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细胞功能测定

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Design of Experiments to Investigate Dynamic Cell Signaling Models

This chapter describes approaches to make use of dynamic models of cell signaling systems in order to optimize experiments in cell biology. We are particularly focusing on the question of how small molecule inhibitors or activators can best be used to get the most information out of a limited numb ...

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Modeling miRNA Regulation in Cancer Signaling Systems: miR-34a Regulation of the p53/Sirt1 Signaling Module

MicroRNAs (miRNAs) are a family of small regulatory RNAs whose function is to regulate the activity and stability of specific messenger RNA targets through posttranscriptional regulatory mechanisms. Most of the times signaling systems involving miRNA modulation are not linear pa ...

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Mathematical Investigation of How Oncogenic Ras Mutants Promote Ras Signaling

We have used a mathematical model of the Ras signaling network to link observable biochemical properties with cellular levels of RasGTP. Although there is abundant data characterizing Ras biochemistry, attributing specific changes in biochemical properties to observed phenot ...

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Bistability in One Equation or Fewer

When several genes or proteins modulate one another’s activity as part of a network, they sometimes produce behaviors that no protein could accomplish on its own. Intuition for these emergent behaviors often cannot be obtained simply by tracing causality through the network in discreet st ...

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A Tutorial on Mathematical Modeling of Biological Signaling Pathways

Mathematical models have been widely used in the studies of biological signaling pathways. Among these studies, two systems biology approaches have been applied: top-down and bottom-up systems biology. The former approach focuses on X-omics researches involving the measurement of ...

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Analyzing and Constraining Signaling Networks: Parameter Estimation for the User

The behavior of most dynamical models not only depends on the wiring but also on the kind and strength of interactions which are reflected in the parameter values of the model. The predictive value of mathematical models therefore critically hinges on the quality of the parameter estimates. Con ...

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Predictive Models for Cellular Signaling Networks

This chapter provides an introduction to the formulation and analysis of differential-equation-based models for biological regulatory networks. In the first part, we discuss basic reaction types and the use of mass action kinetics and of simplifying approximations in the developm ...

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Analytic Methods for Modeling Stochastic Regulatory Networks

Recent single-cell experiments have revived interest in the unavoidable or intrinsic noise in biochemical and genetic networks arising from the small number of molecules of the participating species. That is, rather than modeling regulatory networks in terms of the deterministic d ...

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Discrete Dynamic Modeling of Signal Transduction Networks

Newly available experimental data characterizing different processes involved in signaling pathways have provided the opportunity for network analysis and modeling of these interacting pathways. Current approaches in studying the dynamics of signaling networks fall in ...

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Modeling Spatiotemporal Dynamics of Bacterial Populations

Quantitative modeling of spatiotemporal dynamics of cells facilitates understanding and engineering of biological systems. Using a synthetic bacterial ecosystem as a workbench, we present the approach to mathematically simulate the spatiotemporal population dynamics ...

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Computational Modeling of Signal Transduction Networks: A Pedagogical Exposition

We give a pedagogical introduction to computational modeling of signal transduction networks, starting from explaining the representations of chemical reactions by differential equations via the law of mass action. We discuss elementary biochemical reactions such as Michae ...

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Heart Xenotransplantation in Primate Models

Xenotransplantation is a potential solution for the worldwide persisting donor organ shortage. However, immunological and physiological barriers need to be overcome before the first clinical trials can be started. Nonhuman primates are considered the most suitable recipien ...

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Xenogeneic Lung Transplantation Models

Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation are briefly reviewed and two different experimental models, the ex v ...

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Thymic Transplantation in Pig-to-Nonhuman Primates for the Induction of Tolerance Across Xenogeneic Barriers

With the advent of knockout pigs for α1,3-galactosyltransferease (GalT-KO, which lack a cell-surface antigen to which humans have preformed antibodies), investigators have extended the survival of life-supporting xenorenal grafts. However, despite these increases, nonhum ...

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Isolation of Porcine Pancreatic Islets for Xenotransplantation

This chapter deals with a technique for isolating intact islets of Langerhans from the pig pancreas based on our experience performing approximately 750 isolations. The procedure we describe involves identification of an optimal donor pancreas, purification and in vitro culture of i ...

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Pig Neural Cells Derived from Foetal Mesencephalon as Cell Source for Intracerebral Xenotransplantation

Intracerebral cell transplantation offers the possibility of replacing lost neurons in case of neurodegenerative disorders. To date, the best functional recovery for Parkinson’s patients has been obtained using neuroblasts derived from human foetal mesencephalon, but the et ...

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Hepatocyte Xenotransplantation

Xenotransplantation of hepatocytes is a future promise to treat liver diseases when there is a formal indication for transplantation. In this chapter, we describe techniques for hepatocyte xenotransplantation. The process was divided into three main steps: hepatocyte isolatio ...

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Potential Zoonotic Infection of Porcine Endogenous Retrovirus in Xenotransplantation

Porcine endogenous retrovirus (PERV) is considered the major biosafety issue in xenotransplantation. Several techniques have been employed for the analysis of the PERV status in the animal donor and for the assessment of PERV transmission/infection in the xenograft recipient. In th ...

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In Vitro Repair Model of Focal Articular Cartilage Defects in Humans

Articular cartilage lesions, which do not affect the integrity of subchondral bone, are not able to be repaired spontaneously, thus inducing cartilage degeneration and developing an arthrosic process. To avoid the need for prosthetic replacement, different cell treatments were de ...

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Ethical and Regulatory Issues for Clinical Trials in Xenotransplantation

Clinical trials in xenotransplantation (XTx) that have just started to fulfil a long delayed promise should certainly be performed under the same guarantees for the subjects involved as any other experimentation in human medicine. The most important is the absolute respect for their fun ...

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