LISA observations of massive black hole mergers: event rates and issues in waveform modelling

The observability of gravitational waves from supermassive and intermediate-mass black holes by the forecoming Laser Interferometer Space Antenna (LISA), and the physics we can learn from the observations, will depend on two basic factors: the event rates for massive black hole mergers occurring in the LISA best sensitivity window, and our theoretical knowledge of the gravitational waveforms. We first provide a concise review of the literature on LISA event rates for massive black hole mergers, as predicted by different formation scenarios. Then we discuss what (in our view) are the most urgent issues to address in terms of waveform modelling. For massive black hole binary inspiral these include spin precession, eccentricity, the effect of high-order Post-Newtonian terms in the amplitude and phase, and an accurate prediction of the transition from inspiral to plunge. For black hole ringdown, numerical relativity will ultimately be required to determine the relative quasinormal mode excitation, and to reduce the dimensionality of the template space in matched filtering.Comment: 14 pages, 2 figures. Added section with conclusions and outlook. Matches version to appear in the proceedings of 10th Annual Gravitational Wave Data Analysis Workshop (GWDAW 10), Brownsville, Texas, 14-17 Dec 200

The Enteropathogenic E. coli (EPEC) Tir Effector Inhibits NF-κB Activity by Targeting TNFα Receptor-Associated Factors

Enteropathogenic Escherichia coli (EPEC) disease depends on the transfer of effector proteins into epithelia lining the human small intestine. EPEC E2348/69 has at least 20 effector genes of which six are located with the effector-delivery system genes on the Locus of Enterocyte Effacement (LEE) Pathogenicity Island. Our previous work implied that non-LEE-encoded (Nle) effectors possess functions that inhibit epithelial anti-microbial and inflammation-inducing responses by blocking NF-κB transcription factor activity. Indeed, screens by us and others have identified novel inhibitory mechanisms for NleC and NleH, with key co-operative functions for NleB1 and NleE1. Here, we demonstrate that the LEE-encoded Translocated-intimin receptor (Tir) effector has a potent and specific ability to inhibit NF-κB activation. Indeed, biochemical, imaging and immunoprecipitation studies reveal a novel inhibitory mechanism whereby Tir interaction with cytoplasm-located TNFα receptor-associated factor (TRAF) adaptor proteins induces their proteasomal-independent degradation. Infection studies support this Tir-TRAF relationship but reveal that Tir, like NleC and NleH, has a non-essential contribution in EPEC's NF-κB inhibitory capacity linked to Tir's activity being suppressed by undefined EPEC factors. Infections in a disease-relevant intestinal model confirm key NF-κB inhibitory roles for the NleB1/NleE1 effectors, with other studies providing insights on host targets. The work not only reveals a second Intimin-independent property for Tir and a novel EPEC effector-mediated NF-κB inhibitory mechanism but also lends itself to speculations on the evolution of EPEC's capacity to inhibit NF-κB function

Large‐scale heparin‐based bind‐and‐elute chromatography identifies two biologically distinct populations of extracellular vesicles

ABSTRACT Purifying extracellular vesicles (EVs) has been challenging because EVs are heterogeneous in cargo yet share similar sizes and densities. Most surface marker‐based affinity separation methods are limited to research or diagnostic scales. We report that heparin chromatography can separate purified EVs into two distinct subpopulations as ascertained by MS/MS: a non‐heparin‐binding (NHB) fraction that contains classical EV markers such as tetraspanins and a heparin‐binding (HB) fraction enriched in fibronectins and histones. Both fractions were similarly fusogenic but induced different transcriptional responses in endothelial cells. While EVs that were purified by conventional, non‐affinity methods alone induced ERK1/2 phosphorylation and Ki67, the NHB fraction did not. This result suggests heparin chromatography as an additional novel fractionation step that is inherently scalable, does not lead to loss of material, and separates inflammatory and pyrogenic EVs from unreactive EVs, which will improve clinical applications

Looking in through Outdoor: A Socio-Cultural and Historical Perspective on the Evolution of Advertising Humour

This study examines the evolving acceptance and use of humour in advertising over the past century. Sociologists point to humour as an expression of the macro-societal mood. Consistent with this thesis, we analyse two data sets of outdoor advertisements that span over 100 years. We use a socio-cultural and historical perspective to understand the underlying drivers and changes in humour use at both the macro-cultural level and at the micro-industry level in the US. The results reveal the contextual interplay that led to changes in the acceptance of humorous advertisements as well as the evolution of humour styles and elements