Ramp Test Research Articles

The quiet eye is sensitive to exercise-induced physiological stress.

The current study sought to explore attentional mechanisms underpinning visuomotor performance degradation following acute exercise. Ten experienced basketball players took free throws while wearing mobile eye tracking glasses, before and after performing a bout of cycling exercise. Shooting accuracy was measured using a 6-point scoring system, and quiet eye duration (the final fixation to a target) was adopted as an objective measure of top-down attentional control. Four intensities of exercise (based on an initial ramp test) were performed in a counterbalanced order: rest, moderate, heavy and severe. The four intensities resulted in participants reaching 52±4%, 58±4%, 76±6% and 86±5% of their heart rate max, respectively. Performance and quiet eye were only significantly impaired (19% and 45% drops, respectively) between pre- and post-intervention at the severe intensity workload level. Additionally, exercise-induced changes in quiet eye predicted 33% of the subsequent change in performance accuracy. The results suggest that attentional disruptions may at least partially explain why sporting skills break down under acute fatigue. Implications for training to mitigate against these impairments are discussed.

The accuracy of two equations for predicting maximal oxygen uptake on individualized ramp protocol

PurposeValid protocols use nomograms based on standardized stages to calculate maximal oxygen uptake (VO<sub>2</sub>max). Although the maximal ramp exercise protocol offers advantages over traditional protocols, it is not known if the non-standardized stages approach affects the accuracy to estimate VO<sub>2</sub>max. The study aims to examine the accuracy of 2 equations for predicting VO<sub>2</sub>max in a maximal ramp exercise test.MethodsOverall, 11 men (age: 26 ± 5 years, height: 178 ± 7 cm, weight: 77.6 ± 9.9 kg) underwent 3 sessions of a maximal ramp test on a motorized treadmill; the speed increments were equal but with 0, 3, and 6% grades. Expired gases were analysed with a portable metabolic system. The VO<sub>2</sub>max measured was set as the highest mean value observed from 7 consecutive breaths and it was predicted from 2 equations: American College Sports Medicine (ACSM) and Myers.ResultsVO<sub>2</sub>max predicted by ACSM equation (54.3 ± 6.7 mL • kg<sup>–1</sup> • min<sup>–1</sup>) was approximately 10 ± 10% higher and by Myers equation (30.6 ± 6.1 mL • kg<sup>–1</sup> • min<sup>–1</sup>) approximately 38 ± 11% lower than directly measured (49.6 ± 6.7 mL • kg<sup>–1</sup> • min<sup>–1</sup>, <i>p</i> < 0.05). Bland-Altman graphs indicate low and no agreement for ACSM and Myers equations, respectively. The calculated standard error of the estimates was 6.5 mL • kg<sup>–1</sup> • min<sup>–1</sup> for ACSM equation and 19.9 mL • kg<sup>–1</sup> • min<sup>–1</sup> for Myers equation.ConclusionsThe ACSM and Myers equations significantly over- and under-predict the VO<sub>2</sub>max of young adults, respectively. Although the former overestimated VO<sub>2</sub>max, we recommend its use with caution.

Slip safety risk analysis of surface properties using the coefficients of friction of rocks

This study was conducted to determine the most appropriate surface processing techniques (SPT), environmental conditions (EC) and surface roughness (SR) to minimize the risk of slipping when pedestrians walk on a floor covering of rocks barefoot and with shoes. Coefficients of friction (COFs) and values of SR were found using five different types of rocks, four SPT and two (ramp and pendulum) tests. Results indicate that the parameters which affect the COF values of rocks include SR, EC and SPT. Simple linear regression was performed to examine the relationship between the values of the COF and the SR. The value of the COF was identified as R2 ≥ 0.864. Statistical results, which are based on experimental measurements, show that rocks are classified according to their safe use areas depending on their COF and SR values.

Interdependency between mechanical parameters and afferent nerve discharge in remodeled diabetic Goto-Kakizaki rat intestine.

BackgroundGastrointestinal disorders are very common in diabetic patients, but the pathogenesis is still not well understood. Peripheral afferent nerves may be involved due to the complex regulation of gastrointestinal function by the enteric nervous system.ObjectiveWe aimed to characterize the stimulus–response function of afferent fibers innervating the jejunum in the Goto-Kakizaki (GK) type 2 diabetic rat model. A key question is whether changes in afferent firing arise from remodeled tissue or from adaptive afferent processes.DesignSeven 32-week-old male GK rats and seven age-matched normal Wistar rats were studied. Firing from mesenteric afferent nerves was recorded in excised jejunal segments of seven GK rats and seven normal Wistar rats during ramp test, stress relaxation test, and creep test. The circumferential stress–strain, spike rate increase ratio (SRIR), and single unit firing rates were calculated for evaluation of interdependency of the mechanical stimulations and the afferent nerve discharge.ResultsElevated sensitivity to mechanical stimuli was found for diabetic nerve bundles and single unit activity (P<0.05). The stress relaxed less in the diabetic intestinal segment (P<0.05). Linear association between SRIR and the thickness of circumferential muscle layer was found at high stress levels as well as for SRIR and the glucose level.ConclusionAltered viscoelastic properties and elevated mechanosensitivity were found in the GK rat intestine. The altered nerve signaling is related to muscle layer remodeling and glucose levels and may contribute to gastrointestinal symptoms experienced by diabetic patients.

Computer-Aided Stroke-by-Stroke Visualization of Actual and Target Power Allows for Continuously Increasing Ramp Tests on Wind-Braked Rowing Ergometers.

Ramp tests are continuously increasing exercise tests used for the determination of maximal oxygen uptake ( V ˙ O 2 max ), which is identifiable by a plateau in oxygen uptake despite increasing mechanical power output (LOAD). On wind-braked rowing ergometers (RowErg), it is hardly feasible to ensure a continuous increase in LOAD until test termination, as neither resistance nor stroke frequency is externally adjustable but depends on the rower. To enable ramp tests on RowErg, the authors produced visual stroke-by-stroke feedback showing target and actual LOAD to the rower. The software supports automatic test termination (TERMauto) if LOAD ceases to increase. The authors aimed to evaluate linearity of the LOAD increment and calculate the difference between TERMauto and test duration at subjective exhaustion. Twenty-eight highly trained male rowers performed a ramp test until subjective exhaustion on RowErg, targeting an increment of 35W·min-1. LOAD was measured as work per time via external force and position sensors and visualized on a computer screen. TERMauto was deactivated, but all data were logged. Test duration at subjective exhaustion was subsequently compared with virtual test duration at TERMauto calculated from the log files. Regression between time and LOAD was y = 167 + 34.6W (r = .99). Individual correlations ranged from .97 to 1.0. TERMauto caused 12- to 35-s-shorter test durations than subjective exhaustion in 4 rowers, leading to an underestimation in V ˙ O 2 max not higher than 1.2% or 3.7%. This setup allows one to perform ramp tests on RowErg with continuously increasing LOAD until TERMauto. In particular cases V ˙ O 2 max might be slightly underestimated at TERMauto.

Cannula and Pump Positions Are Associated With Left Ventricular Unloading and Clinical Outcome in Patients With HeartWare Left Ventricular Assist Device

BackgroundCannula and pump positions are associated with clinical outcomes such as device thrombosis in patients with HeartMate II; however, clinical implications of HVAD (HeartWare International, Framingham, Massachusetts) cannula position are unknown. This study aims to assess the relationship among cannula position, left ventricular (LV) unloading, and patient prognosis. Methods and resultsTwenty-seven HVAD patients (60.0 ± 12.6 years of age and 19 males [70%]) underwent ramp test. Device position was quantified from chest X-ray parameters obtained at the time of the hemodyamic ramp test: (1) cannula coronal angle, (2) pump depth, (3) cannula sagittal angle, and (4) pump area. Lower cannula coronal angle was associated with LV unloading (as measured by smaller LV diastolic dimension and lower pulmonary capillary wedge pressure). Smaller pump area was associated with LV dynamic unloading, as assessed by steeper negative slopes of LV diastolic dimension and pulmonary capillary wedge pressure during incremental rotational speed change. Cannula coronal angle ≤65° was associated with reduced heart failure readmission rate (hazard ratio, 10.33; P = .007 by log-rank test). ConclusionHVAD cannula and pump positions are associated with LV unloading and improved clinical outcomes. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on clinical outcomes are warranted.

Reproducibility of peak oxygen consumption and the impact of test variability on classification of individual training responses in young recreationally active adults

This study investigated whether VO2 peak is reproducible across repeated tests before (PRE) and after (POST) training, and whether variability across tests impacts how individual responses are classified following 3weeks of aerobic exercise training (cycle ergometry). Data from 45 young healthy adults (age: 20·1±0·9years; VO2 peak, 42·0±6·7ml·min-1 ) from two previously published studies were utilized in the current analysis. Non-responders were classified as individuals who failed to demonstrate an increase or decrease in VO2 peak that was greater than 2·0 times the typical error of measurement (107ml·min-1 ) away from zero, while responders and adverse responders were above and below this cut-off, respectively. VO2 peak tests at PRE (three total) and POST (three total) were highly reproducible (PRE and POST average and single measures ICCs: range 0·938-0·992), with low coefficients of variation (PRE:4·9±3·1%, POST: 4·8±2·7%). However, a potential learning effect was observed in the VO2 peak tests prior to training, as the initial pretraining test was significantly lower than the third (p=0·010, PRE 1: 2946±924 ml·min-1 , PRE 3: 3042±919 ml·min-1 ). This resulted in fewer individuals classified as adverse responders for Test 3 compared to any combination of tests that included Test 1, suggesting that a single ramp test at baseline may not be sufficient to accurately classify the VO2 peak response in young recreationally active individuals. Thus, it is our recommendation that the initial VO2 peak test be used as a familiarization visit and not included for analysis.

Changes in rheological properties of wheat due to storage.

The present study aimed to investigate changes in the fundamental rheological properties of dough prepared from wheat grains stored for 6 months at 20 °C, at ambient temperature (temperature varied with time) and at 4 °C. Stress/shear rate ramp, oscillation and creep-recovery tests were performed to assess the changes in rheological properties as a result of storage. Samples were observed to be non-Newtonian; thus, the Bingham model estimated the yield stress, which was maximum for the wheat stored under ambient conditions and minimum for wheat stored at 20 °C. The stress required to break the bonds was maximum for wheat-dough stored under ambient conditions and minimum for wheat stored at 20 °C. Wheat stored at 20 °C also had the highest maximum creep and recovery strain. The viscoelastic properties of the three wheat-dough samples were compared. The results obtained in the present study show that the wheat-dough prepared under ambient conditions behaves as a rigid and stiff material. The dough prepared from wheat stored at 20 °C had the maximum elasticity. © 2017 Society of Chemical Industry.

PCI analysis of a commercial PWR using BISON fuel performance code

Through the early 2000’s, nuclear fuel cladding failure resulting from pellet-cladding interaction in commercial pressurized water reactor fuel was managed successfully by incorporating power ramp restrictions. Within the past decade, however, cladding failures have again begun to appear, often correlated to missing pellet surface defects, and further aggravated by modern reactor operating strategies demanding higher fuel duty operations. In response, renewed efforts in fuel behavior modeling and simulation are being pursued to improve our understanding of the conditions that can lead to missing pellet surface related cladding failure. This paper describes a methodology used to model pellet-cladding interaction related failures observed in commercial pressurized water reactors using the BISON fuel performance code developed at Idaho National Laboratory. In order to accomplish this goal, a three-step process is followed: 1) A failure-stress threshold is developed by using BISON code to model ramp test with known pellet-clad interaction related failures, 2) BISON analysis is applied to a commercial pressurized water reactor cycle startup with one rod confirmed to contain a missing pellet surface defect, and 3) an missing pellet surface sensitivity study of a cycle startup of the same commercial pressurized water reactor which contained a failed fuel rod of un-identified type. The analysis results described in this paper serve to illustrate the BISON code capabilities for modeling pressurized water reactor fuel subjected to higher duty power events.

Strain characteristics of additive manufactured polyvinylidene fluoride (PVDF) actuators

Polyvinyldene fluoride (PVDF) polymer piezoelectric actuators were manufactured using an electric poling-assisted additive manufacturing (EPAM) process and tested for actuation strain in the thickness direction. A heterodyne interferometer was used to measure the strain developed by the actuators as a function of applied voltage. Results were compared to a commercially available ceramic lead–zirconium–titanate (PZT) actuator. The EPAM PVDF samples exhibit strains up to 8.78mϵ, compared to 1.7mϵ developed by PZT samples at their maximum working voltages in linear ramp testing (860V for EPAM PVDF and 200V for PZT). The response of the EPAM PVDF samples to an applied force was tested to measure the piezoelectric effect, although no actual piezoelectric constants are calculated with this method. Results show that strain measurements of EPAM PVDF samples were up to 5.2 times greater than comparable measurements of PZT samples. However, the degree of piezoelectricity between EPAM PVDF samples varies so quality control is required for the EPAM process to ensure sample performance.

Decoupling Between Diastolic Pulmonary Artery Pressure and Pulmonary Capillary Wedge Pressure as a Prognostic Factor After Continuous Flow Ventricular Assist Device Implantation.

A cohort of heart failure (HF) patients receiving left ventricular assist devices (LVADs) has decoupling of their diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. However, the clinical implications of this decoupling remain unclear. In this prospective study, patients with LVADs underwent routine invasive hemodynamic ramp testing with right heart catheterization, during which LVAD speeds were adjusted. Inappropriate decoupling was defined as a >5 mm Hg difference between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. The primary outcomes of survival and heart failure readmission rates after ramp testing were assessed. Among 63 LVAD patients (60±12 years old and 25 female [40%]), 27 patients (43%) had inappropriate decoupling at their baseline speed. After adjustment of their rotation speed during ramp testing, 30 patients (48%) had inappropriate decoupling. Uni/multivariable Cox analyses demonstrated that decoupling was the only significant predictor for the composite end point of death and heart failure readmission during the 1 year following the ramp study (total of 18 events; hazards ratio, 1.09; 95% confidence interval, 1.04-1.24; P<0.05). Furthermore, normalization of decoupling (n=8) during ramp testing was significantly associated with higher 1-year heart failure readmission-free survival rate compared with the non-normalized group (n=19, 100% versus 53%; P=0.035). The presence of inappropriate decoupling was associated with worse outcomes in patients with LVADs. Prospective, large-scale multicenter studies to validate the result are warranted.

Characterisation of Heat and Gas Emissions in Thermally Induced Battery Failure on Commercially Available 18650 Li-Ion Cells

Lithium ion battery systems are wide spread commercial products found in present day electric and electronic applications. For portable devices like laptop computers and mobile phones as well as electric vehicles high energy density and reliability are crucial [1]. High energy density also creates risks in the case of malfunction. In batteries energy is stored electrochemically within the electrodes, thus fuel and oxidiser are confined within a single container. This allows easy discharging and recharging of secondary batteries as the charge transfer is achieved over small distances and on defined surfaces. In the event of failure, chemical reactions occurring between the highly reactive electrodes or between single electrodes and electrolyte pose a serious threat to operator, device and environment. One of these failure scenarios is associated to the thermal runaway of lithium ion cells [2,3]. The thermal runaway is initiated by exothermic degradation of the battery’s components. These effects occur due to accumulation of heat within the cell, i.e. the self-heating rate surpassing the heat dissipation rate [3,4]. During these deterioration processes several effects are observable. Decay and evaporation of the organic electrolyte invokes pressurisation of the can, eventually leading to the emission of gas. The solid electrolyte interphase also degrades at elevated temperature, thus it no longer screens the electrodes. Chemical reactions of the electrolyte with the electrodes further promote the generation of gaseous components [5]. Internal short circuits occur at higher temperature after melting or thermal shrinking of the polymer separator. Exothermic reactions drive the thermal deterioration of the whole electrochemical cell. The self-heating and thus promotion of the catastrophic cell failure culminates in the emission of large quantities of heat and both toxic and flammable gas. As neighbouring cells within a battery pack are also affected by these incidents, thorough characterisation of these events is paramount for improving battery safety. In this work we present a holistic approach to the characterisation of cylindrical Li-ion cells of the 18650 format by thermal ramp tests and consecutive as well as online analysis. Single cells are heated with constant power. Monitoring of the cell temperature and calculation of the self-heating rates offer a reproducible way of identifying and interpreting characteristic events [6–8]. These events comprise the first venting, the exothermic onset and the beginning of the thermal runaway. Volumetric determination of the gaseous emission is achieved online by displacement of liquid from communicating vessels. This method allows the time resolved measurement without pressurisation of the test setup. A custom made gas sampler is used for automatic collection of GC samples at the characteristic events. The first phase showed no gas release which was also confirmed by GC analysis. The second phase is characterised by the sudden venting of mainly CO2. This emission is accompanied by slight Joule-Thompson cooling. The third phase, the thermal runaway, is characterised by a self-heating rate of ≥2 °C min-1. It is concluded by a rapid temperature increase associated with the deflagration of cell components. This is accompanied by an emission of mainly H2 and CO (depicted in figure). [1] J.M. Tarascon, M. Armand, Nature. 414 (2001) 359–67. [2] J. Lamb, C.J. Orendorff, E.P. Roth, J. Langendorf, J. Electrochem. Soc. 162 (2015) A2131–A2135. [3] S.J. Drake, M. Martin, D.A. Wetz, J.K. Ostanek, S.P. Miller, J.M. Heinzel, A. Jain, J. Power Sources. 285 (2015) 266–273. [4] A.W. Golubkov, S. Scheikl, R. Planteu, G. Voitic, H. Wiltsche, C. Stangl, G. Fauler, A. Thaler, V. Hacker, RSC Adv. 5 (2015) 57171–57186. [5] J.L. Tebbe, T.F. Fuerst, C.B. Musgrave, ACS Appl. Mater. Interfaces. (2016) acsami.6b06157. [6] Q. Wang, P. Ping, X. Zhao, G. Chu, J. Sun, C. Chen, J. Power Sources. 208 (2012) 210–224. [7] F. Larsson, B.-E. Mellander, J. Electrochem. Soc. 161 (2014) A1611–A1617. [8] M. Lammer, A. Königseder, V. Hacker, RSC Adv. (2017). Figure 1

Reply to Pettitt and Jamnick's letter in reference to: Measurement of the maximum oxygen uptake V̇o2max: V̇o2peak is no longer acceptable.

to the editor: We appreciate Drs. Pettitt and Jamnick’s endorsement of our CORP and their recommendations for helping standardize the ramp test duration. We cited precedence for a maximal ramp test duration of 8–12 min ([1][1], [5][2]) to optimize extraction of four key parameters of aerobic

Elevated temperature repetitive micro-scratch testing of AlCrN, TiAlN and AlTiN PVD coatings

In developing advanced wear-resistant coatings for tribologically extreme highly loaded applications such as high speed metal cutting a critical requirement is to investigate their behaviour at elevated temperature since the cutting process generates frictional heat which can raise the temperature in the cutting zone to 700–900°C or more. High temperature micro-tribological tests provide severe tests for coatings that can simulate high contact pressure sliding/abrasive contacts at elevated temperature. In this study ramped load micro-scratch tests and repetitive micro-scratch tests were performed at 25 and 500°C on commercial monolayer coatings (AlCrN, TiAlN and AlTiN) deposited on cemented carbide cutting tool inserts. AlCrN exhibited the highest critical load for film failure in front of the moving scratch probe at both temperatures but it was prone to an unloading failure behind the moving probe. Scanning electron microscopy showed significant chipping outside the scratch track which was more extensive for AlCrN at both room and elevated temperature. Chipping was more localised on TiAlN although this coating showed the lowest critical loads at both test temperatures. EDX analysis of scratch tracks after coating failure showed tribo-oxidation of the cemented carbide substrate. AlTiN showed improved scratch resistance at higher temperature. The von Mises, tensile and shear stresses acting on the coating and substrate sides of the interface were evaluated analytically to determine the main stresses acting on the interface. At 1N there are high stresses near the coating-substrate interface. Repetitive scratch tests at this load can be considered as a sub-critical load micro-scale wear test which is more sensitive to adhesion differences than the ramped load scratch test. The analytical modelling showed that a dramatic improvement in the performance of AlTiN in the 1N test at 500°C could be explained by the stress distribution in contact resulting in a change in yield location due to the high temperature mechanical properties. The increase in critical load with temperature on AlTiN and AlCrN is primarily a result of the changing stress distribution in the highly loaded sliding contact rather than an improvement in adhesion strength.

Aging effect on the thermal transient behavior of the fuel cladding of a sodium-cooled fast reactor

The transient behavior of the fuel cladding of a sodium-cooled fast reactor (SFR) is one of the main design issues concerning the safety of a reactor. The safety margin of the cladding during transient events has been widely studied in the past. However, previously, the transient testing was conducted using as-received specimens (and not aged specimens). For ensuring safety margin of the fuel rod of an SFR, the effect of aging on the transient behavior of the fuel cladding should be considered. This study examines this effect on the transient behavior of HT9 cladding by correlating between the UTS and the result of the ramp test and proposes a modified Dorn parameter that reflects the aging effect. At 100 MPa of the hoop stress, the modified Dorn parameter, which reflects an aging effect, is 7.7266 × 10−14 and the Dorn parameter of as-received specimen is 1.749 × 10−12. This results in the enhanced safety during transient event by considering aging effect.

Non-Invasive Mapping of Intraventricular Flow Patterns in Patients Treated with Left Ventricular Assist Devices

Introduction: In patients with advanced heart failure, refractory to medical therapy, treatment with left ventricular assist devices (LVADs) decreases mortality and improves quality of life. However, the success of LVAD therapy is hampered by complications such as thrombosis and right ventricular heart failure. Understanding the interactions between the heart, vascular bed and the LVAD might help improve pump settings and decrease the rate of complications. We recently developed 2D echo color Doppler velocimetry (echo-CDV), a novel echocardiographic modality to map blood flow inside the LV and its changes during the cardiac cycle. Hypothesis: We hypothesize that echo-CDV can be used to non-invasively characterize the effect of LVAD support in LV hemodynamics, in order to help understand the ventricular-vascular-LVAD interplay. Our overarching goal is to use this tool to optimize device and patient management. Methods: We used echo-CDV to image LV flow patterns at baseline LVAD speed and during a ramp test in patients with ongoing LVAD support (Heartmate II, N = 6). We tracked diastolic vortices and mapped LV blood stasis. We compared flow features with data from patients with dilated cardiomyopathy (DCM) not treated with an LVAD. Results: Compared to patients with DCM and no LVAD support (panel A), the flow pattern during LVAD support (panels B-C) had a less prominent diastolic vortex ring, and transited directly from the mitral valve to the cannula forming a straight path. The changes elicited by LVAD support displaced blood stasis regions from the LV apex towards the base along the antero-septal and infero-posterior walls. Quantitative metrics of blood stasis were sensitive to the LVAD speed, with different trends in different patients (compare panels B and C). Conclusions: Using 2D echo-CDV in patients with ongoing LVAD treatment yields detailed information about the effect of this treatment on LV flow patterns and blood stasis. This new methodology could potentially be used in combination with standard echo, hemodynamics and clinical information to find the LVAD setting that optimizes LV flow transport and minimizes stasis for each patient.

Can the Critical Power Model Explain the Increased Peak Velocity/Power During Incremental Test After Concurrent Strength and Endurance Training?

Denadai, BS and Greco, CC. Can the critical power model explain the increased peak velocity/power during incremental test after concurrent strength and endurance training? J Strength Cond Res 31(8): 2319-2323, 2017-The highest exercise intensity that can be maintained at the end of a ramp or step incremental test (i.e., velocity or work rate at V[Combining Dot Above]O2max - Vpeak/Wpeak) can be used for endurance performance prediction and individualization of aerobic training. The interindividual variability in Vpeak/Wpeak has been attributed to exercise economy, anaerobic capacity, and neuromuscular capability, alongside the major determinant of aerobic capacity. Interestingly, findings after concurrent strength and endurance training performed by endurance athletes have challenged the actual contribution of these variables. The critical power model usually derived from the performance of constant-work rate exercise can also explain tolerance to a ramp incremental exercise so that, Vpeak/Wpeak can be predicted accurately. However, there is not yet discussion of possible concomitant improvements in the parameters of the critical power model and Vpeak/Wpeak after concurrent training and whether they can be associated with and therefore depend on different neuromuscular adaptations. Therefore, this brief review presents some evidence that the critical power model could explain the improvement of Vpeak/Wpeak and should be used to monitor aerobic performance enhancement after different concurrent strength- and endurance-training designs.

Readthrough of SCN5A Nonsense Mutations p.R1623X and p.S1812X Questions Gene-therapy in Brugada Syndrome.

Nonsense mutation readthrough is used as a gene-specific treatment in some genetic diseases. The response to readthrough treatment is determined by the readthrough efficiency of various nonsense mutations. In this manuscript, we aimed to explore the harmful effects of nonsense mutation suppression. HEK293 cells were transfected with two SCN5A (encode cardiac Na+ channel) nonsense mutations, p.R1623X and p.S1812X. We applied two readthrough-enhancing methods (either aminoglycosides or a siRNA-targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1)) to suppress these SCN5A nonsense mutations. When either of readthrough methods was used, the sodium channel proteins were examined by western blot and immunoblotting and recorded by whole cell patch-clamp to observe the functional characterization of the restored channels. Upon readthrough treatment, the sodium currents were restored to the mutant cDNAs. These mutations reduced full-length sodium channel protein levels, and the sodium currents were reduced to 3% of wild-type. The mutant cDNA sodium currents were increased to 30% of wild-type, and the fulllength proteins also increased. However, the functional characterization of these channels from cDNAs carrying p.R1623X and p.S1812X exhibited abnormal biophysical properties, including a negative shift in steady-state sodium channel inactivation, a positive shift in sodium channel activation and robust late sodium currents. The ramp test showed prolonged QT intervals. These results demonstrated that readthrough-enhancing methods effectively suppressed nonsense mutations in SCN5A and restored the expression of full-length channels. However, the restored channels may increase the risk of arrhythmia.

Rheology of ethylene- and propylene-glycol ice slurries: Experiments and ANN model

An experimental investigation combined with a numerical study is performed to characterize the rheological behavior of ice slurries. Two additives, namely ethylene glycol and propylene glycol, are considered at three initial concentrations Xa = 5, 14 and 24%. The ice fraction is varied from 5 to 65%. Flow ramp tests are carried out using a hybrid HR-2 rheometer. The Herschel–Bulkley model is then employed to predict the rheological behavior of ice. Using a least-square approach, the flow index n and the consistency index k are deduced from the rheograms. The ice slurries exhibit either a shear-thinning or a shear-thickening behavior depending on the operating conditions. An experimental database is produced based on the present experiments and on experimental data retrieved from the literature. An Artificial Neural Network (ANN) model is then developed and validated using this database and appears to be a valuable tool for predicting the rheological behavior of ice slurries.

Strategies of adaptation of small arteries in diaphragm and gastrocnemius muscle to aerobic exercise training

Aerobic exercise training is associated with adaptive changes in skeletal muscles and their vascular bed; such changes in individual muscles may vary depending on their characteristics and recruitment. This study was aimed at comparing the effects of eight-week treadmill training on the locomotor and respiratory muscles in rats. The training course increased the aerobic performance in rats, which was evidenced by an increase in maximum O2 consumption and a decrease in the blood lactate concentration in ramp test. The succinate dehydrogenase activity was increased in the red portion of the gastrocnemius muscle, but not in the diaphragm of trained rats. Arterial segments were isolated from feed arteries and studied by wire myography. The relaxation in response to acetylcholine in gastrocnemius arteries in trained animals was higher as compared with controls (due to higher NO production), while contractile responses to noradrenaline (in the presence of propranolol) were not changed. On the contrary, the endothelial function of diaphragm arteries was not affected by training, but contractile responses to activation of α-adrenoceptors were markedly increased. Thus, aerobic training may increase the blood supply rate to both locomotor and respiratory muscles, but the underlying regulatory mechanisms are different. The results obtained allow us to reveal the physiological mechanisms that determine the physical performance of the body under conditions of compromised functioning of the respiratory system.