Effect of central and non-central frequency components on the quality of damage imaging

Accurate image reconstruction of damage through Lamb wave diffraction tomography (LWDT) requires substantial information of scatter field. This can be achieved using transducer network to collect the scatter field data. However, this requires a large number of transducers that creates logistical constraints for the practical applications of the technique. Various methods have been developed to improve the practicability of LWDT. One of the main approaches is to employ data at multiple frequencies within the bandwidth of the excitation signal. The objective of this study is to investigate the performance of using the data at non-central frequencies to reconstruct the damage image using LWDT. This provides an understanding on the influence of data at each individual frequency in the damage image reconstruction.In this paper, a series of numerical case studies with consideration of different damage sizes and shapes are carried out. Different non-central frequencies data is used to reconstruct the damage image. The results show that using the data at different non-central frequencies leads to different qualities of the reconstructed damage images. The quality of these reconstructed damage images are then compared to investigate the information contained of the data at each individual frequency. The study shows that the non-central frequencies data can provide additional information in the damage image reconstruction. Overall, the results of this study provide insights into the influences of the data at different frequencies, which is essential to advance the developments of the LWDT.Gnana Teja Pudipeddi, Ching-Tai Ng, Andrei Kotouso

A Short History of the Drug Receptor Concept

Humans have long used plant and animal extracts for their medicinal properties but until the end of the 19th century their actions were often explained in a speculative manner. The systematic study of drugs did not begin until the 1860s, and the concept of receptors as the target of their effects in the body only emerged at the end of the 19th century from the brilliant and independent studies of John Newport Langley (1852-1925) and Paul Ehrlich (1854-1915). This book address the people and the key discoveries that led to the development of the receptor concept and its impact on 20th-century medicine: A.J Clark in the 1930s, and later E.J Ariens and R.P Stephenson in the 1950s provided the quantitative basis of drug receptor occupancy theory. R.P Ahlquist's investigations gave rise to the proposal of receptor subtypes in 1948 and facilitated Sir James Black (and subsequently others) to apply the receptor concept to clinical therapy (beta blockers) in the mid 1960s. By the early 1980s, the first (acetylcholine) receptor had been isolated and cloned. Today, we recognize a large and diverse number of physiological receptors which can be delineated into 'receptor super-families' on the basis of their pharmacology and molecular properties. These receptors are now the focus of a multi-national, multi-billion dollar pharmaceutical industry. This book reveals that these successes were by no means foreseeable, since chance, coincidence, competition among scientists, and other factors played important roles in the history of the receptor concept

Detection of Fatigue Cracks in Train Structures Using Nonlinear Lamb Waves

1st International Workshop on High-Speed and Intercity Railways, IWHIR 2011, Shenzhen, Hong Kong, 19-22 July 2011Envisioning the rapid development of high-speed railway network worldwide but envisaging potential threats to the safe operation of the network due to continuous ageing of train structures, a fatigue damage detection technique for train structures was developed. For metal structures used in high-seeped trains, fatigue crack may take place under cyclic loads, causing unexpected accident. However inspection of fatigue damage can be a difficult task during the normal operation of the train using tradition nondestructive evaluation techniques. In this study, nonlinear Lamb waves were used to interrogate train structures. Higher-order harmonic wave fields were generated, to observe that under certain conditions the second harmonic was cumulative. The fatigue damage modulated the nonlinearity of the structure due to the plastic deformation or micro-cracks, influencing the cumulative character of the second harmonic Lamb wave. To quantify the degree of such cumulative second harmonic, a nonlinearity parameter was used. A short-time Fourier transformation-based signal processing was applied to the collected signals to extract the amplitudes of the first and second harmonics. Experiments on an aluminum plate containing fatigue damage validated the proposed method. The results indicated that the fatigue crack can break the cumulative character of the nonlinearity parameter whereby the fatigue damage can be detected. It is noteworthy that this method can be carried out without any baseline data or a benchmark structure, increasing the flexibility of the application.Department of Mechanical EngineeringRefereed conference pape

Abstract 4752: Selective inhibition of cancer metastasis with a novel small therapeutic molecule

Abstract Prostate cancer (PCa) is the second most common cause of cancer death in US males. Death is typically caused by metastasis. Naturally occurring isoflavanones have been reported to be a class of compounds that effectively inhibit PCa motility and metastasis. This led us to use these compounds as a synthetic scaffold starting point. By integrating fragment-based diversification synthesis with chemi-driven biological selection, we discovered novel small molecule therapeutics with increased selectivity and potent efficacy. We thereby efficiently synthesized a new class of bioactive compounds that inhibit cell motility in vitro and inhibit human PCa metastasis in a murine model at low nanomolar concentrations. Extensive investigations indicate high specificity at the molecular and cellular levels, and failed to identify toxicity, even at high doses administered over extended periods. Importantly, efficacy against several cancer types was also demonstrated. Target validation studies used our lead as a chemical probe, and point to inhibition of ATM/ATR interaction with specific substrate proteins as important. Together, these studies indicate that we have successfully discovered a novel compound, acting upon a novel pharmacologic target, which selectively inhibits human PCa metastasis. Taken with our favorable preclinical toxicological data, these findings support movement of our lead compound into early phase human trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4752. doi:1538-7445.AM2012-4752</jats:p

Abstract C177: Chemical-driven biological probing: Discovery of a novel antimetastatic drug.

Abstract Chemicals constitute richly informative probes, have high resolving potential and are able to uncover complex biological processes. Harnessing this potential provides an avenue for the discovery of new therapeutics that act via novel mechanisms. We focused these principles upon an intractable problem: cancer metastasis. We started with a chemical scaffold with broad bioactivity, with desirable drug-like properties and that would support synthetic diversification. Initially focusing upon human prostate cancer (PCa) we then coupled fragment-diversification and novel synthetic routes to upfront positive selection screens (inhibition of cell motility) and negative selection screens (cell toxicity) in an iterative fashion. We thereby efficiently synthesized a new class of bioactive compounds that inhibits systemic PCa metastasis at low nanomolar concentrations. Efficacy against other cancer types was demonstrated. Extensive investigations indicate high specificity and no toxicity. Target validation studies point to inhibition of protein-protein interaction motifs. Together, these studies support the notion that this approach is powerful, can be broadly applied across biological systems, and constitutes a paradigm. Specifically, they have led to the discovery of a novel acting drug that inhibits human cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C177.</jats:p