scholarly journals Within-host viral dynamics of dengue serotype 1 infection

2014 ◽  
Vol 11 (96) ◽  
pp. 20140094 ◽  
Author(s):  
Hannah E. Clapham ◽  
Vianney Tricou ◽  
Nguyen Van Vinh Chau ◽  
Cameron P. Simmons ◽  
Neil M. Ferguson

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.

2012 ◽  
Vol 13 (1) ◽  
pp. 239-254 ◽  
Author(s):  
Shusen Wang

Abstract The impact of water stress on plant stomatal conductance (g) has been widely studied but with little consensus as to the processes governing its responses. The photosynthesis-driven stomatal conductance models usually employ constant model parameters and attribute the decrease of g from water stress to the reduction of leaf photosynthesis. This has been challenged by studies showing that the model parameter values decrease when the plant is under water stress. In this study, the impact of plant water stress on the parameter values in stomatal conductance models is evaluated using the approach recently developed by S. Wang et al. and the tower flux measurements at a Canadian boreal aspen forest. Results show that the slope parameter (α) in the stomatal conductance models decreases substantially with the development of plant water stress. The magnitude of this reduction is dependent on how plant water stress is represented. Overall, the relative reduction of α from its maximum value is 28% when soil water content decreases from 0.38 to 0.18 m3 m−3, and is 38% when Bowen ratio increases from 0.25 to 3.5. Equations for α correction to account for water stress impacts are proposed. Further studies on different ecosystems are necessary to quantify the parameter variations with water stress among different climate regions and plant species.


1998 ◽  
Vol 72 (5) ◽  
pp. 3547-3553 ◽  
Author(s):  
Deniz Durali ◽  
Jacques Morvan ◽  
Franck Letourneur ◽  
Doris Schmitt ◽  
Nelly Guegan ◽  
...  

ABSTRACT The great variability of protein sequences from human immunodeficiency virus (HIV) type 1 (HIV-1) isolates represents a major obstacle to the development of an effective vaccine against this virus. The surface protein (Env), which is the predominant target of neutralizing antibodies, is particularly variable. Here we examine the impact of variability among different HIV-1 subtypes (clades) on cytotoxic T-lymphocyte (CTL) activities, the other major component of the antiviral immune response. CTLs are produced not only against Env but also against other structural proteins, as well as some regulatory proteins. The genetic subtypes of HIV-1 were determined for Env and Gag from several patients infected either in France or in Africa. The cross-reactivities of the CTLs were tested with target cells expressing selected proteins from HIV-1 isolates of clade A or B or from HIV type 2 isolates. All African patients were infected with viruses belonging to clade A for Env and for Gag, except for one patient who was infected with a clade A Env-clade G Gag recombinant virus. All patients infected in France were infected with clade B viruses. The CTL responses obtained from all the African and all the French individuals tested showed frequent cross-reactions with proteins of the heterologous clade. Epitopes conserved between the viruses of clades A and B appeared especially frequent in Gag p24, Gag p18, integrase, and the central region of Nef. Cross-reactivity also existed among Gag epitopes of clades A, B, and G, as shown by the results for the patient infected with the clade A Env-clade G Gag recombinant virus. These results show that CTLs raised against viral antigens from different clades are able to cross-react, emphasizing the possibility of obtaining cross-immunizations for this part of the immune response in vaccinated individuals.


2016 ◽  
Vol 2016 ◽  
pp. 1-19 ◽  
Author(s):  
E. A. Bakare ◽  
C. R. Nwozo

We formulated and analysed a mathematical model to explore the cointeraction between malaria and schistosomiasis. Qualitative and comprehensive mathematical techniques have been applied to analyse the model. The local stability of the disease-free and endemic equilibrium was analysed, respectively. However, the main theorem shows that if RMS<1, then the disease-free equilibrium is locally asymptotically stable and the phase will vanish out of the host and if RMS>1, a unique endemic equilibrium is also locally asymptotically stable and the disease persists at the endemic steady state. The impact of schistosomiasis and its treatment on malaria dynamics is also investigated. Numerical simulations using a set of reasonable parameter values show that the two epidemics coexist whenever their reproduction numbers exceed unity. Further, results of the full malaria-schistosomiasis model also suggest that an increase in the number of individuals infected with schistosomiasis in the presence of treatment results in a decrease in malaria cases. Sensitivity analysis was further carried out to investigate the influence of the model parameters on the transmission and spread of malaria-schistosomiasis coinfection. Numerical simulations were carried out to confirm our theoretical findings.


Author(s):  
Nikolaos Papakonstantinou ◽  
Seppo Sierla ◽  
David C. Jensen ◽  
Irem Y. Tumer

Emergent behavior is a unique aspect of complex systems, where they exhibit behavior that is more complex than the sum of the behavior of their constituent parts. This behavior includes the propagation of faults between parts, and requires information on how the parts are connected. These parts can include software, electronic and mechanical components, hence requiring a capability to track emergent fault propagation paths as they cross the boundaries of technical disciplines. Prior work has introduced the functional failure identification and propagation (FFIP) simulation framework, which reveals the propagation of abnormal flow states and can thus be used to infer emergent system-wide behavior that may compromise the reliability of the system. An advantage of FFIP is that it is used to model early phase designs, before high cost commitments are made and before high fidelity models are available. This has also been a weakness in previous research on FFIP, since results depend on arbitrary choices for the values of model parameters and timing of critical events. Previously, FFIP has used a discrete set of flow state values and a simple behavioral logic; this has had the advantage of limiting the range of possible parameter values, but it has not been possible to model continuous process dynamics. In this paper, the FFIP framework has been extended to support continuous flow levels and linear modeling of component behavior based on first principles. Since this extension further expands the range of model parameter values, methods and tools for studying the impact of parameter value changes are introduced. The result is an evaluation of how the FFIP results are impacted by changes in the model parameters and the timing of critical events. The method is demonstrated on a boiling water reactor model (limited to the coolant recirculation and steam outlets) in order to focus the analysis of emergent fault behavior that could not have been identified with previously published versions of the FFIP framework.


Author(s):  
Clara Burgos ◽  
Noemí García-Medina ◽  
David Martínez-Rodríguez ◽  
José-Luis Pontones ◽  
David Ramos ◽  
...  

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.


1999 ◽  
Vol 73 (9) ◽  
pp. 7633-7640 ◽  
Author(s):  
S. Bhargava Periwal ◽  
John J. Cebra

ABSTRACT Respiratory virus infections are a serious health challenge. A number of models that examine the nature of the respiratory immune response to particular pathogens exist. However, many pathogens that stimulate specific immunity in the lung are frequently not effective immunogens at other mucosal sites. A pathogen that is an effective respiratory as well as gastrointestinal immunogen would allow studies of the interaction between the mucosal sites. Reovirus (respiratory enteric orphan virus) serotype 1 is known to be an effective gut mucosal immunogen and provides a potential model for the relationship between the respiratory and the gut mucosal immune systems. In this study, we demonstrate that intratracheal immunization with reovirus 1/Lang (1/L) in C3H mice resulted in high titers of virus in the respiratory tract-associated lymphoid tissue (RALT). High levels of reovirus-specific immunoglobulin A were determined in the RALT fragment cultures. The major responding components of the bronchus-associated lymphoid tissue were the CD8+ T lymphocytes. Cells from draining lymph nodes also exhibited lysis of reovirus-infected target cells after an in vitro culture. The present study also describes the distribution of transiently present CD4+/CD8+double-positive (DP) T cells in the mediastinal and tracheobronchial lymph nodes of RALT. CD4+/CD8+ DP lymphocytes were able to proliferate in response to stimulation with viral antigen in culture. Furthermore, these cells exhibited lysis of reovirus-infected target cells after in vitro culture. These results establish reovirus 1/L as a viable model for future investigation of the mucosal immune response in the RALT and its relationship to the common mucosal immune system.


2019 ◽  
Vol 2019 (1) ◽  
pp. 331-338 ◽  
Author(s):  
Jérémie Gerhardt ◽  
Michael E. Miller ◽  
Hyunjin Yoo ◽  
Tara Akhavan

In this paper we discuss a model to estimate the power consumption and lifetime (LT) of an OLED display based on its pixel value and the brightness setting of the screen (scbr). This model is used to illustrate the effect of OLED aging on display color characteristics. Model parameters are based on power consumption measurement of a given display for a number of pixel and scbr combinations. OLED LT is often given for the most stressful display operating situation, i.e. white image at maximum scbr, but having the ability to predict the LT for other configurations can be meaningful to estimate the impact and quality of new image processing algorithms. After explaining our model we present a use case to illustrate how we use it to evaluate the impact of an image processing algorithm for brightness adaptation.


2006 ◽  
Vol 41 (1) ◽  
pp. 72-83 ◽  
Author(s):  
Zhe Zhang ◽  
Eric R. Hall

Abstract Parameter estimation and wastewater characterization are crucial for modelling of the membrane enhanced biological phosphorus removal (MEBPR) process. Prior to determining the values of a subset of kinetic and stoichiometric parameters used in ASM No. 2 (ASM2), the carbon, nitrogen and phosphorus fractions of influent wastewater at the University of British Columbia (UBC) pilot plant were characterized. It was found that the UBC wastewater contained fractions of volatile acids (SA), readily fermentable biodegradable COD (SF) and slowly biodegradable COD (XS) that fell within the ASM2 default value ranges. The contents of soluble inert COD (SI) and particulate inert COD (XI) were somewhat higher than ASM2 default values. Mixed liquor samples from pilot-scale MEBPR and conventional enhanced biological phosphorus removal (CEBPR) processes operated under parallel conditions, were then analyzed experimentally to assess the impact of operation in a membrane-assisted mode on the growth yield (YH), decay coefficient (bH) and maximum specific growth rate of heterotrophic biomass (µH). The resulting values for YH, bH and µH were slightly lower for the MEBPR train than for the CEBPR train, but the differences were not statistically significant. It is suggested that MEBPR simulation using ASM2 could be accomplished satisfactorily using parameter values determined for a conventional biological phosphorus removal process, if MEBPR parameter values are not available.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2999
Author(s):  
Deborah Reynaud ◽  
Roland Abi Nahed ◽  
Nicolas Lemaitre ◽  
Pierre-Adrien Bolze ◽  
Wael Traboulsi ◽  
...  

The inflammatory gene NLRP7 is the major gene responsible for recurrent complete hydatidiform moles (CHM), an abnormal pregnancy that can develop into gestational choriocarcinoma (CC). However, the role of NLRP7 in the development and immune tolerance of CC has not been investigated. Three approaches were employed to define the role of NLRP7 in CC development: (i) a clinical study that analyzed human placenta and sera collected from women with normal pregnancies, CHM or CC; (ii) an in vitro study that investigated the impact of NLRP7 knockdown on tumor growth and organization; and (iii) an in vivo study that used two CC mouse models, including an orthotopic model. NLRP7 and circulating inflammatory cytokines were upregulated in tumor cells and in CHM and CC. In tumor cells, NLRP7 functions in an inflammasome-independent manner and promoted their proliferation and 3D organization. Gravid mice placentas injected with CC cells invalidated for NLRP7, exhibited higher maternal immune response, developed smaller tumors, and displayed less metastases. Our data characterized the critical role of NLRP7 in CC and provided evidence of its contribution to the development of an immunosuppressive maternal microenvironment that not only downregulates the maternal immune response but also fosters the growth and progression of CC.


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