Transcriptomic profiling of 39 commonly-used neuroblastoma cell lines

Neuroblastoma cell lines are an important and cost-effective model used to study oncogenic drivers of the disease. While many of these cell lines have been previously characterized with SNP, methylation, and/or mRNA expression microarrays, there has not been an effort to comprehensively sequence these cell lines. Here, we present raw whole transcriptome data generated by RNA sequencing of 39 commonly-used neuroblastoma cell lines. These data can be used to perform differential expression analysis based on a genetic aberration or phenotype in neuroblastoma (e.g., MYCN amplification status, ALK mutation status, chromosome arm 1p, 11q and/or 17q status, sensitivity to pharmacologic perturbation). Additionally, we designed this experiment to enable structural variant and/or long-noncoding RNA analysis across these cell lines. Finally, as more DNase/ATAC and histone/transcription factor ChIP sequencing is performed in these cell lines, our RNA-Seq data will be an important complement to inform transcriptional targets as well as regulatory (enhancer or repressor) elements in neuroblastoma

How to measure redshift-space distortions without sample variance

We show how to use multiple tracers of large-scale density with different biases to measure the redshift-space distortion parameter beta=f/b=(dlnD/dlna)/b (where D is the growth rate and a the expansion factor), to a much better precision than one could achieve with a single tracer, to an arbitrary precision in the low noise limit. In combination with the power spectrum of the tracers this allows a much more precise measurement of the bias-free velocity divergence power spectrum, f^2 P_m - in fact, in the low noise limit f^2 P_m can be measured as well as would be possible if velocity divergence was observed directly, with rms improvement factor ~[5.2(beta^2+2 beta+2)/beta^2]^0.5 (e.g., ~10 times better than a single tracer for beta=0.4). This would allow a high precision determination of f D as a function of redshift with an error as low as 0.1%. We find up to two orders of magnitude improvement in Figure of Merit for the Dark Energy equation of state relative to Stage II, a factor of several better than other proposed Stage IV Dark Energy surveys. The ratio b_2/b_1 will be determined with an even greater precision than beta, producing, when measured as a function of scale, an exquisitely sensitive probe of the onset of non-linear bias. We also extend in more detail previous work on the use of the same technique to measure non-Gaussianity. Currently planned redshift surveys are typically designed with signal to noise of unity on scales of interest, and are not optimized for this technique. Our results suggest that this strategy may need to be revisited as there are large gains to be achieved from surveys with higher number densities of galaxies.Comment: 22 pages, 13 figure

Soft contact lens extended wear affects corneal epithelial permeability: hypoxic or mechanical etiology?

Contact lens extended wear increases the permeability of epithelium to sodium fluorescein (P(dc)). The exact mechanism is not known. However, changes in P(dc) likely result from either corneal hypoxia or mechanical trauma, or both. We explored the effects of one-night continuous wear with either high- or low-Dk/t soft lenses on P(dc). The results show that corneal epithelial barrier function decreases significantly with both lens groups. We also observed that Asian eyes had higher P(dc) after overnight wear compared to non-Asian and that for both Asian and non-Asian eyes, the elimination of corneal hypoxia did not prevent changes in epithelial permeability

Variability of extracorporeal cardiopulmonary resuscitation utilization for refractory adult out-of-hospital cardiac arrest: an international survey study.

Objective: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea. Methods: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey. Results: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for \u3e75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers. Conclusion: A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies

The Tevatron at the Frontier of Dark Matter Direct Detection

Direct detection of dark matter (DM) requires an interaction of dark matter particles with nucleons. The same interaction can lead to dark matter pair production at a hadron collider, and with the addition of initial state radiation this may lead to mono-jet signals. Mono-jet searches at the Tevatron can thus place limits on DM direct detection rates. We study these bounds both in the case where there is a contact interaction between DM and the standard model and where there is a mediator kinematically accessible at the Tevatron. We find that in many cases the Tevatron provides the current best limit, particularly for light dark matter, below 5 GeV, and for spin dependent interactions. Non-standard dark matter candidates are also constrained. The introduction of a light mediator significantly weakens the collider bound. A direct detection discovery that is in apparent conflict with mono-jet limits will thus point to a new light state coupling the standard model to the dark sector. Mono-jet searches with more luminosity and including the spectrum shape in the analysis can improve the constraints on DM-nucleon scattering cross section.Comment: 20 pages, 8 figures, final version in JHE

Predicting response to combination evofosfamide and immunotherapy under hypoxic conditions in murine models of colon cancer

The goal of this study is to develop a mathematical model that captures the interaction between evofosfamide, immunotherapy, and the hypoxic landscape of the tumor in the treatment of tumors. Recently, we showed that evofosfamide, a hypoxia-activated prodrug, can synergistically improve treatment outcomes when combined with immunotherapy, while evofosfamide alone showed no effects in an in vivo syngeneic model of colorectal cancer. However, the mechanisms behind the interaction between the tumor microenvironment in the context of oxygenation (hypoxic, normoxic), immunotherapy, and tumor cells are not fully understood. To begin to understand this issue, we develop a system of ordinary differential equations to simulate the growth and decline of tumors and their vascularization (oxygenation) in response to treatment with evofosfamide and immunotherapy (6 combinations of scenarios). The model is calibrated to data from in vivo experiments on mice implanted with colon adenocarcinoma cells and longitudinally imaged with [18F]-fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to quantify hypoxia. The results show that evofosfamide is able to rescue the immune response and sensitize hypoxic tumors to immunotherapy. In the hypoxic scenario, evofosfamide reduces tumor burden by $45.07 \pm 2.55$%, compared to immunotherapy alone, as measured by tumor volume. The model accurately predicts the temporal evolution of five different treatment scenarios, including control, hypoxic tumors that received immunotherapy, normoxic tumors that received immunotherapy, evofosfamide alone, and hypoxic tumors that received combination immunotherapy and evofosfamide. The average concordance correlation coefficient (CCC) between predicted and observed tumor volume is $0.86 \pm 0.05$. Interestingly, the model values to fit those five treatment arms was unable to accurately predict the response of normoxic tumors to combination evofosfamide and immunotherapy (CCC = $-0.064 \pm 0.003$). However, guided by the sensitivity analysis to rank the most influential parameters on the tumor volume, we found that increasing the tumor death rate due to immunotherapy by a factor of $18.6 \pm 9.3$ increases CCC of $0.981 \pm 0.001$. To the best of our knowledge, this is the first study to mathematically predict and describe the increased efficacy of immunotherapy following evofosfamide

PSR J1926-0652: A Pulsar with Interesting Emission Properties Discovered at FAST

We describe PSR J1926-0652, a pulsar recently discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Using sensitive single-pulse detections from FAST and long-term timing observations from the Parkes 64-m radio telescope, we probed phenomena on both long and short time scales. The FAST observations covered a wide frequency range from 270 to 800 MHz, enabling individual pulses to be studied in detail. The pulsar exhibits at least four profile components, short-term nulling lasting from 4 to 450 pulses, complex subpulse drifting behaviours and intermittency on scales of tens of minutes. While the average band spacing P3 is relatively constant across different bursts and components, significant variations in the separation of adjacent bands are seen, especially near the beginning and end of a burst. Band shapes and slopes are quite variable, especially for the trailing components and for the shorter bursts. We show that for each burst the last detectable pulse prior to emission ceasing has different properties compared to other pulses. These complexities pose challenges for the classic carousel-type models.Comment: 13pages with 12 figure

Socio-geography of human mobility: a study using longitudinal mobile phone data

A relationship between people’s mobility and their social networks is presented based on an analysis of calling and mobility traces for one year of anonymized call detail records of over one million mobile phone users in Portugal. We find that about 80% of places visited are within just 20 km of their nearest (geographical) social ties’ locations. This figure rises to 90% at a ‘geo-social radius’ of 45 km. In terms of their travel scope, people are geographically closer to their weak ties than strong ties. Specifically, they are 15% more likely to be at some distance away from their weak ties than strong ties. The likelihood of being at some distance from social ties increases with the population density, and the rates of increase are higher for shorter geo-social radii. In addition, we find that area population density is indicative of geo-social radius where denser areas imply shorter radii. For example, in urban areas such as Lisbon and Porto, the geo-social radius is approximately 7 km and this increases to approximately 15 km for less densely populated areas such as Parades and Santa Maria da Feira

Transgenic expression of the dicotyledonous pattern recognition receptor EFR in rice leads to ligand-dependent activation of defense responses

Plant plasma membrane localized pattern recognition receptors (PRRs) detect extracellular pathogen-associated molecules. PRRs such as Arabidopsis EFR and rice XA21 are taxonomically restricted and are absent from most plant genomes. Here we show that rice plants expressing EFR or the chimeric receptor EFR::XA21, containing the EFR ectodomain and the XA21 intracellular domain, sense both Escherichia coli- and Xanthomonas oryzae pv. oryzae (Xoo)-derived elf18 peptides at sub-nanomolar concentrations. Treatment of EFR and EFR::XA21 rice leaf tissue with elf18 leads to MAP kinase activation, reactive oxygen production and defense gene expression. Although expression of EFR does not lead to robust enhanced resistance to fully virulent Xoo isolates, it does lead to quantitatively enhanced resistance to weakly virulent Xoo isolates. EFR interacts with OsSERK2 and the XA21 binding protein 24 (XB24), two key components of the rice XA21-mediated immune response. Rice-EFR plants silenced for OsSERK2, or overexpressing rice XB24 are compromised in elf18-induced reactive oxygen production and defense gene expression indicating that these proteins are also important for EFR-mediated signaling in transgenic rice. Taken together, our results demonstrate the potential feasibility of enhancing disease resistance in rice and possibly other monocotyledonous crop species by expression of dicotyledonous PRRs. Our results also suggest that Arabidopsis EFR utilizes at least a subset of the known endogenous rice XA21 signaling components

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH