Molecular brakes regulating mTORC1 activation in skeletal muscle following synergist ablation

The goal of the current work was to profile positive (mTORC1 activation, autocrine/paracrine growth factors) and negative [AMPK, unfolded protein response (UPR)] pathways that might regulate overload-induced mTORC1 (mTOR complex 1) activation with the hypothesis that a number of negative regulators of mTORC1 will be engaged during a supraphysiological model of hypertrophy. To achieve this, mTORC1- IRS-1/2 signaling, BiP/CHOP/IRE1, and AMPK activation were determined in rat plantaris muscle following synergist ablation (SA). SA resulted in significant increases in muscle mass of 4% per day throughout the 21 days of the experiment. The expression of the insulin-like growth factors (IGF) were high throughout the 21st day of overload. However, IGF signaling was limited, since IRS-1 and -2 were undetectable in the overloaded muscle from day 3 to day 9. The decreases in IRS-1/2 protein were paralleled by increases in GRB10 Ser501/503 and S6K1 Thr389 phosphorylation, two mTORC1 targets that can destabilize IRS proteins. PKB Ser473 phosphorylation was higher from 3– 6 days, and this was associated with increased TSC2 Thr939 phosphorylation. The phosphorylation of TSC2 Thr1345 (an AMPK site) was also elevated, whereas phosphorylation at the other PKB site, Thr1462, was unchanged at 6 days. In agreement with the phosphorylation of Thr1345, SA led to activation of AMPK1 during the initial growth phase, lasting the first 9 days before returning to baseline by day 12. The UPR markers CHOP and BiP were elevated over the first 12 days following ablation, whereas IRE1 levels decreased. These data suggest that during supraphysiological muscle loading at least three potential molecular brakes engage to downregulate mTORC1. m

Haptic Shared Control in Tele-Manipulation: Effects of Inaccuracies in Guidance on Task Execution

Haptic shared control is a promising approach to improve tele-manipulated task execution, by making safe and effective control actions tangible through guidance forces. In current research, these guidance forces are most often generated based on pre-generated, errorless models of the remote environment. Hence such guidance forces are exempt from the inaccuracies that can be expected in practical implementations. The goal of this research is to quantify the extent to which task execution is degraded by inaccuracies in the model on which haptic guidance forces are based. In a human-in-the-loop experiment, subjects (n = 14) performed a realistic tele-manipulated assembly task in a virtual environment. Operators were provided with various levels of haptic guidance, namely no haptic guidance (conventional tele-manipulation), haptic guidance without inaccuracies, and haptic guidance with translational inaccuracies (one large inaccuracy, in the order of magnitude of the task, and a second smaller inaccuracy). The quality of natural haptic feedback (i.e., haptic transparency) was varied between high and low to identify the operator\u27s ability to detect and cope with inaccuracies in haptic guidance. The results indicate that haptic guidance is beneficial for task execution when no inaccuracies are present in the guidance. When inaccuracies are present, this may degrade task execution, depending on the magnitude and the direction of the inaccuracy. The effect of inaccuracies on overall task performance is dominated by effects found for the Constrained Translational Movement, due to its potential for jamming. No evidence was found that a higher quality of haptic transparency helps operators to detect and cope with inaccuracies in the haptic guidance.</p

Large Polarization Degree of Comet 2P/Encke Continuum Based on Spectropolarimetric Signals During Its 2017 Apparition

Spectropolarimetry is a powerful technique for investigating the physical properties of gas and solid materials in cometary comae without mutual contamination, but there have been few spectropolarimetric studies to extract each component. We attempt to derive the continuum polarization degree of comet 2P/Encke, free from influence of molecular emissions. The target is unique in that it has an orbit dynamically decoupled from Jupiter like main-belt asteroids, while ejecting gas and dust like ordinary comets. We observed the comet using the Higashi-Hiroshima Optical and Near-Infrared Camera attached to the Cassegrain focus of the 150-cm Kanata telescope on UT 2017 February 21 when the comet was at the solar phase angle of 75.7 deg. We find that the continuum polarization degree with respect to the scattering plane is 33.8+/-2.7 % at the effective wavelength of 0.815 um, which is significantly higher than those of cometary dust in a high-Pmax group at similar phase angles. Assuming that an ensemble polarimetric response of 2P/Encke's dust as a function of phase angle is morphologically similar with those of other comets, its maximum polarization degree is estimated to > 40 % at the phase angle of ~100 deg. In addition, we obtain the polarization degrees of the C2 swan bands (0.51-0.56 um), the NH2 alpha bands (0.62-0.69 um) and the CN-red system (0.78-0.94 um) in a range of 3-19 %, which depend on the molecular species and rotational quantum numbers of each branch. The polarization vector aligns nearly perpendicularly to the scattering plane with the average of 0.4 deg over a wavelength range of 0.50-0.97 um. From the observational evidence, we conjecture that the large polarization degree of 2P/Encke would be attributable to a dominance of large dust particles around the nucleus, which have remained after frequent perihelion passages near the Sun.Comment: 9 pages, 4 figures, accepted for publication in Astronomy & Astrophysic

Optimizing training adaptations by manipulating glycogen

For decades, glycogen has been recognized as a storage form of glucose within the liver and muscles. Only recently has a greater role for glycogen as a regulator of metabolic signalling been suggested. Glycogen either directly or indirectly regulates a number of signalling proteins, including the adenosine-5\u27-phosphate- (AMP-) activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK). AMPK and p38 MAPK play a significant role in controlling the expression and activity of the peroxisome proliferator activated receptor &gamma; coactivators (PGCs), respectively. The PGCs can directly increase muscle mitochondrial mass and endurance exercise performance. As low muscle glycogen is generally associated with greater activation of these pathways, the concept of training with low glycogen to maximize the physiological adaptations to endurance exercise is gaining acceptance in the scientific community. In this review, we evaluate the scientific basis for this philosophy and propose some practical applications of this philosophy for the general population as well as elite endurance athletes.<br /

Mesoscale features create hotspots of carbon uptake in the Antarctic Circumpolar Current

The influence of eddy structures on the seasonal depletion of dissolved inorganic carbon (DIC) and carbon dioxide (CO2) disequilibrium was investigated during a trans-Atlantic crossing of the Antarctic Circumpolar Current (ACC) in austral summer 2012. The Georgia Basin, downstream of the island of South Georgia (54-55°S, 36-38°W) is a highly dynamic region due to the mesoscale activity associated with the flow of the Subantarctic Front (SAF) and Polar Front (PF). Satellite sea-surface height and chlorophyll-a anomalies revealed a cyclonic cold core that dominated the northern Georgia Basin that was formed from a large meander of the PF. Warmer waters influenced by the SAF formed a smaller anticyclonic structure to the east of the basin. Both the cold core and warm core eddy structures were hotspots of carbon uptake relative to the rest of the ACC section during austral summer. This was most amplified in the cold core where greatest CO2 undersaturation (-78 µatm) and substantial surface ocean DIC deficit (5.1 mol m-2) occurred. In the presence of high wind speeds, the cold core eddy acted as a strong sink for atmospheric CO2 of 25.5 mmol m-2 day-1. Waters of the warm core displayed characteristics of the Polar Frontal Zone (PFZ), with warmer upper ocean waters and enhanced CO2 undersaturation (-59 µatm) and depletion of DIC (4.9mol m-2). A proposed mechanism for the enhanced carbon uptake across both eddy structures is based on the Ekman eddy pumping theory: (i) the cold core is seeded with productive (high chlorophyll-a) waters from the Antarctic Zone and sustained biological productivity through upwelled nutrient supply that counteracts DIC inputs from deep waters; (ii) horizontal entrainment of low-DIC surface waters (biological uptake) from the PFZ downwell within the warm core and cause relative DIC-depletion in the upper water column. The observations suggest that the formation and northward propagation of cold core eddies in the region of the PF could project low-DIC waters towards the site of Antarctic Intermediate Water formation and enhance CO2 drawdown into the deep ocean

Mercury in the Black Sea:New Insights From Measurements and Numerical Modeling

Redox conditions and organic matter control marine methylmercury (MeHg) production. The Black Sea is the world's largest and deepest anoxic basin and is thus ideal to study Hg species along the extended redox gradient. Here we present new dissolved Hg and MeHg data from the 2013 GEOTRACES MEDBlack cruise (GN04_leg2) that we integrated into a numerical 1-D model, to track the fate and dynamics of Hg and MeHg. Contrary to a previous study, our new data show highest MeHg concentrations in the permanently anoxic waters. Observed MeHg/Hg percentage (range 9-57%) in the anoxic waters is comparable to other subsurface maxima in oxic open-ocean waters. With the modeling we tested for various Hg methylation and demethylation scenarios along the redox gradient. The results show that Hg methylation must occur in the anoxic waters. The model was then used to simulate the time evolution (1850-2050) of Hg species in the Black Sea. Our findings quantify (1) inputs and outputs of Hg-T (similar to 31 and similar to 28 kmol yr(-1)) and MeHgT (similar to 5 and similar to 4 kmol yr(-1)) to the basin, (2) the extent of net demethylation occurring in oxic (similar to 1 kmol yr(-1)) and suboxic water (similar to 6 kmol yr(-1)), (3) and the net Hg methylation in the anoxic waters of the Black Sea (similar to 11 kmol yr(-1)). The model was also used to estimate the amount of anthropogenic Hg (85-93%) in the Black Sea

Experimental validation of a one-dimensional twin-entry radial turbine model under non-linear pulse conditions

This is the author¿s version of a work that was accepted for publication in International Journal of Engine Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published as https://doi.org/10.1177/1468087419869157[EN] This article presents the experimental validation of a complete integrated one-dimensional twin-scroll turbine model able to be used in reciprocating internal combustion engine unsteady simulations. A passenger car with a twin-entry-type turbine has been tested under engine-like pulse conditions by means of a specifically built gas stand. To obtain high-resolution quality data, the turbine and turbine line pipes have been instrumented with mean and instantaneous pressure sensors as well as temperature and mass flow sensors, employing a uniquely designed rotating valve for the pulse generation. This experimental configuration enables to obtain the pressure decomposition in both inlets and outlets of the turbine. Using the experimental data obtained, the model is fully validated, with special focus on the reflected and transmitted components for analysing the performance of the model and its non-linear acoustics prediction capabilities. The model presents a very high degree of correlation with the experimental results, providing a range of errors similar to the uncertainty of the measurements, even in the medium- and high-frequency spectra.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the 'Ayuda a Primeros Proyectos de Investigacion' (PAID-06-18), Vicerrectorado de Investigacion, Innovacion y Transferencia de la Universitat Politecnica de Valencia (UPV), Valencia, Spain. P.S. was partially supported through contract FPI-2017-S2-1428 of Programa de Apoyo para la Investigacion y Desarrollo (PAID) of Universitat Politecnica de Valencia.Serrano, J.; Arnau Martínez, FJ.; García-Cuevas González, LM.; Soler-Blanco, P.; Cheung, R. (2021). Experimental validation of a one-dimensional twin-entry radial turbine model under non-linear pulse conditions. 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A detailed one-dimensional model to predict the unsteady behavior of turbocharger turbines for internal combustion engine applications. International Journal of Engine Research, 20(3), 327-349. doi:10.1177/1468087417752525Galindo, J., Arnau, F. J., García-Cuevas, L. M., & Soler, P. (2018). Experimental validation of a quasi-two-dimensional radial turbine model. International Journal of Engine Research, 21(6), 915-926. doi:10.1177/1468087418788502Rajoo, S., Romagnoli, A., & Martinez-Botas, R. F. (2012). Unsteady performance analysis of a twin-entry variable geometry turbocharger turbine. Energy, 38(1), 176-189. doi:10.1016/j.energy.2011.12.017Rajoo, S., & Martinez-Botas, R. (2008). Variable Geometry Mixed Flow Turbine for Turbochargers: An Experimental Study. International Journal of Fluid Machinery and Systems, 1(1), 155-168. doi:10.5293/ijfms.2008.1.1.155Copeland, C. D., Martinez-Botas, R., & Seiler, M. (2010). Comparison Between Steady and Unsteady Double-Entry Turbine Performance Using the Quasi-Steady Assumption. Journal of Turbomachinery, 133(3). doi:10.1115/1.4000580Copeland, C. D., Martinez-Botas, R., & Seiler, M. (2011). Unsteady Performance of a Double Entry Turbocharger Turbine With a Comparison to Steady Flow Conditions. Journal of Turbomachinery, 134(2). doi:10.1115/1.4003171Costall, A. W., McDavid, R. M., Martinez-Botas, R. F., & Baines, N. C. (2010). Pulse Performance Modeling of a Twin Entry Turbocharger Turbine Under Full and Unequal Admission. Journal of Turbomachinery, 133(2). doi:10.1115/1.4000566Yang, M., Martinez-Botas, R., Rajoo, S., Yokoyama, T., & Ibaraki, S. (2015). An investigation of volute cross-sectional shape on turbocharger turbine under pulsating conditions in internal combustion engine. Energy Conversion and Management, 105, 167-177. doi:10.1016/j.enconman.2015.06.038Copeland, C. D., Newton, P. J., Martinez-Botas, R., & Seiler, M. (2011). 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Primary bony non-Hodgkin lymphoma of the cervical spine: a case report

<p>Abstract</p> <p>Introduction</p> <p>Non-Hodgkin lymphoma primarily originating from the bone is exceedingly rare. To our knowledge, this is the first report of primary bone lymphoma presenting with progressive cord compression from an origin in the cervical spine. Herein, we discuss the unusual location in this case, the presenting symptoms, and the management of this disease.</p> <p>Case presentation</p> <p>We report on a 23-year-old Caucasian-American man who presented with two months of night sweats, fatigue, parasthesias, and progressive weakness that had progressed to near quadriplegia. Magnetic resonance (MR) imaging demonstrated significant cord compression seen primarily at C7. Surgical management, with corpectomy and dorsal segmental fusion, in combination with adjuvant chemotherapy and radiation therapy, halted the progression of the primary disease and preserved neurological function. Histological analysis demonstrated an aggressive anaplastic large cell lymphoma.</p> <p>Conclusion</p> <p>Isolated primary bony lymphoma of the spine is exceedingly rare. As in our case, the initial symptoms may be the result of progressive cervical cord compression. Anterior corpectomy with posterolateral decompression and fusion succeeded in preventing progressive neurologic decline and maintaining quality of life. The reader should be aware of the unique presentation of this disease and that surgical management is a successful treatment strategy.</p

Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol

Introduction: A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. Areas covered: This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). Expert opinion: The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosin