Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.

BH3 mimetics such as ABT-737 and navitoclax bind to the BCL-2 family of proteins and induce apoptosis through the intrinsic apoptosis pathway. There is considerable variability in the sensitivity of different cells to these drugs. Understanding the molecular basis of this variability will help to determine which patients will benefit from these drugs. Furthermore, this understanding aids in the design of rational strategies to increase the sensitivity of cells which are otherwise resistant to BH3 mimetics. We discuss how the expression of BCL-2 family proteins regulates the sensitivity to ABT-737. One of these, MCL-1, has been widely described as contributing to resistance to ABT-737 which might suggest a poor response in patients with cancers that express levels of MCL-1. In some cases, resistance to ABT-737 conferred by MCL-1 is overcome by the expression of pro-apoptotic proteins that bind to apoptosis inhibitors such as MCL-1. However, the distribution of the pro-apoptotic proteins amongst the various apoptosis inhibitors also influences sensitivity to ABT-737. Furthermore, the expression of both pro- and anti-apoptotic proteins can change dynamically in response to exposure to ABT-737. Thus, there is significant complexity associated with predicting response to ABT-737. This provides a paradigm for the multiplicity of intricate factors that determine drug sensitivity which must be considered for the full implementation of personalized medicine

Software Product and Process Assessment Through Profile-Based Evaluation

Software entities (software products or processes) are characterized by many attributes, each one in its turn can be measured by one or more measures. In several cases the software entities have to be evaluated as a whole, thus raising the problem of aggregating measures to give an overall, single view on the software entity. This paper presents a method to aggregate measures, which works by comparing the product/process with predefined, ideal entities, or profiles. Profiles are defined starting from ranges of values on measures of attributes. The method is based on two main phases, namely definition of the evaluation model and application of the evaluation model. It is presented through a simplified case study that deals with evaluating the level of quality of an asset to decide whether to accept it in a reuse repository. A plausible way of how the method could be applied to process maturity assessment is also provided. The advantages of the method are that it allows using ordinal scales, while it deals explicitly with preferences expressed, implicitly or explicitly, by the evaluator.ou

Enhancing Software Engineering Education through Open Source Projects: Four Years of Students' Perspectives

This paper presents the results after four years of running of an instructional method that utilizes free/libre open source software (FLOSS) projects as tools for teaching software engineering in formal education. In the last four academic years, a total of 408 juniors majoring in Informatics (in a 4-year program) participated in the study, assuming the roles of requirements engineers, testers, developers, and designers/analysts. Students appreciated the benefits gained by the method and identified aspects that require further improvement. In the paper, we present (a) the details of our method, (b) students’ opinions as recorded through a questionnaire including both closed and open ended questions, and (c) conclusions on how the use of FLOSS projects can be applied, and be beneficial for the students

A New Method to Evaluate Software Artifacts against Predefined Profiles

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