Neuromuscular factors contributing to reductions in muscle force after repeated, high-intensity muscular efforts

Fatigue can accumulate sufficiently to limit muscular force production during repeated, forceful muscle contractions, including those that occur in the occupational, clinical and athletic settings. Fatigue during such efforts is likely to result from disturbances to multiple processes in the nervous system and muscle. However, previous research examining the mechanisms underpinning fatigue have typically required subjects to perform low-level constant-force contractions or to repeat maximal efforts in a single set format. Such tasks do not translate well to occupational, daily living or athletic situations where high-intensity, yet submaximal, repeated efforts may be performed in work bouts (or sets) with brief rest periods for recovery. Therefore, the overall aim of the present research was to investigate the neuromuscular mechanisms contributing to force loss after repeated, high-intensity muscular efforts with longer (90 s) periods of rest separating repetitions into sets of contractions. In Experiment 1, 16 resistance trained men performed 6 sets of unilateral isometric plantar flexor contractions of the right leg (3 s contraction/2 s rest) reaching a target level of 85% maximal voluntary contraction (MVC). Sets were separated by a 90-s inter-set rest and completed to failure (i.e. In Experiment 1, a significant reduction in maximum voluntary isometric plantar flexion torque (12.2%; p \u3c 0.001) was observed post-exercise, which did not recover by POST-20. Significant reductions in triceps surae EMG/M (-6%; p = 0.024) and MEP/M amplitude (9%; p = 0.01) were found post-exercise but recovered by POST-10. Cortical silent period (an indicator of GABAB-mediated intracortical inhibition) was reduced (-4%; p = 0.016) post-exercise and did not recover by POST-20. In Experiment 2, temporal changes in torque were similar to Experiment 1. Significant reductions in the evoked torque response from 20 Hz (p \u3c 0.001), 80 Hz (p \u3c 0.001) and VFT (p \u3c 0.001) stimulations were observed at POST and did not recover by POST-20, however no changes in 20:80 and 20:VFT ratios were observed. Finally, significant reductions in both Tvib (-13%; p = 0.035) and Tsust (-25%; p = 0.035) were found post-exercise but recovered by POST-10. The ingestion of caffeine allowed for a greater overall torque production and neural drive (EMG/M) but the lack of condition time interaction effect indicated that it did not clearly affect the time course of fatigue or recovery. Further, no detectable effects were observed compared to the non-caffeine condition in corticospinal excitability, MN excitability or E-C coupling, as shown by the negligible changes in MEP/M amplitude, PIC facilitation, and torque during 20-Hz, 80-Hz and VFT stimulations. These data suggest that corticospinal tract efficiency and PIC-mediated facilitation of the MN pool can be compromised and are likely to account in part for the force loss immediately following an acute bout of repeated, high-intensity muscular efforts performed in sets (with 90 s rest). However, changes in E-C coupling efficiency (i.e. ‘peripheral fatigue) are likely to explain the ongoing, prolonged loss of force, at least to 20 min post-exercise. Therefore, it is likely that both changes in the nervous system as well as the muscle contribute to the loss of force following repeated, high-intensity muscular efforts

BLIMPK/Streamline Surface Catalytic Heating Predictions on the Space Shuttle Orbiter

This paper describes the results of an analysis of localized catalytic heating effects to the U.S. Space Shuttle Orbiter Thermal Protection System (TPS). The analysis applies to the High-temperature Reusable Surface Insulation (HRSI) on the lower fuselage and wing acreage, as well as the critical Reinforced Carbon-Carbon on the nose cap, chin panel and the wing leading edge. The object of the analysis was to use a modified two-layer approach to predict the catalytic heating effects on the Orbiter windward HRSI tile acreage, nose cap, and wing leading edge assuming localized highly catalytic or fully catalytic surfaces. The method incorporated the Boundary Layer Integral Matrix Procedure Kinetic (BLIMPK) code with streamline inputs from viscous Navier-Stokes solutions to produce heating rates for localized fully catalytic and highly catalytic surfaces as well as for nominal partially catalytic surfaces (either Reinforced Carbon-Carbon or Reaction Cured Glass) with temperature-dependent recombination coefficients. The highly catalytic heating results showed very good correlation with Orbiter Experiments STS-2, -3, and -5 centerline and STS-5 wing flight data for the HRSI tiles. Recommended catalytic heating factors were generated for use in future Shuttle missions in the event of quick-time analysis of damaged or repaired TPS areas during atmospheric reentry. The catalytic factors are presented along the streamlines as well as a function of stagnation enthalpy so they can be used for arbitrary trajectories

Neuromuscular factors contributing to reductions in muscle force after repeated, high-intensity muscular efforts

Multiple neuromuscular processes contribute to the loss of force production following repeated, high-intensity muscular efforts; however, the relative contribution of each process is unclear. In Experiment 1, 16 resistance trained men performed six sets of unilateral isometric plantar flexor contractions of the right leg (3 s contraction/2 s rest; 85% maximal voluntary contraction torque; 90-s inter-set rest) until failure with and without caffeine ingestion (3 mg kg-1) on two separate days. Corticospinal excitability and cortical silent period (cSP) were assessed before and immediately, 10 and 20 min after the exercise. In Experiment 2, electrically evoked tetanic force and persistent inward current (PIC)-mediated facilitation of the motor neuron pool (estimated using neuromuscular electrical stimulation with tendon vibration) were assessed before and after the same exercise intervention in 17 resistance trained men. Results showed decreases in peak plantar flexion torque (Experiment 1: -12.2%, Experiment 2: -16.9%), electrically evoked torque (20 Hz -15.3%, 80 Hz -15.3%, variable-frequency train -17.9%), and cSP (-3.8%; i.e., reduced inhibition) post-exercise which did not recover by 20 min. Electromyographic activity (EMG; -6%), corticospinal excitability (-9%), and PIC facilitation (-24.8%) were also reduced post-exercise but recovered by 10 min. Caffeine ingestion increased torque and EMG but did not notably affect corticospinal excitability, PIC amplification, or electrically evoked torque. The data indicate that a decrease in muscle function largely underpins the loss of force after repeated, high-intensity muscular efforts, but that the loss is exacerbated immediately after the exercise by simultaneous decreases in corticospinal excitability and PIC amplitudes at the motor neurons

Boundary Layer Transition Results From STS-114

The tool for predicting the onset of boundary layer transition from damage to and/or repair of the thermal protection system developed in support of Shuttle Return to Flight is compared to the STS-114 flight results. The Boundary Layer Transition (BLT) Tool is part of a suite of tools that analyze the aerothermodynamic environment of the local thermal protection system to allow informed disposition of damage for making recommendations to fly as is or to repair. Using mission specific trajectory information and details of each damage site or repair, the expected time of transition onset is predicted to help determine the proper aerothermodynamic environment to use in the subsequent thermal and stress analysis of the local structure. The boundary layer transition criteria utilized for the tool was developed from ground-based measurements to account for the effect of both protuberances and cavities and has been calibrated against flight data. Computed local boundary layer edge conditions provided the means to correlate the experimental results and then to extrapolate to flight. During STS-114, the BLT Tool was utilized and was part of the decision making process to perform an extravehicular activity to remove the large gap fillers. The role of the BLT Tool during this mission, along with the supporting information that was acquired for the on-orbit analysis, is reviewed. Once the large gap fillers were removed, all remaining damage sites were cleared for reentry as is. Post-flight analysis of the transition onset time revealed excellent agreement with BLT Tool predictions

Cytoplasmic chromatin triggers inflammation in senescence and cancer

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

ACCESS: An optical transmission spectrum of the high-gravity, hot Jupiter HAT-P-23b

We present a new ground-based visible transmission spectrum of the high-gravity, hot Jupiter HAT-P-23b, obtained as part of the ACCESS project. We derive the spectrum from five transits observed between 2016 and 2018, with combined wavelength coverage between 5200 {\AA} - 9269 {\AA} in 200 {\AA} bins, and with a median precision of 247 ppm per bin. HAT-P-23b's relatively high surface gravity (g ~ 30 m/s^2), combined with updated stellar and planetary parameters from Gaia DR2, gives a 5-scale-height signal of 384 ppm for a hydrogen-dominated atmosphere. Bayesian models favor a clear atmosphere for the planet with the tentative presence of TiO, after simultaneously modeling stellar contamination, using spots parameter constraints from photometry. If confirmed, HAT-P-23b would be the first example of a high-gravity gas giant with a clear atmosphere observed in transmission at optical/NIR wavelengths; therefore, we recommend expanding observations to the UV and IR to confirm our results and further characterize this planet. This result demonstrates how combining transmission spectroscopy of exoplanet atmospheres with long-term photometric monitoring of the host stars can help disentangle the exoplanet and stellar activity signals.Comment: 28 pages, 18 Figures, accepted for publication in AJ. arXiv admin note: text overlap with arXiv:1911.0335

ACCESS: Confirmation of a Clear Atmosphere for WASP-96b and a Comparison of Light Curve Detrending Techniques

One of the strongest ${\rm Na~I}$ features was observed in WASP-96b. To confirm this novel detection, we provide a new 475-825nm transmission spectrum obtained with Magellan/IMACS, which indeed confirms the presence of a broad sodium absorption feature. We find the same result when reanalyzing the 400-825nm VLT/FORS2 data. We also utilize synthetic data to test the effectiveness of two common detrending techniques: (1) a Gaussian processes (GP) routine, and (2) common-mode correction followed by polynomial correction (CMC+Poly). We find that both methods poorly reproduce the absolute transit depths but maintain their true spectral shape. This emphasizes the importance of fitting for offsets when combining spectra from different sources or epochs. Additionally, we find that for our datasets both methods give consistent results, but CMC+Poly is more accurate and precise. We combine the Magellan/IMACS and VLT/FORS2 spectra with literature 800-1644nm HST/WFC3 spectra, yielding a global spectrum from 400-1644nm. We used the PLATON and Exoretrievals retrieval codes to interpret this spectrum, and find that both yield relatively deeper pressures where the atmosphere is optically thick at log-pressures between $1.3^{+1.0}_{-1.1}$ and 0.29$^{+1.86}_{-2.02}$ bars, respectively. Exoretrievals finds a solar to super-solar ${\rm Na~I}$ and ${\rm H_2O}$ log-mixing ratios of $-5.4^{+2.0}_{-1.9}$ and $-4.5^{+2.0}_{-2.0}$, respectively, while PLATON finds an overall metallicity of $log_{10}(Z/Z_{\odot}) = -0.49^{+1.0}_{-0.37}$dex. Therefore, our findings are in agreement with literature and support the inference that the terminator of WASP-96b has few aerosols obscuring prominent features in the optical to near-infrared (near-IR) spectrum.Comment: ACCEPT by AJ July 5th 202

ACCESS: A Visual to Near-infrared Spectrum of the Hot Jupiter WASP-43b with Evidence of H2O\rm H_2O, but no evidence of Na or K

We present a new ground-based visual transmission spectrum of the hot Jupiter WASP-43b, obtained as part of the ACCESS Survey. The spectrum was derived from four transits observed between 2015 and 2018, with combined wavelength coverage between 5,300 \r{A}-9,000 \r{A} and an average photometric precision of 708 ppm in 230 \r{A} bins. We perform an atmospheric retrieval of our transmission spectrum combined with literature HST/WFC3 observations to search for the presence of clouds/hazes as well as Na, K, H$\alpha$, and $\rm H_2O$ planetary absorption and stellar spot contamination over a combined spectral range of 5,318 \r{A}-16,420 \r{A}. We do not detect a statistically significant presence of Na I or K I alkali lines, or H$\alpha$ in the atmosphere of WASP-43b. We find that the observed transmission spectrum can be best explained by a combination of heterogeneities on the photosphere of the host star and a clear planetary atmosphere with $\rm H_2O$. This model yields a log-evidence of $8.26\pm0.42$ higher than a flat (featureless) spectrum. In particular, the observations marginally favor the presence of large, low-contrast spots over the four ACCESS transit epochs with an average covering fraction $f_\text{het} = 0.27^{+0.42}_{-0.16}$ and temperature contrast $\Delta T = 132\text{ K} \pm 132\text{ K}$. Within the planet's atmosphere, we recover a log $\rm H_2O$ volume mixing ratio of $-2.78^{+1.38}_{-1.47}$, which is consistent with previous $\rm H_2O$ abundance determinations for this planet.Comment: 27 pages, 18 figures, 7 tables. Accepted for publication in AJ. Updated affiliation

Localization of supersymmetric field theories on non-compact hyperbolic three-manifolds

We study supersymmetric gauge theories with an R-symmetry, defined on non-compact, hyperbolic, Riemannian three-manifolds, focusing on the case of a supersymmetry-preserving quotient of Euclidean AdS$_3$. We compute the exact partition function in these theories, using the method of localization, thus reducing the problem to the computation of one-loop determinants around a supersymmetric locus. We evaluate the one-loop determinants employing three different techniques: an index theorem, the method of pairing of eigenvalues, and the heat kernel method. Along the way, we discuss aspects of supersymmetry in manifolds with a conformal boundary, including supersymmetric actions and boundary conditions.Comment: v3:79p, minor clarifications and references adde