Effects of Nitrate Supplementation on In Vivo Muscle Torque Recovery From BaCl2-Induced Injury

During repair from muscle injury, muscle satellite cells depend on nitric oxide production by immune cells to proliferate and differentiate. Nitrate supplementation has been shown to improve muscle endurance and oxygen consumption, but little is known about the ability of nitrate supplementation to interfere with muscle regeneration following injury. PURPOSE: To investigate whether nitrate supplementation affects muscle recovery of force after muscle injury produced by intramuscular injection of barium chloride. METHODS: Transgenic male mice (12 weeks old) that express Td-Tomato fluorescent protein in Pax7+ cells (i.e., satellite cells; Pax7CreER-Ai9 mice) were treated with tamoxifen (2 mg in corn oil, i.p.) once a day for 5 days. Four days after the last tamoxifen injection, both legs were subjected to stimulation of the peroneal nerve to evoke contractions of the anterior crural muscles at different frequencies of stimulation (1-200 Hz; i.e., Torque-frequency curve), followed by intramuscular injections of 1.2% BaCl2 (w/v) to produce injury of the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of the right leg. The contralateral leg served as a non-injured control. Torque-frequency curves were tested for both legs on days 2, 7, 14 and 21 post injury. At day 21, mice were euthanized, and muscles were dissected for histology (TA) and ex-vivo muscle contractility (EDL). A group of mice was treated with 1 g/L of NaNO3 in drinking water (nitrate group) 1 week before muscle injury, and a second group of mice was not treated (water group). RESULTS: Mice treated with NaNO3 (nitrate group) showed smaller torque in the non-injured leg compared to water group (103 ± 3 vs 84 ± 2 Nmm/kg, for water vs nitrate groups, respectively). However, the torque produced by the injured leg normalized by the torque developed by the non-injured leg was not different between groups on days 2 (28 ± 13% vs 25 ± 1%), 7 (41 ± 4% vs 35 ± 2%), 14 (81 ± 7% vs 87 ± 1%) and 21 (104 ± 3% vs 105 ± 3%) for water and nitrate groups respectively. CONCLUSION: The data suggest that nitrate supplementation decreases nerve-stimulated torque development in uninjured leg but does not change the recovery of torque after BaCl2 injury. Support: TRDRP grant # T29KT0397CA (to L.N.

Single-Leg Resistance Exercise Training in Mice Leads to a Fast Increase in In Vivo Torque of Anterior Crural Muscles

Resistance exercise is known to produce muscle hypertrophy. However, little is known about the role of muscle satellite cells in generating new myofibers or in incorporating satellite cells to live myofibers during exercise training. PURPOSE: To investigate whether single-leg resistance exercise training can activate the incorporation of muscle satellite cells in mice. METHODS: Transgenic male mice (12 weeks old) that express Td-Tomato fluorescent protein in Pax7+ (i.e., satellite cells) cells (Pax7CreER-Ai9) were treated with tamoxifen (2 mg in corn oil, i.p.) once a day for 5 days. Three days later, mice were single-leg exercise trained (i.e stimulation of the peroneal nerve of the right leg of each mouse to evoke fused tetanic contractions [100 Hz] of the anterior crural muscles), 3x per week for either 1 or 2 weeks. Each training session was composed of 3-s contractions with 7 s recovery between contractions, 10 contractions each set, 5 sets with 5 min rest between sets. Before the first training session and 3 days after the last training session (1 week or 2 weeks training), torque produced by the ankle was measured at different frequencies of pulse-stimulation (1-200 Hz), mice were euthanized, and muscles were frozen for histological measurements. RESULTS: During each session of training, peak torque developed at the last contraction was ~30% of the torque developed in the initial contraction of the session suggesting fatigue development. Between sessions of training, initial torque was not significantly different suggesting that muscle recovered function between sessions. Torque measurements at different frequencies of stimulation 3 days after 1 week or 2 weeks of training showed a ~50% increase in maximal tetanic torque relative to the mice body weight, after 1 week of training but there were no additional changes at 2 weeks of training. Tibialis anterior muscle cross sectional area and number of Td-tomato positive myofibers were also measured in these mice. CONCLUSION: Resistance exercise training in mice by using single-leg electrical stimulations leads to a fast (i.e., 1 week) increase in muscle force development

The Virtual Refraction: Useful Spurious Energy in Seismic Interferometry

Seismic interferometry is rapidly becoming an established technique to recover the Green’s function between receivers, but practical limitations in the source-energy distribution inevitably lead to spurious energy in the results. Instead of attempting to suppress all such energy, we use a spurious wave associated with the crosscorrelation of refracted energy at both receivers to infer estimates of subsurface parameters. We named this spurious event the virtual refraction. Illustrated by a numerical two-layer example, we found that the slope of the virtual refraction defines the velocity of the faster medium and that the stationary-phase point in the correlation gather provides the critical offset. With the associated critical time derived from the real shot record, this approach includes all of the necessary information to estimate wave speeds and interface depth without the need of inferences from other wave types

Performance and structure of single-mode bosonic codes

The early Gottesman, Kitaev, and Preskill (GKP) proposal for encoding a qubit in an oscillator has recently been followed by cat- and binomial-code proposals. Numerically optimized codes have also been proposed, and we introduce new codes of this type here. These codes have yet to be compared using the same error model; we provide such a comparison by determining the entanglement fidelity of all codes with respect to the bosonic pure-loss channel (i.e., photon loss) after the optimal recovery operation. We then compare achievable communication rates of the combined encoding-error-recovery channel by calculating the channel's hashing bound for each code. Cat and binomial codes perform similarly, with binomial codes outperforming cat codes at small loss rates. Despite not being designed to protect against the pure-loss channel, GKP codes significantly outperform all other codes for most values of the loss rate. We show that the performance of GKP and some binomial codes increases monotonically with increasing average photon number of the codes. In order to corroborate our numerical evidence of the cat/binomial/GKP order of performance occurring at small loss rates, we analytically evaluate the quantum error-correction conditions of those codes. For GKP codes, we find an essential singularity in the entanglement fidelity in the limit of vanishing loss rate. In addition to comparing the codes, we draw parallels between binomial codes and discrete-variable systems. First, we characterize one- and two-mode binomial as well as multi-qubit permutation-invariant codes in terms of spin-coherent states. Such a characterization allows us to introduce check operators and error-correction procedures for binomial codes. Second, we introduce a generalization of spin-coherent states, extending our characterization to qudit binomial codes and yielding a new multi-qudit code.Comment: 34 pages, 11 figures, 4 tables. v3: published version. See related talk at https://absuploads.aps.org/presentation.cfm?pid=1351

The Spatial Cross-Correlation Method for Dispersive Surface Waves

Dispersive surface waves are routinely used to estimate the subsurface shear-wave velocity distribution, at all length scales. In the well-known Spatial Autocorrelation method, dispersion information is gained from the correlation of seismic noise signals recorded on the vertical (or radial) components. We demonstrate practical advantages of including the cross-correlation between radial and vertical components of the wavefield in a spatial cross-correlation method. The addition of cross-correlation information increases the resolution and robustness of the phase velocity dispersion information, as demonstrated in numerical simulations and a near-surface field study with active seismic sources, where our method confirms the presence of a fault-zone conduit in a geothermal field

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Extension of the Spatial Autocorrelation (SPAC) Method to Mixed-Component Correlations of Surface Waves

Using ambient seismic noise for imaging subsurface structure dates back to the development of the spatial autocorrelation (SPAC) method in the 1950s. We present a theoretical analysis of the SPAC method for multicomponent recordings of surface waves to determine the complete 3 × 3 matrix of correlations between all pairs of three-component motions, called the correlation matrix. In the case of isotropic incidence, when either Rayleigh or Love waves arrive from all directions with equal power, the only non-zero off-diagonal terms in the matrix are the vertical–radial (ZR) and radial–vertical (RZ) correlations in the presence of Rayleigh waves. Such combinations were not considered in the development of the SPAC method. The method originally addressed the vertical–vertical (ZZ), RR and TT correlations, hence the name spatial autocorrelation. The theoretical expressions we derive for the ZR and RZ correlations offer additional ways to measure Rayleigh wave dispersion within the SPAC framework. Expanding on the results for isotropic incidence, we derive the complete correlation matrix in the case of generally anisotropic incidence. We show that the ZR and RZ correlations have advantageous properties in the presence of an out-of-plane directional wavefield compared to ZZ and RR correlations. We apply the results for mixed-component correlations to a data set from Akutan Volcano, Alaska and find consistent estimates of Rayleigh wave phase velocity from ZR compared to ZZ correlations. This work together with the recently discovered connections between the SPAC method and time-domain correlations of ambient noise provide further insights into the retrieval of surface wave Green’s functions from seismic noise

Analyzing the Coda from Correlating Scattered Surface Waves

The accuracy of scattered Rayleigh waves estimated using an interferometric method is investigated. Summing the cross correlations of the wave fields measured all around the scatterers yields the Green’s function between two excitation points. This accounts for the direct wave and the scattered field (coda). The correlations themselves provide insights into the location of the scatterers, as well as which scatterer is responsible for particular parts of the coda. Furthermore, these measurements confirm a constant-time arrival in the correlations, not part of the Green’s function, but which has previously been derived as a result of the generalized optical theorem