Research Topics
| DANIEL BEARDSummaryAffiliation: Medical College of Wisconsin Country: USA Publications
Research Grants
| Collaborators
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Detail Information
Publications
Linear analysis near a steady-state of biochemical networks: control analysis, correlation metrics and circuit theoryWilliam J Heuett
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
BMC Syst Biol 2:44. 2008..Here, we present a comprehensive theory of linear analysis for nonequilibrium steady-state (NESS) biochemical reaction networks that unites these disparate approaches in a common mathematical framework and thermodynamic basis...- Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heartFan Wu
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
BMC Syst Biol 3:22. 2009.... - Generating rate equations for complex enzyme systems by a computer-assisted systematic methodFeng Qi
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
BMC Bioinformatics 10:238. 2009..Furthermore, none is freely available for download and use by the community... - Understanding Guyton's venous return curvesDaniel A Beard
Department of Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Am J Physiol Heart Circ Physiol 301:H629-33. 2011..Because Guyton's venous return curves have generated much confusion and little clarity, we suggest that the concept and previous interpretations of venous return be removed from educational materials... 
Relationship between thermodynamic driving force and one-way fluxes in reversible processesDaniel A Beard
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
PLoS ONE 2:e144. 2007....- Detailed enzyme kinetics in terms of biochemical species: study of citrate synthaseDaniel A Beard
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
PLoS ONE 3:e1825. 2008..This analysis provides a mechanistic model that is consistent with the data that have been used support competing hypotheses regarding the catalytic mechanism of this enzyme... - A biophysical model of the mitochondrial respiratory system and oxidative phosphorylationDaniel A Beard
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
PLoS Comput Biol 1:e36. 2005..The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics... - Modeling of oxygen transport and cellular energetics explains observations on in vivo cardiac energy metabolismDaniel A Beard
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America
PLoS Comput Biol 2:e107. 2006..In addition, the validated model provides quantitative predictions of changes in phosphate metabolites during cardiac ischemia... 
Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolismDaniel A Beard
Biotechnology and Bioengineering Center, Dept of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
Am J Physiol Endocrinol Metab 288:E633-44. 2005....- Thermodynamic constraints for biochemical networksDaniel A Beard
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
J Theor Biol 228:327-33. 2004.... 
Modeling of cellular metabolism and microcirculatory transportDaniel A Beard
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Microcirculation 15:777-93. 2008..This tight integration between cellular metabolism and microcirculatory transport begs for integrative simulations that span the cell, tissue, and organ scales...- Apparent diffusivity and Taylor dispersion of water and solutes in capillary bedsDaniel A Beard
Department of Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Bull Math Biol 71:1366-77. 2009..Measurement of the ratio of axial to transverse diffusivity may be combined with an independent measurement of perfusion to provide an estimate of capillary vessel density in the tissue... - Creatine and phosphate pools are maintained at energetically optimal levels in the heart during hypertrophic remodeling and heart failureDaniel A Beard
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Conf Proc IEEE Eng Med Biol Soc 2009:4487-90. 2009.... - Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiologyFan Wu
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 282:24525-37. 2007.... - Phosphate metabolite concentrations and ATP hydrolysis potential in normal and ischaemic heartsFan Wu
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wiscosin, Milwaukee, WI 53213, USA
J Physiol 586:4193-208. 2008..Due to the lack of precise quantification of P(i) in vivo, these hypotheses and associated model predictions remain to be carefully tested experimentally... - A biophysically based mathematical model for the kinetics of mitochondrial Na+-Ca2+ antiporterRanjan K Pradhan
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Biophys J 98:218-30. 2010.... - Mitochondrial free [Ca2+] increases during ATP/ADP antiport and ADP phosphorylation: exploration of mechanismsJohan Haumann
Anesthesiology Research Laboratories, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Biophys J 99:997-1006. 2010..These data suggest that matrix ADP influx and subsequent phosphorylation increase [Ca2+](m) largely due to the interaction of matrix Ca2+ with ATP, ADP, P(i), and cation buffering proteins in the matrix... - Detailed kinetics and regulation of mammalian NAD-linked isocitrate dehydrogenaseFeng Qi
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, USA
Biochim Biophys Acta 1784:1641-51. 2008..In addition, the enzyme is highly sensitive to Mg(2+) concentration in the physiological range, pointing to a potential regulatory role of [Mg(2+)] in mitochondrial energy metabolism... - Oxidative ATP synthesis in skeletal muscle is controlled by substrate feedbackFan Wu
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Am J Physiol Cell Physiol 292:C115-24. 2007.... - Kinetics and regulation of mammalian NADH-ubiquinone oxidoreductase (Complex I)Xuewen Chen
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Biophys J 99:1426-36. 2010..The overall kinetic analysis demonstrates a hybrid ping-pong rapid-equilibrium random bi-bi mechanism, consolidating the characteristics from previously reported kinetic mechanisms and data... - A biophysically based mathematical model for the kinetics of mitochondrial calcium uniporterRanjan K Dash
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Biophys J 96:1318-32. 2009.... - Design of experiments for identification of complex biochemical systems with applications to mitochondrial bioenergeticsKalyan C Vinnakota
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Conf Proc IEEE Eng Med Biol Soc 2009:4171-4. 2009..Experimental perturbations and variables yielding the most number of parameters above a 5% sensitivity level are presented and discussed... - The role of theoretical modeling in microcirculation researchTimothy W Secomb
Department of Physiology, University of Arizona, Tucson, Arizona 85724, USA
Microcirculation 15:693-8. 2008..The concepts discussed are generally applicable to the theoretical modeling of biological systems and are illustrated by using examples of modeling in microcirculation research... - Experimentally observed phenomena on cardiac energetics in heart failure emerge from simulations of cardiac metabolismFan Wu
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Proc Natl Acad Sci U S A 106:7143-8. 2009..Thus, both increases and decreases to the creatine pool are predicted to result in diminished energetic state unless accompanied by appropriate simultaneous changes in the other pools... - Ab initio prediction of thermodynamically feasible reaction directions from biochemical network stoichiometryFeng Yang
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
Metab Eng 7:251-9. 2005..We show that for a reaction network of 44 internal reactions representing energy metabolism, the computed linear inequality constraints represent necessary and sufficient conditions for thermodynamic feasibility... - Analysis of cardiac mitochondrial Na+-Ca2+ exchanger kinetics with a biophysical model of mitochondrial Ca2+ handling suggests a 3:1 stoichiometryRanjan K Dash
Biotechnology and Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226 6509, USA
J Physiol 586:3267-85. 2008..Based on these analyses, it is concluded that the mitochondrial NCE is electrogenic with a stoichiometry of 3:1... - Identifying physiological origins of baroreflex dysfunction in salt-sensitive hypertension in the Dahl SS ratScott M Bugenhagen
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Physiol Genomics 42:23-41. 2010.... - Thermodynamically based profiling of drug metabolism and drug-drug metabolic interactions: a case study of acetaminophen and ethanol toxic interactionFeng Yang
Biotechnology and Bioengineering Center, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States
Biophys Chem 120:121-34. 2006..These results point to the potential utility of thermodynamically based profiling of metabolic network interactions in screening of drug candidates and analysis of potential toxicity... - Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic modelFeng Yang
Department of Physiology, Medical College of Wisconsin, Biotechnology and Bioengineering Center, Milwaukee, WI 53226, USA
J Pharmacokinet Pharmacodyn 33:485-518. 2006..In addition, it is shown that when doses are designed for individuals based on prior protein expression information, inter-individual variability in methadone kinetics may be greatly reduced... - Multiple ion binding equilibria, reaction kinetics, and thermodynamics in dynamic models of biochemical pathwaysKalyan C Vinnakota
Biotechnology and Bioengineering Center and Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Methods Enzymol 454:29-68. 2009..Several applications to physiological systems are demonstrated based on this coherent simulation framework... - Computational analyses of intravascular tracer washout reveal altered capillary-level flow distributions in obese Zucker ratsFan Wu
Biotechnology and Bioengineering Centre and Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
J Physiol 589:4527-43. 2011.... - Differential expression of cardiac mitochondrial proteinsJulia R Smith
Biotechnology Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
Proteomics 8:446-62. 2008..Mathematical modeling of mitochondrial electron transport predicted that the observed change in ETFA expression may result in decreased activity of the electron transport chain... - The effects of reversibility and noise on stochastic phosphorylation cycles and cascadesClark A Miller
Department of Chemical and Biological Engineering, University of Wisconsin Madison, USA
Biophys J 95:2183-92. 2008..Likewise, the variance in the response can be maximized or minimized by tuning the number of enzymes in the second cycle... - Energy balance for analysis of complex metabolic networksDaniel A Beard
Department of Bioengineering, University of Washington, Seattle, Washington 98915, USA
Biophys J 83:79-86. 2002..We show that EBA eliminates thermodynamically infeasible results associated with FBA... - Optical spectroscopy demonstrates elevated intracellular oxygenation in an endotoxic model of sepsis in the perfused heartKenneth A Schenkman
Departments of Pediatrics, University of Washington, Seattle, Washington, USA
Shock 27:695-700. 2007..Cellular dysfunction seen in sepsis may be caused by compromised oxygen use rather than insufficient oxygen delivery. Optical spectroscopy has the potential to noninvasively monitor patients and their responses to therapy... - Myocardial oxygenation in isolated hearts predicted by an anatomically realistic microvascular transport modelDaniel A Beard
Department of Bioengineering, University of Washington, Box 352255, Seattle, WA 98195, USA
Am J Physiol Heart Circ Physiol 285:H1826-36. 2003..It is incorrect to assume that the usual buffer-perfused Langendorff heart preparation is adequately oxygenated for flows in the range of < or =10 ml. min-1. ml tissue-1... - Extreme pathways and Kirchhoff's second lawNathan D Price
Biophys J 83:2879-82. 2002 - Computational modeling of physiological systemsDaniel A Beard
Physiol Genomics 23:1-3; discussion 4. 2005 - Constructing irregular surfaces to enclose macromolecular complexes for mesoscale modeling using the discrete surface charge optimization (DISCO) algorithmQing Zhang
Department of Chemistry and Courant Institute of Mathematical Sciences, New York University and the Howard Hughes Medical Institute, 251 Mercer St, New York, New York 10012, USA
J Comput Chem 24:2063-74. 2003..DiSCO is generally applicable to other interesting macromolecular systems for which mesoscale models are appropriate, to yield a resolution between the all-atom representative and the polymer level... - Myocardial oxygenation and adenosine release in isolated guinea pig hearts during changes in contractilityJ Chiaka Ejike
Department of Pediatrics, University of Washington, Seattle, Washington 98105, USA
Am J Physiol Heart Circ Physiol 288:H2062-7. 2005.... - Stoichiometric network theory for nonequilibrium biochemical systemsHong Qian
Department of Applied Mathematics and Bioengineering, University of Washington, Seattle, USA
Eur J Biochem 270:415-21. 2003..For sufficiently small flux a linear relationship between J and deltamu can be established as the linear flux-force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits... - Comparison of buffer and red blood cell perfusion of guinea pig heart oxygenationKenneth A Schenkman
Anesthesia and Critical Care 9 G1, Children s Hospital and Regional Medical Center, 4800 Sand Point Way NE, Seattle, WA 98105, USA
Am J Physiol Heart Circ Physiol 285:H1819-25. 2003..These results suggest that caution should be used in extrapolating intracellular oxygen dynamics from buffer-perfused to blood-perfused hearts... - Unbiased rotational moves for rigid-body dynamicsDaniel A Beard
Department of Bioengineering, University of Washington, Seattle, Washington, USA
Biophys J 85:2973-6. 2003..Our algorithm should thus replace standard approaches to rotate local coordinate frames in Langevin and Brownian dynamics simulations... - Thermodynamics of stoichiometric biochemical networks in living systems far from equilibriumHong Qian
Departments of Applied Mathematics and Bioengineering, University of Washington, Seattle, 98195, USA
Biophys Chem 114:213-20. 2005..Energy conservation and the Second Law are established for steady-state and dynamic biochemical networks. The theory provides the physiochemical basis for analyzing large-scale metabolic networks in living organisms... - Systems biology of the mitochondrionDaniel A Beard
Am J Physiol Cell Physiol 291:C1101-3. 2006
Research Grants
- Mechanisms of Metabolic Dysfunction in Heart DiseaseDaniel A Beard; Fiscal Year: 2010..These data will be used in Aim 2 for model development, parameterization, and validation. Development and application of tissue-level modeling and simulation tools are pursued in Aim 3. ..
- Integrated Modeling of Cardiac Metabolism and TransportDANIEL BEARD; Fiscal Year: 2009..In addition, our proposed tools for simulation of the pathophysiological operation of metabolic control mechanisms in heart disease may be used to guide clinical interventions aimed at modulation of cardiac energy metabolism. ..
- Mechanisms of Metabolic Dysfunction in Heart DiseaseDANIEL BEARD; Fiscal Year: 2009..These data will be used in Aim 2 for model development, parameterization, and validation. Development and application of tissue-level modeling and simulation tools are pursued in Aim 3. ..
- Analysis of Large-Scale Biochemical SystemsDANIEL BEARD; Fiscal Year: 2007..In addition, the computational tools that are developed by this research program will be disseminated through a partnership with a software company. ..
- MSM Multiscale Modeling of the Heart in CardiovascularDANIEL BEARD; Fiscal Year: 2007..abstract_text> ..
- Integrated Modeling of Cardiac Metabolism and TransportDANIEL BEARD; Fiscal Year: 2007..Further applications of the proposed integrated model include profiling physiological responses to several challenges, such as (1) exercise; (2) ischemia; and (3) myoglobin and adenylate kinase gene deletions. ..
- Integrated Modeling of Cardiac Metabolism and TransportDaniel A Beard; Fiscal Year: 2010..In addition, our proposed tools for simulation of the pathophysiological operation of metabolic control mechanisms in heart disease may be used to guide clinical interventions aimed at modulation of cardiac energy metabolism. ..