Daniel Beard
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View article: A Microstructurally-Motivated Framework to Study Autoregulation in the Coronary Circulation
A Microstructurally-Motivated Framework to Study Autoregulation in the Coronary Circulation Open
Coronary autoregulation maintains relatively constant myocardial flow over a wide range of perfusion pressures through myogenic, shear-dependent, and metabolic control mechanisms. Understanding this phenomenon is challenging due to the cou…
View article: Impairment of local metabolic coronary control involves perfusion-contraction matching not supply–demand imbalance
Impairment of local metabolic coronary control involves perfusion-contraction matching not supply–demand imbalance Open
View article: Deep learning-based phenotyping and assessment of treatment responses in heart failure with preserved ejection fraction
Deep learning-based phenotyping and assessment of treatment responses in heart failure with preserved ejection fraction Open
Background Heart failure with preserved ejection fraction (HFpEF) accounts for over half of heart failure cases, yet effective treatments remain limited due to the syndrome’s clinical heterogeneity. Purpose This study aimed to identify dis…
View article: Immersion‐Based Clearing and Autofluorescence Quenching in Myocardial Tissue
Immersion‐Based Clearing and Autofluorescence Quenching in Myocardial Tissue Open
Objective Recent innovations in optical microscopy and tissue preparation permit 3D visualization of complex microvascular networks. Tissue clearing techniques improve light penetration and extend imaging depth. Typically, perfusion‐based …
View article: Multiscale Computational Modeling of the Cardiopulmonary Consequences of Postnatal Hyperoxia with Implications for Preterm Born Children
Multiscale Computational Modeling of the Cardiopulmonary Consequences of Postnatal Hyperoxia with Implications for Preterm Born Children Open
Moderate to extreme preterm birth (<32 weeks gestation) affects cardiopulmonary structure and function and is associated with increased risk of heart failure through adulthood. Rodent models capture biventricular changes, including at the …
View article: Machine learning-based phenotyping and assessment of treatment responses in heart failure with preserved ejection fraction
Machine learning-based phenotyping and assessment of treatment responses in heart failure with preserved ejection fraction Open
View article: Theoretical analysis of power‐law stress relaxation and calcium‐dependent passive mechanics in cardiac muscle
Theoretical analysis of power‐law stress relaxation and calcium‐dependent passive mechanics in cardiac muscle Open
This study investigates the passive viscoelastic properties of cardiac muscle by introducing a theoretical model that explains the observed power‐law kinetics of murine cardiac trabeculae passive stress decay. The model accounts for two pa…
View article: Kinetic Modeling of mant-ATP Turnover to Interpret the Biochemically Defined Myosin Super-Relaxed State
Kinetic Modeling of mant-ATP Turnover to Interpret the Biochemically Defined Myosin Super-Relaxed State Open
The fluorescent ATP analog mant-ATP has become a valuable tool for quantifying occupancy of the myosin super-relaxed (SRX) state, a biochemically inactive conformation of myosin in striated muscle. Interpretation of mant-ATP fluorescence d…
View article: Ca2+ increases cardiac muscle viscoelasticity independent of active force development
Ca2+ increases cardiac muscle viscoelasticity independent of active force development Open
In addition to activation of muscle contraction by Ca2+, previous studies suggest that Ca2+ also affects muscle passive mechanical properties. The goal of this study was to determine if Ca2+ regulates the s…
View article: Development of a Quantitative Systems Pharmacology Model to Interrogate Mitochondrial Metabolism in Heart Failure
Development of a Quantitative Systems Pharmacology Model to Interrogate Mitochondrial Metabolism in Heart Failure Open
The metabolic hallmarks of heart failure (HF) include diminished ATP hydrolysis potential and alterations in myocardial energy substrate metabolism, such as a switch in substrate utilization away from fatty acid (FA) to carbohydrate oxidat…
View article: Dynamic balance of myoplasmic energetics and redox state in a fast-twitch oxidative glycolytic skeletal muscle fiber
Dynamic balance of myoplasmic energetics and redox state in a fast-twitch oxidative glycolytic skeletal muscle fiber Open
In order to investigate the mechanisms governing energy and redox balance in skeletal muscle, we developed a computational model describing the coupled biochemical reaction network of glycolysis and mitochondrial oxidative phosphorylation …
View article: Ca<sup>2+</sup>increases cardiac muscle viscoelasticity independent of active force development
Ca<sup>2+</sup>increases cardiac muscle viscoelasticity independent of active force development Open
In addition to activation of muscle contraction by Ca 2+ , recent studies suggest that Ca 2+ also affects muscle passive mechanical properties. The goal of this study was to determine if Ca 2+ regulates the stiffness of cardiac muscle, ind…
View article: Theoretical Analysis of Power-Law Stress Relaxation and Calcium-Dependent Passive Mechanics in Cardiac Muscle
Theoretical Analysis of Power-Law Stress Relaxation and Calcium-Dependent Passive Mechanics in Cardiac Muscle Open
This study investigates the passive viscoelastic mechanical properties of cardiac muscle by introducing a theoretical model that explains the power-law kinetics of passive stress decay. The model accounts for two parallel processes contrib…
View article: Identification of digital twins to guide interpretable AI for diagnosis and prognosis in heart failure
Identification of digital twins to guide interpretable AI for diagnosis and prognosis in heart failure Open
View article: A Hands-On Introduction to Data Analytics for Biomedical Research
A Hands-On Introduction to Data Analytics for Biomedical Research Open
Artificial intelligence (AI) applications are having increasing impacts in the biomedical sciences. Modern AI tools enable uncovering hidden patterns in large datasets, forecasting outcomes, and numerous other applications. Despite the ava…
View article: Hypothesis Article: Blockers of Store-Operated Calcium Entry (SOCE) Inhibit Mitochondrial ATP Production
Hypothesis Article: Blockers of Store-Operated Calcium Entry (SOCE) Inhibit Mitochondrial ATP Production Open
View article: Identification of Digital Twins to Guide Interpretable AI for Diagnosis and Prognosis in Heart Failure
Identification of Digital Twins to Guide Interpretable AI for Diagnosis and Prognosis in Heart Failure Open
Summary Background Heart failure (HF) is a highly heterogeneous and complex condition. Although patient care generates vast amounts of clinical data, robust methods to synthesize available data for individualized management are lacking. Me…
View article: Deficiency of mitophagy mediator Parkin in aortic smooth muscle cells exacerbates abdominal aortic aneurysm
Deficiency of mitophagy mediator Parkin in aortic smooth muscle cells exacerbates abdominal aortic aneurysm Open
Abdominal aortic aneurysms (AAAs) are a degenerative aortic disease and associated with hallmarks of aging, such as mitophagy. Despite this, the exact associations among mitophagy, aging, and AAA progression remain unknown. In our study, g…
View article: Multiscale modeling shows how 2’-deoxy-ATP rescues ventricular function in heart failure
Multiscale modeling shows how 2’-deoxy-ATP rescues ventricular function in heart failure Open
2’-deoxy-ATP (dATP) improves cardiac function by increasing the rate of crossbridge cycling and Ca transient decay. However, the mechanisms of these effects and how therapeutic responses to dATP are achieved when dATP is only a small …
View article: Guidelines for mechanistic modeling and analysis in cardiovascular research
Guidelines for mechanistic modeling and analysis in cardiovascular research Open
Computational, or in silico, models are an effective, noninvasive tool for investigating cardiovascular function. These models can be used in the analysis of experimental and clinical data to identify possible mechanisms of (ab)normal card…
View article: Inherent Metabolic Adaptations in Adult Spiny Mouse (<i>Acomys</i>) Cardiomyocytes Facilitate Enhanced Cardiac Recovery Following Myocardial Infarction
Inherent Metabolic Adaptations in Adult Spiny Mouse (<i>Acomys</i>) Cardiomyocytes Facilitate Enhanced Cardiac Recovery Following Myocardial Infarction Open
The adult mammalian heart has limited regenerative capacity following injury, leading to progressive heart failure and mortality. Recent studies have identified the spiny mouse ( Acomys ) as a unique model for mammalian cardiac isch3emic r…
View article: Unraveling the Gordian knot of coronary pressure-flow autoregulation
Unraveling the Gordian knot of coronary pressure-flow autoregulation Open
View article: Integrated Modeling and Simulation of Recruitment of Myocardial Perfusion and Oxygen Delivery in Exercise
Integrated Modeling and Simulation of Recruitment of Myocardial Perfusion and Oxygen Delivery in Exercise Open
View article: Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism
Integrated Functions of Cardiac Energetics, Mechanics, and Purine Nucleotide Metabolism Open
Purine nucleotides play central roles in energy metabolism in the heart. Most fundamentally, the free energy of hydrolysis of the adenine nucleotide adenosine triphosphate (ATP) provides the thermodynamic driving force for numerous cellula…
View article: Computational modeling of ventricular-ventricular interactions suggest a role in clinical conditions involving heart failure
Computational modeling of ventricular-ventricular interactions suggest a role in clinical conditions involving heart failure Open
Introduction: The left (LV) and right (RV) ventricles are linked biologically, hemodynamically, and mechanically, a phenomenon known as ventricular interdependence. While LV function has long been known to impact RV function, the reverse i…
View article: Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness
Higher mitochondrial oxidative capacity is the primary molecular differentiator in muscle of rats with high and low intrinsic cardiorespiratory fitness Open
The capacity for increased fatty acid oxidation in the HCR rat is a result of selection for running capacity and is likely a key contributor to the healthy metabolic phenotype of individuals with high CRF.
View article: Portal Venous Remodeling Determines the Pattern of Cirrhosis Decompensation: A Systems Analysis
Portal Venous Remodeling Determines the Pattern of Cirrhosis Decompensation: A Systems Analysis Open
INTRODUCTION: As liver disease progresses, scarring results in worsening hemodynamics ultimately culminating in portal hypertension. This process has classically been quantified through the portosystemic pressure gradient (PSG), which is c…
View article: Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure
Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure Open
View article: FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans
FMO rewires metabolism to promote longevity through tryptophan and one carbon metabolism in C. elegans Open
Flavin containing monooxygenases (FMOs) are promiscuous enzymes known for metabolizing a wide range of exogenous compounds. In C. elegans , fmo-2 expression increases lifespan and healthspan downstream of multiple longevity-promoting pathw…
View article: Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells
Differential integrated stress response and asparagine production drive symbiosis and therapy resistance of pancreatic adenocarcinoma cells Open