X-ray and Radio Interactions in the Cores of Cooling Flow Clusters

We present high resolution ROSAT x-ray and radio observations of three cooling flow clusters containing steep spectrum radio sources at their cores. All three systems exhibit strong signs of interaction between the radio plasma and the hot intracluster medium. Two clusters, A133 and A2626, show enhanced x-ray emission spatially coincident with the radio source whereas the third cluster, A2052, exhibits a large region of x-ray excess surrounding much of the radio source. Using 3-D numerical simulations, we show that a perturbed jet propagating through a cooling flow atmosphere can give rise to amorphous radio morphologies, particularly in the case where the jet was ``turned off'' and allowed to age passively. In addition, the simulated x-ray surface brightness produced both excesses and deficits as seen observationally.Comment: 25 pages, 10 figures, accepted for publication in A

Artificial intelligence for radiological paediatric fracture assessment: a systematic review

BACKGROUND: Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers. MATERIALS AND METHODS: MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to 'fracture', 'artificial intelligence', 'imaging' and 'children'. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated. RESULTS: Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant. CONCLUSIONS: Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools

VLA 1.4 GHz Catalogs of the Abell 370 and Abell 2390 Cluster Fields

We present 1.4 GHz catalogs for the cluster fields Abell 370 and Abell 2390 observed with the Very Large Array. These are two of the deepest radio images of cluster fields ever taken. The Abell 370 image covers an area of 40'x40' with a synthesized beam of ~1.7" and a noise level of ~5.7 uJy near field center. The Abell 2390 image covers an area of 34'x34' with a synthesized beam of ~1.4" and a noise level of ~5.6 uJy near field center. We catalog 200 redshifts for the Abell 370 field. We construct differential number counts for the central regions (radius < 16') of both clusters. We find that the faint (S_1.4GHz < 3 mJy) counts of Abell 370 are roughly consistent with the highest blank field number counts, while the faint number counts of Abell 2390 are roughly consistent with the lowest blank field number counts. Our analyses indicate that the number counts are primarily from field radio galaxies. We suggest that the disagreement of our counts can be largely attributed to cosmic variance.Comment: 13 pages, accepted for publication in ApJ

Advancing the Microbiome Research Community

The human microbiome has become a recognized factor in promoting and maintaining health. We outline opportunities in interdisciplinary research, analytical rigor, standardization, and policy development for this relatively new and rapidly developing field. Advances in these aspects of the research community may in turn advance our understanding of human microbiome biology. It is now widely recognized that disturbances in our normal microbial populations may be linked to acute infections such as Clostridium difficile and to chronic diseases such as heart disease, cancer, obesity, and autoimmune disorders (Clemente et al., 2012). This has prompted substantial interest in the microbiome from both basic and clinical perspectives. Although our genome is relatively static throughout life, each of our microbial communities changes profoundly from infancy through adulthood, continuing to adapt through ongoing exposures to diet, drugs and environment. Understanding the microbiome and its dynamic nature may be critical for diagnostics and, eventually, interventions based on the microbiome itself. However, several important challenges limit the ability of researchers to enter the microbiome field and/or conduct research most effectively

Constraints on UV Absorption in the Intracluster Medium of Abell 1030

We present results from an extensive HST spectroscopic search for UV absorption lines in the spectrum of the quasar B2~1028+313, which is associated with the central dominant galaxy in the cluster Abell~1030 ($z=0.178$). This is one of the brightest known UV continuum sources located in a cluster, and therefore provides an ideal opportunity to obtain stringent constraints on the column densities of any cool absorbing gas that may be associated with the intracluster medium (ICM). Our HST spectra were obtained with the FOS and GHRS, and provide continuous coverage at rest-frame wavelengths from $\sim 975$ to 4060~\AA, thereby allowing the investigation of many different elements and ionization levels. We utilize a new technique that involves simultaneous fitting of large numbers of different transitions for each species, thereby yielding more robust constraints on column densities than can be obtained from a single transition. This method yields upper limits of $\lesssim 10^{11} - 10^{13}$ cm$^{-2}$ on the column densities of a wide range of molecular, atomic and ionized species that may be associated with the ICM. We also discuss a possible \Lya and C IV absorption system associated with the quasar. We discuss the implications of the upper limits on cool intracluster gas in the context of the physical properties of the ICM and its relationship to the quasar.Comment: Astrophysical Journal, in press, 19 pages, includes 5 PostScript figures. Latex format, uses aas2pp4.sty and epsfig.sty file

Quasars in the MAMBO blank field survey

Our MAMBO 1.2 mm blank field imaging survey of ~0.75 sqd has uncovered four unusually bright sources, with flux densities between 10 and 90 mJy, all located in the Abell 2125 field. The three brightest are flat spectrum radio sources with bright optical and X-ray counterparts. Their mm and radio flux densities are variable on timescales of months. Their X-ray luminosities classify them as quasars. The faintest of the four mm bright sources appears to be a bright, radio-quiet starburst at z~3, similar to the sources seen at lower flux densities in the MAMBO and SCUBA surveys. It may also host a mildly obscured AGN of quasar-like X-ray luminosity. The three non-thermal mm sources imply an areal density of flat spectrum radio sources higher by at least 7 compared with that expected from an extrapolation of the lower frequency radio number counts.Comment: 8 pages, 7 figures. Accepted for publication by A&

Inhibition of Ral GTPases Using a Stapled Peptide Approach

Aberrant Ras signalling drives numerous cancers and drugs to inhibit this are urgently required. This compelling clinical need, combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly and the focus has moved to the main downstream Ras-signalling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets, which were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development and there have therefore been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This therefore provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

ROSAT PSPC observations of 36 high-luminosity clusters of galaxies: constraints on the gas fraction

We present a detailed and homogeneous analysis of the ROSAT PSPC surface brightness profiles of 36 clusters of galaxies with high X-ray luminosity (L_X > 10^{45} erg s^{-1}) and redshifts between 0.05 and 0.44. Using recent ASCA estimates of the temperature of the gas for most of the clusters in the sample, we apply both the deprojection technique and model fitting to the surface brightness profiles to constrain the gas and dark matter distributions under the assumption that the gas is both isothermal and hydrostatic. Applying robust estimators, we find that the gas fraction within r_{500} of the clusters in our sample has a distribution centred on f_gas(r_{500}) = 0.168 h_{50}^{-1.5}. The gas fraction ranges from 0.101 to 0.245 at the 95 per cent confidence level. The values of f_gas show highly significant variations between individual clusters, which may be explained if the dark matter has a significant baryonic component. Within a cluster, the average radial dependence of the gas mass fraction increases outward as r^s, with s~0.20. Combining these results with those of primordial nucleosynthesis calculations and the current estimate of H_0, the above central location implies \Omega_{0, m} < 0.56 at the 95 per cent confidence level. This upper limit decreases to 0.34 if we take the highest significant estimates for f_gas. A significant decrease in cluster gas fraction with redshift from the local value, f_{gas, 0}, of 0.21, found assuming \Omega_{0, m} =1, is also reduced if \Omega_{0, m} is low.Comment: 17 pages, 15 figures, MNRAS in press. Also available at http://xalph3.ast.cam.ac.uk/~settori/paper.htm

Inhibition of Ral GTPases Using a Stapled Peptide Approach.

Aberrant Ras signaling drives numerous cancers, and drugs to inhibit this are urgently required. This compelling clinical need combined with recent innovations in drug discovery including the advent of biologic therapeutic agents, has propelled Ras back to the forefront of targeting efforts. Activated Ras has proved extremely difficult to target directly, and the focus has moved to the main downstream Ras-signaling pathways. In particular, the Ras-Raf and Ras-PI3K pathways have provided conspicuous enzyme therapeutic targets that were more accessible to conventional drug-discovery strategies. The Ras-RalGEF-Ral pathway is a more difficult challenge for traditional medicinal development, and there have, therefore, been few inhibitors reported that disrupt this axis. We have used our structure of a Ral-effector complex as a basis for the design and characterization of α-helical-stapled peptides that bind selectively to active, GTP-bound Ral proteins and that compete with downstream effector proteins. The peptides have been thoroughly characterized biophysically. Crucially, the lead peptide enters cells and is biologically active, inhibiting isoform-specific RalB-driven cellular processes. This, therefore, provides a starting point for therapeutic inhibition of the Ras-RalGEF-Ral pathway.This work was supported by a Cambridge Cancer Centre Pump Priming award to CA, DO and HRM, a BBSRC Studentship to NSC, and a National Institutes for Health grant (CA71443) and the Welch Foundation (grant number I-1414) to MAW.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via https://doi.org/10.1074/jbc.M116.72024

The microbiome quality control project: baseline study design and future directions

Microbiome research has grown exponentially over the past several years, but studies have been difficult to reproduce across investigations. Relevant variation in measurements between laboratories, from a variety of sources, has not been systematically assessed. This is coupled with a growing concern in the scientific community about the lack of reproducibility in biomedical research. The Microbiome Quality Control project (MBQC) was initiated to identify sources of variation in microbiome studies, to quantify their magnitudes, and to assess the design and utility of different positive and negative control strategies. Here we report on the first MBQC baseline study project and workshop