Fast Bayesian parameter estimation for stochastic logistic growth models

The transition density of a stochastic, logistic population growth model with multiplicative intrinsic noise is analytically intractable. Inferring model parameter values by fitting such stochastic differential equation (SDE) models to data therefore requires relatively slow numerical simulation. Where such simulation is prohibitively slow, an alternative is to use model approximations which do have an analytically tractable transition density, enabling fast inference. We introduce two such approximations, with either multiplicative or additive intrinsic noise, each derived from the linear noise approximation of the logistic growth SDE. After Bayesian inference we find that our fast LNA models, using Kalman filter recursion for computation of marginal likelihoods, give similar posterior distributions to slow arbitrarily exact models. We also demonstrate that simulations from our LNA models better describe the characteristics of the stochastic logistic growth models than a related approach. Finally, we demonstrate that our LNA model with additive intrinsic noise and measurement error best describes an example set of longitudinal observations of microbial population size taken from a typical, genome-wide screening experiment.Comment: 24 pages, 5 figures and 2 table

Marriage, Residential Movement and Cultural Innovation of Women in the Hamar-Banna-Bashada Cluster

Shada Alma:“What hunt does a girl have? A girl’s hunt is when she marries. (laugh)Otherwise does she go hunting? She just stays at home with her mother.”(Two girls go hunting, Lydall and Head 1991) Duka Aike: “A girl’s hunt is when she marries. That’s when I’ll go hunting.”(The women who smile, Lydall and Head 1990) Introduction: marriage and the movement of women The idea for this paper arose from a seemingly simple fact: as in most patrilineal societies, it is the women in the Hamar-Banna-B..

Give Sorrow Words: The Meaning of Parental Bereavement

A fundamental tenet of hermeneutic phenomenology is that people seek to create meaning of their experience from the response sited within human consciousness. The focus of this study is on the world of the lived experience as it is interpreted by participants through memory and language as accessed by interviews in order to produce an understanding of the participants’ experience. Three participants were interviewed whose adult children had died as a result of an AIDS-related illness. The interviews were recorded and transcribed, and interwoven analyses sought to illustrate the participants’ lived experience of the phenomenon. An attempt was made to understand how the various phenomena relating to parental bereavement were reflected by participants in the interviews. Common themes included reactions to the knowledge of the illness, the experience of being with their dying child, coping with the pain of the loss, and spiritual and existential concerns. There are references to how others judge their grieving behaviour. Issues of retribution and punishment are prominent and these appear to place a particular burden of sorrow on the grieving parent. The study provided insight into the lived experience of bereavement and the forging of new meaning structures that can accommodate the loss. Indo-Pacific Journal of Phenomenology, Volume 5, Edition 2 December 200

Palatability and animal models of schizophrenia

Schizophrenia is one of the most serious mental disorders of humankind. It affects about 1% of the population worldwide and has devastating consequences, including suicide in 10% of sufferers (e.g. Lewis & Lieberman, 2000). Schizophrenia also has serious social impact with sufferers accounting for more than one third of the homeless population in western society (Folsom & Jeste, 2002)

The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks

DNA-end resection, the generation of single-stranded DNA at DNA double strand break (DSB) ends, is critical for controlling the many cellular responses to breaks. Here we show that the conserved DNA damage checkpoint sliding clamp (the 9-1-1 complex) plays two opposing roles coordinating DSB resection in budding yeast. We show that the major effect of 9-1-1 is to inhibit resection by promoting the recruitment of Rad953BP1 near DSBs. However, 9-1-1 also stimulates resection by Exo1- and Dna2-Sgs1-dependent nuclease/helicase activities, and this can be observed in the absence of Rad953BP1. Our new data resolve the controversy in the literature about the effect of the 9-1-1 complex on DSB resection. Interestingly, the inhibitory role of 9-1-1 on resection is not observed near uncapped telomeres because less Rad953BP1 is recruited near uncapped telomeres. Thus, 9-1-1 both stimulates and inhibits resection and the effects of 9-1-1 are modulated by different regions of the genome. Our experiments illustrate the central role of the 9-1-1 checkpoint sliding clamp in the DNA damage response network that coordinates the response to broken DNA ends. Our results have implications in all eukaryotic cells

The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1

Single-stranded DNA (ssDNA) at DNA ends is an important regulator of the DNA damage response. Resection, the generation of ssDNA, affects DNA damage checkpoint activation, DNA repair pathway choice, ssDNA-associated mutation and replication fork stability. In eukaryotes, extensive DNA resection requires the nuclease Exo1 and nuclease/helicase pair: Dna2 and Sgs1^(BLM). How Exo1 and Dna2-Sgs1^(BLM) coordinate during resection remains poorly understood. The DNA damage checkpoint clamp (the 9-1-1 complex) has been reported to play an important role in stimulating resection but the exact mechanism remains unclear. Here we show that the human 9-1-1 complex enhances the cleavage of DNA by both DNA2 and EXO1 in vitro, showing that the resection-stimulatory role of the 9-1-1 complex is direct. We also show that in Saccharomyces cerevisiae, the 9-1-1 complex promotes both Dna2-Sgs1 and Exo1-dependent resection in response to uncapped telomeres. Our results suggest that the 9-1-1 complex facilitates resection by recruiting both Dna2-Sgs1 and Exo1 to sites of resection. This activity of the 9-1-1 complex in supporting resection is strongly inhibited by the checkpoint adaptor Rad9^(53BP1). Our results provide important mechanistic insights into how DNA resection is regulated by checkpoint proteins and have implications for genome stability in eukaryotes