Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate

The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGpo′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2 mM/s). Model analyses including Monte Carlo simulation approaches and metabolic control analysis (MCA) showed that this problem could not be amended by model re-parameterization, but instead required reformulation of ADP and Pi feedback control or introduction of additional control mechanisms (feed forward activation), specifically at respiratory Complex III. Both hypotheses were implemented and tested against time course data of phosphocreatine (PCr), Pi and ATP dynamics during post-exercise recovery and validation data obtained by 31P MRS of sedentary subjects and track athletes. The results rejected the hypothesis of regulation by feed forward activation. Instead, it was concluded that feedback control of respiratory chain complexes by inorganic phosphate is essential to explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle throughout its full dynamic range

Solid-state impedance-matched Marx generators for PAW generation

To research the influence of the pulsed high voltage waveform on the generation of radicals in plasma and in plasma activated water, we developed a fast and flexible Marx generator. This generator is both able to generate fast rise-time pulses (20kV, 400A in 8ns) and various pulse shapes (pulse length 25ns-100us, burst mode, 1Hz-30kHz rep.rate). The generator layout is fully impedance matched, allowing for future upgrades for even shorter rise-times

Impact of Impedance-Matching on Internal Reflections and Output Pulse Shape in Impedance-Matched Pulse Generators

Recently we developed the concept and multiple implementations of the Solid-State Impedance-Matched Marx generator (IMG). The generator combines the high-repetition rate and controllability of a solid-state (SiC MOSFET switched) Marx with the fast rise-time possibilities of the impedance-matched topology as proposed by Sandia in 2017. Proper impedance matching should maintain the rise time of the individual Marx stages at the output, regardless of the physical size of the generator. Simulations support this, and practical implementations give good results, but so far, our generators where physically smaller than the propagation time of the pulse front through the generator. When the generators become larger in comparison to pulse rise-time, improperly matched systems will show deteriorated pulse shapes, which we did not show yet. This contribution shows the effect of impedance-matching on both the generator and the load: how the physical size influences the pulse rise-time. More specifically, we take three stages of the IMG, and we connect them either with 15 mm in between, or couple them with a 600-mm coaxial transmission line, with matched and intentionally mismatched versions. This allows us to measure voltages in between the stages and increases the propagation time, which allows us to evaluate reflections on each stage. These results show that proper impedance matching makes the rise-time independent of the physical size of the generator and will lead the way for future IMGs designs

Fast and Flexible, Arbitrary Waveform, 20-kV, Solid-State, Impedance-matched Marx Generator

We developed a new pulsed power supply to study the influence of the high-voltage (HV) pulse shape on the generation of plasma-activated water (PAW). This article shows the design and implementation of the generator and evaluates its performance on resistive loads. The design is an improved version of the solid-state impedance-matched Marx generator (SS-IMG) concept as previously developed at Eindhoven University of Technology. The IMG concept allows for sub-nanosecond rise time pulses, to be able to create a nonthermal plasma very efficiently. A conventional SS-Marx generator (SS-Marx) circuit is taken as the starting point, and a careful implementation is made with most electrical connections analyzed as transmission lines (TLs). All these TLs are impedance-matched to each other and the load. The implemented generator is able to generate 25 ns to μ s duration pulses of 20 kV up to 10-kHz repetition rate in a 50- Ω load with about 8 ns rise time and arbitrary pulse shape. Future improvements are suggested which will increase the repetition rate and decrease the pulse rise time to the sub-nanosecond regime