Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria

Individuals living in regions where malaria is endemic develop an acquired immunity to malaria which enables them to remain asymptomatic while still carrying parasites. Field studies indicate that cumulative exposure to a variety of diverse Plasmodium parasites is required for the transition from symptomatic to asymptomatic malaria. This study used a simulation model of the within-host dynamics of P. falciparum to investigate the development of acquired clinical immunity under different transmission conditions and levels of parasite diversity. Antibodies developed to P. falciparum erythrocyte membrane protein 1 (PfEMP1), a clonally variant molecule, were assumed to be a key human immunological response to P. falciparum infection, along with responses to clonally conserved but polymorphic antigens. The time to the development of clinical immunity was found to be proportional to parasite diversity and inversely proportional to transmission intensity. The effect of early termination of symptomatic infections by chemotherapy was investigated and found not to inhibit the host's ability to develop acquired immunity. However, the time required to achieve this state was approximately double that compared to when no treatment was administered. This study demonstrates that an immune response primarily targeted against PfEMP1 has the ability to reduce clinical symptoms of infections irrespective of whether treatment is administered, supporting its role in the development of acquired clinical immunity. The results also illustrate a novel use for simulation models of P. falciparum infections, investigation of the influence of intervention strategies on the development of naturally acquired clinical immunity.

Measuring and incorporating vulnerability into conservation planning

Conservation planning is the process of locating and designing conservation areas to promote the persistence of biodiversity in situ. To do this, conservation areas must be able to mitigate at least some of the proximate threats to biodiversity. Information on threatening processes and the relative vulnerability of areas and natural features to these processes is therefore crucial for effective conservation planning. However, measuring and incorporating vulnerability into conservation planning have been problematic. We develop a conceptual framework of the role of vulnerability assessments in conservation planning and propose a definition of vulnerability that incorporates three dimensions: exposure, intensity, and impact. We review and categorize methods for assessing the vulnerability of areas and the features they contain and identify the relative strengths and weaknesses of each broad approach, Our review highlights the need for further development and evaluation of approaches to assess vulnerability and for comparisons of their relative effectiveness.

Comparative evaluation of microscopic car-following behavior

Microscopic traffic-simulation tools are increasingly being applied to evaluate the impacts of a wide variety of intelligent transport, systems (ITS) applications and other dynamic problems that are difficult to solve using traditional analytical models. The accuracy of a traffic-simulation system depends highly on the quality of the traffic-flow model at its core, with the two main critical components being the car-following and lane-changing models. This paper presents findings from a comparative evaluation of car-following behavior in a number of traffic simulators [advanced interactive microscopic simulator for urban and nonurban networks (AIMSUN), parallel microscopic simulation (PARAMICS), and Verkehr in Statiten-simulation (VISSIM)]. The car-following algorithms used in these simulators have been developed from a variety of theoretical backgrounds and are reported to have been calibrated on a number of different data sets. Very few independent studies have attempted to evaluate the performance of the underlying algorithms based on the same data set. The results reported in this study are based on a car-following experiment that used instrumented vehicles to record the speed and relative distance between follower and leader vehicles on a one-lane road. The experiment was replicated in each tool and the simulated car-following behavior was compared to the field data using a number of error tests. The results showed lower error values for the Gipps-based models implemented in AIMSUN and similar error values for the psychophysical spacing models used in VISSIM and PARAMICS. A qualitative drift and goal-seeking behavior test, which essentially shows how the distance headway between leader and follower vehicles should oscillate around a stable distance, also confirmed the findings.

Rice morphogenesis and plant architecture: Measurement, specification and the reconstruction of structural development by 3D architectural modelling

Background and Aims The morphogenesis and architecture of a rice plant, Oryza sativa, are critical factors in the yield equation, but they are not well studied because of the lack of appropriate tools for 3D measurement. The architecture of rice plants is characterized by a large number of tillers and leaves. The aims of this study were to specify rice plant architecture and to find appropriate functions to represent the 3D growth across all growth stages. Methods A japonica type rice, 'Namaga', was grown in pots under outdoor conditions. A 3D digitizer was used to measure the rice plant structure at intervals from the young seedling stage to maturity. The L-system formalism was applied to create '3D virtual rice' plants, incorporating models of phenological development and leaf emergence period as a function of temperature and photoperiod, which were used to determine the timing of tiller emergence. Key Results The relationships between the nodal positions and leaf lengths, leaf angles and tiller angles were analysed and used to determine growth functions for the models. The '3D virtual rice' reproduces the structural development of isolated plants and provides a good estimation of the fillering process, and of the accumulation of leaves. Conclusions The results indicated that the '3D virtual rice' has a possibility to demonstrate the differences in the structure and development between cultivars and under different environmental conditions. Future work, necessary to reflect both cultivar and environmental effects on the model performance, and to link with physiological models, is proposed in the discussion.

Does colonization asymmetry matter in metapopulations?

Despite the considerable evidence showing that dispersal between habitat patches is often asymmetric, most of the metapopulation models assume symmetric dispersal. In this paper, we develop a Monte Carlo simulation model to quantify the effect of asymmetric dispersal on metapopulation persistence. Our results suggest that metapopulation extinctions are more likely when dispersal is asymmetric. Metapopulation viability in systems with symmetric dispersal mirrors results from a mean field approximation, where the system persists if the expected per patch colonization probability exceeds the expected per patch local extinction rate. For asymmetric cases, the mean field approximation underestimates the number of patches necessary for maintaining population persistence. If we use a model assuming symmetric dispersal when dispersal is actually asymmetric, the estimation of metapopulation persistence is wrong in more than 50% of the cases. Metapopulation viability depends on patch connectivity in symmetric systems, whereas in the asymmetric case the number of patches is more important. These results have important implications for managing spatially structured populations, when asymmetric dispersal may occur. Future metapopulation models should account for asymmetric dispersal, while empirical work is needed to quantify the patterns and the consequences of asymmetric dispersal in natural metapopulations.

Cattle, crops and clearing: Regional drivers of landscape change in the Brigalow Belt, Queensland, Australia, 1840-2004

Landscape change occurs through the interaction of a multitude of natural and human driving forces at a range of organisational levels, with humans playing an increasingly dominant role in many regions of the world. Building on the current knowledge of the underlying drivers of landscape change, a conceptual framework of regional landscape change was developed which integrated population, economic and cultural values, policy and science/technology. Using the Southern Brigalow Belt biogeographic region of Queensland as a case study, the role of natural and human drivers in landscape change was investigated in four phases of settlement since 1840. The Brigalow Belt has experienced comparable rates of vegetation clearance over the past 50 years to areas of tropical deforestation. Economic factors were important during all phases of development, but the five regional drivers often acted in synergy. Environmental constraints played a significant role in slowing rates of change. Temporal trends of deforestation followed a sigmoidal curve, with initial slow change accelerating though the middle phases then slowing in recent times. Future landscape management needs to take account of the influence of all the components of the conceptual framework, at a range of organisational levels, if more ecologically sustainable outcomes are to be achieved. (c) 2006 Elsevier B.V. All rights reserved.

Unplanned land clearing of Colombian rainforests: Spreading like disease?

Deforestation often occurs as temporal waves and in localized fronts termed 'deforestation hotspots' driven by economic pulses and population pressure. Of particular concern for conservation planning are 'biodiversity hotspots' where high concentrations of endemic species undergo rapid loss and fragmentation of habitat. We investigate the deforestation process in Caqueta, a biodiversity hotspot and major colonization front of the Colombian Amazon using multi-temporal satellite imagery of the periods 1989-1996-1999-2002. The probabilities of deforestation and regeneration were modeled against soil fertility, accessibility and neighborhood terms, using logistic regression analysis. Deforestation and regeneration patterns and rates were highly variable across the colonization front. The regional average annual deforestation rate was 2.6%, but varied locally between -1.8% (regeneration) and 5.3%, with maximum rates in landscapes with 40-60% forest cover and highest edge densities, showing an analogous pattern to the spread of disease. Soil fertility and forest and secondary vegetation neighbors showed positive and significant relationships with the probability of deforestation. For forest regeneration, soil fertility had a significant negative effect while the other parameters were marginally significant. The logistic regression models across all periods showed a high level of discrimination power for both deforestation and forest regeneration, with ROC values > 0.80. We document the effect of policies and institutional changes on the land clearing process, such as the failed peace process between government and guerillas in 1999-2002, which redirected the spread of deforestation and increased forest regeneration. The implications for conservation in biologically rich areas, such as Caqueta are discussed. (c) 2005 Elsevier B.V All rights reserved.

Investigation of the Effect of Array Geometry on the Performance of Free-Space Optical Interconnects

The effect of transmitter and receiver array configurations on the stray-light and diffraction-caused crosstalk in free-space optical interconnects was investigated. The optical system simulation software (Code V) is used to simulate both the stray-light and diffraction-caused crosstalk. Experimentally measured, spectrally-resolved, near-field images of VCSEL higher order modes were used as extended sources in our simulation model. In addition, we have included the electrical and optical noise in our analysis to give more accurate overall performance of the FSOI system. Our results show that by changing the square lattice geometry to a hexagonal configuration, we obtain an overall signal-to-noise ratio improvement of 3 dB. Furthermore, system density is increased by up to 4 channels/mm2.

Novel array geometries for free-space optical interconnects with improved signal-to-noise ratio

We investigate the effect of transmitter and receiver array configurations on the stray-light and diffraction-caused crosstalk in free-space optical interconnects. The optical system simulation software (Code V) is used to simulate both the stray-light and diffraction-caused crosstalk. Experimentally measured, spectrally-resolved, near-field images of VCSEL higher order modes were used as extended sources in our simulation model. Our results show that by changing the square lattice geometry to a hexagonal configuration, we obtain the reduction in the stray-light crosstalk of up to 9 dB and an overall signal-to-noise ratio improvement of 3 dB.

The impact of supply chain performance measurement systems on dynamic behaviour in supply chains

The amplification of demand variation up a supply chain widely termed ‘the Bullwhip Effect’ is disruptive, costly and something that supply chain management generally seeks to minimise. Originally attributed to poor system design; deficiencies in policies, organisation structure and delays in material and information flow all lead to sub-optimal reorder point calculation. It has since been attributed to exogenous random factors such as: uncertainties in demand, supply and distribution lead time but these causes are not exclusive as academic and operational studies since have shown that orders and/or inventories can exhibit significant variability even if customer demand and lead time are deterministic. This increase in the range of possible causes of dynamic behaviour indicates that our understanding of the phenomenon is far from complete. One possible, yet previously unexplored, factor that may influence dynamic behaviour in supply chains is the application and operation of supply chain performance measures. Organisations monitoring and responding to their adopted key performance metrics will make operational changes and this action may influence the level of dynamics within the supply chain, possibly degrading the performance of the very system they were intended to measure. In order to explore this a plausible abstraction of the operational responses to the Supply Chain Council’s SCOR® (Supply Chain Operations Reference) model was incorporated into a classic Beer Game distribution representation, using the dynamic discrete event simulation software Simul8. During the simulation the five SCOR Supply Chain Performance Attributes: Reliability, Responsiveness, Flexibility, Cost and Utilisation were continuously monitored and compared to established targets. Operational adjustments to the; reorder point, transportation modes and production capacity (where appropriate) for three independent supply chain roles were made and the degree of dynamic behaviour in the Supply Chain measured, using the ratio of the standard deviation of upstream demand relative to the standard deviation of the downstream demand. Factors employed to build the detailed model include: variable retail demand, order transmission, transportation delays, production delays, capacity constraints demand multipliers and demand averaging periods. Five dimensions of supply chain performance were monitored independently in three autonomous supply chain roles and operational settings adjusted accordingly. Uniqueness of this research stems from the application of the five SCOR performance attributes with modelled operational responses in a dynamic discrete event simulation model. This project makes its primary contribution to knowledge by measuring the impact, on supply chain dynamics, of applying a representative performance measurement system.

Why are MD simulated protein folding times wrong?

The question of significant deviations of protein folding times simulated using molecular dynamics from experimental values is investigated. It is shown that in the framework of Markov State Model (MSM) describing the conformational dynamics of peptides and proteins, the folding time is very sensitive to the simulation model parameters, such as forcefield and temperature. Using two peptides as examples, we show that the deviations in the folding times can reach an order of magnitude for modest variations of the molecular model. We, therefore, conclude that the folding rate values obtained in molecular dynamics simulations have to be treated with care.

The relative performance of scalable load balancing algorithms in loosely-coupled distributed systems. Available in 2 volumes.

The computer systems of today are characterised by data and program control that are distributed functionally and geographically across a network. A major issue of concern in this environment is the operating system activity of resource management for different processors in the network. To ensure equity in load distribution and improved system performance, load balancing is often undertaken. The research conducted in this field so far, has been primarily concerned with a small set of algorithms operating on tightly-coupled distributed systems. More recent studies have investigated the performance of such algorithms in loosely-coupled architectures but using a small set of processors. This thesis describes a simulation model developed to study the behaviour and general performance characteristics of a range of dynamic load balancing algorithms. Further, the scalability of these algorithms are discussed and a range of regionalised load balancing algorithms developed. In particular, we examine the impact of network diameter and delay on the performance of such algorithms across a range of system workloads. The results produced seem to suggest that the performance of simple dynamic policies are scalable but lack the load stability of more complex global average algorithms.

An investigation of the dynamic characteristics of a bolted-rotor system

A Jeffcott rotor consists of a disc at the centre of an axle supported at its end by bearings. A bolted Jeffcott rotor is formed by two discs, each with a shaft on one side. The discs are held together by spring loaded bolts near the outer edge. When the rotor turns there is tendency for the discs to separate on one side. This effect is more marked if the rotor is unbalanced, especially at resonance speeds. The equations of motion of the system have been developed with four degrees of freedom to include the rotor and bearing movements in the respective axes. These equations which include non-linear terms caused by the rotor opening, are subjected to external force such from rotor imbalance. A simulation model based on these equations was created using SIMULINK. An experimental test rig was used to characterise the dynamic features. Rotor discs open at a lateral displacement of the rotor of 0.8 mm. This is the threshold value used to show the change of stiffness from high stiffness to low stiffness. The experimental results, which measure the vibration amplitude of the rotor, show the dynamic behaviour of the bolted rotor due to imbalance. Close agreement of the experimental and theoretical results from time histories, waterfall plots, pseudo-phase plots and rotor orbit plot, indicated the validity of the model and existence of the non-linear jump phenomenon.

An appraisal of employment problems and policies at the micro-economic level

This study has concentrated on the development of an impact simulation model for use at the sub-national level. The necessity for the development of this model was demonstrated by the growth of local economic initiatives during the 1970's, and the lack of monitoring and evaluation exercise to assess their success and cost-effectiveness. The first stage of research involved the confirmation that the potential for micro-economic and spatial initiatives existed. This was done by identifying the existence of involuntary structural unemployment. The second stage examined the range of employment policy options from the macroeconomic, micro-economic and spatial perspectives, and focused on the need for evaluation of those policies. The need for spatial impact evaluation exercise in respect of other exogenous shocks, and structural changes was also recognised. The final stage involved the investigation of current techniques of evaluation and their adaptation for the purpose in hand. This led to a recognition of a gap in the armoury of techniques. The employment-dependency model has been developed to fill that gap, providing a low-budget model, capable of implementation at the small area level and generating a vast array of industrially disaggregate data, in terms of employment, employment-income, profits, value-added and gross income, related to levels of United Kingdom final demand. Thus providing scope for a variety of impact simulation exercises.