After the war is over: the role of General Sir Arthur Currie in the development of academic medicine in Canada

Canadian universities faced a challenge with the return of a large cohort of battle-hardened students and faculty from the First World War. General Sir Arthur Currie, considered one of the few successful generals of the war, returned to a welcome of silence in Canada. McGill University exploited the opportunity to recruit him as its president. Currie oversaw a campaign of building construction and faculty development at McGill that also had a significant effect on the rest of Canada. Through his fostering of the Montreal Neurological Institute and the recruitment of Dr. Wilder Penfield, Currie facilitated the development of multidisciplinary medicine, which integrates clinical care with research — an aspiration still held by specialty medicine in Canada today

Digging by Debating: Linking massive datasets to specific arguments

We will develop and implement a multi-scale workbench, called "InterDebates", with the goal of digging into data provided by hundreds of thousands, eventually millions, of digitized books, bibliographic databases of journal articles, and comprehensive reference works written by experts. Our hypotheses are: that detailed and identifiable arguments drive many aspects of research in the sciences and the humanities; that argumentative structures can be extracted from large datasets using a mixture of automated and social computing techniques; and, that the availability of such analyses will enable innovative interdisciplinary research, and may also play a role in supporting better-informed critical debates among students and the general public. A key challenge tackled by this project is thus to uncover and represent the argumentative structure of digitized documents, allowing users to find and interpret detailed arguments in the broad semantic landscape of books and articles

Pofatu, a curated and open-access database for geochemical sourcing of archaeological materials

Compositional analyses have long been used to determine the geological sources of artefacts.Geochemical “fingerprinting” of artefacts and sources is the most effective way to reconstruct strategies of raw material and artefact procurement, exchange or interaction systems, and mobility patterns during prehistory. The efficacy and popularity of geochemical sourcing has led to many projects using various analytical techniques to produce independent datasets. In order to facilitate access to this growing body of data and to promote comparability and reproducibility in provenance studies, we designed Pofatu, the first online and open-access database to present geochemical compositions and contextual information for archaeological sources and artefacts in a form that can be readily accessed by the scientific community. This relational database currently contains 7759 individual samples from archaeological sites and geological sources across the Pacific Islands. Each sample is comprehensively documented and includes elemental and isotopic compositions, detailed archaeological provenance, and supporting analytical metadata, such as sampling processes, analytical procedures, and quality control

The use of non-uniform drowning terminology: a follow-up study

Background: In 2002, the World Congress on Drowning developed a uniform definition for drowning. The aim of this study is to determine the prevalence of “non-uniform drowning terminology� (NUDT) and “non-uniform drowning definitions� (NUDD) in peer-reviewed scientific literature from 2010 to 2016, and compare these findings with those from our unpublished study performing a similar analysis on literature from 2003 to 2010. Methods: A systematic review was performed using drowning-specific search terms in Pubmed and Web of Science. Titles and abstracts published between July 2010 and January 2016 were screened for relevance to the study focus. Articles meeting screening criteria were reviewed for exclusion criteria to produce the final group of studies. These articles were reviewed by four reviewers for NUDT and NUDD. The Fisher exact test was used to determine any statistically significant changes. Results: The final group of studies included 167 articles. A total of 53 articles (32%) utilized NUDT, with 100% of these including the term “near drowning�. The proportion of articles utilizing NUDT was significantly less than reported by our previous study (p < 0.05). In addition, 32% of the articles included a definition for drowning (uniform or non-uniform), with 15% of these utilizing NUDD. Discussion: Our study reveals a statistically significant improvement over the past thirteen years in the use of uniform drowning terminology in peer-reviewed scientific literature, although year-to-year variability over the current study period does not yield an obvious trend. Conclusions: Of the articles reviewed during the 2010-2016 study period, 32% included outdated and non-uniform drowning terminology and definitions. While this reveals an absolute decrease of 11% as compared with the previous study period (2003-2010), there is still significant room for improvement

Phosphorylation-dependent BRD4 dimerization and implications for therapeutic inhibition of BET family proteins.

Funder: AstraZenecaFunder: AstraZeneca postdoc fundBromodomain-containing protein 4 (BRD4) is an epigenetic reader and oncology drug target that regulates gene transcription through binding to acetylated chromatin via bromodomains. Phosphorylation by casein kinase II (CK2) regulates BRD4 function, is necessary for active transcription and is involved in resistance to BRD4 drug inhibition in triple-negative breast cancer. Here, we provide the first biophysical analysis of BRD4 phospho-regulation. Using integrative structural biology, we show that phosphorylation by CK2 modulates the dimerization of human BRD4. We identify two conserved regions, a coiled-coil motif and the Basic-residue enriched Interaction Domain (BID), essential for the BRD4 structural rearrangement, which we term the phosphorylation-dependent dimerization domain (PDD). Finally, we demonstrate that bivalent inhibitors induce a conformational change within BRD4 dimers in vitro and in cancer cells. Our results enable the proposal of a model for BRD4 activation critical for the characterization of its protein-protein interaction network and for the development of more specific therapeutics

The effect of interfacial phenomena on gas solubility measurements in molten salts

The behavior of fission gases in molten fuel salt reactors governs activity transport from the reactor and can also affect the performance of the reactor itself. The gas solubility can be described thermodynamically by Henry’s law. However, the coupling of the condensed and gas phases depends on the interfacial area, which is difficult to measure or even to estimate. Surfaces of materials in the reactor will include disperse phases in the salt and porosity within the structural materials, covering a range of compositions and sizes. These attributes can affect measurements of fundamental properties such as gas solubility. Methods to obtain gas solubility, surface tension, interfacial energies, and bubble gas transport are reviewed. Recent data from manometric experiments are interpreted based on xenon sorption onto salt-wetted quartz

Novel virus discovery and genome reconstruction from field RNA samples reveals highly divergent viruses in dipteran hosts.

We investigated whether small RNA (sRNA) sequenced from field-collected mosquitoes and chironomids (Diptera) can be used as a proxy signature of viral prevalence within a range of species and viral groups, using sRNAs sequenced from wild-caught specimens, to inform total RNA deep sequencing of samples of particular interest. Using this strategy, we sequenced from adult Anopheles maculipennis s.l. mosquitoes the apparently nearly complete genome of one previously undescribed virus related to chronic bee paralysis virus, and, from a pool of Ochlerotatus caspius and Oc. detritus mosquitoes, a nearly complete entomobirnavirus genome. We also reconstructed long sequences (1503-6557 nt) related to at least nine other viruses. Crucially, several of the sequences detected were reconstructed from host organisms highly divergent from those in which related viruses have been previously isolated or discovered. It is clear that viral transmission and maintenance cycles in nature are likely to be significantly more complex and taxonomically diverse than previously expected

Immune-mediated competition in rodent malaria is most likely caused by induced changes in innate immune clearance of merozoites

Malarial infections are often genetically diverse, leading to competitive interactions between parasites. A quantitative understanding of the competition between strains is essential to understand a wide range of issues, including the evolution of virulence and drug resistance. In this study, we use dynamical-model based Bayesian inference to investigate the cause of competitive suppression of an avirulent clone of Plasmodium chabaudi (AS) by a virulent clone (AJ) in immuno-deficient and competent mice. We test whether competitive suppression is caused by clone-specific differences in one or more of the following processes: adaptive immune clearance of merozoites and parasitised red blood cells (RBCs), background loss of merozoites and parasitised RBCs, RBC age preference, RBC infection rate, burst size, and within-RBC interference. These processes were parameterised in dynamical mathematical models and fitted to experimental data. We found that just one parameter μ, the ratio of background loss rate of merozoites to invasion rate of mature RBCs, needed to be clone-specific to predict the data. Interestingly, μ was found to be the same for both clones in single-clone infections, but different between the clones in mixed infections. The size of this difference was largest in immuno-competent mice and smallest in immuno-deficient mice. This explains why competitive suppression was alleviated in immuno-deficient mice. We found that competitive suppression acts early in infection, even before the day of peak parasitaemia. These results lead us to argue that the innate immune response clearing merozoites is the most likely, but not necessarily the only, mediator of competitive interactions between virulent and avirulent clones. Moreover, in mixed infections we predict there to be an interaction between the clones and the innate immune response which induces changes in the strength of its clearance of merozoites. What this interaction is unknown, but future refinement of the model, challenged with other datasets, may lead to its discovery

Geochemical Sourcing of New Zealand Obsidians by Portable X-Ray Fluorescence from 2011 to 2018

This dataset includes 4,582 obsidian artefacts matched to their natural geological source from 45 archaeological sites in New Zealand (Aotearoa). It is a compilation of a number of independent projects conducted in the laboratories of the University of Auckland and University of Otago from 2011 to 2018 [1–13]. It combines previously published studies [3, 5–13], an MA thesis [1], a BA(Hons) dissertation [2], a site report [4], and other previously unpublished primary data. The dataset has high reuse potential for future non-destructive studies of artefacts and social network analyses.   Funding statement: This database began as part of a project funded by Royal Society of New Zealand Marsden Grant (UOA1619) and the support of Te Pūnaha Matatini