Implementation of Code Properties via Transducers

The FAdo system is a symbolic manipulator of formal language objects, implemented in Python. In this work, we extend its capabilities by implementing methods to manipulate transducers and we go one level higher than existing formal language systems and implement methods to manipulate objects representing classes of independent languages (widely known as code properties). Our methods allow users to define their own code properties and combine them between themselves or with fixed properties such as prefix codes, suffix codes, error detecting codes, etc. The satisfaction and maximality decision questions are solvable for any of the definable properties. The new online system LaSer allows one to query about a code property and obtain the answer in a batch mode. Our work is founded on independence theory as well as the theory of rational relations and transducers, and contributes with improved algorithms on these objects

PTEN status is a crucial determinant of the functional outcome of combined MEK and mTOR inhibition in cancer

Combined MAPK/PI3K pathway inhibition represents an attractive, albeit toxic, therapeutic strategy in oncology. Since PTEN lies at the intersection of these two pathways, we investigated whether PTEN status determines the functional response to combined pathway inhibition. PTEN (gene, mRNA, and protein) status was extensively characterized in a panel of cancer cell lines and combined MEK/mTOR inhibition displayed highly synergistic pharmacologic interactions almost exclusively in PTEN-loss models. Genetic manipulation of PTEN status confirmed a mechanistic role for PTEN in determining the functional outcome of combined pathway blockade. Proteomic analysis showed greater phosphoproteomic profile modification(s) in response to combined MEK/mTOR inhibition in PTEN- loss contexts and identified JAK1/STAT3 activation as a potential mediator of synergistic interactions. Overall, our results show that PTEN-loss is a crucial determinant of synergistic interactions between MAPK and PI3K pathway inhibitors, potentially exploitable for the selection of cancer patients at the highest chance of benefit from combined therapeutic strategies