Revisiting the 'Missing Middle' in English Sub-National Governance

In the light of the new Coalition Government’s proposed ‘rescaling’ of sub-national governance away from the regional level, it is an opportune time to re-consider the strength and weaknesses of the city or sub-regional approach to economic development and to search, once more, for the ‘missing middle’ in English Governance. In this context, the article initially assesses the case for city or sub regions as tiers of economic governance, before examining the lessons to be learnt from the experiences of the existing city regions in the North East of England. It argues that while contemporary plans to develop Local Enterprise Partnerships (LEPs) can be usefully considered within the context of the emerging city regional developments under the previous Labour Governments, a number of important challenges remain, particularly in relation to ensuring accountable structures of governance, a range of appropriate functions, adequate funding, and comprehensive coverage across a variety of sub-regional contexts. While the proposals of the new Government create the necessary ‘space’ to develop sub-regional bodies and offer genuine opportunities for both city and county LEPs, the scale of the sub-regional challenge should not be underestimated, particularly given the context of economic recession and major reductions in the public sector

Ligand-Receptor Interactions

The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the interest of biologists to the kinetic and mechanical properties of cell membrane receptors. The aim of this review is to give a description of these advances that benefitted from a largely multidisciplinar approach

Force Measurements of TCR/pMHC Recognition at T Cell Surface

The rupture forces and adhesion frequencies of single recognition complexes between an affinity selected peptide/MHC complex and a TCR at a murine hybridoma surface were measured using Atomic Force Microscopy. When the CD8 coreceptor is absent, the adhesion frequency depends on the nature of the peptide but the rupture force does not. When CD8 is present, no effect of the nature of the peptide is observed. CD8 is proposed to act as a time and distance lock, enabling the shorter TCR molecule to bridge the pMHC and have time to finely read the peptide. Ultimately, such experiments could help the dissection of the sequential steps by which the TCR reads the peptide/MHC complex in order to control T cell activation