Expand+Functional selection and systematic analysis of intronic splicing elements identify active sequence motifs and associated splicing factors

Despite the critical role of pre-mRNA splicing in generating proteomic diversity and regulating gene expression, the sequence composition and function of intronic splicing regulatory elements (ISREs) have not been well elucidated. Here, we employed a high-throughput in vivo Screening PLatform for Intronic Control Elements (SPLICE) to identify 125 unique ISRE sequences from a random nucleotide library in human cells. Bioinformatic analyses reveal consensus motifs that resemble splicing regulatory elements and binding sites for characterized splicing factors and that are enriched in the introns of naturally occurring spliced genes, supporting their biological relevance. In vivo characterization, including an RNAi silencing study, demonstrate that ISRE sequences can exhibit combinatorial regulatory activity and that multiple trans-acting factors are involved in the regulatory effect of a single ISRE. Our work provides an initial examination into the sequence characteristics and function of ISREs, providing an important contribution to the splicing code

Detecting and characterizing lateral phishing at scale

We present the first large-scale characterization of lateral phishing attacks, based on a dataset of 113 million employee-sent emails from 92 enterprise organizations. In a lateral phishing attack, adversaries leverage a compromised enterprise account to send phishing emails to other users, benefit-ting from both the implicit trust and the information in the hijacked user's account. We develop a classifier that finds hundreds of real-world lateral phishing emails, while generating under four false positives per every one-million employee-sent emails. Drawing on the attacks we detect, as well as a corpus of user-reported incidents, we quantify the scale of lateral phishing, identify several thematic content and recipient targeting strategies that attackers follow, illuminate two types of sophisticated behaviors that attackers exhibit, and estimate the success rate of these attacks. Collectively, these results expand our mental models of the 'enterprise attacker' and shed light on the current state of enterprise phishing attacks

The transient IDEMIX model as a nonorographic gravity wave parameterization in an atmospheric circulation model

The Internal wave Dissipation, Energy and Mixing (IDEMIX) model presents a novel way of parameterizing internal gravity waves in the atmosphere. Using a continuous full wave spectrum in the energy balance equation and integrating over all vertical wavenumbers and frequencies results in prognostic equations for the energy density of gravity waves in multiple azimuthal compartments. It includes their non-dissipative interaction with the mean flow, allowing for an evolving and local description of momentum flux and gravity wave drag. A saturation mechanism maintains the wave field within convective stability limits, and an energetically consistent closure for critical-layer effects controls how much wave flux propagates from the troposphere into the middle atmosphere. IDEMIX can simulate zonal gravity wave drag around the mesopause, similar to a traditional gravity wave parameterization and to a state-of-the-art wave ray tracing model in an atmospheric circulation model. In addition, IDEMIX shows a reversal of the gravity wave drag around the mesopause region due to changes in the momentum flux there. When compared to empirical model data, IDEMIX captures well the summer hemisphere flow reversal, the cold summer mesospheric pole and the alternate positive and negative structures in the meridional mean flow.Comment: 21 pages, 19 figure

Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds - Gastrointestinal adverse effects: A meta-analysis of randomized clinical trials

Background and Aim: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over-the-counter drug for the treatment of pain, fever, or colds, but data on the safety of this use are very limited. The aim of this study was to provide data on the safety of this treatment pattern, which is of interest to clinicians, regulators, and the public. Methods: A meta-analysis of individual patient data from 67 studies sponsored by Bayer HealthCare was completed. The primary endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the secondary endpoints were the incidence of patient-reported non-GI AEs. Event incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145 with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was short term (82.5% of patients had a single dose). Results: GI AEs were more frequent with ASA (9.9%) than with placebo (9.0%) [OR 1.3; 95% CI 1.1, 1.5]. Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few serious GI AEs (one ASA case; three placebo cases). No differences were found for non-GI AEs and no cases of cerebral hemorrhage were reported. Conclusion: Short-term, mostly single-dose exposure to ASA for the treatment of pain, fever, or colds was associated with a small but significant increase in the risk of dyspepsia relative to placebo.No serious GI complications were reported

A Fistful of Bitcoins: Characterizing Payments among Men with No Names

Bitcoin is a purely online virtual currency, unbacked by either physical commodities or sovereign obligation; instead, it relies on a combination of cryptographic protection and a peer-to-peer protocol for witnessing settlements. Consequently, Bitcoin has the unintuitive property that while the ownership of money is implicitly anonymous, its flow is globally visible. In this paper we explore this unique characteristic further, using heuristic clustering to group Bitcoin wallets based on evidence of shared authority, and then using re-identification attacks (i.e., empirical purchasing of goods and services) to classify the operators of those clusters. From this analysis, we consider the challenges for those seeking to use Bitcoin for criminal or fraudulent purposes at scale