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1.
Article in English | MEDLINE | ID: mdl-26960223

ABSTRACT

A three-dimensional generic hybrid model is developed for the simulation of elastic waves in applications in Non- Destructive Evaluation that efficiently links different solution strategies but, crucially, is independent of the particular schemes employed. This is an important step forward in facilitating rapid and accurate large-scale simulations and this advances the twodimensional generic hybrid methodology recently developed by the authors. The hybrid model provides an efficient and effective tool for creating highly accurate simulations that model the wave propagation and scattering, enabling the interpretation of inspection data; the new methodology is verified against other numerical simulations. Furthermore, its deployment to simulate wave reflection from side-drilled holes, comparing the results with experimental measurements, provides a realistic demonstration as well as further validation.

2.
Article in English | MEDLINE | ID: mdl-26470042

ABSTRACT

Defects which possess rough surfaces greatly affect ultrasonic wave scattering behavior, usually reducing the magnitude of reflected signals. Understanding and accurately predicting the influence of roughness on signal amplitudes is crucial, especially in nondestructive evaluation (NDE) for the inspection of safety-critical components. An extension of Kirchhoff theory has formed the basis for many practical applications; however, it is widely recognized that these predictions are pessimistic because of analytical approximations. A numerical full-field modeling approach does not fall victim to such limitations. Here, a finite element (FE) modeling approach is used to develop a realistic methodology for the prediction of expected backscattering from rough defects. The ultrasonic backscatter from multiple rough surfaces defined by the same statistical class is calculated for normal and oblique incidence. Results from FE models are compared with Kirchhoff theory predictions and experimental measurements to establish confidence in the new approach. At lower levels of roughness, excellent agreement is observed between Kirchhoff theory, FE, and experimental data, whereas at higher values, the pessimism of Kirchhoff theory is confirmed. An important distinction is made between the total, coherent, and diffuse signals and it is observed, significantly, that the total signal amplitude is representative of the information obtained during an inspection. This analysis provides a robust basis for a less sensitive, yet safe, threshold for inspection of rough defects.

3.
Cell Rep ; 12(12): 2111-20, 2015 Sep 29.
Article in English | MEDLINE | ID: mdl-26365189

ABSTRACT

MB-003, a plant-derived monoclonal antibody cocktail used effectively in treatment of Ebola virus infection in non-human primates, was unable to protect two of six animals when initiated 1 or 2 days post-infection. We characterized a mechanism of viral escape in one of the animals, after observation of two clusters of genomic mutations that resulted in five nonsynonymous mutations in the monoclonal antibody target sites. These mutations were linked to a reduction in antibody binding and later confirmed to be present in a viral isolate that was not neutralized in vitro. Retrospective evaluation of a second independent study allowed the identification of a similar case. Four SNPs in previously identified positions were found in this second fatality, suggesting that genetic drift could be a potential cause for treatment failure. These findings highlight the importance selecting different target domains for each component of the cocktail to minimize the potential for viral escape.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Antibodies, Viral/administration & dosage , Ebolavirus/immunology , Hemorrhagic Fever, Ebola/virology , Immune Evasion/genetics , Immunization, Passive , Amino Acid Sequence , Animals , Antibodies, Monoclonal/biosynthesis , Antibodies, Neutralizing/administration & dosage , Antibodies, Neutralizing/biosynthesis , Antibodies, Viral/biosynthesis , Base Sequence , Ebolavirus/genetics , Ebolavirus/pathogenicity , Epitopes/chemistry , Epitopes/immunology , Hemorrhagic Fever, Ebola/immunology , Hemorrhagic Fever, Ebola/mortality , Hemorrhagic Fever, Ebola/prevention & control , Humans , Macaca mulatta , Molecular Sequence Data , Mutation , Protein Binding , Recombinant Proteins/administration & dosage , Recombinant Proteins/biosynthesis , Retrospective Studies , Survival Analysis , Nicotiana/genetics , Virus Replication
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