NASA Experience with CMM and CMMI

This slide presentation reviews the experience NASA has had in using Capability Maturity Model (CMM) and Capability Maturity Model Integration (CMMI). In particular this presentation reviews the agency's experience within the software engineering discipline and the lessons learned and key impacts from using CMMI

Improving Software Engineering on NASA Projects

Software Engineering Initiative: Reduces risk of software failure -Increases mission safety. More predictable software cost estimates and delivery schedules. Smarter buyer of contracted out software. More defects found and removed earlier. Reduces duplication of efforts between projects. Increases ability to meet the challenges of evolving software technology

Direct Regulation of CLOCK Expression by REV-ERB

Circadian rhythms are regulated at the cellular level by transcriptional feedback loops leading to oscillations in expression of key proteins including CLOCK, BMAL1, PERIOD (PER), and CRYPTOCHROME (CRY). The CLOCK and BMAL1 proteins are members of the bHLH class of transcription factors and form a heterodimer that regulates the expression of the PER and CRY genes. The nuclear receptor REV-ERBα plays a key role in regulation of oscillations in BMAL1 expression by directly binding to the BMAL1 promoter and suppressing its expression at certain times of day when REV-ERBα expression levels are elevated. We recently demonstrated that REV-ERBα also regulates the expression of NPAS2, a heterodimer partner of BMAL1. Here, we show that REV-ERBα also regulates the expression another heterodimer partner of BMAL1, CLOCK. We identified a REV-ERBα binding site within the 1st intron of the CLOCK gene using a chromatin immunoprecipitation – microarray screen. Suppression of REV-ERBα expression resulted in elevated CLOCK mRNA expression consistent with REV-ERBα's role as a transcriptional repressor. A REV-ERB response element (RevRE) was identified within this region of the CLOCK gene and was conserved between humans and mice. Additionally, the CLOCK RevRE conferred REV-ERB responsiveness to a heterologous reporter gene. Our data suggests that REV-ERBα plays a dual role in regulation of the activity of the BMAL1/CLOCK heterodimer by regulation of expression of both the BMAL1 and CLOCK genes

Regulation of Expression of Citrate Synthase by the Retinoic Acid Receptor-Related Orphan Receptor α (RORα)

The retinoic acid receptor-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily of transcription factors that plays an important role in regulation of the circadian rhythm and metabolism. Mice lacking a functional RORα display a range of metabolic abnormalities including decreased serum cholesterol and plasma triglycerides. Citrate synthase (CS) is a key enzyme of the citric acid cycle that provides energy for cellular function. Additionally, CS plays a critical role in providing citrate derived acetyl-CoA for lipogenesis and cholesterologenesis. Here, we identified a functional RORα response element (RORE) in the promoter of the CS gene. ChIP analysis demonstrates RORα occupancy of the CS promoter and a putative RORE binds to RORα effectively in an electrophoretic mobility shift assay and confers RORα responsiveness to a reporter gene in a cotransfection assay. We also observed a decrease in CS gene expression and CS enzymatic activity in the staggerer mouse, which has a mutation of in the Rora gene resulting in nonfunctional RORα protein. Furthermore, we found that SR1001 a RORα inverse agonist eliminated the circadian pattern of expression of CS mRNA in mice. These data suggest that CS is a direct RORα target gene and one mechanism by which RORα regulates lipid metabolism is via regulation of CS expression

Internal Ribosomal Entry Site-Mediated Translation Is Important for Rhythmic PERIOD1 Expression

The mouse PERIOD1 (mPER1) plays an important role in the maintenance of circadian rhythm. Translation of mPer1 is directed by both a cap-dependent process and cap-independent translation mediated by an internal ribosomal entry site (IRES) in the 5′ untranslated region (UTR). Here, we compared mPer1 IRES activity with other cellular IRESs. We also found critical region in mPer1 5′UTR for heterogeneous nuclear ribonucleoprotein Q (HNRNPQ) binding. Deletion of HNRNPQ binding region markedly decreased IRES activity and disrupted rhythmicity. A mathematical model also suggests that rhythmic IRES-dependent translation is a key process in mPER1 oscillation. The IRES-mediated translation of mPer1 will help define the post-transcriptional regulation of the core clock genes

Space Flight Software Development Software for Intelligent System Health Management

The slide presentation examines the Marshall Space Flight Center Flight Software Branch, including software development projects, mission critical space flight software development, software technical insight, advanced software development technologies, and continuous improvement in the software development processes and methods

Student\u27s Encyclopedia of Great American Writers (5 volumes)

https://digitalcommons.usu.edu/usufaculty_monographs/1028/thumbnail.jp

Coronary Artery Bypass Grafting With and Without Cardiopulmonary Bypass: A Comparison Analysis

Coronary artery bypass grafting (CABG) using stabilization devices in place of the heart–lung machine is being performed on a wide range of patients. This study retrospectively compared the performance of off-pump coronary artery grafting bypass (OPCAB) with conventional bypass patients over the same 6-month period at The Medical University of South Carolina. Data were collected and compared from the National Cardiac Database of the Society of Thoracic Surgeons (STS). Parameters studied included age, gender, left ventricular ejection fraction (LVEF), previous myocardial infarction (MI), disease severity, number of grafts, complications, blood usage, ventilation times, operating room (OR) time, and hospital length of stay (LOS). There were no significant difference between the patient groups with regard to age, gender, LVEF, previous MI, predicted mortality, and LOS. Operative mortality was also similar in the two groups: conventional bypass 4/117 (3%) and OPCAB 2/86 (2%). The conventional bypass patients (CPB) had significantly (p < 0.05) more diseased vessels (2.9 vs. 2.6) and distal grafts (4.1 vs. 2.7), as compared to the OPCAB group. OPCAB procedures resulted in significantly (p < 0.05) lower mean OR time (365 min vs. 406 min) and reduced mean postoperative ventilation hours (3.4 vs. 8.3 hours), as compared to conventional bypass. There were significantly (p < 0.05) fewer blood transfusions in the OPCAB group (1.1 units vs. 2.4 units), and the percentage of patients transfused blood was significantly less (34.9% vs. 57.3%). Nine out of 95 (9.5%) of patients who presented for OPCAB were converted to conventional bypass. Although there may be potential benefits to OPCAB, further studies must be directed at determining those patients who would benefit most from CABG using the off-pump technique