Theory of Stellar Population Synthesis with an application to N-Body simulations

Aims. We present here a new theoretical approach to population synthesis. The aim is to predict colour magnitude diagrams (CMDs) for huge numbers of stars. With this method we generate synthetic CMDs for N-body simulations of galaxies. Sophisticated hydrodynamic N-body models of galaxies require equal quality simulations of the photometric properties of their stellar content. The only prerequisite for the method to work is very little information on the star formation and chemical enrichment histories, i.e. the age and metallicity of all star-particles as a function of time. The method takes into account the gap between the mass of real stars and that of the star-particles in N-body simulations, which best correspond to the mass of star clusters with different age and metallicity, i.e. a manifold of single stellar sopulations (SSP). Methods. The theory extends the concept of SSP to include the phase-space (position and velocity) of each star. Furthermore, it accelerates the building up of simulated CMD by using a database of theoretical SSPs that extends to all ages and metallicities of interest. Finally, it uses the concept of distribution functions to build up the CMD. The technique is independent of the mass resolution and the way the N-body simulation has been calculated. This allows us to generate CMDs for simulated stellar systems of any kind: from open clusters to globular clusters, dwarf galaxies, or spiral and elliptical galaxies. Results. The new theory is applied to an N-body simulation of a disc galaxy to test its performance and highlight its flexibility.Comment: accepted for publication in A&

pyPcazip: A PCA-based toolkit for compression and analysis of molecular simulation data

AbstractThe biomolecular simulation community is currently in need of novel and optimised software tools that can analyse and process, in reasonable timescales, the large generated amounts of molecular simulation data. In light of this, we have developed and present here pyPcazip: a suite of software tools for compression and analysis of molecular dynamics (MD) simulation data. The software is compatible with trajectory file formats generated by most contemporary MD engines such as AMBER, CHARMM, GROMACS and NAMD, and is MPI parallelised to permit the efficient processing of very large datasets. pyPcazip is a Unix based open-source software (BSD licenced) written in Python

CXCR4 Identifies Transitional Bone Marrow Premonocytes that Replenish the Mature Monocyte Pool for Peripheral Responses

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues

CXCR4 identifies transitional bone marrow premonocytes that replenish the mature monocyte pool for peripheral responses

It is well established that Ly6Chi monocytes develop from common monocyte progenitors (cMoPs) and reside in the bone marrow (BM) until they are mobilized into the circulation. In our study, we found that BM Ly6Chi monocytes are not a homogenous population, as current data would suggest. Using computational analysis approaches to interpret multidimensional datasets, we demonstrate that BM Ly6Chi monocytes consist of two distinct subpopulations (CXCR4hi and CXCR4lo subpopulations) in both mice and humans. Transcriptome studies and in vivo assays revealed functional differences between the two subpopulations. Notably, the CXCR4hi subset proliferates and is immobilized in the BM for the replenishment of functionally mature CXCR4lo monocytes. We propose that the CXCR4hi subset represents a transitional premonocyte population, and that this sequential step of maturation from cMoPs serves to maintain a stable pool of BM monocytes. Additionally, reduced CXCR4 expression on monocytes, upon their exit into the circulation, does not reflect its diminished role in monocyte biology. Specifically, CXCR4 regulates monocyte peripheral cellular activities by governing their circadian oscillations and pulmonary margination, which contributes toward lung injury and sepsis mortality. Together, our study demonstrates the multifaceted role of CXCR4 in defining BM monocyte heterogeneity and in regulating their function in peripheral tissues

Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

Angiogenesis is an essential requirement for tumour growth and metastasis and is regulated by a complex network of factors produced by both stromal cells and neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to promote tumour angiogenesis. We have demonstrated recently that high numbers of tumour-associated macrophages (TAMs) are significantly associated with increased tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We have also shown that TAMs are a major source of TNF-alpha in invasive breast carcinomas, and that macrophage-like stromal cells as well as tumour cells synthesize TP in such tumours. However, little is known of the factors that regulate the production or activity of these factors in the tumour microenvironment. As TNF-alpha has been shown to up-regulate TP expression in tumour cells in vitro we performed an immunohistochemical study to investigate the possibility that TNF-alpha may be involved in the regulation of TP expression by malignant breast epithelial cells in vivo. To do this, we used a cocktail of non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha-expressing macrophages and TNF-alpha bound to its receptors on tumour cells and endothelial cells in a series of 93 invasive carcinomas of the breast. A semiquantitative grading system was then used to compare these staining patterns with that for TP in the same biopsies. TNF-alpha immunoreactivity was also compared with various important tumour variables known to relate to outcome in this disease (microvessel density, node status, grade, stage, receptor status and macrophage infiltration), as well as relapse-free and overall survival data for these patients. Our data show significant positive correlations between TNF-alpha bound to its receptors on tumour cells and: (1) TP protein production by tumour cells, and (2) axillary lymph node status (i.e. metastasis). These results suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring TAMs may play a part in the regulation of TP expression by tumour cells as well as their metastatic behaviour. This may explain, in part, the relationship between increased macrophage infiltration and angiogenesis in breast cancer, and further supports the contention that TAMs may represent an important target for future anti-angiogenic therapies

A wide angle view of the Sagittarius dwarf Spheroidal Galaxy. I: VIMOS photometry and radial velocities across Sgr dSph major and minor axis

The Sagittarius dwarf Spheroidal Galaxy (Sgr dSph) provides us with a unique possibility of studying a dwarf galaxy merging event while still in progress. Due to its low distance (25 kpc), the main body of Sgr dSph covers a vast area in the sky (roughly 15 x 7 degrees). Available photometric and spectroscopic studies have concentrated either on the central part of the galaxy or on the stellar stream, but the overwhelming majority of the galaxy body has never been probed. The aim of the present study is twofold. On the one hand, to produce color magnitude diagrams across the extension of Sgr dSph to study its stellar populations, searching for age and/or composition gradients (or lack thereof). On the other hand, to derive spectroscopic low-resolution radial velocities for a subsample of stars to determine membership to Sgr dSph for the purpose of high resolution spectroscopic follow-up. We used VIMOS-VLT to produce V and I photometry and spectroscopy on 7 fields across the Sgr dSph minor and major axis, plus 3 more centered on the associated globular clusters Terzan 7, Terzan 8 and Arp 2. A last field has been centered on M 54, lying in the center of Sgr dSph. We present photometry for 320,000 stars across the main body of Sgr dSph, one of the richest, and safely the most wide-angle sampling ever produced for this fundamental object. We also provide robust memberships for more than one hundred stars, whose high resolution spectroscopic analysis will be the object of forthcoming papers. Sgr dSph appears remarkably uniform among the observed fields. We confirm the presence of a main Sgr dSph population characterized roughly by the same metallicity of 47 Tuc, but we also found the presence of multiple populations on the peripheral fields of the galaxy, with a metallicity spanning from [Fe/H]=-2.3 to a nearly solar value.Comment: 10 pages, 12 figures, accepted for publication in A&

Prophylactic radiotherapy against heterotopic ossification following internal fixation of acetabular fractures: a comparative estimate of risk.

OBJECTIVE: Radiotherapy (RT) is effective in preventing heterotopic ossification (HO) around acetabular fractures requiring surgical reconstruction. We audited outcomes and estimated risks from RT prophylaxis, and alternatives of indometacin or no prophylaxis. METHODS: 34 patients underwent reconstruction of acetabular fractures through a posterior approach, followed by a 8-Gy single fraction. The mean age was 44 years. The mean time from surgery to RT was 1.1 days. The major RT risk is radiation-induced fatal cancer. The International Commission on Radiological Protection (ICRP) method was used to estimate risk, and compared with a method (Trott and Kemprad) specifically for estimating RT risk for benign disease. These were compared with risks associated with indometacin and no prophylaxis. RESULTS: 28 patients (82%) developed no HO; 6 developed Brooker Class I; and none developed Class II-IV HO. The ICRP method suggests a risk of fatal cancer in the range of 1 in 1000 to 1 in 10,000; the Trott and Kemprad method suggests 1 in 3000. For younger patients, this may rise to 1 in 2000; and for elderly patients, it may fall to 1 in 6000. The risk of death from gastric bleeding or perforation from indometacin is 1 in 180 to 1 in 900 in older patients. Without prophylaxis risk of death from reoperation to remove HO is 1 in 4000 to 1 in 30,000. CONCLUSION: These results are encouraging, consistent with much larger series and endorse our multidisciplinary management. Risk estimates can be used in discussion with patients. ADVANCES IN KNOWLEDGE: The risk from RT prophylaxis is small, it is safer than indometacin and substantially overlaps with the range for no prophylaxis.NGB is supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. JES is supported by Cancer Research UK through the Cambridge Cancer Centre.This is the accepted manuscript version. The final version is available from the BIR at http://www.birpublications.org/doi/abs/10.1259/bjr.20140398?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&

An inverse method to interpret colour-magnitude diagrams

An inverse method is developed to determine the star formation history, the age-metallicity relation, and the IMF slope from a colour-magnitude diagram. The method is applied to the Hipparcos HR diagram. We found that the thin disk of our Galaxy shows a peak of stellar formation 1.6 Gyr ago. The stars close to the Sun have a solar metallicity and a mean IMF index equal to 3.2. However, the model and the evolutionary tracks do not correctly reproduce the horizontal giant branch.Comment: 14 pages, 11 figures. To be published in Astronomy & Astrophysic

Unit root testing under a local break in trend using partial information on the break date*

We consider unit root testing allowing for a break in trend when partial information is available regarding the location of the break date. This takes the form of knowledge of a relatively narrow window of data within which the break takes place, should it occur at all. For such circumstances, we suggest employing a union of rejections strategy, which combines a unit root test that allows for a trend break somewhere within the window, with a unit root test that makes no allowance for a trend break. Asymptotic and _nite sample evidence shows that our suggested strategy works well, provided that, when a break does occur, the partial information is correct. An empirical application to UK interest rate data containing the 1973 ‘oil shock’ is also considered