Fracture Response Enhancement Of Aluminum Using In-Situ Selective Reinforcement

A computer-based parametric study of the effect of reinforcement architectures on fracture response of aluminum compact-tension (CT) specimens is performed. Eleven different reinforcement architectures consisting of rectangular and triangular cross-section reinforcements were evaluated. Reinforced specimens produced between 13 and 28 percent higher fracture load than achieved with the unreinforced case. Reinforcements with blunt leading edges (rectangular reinforcements) exhibited superior performance relative to the triangular reinforcements with sharp leading edges. Relative to the rectangular reinforcements, the most important architectural feature was reinforcement thickness. At failure, the reinforcements carried between 58 and 85 percent of the load applied to the specimen, suggesting that there is considerable load transfer between the base material and the reinforcement

Effect of Reinforcement Architecture on Fracture of Selectively Reinforced Metallic Compact Tension Specimens

A computer-based parametric study of the effect of reinforcement architectures on fracture response of aluminum compact-tension (CT) specimens is performed. Eleven different reinforcement architectures consisting of rectangular and triangular cross-section reinforcements were evaluated. Reinforced specimens produced between 13 and 28 percent higher fracture load than achieved with the non-reinforced case. Reinforcements with blunt leading edges (rectangular reinforcements) exhibited superior performance relative to the triangular reinforcements with sharp leading edges. Relative to the rectangular reinforcements, the most important architectural feature was reinforcement thickness. At failure, the reinforcements carried between 58 and 85 percent of the load applied to the specimen, suggesting that there is considerable load transfer between the base material and the reinforcement

ADAM17 is essential for ectodomain shedding of the EGF-receptor ligand amphiregulin.

The epidermal growth factor (EGF)-receptor ligand amphiregulin (AREG) is a potent growth factor implicated in proliferative skin diseases and in primary and metastatic epithelial cancers. AREG, synthesized as a propeptide, requires conversion to an active peptide by metalloproteases by a process known as ectodomain shedding. Although (ADAM17) a disintegrin and metalloprotease 17 is a key sheddase of AREG, ADAM8-, ADAM15-, and batimastat (broad metalloprotease inhibitor)-sensitive metalloproteases have also been implicated in AREG shedding. In the present study, using a curly bare (Rhbdf2cub ) mouse model that shows loss-of-hair, enlarged sebaceous gland, and rapid cutaneous wound-healing phenotypes mediated by enhanced Areg mRNA and protein levels, we sought to identify the principal ectodomain sheddase of AREG. To this end, we generated Rhbdf2cub mice lacking ADAM17 specifically in the skin and examined the above phenotypes of Rhbdf2cub mice. We find that ADAM17 deficiency in the skin of Rhbdf2cub mice restores a full hair coat, prevents sebaceous gland enlargement, and impairs the rapid wound-healing phenotype observed in Rhbdf2cub mice. Furthermore, in vitro, stimulated shedding of AREG is abolished in Rhbdf2cub mouse embryonic keratinocytes lacking ADAM17. Thus, our data support previous findings demonstrating that ADAM17 is the major ectodomain sheddase of AREG. FEBS Open Bio 2018; 8(4):702-710

RHBDF2-regulated growth factor signaling in a rare human disease tylosis with esophageal cancer: What can we learn from murine models?

Tylosis with esophageal cancer syndrome (TOC) is a rare autosomal dominant proliferative skin disease caused by missense mutations in the rhomboid 5 homolog 2 (RHBDF2) gene. TOC is characterized by thickening of the skin in the palms and feet and is strongly linked with the development of esophageal squamous cell carcinoma. Murine models of human diseases have been valuable tools for investigating the underlying genetic and molecular mechanisms of a broad range of diseases. Although current mouse models do not fully recapitulate all aspects of human TOC, and the molecular mechanisms underlying TOC are still emerging, the available mouse models exhibit several key aspects of the disease, including a proliferative skin phenotype, a rapid wound healing phenotype, susceptibility to epithelial cancer, and aberrant epidermal growth factor receptor (EGFR) signaling. Furthermore, we and other investigators have used these models to generate new insights into the causes and progression of TOC, including findings suggesting a tissue-specific role of the RHBDF2-EGFR pathway, rather than a role of the immune system, in mediating TOC; and indicating that amphiregulin, an EGFR ligand, is a functional driver of the disease. This review highlights the mouse models of TOC available to researchers for use in investigating the disease mechanisms and possible therapies, and the significance of genetic modifiers of the disease identified in these models in delineating the underlying molecular mechanisms

Medication use and medical comorbidity in patients with chronic hepatitis C from a US commercial claims database: high utilization of drugs with interaction potential

With the advent of the direct-acting antiviral agents (DAAs), significant drug-drug interaction (DDI) potential now exists for patients treated for chronic hepatitis C virus (HCV) infection. However, little is known about how often patients with HCV use medications that may interact with newer HCV treatments, especially those with CYP3A DDI potential

Lower limb stiffness and maximal sprint speed in 11-16-year-old boys

The purpose of the study was to examine the relationship between vertical stiffness, leg stiffness and maximal sprint speed in a large cohort of 11-16-year-old boys. Three-hundred and thirty-six boys undertook a 30 m sprint test using a floor-level optical measurement system, positioned in the final 15 m section. Measures of speed, step length, step frequency, contact time and flight time were directly measured whilst force, displacement, vertical stiffness and leg stiffness, were modeled from contact and flight times, from the two fastest consecutive steps for each participant over two trials. All force, displacement and stiffness variables were significantly correlated with maximal sprint speed (p 0.7) relationship with sprint speed, while vertical center of mass displacement, absolute vertical stiffness, relative peak force, and maximal leg spring displacement had large (r > 0.5) relationships. Relative vertical stiffness and relative peak force did not significantly change with advancing age (p > 0.05), but together with maximal leg spring displacement accounted for 96% of the variance in maximal speed. It appears that relative vertical stiffness and relative peak force are important determinants of sprint speed in boys aged 11-16 years, but are qualities that may need to be trained due to no apparent increases from natural development. Practitioners may wish to utilize training modalities such as plyometrics and resistance training to enable adaptation to these qualities due to their importance as predictors of speed in youth

Reputation in European Trade Mark Law: A Re-examination

Under the harmonised European trade mark regime marks with a reputation enjoy expanded protection. This article casts doubt on whether this ‘reputational trigger’ can be justified. It then explores some difficult operational questions about the way the reputation threshold works in cases where the mark enjoys fame only in niche markets or in a limited geographical area, the aim being to illustrate further why reputation is an unsatisfactory trigger for a different type of trade mark protection. Finally, it looks at some of the evidential difficulties involved in adjudicating disputes in which expanded protection is being claimed. It concludes by suggesting that if the evidential problems we identify were tackled the reputation threshold could be abandoned