Contraction Sequence Research Articles

Sustained intermittent and continuous isometric muscle actions induce different levels of fatigue for the same force-time integral

IntroductionThe aim was to compare the fatiguing effects induced by continuous (CONT) and intermittent (INT) tasks of an identical duration by equating the force-time integral. Methodː Fourteen men performed two sequences (4 blocks of 378s) of contractions (CONT or INT) of the quadriceps femoris. The CONT contraction of 378s corresponded to 10% of the maximum voluntary muscle contraction (MVC). The INT 3s contractions corresponded to 70% of the MVC, separated by rest periods of 18s (a 21s cycle) and repeated 18 times (21s x 18) for 378s. Hence, the force-time integral was identical for the both contraction tasks (378s × 10% MVC = 37.8; 3s x 18 repetitions x 70% MVC = 37.8). Resultsː The MVC and central activation ratio were measured before, during and after the sequence of muscle contractions. For a same force-time integral done during an identical duration of activity, the CONT contractions engendered earlier and greater decrease in motor output and voluntary activation than the INT contractions. ConclusionContinuous muscle actions are more fatiguing than intermittent muscle actions. They could therefore be relevant to develop resistance to muscle fatigue but would be not suitable for undertaking long or sustained workloads.

Modeling the atrioventricular conduction axis using human pluripotent stem cell-derived cardiac assembloids.

The atrioventricular (AV) conduction axis provides electrical continuity between the atrial and ventricular chambers. The "nodal" cardiomyocytes populating this region (AV canal in the embryo, AV node from fetal stages onward) propagate impulses slowly, ensuring sequential contraction of the chambers. Dysfunction of AV nodal tissue causes severe disturbances in rhythm and contraction, and human models that capture its salient features are limited. Here, we report an approach for the reproducible generation of AV canal cardiomyocytes (AVCMs) with invivo-like gene expression and electrophysiological profiles. We created the so-called "assembloids" composed of atrial, AVCM, and ventricular spheroids, which effectively recapitulated unidirectional conduction and the "fast-slow-fast" activation pattern typical for the vertebrate heart. We utilized these systems to reveal intracellular calcium mishandling as the basis of LMNA-associated AV conduction block. In sum, our study introduces novel cell differentiation and tissue construction strategies to facilitate the study of complex disorders affecting heart rhythm.

Activation mechanisms of dimeric mechanosensitive OSCA/TMEM63 channels

OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation mechanism of these transporter-like channels is not fully understood. Here we report cryo-EM structures of a dimeric OSCA/TMEM63 pore mutant OSCA1.1-F516A with a sequentially extracellular dilated pore in a detergent environment. These structures suggest that the extracellular pore sequential dilation resembles a flower blooming and couples to a sequential contraction of each monomer subunit towards the dimer interface and subsequent extrusion of the dimer interface lipids. Interestingly, while OSCA1.1-F516A remains non-conducting in the native lipid environment, it can be directly activated by lyso-phosphatidylcholine (Lyso-PC) with reduced single-channel conductance. Structural analysis of OSCA1.1-F516A in lyso-PC-free and lyso-PC-containing lipid nanodiscs indicates that lyso-PC induces intracellular pore dilation by attracting the M6b to upward movement away from the intracellular side thus extending the intracellular pore. Further functional studies indicate that full activation of MS OSCA/TMEM63 dimeric channels by high-threshold mechanical force also involves the opening of both intercellular and extracellular pores. Our results provide the fundamental activation paradigm of the unique transporter-like MS OSCA/TMEM63 channels, which is likely applicable to functional branches of the TMEM63/TMEM16/TMC superfamilies.

Naked exclusion with heterogeneous buyers

We investigate the effects of buyer heterogeneity in a market where an incumbent firm deters entry when it signs enough exclusionary contracts with buyers. With heterogeneous buyers, several well-known results in exclusionary contracting with homogenous buyers are overturned and novel ones emerge. First, inefficient equilibria exist in which exclusionary contracts are signed but entry still occurs, and the loss of consumer surplus falls on small buyers. Second, sequential contracting may be more pro-competitive than simultaneous contracting in the sense that entry occurs under sequential but not simultaneous contracting. When this happens, sequential contracting Pareto dominates simultaneous contracting. We extend our analysis to consider downstream competition and breach of contract.

Incorporating Cost Risk in Supplier Selection for Long Term Contracts

Purchasing firms naturally select the supplier with the lowest total cost. Often overlooked is the impact of the duration of long-term contracts (common in the automotive industry). We provide a method to quantify how risk escalates with contract duration. Our method applies to virtually all cost elements. For clarity, we demonstrate it on logistics costs that can change over a long horizon, resulting in a change in the relative attractiveness of candidate suppliers. We simulate a case study to estimate the likelihood that each supplier will provide the lowest cost over the contract duration. Finally, we quantify the risk reduction afforded by dividing a long contract into a sequence of shorter contracts.

A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN’s protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

Dynamic characteristics of droplets impacting an inclined wall based on a front-tracking method

In the current study, the dynamic characteristics of droplets impacting a hydrophilic/hydrophobic inclined wall are investigated using the front-tracking method. The morphological and kinematic features of the droplets are examined across various contact angles (θ), low Weber numbers (We≤10), and inclination angles (α). A sequence of events, including deposition, spreading, contraction, rebound, and subsequent re-spreading, is observed when a droplet impacts a hydrophobic wall, according to the results. The droplet exhibits both a small dimensionless spreading area (A*) and significant fluctuation, along with a noticeable slip on the wall. As We increases, the spread and rebound effects become more pronounced, and the slipping velocity also increases. As α increases, the slipping velocity becomes greater, and both A* and the dimensionless tangential spreading diameter (β) decrease. When a droplet impacts a hydrophilic wall, continuous deposition, spreading, and a subtle slip with inconspicuous rebound are observed. As We increases, A* expands at an accelerating rate. Furthermore, the wetting effect of hydrophilic surfaces on droplets cannot be overlooked. Consequently, it also shows that as α increases, there is a larger diffusion range along the wall with a longer diffusion film and a larger β. Such behaviors stand in contrast to a droplet impacting a hydrophobic wall.

A Highly Distensible, Cable Loop-Driven Soft Robotic Gastric Simulator for Endoscopy Training

With the increased demand for endoscopic diagnosis in the upper gastrointestinal (GI) tract, gastric simulators have been developed for endoscopy training. However, most of them remain nonideal due to their static and nondistensible nature. This paper presents a new soft robotic gastric simulator, comprising mainly of a silicone-based stomach model that mimics the size and inner surface condition of a human stomach. It also features peristaltic effect on its stomach wall via five cable loop-driven mechanisms, sphincter mechanisms at two ends of the stomach model, and structural pathology phantoms that can be magnetically controlled for multi-location deployment. Finite element simulation of the stomach behavior was performed under different insufflation pressures to determine the cable loop mechanism design parameters. During the simulator evaluation, the performances of the sphincters and cable loop mechanisms were first characterized. The simulator was then actuated to provide sequential contraction across the stomach model at different contraction ratios, leading to intragastric pressures similar to those reported in the literature. Finally, a preliminary user study was performed to face validate the simulator in terms of its realism, usability, and usefulness for endoscopy training. It is envisioned that the soft robotic gastric simulator could be adopted in endoscopy training programs to replace the use of animal models.

Contractual Chains

This paper develops a model of private bilateral contracting, in which an exogenous network determines the pairs of players who can communicate and contract with each other. After contracting, the players interact in an underlying game with globally verifiable productive actions and externally enforced transfers. The paper investigates whether such decentralized contracting can internalize externalities that arise due to parties being unable to contract directly with others whose productive actions affect their payoffs. The contract‐formation protocol, called the “contracting institution,” is treated as a design element. The main result is positive: There is a contracting institution that supports efficient equilibria for any underlying game and connected network. A critical property is that the institution allows for sequential contract formation or revision. The equilibrium construction features assurance contracts and cancellation penalties.

Feet Pumping Function

From the point of view of the physiology of the body, the foot muscles perform one of the most important physiological functions - pumping. Lymph and blood circulation provide the process of cell metabolism, maintaining its energy state. One of the conditions for maintaining effective lymph and blood circulation is correct walking biomechanics, i.e., nature laid down the sequence of muscle contraction, which cannot be the deformation of the arches of the feet, the use of shoes, limiting the work of the muscles of the feet.

Evaluation of nonnatural L-iminosugar C,C-glycosides, a new class of C-branched iminosugars, as glycosidase inhibitors

Capitalizing on a previously developed Staudinger/azaWittig/Grignard (SAWG)-ring contraction sequence that furnished protected six-membered L-iminosugar C,C-glycosides bearing an allyl group and various substituents at the pseudoanomeric position, the synthesis and glycosidase inhibition of a small library of six- and seven-membered L-iminosugar C,C-glycosides is reported. Their hydrogenolysis or cyclization by RCM followed by deprotection afforded eleven L-iminosugars including spirocyclic derivatives. All compounds adopt a 1C4 conformation in solution according to NMR data. Compared to previously reported branched L-iminosugars, the L-iminosugar C,C-glycosides reported herein were less potent glycosidase inhibitors. However, some of these compounds showed micromolar inhibition of human lysosome β-glucocerebrosidase suggesting that such iminosugars could be useful to access potent CGase inhibitors by adjusting the structure/length of the pseudoanomeric substituents.

Absolute Stability and Synchronization in Second-Order Neural Fields with Conduction Delays

We consider a class of neural field models represented by a second-order nonlinear system of integro-differential equations with space-dependent delays. Such a system models interaction of populations of neurons, each with a continuum description. We justify the existence and uniqueness of solution for the system in a suitable function space. Global existence and boundedness of solutions for the system are confirmed. Two methodologies, the comparison argument and sequential contracting, are developed to establish sufficient conditions for absolute stability and synchronization among different populations of the system. Finally, we present some numerical examples to demonstrate the theoretical results.

Conduction delays across the specialized conduction system of the heart: Revisiting atrioventricular node (AVN) and Purkinje-ventricular junction (PVJ) delays.

The specialized conduction system (SCS) of the heart was extensively studied to understand the synchronization of atrial and ventricular contractions, the large atrial to His bundle (A-H) delay through the atrioventricular node (AVN), and delays between Purkinje (P) and ventricular (V) depolarization at distinct junctions (J), PVJs. Here, we use optical mapping of perfused rabbit hearts to revisit the mechanism that explains A-H delay and the role of a passive electrotonic step-delay at the boundary between atria and the AVN. We further visualize how the P anatomy controls papillary activation and valve closure before ventricular activation. Rabbit hearts were perfused with a bolus (100-200 µl) of a voltage-sensitive dye (di4ANEPPS), blebbistatin (10-20 µM for 20 min) then the right atrial appendage and ventricular free-wall were cut to expose the AVN, P fibers (PFs), the septum, papillary muscles, and the endocardium. Fluorescence images were focused on a CMOS camera (SciMedia) captured at 1K-5 K frames/s from 100 × 100 pixels. AP propagation across the AVN-His (A-H) exhibits distinct patterns of delay and conduction blocks during S1-S2 stimulation. Refractory periods were 81 ± 9, 90 ± 21, 185 ± 15 ms for Atrial, AVN, and His, respectively. A large delay (>40 ms) occurs between atrial and AVN activation that increased during rapid atrial pacing contributing to the development of Wenckebach periodicity followed by delays within the AVN through slow or blocked conduction. The temporal resolution of the camera allowed us to identify PVJs by detecting doublets of AP upstrokes. PVJ delays were heterogeneous, fastest in PVJ that immediately trigger ventricular APs (3.4 ± 0.8 ms) and slow in regions where PF appear insulated from the neighboring ventricular myocytes (7.8 ± 2.4 ms). Insulated PF along papillary muscles conducted APs (>2 m/s), then triggered papillary muscle APs (<1 m/s), followed by APs firing of septum and endocardium. The anatomy of PFs and PVJs produced activation patterns that control the sequence of contractions ensuring that papillary contractions close the tricuspid valve 2-5 ms before right ventricular contractions. The specialized conduction system can be accessed optically to investigate the electrical properties of the AVN, PVJ and activation patterns in physiological and pathological conditions.

The optimality of public–private partnerships under financial and fiscal constraints

AbstractThe government may delegate two sequential tasks (e.g., building and operating an infrastructure) to the same or different agents (i.e., partnership vs. sequential contracts). Agents are risk‐neutral but face financial constraints, whereas the government's contractual capacity may be limited by the renegotiation‐proofness and fiscal constraints. By relying on history‐dependent incentives, the partnership contract corrects moral hazard more effectively than sequential contracts. Thus, it is socially preferred unless bundling different tasks deteriorates the agent's financial conditions. Our results shed new light on the role of firms' financial and government's fiscal conditions in driving the cost–benefit analysis of public–private partnerships.

Computational study of biomechanical drivers of renal cystogenesis.

Renal cystogenesis is the pathological hallmark of autosomal dominant polycystic kidney disease, caused by PKD1 and PKD2 mutations. The formation of renal cysts is a common manifestation in ciliopathies, a group of syndromic disorders caused by mutation of proteins involved in the assembly and function of the primary cilium. Cystogenesis is caused by the derailment of the renal tubular architecture and tissue deformation that eventually leads to the impairment of kidney function. However, the biomechanical imbalance of cytoskeletal forces that are altered in cells with Pkd1 mutations has never been investigated, and its nature and extent remain unknown. In this computational study, we explored the feasibility of various biomechanical drivers of renal cystogenesis by examining several hypothetical mechanisms that may promote morphogenetic markers of cystogenesis. Our objective was to provide physics-based guidance for our formulation of hypotheses and our design of experimental studies investigating the role of biomechanical disequilibrium in cystogenesis. We employed the finite element method to explore the role of (1) wild-type versus mutant cell elastic modulus; (2) contractile stress magnitude in mutant cells; (3) localization and orientation of contractile stress in mutant cells; and (4) sequence of cell contraction and cell proliferation. Our objective was to identify the factors that produce the characteristic tubular cystic growth. Results showed that cystogenesis occurred only when mutant cells contracted along the apical-basal axis, followed or accompanied by cell proliferation, as long as mutant cells had comparable or lower elastic modulus than wild-type cells, with their contractile stresses being significantly greater than their modulus. Results of these simulations allow us to focus future in vitro and in vivo experimental studies on these factors, helping us formulate physics-based hypotheses for renal tubule cystogenesis.

MP37-18 A PROSPECTIVE COHORT STUDY DEMONSTRATING EXERCISE EFFECTS FROM HOME BASED PELVIC FLOOR MUSCLE TRAINING TO REHABILITATE NEUROGENIC LOWER URINARY TRACT DYSFUNCTION; 3D REGIONAL EFFECTS

You have accessJournal of UrologyCME1 Apr 2023MP37-18 A PROSPECTIVE COHORT STUDY DEMONSTRATING EXERCISE EFFECTS FROM HOME BASED PELVIC FLOOR MUSCLE TRAINING TO REHABILITATE NEUROGENIC LOWER URINARY TRACT DYSFUNCTION; 3D REGIONAL EFFECTS Lynn Stothers, Andrew Macnab, Naser Hakimi, W. N. J. M. Colier, M. Maresse, and P. Pourabbassi Lynn StothersLynn Stothers More articles by this author , Andrew MacnabAndrew Macnab More articles by this author , Naser HakimiNaser Hakimi More articles by this author , W. N. J. M. ColierW. N. J. M. Colier More articles by this author , M. MaresseM. Maresse More articles by this author , and P. PourabbassiP. Pourabbassi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003275.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Women with neurogenic lower urinary tract dysfunction (NLUTD) rely on pelvic floor muscle rehabilitation therapy (PFMT) to aid continence. However, in NLUTD including spinal cord injury (SCI) PFM function is known to be affected regionally/asymmetrically which is not detected through exam or manometry. Objective: Report clinical translation of a optical PFM system, patient informed design to provide a 3D measures of PFM contractions quantifiable by reoxygenation recovery following sustained maximal voluntary contractions (SMVC) employed in PFMT. METHODS: An optical transvaginal interface was engineered using a circumferential grid of 6 light emitting diodes (LED’s) (wavelengths 750 & 860nm) & 4 photodiode detectors. Engineering design met preferences for size, shape, weight & ergometric features from a prior end user survey (Figure 1) Sampling at 50Hz, changes in oxy and deoxy-hemoglobin concentration (O2Hb/HHb) during PFM contractions monitored in real time, multiple point, from which HbDiff (O2Hb-HHb) is derived. All completed pre/post Qualiveen, were evaluated via NIRS during a standardized sequence of maximum & sustained PFM contractions, engaged in 12 weeks home based PFMT then repeat optical-derived measures of reoxygenation recovery. RESULTS: N=14 women (5 controls 7 NLUTD) 25–82 yrs. Baseline Qualiveen scores range: 0 (controls)-0.7 (NLUTD). Figure 1: output showing post PFMT composite graphics with NIRS data from channels monitoring the right & left sides of both the anterior & posterior segments of the PFM during 3 SMVC’s. All subjects were monitored successfully pre/post PFMT demonstrating 3D detailed functional ability of small segments of the pelvic floor & documenting effects of training. CONCLUSIONS: Optical detection of a validated quantifiable parameter of muscle reoxygenation in the PFM is feasible using this transvaginal optical interface designed based on women with NLUTD end user feedback. The multipoint design allows small regional variations in PFM functionality to be quantified & improvements from PFMT training effects to be measured in NLUTD/SCI to enhance rehabilitation of women living with NLUTD known to impact negatively on quality of life. Source of Funding: Craig H Neilsen Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e521 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lynn Stothers More articles by this author Andrew Macnab More articles by this author Naser Hakimi More articles by this author W. N. J. M. Colier More articles by this author M. Maresse More articles by this author P. Pourabbassi More articles by this author Expand All Advertisement PDF downloadLoading ...

Discrimination and learning of temporal input sequences in a cerebellar Purkinje cell model.

Temporal information processing is essential for sequential contraction of various muscles with the appropriate timing and amplitude for fast and smooth motor control. These functions depend on dynamics of neural circuits, which consist of simple neurons that accumulate incoming spikes and emit other spikes. However, recent studies indicate that individual neurons can perform complex information processing through the nonlinear dynamics of dendrites with complex shapes and ion channels. Although we have extensive evidence that cerebellar circuits play a vital role in motor control, studies investigating the computational ability of single Purkinje cells are few. We found, through computer simulations, that a Purkinje cell can discriminate a series of pulses in two directions (from dendrite tip to soma, and from soma to dendrite), as cortical pyramidal cells do. Such direction sensitivity was observed in whatever compartment types of dendrites (spiny, smooth, and main), although they have dierent sets of ion channels. We found that the shortest and longest discriminable sequences lasted for 60 ms (6 pulses with 10 ms interval) and 4,000 ms (20 pulses with 200 ms interval), respectively. and that the ratio of discriminable sequences within the region of the interesting parameter space was, on average, 3.3% (spiny), 3.2% (smooth), and 1.0% (main). For the direction sensitivity, a T-type Ca2+ channel was necessary, in contrast with cortical pyramidal cells that have N-methyl-D-aspartate receptors (NMDARs). Furthermore, we tested whether the stimulus direction can be reversed by learning, specifically by simulated long-term depression, and obtained positive results. Our results show that individual Purkinje cells can perform more complex information processing than is conventionally assumed for a single neuron, and suggest that Purkinje cells act as sequence discriminators, a useful role in motor control and learning.

Analytical prediction of ground movements due to circular shaft construction in clayey soils

With the rapid expansion of urbanization, shafts are needed to provide access to tunnelling projects or be utilized for permanent works. Their construction causes ground movements, affecting nearby foundations and buried infrastructure. This study presents an analytical equivalent volume loss approach for predicting three-dimensional ground movements resulting from a circular shaft construction: namely, ground losses in the elastic isotropic half space as a sequence of cavity contractions around the shaft are employed. First, the applicability and accuracy of proposed solutions are evaluated with published case studies and centrifuge tests. Thereafter, the method is employed to investigate the influence of the circular shaft construction on the surface and subsurface soil displacements. Considering design ground losses, this method allows for quick estimations of ground deformations and associated risk of serviceability losses.

Sincronismo muscular en patrones de movimiento de miembros superiores descritos por Kabat: latencia al inicio del pico de la máxima activación electromiográfica

IntroductionThe Kabat method argues that normal synchronism occurs from distal to proximal, which requires electromyographic evidence. ObjectiveTo describe the muscular timing of motor patterns of the upper limbs described by Kabat, in seated and supine positions, from the measurement of the latency at the beginning of the peak of the maximum electromyographic activation (BPM-EMG-A) of selected muscles. Material and methodsA comparative analytical study was carried out. Twenty men and 20 women between 19 and 26 years old were evaluated. Each participant performed 3active repetitions without external resistance of each of the movement patterns (flexor and extensor) of the 2diagonals. BPM-EMG-A latency was recorded for each of the 8muscles tested in the 4movement patterns, both supine and seated. These were averaged and ordered from lowest to highest to obtain the sequence of muscle contractions in each movement pattern. The sequences obtained for each pattern in seated and supine were compared and the existence of correlations between them was assessed. ResultsSignificant correlation was observed in the BPM-EMG-A sequences between supine and seated positions, in all movement patterns (P<0.05), except in the extensor pattern of the first diagonal (P=0.139). There were no statistically significant differences between positions in any of the patterns (P>0.05). ConclusionAlthough with variations in BPM-EMG-A, muscle timing was generally found from proximal to distal, more evident in the sitting position and in flexor patterns.

New results of tw-normed approach space

In this paper, a improved convergence theorem, focal point, tw-Cauchy series, tw-convergent, tw-precision and sequential reduction in tw-approach space are defined and studied. The necessity of achieving the contraction condition in order to get the sequential contraction function is also shown. Moreover, a new structure for the norm in tw-approach space is put, which is called tw-approach-Banach space. Furthermore, tw-approach normed space with uniform condition are given to be a Hausdorff space as well as tw-approach normed space is shown to be the metric space formed by is full if and only if tw-approach space is a complete, so, every finite-dimensional tw-approach normed space is proven to be tw-complete. Some important results and properties in this field are introduced and discussed. is more real in its representation of the relationship between quantity demanded and price, whereas the other model takes into account both demand and Expenses incurred.