Size dependent strengthening in particle reinforced aluminium

The tensile behaviour of composites produced by infiltrating ceramic particle beds with high purity (99.99%) At is studied as a function of reinforcement size and chemistry (Al2O3 and B4C). The yield stress is higher in composites containing B4C particles, increasing with decreasing interparticle distance in both composite systems. The flow stress of the composites, when corrected for damage, displays the same dependence on interparticle distance as the yield stress. The overall strain hardening exponent, however, is independent of the microstructural scale. These observations are rationalized based on the theory of geometrically necessary dislocations. (C) 2002 Acta Materialia Inc. Published by Elsevier Science Ltd. All rights reserved

Quantification of microdamage phenomena during tensile straining of high volume fraction particle reinforced aluminum

Particle reinforced composites are produced by infiltrating ceramic particle beds with 99.99% Al. Resulting materials feature a relatively high volume fraction (40-55 vol. pet) of homogeneously distributed reinforcement. The evolution of damage during tensile straining of these composites is monitored using two indirect methods; namely by tracking changes in density and in Young's modulus. Identification and quantification of the active damage mechanisms is conducted on polished sections of failed tensile specimens: particle fracture and void formation in the matrix are the predominant damage micromechanisms in these materials. The damage parameter derived from the change in density at a given strain is found to be one to two orders of magnitude smaller than the parameter based on changes in Young's modulus. A simple micromechanical analysis inspired by the observed damage micromechanisms is used to correlate the two indirect measurements of damage. The predictions of this analysis are in good agreement with experiment. (C) 2001 Acta Materialia Inc. Published by Elsevier Science Ltd. AII rights reserved

Alumina-aluminum interpenetrating-phase composites with three-dimensional periodic architecture

Abstract Robotic deposition was used to create an alumina structure with three-dimensional periodicity and submillimeter feature size. Liquid metal infiltration of this structure resulted in an Al 2 O 3 -Al interpenetrating-phase composite exhibiting low thermal expansion and high compressive strength

A novel small molecule inhibitor of MRCK prevents radiation-driven invasion in glioblastoma

Glioblastoma (GBM) is an aggressive and incurable primary brain tumor that causes severe neurological, cognitive, and psychological symptoms. Symptoms are caused and exacerbated by the infiltrative properties of GBM cells, which enable them to pervade the healthy brain and disrupt normal function. Recent research has indicated that, while radiotherapy (RT) remains the most effective component of multimodality therapy for GBM patients, it can provoke a more infiltrative phenotype in GBM cells that survive treatment. Here we demonstrate an essential role of the actin-myosin regulatory kinase myotonic dystrophy kinase-related CDC42- binding kinase (MRCK) in mediating the pro-invasive effects of radiation. MRCK-mediated invasion occurred via downstream signaling to effector molecules MYPT1 and MLC2. MRCK was activated by clinically relevant doses per fraction of radiation, and this activation was concomitant with an increase in GBM cell motility and invasion. Furthermore, ablation of MRCK activity either by RNAi or by inhibition with the novel small molecule inhibitor BDP-9066 prevented radiation-driven increases in motility both in vitro and in a clinically relevant orthotopic xenograft model of GBM. Crucially, treatment with BDP-9066 in combination with RT significantly increased survival in this model and markedly reduced infiltration of the contralateral cerebral hemisphere

Benefit of chemotherapy as part of treatment for HPV DNA-positive but p16-negative squamous cell carcinoma of the oropharynx

BACKGROUND: To determine (a) the cause of an improvement in survival from oropharyngeal squamous cell carcinoma (OSCC) in South East Scotland and (b) whether this improvement was human papillomavirus (HPV) and p16 subtype-dependent. METHODS: Clinicopathological characteristics and outcome data for patients referred with OSCC from 1999 to 2001 (Cohort-1) and 2003 to 2005 (Cohort-2) were obtained. Molecular HPV detection and immunohistochemistry for p16 were performed from paraffin blocks. RESULTS: Cohort-1 and Cohort-2 contained 118 and 136 patients, respectively. Kaplan–Meier analysis revealed significantly improved survival in Cohort-2 (P<0.0001). Sub-classification according to HPV and p16 status revealed no improvement in survival in Class-I (HPV−ve/p16−ve; 47 patients) or Class-III (HPV+ve/p16+ve; 77 patients). However in Class-II (HPV+ve/p16−ve; 56 patients) an increase in 5-year cause-specific survival from 36% in Cohort-1 to 73% in Cohort-2 was detected (P=0.0001). Proportional hazards analysis of 217 patients treated radically demonstrated that significant variables were p16 (P<0.0001), N stage (P=0.0006) and cohort (P=0.0024). Removing cohort from the variables offered to the model showed that, whereas p16 (P<0.0001) and N stage (P=0.0016) remain significant, chemotherapy (P=0.0163) and T stage (P=0.0139) are now significant. This suggests that much of the cohort effect is due to the higher use of chemotherapy in the second cohort. CONCLUSION: These data suggest that HPV+ve/p16−ve patients constitute a separate subclass of OSCC who may particularly benefit from chemotherapy. They imply that p16 status cannot be considered a surrogate for HPV status, and those trials to de-escalate treatment in HPV+ve OSCC should take p16 status into account

A new and facile synthesis of N-Benzyl-N’-acylureas via reaction of dibenzoylhydrazine carboxamide and benzylamines

Herein, we report a new method of synthesis of N-acylureas (E1-5) via reaction of dibenzoylhydrazine carboxamide (N,2-bis(4-methoxybenzoyl)hydrazine-1-carboxamide) (C) and various benzylamines. Preparation of dibenzoylhydrazine carboxamide was performed by the treatment of 5,6-diaryl-3-methylthio-1,2,4-triazine (B) with Oxone which leads to oxidation and triazine ring cleavage in high yield (82%). Five benzylamine derivatives containing different electron donating and withdrawing substituents were used in this study. Yields for the conversion of dibenzoylhydrazine carboxamide (C) to N-acylureas (E1-5) were in the range of 40-55%. The structures of the intermediates and final products were characterized and confirmed by NMR, mass spectrometry and single-crystal X-ray crystallography