Fracture criteria for discontinuously reinforced metal matrix composites

Summarized is the progress achieved during the period September 16, 1987 to August 15, l988 on NASA Grant NAG1-724, Fracture Criteria for Discontinuously Reinforced Metal Matrix Composites. Appended are copies of three manuscripts prepared under NASA funding during the performance period

Fracture criteria for discontinuously reinforced metal matrix composites

The effect of sample configuration on the details of initial crack propagation in discontinuously whisker reinforced aluminum metal matrix composites was investigated. Care was taken to allow direct comparison of fracture toughness values utilizing differing sample configurations and orientations, holding all materials variables constant, e.g., extrusion ration, heat treatment, and chemistry

Clinical disease course and survival outcomes following disease recurrence in adenoid cystic carcinoma with and without NOTCH signaling pathway activation.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare salivary cancer. The highest rates of disease recurrence are in patients with NOTCH pathway activation, reported in up to 20%. Novel drugs targeting NOTCH signaling are under investigation in the recurrent/metastatic (R/M) setting. To understand their clinical utility, there is an urgent need to better characterize the disease course and outcomes following current standard of care treatment. METHODS: 120 patients with R/M ACC underwent clinical review at a single UK Cancer Centre. Patients were retrospectively assessed for tumor NOTCH pathway activation using next generation sequencing (NGS) targeting NOTCH1/2/3 genes and/or NOTCH1 intra-cellular domain (NICD1) immunohistochemistry. Demographic and treatment data were extracted from the clinical notes. Kaplan-Meier survival analysis was performed using log rank test. RESULTS: NOTCH pathway activation was identified in 13/120 patients (11 %). In 12/101 patients analyzed by NGS, NOTCH1/3 activating somatic mutations were identified, and a further patient was identified with NICD1 diffuse nuclear staining in whom NGS testing was not possible. Patients with NOTCH pathway activation had shorter median RFS (1.1 vs 3.4 years, p = 0.2032) and significantly reduced median OS from diagnosis (4.0 vs 16.3 years, p < 0.0001). There was significantly reduced median OS from time of disease recurrence/metastasis (1.9 vs 9.6 years, p < 0.0001). CONCLUSION: This study clearly demonstrates a reduction in OS from time of first confirmed disease recurrence/metastasis for patients with NOTCH pathway activated ACC. This provides support for developing new drugs for this sub-group of patients, for whom clinical outcomes are significantly worse and effective treatments are lacking

What lies beneath? Interdisciplinary outcomes of the ANDRILL Coulman High Project site surveys on the Ross Ice Shelf

Author Posting. © The Oceanography Society, 2012. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 25, no. 3 (2012): 84-89, doi:10.5670/oceanog.2012.79.Extensive field operations were conducted on the northwestern Ross Ice Shelf in Antarctica from November 2010 through January 2011. A significant amount of equipment, supplies, and people safely traversed from McMurdo Station to establish a series of combined United States–New Zealand field camps at locations northeast of Ross Island. The ANDRILL (ANtarctic geological DRILLing) hot water drill system was used to melt multiple access holes through the ice shelf at each site to deploy a variety of sediment coring tools, cameras, and oceanographic instruments, as well as a remotely operated vehicle to characterize the ice shelf and sub-ice environment. These studies will contribute to future proposed geological drilling as part of the ANDRILL Coulman High Project.This work is funded by US NSF-OPP Grant ANT-0838914 and by the NZ Foundation for Research, Science and Technology

Methylation patterns in serum DNA for early identification of disseminated breast cancer

BACKGROUND: Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need. Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of substantial quantities of background DNA. METHODS: We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer (which will or will not lead to death), respectively, as primary endpoints. RESULTS: A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs) (HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25% of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC. CONCLUSIONS: Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become clinically apparent

High-Fidelity 3D-Nanoprinting via Focused Electron Beams: Computer-Aided Design (3BID)

Currently, there are few techniques that allow true 3D-printing on the nanoscale. The most promising candidate to fill this void is focused electron-beam-induced deposition (FEBID), a resist-free, nanofabrication compatible, direct-write method. The basic working principles of a computer-aided design (CAD) program (3BID) enabling 3D-FEBID is presented and simultaneously released for download. The 3BID capability significantly expands the currently limited toolbox for 3D-nanoprinting, providing access to geometries for optoelectronic, plasmonic, and nanomagnetic applications that were previously unattainable due to the lack of a suitable method for synthesis. The CAD approach supplants trial and error toward more precise/accurate FEBID required for real applications/device prototyping.J.D.F., R.W., P.D.R., A.F.P., and H.P. acknowledge that the creation of the CAD environment was conducted at the Center for Nanophase Materials Sciences, which is a DOE Office of Science User Facility. R.W. and H.P. gratefully acknowledge the valuable support provided from Prof. Dr. Ferdinand Hofer. R.W. and H.P. also acknowledge financial support by the COST action CELINA (Nr. CM1301), EUROSTARS project TRIPLE-S (Nr. E! 8213), the bmvit exchange program, and FFG—Production of the Future project SENTINEL (Nr. 850652). L.S., D.S.H., and A.F.P. acknowledge funding from EPSRC, grant numbers EP/M008517/1 and EP/L015978/1, and from the Winton Program for the Physics of Sustainability

Analysis of reflex modulation with a biologically realistic neural network

In this study, a neuromusculoskeletal model was built to give insight into the mechanisms behind the modulation of reflexive feedback strength as experimentally identified in the human shoulder joint. The model is an integration of a biologically realistic neural network consisting of motoneurons and interneurons, modeling 12 populations of spinal neurons, and a one degree-of-freedom musculoskeletal model, including proprioceptors. The model could mimic the findings of human postural experiments, using presynaptic inhibition of the Ia afferents to modulate the feedback gains. In a pathological case, disabling one specific neural connection between the inhibitory interneurons and the motoneurons could mimic the experimental findings in complex regional pain syndrome patients. It is concluded that the model is a valuable tool to gain insight into the spinal contributions to human motor control. Applications lay in the fields of human motor control and neurological disorders, where hypotheses on motor dysfunction can be tested, like spasticity, clonus, and tremor