A Fully Integrated High-Temperature, High-Voltage, BCD-on-SOI Voltage Regulator

Developments in automotive (particularly hybrid electric vehicles), aerospace, and energy production industries over the recent years have led to expanding research interest in integrated circuit (IC) design toward high-temperature applications. A high-voltage, high-temperature SOI process allows for circuit design to expand into these extreme environment applications. Nearly all electronic devices require a reliable supply voltage capable of operating under various input voltages and load currents. These input voltages and load currents can be either DC or time-varying signals. In this work, a stable supply voltage for embedded circuit functions is generated on chip via a voltage regulator circuit producing a stable 5-V output voltage. Although applications of this voltage regulator are not limited to gate driver circuits, this regulator was developed to meet the demands of a gate driver IC. The voltage regulator must provide reliable output voltage over an input range from 10 V to 30 V, a temperature range of −50 ºC to 200 ºC, and output loads from 0 mA to 200 mA. Additionally, low power stand-by operation is provided to help reduce heat generation and thus lower operating junction temperature. This regulator is based on the LM723 Zener reference voltage regulator which allows stable performance over temperature (provided proper design of the temperature compensation scheme). This circuit topology and the SOI silicon process allow for reliable operation under all application demands. The designed voltage regulator has been successfully tested from −50 ºC to 200 ºC while demonstrating an output voltage variation of less than 25 mV under the full range of input voltage. Line regulation tests from 10 V to 35 V show a 3.7-ppm/V supply sensitivity. With the use of a high-temperature ceramic output capacitor, a 5-nsec edge, 0 to 220 mA, 1-µsec pulse width load current induced only a 55 mV drop in regulator output voltage. In the targeted application, load current pulse widths will be much shorter, thereby improving the load transient performance. Full temperature and input voltage range tests reveal the no-load supply current draw is within 330 µA while still providing an excess of 200 mA of load current upon demand

A GHz-range, High-resolution Multi-modulus Prescaler for Extreme Environment Applications

The generation of a precise, low-noise, reliable clock source is critical to developing mixed-signal and digital electronic systems. The applications of such a clock source are greatly expanded if the clock source can be configured to output different clock frequencies. The phase-locked loop (PLL) is a well-documented architecture for realizing this configurable clock source. Principle to the configurability of a PLL is a multi-modulus divider. The resolution of this divider (or prescaler) dictates the resolution of the configurable PLL output frequency. In integrated PLL designs, such a multi-modulus prescaler is usually sourced from a GHz-range voltage-controlled oscillator. Therefore, a fully-integrated PLL ASIC requires the development of a high-speed, high-resolution multi-modulus prescaler. The design challenges associated with developing such a prescaler are compounded when the application requires the device to operate in an extreme environment. In these extreme environments (often extra-terrestrial), wide temperature ranges and radiation effects can adversely affect the operation of electronic systems. Even more problematic is that extreme temperatures and ionizing radiation can cause permanent damage to electronic devices. Typical commercial-off-the-shelf (COTS) components are not able withstand such an environment, and any electronics operating in these extreme conditions must be designed to accommodate such operation. This dissertation describes the development of a high-speed, high-resolution, multi-modulus prescaler capable of operating in an extreme environment. This prescaler has been developed using current-mode logic (CML) on a 180-nm silicon-germanium (SiGe) BiCMOS process. The prescaler is capable of operating up to at least 5.4 GHz over a division range of 16-48 with a total of 27 configurable moduli. The prescaler is designed to provide excellent ionizing radiation hardness, single-event latch-up (SEL) immunity, and single-event upset (SEU) resistance over a temperature range of −180°C to 125°C

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Perspectives on ENCODE

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.11Nsciescopu

Expanded encyclopaedias of DNA elements in the human and mouse genomes

AbstractThe human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE1 and Roadmap Epigenomics2 data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.11Nsciescopu