Convergence Analysis of MCMC Method in the Study of Genetic Linkage with Missing Data

Computational infeasibility of exact methods for solving genetic linkage analysis problems has led to the development of a new collection of stochastic methods, all of which require the use of Markov chains. The purpose of this work is to investigate the complexities of missing data in pedigree analysis using the Monte Carlo Markov Chain (MCMC) method as compared to the exact results. Also, we attempt to determine an association between missing data in a familial pedigree and the convergence to stationarity of a descent graph Markov chain implemented in the stochastic method for parametric linkage analysis. In particular, we will implement the stochastic method to solve a pedigree problem for a disease trait, in order to look at the associated problems with missing data from the pedigree, and investigate the deviation between the MCMC method and the exact results. Using the method for maximum autocorrelation and bounding of the second largest eigenvalue, we will study the effects of missing data on the convergence rate and the accuracy of the MCMC method in solving the pedigree analysis problem. Finally, we will use the computational implementation of SimWalk2 to study the convergence rate and accuracy of the MCMC method for the disease Episodic Ataxia. The implementation of the MCMC method through SimWalk2 for the disease gene Episodic Ataxia found evidence to suggest that both the efficiency and accuracy of the method may be severely reduced by an increase in missing data in the pedigree. Certain variations of model parameters influenced the ability of the method to produce accurate results, but the most crucial of the variables studied was the level of missing information from the pedigree itself. This can be seen as a detriment to the implementation, as pedigree information is very often missing from the model. Further research in this topic would need to include the implementation of this method on more genetic parameters and differing pedigree variations. Also, it might be of interest to look into possible ways to combat the effects of missing data on the MCMC method

African black beetle in vineyards

The African black beetle, Heteronychus arator, is an important pest of horticultural crops, ornamentals and pastures in Western Australia. They also attack lawns and are commonly referred to as the black lawn beetle. This beetle was first recorded in Australia during the 1920s and originates from southern Africa where it is a major establishment pest of maize.https://researchlibrary.agric.wa.gov.au/bulletins/1144/thumbnail.jp

Powdery mildew in wine grapes in Western Australia

Powdery mildew is caused by the fungal pathogen Uncinula necator. It is the most persistent fungal problem of grapes in WA and one of the most widespread fungal diseases of grapevines in the world. It is characterised by ash-grey to white powdery growth on green tissue of the vine. If uncontrolled it can cause serious crop losses and impair wine quality.https://researchlibrary.agric.wa.gov.au/bulletins/1076/thumbnail.jp

Systems thinking activities used in K-12 for up to two decades

Infusing systems thinking activities in pre-college education (grades K-12) means updating precollege education so it includes a study of many systemic behavior patterns that are ubiquitous in the real world. Systems thinking tools include those using both paper and pencil and the computer and enhance learning in the classroom making it more student-centered, more active, and allowing students to analyze problems that have been heretofore beyond the scope of K-12 classrooms. Students in primary school have used behavior over time graphs to demonstrate dynamics described in story books, like the Lorax, and created stock-flow diagrams to describe what was needed to make a garden flourish. Middle school students have created larger stockflow diagrams to study how composting helps to reduce pollution and have created small simulations to study population dynamics and the spread of epidemics. High school students have created/used numerous computer models to study systemic problems in mathematics, physical science, physics, biology, environmental science, global studies, and history. Some high schools developed modeling courses allowing students to create System Dynamics computer models to study problems of their choice, write technical papers explaining their models, and present their models and model results to an audience. This paper contains explanations of some of the systems thinking lessons that have been used with precollege students, some for just 5–6 years (especially the primary and middle school examples), others (especially the mathematics and system dynamics model courses for high school students) for decades

Solomon Islands forest life: information on biology and management of forest resources

Solomon Islands Forest Life is a collaborative effort drawing on the experience and knowledge of many individuals. The book was compiled as part of a project funded by the Critical Ecosystem Partnership Fund with support from John D and Catherine T MacArthur Foundation and will be distributed for free among secondary schools throughout Solomon Islands. Solomon Islands Forest Life gives an overview of the terrestrial environments of the Solomon Islands, their ecology, important species, and some of the key threats they face. The Solomon Islands are one of the most biologically rich archipelagos on earth. Huge proportions of the animals and plants found there are endemic, meaning they are found nowhere else on earth. These species are closely linked to the culture, livelihoods and well being of people. Commercial logging, mining and a fast rate of population growth threaten the forests of Solomon Islands and are placing increasing pressure on natural resources. This book aims to complement the already deep understanding of the terrestrial environment by Solomon Islanders, allowing them to learn more and assist them in understanding how to manage new threats

Botrytis in wine grapes in Western Australia

Botrytis, causal agent Botrytis cinerea, is a fungal disease of grapevines that is commonly referred to as Botrytis bunch rot or grey mould. Botrytis is most prevalent where warm, wet conditions are frequent, but symptoms can occur in cool, wet weather and high humidity. All grape varieties are susceptible. Varieties most at risk are those with berries that are thin-skinned and/or have tight bunches. Some white wine grape varieties infected with Botrytis may decay, in certain conditions to produce noble rot . Wine produced from these infected bunches produce unique aromatic characters with high residual sugar and are usually sold as dessert wines.https://researchlibrary.agric.wa.gov.au/bulletins/1092/thumbnail.jp

Proinflammatory Mediators of Toxic Shock and Their Correlation to Lethality

Bacterial exotoxins and endotoxins both stimulate proinflammatory mediators but the contribution of each individual toxin in the release of mediators causing lethal shock is incompletely understood. This study examines the cytokine response and lethality of mice exposed to varying doses of staphylococcal enterotoxin B (SEB) or lipopolysaccharide (LPS) and their combinations. In vivo, SEB alone induced moderate levels of IL-2 and MCP-1 and all mice survived even with a high dose of SEB (100 μg/mouse). LPS (80 μg/mouse) caused 48% lethality and induced high levels of IL-6 and MCP-1. SEB induced low levels of TNFα, IL-1, IFNγ, MIP-2, and LPS synergized with SEB in the expression of these cytokines and that of IL-6 and MCP-1. Importantly, the synergistic action of SEB and LPS resulted in lethal shock and hypothermia. ANOVA of cytokine levels by survival status of SEB-plus-LPS groups revealed significantly higher levels of TNFα, IL-6, MIP-2, and MCP-1 in nonsurvivors measured at 8 hours. Significantly higher levels of IFNγ and IL-2 were observed at 21 hours in nonsurvivors of toxic shock compared to those in survivors. Overall, synergistic action of SEB and LPS resulted in higher and prolonged levels of these key cytokines leading to toxic shock

Downy mildew in vineyards

Downy mildew, caused by Plasmopara viticola, is a major fungal disease of grapevines that originates from North America. This disease was first detected in a commercial Western Australian vineyard in October 1998 and has since been found in most grape growing areas within the State. It is found in all other grape growing areas of Australia. Plasmopara viticola is specific to grapevines (e.g. Vitis vinifera), although not all Vitis spp. are susceptible. The American rootstock species and hybrids are less susceptible or are resistant (refer to ‘Varietal susceptibility’). Other species of downy mildew, such as those found on cucurbits and roses, do not attack grapevines. Although, weather conditions that favour the development and spread of grapevine downy mildew also may encourage the development and spread of cucurbit and rose downy mildews.https://researchlibrary.agric.wa.gov.au/bulletins/1081/thumbnail.jp

Sequestration of Muscarinic Cholinergic Receptors in Permeabilized Neuroblastoma Cells

The feasibility of using a permeabilized preparation of human SH-SY-5Y neuroblastoma cells for studies of muscarinic acetylcholine receptor (mAChR) sequestration has been evaluated. Exposure of cells permeabilized with digitonin, streptolysin-O, or the Α-toxin from Staphylococcus aureus to oxotremorine-M (Oxo-M) for 30 min resulted in a 25–30% reduction in the number of cell surface mAChRs, as monitored by the loss of N [ 3 H]methyl- scopolamine ([ 3 H]NMS) binding sites. The corresponding value for intact cells was 40%. For cells permeabilized with 20 Μ M digitonin, the Oxo-M-mediated reduction in [ 3 H]NMS binding was time ( t 1/2 ∼ 5 min) and concentration (EC 50 ∼ 10 Μ M ) dependent and was agonist specific (Oxo M > bethanechol = arecoline = pilocarpine). In contrast, no reduction in total mAChR number, as monitored by the binding of [ 3 H]quinuclidinyl benzilate, occurred following Oxo-M treatment. The loss of [ 3 H]NMS sites observed in the presence of Oxo-M was unaffected by omission of either ATP or Ca 2+ , both of which are required for stimulated phosphoinositide hydrolysis, but could be inhibited by the inclusion of guanosine 5′- O -(2-thiodiphosphate). mAChRs sequestered in response to Oxo-M addition were unmasked when the cells were permeabilized in the presence of higher concentrations of digitonin (80 Μ M ). The results indicate (a) that permeabilized SH-SY-5Y cells support an agonist-induced sequestration of mAChRs, the magnitude of which is ∼ 65–70% of that observed for intact cells, (b) that when internalized, mAChRs are located in a cellular compartment to which [ 3 H]NMS has only a limited access despite the removal of the plasma membrane barrier, and (c) that the production of phosphoinositide-derived second messengers is not a prerequisite for mAChR sequestration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65736/1/j.1471-4159.1994.62051795.x.pd