Using competition assays to quantitatively model cooperative binding by transcription factors and other ligands.

BACKGROUND: The affinities of DNA binding proteins for target sites can be used to model the regulation of gene expression. These proteins can bind to DNA cooperatively, strongly impacting their affinity and specificity. However, current methods for measuring cooperativity do not provide the means to accurately predict binding behavior over a wide range of concentrations. METHODS: We use standard computational and mathematical methods, and develop novel methods as described in Results. RESULTS: We explore some complexities of cooperative binding, and develop an improved method for relating in vitro measurements to in vivo function, based on ternary complex formation. We derive expressions for the equilibria among the various complexes, and explore the limitations of binding experiments that model the system using a single parameter. We describe how to use single-ligand binding and ternary complex formation in tandem to determine parameters that have thermodynamic relevance. We develop an improved method for finding both single-ligand dissociation constants and concentrations simultaneously. We show how the cooperativity factor can be found when only one of the single-ligand dissociation constants can be measured. CONCLUSIONS: The methods that we develop constitute an optimized approach to accurately model cooperative binding. GENERAL SIGNIFICANCE: The expressions and methods we develop for modeling and analyzing DNA binding and cooperativity are applicable to most cases where multiple ligands bind to distinct sites on a common substrate. The parameters determined using these methods can be fed into models of higher-order cooperativity to increase their predictive power

Data-driven personalisation and the law - a primer: collective interests engaged by personalisation in markets, politics and law

Interdisciplinary Workshop on â��Data-Driven Personalisation in Markets, Politics and Law' on 28 June 2019Southampton Law School will be hosting an interdisciplinary workshop on the topic of â��Data-Driven Personalisation in Markets, Politics and Law' on Friday 28 June 2019, which will explore the pervasive and growing phenomenon of â��personalisationâ�� â�� from behavioural advertising in commerce and micro-targeting in politics, to personalised pricing and contracting and predictive policing and recruitment. This is a huge area which touches upon many legal disciplines as well as social science concerns and, of course, computer science and mathematics. Within law, it goes well beyond data protection law, raising questions for criminal law, consumer protection, competition and IP law, tort law, administrative law, human rights and anti-discrimination law, law and economics as well as legal and constitutional theory. Weâ��ve written a position paper, https://eprints.soton.ac.uk/428082/1/Data_Driven_Personalisation_and_the_Law_A_Primer.pdf which is designed to give focus and structure to a workshop that we expect will be strongly interdisciplinary, creative, thought-provoking and entertaining. We like to hear your thoughts! Call for papers! Should you be interested in disagreeing, elaborating, confirming, contradicting, dismissing or just reflecting on anything in the paper and present those ideas at the workshop, send us an abstract by Friday 5 April 2019 (Ms Clare Brady [email protected] ). We aim to publish an edited popular law/social science book with the most compelling contributions after the workshop.Prof Uta Kohl, Prof James Davey, Dr Jacob Eisler<br/

Rethinking Te Aro in the 1910s

Wellington's Te Aro neighbourhood is particularly notable for both its broad expanse of relatively flat land and for its rectilinear grid of streets and associated superblocks in a city otherwise known for its hills and irregular road system. Over the course of the nineteenth-century after the start of European settlement in 1840, the town acres within the superblocks of Te Aro were more intensively developed in myriad ways, resulting in a haphazard arrangement of worker dwellings, commercial premises, and industrial outfits aligned along largely private lanes and alleys. With the notable exception of the street grid, nearly all vestiges of this initial, Victorian-era development were progressively destroyed during the twentieth century. Although most of the architectural and urban reinvention of Te Aro did not occur until the decades following World War II, acknowledgment of the major factors that would ultimately contribute to this process - traffic congestion, the low quality of the existing building stock, and a strong shift away from residential functions - became more and more emphasised during the 1910s. A writer for the Evening Post in 1913 imagined the neighbourhood just seven years in the future: "the dingy wooden boxes on Te Aro Flat will have given place to handsome warehouses and shops and factories …The problem of traffic, already threatening trouble … is certainly a task for the ablest engineer nowadays to suggest a way out" (Autos "The Future" p 3). This degree of optimism for rapid change was quickly tempered by the realities of world war and, in retrospect, the 1910s can be interpreted as a period of incubation for ideas about architecture urban planning in Te Aro that would only come to fruition later in the century

Academic Council Meeting Agenda and Minutes, November 7, 1983

Agenda and minutes from the Wright State University Academic Council Meeting held on November 7, 1983

δ13C tracing of dissolved inorganic carbon sources in major world rivers

δ13C tracing of dissolved inorganic carbon sources in major world river