Without magic bullets: the biological basis for public health interventions against protein folding disorders

Protein folding disorders of aging like Alzheimer's and Parkinson's diseases currently present intractable medical challenges. 'Small molecule' interventions - drug treatments - often have, at best, palliative impact, failing to alter disease course. The design of individual or population level interventions will likely require a deeper understanding of protein folding and its regulation than currently provided by contemporary 'physics' or culture-bound medical magic bullet models. Here, a topological rate distortion analysis is applied to the problem of protein folding and regulation that is similar in spirit to Tlusty's (2010a) elegant exploration of the genetic code. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding regulation under a cellular-level cognitive paradigm similar to that proposed by Atlan and Cohen (1998) for the immune system. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of regulatory failure, in essence, a premature aging driven by familiar synergisms between disjunctions of resource allocation and need in the context of socially or physiologically toxic exposures and chronic powerlessness at individual and group scales. Application of an HPA axis model is made to recent observed differences in Alzheimer's onset rates in White and African American subpopulations as a function of an index of distress-proneness

Joint Antenna Selection and Phase-Only Beamforming Using Mixed-Integer Nonlinear Programming

In this paper, we consider the problem of joint antenna selection and analog beamformer design in downlink single-group multicast networks. Our objective is to reduce the hardware costs by minimizing the number of required phase shifters at the transmitter while fulfilling given distortion limits at the receivers. We formulate the problem as an L0 minimization problem and devise a novel branch-and-cut based algorithm to solve the resulting mixed-integer nonlinear program to optimality. We also propose a suboptimal heuristic algorithm to solve the above problem approximately with a low computational complexity. Computational results illustrate that the solutions produced by the proposed heuristic algorithm are optimal in most cases. The results also indicate that the performance of the optimal methods can be significantly improved by initializing with the result of the suboptimal method.Comment: to be presented at WSA 201

Motif Statistics and Spike Correlations in Neuronal Networks

Motifs are patterns of subgraphs of complex networks. We studied the impact of such patterns of connectivity on the level of correlated, or synchronized, spiking activity among pairs of cells in a recurrent network model of integrate and fire neurons. For a range of network architectures, we find that the pairwise correlation coefficients, averaged across the network, can be closely approximated using only three statistics of network connectivity. These are the overall network connection probability and the frequencies of two second-order motifs: diverging motifs, in which one cell provides input to two others, and chain motifs, in which two cells are connected via a third intermediary cell. Specifically, the prevalence of diverging and chain motifs tends to increase correlation. Our method is based on linear response theory, which enables us to express spiking statistics using linear algebra, and a resumming technique, which extrapolates from second order motifs to predict the overall effect of coupling on network correlation. Our motif-based results seek to isolate the effect of network architecture perturbatively from a known network state