Radiative Shock-Induced Collapse of Intergalactic Clouds

Accumulating observational evidence for a number of radio galaxies suggests an association between their jets and regions of active star formation. The standard picture is that shocks generated by the jet propagate through an inhomogeneous medium and trigger the collapse of overdense clouds, which then become active star-forming regions. In this contribution, we report on recent hydrodynamic simulations of radiative shock-cloud interactions using two different cooling models: an equilibrium cooling-curve model assuming solar metallicities and a non-equilibrium chemistry model appropriate for primordial gas clouds. We consider a range of initial cloud densities and shock speeds in order to quantify the role of cooling in the evolution. Our results indicate that for moderate cloud densities (>1 cm^{-3}) and shock Mach numbers (<20), cooling processes can be highly efficient and result in more than 50% of the initial cloud mass cooling to below 100 K. We also use our results to estimate the final H_2 mass fraction for the simulations that use the non-equilibrium chemistry package. This is an important measurement, since H_2 is the dominant coolant for a primordial gas cloud. We find peak H_2 mass fractions of >0.01 and total H_2 mass fractions of >10^{-5} for the cloud gas. Finally, we compare our results with the observations of jet-induced star formation in ``Minkowski's Object.'' We conclude that its morphology, star formation rate (~ 0.3M_solar/yr) and stellar mass (~ 1.2 x 10^7 M_solar) can be explained by the interaction of a 90,000 km/s jet with an ensemble of moderately dense (~ 10 cm^{-3}), warm (10^4 K) intergalactic clouds in the vicinity of its associated radio galaxy at the center of the galaxy cluster.Comment: 30 pages, 7 figures, submitted to Astrophysical Journa

Phylesystem: a git-based data store for community-curated phylogenetic estimates

Motivation: Phylogenetic estimates from published studies can be archived using general platforms like Dryad (Vision, 2010) or TreeBASE (Sanderson et al., 1994). Such services fulfill a crucial role in ensuring transparency and reproducibility in phylogenetic research. However, digital tree data files often require some editing (e.g. rerooting) to improve the accuracy and reusability of the phylogenetic statements. Furthermore, establishing the mapping between tip labels used in a tree and taxa in a single common taxonomy dramatically improves the ability of other researchers to reuse phylogenetic estimates. As the process of curating a published phylogenetic estimate is not error-free, retaining a full record of the provenance of edits to a tree is crucial for openness, allowing editors to receive credit for their work and making errors introduced during curation easier to correct. Results: Here, we report the development of software infrastructure to support the open curation of phylogenetic data by the community of biologists. The backend of the system provides an interface for the standard database operations of creating, reading, updating and deleting records by making commits to a git repository. The record of the history of edits to a tree is preserved by git’s version control features. Hosting this data store on GitHub (http://github.com/) provides open access to the data store using tools familiar to many developers. We have deployed a server running the ‘phylesystem-api’, which wraps the interactions with git and GitHub. The Open Tree of Life project has also developed and deployed a JavaScript application that uses the phylesystem-api and other web services to enable input and curation of published phylogenetic statements

Allocation under dictatorship : research in Stalin’s archives

We survey recent research on the Soviet economy in the state, party, and military archives of the Stalin era. The archives have provided rich new evidence on the economic arrangements of a command system under a powerful dictator including Stalin’s role in the making of the economic system and economic policy, Stalin’s accumulation objectives and the constraints that limited his power to achieve them, the limits to administrative allocation, the information flows and incentives that governed the behavior of economic managers, the scope and significance of corruption and market-oriented behavior, and the prospects for economic reform

A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma.

BACKGROUND: This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. METHODS: Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils  1. Baseline HR23B expression was assessed by immunohistochemistry. RESULTS: Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3-4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2-5.4) in solid-organ cancers and 2.6 months (95%CI 1.2-5.6) in lymphomas. HR23B status did not predict response. CONCLUSIONS: CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Counting the bodies: Estimating the numbers and spatial variation of Australian reptiles, birds and mammals killed by two invasive mesopredators

Aim Introduced predators negatively impact biodiversity globally, with insular fauna often most severely affected. Here, we assess spatial variation in the number of terrestrial vertebrates (excluding amphibians) killed by two mammalian mesopredators introduced to Australia, the red fox (Vulpes vulpes) and feral cat (Felis catus). We aim to identify prey groups that suffer especially high rates of predation, and regions where losses to foxes and/or cats are most substantial. Location Australia. Methods We draw information on the spatial variation in tallies of reptiles, birds and mammals killed by cats in Australia from published studies. We derive tallies for fox predation by (i) modelling continental-scale spatial variation in fox density, (ii) modelling spatial variation in the frequency of occurrence of prey groups in fox diet, (iii) analysing the number of prey individuals within dietary samples and (iv) discounting animals taken as carrion. We derive point estimates of the numbers of individuals killed annually by foxes and by cats and map spatial variation in these tallies. Results Foxes kill more reptiles, birds and mammals (peaking at 1071 km−2 year−1) than cats (55 km−2 year−1) across most of the unmodified temperate and forested areas of mainland Australia, reflecting the generally higher density of foxes than cats in these environments. However, across most of the continent – mainly the arid central and tropical northern regions (and on most Australian islands) – cats kill more animals than foxes. We estimate that foxes and cats together kill 697 million reptiles annually in Australia, 510 million birds and 1435 million mammals. Main conclusions This continental-scale analysis demonstrates that predation by two introduced species takes a substantial and ongoing toll on Australian reptiles, birds and mammals. Continuing population declines and potential extinctions of some of these species threatens to further compound Australia's poor contemporary conservation record

Abrogation of Stem Loop Binding Protein (Slbp) function leads to a failure of cells to transition from proliferation to differentiation, retinal coloboma and midline axon guidance deficits

Through forward genetic screening for mutations affecting visual system development, we identified prominent coloboma and cell-autonomous retinal neuron differentiation, lamination and retinal axon projection defects in eisspalte (ele) mutant zebrafish. Additional axonal deficits were present, most notably at midline axon commissures. Genetic mapping and cloning of the ele mutation showed that the affected gene is slbp, which encodes a conserved RNA stem-loop binding protein involved in replication dependent histone mRNA metabolism. Cells throughout the central nervous system remained in the cell cycle in ele mutant embryos at stages when, and locations where, post-mitotic cells have differentiated in wild-type siblings. Indeed, RNAseq analysis showed down-regulation of many genes associated with neuronal differentiation. This was coincident with changes in the levels and spatial localisation of expression of various genes implicated, for instance, in axon guidance, that likely underlie specific ele phenotypes. These results suggest that many of the cell and tissue specific phenotypes in ele mutant embryos are secondary to altered expression of modules of developmental regulatory genes that characterise, or promote transitions in, cell state and require the correct function of Slbp-dependent histone and chromatin regulatory genes