Theory and practice of optimal mutation rate control in Hamming spaces of DNA sequences

We investigate the problem of optimal control of mutation by asexual self-replicating organisms represented by points in a metric space. We introduce the notion of a relatively monotonic fitness landscape and consider a generalisation of Fisher's geometric model of adaptation for such spaces. Using a Hamming space as a prime example, we derive the probability of adaptation as a function of reproduction parameters (e.g. mutation size or rate). Optimal control rules for the parameters are derived explicitly for some relatively monotonic landscapes, and then a general information-based heuristic is introduced. We then evaluate our theoretical control functions against optimal mutation functions evolved from a random population of functions using a meta genetic algorithm. Our experimental results show a close match between theory and experiment. We demonstrate this result both in artificial fitness landscapes, defined by a Hamming distance, and a natural landscape, where fitness is defined by a DNA-protein affinity. We discuss how a control of mutation rate could occur and evolve in natural organisms. We also outline future directions of this work

Monotonicity of fitness landscapes and mutation rate control

A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms

Community-Acquired Pneumonia in Sub-Saharan Africa

Community-acquired pneumonia (CAP) in sub-Saharan Africa is a common cause of adult hospitalization and is associated with significant mortality. Human immunodeficiency virus (HIV) prevalence in the region leads to differences in CAP epidemiology compared with most high-income settings: patients are younger, and coinfection with tuberculosis and opportunistic infections is common and difficult to diagnose. Resource limitations affect the availability of medical expertise as well as radiological and laboratory diagnostic services. These factors impact on key aspects of health care, including pathways of investigation, severity assessment, and the selection of empirical antimicrobial therapy. This review summarizes recent data from sub-Saharan Africa describing the burden, etiology, risk factors, and outcome of CAP. We describe the rational and context-appropriate approach to CAP diagnosis and management, including supportive therapy. Priorities for future research to inform strategies for CAP prevention and initial management are suggested

Strong Decays of Strange Quarkonia

In this paper we evaluate strong decay amplitudes and partial widths of strange mesons (strangeonia and kaonia) in the 3P0 decay model. We give numerical results for all energetically allowed open-flavor two-body decay modes of all nsbar and ssbar strange mesons in the 1S, 2S, 3S, 1P, 2P, 1D and 1F multiplets, comprising strong decays of a total of 43 resonances into 525 two-body modes, with 891 numerically evaluated amplitudes. This set of resonances includes all strange qqbar states with allowed strong decays expected in the quark model up to ca. 2.2 GeV. We use standard nonrelativistic quark model SHO wavefunctions to evaluate these amplitudes, and quote numerical results for all amplitudes present in each decay mode. We also discuss the status of the associated experimental candidates, and note which states and decay modes would be especially interesting for future experimental study at hadronic, e+e- and photoproduction facilities. These results should also be useful in distinguishing conventional quark model mesons from exotica such as glueballs and hybrids through their strong decays.Comment: 69 pages, 5 figures, 39 table

Interactive multimedia ethnography: Archiving workflow, interface aesthetics and metadata

Digital heritage archives often lack engaging user interfaces that strike a balance between providing narrative context and affording user interaction and exploration. It seems nevertheless feasible for metadata tagging and a "joined up" workflow to provide a basis for such rich interaction. After outlining relevant research from within and outside the heritage domain, we present our project, FINE (Fluid Interfaces for Narrative Exploration), an effort to develop such a system. Based on content from Wendy James' archive of anthropological research material from the Sudan/Ethiopian borderlands, the FINE project attempts to use structural and thematic metadata to drive exploratory interfaces which link video, images, audio, and text to relevant narrative units. The interfaces also benefit from the temporal and spatial variety of the collection to provide opportunities to discover contrasts and juxtaposition in the material across place and time. © 2012 ACM

Fine motor function and neuropsychological deficits in individuals at risk for schizophrenia

Deficits in fine motor function and neuropsychological performance have been described as risk factors for schizophrenia. In the Basel FEPSY study (Früherkennung von Psychosen; English: Early Detection of Psychosis) individuals at risk for psychosis were identified in a screening procedure (Riecher-Rössler et al. 2005). As a part of the multilevel assessment, 40 individuals at risk for psychosis and 42 healthy controls matched for age, sex and handedness were investigated with a fine motor function test battery and a neuropsychological test battery. Individuals at risk showed lower performances in all subtests of the fine motor function tests, predominantly in dexterity and velocity (wrist/fingers and arm/hand). In the neuropsychological test battery, individuals at risk performed less well compared to healthy controls regarding sustained attention, working memory and perseveration. The combined evaluation of the two test batteries (neuropsychological and fine motor function) separates the two groups into individuals at risk and healthy controls better than each test battery alone. A multilevel approach might therefore be a valuable contribution to detecting beginning schizophreni