Prediction of soft error response of integrated circuits to electrostatic discharge injection via simulation field; Package interaction for electrostatic discharge soft error prediction; Full wave model for simulating noise ken electrostatic discharge generator

In the first section, a concept for analyzing soft error response in ICs to ESD via coupling through flex cable structures is presented. Its novelty lies in accounting for the transient electromagnetic fields radiated by the ESD generator that couples to the flex cable PCB thereby causing disturbance on the IC under test. This is accomplished in three stages; first by developing a full wave model of the DUT which includes modeling the PCB and flex cable geometry and validating it in frequency domain with regard to the transfer impedance. This followed by combining the ESD generator with the DUT model to simulate the voltage at the IC input in time domain. Finally the time domain results from full wave simulation are combined with an equivalent IC response model in SPICE to predict soft error failures due ESD. In the second section, a more detailed modeling of the IC including the lead frame geometry, bond wires and IBIS/ICEM models are incorporated to investigate coupling of fields from three different injection techniques - H field loop probes, TEM cell and ESD generator. For the first time a complete simulation model which includes the ESD generator, passive elements of the DUT structure (PCB) and a detailed model of the IC has been developed to predict interaction of radiated field from the generator to the IC. The third section shows a CST MWS model was generated to simulate the discharge current and the transient field of an ESD generator. Individual components of the Noise Ken ESD generator (ESS-2000) were modeled, validated and combined. The complete full wave model was verified by comparing the simulated discharge current waveforms and induced loop voltages with the measured results --Abstract, page iii

Advanced Full Wave ESD Generator Model for System Level Coupling Simulation

System level ESD tests can only be performed after hardware is available. Simulating the ESD coupling into a circuit allows at least parametric and quantitative studies of the expected ESD behavior. A complete simulation requires us to model the ESD generator, the passive elements of the DUT and the response of the ICs to injected noise. Having the ultimate objective of combining IC soft error response models with the DUT structure and the ESD generator we report on progresses in modeling the ESD generator and its coupling. The model improves the useful frequency range from a few hundred MHz to about 3 GHz

A Circuit Model for ESD Performance Analysis of Printed Circuit Boards

This paper provides a SPICE-compatible circuit model for characterizing electrostatic discharge (ESD) clamping performance of protection devices mounted on printed circuit boards (PCBs). An equivalent circuit model for a commercial ESD generator is introduced and a simulation methodology of an ESD protection device with non-linear resistance characteristic using voltage controlled current source is described. These models combined to create a full circuit model with a PCB model in a SPICE-like circuit simulator. Comparison results between the simulated and measured are presented to verify the accuracy of the proposed circuit model. A trade-off analysis between the ESD clamping performance and signal integrity with the ESD protection device in high-speed applications is also presented as a case study

Development of drugs targeting the human tRNA ligase RtcB in breast cancer

The RNA ligase RtcB has been shown to regulate RNA function by direct exon ligation of spliced XBP1 messenger RNA cleaved by the endoplasmic reticulum (ER) stress sensor IRE1α. Ligation by RtcB leads to the expression of the transcription factor XBP1s that controls ER homeostasis and is surprisingly also utilized for oncogenic transformation, survival, and progress. Through elevated levels of XBP1s, tumor cells acquire a pro-survival advantage and promote tumor aggressiveness by an increase in tumor immune infiltration, angiogenesis, and cell invasive properties. Using RNA interference (RNAi), depleting human RtcB (hRtcB) in MDA-MB-231 triple-negative breast cancer (TNBC) cells significantly reduced basal XBP1s expression both at the mRNA and protein level. As the crystal structure of hRtcB is yet to be resolved, in silico techniques were therefore employed to develop a 3-dimensional predicted model of the hRtcB protein for the first time. Built from the Pyrococcus horikoshii RtcB (bacterial RtcB) crystal structure, PDB ID 4DWQA, the hRtcB homology model is in complex with manganese and covalently bound ligand GMP. The developed model clearly showed that the GTP binding site of the enzyme is a well-defined pocket that can be utilized as a target site for in silico drug discovery. A virtual high throughput screening (VHTS) campaign was thereafter executed to develop drugs that would halt or modulate the hRtcB-mediated XBP1s formation in TNBC. ~Eighteen million small molecule compounds were screened against the ligand binding site/active site of the hRtcB homology model. From the 3129 hits generated, the top 200 highest scoring binders were subjected to the structural hit fingerprint analysis. The top 100 highest scoring binders that exhibited similar interactions to the natural ligand GMP in the active site of the hRtcB homology model were further narrowed down to the top 20 and finally to the top 8 hit candidates based on criteria including high, medium, and poor scoring binders and purchasability. Through establishing an in vitro screening platform (MDA-MB-231/XBP1-Luciferase cell line), the top 8 hit candidates were tested in the luciferase assay from which compound-001 yielded a significant reduction (~50%) in XBP1s-luciferase under ER stress. Additionally, compound-007 showed a trend in the reduction of XBP1s-luciferase under stress in the assay. Testing these 2 compounds further in MDA-MB-231 TNBC cells didn’t yield any reduction in XBP1s under ER stress. Based on the luciferase assay results, these two hit compounds can become potential leads once tested in a biochemical assay setting and if successful, further optimized towards structure-activity relationships.2023-07-0

Development of drugs targeting the human tRNA ligase RtcB in breast cancer

The RNA ligase RtcB has been shown to regulate RNA function by direct exon ligation of spliced XBP1 messenger RNA cleaved by the endoplasmic reticulum (ER) stress sensor IRE1α. Ligation by RtcB leads to the expression of the transcription factor XBP1s that controls ER homeostasis and is surprisingly also utilized for oncogenic transformation, survival, and progress. Through elevated levels of XBP1s, tumor cells acquire a pro-survival advantage and promote tumor aggressiveness by an increase in tumor immune infiltration, angiogenesis, and cell invasive properties. Using RNA interference (RNAi), depleting human RtcB (hRtcB) in MDA-MB-231 triple-negative breast cancer (TNBC) cells significantly reduced basal XBP1s expression both at the mRNA and protein level. As the crystal structure of hRtcB is yet to be resolved, in silico techniques were therefore employed to develop a 3-dimensional predicted model of the hRtcB protein for the first time. Built from the Pyrococcus horikoshii RtcB (bacterial RtcB) crystal structure, PDB ID 4DWQA, the hRtcB homology model is in complex with manganese and covalently bound ligand GMP. The developed model clearly showed that the GTP binding site of the enzyme is a well-defined pocket that can be utilized as a target site for in silico drug discovery. A virtual high throughput screening (VHTS) campaign was thereafter executed to develop drugs that would halt or modulate the hRtcB-mediated XBP1s formation in TNBC. ~Eighteen million small molecule compounds were screened against the ligand binding site/active site of the hRtcB homology model. From the 3129 hits generated, the top 200 highest scoring binders were subjected to the structural hit fingerprint analysis. The top 100 highest scoring binders that exhibited similar interactions to the natural ligand GMP in the active site of the hRtcB homology model were further narrowed down to the top 20 and finally to the top 8 hit candidates based on criteria including high, medium, and poor scoring binders and purchasability. Through establishing an in vitro screening platform (MDA-MB-231/XBP1-Luciferase cell line), the top 8 hit candidates were tested in the luciferase assay from which compound-001 yielded a significant reduction (~50%) in XBP1s-luciferase under ER stress. Additionally, compound-007 showed a trend in the reduction of XBP1s-luciferase under stress in the assay. Testing these 2 compounds further in MDA-MB-231 TNBC cells didn’t yield any reduction in XBP1s under ER stress. Based on the luciferase assay results, these two hit compounds can become potential leads once tested in a biochemical assay setting and if successful, further optimized towards structure-activity relationships.2023-07-0

The Evaluation Method for ESD Immunity of Components in Terms of Soft Error

A hand-held product like a camera and a mobile-phone must be satisfied with ESD Standard. Mostly IEC 61000-4-2 is applied. In this SET-level ESD test, considerable reason of failure is malfunction of major semiconductor parts (CPU, Memory and Sensor etc.) Recently, due to the semiconductor becoming more refined, high speed and multifunction, that failure trend is getting more general. The importance of cooperation between set developer and component developer has been emphasized in ESD field. Especially, making a correlation in measurement and analytical method is very important. Through this paper, the evaluation method for ESD immunity of components will be suggested for designing ESD robust product

A Study of a Measurement and Simulation Method on ESD Noise Causing Soft-Errors by Disturbing Signals

A methodology to measure and simulate ESD induced noise on active IC Pins is introduced. A simple experimental setup injects ESD noise from an ESD generator and captures the waveforms. Secondly, the waveforms are simulated using a combination of 3D simulation and SPICE modeling

Full-Wave Simulation of an Electrostatic Discharge Generator Discharging in Air-Discharge Mode into a Product

This paper introduces a methodology to simulate the currents and fields during an air discharge electrostatic discharge (ESD) into a product by combining a linear description of the behavior of the DUT with a nonlinear arc resistance equation. The most commonly used test standard IEC 61000-4-2 requires using contact-mode discharges to metallic surfaces and air-discharge mode to nonconducting surfaces. In the contact mode, an ESD generator is a linear system. In the air-discharge mode, a highly nonlinear arc is a part of the current loop. This paper proposes a method that combines the linear ESD generator full-wave model and the nonlinear arc model to simulate currents and fields in air-discharge mode. Measurements are presented comparing discharge currents and fields for two cases: ESD generator discharges into a ground plane, and ESD generator discharges into a small product