Examination of optimizing information flow in networks

The central role of the Internet and the World-Wide-Web in global communications has refocused much attention on problems involving optimizing information flow through networks. The most basic formulation of the question is called the "max flow" optimization problem: given a set of channels with prescribed capacities that connect a set of nodes in a network, how should the materials or information be distributed among the various routes to maximize the total flow rate from the source to the destination. Theory in linear programming has been well developed to solve the classic max flow problem. Modern contexts have demanded the examination of more complicated variations of the max flow problem to take new factors or constraints into consideration; these changes lead to more difficult problems where linear programming is insufficient. In the workshop we examined models for information flow on networks that considered trade-offs between the overall network utility (or flow rate) and path diversity to ensure balanced usage of all parts of the network (and to ensure stability and robustness against local disruptions in parts of the network). While the linear programming solution of the basic max flow problem cannot handle the current problem, the approaches primal/dual formulation for describing the constrained optimization problem can be applied to the current generation of problems, called network utility maximization (NUM) problems. In particular, primal/dual formulations have been used extensively in studies of such networks. A key feature of the traffic-routing model we are considering is its formulation as an economic system, governed by principles of supply and demand. Considering channel capacities as a commodity of limited supply, we might suspect that a system that regulates traffic via a pricing scheme would assign prices to channels in a manner inversely proportional to their respective capacities. Once an appropriate network optimization problem has been formulated, it remains to solve the optimization problem; this will need to be done numerically, but the process can greatly benefit from simplifications and reductions that follow from analysis of the problem. Ideally the form of the numerical solution scheme can give insight on the design of a distributed algorithm for a Transmission Control Protocol (TCP) that can be directly implemented on the network. At the workshop we considered the optimization problems for two small prototype network topologies: the two-link network and the diamond network. These examples are small enough to be tractable during the workshop, but retain some of the key features relevant to larger networks (competing routes with different capacities from the source to the destination, and routes with overlapping channels, respectively). We have studied a gradient descent method for solving obtaining the optimal solution via the dual problem. The numerical method was implemented in MATLAB and further analysis of the dual problem and properties of the gradient method were carried out. Another thrust of the group's work was in direct simulations of information flow in these small networks via Monte Carlo simulations as a means of directly testing the efficiencies of various allocation strategies

Mitochondrial Bioenergetic Alterations in Mouse Neuroblastoma Cells Infected with Sindbis Virus: Implications to Viral Replication and Neuronal Death

The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal dysfunction and Sindbis virus-induced encephalitis

Iron, Meat and Health

This article is a summary of the publication “Iron and Health” by the Scientific Advisory Committee on Nutrition (SACN) to the U.K. Government (2010), which reviews the dietary intake of iron and the impact of different dietary patterns on the nutritional and health status of the U.K. population. It concludes that several uncertainties make it difficult to determine dose-response relationships or to confidently characterize the risks associated with iron deficiency or excess. The publication makes several recommendations concerning iron intakes from food, including meat, and from supplements, as well as recommendations for further research