Marginal likelihoods in phylogenetics: a review of methods and applications

By providing a framework of accounting for the shared ancestry inherent to all life, phylogenetics is becoming the statistical foundation of biology. The importance of model choice continues to grow as phylogenetic models continue to increase in complexity to better capture micro and macroevolutionary processes. In a Bayesian framework, the marginal likelihood is how data update our prior beliefs about models, which gives us an intuitive measure of comparing model fit that is grounded in probability theory. Given the rapid increase in the number and complexity of phylogenetic models, methods for approximating marginal likelihoods are increasingly important. Here we try to provide an intuitive description of marginal likelihoods and why they are important in Bayesian model testing. We also categorize and review methods for estimating marginal likelihoods of phylogenetic models, highlighting several recent methods that provide well-behaved estimates. Furthermore, we review some empirical studies that demonstrate how marginal likelihoods can be used to learn about models of evolution from biological data. We discuss promising alternatives that can complement marginal likelihoods for Bayesian model choice, including posterior-predictive methods. Using simulations, we find one alternative method based on approximate-Bayesian computation (ABC) to be biased. We conclude by discussing the challenges of Bayesian model choice and future directions that promise to improve the approximation of marginal likelihoods and Bayesian phylogenetics as a whole.Comment: 33 pages, 3 figure

Submicrosecond comparisons of time standards via the Navigation Technology Satellites (NTS)

An interim demonstration was performed of the time transfer capability of the NAVSTAR GPS system using a single NTS satellite. Measurements of time difference (pseudo-range) are made from the NTS tracking network and at the participating observatories. The NTS network measurements are used to compute the NTS orbit trajectory. The central NTS tracking station has a time link to the Naval Observatory UTC (USNO,MC1) master clock. Measurements are used with the NTS receiver at the remote observatory, the time transfer value UTC (USNO,MC1)-UTC (REMOTE, VIA NTS) is calculated. Intercomparisons were computed using predicted values of satellite clock offset and ephemeus

Antibody Response of Monkeys to Invasion Plasmid Antigen D after Infection with Shigella spp.

The antigen preparation most often used for determining the levels of antibodies to virulence-associated proteins of Shigella spp. consists of a mixture of proteins (including IpaB, IpaC, IpaD, and VirG*) extracted from virulent shigellae with water (water extract). To overcome the lack of specificity for individual antigens in the water-extract enzyme-linked immunosorbent assay (ELISA), the ipaD gene from S. flexneri has been cloned, expressed to a high level, and purified for use in a new ELISA for the determination of the levels of antibody against IpaD in monkeys and humans challenged with shigellae. The IpaD ELISA for serum immunoglobulins G and A correlated well with the water-extract ELISA in that monkeys infected with S. flexneri or S. sonnei responded with high serum antibody titers in both assays. The IpaD assay required less antigen per well, had much lower background levels, and did not require correction with antigens from an avirulent organism. In conjunction with the water-extract ELISA, it was possible to identify infected animals that did not respond to IpaD but did produce antibodies that reacted in the water-extract ELISA. This indicates that even though IpaB, IpaC, and IpaD are essential for the invasiveness phenotype, the infected host does not always produce antibodies against all components of the invasiveness apparatus

Improving Transformational Teaching and Learning by Advancing Higher Education Feedback-Based Dialogues at Texas A&M University

Feedback mechanisms are critical to iteratively improving most societal systems, and yet there is minimal documentation on the best practices of leveraging feedback to improve teaching and learning in higher education. We attest that facilitated dialogues have the potential to start conversations relevant to improving policy that otherwise would not transpire. In higher education, facilitated dialogues between students, faculty, staff, and administration provide a unique face-to-face opportunity for all participants to provide feedback to one another on real-time institutional strengths and weaknesses. More specifically, facilitated dialogues have the potential to start a conversation on improving the learning in higher education. This work notes the theory facilitated dialogues and offers discussion on the long-term potential for such conversations to serve as a medium for iterative feedback in larger societal systems. Further, this thesis documents our development of a facilitated dialogue, The Student-Faculty Dialogue, which will act as a plenary event at Texas A&M’s inaugural Transformational Teaching and Learning Conference on April 17, 2018

MCH Pheromone for Preventing Douglas-Fir Beetle Infestation in Windthrown Trees

A granular controlled-release formulation (98 percent inert, 2 percent 3-methyl-2-cyclohexen-1-one) was applied May 11-13, 1982, at 4.48 kg/ha to 76.9 ha of uninfested windthrown Douglas-fir by helicopter with a modified aerial spreader of 1.13 m³ capacity. Granules measured on treated plots averaged 2.04-2.69 kg/ha, sufficient to reduce Douglas-fir beetle (Dendroctonus pseudotsugae) infestation 96.4 percent by late June. The same MCH treatment reduced spruce beetle (Dendroctonus rufipennis) attacks by 55 percent in fewer, intermingled windthrown Engelmann spruce

Improving Transformational Teaching and Learning by Advancing Higher Education Feedback-Based Dialogues at Texas A&M University

Feedback mechanisms are critical to iteratively improving most societal systems, and yet there is minimal documentation on the best practices of leveraging feedback to improve teaching and learning in higher education. We attest that facilitated dialogues have the potential to start conversations relevant to improving policy that otherwise would not transpire. In higher education, facilitated dialogues between students, faculty, staff, and administration provide a unique face-to-face opportunity for all participants to provide feedback to one another on real-time institutional strengths and weaknesses. More specifically, facilitated dialogues have the potential to start a conversation on improving the learning in higher education. This work notes the theory facilitated dialogues and offers discussion on the long-term potential for such conversations to serve as a medium for iterative feedback in larger societal systems. Further, this thesis documents our development of a facilitated dialogue, The Student-Faculty Dialogue, which will act as a plenary event at Texas A&M’s inaugural Transformational Teaching and Learning Conference on April 17, 2018

Immunomagnetic t-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (0×19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival. A highly efficient technique of T-lymphocyte depletion using rat bone marrow is described. It involves the binding of OX-19, a MoAb directed against all rat thy-mocytes and mature peripheral T lymphocytes, to monosized, magnetic polymer spheres. Magnetic separation of T lymphocytes after mixing the allogeneic bone marrow with the bead/OX-19 complex provides for a simple, rapid depletion of T lymphocytes from the bone marrow. In vitro studies using flow cytometry and the prevention of GVHD in a fully allogeneic rat bone marrow model have been used to demonstrate the effectiveness of the depletion procedure. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

IpaD Localizes to the Tip of the Type III Secretion System Needle of Shigella flexneri

This is the publisher's version, also available electronically from http://iai.asm.org/content/74/8/4391Shigella flexneri, the causative agent of shigellosis, is a gram-negative bacterial pathogen that initiates infection by invading cells within the colonic epithelium. Contact with host cell surfaces induces a rapid burst of protein secretion via the Shigella type III secretion system (TTSS). The first proteins secreted are IpaD, IpaB, and IpaC, with IpaB and IpaC being inserted into the host cell membrane to form a pore for translocating late effectors into the target cell cytoplasm. The resulting pathogen-host cross talk results in localized actin polymerization, membrane ruffling, and, ultimately, pathogen entry. IpaD is essential for host cell invasion, but its role in this process is just now coming to light. IpaD is a multifunctional protein that controls the secretion and presentation of IpaB and IpaC at the pathogen-host interface. We show here that antibodies recognizing the surface-exposed N terminus of IpaD neutralize Shigella's ability to promote pore formation in erythrocyte membranes. We further show that MxiH and IpaD colocalize on the bacterial surface. When TTSS needles were sheared from the Shigella surface, IpaD was found at only the needle tips. Consistent with this, IpaD localized to the exposed tips of needles that were still attached to the bacterium. Molecular analyses then showed that the IpaD C terminus is required for this surface localization and function. Furthermore, mutations that prevent IpaD surface localization also eliminate all IpaD-related functions. Thus, this study demonstrates that IpaD localizes to the TTSA needle tip, where it functions to control the secretion and proper insertion of translocators into host cell membrane

IpaD Localizes to the Tip of the Type III Secretion System Needle of Shigella flexneri

This is the publisher's version, also available electronically from http://iai.asm.org/content/74/8/4391Shigella flexneri, the causative agent of shigellosis, is a gram-negative bacterial pathogen that initiates infection by invading cells within the colonic epithelium. Contact with host cell surfaces induces a rapid burst of protein secretion via the Shigella type III secretion system (TTSS). The first proteins secreted are IpaD, IpaB, and IpaC, with IpaB and IpaC being inserted into the host cell membrane to form a pore for translocating late effectors into the target cell cytoplasm. The resulting pathogen-host cross talk results in localized actin polymerization, membrane ruffling, and, ultimately, pathogen entry. IpaD is essential for host cell invasion, but its role in this process is just now coming to light. IpaD is a multifunctional protein that controls the secretion and presentation of IpaB and IpaC at the pathogen-host interface. We show here that antibodies recognizing the surface-exposed N terminus of IpaD neutralize Shigella's ability to promote pore formation in erythrocyte membranes. We further show that MxiH and IpaD colocalize on the bacterial surface. When TTSS needles were sheared from the Shigella surface, IpaD was found at only the needle tips. Consistent with this, IpaD localized to the exposed tips of needles that were still attached to the bacterium. Molecular analyses then showed that the IpaD C terminus is required for this surface localization and function. Furthermore, mutations that prevent IpaD surface localization also eliminate all IpaD-related functions. Thus, this study demonstrates that IpaD localizes to the TTSA needle tip, where it functions to control the secretion and proper insertion of translocators into host cell membrane