Carotid smooth muscle contractility changes after severe burn

Severe burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine (p < 0.05) and to 10−7 M angiotensin II (p < 0.05). Notably, pre-constricted carotid arteries also demonstrated reduced relaxation responses to acetylcholine (p < 0.05) 6 h after burn, but not to sodium nitroprusside. Histologic examination of cross-sectional planes revealed significant increases in carotid artery wall thickness in burned rats at 6 h versus 3 days, with increased collagen expression in tunica media at 3 days (p < 0.05). Carotid artery dysfunction occurs within 6 h after severe burn, demonstrating decreased sensitivity to adrenergic- and angiotensin II-induced vasoconstriction and acetylcholine-induced relaxation.

Unearthing real-time 3D ant tunneling mechanics

Granular excavation is the removal of solid, discrete particles from a structure composed of these objects. Efficiently predicting the stability of an excavation during particle removal is an unsolved and highly nonlinear problem, as the movement of each grain is coupled to its neighbors. Despite this, insects such as ants have evolved to be astonishingly proficient excavators, successfully removing grains such that their tunnels are stable. Currently, it is unclear how ants use their limited information about the environment to construct lasting tunnels. We attempt to unearth the ants’ tunneling algorithm by taking three-dimensional (3D) X-ray computed tomographic imaging (XRCT), in real time, of Pogonomyrmex ant tunnel construction. By capturing the location and shape of each grain in the domain, we characterize the relationship between particle properties and ant decision-making within an accurate, virtual recreation of the experiment. We discover that intergranular forces decrease significantly around ant tunnels due to arches forming within the soil. Due to this force relaxation, any grain the ants pick from the tunnel surface will likely be under low stress. Thus, ants avoid removing grains compressed under high forces without needing to be aware of the force network in the surrounding material. Even more, such arches shield tunnels from high forces, providing tunnel robustness. Finally, we observe that ants tend to dig piecewise linearly downward. These results are a step toward understanding granular tunnel stability in heterogeneous 3D systems. We expect that such findings may be leveraged for robotic excavation.

Effective Stimulation Type and Waveform for Force Control of the Motor Unit System: Implications for Intraspinal Microstimulation

The input–output properties of spinal motoneurons and muscle fibers comprising motor units are highly non-linear. The goal of this study was to investigate the stimulation type (continuous versus discrete) and waveform (linear versus non-linear) controlling force production at the motor unit level under intraspinal microstimulation. We constructed a physiological model of the motor unit with computer software enabling virtual experiments on single motor units under a wide range of input conditions, including intracellular and synaptic stimulation of the motoneuron and variation in the muscle length under neuromodulatory inputs originating from the brainstem. Continuous current intensity and impulse current frequency waveforms were inversely estimated such that the motor unit could linearly develop and relax the muscle force within a broad range of contraction speeds and levels during isometric contraction at various muscle lengths. Under both continuous and discrete stimulation, the stimulation waveform non-linearity increased with increasing speed and level of force production and with decreasing muscle length. Only discrete stimulation could control force relaxation at all muscle lengths. In contrast, continuous stimulation could not control force relaxation at high contraction levels in shorter-than-optimal muscles due to persistent inward current saturation on the motoneuron dendrites. These results indicate that non-linear adjustment of the stimulation waveform is more effective in regard to varying the force profile and muscle length and that the discrete stimulation protocol is a more robust approach for designing stimulation patterns aimed at neural interfaces for precise movement control under pathological conditions.

AFM Force Relaxation Curve Reveals That the Decrease of Membrane Tension Is the Essential Reason for the Softening of Cancer Cells

Differences in stiffness constitute an extremely important aspect of the mechanical differences between cancer cells and normal cells, and atomic force microscopy (AFM) is the most commonly used tool to characterize the difference in stiffness. However, the process of mechanical characterization using AFM has been controversial and the influence of the membrane tension on AFM measurement results was often ignored. Here, a physical model involving a simultaneous consideration of the effects of the cell membrane, cytoskeleton network and cytosol was proposed. We carried out a theoretical analysis of AFM force relaxation curves, and as a result solved many of the remaining controversial issues regarding AFM-based mechanical characterization of cells, and provided a quantitative solution for the membrane tension measured using AFM indentation experiments for the first time. From the results of experiments on cells with different adherent shapes and different pairs of normal cells and cancer cells, we found additional force provided by membrane tension to be the main component of the force applied to the AFM probe, with decreased cell membrane tension being the essential reason for the greater softness of cancer cells than of normal cells. Hence, regulating membrane tension may become an important method for regulating the behavior of cancer cells.

Mavacamten has a differential impact on force generation in myofibrils from rabbit psoas and human cardiac muscle

Mavacamten (MYK-461) is a small-molecule allosteric inhibitor of sarcomeric myosins being used in preclinical/clinical trials for hypertrophic cardiomyopathy treatment. A better understanding of its impact on force generation in intact or skinned striated muscle preparations, especially for human cardiac muscle, has been hindered by diffusional barriers. These limitations have been overcome by mechanical experiments using myofibrils subject to perturbations of the contractile environment by sudden solution changes. Here, we characterize the action of mavacamten in human ventricular myofibrils compared with fast skeletal myofibrils from rabbit psoas. Mavacamten had a fast, fully reversible, and dose-dependent negative effect on maximal Ca2+-activated isometric force at 15°C, which can be explained by a sudden decrease in the number of heads functionally available for interaction with actin. It also decreased the kinetics of force development in fast skeletal myofibrils, while it had no effect in human ventricular myofibrils. For both myofibril types, the effects of mavacamten were independent from phosphate in the low-concentration range. Mavacamten did not alter force relaxation of fast skeletal myofibrils, but it significantly accelerated the relaxation of human ventricular myofibrils. Lastly, mavacamten had no effect on resting tension but inhibited the ADP-stimulated force in the absence of Ca2+. Altogether, these effects outline a motor isoform–specific dependence of the inhibitory effect of mavacamten on force generation, which is mediated by a reduction in the availability of strongly actin-binding heads. Mavacamten may thus alter the interplay between thick and thin filament regulation mechanisms of contraction in association with the widely documented drug effect of stabilizing myosin motor heads into autoinhibited states.

Comparative evaluation of force decay pattern in orthodontic active tiebacks exposed to five different mouth rinses: An in vitro Study

Background. This study compared the force decay pattern of two different orthodontic active tiebacks (ATBs) exposed to five different commercially available mouth rinses. Methods. In this in vitro study, 90 transparent ATBs and 90 gray ATBs were divided into six groups; one was the control group, and the others were exposed to one of these mouth rinses twice a day for 60 seconds: Listerine, chlorhexidine, Orthokin, Persica, and fluoride. The initial force of each ATB was 250 g at a 24-mm extension. The force of ATBs was measured on days 1, 7, 14, and 28 using a digital gauge. Results. The highest percentage of force loss was observed between days 14 and 28 (P<0.05). At the end of the study, the Persica group exhibited the highest force degradation in both ATB types. In the transparent ATBs, it was followed by Orthokin, Listerine, fluoride, chlorhexidine, and control groups, respectively. In the gray ATBs, Orthokin, chlorhexidine, control, Listerine, and fluoride groups exhibited the highest force decay in descending order. In some groups, the differences between transparent and gray ATBs were significant. In the control group, the force of transparent ATB was significantly higher than gray ones on days 7 and 14 but not significantly after four weeks. Conclusion. ATBs’ force degradation could be exacerbated by the use of some mouth rinses. There were some differences between force relaxation patterns of transparent and gray ATBs. The data could be beneficial in choosing appropriate O-rings for making ATBs.

Experimental Study on the Performance of GFRP–GFRP Slip-Critical Connections with and without Stainless-Steel Cover Plates

Composite structures have become increasingly popular in civil engineering due to many advantages, such as light weight, excellent corrosion resistance and high productivity. However, they still lack the strength, stiffness, and convenience of constructions of fastener connections in steel structures. The most popular fastener connections in steel structures are slip-critical connections, and the major factors that influence their strength are the slip factors between faying surfaces and the clamping force due to the prevailing torque. This paper therefore examined the effect that changing the following parameters had on the slip factor: (1) replacing glass fiber reinforced plastic (GFRP) cover plates with stainless-steel cover plates; (2) adopting different surface treatments for GFRP-connecting plates and stainless-steel cover plates, respectively; and (3) applying different prevailing torques to the high-strength bolts. The impact on the long-term effects of the creep property in composite elements under the pressure of high-strength bolts was also studied with pre-tension force relaxation tests. It is shown that a high-efficiency fastener connection can be obtained by using stainless-steel cover plates with a grit-blasting surface treatment, with the maximum slip factor reaching 0.45, while the effects of the creep property are negligible.

Optimum cork stopper diameter for a proper wine sealing performance when modifying bottleneck diameter: a first approach

Aim of study: This study present a theoretical model that allow establishing the proper relationship between forces and diameters that take part in sealing for ensuring an adequate closure during storage time, and obtained the optimum stopper diameter for a proper sealing performance when modifying bottleneck diameter.Area of study: The proposed model is of interested to the whole cork value chain from forest owners to natural cork stoppers manufacturers.Material and methods: The optimum cork stopper diameter depends mainly on stopper quality and the compression rate applied in the bottling operation. In this study, we establish the stopper diameter when reducing bottleneck diameter, applying a compression rate of 33% when corking, and for natural cork stoppers which quality allows to recover its initial diameter to 96% after 24 h since compression.Main results: For a bottleneck diameter of 18 mm, the value of the stopper diameter should be at least of 22.3 mm, and for a bottleneck diameter of 17 mm, the value of the stopper diameter should be at least of 20.3 mm.Research highlights: These results try to solve one of the main worries of natural cork stopper manufacturers, which is the scarcity of raw cork suitable for manufacturing them. However this study is also of interested to forest owners because the increment of cork suitable for natural cork stoppers manufacturing means an increment in cork value.Key words: bottling; corking; compression force; compression rate; diameter recovery; relaxation force; relaxation ratio.Abbreviations used: Ds (Cork Stopper Diameter); Dg (Caliper Diameter the Corking Machine); Db (Bottleneck Diameter); Dr (Recovered Diameter); Fc (Compression Force); Fr (Relaxation Force); CR (Compression Rate); RR (Relaxation Ratio); RD (Diameter Recovery).