Two-Component Signal Transduction System SaeRS Positively Regulates Staphylococcus epidermidis

Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between the S. epidermidis 1457 wild-type and saeRS mutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS). Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized in S. epidermidis when saeRS was deleted. The study will be helpful for treatment of S. epidermidis infection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS

Global dynamics of some malaria models in heterogeneous environments

Malaria is on of the most important parasitic infections in humans and more than two billion people are at risk every year. There were an estimated 247 million malaria cases in 2006, causing nearly a million deaths. Currently, malaria is still endemic in 109 countries. Human malaria is caused by protozoan parasites of the genus Plasmodium, transmitted from human-to-human by the female Anopheles mosquito. Over the past century, considerable work has been invested in the study of malaria transmission. However, only a few studies with malaria consider the spatial and temporal heterogeneities of this disease. Hence, there is an essential need for more information on the spatial and temporal patterns of disease burden, distribution and control strategies. The aim of this thesis is to study the malaria transmission in heterogeneous environments. -- We begin with a brief introduction of mathematical background for this thesis in chapter 1. We shall provide some mathematical terminologies and theorems related to the theories of monotone dynamical systems, uniform persistence, basic reproduction ratio, spreading speeds and traveling waves. -- Chapter 2 is devoted to the study of global dynamics of a periodic susceptible-infected-susceptible compartmental model with maturation delay. We first obtain sufficient conditions for the single population growth equation to admit a globally attractive positive periodic solution. Then we introduce the basic reproduction ratio Rₒ for the epidemic model, and show that the disease dies out when Rₒ 1. Numerical simulations are also provided to confirm our analytic results. The study in this chapter also enables us to consider time-delayed and periodic malaria results. The study in this chapter also enables us to consider time-delayed and periodic malaria models. -- In chapter 3, we present a malaria transmission model with periodic birth rate and age structure for the vector population. We first introduce the basic reproduction ratio for this model and then show that there exists at least one positive periodic state and that the disease persists when Rₒ > 1. It is also shown that the disease will die out if Rₒ < 1, provided that the invasion intensity is not strong. We further use these analytic results to study the malaria transmission cases in KwaZulu-Natal Province, South Africa. Some sensitivity analysis of Rₒ is performed, and in particular, the potential impact of climate change on seasonal transmission and populations at risk of the disease is analyzed. -- Based on the classical Ross-Macdonald model, we propose in chapter 4 a periodic model with diffusion and advection to study the possible impact of the mobility of humans and mosquitoes on malaria transmission. We establish the existence of the leftward and rightward spreading speeds and their coincidence with the minimum wave speeds in the left and right directions, respectively. For the model in a bounded domain, we obtain a threshold result on the global attractivity of either zero or a positive periodic solution. -- To understand how the spatial heterogeneity and extrinsic incubation period (EIP) of the parasite within the mosquito affect the dynamics of malaria epidemiology, we formulate a nonlocal and time-delayed reaction-diffusion model in chapter 5. We thin define the basic reproduction ratio Rₒ and show that Rₒ serves as a threshold parameter that predicts whether malaria will spread. Furthermore, a sufficient condition is obtained to guarantee that the disease will stabilize at a positive steady state eventually in the case where all the parameters are spatially independent. Numerically, we show that the use of the spatially averaged system my highly underestimate the malaria risk. The spatially heterogeneous framework in this chapter can be used to design the spatial allocation of control resources. -- At last, we summarize the results in this thesis, and also point out some problems for future research in chapter 6

Threshold virus dynamics with impulsive antiretroviral drug effects

The purposes of this paper are twofold: to develop a rigorous approach to analyze the threshold behaviors of nonlinear virus dynamics models with impulsive drug effects and to examine the feasibility of virus clearance following the Manuals of National AIDS Free Antiviral Treatment in China. An impulsive system of differential equations is developed to describe the within-host virus dynamics of both wild-type and drug-resistant strains when a combination of antiretroviral drugs is used to induce instantaneous drug effects at a sequence of dosing times equally spaced while drug concentrations decay exponentially after the dosing time. Threshold parameters are derived using the basic reproduction number of periodic epidemic models, and are used to depict virus clearance/persistence scenarios using the theory of asymptotic periodic systems and the persistence theory of discrete dynamical systems. Numerical simulations using model systems parametrized in terms of the antiretroviral therapy recommended in the aforementioned Manuals illustrate the theoretical threshold virus dynamics, and examine conditions under which the impulsive antiretroviral therapy leads to treatment success. In particular, our results show that only the drug-resistant strain can dominate (the first-line treatment program guided by the Manuals) or both strains may be rapidly eliminated (the second-line treatment program), thus the work indicates the importance of implementing the second-line treatment program as soon as possible

Characteristics of an epidemic outbreak with a large initial infection size

A deterministic model proposed in previous literatures to approximate the well-known Richards model is investigated. However, the model assumption of small initial value for infection size is released in the current manuscript. Taking the advantage of the closed form of solutions, we establish the epidemic characteristics of disease transmission: the outbreak size, the peak size and the turning point for the cumulative infected cases. It is shown that the usual disease outbreak threshold condition (the basic reproduction number $\mathcal {R}_0$ is greater than unity) fails to fully guarantee the existence of peaking time and turning point when the initial infection size is not relatively small. The epidemic characteristics not only depend on $\mathcal {R}_0$ but also on another index, the net reproduction number $\mathcal {R}^*_0$

Modeling Lyme disease transmission

Lyme disease, a typical tick-borne disease, imposes increasing global public health challenges. A growing body of theoretical models have been proposed to better understand various factors determining the disease risk, which not only enrich our understanding on the ecological cycle of disease transmission but also promote new theoretical developments on model formulation, analysis and simulation. In this paper, we provide a review about the models and results we have obtained recently on modeling and analyzing Lyme disease transmission, with the purpose to highlight various aspects in the ecological cycle of disease transmission to be incorporated, including the growth of ticks with different stages in the life cycle, the seasonality, host diversity, spatial disease pattern due to host short distance movement and bird migration, co-infection with other tick-borne pathogens, and climate change impact. Keywords: Mathematical model, Lyme disease, Tick-borne disease, Basic reproduction number, Seasonality, Spatial model, Biodiversity, Co-infection, Bird migratio

A PERIODIC ROSS-MACDONALD MODEL IN A PATCHY ENVIRONMENT

Based on the classical Ross-Macdonald model, in this paper we propose a periodic malaria model to incorporate the effects of temporal and spatial heterogeneity on disease transmission. The temporal heterogeneity is described by assuming that some model coefficients are time-periodic, while the spatial heterogeneity is modeled by using a multi-patch structure and assuming that individuals travel among patches. We calculate the basic reproduction number [Formula: see text] and show that either the disease-free periodic solution is globally asymptotically stable if [Formula: see text] or the positive periodic solution is globally asymptotically stable if [Formula: see text]. Numerical simulations are conducted to confirm the analytical results and explore the effect of travel control on the disease prevalence

CFD-based optimization algorithm for thermocline evolution by control of thermal front movement in high temperature

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