Model and Appearance Based Analysis of Neuronal Morphology from Different Microscopy Imaging Modalities

The neuronal morphology analysis is key for understanding how a brain works. This process requires the neuron imaging system with single-cell resolution; however, there is no feasible system for the human brain. Fortunately, the knowledge can be inferred from the model organism, Drosophila melanogaster, to the human system. This dissertation explores the morphology analysis of Drosophila larvae at single-cell resolution in static images and image sequences, as well as multiple microscopy imaging modalities. Our contributions are on both computational methods for morphology quantification and analysis of the influence of the anatomical aspect. We develop novel model-and-appearance-based methods for morphology quantification and illustrate their significance in three neuroscience studies. Modeling of the structure and dynamics of neuronal circuits creates understanding about how connectivity patterns are formed within a motor circuit and determining whether the connectivity map of neurons can be deduced by estimations of neuronal morphology. To address this problem, we study both boundary-based and centerline-based approaches for neuron reconstruction in static volumes. Neuronal mechanisms are related to the morphology dynamics; so the patterns of neuronal morphology changes are analyzed along with other aspects. In this case, the relationship between neuronal activity and morphology dynamics is explored to analyze locomotion procedures. Our tracking method models the morphology dynamics in the calcium image sequence designed for detecting neuronal activity. It follows the local-to-global design to handle calcium imaging issues and neuronal movement characteristics. Lastly, modeling the link between structural and functional development depicts the correlation between neuron growth and protein interactions. This requires the morphology analysis of different imaging modalities. It can be solved using the part-wise volume segmentation with artificial templates, the standardized representation of neurons. Our method follows the global-to-local approach to solve both part-wise segmentation and registration across modalities. Our methods address common issues in automated morphology analysis from extracting morphological features to tracking neurons, as well as mapping neurons across imaging modalities. The quantitative analysis delivered by our techniques enables a number of new applications and visualizations for advancing the investigation of phenomena in the nervous system

FIMCAR XIV: Potential of Simulation Tools

For the assessment of vehicle safety in frontal collisions compatibility (which consist of self and partner protection) between opponents is crucial. The use of simulation tools is the only way to a realistic and wide coverage (w.r.t. the real accident situations that may happen on the road) of car-to-car compatibility issues with acceptable costs. This report reviews the use of Virtual Testing (VT) in today’s European vehicle and product type approval, and the on-going work for future implementation of VT in vehicle type approval and rating. The modelling requirements and validation process are discussed both regarding barrier models and car models. Combined with the experience from the use of simulation tools in the FIMCAR project, a 4-step roadmap for implementation of VT tools in the compatibility development is proposed

Dynamic and Integrative Properties of the Primary Visual Cortex

The ability to derive meaning from complex, ambiguous sensory input requires the integration of information over both space and time, as well as cognitive mechanisms to dynamically shape that integration. We have studied these processes in the primary visual cortex (V1), where neurons have been proposed to integrate visual inputs along a geometric pattern known as the association field (AF). We first used cortical reorganization as a model to investigate the role that a specific network of V1 connections, the long-range horizontal connections, might play in temporal and spatial integration across the AF. When retinal lesions ablate sensory information from portions of the visual field, V1 undergoes a process of reorganization mediated by compensatory changes in the network of horizontal collaterals. The reorganization accompanies the brain’s amazing ability to perceptually “fill-inâ€, or “seeâ€, the lost visual input. We developed a computational model to simulate cortical reorganization and perceptual fill-in mediated by a plexus of horizontal connections that encode the AF. The model reproduces the major features of the perceptual fill-in reported by human subjects with retinal lesions, and it suggests that V1 neurons, empowered by their horizontal connections, underlie both perceptual fill-in and normal integrative mechanisms that are crucial to our visual perception. These results motivated the second prong of our work, which was to experimentally study the normal integration of information in V1. Since psychophysical and physiological studies suggest that spatial interactions in V1 may be under cognitive control, we investigated the integrative properties of V1 neurons under different cognitive states. We performed extracellular recordings from single V1 neurons in macaques that were trained to perform a delayed-match-to-sample contour detection task. We found that the ability of V1 neurons to summate visual inputs from beyond the classical receptive field (cRF) imbues them with selectivity for complex contour shapes, and that neuronal shape selectivity in V1 changed dynamically according to the shapes monkeys were cued to detect. Over the population, V1 encoded subsets of the AF, predicted by the computational model, that shifted as a function of the monkeys’ expectations. These results support the major conclusions of the theoretical work; even more, they reveal a sophisticated mode of form processing, whereby the selectivity of the whole network in V1 is reshaped by cognitive state

Phase 1 of the near team hybrid passenger vehicle development program. Appendix C: Preliminary design data package, volume 1

The methodology used for vehicle layout and component definition is described as well as techniques for system optimization and energy evaluation. The preliminary design is examined with particular attention given to body and structure; propulsion system; crash analysis and handling; internal combustion engine; DC motor separately excited; Ni-Zn battery; transmission; control system; vehicle auxiliarries; weight breakdown, and life cycle costs. Formulas are given for the quantification of energy consumption and results are compared with the reference vehicle

Exergoeconomic optimization of a shell-and-tube heat exchanger

The paper presents an economic optimization of a STHX with two commonly adopted (i.e., Kern and Bell-Delaware) and one rarely explored (i.e., Wills-Johnston) methods. A detailed numerical code concerning thermal, hydraulic, exergy, and economic analysis of STHX is developed for all three methods. Normalized sensitivity analysis, parametric study, and Genetic Algorithm are used to ascertain the most influential parameters and optimize the total cost. It is observed that the calculations made using the Wills-Johnston method were reasonably close to the Bell-Delaware method. While the Kern method showed a significant deviation in the shell side calculations because of the several assumptions in this method. The parametric analysis showed that increasing the mass flow rate and the number of baffles increased the operating cost because of an exponential increase in the pressure drops. Finally, the optimization reduced the heat transfer area by ~26.4%, capital cost by ~20%, operational cost by ~50%, total cost by ~22%, and the stream cost by ~21%

Disease progression in Human Immunodeficiency Virus type 1 infected viraemic controllers

PhDBackground: The mechanism of CD4+ T-cell decline in Human Immunodeficiency Virus-1 (HIV-1) infection is unclear, but the association with plasma HIV-1 RNA-load suggests viral replication is involved. Viraemic controller patients with low HIV-1 RNA-loads (<2000 copies/ml) typically maintain good CD4+ T-cell counts (>450 CD4+ T-cells/mm3). However, within a cohort of 86 viraemic controllers, a subgroup (18 ‘discord controllers’) was identified with low CD4+ T-cell counts (<450 CD4+ T-cells/mm3) which present clinical uncertainty. The underlying mechanism accounting for CD4+ T-cell decline in the face of low or undetectable HIV-1 RNAloads is unknown. The objective of the work described in this thesis was to investigate the virological and host immune system dynamics in discord controllers compared with typical controllers. Method Epidemiological features, HIV-1 subtype, cellular HIV-1 DNA-load, T-cell populations (CD4+/CD8+ naïve/ central-memory/ effector-memory subsets; CD45RA/RO ± CD62L) and Tcell activation markers (CD38, HLA-DR) were examined for discord controllers and typical controllers as well as progressors with HIV-1 RNA-load >10000 copies/ml, <450 CD4+ Tcells/ mm3. Results Discord controllers and typical controllers were similar, based on epidemiological features and viral subtype distribution. They resembled progressors, showing high HIV-1 DNA-load, depletion of naïve CD4+ T-cells and higher activation in all CD4+ T-cell subsets. However, the CD8+ T-cell compartment in discord controllers was similar to typical controllers with preserved naïve CD8+ T-cells and low level CD8+ T-cells activation. Conclusion The data presented in this thesis is consistent with a relationship between CD4+ T-cell activation, HIV-1 DNA-load and disease progression but not HIV-1 RNA-load. This suggests that in viraemic controllers, HIV-1 DNA-load may be a better marker of viral replication and disease progression than HIV-1 RNA-load. Furthermore, low level CD8+ T-cell activation correlate with low plasma HIV-1 RNA-load but not with HIV-1 DNA-load.Barts and the London Charity Grant(MMBG1E7R); BHIVA SpR Research Grant (MMBG1F2R); MRC Senior Non-Clinical Fellowship awarded to supervisor A.M. (G117/547); Wellcome Trust grant awarded to supervisor A.M. (WT075853MA)