Notch and strain rate sensitivity of non crimp fabric composites

The notch and strain rate sensitivity of non-crimp glass fibre/vinyl-ester laminates subjected to uniaxial tensile loads has been investigated experimentally. Two set of notch configurations were tested; one where circular holes were drilled and another where fragment simulating projectiles were fired through the plate creating a notch. Experiments were conducted for strain rates ranging from 10-4/s to 102/s using servo hydraulic machines. A significant increase in strength with increasing strain rate was observed for both notched and unnotched specimens. High speed photography revealed changes in failure mode, for certain laminate configurations, as the strain rate increased. The tested laminate configurations showed fairly small notch sensitivity for the whole range of strain rates.

A fracture criterion for the notch strength of high strength steels in the presence of hydrogen

High strength steels can suffer from a loss of ductility when exposed to hydrogen, and this may lead to sudden failure. The hydrogen is either accommodated in the lattice or is trapped at defects, such as dislocations, grain boundaries and carbides. The challenge is to identify the effect of hydrogen located at different sites upon the drop in tensile strength of a high strength steel. For this purpose, literature data on the failure stress of notched and un-notched steel bars are re-analysed; the bars were tested over a wide range of strain rates and hydrogen concentrations. The local stress state at failure has been determined by the finite element (FE) method, and the concentration of both lattice and trapped hydrogen is predicted using Oriani's theory along with the stress-driven diffusion equation. The experimental data are rationalised in terms of a postulated failure locus of peak maximum principal stress versus lattice hydrogen concentration. This failure locus is treated as a unique material property for the given steel and heat treatment condition. We conclude that the presence of lattice hydrogen increases the susceptibility to hydrogen embrittlement whereas trapped hydrogen has only a negligible effect. It is also found that the observed failure strength of hydrogen charged un-notched bars is less than the peak local stress within the notched geometries. Weakest link statistics are used to account for this stressed volume effect. © 2013 Elsevier Ltd.

FET ACTIVE SLOTLINE NOTCH ANTENNAS FOR QUASI-OPTICAL POWER COMBINING

A new active antenna structure with applications in quasi-optical power combining is described. The active antenna combines a slotline FET oscillator with a notch antenna. The new structure was successfully used to create both E-plane and H-plane linear arrays as well as a 2-D array. Preliminary results of radiation patterns and the power combining efficiencies of the arrays are discussed.

Brittle-ductile transition in PP/EPDM blends: effect of notch radius

The toughness of polypropylene (PP)/ethylene-propylene-diene monomer (EPDM) blends was studied over wide ranges of EPDM content and temperature. In order to study the effect of notch radius (R), the toughness of the samples with different notch radii was determined from Izod impact test. The results showed that both toughness and brittle-ductile transition (BDT) of the blends were a function of R, respectively. At test temperatures, the toughness tended to decrease with increasing 1/R for various PP/EPDM blends. Moreover, the brittle-ductile transition temperature (T-BT) increased with increasing 1/R, whereas the critical interparticle distance (IDc) reduced with increasing 1/R. Finally, it was found that the different curves of IDc versus test temperature (T) for different notches reduced down to a master curve if plotting IDc versus T-BT(m)-T, where T-BT(m) was the T-BT of PP itself for a given notch, indicating that T-BT(m)-T was a more universal parameter that determined the BDT of polymers. This conclusion was well in agreement with the theoretical prediction.

Dynamics of Delta/Notch signaling on endomesoderm segregation in the sea urchin embryo.

Endomesoderm is the common progenitor of endoderm and mesoderm early in the development of many animals. In the sea urchin embryo, the Delta/Notch pathway is necessary for the diversification of this tissue, as are two early transcription factors, Gcm and FoxA, which are expressed in mesoderm and endoderm, respectively. Here, we provide a detailed lineage analysis of the cleavages leading to endomesoderm segregation, and examine the expression patterns and the regulatory relationships of three known regulators of this cell fate dichotomy in the context of the lineages. We observed that endomesoderm segregation first occurs at hatched blastula stage. Prior to this stage, Gcm and FoxA are co-expressed in the same cells, whereas at hatching these genes are detected in two distinct cell populations. Gcm remains expressed in the most vegetal endomesoderm descendant cells, while FoxA is downregulated in those cells and activated in the above neighboring cells. Initially, Delta is expressed exclusively in the micromeres, where it is necessary for the most vegetal endomesoderm cell descendants to express Gcm and become mesoderm. Our experiments show a requirement for a continuous Delta input for more than two cleavages (or about 2.5 hours) before Gcm expression continues in those cells independently of further Delta input. Thus, this study provides new insights into the timing mechanisms and the molecular dynamics of endomesoderm segregation during sea urchin embryogenesis and into the mode of action of the Delta/Notch pathway in mediating mesoderm fate.

Functional Variants in Notch Pathway Genes NCOR2, NCSTN, and MAML2 Predict Survival of Patients with Cutaneous Melanoma.

BACKGROUND: The Notch signaling pathway is constitutively activated in human cutaneous melanoma to promote growth and aggressive metastatic potential of primary melanoma cells. Therefore, genetic variants in Notch pathway genes may affect the prognosis of cutaneous melanoma patients. METHODS: We identified 6,256 SNPs in 48 Notch genes in 858 cutaneous melanoma patients included in a previously published cutaneous melanoma genome-wide association study dataset. Multivariate and stepwise Cox proportional hazards regression and false-positive report probability corrections were performed to evaluate associations between putative functional SNPs and cutaneous melanoma disease-specific survival. Receiver operating characteristic curve was constructed, and area under the curve was used to assess the classification performance of the model. RESULTS: Four putative functional SNPs of Notch pathway genes had independent and joint predictive roles in survival of cutaneous melanoma patients. The most significant variant was NCOR2 rs2342924 T>C (adjusted HR, 2.71; 95% confidence interval, 1.73-4.23; Ptrend = 9.62 × 10(-7)), followed by NCSTN rs1124379 G>A, NCOR2 rs10846684 G>A, and MAML2 rs7953425 G>A (Ptrend = 0.005, 0.005, and 0.013, respectively). The receiver operating characteristic analysis revealed that area under the curve was significantly increased after adding the combined unfavorable genotype score to the model containing the known clinicopathologic factors. CONCLUSIONS: Our results suggest that SNPs in Notch pathway genes may be predictors of cutaneous melanoma disease-specific survival. IMPACT: Our discovery offers a translational potential for using genetic variants in Notch pathway genes as a genotype score of biomarkers for developing an improved prognostic assessment and personalized management of cutaneous melanoma patients.

Docetaxel Resistance in Prostate Cancer: Taking It Up a Notch.

Notch signaling is implicated in prostate cancer progression and docetaxel resistance. Cui and colleagues describe the additive efficacy and mechanisms of a γ-secretase inhibitor, PF-03084014, and docetaxel in preclinical models of prostate cancer, suggesting the need for further clinical development of Notch pathway modulators in men with metastatic prostate cancer.

Co-regulation of Gremlin and Notch signalling in diabetic nephropathy

Diabetic nephropathy is currently the leading cause of end-stage renal disease worldwide, and occurs in approximately one third of all diabetic patients. The molecular pathogenesis of diabetic nephropathy has not been fully characterized and novel mediators and drivers of the disease are still being described. Previous data from our laboratory has identified the developmentally regulated gene Gremlin as a novel target implicated in diabetic nephropathy in vitro and in vivo. We used bioinformatic analysis to examine whether Gremlin gene sequence and structure could be used to identify other genes implicated in diabetic nephropathy. The Notch ligand Jagged1 and its downstream effector, hairy enhancer of split-1 (Hes1), were identified as genes with significant similarity to Gremlin in terms of promoter structure and predicted microRNA binding elements. This led us to discover that transforming growth factor-beta (TGFß1), a primary driver of cellular changes in the kidney during nephropathy, increased Gremlin, Jagged1 and Hes1 expression in human kidney epithelial cells. Elevated levels of Gremlin, Jagged1 and Hes1 were also detected in extracts from renal biopsies from diabetic nephropathy patients, but not in control living donors. In situ hybridization identified specific upregulation and co-expression of Gremlin, Jagged1 and Hes1 in the same tubuli of kidneys from diabetic nephropathy patients, but not controls. Finally, Notch pathway gene clustering showed that samples from diabetic nephropathy patients grouped together, distinct from both control living donors and patients with minimal change disease. Together, these data suggest that Notch pathway gene expression is elevated in diabetic nephropathy, co-incident with Gremlin, and may contribute to the pathogenesis of this disease.

Jagged/Notch signalling is required for a subset of TGFβ1 responses in human kidney epithelial cells.

The Jagged/Notch pathway has been implicated in TGFß1 responses in epithelial cells in diabetic nephropathy and other fibrotic conditions in vivo. Here, we identify that Jagged/Notch signalling is required for a subset of TGFß1-stimulated gene responses in human kidney epithelial cells in vitro. TGFß1 treatment of HK-2 and RPTEC cells for 24 h increased Jagged1 (a Notch ligand) and Hes1 (a Notch target) mRNA. This response was inhibited by co-incubation with Compound E, an inhibitor of ?-secretase (GSI), an enzyme required for Notch receptor cleavage and transcription regulation. In both cell types, TGFß1-responsive genes associated with epithelial–mesenchymal transition such as E-cadherin and vimentin were also affected by ?-secretase inhibition, but other TGFß1 targets such as connective tissue growth factor (CTGF) and thrombospondin-1 (THBS1) were not. TGFß1-induced changes in Jagged1 expression preceded EMT-associated gene changes, and co-incubation with GSI altered TGFß1-induced changes in cell shape and cytoskeleton. Transfection of cells with the activated, cleaved form of Notch (NICD) triggered decreased expression of E-cadherin in the absence of TGFß1, but did not affect a-smooth muscle actin expression, suggesting differential requirements for Notch signalling within the TGFß1-responsive gene subset. Increased Jagged1 expression upon TGFß1 exposure required Smad3 signalling, and was also regulated by PI3K and ERK. These data suggest that Jagged/Notch signalling is required for a subset of TGFß1-responsive genes, and that complex signalling pathways are involved in the crosstalk between TGFß1 and Notch cascades in kidney epithelia.


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