Literature-based priors for gene regulatory networks

Motivation: The use of prior knowledge to improve gene regulatory network modelling has often been proposed. In this paper we present the first research on the massive incorporation of prior knowledge from literature for Bayesian network learning of gene networks. As the publication rate of scientific papers grows, updating online databases, which have been proposed as potential prior knowledge in past rese-arch, becomes increasingly challenging. The novelty of our approach lies in the use of gene-pair association scores that describe the over-lap in the contexts in which the genes are mentioned, generated from a large database of scientific literature, harnessing the information contained in a huge number of documents into a simple, clear format. Results: We present a method to transform such literature-based gene association scores to network prior probabilities, and apply it to learn gene sub-networks for yeast, E. coli and Human organisms. We also investigate the effect of weighting the influence of the prior know-ledge. Our findings show that literature-based priors can improve both the number of true regulatory interactions present in the network and the accuracy of expression value prediction on genes, in comparison to a network learnt solely from expression data. Networks learnt with priors also show an improved biological interpretation, with identified subnetworks that coincide with known biological pathways. Contact

A Luminous Red Nova in M31 and its Progenitor System

We present observations of M31LRN 2015 (MASTER OT J004207.99+405501.1), discovered in M31 in January 2015, and identified as a rare and enigmatic luminous red nova (LRN). Spectroscopic and photometric observations obtained by the Liverpool Telescope showed the LRN becoming extremely red as it faded from its M(V) = -9.4 +/- 0.2 peak. Early spectra showed strong Halpha emission that weakened over time as a number of absorption features appeared, including Na I D and Ba II. At later times strong TiO absorption bands were also seen. A search of archival Hubble Space Telescope data revealed a luminous red source to be the likely progenitor system, with pre-outburst Halpha emission also detected in ground-based data. The outburst of M31LRN 2015 shows many similarities, both spectroscopically and photometrically, with that of V838 Mon, the best studied LRN. We finally discuss the possible progenitor scenarios

Follow the blue bird: A study on threat data published on Twitter

Open Source Intelligence (OSINT) has taken the interest of cybersecurity practitioners due to its completeness and timeliness. In particular, Twitter has proven to be a discussion hub regarding the latest vulnerabilities and exploits. In this paper, we present a study comparing vulnerability databases between themselves and against Twitter. Although there is evidence of OSINT advantages, no methodological studies have addressed the quality and benefits of the sources available. We compare the publishing dates of more than nine-thousand vulnerabilities in the sources considered. We show that NVD is not the most timely or the most complete vulnerability database, that Twitter provides timely and impactful security alerts, that using diverse OSINT sources provides better completeness and timeliness of vulnerabilities, and provide insights on how to capture cybersecurity-relevant tweets

Magma mixing and high fountaining during the 1959 K īlauea Iki eruption, Hawai'i

The 1959 Kīlauea Iki eruption provides a unique opportunity to investigate the process of shallow magma mixing, its impact on the magmatic volatile budget and its role in triggering and driving episodes of Hawaiian fountaining. Melt inclusions hosted by olivine record a continuous decrease in H2O concentration through the 17 episodes of the eruption, while CO2 concentrations correlate with the degree of post-entrapment crystallization of olivine on the inclusion walls. Geochemical data, when combined with the magma budget and with contemporaneous eruption observations, show complex mixing between episodes involving hot, geochemically heterogeneous melts from depth, likely carrying exsolved vapour, and melts which had erupted at the surface, degassed and drained-back into the vent. The drained-back melts acted as a coolant, inducing rapid cooling of the more primitive melts and their olivines at shallow depths and inducing crystallization and vesiculation and triggering renewed fountaining. A consequence of the mixing is that the melts became vapor-undersaturated, so equilibration pressures cannot be inferred from them using saturation models. After the melt inclusions were trapped, continued growth of vapor bubbles, caused by enhanced post-entrapment crystallization, sequestered a large fraction of CO2 from the melt within the inclusions. This study, while cautioning against accepting melt inclusion CO2 concentrations “as measured” in mixed magmas, also illustrates that careful analysis and interpretation of post-entrapment modifications can turn this apparent challenge into a way to yield novel useful insights into the geochemical controls on eruption intensity.IS was supported by a NERC-funded studentship and a USGS Jack Kleinman Grant for Volcano Research. ME acknowledges NERC ion probe grant IMF376/0509. BH’s participation was funded by NSF EAR-1145159. We acknowledge the NERC Edinburgh Ion Microprobe facility, where we undertook the SIMS analyses.This version is the author accepted manuscript and will be under embargo until the 6th of June 2015. The final version has been published by Elsevier in Earth and Planetary Science Letters here: http://www.sciencedirect.com/science/article/pii/S0012821X14003264

Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia.

Sporadic late onset cerebellar ataxia is a well-described clinical presentation with a broad differential diagnosis that adult neurologists should be familiar with. However, despite extensive clinical investigations, an acquired cause is identified in only a minority of cases. Thereafter, an underlying genetic basis is often considered, even in those without a family history. Here we apply whole exome sequencing to a cohort of 12 patients with late onset cerebellar ataxia. We show that 33% of 'idiopathic' cases harbor compound heterozygous mutations in known ataxia genes, including genes not included on multi-gene panels, or primarily associated with an ataxic presentation

Requirement of RIZ1 for cancer prevention by methyl-balanced diet

The typical Western diet is not balanced in methyl nutrients that regulate the level of the methyl donor S-adenosylmethionine (SAM) and its derivative metabolite S-adenosylhomocysteine (SAH), which in turn may control the activity of certain methyltransferases. Feeding rodents with amino acid defined and methyl-imbalanced diet decreases hepatic SAM and causes liver cancers. RIZ1 (PRDM2 or KMT8) is a tumor suppressor and functions in transcriptional repression by methylating histone H3 lysine 9. Here we show that a methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1. While absence of RIZ1 was tumorigenic in mice fed the balanced diet, its presence did not prevent tumor formation in mice fed the imbalanced diet. Unlike most of its related enzymes, RIZ1 was upregulated by methyl-balanced diet. Methyl-balanced diet did not fully repress oncogenes such as c-Jun in the absence of RIZ1. The data identify RIZ1 as a critical target of methyl-balanced diet in cancer prevention. The molecular understanding of dietary carcinogenesis may help people make informed choices on diet, which may greatly reduce the incidence of cancer

Health care's response to climate change: a carbon footprint assessment of the NHS in England

Background: Climate change threatens to undermine the past 50 years of gains in public health. In response, the National Health Service (NHS) in England has been working since 2008 to quantify and reduce its carbon footprint. This Article presents the latest update to its greenhouse gas accounting, identifying interventions for mitigation efforts and describing an approach applicable to other health systems across the world. Methods: A hybrid model was used to quantify emissions within Scopes 1, 2, and 3 of the Greenhouse Gas Protocol, as well as patient and visitor travel emissions, from 1990 to 2019. This approach complements the broad coverage of top-down economic modelling with the high accuracy of bottom-up data wherever available. Available data were backcasted or forecasted to cover all years. To enable the identification of measures to reduce carbon emissions, results were disaggregated by organisation type. Findings: In 2019, the health service's emissions totalled 25 megatonnes of carbon dioxide equivalent, a reduction of 26% since 1990, and a decrease of 64% in the emissions per inpatient finished admission episode. Of the 2019 footprint, 62% came from the supply chain, 24% from the direct delivery of care, 10% from staff commute and patient and visitor travel, and 4% from private health and care services commissioned by the NHS. Interpretation: This work represents the longest and most comprehensive accounting of national health-care emissions globally, and underscores the importance of incorporating bottom-up data to improve the accuracy of top-down modelling and enabling detailed monitoring of progress as health systems act to reduce emissions. Funding: Wellcome Trust

Lack of trust in maternal support is associated with negative interpretations of ambiguous maternal behavior

Attachment theory assumes that children who lack trust in maternal availability for support are more inclined to interpret maternal behavior in congruence with their expectation that mother will remain unavailable for support. To provide the first test of this assumption, early adolescents (9-13 years old) were asked to assess whether ambiguous interactions with mother should be interpreted in a positive or a negative way. In our sample (n = 322), results showed that early adolescents' lack of trust in their mother's availability for support was related to more negative interpretations of maternal behavior. The associations remained significant after controlling for depressive mood. The importance of these findings for our understanding of attachment theory, attachment stability, and clinical practice are discussed

Maximum-Reward Motion in a Stochastic Environment: The Nonequilibrium Statistical Mechanics Perspective

We consider the problem of computing the maximum-reward motion in a reward field in an online setting. We assume that the robot has a limited perception range, and it discovers the reward field on the fly. We analyze the performance of a simple, practical lattice-based algorithm with respect to the perception range. Our main result is that, with very little perception range, the robot can collect as much reward as if it could see the whole reward field, under certain assumptions. Along the way, we establish novel connections between this class of problems and certain fundamental problems of nonequilibrium statistical mechanics . We demonstrate our results in simulation examples

The leading digit distribution of the worldwide Illicit Financial Flows

Benford's law states that in data sets from different phenomena leading digits tend to be distributed logarithmically such that the numbers beginning with smaller digits occur more often than those with larger ones. Particularly, the law is known to hold for different types of financial data. The Illicit Financial Flows (IFFs) exiting the developing countries are frequently discussed as hidden resources which could have been otherwise properly utilized for their development. We investigate here the distribution of the leading digits in the recent data on estimates of IFFs to look for the existence of a pattern as predicted by Benford's law and establish that the frequency of occurrence of the leading digits in these estimates does closely follow the law.Comment: 13 pages, 10 figures, 6 tables, additional data analyi