A direct image of the obscuring disk surrounding an active galactic nucleus

Active galactic nuclei (AGN) are generally accepted to be powered by the release of gravitational energy in a compact accretion disk surrounding a massive black hole. Such disks are also necessary to collimate powerful radio jets seen in some AGN. The unifying classification schemes for AGN further propose that differences in their appearance can be attributed to the opacity of the accreting material, which may obstruct our view of the central region of some systems. The popular model for the obscuring medium is a parsec-scale disk of dense molecular gas, although evidence for such disks has been mostly indirect, as their angular size is much smaller than the resolution of conventional telescopes. Here we report the first direct images of a pc-scale disk of ionised gas within the nucleus of NGC 1068, the archetype of obscured AGN. The disk is viewed nearly edge-on, and individual clouds within the ionised disk are opaque to high-energy radiation, consistent with the unifying classification scheme. In projection, the disk and AGN axes align, from which we infer that the ionised gas disk traces the outer regions of the long-sought inner accretion disk.Comment: 14 pages, LaTeX, PSfig, to appear in Nature. also available at http://hethp.mpe-garching.mpg.de/Preprint

Precision Gauge Unification from Extra Yukawa Couplings

We investigate the impact of extra vector-like GUT multiplets on the predicted value of the strong coupling. We find in particular that Yukawa couplings between such extra multiplets and the MSSM Higgs doublets can resolve the familiar two-loop discrepancy between the SUSY GUT prediction and the measured value of alpha_3. Our analysis highlights the advantages of the holomorphic scheme, where the perturbative running of gauge couplings is saturated at one loop and further corrections are conveniently described in terms of wavefunction renormalization factors. If the gauge couplings as well as the extra Yukawas are of O(1) at the unification scale, the relevant two-loop correction can be obtained analytically. However, the effect persists also in the weakly-coupled domain, where possible non-perturbative corrections at the GUT scale are under better control.Comment: 26 pages, LaTeX. v6: Important early reference adde

Privacy Utility and Privacy Disutility Expectancy: An Empirical Study on Social App Usage

Social apps fundamentally transform the way individuals manage their online identities through proxy-disclosure. While individuals do enjoy the potential enhancement to reputation that is realized through social app postings, they could have their privacy threatened when these apps make posting in an uncontrolled fashion. Drawing on the APCO model, this research elucidates the impact of the two key aspects of online proxy-disclosure on privacy expectancy formulation, which in turn influence usage intention of social apps. A survey was conducted to operationalize the research model. Results provide strong evidence that the two determinants of privacy expectancy strongly influence individuals’ perceptions of privacy utility and privacy disutility. Furthermore, the two types of privacy utility powerful drive usage intention of social apps. The implications of the findings are discussed

MICRO-Foundations in Strategic Management: Squaring Coleman's Diagram

Abell, Felin and Foss argue that "macro-explanations" in strategic management, explanations in which organizational routines figure prominently and in which both the explanandum and explanans are at the macro-level, are necessarily incomplete. They take a diagram (which has the form of a trapezoid) from Coleman, Foundations of Social Theory, The Belknap Press of Harvard University Press, Cambridge (Mass.)/London, (1990) to task to show that causal chains connecting two macro-phenomena always involve "macro-to-micro" and "micro-to-macro" links, links that macro-explanations allegedly fail to recognize. Their plea for micro-foundations in strategic management is meant to shed light on these "missing links". The paper argues that while there are good reasons for providing micro-foundations, Abell, Felin and Foss's causal incompleteness argument is not one of them. Their argument does not sufficiently distinguish between causal and constitutive relations. Once these relations are carefully distinguished, it follows that Coleman's diagram has to be squared. This in turn allows us to see that macro-explanations need not be incomplete

SOCIAL NETWORK PRIVACY DISPOSITIONS: AN OBJECTIVE MEASUREMENT SCALE AND A CAUSAL MODEL

The Information Systems literature has substantially advanced understanding of privacy in both offline contexts and online environments. Despite the rich understanding, existing studies predominately focused on elucidating privacy issues specific to individuals. The increasingly popular usage of mobile apps with social media integration has fundamentally challenged current understanding and conceptualization of information privacy. In particular, mobile apps allow information collection beyond individuals’ personal scope (i.e., his/her personal information) and extend the scope of acquisition into individuals’ online social networks (i.e., his/her list of friends on Facebook). To fill this gap in the literature, drawing on the Communication Privacy Management Theory, this proposal focuses on three unique dimensions of social network privacy dispositions, namely permeability, ownership, and linkage. Second, we propose to operationalize these three dimensions of social network privacy dispositions using a second-order reflective construct, and we plan to develop an objective measurement scale for it. Lastly, we plan to validate the construct using a nomological network

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Current understanding of the human microbiome

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Medicine 24 (2018): 392–400, doi:10.1038/nm.4517.Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.Many of the studies described here in our laboratories were supported by the NIH, NSF, DOE, and the Alfred P. Sloan Foundation.2018-10-1

Lectin-Dependent Enhancement of Ebola Virus Infection via Soluble and Transmembrane C-type Lectin Receptors

Mannose-binding lectin (MBL) is a key soluble effector of the innate immune system that recognizes pathogen-specific surface glycans. Surprisingly, low-producing MBL genetic variants that may predispose children and immunocompromised individuals to infectious diseases are more common than would be expected in human populations. Since certain immune defense molecules, such as immunoglobulins, can be exploited by invasive pathogens, we hypothesized that MBL might also enhance infections in some circumstances. Consequently, the low and intermediate MBL levels commonly found in human populations might be the result of balancing selection. Using model infection systems with pseudotyped and authentic glycosylated viruses, we demonstrated that MBL indeed enhances infection of Ebola, Hendra, Nipah and West Nile viruses in low complement conditions. Mechanistic studies with Ebola virus (EBOV) glycoprotein pseudotyped lentiviruses confirmed that MBL binds to N-linked glycan epitopes on viral surfaces in a specific manner via the MBL carbohydrate recognition domain, which is necessary for enhanced infection. MBL mediates lipid-raft-dependent macropinocytosis of EBOV via a pathway that appears to require less actin or early endosomal processing compared with the filovirus canonical endocytic pathway. Using a validated RNA interference screen, we identified C1QBP (gC1qR) as a candidate surface receptor that mediates MBL-dependent enhancement of EBOV infection. We also identified dectin-2 (CLEC6A) as a potentially novel candidate attachment factor for EBOV. Our findings support the concept of an innate immune haplotype that represents critical interactions between MBL and complement component C4 genes and that may modify susceptibility or resistance to certain glycosylated pathogens. Therefore, higher levels of native or exogenous MBL could be deleterious in the setting of relative hypocomplementemia which can occur genetically or because of immunodepletion during active infections. Our findings confirm our hypothesis that the pressure of infectious diseases may have contributed in part to evolutionary selection of MBL mutant haplotypes

Sequence Specificity of BAL 31 Nuclease for ssDNA Revealed by Synthetic Oligomer Substrates Containing Homopolymeric Guanine Tracts

Background: The extracellular nuclease from Alteromonas espejiana, BAL 31 catalyzes the degradation of single-stranded and linear duplex DNA to 59-mononucleotides, cleaves negatively supercoiled DNA to the linear duplex form, and cleaves duplex DNA in response to the presence of apurinic sites. Principal Findings: In this work we demonstrate that BAL 31 activity is affected by the presence of guanine in singlestranded DNA oligomers. Specifically, nuclease activity is shown to be affected by guanine’s presence in minimal homopolymeric tracts in the middle of short oligomer substrates and also by its presence at the 39 end of ten and twenty base oligomers. GNC rich regions in dsDNA are known to cause a decrease in the enzyme’s nuclease activity which has been attributed to the increased thermal stability of these regions, thus making it more difficult to unwind the strands required for enzyme access. Our results indicate that an additional phenomenon could be wholly or partly responsible for the loss of activity in these GNC rich regions. Thus the presence of a guanine tract per se impairs the enzyme’s functionality, possibly due to the tract’s bulky nature and preventing efficient progression through the active site. Conclusions: This study has revealed that the general purpose BAL 31 nuclease commonly used in molecular genetics exhibits a hithertofore non-characterized degree of substrate specificity with respect to single-stranded DNA (ssDNA