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Application of minimum description length criterion to assess the complexity of models in mathematical immunology 最小描述长度准则在数学免疫学模型复杂性评价中的应用
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-11-01 DOI: 10.1515/rnam-2022-0022
D. Grebennikov, V. V. Zheltkova, G. Bocharov
Abstract Mathematical models in immunology differ enormously in the dimensionality of the state space, the number of parameters and the parameterizations used to describe the immune processes. The ongoing diversification of the models needs to be complemented by rigorous ways to evaluate their complexity and select the parsimonious ones in relation to the data available/used for their calibration. A broadly applied metrics for ranking the models in mathematical immunology with respect to their complexity/parsimony is provided by the Akaike information criterion. In the present study, a computational framework is elaborated to characterize the complexity of mathematical models in immunology using a more general approach, namely, the Minimum Description Length criterion. It balances the model goodness-of-fit with the dimensionality and geometrical complexity of the model. Four representative models of the immune response to acute viral infection formulated with either ordinary or delay differential equations are studied. Essential numerical details enabling the assessment and ranking of the viral infection models include: (1) the optimization of the likelihood function, (2) the computation of the model sensitivity functions, (3) the evaluation of the Fisher information matrix and (4) the estimation of multidimensional integrals over the model parameter space.
免疫学中的数学模型在状态空间的维数、参数的数量和用于描述免疫过程的参数化方面存在很大差异。模型的不断多样化需要辅以严格的方法来评估其复杂性,并根据可获得/用于其校准的数据选择最简洁的模型。Akaike信息标准提供了一种广泛应用的数学免疫学模型复杂性/简约性排名指标。在本研究中,阐述了一个计算框架,使用更一般的方法来表征免疫学数学模型的复杂性,即最小描述长度标准。它平衡了模型的拟合优度与模型的维数和几何复杂性。研究了用常微分方程或时滞微分方程表述的急性病毒感染免疫反应的四个代表性模型。对病毒感染模型进行评估和排序的关键数值细节包括:(1)似然函数的优化;(2)模型灵敏度函数的计算;(3)Fisher信息矩阵的评估;(4)模型参数空间上多维积分的估计。
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引用次数: 2
Personalized computational estimation of relative change in coronary blood flow after percutaneous coronary intervention in short-term and long-term perspectives 短期和长期经皮冠状动脉介入治疗后冠状动脉血流相对变化的个性化计算估计
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-11-01 DOI: 10.1515/rnam-2022-0024
S. Simakov, T. Gamilov, A. Danilov, F. Liang, P. Chomakhidze, Mariam K. Gappoeva, Alina A. Rebrova, P. Kopylov
Abstract Coronary artery disease is the leading cause of mortality worldwide, accounting for 12.8% of all deaths. Although the clinical benefits of treating stenosis with percutaneous coronary intervention (PCI) have been extensively demonstrated, residual myocardial ischemia remains in about 30–50% of patients even after a formally successful PCI. We apply previously developed and validated 1D model of haemodynamics, which distributes terminal hydraulic resistance based on the diameters of the parent vessels and Murray’s law by a recursive algorithm. In our new model the terminal resistance is decreased according to a transmural perfusion ratio increase. In contrast to our previous work we calculate the transmural perfusion ratio for personally defined zones. Thus, peripheral hydraulic resistance of myocardial perfusion is personalized based on patient data, whichwere extracted from computed tomography perfusion images. The model serves as a computational tool for simulating pre- to post-PCI changes in coronary haemodynamics of four patients. We simulate fractional flow reserve (FFR), coronary flow reserve (CFR), instantaneous wave-free ratio (iFR), average flow in selected arteries in hyperemic and rest conditions before PCI and after PCI immediately after the surgery (in a short-term) and in a long-term (several months) perspectives. We conclude that high FFR and iFR values in short-term and long-term perspectives are not necessary correlate with CFR improvement and long-term blood flow recovery in coronary arteries.
冠状动脉疾病是世界范围内死亡的主要原因,占总死亡人数的12.8%。尽管经皮冠状动脉介入治疗狭窄的临床益处已被广泛证实,但即使在正式成功的PCI治疗后,仍有大约30-50%的患者存在残余心肌缺血。我们采用了先前开发和验证的一维血流动力学模型,该模型根据母血管直径和默里定律通过递归算法分配末端水力阻力。在我们的新模型中,终端电阻随着跨壁灌注比的增加而降低。与我们之前的工作相反,我们计算了个人定义区域的跨壁灌注比。因此,基于从计算机断层扫描灌注图像中提取的患者数据,可以个性化心肌灌注的周围水力阻力。该模型作为一种计算工具,用于模拟4例患者pci术前至术后冠状动脉血流动力学的变化。我们模拟血流储备分数(FFR),冠状动脉血流储备(CFR),瞬时无波比(iFR),在充血和休息条件下选定动脉的平均血流在PCI术前和术后立即(短期)和长期(几个月)的角度。我们得出结论,短期和长期来看,高FFR和iFR值与CFR改善和冠状动脉长期血流恢复没有必然的相关性。
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引用次数: 2
Computational mimicking of surgical leaflet suturing for virtual aortic valve neocuspidization 虚拟主动脉瓣新冠手术小叶缝合的计算模拟
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-11-01 DOI: 10.1515/rnam-2022-0023
A. Liogky
Abstract The aortic valve neocuspidization (AVNeo) procedure requires the design of patient-specific neo-cusps which can be made numerically through the neovalve closure modelling. Prior the simulation, it is required to ‘suture virtually’ the neocusps into the patient’s aortic geometry, i.e., to find such state in which the neocusps are placed in the aortic root lumen without intersections of physical surfaces and neo-valve prolapse, and the position of the suture boundary satisfies the boundary conditions. To solve this problem, we tried to mimic neocusps suturing in Ozaki’s operation. As a result, we propose a new algorithm for ‘virtual suturing’ of given neocusps, considered as thin shells. The approach is able to work with both small and large (compared to an optimal size) neocusps and to handle each cusp independently of the others.
摘要主动脉瓣新尖瓣切除术(AVNeo)需要设计特定于患者的新尖瓣,可以通过新瓣膜闭合模型进行数字制作。在模拟之前,需要将新叶“虚拟缝合”到患者的主动脉几何结构中,即找到这样的状态,即新叶被放置在主动脉根腔内,没有物理表面和新瓣膜脱垂的交叉,并且缝合边界的位置满足边界条件。为了解决这个问题,我们尝试在Ozaki的手术中模仿新冠缝合。因此,我们提出了一种新的算法来“虚拟缝合”给定的新冠,被认为是薄壳。该方法能够同时适用于小型和大型(与最佳尺寸相比)新冠,并独立于其他尖端处理每个尖端。
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引用次数: 0
Computational analysis of the impact of aortic bifurcation geometry to AAA haemodynamics 主动脉分叉几何形状对AAA血流动力学影响的计算分析
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-11-01 DOI: 10.1515/rnam-2022-0026
D. Tikhvinskii, Lema R. Merzhoeva, A. Chupakhin, A. Karpenko, D. Parshin
Abstract Abdominal aortic aneurysm is a widespread disease of cardiovascular system. Predicting a moment of its rupture is an important task for modern vascular surgery. At the same time, little attention is paid to the comorbidities, which are often the causes of severe postoperative complications or even death. This work is devoted to a numerical study of the haemodynamics of the model geometry for possible localizations of abdominal aortic aneurysm: on the aortic trunk or on its bifurcation. Both rigid and FSI numerical simulations are considered and compared with the model aortic configuration without aneurysm. It is shown that in the case of localization of the aneurysm on the bifurcation, the pressure in aorta increases upstream. Moreover, only in the case of a special geometry,when the radii of the iliac arteries are equal (r1 = r2), and the angle between them is 60 degrees, there is a linear relationship between the pressure in the aorta above the aneurysm and the size of the aneurysm itself: the slope of the straight line is in the interval a ∈ (0.003; 0.857), and the coefficient of determination is R2 ⩾ 0.75. The area bounded by the curve of the ‘pressure–velocity’ diagram for the values of velocity and pressure upstream in the presence of an aneurysm decreases compared to a healthy case (a vessel without an aneurysm). The simulation results in the rigid and FSI formulations agree qualitatively with each other. The obtained results provide a better understanding of the relationship between the geometrical parameters of the aneurysm and the changing of haemodynamics in the aortic bifurcation and its effect on the cardiovascular system upstream of the aneurysm.
摘要腹主动脉瘤是一种广泛存在的心血管系统疾病。预测其破裂时刻是现代血管外科的一项重要任务。同时,很少关注合并症,这些合并症往往是导致严重术后并发症甚至死亡的原因。这项工作致力于对腹主动脉瘤可能定位的模型几何结构的血液动力学进行数值研究:在主动脉干或其分叉处。考虑了刚性和FSI数值模拟,并与没有动脉瘤的模型主动脉结构进行了比较。结果表明,在动脉瘤位于分叉处的情况下,主动脉上游的压力增加。此外,只有在特殊几何形状的情况下,当髂动脉的半径相等(r1=r2),并且它们之间的角度为60度时,动脉瘤上方主动脉中的压力与动脉瘤本身的大小之间存在线性关系:直线的斜率在区间a∈(0.003;0.857)内,确定系数为r2⩾0.75。与健康病例(没有动脉瘤的血管)相比,存在动脉瘤的情况下,上游速度和压力值的“压力-速度”图曲线所限定的面积减少。刚性公式和FSI公式的模拟结果在质量上相互一致。所获得的结果更好地理解了动脉瘤的几何参数与主动脉分叉处血流动力学变化之间的关系及其对动脉瘤上游心血管系统的影响。
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引用次数: 0
Algorithms and methodological challenges in the development and application of quantitative systems pharmacology models: a case study in type 2 diabetes 定量系统药理学模型开发和应用中的算法和方法挑战:2型糖尿病的案例研究
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-11-01 DOI: 10.1515/rnam-2022-0025
V. Sokolov
Abstract Quantitative systems pharmacology (QSP) is a relatively new modelling discipline, formed within the ever-growing domain of model-informed drug development and actively evolving throughout the last decade. This modelling technique is based on the systems analysis and is used to get a quantitative rather than qualitative understanding of systems dynamics and explore the mechanisms of action of a drug. However, there is no well-defined methodology for the QSP model development, which significantly complicates the practical application of these models. In the current work, we overview the existing mathematical models of antidiabetic therapies and propose a modelling method, which overcomes common limitations and is able to produce a physiologically based mechanistic model describing gliflozin action in type 2 diabetes mellitus. From the practical standpoint, sensitivity analysis preformed in this work helped to reveal subpopulation of patients with better response to gliflozin therapy.
摘要定量系统药理学(QSP)是一门相对较新的建模学科,形成于不断增长的模型知情药物开发领域,并在过去十年中积极发展。这种建模技术基于系统分析,用于对系统动力学进行定量而非定性的理解,并探索药物的作用机制。然而,QSP模型开发没有定义明确的方法,这使这些模型的实际应用变得非常复杂。在目前的工作中,我们概述了现有的抗糖尿病治疗数学模型,并提出了一种建模方法,该方法克服了常见的局限性,能够产生一个基于生理学的机制模型来描述格列净在2型糖尿病中的作用。从实用的角度来看,这项工作中进行的敏感性分析有助于揭示对格列净治疗有更好反应的患者亚群。
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引用次数: 0
Optimal disturbances for periodic solutions of time-delay differential equations 时滞微分方程周期解的最优扰动
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-08-01 DOI: 10.1515/rnam-2022-0017
M. Y. Khristichenko, Y. Nechepurenko
Abstract A concept of optimal disturbances of periodic solutions for a system of time-delay differential equations is defined. An algorithm for computing the optimal disturbances is proposed and justified. This algorithm is tested on the known system of four nonlinear time-delay differential equations modelling the dynamics of the experimental infection caused by the lymphocytic choriomeningitis virus. The results of numerical experiments are discussed.
摘要定义了一类时滞微分方程组周期解的最优扰动概念。提出并证明了一种计算最优扰动的算法。该算法在已知的四个非线性时滞微分方程组上进行了测试,该方程组模拟了淋巴细胞性脉络膜脑膜炎病毒引起的实验性感染的动力学。讨论了数值实验的结果。
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引用次数: 1
Linear regularized finite difference scheme for the quasilinear subdiffusion equation 拟线性次扩散方程的线性正则化有限差分格式
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-08-01 DOI: 10.1515/rnam-2022-0019
A. Lapin, E. Laitinen
Abstract A homogeneous Dirichlet initial-boundary value problem for a quasilinear parabolic equation with a time-fractional derivative and coefficients at the elliptic part that depend on the gradient of the solution is considered. Conditions on the coefficients ensure the monotonicity and Lipschitz property of the elliptic operator on the set of functions whose gradients in space variables are uniformly bounded. For this problem, a linear regularized mesh scheme is constructed and investigated. A sufficient condition is derived for the regularization parameter that ensures the so-called local correctness of the mesh scheme. On the basis of correctness and approximation estimates for model problems with time-fractional Caputo or Caputo–Fabrizio derivatives, accuracy estimates are given in terms of mesh and regularization parameters under the assumption of the existence of a smooth solution to the differential problem. The presented results of the numerical experiments confirm the obtained asymptotic accuracy estimates.
摘要考虑一类导数为时间分数阶的拟线性抛物方程的齐次Dirichlet初边值问题,椭圆部分的系数依赖于解的梯度。系数的条件保证了椭圆算子在梯度在空间变量上一致有界的函数集合上的单调性和Lipschitz性质。针对这一问题,构造并研究了线性正则化网格格式。导出了保证网格方案局部正确性的正则化参数的充分条件。在时间分数Caputo或Caputo - fabrizio导数模型问题的正确性和近似估计的基础上,在微分问题光滑解存在的假设下,给出了基于网格和正则化参数的精度估计。给出的数值实验结果证实了所得到的渐近精度估计。
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引用次数: 0
Glacier parameterization in SLAV numerical weather prediction model SLAV数值天气预报模型中的冰川参数化
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-08-01 DOI: 10.1515/rnam-2022-0016
R. Fadeev, K. Alipova, Anna S. Koshkina, Timofey E. Lapin, N. Ozerova, Alina E. Pereladova, Andrey V. Sakhno, M. Tolstykh
Abstract In the present paper, we describe a one-dimensional glacier parameterization for use in the numerical weather prediction models. The proposed scheme is implemented into the global atmospheric model SLAV. To avoid inconsistency of surface temperature and turbulent heat fluxes in the lower troposphere, glacier parameterization has been iteratively coupled with both planetary boundary layer and land surface schemes. First results from numerical experiments with the SLAV model show that the introduction of a simplified description of the glacier heat capacity can significantly improve the 2-meter temperature long-range weather forecast skill.
摘要在本文中,我们描述了一种用于数值天气预测模型的一维冰川参数化。该方案已应用于全球大气模式SLAV中。为了避免对流层低层表面温度和湍流热通量的不一致性,冰川参数化与行星边界层和陆地表面方案反复耦合。SLAV模型的首次数值实验结果表明,引入冰川热容的简化描述可以显著提高2米温度的长期天气预报技能。
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引用次数: 0
On the efficiency of using correlative randomized algorithms for solving problems of gamma radiation transfer in stochastic medium 用相关随机算法求解随机介质中伽马辐射传递问题的效率
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-08-01 DOI: 10.1515/rnam-2022-0020
I. N. Medvedev
Abstract To solve problems of radiation balance, optical sounding, and tomography, it may be necessary to take into account multiple scattering of radiation in a stochastically inhomogeneous medium. In real radiation models, for this purpose, the numerical-statistical ‘majorant cross-section method’ (MCM, delta-Woodcock tracking) is used based on the alignment of the optical density field by adding an artificial ‘delta scattering’ event. However, the computation cost of the corresponding unbiased estimate of the averaged problem solution infinitely increases as the correlation scale (correlation radius L) of standard mosaic models for a random medium density decreases. Previously, we constructed the MCM randomization providing asymptotically (for L → 0) unbiased estimates of the required functionals, in which the value of the physical attenuation coefficient is randomly chosen at the end of the particle free path l under condition l > L. Otherwise the value of the physical attenuation coefficient is the same as at the starting point of the particle (CR algorithm). In a more accurate functional correlative randomized algorithm (FCR algorithm), the coefficient remains the same with a probability determined by the correlation function. These correlative randomized algorithms were implemented for a mixture of homogeneous substance (water) and a Poisson ensemble of ‘empty’ balls. In the present paper, we construct correlative randomized algorithms for problems related to transfer through a ‘thick’ layer containing a water and a Poisson ensemble of ‘empty’ layers. A detailed comparative analysis of the results obtained by exact direct simulation (MCM) and approximate algorithms (CR, FCR) for the problems of gamma radiation transfer through a ‘thick’ water layer containing a Poisson ensemble of ‘empty’ layers or balls is presented.
为了解决辐射平衡、光学探测和层析成像等问题,可能需要考虑随机非均匀介质中辐射的多次散射。在真实的辐射模型中,为此目的,通过添加人工的“三角洲散射”事件,基于光密度场的对准,使用了数值统计的“主截面法”(MCM, delta- woodcock跟踪)。然而,对于随机介质密度,随着标准镶嵌模型的相关尺度(相关半径L)的减小,相应的平均问题解的无偏估计的计算量会无限增加。之前,我们构建了MCM随机化,提供了所需函数的渐近(对于L→0)无偏估计,其中物理衰减系数的值在条件L > L下随机选择在粒子自由路径L的末端,否则物理衰减系数的值与粒子的起点相同(CR算法)。在更精确的函数相关随机化算法(FCR算法)中,系数保持不变,其概率由相关函数决定。这些相关的随机算法被用于均质物质(水)和“空”球的泊松系综的混合物。在本文中,我们构造了相关的随机化算法,用于解决通过含有水的“厚”层和“空”层的泊松系综的传输问题。对伽玛辐射通过含有“空”层或球的泊松系综的“厚”水层传输问题,用精确直接模拟(MCM)和近似算法(CR, FCR)得到的结果进行了详细的比较分析。
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引用次数: 0
Error identities for the reaction–convection–diffusion problem and applications to a posteriori error control 反应-对流-扩散问题的误差恒等式及其在后验误差控制中的应用
IF 0.6 4区 数学 Q4 MATHEMATICS, APPLIED Pub Date : 2022-08-01 DOI: 10.1515/rnam-2022-0021
S. Repin
Abstract The paper is devoted to a posteriori error identities for the stationary reaction–convection–diffusion problem with mixed Dirichlét–Neumann boundary conditions. They reflect the most general relations between deviations of approximations from the exact solutions and those values that can be observed in a numerical experiment. The identities contain no mesh dependent constants and are valid for any function in the admissible (energy) class. Therefore, the identities and the estimates that follow from them generate universal and fully reliable tools of a posteriori error control.
研究了一类具有混合dirichl - neumann边界条件的稳态反应-对流-扩散问题的后验误差恒等式。它们反映了从精确解的近似偏差和在数值实验中可以观察到的那些值之间的最一般的关系。恒等式不包含网格相关常数,并且对可容许(能量)类中的任何函数都有效。因此,恒等式和由此产生的估计产生了普遍和完全可靠的后验误差控制工具。
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引用次数: 0
期刊
Russian Journal of Numerical Analysis and Mathematical Modelling
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