Made-to-Measure Modelling of Globular Clusters

We present the first application of the made-to-measure method for modelling dynamical systems to globular clusters. Through the made-to-measure algorithm, the masses of individual particles within a model cluster are adjusted while the system evolves forward in time via a gravitational $N$-body code until the model cluster is able to reproduce select properties of an observed cluster. The method is first applied to observations of mock isotropic and anisotropic clusters while fitting against the cluster's three dimensional or projected density profile, density weighted mean-squared velocity profile, or its density profile with individual mean-squared velocity profiles. We find that a cluster's three-dimensional density profile can easily be reproduced by the made-to-measure method, with minor discrepancies in the outer regions if fitting against a cluster's projected surface density or projected kinematic properties. If an observed cluster is anisotropic, only fitting against the cluster's density profile and individual mean-squared velocity profiles will fully recover the full degree of anisotropy. Partial anisotropy can be recovered as long as two kinematic properties are included in the fit. We further apply the method to observations of the Galactic globular cluster M4 and generate a complete six-dimensional representation of the cluster that reproduces observations of its surface density profile, mean-squared proper motion velocity profile, and mean-squared line of sight velocity profile. The M2M method predicts M4 is primarily isotropic with a mass of $9.2 \pm 0.4 \times 10^4\, M_{\odot}$ and a half-mass radius of $3.7 \pm 0.1$ pc.Comment: 11 pages, 10 figures, submitted to MNRAS for publicatio

Hierarchical Bayesian Inference of Globular Cluster Properties

We present a hierarchical Bayesian inference approach to estimating the structural properties and the phase space center of a globular cluster (GC) given the spatial and kinematic information of its stars based on lowered isothermal cluster models. As a first step towards more realistic modelling of GCs, we built a differentiable, accurate emulator of the lowered isothermal distribution function using interpolation. The reliable gradient information provided by the emulator allows the use of Hamiltonian Monte Carlo methods to sample large Bayesian models with hundreds of parameters, thereby enabling inference on hierarchical models. We explore the use of hierarchical Bayesian modelling to address several issues encountered in observations of GC including an unknown GC center, incomplete data, and measurement errors. Our approach not only avoids the common technique of radial binning but also incorporates the aforementioned uncertainties in a robust and statistically consistent way. Through demonstrating the reliability of our hierarchical Bayesian model on simulations, our work lays out the foundation for more realistic and complex modelling of real GC data.Comment: 16 pages, 12 figures, and 2 table

Searching for the extra-tidal stars of globular clusters using high-dimensional analysis and a core particle spray code

Three-body interactions can eject stars from the core of a globular cluster, causing them to enter the Galactic halo as extra-tidal stars. While finding extra-tidal stars is imperative for understanding cluster evolution, connecting isolated extra-tidal field stars back to their birth cluster is extremely difficult. In this work, we present a new methodology consisting of high-dimensional data analysis and a particle spray code to identify extra-tidal stars of any Galactic globular cluster using M3 as a case study. Using the t-Stochastic Neighbour Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP) machine learning dimensionality reduction algorithms, we first identify a set of 103 extra-tidal candidates in the APOGEE DR17 data catalogue with chemical abundances similar to M3 stars. To confirm each candidate's extra-tidal nature, we introduce Corespray; a new Python-based three-body particle spray code that simulates extra-tidal stars for any Galactic globular cluster. Using Gaia EDR3 proper motions and APOGEE DR17 radial velocities, we apply multivariate Gaussian modelling and an extreme deconvolution to identify the extra-tidal candidates that are more likely to be associated with a distribution of Corespray-simulated M3 extra-tidal stars than the field. Through these methods, we identify 13 new high-probability extra-tidal stars of M3. Future applications of Corespray will yield better understandings of core dynamics, star formation histories and binary fractions in globular clusters.Comment: 15 pages, 8 figures, 2 tables. Submitted to Monthly Notices of the Royal Astronomical Societ

The dominant mechanism(s) for populating the outskirts of star clusters with neutron star binaries

It has been argued that heavy binaries composed of neutron stars (NSs) and millisecond pulsars (MSPs) can end up in the outskirts of star clusters via an interaction with a massive black hole (BH) binary expelling them from the core. We argue here, however, that this mechanism will rarely account for such observed objects. Only for primary masses $\lesssim$ 100 M$_{\odot}$ and a narrow range of orbital separations should a BH-BH binary be both dynamically hard and produce a sufficiently low recoil velocity to retain the NS binary in the cluster. Hence, BH binaries are in general likely to eject NSs from clusters. We explore several alternative mechanisms that would cause NS/MSP binaries to be observed in the outskirts of their host clusters after a Hubble time. The most likely mechanism is a three-body interaction involving the NS/MSP binary and a normal star. We compare to Monte Carlo simulations of cluster evolution for the globular clusters NGC 6752 and 47 Tuc, and show that the models not only confirm that normal three-body interactions involving all stellar-mass objects are the dominant mechanism for putting NS/MSP binaries into the cluster outskirts, they also reproduce the observed NS/MSP binary radial distributions without needing to invoke the presence of a massive BH binary. Higher central densities and an episode of core-collapse can broaden the radial distributions of NSs/MSPs and NS/MSP binaries due to three-body interactions, making these clusters more likely to host NSs in the cluster outskirts.Comment: 13 pages, 7 figures, 2 tables, submitted to MNRA

Comparative Genomics of Carriage and Disease Isolates of Streptococcus pneumoniae Serotype 22F Reveals Lineage-Specific Divergence and Niche Adaptation

Streptococcus pneumoniae is a major cause of meningitis, sepsis, and pneumonia worldwide. Pneumococcal conjugate vaccines have been part of the United Kingdom’s childhood immunization program since 2006 and have significantly reduced the incidence of disease due to vaccine efficacy in reducing carriage in the population. Here we isolated two clones of 22F (an emerging serotype of clinical concern, multilocus sequence types 433 and 698) and conducted comparative genomic analysis on four isolates, paired by Sequence Type (ST) with one of each pair being derived from carriage and the other disease (sepsis). The most compelling observation was of nonsynonymous mutations in pgdA, encoding peptidoglycan N-acetylglucosamine deacetylase A, which was found in the carriage isolates of both ST433 and 698. Deacetylation of pneumococcal peptidoglycan is known to enable resistance to lysozyme upon invasion. Althought no other clear genotypic signatures related to disease or carriage could be determined, additional intriguing comparisons between the two STs were possible. These include the presence of an intact prophage, in addition to numerous additional phage insertions, within the carriage isolate of ST433. Contrasting gene repertoires related to virulence and colonization, including bacteriocins, lantibiotics, and toxin-–antitoxin systems, were also observed

SNAVI: Desktop application for analysis and visualization of large-scale signaling networks

<p>Abstract</p> <p>Background</p> <p>Studies of cellular signaling indicate that signal transduction pathways combine to form large networks of interactions. Viewing protein-protein and ligand-protein interactions as graphs (networks), where biomolecules are represented as nodes and their interactions are represented as links, is a promising approach for integrating experimental results from different sources to achieve a systematic understanding of the molecular mechanisms driving cell phenotype. The emergence of large-scale signaling networks provides an opportunity for topological statistical analysis while visualization of such networks represents a challenge.</p> <p>Results</p> <p>SNAVI is Windows-based desktop application that implements standard network analysis methods to compute the clustering, connectivity distribution, and detection of network motifs, as well as provides means to visualize networks and network motifs. SNAVI is capable of generating linked web pages from network datasets loaded in text format. SNAVI can also create networks from lists of gene or protein names.</p> <p>Conclusion</p> <p>SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software. The installation may be downloaded from: <url>http://snavi.googlecode.com</url>. The source code can be accessed from: <url>http://snavi.googlecode.com/svn/trunk</url></p

Using the theory of planned behaviour as a process evaluation tool in randomised trials of knowledge translation strategies : A case study from UK primary care

Peer reviewedPublisher PD

Parallel evolution in streptococcus pneumoniae biofilms

Streptococcus pneumoniae is a commensal human pathogen and the causative agent of various invasive and noninvasive diseases. Carriage of the pneumococcus in the nasopharynx is thought to be mediated by biofilm formation, an environment where isogenic populations frequently give rise to morphological colony variants, including small colony variant (SCV) phenotypes. We employed metabolic characterization and whole-genome sequencing of biofilm-derived S. pneumoniae serotype 22F pneumococcal SCVs to investigate diversification during biofilm formation. Phenotypic profiling revealed that SCVs exhibit reduced growth rates, reduced capsule expression, altered metabolic profiles, and increased biofilm formation compared to the ancestral strain. Whole-genome sequencing of 12 SCVs from independent biofilm experiments revealed that all SCVs studied had mutations within the DNA-directed RNA polymerase delta subunit (RpoE). Mutations included four large-scale deletions ranging from 51 to 264 bp, one insertion resulting in a coding frameshift, and seven nonsense single-nucleotide substitutions that result in a truncated gene product. This work links mutations in the rpoE gene to SCV formation and enhanced biofilm development in S. pneumoniae and therefore may have important implications for colonization, carriage, and persistence of the organism. Furthermore, recurrent mutation of the pneumococcal rpoE gene presents an unprecedented level of parallel evolution in pneumococcal biofilm development