Genetic Correlations in Mutation Processes

We study the role of phylogenetic trees on correlations in mutation processes. Generally, correlations decay exponentially with the generation number. We find that two distinct regimes of behavior exist. For mutation rates smaller than a critical rate, the underlying tree morphology is almost irrelevant, while mutation rates higher than this critical rate lead to strong tree-dependent correlations. We show analytically that identical critical behavior underlies all multiple point correlations. This behavior generally characterizes branching processes undergoing mutation.Comment: revtex, 8 pages, 2 fig

A circular order on edge-coloured trees and RNA m-diagrams

We study a circular order on labelled, m-edge-coloured trees with k vertices, and show that the set of such trees with a fixed circular order is in bijection with the set of RNA m-diagrams of degree k, combinatorial objects which can be regarded as RNA secondary structures of a certain kind. We enumerate these sets and show that the set of trees with a fixed circular order can be characterized as an equivalence class for the transitive closure of an operation which, in the case m=3, arises as an induction in the context of interval exchange transformations.Comment: 15 pages, 7 figures. New title. Shortened version, presenting the results more efficientl

Large Deviations for Random Trees

We consider large random trees under Gibbs distributions and prove a Large Deviation Principle (LDP) for the distribution of degrees of vertices of the tree. The LDP rate function is given explicitly. An immediate consequence is a Law of Large Numbers for the distribution of vertex degrees in a large random tree. Our motivation for this study comes from the analysis of RNA secondary structures.Comment: 10 page

Medical Care Capacity for Influenza Outbreaks, Los Angeles

In December 1997, media reported hospital overcrowding and “the worst [flu epidemic] in the past two decades” in Los Angeles County (LAC). We found that rates of pneumonia and influenza deaths, hospitalizations, and claims were substantially higher for the 1997–98 influenza season than the previous six seasons. Hours of emergency medical services (EMS) diversion (when emergency departments could not receive incoming patients) peaked during the influenza seasons studied; the number of EMS diversion hours per season also increased during the seasons 1993–94 to 1997–98, suggesting a decrease in medical care capacity during influenza seasons. Over the seven influenza seasons studied, the number of licensed beds decreased 12%, while the LAC population increased 5%. Our findings suggest that the capacity of health-care systems to handle patient visits during influenza seasons is diminishing

Forcing of the overturning circulation across a circumpolar channel by internal wave breaking

The hypothesis that the impingement of mesoscale eddy flows on small-scale topography regulates diapycnal mixing and meridional overturning across the deep Southern Ocean is assessed in an idealized model. The model simulates an eddying circumpolar current coupled to a double-celled meridional overturning with properties broadly resembling those of the Southern Ocean circulation and represents lee wave-induced diapycnal mixing using an online formulation grounded on wave radiation theory. The diapycnal mixing generated by the simulated eddy field is found to play a major role in sustaining the lower overturning cell in the model, and to underpin a significant sensitivity of this cell to wind forcing. The vertical structure of lower overturning is set by mesoscale eddies, which propagate the effects of near-bottom diapycnal mixing by displacing isopycnals vertically

John Newsom-Davis: clinician-scientist and so much more

John Newsom-Davis was born in 1932 and died, aged 74, in 2007. After national service in the Royal Air Force, he read Natural Sciences at Cambridge. Following clinical studies at the Middlesex Hospital, he began research into respiratory neurophysiology with Tom Sears at the National Hospital, Queen Square, in London, and spent 1 year with Fred Plum at Cornell University in New York. After neurology specialist training at Queen Square, he became the director of the Batten Unit, continuing his interest in respiratory physiology. There he began to work on myasthenia gravis in collaboration with Ricardo Miledi at University College London and in 1978, after performing the first studies on plasma exchange in that disease, he established a myasthenia gravis research group at the Royal Free Hospital. There he investigated the role of the thymus in this disease and demonstrated an autoimmune basis for the Lambert Eaton myasthenic syndrome and ‘seronegative’ myasthenia. He was awarded the first Medical Research Council Clinical Research Professorship in 1979 but moved to Oxford in 1987 when he was elected Action Research Professor of Neurology. While at Oxford, he continued to run a very successful multidisciplinary group, researched further into the thymic abnormalities and cellular immunology of myasthenia, identified antibody-mediated mechanisms in acquired neuromyotonia, and began the molecular work that identified the genetic basis for many forms of congenital myasthenic syndrome. Meanwhile, he was also involved in university and college governance and contributed widely to the Medical Research Council, government committees, research charities and the Association of British Neurologists. Among many honours, he was elected Fellow of the Royal Society in 1991, appointed Commander of the British Empire in 1996 and made a Foreign Associate Member of the Institute of Medicine of the United States in 2001. Nearing and following retirement from Oxford, where he continued to see patients with myasthenia, he was the President of the Association of British Neurologists and Editor of Brain, and led a National Institutes of Health-funded international trial of thymectomy

Analysis of Interactions of Salmonella Type Three Secretion Mutants with 3-D Intestinal Epithelial Cells

The prevailing paradigm of Salmonella enteropathogenesis based on monolayers asserts that Salmonella pathogenicity island-1 Type Three Secretion System (SPI-1 T3SS) is required for bacterial invasion into intestinal epithelium. However, little is known about the role of SPI-1 in mediating gastrointestinal disease in humans. Recently, SPI-1 deficient nontyphoidal Salmonella strains were isolated from infected humans and animals, indicating that SPI-1 is not required to cause enteropathogenesis and demonstrating the need for more in vivo-like models. Here, we utilized a previously characterized 3-D organotypic model of human intestinal epithelium to elucidate the role of all characterized Salmonella enterica T3SSs. Similar to in vivo reports, the Salmonella SPI-1 T3SS was not required to invade 3-D intestinal cells. Additionally, Salmonella strains carrying single (SPI-1 or SPI-2), double (SPI-1/2) and complete T3SS knockout (SPI-1/SPI-2: flhDC) also invaded 3-D intestinal cells to wildtype levels. Invasion of wildtype and TTSS mutants was a Salmonella active process, whereas non-invasive bacterial strains, bacterial size beads, and heat-killed Salmonella did not invade 3-D cells. Wildtype and T3SS mutants did not preferentially target different cell types identified within the 3-D intestinal aggregates, including M-cells/M-like cells, enterocytes, or Paneth cells. Moreover, each T3SS was necessary for substantial intracellular bacterial replication within 3-D cells. Collectively, these results indicate that T3SSs are dispensable for Salmonella invasion into highly differentiated 3-D models of human intestinal epithelial cells, but are required for intracellular bacterial growth, paralleling in vivo infection observations and demonstrating the utility of these models in predicting in vivo-like pathogenic mechanisms