Dealing with the Likelihood of Failure over the Long-Term: Adaptive Policy Design under Uncertainty

10.2139/ssrn.23943481-2

The Achilles Heel of Governance: Critical Capacity Deficits and Their Role in Governance Failures

10.2139/ssrn.24231661-2

A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability

Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and other neurological disorders; however, neither the link between type II mGluRs and PI3K, nor the role of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability

Patching vs Packaging: Complementary Effects, Goodness of Fit, Degrees of Freedom and Intentionality in Policy ...

10.2139/ssrn.22733421-2

Supply of Policy and Management Consultancies to Canadian Federal Departments: New Evidence on Contract Size, Type and Structure

10.2139/ssrn.22484021-3

The Politics of Policy Anomalies: Bricolage and the Hermeneutics of Paradigms

10.2139/ssrn.230045582183-20

The left atrial appendage in health and disease

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmiaand results in significant morbidity and mortality. The left atrial appendage (LAA), a small embryonic remnant of the left atrium (LA), has been shown to play a key role in the pathophysiology of AF-related stroke and thromboembolism. As a consequence the LAA, in spite of its meagre size, has been described as ‘our most lethal human attachment’. Despite being a recognised harbinger of disease, the LAA has also been shown to play an important role in health. This review seeks to address our current understanding of this vital structure in both health and disease states

Design and Scaling up of Policy Experiments and Pilots: Lessons for the Water Sector

14351-2