A deep search for planets in the inner 15 au around Vega

We present the results of a deep high-contrast imaging search for planets around Vega. Vega is an ideal target for high-contrast imaging because it is bright, nearby, and young with a face-on two-belt debris disk which may be shaped by unseen planets. We obtained $J-$ and $H-$band data on Vega with the coronagraphic integral-field spectrograph Project 1640 (P1640) at Palomar Observatory. Two nights of data were obtained in 2016, in poor seeing conditions, and two additional nights in more favorable conditions in 2017. In total, we obtained 5.5 hours of integration time on Vega in moderate to good seeing conditions (<1.5"). We did not detect any low mass companions in this system. Our data present the most sensitive contrast limits around Vega at very small separations (2-15 au) thus far, allowing us to place new constraints on the companions which may be sculpting the Vega system. In addition to new constraints, as the deepest data obtained with P1640, these observations form the final legacy of the now decommissioned instrument.Comment: Accepted for publication in A

A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator

International audienceMiRNAs are key regulators of gene expression. By binding to many genes, they create a complex network of gene co-regulation. Here, using a network-based approach, we identified miRNA hub groups by their close connections and common targets. In one cluster containing three miRNAs, miR-612, miR-661 and miR-940, the annotated functions of the co-regulated genes suggested a role in small GTPase signalling. Although the three members of this cluster targeted the same subset of predicted genes, we showed that their overexpression impacted cell fates differently. miR-661 demonstrated enhanced phosphorylation of myosin II and an increase in cell invasion, indicating a possible oncogenic miRNA. On the contrary, miR-612 and miR-940 inhibit phosphorylation of myosin II and cell invasion. Finally, expression profiling in human breast tissues showed that miR-940 was consistently downregulated in breast cancer tissues M icroRNAs are a class of endogenous, small (19–25 nucleotides), single-stranded non-coding RNAs that regulate gene expression in all eukaryotic organisms. In metazoans, microRNAs most commonly bind to the 39 untranslated region (39UTR) of their mRNA target transcript and cause translational repression and/or mRNA degradation. Every microRNA is predicted to regulate from a dozen to thousands of genes, including transcription factors. This fine-tuning of protein expression is known to be involved in many physiological processes, such as development, apoptosis, signal transduction and even cancer progression 1,2. More than 2,000 mature human microRNAs are listed in the 20 th release of miRBase: http://www.mirbase.org (2014) (Date of access:19/08/2013), and some authors hypothesise that the majority of human genes are regulated by microRNAs 3. Since their discovery in 1993 4 , a fair understanding of their role in animal development and in the onset and progression of diseases 2 , as well as of their potential use in therapies 5 , has been gathered. However, the cooperative behaviour of microRNAs is still under investigation. A growing body of experimental evidence suggests that microRNAs can regulate genes through complementarity, meaning that microRNAs can act together to regulate individual genes or groups of genes involved in similar processes 6. For example, Hu and co-workers demonstrated that transducing a cocktail of precursor microRNAs (miR-21, miR-24 and miR-221) can result in more effective engraftment of transplanted cardiac progenitor cells 7. Consistent with these discoveries, Zhu et al. demonstrated that miR-21 and miR-221 coregulate 56 gene ontology (GO) processes 8. In the same study, the authors also showed that cotransfection of miR-1 and miR-21 increases H 2 O 2-induced myocardial apoptosis and oxidative stress. These recent findings support the idea of microRNA-mediated cooperative regulation but also argue for the use of systemic approaches, notably based on graph theory, to decipher individual and complementary roles of microRNAs. Some work has been conducted to use recent high-throughput experiment-derived data sets to infer microRNA synergistic relationships 9–12. Herein, we present a microRNA network based on target similarities among microRNAs to infer clusters of microRNAs. Clusters are defined as groups of microRNAs sharing a set of common targets, predicted by either DIANA-microT v3 13 or TargetScan v6.2 14. Some authors have used GO enrichment analysis as a confirmatory tool for their clustering approach 11. In our case, GO enrichment is not used to infer networks but as a way to estimate the probable metabolic pathway(s) a cluster of microRNAs could co-regulate. Moreover, the novelty of our approach is to consider not only clusters of microRNAs but also OPE

Cryoablation or Drug Therapy for Initial Treatment of Atrial Fibrillation

AF is a common chronic and progressive disorder. Without treatment, AF will recur in up to 75% of patients within a year of their index diagnosis. Antiarrhythmic drugs (AADs) have been proven to be more effective than placebo at maintaining sinus rhythm and remain the recommended initial therapeutic option for AF. However, the emergence of ‘single-shot’ AF ablation toolsets, which have enabled enhanced procedural standardisation and consistent outcomes with low rates of complications, has led to renewed interest in determining whether first-line catheter ablation may improve outcomes. The recently published EARLY-AF trial evaluated the role of initial cryoballoon ablation versus guideline-directed AAD therapy. Compared to AADs, an initial treatment cryoballoon ablation strategy resulted in greater freedom from atrial tachyarrhythmia, superior reduction in AF burden, greater improvement in quality of life and lower healthcare resource utilisation. These findings are relevant to patients, providers and healthcare systems when considering the initial treatment choice for rhythm-control therapy

Phi-score: A cell-to-cell phenotypic scoring method for sensitive and selective hit discovery in cell-based assays

International audiencePhenotypic screening monitors phenotypic changes induced by perturbations, including those generated by drugs or RNA interference. Currently-used methods for scoring screen hits have proven to be problematic, particularly when applied to physiologically relevant conditions such as low cell numbers or inefficient transfection. Here, we describe the Phi-score, which is a novel scoring method for the identification of phenotypic modifiers or hits in cell-based screens. Phi-score performance was assessed with simulations, a validation experiment and its application to gene identification in a large-scale RNAi screen. Using robust statistics and a variance model, we demonstrated that the Phi-score showed better sensitivity, selectivity and reproducibility compared to classical approaches. The improved performance of the Phi-score paves the way for cell-based screening of primary cells, which are often difficult to obtain from patients in sufficient numbers. We also describe a dedicated merging procedure to pool scores from small interfering RNAs targeting the same gene so as to provide improved visualization and hit selection

Direct Spectrum of the Benchmark T Dwarf HD 19467 B

HD 19467 B is presently the only directly imaged T dwarf companion known to induce a measurable Doppler acceleration around a solar-type star. We present spectroscopy measurements of this important benchmark object taken with the Project 1640 integral field unit at Palomar Observatory. Our high-contrast R ≈ 30 observations obtained simultaneously across the JH bands confirm the cold nature of the companion as reported from the discovery article and determine its spectral type for the first time. Fitting the measured spectral energy distribution to SpeX/IRTF T dwarf standards and synthetic spectra from BT-Settl atmospheric models, we find that HD 19467 B is a T5.5 ± 1 dwarf with effective temperature T_eff=978^(+20)_(-43) K. Our observations reveal significant methane absorption affirming its substellar nature. HD 19467 B shows promise to become the first T dwarf that simultaneously reveals its mass, age, and metallicity independent from the spectrum of light that it emits

A Deep Search for Planets in the Inner 15 au around Vega

We present the results of a deep high-contrast imaging search for planets around Vega. Vega is an ideal target for high-contrast imaging because it is bright, nearby, and young with a face-on two-belt debris disk that may be shaped by unseen planets. We obtained J- and H-band data on Vega with the coronagraphic integral-field spectrograph Project 1640 (P1640) at Palomar Observatory. Two nights of data were obtained in 2016, in poor seeing conditions, and two additional nights in more favorable conditions in 2017. In total, we obtained 5.5 hours of integration time on Vega in moderate to good seeing conditions (<1farcs5). We did not detect any low-mass companions in this system. Our data present the most sensitive contrast limits around Vega at very small separations (2–15 au) thus far, allowing us to place new constraints on the companions that may be sculpting the Vega system. In addition to new constraints, as the deepest data obtained with P1640, these observations form the final legacy of the now decommissioned instrument