Cool Core Clusters from Cosmological Simulations

We present results obtained from a set of cosmological hydrodynamic simulations of galaxy clusters, aimed at comparing predictions with observational data on the diversity between cool-core (CC) and non-cool-core (NCC) clusters. Our simulations include the effects of stellar and AGN feedback and are based on an improved version of the smoothed particle hydrodynamics code GADGET-3, which ameliorates gas mixing and better captures gas-dynamical instabilities by including a suitable artificial thermal diffusion. In this Letter, we focus our analysis on the entropy profiles, the primary diagnostic we used to classify the degree of cool-coreness of clusters, and on the iron profiles. In keeping with observations, our simulated clusters display a variety of behaviors in entropy profiles: they range from steadily decreasing profiles at small radii, characteristic of cool-core systems, to nearly flat core isentropic profiles, characteristic of non-cool-core systems. Using observational criteria to distinguish between the two classes of objects, we find that they occur in similar proportions in both simulations and in observations. Furthermore, we also find that simulated cool-core clusters have profiles of iron abundance that are steeper than those of NCC clusters, which is also in agreement with observational results. We show that the capability of our simulations to generate a realistic cool-core structure in the cluster population is due to AGN feedback and artificial thermal diffusion: their combined action allows us to naturally distribute the energy extracted from super-massive black holes and to compensate for the radiative losses of low-entropy gas with short cooling time residing in the cluster core.Comment: 6 pages, 4 figures, accepted in ApJL, v2 contains some modifications on the text (results unchanged

The Overlooked Potential of Generalized Linear Models in Astronomy - I: Binomial Regression

Revealing hidden patterns in astronomical data is often the path to fundamental scientific breakthroughs; meanwhile the complexity of scientific inquiry increases as more subtle relationships are sought. Contemporary data analysis problems often elude the capabilities of classical statistical techniques, suggesting the use of cutting edge statistical methods. In this light, astronomers have overlooked a whole family of statistical techniques for exploratory data analysis and robust regression, the so-called Generalized Linear Models (GLMs). In this paper -- the first in a series aimed at illustrating the power of these methods in astronomical applications -- we elucidate the potential of a particular class of GLMs for handling binary/binomial data, the so-called logit and probit regression techniques, from both a maximum likelihood and a Bayesian perspective. As a case in point, we present the use of these GLMs to explore the conditions of star formation activity and metal enrichment in primordial minihaloes from cosmological hydro-simulations including detailed chemistry, gas physics, and stellar feedback. We predict that for a dark mini-halo with metallicity $\approx 1.3 \times 10^{-4} Z_{\bigodot}$, an increase of $1.2 \times 10^{-2}$ in the gas molecular fraction, increases the probability of star formation occurrence by a factor of 75%. Finally, we highlight the use of receiver operating characteristic curves as a diagnostic for binary classifiers, and ultimately we use these to demonstrate the competitive predictive performance of GLMs against the popular technique of artificial neural networks.Comment: 20 pages, 10 figures, 3 tables, accepted for publication in Astronomy and Computin

Deep learning cardiac motion analysis for human survival prediction

Motion analysis is used in computer vision to understand the behaviour of moving objects in sequences of images. Optimising the interpretation of dynamic biological systems requires accurate and precise motion tracking as well as efficient representations of high-dimensional motion trajectories so that these can be used for prediction tasks. Here we use image sequences of the heart, acquired using cardiac magnetic resonance imaging, to create time-resolved three-dimensional segmentations using a fully convolutional network trained on anatomical shape priors. This dense motion model formed the input to a supervised denoising autoencoder (4Dsurvival), which is a hybrid network consisting of an autoencoder that learns a task-specific latent code representation trained on observed outcome data, yielding a latent representation optimised for survival prediction. To handle right-censored survival outcomes, our network used a Cox partial likelihood loss function. In a study of 302 patients the predictive accuracy (quantified by Harrell's C-index) was significantly higher (p < .0001) for our model C=0.73 (95$\%$ CI: 0.68 - 0.78) than the human benchmark of C=0.59 (95$\%$ CI: 0.53 - 0.65). This work demonstrates how a complex computer vision task using high-dimensional medical image data can efficiently predict human survival

In vivo biodistribution and lifetime analysis of cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft using time-domain near-infrared optical imaging

Rituximab is a chimeric monoclonal antibody directed against human CD20 antigen, which is expressed on B-cell lymphocytes and on the majority of B-cell lymphoid malignancies. Herein we report the conjugate of rituximab with the near-infrared (NIR) fluorophore Cy5.5 (RI-Cy5.5) as a tool for in vitro, in vivo, and ex vivo NIR time-domain (TD) optical imaging. In vitro, RI-Cy5.5 retained biologic activity and led to elevated cell-associated fluorescence on tumor cells. In vivo, TD optical imaging analysis of RI-Cy5.5 injected into lymphoma-bearing mice revealed a slow tumor uptake and a specific long-lasting persistence of the probe within the tumor. Biodistribution studies after intraperitoneal and endovenous administration were undertaken to evaluate differences in the tumor uptake. RI-Cy5.5 concentration in the organs after intraperitoneal injection was not as high as after endovenous injection. Ex vivo analysis of biologic tissues and organs by both TD optical imaging and immunohistochemistry confirmed the probe distribution, as demonstrated by imaging experiment in vivo, showing that RI-Cy5.5 selectively accumulated in the tumor tissue and major excretion organs. In summary, the study indicates that NIR TD optical imaging is a powerful tool for rituximab-targeting investigation, furthering understanding of its administration outcome in lymphoma treatment

The history of chemical enrichment in the intracluster medium from cosmological simulations

The distribution of metals in the intracluster medium (ICM) of galaxy clusters provides valuable information on their formation and evolution, on the connection with the cosmic star formation and on the effects of different gas processes. By analysing a sample of simulated galaxy clusters, we study the chemical enrichment of the ICM, its evolution, and its relation with the physical processes included in the simulation and with the thermal properties of the core. These simulations, consisting of re-simulations of 29 Lagrangian regions performed with an upgraded version of the smoothed particle hydrodynamics (SPH) gadget-3 code, have been run including two different sets of baryonic physics: one accounts for radiative cooling, star formation, metal enrichment and supernova (SN) feedback, and the other one further includes the effects of feedback from active galactic nuclei (AGN). In agreement with observations, we find an anti-correlation between entropy and metallicity in cluster cores, and similar radial distributions of heavy-element abundances and abundance ratios out to large cluster-centric distances ( 3cR180). In the outskirts, namely outside of 3c0.2 R180, we find a remarkably homogeneous metallicity distribution, with almost flat profiles of the elements produced by either SNIa or SNII. We investigated the origin of this phenomenon and discovered that it is due to the widespread displacement of metal-rich gas by early (z > 2-3) AGN powerful bursts, acting on small high-redshift haloes. Our results also indicate that the intrinsic metallicity of the hot gas for this sample is on average consistent with no evolution between z = 2 and z = 0, across the entire radial range

Cosmological hydrodynamical simulations of galaxy clusters: X-ray scaling relations and their evolution

We analyse cosmological hydrodynamical simulations of galaxy clusters to study the X-ray scaling relations between total masses and observable quantities such as X-ray luminosity, gas mass, X-ray temperature, and $Y_{X}$. Three sets of simulations are performed with an improved version of the smoothed particle hydrodynamics GADGET-3 code. These consider the following: non-radiative gas, star formation and stellar feedback, and the addition of feedback by active galactic nuclei (AGN). We select clusters with $M_{500} > 10^{14} M_{\odot} E(z)^{-1}$, mimicking the typical selection of Sunyaev-Zeldovich samples. This permits to have a mass range large enough to enable robust fitting of the relations even at $z \sim 2$. The results of the analysis show a general agreement with observations. The values of the slope of the mass-gas mass and mass-temperature relations at $z=2$ are 10 per cent lower with respect to $z=0$ due to the applied mass selection, in the former case, and to the effect of early merger in the latter. We investigate the impact of the slope variation on the study of the evolution of the normalization. We conclude that cosmological studies through scaling relations should be limited to the redshift range $z=0-1$, where we find that the slope, the scatter, and the covariance matrix of the relations are stable. The scaling between mass and $Y_X$ is confirmed to be the most robust relation, being almost independent of the gas physics. At higher redshifts, the scaling relations are sensitive to the inclusion of AGNs which influences low-mass systems. The detailed study of these objects will be crucial to evaluate the AGN effect on the ICM.Comment: 24 pages, 11 figures, 5 tables, replaced to match accepted versio

Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences

Biophysical studies of ligand interactions with three human telomeric repeat sequences (d(AGGG(TTAGGG)n, n = 3, 7 and 11)) show that an oxazole-based ‘click’ ligand, which induces parallel folded quadruplexes, preferentially stabilises longer telomeric repeats providing evidence for selectivity in binding at the interface between tandem quadruplex motifs

Pressure of the hot gas in simulations of galaxy clusters

14siWe analyse the radial pressure profiles, the intracluster medium (ICM) clumping factor and the Sunyaev-Zel'dovich (SZ) scaling relations of a sample of simulated galaxy clusters and groups identified in a set of hydrodynamical simulations based on an updated version of the treepm-SPH GADGET-3 code. Three different sets of simulations are performed: the first assumes non-radiative physics, the others include, among other processes, active galactic nucleus (AGN) and/or stellar feedback. Our results are analysed as a function of redshift, ICM physics, cluster mass and cluster cool-coreness or dynamical state. In general, the mean pressure profiles obtained for our sample of groups and clusters show a good agreement with X-ray and SZ observations. Simulated cool-core (CC) and non-cool-core (NCC) clusters also show a good match with real data. We obtain in all cases a small (if any) redshift evolution of the pressure profiles of massive clusters, at least back to z = 1. We find that the clumpiness of gas density and pressure increases with the distance from the cluster centre and with the dynamical activity. The inclusion of AGN feedback in our simulations generates values for the gas clumping (√{C}_{ρ }˜ 1.2 at R200) in good agreement with recent observational estimates. The simulated YSZ-M scaling relations are in good accordance with several observed samples, especially for massive clusters. As for the scatter of these relations, we obtain a clear dependence on the cluster dynamical state, whereas this distinction is not so evident when looking at the subsamples of CC and NCC clusters.openopenPlanelles, S.; Fabjan, D.; Borgani, S.; Murante, G.; Rasia, E.; Biffi, V.; Truong, N.; Ragone-Figueroa, C.; Granato, G. L.; Dolag, K.; Pierpaoli, E.; Beck, A. M.; Steinborn, Lisa K.; Gaspari, M.Planelles, S.; Fabjan, D.; Borgani, Stefano; Murante, G.; Rasia, E.; Biffi, Veronica; Truong, N.; Ragone Figueroa, C.; Granato, G. L.; Dolag, K.; Pierpaoli, E.; Beck, A. M.; Steinborn, Lisa K.; Gaspari, M

Epidemiology and natural history of central venous access device use and infusion pump function in the NO16966 trial

Background: Central venous access devices in fluoropyrimidine therapy are associated with complications; however, reliable data are lacking regarding their natural history, associated complications and infusion pump performance in patients with metastatic colorectal cancer.&lt;p&gt;&lt;/p&gt; Methods: We assessed device placement, use during treatment, associated clinical outcomes and infusion pump perfomance in the NO16966 trial.&lt;p&gt;&lt;/p&gt; Results: Device replacement was more common with FOLFOX-4 (5-fluorouracil (5-FU)+oxaliplatin) than XELOX (capecitabine+oxaliplatin) (14.1% vs 5.1%). Baseline device-associated events and post-baseline removal-/placement-related events occurred more frequently with FOLFOX-4 than XELOX (11.5% vs 2.4% and 8.5% vs 2.1%). Pump malfunctions, primarily infusion accelerations in 16% of patients, occurred within 1.6–4.3% of cycles. Fluoropyrimidine-associated grade 3/4 toxicity was increased in FOLFOX-4-treated patients experiencing a malfunction compared with those who did not (97 out of 155 vs 452 out of 825 patients), predominantly with increased grade 3/4 neutropenia (53.5% vs 39.8%). Febrile neutropenia rates were comparable between patient cohorts±malfunction. Efficacy outcomes were similar in patient cohorts±malfunction.&lt;p&gt;&lt;/p&gt; Conclusions: Central venous access device removal or replacement was common and more frequent in patients receiving FOLFOX-4. Pump malfunctions were also common and were associated with increased rates of grade 3/4 haematological adverse events. Oral fluoropyrimidine-based regimens may be preferable to infusional 5-FU based on these findings

Screening for Familial APP Mutations in Sporadic Cerebral Amyloid Angiopathy

Background Advances in genetic technology have revealed that variation in the same gene can cause both rare familial and common sporadic forms of the same disease. Cerebral amyloid angiopathy (CAA), a common cause of symptomatic intracerebral hemorrhage (ICH) in the elderly, can also occur in families in an autosomal dominant pattern. The majority of affected families harbor mutations in the Beta amyloid Peptide (Aβ) coding region of the gene for amyloid precursor protein (APP) or have duplications of chromosomal segments containing APP. Methodology/Principal Findings A total of 58 subjects with a diagnosis of probable or definite CAA according to validated criteria were included in the present study. We sequenced the Aβ coding region of APP in 58 individuals and performed multiplex ligation-dependent probe amplification to determine APP gene dosage in 60. No patient harbored a known or novel APP mutation or gene duplication. The frequency of mutations investigated in the present study is estimated to range from 0% to 8% in individuals with probable CAA in the general population, based on the ascertained sample size. Conclusions/Significance We found no evidence that variants at loci associated with familial CAA play a role in sporadic CAA. Based on our findings, these rare highly-penetrant mutations are unlikely to be seen in sporadic CAA patients. Therefore, our results do not support systematic genetic screening of CAA patients who lack a strong family history of hemorrhage or dementia.National Institute of Neurological Disorders and Stroke (U.S.) (grant K23NS042695)American Heart AssociationAmerican Stroke Association (Bugher Foundation for Stroke Prevention Research