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您的检索式：作者名="Philippos C"
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| 1 | Giant hepatic hemangiomas: Diagnostic and therapeutic dilemmas 显示文摘 | Philippos C Bornman M John Terblanche C H | 1986 | Surgery1986，101，2： | 1 |
| 2 | Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial engagement显示文摘B-cell receptor signaling in response to membrane-bound antigen increases with antigen affinity,a process known as affinity discrimination.We use computational modeling to show that B-cell affinity discrimination requires that kinetic proofreading predominate over serial engagement.We find that if B-cell receptors become signaling-capable immediately upon antigen binding,which results in decreasing serial engagement as affinity increases,then increasing affinity can lead to weaker signaling.Rather,antigen must stay bound to B-cell receptors for a threshold time of several seconds before becoming signaling-capable,a process similar to kinetic proofreading.This process overcomes the loss in serial engagement due to increasing antigen affinity,and replicates the monotonic increase in B-cell signaling with increasing affinity that has been observed in B-cell activation experiments.This finding matches well with the experimentally observed time(,20 s)required for the B-cell receptor signaling domains to undergo antigen and lipid raft-mediated conformational changes that lead to Src-family kinase recruitment.We hypothesize that the physical basis for a threshold time of antigen binding might lie in the formation timescale of B-cell receptor dimers.The time required for dimer formation decreases with increasing antigen affinity,thereby resulting in shorter threshold antigen binding times as affinity increases.Such an affinity-dependent kinetic proofreading requirement results in affinity discrimination very similar to that observed in biological experiments.B-cell affinity discrimination is critical to the process of affinity maturation and the production of high-affinity antibodies,and thus our results have important implications in applications such as vaccine design. | Philippos K Tsourkas Wanli Liu Somkanya C Das Susan K Pierce Subhadip Raychaudhuri | 2012 | Cellular & Molecular Immunology2012，9，1： | 0 |
| 3 | Comparison of next generation sequencing-based and methylated DNA immunoprecipitation-based approaches for fetal aneuploidy non-invasive prenatal testing显示文摘Over the past few years, many researchers have attempted to develop non-invasive prenatal testing methods in order to investigate the genetic status of the fetus. The aim is to avoid invasive procedures such as chorionic villus and amniotic fluid sampling, which result in a significant risk for pregnancy loss. The discovery of cell free fetal DNA circulating in the maternal blood has great potential for the development of non-invasive prenatal testing(NIPT) methodologies. Such strategies have been successfully applied for the determination of the fetal rhesus status and inherited monogenic disease but the field of fetal aneuploidy investigation seems to be more challenging. The main reason for this is that the maternal cell free DNA in the mother's plasma is far more abundant, and because it is identical to half of the corresponding fetal DNA. Approaches developed are mainly based on next generation sequencing(NGS) technologies and epigenetic genetic modifications, such as fetal-maternal DNA differential methylation. At present, genetic services for non-invasive fetal aneuploidy detection are offered using NGS-based approaches but, for reasons that are presented herein, they still serve as screening tests which are not readily accessed by the majority of couples. Here we discuss the limitations of both strategies for NIPT and the future potential of the methods developed. | Georgia Christopoulou Elisavet A Papageorgiou Philippos C Patsalis Voula Velissariou | 2015 | World Journal of Medical Genetics2015，5，2： | 0 |
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