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Brown R.M.,University of Kansas | Linkem C.W.,University of Kansas | Siler C.D.,University of Kansas | Sukumaran J.,University of Kansas | And 9 more authors.
Molecular Phylogenetics and Evolution | Year: 2010

Southeast Asia's widespread species offer unique opportunities to explore the effects of geographical barriers to dispersal on patterns of vertebrate lineage diversification. We analyzed mitochondrial gene sequences (16S rDNA) from a geographically widespread sample of 266 Southeast Asian tree frogs, including 244 individuals of Polypedates leucomystax and its close relatives. Our expectation was that lineages on island archipelagos would exhibit more substantial geographic structure, corresponding to the geological history of terrestrial connectivity in this region, compared to the Asian mainland. Contrary to predictions, we found evidence of numerous highly divergent lineages from a limited area on the Asian mainland, but fewer lineages with shallower divergences throughout oceanic islands of the Philippines and Indonesia. Surprisingly and in numerous instances, lineages in the archipelagos span distinct biogeographical provinces. Phylogeographic analyses identified four major haplotype clades; summary statistics, mismatch distributions, and Bayesian coalescent inference of demography provide support for recent range expansion, population growth, and/or admixture in the Philippine and some Sulawesi populations. We speculate that the current range of P. leucomystax in Southeast Asia is much larger now than in the recent past. Conversion of forested areas to monoculture agriculture and transportation of agricultural products between islands may have facilitated unprecedented population and range expansion in P. leucomystax throughout thousands of islands in the Philippine and Indonesian archipelagos. © 2010 Elsevier Inc.


The study of the space between the state and the market (referred as “the study of the in-between space” throughout the article) has suffered from somewhat of an identity crisis since its inception. The crisis is reflected by the lack of a unified terminology, the lack of consensus on the principal characteristic of organizations in the space, and the debates on blurring sectoral boundaries. This article first provides a critical review of the intellectual trajectories of the search for publicness and the search for nonprofitness through the lens of organizational theory. By contrasting and analyzing the underlying reasons of both intellectual trajectories, this review concludes ownership (nonprofitness or publicness) is not the definitive characteristic of the subject organizations, and an open and multidimensional approach is more suitable. Second, this article then introduces articles included in this special issue and analyzing their common theme-context matters. © 2014, International Society for Third-Sector Research and The Johns Hopkins University.


Bewick A.J.,Room 328 | Anderson D.W.,Room 328 | Evans B.J.,Room 328
Evolution | Year: 2011

DM-W is a dominant, female-specific, regulator of sex determination in the African clawed frog Xenopus laevis. This gene is derived from partial duplication of DMRT1, a male-related autosomal gene. We set out to better understand sex determination in Xenopus by studying this pair of genes. We found that DM-W evolved in Xenopus after divergence from the sister genus Silurana but before divergence of X. laevis and X. clivii, and that DM-W arose from partial duplication of DMRT1β, which is one of the two DMRT1 paralogs in the tetraploid ancestor of Xenopus. Using the rate ratio of nonsynonymous to synonymous substitutions per site and multilocus polymorphism data, we show that DM-W evolved non-neutrally. By cloning paralogs and using a pyrosequencing assay, we also demonstrate that DMRT1 underwent phylogenetically biased pseudogenization after polyploidization, and that expression of this gene is regulated by mechanisms that vary through development. One explanation for these observations is that the expression domain of DMRT1β was marginalized, which would explain why this paralog is dispensable in Xenopus polyploids and why DM-W has a narrow expression domain. These findings illustrate how evolution of the genetic control of stable phenotypes is facilitated by redundancy, degeneration, and compartmentalized regulation. © 2010 The Author(s). Evolution © 2010 The Society for the Study of Evolution.


Liu M.,University of Sydney | Calvo R.A.,University of Sydney | Aditomo A.,University of Sydney | Pizzato L.A.,Room 328
IEEE Transactions on Learning Technologies | Year: 2012

In this paper, we present a novel approach for semiautomatic question generation to support academic writing. Our system first extracts key phrases from students' literature review papers. Each key phrase is matched with a Wikipedia article and classified into one of five abstract concept categories: Research Field, Technology, System, Term, and Other. Using the content of the matched Wikipedia article, the system then constructs a conceptual graph structure representation for each key phrase and the questions are then generated based the structure. To evaluate the quality of the computer generated questions, we conducted a version of the Bystander Turing test, which involved 20 research students who had written literature reviews for an IT methods course. The pedagogical values of generated questions were evaluated using a semiautomated process. The results indicate that the students had difficulty distinguishing between computer-generated and supervisor-generated questions. Computer-generated questions were also rated as being as pedagogically useful as supervisor-generated questions, and more useful than generic questions. The findings also suggest that the computer-generated questions were more useful for the first-year students than for second or third-year students. © 2008-2011 IEEE.


PubMed | Room 328
Type: Journal Article | Journal: Clinical pharmacokinetics | Year: 2013

Organic anion-transporting polypeptide (OATP)-mediated drug-drug interactions (DDIs) are among the most important classes of clinically relevant DDIs. Accurate prediction of the OATP-mediated DDIs is not successful due to the sequential disposition pathways of OATP substrates in humans. Intestinal and hepatic uptake transporters, efflux transporters, and cytochrome P450 (CYP) enzymes are often involved in the sequential disposition pathways of typical OATP substrates. The aim of this proof-of-concept study is to develop and validate a novel approach which can be used to predict OATP-mediated DDIs with significantly increased accuracy and decreased false-negatives.The feasibility of using a disposition pathway-dependent prediction (DPDP) approach to predict the ratios of the area under the plasma concentration-time curve (AUC(R)) in the presence and absence of the inhibitor was investigated. A total of 62 clinical DDI studies were included in this feasibility study. The disposition pathways governing the outcome of DDIs were first identified for each substrate using the information within learning sets, and then substrate-specific algorithms were used to predict the DDI risks of the external validation set (51 DDIs).The method predicted AUC(R) within 50-200 % for 50 studies (98 %), and the false-negative rate was 9.8 %. The DPDP approach showed significant improvement over an existing approach and was used to forecast the magnitude of 198 DDIs that have not been studied.This approach can be used to avoid unnecessary clinical DDI studies during new drug development.


PubMed | Room 328
Type: Journal Article | Journal: Drug metabolism and disposition: the biological fate of chemicals | Year: 2012

The in vivo drug-drug interaction (DDI) risks associated with cytochrome P450 inhibitors that have circulating inhibitory metabolites cannot be accurately predicted by conventional in vitro-based methods. A novel approach, in vivo information-guided prediction (IVIP), was recently introduced for CYP3A- and CYP2D6-mediated DDIs. This technique should be applicable to the prediction of DDIs involving other important cytochrome P450 metabolic pathways. Therefore, the aims of this study were to extend the IVIP approach to CYP2C9-mediated DDIs and evaluate the IVIP approach for predicting DDIs associated with inhibitory metabolites. The analysis was based on data from reported DDIs in the literature. The IVIP approach was modified and extended to CYP2C9-mediated DDIs. Thereafter, the IVIP approach was evaluated for predicting the DDI risks of various inhibitors with inhibitory metabolites. Although the data on CYP2C9-mediated DDIs were limited compared with those for CYP3A- and CYP2D6-mediated DDIs, the modified IVIP approach successfully predicted CYP2C9-mediated DDIs. For the external validation set, the prediction accuracy for area under the plasma concentration-time curve (AUC) ratios ranged from 70 to 125%. The accuracy (75-128%) of the IVIP approach in predicting DDI risks of inhibitors with circulating inhibitory metabolites was more accurate than in vitro-based methods (28-805%). The IVIP model accommodates important confounding factors in the prediction of DDIs, which are difficult to handle using in vitro-based methods. In conclusion, the IVIP approach could be used to predict CYP2C9-mediated DDIs and is easily modified to incorporate the additive effect of circulating inhibitory metabolites.


PubMed | Room 328
Type: Journal Article | Journal: Molecular ecology | Year: 2013

The Ethiopian highlands - home to striking species diversity and endemism - are bisected by the Rift Valley, a zone of tectonic divergence. Using molecular data we examined the evolutionary history of two co-distributed species of African clawed frog (Xenopus clivii and X. largeni) that are endemic to this region. Our field collections substantially extend the known distribution of X. largeni, a species formerly known from highlands southeast of the Rift, but that also occurs to the northwest. In both species, analysis of mitochondrial DNA and 19 autosomal loci identifies significant population structure, suggests little or no recent migration across the Rift Valley, and provides divergence time estimates across the Rift of 1-3.5 million years. These results indicate that the Ethiopian Rift Valley is a major obstacle to dispersal of highland-adapted amphibians.


PubMed | Room 328
Type: Journal Article | Journal: Systematic biology | Year: 2012

The estimation of phylogenetic relationships is an essential component of understanding evolution. Accurate phylogenetic estimation is difficult, however, when internodes are short and old, when genealogical discordance is common due to large ancestral effective population sizes or ancestral population structure, and when homoplasy is prevalent. Inference of divergence times is also hampered by unknown and uneven rates of evolution, the incomplete fossil record, uncertainty in relationships between fossil and extant lineages, and uncertainty in the age of fossils. Ideally, these challenges can be overcome by developing large phylogenomic data sets and by analyzing them with methods that accommodate features of the evolutionary process, such as genealogical discordance, recurrent substitution, recombination, ancestral population structure, gene flow after speciation among sampled and unsampled taxa, and variation in evolutionary rates. In some phylogenetic problems, it is possible to use information that is independent of fossils, such as the geological record, to identify putative triggers for diversification whose associated estimated divergence times can then be compared a posteriori with estimated relationships and ages of fossils. The history of diversification of pipid frog genera Pipa, Hymenochirus, Silurana, and Xenopus, for instance, is characterized by many of these evolutionary and analytical challenges. These frogs diversified dozens of millions of years ago, they have a relatively rich fossil record, their distributions span continental plates with a well characterized geological record of ancient connectivity, and there is considerable disagreement across studies in estimated evolutionary relationships. We used high throughput sequencing and public databases to generate a large phylogenomic data set with which we estimated evolutionary relationships using multilocus coalescence methods. We collected sequence data from Pipa, Hymenochirus, Silurana, and Xenopus and the outgroup taxon Rhinophrynus dorsalis from coding sequence of 113 autosomal regions, averaging 300 bp in length (range: 102-1695 bp) and also a portion of the mitochondrial genome. Analysis of these data using multiple approaches recovers strong support for the ((Xenopus, Silurana)(Pipa, Hymenochirus)) topology, and geologically calibrated divergence time estimates that are consistent with estimated ages and phylogenetic affinities of many fossils. These results provide new insights into the biogeography and chronology of pipid diversification during the breakup of Gondwanaland and illustrate how phylogenomic data may be necessary to tackle tough problems in molecular systematics. [Coalescence; gene tree; high-throughout sequencing; lineage sorting; pipid; species tree; Xenopus.].


PubMed | Anglia, Health Science University and Room 328
Type: Journal Article | Journal: British journal of clinical pharmacology | Year: 2015

The aim of this review was to summarize the prevalence, frequency and comparative value of information on the adverse events of healthcare interventions from user comments and videos in social media.A systematic review of assessments of the prevalence or type of information on adverse events in social media was undertaken. Sixteen databases and two internet search engines were searched in addition to handsearching, reference checking and contacting experts. The results were sifted independently by two researchers. Data extraction and quality assessment were carried out by one researcher and checked by a second. The quality assessment tool was devised in-house and a narrative synthesis of the results followed.From 3064 records, 51 studies met the inclusion criteria. The studies assessed over 174 social media sites with discussion forums (71%) being the most popular. The overall prevalence of adverse events reports in social media varied from 0.2% to 8% of posts. Twenty-nine studies compared the results from searching social media with using other data sources to identify adverse events. There was general agreement that a higher frequency of adverse events was found in social media and that this was particularly true for symptom related and mild adverse events. Those adverse events that were under-represented in social media were laboratory-based and serious adverse events.Reports of adverse events are identifiable within social media. However, there is considerable heterogeneity in the frequency and type of events reported, and the reliability or validity of the data has not been thoroughly evaluated.


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