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At least 181 records · Page 10

Development of a continuous synthesis process for carbamazepine using validated in-line Raman spectroscopy and kinetic modelling for disturbance simulation

Mitigation of failure modes in the continuous synthesis (CS) of a drug substance (DS) has the potential to widen the adoption of continuous manufacturing (CM) technologies by the pharmaceutical industry. Here, this work demonstrates the development of a robust continuous process for the synthesis of carbamazepine (CBZ), an essential medicine as per the World Health Organization (WHO), facilitated by kinetic modelling and monitored by in-line Raman spectroscopy. Accurate kinetic modelling and the use of validated process analytical technology (PAT) models for quantitative measurement were found to play an important role in developing CS of drug substances. Kinetic data for the formation of CBZ from iminostilbene (ISB) were collected by batch reaction sampling and high-performance liquid chromatography (HPLC) analysis. A non-linear solver and iterative method was applied to determine two sets of Arrhenius parameters simultaneously for the reaction system by minimizing the standard error of the model fit. The start-up and dynamic equilibrium stages for the CS of CBZ using a continuous stirred tank reactor (CSTR) were modelled based on the batch kinetic data and employed to optimize conversion and simulate process disturbances. An in-line Raman spectroscopy method was successfully developed, validated, and integrated to determine the concentrations of CBZ and ISB within the operating range for the CS. The CS kinetic model was evaluated experimentally from startup to dynamic equilibrium over 10 residence times with monitoring by HPLC and in-line Raman spectroscopy. The developed kinetic model in tandem with in-line Raman spectroscopy successfully predicted disturbances due to changes in process variables and can serve as a useful tool in the future design of advanced process control strategies for the continuous synthesis of CBZ.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Data-Driven Anomaly Detection Performance for the Ares I-X Ground Diagnostic Prototype

In this paper, we will assess the performance of a data-driven anomaly detection algorithm, the Inductive Monitoring System (IMS), which can be used to detect simulated Thrust Vector Control (TVC) system failures. However, the ability of IMS to detect these failures in a true operational setting may be related to the realistic nature of how they are simulated. As such, we will investigate both a low fidelity and high fidelity approach to simulating such failures, with the latter based upon the underlying physics. Furthermore, the ability of IMS to detect anomalies that were previously unknown and not previously simulated will be studied in earnest, as well as apparent deficiencies or misapplications that result from using the data-driven paradigm. Our conclusions indicate that robust detection performance of simulated failures using IMS is not appreciably affected by the use of a high fidelity simulation. However, we have found that the inclusion of a data-driven algorithm such as IMS into a suite of deployable health management technologies does add significant value.

Martin, Rodney A.↗

Real-time failure control (SAFD)

The Real Time Failure Control program involves development of a failure detection algorithm, referred as System for Failure and Anomaly Detection (SAFD), for the Space Shuttle Main Engine (SSME). This failure detection approach is signal-based and it entails monitoring SSME measurement signals based on predetermined and computed mean values and standard deviations. Twenty four engine measurements are included in the algorithm and provisions are made to add more parameters if needed. Six major sections of research are presented: (1) SAFD algorithm development; (2) SAFD simulations; (3) Digital Transient Model failure simulation; (4) closed-loop simulation; (5) SAFD current limitations; and (6) enhancements planned for.

Panossian, Hagop V.↗

Mesoscale simulations of pressure-shear loading of granular tungsten carbide

Numerical simulations of pressure-shear loading of a granular material are performed using the shock physics code CTH. A simple mesoscale model for the granular material is used that consists of a randomly packed arrangement of solid circular or spherical grains of uniform size separated by vacuum. The grain material is described by a simple shock equation of state, elastic perfectly plastic strength model, and fracture model with baseline parameters for WC taken from previous mesoscale modeling work. Simulations using the baseline material parameters are performed at the same initial conditions of pressure-shear experiments on dry WC powders. Except for some localized flow regions appearing in simulations with an approximate treatment of sliding interfaces among grains, the samples respond elastically during shear, which is in contrast to experimental observations. By extending the simulations to higher shear wave amplitudes, macroscopic shear failure of the simulated samples is observed with the shear strength increasing with increasing stress confinement. The shear strength is also found to be strongly dependent on the grain interface treatment and on the fracture stress of the grains, though the variation in shear strength due to fracture stress decreases with increasing stress confinement. At partial compactions, the transverse velocity histories show strain-hardening behavior followed by formation of a shear interface that extends through the transverse dimensions of the sample. Near full compaction, no strain hardening is observed and, instead, the sample transitions sharply from an elastic response to formation of an internal shear interface. Agreement with experiment is shown to worsen with increasing confinement stress with simulations overpredicting the shear strengths measured in experiment. The source of the disagreement can be ultimately attributed to the Eulerian nature of the simulations, which do not treat contact and fracture realistically.

36 MATERIALS SCIENCE↗

Medium Fidelity Simulation of Oxygen Tank Venting

The item to he cleared is a medium-fidelity software simulation model of a vented cryogenic tank. Such tanks are commonly used to transport cryogenic liquids such as liquid oxygen via truck, and have appeared on liquid-fueled rockets for decades. This simulation model works with the HCC simulation system that was developed by Xerox PARC and NASA Ames Research Center. HCC has been previously cleared for distribution. When used with the HCC software, the model generates simulated readings for the tank pressure and temperature as the simulated cryogenic liquid boils off and is vented. Failures (such as a broken vent valve) can be injected into the simulation to produce readings corresponding to the failure. Release of this simulation will allow researchers to test their software diagnosis systems by attempting to diagnose the simulated failure from the simulated readings. This model does not contain any encryption software nor can it perform any control tasks that might be export controlled.

Sweet, Adam↗

Life Support with Failures and Variable Supply

The life support system for long duration missions will recycle oxygen and water to reduce the material resupply mass from Earth. The impact of life support failures was investigated by dynamic simulation of a lunar outpost habitat life support model. The model was modified to simulate resupply delays, power failures, recycling system failures, and storage failures. Many failures impact the lunar outpost water supply directly or indirectly, depending on the water balance and water storage. Failure effects on the water supply are reduced if Extra Vehicular Activity (EVA) water use is low and the water supply is ample. Additional oxygen can be supplied by scavenging unused propellant or by production from regolith, but the amounts obtained can vary significantly. The requirements for oxygen and water can also vary significantly, especially for EVA. Providing storage buffers can improve efficiency and reliability, and minimize the chance of supply failing to meet demand. Life support failures and supply variations can be survivable if effective solutions are provided by the system design

Jones, Harry↗

Predicting Failure Progression and Failure Loads in Composite Open-Hole Tension Coupons

Failure types and failure loads in carbon-epoxy [45n/90n/-45n/0n]ms laminate coupons with central circular holes subjected to tensile load are simulated using progressive failure analysis (PFA) methodology. The progressive failure methodology is implemented using VUMAT subroutine within the ABAQUS(TradeMark)/Explicit nonlinear finite element code. The degradation model adopted in the present PFA methodology uses an instantaneous complete stress reduction (COSTR) approach to simulate damage at a material point when failure occurs. In-plane modeling parameters such as element size and shape are held constant in the finite element models, irrespective of laminate thickness and hole size, to predict failure loads and failure progression. Comparison to published test data indicates that this methodology accurately simulates brittle, pull-out and delamination failure types. The sensitivity of the failure progression and the failure load to analytical loading rates and solvers precision is demonstrated.

Arunkumar, Satyanarayana↗

Performance and sensitivity analysis of the generalized likelihood ratio method for failure detection

Results of the generalized likelihood ratio (GLR) technique for the detection of failures in aircraft application are presented, and its relationship to the properties of the Kalman-Bucy filter is examined. Under the assumption that the system is perfectly modeled, the detectability and distinguishability of four failure types are investigated by means of analysis and simulations. Detection of failures is found satisfactory, but problems in identifying correctly the mode of a failure may arise. These issues are closely examined as well as the sensitivity of GLR to modeling errors. The advantages and disadvantages of this technique are discussed, and various modifications are suggested to reduce its limitations in performance and computational complexity.

Bueno, R. A.↗

Simulation of hardened cement degradation and estimation of uncertainty in predicted failure times with peridynamics

Modeling the degradation of cement-based infrastructure due to aqueous environmental conditions continues to be a challenge. In order to develop a capability to predict concrete infrastructure failure due to chemical degradation, here we created a chemomechanical model of the effects of long-term water exposure on cement paste. The model couples the mechanical static equilibrium balance with reactive–diffusive transport and incorporates fracture and failure via peridynamics (a meshless simulation method). The model includes fundamental aspects of degradation of ordinary Portland cement (OPC) paste, including the observed softening, reduced toughness, and shrinkage of the cement paste, and increased reactivity and transport with water induced degradation. This version of the model focuses on the first stage of cement paste decalcification, the dissolution of portlandite. Given unknowns in the cement paste degradation process and the cost of uncertainty quantification (UQ), we adopt a minimally complex model in two dimensions (2D) in order to perform sensitivity analysis and UQ. We calibrate the model to existing experimental data using simulations of common tests such as flexure, compression and diffusion. Then we calculate the global sensitivity and uncertainty of predicted failure times based on variation of eleven unique and fundamental material properties. We observed particularly strong sensitivities to the diffusion coefficient, the reaction rate, and the shrinkage with degradation. Also, the predicted time of first fracture is highly correlated with the time to total failure in compression, which implies fracture can indicate impending degradation induced failure; however, the distributions of the two events overlap so the lead time may be minimal. Extension of the model to include the multiple reactions that describe complete degradation, viscous relaxation, post-peak load mechanisms, and to three dimensions to explore the interactions of complex fracture patterns evoked by more realistic geometry is straightforward and ongoing.

36 MATERIALS SCIENCE↗

GENOA-PFA: Progressive Fracture in Composites Simulated Computationally

GENOA-PFA is a commercial version of the Composite Durability Structural Analysis (CODSTRAN) computer program that simulates the progression of damage ultimately leading to fracture in polymer-matrix-composite (PMC) material structures under various loading and environmental conditions. GENOA-PFA offers several capabilities not available in other programs developed for this purpose, making it preferable for use in analyzing the durability and damage tolerance of complex PMC structures in which the fiber reinforcements occur in two- and three-dimensional weaves and braids. GENOA-PFA implements a progressive-fracture methodology based on the idea that a structure fails when flaws that may initially be small (even microscopic) grow and/or coalesce to a critical dimension where the structure no longer has an adequate safety margin to avoid catastrophic global fracture. Damage is considered to progress through five stages: (1) initiation, (2) growth, (3) accumulation (coalescence of propagating flaws), (4) stable propagation (up to the critical dimension), and (5) unstable or very rapid propagation (beyond the critical dimension) to catastrophic failure. The computational simulation of progressive failure involves formal procedures for identifying the five different stages of damage and for relating the amount of damage at each stage to the overall behavior of the deteriorating structure. In GENOA-PFA, mathematical modeling of the composite physical behavior involves an integration of simulations at multiple, hierarchical scales ranging from the macroscopic (lamina, laminate, and structure) to the microscopic (fiber, matrix, and fiber/matrix interface), as shown in the figure. The code includes algorithms to simulate the progression of damage from various source defects, including (1) through-the-thickness cracks and (2) voids with edge, pocket, internal, or mixed-mode delaminations.

Murthy, Pappu L. N.↗

Development of Airport Surface Required Navigation Performance (RNP)

The U.S. and international aviation communities have adopted the Required Navigation Performance (RNP) process for defining aircraft performance when operating the en-route, approach and landing phases of flight. RNP consists primarily of the following key parameters - accuracy, integrity, continuity, and availability. The processes and analytical techniques employed to define en-route, approach and landing RNP have been applied in the development of RNP for the airport surface. To validate the proposed RNP requirements several methods were used. Operational and flight demonstration data were analyzed for conformance with proposed requirements, as were several aircraft flight simulation studies. The pilot failure risk component was analyzed through several hypothetical scenarios. Additional simulator studies are recommended to better quantify crew reactions to failures as well as additional simulator and field testing to validate achieved accuracy performance, This research was performed in support of the NASA Low Visibility Landing and Surface Operations Programs.

Cassell, Rick↗

N(N)-nicotinic blockade as an acute human model of autonomic failure

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Non-NASA Center↗

Demonstrating Distribution System Resiliency through Grid-Edge Microgrids, on a Multi-Site Networked Hardware-in-Loop Platform

With the increasing penetration of Distributed Energy Resources (DERs) at the grid-edge, power systems include more energy storage, remote switches, relays, voltage regulators, and other intelligent electronic devices (IED). Effective control of these grid-edge devices by using Advanced Distribution Management Systems (ADMS) can yield substantial improvements to the resiliency and power quality of distribution systems. In this paper, improvements to the resiliency of a distribution system are demonstrated using a multi-site evaluation environment consisting of a real-time Hardware-in-Loop (HIL) setup in which DERs and other IEDs are modeled; and an ADMS which monitors and is able to control the distribution system assets. The HIL model and the ADMS are located 2400 km away, with communication between the sites enabled by a data manager using Distributed Network Protocol 3 (DNP3), demonstrating the system's capabilities even over long distances. After a simulated transmission system failure in the HIL demonstration setup, DERs and other devices are operated to restore critical loads and node voltage profile (to within the 'nominal +/-5%' band) in the distribution system.

ADMS↗

Operations analysis of gravity assisted rapid transit

Gravity assisted rapid transit (GART) with 6 percent grades before and after each station are compared with conventional systems in terms of energy consumption, run time, line capacity and schedule stability under abnormal circumstances. Parametric analyses of run times and energy consumption include the impact of alternate accelerating and braking levels. The capcity analysis uses a network simulation program to determine the location and severity of all signal delays. Based on results of initial simulations, the block design was revised to eliminate bottlenecks in normal operations. The systems are then compared at headways of 80 to 180 seconds. One month of incidence reports of a modern operating transit system are reviewed to determine the failures to be simulated. The impact of failures resulting in station delays (30 to 360 seconds), speed limit reduction (20 mph and 30 mph to one or more trains), vehicle performance (75 percent acceleration) are compared at scheduled headway of 90 to 180 seconds.

Source record↗

Accelerating high-strain continuum-scale brittle fracture simulations with machine learning

Failure in brittle materials under dynamic loading conditions is a result of the propagation and coalescence of microcracks. Simulating this discrete crack evolution at the continuum level is computationally expensive or, in some cases, intractable, resulting in the need to make broad assumptions or neglect key physics. In this work, we have developed an approach using machine learning that overcomes the current inability to represent meso-scale physics at the macro-scale. Our approach leverages damage and stress data from a computationally expensive high-fidelity model that explicitly resolves microcrack behavior to build an inexpensive machine learning emulator. Once trained, the machine learning emulator is used to predict the evolution of crack length statistics, which then informs a continuum-scale constitutive model. This results in a significant speed-up of the workflow by four orders of magnitude. Both the machine learning emulator and the continuum-scale model are validated against the high-fidelity model and experimental data, respectively, showing excellent agreement. There are two key findings. The first is that we can reduce the dimensionality of the problem, establishing that the machine learning emulator only needs the length of the longest crack and one of the maximum stress components to capture the necessary physics. Another compelling finding is that the emulator can be trained in one experimental setting and transferred successfully to predict behavior in a different setting.

36 MATERIALS SCIENCE↗

Model-Biased, Data-Driven Adaptive Failure Prediction

This final report, which contains a research summary and a viewgraph presentation, addresses clustering and data simulation techniques for failure prediction. The researchers applied their techniques to both helicopter gearbox anomaly detection and segmentation of Earth Observing System (EOS) satellite imagery.

Leen, Todd K.↗

Investigation of Asymmetric Thrust Detection with Demonstration in a Real-Time Simulation Testbed

The purpose of this effort is to develop, demonstrate, and evaluate three asymmetric thrust detection approaches to aid in the reduction of asymmetric thrust-induced aviation accidents. This paper presents the results from that effort and their evaluation in simulation studies, including those from a real-time flight simulation testbed. Asymmetric thrust is recognized as a contributing factor in several Propulsion System Malfunction plus Inappropriate Crew Response (PSM+ICR) aviation accidents. As an improvement over the state-of-the-art, providing annunciation of asymmetric thrust to alert the crew may hold safety benefits. For this, the reliable detection and confirmation of asymmetric thrust conditions is required. For this work, three asymmetric thrust detection methods are presented along with their results obtained through simulation studies. Representative asymmetric thrust conditions are modeled in simulation based on failure scenarios similar to those reported in aviation incident and accident descriptions. These simulated asymmetric thrust scenarios, combined with actual aircraft operational flight data, are then used to conduct a sensitivity study regarding the detection capabilities of the three methods. Additional evaluation results are presented based on pilot-in-the-loop simulation studies conducted in the NASA Glenn Research Center (GRC) flight simulation testbed. Data obtained from this flight simulation facility are used to further evaluate the effectiveness and accuracy of the asymmetric thrust detection approaches. Generally, the asymmetric thrust conditions are correctly detected and confirmed.

aircraft safety↗

Investigation of Asymmetric Thrust Detection with Demonstration in a Real-Time Simulation Testbed

The purpose of this effort is to develop, demonstrate, and evaluate three asymmetric thrust detection approaches to aid in the reduction of asymmetric thrust-induced aviation accidents. This paper presents the results from that effort and their evaluation in simulation studies, including those from a real-time flight simulation testbed. Asymmetric thrust is recognized as a contributing factor in several Propulsion System Malfunction plus Inappropriate Crew Response (PSM+ICR) aviation accidents. As an improvement over the state-of-the-art, providing annunciation of asymmetric thrust to alert the crew may hold safety benefits. For this, the reliable detection and confirmation of asymmetric thrust conditions is required. For this work, three asymmetric thrust detection methods are presented along with their results obtained through simulation studies. Representative asymmetric thrust conditions are modeled in simulation based on failure scenarios similar to those reported in aviation incident and accident descriptions. These simulated asymmetric thrust scenarios, combined with actual aircraft operational flight data, are then used to conduct a sensitivity study regarding the detection capabilities of the three methods. Additional evaluation results are presented based on pilot-in-the-loop simulation studies conducted in the NASA Glenn Research Center (GRC) flight simulation testbed. Data obtained from this flight simulation facility are used to further evaluate the effectiveness and accuracy of the asymmetric thrust detection approaches. Generally, the asymmetric thrust conditions are correctly detected and confirmed.

gas turbine engines↗