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Neutralizing the EGF receptor in glioblastoma cells stimulates cell migration by activating uPAR-initiated cell signaling.
In glioblastoma (GBM), the EGF receptor (EGFR) and Src family kinases (SFKs) contribute to an aggressive phenotype. EGFR may be targeted therapeutically; however, resistance to EGFR-targeting drugs such as Erlotinib and Gefitinib develops quickly. In many GBMs, a truncated form of the EGFR (EGFRvIII) is expressed. Although EGFRvIII is constitutively active and promotes cancer progression, its activity is attenuated compared with EGF-ligated wild-type EGFR, suggesting that EGFRvIII may function together with other signaling receptors in cancer cells to induce an aggressive phenotype. In this study, we demonstrate that in EGFRvIII-expressing GBM cells, the urokinase receptor (uPAR) functions as a major activator of SFKs, controlling phosphorylation of downstream targets, such as p130Cas and Tyr-845 in the EGFR in vitro and in vivo. When EGFRvIII expression in GBM cells was neutralized, either genetically or by treating the cells with Gefitinib, paradoxically, the cells demonstrated increased cell migration. The increase in cell migration was explained by a compensatory increase in expression of urokinase-type plasminogen activator, which activates uPAR-dependent cell signaling. GBM cells that were selected for their ability to grow in vivo in the absence of EGFRvIII also demonstrated increased cell migration, due to activation of the uPAR signaling system. The increase in GBM cell migration, induced by genetic or pharmacologic targeting of the EGFR, was blocked by Dasatinib, highlighting the central role of SFKs in uPAR-promoted cell migration. These results suggest that compensatory activation of uPAR-dependent cell signaling, in GBM cells treated with targeted therapeutics, may adversely affect the course of the disease by promoting cell migration, which may be associated with tumor progression
Interpreting DNA mixtures with relatives of a missing suspect
Recent advances in DNA profiling have been proven extremely useful for forensic human identification. DNA mixtures are commonly found in serious crimes such as rape as well as voluminous crimes like theft. In this paper, one general formula is obtained for the evaluation of DNA mixtures when the suspect is unavailable for typing, but one maternal and one paternal relatives of the suspect are typed instead. In principle, closer relatives of the suspect will provide more genetic information on the genotype of the unavailable suspect. The effect of the relatives' DNA profiles on the interpretation of DNA mixtures is illustrated with case example. © 2011 IEEE.published_or_final_versionThe 1st International Conference on Remote Sensing, Environment and Transportation Engineering (RSETE 2011), Nanjing, China, 24-26 June 2011. In Proceedings of the 1st RSETE, 2011, p. 7649-765
An empirical comparison between direct and indirect test result checking approaches
The SOQUA 2006 Workshop was held in conjunction with the 14th ACM SIGSOFT International Symposium on Foundations of Software Engineering (SIGSOFT 2006/FSE-14) ACM Press, New York, NY.An oracle on software testing is a mechanism for checking whether the system under test has behaved correctly for any executions. In some situations, oracles are unavailable or too expensive to apply. This is known as the oracle problem. It is crucial to develop techniques to address it, and metamorphic testing (MT) was one of such proposals. This paper conducts a controlled experiment to investigate the cost effectiveness of using MT by 38 testers on three open-source programs. The fault detection capability and time cost of MT are compared with the popular assertion checking method. Our results show that MT is cost-efficient and has potentials for detecting more faults than the assertion checking method. Copyright 2006 ACM.preprintThis research is supported in part by a grant of the Research Grants
Council of Hong Kong (project no. HKU 7145/04E), a grant of City
University of Hong Kong and a grant of The University of Hong Kong
NEW INTERPRETATION ON EMG CHARATERISTICS OF SPASTIC CEREBRAL PALSY DURING A REHABILITATIVE WALKING EXERCISE
The purpose of this study is to interpret the EMG characteristics of spastic cerebral palsy children during walking with power spectrum analysis. The EMG signal of 16 cerebral palsy patients (GP) and 18 age matched control (Normal) were collected during several walking trial. It was found that our CP participants ha:d significantly longer firing duration and higher median frequency within a gait cycle for al.l the muscle groups, these indicated of the EMG characteristics of in the spastic muscles. In addition, the CP produced significantly smaller root mean square value in tibialis anterior muscle than the normal; this indicated that the tibialis anterior muscle of GP was weakness or atrophy. Because of good objectivity and reproducibility, employing RMS and the MF could :be suggested to be the parameters for further gait studies
The impact of aging on ciliary function and ultrastructive in human respiratory epithelium
Session - Respiratory & Critical Care Medicine: no. G-RC-8published_or_final_versio
The impact of aging on ciliary function and ultrastructive in human respiratory epithelium
Session - Respiratory & Critical Care Medicine: no. G-RC-8published_or_final_versio
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