Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity

Computer Aided Printed Circuit Design.

This paper presents some of the engineering and programming developments wtuch have resulted from the University of Maryland RAMCAD (Reliability and Maintainability using Computer Aided Design) effort for printed circuit boards (PCBs) and wiring assemblies (PWA)s. The paper overviews some of the problems associated with the PCB design process, examines the present status of computer aided PCB design, and then dicusses the development of the University of Maryland RAMCAD system and the methods used to program for goal oriented design

Effect of Solder Joint Degradation on RF Impedance

The trend for many types of electronic products is toward higher operating frequencies or digital bit rates. At high frequencies, signal propagation is concentrated at the surface of interconnects, a phenomenon known as the skin effect. Degradation of interconnects, such as cracking of solder joints due to fatigue or shock loading, also usually initiates at the surface and propagates inward. Therefore, even a small crack at the surface of a solder joint may change RF impedance and adversely affects the performance of high speed electronic circuits. Traditional methods used to monitor interconnect reliability are based on measurement of DC resistance. More accurate and sensitive alternatives are required for monitoring the reliability of current and future electronic products. RF impedance analysis offers an improved means of sensing interconnect degradation. This study demonstrates the value of RF impedance measurements as an early indicator of physical degradation of solder joints compared to DC resistance measurements. Mechanical fatigue tests have been conducted with an impedance-controlled circuit board on which a surface mount component was soldered. Simultaneous measurements were performed of DC resistance and the time domain reflection coefficient, as a measure of RF impedance, while the solder joints were stressed. The RF impedance was observed to increase in response to cracking of the solder joint while DC resistance remained constant. Failure analysis revealed that the RF impedance increase resulted from a physical crack initiated at the surface of the solder joint, which had propagated only partway across the solder joint

Early detection of interconnect degradation using RF impedance and SPRT

Many types of electronic products are now operating at higher frequencies or digital bit rates. At high frequencies, signal propagation is concentrated at the surface of interconnects, a phenomenon known as the skin effect. Degradation of interconnects, such as cracking of the solder joints due to fatigue or shock loading, also usually initiates at the surface and propagates inward. Therefore, even a small crack at the surface of an interconnect may change RF impedance and adversely affect the performance of high speed electronic circuits. Traditional methods used to monitor interconnect reliability are based on a measurement of DC resistance. But, more accurate and sensitive alternatives are required for monitoring the reliability of current and future electronic products. RF impedance analysis offers an improved means of sensing interconnect degradation. This study demonstrates the value of RF impedance measurements as an early indicator of physical degradation of solder joints compared to DC resistance measurements. Mechanical fatigue tests have been conducted with an impedance-controlled circuit board on which a surface mount component was soldered. Simultaneous measurements were performed of DC resistance and the time domain reflection coefficient as a measure of RF impedance while the solder joints were stressed. During the test, the RF impedance provided detectable failure precursors by the sequential probability ratio test (SPRT), while the DC resistance remained constant with no precursors. Failure analysis revealed that the change in RF impedance resulted from a physical crack that initiated at the surface of the solder joint and propagated only part of the way across the solder joint. These test results indicate that the combination of RF impedance and the SPRT can serve as a non-destructive early indicator of solder joint degradation

Optimized Redundancy Allocation for Electronic Equipment.

This paper describes a methodology for optimizing the temperature dependent reliability of electronic equipment using active redundancy, while satisfying an area constraint. The process consists of transforming the objective unreliability function by adding to it a suitable penalty term so as to force the optimum solution to an almost integer" value, and minimizing the transformed objective function by a sequential quadratic programming technique. A sensitivity analysis, which avoids "perturb-and-reoptimize" methods, is then conducted to show how an incremental change in an input parameter affects the optimum solution