7 research outputs found
The Emergence and Development of Association Football: Influential Sociocultural Factors in Victorian Birmingham
This article explores the interdependent, complex sociocultural factors that facilitated the emergence and diffusion of football in Birmingham. The focus is the development of football in the city, against the backdrop of the numerous social changes in Victorian Birmingham. The aim is to fill a gap in the existing literature which seemingly overlooked Birmingham as a significant footballing centre, and the ‘ordinary and everyday’ aspects of the game’s early progression. Among other aspects, particular heed is paid to the working classes’ involvement in football, as previous literature has often focused on the middle classes and their influence on and participation in organized sport. As the agency of the working classes along with their mass participation and central role in the game’s development is unfolded, it is argued that far from being passive cultural beings, the working classes, from the beginnings, actively negotiated the development of their own emergent football culture
Protein–Ligand Crystal Structures Can Guide the Design of Selective Inhibitors of the FGFR Tyrosine Kinase
The design of compounds that selectively inhibit a single
kinase
is a significant challenge, particularly for compounds that bind to
the ATP site. We describe here how protein–ligand crystal structure
information was able both to rationalize observed selectivity and
to guide the design of more selective compounds. Inhibition data from
enzyme and cellular screens and the crystal structures of a range
of ligands tested during the process of identifying selective inhibitors
of FGFR provide a step-by-step illustration of the process. Steric
effects were exploited by increasing the size of ligands in specific
regions in such a way as to be tolerated in the primary target and
not in other related kinases. Kinases are an excellent target class
to exploit such approaches because of the conserved fold and small
side chain mobility of the active form