Constructivism, constitutionalism and the EU's area of freedom security and justice post-Lisbon

This essay addresses the fundamental conceptual challenges which face the development of the Area of Freedom Security and Justice (AFSJ) in the post-Lisbon Treaty era. It argues that Onuf style constructivism is a valid lens with which to examine the development of the AFSJ to date, involving as it does the development of a shared understanding by practitioners, predominantly law enforcement and prosecution professionals, within the structures provided for them, in order to develop a completely new area of law and practice. While this approach will continue to need to be deployed in the development of further new operational areas, such as cybercrime, a new approach is now required, that of constitutionalism. A variety of forms of constitutionalism are then examined in order to establish their suitability as a mode of analysis for these developments.

A signaling visualization toolkit to support rational design of combination therapies and biomarker discovery: SiViT

Targeted cancer therapy aims to disrupt aberrant cellular signalling pathways. Biomarkers are surrogates of pathway state, but there is limited success in translating candidate biomarkers to clinical practice due to the intrinsic complexity of pathway networks. Systems biology approaches afford better understanding of complex, dynamical interactions in signalling pathways targeted by anticancer drugs. However, adoption of dynamical modelling by clinicians and biologists is impeded by model inaccessibility. Drawing on computer games technology, we present a novel visualisation toolkit, SiViT, that converts systems biology models of cancer cell signalling into interactive simulations that can be used without specialist computational expertise. SiViT allows clinicians and biologists to directly introduce for example loss of function mutations and specific inhibitors. SiViT animates the effects of these introductions on pathway dynamics, suggesting further experiments and assessing candidate biomarker effectiveness. In a systems biology model of Her2 signalling we experimentally validated predictions using SiViT, revealing the dynamics of biomarkers of drug resistance and highlighting the role of pathway crosstalk. No model is ever complete: the iteration of real data and simulation facilitates continued evolution of more accurate, useful models. SiViT will make accessible libraries of models to support preclinical research, combinatorial strategy design and biomarker discovery.