Ephaptic Coupling as a Resolution to the Paradox of Action Potential Wave Speed and Discordant Alternans Spatial Scales in the Heart.

Previous computer simulations have suggested that existing models of action potential wave propagation in the heart are not consistent with observed wave propagation behavior. Specifically, computer models cannot simultaneously reproduce the rapid wave speeds and small spatial scales of discordant alternans patterns measured experimentally in the same simulation. The discrepancy is important, because discordant alternans can be a key precursor to the development of abnormal and dangerous rapid rhythms in the heart. In this Letter, we show that this paradox can be resolved by allowing so-called ephaptic coupling to play a primary role in wave front propagation in place of conventional gap-junction coupling. With this modification, physiological wave speeds and small discordant alternans spatial scales both occur with gap-junction resistance values that are more in line with those observed in experiments. Our theory thus also provides support to the hypothesis that ephaptic coupling plays an important role in normal wave propagation.

Probing Ground-State Phase Transitions through Quench Dynamics.

The study of quantum phase transitions requires the preparation of a many-body system near its ground state, a challenging task for many experimental systems. The measurement of quench dynamics, on the other hand, is now a routine practice in most cold atom platforms. Here we show that quintessential ingredients of quantum phase transitions can be probed directly with quench dynamics in integrable and nearly integrable systems. As a paradigmatic example, we study global quench dynamics in a transverse-field Ising model with either short-range or long-range interactions. When the model is integrable, we discover a new dynamical critical point with a nonanalytic signature in the short-range correlators. The location of the dynamical critical point matches that of the quantum critical point and can be identified using a finite-time scaling method. We extend this scaling picture to systems near integrability and demonstrate the continued existence of a dynamical critical point detectable at prethermal timescales. We quantify the difference in the locations of the dynamical and quantum critical points away from (but near) integrability. Thus, we demonstrate that this method can be used to approximately locate the quantum critical point near integrability. The scaling method is also relevant to experiments with finite time and system size, and our predictions are testable in near-term experiments with trapped ions and Rydberg atoms.

Scale-Invariant Continuous Entanglement Renormalization of a Chern Insulator.

The multiscale entanglement renormalization ansatz (MERA) postulates the existence of quantum circuits that renormalize entanglement in real space at different length scales. Chern insulators, however, cannot have scale-invariant discrete MERA circuits with a finite bond dimension. In this Letter, we show that the continuous MERA (cMERA), a modified version of MERA adapted for field theories, possesses a fixed point wave function with a nonzero Chern number. Additionally, it is well known that reversed MERA circuits can be used to prepare quantum states efficiently in time that scales logarithmically with the size of the system. However, state preparation via MERA typically requires the advent of a full-fledged universal quantum computer. In this Letter, we demonstrate that our cMERA circuit can potentially be realized in existing analog quantum computers, i.e., an ultracold atomic Fermi gas in an optical lattice with light-induced spin-orbit coupling.

Non-Fermi-liquid d-wave metal phase of strongly interacting electrons.

Developing a theoretical framework for conducting electronic fluids qualitatively distinct from those described by Landau's Fermi-liquid theory is of central importance to many outstanding problems in condensed matter physics. One such problem is that, above the transition temperature and near optimal doping, high-transition-temperature copper-oxide superconductors exhibit 'strange metal' behaviour that is inconsistent with being a traditional Landau Fermi liquid. Indeed, a microscopic theory of a strange-metal quantum phase could shed new light on the interesting low-temperature behaviour in the pseudogap regime and on the d-wave superconductor itself. Here we present a theory for a specific example of a strange metal--the 'd-wave metal'. Using variational wavefunctions, gauge theoretic arguments, and ultimately large-scale density matrix renormalization group calculations, we show that this remarkable quantum phase is the ground state of a reasonable microscopic Hamiltonian--the usual t-J model with electron kinetic energy t and two-spin exchange J supplemented with a frustrated electron 'ring-exchange' term, which we here examine extensively on the square lattice two-leg ladder. These findings constitute an explicit theoretical example of a genuine non-Fermi-liquid metal existing as the ground state of a realistic model.

Asymmetric Particle Transport and Light-Cone Dynamics Induced by Anyonic Statistics.

We study the nonequilibrium dynamics of Abelian anyons in a one-dimensional system. We find that the interplay of anyonic statistics and interactions gives rise to spatially asymmetric particle transport together with a novel dynamical symmetry that depends on the anyonic statistical angle and the sign of interactions. Moreover, we show that anyonic statistics induces asymmetric spreading of quantum information, characterized by asymmetric light cones of out-of-time-ordered correlators. Such asymmetric dynamics is in sharp contrast to the dynamics of conventional fermions or bosons, where both the transport and information dynamics are spatially symmetric. We further discuss experiments with cold atoms where the predicted phenomena can be observed using state-of-the-art technologies. Our results pave the way toward experimentally probing anyonic statistics through nonequilibrium dynamics.

Extracting Entanglement Geometry from Quantum States.

Tensor networks impose a notion of geometry on the entanglement of a quantum system. In some cases, this geometry is found to reproduce key properties of holographic dualities, and subsequently much work has focused on using tensor networks as tractable models for holographic dualities. Conventionally, the structure of the network-and hence the geometry-is largely fixed a priori by the choice of the tensor network ansatz. Here, we evade this restriction and describe an unbiased approach that allows us to extract the appropriate geometry from a given quantum state. We develop an algorithm that iteratively finds a unitary circuit that transforms a given quantum state into an unentangled product state. We then analyze the structure of the resulting unitary circuits. In the case of noninteracting, critical systems in one dimension, we recover signatures of scale invariance in the unitary network, and we show that appropriately defined geodesic paths between physical degrees of freedom exhibit known properties of a hyperbolic geometry.

G protein ß4 as a structural determinant of enhanced nucleotide exchange in the A2AAR-Gs complex.

Adenosine A2A receptors (A2AAR) evoke pleiotropic intracellular signaling events via activation of the stimulatory heterotrimeric G protein, Gs. Here, we used cryoEM to solve the agonist-bound structure of A2AAR in a complex with full-length Gs α and Gß4γ2 (A2AAR-Gs α:ß4γ2). The orthosteric binding site of A2AAR-Gs α:ß4γ2 was similar to other structures of agonist-bound A2AAR, with or without Gs. Unexpectedly, the solvent accessible surface area within the interior of the complex was substantially larger for the complex with Gß4 versus the closest analog, A2AAR-miniGs α:ß1γ2. Consequently, there are fewer interactions between the switch II in Gs α and the Gß4 torus. In reconstitution experiments Gß4γ2 displayed a ten-fold higher efficiency over Gß1γ2 in catalyzing A2AAR dependent GTPγS binding to Gs α. We propose that the less constrained switch II in A2AAR-Gs α:ß4γ2 accounts for this increased efficiency. These results suggest that Gß4 functions as a positive allosteric enhancer versus Gß1.

Atrial fibrillation symptom reduction and improved quality of life following the hybrid convergent procedure: a CONVERGE trial subanalysis.

Background: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Methods: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. Results: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). Conclusions: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. ClinicalTrialsgov Identifier: NCT01984346.

Theory of a competitive spin liquid state for weak Mott insulators on the triangular lattice.

We propose a novel quantum spin liquid state that can explain many of the intriguing experimental properties of the low-temperature phase of the organic spin liquid candidate materials κ-(BEDT-TTF)2Cu2(CN)3 and EtMe3Sb[Pd(dmit)2]2. This state of paired fermionic spinons preserves all symmetries of the system, and it has a gapless excitation spectrum with quadratic bands that touch at momentum k[over →]=0. This quadratic band touching is protected by symmetries. Using variational Monte Carlo techniques, we show that this state has highly competitive energy in the triangular lattice Heisenberg model supplemented with a realistically large ring-exchange term.

Role of ephaptic coupling in discordant alternans domain sizes and action potential propagation in the heart.

Discordant alternans, the spatially out-of-phase alternation of the durations of propagating action potentials in the heart, has been linked to the onset of fibrillation, a major cardiac rhythm disorder. The sizes of the regions, or domains, within which these alternations are synchronized are critical in this link. However, computer models employing standard gap junction-based coupling between cells have been unable to reproduce simultaneously the small domain sizes and rapid action potential propagation speeds seen in experiments. Here we use computational methods to show that rapid wave speeds and small domain sizes are possible when a more detailed model of intercellular coupling that accounts for so-called ephaptic effects is used. We provide evidence that the smaller domain sizes are possible, because different coupling strengths can exist on the wavefronts, for which both ephaptic and gap-junction coupling are involved, in contrast to the wavebacks, where only gap-junction coupling plays an active role. The differences in coupling strength are due to the high density of fast-inward (sodium) channels known to localize on the ends of cardiac cells, which are only active (and thus engage ephaptic coupling) during wavefront propagation. Thus, our results suggest that this distribution of fast-inward channels, as well as other factors responsible for the critical involvement of ephaptic coupling in wave propagation, including intercellular cleft spacing, play important roles in increasing the vulnerability of the heart to life-threatening tachyarrhythmias. Our results, combined with the absence of short-wavelength discordant alternans domains in standard gap-junction-dominated coupling models, also provide evidence that both gap-junction and ephaptic coupling are critical in wavefront propagation and waveback dynamics.

Hybrid epicardial-endocardial ablation for long-standing persistent atrial fibrillation: A subanalysis of the CONVERGE Trial.

Background: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA. Objective: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial. Methods: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom. Results: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC. Conclusion: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.

Much ado about adenosine: adenosine synthesis and function in regulatory T cell biology.

Recent studies have reported that adenosine is a significant mediator of regulatory T cell (Treg) function. Indeed, activation of the adenosine receptor subtypes expressed by a broad range of immune and inflammatory cells attenuates inflammation in several disease models. This anti-inflammatory response is associated with an increase in intracellular cAMP that inhibits cytokine responses of many immune/inflammatory cells, including T cells and APCs. Thus, adenosine produced by Tregs can provide a paracrine feedback that shapes the host response following an immunologic provocation. This review discusses the evidence that adenosine is an integral part of Treg biology and presents some of the mechanisms that may account for its contribution to the resolution of inflammation and the regulation of the immune/inflammatory cell phenotype.

A key role for the phosphorylation of Ser440 by the cyclic AMP-dependent protein kinase in regulating the activity of the Src homology 2 domain-containing Inositol 5'-phosphatase (SHIP1).

The Src homology 2 domain-containing inositol 5'-phosphatase 1 (SHIP1) dephosphorylates phosphatidylinositol 3,4,5-trisphosphate to phophatidylinositol 3,4-bisphosphate in hematopoietic cells to regulate multiple cell signaling pathways. SHIP1 can be phosphorylated by the cyclic AMP-dependent protein kinase (PKA), resulting in an increase in SHIP1 activity (Zhang, J., Walk, S. F., Ravichandran, K. S., and Garrison, J. C. (2009) J. Biol. Chem. 284, 20070-20078). Using a combination of approaches, we identified the serine residue regulating SHIP1 activity. After mass spectrometric identification of 17 serine and threonine residues on SHIP1 as being phosphorylated by PKA in vitro, studies with truncation mutants of SHIP1 narrowed the phosphorylation site to the catalytic region between residues 400 and 866. Of the two candidate phosphorylation sites located in this region (Ser(440) and Ser(774)), only mutation of Ser(440) to Ala abolished the ability of PKA to phosphorylate the purified, catalytic domain of SHIP1 (residues 401-866). Mutation of Ser(440) to Ala in full-length SHIP1 abrogated the ability of PKA to increase the activity of SHIP1 in mammalian cells. Using flow cytometry, we found that the PKA activator, Sp-adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Sp-cAMPS) blunted the phosphorylation of Akt downstream of B cell antigen receptor engagement in SHIP1-null DT40 B lymphocytes expressing native mouse SHIP1. The inhibitory effect of Sp-cAMPS was absent in cells expressing the S440A mutant of SHIP1. These results suggest that activation of SHIP1 by PKA via phosphorylation on Ser(440) is an important regulatory event in hematopoietic cells.

T-type calcium channel regulation by specific G-protein betagamma subunits.

Low-voltage-activated (LVA) T-type calcium channels have a wide tissue distribution and have well-documented roles in the control of action potential burst generation and hormone secretion. In neurons of the central nervous system and secretory cells of the adrenal and pituitary, LVA channels are inhibited by activation of G-protein-coupled receptors that generate membrane-delimited signals, yet these signals have not been identified. Here we show that the inhibition of alpha1H (Ca(v)3.2), but not alpha(1G) (Ca(v)3.1) LVA Ca2+ channels is mediated selectively by beta2gamma2 subunits that bind to the intracellular loop connecting channel transmembrane domains II and III. This region of the alpha1H channel is crucial for inhibition, because its replacement abrogates inhibition and its transfer to non-modulated alpha1G channels confers beta2gamma2-dependent inhibition. betagamma reduces channel activity independent of voltage, a mechanism distinct from the established betagamma-dependent inhibition of non-L-type high-voltage-activated channels of the Ca(v)2 family. These studies identify the alpha1H channel as a new effector for G-protein betagamma subunits, and highlight the selective signalling roles available for particular betagamma combinations.

Entanglement bounds on the performance of quantum computing architectures.

There are many possible architectures of qubit connectivity that designers of future quantum computers will need to choose between. However, the process of evaluating a particular connectivity graph's performance as a quantum architecture can be difficult. In this paper, we show that a quantity known as the isoperimetric number establishes a lower bound on the time required to create highly entangled states. This metric we propose counts resources based on the use of two-qubit unitary operations, while allowing for arbitrarily fast measurements and classical feedback. We use this metric to evaluate the hierarchical architecture proposed by A. Bapat et al. [Phys. Rev. A 98, 062328 (2018)] and find it to be a promising alternative to the conventional grid architecture. We also show that the lower bound that this metric places on the creation time of highly entangled states can be saturated with a constructive protocol, up to a factor logarithmic in the number of qubits.

Cramer-Rao Lower Bound for SoOp-R-Based Root-Zone Soil Moisture Remote Sensing.

Signals of opportunity (SoOp) reflectometry (SoOp-R) is a maturing field for geophysical remote sensing as evidenced by the growing number of airborne and spaceborne experiments. As this approach receives more attention, it is worth analyzing SoOp-R's capabilities to retrieve subsurface soil moisture (SM) by leveraging communication and navigation satellite transmitters. In this research, the CRLB is used to identify the effects of variable SoOp-R parameters on the best achievable estimation error for root-zone soil moisture (RZSM). This study investigates the use of multiple frequency, polarization, and incidence angle measurement configurations on a two-layered dielectric profile. The results also detail the effects of variable SM conditions on the capability of SoOp-R systems to predict subsurface SM. The most prevalent observation is the importance of using at least two frequencies to limit uncertainties from subsurface SM estimates. If at least two frequencies are used, the CRLB of a profile is retrievable within the root-zone depending on the surface SM content as well as the number of independent measurements of the profile. For a depth of 30 cm, it is observed that a CRLB corresponding to 4% RZSM estimation accuracy is achievable with as few as 2 dual-frequency-based SoOp-R measurements. For this depth, increasing number of measurements provided by polarization and incidence angle allow for sensing of increasingly wet SM profile structures. This study, overall, details a methodology by which SoOp-R receiver system can be designed to achieve a desired CRLB using a trade-off study between the available measurements and SM profile.

RESIDENTS CASE REPORT: MUSCULOCUTANEOUS NERVE INJURY IN A COLLEGIATE BASEBALL PITCHER.

BACKGROUND: Literature regarding musculocutaneous nerve injuries among the athletic population is scarce, with only several reported clinical cases among baseball and softball pitchers. PURPOSE: To present a unique case of a musculocutaneous nerve injury to aid in clinician awareness and propose innovative rehabilitation practices that may facilitate improved patient outcomes during recovery. CASE DESCRIPTION: A 23-year-old Division 1 NCAA collegiate baseball pitcher presented with vague anterior arm pain following a pre-season game. The athlete described the pain as an "intense stretch" of his right arm that occurred during his last pitch. The initial evaluation identified tenderness over the right distal bicep. All shoulder and elbow orthopedic tests to assess shoulder impingement, labral pathologies, and glenohumeral instability were unremarkable. Increased neural tension was also noted with upper limb neurodynamic testing of the median and ulnar nerves on the right arm compared bilaterally. Electromyography (EMG) testing confirmed a right upper and mid-brachial plexus stretch injury with the primary involvement of the musculocutaneous nerve. Rehabilitation focused on restoring strength deficits and diminishing neural tension. Blood flow restriction (BFR) was introduced on the uninvolved limb to reduce deficits in bicep musculature strength. Once the athlete regained bicep strength and forearm sensation, he was progressed from flat-ground throwing activities to throwing off the mound. OUTCOMES: A reduction in neural tension during neurodynamic testing of the right arm, improvement of bicep brachii deficits seen between the right and left limbs, and restoration of sensation in the right lateral forearm enabled a progressive return to sport. DISCUSSION: Due to vague reports and inconclusive findings, the initial presentation of musculocutaneous nerve injuries may be mistaken for other conditions such as a biceps brachii strain. Further -documentation of this injury and rehabilitation procedures are needed to enhance patient outcomes.

Locality and Digital Quantum Simulation of Power-Law Interactions.

The propagation of information in nonrelativistic quantum systems obeys a speed limit known as a Lieb-Robinson bound. We derive a new Lieb-Robinson bound for systems with interactions that decay with distance r as a power law, 1/r α . The bound implies an effective light cone tighter than all previous bounds. Our approach is based on a technique for approximating the time evolution of a system, which was first introduced as part of a quantum simulation algorithm by Haah et al., FOCS'18. To bound the error of the approximation, we use a known Lieb-Robinson bound that is weaker than the bound we establish. This result brings the analysis full circle, suggesting a deep connection between Lieb-Robinson bounds and digital quantum simulation. In addition to the new Lieb-Robinson bound, our analysis also gives an error bound for the Haah et al. quantum simulation algorithm when used to simulate power-law decaying interactions. In particular, we show that the gate count of the algorithm scales with the system size better than existing algorithms when α > 3D (where D is the number of dimensions).

Joint-Level Analyses of the Back Squat With and Without Intraset Rest.

Purpose: To provide a joint-level analysis of traditional (TS) and cluster (CS) set structure during the back-squat exercise. Methods: Eight men (24 [3] y, 177.3 [7.9] cm, 82.7 [11.0] kg, 11.9 [3.5] % body fat, and 150.3 [23.0] kg 1-repetition maximum [1RM]) performed the back-squat exercise (80%1RM) using TS (4 × 6, 2-min interset rest) and CS (4 × [2 × 3], 30-s intraset rest, 90-s interset rest), randomly. Lower-limb kinematics were collected by motion capture, as well as kinetic data by bilateral force platforms. Results: CS attenuated the loss in mean power (TS -21.6% [3.9%]; CS -12.4% [7.5%]; P = .042), although no differences in gross movement pattern (sagittal-plane joint angles) within and between conditions were observed (P ≥ .05). However, joint power produced at the hip increased from repetition (REP) 1 through REP 6 during TS, while a decrease was noted at the knee. A similar pattern was observed in the CS condition but was limited to the hip. Joint power produced at the hip increased from REP 1 through REP 3 but returned to REP 1 values before a similar increase through REP 6, resulting in differences between conditions (REP 4, P = .018; REP 5, P = .022). Conclusions: Sagittal-plane joint angles did not change in either condition, although CS elicited greater power. Differing joint power contributions (hip and knee) suggest potential central mechanism that may contribute to enhanced power output during CS and warrant further study. Practitioners should consider incorporating CS into training to promote greater power adaptations and to mitigate fatigue.

Unitary entanglement construction in hierarchical networks.

The construction of large-scale quantum computers will require modular architectures that allow physical resources to be localized in easy-to-manage packages. In this work we examine the impact of different graph structures on the preparation of entangled states. We begin by explaining a formal framework, the hierarchical product, in which modular graphs can be easily constructed. This framework naturally leads us to suggest a class of graphs, which we dub hierarchies. We argue that such graphs have favorable properties for quantum information processing, such as a small diameter and small total edge weight, and use the concept of Pareto efficiency to identify promising quantum graph architectures. We present numerical and analytical results on the speed at which large entangled states can be created on nearest-neighbor grids and hierarchy graphs. We also present a scheme for performing circuit placement-the translation from circuit diagrams to machine qubits-on quantum systems whose connectivity is described by hierarchies.