939 resultados para within-host modelling
Resumo:
Entrainment in flotation can be considered as a two-step process, including the transfer of the suspended solids in the top of the pulp region just below the pulp-froth interface to the froth phase and the transfer of the entrained particles in the froth phase to the concentrate. Both steps have a strong classification characteristic. The degree of entrainment describes the classification effect of the drainage process in the froth phase. This paper briefly reviews two existing models of degree of entrainment. Experimental data were collected from an Outokumpu 3 m(3) tank cell in the Xstrata Mt. Isa Mines copper concentrator. The data are fitted to the models and the effect of cell operating conditions including air rate and froth height on the degree of entrainment is examined on a size-by-size basis. It is found that there is a strong correlation between the entrainment and the water recovery, which is close to lineal. for the fines. The degree of entrainment decreases with increase in particle size. Within the normal range of cell operating conditions, few particles coarser than 50 mu m are recovered by entrainment. In general, the degree of entrainment increases with increase in the ail rate and decreases with increase in the froth height. Air rate and froth height strongly interact with each other and affect the entrainment process mainly via changes in the froth retention time, the froth structure and froth properties. As a result, other mechanisms such as entrapment may become important in recovering the coarse entrained particles. (c) 2005 Elsevier Ltd. All rights reserved.
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Aim To develop an appropriate dosing strategy for continuous intravenous infusions (CII) of enoxaparin by minimizing the percentage of steady-state anti-Xa concentration (C-ss) outside the therapeutic range of 0.5-1.2 IU ml(-1). Methods A nonlinear mixed effects model was developed with NONMEM (R) for 48 adult patients who received CII of enoxaparin with infusion durations that ranged from 8 to 894 h at rates between 100 and 1600 IU h(-1). Three hundred and sixty-three anti-Xa concentration measurements were available from patients who received CII. These were combined with 309 anti-Xa concentrations from 35 patients who received subcutaneous enoxaparin. The effects of age, body size, height, sex, creatinine clearance (CrCL) and patient location [intensive care unit (ICU) or general medical unit] on pharmacokinetic (PK) parameters were evaluated. Monte Carlo simulations were used to (i) evaluate covariate effects on C-ss and (ii) compare the impact of different infusion rates on predicted C-ss. The best dose was selected based on the highest probability that the C-ss achieved would lie within the therapeutic range. Results A two-compartment linear model with additive and proportional residual error for general medical unit patients and only a proportional error for patients in ICU provided the best description of the data. Both CrCL and weight were found to affect significantly clearance and volume of distribution of the central compartment, respectively. Simulations suggested that the best doses for patients in the ICU setting were 50 IU kg(-1) per 12 h (4.2 IU kg(-1) h(-1)) if CrCL < 30 ml min(-1); 60 IU kg(-1) per 12 h (5.0 IU kg(-1) h(-1)) if CrCL was 30-50 ml min(-1); and 70 IU kg(-1) per 12 h (5.8 IU kg(-1) h(-1)) if CrCL > 50 ml min(-1). The best doses for patients in the general medical unit were 60 IU kg(-1) per 12 h (5.0 IU kg(-1) h(-1)) if CrCL < 30 ml min(-1); 70 IU kg(-1) per 12 h (5.8 IU kg(-1) h(-1)) if CrCL was 30-50 ml min(-1); and 100 IU kg(-1) per 12 h (8.3 IU kg(-1) h(-1)) if CrCL > 50 ml min(-1). These best doses were selected based on providing the lowest equal probability of either being above or below the therapeutic range and the highest probability that the C-ss achieved would lie within the therapeutic range. Conclusion The dose of enoxaparin should be individualized to the patients' renal function and weight. There is some evidence to support slightly lower doses of CII enoxaparin in patients in the ICU setting.
Resumo:
The treatment and hydraulic mechanisms in a septic tank-soil absorption system ( SAS) are highly influenced by the clogging layer or biomat zone which develops on bottom and lower sidewall surfaces within the trench. Flow rates through the biomat and sub-biomat zones are governed largely by the biomat hydraulic properties (resistance and hydraulic conductivity) and the unsaturated hydraulic conductivity of the underlying soil. One- and 2-dimensional models were used to investigate the relative importance of sidewall and vertical flow rates and pathways in SAS. Results of 1-dimensional modelling show that several orders of magnitude variation in saturated hydraulic conductivity (Ks) reduce to a 1 order of magnitude variation in long-term flow rates. To increase the reliability of prediction of septic trench hydrology, HYDRUS-2D was used to model 2-dimensional flow. In the permeable soils, under high trench loading, effluent preferentially flowed in the upper region of the trench where no resistant biomat was present (the exfiltration zone). By comparison, flow was more evenly partitioned between the biomat zones and the exfiltration zones of the low permeability soil. An increase in effluent infiltration corresponded with a greater availability of exfiltration zone, rather than a lower resistance of biomat. Results of modelling simulations demonstrated the important role that a permeable A horizon may play in limiting surface surcharge of effluent under high trench hydraulic loading.
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Host antigen-presenting cells (APCs) are known to be critical for the induction of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), but the relative contribution of specific APC subsets remains unclear. We have studied the role of host B cells in GVHD by using B-cell-deficient mu MT mice as BMT recipients in a model of CD4-dependent GVHD to major histocompatlibility complex antigens. We demonstrate that acute GVHD is initially augmented in mu MT recipients relative to wild-type recipients (mortality: 85% vs 44%, P < .01), and this is the result of an increase in donor T-cell proliferation, expansion, and inflammatory cytokine production early after BMT. Recipient B cells were depleted 28-fold at the time of BMT by total body irradiation (TBI) administered 24 hours earlier, and we demonstrate that TBI rapidly induces sustained interleukin-110 (IL-10) generation from B cells but not dendritic cells (DCs) or other cellular populations within the spleen. Finally, recipient mice in which B cells are unable to produce IL-10 due to homologous gene deletion develop more severe acute GVHD than recipient mice in which B cells are wild type. Thus, the induction of IL-10 in host B cells during conditioning attenuates experimental acute GVHD.
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Computer modelling promises to. be an important tool for analysing and predicting interactions between trees within mixed species forest plantations. This study explored the use of an individual-based mechanistic model as a predictive tool for designing mixed species plantations of Australian tropical trees. The 'spatially explicit individually based-forest simulator' (SeXI-FS) modelling system was used to describe the spatial interaction of individual tree crowns within a binary mixed-species experiment. The three-dimensional model was developed and verified with field data from three forest tree species grown in tropical Australia. The model predicted the interactions within monocultures and binary mixtures of Flindersia brayleyana, Eucalyptus pellita and Elaeocarpus grandis, accounting for an average of 42% of the growth variation exhibited by species in different treatments. The model requires only structural dimensions and shade tolerance as species parameters. By modelling interactions in existing tree mixtures, the model predicted both increases and reductions in the growth of mixtures (up to +/- 50% of stem volume at 7 years) compared to monocultures. This modelling approach may be useful for designing mixed tree plantations. (c) 2006 Published by Elsevier B.V.
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We have determined the three-dimensional structure of the protein complex between latexin and carboxypeptidase A using a combination of chemical cross-linking, mass spectrometry and molecular docking. The locations of three intermolecular cross-links were identified using mass spectrometry and these constraints were used in combination with a speed-optimised docking algorithm allowing us to evaluate more than 3 x 10(11) possible conformations. While cross-links represent only limited structural constraints, the combination of only three experimental cross-links with very basic molecular docking was sufficient to determine the complex structure. The crystal structure of the complex between latexin and carboxypeptidase A4 determined recently allowed us to assess the success of this structure determination approach. Our structure was shown to be within 4 angstrom r.m.s. deviation of C alpha atoms of the crystal structure. The study demonstrates that cross-linking in combination with mass spectrometry can lead to efficient and accurate structural modelling of protein complexes.
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An experimental investigation of host specificity within the Thelastomatoidea is presented by means of a comparison of the thelastomatoids of two panesthiine cockroaches, Panesthia cribrata and R tryoni tryoni, with those of other log-dwelling arthropods and those of leaf litter dwelling arthropods found near by. 145 log-dwelling and leaf-litter dwelling arthropods, representing adjacent ecological niches, were collected from Lamington National Park, Queensland, Australia. A high degree of thelastomatoid species sharing (19 incidences from 26 specimens) occurs between log-dwelling arthropods and the two cockroach species. No overlap in thelastomatoid fauna was observed between the log dwelling and leaf-litter dwelling groups. Our results suggest that host specificity of thelastomatoids is largely dictated by host ecology. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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This paper presents a scientific and technical description of the modelling framework and the main results of modelling the long-term average sediment delivery at hillslope to medium-scale catchments over the entire Murray Darling Basin (MDB). A theoretical development that relates long-term averaged sediment delivery to the statistics of rainfall and catchment parameters is presented. The derived flood frequency approach was adapted to investigate the problem of regionalization of the sediment delivery ratio (SDR) across the Basin. SDR, a measure of catchment response to the upland erosion rate, was modeled by two lumped linear stores arranged in series: hillslope transport to the nearest streams and flow routing in the channel network. The theory shows that the ratio of catchment sediment residence time (SRT) to average effective rainfall duration is the most important control in the sediment delivery processes. In this study, catchment SRTs were estimated using travel time for overland flow multiplied by an enlargement factor which is a function of particle size. Rainfall intensity and effective duration statistics were regionalized by using long-term measurements from 195 pluviograph sites within and around the Basin. Finally, the model was implemented across the MDB by using spatially distributed soil, vegetation, topographical and land use properties under Geographic Information System (GIs) environment. The results predict strong variations in SDR from close to 0 in floodplains to 70% in the eastern uplands of the Basin. (c) 2005 Elsevier Ltd. All rights reserved.
Resumo:
Monogeneans (flatworms) are among the most host-specific of parasites in general and may be the most host-specific of all fish parasites. Specificity, in terms of a restricted spatial distribution within an environment, is not unique to parasites and is displayed by some fungi, insects, birds, symbionts and pelagic larvae of free-living marine invertebrates. The nature of cues, how habitats are recognised and how interactions between partners are mediated and maintained is of interest across these diverse associations. We review some experiments that demonstrate important factors that contribute to host-specificity at the level of infective stages (larvae of oviparous monogeneans; juveniles of viviparous gyrodactylids) and adult parasites. Recent research on immune responses by fish to monogenean infections is considered. We emphasise the critical importance of host epidermis to the Monogenea. Monogeneans live on host epidermis, they live in its products (e.g. mucus), monopisthocotyleans feed on it, some of its products are attractants and it may be an inhospitable surface because of its immunological activity. We focus attention on fish but reference is made to amphibian hosts. We develop the concept for a potential role in host-speciality by the anterior adhesive areas, either the specialised tegument and/or anterior secretions produced by monogeneans for temporary but firm attachment during locomotion on host epithelial surfaces. Initial contact between the anterior adhesive areas of infective stages and host epidermis may serve two important purposes. (1) Appropriate sense organs or receptors on the parasite interact with a specific chemical or chemicals or with surface structures on host epidermis. (2) A specific but instant recognition or reaction occurs between component(s) of host mucus and the adhesive(s) secreted by monogeneans. The chemical composition of fish skin is known to be species-specific and our preliminary analysis of the chemistry of some monogenean adhesives indicates they are novel proteins that display some differences between parasite families and species. (C) 2000 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.
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We demonstrate an end-to-end computational model of the HEG shock tunnel as a way to extract more precise test flow conditions and as a way of getting predictions of new operating conditions. For a selection of established operating conditions, the L1d program was used to simulate the one-dimensional gas-dynamic processes within the whole of the facility. The program reproduces the compression tube performance reliably and, with the inclusion of a loss factor near the upstream-end of the compression tube, it provides a good estimate of the equilibrium pressure in the shock-reflection region over the set of six standard operating conditions for HEG.
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Time-course experiments with microarrays are often used to study dynamic biological systems and genetic regulatory networks (GRNs) that model how genes influence each other in cell-level development of organisms. The inference for GRNs provides important insights into the fundamental biological processes such as growth and is useful in disease diagnosis and genomic drug design. Due to the experimental design, multilevel data hierarchies are often present in time-course gene expression data. Most existing methods, however, ignore the dependency of the expression measurements over time and the correlation among gene expression profiles. Such independence assumptions violate regulatory interactions and can result in overlooking certain important subject effects and lead to spurious inference for regulatory networks or mechanisms. In this paper, a multilevel mixed-effects model is adopted to incorporate data hierarchies in the analysis of time-course data, where temporal and subject effects are both assumed to be random. The method starts with the clustering of genes by fitting the mixture model within the multilevel random-effects model framework using the expectation-maximization (EM) algorithm. The network of regulatory interactions is then determined by searching for regulatory control elements (activators and inhibitors) shared by the clusters of co-expressed genes, based on a time-lagged correlation coefficients measurement. The method is applied to two real time-course datasets from the budding yeast (Saccharomyces cerevisiae) genome. It is shown that the proposed method provides clusters of cell-cycle regulated genes that are supported by existing gene function annotations, and hence enables inference on regulatory interactions for the genetic network.
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Three-dimensional computer modelling techniques are being used to develop a probabilistic model of turbulence-related spray transport around various plant architectures to investigate the influence of plant architectures and crop geometry on the sprayapplication process. Plant architecture models that utilise a set of growth rules expressed in the Lindenmayer systems (L-systems) formalism have been developed and programmed using L-studio software. Modules have been added to simulate the movement ofdroplets through the air and deposition on the plant canopy. Deposition of spray on an artificial plant structure was measured in the wind tunnel at the University of Queensland, Gatton campus and the results compared to the model simulation. Further trials are planned to measure the deposition of spray droplets on various crop and weed species and the results from these trials will be used to refine and validate the combined spray and plant architecture model.
Resumo:
In mantle convection models it has become common to make use of a modified (pressure sensitive, Boussinesq) von Mises yield criterion to limit the maximum stress the lithosphere can support. This approach allows the viscous, cool thermal boundary layer to deform in a relatively plate-like mode even in a fully Eulerian representation. In large-scale models with embedded continental crust where the mobile boundary layer represents the oceanic lithosphere, the von Mises yield criterion for the oceans ensures that the continents experience a realistic broad-scale stress regime. In detailed models of crustal deformation it is, however, more appropriate to choose a Mohr-Coulomb yield criterion based upon the idea that frictional slip occurs on whichever one of many randomly oriented planes happens to be favorably oriented with respect to the stress field. As coupled crust/mantle models become more sophisticated it is important to be able to use whichever failure model is appropriate to a given part of the system. We have therefore developed a way to represent Mohr-Coulomb failure within a code which is suited to mantle convection problems coupled to large-scale crustal deformation. Our approach uses an orthotropic viscous rheology (a different viscosity for pure shear to that for simple shear) to define a prefered plane for slip to occur given the local stress field. The simple-shear viscosity and the deformation can then be iterated to ensure that the yield criterion is always satisfied. We again assume the Boussinesq approximation - neglecting any effect of dilatancy on the stress field. An additional criterion is required to ensure that deformation occurs along the plane aligned with maximum shear strain-rate rather than the perpendicular plane which is formally equivalent in any symmetric formulation. It is also important to allow strain-weakening of the material. The material should remember both the accumulated failure history and the direction of failure. We have included this capacity in a Lagrangian-Integration-point finite element code and will show a number of examples of extension and compression of a crustal block with a Mohr-Coulomb failure criterion, and comparisons between mantle convection models using the von Mises versus the Mohr-Coulomb yield criteria. The formulation itself is general and applies to 2D and 3D problems, although it is somewhat more complicated to identify the slip plane in 3D.
Resumo:
Deposition of insoluble prion protein (PrP) in the brain in the form of protein aggregates or deposits is characteristic of the ‘transmissible spongiform encephalopathies’ (TSEs). Understanding the growth and development of these PrP aggregates is important both in attempting to the elucidate of the pathogenesis of prion disease and in the development of treatments designed to prevent or inhibit the spread of prion pathology within the brain. Aggregation and disaggregation of proteins and the diffusion of substances into the developing aggregates (surface diffusion) are important factors in the development of protein aggregates. Mathematical models suggest that if aggregation/disaggregation or surface diffusion is the predominant factor, the size frequency distribution of the resulting protein aggregates in the brain should be described by either a power-law or a log-normal model respectively. This study tested this hypothesis for two different types of PrP deposit, viz., the diffuse and florid-type PrP deposits in patients with variant Creutzfeldt-Jakob disease (vCJD). The size distributions of the florid and diffuse plaques were fitted by a power-law function in 100% and 42% of brain areas studied respectively. By contrast, the size distributions of both types of plaque deviated significantly from a log-normal model in all brain areas. Hence, protein aggregation and disaggregation may be the predominant factor in the development of the florid plaques. A more complex combination of factors appears to be involved in the pathogenesis of the diffuse plaques. These results may be useful in the design of treatments to inhibit the development of protein aggregates in vCJD.
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A formalism for modelling the dynamics of Genetic Algorithms (GAs) using methods from statistical mechanics, originally due to Prugel-Bennett and Shapiro, is reviewed, generalized and improved upon. This formalism can be used to predict the averaged trajectory of macroscopic statistics describing the GA's population. These macroscopics are chosen to average well between runs, so that fluctuations from mean behaviour can often be neglected. Where necessary, non-trivial terms are determined by assuming maximum entropy with constraints on known macroscopics. Problems of realistic size are described in compact form and finite population effects are included, often proving to be of fundamental importance. The macroscopics used here are cumulants of an appropriate quantity within the population and the mean correlation (Hamming distance) within the population. Including the correlation as an explicit macroscopic provides a significant improvement over the original formulation. The formalism is applied to a number of simple optimization problems in order to determine its predictive power and to gain insight into GA dynamics. Problems which are most amenable to analysis come from the class where alleles within the genotype contribute additively to the phenotype. This class can be treated with some generality, including problems with inhomogeneous contributions from each site, non-linear or noisy fitness measures, simple diploid representations and temporally varying fitness. The results can also be applied to a simple learning problem, generalization in a binary perceptron, and a limit is identified for which the optimal training batch size can be determined for this problem. The theory is compared to averaged results from a real GA in each case, showing excellent agreement if the maximum entropy principle holds. Some situations where this approximation brakes down are identified. In order to fully test the formalism, an attempt is made on the strong sc np-hard problem of storing random patterns in a binary perceptron. Here, the relationship between the genotype and phenotype (training error) is strongly non-linear. Mutation is modelled under the assumption that perceptron configurations are typical of perceptrons with a given training error. Unfortunately, this assumption does not provide a good approximation in general. It is conjectured that perceptron configurations would have to be constrained by other statistics in order to accurately model mutation for this problem. Issues arising from this study are discussed in conclusion and some possible areas of further research are outlined.