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At least 1,603 records · Page 89

Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy

Background: Local control remains a challenge in pediatric parameningeal rhabdomyosarcoma (PM-RMS), and survival after local failure (LF) is poor. Identifying patients with a high risk of LF is of great interest to clinicians. In this study, we examined whether tumor response to induction chemotherapy (CT) could predict LF in embryonal PM-RMS. Methods: We identified 24 patients with embryonal PM-RMS, age 2 to 18 years, with complete magnetic resonance imaging and gross residual disease after surgical resection. All patients received proton radiation therapy (RT), median dose 50.4 Gy{sub RBE} (50.4-55.8 Gy{sub RBE}). Tumor size was measured before initial CT and before RT. Results: With a median follow-up time of 4.1 years for survivors, LF was seen in 9 patients (37.5%). The median time from the initiation of CT to the start of RT was 4.8 weeks. Patients with LF had a similar initial (pre-CT) tumor volume compared with patients with local controlled (LC) (54 cm{sup 3} vs 43 cm{sup 3}, P=.9) but a greater median volume before RT (pre-RT) (40 cm{sup 3} vs 7 cm{sup 3}, P=.009) and a smaller median relative percent volume reduction (RPVR) in tumor size (0.4% vs 78%, P<.001). Older age (P=.05), larger pre-RT tumor volume (P=.03), and smaller RPVR (P=.003) were significantly associated with actuarial LF on univariate Cox analysis. Conclusions: Poor response to induction CT appears to be associated with an increased risk of LF in pediatric embryonal PM-RMS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas After Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A dislocation-based crystal plasticity framework for dynamic ductile failure of single crystals

We developed a framework for dislocation-based viscoplasticity and dynamic ductile failure to model high strain rate deformation and damage in single crystals. The rate-dependence of the crystal plasticity formulation is based on the physics of relativistic dislocation kinetics suited for extremely high strain rates. The damage evolution is based on the dynamics of void growth, which are governed by both micro-inertia as well as dislocation kinetics and dislocation substructure evolution. Furthermore, an averaging scheme is proposed in order to approximate the evolution of the dislocation substructure in both the macroscale as well as its spatial distribution at the microscale. In addition, a concept of a single equivalent dislocation density that effectively captures the collective influence of dislocation density on all active slip systems is proposed here. Together, these concepts and approximations enable the use of semi-analytic solutions for void growth dynamics developed in [J. Wilkerson and K. Ramesh. A dynamic void growth model governed by dislocation kinetics. J. Mech. Phys. Solids, 70:262–280, 2014.], which greatly reduce the computational overhead that would otherwise be required. The resulting homogenized framework has been implemented into a commercially available finite element package, and a validation study against a suite of direct numerical simulations was carried out.

36 MATERIALS SCIENCE↗

Internal short circuit and failure mechanisms of lithium-ion pouch cells under mechanical indentation abuse conditions: An experimental study

Electromechanical structural integrity and thermal stability dictate the safety performance of lithium-ion batteries. Progressive deformation and failure across microscopic and macroscopic lengths scales that are responsible for internal short circuit (ISC) in lithium-ion cells under mechanical abuse conditions remains elusive. In this study, a series of indentation tests were conducted on lithium-ion cells with different capacities up to the occurrence of ISC. The external response and internal configuration of these cells were investigated. It is discovered that cells with different capacities and state of charges exhibited different behaviors. Maximum temperature, which is often regarded as the most important parameter related to thermal runaway (TR), varied considerably due to the complicated contact configurations. X-ray computed tomography (XCT) showed that ISC was a collective result of shear band or other strain-localization modes in the electrode assembly, shear offsets in the granular coatings of electrodes, and the accompanying ductile fracture in the metal foils. We believe that the irregular strain-localization modes (kinks, cusps, and buckles), radical mismatches in mechanical properties of different layers, and geometric features of the indenter eventually lead to the tearing/puncture of cell separator at various locations. Furthermore, the results could provide useful guidance for the micromechanical modeling of lithium-ion cells.

25 ENERGY STORAGE↗

Exploring pressure-dependent inelastic deformation and failure in bonded granular composites: An energetic materials perspective

In polymer-filled granular composites, damage may develop in mechanical loading prior to material failure. Damage mechanisms such as microcracking or plastic deformation in the binder phase can substantially alter the material’s mesostructure. For energetic materials, such as solid propellants and plastic bonded explosives, these mesostructural changes can have far reaching effects including degraded mechanical properties, potentially increased sensitivity to further insults, and changes in expected performance. Unfortunately, predicting damage is nontrivial due to the complex nature of these composites and the entangled interactions between inelastic mechanisms. In this work, we assess the current literature of experimental knowledge, focusing on the pressure-dependent shear response, and propose a simple simulation framework of bonded particles to study four limiting-case material formulations at both meso- and macro-scales. Further, to construct the four cases, we systematically vary the relative interfacial strength between the polymer binder and granular filler phase and also vary the polymer’s glass transition temperature relative to operating temperature which determines how much the binder can plastically deform. These simulations identify key trends in global mechanical response, such as the emergence of strain hardening or softening regimes with increasing pressure which qualitatively resemble experimental results. By quantifying the activation of different inelastic mechanisms, such as bonds breaking and plastically straining, we identify when each mechanism becomes relevant and provide insight into potential origins for changes in mechanical responses. The locations of broken bonds are also used to define larger, mesoscopic cracks to test various metrics of damage. We primarily focus on triaxial compression, but also test the opposite case of triaxial extension to highlight the impact of Lode angle on mechanical behavior.

36 MATERIALS SCIENCE↗

The influence of steel microstructure and inclusion characteristics on the formation of premature bearing failures with microstructural alterations

The formation of premature cracking damage associated with local microstructural alterations, commonly referred to as "white etching cracks" (WECs) has led to unpredictable bearing failures in numerous industrial applications. WECs are known to occur in the field independent of material characteristics such as heat treatment, predominant microstructure and surface coatings, as well as lubricant characteristics such as additive packages and viscosity. However, WECs have proven difficult to recreate at a benchtop scale; to date, no benchtop test has been reported to recreate WECs using commercially available field lubricants. The present work intends to identify key differences between the microstructure of field bearings and the microstructure of benchtop samples, focusing on the characteristics of the inclusions contained in both steels. Synchrotron scale X-ray tomography revealed that AISI 52100 steel used in industrial scale field bearings contained a drastically different inclusion microstructure then the AISI 52100 steels used in standard benchtop test specimens. Additionally, the authors were able to form WECs in test samples manufactured out of the steel of a field bearing using fully formulated field lubricants; a finding which has not yet been reported in open literature.

36 MATERIALS SCIENCE↗

Improvements of pre-emptive identification of particle accelerator failures using binary classifiers and dimensionality reduction

In this paper we look at the properties of the Spallation Neutron Source (SNS) Differential Beam Current Monitor (DCM) data and various methods of data transformation to improve pre-emptive detection of machine trips. In this study, the foundation of the approach is the analysis of new underlying data and understanding various properties with the goal of faster classification, higher precision and higher recall with the aim to reduce false positives as low as required. The result of the research presented in this paper are a binary classifier capable of predicting accelerator failures with millisecond classification time, 96% precision, 58% true positive and 0% false positive rate and optimization techniques enabling real-time implementations.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Quantitative evaluation of common cause failures in high safety-significant safety-related digital instrumentation and control systems in nuclear power plants

Digital instrumentation and control (DI&C) systems at nuclear power plants (NPPs) have many advantages over analog systems. They are proven to be more reliable, cheaper, and easier to maintain given obsolescence of analog components. However, they also pose new engineering and technical challenges, such as possibility of common cause failures (CCFs) unique to digital systems. Here this paper proposes a Platform for Risk Assessment of DI&C (PRADIC) that is developed by Idaho National Laboratory (INL). A methodology for evaluation of software CCFs in high safety-significant safety-related DI&C systems of NPPs was developed as part of the framework. The framework integrates three stages of a typical risk assessment—qualitative hazard analysis and quantitative reliability and consequence analyses. The quantified risks compared with respective acceptance criteria provide valuable insights for system architecture alternatives allowing design optimization in terms of risk reduction and cost savings. A comprehensive case study performed to demonstrate the framework's capabilities is documented here in this paper. Results show that the PRADIC is a powerful tool capable to identify potential digital-based CCFs, estimate their probabilities, and evaluate their impacts on system and plant safety.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Distributed optimization and control for autonomous distributed energy resource power dispatch and frequency regulation considering communication failures

Distributed energy resources (DERs) can significantly enhance grid flexibility by supplying power and secondary frequency regulation (SFR) services. Yet, their large number and dispersed nature limit the effectiveness of traditional centralized power dispatch and frequency control schemes, and expose the system to single-point communication failures. This paper presents a unified distributed optimization and control framework for DER power dispatch and SFR provision. A transmission-loss-aware distributed direct current optimal power flow is first formulated to optimize DER power dispatch and reserve scheduling. On top of this, a fully distributed control scheme for DER autonomous SFR provision is developed to allocate automatic generation control signals cost-effectively while ensuring robustness to communication link disruptions. The framework is validated on IEEE 14-bus and 39-bus transmission systems with large-scale distribution feeders using transmission-distribution dynamic co-simulation, demonstrating reliable and autonomous DER power dispatch and SFR provision under diverse operating conditions and communication contingencies.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Differential cardiotoxicity in response to chronic doxorubicin treatment in male spontaneous hypertension-heart failure (SHHF), spontaneously hypertensive (SHR), and Wistar Kyoto (WKY) rats

Life threatening complications from chemotherapy occur frequently in cancer survivors, however little is known about genetic risk factors. We treated male normotensive rats (WKY) and strains with hypertension (SHR) and hypertension with cardiomyopathy (SHHF) with 8 weekly doses of doxorubicin (DOX) followed by 12 weeks of observation to test the hypothesis that genetic cardiovascular disease would worsen delayed cardiotoxicity. Compared with WKY, SHR demonstrated weight loss, decreased systolic blood pressure, increased kidney weights, greater cardiac and renal histopathologic lesions and greater mortality. SHHF showed growth restriction, increased kidney weights and renal histopathology but no effect on systolic blood pressure or mortality. SHHF had less severe cardiac lesions than SHR. We evaluated cardiac soluble epoxide hydrolase (sEH) content and arachidonic acid metabolites after acute DOX exposure as potential mediators of genetic risk. Before DOX, SHHF and SHR had significantly greater cardiac sEH and decreased epoxyeicosatrienoic acid (EET) (4 of 4 isomers in SHHF and 2 of 4 isomers in SHR) than WKY. After DOX, sEH was unchanged in all strains, but SHHF and SHR rats increased EETs to a level similar to WKY. Leukotriene D4 increased after treatment in SHR. Genetic predisposition to heart failure superimposed on genetic hypertension failed to generate greater toxicity compared with hypertension alone. The relative resistance of DOX-treated SHHF males to the cardiotoxic effects of DOX in the delayed phase despite progression of genetic disease was unexpected and a key finding. Strain differences in arachidonic acid metabolism may contribute to variation in response to DOX toxicity. - Highlights: • Late doxorubicin toxicity evaluated in normal, hypertensive, and cardiomyopathic rats. • Hypertension enhances the delayed toxicity of doxorubicin. • Genetic predisposition to cardiomyopathy did not further enhance toxicity. • Epoxyeicosatrienoic acids increased in response to doxorubicin in SHR and SHHF. • Altered leukotriene metabolism may contribute greater toxicity in SHR vs. SHHF rats.

60 APPLIED LIFE SCIENCES↗

Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in D-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M

Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100 mg/kg) 1 h before lipopolysaccharide (LPS)/D-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production. - Highlights: • Glycyrrhetinic acid protected from LPS/D-GalN-induced liver injury in mice. • Glycyrrhetinic acid inhibited LPS-induced TNF-α production in vivo and in vitro. • Glycyrrhetinic acid alleviated LPS-activated TLR4 signal pathway in vivo and in vitro. • Glycyrrhetinic acid upregulated the expression of IRAK-M in vivo and in vitro. • IRAK-M mediated the protective effect of Glycyrrhetinic acid on LPS-induced inflammation.

60 APPLIED LIFE SCIENCES↗

Modeling the pressure increase in liquid helium cryostats after failure of the insulating vacuum

The pressure relief system of liquid helium cryostats requires a careful design, due to helium's low enthalpy of vaporization and due to the low operating temperature. Hazard analyses often involve the failure of the insulating vacuum in the worst-case scenario. The venting of the insulating vacuum and the implications for the pressure increase in the helium vessel, however, have not yet been fully analyzed. Therefore, the dimensioning of safety devices often requires experience and reference to very few experimental data. In order to provide a better foundation for the design of cryogenic pressure relief systems, this paper presents an analytic approach for the strongly dynamic process induced by the loss of insulating vacuum. The model is based on theoretical considerations and on differential equation modeling. It contains only few simplifying assumptions, which will be further investigated in future experiments. The numerical solutions of example calculations are presented with regard to the heat flux into the helium vessel, the helium pressure increase and the helium flow rate through the pressure relief device. Implications concerning two-phase flow and the influence of kinetic energy are discussed.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Risk assessment of turbine rotor failure using probabilistic ultrasonic non-destructive evaluations

The study presents a method and application of risk assessment methodology for turbine rotor fatigue failure using probabilistic ultrasonic nondestructive evaluations. A rigorous probabilistic modeling for ultrasonic flaw sizing is developed by incorporating the model-assisted probability of detection, and the probability density function (PDF) of the actual flaw size is derived. Two general scenarios, namely the ultrasonic inspection with an identified flaw indication and the ultrasonic inspection without flaw indication, are considered in the derivation. To perform estimations for fatigue reliability and remaining useful life, uncertainties from ultrasonic flaw sizing and fatigue model parameters are systematically included and quantified. The model parameter PDF is estimated using Bayesian parameter estimation and actual fatigue testing data. The overall method is demonstrated using a realistic application of steam turbine rotor, and the risk analysis under given safety criteria is provided to support maintenance planning.

42 ENGINEERING↗

Failure of semiclassical models to describe resistivity of nanometric, polycrystalline tungsten films

The impact of electron scattering at surfaces and grain boundaries in nanometric polycrystalline tungsten (W) films was studied. A series of polycrystalline W films ranging in thickness from 10 to 310 nm and lateral grain size from 74 to 133 nm were prepared on thermally oxidized Si. The Fuchs-Sondheimer surface-scattering model and Mayadas-Shatzkes grain-boundary scattering model were employed for quantitative analyses. Predictions from the theoretical models were found to deviate systematically from the experimental data. Possible reasons for the failure of the theoretical models to describe the experimental data are explored. Finally, a discussion of the crucial features lacking from existing models is presented, along with possible avenues for improving the models to result in better agreement with experimental data.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Simulation of the dissipated and stored energy under deformation and failure of metallic materials

This work is devoted to the development of the statistical model of the structural defect evolution which was developed at the Institute of continuous media mechanics UB RAS. This model takes into account stochastic properties of the defect evolution process, nonlinear interaction of defects, and connection between microplasticity and damage accumulation. The obtained constitutive equations allow us to propose a model of the energy storage and dissipation in the process of plastic deformation and failure of metallic materials. The obtained relations were adapted for standard finite-element package. Applicability of this model was demonstrated in three-dimensional simulation of the strain localization and crack propagation in metals.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Buckling failure of square ice-nanotube arrays constrained in graphene nanocapillaries

Graphene confinement provides a new physical and mechanical environment with ultrahigh van der Waals pressure, resulting in new quasi-two-dimensional phases of few-layer ice. Polymorphic transition can occur in bilayer constrained water/ice system. Here, we perform a comprehensive study of the phase transition of AA-stacked bilayer water constrained within a graphene nanocapillary. The compression-limit and superheating-limit (phase) diagrams are obtained, based on the extensive molecular-dynamics simulations at numerous thermodynamic states. Liquid-to-solid, solid-to-solid, and solid-to-liquid-to-solid phase transitions are observed in the compression and superheating of bilayer water. Interestingly, there is a temperature threshold (∼275 K) in the compression-limit diagram, which indicates that the first-order and continuous-like phase transitions of bilayer water depend on the temperature. Two obviously different physical processes, compression and superheating, display similar structural evolution; that is, square ice-nanotube arrays (BL-VHDI) will bend first and then transform into bilayer triangular AA stacking ice (BL-AAI). The superheating limit of BL-VHDI exhibits local maxima, while that of BL-AAI increases monotonically. More importantly, from a mechanics point of view, we propose a novel mechanism of the transformation from BL-VHDI to BL-AAI, both for the compression and superheating limits. This structural transformation can be regarded as the “buckling failure” of the square-ice-nanotube columns, which is dominated by the lateral pressure.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗