A Strategy for Integrative Computational Physiology

Hunter, Peter; Nielsen, Poul

doi:10.1152/physiol.00022.2005

Cited by 118 publications

(76 citation statements)

References 56 publications

(48 reference statements)

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“…For example, the SHG signal from semicrystalline myosin structures may infer the etiology of muscular dystrophy, 26,27 ascertain the basis of tissue contractility, 28 or reveal sarcomere disruption. 29 By linking such cellular and molecular scale information with tissue scale myoarchitecture and mechanics, it may thus be feasible to consider multiscale models 30 of normal and pathological organ function. …”

Section: Resultsmentioning

confidence: 99%

Multiscale structural analysis of mouse lingual myoarchitecture employing diffusion spectrum magnetic resonance imaging and multiphoton microscopy

et al. 2008

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Abstract. The tongue consists of a complex, multiscale array of myofibers that comprise the anatomical underpinning of lingual mechanical function. 3-D myoarchitecture was imaged in mouse tongues with diffusion spectrum magnetic resonance imaging ͑DSI͒ at 9.4 T ͑b max 7000 s / mm, 150-m isotropic voxels͒, a method that derives the preferential diffusion of water/voxel, and high-throughput ͑10 fps͒ two-photon microscope ͑TPM͒. Net fiber alignment was represented for each method in terms of the local maxima of an orientational distribution function ͑ODF͒ derived from the local diffusion ͑DSI͒ and 3-D structural autocorrelation ͑TPM͒, respectively. Mesoscale myofiber tracts were generated by alignment of the principal orientation vectors of the ODFs. These data revealed a consistent relationship between the properties of the respective ODFs and the virtual superimposition of the distributed mesoscale myofiber tracts. The identification of a mesoscale anatomical construct, which specifically links the microscopic and macroscopic spatial scales, provides a method for relating the orientation and distribution of cells and subcellular components with overall tissue morphology, thus contributing to the development of multiscale methods for mechanical analysis.

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Section: Resultsmentioning

confidence: 99%

Multiscale structural analysis of mouse lingual myoarchitecture employing diffusion spectrum magnetic resonance imaging and multiphoton microscopy

et al. 2008

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“…For example, the recent work of Burrowes et al 77,86 and Huang et al 87 using computational fluid dynamics to describe blood transport within large and small pulmonary vessels has the potential to be incorporated into a global model of the lung circulatory system, along the lines suggested recently by Hunter and Nielsen. 79 Multiscale mathematical modeling link in the citation at the bottom of the page. …”

Section: Resultsmentioning

confidence: 99%

“…Although cardiac output, and hence pulmonary input, is pulsatile, their work, and other models that assume steady flow, is relevant because measurements of the pulmonary circulation indicate that the dominant component of pulmonary vascular impedance resides at the zero frequency. 78 Thus, in the pulmonary circulation model presented here, particularly for studies in which the pulmonary circulation is perfused with a constant pump flow, Occam's razor is employed 79 and pulmonary vessels are modeled using the assumption of steady flow in an idealized cylindrical blood vessel. Fig.…”

Section: Functional Implicationsmentioning

confidence: 99%

Lung Circulation Modeling: Status and Prospect

Clough

Audi²,

Molthen³

et al. 2006

Proc. IEEE

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Mathematical modeling has been used to interpret anatomical and physiological data obtained from metabolic and hemodynamic studies aimed at investigating structure-function relationships in the vasculature of the lung, and how these relationships are affected by lung injury and disease. The indicator dilution method was used to study the activity of redox processes within the lung. A steadystate model of the data was constructed and used to show that pulmonary endothelial cells may play an important role in reducing redox active compounds and that those reduction rates can be altered with oxidative stress induced by exposure to high oxygen environments. In addition, a morphometric model NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page. 2 of the pulmonary vasculature was described and used to detect, describe,and predict changes in vascular morphology that occur in response to chronic exposure to low-oxygen environments, a common model of pulmonary hypertension. Finally, the model was used to construct simulated circulatory networks designed to aid in evaluation of competing hypotheses regarding the relative contribution of various morphological and biomechanical changes observed with hypoxia. These examples illustrate the role of mathematical modeling in the integration of the emerging metabolic, hemodynamic, and morphometric databases. Proceedings of the IEEE,

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“…Examples of mechanistic modeling on the level of organs can also be seen in the modeling of human organs in the International Union of Physiological Sciences (IUPS) Physiome Project (www.physiome.org.nz/), for instance, the mechanical and anatomical/physiological modeling of the human heart (Noble, 2008). Although the ambition of the Physiome project is to span and integrate levels of organization ranging from molecular components to organs and beyond, it is acknowledged that no one model can encompass this wide range of organization levels in all detail (Hunter and Nielsen, 2005). Instead, the ambition is to establish a framework for handling a hierarchy of computational models in which the parameters of a particular model in the hierarchy can be understood in terms of the physics or chemistry of the appropriate model(s) at a lower hierarchical level.…”

Section: Iterative and Integrativementioning

confidence: 99%

Systems biology in animal sciences

Woelders

Pas

Bannink

et al. 2011

Animal

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Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed 'omics' technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A 'system' approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with 'system approaches' in animal sciences, providing exciting opportunities to predict and modulate animal traits.

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A Strategy for Integrative Computational Physiology

Cited by 118 publications

References 56 publications

Multiscale structural analysis of mouse lingual myoarchitecture employing diffusion spectrum magnetic resonance imaging and multiphoton microscopy

Multiscale structural analysis of mouse lingual myoarchitecture employing diffusion spectrum magnetic resonance imaging and multiphoton microscopy

Lung Circulation Modeling: Status and Prospect

Systems biology in animal sciences

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