The effect of phase angle on crack growth mechanisms under thermo-mechanical fatigue loading

The current paper describes TMF crack growth behaviour in an advanced nickel-based superalloy. Changes in behaviour are examined which occur as a function of the phase angle between applied stress and temperature. The fractography of the failed specimens reveals changes from transgranular to intergranular growth between high and low phase angle tests as a result of the onset of high temperature damage mechanisms. More targeted testing has also been undertaken to isolate the contributions of these mechanisms, with specific transitions in behaviour becoming clear in 90° diamond cycles, where dynamic crack growth and oxidation strongly interact

DevTMF – Towards code of practice for thermo-mechanical fatigue crack growth

The current paper presents work on identification and evaluation of a range of factors influencing accuracy and comparability of data generated by three laboratories carrying out stress-controlled thermo-mechanical fatigue crack growth tests. It addresses crack length measurements, heating methods and temperature measurement techniques. It also provides guidance for pre-cracking and use of different specimen geometries as well as Digital Image Correlation imaging for crack monitoring. The majority of the tests have been carried out on a coarse grain polycrystalline nickel-base superalloy using two phase angles, Out-of-Phase and In-Phase cycles with a triangular waveform and a temperature range of 400–750 °C

Effects of Spermidine Supplementation on Cognition and Biomarkers in Older Adults With Subjective Cognitive Decline : Decline A Randomized Clinical Trial

IMPORTANCE Developing interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline. OBJECTIVE To determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group. DESIGN, SETTING, AND PARTICIPANTS This 12-month randomized, double-masked, placebocontrolled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021. INTERVENTIONS One hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (O.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention. MAIN OUTCOMES AND MEASURES Primary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed. RESULTS A total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.Peer reviewe

Dietary spermidine for lowering high blood pressure

Loss of cardiac macroautophagy/autophagy impairs heart function, and evidence accumulates that an increased autophagic flux may protect against cardiovascular disease. We therefore tested the protective capacity of the natural autophagy inducer spermidine in animal models of aging and hypertension, which both represent major risk factors for the development of cardiovascular disease. Dietary spermidine elicits cardioprotective effects in aged mice through enhancing cardiac autophagy and mitophagy. In salt-sensitive rats, spermidine supplementation also delays the development of hypertensive heart disease, coinciding with reduced arterial blood pressure. The high blood pressure-lowering effect likely results from improved global arginine bioavailability and protection from hypertension-associated renal damage. The polyamine spermidine is naturally present in human diets, though to a varying amount depending on food type and preparation. In humans, high dietary spermidine intake correlates with reduced blood pressure and decreased risk of cardiovascular disease and related death. Altogether, spermidine represents a cardio- and vascular- protective autophagy inducer that can be readily integrated in common diets

Brain energy rescue:an emerging therapeutic concept for neurodegenerative disorders of ageing

The brain requires a continuous supply of energy in the form of ATP, most of which is produced from glucose by oxidative phosphorylation in mitochondria, complemented by aerobic glycolysis in the cytoplasm. When glucose levels are limited, ketone bodies generated in the liver and lactate derived from exercising skeletal muscle can also become important energy substrates for the brain. In neurodegenerative disorders of ageing, brain glucose metabolism deteriorates in a progressive, region-specific and disease-specific manner — a problem that is best characterized in Alzheimer disease, where it begins presymptomatically. This Review discusses the status and prospects of therapeutic strategies for countering neurodegenerative disorders of ageing by improving, preserving or rescuing brain energetics. The approaches described include restoring oxidative phosphorylation and glycolysis, increasing insulin sensitivity, correcting mitochondrial dysfunction, ketone-based interventions, acting via hormones that modulate cerebral energetics, RNA therapeutics and complementary multimodal lifestyle changes

Cardioprotection and lifespan extension by the natural polyamine spermidine

Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease

A quantitative approach to study the effect of local texture and heterogeneous plastic strain on the deformation micromechanism in RR1000 nickel-based superalloy

In a weakly textured material with relatively pore-free and homogeneous microstructure, the local texture can influence primary crack propagation and secondary crack initiation, depending on specific microtexture cluster size. Moreover, the plastic strain assessment and strain quantity within individual grains are essential for understanding the material susceptibility to crack initiation and propagation at various loading conditions and temperature ranges. In the current study, electron backscatter diffraction (EBSD) is applied to measure the plastic strain present in RR1000 nickel-based superalloy microstructure following thermo-mechanical fatigue tests. The EBSD plastic strain measurements are evaluated to identify the distinctive deformation mode within individual grains. It was evident from the overall statistical analyses carried out for over 2000 grains that cube (〈0 0 1〉//loading direction) and near cube orientations (φ1, Φ, φ2: 0, 0–15, 0) behaved as “soft” grains with a high Schmid factor and contained low geometrically necessary dislocation (GND) density as a result of low strain hardening at the early stage of deformation for such grains. The near cube orientation (typically φ1, Φ, φ2: 0, 9, 0) was the softest orientation among the cube family. While the brass grains (〈1 1 1〉//loading direction) acted as “hard” grains that have the lowest Schmid factor with the highest Taylor factor and GND density compared with other oriented grains. A high GND content was found in the vicinity of the grain boundaries in the soft grains and on slip plane traces within the hard grains. It is concluded that GND absolute value for each grain can vary, as it is interrelated with deformation degree, but the GND locations within the grains give indications of the strain hardening state and deformation stages in hard and soft grains. Furthermore, the areas with random local texture contained high strain incompatibilities between neighbouring grains, and generated microtexture clusters that prompt preferential secondary crack initiation and propagation