Modelling the dynamics of viral suppressors of RNA silencing

Virus infection in plants is limited by RNA silencing. In turn, viruses can counter RNA silencing with silencing suppressors. Viral suppressors of RNA silencing have been shown to play a role in symptom development in plants. We here study four different strategies employed by silencing suppressors: small interfering RNA (siRNA) binding, double-strand RNA (dsRNA) binding and degrading or inactivating Argonaute. We study the effect of the suppressors on viral accumulation within the cell as well as its spread on a tissue with mathematical and computational models. We find that suppressors which target Argonaute are very effective in a single cell, but that targeting dsRNA or siRNA is much more effective at the tissue level. Although targeting Argonaute can be beneficial for viral spread, it can also cause hindrance in some cases owing to raised levels of siRNAs that can spread to other cells.     

Within-host viral dynamics of dengue serotype 1 infection

Dengue, the most common mosquito-borne viral infection of humans, is endemic across much of the world, including much of tropical Asia and is increasing in its geographical range. Here, we present a mathematical model of dengue virus dynamics within infected individuals, detailing the interaction between virus and a simple immune response. We fit this model to measurements of plasma viral titre from cases of primary and secondary DENV 1 infection in Vietnam. We show that variation in model parameters governing the immune response is sufficient to create the observed variation in virus dynamics between individuals. Estimating model parameter values, we find parameter differences between primary and secondary cases consistent with the theory of antibody-dependent enhancement (namely enhanced rates of viral entry to target cells in secondary cases). Finally, we use our model to examine the potential impact of an antiviral drug on the within-host dynamics of dengue. We conclude that the impact of antiviral therapy on virus dynamics is likely to be limited if therapy is only started at the onset of symptoms, owing to the typically late stage of viral pathogenesis reached by the time symptoms are manifested and thus treatment is started.     

Modelling immune response to BK virus infection and donor kidney in renal transplant recipients

In this paper, we develop and validate with bootstrapping techniques a mechanistic mathematical model of immune response to both BK virus infection and a donor kidney based on known and hypothesized mechanisms in the literature. The model presented does not capture all the details of the immune response but possesses key features that describe a very complex immunological process. We then estimate model parameters using a least squares approach with a typical set of available clinical data. Sensitivity analysis combined with asymptotic theory is used to determine the number of parameters that can be reliably estimated given the limited number of observations.     

Modelling the checkpoint response to telomere uncapping in budding yeast

One of the DNA damage-response mechanisms in budding yeast is temporary cell-cycle arrest while DNA repair takes place. The DNA damage response requires the coordinated interaction between DNA repair and checkpoint pathways. Telomeres of budding yeast are capped by the Cdc13 complex. In the temperature-sensitive cdc13-1 strain, telomeres are unprotected over a specific temperature range leading to activation of the DNA damage response and subsequently cell-cycle arrest. Inactivation of cdc13-1 results in the generation of long regions of single-stranded DNA (ssDNA) and is affected by the activity of various checkpoint proteins and nucleases.This paper describes a mathematical model of how uncapped telomeres in budding yeast initiate the checkpoint pathway leading to cell-cycle arrest. The model was encoded in the Systems Biology Markup Language (SBML) and simulated using the stochastic simulation system Biology of Ageing e-Science Integration and Simulation (BASIS). Each simulation follows the time course of one mother cell keeping track of the number of cell divisions, the level of activity of each of the checkpoint proteins, the activity of nucleases and the amount of ssDNA generated. The model can be used to carry out a variety of in silico experiments in which different genes are knocked out and the results of simulation are compared to experimental data. Possible extensions to the model are also discussed.     

Modelling the long-term dynamics of pre-vaccination pertussis

The dynamics of strongly immunizing childhood infections is still not well understood. Although reports of successful modelling of several data records can be found in the previous literature, the key determinants of the observed temporal patterns have not yet been clearly identified. In particular, different models of immunity waning and degree of protection applied to disease- and vaccine-induced immunity have been debated in the previous literature on pertussis. Here, we study the effect of disease-acquired immunity on the long-term patterns of pertussis prevalence. We compare five minimal models, all of which are stochastic, seasonally forced, well-mixed models of infection, based on susceptible–infective–recovered dynamics in a closed population. These models reflect different assumptions about the immune response of naive hosts, namely total permanent immunity, immunity waning, immunity waning together with immunity boosting, reinfection of recovered and repeat infection after partial immunity waning. The power spectra of the output prevalence time series characterize the long-term dynamics of the models. For epidemiological parameters consistent with published data, the power spectra show quantitative and even qualitative differences, which can be used to test their assumptions by comparison with ensembles of several-decades-long pre-vaccination data records. We illustrate this strategy on two publicly available historical datasets.     

Modelling the dynamics of dengue real epidemics

In this work, we use a mathematical model for dengue transmission with the aim of analysing and comparing two dengue epidemics that occurred in Salvador, Brazil, in 1995-1996 and 2002. Using real data, we obtain the force of infection, Λ, and the basic reproductive number, R(0), for both epidemics. We also obtain the time evolution of the effective reproduction number, R(t), which results in a very suitable measure to compare the patterns of both epidemics. Based on the analysis of the behaviour of R(0) and R(t) in relation to the adult mosquito control parameter of the model, we show that the control applied only to the adult stage of the mosquito population is not sufficient to stop dengue transmission, emphasizing the importance of applying the control to the aquatic phase of the mosquito.     

Modelling the structural response of GLARE panels to blast load

This paper deals with the structural response of fully-clamped quadrangular GLARE panels subjected to an intense air-blast load using the commercial finite element software, LS-DYNA. A cohesive tie-break algorithm is implemented to model interfacial debonding between adjacent plies. The blast loads was simulated using a ConWep blast algorithm and a multi-material ALE formulation with fluid–structure interaction to determine the performance of each method. Numerical model validation have been performed considering case studies of GLARE panels subjected to spherical explosive charges of C-4, for which experimental data on the back face-displacement and post-damage observations were available. Excellent agreement of mid-point deflections and evidence of severe yield line deformation were presented and discussed against the performed blast tests.     

Modelling the structural response of GLARE panels to blast load

This paper deals with the structural response of fully-clamped quadrangular GLARE panels subjected to an intense air-blast load using the commercial finite element software, LS-DYNA. A cohesive tie-break algorithm is implemented to model interfacial debonding between adjacent plies. The blast loads was simulated using a ConWep blast algorithm and a multi-material ALE formulation with fluid–structure interaction to determine the performance of each method. Numerical model validation have been performed considering case studies of GLARE panels subjected to spherical explosive charges of C-4, for which experimental data on the back face-displacement and post-damage observations were available. Excellent agreement of mid-point deflections and evidence of severe yield line deformation were presented and discussed against the performed blast tests.     

Effect of different modes of viral spread on the dynamics of multiply infected cells in human immunodeficiency virus infection

Infection of individual cells with more than one HIV particle is an important feature of HIV replication, which may contribute to HIV pathogenesis via the occurrence of recombination, viral complementation and other outcomes that influence HIV replication and evolutionary dynamics. A previous mathematical model of co-infection has shown that the number of cells infected with i viruses correlates with the ith power of the singly infected cell population, and this has partly been observed in experiments. This model, however, assumed that virus spread from cell to cell occurs only via free virus particles, and that viruses and cells mix perfectly. Here, we introduce a cellular automaton model that takes into account different modes of virus spread among cells, including cell to cell transmission via the virological synapse, and spatially constrained virus spread. In these scenarios, it is found that the number of multiply infected cells correlates linearly with the number of singly infected cells, meaning that co-infection plays a greater role at lower virus loads. The model further indicates that current experimental systems that are used to study co-infection dynamics fail to reflect the true dynamics of multiply infected cells under these specific assumptions, and that new experimental techniques need to be designed to distinguish between the different assumptions.     

In vitro release properties of caffeine. I. effect of concentration and type of ointment base

Abstract

Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic ointment (USP XVIII), and a w/o type emulsifying ointment. It was incorporated into ointment bases at 1,5,10,20 and 30% (w/w) concentrations, by simple trituration technique.

Release experiments were carried out at 37°C, with diffusion cells which were placed in distilled water filled beakers.

For all caffeine concentrations used, the release was highest from the PEG ointment. It decreased with the hydrophilic ointment, the emulsifying ointment, and petrolatum A, in that order. From both petrolatum base and the PEG ointment, release of caffeine increased significantly with increasing concentrations. As for the hydrophilic and emulsifying ointments, release patterns were found to be independent of concentration for some percentages of caffeine.     

In vitro release properties of caffeine. I. effect of concentration and type of ointment base

Caffeine has recently been found to cure atopic dermatitis, presumably by increasing skin levels of cAMP.In the light of these findings, its release from different ointment bases at varying concentrations was investigated in vitro. The ointment bases used were a petrolatum (named as petrolatum A), a PEG ointment (USP XVIII), a hydrophilic ointment (USP XVIII), and a w/o type emulsifying ointment. It was incorporated into ointment bases at 1,5,10,20 and 30% (w/w) concentrations, by simple trituration technique.

Release experiments were carried out at 37°C, with diffusion cells which were placed in distilled water filled beakers.

For all caffeine concentrations used, the release was highest from the PEG ointment. It decreased with the hydrophilic ointment, the emulsifying ointment, and petrolatum A, in that order. From both petrolatum base and the PEG ointment, release of caffeine increased significantly with increasing concentrations. As for the hydrophilic and emulsifying ointments, release patterns were found to be independent of concentration for some percentages of caffeine.     

Modelling the nonlinear viscoelastic response of asphalt binders

In a recent article, Narayan et al. [Narayan, S.P.A., et al., 2012b. Nonlinear viscoelastic response of asphalt binders: experimental study of relaxation of torque and normal force in torsion. Mechanics Research Communications, 43, 66–74] recorded both torque and normal force in torsional relaxation experiments on asphalt binders. The data are three-dimensional and thus, require interpretation using three-dimensional constitutive relations. In this article, we develop such a three-dimensional nonlinear viscoelastic model for asphalt binder. The predictions of the model fit the experimental data reasonably well. While there are already some three-dimensional constitutive relations available in the literature for asphalt binders which can describe the normal forces that are developed during torsion, they do not capture the relaxation behaviour presented by Narayan et al. (2012b). This new model, however, captures most of the key features of the experimental data including the development of normal forces in torsion and the relaxation behaviour. In this respect, the new model performs considerably better than the existing models.     

Quality and exposure control in semiconductor manufacturing. Part I: Modelling

The purpose of this paper is to present a heuristic algorithm for quality control planning from an insurance perspective. The approach proposed here is designed to judiciously allocate controls in two stages: one to manage risk exposure, in terms of potential product loss, and the second to improve the effectiveness of the controls themselves. The method employed to evaluate this algorithm is based on three comparisons. One of these is presented in the first part of the paper and the other two in the second part. The test provided in this first part of the paper is performed on a simplified case study and compares the proposed heuristic algorithm (HA) to an optimised allocation (OA) method. The main objective of this paper is to present, in detail, a quality control planning method which allocates measurement resources with the aim of remaining below a threshold limit of risk exposure and of improving the effectiveness of the controls. The evaluation presented in the second part of the paper underscores the potential, as well as the limitations, of the proposed algorithm.     

Evaluation of the osteoblast response to a silica gel in vitro

Many bioactive glasses and glass ceramics contain silica, yet the effect of silica on the osteoblast is not well understood. The osteoblast cell response to a silica surface, without the interference of the other ions present in glasses and glass ceramics has been investigated. A silica sol–gel was prepared which gave a molar ratio of 1:4:4 tetraethyl orthosilicate (TEOS): ethanol:acidified water 0.2 M HCl) and spin cast on to thermanox discs. The gel was characterized in terms of bioactivity and release of silicic acid. Primary human osteoblasts (HOBs) were seeded on the surface of upright or inverted silica discs. Cell activity (alamar blue reduction), number (DNA content) and differentiation (alkaline phosphatase activity, nodule formation and mineralization) were measured. There was no apparant difference in cell number, activity or alkaline phosphatase activity between silica discs and controls. Nodules formed much earlier on the silica surfaces and these eventually mineralized. Nodule formation was reproducibly enhanced on the silica surface and less markedly on the inverted discs. It is likely that both the surface characteristics of the silica gel and silicic acid release from the disc affect osteoblast behaviour. © 1998 Kluwer Academic Publishers     

Role of body temperature variations in bat immune response to viral infections

The ability of bats to coexist with viruses without being harmed is an interesting issue that is still under investigation. Here we use a mathematical model to show that the pattern of body temperature variations observed in bats between day and night is responsible for their ability to keep viruses in check. From the dynamical systems point of view, our model displays an intriguing quasi-periodic behaviour that might be relevant in making the system robust by avoiding viral escape due to perturbations in the body temperature cycle.     

In vitro formation and thermal transition of novel hybrid fibrils from type I fish scale collagen and type I porcine collagen

Novel type I collagen hybrid fibrils were fabricated by neutralizing a mixture of type I fish scale collagen solution and type I porcine collagen solution with a phosphate buffer saline at 28 °C. Their structure was discussed in terms of the volume ratio of fish/porcine collagen solution. Scanning electron and atomic force micrographs showed that the diameter of collagen fibrils derived from the collagen mixture was larger than those derived from each collagen, and all resultant fibrils exhibited a typical D-periodic unit of ∼67 nm, irrespective of volume ratio of both collagens. Differential scanning calorimetry revealed only one endothermic peak for the fibrils derived from collagen mixture or from each collagen solution, indicating that the resultant collagen fibrils were hybrids of type I fish scale collagen and type I porcine collagen.     

In vitro formation and thermal transition of novel hybrid fibrils from type I fish scale collagen and type I porcine collagen

Abstract

Novel type I collagen hybrid fibrils were fabricated by neutralizing a mixture of type I fish scale collagen solution and type I porcine collagen solution with a phosphate buffer saline at 28 °C. Their structure was discussed in terms of the volume ratio of fish/porcine collagen solution. Scanning electron and atomic force micrographs showed that the diameter of collagen fibrils derived from the collagen mixture was larger than those derived from each collagen, and all resultant fibrils exhibited a typical D-periodic unit of ～67 nm, irrespective of volume ratio of both collagens. Differential scanning calorimetry revealed only one endothermic peak for the fibrils derived from collagen mixture or from each collagen solution, indicating that the resultant collagen fibrils were hybrids of type I fish scale collagen and type I porcine collagen.     

Modelling and calculations of the response of tissue equivalent proportional counter to charged particles

Space activities in earth orbit or in deep space pose challenges to the estimation of risk factors for both astronauts and instrumentation. In space, risk from exposure to ionising radiation is one of the main factors limiting manned space exploration. Therefore, characterising the radiation environment in terms of the types of radiations and the quantity of radiation that the astronauts are exposed to is of critical importance in planning space missions. In this paper, calculations of the response of TEPC to protons and carbon ions were reported. The calculations have been carried out using Monte Carlo track structure simulation codes for the walled and the wall-less TEPC counters. The model simulates nonhomogenous tracks in the sensitive volume of the counter and accounts for direct and indirect events. Calculated frequency- and dose-averaged lineal energies 0.3 MeV-1 GeV protons are presented and compared with the experimental data. The calculation of quality factors (QF) were made using individual track histories. Additionally, calculations of absolute frequencies of energy depositions in cylindrical targets, 100 nm height by 100 nm diameter, when randomly positioned and oriented in water irradiated with 1 Gy of protons of energy 0.3-100 MeV, is presented. The distributions show the clustering properties of protons of different energies in a 100 nm by 100 nm cylinder.