Morphological convergence obscures functional diversity in sabre-toothed carnivores

The acquisition of elongated, sabre-like canines in multiple vertebrate clades during the last 265 Myr represents a remarkable example for convergent evolution. Due to striking superficial similarities in the cranial skeleton, the same or similar skull and jaw functions have been inferred for sabre-toothed species and interpreted as an adaptation to subdue large-bodied prey. However, although some sabre-tooth lineages have been classified into different ecomorphs (dirk-tooths and scimitar-tooths) the functional diversity within and between groups and the evolutionary paths leading to these specializations are unknown. Here, we use a suite of biomechanical simulations to analyse key functional parameters (mandibular gape angle, bending strength, bite force) to compare the functional performance of different groups and to quantify evolutionary rates across sabre-tooth vertebrates. Our results demonstrate a remarkably high functional diversity between sabre-tooth lineages and that different cranial function and prey killing strategies evolved within clades. Moreover, different biomechanical adaptations in coexisting sabre-tooth species further suggest that this functional diversity was at least partially driven by niche partitioning

Excess mortality in Glasgow: further evidence of ‘political effects’ on population health

Objectives: The aim of the study was to update previous analyses of ‘excess mortality’ in Glasgow (Scotland) relative to the similar postindustrial cities of Liverpool and Manchester (England). The excess is defined as mortality after adjustment for socio-economic deprivation; thus, we sought to compare changes over time in both the deprivation profiles of the cities and the levels of deprivation-adjusted mortality in Glasgow relative to the other cities. This is important not only because the original analyses are now increasingly out of date but also because since publication, important (prepandemic) changes to mortality trends have been observed across all parts of the United Kingdom. Study design and methods: Replicating as far as possible the methods of the original study, we developed a three-city deprivation index based on the creation of spatial units in Glasgow that were of similar size to those in Liverpool and Manchester (average population sizes of approximately 1600, 1500 and 1700 respectively) and an area-based measure of ‘employment deprivation’. Mortality and matching population data by age, sex and small area were obtained from national agencies for two periods: 2003–2007 (the period covered by the original study) and 2014–2018. The rates of employment deprivation for each city's small areas were calculated for both periods. Indirectly standardised mortality ratios (SMRs) were calculated for Glasgow relative to Liverpool and Manchester, standardised by age and three-city deprivation decile. For context, city-level trends in age-standardised mortality rates by year, sex and city were also calculated. Results: There was evidence of a stalling of improvement in mortality rates in all three cities from the early 2010s. After adjustment for area deprivation, all-cause mortality in Glasgow in 2014–2018 was c.12% higher than in Liverpool and Manchester for all ages (SMR 112.4, 95% CI 111.1–113.6) and c.17% higher for deaths under 65 years (SMR 117.1, 95% CI 114.5–119.7). The excess was higher for males (17% compared with 9% for deaths at all ages; 25% compared with 5% for 0–64 years) and for particular causes of death such as suicide and drug-related and alcohol-related causes. The results were broadly similar to those previously described for 2003–2007, although the excess for premature mortality was notably lower. In part, this was explained by changes in levels of employment deprivation, which had decreased to a greater degree in the English cities: this was particularly true of Manchester (a reduction of −43%, compared with −38% in Liverpool and −31% in Glasgow) where the overall population size had also increased to a much greater extent than in the other cities. Conclusions: High levels of excess mortality persist in Glasgow. With the political causes recently established – the excess is a ‘political effect’, not a ‘Glasgow effect’ – political solutions are required. Thus, previously published recommendations aimed at addressing poverty, inequality and vulnerability in the city are still highly relevant. However, given the evidence of more recent, UK-wide, political effects on mortality – widening mortality inequalities resulting from UK Government ‘austerity’ measures – additional policies at UK Government level to protect, and restore, the income of the poorest in society are also urgently needed

Absolute Quantification of sp3^3 Defects in Semiconducting Single-Wall Carbon Nanotubes by Raman Spectroscopy

The functionalization of semiconducting single-wall carbon nanotubes (SWCNTs) with luminescent sp$^3$ defects creates red-shifted emission features in the near-infrared and boosts their photoluminescence quantum yields (PLQYs). While multiple synthetic routes for the selective introduction of sp$^3$ defects have been developed, a convenient metric to precisely quantify the number of defects on a SWCNT lattice is not available. Here, we present a direct and simple quantification protocol based on a linear correlation of the integrated Raman D/G+ signal ratios and defect densities as extracted from PLQY measurements. Corroborated by a statistical analysis of single-nanotube emission spectra at cryogenic temperature, this method enables the quantitative evaluation of sp$^3$ defect densities in (6,5) SWCNTs with an error of ±3 defects per micrometer and the determination of oscillator strengths for different defect types. The developed protocol requires only standard Raman spectroscopy and is independent of the defect configuration, dispersion solvent, and nanotube length

Absolute Quantification of sp3^3 Defects in Semiconducting Single-Wall Carbon Nanotubes by Raman Spectroscopy

The functionalization of semiconducting single-wall carbon nanotubes (SWCNTs) with luminescent sp$^3$ defects creates red-shifted emission features in the near-infrared and boosts their photoluminescence quantum yields (PLQYs). While multiple synthetic routes for the selective introduction of sp$^3$ defects have been developed, a convenient metric to precisely quantify the number of defects on a SWCNT lattice is not available. Here, we present a direct and simple quantification protocol based on a linear correlation of the integrated Raman D/G+ signal ratios and defect densities as extracted from PLQY measurements. Corroborated by a statistical analysis of single-nanotube emission spectra at cryogenic temperature, this method enables the quantitative evaluation of sp$^3$ defect densities in (6,5) SWCNTs with an error of ±3 defects per micrometer and the determination of oscillator strengths for different defect types. The developed protocol requires only standard Raman spectroscopy and is independent of the defect configuration, dispersion solvent, and nanotube length

Building better Sex Robots: Lessons from Feminist Pornography

How should we react to the development of sexbot technology? Taking their cue from anti-porn feminism, several academic critics lament the development of sexbot technology, arguing that it objectifies and subordinates women, is likely to promote misogynistic attitudes toward sex, and may need to be banned or restricted. In this chapter I argue for an alternative response. Taking my cue from the sex positive ‘feminist porn’ movement, I argue that the best response to the development of ‘bad’ sexbots is to make better ones. This will require changes to the content, process and context of sexbot development. Doing so will acknowledge the valuable role that technology can play in human sexuality, and allow us to challenge gendered norms and assumptions about male and female sexual desire. This will not be a panacea to the social problems that could arise from sexbot development, but it offers a more realistic and hopeful vision for the future of this technology in a pluralistic and progressive society

Pharmacologic Targeting of Bacterial -Glucuronidase Alleviates Nonsteroidal Anti-Inflammatory Drug-Induced Enteropathy in Mice

Small intestinal mucosal injury is a frequent adverse effect caused by nonsteroidal anti-inflammatory drugs (NSAIDs). The underlying mechanisms are not completely understood, but topical (luminal) effects have been implicated. Many carboxylic acid-containing NSAIDs, including diclofenac (DCF), are metabolized to acyl glucuronides (AGs), and/or ether glucuronides after ring hydroxylation, and exported into the biliary tree. In the gut, these conjugates are cleaved by bacterial β-glucuronidase, releasing the potentially harmful aglycone. We first confirmed that DCF-AG was an excellent substrate for purified Escherichia coli β-d-glucuronidase. Using a previously characterized novel bacteria-specific β-glucuronidase inhibitor (Inhibitor-1), we then found that the enzymatic hydrolysis of DCF-AG in vitro was inhibited concentration dependently (IC50 ∼164 nM). We next hypothesized that pharmacologic inhibition of bacterial β-glucuronidase would reduce exposure of enterocytes to the aglycone and, as a result, alleviate enteropathy. C57BL/6J mice were administered an ulcerogenic dose of DCF (60 mg/kg i.p.) with or without oral pretreatment with Inhibitor-1 (10 μg per mouse, b.i.d.). Whereas DCF alone caused the formation of numerous large ulcers in the distal parts of the small intestine and increased (2-fold) the intestinal permeability to fluorescein isothiocyanate-dextran, Inhibitor-1 cotreatment significantly alleviated mucosal injury and reduced all parameters of enteropathy. Pharmacokinetic profiling of DCF plasma levels in mice revealed that Inhibitor-1 coadministration did not significantly alter the Cmax, half-life, or area under the plasma concentration versus time curve of DCF. Thus, highly selective pharmacologic targeting of luminal bacterial β-d-glucuronidase by a novel class of small-molecule inhibitors protects against DCF-induced enteropathy without altering systemic drug exposure

Neurofilament light compared to neuron-specific enolase as a predictor of unfavourable outcome after out-of-hospital cardiac arrest

Aim: We compared the prognostic abilities of neurofilament light (NfL) and neuron-specific enolase (NSE) in patients resuscitated from out-ofhospital cardiac arrest (OHCA) of various aetiologies. Methods: We analysed frozen blood samples obtained at 24 and 48 hours from OHCA patients treated in 21 Finnish intensive care units in 2010 and 2011. We defined unfavourable outcome as Cerebral Performance Category (CPC) 3-5 at 12 months after OHCA. We evaluated the prognostic ability of the biomarkers by calculating the area under the receiver operating characteristic curves (AUROCs [95% confidence intervals]) and compared these with a bootstrap method. Results: Out of 248 adult patients, 12-month outcome was unfavourable in 120 (48.4%). The median (interquartile range) NfL concentrations for patients with unfavourable and those with favourable outcome, respectively, were 689 (146-1804) pg/mL vs. 31 (17-61) pg/mL at 24 h and 1162 (147-4360) pg/mL vs. 36 (21-87) pg/mL at 48 h, p < 0.001 for both. The corresponding NSE concentrations were 13.3 (7.2-27.3) mg/L vs. 8.5 (5.8- 13.2) mg/L at 24 h and 20.4 (8.1-56.6) mg/L vs. 8.2 (5.9-12.1) mg/L at 48 h, p < 0.001 for both. The AUROCs to predict an unfavourable outcome were 0.90 (0.86-0.94) for NfL vs. 0.65 (0.58-0.72) for NSE at 24 h, p < 0.001 and 0.88 (0.83-0.93) for NfL and 0.73 (0.66-0.81) for NSE at 48 h, p < 0.001. Conclusion: Compared to NSE, NfL demonstrated superior accuracy in predicting long-term unfavourable outcome after OHCA.Peer reviewe

Ptch2/Gas1 and Ptch1/Boc differentially regulate Hedgehog signalling in murine primordial germ cell migration.

Gas1 and Boc/Cdon act as co-receptors in the vertebrate Hedgehog signalling pathway, but the nature of their interaction with the primary Ptch1/2 receptors remains unclear. Here we demonstrate, using primordial germ cell migration in mouse as a developmental model, that specific hetero-complexes of Ptch2/Gas1 and Ptch1/Boc mediate the process of Smo de-repression with different kinetics, through distinct modes of Hedgehog ligand reception. Moreover, Ptch2-mediated Hedgehog signalling induces the phosphorylation of Creb and Src proteins in parallel to Gli induction, identifying a previously unknown Ptch2-specific signal pathway. We propose that although Ptch1 and Ptch2 functionally overlap in the sequestration of Smo, the spatiotemporal expression of Boc and Gas1 may determine the outcome of Hedgehog signalling through compartmentalisation and modulation of Smo-downstream signalling. Our study identifies the existence of a divergent Hedgehog signal pathway mediated by Ptch2 and provides a mechanism for differential interpretation of Hedgehog signalling in the germ cell niche

Business Analytics in (a) Blink

The Blink project’s ambitious goal is to answer all Business Intelligence (BI) queries in mere seconds, regardless of the database size, with an extremely low total cost of ownership. Blink is a new DBMS aimed primarily at read-mostly BI query processing that exploits scale-out of commodity multi-core processors and cheap DRAM to retain a (copy of a) data mart completely in main memory. Additionally, it exploits proprietary compression technology and cache-conscious algorithms that reduce memory bandwidth consumption and allow most SQL query processing to be performed on the compressed data. Blink always scans (portions of) the data mart in parallel on all nodes, without using any indexes or materialized views, and without any query optimizer to choose among them. The Blink technology has thus far been incorp

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal