Fatigue crack growth retardation in plane stress and plane strain

The fatigue crack growth retardation phenomenon following a single peak overload applied tothick andthin SEN bend specimens has been studied for a low carbon structural steel. Fatigue tests were performed under a constant load ratio of 0.6, constant stress intensity range of 10 MPam^1/2 and a constant overload ratio of 2.5. An immediate increase followed by a transient retardation in the fatigue crack growth rate, due to the applied overload, was observed for thethick specimen but complete crack arrest was obtained for thethin specimen. The immediate increase in the fatigue crack growth rate following the single peak overload in thethick specimen was attributed to the coincidence of monotonic fracture modes.     

Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer’s Disease,Lithium, and Autophagy

Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug’s neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium’s neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug’s inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium’s neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer’s disease (AD) and in patients, discussing the rationale for the drug’s use in the treatment of AD.     

Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells?

Mitochondrial function is at the nexus of pathways regulating synaptic-plasticity and cellular resilience. The involvement of brain mitochondrial dysfunction along with increased reactive oxygen species (ROS) levels, accumulating mtDNA mutations, and attenuated autophagy is implicated in psychiatric and neurodegenerative diseases. We have previously modeled mild mitochondrial dysfunction assumed to occur in bipolar disorder (BPD) using exposure of human neuronal cells (SH-SY5Y) to rotenone (an inhibitor of mitochondrial-respiration complex-I) for 72 and 96 h, which exhibited up- and down-regulation of mitochondrial respiration, respectively. In this study, we aimed to find out whether autophagy enhancers (lithium, trehalose, rapamycin, and resveratrol) and/or ROS scavengers [resveratrol, N-acetylcysteine (NAC), and Mn-Tbap) can ameliorate neuronal mild mitochondrial dysfunction. Only lithium (added for the last 24/48 h of the exposure to rotenone for 72/96 h, respectively) counteracted the effect of rotenone on most of the mitochondrial respiration parameters (measured as oxygen consumption rate (OCR)). Rapamycin, resveratrol, NAC, and Mn-Tbap counteracted most of rotenone’s effects on OCR parameters after 72 h, possibly via different mechanisms, which are not necessarily related to their ROS scavenging and/or autophagy enhancement effects. The effect of lithium reversing rotenone’s effect on OCR parameters is compatible with lithium’s known positive effects on mitochondrial function and is possibly mediated via its effect on autophagy. By-and-large it may be summarized that some autophagy enhancers/ROS scavengers alleviate some rotenone-induced mild mitochondrial changes in SH-SY5Y cells.     

Neuroinflammation as a Common Denominator of Complex Diseases (Cancer,Diabetes Type 2, and Neuropsychiatric Disorders)

The term neuroinflammation refers to inflammation of the nervous tissue, in general, and in the central nervous system (CNS), in particular. It is a driver of neurotoxicity, it is detrimental, and implies that glial cell activation happens prior to neuronal degeneration and, possibly, even causes it. The inflammation-like glial responses may be initiated in response to a variety of cues such as infection, traumatic brain injury, toxic metabolites, or autoimmunity. The inflammatory response of activated microglia engages the immune system and initiates tissue repair. Through translational research the role played by neuroinflammation has been acknowledged in different disease entities. Intriguingly, these entities include both those directly related to the CNS (commonly designated neuropsychiatric disorders) and those not directly related to the CNS (e.g., cancer and diabetes type 2). Interestingly, all the above-mentioned entities belong to the same group of “complex disorders”. This review aims to summarize cumulated data supporting the hypothesis that neuroinflammation is a common denominator of a wide variety of complex diseases. We will concentrate on cancer, type 2 diabetes (T2DM), and neuropsychiatric disorders (focusing on mood disorders).     

TRANSIENT RETARDATIONS IN FATIGUE CRACK GROWTH FOLLOWING A SINGLE PEAK OVERLOAD

Retardation in the fatigue crack growth rate following the application of a single peak overload in a fatigue loading sequence has been studied for a low carbon structural steel. Tests have been performed at load ratios of R= 0.2 and R= 0.6 at a baseline stress intensity range, ΔK_b, corresponding to fatigue crack growth rates in the Paris regime. Single peak overloads were applied at a crack-length to specimen-width ratio of a/W= 0.5. At the load ratio of R= 0.6 monotonic or “static” fracture modes were observed upon application of the overload, and these produced an immediate increase in growth rate. A subsequent retardation is attributed to the presence of a residual compressive stress field ahead of the crack tip. A similar retardation was observed at a load ratio of 0.2. The importance of residual stress was established by performing stress relieving experiments. In addition, removal of the surface deformation after an overload by machining “T” sidegrooves resulted in an extended transient, which could not be explained by residual machining stresses.