Quantifying Tensions between CMB and Distance Datasets in Models with Free Curvature or Lensing Amplitude

Recent measurements of the Cosmic Microwave Background (CMB) by the Planck Collaboration have produced arguably the most powerful observational evidence in support of the standard model of cosmology, i.e. the spatially flat $\Lambda$CDM paradigm. In this work, we perform model selection tests to examine whether the base CMB temperature and large scale polarization anisotropy data from Planck 2015 (P15) prefer any of eight commonly used one-parameter model extensions with respect to flat $\Lambda$CDM. We find a clear preference for models with free curvature, $\Omega_\mathrm{K}$, or free amplitude of the CMB lensing potential, $A_\mathrm{L}$. We also further develop statistical tools to measure tension between datasets. We use a Gaussianization scheme to compute tensions directly from the posterior samples using an entropy-based method, the surprise, as well as a calibrated evidence ratio presented here for the first time. We then proceed to investigate the consistency between the base P15~CMB data and six other CMB and distance datasets. In flat $\Lambda$CDM we find a $4.8\sigma$ tension between the base P15~CMB data and a distance ladder measurement, whereas the former are consistent with the other datasets. In the curved $\Lambda$CDM model we find significant tensions in most of the cases, arising from the well-known low power of the low-$\ell$ multipoles of the CMB data. In the flat $\Lambda$CDM $+A_\mathrm{L}$ model, however, all datasets are consistent with the base P15~CMB observations except for the CMB lensing measurement, which remains in significant tension. This tension is driven by the increased power of the CMB lensing potential derived from the base P15~CMB constraints in both models, pointing at either potentially unresolved systematic effects or the need for new physics beyond the standard flat $\Lambda$CDM model.Comment: 16 pages, 8 figures, 6 table

Impact of Weak Lensing Mass Calibration on eROSITA Galaxy Cluster Cosmological Studies -- a Forecast

We forecast the impact of weak lensing (WL) cluster mass calibration on the cosmological constraints from the X-ray selected galaxy cluster counts in the upcoming eROSITA survey. We employ a prototype cosmology pipeline to analyze mock cluster catalogs. Each cluster is sampled from the mass function in a fiducial cosmology and given an eROSITA count rate and redshift, where count rates are modeled using the eROSITA effective area, a typical exposure time, Poisson noise and the scatter and form of the observed X-ray luminosity-- and temperature--mass--redshift relations. A subset of clusters have mock shear profiles to mimic either those from DES and HSC or from the future Euclid and LSST surveys. Using a count rate selection, we generate a baseline cluster cosmology catalog that contains 13k clusters over 14,892~deg$^2$ of extragalactic sky. Low mass groups are excluded using raised count rate thresholds at low redshift. Forecast parameter uncertainties for $\Omega_\mathrm{M}$, $\sigma_8$ and $w$ are 0.023 (0.016; 0.014), 0.017 (0.012; 0.010), and 0.085 (0.074; 0.071), respectively, when adopting DES+HSC WL (Euclid; LSST), while marginalizing over the sum of the neutrino masses. A degeneracy between the distance--redshift relation and the parameters of the observable--mass scaling relation limits the impact of the WL calibration on the $w$ constraints, but with BAO measurements from DESI an improved determination of $w$ to 0.043 becomes possible. With Planck CMB priors, $\Omega_\text{M}$ ($\sigma_8$) can be determined to $0.005$ ($0.007$), and the summed neutrino mass limited to $\sum m_\nu < 0.241$ eV (at 95\%). If systematics on the group mass scale can be controlled, the eROSITA group and cluster sample with 43k objects and LSST WL could constrain $\Omega_\mathrm{M}$ and $\sigma_8$ to 0.007 and $w$ to 0.050.Comment: 28 pages, 13 figur

Liquid-liquid coexistence in the phase diagram of a fluid confined in fractal porous materials

Multicanonical ensemble sampling simulations have been performed to calculate the phase diagram of a Lennard-Jones fluid embedded in a fractal random matrix generated through diffusion limited cluster aggregation. The study of the system at increasing size and constant porosity shows that the results are independent from the matrix realization but not from the size effects. A gas-liquid transition shifted with respect to bulk is found. On growing the size of the system on the high density side of the gas-liquid coexistence curve it appears a second coexistence region between two liquid phases. These two phases are characterized by a different behaviour of the local density inside the interconnected porous structure at the same temperature and chemical potential.Comment: 5 pages, 4 figures. To be published in Europhys. Letter

Severe cutaneous toxicity following treatment with radiotherapy and cetuximab: a case report

While the addition of cetuximab to radiotherapy improves clinical outcomes in locoregionally advanced head and neck squamous cell cancers, there are a small number of reports of severe radiation dermatitis occurring with this therapeutic combination. We present the case of a 69 year old male who developed severe radiation dermatitis following treatment with cetuximab and radiotherapy for a locoregionally advanced head and neck squamous cell cancer

Identifying and quantifying heterogeneity in high content analysis: Application of heterogeneity indices to drug discovery

One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology. © 2014 Gough et al

Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

Understanding the small object argument

The small object argument is a transfinite construction which, starting from a set of maps in a category, generates a weak factorisation system on that category. As useful as it is, the small object argument has some problematic aspects: it possesses no universal property; it does not converge; and it does not seem to be related to other transfinite constructions occurring in categorical algebra. In this paper, we give an "algebraic" refinement of the small object argument, cast in terms of Grandis and Tholen's natural weak factorisation systems, which rectifies each of these three deficiencies.Comment: 42 pages; supersedes the earlier arXiv preprint math/0702290; v2: final journal version, minor corrections onl

High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways

The non-coding landscape of head and neck squamous cell carcinoma

published_or_final_versio