Epidemics of panic during a bioterrorist attack – A mathematical model

A bioterrorist attacks usually cause epidemics of panic in a targeted population. We have presented epidemiologic aspect of this phenomenon as a three-component model – host, information on an attack and social network. We have proposed a mathematical model of panic and counter-measures as the function of time in a population exposed to a bioterrorist attack. The model comprises ordinary differential equations and graphically presented combinations of the equations parameters. Clinically, we have presented a model through a sequence of psychic conditions and disorders initiated by an act of bioterrorism. This model might be helpful for an attacked community to timely and properly apply counter-measures and to minimize human mental suffering during a bioterrorist attack.     

Finite element modeling of cooled-tip probe radiofrequency ablation processes in liver tissue

Finite element model of radiofrequency ablation (RFA) with cooled-tip probe in liver has been developed by employing COMSOL Multiphysics software. It describes coupled electric, thermal and sodium chloride solution infiltration flow phenomena taking place during ablation processes. Features of hydraulic capacity, saturation of the tissue by infiltration, and dependency of electrical conductivity on the damage integral of the tissue have been supplied to the model. RFA experiments have validated the model. Physical parameters describing hydraulic capacity and hydraulic conductivity in the tissue, as well as, the relation of electrical conductivity against the value of damage integral have been determined.     

模式生物斑马鱼在免疫学研究中的应用

斑马鱼是目前新兴的免疫学研究模式生物。基因突变技术、细胞移植技术、显微注射技术等已经在斑马鱼上得以应用。荧光标记使斑马鱼成为可以跟踪研究免疫细胞的活体动物模型。PCR与芯片技术有助于寻找重要的免疫相关基因。胚胎培养与移植技术为建立斑马鱼病原体感染模型提供了技术保障。结合荧光标记,斑马鱼模型可以用来筛选免疫增强药物和免疫抑制剂。目前已经建立了细菌病毒感染斑马鱼模型、白血病斑马鱼模型、免疫基因筛选斑马鱼模型与药物筛选斑马鱼模型。研究斑马鱼具有很重要的医学与生物学价值。     

Is there utility in the transtheoretical model?

Objectives The transtheoretical model is arguably the dominant model of health behaviour change, having received unprecedented research attention, yet it has simultaneously attracted exceptional criticism. However, the criticisms have been directed almost exclusively at the stages of change, just one of fourteen components of the transtheoretical model, which may have diverted attention away from more fruitful avenues of research based on the model. Design and methods Narrative review. Results The evidence would suggest some flaws in the concept of stages of change as currently articulated in the transtheoretical model. On a conceptual level, even studies incorporating the five stages of change point to a model that better fits Gollwitzer (1993) and Heckhausen's (1991) idea of a motivational phase followed by a volitional phase. Potentially the processes of change components of the transtheoretical model may actually prove the most useful, yet have been under‐researched, at least experimentally. Three studies that successfully utilise the processes of change to reduce alcohol consumption, encourage smoking cessation and increase physical activity are described. Conclusions Elements of the transtheoretical model offer promise in developing effective health behaviour change interventions, but the question arises as to whether extracting these elements undermines completely the idea of a transtheoretical model.     

The PC12 cell as model for neurosecretion

This review attempts to touch on the history and application of amperometry at PC12 cells for fundamental investigation into the exocytosis process. PC12 cells have been widely used as a model for neural differentiation and as such they have been used to examine the effects of differentiation on exocytotic release and specifically release at varicosities. In addition, dexamethasone-differentiated cells have been shown to have an increased number of releasable vesicles with increased quantal size, thereby allowing for an even broader range of applications including neuropharmacological and neurotoxicological studies. PC12 cells exhibiting large numbers of events have two distinct pools of vesicles, one about twice the quantal size of the other and each about half the total releasable vesicles. As will be outlined in this review, these cells have served as an extremely useful model of exocytosis in the study of the latency of stimulation-release coupling, the role of exocytotic proteins in regulation of release, effect of drugs on quantal size, autoreceptors, fusion pore biophysics, environmental factors, health and disease. As PC12 cells have some advantages over other models for neurosecretion, including chromaffin cells, it is more than likely that in the following decade PC12 cells will continue to serve as a model to study exocytosis.     

Familial association of disease and the structure of trivariate distributions

In its usual form, the multifactorial model of disease transmission assumes that the liabilities to disease have a multivariate normal distribution. This paper studies how sensitive to this assumption are the quantitative results from the model. Accordingly, bounds are established for the probability of a child having a disease, given that both parents have it and taking the heritability of the disease to be known. Unfortunately, these bounds turn out to be wide. For example, a probability that is 0.38 under the trivariate normal model may be as low as 0.12 or as high as 0.78 under other trivariate models, even if attention is restricted to those of variables-in-common form. The broader statistical issue of the meaning of trivariate dependence, as distinct from bivariate dependence, is also discussed.     

A model for the formation and lysis of blood clots

Both biochemical and mechanical factors have to be taken into account if a meaningful model for the formation, growth, and lysis of clots in flowing blood is to be developed. Most models that are currently in use neglect one or the other of these factors. We have previously reported a model [J Theoret Med 2003;5:183-218] that we believe is a step in this direction, incorporating many of the crucial biochemical and rheological factors that play a role in the formation, growth, and lysis of clots. While this model takes into account the extrinsic pathway of coagulation, it largely ignores the intrinsic pathway. Here, we discuss some of the general issues with respect to mathematical modeling of thrombus formation and lysis, as well as specific aspects of the model that we have developed.     

On a simple model of insulin secretion

A model of the insulin secretion process is presented. The model aims to be a simple one as compared with previous models, i.e. it predicts experimental evidence on insulin secretion under a variety of glucose inputs with a mathematical structure of low complexity. The model predicts in the β-pancreas two linearly connected pools of stored and promptly releasable insulin. Insulin synthesis and release have been modelled as nonlinear glucose-controlled processes. Validation of the model is made by simulation studies both on insulin secretion data as well as on blood insulin concentration data, by aggregating the proposed model to a compartmental model of insulin kinetics.     

An integrative model of regulation centered on recognition of TCR peptide/MHC complexes

Summary: We have described a T-cell receptor (TCR)-centered model of immune regulation, in which MHC/TCR peptide complexes provide for the activation of regulatory T cells and likewise act as their target structures. In this model, the disease-causing effectors are TCR Vβ8.2⁺ and each of the required CD4 and CD8 regulatory T-cell populations are specific for different conserved regions of the Vβ8.2 chain, in the appropriate MHC context. We have characterized the dominance, the dynamics as well as the TCR usage of both effector and regulatory T cells. We have begun to characterize the essential elements of the regulatory program, including the mechanism of interaction among effector and regulatory T-cell populations. Principles learned in this model have important implications for immune regulation in general.     

Immunity to viruses: learning from successful human vaccines

For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using ‘model antigens’, such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such ‘systems vaccinology’ studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the yellow fever and the seasonal influenza vaccines. Vaccination with the yellow fever vaccine causes a systemic acute viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated influenza vaccine causes a localized acute viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to influenza, and thus provides a unique opportunity to study innate and antigen-specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity. Vaccines that have been proven to be of immense benefit in saving lives offer us a new fringe benefit: lessons in viral immunology.     

一种模拟三维红细胞变形的前向跟踪式格子B0ltzmann方法

将前向跟踪法与晶格波尔兹曼法相结合,研究三维双凹碟形胶囊式红细胞的变形.将红细胞模拟为内含牛顿流体的双凹碟形弹性薄膜胶囊,将薄膜内外的液体看做是具有不同物理特性的流体;使用晶格波尔兹曼方法的多块策略,改善细胞模型附近的网格,增加三维计算的准确度和效率.使用的细网格仅覆盖每个计算轴的40%,较同时选用离散为连接4 098个点的8 192个三角元的细胞薄膜模型,这不仅可以提高网格分辨率,而且还能节省计算时间.从理论上证明,在雷诺数不大于0.25的剪切流中,惯性作用对细胞变性的影响很小,同时得到无因次参数为0.05、细胞内外黏度比为0.2时三维健康红细胞的360.稳定坦克履行为.不仅成功模拟了惯性作用下典型的三维红细胞坦克履行为,而且使用的细网格仅占整个计算区域的6.4%,在保证计算准确度的同时,提高了计算效率,为模拟三维红细胞变形提供了一种更加可行的途径.     

Characteristics of chemically aggregated IgM in an immunoglobulin class-specific immune complex assay

Immune complexes have been implicated in the pathogenesis of a number of infectious diseases. The predominant immunoglobulin class associated with circulating immune complexes is IgG, although immune complexes containing IgM have been described. The role of IgM immune complexes in disease pathogenesis has been difficult to characterize due to the lack of a reliable in vitro model. Immunoglobulins aggregated with bis-diazotized benzidine (BDB) are known to function as model immune complexes. We have developed an IgM immune complex using BDB-aggregated IgM which can be used as a reference in a conglutinin-based immune complex assay. Using this assay system, humans and chimpanzees with acute hepatitis A were found to have circulating immune complexes that contained IgM as the predominant antibody.     

Secondary injury after musculoskeletal trauma: a review and update

Objectives: To revisit the secondary injury model, to incorporate several current pathophysiologic theories into the model, and to show the need for more direct research examining the model.Data Sources: I searched MEDLINE and CINAHL from 1976 to 2001 for literature related to acute injury pathology and pathophysiology and selected classic articles and pathology, pathophysiology, and immunology texts.Data Synthesis: Acute musculoskeletal injury management is based on a pathophysiologic model, often referred to as the secondary injury model, which was originally developed more than 25 years ago. In this model, acute trauma is referred to as primary injury, whereas secondary injury refers to damage to otherwise uninjured cells that was a direct consequence of the physiologic response to primary injury. In the original model, mechanisms for secondary injury were hypothesized based on then-contemporary understandings of immunology and cellular pathology. These mechanisms were broadly categorized as either enzymatic or hypoxic. Since this time, the pathologic paradigms for cell death from trauma have evolved, and the secondary injury model requires some updating. Some controversy now exists regarding the categorization of injury as primary or secondary, specifically whether posttraumatic damage is actually secondary injury in previously uninjured tissue or delayed death of primary injured cells. Similarly, the postulated mechanisms that lead to secondary injury now appear to be considerably more complex than originally anticipated.Conclusions/Recommendations: The secondary injury model has been reconciled with our contemporary understanding of pathophysiology. Specifically, secondary hypoxic injury has been clarified to be secondary ischemic injury, and several specific mechanisms for ischemic injury have been identified. Similarly, secondary injury from mitochondrial failure and other potential mechanisms has been identified, and the role and interaction of these mechanisms in relation to total secondary injury have been expanded.     

Caco-2细胞生物膜模型研究进展

Caco-2细胞生物膜因在结构和生物学性质上与人小肠吸收细胞相似而广泛用于肠道药物吸收机制研究.Caco-2细胞模型的应用将人们对药物吸收、生物转化和生物利用度等机制的认识提高到细胞分子水平,同时Caco-2细胞能在药物开发早期对药物先导化合物的肠道吸收性质作出评价而深受制药业关注.但是,Caco-2细胞模型存在的不足制约着其应用,如:形成的细胞间紧密联结限制了水溶性小分子药物穿细胞间转运的应用研究,Caco-2细胞膜上缺乏人肠道药物吸收主要屏障之一的黏液层,人肠道表达的药物代谢酶细胞色素P450等.为了更好地在体外模拟体内生理环境,预测体内肠道药物转运、代谢行为,研究者应用细胞培养技术、分子克隆技术和生化诱导技术对Caco-2细胞模型进行优化,改善Caco-2细胞模型的性质.本文对用各种技术改良Caco-2细胞模型的研究进展进行综述.     

Efficient determination of the epidermal optical properties using a diffusion model-based approach: Monte Carlo studies

In our previous studies, we have shown that the diffusing probe geometry can be used in conjunction with a two-layer diffusion model to accurately recover the absorption and scattering properties of skin in vivo. By modifying the original design to the diffusing probe with planar source (DPPS) geometry, we have also demonstrated that the efficiency of the accompanying multilayer diffusion model is comparable to that of a standard semi-infinite diffusion model; thus, precise quantification of superficial tissue optical properties in real time using a diffusion model becomes possible. In this study, the performance of the DPPS diffusion model is evaluated using Monte Carlo simulations and phantom measurements. It is found that the DPPS geometry is advantageous over the conventional planar source illumination geometry in interrogating superficial volumes of samples. In addition, our simulation results have shown that the DPPS geometry is capable of accurately recovering the optical properties of 50-μm thick epidermis and could be very useful in detecting cutaneous melanoma that has a radius as small as 250 μm.     

Vascular endothelial growth factor and ocular neovascularization.

Okamoto et al have developed an extremely useful and interesting model of retinal and subretinal neovascularization. Using molecular techniques, they have developed a transgenic model driven by overexpression of VEGF, a growth factor demonstrated to play an important role in neovascularization in many ocular diseases. They have been able to demonstrate that VEGF overexpression is sufficient to cause intraretinal and subretinal neovascularization. The mouse model is relatively cheap and reliable, does not require any exogenous agent, and has many characteristics of clinical intraocular neovascularization. The new vessels develop in the outer retina and subretinal space and have a characteristic histological appearance. They leak fluorescein on angiography, demonstrating their similarity to human disease and allowing identification and grading of neovascularization in vivo. The model can be used to investigate molecular mechanisms of VEGF-dependent neovascularization, with applications beyond ocular eye disease. The model can also be used to study anti-angiogenic agents that have the potential to treat common blinding diseases such as age-related macular degeneration. Okamoto et al have made a substantial contribution to the angiogenesis field with this work, and one looks forward to future investigations.     

An insight into cortisol and polymyositis control with steroid therapy.

In the present report we have developed a mathematical model to describe the processes involved during high steroid therapy. We have shown that the model can predict clinical observations as well as determine the optimum steroid regimen without relying on trial and error methods. The model incorporates rate processes that simplify the physiological complexity as a few representative steps. In this way, it is possible to simulate clinical observations and then to predict clinical outcomes due to drug concentrations or additional reactions within the body. Specific examples are provided from patients with polymyositis and Becker's disease. For the first time, we provide an explanation into the control of cortisol production, and determine an optimum prednisolone concentration in order to minimize steroid side effects while maintaining adequate control of muscle degradation.     

Using Non-Normal SEM to Resolve the ACDE Model in the Classical Twin Design

One of the biggest problems in classical twin studies is that it cannot estimate additive genetic (A), non-additive genetic (D), shared environmental (C), and non-shared environmental (E) effects, simultaneously, because the model, referred to as the ACDE model, has negative degrees of freedom when using Structural Equation Modeling (SEM). Therefore, instead of the ACDE model, the ACE model or the ADE model is actually used. However, using the ACE or ADE models almost always leads to biased estimates. In the present paper, the univariate ACDE model is developed using non-normal Structural Equation Modeling (nnSEM). In SEM, (1st- and) 2nd-order moments, namely, (means and) covariances are used as information. However, nnSEM uses higher-order moments as well as (1st- and) 2nd-order moments. nnSEM has a number of advantages over SEM. One of which is that nnSEM can specify models that cannot be specified using SEM because of the negative degrees of freedom. Simulation studies have shown that the proposed method can decrease the biases. There are other factors that have possible effects on phenotypes, such as higher-order epistasis. Since the proposed method cannot estimate these effects, further research on developing a more exhaustive model is needed.     

The inclusion of capillary distribution in the adiabatic tissue homogeneity model of blood flow

We have developed a non-invasive imaging tracer kinetic model for blood flow which takes into account the distribution of capillaries in tissue. Each individual capillary is assumed to follow the adiabatic tissue homogeneity model. The main strength of our new model is in its ability to quantify the functional distribution of capillaries by the standard deviation in the time taken by blood to pass through the tissue. We have applied our model to the human prostate and have tested two different types of distribution functions. Both distribution functions yielded very similar predictions for the various model parameters, and in particular for the standard deviation in transit time. Our motivation for developing this model is the fact that the capillary distribution in cancerous tissue is drastically different from in normal tissue. We believe that there is great potential for our model to be used as a prognostic tool in cancer treatment. For example, an accurate knowledge of the distribution in transit times might result in an accurate estimate of the degree of tumour hypoxia, which is crucial to the success of radiation therapy.     

Cross sections and partial kerma factors for elastic and inelastic neutron scattering from nitrogen, oxygen and calcium at En = 21.6 MeV

The Studsvik high-resolution, low-background time-of-flight facility has been used to measure differential neutron scattering cross sections for nitrogen, oxygen and calcium at a neutron energy of 21.6 MeV. Angular distributions in the range 10 degrees-160 degrees have been measured for both elastic and inelastic scattering from some low-lying levels in the three nuclei. Angle-integrated cross sections have been determined by fitting Legendre polynomial expansions to the differential data. Partial kerma factors for elastic and inelastic scattering have been deduced from these fits. Analyses in terms of the spherical optical model and the distorted-wave Born approximation have provided information on potential parameters and deformations, which have been used to calculate cross sections and partial kerma factors. Comparisons have been made with other recent data sets and model predictions, as well as with the evaluated neutron data file ENDF/B-V.