Marrying the Merits of Nagelian Reduction and Functional Reduction

This paper points out the merit of Nagelian reduction, namely to propose a model of inter-theoretic reduction that retains the scientific quality of the reduced theory and the merit of functional reduction, namely to take multiple realization into account and to offer reductive explanations. By considering Lewis and Kim's proposal for local reductions, we establish that functional reduction fails to achieve a theory reduction and cannot retain the scientific quality of the reduced theory. We improve on that proposal by showing how one can build functional sub-types that are coextensive with physical realizer types and thereby obtain a theory reduction that is explanatory and that vindicates the scientific quality of the special science

Modeling effects of L-type ca(2+) current and na(+)-ca(2+) exchanger on ca(2+) trigger flux in rabbit myocytes with realistic T-tubule geometries.

The transverse tubular system of rabbit ventricular myocytes consists of cell membrane invaginations (t-tubules) that are essential for efficient cardiac excitation-contraction coupling. In this study, we investigate how t-tubule micro-anatomy, L-type Ca(2+) channel (LCC) clustering, and allosteric activation of Na(+)/Ca(2+) exchanger by L-type Ca(2+) current affects intracellular Ca(2+) dynamics. Our model includes a realistic 3D geometry of a single t-tubule and its surrounding half-sarcomeres for rabbit ventricular myocytes. The effects of spatially distributed membrane ion-transporters (LCC, Na(+)/Ca(2+) exchanger, sarcolemmal Ca(2+) pump, and sarcolemmal Ca(2+) leak), and stationary and mobile Ca(2+) buffers (troponin C, ATP, calmodulin, and Fluo-3) are also considered. We used a coupled reaction-diffusion system to describe the spatio-temporal concentration profiles of free and buffered intracellular Ca(2+). We obtained parameters from voltage-clamp protocols of L-type Ca(2+) current and line-scan recordings of Ca(2+) concentration profiles in rabbit cells, in which the sarcoplasmic reticulum is disabled. Our model results agree with experimental measurements of global Ca(2+) transient in myocytes loaded with 50 μM Fluo-3. We found that local Ca(2+) concentrations within the cytosol and sub-sarcolemma, as well as the local trigger fluxes of Ca(2+) crossing the cell membrane, are sensitive to details of t-tubule micro-structure and membrane Ca(2+) flux distribution. The model additionally predicts that local Ca(2+) trigger fluxes are at least threefold to eightfold higher than the whole-cell Ca(2+) trigger flux. We found also that the activation of allosteric Ca(2+)-binding sites on the Na(+)/Ca(2+) exchanger could provide a mechanism for regulating global and local Ca(2+) trigger fluxes in vivo. Our studies indicate that improved structural and functional models could improve our understanding of the contributions of L-type and Na(+)/Ca(2+) exchanger fluxes to intracellular Ca(2+) dynamics

Comparison of H2O2 screen-printed sensors with different Prussian blue nanoparticles as electrode material

In order to determine hydrogen peroxide condensing from gaseous and liquid phases screen-printed electrodes with controlled and adjustable thickness, shape and size of the working electrode as well as electrode paste composition were investigated. For this purpose Prussian blue (PB) nanoparticles with a different particle size distribution of 20- 30 nm (synthesized) and 60-100 nm (commercially available) were mixed with carbon paste and screen-printed on Al2O3 templates to establish H2O2-sensitive electrode. These two types of screen-printed sensors were compared to the commercial one during measurements in H2O2/water solutions at concentrations between 10-5 and 10-2 M H2O2. The linear signal in the investigated concentration range was found only for the sensor with the commercially available PB particles. Thus, this sensor prepared with PB particles of the size 60-100 nm showed the most reproducible and time-stable response versus the analyte in comparison to the others. This result offers the possibility to create sensors with adjustable design adapted to the concrete functionality. Thin films of collecting electrolytes based on agarose gels were printed on the sensor structures. They showed a distinct response on the application of H2O2-containing aerosols and gaseous phase

Tribes\u27 Reply to the State

The Tribes\u27 response to basic arguments made by the State, with reference to its proposed findings and the Tribes\u27 proposed findings, where appropriate

Tribes\u27 Reply to the State

The Tribes\u27 response to basic arguments made by the State, with reference to its proposed findings and the Tribes\u27 proposed findings, where appropriate

A Large-scale 3D Micromechanical Computational Myocardium Model

The right ventricle (RV) of the heart experiences substantial adaptions in structure and mechanical properties under pulmonary arterial hypertension (PAH). Developing computational models of RV myocardium can provide crucial insight into the factors influencing the onset, progression, and potential reversibility of post-PAH remodeling. However, knowledge of the mechanical interactions between myocardial constituents like myofibers and extracellular matrix (ECM) collagen, previously shown to be essential for capturing tissue behavior, remains incomplete, necessitating a micromechanical framework to link tissue-scale mechanical behavior to myocardial microanatomy. We developed a micromechanical finite element (FE) model leveraging high-fidelity imaging of myocardial microstructure to elucidate micro-scale myofiber-collagen interactions and their contribution to bulk tissue properties. We generated a 1.1-million tetrahedral mesh from a confocal microscopy dataset of a 204x204x40 μm myocardium sample. The material behaviors of the myofiber and ECM were modeled with hyperelastic, anisotropic, nearly incompressible constitutive forms derived from previous structurally-based models. The FE model was used to simulate physiologically informed equibiaxial and non-equibiaxial planar biaxial deformations, and the material parameters were fitted to the total stress-strain response of our previously developed tissue- scale model. Simulations were performed on the Stampede2 supercomputer at the Texas Advanced Computing Center using the finite element solver FEniCS, parallelized over 68 processors. We then employed a multiscale homogenization technique to predict tissue-level (5x5x0.7-mm) biaxial behavior from the localized micromechanical response via emulation of the tissue-scale histological structure and experimental biaxial deformation protocols. Recapitulation of the myocardial microanatomy successfully reproduced the tissue-level results in all deformation modes, suggesting that the micro-scale arrangement of myofibers and ECM is a primary mechanism driving myofiber-collagen coupling at the bulk tissue level. This work establishes the feasibility of incorporating microanatomy into high-fidelity supercomputer-based modeling of myocardium to investigate post-PAH remodeling of the cardiac microstructure and identify mechanical attributes critical to heart disease therapies

Locating air leaks in manned spacecraft using structure-borne noise

All manned spacecraft are vulnerable to leaks generated by micrometeorite or debris impacts. Methods for locating such leaks using leak-generated, structure-borne ultrasonic noise are discussed and demonstrated. Cross-correlations of ultrasonic noise waveforms from a leak into vacuum are used to find the location of the leak. Four methods for sensing and processing leak noise have been developed and tested and each of these can be used to reveal the leak location. The methods, based on phased-array, distributed sensor, and dual sensor approaches, utilize the propagation patterns of guided ultrasonic Lamb waves in the spacecraft skin structure to find the source or direction of the leak noise. It is shown that each method can be used to successfully locate the leak to within a few millimeters on a 0.6-m2 aluminum plate. The relative merits of the four methods are discussed