Steady-state Force Research Articles

Modeling and Investigation of the Velocity-Dependent Cutting Process with PDC Cutters Using the Discrete Element Method

Polycrystalline diamond compact (PDC) bits with multiple fixed cutters drill through deep formations and are used in oil and gas, geothermal, and mining industry. The bit-rock interaction excites drill string vibrations, which need to be mitigated to improve drilling performance. A velocity-weakening characteristic of the bit torque can cause severe self-excited high-frequency torsional oscillations (HFTO) of the bottom hole assembly (BHA). The dependency on velocity can be attributed to rate-sensitive rock cutting forces at each cutter. The purpose of this paper is to model the rate effect of cutting forces and determine influencing factors in the single-PDC cutting process. In this paper, a modified bonded-particle model (discrete element method, DEM) for rock in deep drilling environments is applied to the pressurized cutting process. Potential modification strategies considering rate indicators at different scales are compared and discussed to reproduce rate dependency in the particle contact model. Two specific models, incorporating cutting-speed-dependent bond strength or grain elastoplasticity, are implemented and verified. The relationship between rate-sensitive cutting forces and the causal rock failure mechanisms is then clarified by interpreting the results from a continuum perspective. Moreover, the influences of axial force and cutter wear state on the rate dependency are investigated. In cutting simulations at a constant depth of cut and various cutting speeds, both models result in rate-dependent cutting forces in good qualitative agreement with rock experiments: Significant hardening is reflected in the axial force component. The modification of contact models combined with a macroscopic rate indicator (i.e. cutting speed) has proven to be a feasible and effective way to reproduce the rate effects in the cutting simulations. In subsequent simulations with constant axial force, the steady-state tangential force decreases as the cutting speed increases, matching the reduction of torque on the bit with increasing RPM. Rate dependency intensifies at higher axial forces or with dull cutters, which agrees with laboratory full-scale bit tests in the literature. This study proposes a practical approach to integrating observed rate effects of downhole rock cutting processes into numerical rock models. The results enhance our understanding of the rock cutting process and have positive implications for the improvement of the cutter design against undesirable rate effects.

Investigating the sarcolemma-sarcomere connection and force transmission in the heart.

External mechanical signals are communicated through cardiac muscle cells by converting them to internal biochemical signals during mechanotransduction. In the heart, altered transmission of these signals can affect myocardial structure and function. This study examines the impact of sarcospan deletion, a sarcolemma protein, on cardiac muscle mechanics. Sarcospan is an integral member of the dystrophin-glycoprotein complex (DGC) and we are interested in investigating how it influences sarcomere contractile function. Measurements of cardiac contractile parameters were conducted using permeabilized left ventricular papillary muscle bundles obtained from wild-type and SSPN-deficient (SSPN-/-) mouse hearts. Myofilament Ca2+-sensitivity and cooperativity of thin filament activation was similar between WT and SSPN-/- cardiac muscle preparations. However, SSPN-/- muscle bundles exhibited a significantly faster rate of tension redevelopment (kTR) at submaximal activation conditions (pCa 5.8) but no significant changes in maximal kTR (recorded at maximal Ca2+ activation, pCa 4.5). Maximal steady-state isometric force and sinusoidal stiffness were proportionally increased in SSPN-/- cardiac muscle preparations during Ca2+ activation. These intriguing observations suggest that SSPN may play an inherent role in balancing pathways involved in force transmission and its deletion may cause compensatory remodeling of sarcomeric proteins (e.g. isoform switching or protein modification) changing mechanical properties of cardiac muscle. Mouse hearts lacking SSPN-/- exhibit increased sarcolemmal expression of integrin-linked kinase (ILK) and vinculin. ILK is an important biomechanical sensor shown to regulate cardiac contractility and ventricular hypertrophy whereas increasing vinculin expression has been shown to improve heart function and impact myofilament organization. Further examination of the WT and SSPN-/- myofibrils will allow us to assess sarcomere protein alterations that contribute to increased force at submax and max levels of Ca2+ activation. Therefore, the concentric enlargement observed in SSPN-/- mouse hearts could be explained by remodeling of the sarcomere itself.

Passive force enhancement is not abolished by shortening of single fibres.

Passive force enhancement is defined as the increase in steady-state passive force following active muscle stretching compared to the corresponding passive force following passive muscle stretching. This mechanical property has been discovered just two decades ago (Herzog & Leonard, 2002), and has been associated with contributing to the residual force enhancement property, stability of sarcomeres, and preventing over-stretching during eccentric contractions. The molecular mechanisms underlying passive force enhancement development and abolishment remain unknown. An incidental observation on cat soleus muscle led to the speculation that passive force enhancement could be abolished instantaneously when the actively stretched muscle was deactivated and then passively shortened to its pre-stretched length (Herzog et al., 2003). We tested this hypothesis systematically using single skinned fibres from rabbit psoas. However, initial results led to the rejection of this hypothesis. Rather, we found that passive force enhancement increased following a shortening-stretch cycle of fibres to their pre-stretched length (2.4 µm), and back. Furthermore, we observed that the passive force enhancement increased by 70-106% when the shortening and subsequent stretch to the original length (3.6 µm) increased in duration (200 ms, 6 s, and 14 s). When reversing the order of the shortening-stretch experiments from slowest to fastest, the general result was the same as that of the primary experiment. These findings indicated that passive force enhancement increases during a shortening-stretch cycle, and that this increase is time-dependent. We propose that this increase in passive force enhancement may be caused by titin; specifically, with a refolding of titin's immunoglobulin domains that were unfolded during the active fibre stretching that produced the residual and passive force enhancement. Using fluorescent antibody labeling of selected titin segments, we will be testing this hypothesis in the near future.

MYH7 G256E induced changes in myosin biomechanics influence function of myofibril contractile organelles.

We studied the contractile properties of the MYH7 G256E mutation using engineered human stem cell derived cardiomyocytes (hSC-CMs). When hSC-CMs were cultured to 40-45 days post-differentiation and Western blot analysis demonstrated near 100% β-myosin (MYH7). Single sub-cellular contractile organelles (myofibrils) were mounted in a custom built apparatus between a force transducer and linear motor. Rapid solutions switching to maximal activation solution (pCa 4.0) resulted in a doubling of steady-state force and rate of force development for G256E myofibrils compared with wild type (WT) controls. Upon switching to relaxation solution (pCa 9.0), the slope of the initial linear, slow phase relaxation was significantly slower (∼4-fold) for G256E vs WT myofibrils, suggesting the mutation slows the crossbridge detachment rate in loaded contractions. Crossbridge detachment rate can be reduced by slower ADP release or slower ATP binding to myosin. Analysis using stopped flow kinetics showed the ATP binding rate was slightly, but significantly reduced for G256E vs WT myofibrils. Preliminary data from myofibril mechanical analysis suggests that ADP release is also slower with the G256E mutation. Molecular dynamics (MD) simulations of the rigor and myosin.ATP states showed that G256E led to reorganization of hydrogen bonding networks within the transducer region. Enhanced sampling MD simulations of the rigor to post-rigor (ATP-bound) structural transition indicated G256E myosin surmounts a greater energetic barrier describing the binding of switch 1 to ATP, rotation of the transducer backbone, and opening of the actin binding cleft. This increased barrier is attributed to salt bridges formed by the mutant Glu residue. Combined, our results suggest that G256E leads to hypercontraction and delayed relaxation phenotype via modulation of the transducer structure that alters communication between the nucleotide binding pocket and the actin binding surface during the chemo-mechanical cycle.

Do actin-myosin cross-bridges exhibit a viscoelastic behaviour?

The S2 domain of myosin is the segment that links the myosin head (S1 domain) to the thick filament backbone and elongates to allow S1 to execute the power stroke. It has been suggested that S2 exhibits non-viscous behaviour, implying no lag in reaching steady-state force following power stroke elongation. However, the elongation step in the cross-bridge cycle occurs extremely fast, and the cross-bridge detaches rapidly following it without allowing perceptible changes in force. If a muscle is transferred to a rigor solution following activation, all cross-bridges become stuck in a post power stroke state, which allows for investigation of their viscoelastic behaviour. The objective of this study was to investigate the viscoelastic behaviour of cross-bridges by examining their force following transfer to a rigor solution. Fibres (n = 8) were activated at an average sarcomere length (SL) of 3.0 µm, and then transferred into a rigor solution for 90 s. Since active stretch has the potential to influence the behaviour of cross-bridges, fibres were activated at a SL of 2.4 µm, actively stretched to a SL of 3.0 µm, and at steady-state transferred to a rigor solution for 90 s. Active force and stiffness were compared before and after incubation in rigor, and between purely isomeric and active stretch contractions. Although stiffness, and thus the presumed proportion of attached cross-bridges, increased when fibres were transferred to rigor, force at steady-state decreased by 16.5 +/- 4.0% and 10.0 +/- 1.3%, in the purely isometric and active stretch conditions, respectively. These results suggest that cross-bridges exhibit a viscoelastic behaviour, where their force decreases while they remain attached in a constant conformation. The difference in force decrease between the purely isometric and active stretch conditions suggests that active stretch modulates cross-bridge properties. Further research is warranted to investigate the cross-bridge nanostructure before and after rigor incubation.

Simulation and Experiment of Electromagnet for High-Speed On-off Valve for Vehicle Shifting System

The high-speed on-off valve is the core component for adjusting the oil pressure of the pressure reducing valve in the clutch shifting system of engineering vehicles, and its response speed is one of the important indicators to measure its performance. In order to improve the dynamic performance of high-speed on-off valve, the electromagnet with solid magnetic isolation structure was designed and simulated by considering the eddy current loss factor. A high-speed on-off valve electromagnetic actuator with high response speed was obtained. Firstly, the theoretical calculation and verification of the theory were carried out by using the electromagnet design theory, and the theoretical model of the electromagnet was built. Secondly, the electromagnet parameter model was brought into the finite element simulation software ANSYS Electronics to simulate and optimize the static magnetic field and the transient magnetic field respectively. The different structural parameters (guide bush thickness, outer magnetic pole thickness, magnetic isolation structure, armature length) were analyzed. And the effect of the coil parameters (number of strands) on the steady-state electromagnetic force and the dynamic displacement of the armature was analyzed. The values of the structural parameters of the electromagnet were subsequently determined. Finally, the static and dynamic characteristics experiment of the magnetically separated solid electromagnet is designed and processed. The experiment and simulation results are in good agreement. The feasibility of the high-resistance electromagnet structure design and the correctness of the simulation are verified. Reasonable optimization of structural parameters and coil parameters has obvious significance for improving the dynamic characteristics of high-speed on-off valve electromagnets.

Mitigation of ice-induced vibrations for wind turbine foundation using damping vibration isolation

The single pile offshore wind turbine foundation is a typical flexible structure, and the dynamic interac-tion between ice and structure is complex. Ice-induced vibrations can affect the normal operation of the upper motor and the safety of the foundation structure. This paper takes the interaction between ice and offshore platform in the Bohai Sea as the research object and discusses the strategies to mitigate the ice- induced vibrations of offshore wind turbine foundation. Through a simplified mechanical model of a damping vibration isolation system, the relationship between the parameters of the damping isolation layer and the structural damping ratio was analyzed. Based on the numerical simulation results, it was found that the damping isolation layer with a damping ratio of 0.2 can play a better role in controlling structural displacement and acceleration response under the action of steady-state and random ice forces. It provides a reference for the design of ice-resistant and safe operation of the offshore wind turbine.

The energy absorption of a shrinking–expanding circular tube: An experimental and numerical investigation

A new type of combined energy absorber working on the principle of shrinking and expanding of the circular metal tube was proposed. First, quasi-static experiments of aluminum alloy tubes were conducted. The results show that this type of energy absorber is completely feasible. Afterward, finite element models were established to estimate the tube deformation and force–displacement response, which were in good agreement with the experimental results. A theoretical solution for the steady-state crushing force of the tube was derived. Moreover, the effects of various structural parameters were investigated using a validated finite element model. According to the results, the force increases with the increase of the wall thickness and has a monotonically decreasing relationship with the radius of the shrinking die, but it first decreases, then increases with the increase in the cone angle of the expanding die. Compared with the energy absorber that only produces shrinking deformation, the steady-state force of the combined absorber is increased by 123%, and the energy absorption under the same stroke is higher. The result can provide guidance for the optimal design of the collision energy-absorbing structure on a rail vehicle.

Development of Dummy Based on Impedance Properties of Human Soft Tissue Using a Nonlinear Viscoelastic Model

Securing human safety in a physical human–robot interaction (pHRI) has been extensively studied to allow for the expansion of robotic applications. Dummies with the same impedance properties as those of human soft tissues are suitable substitutes for the validation of the safety assurance of the pHRI experiment. This study demonstrated the development process of dummies with high biofidelity. A psychophysiological experiment was designed to replicate the clamping scenario, and the center of the palm, thenar eminence, and forefinger pad were selected as three soft tissues of the human hand to be impacted to obtain the dynamic response of the contact force. A nonlinear five-element viscoelastic model was developed to quantify the viscoelasticity of the three soft tissues through curve fitting of the contact force. Subsequently, three dummies were fabricated using a polyurethane resin material. The biofidelity of the dummies was examined via a parametric comparison with the soft tissues and curve comparisons to examine whether the steady-state force and the dynamic response of the contact force were located within the corresponding ranges enclosed by the calibration curves of the soft tissues. All three dummies showed high biofidelity in the case where the steady-state force exceeded approximately 5 N, even though they have different nonlinearity of elasticity from that of soft tissues.

Influence of valve spool shoulder wall angle on steady-state hydraulic force

Influence of valve spool shoulder wall angle on steady-state hydraulic force

Influence of valve spool shoulder wall angle on steady-state hydraulic force

Influence of valve spool shoulder wall angle on steady-state hydraulic force

A Multidimensional Visible Evaluation Model for Stroke Rehabilitation: A Pilot Study.

Efficient rehabilitation state evaluation is important to the design of rehabilitation strategies after stroke. However, most traditional evaluations have depended on subjective clinical scales, which do not entail quantitative evaluation of the motor function. Functional corticomuscular coupling (FCMC) can be used to quantitatively describe the rehabilitation state. However, how to apply FCMC to clinical evaluation still needs to be studied. In this study, we propose a visible evaluation model which can combine the FCMC indicators with a Ueda score to comprehensively evaluate the motor function. In this model, we first calculated the FCMC indicators based on our previous study, including transfer spectral entropy (TSE), wavelet package transfer entropy (WPTE) and multiscale transfer entropy (MSTE). We then apply Pearson correlation analysis to determine which FCMC indicators are significantly correlated with the Ueda score. Then, we simultaneously introduced a radar map to present the selected FCMC indicators and the Ueda score, and described the relation between them. Finally, we calculated the comprehensive evaluation function (CEF) of the radar map and applied it as a comprehensive score of the rehabilitation state. To verify the model's effectiveness, we synchronously collected the electroencephalogram (EEG) and electrocardiogram (EMG) data from stroke patients under the steady-state force task and evaluated the state by the model. This model visualized the evaluation results by constructing a radar map and presented the physiological electrical signal features and the clinical scales at the same time. The CEF indicator calculated from this model was significantly correlated with the Ueda score (P=0.001<0.01). This research provides a new approach to evaluation and rehabilitation training after stroke, and explicates possible pathomechanisms.

Dynamic analysis of train and bridge in crosswinds based on a coupled wind-train-track-bridge model

The dynamic performance and safety of both the train and the bridge are great concerns for long-span bridges subjected to crosswinds. For railway bridges, there is track laid on the bridge deck. The wind, train, track, and bridge subsystems form a complicated coupling system. This paper presents the dynamic responses of both the train and the bridge under crosswinds based on a wind-train-track-bridge coupled model, in which the vibration effect of the track structure involved in the coupling system is especially considered. For studying the dynamic responses of both the train and the bridge, models of railway vehicle dynamics are used for the train and a three-dimensional finite element model is used for the bridge. The train-track interaction and the track-bridge interaction are respectively considered. The wind action on the train and the bridge consists of a steady-state force and an unsteady-state force. Based on an in-situ test, the proposed numerical wind-train-track-bridge model involving the vibration effect of the track is validated. Then, the application of this proposed model on a long-span cable-stayed bridge on the Shanghai-Suzhou-Nantong HSR (high-speed railway) is presented as a case study. The typical running train and track currently serving in the Chinese railway transportation system are modeled in this study. Excitations from track irregularities are also taken into account. Finally, with the proposed wind-train-track-bridge coupled model, the dynamic performance of both the train and the bridge subjected to crosswinds are investigated.

The day-to-day reliability of residual force enhancement during voluntary and electrically stimulated contractions.

Residual force enhancement (rFE) is characterized by increased steady-state isometric force following active muscle lengthening compared to a fixed-end isometric contraction at the same muscle length and level of neuromuscular activation. Many studies have characterized rFE in humans; however, the day-to-day reliability of rFE is unclear. We aimed to examine day-to-day reliability of rFE across various contraction types in the dorsiflexors in males and females. Twenty-five recreationally active young adults completed 2 visits, 1 week apart. Following determination of maximum voluntary contraction (MVC) strength, rFE was assessed during maximal voluntary effort, 20% MVC electrically stimulated, and 20% MVC torque-matching conditions. Each rFE condition was completed at 2 joint excursions: 0-20º plantar flexion (PF) and 0-40ºPF. Intraclass correlation coefficients (ICC) assessed relative reliability, and typical error of measurement (TEM), and the correlation variability of TEM (CVTEM) assessed absolute reliability. Electrically stimulated contractions demonstrated the highest reliability at 40ºPF (ICC:0.9; CVTEM:22.8 %) and 20ºPF (ICC:0.8; CVTEM:34.3 %), followed by maximal voluntary contractions at 40ºPF (ICC:0.7; CVTEM:55.1%) and 20ºPF (ICC:0.1; CVTEM:81.1%). The torque-matching trials showed poor reliability for 20º and 40ºPF (ICC: -0.1-0.3; CVTEM: 118.1 %-155.2 %). Our results demonstrate higher reliability of rFE when stretching to the descending limb of the torque-angle relationship compared to the plateau region, and in electrically stimulated compared to voluntary contractions in the dorsiflexors for both males and females.

Effect of active shortening and stretching on the rate of force re-development in rabbit psoas muscle fibres

The steady-state isometric force produced by skeletal muscle after active shortening and stretching is depressed and enhanced, respectively, compared with purely isometric force produced at corresponding final lengths and at the same level of activation. One hypothesis proposed to account for these force depression (FD) and force enhancement (FE) properties is a change in cross-bridge cycling kinetics. The rate of cross-bridge attachment (f) and/or cross-bridge detachment (g) may be altered following active shortening and active stretching, leading to FD and FE, respectively. Experiments elucidating cross-bridge kinetics in actively shortened and stretched muscle preparations and their corresponding purely isometric contractions have yet to be performed. The aim of this study was to investigate cross-bridge cycling kinetics of muscle fibres at steady-state following active shortening and stretching. This was done by determining muscle fibre stiffness and rate of active force redevelopment following a quick release-re-stretch protocol (kTR). Applying these measures to equations previously used in the literature for a two-state cross-bridge cycling model (attached/detached cross-bridges) allowed us to determine apparent f and g, the proportion of attached cross-bridges, and the force produced per cross-bridge. kTR, apparent f and g, the proportion of attached cross-bridges and the force produced per cross-bridge were significantly decreased following active shortening compared with corresponding purely isometric contractions, indicating a change in cross-bridge cycling kinetics. Additionally, we showed no change in cross-bridge cycling kinetics following active stretch compared with corresponding purely isometric contractions. These findings suggest that FD is associated with changes in cross-bridge kinetics, whereas FE is not.

Passive force enhancement is not abolished by shortening of single rabbit psoas fibres

Passive force enhancement is defined as the increase in steady-state passive force following deactivation of an actively stretched muscle compared to the corresponding passive force following passive stretching of the muscle. Passive force enhancement has been associated with contributing to the residual force enhancement property, providing stability to sarcomeres, and preventing sarcomeres from over-stretching during eccentric muscle action. Despite its functional importance, the molecular mechanisms underlying passive force enhancement remain unknown. Specifically, it remains unknown how passive force enhancement develops and how it is abolished. Incidental observations on cat soleus muscles led to the speculation that passive force enhancement is abolished when the actively stretched muscle is deactivated and then passively shortened to its pre-stretched length. Here, we tested this hypothesis using skinned fibres from rabbit psoas and rejected it. Rather, we found that passive force enhancement increased following shortening of the fibres to their pre-stretched length (2.4 µm), and furthermore, that the passive force enhancement increased by 70–106% when the shortening and subsequent stretch to the original length (3.6 µm) increased in duration (200 ms, 6 s, and 14 s). These results indicate that passive force enhancement increases during a shortening–stretch cycle, and that this increase is time-dependent. We propose that this increase in passive force enhancement is caused by titin; specifically, with a refolding of titin’s immunoglobulin domains that were unfolded during the active fibre stretching that produced the residual and passive force enhancement. Molecular level experiments are required to test this proposal.

Molecular regulation of stretch activation.

Stretch activation is defined as a delayed increase in force after rapid stretches. Although there is considerable evidence for stretch activation in isolated cardiac myofibrillar preparations, few studies have measured mechanisms of stretch activation in mammalian skeletal muscle fibers. We measured stretch activation following rapid step stretches [∼1%-4% sarcomere length (SL)] during submaximal Ca2+ activations of rat permeabilized slow-twitch skeletal muscle fibers before and after protein kinase A (PKA), which phosphorylates slow myosin binding protein-C. PKA significantly increased stretch activation during low (∼25%) Ca2+ activation and accelerated rates of delayed force development (kef) during both low and half-maximal Ca2+ activation. Following the step stretches and subsequent force development, fibers were rapidly shortened to original sarcomere length, which often elicited a shortening-induced transient force overshoot. After PKA, step shortening-induced transient force overshoot increased ∼10-fold following an ∼4% SL shortening during low Ca2+ activation levels. kdf following step shortening also increased after PKA during low and half-maximal Ca2+ activations. We next investigated thin filament regulation of stretch activation. We tested the interplay between cardiac troponin I (cTnI) phosphorylation at the canonical PKA and novel tyrosine kinase sites on stretch activation. Native slow-skeletal Tn complexes were exchanged with recombinant human cTn complex with different human cTnI N-terminal pseudo-phosphorylation molecules: 1) nonphosphorylated wild type (WT), 2) the canonical S22/23D PKA sites, 3) the tyrosine kinase Y26E site, and 4) the combinatorial S22/23D + Y26E cTnI. All three pseudo-phosphorylated cTnIs elicited greater stretch activation than WT. Following stretch activation, a new, elevated stretch-induced steady-state force was reached with pseudo-phosphorylated cTnI. Combinatorial S22/23D + Y26E pseudo-phosphorylated cTnI increased kdf. These results suggest that slow-skeletal myosin binding protein-C (sMyBP-C) phosphorylation modulates stretch activation by a combination of cross-bridge recruitment and faster cycling kinetics, whereas cTnI phosphorylation regulates stretch activation by both redundant and synergistic mechanisms; and, taken together, these sarcomere phosphoproteins offer precision targets for enhanced contractility.

The behavior of thiacarbocyanine dyes on the surface of few-layered hexagonal boron nitride

The adsorption and self-assembly of several thiacarbocyanine dyes on hexagonal boron nitride (hBN) was investigated by combining steady-state spectroscopy and atomic force microscopy. The adsorption isotherms indicate that at saturation the density of the cationic TDC (5,5-dichloro-3-3′-diethyl-9-ethyl-thiacarbocyanine) molecules on hBN is similar to that of TD2 (3-3′-diethyl-9-ethyl-thiacarbocyanine) molecules, while the densities of TD0 (3-3′-diethyl-thiacarbocyanine) molecules and the zwitterionic THIATS (5,5-dichloro-3-3′-disulfopropyl-9-ethyl-thiacarbocyanine) molecules are significantly higher. The intermolecular distances between neighboring adsorbed dyes, calculated from these saturation densities indicate a flat-on adsorption for TDC, TD2 and TD0 and a partial edge-on adsorption for THIATS. AFM micrographs of the adsorbed TDC, TD0 and THIATS molecules indicate that already at low dye concentrations in the solution, where only a small fraction of the hBN surface is covered, the dye molecules already form upon adsorption to hBN aggregates of at least 10 nm, separated by areas where no adsorbed dye molecules can be detected. The resolution of the micrographs was however insufficient to show details of the packing of the adsorbed molecules. For THIATS, the thickness of the adsorbed layer is compatible with an edge-on adsorption, while for TDC and TD0, the thickness of the adsorbed layer is twice the thickness expected for flat-on adsorption. The exciton interaction extracted from the steady-state spectroscopy of the adsorbed dyes is much smaller than observed for H- or J-aggregates of the same dyes in solution or adsorbed to other surfaces such as Langmuir films or silver halides. For TDC, TD2 and TD0, the values of the exciton interaction are compatible with a close packed flat-on adsorption. Hence, optimizing the interaction between the adsorbed dye and hBN rather than between the adsorbed dye molecules governs the packing of the adsorbed dye molecules. The observation of the spectral shifts attributed to the exciton interaction at low average coverage of the hBN surface indicates that the exciton interaction already occurs at low coverage of the hBN surface. This observation is in agreement with the AFM micrographs, which show clustering of the adsorbed dye molecules already at low coverages.

A Dynamical Approach to the Uncontrolled Manifold: Predicting Performance Error During Steady-State Isometric Force Production.

The uncontrolled manifold (UCM) approach quantifies the presence of compensatory variability between musculoskeletal elements involved in a motor task. This approach has proved useful for identifying synergistic control strategies for a variety of everyday motor tasks and for investigating how control strategies are affected by motor pathology. However, the UCM approach is limited in its ability to relate compensatory motor variance directly to task performance because variability along the UCM is mathematically agnostic to performance. We present a new approach to UCM analysis that quantifies patterns of irregularity in the compensatory variability between motor elements over time. In a bimanual isometric force stabilization task, irregular patterns of compensation between index fingers predicted greater performance error associated with difficult task conditions, in particular for individuals who exploited a larger set of compensatory strategies (i.e.,a larger subspace of the UCM). This relationship between the amount and structure of compensatory motor variance might be an expression of underlying processes supporting performance resilience.

Functional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.

In this study, we investigated the rescue potential of two phosphomimetic mutants of the myosin regulatory light chain (RLC, MYL2 gene), S15D, and T160D RLCs. S15D-RLC mimics phosphorylation of the established serine-15 site of the human cardiac RLC. T160D-RLC mimics the phosphorylation of threonine-160, identified by computational analysis as a high-score phosphorylation site of myosin RLC. Cardiac myosin and left ventricular papillary muscle (LVPM) fibers were isolated from a previously generated model of hypertrophic cardiomyopathy (HCM), Tg-R58Q, and Tg-wild-type (WT) mice. Muscle specimens were first depleted of endogenous RLC and then reconstituted with recombinant human cardiac S15D and T160D phosphomimetic RLCs. Preparations reconstituted with recombinant human cardiac WT-RLC and R58Q-RLC served as controls. Mouse myosins were then tested for the actin-activated myosin ATPase activity and LVPM fibers for the steady-state force development and Ca2+-sensitivity of force. The data showed that S15D-RLC significantly increased myosin ATPase activity compared with T160D-RLC or WT-RLC reconstituted preparations. The two S15D and T160D phosphomimetic RLCs were able to rescue Vmax of Tg-R58Q myosin reconstituted with recombinant R58Q-RLC, but the effect of S15D-RLC was more pronounced than T160D-RLC. Low tension observed for R58Q-RLC reconstituted LVPM from Tg-R58Q mice was equally rescued by both phosphomimetic RLCs. In the HCM Tg-R58Q myocardium, the S15D-RLC caused a shift from the super-relaxed (SRX) state to the disordered relaxed (DRX) state, and the number of heads readily available to interact with actin and produce force was increased. At the same time, T160D-RLC stabilized the SRX state at a level similar to R58Q-RLC reconstituted fibers. We report here on the functional superiority of the established S15 phospho-site of the human cardiac RLC vs. C-terminus T160-RLC, with S15D-RLC showing therapeutic potential in mitigating a non-canonical HCM behavior underlined by hypocontractile behavior of Tg-R58Q myocardium.