Quantitative biomarkers are needed for the diagnosis, monitoring and therapeutic assessment of postural instability in movement disorder patients. The goal of this study was to create a practical, objective measure of postural instability using kinematic measurements of the pull test. Twenty-one patients with normal pressure hydrocephalus and 20 age-matched control subjects were fitted with inertial measurement units and underwent 10-20 pull tests of varying intensities performed by a trained clinician. Kinematic data were extracted for each pull test and aggregated. Patients participated in 103 sessions for a total of 1555 trials while controls participated in 20 sessions for a total of 299 trials. Patients were separated into groups by MDS-Unified Parkinson\'s Disease Rating Scale (MDS-UPDRS) pull test score. The center of mass velocity profile easily distinguished between patient groups such that score increases correlated with decreases in peak velocity and later peak velocity onset. All patients except those scored as \"3\" demonstrated an increase in step length and decrease in reaction time with increasing pull intensity. Groups were distinguished by differences in the relationship of step length to pull intensity (slope) and their overall step length or reaction time regardless of pull intensity (y-intercept). NPH patients scored as \"normal\" on the MDS-UPDRS scale were kinematically indistinguishable from age-matched control subjects during a standardized perturbation, but could be distinguished from controls by their response to a range of pull intensities. An instrumented, purposefully varied pull test produces kinematic metrics useful for distinguishing clinically meaningful differences within hydrocephalus patients as well as distinguishing these patients from healthy, control subjects.

This note adds historical context into solving the problem of improving the speed of the step response of a low-order plant in two different types of control systems, a chemical mixing system and the human saccadic system. Two electrical engineers studied the above problem: one to understand and model how nature and evolution solved it and the other to design a control system to solve it in a man-made commercial system. David A. Robinson discovered that fast and accurate saccades were produced by a pulse-step of neural innervation applied to the extraocular plant. Leonidas M. Mantgiaris invented a method to achieve rapid and accurate chemical mixing by applying a large stimulus for a short period of time and then replacing it with the desired steady-state value (i.e., a \"pulse-step\" input). Thus, two humans used their brains to: 1) determine how the human brain produced human saccades; and 2) invent a control-system method to produce fast and accurate chemical mixing. That the second person came up with the same method by which his own brain was making saccades may shed light on the question of whether the human brain can fully understand itself.

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament protein that influences sarcomere stiffness and modulates cardiac contraction-relaxation through its phosphorylation. Phosphorylation of cMyBP-C and ablation of cMyBP-C have been shown to increase the rate of MgADP release in the acto-myosin cross-bridge cycle in the intact sarcomere. The influence of cMyBP-C on Pi-dependent myosin kinetics has not yet been examined. We investigated the effect of cMyBP-C, and its phosphorylation, on myosin kinetics in demembranated papillary muscle strips bearing the β-cardiac myosin isoform from nontransgenic and homozygous transgenic mice lacking cMyBP-C. We used quick stretch and stochastic length-perturbation analysis to characterize rates of myosin detachment and force development over 0-12 mM Pi and at maximal (pCa 4.8) and near-half maximal (pCa 5.75) Ca2+ activation. Protein kinase A (PKA) treatment was applied to half the strips to probe the effect of cMyBP-C phosphorylation on Pi sensitivity of myosin kinetics. Increasing Pi increased myosin cross-bridge detachment rate similarly for muscles with and without cMyBP-C, although these rates were higher in muscle without cMyBP-C. Treating myocardial strips with PKA accelerated detachment rate when cMyBP-C was present over all Pi, but not when cMyBP-C was absent. The rate of force development increased with Pi in all muscles. However, Pi sensitivity of the rate force development was reduced when cMyBP-C was present versus absent, suggesting that cMyBP-C inhibits Pi-dependent reversal of the power stroke or stabilizes cross-bridge attachment to enhance the probability of completing the power stroke. These results support a functional role for cMyBP-C in slowing myosin detachment rate, possibly through a direct interaction with myosin or by altering strain-dependent myosin detachment via cMyBP-C-dependent stiffness of the thick filament and myofilament lattice. PKA treatment reduces the role for cMyBP-C to slow myosin detachment and thus effectively accelerates β-myosin detachment in the intact myofilament lattice.NEW & NOTEWORTHY Length perturbation analysis was used to demonstrate that β-cardiac myosin characteristic rates of detachment and recruitment in the intact myofilament lattice are accelerated by Pi, phosphorylation of cMyBP-C, and the absence of cMyBP-C. The results suggest that cMyBP-C normally slows myosin detachment, including Pi-dependent detachment, and that this inhibition is released with phosphorylation or absence of cMyBP-C.

Kinematic characteristics of the double-leg stance (DLS) to a single-leg stance (SLS) transition were analyzed in a group of young adolescent girls to assess their postural stability control. Twenty volunteers participated in a single experimental session during which their postural stability was assessed based upon the center of pressure (COP) trajectories during the transitions in two typical sensory conditions: with eyes open (EO) and with eyes closed (EC). To quantify the postural control we applied Fitts\' model treating the postural sway as the noise at the initial and the target setpoint control. Results showed that in young healthy subjects characteristics of the transition to either left or right single-leg stance were quite symmetrical. The postural sway at the target posture was characterized by the double increase of postural sway when tested with EO and by the almost quadrupled amount of sway in EC trials. The sway at the target resulted in the decline of the COP mean and peak velocity proportionally to the movement index of difficulty (ID). The estimated ID value increased by 74% in EC trials while the probability of instability increased to 70%. The DLS-SLS test can be recommended for clinical and laboratory assessment of postural stability.

Examine the feasibility of characterizing the regulation of renal oxygenation using high-temporal-resolution monitoring of the T 2 ∗ response to a step-like oxygenation stimulus.
For T 2 ∗ mapping, multi-echo gradient-echo imaging was used (temporal resolution = 9 seconds). A step-like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O2 ), hypoxia (10% O2 + 90% N2 ), and hyperoxia (100% O2 ). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia-reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second-order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla.
The second-order exponential model permitted us to model the exponential T 2 ∗ recovery and the superimposed T 2 ∗ oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in Douter medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia-reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in Douter medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes.
This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step-like oxygenation challenge using high-temporal-resolution T 2 ∗ mapping. Our results suggest that the implemented system analysis approach may help to unlock questions regarding regulation of renal oxygenation, with the ultimate goal of providing imaging means for diagnostics and therapy of renal diseases.

This report deals with the analysis of a cryocooler as a linear dynamical system around a set point, over a range of temperatures where the thermal properties can be considered constant. The accurate knowledge of the cryocooler temperature dependence with a time dependent power stimulus allows to analyze the thermodynamical properties of the system and understand the power flow related, for example, to the cryocooler temperature fluctuations. This is useful for the design of efficient thermal dampers that are necessary for the thermal stabilization of the device under test Sosso et al. [1], Trinchera et al. [2]. Two different and independent methods for deriving the cooler dynamic (i.e. non-stationary) behavior are described using the two main approaches to mathematically represent a dynamical system: step response and transfer function. •Using both approaches we were able to cross check results and provide an estimate of the accuracy of each method.•The instrumentation required is typically available in physics and engineering laboratories.•These results provide insights on cryocooler thermodynamics and design tools for cryocooler engineering.

The sensor response has been reported to become highly nonlinear when the acceleration added to a thermal accelerator is very large, so the same response can be observed for two accelerations with different magnitudes and opposite signs. Some papers have reported the frequency response for the horizontal acceleration to be a first-order system, while others have reported it to be a second-order system. The response for the vertical acceleration has not been studied. In this study, computational experiments were performed to examine the step and frequency responses of a three-axis thermal accelerometer. The results showed that monitoring the temperatures at two positions and making use of cross-axis sensitivity allow a unique acceleration to be determined even when the range of the vertical acceleration is very large (e.g., -10,000-10,000 g). The frequency response was proven to be a second-order system for horizontal acceleration and a third-order system for vertical acceleration.

Experiments and numerical simulations have been used in this work to understand the step response characteristics of Polymer/Ceramic Pressure-Sensitive Paint (PC-PSP). A recently developed analytical model describing the essential physics in PC-PSP quenching kinetics is used, which includes the effect of both diffusion time scale and luminescent lifetime on the net response of PC-PSP. Step response simulations using this model enables an understanding of the effects of parameters, such as the diffusion coefficient of O₂ in the polymer/ceramic coating, attenuation of excitation light, ambient luminescent lifetime, sensitivity, and the magnitude and direction of pressure change on the observed response time scales of PC-PSP. It was found that higher diffusion coefficient and greater light attenuation lead to faster response, whereas longer ambient lifetime and larger sensitivity lead to slower response characteristics. Due to the inherent non-linearity of the Stern-Volmer equation, response functions also change with magnitude and direction of the pressure change. Experimental results from a shock tube are presented where the effects of varying the roughness, pressure jump magnitude and luminophore probe have been studied. Model parameters have been varied to obtain a good fit to experimental results and this optimized model is then used to obtain the response time for a step decrease in pressure, an estimate of which is currently not obtainable from experiments.