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1.
Immunotherapy with Bacillus Calmette–Guérin (BCG)—an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization—is a clinically established procedure for the treatment of superficial bladder cancer.
However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of
this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of
BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties,
and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free
equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating
the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy
must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can
lead to an over-stimulated immune system having dangerous side effects for the patient. 相似文献
2.
Bassidy Dembele Avner Friedman Abdul-Aziz Yakubu 《Bulletin of mathematical biology》2010,72(4):914-930
In this paper, we introduce a deterministic malaria model for determining the drug administration protocol that leads to the
smallest first malaria episodes during the wet season. To explore the effects of administering the malaria drug on different
days during the wet season while minimizing the potential harmful effects of drug overdose, we define 40 drug administration
protocols. Our results fit well with the clinical studies of Coulibaly et al. at a site in Mali. In addition, we provide protocols
that lead to smaller number of first malaria episodes during the wet season than the protocol of Coulibaly et al. 相似文献
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This paper is concerned with early development of transformed epithelial cells (TECs) in the presence of fibroblasts in the
tumor micro-environment. These two types of cells interact by means of cytokines such as transforming growth factor (TGF-β) and epidermal growth factor (EGF) secreted, respectively, by the TECs and the fibroblasts. As this interaction proceeds,
TGF-β induces fibroblasts to differentiate into myofibroblasts which secrete EGF at a larger rate than fibroblasts. We monitor
the entire process in silico, in a setup which mimics experiments in a Tumor Chamber Invasion Assay, where a semi-permeable
membrane coated by extracellular matrix (ECM) is placed between two chambers, one containing TECs and another containing fibroblasts.
We develop a mathematical model, based on a system of PDEs, that includes the interaction between TECs, fibroblasts, myofibroblasts,
TGF-β, and EGF, and we show how model parameters affect tumor progression. The model is used to generate several hypotheses on
how to slow tumor growth and invasion. In an Appendix, it is proved that the mathematical model has a unique global in-time
solution. 相似文献
5.
This paper deals with the spatio-temporal dynamics of a pollinator–plant–herbivore mathematical model. The full model consists
of three nonlinear reaction–diffusion–advection equations defined on a rectangular region. In view of analyzing the full model,
we firstly consider the temporal dynamics of three homogeneous cases. The first one is a model for a mutualistic interaction
(pollinator–plant), later on a sort of predator–prey (plant–herbivore) interaction model is studied. In both cases, the interaction
term is described by a Holling response of type II. Finally, by considering that the plant population is the unique feeding
source for the herbivores, a mathematical model for the three interacting populations is considered. By incorporating a constant
diffusion term into the equations for the pollinators and herbivores, we numerically study the spatiotemporal dynamics of
the first two mentioned models. For the full model, a constant diffusion and advection terms are included in the equation
for the pollinators. For the resulting model, we sketch the proof of the existence, positiveness, and boundedness of solution
for an initial and boundary values problem. In order to see the separated effect of the diffusion and advection terms on the
final population distributions, a set of numerical simulations are included. We used homogeneous Dirichlet and Neumann boundary
conditions. 相似文献
6.
We describe and analyze a mathematical model for schistosomiasis in which infected snails are distinguished from susceptible
through increased mortality and no reproduction. We based the model on the same derivation as Anderson and May (J. Anim. Ecol.
47:219–247, 1978), Feng and Milner (A New Mathematical Model of Schistosomiasis, Mathematical Models in Medical and Health Science, Nashville,
TN, 1997. Innov. Appl. Math., Vanderbilt Univ. Press, Nashville, pp. 117–128, 1998), and May and Anderson (J. Anim. Ecol. 47:249–267, 1978), but used logistic growth both in human and snail hosts. We introduce a parameter r, the effective coverage of medical treatment/prevention to control the infection. We determine a reproductive number for
the disease directly related to its persistence and extinction. Finally, we obtain a critical value for r that indicates the minimum treatment effort needed in order to clear out the disease from the population. 相似文献
7.
This paper studies a class of dynamical systems that model multi-species ecosystems. These systems are ‘resource bounded’
in the sense that species compete to utilize an underlying limiting resource or substrate. This boundedness means that the
relevant state space can be reduced to a simplex, with coordinates representing the proportions of substrate utilized by the
various species. If the vector field is inward pointing on the boundary of the simplex, the state space is forward invariant
under the system flow, a requirement that can be interpreted as the presence of non-zero exogenous recruitment. We consider
conditions under which these model systems have a unique interior equilibrium that is globally asymptotically stable. The
systems we consider generalize classical multi-species Lotka–Volterra systems, the behaviour of which is characterized by
properties of the community (or interaction) matrix. However, the more general systems considered here are not characterized
by a single matrix, but rather a family of matrices. We develop a set of ‘explicit conditions’ on the basis of a notion of
‘uniform diagonal dominance’ for such a family of matrices, that allows us to extract a set of sufficient conditions for global
asymptotic stability based on properties of a single, derived matrix. Examples of these explicit conditions are discussed. 相似文献
8.
Hinkelmann F Murrugarra D Jarrah AS Laubenbacher R 《Bulletin of mathematical biology》2011,73(7):1583-1602
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Age and sex structured HIV/AIDS model with explicit incubation period is proposed as a system of delay differential equations.
The model consists of two age groups that are children (0–14 years) and adults (15–49 years). Thus, the model considers both
mother-to-child transmission (MTCT) and heterosexual transmission of HIV in a community. MTCT can occur prenatally, at labour
and delivery or postnatally through breastfeeding. In the model, we consider the children age group as a one-sex formulation
and divide the adult age group into a two-sex structure consisting of females and males. The important mathematical features
of the model are analysed. The disease-free and endemic equilibria are found and their stabilities investigated. We use the
Lyapunov functional approach to show the local stability of the endemic equilibrium. Qualitative analysis of the model including
positivity and boundedness of solutions, and persistence are also presented. The basic reproductive number (ℛ0) for the model shows that the adult population is responsible for the spread HIV/AIDS epidemic, thus up-to-date developed
HIV/AIDS models to assess intervention strategies have focused much on heterosexual transmission by the adult population and
the children population has received little attention. We numerically analyse the HIV/AIDS model to assess the community benefits
of using antiretroviral drugs in reducing MTCT and the effects of breastfeeding in settings with high HIV/AIDS prevalence
ratio using demographic and epidemiological parameters for Zimbabwe. 相似文献
13.
Statistics in Biosciences - 相似文献
14.
Ferrantini M Capone I Marincola FM Parmiani G Belardelli F 《Cancer immunology, immunotherapy : CII》2007,56(4):581-585
The main aims of the international meeting “Immunotherapy of Cancer: Challenges and Needs” were to review the state of the
art of cancer immunotherapy and to identify critical issues which deserve special attention for promoting progress of research
in this field, with a particular focus on the perspectives of clinical research. Novel concepts and strategies for identifying,
monitoring and predicting effective responses to cancer immunotherapy protocols were presented, focused on the use of adjuvants
(CpG oligonucleotides) or cytokines (IFN-alpha) to enhance the efficacy of cancer vaccines. Moreover, the possible advantages
of using different types of dendritic cells (for active immunization strategies) or T cells (for adoptive immunotherapy protocols)
were debated. A consensus was achieved on the need for enhancing the efficacy of cancer vaccines or adoptive cell immunotherapy by combining these
strategies with other anti-cancer treatments, including chemotherapy. Finally, initiatives for promoting clinical research
by establishing a strategic cooperation in the field of cancer immunotherapy based on the active participation of all the
relevant actors, including public institutions responsible of Public Health, National Cancer Institutes, industry, representatives
of regulatory bodies, and patients’ organizations were proposed. 相似文献
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We consider the efficient estimation of a regression parameter in a partially linear additive nonparametric regression model from repeated measures data when the covariates are multivariate. To date, while there is some literature in the scalar covariate case, the problem has not been addressed in the multivariate additive model case. Ours represents a first contribution in this direction. As part of this work, we first describe the behavior of nonparametric estimators for additive models with repeated measures when the underlying model is not additive. These results are critical when one considers variants of the basic additive model. We apply them to the partially linear additive repeated-measures model, deriving an explicit consistent estimator of the parametric component; if the errors are in addition Gaussian, the estimator is semiparametric efficient. We also apply our basic methods to a unique testing problem that arises in genetic epidemiology; in combination with a projection argument we develop an efficient and easily computed testing scheme. Simulations and an empirical example from nutritional epidemiology illustrate our methods. 相似文献
17.
In this paper, we propose a mathematical model of viral infection in pest control. As the viral infection induces host lysis
which releases more virus into the environment, on the average ‘κ’ viruses per host, κ∈(1,∞), so the ‘virus replication parameter’ is chosen as the main parameter on which the dynamics of the infection depends.
There exists a threshold value κ
0 beyond which the infection persists in the system. Still for increasing the value of κ, the endemic equilibrium bifurcates towards a periodic solution, which essentially indicates that the viral pesticide has
a density-dependent ‘numerical response’ component to its action. Investigation also includes the dependence of the process
on predation of natural enemy into the system. A concluding discussion with numerical simulation of the model is also presented. 相似文献
18.
Bistability in apoptosis, or programmed cell death, is crucial for the healthy functioning of multicellular organisms. The
aim in this study is to show the presence of bistability in a mitochondria-dependent apoptosis model under nitric oxide effects
using chemical reaction network theory. The model equations are a set of coupled ordinary differential equations arising from
the assumed mass action kinetics. Whether these equations have a capacity for bistability (cell survival and apoptosis) is
determined using a modular approach in which the model is decomposed into modules. Each module contains only a subset of the
whole model and is analyzed separately. It is seen that bistability in a module is preserved throughout the whole model after
adding the remaining reactions in the pathway on these modules. It is also found that inhibitor effect of some proteins and
the appearance of a reacting protein in a later stage as a product is a desired feature but not sufficient for bistability
(in the absence of cooperativity effects). On the whole model, two apoptotic and two cell survival states are obtained depending
on the initial cell conditions. The results suggest that the antiapoptotic effects of nitric oxide species are responsible
for the bistable character of the apoptotic pathway when cooperativity is not assumed in the apoptosome formation. 相似文献
19.
Both uniform persistence and the existence of periodic coexistence state are established for a periodically forced Droop model
on two phytoplankton species competition in a chemostat under some appropriate conditions. Numerical simulations using biological
data are presented as well to illustrate the main result.
Research supported in part by the NSERC of Canada and the MITACS of Canada. 相似文献
20.
Miranda I. Teboh-Ewungkem Chandra N. Podder Abba B. Gumel 《Bulletin of mathematical biology》2010,72(1):63-93
A mathematical model is developed to assess the role of gametocytes (the infectious sexual stage of the malaria parasite)
in malaria transmission dynamics in a community. The model is rigorously analysed to gain insights into its dynamical features.
It is shown that, in the absence of disease-induced mortality, the model has a globally-asymptotically stable disease-free
equilibrium whenever a certain epidemiological threshold, known as the basic reproduction number (denoted by ℛ0), is less than unity. Further, it has a unique endemic equilibrium if ℛ0>1. The model is extended to incorporate an imperfect vaccine with some assumed therapeutic characteristics. Theoretical analyses
of the model with vaccination show that an imperfect malaria vaccine could have negative or positive impact (in reducing disease
burden) depending on whether or not a certain threshold (denoted by ∇) is less than unity. Numerical simulations of the vaccination model show that such an imperfect anti-malaria vaccine (with
a modest efficacy and coverage rate) can lead to effective disease control if the reproduction threshold (denoted by ℛvac) of the disease is reasonably small. On the other hand, the disease cannot be effectively controlled using such a vaccine
if ℛvac is high. Finally, it is shown that the average number of days spent in the class of infectious individuals with higher level
of gametocyte is critically important to the malaria burden in the community. 相似文献