Advanced Gear Alloys for Ultra High Strength Applications

Single tooth bending fatigue (STBF) test data of UHS Ferrium C61 and C64 alloys are presented in comparison with historical test data of conventional gear steels (9310 and Pyrowear 53) with comparable statistical analysis methods. Pitting and scoring tests of C61 and C64 are works in progress. Boeing statistical analysis of STBF test data for the four gear steels (C61, C64, 9310 and Pyrowear 53) indicates that the UHS grades exhibit increases in fatigue strength in the low cycle fatigue (LCF) regime. In the high cycle fatigue (HCF) regime, the UHS steels exhibit better mean fatigue strength endurance limit behavior (particularly as compared to Pyrowear 53). However, due to considerable scatter in the UHS test data, the anticipated overall benefits of the UHS grades in bending fatigue have not been fully demonstrated. Based on all the test data and on Boeing s analysis, C61 has been selected by Boeing as the gear steel for the final ERDS demonstrator test gearboxes. In terms of potential follow-up work, detailed physics-based, micromechanical analysis and modeling of the fatigue data would allow for a better understanding of the causes of the experimental scatter, and of the transition from high-stress LCF (surface-dominated) to low-stress HCF (subsurface-dominated) fatigue failure. Additional STBF test data and failure analysis work, particularly in the HCF regime and around the endurance limit stress, could allow for better statistical confidence and could reduce the observed effects of experimental test scatter. Finally, the need for further optimization of the residual compressive stress profiles of the UHS steels (resulting from carburization and peening) is noted, particularly for the case of the higher hardness C64 material

Testing Aerospace Gears for Bending Fatigue, Pitting, and Scuffing

This work was motivated by the goal to increase the power to weight ratio of rotorcraft drive systems. Experiments were conducted to establish the performance of gears made from an aerospace alloy used in production aircraft. Bending fatigue, pitting, and scuffing test procedures and results are documented. The data establishes a baseline for evaluation of new technologies. Recommendations are made to improve test procedures for future work

Expressions 2006-2008

https://openspace.dmacc.edu/expressions/1042/thumbnail.jp

Synthetic Multivalent Ligands as Probes of Signal Transduction

Cell-surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Many receptors do not operate as individual entities, but rather as part of dimeric or oligomeric complexes. Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Understanding the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication is critical; chemical synthesis can provide compounds to address the role of receptor assembly in signal transduction. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. This Review focuses on the use of synthetic multivalent ligands to characterize receptor function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50669/1/2348_ftp.pd

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation