA for receptor (calcitonin) activity-modifying protein 3 precursor variant) revealed several nucleotide differences, three of which encoded amino acid changes (Cys40Trp, Phe100Ser, Leu147Pro). Trp56Arg RAMP3 is a polymorphic variant of human RAMP3 at a conserved amino acid position. To determine their function we used wild-type (WT) human RAMP3 as a template for introducing amino acid mutations. Mutant or WT RAMP3 function was determined in Cos-7 cells with CLR or the calcitonin receptor (CT((a))). Cys40Trp/Phe100Ser/Leu147Pro RAMP3 was functionally compromised, with reduced AM and amylin potency at the respective AM(2) and AMY(3(a)) receptor complexes. Cys40Trp and Phe100Ser mutations contributed to this phenotype, unlike Leu147Pro. Reduced cell-surface expression of mutant receptor complexes probably explains the functional data. In contrast, Trp56Arg RAMP3 was WT in phenotype. This study provides insight into the role of these residues in RAMP3. The existence of AK222469 in the human population has implications for the function of RAMP3/GPCR complexes, particularly AM and amylin receptors.

An insight into the activation mechanism of the calcatonin-gene-related peptide receptor

The calcitonin-gene- related peptide (CGRP) receptor is unique among G-protein coupled receptors (GPCRs) as it consists of at least three proteins: calcitonin receptor like receptor (CLR), receptor activity modifying protein (RAMP)1 and receptor component protein (RCP). An endogenous agonist for this curious receptor is aCGRP, which is a sensory nerve-derived peptide made up of 37 amino acids. aCGRP acts as a potent vasodilator having pronounced effects on arterioles and capillaries. Understanding the pharmacodynamics of the CGRP receptor may have pharmaceutical benefit as the receptor has been associated with the onset of migraines and implicated in Raynauds syndrome. The primary aim of this thesis was to identify functionally important residues in the extracellular face of the CGRP receptor. Three areas of interest were selected including the extreme N-terminus of the CLR, extracellular loop 1 (ECL1) of the CLR and its associated transmembrane (TM) regions, and finally extracellular loop 3 (ECL3) of the CLR and its juxtamembrane regions. A site-directed mutagenesis (SDM) strategy was used to investigate these regions, primarily substituting the innate residues of CLR with alanine and assessing the mutation on multiple criteria including a functional cAMP assay, cell-surface expression, total expression, agonist-mediated internalisation and aCGRP binding. The results are interpreted and discussed taking into consideration contemporary concepts surrounding Secretin-like GPCRs. Moreover, the thesis also contains details of RAMP purification. Overall the thesis provides novel data that furthers insight into the complex phenomenon of CGRP receptor activation. Site-directed mutants have been identified that affect aCGRP binding, receptor signal transduction, the CLR/RAMP1 interface and the integrity of the protein complex structure.

Low level feature detection in human vision

Influential models of edge detection have generally supposed that an edge is detected at peaks in the 1st derivative of the luminance profile, or at zero-crossings in the 2nd derivative. However, when presented with blurred triangle-wave images, observers consistently marked edges not at these locations, but at peaks in the 3rd derivative. This new phenomenon, termed ‘Mach edges’ persisted when a luminance ramp was added to the blurred triangle-wave. Modelling of these Mach edge detection data required the addition of a physiologically plausible filter, prior to the 3rd derivative computation. A viable alternative model was examined, on the basis of data obtained with short-duration, high spatial-frequency stimuli. Detection and feature-making methods were used to examine the perception of Mach bands in an image set that spanned a range of Mach band detectabilities. A scale-space model that computed edge and bar features in parallel provided a better fit to the data than 4 competing models that combined information across scale in a different manner, or computed edge or bar features at a single scale. The perception of luminance bars was examined in 2 experiments. Data for one image-set suggested a simple rule for perception of a small Gaussian bar on a larger inverted Gaussian bar background. In previous research, discriminability (d’) has typically been reported to be a power function of contrast, where the exponent (p) is 2 to 3. However, using bar, grating, and Gaussian edge stimuli, with several methodologies, values of p were obtained that ranged from 1 to 1.7 across 6 experiments. This novel finding was explained by appealing to low stimulus uncertainty, or a near-linear transducer.

RAMPs and CGRP receptors

Receptor activity modifying protein 1 (RAMP1) forms a complex with calcitonin receptor-like receptor (CLR) to produce the receptor for calcitonin gene-related peptide (CGRP). RAMP1 has two main roles. It facilitates the cell-surface expression of CLR. It is also essential for the binding of CGRP to the receptor. It seems likely that Y66, F93, H97 and F101, amongst other residues, form a binding site for CLR. These cluster together on the same face of the extracellular portion of RAMP1, probably close to where it enters the plasma membrane. Residues at the other end of RAMP1 are most likely to be involved in CGRP recognition, although it is currently unclear how they do this. Within this area, W74 is important for the binding of the nonpeptide antagonist, BIBN4096BS, although it does not seem to be involved in the binding of CGRP itself. It has been shown that there is an epitope within residues 23-60 of CLR that are essential for RAMP recognition. Under some circumstances, changes in the expression of RAMP1 can alter the sensitivity of cells to CGRP, demonstrating that regulation of its levels may be of physiological or pathophysiological importance.