203,261 research outputs found
A crack-like notch analogue for a safe-life fretting fatigue design methodology
Various analogies have recently been proposed for comparing the stress fields induced in fretting fatigue contact situations, with those of a crack and a sharp or a rounded notch, resulting in a degree of uncertainty over which model is most appropriate in a given situation. However, a simple recent approach of Atzori–Lazzarin for infinite-life fatigue design in the presence of a geometrical notch suggests a corresponding unified model also for fretting fatigue (called Crack-Like Notch Analogue model) considering only two possible behaviours: either 'crack-like' or 'large blunt notch.' In a general fretting fatigue situation, the former condition is treated with a single contact problem corresponding to a Crack Analogue model; the latter, with a simple peak stress condition (as in previous Notch Analogue models), simply stating that below the fatigue limit, infinite life is predicted for any size of contact. In the typical situation of constant normal load and in phase oscillating tangential and bulk loads, both limiting conditions can be readily stated. Not only is the model asymptotically correct if friction is infinitely high or the contact area is very small, but also remarkably accurate in realistic conditions, as shown by excellent agreement with Hertzian experimental results on Al and Ti alloys. The model is useful for preliminary design or planning of experiments reducing spurious dependences on an otherwise too large number of parameters. In fact, for not too large contact areas ('crack-like' contact) no dependence at all on geometry is predicted, but only on three load factors (bulk stress, tangential load and average pressure) and size of the contact. Only in the 'large blunt notch' region occurring typically only at very large sizes of contact, does the size-effect disappear, but the dependence is on all other factors including geometry
Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle.
Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues
Effect of Notches on the Axial Fatigue Properties of Structural Steels
The effect of the stress concentration on the zero-to-tension axial fatigue
strength of notched members of four structural steels has been studied. For
each of the four steels a critical notch severity was found at which a transition
in behavior takes place. When the theoretical stress concentration exceeds this
critical value the fatigue strength increases instead of continuing to decrease as
would normally be expected. The maximum effective stress concentration determined
from these tests corresponds to a critical notch severity which is dependent on the
material) the geometry of the specimen) and the cyclic conditions of stress.
Microscopic examinations of the roots of the notched specimens which did
not fail revealed cracking in most cases. Some of the cracks apparently were nonpropagating
cracks but the test lives in most cases were insufficient to isolate
such cracks positively as non-propagating. A study of other data on non-propagating
cracks revealed that the laws governing their formation are not yet fully
understood. However, there are indications that the increase in fatigue strength
obtained above the critical notch severity is coincident with the formation of
non~propagating cracks.The Engineering FoundationAmerican Iron and Steel InstituteChicago Bridge and Iron FoundationThe Welding Research Counci
Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.
BackgroundDevelopment of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.ResultsIn this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.ConclusionsOur results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems
Compression strength failure mechanisms in unidirectional composite laminates containing a hole
Experiments on graphite-epoxy laminated plates containing unloaded small holes show that these laminates are notch insensitive. That is, the uniaxial strength of these laminates with small holes exceeds the strength predicted by a point stress criterion using the stress concentration factor for the in-plane stress field. Laminates containing large holes exhibit notch sensitive behavior and consequently their strength is reasonably well predicted by the stress concentration effect. This hole size effect is manifested both in tension and in compression. Apparently, some mechanism must cause in-plane stress relief for laminates containing small holes. The purpose of this research was to study the influence of geometric nonlinearity on the micromechanical response of a filamentary composite material in the presence of a strain gradient caused by a discontinuity such as a hole. A mathematical model was developed at the micromechanical level to investigate this geometrically nonlinear effect
Investigation of the effects of notch width on eddy current response and comparison of signals from notches and cracks
This paper reports on work conducted to investigate the effect that electrical discharge machining (EDM) notch width has on the eddy current (EC) signal as a function of coil drive frequency. The notch results are also compared to EC signals from laboratory‐grown fatigue cracks. This study builds upon previous work with titanium, Inconel and aluminum materials where the signal amplitude was shown to decrease, as expected, as the notch width decreases. The trend was captured well by numerical results and this allowed estimates to be made about the signals from idealized “zero‐width” notches. The results indicated that the signal reduction factor from a 0.127 mm (0.005 inch) wide, rectangular notch to a theoretical zero‐width semi‐elliptical notch of the same size ranged from 25 to 42% for low conductivity materials when data was collected at 2 MHz. For aluminum, the difference between signals from 0.127 mm wide notches and estimated signals for zero‐width notches was approximately 50%. However, 2 MHz is an uncommonly high frequency for inspecting aluminum alloys so additional work was necessary to investigate the notch width effect at lower frequencies. This study sought to determine how the notch‐width effect changed as a function of frequency for high conductivity materials such as aluminum
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