Using a State-Space Model and Location Analysis to Infer Time-Delayed Regulatory Networks

Computational gene regulation models provide a means for scientists to draw biological inferences from time-course gene expression data. Based on the state-space approach, we developed a new modeling tool for inferring gene regulatory networks, called time-delayed Gene Regulatory Networks (tdGRNs). tdGRN takes time-delayed regulatory relationships into consideration when developing the model. In addition, a priori biological knowledge from genome-wide location analysis is incorporated into the structure of the gene regulatory network. tdGRN is evaluated on both an artificial dataset and a published gene expression data set. It not only determines regulatory relationships that are known to exist but also uncovers potential new ones. The results indicate that the proposed tool is effective in inferring gene regulatory relationships with time delay. tdGRN is complementary to existing methods for inferring gene regulatory networks. The novel part of the proposed tool is that it is able to infer time-delayed regulatory relationships.     

Patterns of Urban Violent Injury: A Spatio-Temporal Analysis

Objectives

Injury related to violent acts is a problem in every society. Although some authors have examined the geography of violent crime, few have focused on the spatio-temporal patterns of violent injury and none have used an ambulance dataset to explore the spatial characteristics of injury. The purpose of this study was to describe the combined spatial and temporal characteristics of violent injury in a large urban centre.

Methodology/Principal Findings

Using a geomatics framework and geographic information systems software, we studied 4,587 ambulance dispatches and 10,693 emergency room admissions for violent injury occurrences among adults (aged 18–64) in Toronto, Canada, during 2002 and 2004, using population-based datasets. We created kernel density and choropleth maps for 24-hour periods and four-hour daily time periods and compared location of ambulance dispatches and patient residences with local land use and socioeconomic characteristics. We used multivariate regressions to control for confounding factors. We found the locations of violent injury and the residence locations of those injured were both closely related to each other and clearly clustered in certain parts of the city characterised by high numbers of bars, social housing units, and homeless shelters, as well as lower household incomes. The night and early morning showed a distinctive peak in injuries and a shift in the location of injuries to a “nightlife” district. The locational pattern of patient residences remained unchanged during those times.

Conclusions/Significance

Our results demonstrate that there is a distinctive spatio-temporal pattern in violent injury reflected in the ambulance data. People injured in this urban centre more commonly live in areas of social deprivation. During the day, locations of injury and locations of residences are similar. However, later at night, the injury location of highest density shifts to a “nightlife” district, whereas the residence locations of those most at risk of injury do not change.     

Estimating Urban Traffic Patterns through Probabilistic Interconnectivity of Road Network Junctions

The emergence of large, fine-grained mobility datasets offers significant opportunities for the development and application of new methodologies for transportation analysis. In this paper, the link between routing behaviour and traffic patterns in urban areas is examined, introducing a method to derive estimates of traffic patterns from a large collection of fine-grained routing data. Using this dataset, the interconnectivity between road network junctions is extracted in the form of a Markov chain. This representation encodes the probability of the successive usage of adjacent road junctions, encoding routes as flows between decision points rather than flows along road segments. This network of functional interactions is then integrated within a modified Markov chain Monte Carlo (MCMC) framework, adapted for the estimation of urban traffic patterns. As part of this approach, the data-derived links between major junctions influence the movement of directed random walks executed across the network to model origin-destination journeys. The simulation process yields estimates of traffic distribution across the road network. The paper presents an implementation of the modified MCMC approach for London, United Kingdom, building an MCMC model based on a dataset of nearly 700000 minicab routes. Validation of the approach clarifies how each element of the MCMC framework contributes to junction prediction performance, and finds promising results in relation to the estimation of junction choice and minicab traffic distribution. The paper concludes by summarising the potential for the development and extension of this approach to the wider urban modelling domain.     

Quantitative Agent Based Model of User Behavior in an Internet Discussion Forum

The paper presents an agent based simulation of opinion evolution, based on a nonlinear emotion/information/opinion (E/I/O) individual dynamics, to an actual Internet discussion forum. The goal is to reproduce the results of two-year long observations and analyses of the user communication behavior and of the expressed opinions and emotions, via simulations using an agent based model. The model allowed to derive various characteristics of the forum, including the distribution of user activity and popularity (outdegree and indegree), the distribution of length of dialogs between the participants, their political sympathies and the emotional content and purpose of the comments. The parameters used in the model have intuitive meanings, and can be translated into psychological observables.     

The Olfactory System as a Model to Study Axonal Growth Patterns and Morphology In Vivo

The olfactory system has the unusual capacity to generate new neurons throughout the lifetime of an organism. Olfactory stem cells in the basal portion of the olfactory epithelium continuously give rise to new sensory neurons that extend their axons into the olfactory bulb, where they face the challenge to integrate into existing circuitry. Because of this particular feature, the olfactory system represents a unique opportunity to monitor axonal wiring and guidance, and to investigate synapse formation. Here we describe a procedure for in vivo labeling of sensory neurons and subsequent visualization of axons in the olfactory system of larvae of the amphibian Xenopus laevis. To stain sensory neurons in the olfactory organ we adopt the electroporation technique. In vivo electroporation is an established technique for delivering fluorophore-coupled dextrans or other macromolecules into living cells. Stained sensory neurons and their axonal processes can then be monitored in the living animal either using confocal laser-scanning or multiphoton microscopy. By reducing the number of labeled cells to few or single cells per animal, single axons can be tracked into the olfactory bulb and their morphological changes can be monitored over weeks by conducting series of in vivo time lapse imaging experiments. While the described protocol exemplifies the labeling and monitoring of olfactory sensory neurons, it can also be adopted to other cell types within the olfactory and other systems.     

Use of A Mouse Chimaeric Model to Study Cell Migration Patterns In the Small Intestinal Epithelium

The pattern of cells migration in the small intestinal epithelia of a RIII/?ro C57BL/6J mouse aggregation chimaera is demonstrated using Dolichos biflorus agglutinin-peroxidase (DBA) conjugate as a strain-specific marker. Using serial tangential sections of heterogeneously stained villi and plotting the distribution of labelled/unlabelled cells with a drawing tube, and by three-dimensional reconstruction with the aid of computer graphics, we show the migration pathway to be in tight cohorts of similar DBA-peroxidase staining type, which move upwards in straight lines. There is little cell mixing either on the villus or along the crypt-villus junctions. Our observations also show for the first time that a single crypt can feed cells to more than one villus. They also suggest that either cell loss is not confined to the villus tips but can take place from the villus sides, or that there is marked asynchrony of cell production between crypts.     

Host Location of a Pupal Parasitoid in a Tritrophic System Compared to a Model Offering Mechanosensory Cues Only

Several species of hymenopteran parasitoids are able to locate concealed pupal hosts by vibrational sounding. However, the specific role of this technique of mechanosensory host location has not yet been investigated in a natural, tritrophic system with multiple cues. Here we compared the host location of the pupal parasitoid Xanthopimpla stemmator in a tritrophic system with corn borer pupae in maize stem to the behavior on a paper model offering mechanosensory cues only. In general, the behavioral pattern and the behavioral states exhibited by host-searching female parasitoid were identical in the model and in the tritrophic system, while quantitative aspects differed. Our results demonstrate that vibrational sounding maintains its significance for host location in an environment with multiple cues, and that additional cues may increase responsiveness of females.     

Location of cellular adhesions to solid substrata

Micromanipulation and time lapse cinemicrography were used to locate the adhesions to glass and polystyrene formed in culture by a variety of different cell types. These adhesions were observed to be confined to relatively narrow areas near the cell margins, principally in the vicinity of ruffling activity. During mitosis and after certain treatments, cell-substratum adhesion was found to be restricted to many tiny points connected to the cell body by narrow, nearly invisible retraction fibers. The relationship of these phenomena to cell locomotion, contact inhibition, and contact retraction is discussed.     

Application of Spatial Location Information to SIP

This paper introduces an approach for providing the Spatial Location (SLO) information of the Session Initiation Protocol (SIP) devices connected to wire and wireless IP networks. The aim of the paper is to set up the framework for providing emergency call services. This method uses SIP as transport and the SLO as data format inserted in the SIP payload. It analyses the relationship among the network elements involved in the architecture, and its functionality for providing emergency call services using SIP. In conclusion, this proposal track down an emergency call via SIP, and additionally enables SIP to support some other location-related services such as messaging, and location-based commerce.     

Spatio-Temporal Analysis of Micro Economic Activities in Rome Reveals Patterns of Mixed-Use Urban Evolution

Understanding urban growth is one with understanding how society evolves to satisfy the needs of its individuals in sharing a common space and adapting to the territory. We propose here a quantitative analysis of the historical development of a large urban area by investigating the spatial distribution and the age of commercial activities in the whole city of Rome. We find that the age of activities of various categories presents a very interesting double exponential trend, with a transition possibly related to the long-term economical effects determined by the oil crisis of the Seventies. The diversification of commercial categories, studied through various measures of entropy, shows, among other interesting features, a saturating behaviour with the density of activities. Moreover, different couples of commercial categories exhibit over the years a tendency to attract in space. Our results demonstrate that the spatio-temporal distribution of commercial activities can provide important insights on the urbanisation processes at work, revealing specific and non trivial socio-economical dynamics, as the presence of crisis periods and expansion trends, and contributing to the characterisation of the maturity of urban areas.     

Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model

Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T₂-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across time is essential for gaining a real understanding of disease processes in-vivo. MTR increases in healthy mice throughout adolescence and adulthood were observed, illustrating the need for appropriate age-matched controls. Elucidating the unique and site-specific demyelination in the cuprizone model may offer new insights into in mechanisms of both damage and repair in human demyelinating diseases.     

Chemically Based Mathematical Model for Development of Cerebral Cortical Folding Patterns

The mechanism for cortical folding pattern formation is not fully understood. Current models represent scenarios that describe pattern formation through local interactions, and one recent model is the intermediate progenitor model. The intermediate progenitor (IP) model describes a local chemically driven scenario, where an increase in intermediate progenitor cells in the subventricular zone correlates to gyral formation. Here we present a mathematical model that uses features of the IP model and further captures global characteristics of cortical pattern formation. A prolate spheroidal surface is used to approximate the ventricular zone. Prolate spheroidal harmonics are applied to a Turing reaction-diffusion system, providing a chemically based framework for cortical folding. Our model reveals a direct correlation between pattern formation and the size and shape of the lateral ventricle. Additionally, placement and directionality of sulci and the relationship between domain scaling and cortical pattern elaboration are explained. The significance of this model is that it elucidates the consistency of cortical patterns among individuals within a species and addresses inter-species variability based on global characteristics and provides a critical piece to the puzzle of cortical pattern formation.     

Culturally Determined Patterns of Violence: Biological Anthropological Investigations at a Historic Urban Cemetery

Patterns of violence and the type and distribution of resulting injuries are highly culturally specific. In this study, skeletal data from a historic cemetery (St. Martin's, England) are combined with contemporary sources and modern clinical data to enable the patterning of violence-related injuries to be interpreted. Particular consideration was given to the possibility of a relationship between commonly occurring types of violence and those that are popular in sport. Phillip Walker (1997) suggested that the growth of fist fighting in the early-20th-century United States was stimulated by the rising popularity of boxing. At St. Martin's, a pattern of injuries consistent with fighting in a style specific to boxing is evident, suggesting that developing boxing styles were influential in 18th- and 19th-century Britain as the accepted way of settling interpersonal disputes. This research underlines the importance of interpreting skeletal data in their specific cultural context to gain the maximum information on patterns of behavior.     

Automated Learning of Subcellular Variation among Punctate Protein Patterns and a Generative Model of Their Relation to Microtubules

Characterizing the spatial distribution of proteins directly from microscopy images is a difficult problem with numerous applications in cell biology (e.g. identifying motor-related proteins) and clinical research (e.g. identification of cancer biomarkers). Here we describe the design of a system that provides automated analysis of punctate protein patterns in microscope images, including quantification of their relationships to microtubules. We constructed the system using confocal immunofluorescence microscopy images from the Human Protein Atlas project for 11 punctate proteins in three cultured cell lines. These proteins have previously been characterized as being primarily located in punctate structures, but their images had all been annotated by visual examination as being simply “vesicular”. We were able to show that these patterns could be distinguished from each other with high accuracy, and we were able to assign to one of these subclasses hundreds of proteins whose subcellular localization had not previously been well defined. In addition to providing these novel annotations, we built a generative approach to modeling of punctate distributions that captures the essential characteristics of the distinct patterns. Such models are expected to be valuable for representing and summarizing each pattern and for constructing systems biology simulations of cell behaviors.     

New Procedure for Selection of Variables in Location Model for Mixed Variable Discrimination

A new method for the choice of variables with the greatest discriminatory power in the location model for mixed variable discriminant analysis is presented in the paper. The procedure based on the multivariate discriminatory measure enables a simultaneous reduction of the number of discrete and continuous variables. The introduced criterion can be used for both optimal or step-wise selection of variable subset. As an example the results of the stepwise variable selection for some medical data are presented in the paper.