Fatigue damage modeling for coated single crystal superalloys

A high temperature, low-cycle fatigue life prediction method for coated single crystal nickel-base superalloys is being developed. The method is being developed for use in predicting crack initiation life of coated single crystal turbine airfoils. Although the models are being developed using coated single crystal PWA 1480, they should be readily adaptable to other coated nickel-base single crystal materials. The coatings choosen for this effort were of two generic types: a low pressure plasma sprayed NiCoCrAlY overlay, designated PWA 286, and an aluminide diffusion, designated PWA 273. In order to predict the useful crack initiation life of airfoils, the constitutive and failure behavior of the coating/substrate combination must be taken into account. Coatings alter the airfoil surface microstructure and are a primary source from which cracks originate. The adopted life prediction approach addresses this complexity by separating the coating and single crystal crack initiation regimes. This provides a flexible means for using different life model formulations for the coating and single crystal materials. At the completion of this program, all constitutive and life model formulations will be available in equation form and as software. The software will use the MARC general purpose finite element code to drive the constitutive models and calculate life parameters

High temperature constitutive and crack initiation modeling of coated single crystal superalloys

The purpose of this program is to develop life prediction models for anisotropic materials used in gas turbine airfoils. In the base portion of the program, two coated single crystal alloys are being tested. They are PWA 286 overlay coated and PWA 273 aluminide coated PWA 1480 and PWA 286 overlay coated Alloy 185. Viscoplastic constitutive models for these materials are also being developed to predict the cyclic stress-strain histories required for life prediction of the lab specimens and actual airfoil designs

Increased SIRT3 combined with PARP inhibition rescues motor function of SBMA mice.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity by replenishing diminished NAD+ with PARP inhibition. Although NAD+ was not affected, overexpressing SIRT3 with PARP inhibition fully restored hexokinase activity, correcting the glycolytic pathway in AR100Q quadriceps, and rescued motor endurance of SBMA mice. These data demonstrate that targeting metabolic anomalies can restore motor function downstream of polyQ-expanded AR

Who Controls the Looking Glass? Towards a Conversational Understanding of Organizational Theatre

This paper presents a longitudinal study of interactive organizational theatre. Managers of a large home care organization used 30 instances of organizational theatre over a one year period to effect organizational change. We found that neither management, who had hoped that employees would accept and internalize the messages accompanying the play, nor employees, who used the liminal spaces to express their own take on the organization’s issues, achieved their aims directly. Yet a year later, organizational performance and satisfaction were significantly improved—much of this was attributed to the play. To explain this, we develop a conversational theory of change, one where ‘conversation pieces’ are central. We also speculate on the properties that conversation pieces and conversational systems like organizational theatre must have if they are to effect change.N/

Increased SIRT3 Combined With PARP Inhibition Rescues Motor Function of SBMA Mice

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity by replenishing diminished NAD+ with PARP inhibition. Although NAD+ was not affected, overexpressing SIRT3 with PARP inhibition fully restored hexokinase activity, correcting the glycolytic pathway in AR100Q quadriceps, and rescued motor endurance of SBMA mice. These data demonstrate that targeting metabolic anomalies can restore motor function downstream of polyQ-expanded AR

Increased SIRT3 combined with PARP inhibition rescues motor function of SBMA mice

Summary: Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease with substantial mitochondrial and metabolic dysfunctions. SBMA is caused by polyglutamine (polyQ) expansion in the androgen receptor (AR). Activating or increasing the NAD+-dependent deacetylase, SIRT3, reduced oxidative stress and death of cells modeling SBMA. However, increasing diminished SIRT3 in AR100Q mice failed to reduce acetylation of the SIRT3 target/antioxidant, SOD2, and had no effect on increased total acetylated peptides in quadriceps. Yet, overexpressing SIRT3 resulted in a trend of motor recovery, and corrected TCA cycle activity by decreasing acetylation of SIRT3 target proteins. We sought to boost blunted SIRT3 activity by replenishing diminished NAD+ with PARP inhibition. Although NAD+ was not affected, overexpressing SIRT3 with PARP inhibition fully restored hexokinase activity, correcting the glycolytic pathway in AR100Q quadriceps, and rescued motor endurance of SBMA mice. These data demonstrate that targeting metabolic anomalies can restore motor function downstream of polyQ-expanded AR