Time-dependent Component Research Articles

Geostrophic adjustment on the f-plane: Symmetric versus anti-symmetric initial height distributions

We study the fundamental process of geostrophic adjustment in infinitely long zonal and meridional channels of widths Ly and Lx, respectively, by deriving analytic solutions and simulating the linearized rotating shallow water equations (LRSWE). All LRSWE's variables are divided into time-independent (geostrophic) and time-dependent components. The latter includes Kelvin waves, Poincaré waves, and inertial oscillations. Explicit expressions are derived for both components, which are confirmed numerically. Anti-symmetric and symmetric initial height distributions, η0(x), are considered, both of which introduce a length scale, D, into the problem. We show that for an anti-symmetric η0(x), (i) the rate of approach to geostrophy is D-independent; (ii) the decay rate of inertial oscillations is ∝t−1/2; and (iii) for DLy≫1, the energy of the final state in any finite sub-domain of the channel exceeds that of the initial state, while for DLy≪1 the energy in the final state is smaller than in the initial state. In contrast, for a symmetric η0(x): (i) the rate of approach to geostrophy increases with D; (ii) the decay rate of inertial oscillations is ∝t−3/2, and (iii) the energy of the final state is always smaller than that of the initial state. In meridional channels, the effect of boundaries is to (i) block the waves, propagation to infinity; (ii) alter the spatial structure of the geostrophic flow; and (iii) discretize the frequency spectrum, thus eliminating the inertial oscillations. The ratio of wave energy to initial energy decreases with Lx for anti-symmetric η0(x) and increases with Lx for symmetric η0(x).

Abstract 1366: Integrated population modeling of loncastuximab tesirine (Lonca) exposure in B-cell non-Hodgkin lymphoma (B-NHL)

Abstract Lonca is an antibody (Ab) drug conjugate comprising a humanized monoclonal Ab directed against B-cell antigen CD19, conjugated with a potent pyrrolobenzodiazepine (PBD) dimer toxin. In a Phase 1 (NCT02669017) study in relapsed or refractory (R/R) B-NHL, a recommended Phase 2 dosing regimen for Lonca of 150 µg/kg once every 3 weeks (Q3W) for two doses, followed by 75 µg/kg Q3W was identified then evaluated in a Phase 2 (NCT03589469) study in R/R diffuse large B-cell lymphoma (DLBCL). A population pharmacokinetic (PPK) model was developed to characterize the pharmacokinetics (PK) of the Lonca dosing regimen and evaluate exposure covariates. The integrated PPK model was used to describe drug concentrations for Lonca PBD-conjugated Ab (5,301 samples), total Ab (5,241 samples), and unconjugated warhead SG3199 (239 samples) in serum from 328 patients. Samples were taken pre-dose, at end of infusion and at pre-determined timepoints post-infusion throughout the trials. Analysis was performed using non-linear mixed-effects modeling (NONMEM, v7.4 [ICON Solutions]). Subgroup analyses were conducted on model-predicted exposure metrics derived from simulation of Lonca PK profiles based on empirical Bayesian estimates of individual PK parameters. Concentration-time data of Lonca PBD-conjugated Ab and total Ab were best characterized by a two-compartment model with parallel linear clearance (0.218 L/day), and a time-dependent clearance component which approached zero by ~15 weeks. The estimated volume of distribution of central compartment was 3.86 L and the estimated typical half-life at steady state of Lonca is ~3 weeks. The effect of body weight, age, sex, race, renal impairment, drug formulation, anti-drug Ab, ECOG, and concomitant P-gp inhibitors did not show clinically important influence on exposure (< ±30% change relative to reference). Based on model-predicted Cycle 1 average concentration (Cavg) patients with low albumin (<35 g/L, n=49) had 52% lower Cavg than patients with normal albumin levels (≥35 g/L, n=279). Patients with non-DLBCL (n=44) had 61% lower Cavg than patients with DLBCL (n=284). Trends of lower exposures with baseline mild/moderate hepatic impairment and ECOG status >1 were noted but did not appear to be of clinical relevance. In conclusion, Lonca exposure was well described by a two-compartment model with linear and time-dependent clearance; the latter is thought to reflect reduction of tumor cells. Lonca exposure was lower in non-DLBCL patients, and lower in patients with hypoalbuminemia secondary to enhanced protein clearance in patients with critical illness. Overall, modeling demonstrates rapid attainment of steady-state exposure for Lonca given 150 µg/kg Q3W for two doses, and a sustaining profile for Lonca given 75 µg/kg Q3W thereafter for patients with DLBCL. Citation Format: Melhem Solh, Juan Pablo Alderuccio, Anastasios Stathis, David Ungar, Sam Liao, Lisa Khouri, Xiaoyan Zhang, Joseph Boni. Integrated population modeling of loncastuximab tesirine (Lonca) exposure in B-cell non-Hodgkin lymphoma (B-NHL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1366.

Human adrenal glomerulosa cells express K2P and GIRK potassium channels that are inhibited by ANG II and ACTH.

In whole cell patch clamp recordings, it was discovered that normal human adrenal zona glomerulosa (AZG) cells express members of the three major families of K+ channels. Among these are a two-pore (K2P) leak-type and a G protein-coupled, inwardly rectifying (GIRK) channel, both inhibited by peptide hormones that stimulate aldosterone secretion. The K2P current displayed properties identifying it as TREK-1 (KCNK2). This outwardly rectifying current was activated by arachidonic acid and inhibited by angiotensin II (ANG II), adrenocorticotrophic hormone (ACTH), and forskolin. The activation and inhibition of TREK-1 was coupled to AZG cell hyperpolarization and depolarization, respectively. A second K2P channel, TASK-1 (KCNK3), was expressed at a lower density in AZG cells. Human AZG cells also express inwardly rectifying K+ current(s) (KIR) that include quasi-instantaneous and time-dependent components. This is the first report demonstrating the presence of KIR in whole cell recordings from AZG cells of any species. The time-dependent current was selectively inhibited by ANG II, and ACTH, identifying it as a G protein-coupled (GIRK) channel, most likely KIR3.4 (KCNJ5). The quasi-instantaneous KIR current was not inhibited by ANG II or ACTH and may be a separate non-GIRK current. Finally, AZG cells express a voltage-gated, rapidly inactivating K+ current whose properties identified as KV1.4 (KCNA4), a conclusion confirmed by Northern blot. These findings demonstrate that human AZG cells express K2P and GIRK channels whose inhibition by ANG II and ACTH is likely coupled to depolarization-dependent secretion. They further demonstrate that human AZG K+ channels differ fundamentally from the widely adopted rodent models for human aldosterone secretion.

On-the-fly reduced order modeling of passive and reactive species via time-dependent manifolds

One of the principal barriers in developing accurate and tractable predictive models in turbulent flows with a large number of species is to track every species by solving a separate transport equation, which can be computationally impracticable. In this paper, we present an on-the-fly reduced order modeling of reactive as well as passive transport equations to reduce the computational cost. The presented approach seeks a low-rank decomposition of the species to three time-dependent components: (i) a set of orthonormal spatial modes, (ii) a low-rank factorization of the instantaneous species correlation matrix, and (iii) a set of orthonormal species modes, which represents a low-dimensional time-dependent manifold. Our approach bypasses the need to solve the full-dimensional species to generate high-fidelity data — as it is commonly performed in data-driven dimension reduction techniques such as the principle component analysis. Instead, the low-rank components are directly extracted from the species transport equation. The evolution equations for the three components are obtained from optimality conditions of a variational principle. The time-dependence of the three components enables an on-the-fly adaptation of the low-rank decomposition to transient changes in the species. Several demonstration cases of reduced order modeling of passive and reactive transport equations are presented.

Determination of the geopotential value on the permanent GNSS stations in Vietnam based on the Geodetic Boundary Value Problem approach

SUMMARY In the realisation of the International Height Reference System, the determination of the geopotential value and its variations in time plays an important role. In this study, the geodetic boundary value problem approach is applied for direct determination of the gravity potential value using a GOCE global gravity field model enhanced with terrestrial gravity data. This determination is carried out on the Global Navigation Satellite System-Continuously Operating Reference Stations (GNSS-CORS) stations towards the realisation of the International Height Reference System in Vietnam. First, the effects of the GOCE global gravity field model omission error, the indirect bias term on the disturbing potential and the systematic cumulative errors in levelling data are estimated. These errors affect the estimated geopotential value. The results calculated on the GNSS/levelling points show that the effect of the GOCE DIR-R5 (up to degree/order 260) omission error on the offset potential value is quite significant. This effect was eliminated using high-resolution terrestrial gravity data using the remove-compute-restore technique. The indirect bias term on the disturbing potential can be safely neglected by using a GOCE global gravity field model for degrees higher than 60 for this study region. The systematic cumulative errors in levelling data can be modelled and removed using a third-order polynomial model. Then, the mean zero-height gravity potential of the Vietnam local vertical datum is estimated equal to ${\rm{W}}_0^{{\rm{LVD}}}$ = 62 636 846.69 m2 s–2 with standard deviation of 0.70 m2 s–2 based on the proposed approach. Finally, the geodetic boundary value problem approach was used to determine the geopotential on the surface of three GNSS-CORS stations in Vietnam. Based on time-series of the vertical component derived from the GNSS observations as well as InSAR data, temporal variations in geopotential are also estimated on these permanent GNSS stations. The purpose is to monitor deformation of the vertical datum. The results indicate that the geopotential value needs to be monitored and determined with the time-dependent component on the three Vietnamese permanent GNSS stations for a vertical datum. These stations may contribute to increase the density of reference points in the International Terrestrial Reference Frame, which is being researched and implemented by the International Association of Geodesy.

Nonlinear dynamics of the rotating beam with time-varying speed under aerodynamic loads

In this research, the bifurcation analysis is inspected for a rotatory pre-twisted beam which is subjected to the time varying angular velocity and aerodynamic forces. Aerodynamic loads are obtained by the Piston and Whitehead theories. It is assumed that a time-dependent periodic component is superposed on the angular velocity. The extended Hamilton's principle is utilized to derive the dynamic equations of motion in flapwise and chordwise directions. Then a combination of the Galerkin and multiple scales methods is established to obtain the modulation equations describing amplitude and phases of the interacting modes. Eigen value analysis is performed on the linear part of the equations and the possibility of 1:1 internal resonance condition is examined. The evolution of amplitudes is obtained versus the amplitude and frequency of the periodic angular velocity function. Primary and subharmonic resonance conditions are tuned between the angular velocity frequency and natural frequencies of the beam. Numerical simulations indicate that the nonlinear phenomena such as jump, saturation, and double jumping appear in nonlinear vibration of rotating beam with varying speed.

Cox Piecewise Constant Hazard Model with Bayesian Method

Cox PH model is one of the survival models that is widely used for analyzing time-to-event data. Cox PH model consists of two main components, the baseline hazard consisting of time-dependent component; and the exponential function accomodating explanatory variables. The baseline hazard is not estimated in the Cox PH model, thus not accommodating the need for hazard rate estimation. Therefore, in this paper we discuss the estimation of baseline hazard through piecewise constant hazard using Bayesian method. Gamma distribution is assumed for the piecewise constant baseline hazard, and normal distribution is assumed for the regression coefficient. Sampling from the posterior is conducted using Markov chain Monte Carlo through Gibbs sampling. Echocardiogram data containing 106 observations and 6 explanatory variables were used in analysis. The result showed that the baseline hazard functions were estimated and each of parameters in the model is converged as shown by the trace plot and posterior density plot.

Sodium Influx and Potassium Efflux Currents in Sunflower Root Cells Under High Salinity.

Helianthus annuus L. is an important oilseed crop, which exhibits moderate salt tolerance and can be cultivated in areas affected by salinity. Using patch-clamp electrophysiology, we have characterized Na+ influx and K+ efflux conductances in protoplasts of salt-tolerant H. annuus L. hybrid KBSH-53 under high salinity. This work demonstrates that the plasma membrane of sunflower root cells has a classic set of ionic conductances dominated by K+ outwardly rectifying channels (KORs) and non-selective cation channels (NSCCs). KORs in sunflower show extreme Na+ sensitivity at high extracellular [Ca2+] that can potentially have a positive adaptive effect under salt stress (decreasing K+ loss). Na+ influx currents in sunflower roots demonstrate voltage-independent activation, lack time-dependent component, and are sensitive to Gd3+. Sunflower Na+-permeable NSCCs mediate a much weaker Na+ influx currents on the background of physiological levels of Ca2+ as compared to other species. This suggests that sunflower NSCCs have greater Ca2+ sensitivity. The responses of Na+ influx to Ca2+ correlates well with protection of sunflower growth by external Ca2+ in seedlings treated with NaCl. It can be, thus, hypothesized that NaCl tolerance in sunflower seedling roots is programmed at the ion channel level via their sensitivity to Ca2+ and Na+.

A review of the role of underground measurements in the historical development of rock engineering in South Africa

SYNOPSIS This paper describes some important aspects associated with historical underground measurements in South African gold and coal mines. Deformation measurements were used to confirm the use of elastic theory to simulate the rock mass behaviour in the Witwatersrand gold mines in the 1960s. Although a prominent time-dependent component of stope closure was measured as early as the 1930s, it was ignored owing to the benefit of adopting elastic theory. Neglecting the time-dependent response of the rock for many decades resulted in important aspects such as the effect of mining rate, the effect of advance per blast, and the need for enhanced design criteria not being explored. Recent work is only now starting to address this gap in knowledge. In-situ measurements of large coal specimens in the 1960s and 1970s indicated that a linear formula may possibly be a better approximation of coal pillar strengths. This alternative formulation was never adopted, however, as the power law strength formula was already deeply entrenched in the industry at that stage. In spite of these apparent failures to continuously generate and adopt new knowledge, a key lesson learnt is that major advances in rock mechanics will not be possible without careful monitoring of the rock mass behaviour in experimental sites. Areas requiring further research, such as pillar strength formulae for the Bushveld Complex and enhanced design criteria for the gold mines, can only be developed using extensive underground monitoring programmes. Keywords: rock engineering, underground monitoring, elastic theory, time-dependence, pillar strength.

Successive estimations of bilateral bounds and trapping/stability regions of solution to some nonlinear nonautonomous systems

Estimation of the degree of stability and the bounds of solutions to nonautonomous nonlinear systems present major concerns in numerous applied problems. Yet, current techniques frequently yield overconservative conditions which are unable to effectively gage these characteristics in time-varying nonlinear systems. This paper develops a novel methodology providing successive approximations to solutions that are stemmed from the trapping/stability regions of these systems and estimate the errors of such approximations. In turn, this leads to successive approximations of both the bilateral bounds of solutions and the boundaries of trapping/stability regions of the underlying systems. Along these lines we formulate enhanced stability/boundedness criteria and contrast our inferences with inclusive simulations which reveal dependence of the trapping/stability regions upon the structure of time-dependent components and initial time moment.

Research on Time-Dependent Component Importance Measures Considering State Duration and Common Cause Failure

Unlike the current risk monitors, Real-time Online Risk Monitoring and Management Technology is characterized by time-dependent modeling on the state duration of components. Given the real-time plant configuration, it eventually provides the time-dependent risk level and importance measures for operation and maintenance management. This paper focuses on the assessment method of time-dependent importance measures and its risk-informed applications in real-time online risk monitoring and management technology, including Fussell-Vesely (FV), risk achievement worth (RAW), and risk reduction worth (RRW). In this study, the values of component importance have been investigated with a time-dependent risk quantification model, as well as the common cause failure treatment model. Here three options of common cause failure treatment have been developed, assuming that the unavailability of a component could be due to an independent factor (Option 1), a common cause factor (Option 2), or an unconfirmed cause (Option 3). In the special case of “what if a component is out-of-service” of the RAW numerator, a hybrid method for the RAW evaluation is presented resulting in a balanced and reasonable RAW value. A simple case study was demonstrated. The results showed that the absolute values and ranking order of time-dependent importance not only reflected the effect of the cumulative state duration of component on risk, but also comprehensively accounted for all possible situations of component unavailability. Moreover, time-dependent importance measures improved and provided novel insights for online configuration management, 1) ranking SSCs/events/human actions for controlling increased risk and optimizing near–term plans; and 2) exempting or limiting temporary configurations during online operation.

Identification of a space-dependent source term in a nonlocal problem for the general time-fractional diffusion equation

The diffusion equation with a general convolutional derivative in time is considered on a bounded domain, as one of the boundary conditions is nonlocal. We are concerned with the inverse source problem of recovery of a space-dependent source term from given final time data. To find the source term and the solution, we resort to generalized eigenfunction expansion, using a bi-orthogonal pair of bases. Estimates for the time-dependent components in the spectral expansions are established and applied to prove uniqueness and existence in the classical sense. Analytical and numerical examples are provided.

Experimental exploration of the vector nature of the dynamic order parameter near dynamic magnetic phase transitions

We have devised an experimental study to explore the vector nature of the dynamic order parameter $Q$ and the corresponding dynamic fluctuation ${\mathbit{\ensuremath{\sigma}}}^{Q}$ and susceptibility ${\mathbit{\ensuremath{\chi}}}^{Q}$ tensors in the vicinity of the dynamic phase transition (DPT). For this purpose, we have fabricated epitaxial Co and CoRu thin films with ($10\underline{1}0$) surface orientation and associated in-plane uniaxial anisotropy to mimic the behavior of an anisotropic Heisenberg model in the absence of magnetostatic interactions. Specifically, we measured the time-dependent magnetization component parallel to the externally applied magnetic field for different orientations of the magnetic easy axis (EA) while exploring the dynamic phase space defined by the applied oscillatory field amplitude ${H}_{0}$ and an additionally applied time-independent bias field ${H}_{b}$. The magnetization dynamics was hereby observed by utilizing an ultrasensitive transverse magneto-optical Kerr effect setup that allowed for real-time observations of the magnetic state evolution. Our experimental results demonstrate that while the position of the critical point changes upon rotating the EA away from the field axis, all qualitative aspects of the dynamic phase diagram close to the critical point are unchanged and the DPT can be universally observed. Also, metamagnetic anomalies occur for all measurement conditions. All our results are in agreement with a domain nucleation initiated magnetization reversal process and indicate that the overall dynamic state is dominated by the magnetization component parallel to the EA, so that a change in orientation in between the field axis and EA leads to a rather trivial rotation of the $Q$ vector, which simply follows the EA.

Athermal strength of pure aluminum is significantly decreased by severe plastic deformation and it is markedly augmented by subsequent annealing

Over the last two decades, it has been considered that fine crystal grains produced by severe plastic deformation (SPD) lead to an extraordinarily high metal strength. The present study reveals that this understanding is basically incorrect. In our uniaxial tensile tests on industrial pure aluminum at an ultralow strain rate of sim 10^{ - 7} /{text{s}}, we observed that SPD accompanied by grain refining significantly softened the material. The fundamental strength effective for real structures and structural materials should mean an eternal capability to bear stresses caused by external forces, which is independent of time, that is, athermal. We tried to extract quantitatively the athermal (time-independent) strength from the total strength measured in uniaxial tensile tests under the assumption that the total stress can be additively divided into athermal and thermal (time-dependent) components. As a result of systematic experimental investigation, we found that the athermal strength is significantly reduced by SPD and then markedly increased by subsequent low-temperature annealing. In addition, we confirmed that SPD promotes an increase in the time dependence (viscosity) of the material and that subsequent annealing removes most of the viscosity caused by SPD. The material processed by SPD acquires its prominent time-independent strength after low-temperature annealing.

System effects of lowered district heating supply temperatures

Lowering temperature levels of a district heating (DH) system may offer several advantages such as reduced distribution losses, increased efficiency of flue gas condensation equipment and increased electricity generation in combined heat and power plants. In a broader perspective this can result in more efficient use of natural resources as well as reduced climate-impacting emissions. This study examines how decreased DH supply temperatures influence the power-to-heat ratio and thereby electricity production and fuel use in a combined heat and power plant. Carbon dioxide equivalent (CO2-eqv.) emissions and primary energy use were calculated with three different marginal electricity perspectives. A regional DH system situated in mid-Sweden was used as a case study and the energy system cost optimization modelling tool MODEST (Model for Optimization of Dynamic Energy Systems with Time-Dependent Components and Boundary Conditions) was used. The results show that decreasing the DH supply temperature results in increased electricity production as well as increased fuel use within the system. Further, there is a significant difference in CO2-eqv. emissions and primary energy use for the studied marginal electricity perspectives.

Enhanced fault diagnosis method using conditional Gaussian network for dynamic processes

Applying fault detection and diagnosis (FDD) technology to the process industry can help to detect faults in time and minimize their impact. The purpose of this study is to propose an enhanced fault diagnosis method under a Conditional Gaussian Network(CGN) efficient and suitable for dynamic processes fault monitoring. The key paths are as follows: first, a time series model is established for the process data and decomposed into time-dependent components and time-independent components; second, time-dependent components are discarded and time-independent components void of auto-correlation are considered instead of the original data to learn the CGN model. A numerical simulation case is used to illustrate the interest of our proposal. The effectiveness of the proposed method is further verified and compared on the Tennessee Eastman Process (TEP). The obtained results show that our method has high and better accuracies regarding the diagnosis of known and unknown faults in dynamic processes.

Time-dependent Mechanical Response at the Nanoscale

Modern nanofabrication processes on metals, polymers, and ceramics often require deforming these materials at strain rates ranging ~101 – 107 s–1. Therefore, there is a need to develop an appropriate methodology capable of measuring and predicting the effects of these deformation rates on the final mechanical response of the nanomaterial being processed. Here we report an experimental study of the indentation response of three materials with different nature and mechanical properties, but with known time-dependent mechanical responses. These materials allow validation of the findings under a wide variety of conditions. One metal (Pb), and two polymers (PMMA and PS), were indented at the sub-20 nm scale using commercial atomic force microscopy (AFM) probes. Based on our experimental findings, we also propose an analytical model for creeping solids in which their nanoscale mechanical behavior is completely described by two components: an elastic component (characterized by the Hertz contact model) and a time-dependent component (characterized by a power-law model). The proposed experimental protocol is easy to implement, and the analytical model can be extended to a large variety of materials. The ability to characterize the time-dependence of the mechanical response of different materials at the nanoscale will enable a better estimation of the effect of manufacturing processes on the properties and performance of nanomaterials.

Chiral Magnonics: Reprogrammable Nanoscale Spin Wave Networks Based on Chiral Domain Walls.

SummarySpin waves offer promising perspectives as information carriers for future computational architectures beyond conventional complementary metal-oxide-semiconductor (CMOS) technology, owing to their benefits for device minimizations and low-ohmic losses. Although plenty of magnonic devices have been proposed previously, scalable nanoscale networks based on spin waves are still missing. Here, we demonstrate a reprogrammable two-dimensional spin wave network by combining the chiral exchange spin waves and chiral domain walls. The spin-wave network can be extended to two dimensions and offers unprecedented control of exchange spin waves. Each cell in the network can excite, transmit, and detect spin waves independently in the chiral domain wall, and spin-wave logics are also demonstrated. Our results open up perspectives for integrating spin waves into future logic and computing circuits and networks.

Digital twin of the rotor-shaft of a lightweight electric motor during aerobatics loads

PurposeThis paper aims to present airworthiness considerations regarding a shaft of an electric motor. A fatigue lifetime prediction analysis based on one-step load spectrum is performed during high-cycle fatigue. Time-dependent normal and shear stress components are estimated using a high-fidelity digital twin built in Siemens PLM Nx Nastran as a finite element model (FEM). Linear and centrifugal acceleration as well as gyroscopic moment, motor torque, propeller thrust and thermal loads are considered. The equivalent cyclic degree of utilisation and a safety margin against the slip of a press-fitted shaft to rotor hub connection is estimated.Design/methodology/approachA load analysis using FEM is presented. The numerically obtained results are verified on an analytical and a semi-empirical basis.FindingsThe shaft of the electric motor can sustain 74 h of operation if burdened with aerobatic loads. Its load capacity equals 48% for the overall safety factor of 2.25.Practical implicationsThe paper presents a specific, easily identifiable advance in knowledge that can be applicable in safety flight analysis issues.Originality/valueThe work presents a rotor of a novel lightweight electric motor for aircraft applications, which is a successor of the electric motor set recently in Extra 330E. The work delivers a computational estimation of the shaft life.

Deep learning-based detection, classification, and localization of defects in semiconductor processes

Defects in semiconductor processes can limit yield, increase overall production cost, and also lead to time-dependent critical component failures. Current state-of-the-art optical and electron beam (EB) inspection systems rely on rule-based techniques for defect detection and classification, which are usually rigid in their comparative processes. This rigidity limits overall capability and increases relative engineering time to classify nuisance defects. This is further challenged due to shrinkage of pattern dimensions for advanced nodes. We propose a deep learning-based workflow that circumvents these challenges and enables accurate defect detection, classification, and localization in a unified framework. In particular, we train convolutional neural network-based models using high-resolution EB images of wafers patterned with various types of intentional defects and achieve robust defect detection and classification performance. Furthermore, we generate class activation maps to demonstrate defect localization capability of the model “without” explicitly training it with defect location information. To understand the underlying decision-making process of these deep models, we analyze the learned filters in pixel space and Fourier space and interpret the various operations at different layers. We achieve high sensitivity (97%) and specificity (100%) along with rapid and accurate defect localization. We also test performance of the proposed workflow on images from two distinct patterns and find that in order to retain high accuracy a modest level of retraining is necessary.