A three-level schema architecture for the conceptual design of web-based information systems: from web-data management to integrated web-data and web-process management

It has been recognized only recently that, like databases, web sites need models and schemes. Data-intensive web sites are best developed using a multi-level design approach proceeding from data design via navigation design to web-page design. Modern web-based information systems are no longer static in nature. Rather they are dynamic. Besides querying, they support workflow tasks and e-commerce transactions. The design of such systems needs to consider the underlying business process next to the data. Their integrated design has been mainly treated in an ad-hoc way so far. In this paper, we present a three-level schema architecture for the conceptual design of dynamic web-based information systems. We employ an object-oriented approach that integrates data and process management and complements previous approaches for the design of data-intensive web sites. This revised version was published online in August 2006 with corrections to the Cover Date.     

Quantitative Analysis of Mutant Subclones in Chronic Myeloid Leukemia: Comparison of Different Methodological Approaches

Identification and quantitative monitoring of mutant BCR-ABL1 subclones displaying resistance to tyrosine kinase inhibitors (TKIs) have become important tasks in patients with Ph-positive leukemias. Different technologies have been established for patient screening. Various next-generation sequencing (NGS) platforms facilitating sensitive detection and quantitative monitoring of mutations in the ABL1-kinase domain (KD) have been introduced recently, and are expected to become the preferred technology in the future. However, broad clinical implementation of NGS methods has been hampered by the limited accessibility at different centers and the current costs of analysis which may not be regarded as readily affordable for routine diagnostic monitoring. It is therefore of interest to determine whether NGS platforms can be adequately substituted by other methodological approaches. We have tested three different techniques including pyrosequencing, LD (ligation-dependent)-PCR and NGS in a series of peripheral blood specimens from chronic myeloid leukemia (CML) patients carrying single or multiple mutations in the BCR-ABL1 KD. The proliferation kinetics of mutant subclones in serial specimens obtained during the course of TKI-treatment revealed similar profiles via all technical approaches, but individual specimens showed statistically significant differences between NGS and the other methods tested. The observations indicate that different approaches to detection and quantification of mutant subclones may be applicable for the monitoring of clonal kinetics, but careful calibration of each method is required for accurate size assessment of mutant subclones at individual time points.