Analysis and modelling of immune cell behaviour in lymph nodes based on multi-photon imaging

This thesis presents quantitative studies of T cell and dendritic cell (DC) behaviour in mouse lymph nodes (LNs) in the naive state and following immunisation. These processes are of importance and interest in basic immunology, and better understanding could improve both diagnostic capacity and therapeutic manipulations, potentially helping in producing more effective vaccines or developing treatments for autoimmune diseases. The problem is also interesting conceptually as it is relevant to other fields where 3D movement of objects is tracked with a discrete scanning interval. A general immunology introduction is presented in chapter 1. In chapter 2, I apply quantitative methods to multi-photon imaging data to measure how T cells and DCs are spatially arranged in LNs. This has been previously studied to describe differences between the naive and immunised state and as an indicator of the magnitude of the immune response in LNs, but previous analyses have been generally descriptive. The quantitative analysis shows that some of the previous conclusions may have been premature. In chapter 3, I use Bayesian state-space models to test some hypotheses about the mode of T cell search for DCs. A two-state mode of movement where T cells can be classified as either interacting to a DC or freely migrating is supported over a model where T cells would home in on DCs at distance through for example the action of chemokines. In chapter 4, I study whether T cell migration is linked to the geometric structure of the fibroblast reticular network (FRC). I find support for the hypothesis that the movement is constrained to the fibroblast reticular cell (FRC) network over an alternative 'random walk with persistence time' model where cells would move randomly, with a short-term persistence driven by a hypothetical T cell intrinsic 'clock'. I also present unexpected results on the FRC network geometry. Finally, a quantitative method is presented for addressing some measurement biases inherent to multi-photon imaging. In all three chapters, novel findings are made, and the methods developed have the potential for further use to address important problems in the field. In chapter 5, I present a summary and synthesis of results from chapters 3-4 and a more speculative discussion of these results and potential future directions.

Estudo de modelos simplificados com interações de longo alcance no ensemble microcanônico

Tese (doutorado)Universidade de Brasília, Instituto de Física, Programa de Pós-Graduação em Física, 2015.

Effects of an asymmetric friction on the nonlinear equilibration of a baroclinic system

Following some recent linear and nonlinear studies the authors examine, using numerical simulations of a classical two-layer model, the effect of an asymmetric friction on the nonlinear equilibrium of moderately unstable baroclinic systems, The results show that the presence of an asymmetric friction leads to a significant wave scale selection: ''long'' waves (in terms of their zonal wavelengths) emerge with a traditional asymmetric friction (with the upper layer less viscous than the lower layer), while only ''short'' waves dominate with a nontraditional asymmetric friction (with the lower layer less viscous than the upper layer). The role of the nonlinear interactions and. more precisely, the effects of an asymmetric friction on the wave-mean flow and wave-wave interactions; and their consequences on the wave scale selection are examined.

Hotelling-downs competition with free entry when voters have an option to contest

Osborne shows that for almost all distributions of voters' preferences, a pure strategy Nash equilibrium does not exist in the classical Hotelling-Downs model of electoral competition with free entry. We show that equilibrium is generically possible if in addition one allows voters an option to announce their candidacy to compete side-by-side with office-seeking players. The model studied in this paper renders Osborne and the celebrated citizen-candidate model à la Osborne and Slivinski as two extreme cases. We characterize the equilibrium set with two central questions: (i) can there be equilibria where only voters contest? and (ii) are equilibria with contesting office-seeking players possible? We also show that in our general setting, extremists are typically voter-candidates so that in every two-party contest, office-seeking politicians stay out of competition.

Properties of polycrystalline gas sensors based on d.c. and a.c. electrical measurements

Electrical properties of polycrystalline gas sensors are analyzed by d.c. and a.c. measurements. d.c. electrical conductivity values compared with those obtained by admittance spectroscopy methods help to obtain a detailed 'on line' analysis of conductivity-modulated gas sensors. The electrical behaviour of grain boundaries is obtained and a new design of sensors can be achieved by enhancing the activity of surface states in the detecting operation. A Schottky barrier model is used to explain the grain boundary action under the presence of surrounding gases. The height of this barrier is a function of gas concentration due to the trapping of excess charge generated by gas adsorption at the interface. A comparison between this dependence, and a plot of the real and imaginary components of the admittance versus frequency at different gas concentrations, provides information on the different parameters that play a role in the conduction mechanisms. These methods have been applied to the design of a CO sensor based on tin oxide films for domestic purposes, the characteristics of which are presented.

Developmentof engineering projects supported by BIM technology: internship report

Building Information Modeling (BIM) concept is able to reshape each AEC project and the industry in general, offering a comprehensive collaboration process over a model of structure with regularly actualized and synchronized information. This report presents an overview of BIM with focus on its core concepts, applications in the project life cycle and benefits for project stakeholders through four case studies carried out during the internship in the engineering office NEWTON - Engineering Consultancy Company. The aim of the four cases studies was to cover multidisciplinary and varied projects. The first case study highlights the engineering project’s workflow and presents a comparison of traditional procedures and BIM concepts applied on the rehabilitation of an existing building. In the second and third case study, attention is focused on the goals achieved, particularly by structural engineer, due to the implementation of the mentioned technology on a full-lifecycle BIM project of a small residence and a complex project of residential building in Porto and on its architectural integration. In addition, through the fourth case study, the spatial coordination of Mechanical, Electrical and Plumbing (MEP) systems at a large-scale hotel project has been analyzed and accomplished, highlighting merits of BIM at this project stage. Through a reduction of the space used for facilities and infrastructures and the ability to identify conflicts and to nullify the related costs, its advantage for a complex building was proved.

A methodological framework to assess the carbon balance of tropical managed forests.

Background: Managed forests are a major component of tropical landscapes. Production forests as designated by national forest services cover up to 400 million ha, i.e. half of the forested area in the humid tropics. Forest management thus plays a major role in the global carbon budget, but with a lack of unified method to estimate carbon fluxes from tropical managed forests. In this study we propose a new time- and spatially-explicit methodology to estimate the above-ground carbon budget of selective logging at regional scale. Results: The yearly balance of a logging unit, i.e. the elementary management unit of a forest estate, is modelled by aggregating three sub-models encompassing (i) emissions from extracted wood, (ii) emissions from logging damage and deforested areas and (iii) carbon storage from post-logging recovery. Models are parametrised and uncertainties are propagated through a MCMC algorithm. As a case study, we used 38 years of National Forest Inventories in French Guiana, northeastern Amazonia, to estimate the above-ground carbon balance (i.e. the net carbon exchange with the atmosphere) of selectively logged forests. Over this period, the net carbon balance of selective logging in the French Guianan Permanent Forest Estate is estimated to be comprised between 0.12 and 1.33 Tg C, with a median value of 0.64 Tg C. Uncertainties over the model could be diminished by improving the accuracy of both logging damage and large woody necromass decay submodels. Conclusions: We propose an innovating carbon accounting framework relying upon basic logging statistics. This flexible tool allows carbon budget of tropical managed forests to be estimated in a wide range of tropical regions

A spatially explicit multi-competitor coexistence model of penaeid (shrimp) distribution on the Australian Great Barrier Reef

A spatially explicit multi-competitor coexistence model was developed for meta-populations of prawns (shrimp) occupying habitat patches across the Great Barrier Reef, where dispersal was localised and dispersal rates varied between species. Prawns were modelled as individuals moving to and from patches or cells according to pre-set decision rules. The landscape was simulated as a matrix of cells with each cell having a spatially explicit survival index for each species. Mixed species prawn assemblages moved over this simplified spatially explicit landscape. A low level of chronic random environmental disturbance was assumed (cyclone and tropical storm damage) with additional acute spatially confined disturbance due to commercial trawling, modelled as an increase in mortality affecting inter-specific competition. The general form of the results was for increased disturbance to favour good-colonising "generalist" species at the expense of good-competitor "specialists". Increasing fishing mortality (local patch extinctions) combined with poor colonising ability resulted in low equilibrium abundance for even the best competitor, while in the same circumstances the poorest competitor but best coloniser could have the highest equilibrium abundance. This mimics the switch from high-value prawn species to lower-value prawn species as trawl effort increases, reflected in historic catch and effort logbook data and reported anecdotaly from the north Queensland trawl fleet. To match the observed distribution and behaviour of prawn assemblages, a combination inter-species competition, a spatially explicit landscape, and a defined pattern of disturbance (trawling) was required. Modelling this combination could simulate not only general trends in spatial distribution of each of prawn species but also localised concentrations observed in the survey data

Double Gaussian distribution of barrier height observed in densely packed GaN nanorods over Si (111) heterostructures

GaN nanorods were grown by plasma assisted molecular beam epitaxy on intrinsic Si (111) substrates which were characterized by powder X-ray diffraction, field emission scanning electron microscopy, and photoluminescence. The current-voltage characteristics of the GaN nanorods on Si (111) heterojunction were obtained from 138 to 493K which showed the inverted rectification behavior. The I-V characteristics were analyzed in terms of thermionic emission model. The temperature variation of the apparent barrier height and ideality factor along with the non-linearity of the activation energy plot indicated the presence of lateral inhomogeneities in the barrier height. The observed two temperature regimes in Richardson's plot could be well explained by assuming two separate Gaussian distribution of the barrier heights. (C) 2014 AIP Publishing LLC.

A modelling study of transient, buoyancy-driven exchange flow over a descending barrier

Results are presented from a series of model studies of the transient exchange flow resulting from the steady descent of an impermeable barrier separating initially-quiescent fresh and saline water bodies having density ρ0 and ρ0 + (Δρ)0, respectively. A set of parametric laboratory experiments has been carried out (i) to determine the characteristic features of the time-dependent exchange flow over the barrier crest and (ii) to quantify the temporal increase in the thickness and spatial extent of the brackish water reservoir formed behind the barrier by the outflowing, partly-mixed saline water. The results of the laboratory experiments have been compared with the predictions of a theoretical model adapted from the steady, so-called maximal exchange flow case and good qualitative agreement between theory and experiment has been demonstrated. The comparisons indicate that head losses of between 7% and 3% are applicable to the flow over the ridge crest in the early and late stages, respectively, of the barrier descent phase, with these losses being attributed to mixing processes associated with the counterflowing layers of fresh and saline water in the vicinity of the ridge crest. The experimental data show (and the theoretical model predictions confirm) that (i) the dimensionless time of detection tdet (g′/Hb)1/2 of the brackish water pool fed by the dense outflow increases (at a given distance from the barrier) with increasing values of the descent rate parameter g'Hb/(dhb/dt)2 and (ii) the normalised thickness δ(x,t)/Hb of the pool at a given reference station increases monotonically with increasing values of the modified time (t - tdet)/(Hb/g′) 1/2, with the rate of thickening decreasing with increasing values of the descent rate parameter g'Hb (dhb/dt)2. Here, g′ = (g/ρ0) (Δρ)0 is the modified gravitational acceleration, Hb is the mean depth of the water and dhb/dt denotes the rate of descent of the barrier height hb with elapsed time t after the two water bodies are first brought into contact. © 2004 Kluwer Academic Publishers.

Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro

Reproducing the characteristics and the functional responses of the blood-brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.

Contrast integration over area is extensive: a three-stage model of spatial summation

Classical studies of area summation measure contrast detection thresholds as a function of grating diameter. Unfortunately, (i) this approach is compromised by retinal inhomogeneity and (ii) it potentially confounds summation of signal with summation of internal noise. The Swiss cheese stimulus of T. S. Meese and R. J. Summers (2007) and the closely related Battenberg stimulus of T. S. Meese (2010) were designed to avoid these problems by keeping target diameter constant and modulating interdigitated checks of first-order carrier contrast within the stimulus region. This approach has revealed a contrast integration process with greater potency than the classical model of spatial probability summation. Here, we used Swiss cheese stimuli to investigate the spatial limits of contrast integration over a range of carrier frequencies (1–16 c/deg) and raised plaid modulator frequencies (0.25–32 cycles/check). Subthreshold summation for interdigitated carrier pairs remained strong (~4 to 6 dB) up to 4 to 8 cycles/check. Our computational analysis of these results implied linear signal combination (following square-law transduction) over either (i) 12 carrier cycles or more or (ii) 1.27 deg or more. Our model has three stages of summation: short-range summation within linear receptive fields, medium-range integration to compute contrast energy for multiple patches of the image, and long-range pooling of the contrast integrators by probability summation. Our analysis legitimizes the inclusion of widespread integration of signal (and noise) within hierarchical image processing models. It also confirms the individual differences in the spatial extent of integration that emerge from our approach.

Classical and technological convergence:beyond the Solow-Swann model

Recent investigations into cross-country convergence follow Mankiw, Romer, and Weil (1992) in using a log-linear approximation to the Swan-Solow growth model to specify regressions. These studies tend to assume a common and exogenous technology. In contrast, the technology catch-up literature endogenises the growth of technology. The use of capital stock data renders the approximations and over-identification of the Mankiw model unnecessary and enables us, using dynamic panel estimation, to estimate the separate contributions of diminishing returns and technology transfer to the rate of conditional convergence. We find that both effects are important.

Cost and feasibility of a barrier to halt the spread of invasive cane toads in arid Australia: incorporating expert knowledge into model-based decision-making

1. Active engagement with practitioners is a crucial component of model-based decision-making in conservation management; it can assist with data acquisition, improve models and help narrow the 'knowing-doing' gap.
2. We worked with practitioners of one of the worst invasive species in Australia, the cane toad Rhinella marina, to revise a model that estimates the effectiveness of landscape barriers to contain spread. The original model predicted that the invasion could be contained by managing artificial watering points on pastoral properties, but was initially met with scepticism by practitioners, in part due to a lack of engagement during model development.
3. We held a workshop with practitioners and experts in cane toad biology. Using structured decision-making, we elicited concerns about the original model, revised its structure, updated relevant input data, added an economic component and found the most cost-effective location for a barrier across a range of fixed budgets and management scenarios. We then conducted scenario analyses to test the sensitivity of management decisions to model revisions.
4. We found that toad spread could be contained for all of the scenarios tested. Our modelling suggests a barrier could cost $4·5 M (2015 AUD) over 50 years for the most likely landscape scenario. The incorporation of practitioner knowledge into the model was crucial. As well as improving engagement, when we incorporated practitioner concerns (particularly regarding the effects of irrigation and dwellings on toad spread), we found a different location for the optimal barrier compared to a previously published study (Tingley et al. 2013).
5. Synthesis and applications. Through engagement with practitioners, we turned an academic modelling exercise into a decision-support tool that integrated local information, and considered more realistic scenarios and constraints. Active engagement with practitioners led to productive revisions of a model that estimates the effectiveness of a landscape barrier to contain spread of the invasive cane toad R. marina. Benefits also include greater confidence in model predictions, improving our assessment of the cost and feasibility of containing the spread of toads.