Intermittent Cycles Research Articles

Ex-Vivo Testing Platform to Predict Clinical Response and Resistance to Proteosome Inhibitors, IMiDs and Daratumumab in Multiple Myeloma

Treatment of Multiple Myeloma (MM) relies on Standard of Care (SoC) schemes that include immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) in combination with dexamethasone (Dexa). More recently, monoclonal antibodies such as Daratumumab (Dara) have become complementary therapeutic strategies to treat newly diagnosed and relapsed MM patients. Despite the multiple therapeutic schemes available, MM remains an incurable disease in which patients transit intermittent cycles of relapse and remission that ultimately lead to multi-drug resistance. It has therefore become clear that novel tools for personalized therapy selection are necessary to improve outcomes and reduce trial and error, particularly when selecting later lines of treatment. At OncoPrecision, we have developed a personalized ex-vivo platform that mimics the tumor microenvironment and promotes the survival of Patient-Derived Cells (PDCs), with the goal to predict the performance of the complete array of FDA-approved drugs, as well as experimental treatments, within 7 days. This technology, which we have named Patient Micro Avatars (PMAs), consists of the co-culture of PDCs with engineered neoplastic (System Control) and stromal (Tox Control) heterologous cells in combination with a multi-tagging approach coupled to high-throughput flow cytometry (Figure: Upper Panel). Our PMAs not only enable us to rank the activity of all approved treatments, but also unveil potential unspecific toxicities of novel treatments on non-tumoral cells, thus unlocking unique insights for early drug development programs. In this work, we introduce our PMA technology for MM by presenting differential response between patients in a Clinical Study performed in collaboration with two healthcare centers which, through approved IRBs, have provided MM patient samples from bone marrow aspiration. We present ex-vivo profiling results with a comprehensive MM drug matrix which includes SoC treatments used in several lines of therapy. We illustrate the potential of PMAs to identify differential activity from individual agents and synergistic drugs combinations in 13 patients (Figure: Lower Panel). By anticipating vulnerability/resistance to SoC treatments, our platform has the potential to become a first-in-class phenotypic biomarker to serve as a decision-support tool for Physicians to select optimal therapeutic regimes, as well as to elucidate valuable pre-clinical patient-derived insights for the development of innovative therapies for MM.

Experimental study about the impact of open cell aluminium foam (OCAF) insertion in salt-based phase change material (PCM) for electronics thermal management

Thermal management of electronic components is a critical task in a harsh thermal environment. Spacecraft and satellites' electronics are susceptible to highly intermittent heating and cooling thermal conditions, which imposes challenges for robust thermal management system design. Phase change materials (PCM) are a promising solution for overcoming these challenges and enhancing thermal control performance. The lower PCM thermal conductivity and PCM supercooling limit PCM utilisation in electronic thermal control systems. The present study aims to provide solutions for enhancing the heat transfer within the PCM, boosting the PCM thermal conductivity, and diminishing the PCM supercooling. The open-cell aluminium foam (OCAF) was adopted for boosting the heat transfer within the PCM. A thermal management module (TMM) integrated with a salt-based PCM/OCAF composite was developed for electronics thermal management. The TMM was tested under intermittent thermal conditions of heating and cooling. An electric heater and Peltier cooler were affixed to the TMM for the heating and cooling process, respectively. Three levels of heat fluxes were adopted: 700, 1000, and 1400 W/m2. The heating process lasted one hour; then, the TMM was cooled by the Peltier element to the initial temperature. The research novelty covers the gap in understanding how OCAF affects salt-based PCM supercooling when subjected to varying heating loads during intermittent cycles. The outcomes reported a remarkable improvement in thermal management efficiency. The PCM-based TMM reduced the highest temperature by about 20.4 %, 21.6 %, and 23 % at the three heating levels. The OCAF diminished the PCM supercooling curiously. The reduction in PCM supercooling was 43.5 % compared to the 100 % PCM case obtained at the heat flux of 1400 W/m2.

Effect of Oil/Water Intermittent Wetting on CO2 Corrosion in the Presence of Acridine and Myristic Acid

The effect of a paraffinic model oil (LVT-200)-containing select surface-active compounds (myristic acid and acridine) on CO2 corrosion with and without intermittent wetting has been studied. Observations have shown that the presence of myristic acid in the oil phase does not affect the corrosion behavior due to its lack of partitioning in the water phase. However, after direct contact between the oil phase-containing myristic acid and the metal surface, there was a significant decrease in the corrosion rate. This phenomenon gradually diminished at pH 4.0 but was more persistent at pH 6.5. The presence of acridine in the oil phase was shown to have a strong inhibitive effect at pH 4.0, even during the partitioning step. The partitioning of acridine from the oil phase to the water phase at pH 4.0 was confirmed by ultraviolet-visible spectroscopy results. However, there was no inhibitive effect conferred by the presence of acridine on the corrosion rate at pH 6.5. An experimental methodology was developed that facilitated improved simulation of the effect of intermittent oil/water wetting on CO2 corrosion. The electrochemical current response during the oil/water intermittent wetting cycles showed that the persistency of model oil (without surface-active compounds) on the mild steel surface is only a matter of seconds. Corrosion rate measurements showed that the presence of myristic acid renders the oil layer more persistent after intermittent wetting compared to one-time direct contact.

The impact of intermittent overcharging on battery capacity and reliability: Electrochemical performance analysis and failure prediction

Due to the inconsistencies among cells within the battery pack and the potential faults in battery management system, intermittent overcharging occurs during the long-term operation of cells. However, the impact of such occurrences on battery capacity and reliability has not been fully revealed. This study investigates the changes in electrochemical performance of the battery after conventional cycling and intermittent overcharge cycling and the causes of the changes through reference performance tests and material characterization techniques. The results indicate that the presence of intermittent overcharging accelerates capacity degradation and impedance rise in cells, which primarily result from secondary particles cracking, Li+/Ni2+ mixture, and transition metals dissolution, ultimately leading to the loss of cathode active material and lithium inventory. Moreover, the cells suddenly fail after about 100 cycles of intermittent overcharging, with the cause identified as the cumulative gas production resulting from side reactions between cathode and electrolyte, which eventually pushes the valve to bend, cutting off the internal electrical circuit. To predict battery failure caused by intermittent overcharging, a method is proposed by monitoring abnormal changes in surface temperature, charging capacity, and charging current during the overcharging stage, thereby enhancing the reliability of cells in practical applications.

Formation temperature range expansion and energy storage properties of CO2 hydrates

A hybrid thermal cycle is developed by storing liquid CO2 using an intermittent heat pump cycle (IHP) and forming CO2 hydrates (CHRs) using a CHR thermal cycle (CHT) with a high charge/discharge efficiency at low temperatures. The proposed technology for physical batteries operates the IHP in summer, when outside temperatures are high, and the CHT in winter. The operating period of a CHT with a high charge/discharge efficiency can be extended and the annual efficiency of IHP/CHT hybrid systems can be improved by increasing the temperature of the low-temperature heat source of the CHT. Therefore, cyclopentane, the crystal structure of which differs from that of CHRs, is added to the host fluid in this study. Then, the CHR formation temperature range is expanded based on the results of the experiment. When the CHR formation temperature (outdoor air temperature as low-temperature heat source) is increased from the conventional 0 °C–15 °C, the amount of generated CHR slightly exceeds the amount generated by a conventional system. These findings show that a CHT system, which conventionally requires a low-temperature heat source (approximately 0 °C), can now be operated at a moderate temperature of 15 °C. When CHR are formed at 0 °C for 18 h and then dissociated at 25 °C, the prototype reactor produces a high-pressure dissociated gas of 20.5 MPa at an initial formation pressure of 5 MPa. When cyclopentane is added to water in a 3500 cm3 vessel at the appropriate concentration, CO2 hydrates large enough to be produced even at outdoor temperatures of about 15 °C or less. The proposed system can be operated at outdoor temperatures below 15 °C. These results represent the close realization of the proposed CHT.

Exhaustive Intermittent Cycling Preferentially Decreases Explosive Over Maximal Voluntary Torque in the Knee Extensors, With No Difference Between Normoxia and Moderate to Severe Hypoxia.

To compare the effects of graded hypoxia during exhaustive intermittent cycling on subsequent rapid and maximal torque-production capacity. Fifteen well-trained cyclists repeated intermittent cycling bouts (15s at 30% of anaerobic power reserve; rest = 45s) until exhaustion at sea level (FiO2 ∼0.21/end-exercise arterial oxygen saturation ∼96%), moderate hypoxia (FiO2 ∼0.16/∼90%), and severe hypoxia (FiO2 ∼0.12/∼79%). Rapid (rate of torque development [RTD]) and maximal isometric torque-production capacities of the knee extensors were assessed at baseline (visit 1) and exhaustion (visits 2-4). Exercise capacity decreased with hypoxia severity (39 [30], 22 [13], and 13 [6] cycle efforts in sea level, moderate hypoxia, and severe hypoxia, respectively; P = .002). Changes in maximal-voluntary-contraction torque between baseline and postexercise in all conditions were not statistically significant (pooled values: -2.6% [5.7%]; P = .162). Peak RTD measured postexercise was reduced below baseline in all conditions (-21.5% [5.1%]; P ≤ .015). Compared with baseline, absolute RTD values were lower at 0- to 30-millisecond (-35.1% [5.3%], P ≤ .020), 0- to 50-millisecond (-40.0% [3.9%], P ≤ .002), 0- to 100-millisecond (-30.7% [3.7%], P ≤ .001), and 0- to 200-millisecond (-18.1% [2.4%], P ≤ .004) time intervals in all conditions. Exhaustive intermittent cycling induces substantial yet comparable impairments in RTD of knee extensors between normoxia and moderate to severe hypoxia.

Effects of combined resistance and aerobic training program on myoelectric activity of Vastus Lateralis in patients with breast cancer during adjuvant chemotherapy period.

Chemotherapy and/or radiation are normally the predominant therapies administered to cancer patients. Commonly, patients express complaints of fatigue during adjuvant treatment. Furthermore, regular practice of physical exercise during adjuvant treatment seems to have positive effects. The aim of this study was to investigate the effects of combined muscle strength, and a supervised aerobic training program on myoelectric activity of Vastus Lateralis during isometric test in patients with breast cancer undergoing adjuvant chemotherapy. Thirty-two women with breast cancer (20 patients in the training group and 12 patients as controls) undergoing adjuvant chemotherapy participated in the study. They took part in a 6-week training period. A muscle-strength program included isometric contraction and electrical muscle stimulation (EMS). Aerobic training program consisted of supervised intermittent cycling exercise and home-based walking exercise. The outcome measures were Root Mean Square (RMS), Mean Power Frequency (MPF), Maximal Voluntary isometric Contraction (MViC), and Endurance Time (ET) of Vastus Lateralis, before and after the training period in the two groups. Compared to controls, a significant increase in MViC (p=0.001) and ET (p=0.005) in quadriceps accompanied by a significant decrease in RMS (p=0.007) and a significant increase in MPF (p=0.002) has been obtained in the training group. Supervised muscle strength and supervised aerobic training programs enhanced muscle activity and muscular performance in women with breast cancer during adjuvant chemotherapy treatment and optimized the decrease of muscular fatigue.

Single versus intermittent cycle exposure effect of 6-mercaptopurine in juvenile Sprague-Dawley rat: a germ cell-specific mechanistic study.

Infertility is a frequent long-term adverse effect of cancer therapy for children. Compromised testicular functions in adolescence are frequent observations after chemotherapy and there are currently no well-established alternatives to avoid this damage. Antimetabolites such as 6-mercaptopurine (6-MP) are used to treat a variety of cancer; however, its treatment-associated adverse effects on the male reproductive functions are overlooked. Here, the molecular processes underlying 6-MP-induced male germ cell damage in juvenile Sprague-Dawley (SD) rats (3weeks) have been investigated. Rats were administered with low (5mg/kg), medium (10mg/kg), and high (20mg/kg) doses of 6-MP per orally either singly (1week × 1 cycle) or intermittently (1week treatment followed by 1week remission period × 3 cycles). The toxicity was evaluated in terms of genotoxicity and testes- and sperm-related cellular and molecular parameters. Single cycle of exposure either produced mild or no toxic manifestations at the end of the 6th week. Intermittent cycles of exposure, particularly at the 10 and 20mg/kg, decreased body and organ weights, increased micronucleated cells in the peripheral blood, induced oxidative/nitrosative stress, altered sperm chromatin quality, reduced serum testosterone and follicle stimulating hormone (FSH) levels, increased testicular structural aberrations, DNA damage, and apoptosis, and upregulated TNF-α expression and downregulated p-AMPK and β-catenin expressions. Conclusively, intermittent cycles of exposure at 10 and 20mg/kg doses to the juvenile rats significantly induced oxidative stress, genotoxicity, and cellular and molecular perturbations in the testes and sperm of adult rats.

Experimental and numerical study on the process of removing kerosene residues in rocket engine chamber

This article conducts experimental and numerical research on the process of removing residual kerosene from the wall of the rocket engine chamber after test run, and proposes a cleaning method of high-pressure nitrogen blowing and low-pressure suction intermittent cycle. The research idea is to simulate the concentration changes of residual kerosene liquid and steam during the removal process using CFD method to analyze the mass transfer mechanism during the process, and to verify the accuracy of the numerical model through experiments. It can be concluded that the intermittent cycle cleaning method proposed in this article can efficiently remove residual kerosene from the wall of the rocket engine chamber. By using this cleaning method for 120 min, the maximum cleaning efficiency reaches 97.86%. At the same time, it was found that the high-pressure nitrogen blowing effect was the most obvious during the cleaning process, and switching between high and low pressure during the circulation process was beneficial for the removal of residual kerosene.

Hypohydration induced by prolonged cycling in the heat increases biomarkers of renal injury in males

PurposeRecent studies have shown that hypohydration can increase renal injury. However, the contribution of hypohydration to the extent of renal injury is often confounded by exercise induced muscle damage. Therefore, the aim of the present study was to investigate the effect of manipulating hydration status during moderate-intensity cycling in the heat on biomarkers of renal injury.MethodsFollowing familiarisation, fourteen active males (age: 21 [20–22] y; BMI: 22.1 ± 1.9 kg/m2; V˙\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\dot{V} $$\\end{document}O2peak: 55 ± 9 mL/kg/min) completed two experimental trials, in a randomised cross-over design. Experimental trials consisted of up to 120 min of intermittent cycling (~ 50% Wpeak) in the heat (~ 35 °C, ~ 50% relative humidity). During exercise, subjects consumed either a water volume equal to 100% body mass losses (EU) or minimal water (HYP; 75–100 mL) to induce ~ 3% body mass loss. Blood and urine samples were collected at baseline, 30 min post-exercise and 24 h post-baseline, with an additional urine sample collected immediately post-exercise.ResultsThirty minutes post-exercise, body mass and plasma volume were lower in HYP than EU (P < 0.001), whereas serum and urine osmolality (P < 0.001), osmolality-corrected urinary kidney injury molecule-1 concentrations (HYP: 2.74 [1.87–5.44] ng/mOsm, EU: 1.15 [0.84–2.37] ng/mOsm; P = 0.024), and percentage change in osmolality-corrected urinary neutrophil gelatinase-associated lipocalin concentrations (HYP: 61 [17–141] %, EU: 7.1 [– 4 to 24] %; P = 0.033) were greater in HYP than EU.ConclusionHypohydration produced by cycling in the heat increased renal tubular injury, compared to maintaining euhydration with water ingestion.

Do Mixtures of Beads with Different Sizes Improve Wet Stirred Media Milling of Drug Suspensions?

The impacts of bead sizes and bead mixtures on breakage kinetics, the number of milling cycles applied to prevent overheating, and power consumption during the nanomilling of drug (griseofulvin) suspensions were investigated from both an experimental and theoretical perspective. Narrowly sized zirconia beads with nominal sizes of 100, 200, and 400 µm and their half-and-half binary mixtures were used at 3000 and 4000 rpm with two bead loadings of 0.35 and 0.50. Particle size evolution was measured during the 3 h milling experiments using laser diffraction. An nth-order breakage model was fitted to the experimental median particle size evolution, and various microhydrodynamic parameters were calculated. In general, the beads and their mixtures with smaller median sizes achieved faster breakage. While the microhydrodynamic model explained the impacts of process parameters, it was limited in describing bead mixtures. For additional test runs performed, the kinetics model augmented with a decision tree model using process parameters outperformed that augmented with an elastic-net regression model using the microhydrodynamic parameters. The evaluation of the process merit scores suggests that the use of bead mixtures did not lead to notable process improvement; 100 µm beads generally outperformed bead mixtures and coarser beads in terms of fast breakage, low power consumption and heat generation, and low intermittent milling cycles.

Highly fluorinated non-aqueous solid-liquid hybrid interface realizes water impermeability for anti-calendar aging zinc metal batteries

The thermodynamic instability of zinc metal in aqueous electrolytes is attributed to severe interfacial problems at the zinc anode. In this study, we designed and synthesized a porous-fluorinated covalent organic framework (FCOF) to encapsulate liquid perfluoropolyether (PFPE) and Zn(OTf)2 using a host-guest strategy to effectively solve the static corrosion problem of the anode. The highly fluorinate solid-liquid interface restricted free water from contacting zinc, thus greatly improving the anti-calendar aging of aqueous zinc-metal batteries. The highly fluorinated solid-liquid hybrid was constructed as a water impermeability and defect-free protection layer on the Zn surface (denoted as P-PFL@Zn). The P-PFL@Zn had integrated advantages: the liquid PFPE filled structural voids to eliminate interfacial defects, improve contact with Zn, and effectively adapt to the dynamic interface fluctuations. The solid FCOF promoted fast ion transport, provided confined space, and exhibited strong adsorption with the liquid phase, restricting the mobility of PFPE and facilitating the tight adherence of FCOF to the Zn surface. Due to the synergistic effect between the FCOF and PFPE, P-PFL@Zn exhibited a 40-day anti-calendar aging cycle, high Zn2+ transference number, ultrafast charging, and dendrite-free features. The assembled high mass-loading (20 mg cm−2) MnO2 cathode-based full cells exhibited good practical level performance under intermittent cycle mode (1000-cycle life with 90% capacity retention) and continuous cycle mode (1000-cycle life with limited Zn usage and high current density).

Enhancing Seasonal Forecast Skills by Optimally Weighting the Ensemble from Fresh Data

Abstract Dynamical climate predictions are produced by assimilating observations and running ensemble simulations of Earth system models. This process is time consuming and by the time the forecast is delivered, new observations are already available, making it obsolete from the release date. Moreover, producing such predictions is computationally demanding, and their production frequency is restricted. We tested the potential of a computationally cheap weighting average technique that can continuously adjust such probabilistic forecasts—in between production intervals—using newly available data. The method estimates local positive weights computed with a Bayesian framework, favoring members closer to observations. We tested the approach with the Norwegian Climate Prediction Model (NorCPM), which assimilates monthly sea surface temperature (SST) and hydrographic profiles with the ensemble Kalman filter. By the time the NorCPM forecast is delivered operationally, a week of unused SST data are available. We demonstrate the benefit of our weighting method on retrospective hindcasts. The weighting method greatly enhanced the NorCPM hindcast skill compared to the standard equal weight approach up to a 2-month lead time (global correlation of 0.71 vs 0.55 at a 1-month lead time and 0.51 vs 0.45 at a 2-month lead time). The skill at a 1-month lead time is comparable to the accuracy of the EnKF analysis. We also show that weights determined using SST data can be used to improve the skill of other quantities, such as the sea ice extent. Our approach can provide a continuous forecast between the intermittent forecast production cycle and be extended to other independent datasets.

Influencing factors of PM2.5 concentration in the typical urban agglomerations in China based on wavelet perspective

PM2.5 is one of the most harmful air pollutants affecting sustainable economic and social development in China. The analysis of influencing factors affecting PM2.5 concentration is significant for the improvement of air quality. In this study, three typical urban agglomerations in China (Beijing‒Tianjin‒Hebei [BTH], the Yangtze River Delta [YRD], and the Pearl River Delta [PRD]) were studied using innovative trend analysis, a Bayesian statistical model, and partial wavelet and multiwavelet coherence to analyze PM2.5 concentration variations and multi-scale coupled oscillations between PM2.5 concentration and air pollutants/meteorological factors. The results showed that: (1) PM2.5 concentration time-series showed significant downward trends, which decreased as follows: BTH > YRD > PRD. The higher the pollution level, the greater the change trend. In BTH and the PRD, PM2.5 had obvious trends and seasonal change points; whereas, the PM2.5 time-series change point in the YRD was not obvious. (2) PM2.5 had significant intermittent resonance cycles with air pollutants and meteorological factors in different time domains. There were differences in the main controlling factors affecting PM2.5 among the three urban agglomerations. (3) The explanatory ability of air pollutant combinations for variations in PM2.5 was higher than that of meteorological factor combinations. However, the synergistic effect of air pollutants/meteorological factors could better explain the PM2.5 concentration variations on all time-frequency scales. The results of this study provide a reference for ecological improvement as well as collaborative governance of air pollution.

Development and validation of dynamic bioenergetic model for intermittent ergometer cycling

PurposeThe aim of this study was to develop and validate a bioenergetic model describing the dynamic behavior of the alactic, lactic, and aerobic metabolic energy supply systems as well as different sources of the total metabolic energy demand.MethodsThe bioenergetic supply model consisted of terms for the alactic, lactic, and aerobic system metabolic rates while the demand model consisted of terms for the corresponding metabolic rates of principal cycling work, pulmonary ventilation, and accumulated metabolites. The bioenergetic model was formulated as a system of differential equations and model parameters were estimated by a non-linear grey-box approach, utilizing power output and aerobic metabolic rate (MRae) data from fourteen cyclists performing an experimental trial (P2) on a cycle ergometer. Validity was assessed by comparing model simulation and measurements on a similar follow-up experimental trial (P3).ResultsThe root mean square error between modelled and measured MRae was 61.9 ± 7.9 W and 79.2 ± 30.5 W for P2 and P3, respectively. The corresponding mean absolute percentage error was 8.6 ± 1.5% and 10.6 ± 3.3% for P2 and P3, respectively.ConclusionThe validation of the model showed excellent overall agreement between measured and modeled MRae during intermittent cycling by well-trained male cyclist. However, the standard deviation was 38.5% of the average root mean square error for P3, indicating not as good reliability.

Cold water immersion of the hand and forearm during half-time improves intermittent exercise performance in the heat

The present study aimed to investigate the effect of cold water immersion of the hand and forearm during half-time (HT) on intermittent exercise performance and thermoregulation by imitating intermittent athletic games in the heat. In a randomized crossover design, 11 physically active men performed the first half (first and second block) and second half (third and fourth block) intermittent cycling exercise protocol, which consisted of a 5-s maximal power pedalling (body weight × 0.075 kp) every minute separated by 25-s of unloaded pedalling and rest (30 s) in the heat (33°C, 50% relative humidity). The two-halves were separated by a 15-min HT. During HT, the participants were assigned to the CON (sedentary resting) or COOL (immersion of hands and forearms in cold water at 15–17°C) condition. The mean power output in the second half was significantly greater (third and fourth block:p&amp;lt; 0.05) in the COOL than in the CON condition. Moreover, there was a significant decrease in the rectal (0.54 ± 0.17°C,p&amp;lt; 0.001) and mean skin (1.86 ± 0.34°C,p&amp;lt; 0.05) temperatures of the COOL condition during HT. Furthermore, the heart rate (16 ± 7 bpm,p&amp;lt; 0.05) and skin blood flow (40.2 ± 10.5%,p&amp;lt; 0.001) decreased at the end of HT in the COOL condition. In the second half, thermal sensation was more comfortable in the COOL condition (p&amp;lt; 0.001). Cold water immersion of the hand and forearm during HT improved physiological and reduced perceived heat stress. Moreover, it prevented a reduction in intermittent exercise performance in the second half.

TMEM41B Is an Interferon-Stimulated Gene That Promotes Pseudorabies Virus Replication.

Pseudorabies virus (PRV) is a double-stranded DNA virus that causes Aujeszky's disease and is responsible for economic loss worldwide. Transmembrane protein 41B (TMEM41B) is a novel endoplasmic reticulum (ER)-localized regulator of autophagosome biogenesis and lipid mobilization; however, the role of TMEM41B in regulating PRV replication remains undocumented. In this study, PRV infection was found to upregulate TMEM41B mRNA and protein levels both in vitro and in vivo. For the first time, we found that TMEM41B could be induced by interferon (IFN), suggesting that TMEM41B is an IFN-stimulated gene (ISG). While TMEM41B knockdown suppressed PRV proliferation, TMEM41B overexpression promoted PRV proliferation. We next studied the specific stages of the virus life cycle and found that TMEM41B knockdown affected PRV entry. Mechanistically, we demonstrated that the knockdown of TMEM41B blocked PRV-stimulated expression of the key enzymes involved in lipid synthesis. Additionally, TMEM41B knockdown played a role in the dynamics of lipid-regulated PRV entry-dependent clathrin-coated pits (CCPs). Lipid replenishment restored the CCP dynamic and PRV entry in TMEM41B knockdown cells. Together, our results indicate that TMEM41B plays a role in PRV infection via regulating lipid homeostasis. IMPORTANCE PRV belongs to the alphaherpesvirus subfamily and can establish and maintain a lifelong latent infection in pigs. As such, an intermittent active cycle presents great challenges to the prevention and control of PRV disease and is responsible for serious economic losses to the pig breeding industry. Studies have shown that lipids play a crucial role in PRV proliferation. Thus, the manipulation of lipid metabolism may represent a new perspective for the prevention and treatment of PRV. In this study, we report that the ER transmembrane protein TMEM41B is a novel ISG involved in PRV infection by regulating lipid synthesis. Therefore, our findings indicate that targeting TMEM41B may be a promising approach for the development of PRV vaccines and therapeutics.

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer.

Reduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls. Age-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise. At 0 h, conventional T cell counts increased by 45%-64% with no differences between groups. T cell frequency decreased by -3.5% for CD3+ and -4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of -4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was -18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h. Following acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

Influence of specimen size and density variation in the foam rise direction on the compressive behavior of PVC foams

Mechanical properties governing the localized deformation mechanisms, apparent elastic modulus and their correlation to specimen geometry in polymeric foams are important phenomena that are not well understood. Despite the well-studied density variation in Functionally Graded Foams (FGF), density variation in the foam rise direction of conventional foams has not received adequate attention in the current literature. The influence of specimen size and density variation on the deformation mechanisms and mechanical properties observed in the rise direction of H-series rigid PVC foams were experimentally investigated in this study by considering four distinct specimen sizes and five nominal densities. PVC foams with different nominal densities exhibited various density variation patterns, in a range of 2.6–26.3 % variation, in the foam rise direction which were found to govern the polymeric foams’ localized deformation mechanisms and the post-yield stress drop-off behavior. The plateau stress was observed as most sensitive to the foam density; specimens with higher densities exhibited up to 19 % higher plateau stress within the foam panel with a 200 kg/m3 nominal density. While specimen thickness significantly influenced the loading elastic modulus. Intermittent unloading-reloading cycle testing was conducted on thick and thin specimens to characterize the influence of specimen thickness on the apparent elastic modulus. The influence of thickness on the unloading elastic modulus was negligible, for example, reducing the specimen thickness from 25.40 mm to 6.35 mm decreased the loading and unloading elastic moduli by 39 % and 7 %, respectively, for PVC foams with a nominal density of 200 kg/m3. Therefore, the unloading elastic modulus should be utilized in future studies for more accurate cross-comparison between the mechanical properties of specimens with significantly different thicknesses.

Corrosion Inhibitor Distribution and Injection Cycle Prediction in a High Water-Cut Oil Well: A Numerical Simulation Study

The wellbore downhole strings corrosion has attracted extensive interest as most of the oilfields in China enter the high water-cut period. Injection of corrosion inhibitors, one of the most effective corrosion protection methods, is employed to mitigate the wellbore corrosion. Nevertheless, its wider application suffers from insufficient knowledge regarding the distribution of corrosion inhibitors inside the tubing, particularly with different inhibitor injection cycles. Thus, in this study, the computational fluid dynamics (CFD) method was first attempted to investigate the hydrodynamics in a tubing and the interactions between the corrosion inhibitor and produced fluid with high water-cut. Key factors including the time, wellbore heights, injection rates, oil phase velocities and corrosion inhibitor viscosities were discussed in detail as regards how they affect the corrosion inhibitor distribution inside the tubing. Feasible formulas were established for predicting the volume fraction of the corrosion inhibitor at different wellbore heights, which showed good agreement with the simulation results. It is noted that the determination of the corrosion inhibitor injection rate depends on both the film quality of the corrosion inhibitor and the stability of the annular flow. Based on the interphase diffusion effect, a new method for determining the intermittent injection cycle of corrosion inhibitor was proposed to maintain the integrity of corrosion inhibitor film at the tubing inner wall.