Doyne lecture 2016:intraocular health and the many faces of inflammation

Dogma for reasons of immune privilege including sequestration (sic) of ocular antigen, lack of lymphatic and immune competent cells in the vital tissues of the eye has long evaporated. Maintaining tissue and cellular health to preserve vision requires active immune responses to prevent damage and respond to danger. A priori the eye must contain immune competent cells, undergo immune surveillance to ensure homoeostasis as well as an ability to promote inflammation. By interrogating immune responses in non-infectious uveitis and compare with age-related macular degeneration (AMD), new concepts of intraocular immune health emerge. The role of macrophage polarisation in the two disorders is a tractable start. TNF-alpha regulation of macrophage responses in uveitis has a pivotal role, supported via experimental evidence and validated by recent trial data. Contrast this with the slow, insidious degeneration in atrophic AMD or in neovasular AMD, with the compelling genetic association with innate immunity and complement, highlights an ability to attenuate pathogenic immune responses and despite known inflammasome activation. Yolk sac-derived microglia maintains tissue immune health. The result of immune cell activation is environmentally dependent, for example, on retinal cell bioenergetics status, autophagy and oxidative stress, and alterations that skew interaction between macrophages and retinal pigment epithelium (RPE). For example, dead RPE eliciting macrophage VEGF secretion but exogenous IL-4 liberates an anti-angiogenic macrophage sFLT-1 response. Impaired autophagy or oxidative stress drives inflammasome activation, increases cytotoxicity, and accentuation of neovascular responses, yet exogenous inflammasome-derived cytokines, such as IL-18 and IL-33, attenuate responses

Variational Bayes and a Problem of Reliable Communication I: Finite Systems

This paper is the first in a two-part study of a variational Bayesian method and its application to a problem of reliable communication. The variational method expresses a Bayesian posterior distribution as the unique minimizer of a quantity dubbed apparent information. This has the same nature as the free energy of statistical mechanics. The minimum apparent information coincides with the full information of the observation. Reliable communication over an error prone channel can be achieved by the use of random block coding, as originally proposed by Shannon. The primary Bayesian problem in this context, is that of estimating the transmitted block from observations of the output of the channel. Scaling limits for the various information quantities are derived for this problem; these show that the primary problem undergoes a second-order phase transition, in a very precise sense, at the channel capacity; the code rate is shown to play the role of absolute temperature. Shannon's reliability function is recovered as the scaling limit of the full information of a secondary Bayesian problem, in which the channel noise and random code are estimated from the observation of a block decoding error. This secondary problem undergoes a third-order phase transition at a second critical code rate

A Strong Approximation Theorem for Stochastic Recursive Algorithm

The constant stepsize analog of Gelfand-Mitter type discrete-time stochastic recursive algorithms is shown to track an associated stochastic differential equation in the strong sense, i.e., with respect to an appropriate divergence measure

Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms.

We hypothesized that endothelial progenitor cells derived from individuals with diabetes would exhibit functional defects including inability to respond to hypoxia and altered paracrine/autocrine function that would impair the angiogenic potential of thes