Modeling ion channel dynamics through reflected stochastic differential equations

Ion channels are membrane proteins that open and close at random and play a vital role in the electrical dynamics of excitable cells. The stochastic nature of the conformational changes these proteins undergo can be significant, however current stochastic modeling methodologies limit the ability to study such systems. Discrete-state Markov chain models are seen as the "gold standard," but are computationally intensive, restricting investigation of stochastic effects to the single-cell level. Continuous stochastic methods that use stochastic differential equations (SDEs) to model the system are more efficient but can lead to simulations that have no biological meaning. In this paper we show that modeling the behavior of ion channel dynamics by a reflected SDE ensures biologically realistic simulations, and we argue that this model follows from the continuous approximation of the discrete-state Markov chain model. Open channel and action potential statistics from simulations of ion channel dynamics using the reflected SDE are compared with those of a discrete-state Markov chain method. Results show that the reflected SDE simulations are in good agreement with the discrete-state approach. The reflected SDE model therefore provides a computationally efficient method to simulate ion channel dynamics while preserving the distributional properties of the discrete-state Markov chain model and also ensuring biologically realistic solutions. This framework could easily be extended to other biochemical reaction networks. © 2012 American Physical Society.

Aromatic l-amino acid decarboxylase : histochemical localization in rat kidney and lack of effect of dietary potassium or sodium loading on enzyme distribution

Utilizing a mono-specific antiserum produced in rabbits to hog kidney aromatic L-amino acid decarboxylase (AADC), the enzyme was localized in rat kidney by immunoperoxidase staining. AADC was located predominantly in the proximal convoluted tubules; there was also weak staining in the distal convoluted tubules and collecting ducts. An increase in dietary potassium or sodium intake produced no change in density or distribution of AADC staining in kidney. An assay of AADC enzyme activity showed no difference in cortex or medulla with chronic potassium loading. A change in distribution or activity of renal AADC does not explain the postulated dopaminergic modulation of renal function that occurs with potassium or sodium loading.

Towards persistent localization and mapping with a continuous appearance-based topology

Appearance-based localization can provide loop closure detection at vast scales regardless of accumulated metric error. However, the computation time and memory requirements of current appearance-based methods scale not only with the size of the environment but also with the operation time of the platform. Additionally, repeated visits to locations will develop multiple competing representations, which will reduce recall performance over time. These properties impose severe restrictions on long-term autonomy for mobile robots, as loop closure performance will inevitably degrade with increased operation time. In this paper we present a graphical extension to CAT-SLAM, a particle filter-based algorithm for appearance-based localization and mapping, to provide constant computation and memory requirements over time and minimal degradation of recall performance during repeated visits to locations. We demonstrate loop closure detection in a large urban environment with capped computation time and memory requirements and performance exceeding previous appearance-based methods by a factor of 2. We discuss the limitations of the algorithm with respect to environment size, appearance change over time and applications in topological planning and navigation for long-term robot operation.

Differential effects of ERP systems on user outcomes : a longitudinal investigation

Adopting a model of job enrichment we report on a longitudinal case investigating the perceived impact of an Enterprise Resource Planning (ERP) system on user job design characteristics. Our results indicated that in the context of an ERP geared towards centralisation and standardisation the extent to which users perceived an increase or decrease in job enrichment was associated with aspects such as formal authority and the nature of their work role. Experienced operational employees proficient in the original legacy system perceived ERP system protocols to constrain their actions, limit training and increase dependence on others in the workflow. Conversely, managerial users reported a number of benefits relating to report availability, improved organisational transparency and increased overall job enrichment. These results supported our argument concerning the relationship between ERPs with a standardisation intent and positive job enrichment outcomes for managerial users and negative job-related outcomes for operational users.

Capping computation time and storage requirements for appearance-based localization with CAT-SLAM

Appearance-based localization is increasingly used for loop closure detection in metric SLAM systems. Since it relies only upon the appearance-based similarity between images from two locations, it can perform loop closure regardless of accumulated metric error. However, the computation time and memory requirements of current appearance-based methods scale linearly not only with the size of the environment but also with the operation time of the platform. These properties impose severe restrictions on longterm autonomy for mobile robots, as loop closure performance will inevitably degrade with increased operation time. We present a set of improvements to the appearance-based SLAM algorithm CAT-SLAM to constrain computation scaling and memory usage with minimal degradation in performance over time. The appearance-based comparison stage is accelerated by exploiting properties of the particle observation update, and nodes in the continuous trajectory map are removed according to minimal information loss criteria. We demonstrate constant time and space loop closure detection in a large urban environment with recall performance exceeding FAB-MAP by a factor of 3 at 100% precision, and investigate the minimum computational and memory requirements for maintaining mapping performance.

Differential expression of chemokine and matrix re-modelling genes is associated with contrasting schistosome-induced hepatopathology in murine models

The pathological outcomes of schistosomiasis are largely dependent on the molecular and cellular mechanisms of the host immune response. In this study, we investigated the contribution of variations in host gene expression to the contrasting hepatic pathology observed between two inbred mouse strains following Schistosoma japonicum infection. Whole genome microarray analysis was employed in conjunction with histological and immunohistochemical analysis to define and compare the hepatic gene expression profiles and cellular composition associated with the hepatopathology observed in S. japonicum-infected BALB/c and CBA mice. We show that the transcriptional profiles differ significantly between the two mouse strains with high statistical confidence. We identified specific genes correlating with the more severe pathology associated with CBA mice, as well as genes which may confer the milder degree of pathology associated with BALB/c mice. In BALB/c mice, neutrophil genes exhibited striking increases in expression, which coincided with the significantly greater accumulation of neutrophils at granulomatous regions seen in histological sections of hepatic tissue. In contrast, up-regulated expression of the eosinophil chemokine CCL24 in CBA mice paralleled the cellular influx of eosinophils to the hepatic granulomas. Additionally, there was greater down-regulation of genes involved in metabolic processes in CBA mice, reflecting the more pronounced hepatic damage in these mice. Profibrotic genes showed similar levels of expression in both mouse strains, as did genes associated with Th1 and Th2 responses. However, imbalances in expression of matrix metalloproteinases (e.g. MMP12, MMP13) and tissue inhibitors of metalloproteinases (TIMP1) may contribute to the contrasting pathology observed in the two strains. Overall, these results provide a more complete picture of the molecular and cellular mechanisms which govern the pathological outcome of hepatic schistosomiasis. This improved understanding of the immunopathogenesis in the murine model schistosomiasis provides the basis for a better appreciation of the complexities associated with chronic human schistosomiasis.

Stable strong order 1.0 schemes for solving stochastic ordinary differential equations

The Balanced method was introduced as a class of quasi-implicit methods, based upon the Euler-Maruyama scheme, for solving stiff stochastic differential equations. We extend the Balanced method to introduce a class of stable strong order 1. 0 numerical schemes for solving stochastic ordinary differential equations. We derive convergence results for this class of numerical schemes. We illustrate the asymptotic stability of this class of schemes is illustrated and is compared with contemporary schemes of strong order 1. 0. We present some evidence on parametric selection with respect to minimising the error convergence terms. Furthermore we provide a convergence result for general Balanced style schemes of higher orders.

Maintaining a cognitive map in darkness : the need to fuse boundary knowledge with path integration

Spatial navigation requires the processing of complex, disparate and often ambiguous sensory data. The neurocomputations underpinning this vital ability remain poorly understood. Controversy remains as to whether multimodal sensory information must be combined into a unified representation, consistent with Tolman's "cognitive map", or whether differential activation of independent navigation modules suffice to explain observed navigation behaviour. Here we demonstrate that key neural correlates of spatial navigation in darkness cannot be explained if the path integration system acted independently of boundary (landmark) information. In vivo recordings demonstrate that the rodent head direction (HD) system becomes unstable within three minutes without vision. In contrast, rodents maintain stable place fields and grid fields for over half an hour without vision. Using a simple HD error model, we show analytically that idiothetic path integration (iPI) alone cannot be used to maintain any stable place representation beyond two to three minutes. We then use a measure of place stability based on information theoretic principles to prove that featureless boundaries alone cannot be used to improve localization above chance level. Having shown that neither iPI nor boundaries alone are sufficient, we then address the question of whether their combination is sufficient and - we conjecture - necessary to maintain place stability for prolonged periods without vision. We addressed this question in simulations and robot experiments using a navigation model comprising of a particle filter and boundary map. The model replicates published experimental results on place field and grid field stability without vision, and makes testable predictions including place field splitting and grid field rescaling if the true arena geometry differs from the acquired boundary map. We discuss our findings in light of current theories of animal navigation and neuronal computation, and elaborate on their implications and significance for the design, analysis and interpretation of experiments.

Fast power line detection and localization using steerable filter for active UAV guidance

In this paper we present a fast power line detection and localisation algorithm as well as propose a high-level guidance architecture for active vision-based Unmanned Aerial Vehicle (UAV) guidance. The detection stage is based on steerable filters for edge ridge detection, followed by a line fitting algorithm to refine candidate power lines in images. The guidance architecture assumes an UAV with an onboard Gimbal camera. We first control the position of the Gimbal such that the power line is in the field of view of the camera. Then its pose is used to generate the appropriate control commands such that the aircraft moves and flies above the lines. We present initial experimental results for the detection stage which shows that the proposed algorithm outperforms two state-of-the-art line detection algorithms for power line detection from aerial imagery.

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell–cell and cell–matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cell infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell–cell and cell–matrix interactions, while syndecan-2 showed a predilection to associate with cell–matrix interactions during hard tissue formation.

Optimization of human papillomavirus type 16 (HPV-16) L1 expression in plants: Comparison of the suitability of different HPV-16 L1 gene variants and different cell-compartment localization

Virus-like particle-based vaccines for high-risk human papillomaviruses (HPVs) appear to have great promise; however, cell culture-derived vaccines will probably be very expensive. The optimization of expression of different codon-optimized versions of the HPV-16 L1 capsid protein gene in plants has been explored by means of transient expression from a novel suite of Agrobacterium tumefaciens binary expression vectors, which allow targeting of recombinant protein to the cytoplasm, endoplasmic reticulum (ER) or chloroplasts. A gene resynthesized to reflect human codon usage expresses better than the native gene, which expresses better than a plant-optimized gene. Moreover, chloroplast localization allows significantly higher levels of accumulation of L1 protein than does cytoplasmic localization, whilst ER retention was least successful. High levels of L1 (>17% total soluble protein) could be produced via transient expression: the protein assembled into higher-order structures visible by electron microscopy, and a concentrated extract was highly immunogenic in mice after subcutaneous injection and elicited high-titre neutralizing antibodies. Transgenic tobacco plants expressing a human codon-optimized gene linked to a chloroplast-targeting signal expressed L1 at levels up to 11% of the total soluble protein. These are the highest levels of HPV L1 expression reported for plants: these results, and the excellent immunogenicity of the product, significantly improve the prospects of making a conventional HPV vaccine by this means. © 2007 SGM.