Body mass estimates of an exceptionally complete Stegosaurus (Ornithischia: Thyreophora): comparing volumetric and linear bivariate mass estimation methods

© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. The file attached is the published version of the article

Response to arXiv:0811.3876 "Comment on a recent conjectured solution of the three dimensional Ising model" by Wu et al

This is a Response to a recent Comment [F.Y. Wu et al., Phil. Mag. 88, 3093 (2008), arXiv:0811.3876] on the conjectured solution of the three-dimensional (3D) Ising model [Z.D. Zhang, Phil. Mag. 87, 5309 (2007), arXiv:0705.1045]. Several points are made: 1) Conjecture 1, regarding the additional rotation, is understood as performing a transformation for smoothing all the crossings of the knots; 2) The weight factors in Conjecture 2 are interpreted as a novel topologic phase; 3) The conjectured solution and its low- and high-temperature expansions are supported by the mathematical theorems for the analytical behavior of the Ising model. The physics behind the extra dimension is also discussed briefly.Comment: 11 pages, 0 figure

Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Dynamic Modelling under Uncertainty: The Case of Trypanosoma brucei Energy Metabolism

Kinetic models of metabolism require detailed knowledge of kinetic parameters. However, due to measurement errors or lack of data this knowledge is often uncertain. The model of glycolysis in the parasitic protozoan Trypanosoma brucei is a particularly well analysed example of a quantitative metabolic model, but so far it has been studied with a fixed set of parameters only. Here we evaluate the effect of parameter uncertainty. In order to define probability distributions for each parameter, information about the experimental sources and confidence intervals for all parameters were collected. We created a wiki-based website dedicated to the detailed documentation of this information: the SilicoTryp wiki (http://silicotryp.ibls.gla.ac.uk/wiki/Glycolysis). Using information collected in the wiki, we then assigned probability distributions to all parameters of the model. This allowed us to sample sets of alternative models, accurately representing our degree of uncertainty. Some properties of the model, such as the repartition of the glycolytic flux between the glycerol and pyruvate producing branches, are robust to these uncertainties. However, our analysis also allowed us to identify fragilities of the model leading to the accumulation of 3-phosphoglycerate and/or pyruvate. The analysis of the control coefficients revealed the importance of taking into account the uncertainties about the parameters, as the ranking of the reactions can be greatly affected. This work will now form the basis for a comprehensive Bayesian analysis and extension of the model considering alternative topologies

Adenosine Kinase of T. b. rhodesiense Identified as the Putative Target of 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine Using Chemical Proteomics

Human African trypanosomiasis (HAT), a devastating and fatal parasitic disease endemic in sub-Saharan Africa, urgently needs novel targets and efficacious chemotherapeutic agents. Recently, we discovered that 4-[5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine exhibits specific antitrypanosomal activity toward T. b. rhodesiense, the causative agent of the acute form of HAT. Here we applied a chemical proteomics approach to find the cellular target of this compound. Adenosine kinase, a key enzyme of the parasite purine salvage pathway, was isolated and identified as compound binding partner. Direct binding assays using recombinant protein, and tests on an adenosine kinase knock-down mutant of the parasite produced by RNA interference confirmed TbrAK as the putative target. Kinetic analyses showed that the title compound is an activator of adenosine kinase and that the observed hyperactivation of TbrAK is due to the abolishment of the intrinsic substrate-inhibition. Whereas hyperactivation as a mechanism of action is well known from drugs targeting cell signaling, this is a novel and hitherto unexplored concept for compounds targeting metabolic enzymes, suggesting that hyperactivation of TbrAK may represent a novel therapeutic strategy for the development of trypanocides

Male characteristics as predictors of genital color and display variation in vervet monkeys

In the animal kingdom, conspicuous colors are often used for inter-and intra-sexual communication. Even though primates are the most colorful mammalian taxon, many questions, including what potential information color signals communicate to social partners, are not fully understood. Vervet monkeys (Chlorocebus pygerythrus) are ideal to examine the covariates of color signals. Males have multi-colored genitals, which they present during distinctive male-male interactions, known as the "Red-White-and-Blue" (RWB) display, but the genitals are also visible across a variety of other contexts, and it is unclear what this color display signals to recipients. We recorded genital color presentations and standardized digital photos of male genitals (N = 405 photos) over one mating season for 20 adult males in three groups at the Samara Private Game Reserve, South Africa. We combined these with data on male characteristics (dominance, age, tenure length, injuries, and fecal glucocorticoid metabolite concentrations). Using visual modeling methods, we measured single colors (red, white, blue) but also the contrasts between colors. We assessed the frequency of the RWB genital display and male variation in genital coloration and linked this to male characteristics. Our data suggest that the number of genital displays increased with male dominance. However, none of the variables investigated explained the inter-and intra-individual variation in male genital coloration. These results suggest that the frequency of the RWB genital display, but not its color value, is related to dominance, providing valuable insights on covariation in color signals and their display in primates. Significance statement Conspicuous colors in animals often communicate individual quality to mates and rivals. By investigating vervet monkeys, a primate species in which males present their colorful genitals within several behavioral displays, we aim to identify the covariates Communicated by E. Huchard Electronic supplementary material The online version of this article (https://doi.org/10

Innovation in assessment: building student confidence in preparation for unfamiliar assessment methods

Innovative assessment methods in which students are active participants promote deeper learning. A group debate and a webfolio were implemented as methods of assessment in the 2015 undergraduate midwifery curriculum, with the assessment tools being evaluated by students. Thematic analysis of the evaluations showed students enjoyed undertaking innovative methods of assessment, they developed confidence and engaged meaningfully with the content to be assessed. Students also commented they developed multiple skills required for future professional practice as a midwife. Thorough preparation of students to undertake an innovative method of assessment however is vital in fostering student confidence

Context-Specific Metabolic Networks Are Consistent with Experiments

Reconstructions of cellular metabolism are publicly available for a variety of different microorganisms and some mammalian genomes. To date, these reconstructions are “genome-scale” and strive to include all reactions implied by the genome annotation, as well as those with direct experimental evidence. Clearly, many of the reactions in a genome-scale reconstruction will not be active under particular conditions or in a particular cell type. Methods to tailor these comprehensive genome-scale reconstructions into context-specific networks will aid predictive in silico modeling for a particular situation. We present a method called Gene Inactivity Moderated by Metabolism and Expression (GIMME) to achieve this goal. The GIMME algorithm uses quantitative gene expression data and one or more presupposed metabolic objectives to produce the context-specific reconstruction that is most consistent with the available data. Furthermore, the algorithm provides a quantitative inconsistency score indicating how consistent a set of gene expression data is with a particular metabolic objective. We show that this algorithm produces results consistent with biological experiments and intuition for adaptive evolution of bacteria, rational design of metabolic engineering strains, and human skeletal muscle cells. This work represents progress towards producing constraint-based models of metabolism that are specific to the conditions where the expression profiling data is available

Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda

Children’s perceptions of dissimilarity in parenting styles are associated with internalizing and externalizing behavior

The purpose of this study was to examine the relationship between children’s perception of dissimilarity in parenting styles, and internalizing and externalizing problems in children. Children from the general population (n = 658) reported on the level of emotional warmth, rejection, and overprotection of both parents by filling out the child version of the Egna Minnen Beträffande Uppfostran (EMBU-C) and mothers completed the child behavior checklist (CBCL). Intraclass correlations were computed as measures of dissimilarity between parenting styles of mothers and fathers. Children’s perceived dissimilarity in parental emotional warmth is associated with internalizing and externalizing problems (β = 0.092, p < 0.05; β = 0.091, p < 0.05). Perceived dissimilarity between parents’ overprotection is associated with externalizing problems (β = 0.097, p < 0.05). Perceived dissimilarity between parenting styles is associated with externalizing and internalizing problems, over and above the effects of the level of the parenting styles. The results highlight the negative consequences of perceived dissimilarity between parents. To conclude, children have more internalizing and externalizing problems when they perceive their parents as more dissimilar in parenting styles