Reverse Stress Research Articles

A cell-based chemical-genetic screen for amino acid stress response inhibitors reveals torins reverse stress kinase GCN2 signaling

mTORC1 and GCN2 are serine/threonine kinases that control how cells adapt to amino acid availability. mTORC1 responds to amino acids to promote translation and cell growth while GCN2 senses limiting amino acids to hinder translation via eIF2α phosphorylation. GCN2 is an appealing target for cancer therapies because malignant cells can harness the GCN2 pathway to temper the rate of translation during rapid amino acid consumption. To isolate new GCN2 inhibitors, we created cell-based, amino acid limitation reporters via genetic manipulation of Ddit3 (encoding the transcription factor CHOP). CHOP is strongly induced by limiting amino acids and in this context, GCN2-dependent. Using leucine starvation as a model for essential amino acid sensing, we unexpectedly discovered ATP-competitive PI3 kinase-related kinase inhibitors, including ATR and mTOR inhibitors like torins, completely reversed GCN2 activation in a time-dependent way. Mechanistically, via inhibiting mTORC1-dependent translation, torins increased intracellular leucine, which was sufficient to reverse GCN2 activation and the downstream integrated stress response including stress-induced transcriptional factor ATF4 expression. Strikingly, we found that general translation inhibitors mirrored the effects of torins. Therefore, we propose that mTOR kinase inhibitors concurrently inhibit different branches of amino acid sensing by a dual mechanism involving direct inhibition of mTOR and indirect suppression of GCN2 that are connected by effects on the translation machinery. Collectively, our results highlight distinct ways of regulating GCN2 activity.

Breakdown Voltage Instability Mechanism on the Field Limiting Rings Edge Termination of Buried Layer Rectifier

In this article, an innovated buried layer rectifier (BLR) breakdown voltage (BV) instability has been tested and analyzed. Under the reverse current stress (RCS) condition, the BV read-out profiles show walk-in and walk-out phenomena. Based on the experimental results and surface traps theory, a sort of time-dependent degraded simulation is developed by TCAD tools, which is considered with hydrogen depassivation and diffusion process. In order to explore the inner mechanism, the dynamic electric parameters are analyzed during the degraded period. Due to the hole interface traps, the termination Si-SiO2 surface leakage current is deteriorated and the depletion boundary is shrunk, which reveal the BV values instability. Thus, the proposed physical model could clearly explain the whole process of degradation, while it fits BV and junction temperature curves to the experimental results identically. Furthermore, the investigated mechanism will be helpful to future device design and failure situations analysis.

Reversal of oxidative stress, cytokine toxicity and DNA fragmentation by quercetin in dizocilpine-induced animal model of Schizophrenia.

Quercetin, a polyphenolic compound found in a variety of plant products possesses various biological activities and beneficial effects on human health. Schizophrenia (SZ) is one of the neuropsychiatric disorders in human beings with rapid mortality and intense morbidity which can be treated with antipsychotics, but these commercial drugs exert adverse effects and have less efficacy to treat the full spectrum of SZ. The present study was conducted to evaluate neuroprotective effects of quercetin in the preventive and therapeutic treatment of SZ. Quercetin was administered as pre- and post-regimens at the dose of 50mg/kg in dizocilpine-induced SZ rat model for two weeks. Rats were then subjected for the assessment of different behaviors followed by biochemical, neurochemical, and inflammatory marker analyses. The present findings revealed that quercetin significantly reverses the effects of dizocilpine-induced psychosis-like symptoms in all behavioral assessments as well as it also combats oxidative stress. This flavonoid also regulates dopaminergic, serotonergic, and glutamatergic neurotransmission. A profound effect on inflammatory cytokines and decreased %DNA fragmentation was also observed following the administration of quercetin. The findings suggest that quercetin can be considered as a preventive as well as therapeutic strategy to attenuate oxidative stress and cytokine toxicity, regulate neurotransmission, and prevent enhanced DNA fragmentation that can lead to the amelioration of psychosis-like symptoms in SZ.

Evolving asymmetric and anisotropic hardening of CP-Ti sheets under monotonic and reverse loading: Characterization and modeling

Commercially pure titanium (CP-Ti) sheets are promising to manufacture high-performance and lightweight components in many fields such as aerospace, marine, energy, electrics and healthcare. However, due to its low symmetric hexagonal close-packed (HCP) structure and complex thermal-mechanical processing history, CP-Ti sheets may exhibit significant asymmetry and anisotropy under monotonic and reverse loading. Therefore, the coupling effect of loading-path dependent asymmetric and anisotropic hardening behaviors of CP-Ti sheets need to be systemically characterized and accurately described under monotonic and reverse loading paths. In this study, firstly, the rheological tests were performed to systemically explore the evolving asymmetric and anisotropic hardening behavior of CP-Ti sheet under monotonic and reverse loading modes. With the help of anti-buckling support fixture and DIC system in tension and compression tests, the coupling effect of asymmetric and anisotropic hardening under monotonic and reverse loading of CP-Ti sheet was identified. Secondly, a loading-path dependent constitutive modeling framework was constructed in which the stress invariants-based model (SIM) integrated with distorted hardening (DH) under reverse loading (RL) conditions (SIM+DH+RL) were considered. Within the proposed modeling framework, a judging criterion of stress reversal for explicit solution method and an activation criterion of different reverse loading modes were introduced. Finally, the proposed SIM+DH+RL model was implemented, calibrated and further applied to simulate typical V-/U-bending of CP-Ti sheets. The results show that the proposed SIM+DH+RL model can significantly improve the prediction accuracy of V-/U-bending springback with the relative errors less than 7.8% and 2.1%, compared with 15.2% and 12% relative errors of Mises+IH, 19.5% and 7.3% relative errors of SIM+DH, 15.1% and 8.4% relative errors of Yoon2014+IH, 14.5% and 5.2% relative errors of CPB06+IH, and 17.3% and 11.5% relative errors of Hill48+IH. It is noted that for the thickness distributions after V-/U-bending springback, the above used models have similar prediction accuracies with the relative errors less than 1.8%.

Fault plane picking from focal mechanisms in reverse faulting stress: Application to the Mw6.9 Boumerdes (Algeria) earthquake sequence

Identification of the fault plane from two nodal planes of the focal mechanism is, in general, ambiguous. This problem is commonly solved using other constraints provided by tectonic, geological or seismic studies. In this paper, we evaluate the probability of identifying the fault plane using knowledge of stress field. We employ two alternative methods: (1) the slip angle method (SA), and (2) the highest instability method (IS). First, the efficiency of the methods was tested on synthetic data consisting of focal mechanisms compatible with a reverse stress regime. The tests revealed that the fraction of faults correctly picked by the IS method is higher than that of the SA method, particularly for large noise values. Second, the methods were applied to the aftershocks of the Boumerdes (Algeria) earthquake of May 21, 2003. This application showed that when taking into account the focal solutions for which the fault planes are determined using the IS method with a high probability, we observe consistency between the selected faults and the tectonics of the study area.

Dynamic Responses Analysis of A 5MW NREL Wind Turbine Blade under Flap-Wise and Edge-Wise Vibrations

A wind turbine is subjected to a regime of varying loads. For example, each rotor revolution causes a complete gravity stress reversal in the low-speed shaft, and there are varying stresses from the out-of-plane loading cycle due to fluctuating wind load. Consequently, wind turbine blade design is governed by fatigue rather than ultimate load considerations. Previous studies have adopted many different beam theories, using different techniques and codes, to model the National Renewable Energy Laboratory (NREL) 5 MW offshore wind turbine blade. There are differences, from study to study, in the free vibration results and the dynamic response. Thecontribution of this study is to apply the code written by the authors to the different beam theories used with the aim of comparing the different beam theories presented in the literature and that developed by the authors. This paper reports the investigation of the effects of deformation parameters on the dynamic characteristics of the NREL 5 MW offshore wind turbine blades predicted by the different beam theories. The investigation of free vibrations is a fundamental step in the analysis of structural dynamics, and this study compares different computational structural methods and investigates their effect on the predicted dynamic response. The modalcharacteristics of every model examined have been combined with strip theory to determine the dynamic response of the blade.

Chronic dietary exposure to a glyphosate-based herbicide results in total or partial reversibility of plasma oxidative stress, cecal microbiota abundance and short-chain fatty acid composition in broiler hens.

Glyphosate-based herbicides (GBHs) are massively used in agriculture. However, few studies have investigated the effects of glyphosate-based herbicides on avian species although they are largely exposed via their food. Here, we investigated the potential reversibility of the effects of chronic dietary exposure to glyphosate-based herbicides in broiler hens. For 42 days, we exposed 32-week-old hens to glyphosate-based herbicides via their food (47 mg/kg/day glyphosate equivalent, glyphosate-based herbicides, n = 75) corresponding to half glyphosate’s no-observed-adverse-effect-level in birds. We compared their performance to that of 75 control animals (CT). Both groups (glyphosate-based herbicides and control animals) were then fed for 28 additional days without glyphosate-based herbicides exposure (Ex-glyphosate-based herbicides and Ex-control animals). Glyphosate-based herbicides temporarily increased the plasma glyphosate and AMPA (aminomethylphosphonic acid) concentrations. Glyphosate and aminomethylphosphonic acid mostly accumulated in the liver and to a lesser extent in the leg muscle and abdominal adipose tissue. Glyphosate-based herbicides also temporarily increased the gizzard weight and plasma oxidative stress monitored by TBARS (thiobarbituric acid reactive substances). Glyphosate-based herbicides temporarily decreased the cecal concentrations of propionate, isobutyrate and propionate but acetate and valerate were durably reduced. The cecal microbiome was also durably affected since glyphosate-based herbicides inhibited Barnesiella and favored Alloprevotella. Body weight, fattening, food intake and feeding behavior as well as plasma lipid and uric acid were unaffected by glyphosate-based herbicides. Taken together, our results show possible disturbances of the cecal microbiota associated with plasma oxidative stress and accumulation of glyphosate in metabolic tissues in response to dietary glyphosate-based herbicides exposure in broiler hens. Luckily, glyphosate-based herbicides at this concentration does not hamper growth and most of the effects on the phenotypes are reversible.

Olivine-rich veins in high-pressure serpentinites: A far-field paleo-stress snapshot during subduction

Field observations within the Atg-serpentinite domain of the subducted ultramafic massif from Cerro del Almirez (SE Spain) reveal the existence of two generations of abundant olivine-rich veins formed as open, mixed mode and shear fractures during prograde metamorphism. Type I veins were synchronous with the development of the serpentinite main foliation (S1) and shearing, whereas Type II veins post-date the S1 surfaces. These structural relationships indicate that, while the Atg-serpentinites underwent ductile plastic deformation at temperatures of 450°-600 °C and pressures of 0.7–1.7 GPa, they also experienced punctuated brittle behaviour events. The brittle fractures were most likely due to fluid overpressures formed by release of H2O during the brucite breakdown reaction for the case of Type I veins (2 vol % H2O) and due to a combination of minor dehydration reactions related to continuous compositional and structural changes in antigorite (0.3 vol % H2O) for Type II veins. Type II olivine-rich veins were formed by brittle failure in a well-defined paleo-stress field and were not significantly deformed after their formation. Comparison of the principal paleo-stress orientation inferred from Type II veins with those formed at peak metamorphic conditions in the ultramafic rocks at Cerro del Almirez shows a relative switch in the orientation of the maximum and minimum principal paleo-stress axes. These relative changes can be attributed to the cyclic evolution of shear stress, fluid pressure and fault-fracture permeability allowing for stress reversal.

Significant Differences in the Reversal of Cellular Stress Induced by Hydrogen Peroxide and Corticosterone by the Application of Mirtazapine or L-Tryptophan

Depression is a prevalent and debilitating disease worldwide. This pathology is very complex and the lack of efficient therapeutic modalities, as well as the high rates of relapse, makes the study and treatment of depression a global healthcare challenge. Thus, an intense investigation of this disease is crucial and urgent. In this study, we focused on hydrogen peroxide and corticosterone-induced stress on SH-SY5Y and HT-22 cells. Additionally, we aimed to study the potential attenuation of these induced stress with the exposure of both cells to mirtazapine and L-tryptophan, focusing on cell viability assays (MTT and Neutral Red) and reactive oxygen species production assays (DCFDA fluorescence). Taken together, our results indicate that mirtazapine and L-tryptophan counteract the cellular stress induced by hydrogen peroxide but not by corticosterone, revealing a potential role of these agents on oxidative stress relief, highlighting the role of serotonergic pathways in the oxidative stress present in depressed individuals. This study allows the investigation of depression using cellular models, enabling the screening of compounds that may have potential to be used in the treatment of depression by acting on cellular mechanisms such as oxidative stress protection.

How severe are the EBA macroeconomic scenarios for the Italian Economy? A joint probability approach

Measures of the severity of macroeconomic scenarios have been widely used in the literature, but a consistent methodology for their calculation has not been developed yet. Against this background, we provide a general method for calculating the joint probability of observing a macroeconomic scenario, which can be applied to various structural models. By doing so, we can attach probabilities to scenarios produced with multidimensional economic models to compare their severity and plausibility. We apply our methodology to the 2016 and 2018 EBA stress test scenarios and also provide reverse stress test applications. Our results show that for the Italian economy, the 2016 and 2018 EBA scenarios are unlikely, especially the 2016 one. The reverse stress tests allow us to identify the key variables that affect our probabilities.

Degradation mechanisms of Mg-doped GaN/AlN superlattices HEMTs under electrical stress

GaN-based high electron mobility transistors (HEMTs) have exhibited great application prospects in power and radio frequency devices, thanks to the superior properties of GaN. Despite the significant commercialization progress, the reliability of GaN-based HEMTs remains a challenge. This work experimentally investigates the time-dependent degradation of Mg-doped GaN/AlN superlattice HEMTs under both OFF-state and SEMI-ON-state bias conditions and proposes that GaN/AlN superlattices as a barrier can solve the Vth instability issues of GaN HEMTs under OFF-state and SEMI-ON-state bias conditions. On the one hand, in the SEMI-ON-state, the hot electron effect leads to the degradation of Ig, gm,max, and Id,sat to varying degrees. However, the as-prepared GaN-based HEMTs exhibit excellent Vth stability (almost no change) under hot electron injection, on the account of the excellent two-dimensional electron gas confinement in the GaN/AlN superlattice structure. On the other hand, in the OFF-state, positive Vth shift (about 0.12 V) is induced by the hole emission in the GaN/AlN superlattice structure under reverse bias stress. In addition, the stress-induced destruction of MgO gate dielectric gives rise to the gate leakage, which increases by 2 orders of magnitude and triggers an irreversible degradation (about 10%) of the gm,max. These results are expected to provide a solution to the Vth instability of GaN HEMTs.

Full paleostress tensor reconstruction using quartz veins of Panasqueira Mine, central Portugal, part II: Final results

We propose a novel method to reconstruct the six parameters of the paleostress tensor. The method involves three major steps: (1) measurement and inversion of vein attitudes to determine the reduced paleostress tensor, (2) determination of pore pressures using fluid inclusion (FI) isochores and mineral geothermometry, (3) final adjustment of the Mohr circle and estimation of stress magnitudes using geomechanical constraints from the literature. Owing to its outstanding 3D exposures, we selected Panasqueira Mine, central Portugal, as natural laboratory to develop and test our approach. We measured 684 quartz veins, ∼800 FIs in quartz and the geochemical composition of 10 arsenopyrite samples. The inversion of the veins resulted in a reverse stress regime with σ1 trending ∼ NW-SE, Φ = 0.6 and a driving stress ratio of R’ = 0.19. We estimated a lithostatic pressure of 270 MPa (min. 230 MPa and max. 300 MPa) during the major mineralisation stage of the veins of Panasqueira (i.e. MOSS-MSS stage). Finally, the adjustment of the Mohr circle resulted in differential stresses too low to trigger shear failure and in the range from 45 to 89 MPa, and pore pressures exceeding lithostatic pressure by 8.5–17 MPa to open the discontinuities during MOSS-MSS mineralisations.

Evaluation of Phase Transformation Strain and Its Influence on Residual Stress Generation in Laser Welded Ti–6Al–4V Alloy

Abstract The assessment of welding-induced residual stress is always of significant interest due to its adverse effect on the structural stability and mechanical performance of the welded structure. Incorporation of intricate phenomena, in particular, thermal gradient, phase development, volumetric dilation, and phase transformation strain during FE modelling, not only acts as a reliable method for residual stress calculation but also serves as a directive to reduce tensile residual stress in a weldment which is sensitive to the selection of materials. In order to investigate the same for continuous and pulse laser-welded Ti–6Al–4V alloy, the sequentially coupled thermal–metallurgical–mechanical models are established. The internal state-dependent variables (SDVs) are implemented to capture the growth of phase evolved during diffusionless β → α′ transformation using Koistinen–Marburger (K–M) theory in the cooling cycle. The role played by a phase transformation induced strain on the generation of residual stress is systematically investigated. The volumetric dilation and associated phase fraction form the basis for the estimation of phase transformation strain in the present study. The accomplishment of highest martensitic fraction (∼95%) produced a phase transformation strain of 7.95 × 10−3 in pulse mode of operation. As a result, reversal of residual stress from tensile to compressive is perceived for pulse laser-welded specimen. Similarly, a sign of enriched martensitic transformation is noticed that puts the weld surface into a compression state and mitigates the overall tensile residual stress. The assumption of diffusional phase transformation during heating cycle and non-diffusional transformation during cooling phase in laser welding is more appropriate to predict the residual stress using thermal–metallurgical–mechanical model.

NIR‐Encoded Shape Recovery and Regulated Reversible Stress of Shape Memory Polymer

AbstractNear‐infrared (NIR) light responsive shape memory polymers (SMPs) can realize remotely and regionally controlled shape changing that shows broad potential applications. Herein, an NIR‐responsive shape memory polymer (G/PNs) is prepared by introducing reduced graphene oxide to liquid crystal elastomers‐based polymer networks (PNs). The G/PNs present regulated reversible stress by tuning the NIR light irradiation. Furthermore, since the G/PNs are 3D‐printed with designed structure, the deformed 3D printing structure can be regionally patterned with varied shapes by controlling the moving path of NIR laser. In addition, the stress relaxation and cyclic stress–strain measurements are further studied to reveal the energy loss during the deformation and shape memory cycles. In compare with the previous work, the SMP networks provide a rather high reversible actuation stress and can realize remotely control by NIR. The NIR‐encoded shape memory effect can be used as actuators, artificial muscles.

Strain gradient plasticity modelling of cyclic loading in dispersion hardened materials

An analytical model, based on an isotropic strain gradient plasticity theory, describing work hardening during cyclic straining in a metal reinforced by a dispersion of non shearable particles is presented. The yield criterion is expressed in terms of isotropic and kinematic hardening contributions and the model is validated against full field finite element (FE) solutions on a 2D axi-symmetric unit cell model. Excellent agreement between analytical and FE results is obtained. The theory presented includes mixed energetic/dissipative contributions from higher order stresses in both bulk and at particle/matrix interfaces. In particular, the influence of a quadratic interface free energy that transitions into a linear form at some threshold value of plastic strain is investigated. It is shown that such an energy is capable of capturing the experimentally observed phenomenon of inflections in the reverse stress–strain curve. It is argued, based on the well known phenomenon where particles are shielded by Orowan dislocation loops during reverse strain, that an energetic interface contribution could be physically relevant for low plastic strains.

Evaluation on Temperature-Dependent Transient VT Instability in p-GaN Gate HEMTs under Negative Gate Stress by Fast Sweeping Characterization.

In this work, temperature-dependent transient threshold voltage (VT) instability behaviors in p-GaN/AlGaN/GaN HEMTs, with both Schottky gate (SG) and Ohmic gate (OG), were investigated systematically, under negative gate bias stress, by a fast voltage sweeping method. For SG devices, a concave-shaped VT evolution gradually occurs with the increase in temperature, and the concave peak appears faster with increasing reverse bias stress, followed by a corresponding convex-shaped VT recovery process. In contrast, the concave-shaped VT evolution for OG devices that occurred at room temperature gradually disappears in the opposite shifting direction with the increasing temperature, but the corresponding convex-shaped VT recovery process is not observed, substituted, instead, with a quick and monotonic recovery process to the initial state. To explain these interesting and different phenomena, we proposed physical mechanisms of time and temperature-dependent hole trapping, releasing, and transport, in terms of the discrepancies in barrier height and space charge region, at the metal/p-GaN junction between SG and OG HEMTs.

Numerical simulation of stress regime transformation during unconventional fossil energy development in Sichuan Basin: from strike-slip stress regime to reverse stress regime via hydraulic fracturing

Numerical simulation of stress regime transformation during unconventional fossil energy development in Sichuan Basin: from strike-slip stress regime to reverse stress regime via hydraulic fracturing

Experimental Investigation of Steel Connections

Experimental results and comparative study has proven to be core for the foundation and development of structural and earthquake engineering. In the recent past, various research has been carried out from full scale to scaled model prototypes on the evaluation of weld and bolt steel connections. Reversal stresses that occur within milliseconds make beam-column connections most vulnerable to lateral loads when exposed. It would result in failure and catastrophe if not designed and erected correctly. The capability to transfer forces through the joint is the index to keep the structure safe and sound to avoid progressive collapse in the case of buildings. It is clear now that failure of beam-column joint will ultimately lead to structural damage, so the importance is self-evident.

Study of residual stress in reactively sputtered epitaxial Si-doped GaN films

Si-doped GaN films were grown epitaxially on c-sapphire by rf magnetron reactive co-sputtering of GaAs and Si at various partial pressures of N2 in Ar–N2 growth atmosphere. Energy dispersive x-ray spectroscopy revealed ∼2 at.% Si in all the films, but the N/Ga ratio decreased substantially as N2 percentage was reduced from 100% to 10%. The lattice parameters (a and c) were obtained independently to determine the in-plane and out-of-plane components of strain in films, which were analyzed to deduce the hydrostatic and biaxial strain contributions. High resolution x-ray diffraction revealed the dominant presence of edge dislocations (∼1012 cm−2) in the films grown at 30%–100% N2, which decreases and becomes comparable to the density of screw dislocations (∼1011 cm−2) at lower N2 percentages. The films grown at 75%–100% N2 displayed compressive biaxial stress along with large hydrostatic strain and micro-strain due to the incorporation of nitrogen at interstitial locations and grain boundaries. Both hydrostatic strain and micro-strain decrease in the films grown below 75% N2, in which, a reversal of biaxial stress to tensile is seen due to the prevalence of in-plane tensile stress generated during coalescence. The decrease of tensile stress in films grown below 30% N2, accompanied by increase in micro-strain and hydrostatic strain are ascribed to Ar incorporation and voided morphology. The presence of Si does not have a significant influence on residual stress of films and appears to be masked by the dominant growth-related intrinsic effects.

4D printed self-helix structure based on internal stress reversibility

Organisms with self-helix structures are widely found in nature. Four-dimensional (4D) printing have been realized by designing structures and programming deformation of smart materials. This paper presents an innovative method of controlled self-helix structures by designing and fabricating of a bilayer structure with smart material polylactic acid. The process of applying internal stress in 4D printing was analyzed. The repeatability of helical deformation of bilayer structure was investigated. The effect of printing angle on helical deformation behavior was simulated by finite element method. And the simulation results are in good agreement with the experimental results, which also verifies the reliability of the established finite element model. Then, the stress distribution in the process of screw deformation was simulated by using the finite element model. An intelligent soft gripper was used as a case study to illustrate this methodology. This method is a guide for the design and manufacture of intelligent structures and can be applied to the design of complex biological structures.