Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

An evaluation of space time cube representation of spatiotemporal patterns.

Space time cube representation is an information visualization technique where spatiotemporal data points are mapped into a cube. Information visualization researchers have previously argued that space time cube representation is beneficial in revealing complex spatiotemporal patterns in a data set to users. The argument is based on the fact that both time and spatial information are displayed simultaneously to users, an effect difficult to achieve in other representations. However, to our knowledge the actual usefulness of space time cube representation in conveying complex spatiotemporal patterns to users has not been empirically validated. To fill this gap, we report on a between-subjects experiment comparing novice users' error rates and response times when answering a set of questions using either space time cube or a baseline 2D representation. For some simple questions, the error rates were lower when using the baseline representation. For complex questions where the participants needed an overall understanding of the spatiotemporal structure of the data set, the space time cube representation resulted in on average twice as fast response times with no difference in error rates compared to the baseline. These results provide an empirical foundation for the hypothesis that space time cube representation benefits users analyzing complex spatiotemporal patterns.

The Trade-offs with Space Time Cube Representation of Spatiotemporal Patterns

Space time cube representation is an information visualization technique where spatiotemporal data points are mapped into a cube. Fast and correct analysis of such information is important in for instance geospatial and social visualization applications. Information visualization researchers have previously argued that space time cube representation is beneficial in revealing complex spatiotemporal patterns in a dataset to users. The argument is based on the fact that both time and spatial information are displayed simultaneously to users, an effect difficult to achieve in other representations. However, to our knowledge the actual usefulness of space time cube representation in conveying complex spatiotemporal patterns to users has not been empirically validated. To fill this gap we report on a between-subjects experiment comparing novice users error rates and response times when answering a set of questions using either space time cube or a baseline 2D representation. For some simple questions the error rates were lower when using the baseline representation. For complex questions where the participants needed an overall understanding of the spatiotemporal structure of the dataset, the space time cube representation resulted in on average twice as fast response times with no difference in error rates compared to the baseline. These results provide an empirical foundation for the hypothesis that space time cube representation benefits users when analyzing complex spatiotemporal patterns.

Differences between FRP bond behavior in cracked and uncracked regions

Based on an analysis of the experimental results of a proposed bond test method, significant differences are shown to exist between the local FRP bond stress-slip relationships in the uncracked anchorage regions and in the regions between cracks. The proposed method simulates the bond behavior between the flexural cracks and anchorage regions of a flexurally FRP-strengthened RC beam. The boundary conditions, including the presence of cracks and steel, are shown to have significant effects on the local bond stress-slip models. The results showed that, at the same force, the bond stresses in the regions between cracks were lower than in regions outside the cracks, so the debonding formed in the anchorage regions. The local bond stress-slip models in the anchorage regions can be obtained from the conventional bond test methods but these do not mimic the conditions between the cracks.

Insight into differences in nanoindentation properties of bone.

Nanoindentation provides the ideal framework to determine mechanical properties of bone at the tissue scale without being affected by the size, shape, and porosity of the bone. However, the values of tissue level mechanical properties vary significantly between studies. Since the differences in the bone sample, hydration state, and test parameters complicate direct comparisons across the various studies, these discrepancies in values cannot be compared directly. The objective of the current study is to evaluate and compare mechanical properties of the same bones using a broad range of testing parameters. Wild type C56BL6 mice tibiae were embedded following different processes and tested in dry and rehydrated conditions. Spherical and Berkovich indenter probes were used, and data analysis was considered within the elasto-plastic (Oliver-Pharr), viscoelastic and visco-elastic-plastic frameworks. The mean values of plane strain modulus varied significantly depending on the hydration state, probe geometry and analysis method. Indentations in dry bone analyzed using a visco-elastic-plastic approach gave values of 34 GPa. After rehydrating the same bones and indenting them with a spherical tip and utilizing a viscoelastic analysis, the mean modulus value was 4 GPa, nearly an order of magnitude smaller. Results suggest that the hydration state, probe geometry and the limitations and assumptions of each analysis method influence significantly the measured mechanical properties. This is the first time that such a systematic study has been carried out and it has been concluded that the discrepancies in the mechanical properties of bone measured by nanoindentation found in the literature should not be attributed only to the differences between the bones themselves, but also to the testing and analysis protocols.