Consciousness: the last 50 years(and the next)

The mind and brain sciences began with consciousness as a central concern. But for much of the 20th century, ideological and methodological concerns relegated its empirical study to the margins. Since the 1990s, studying consciousness has regained a legitimacy and momentum befitting its status as the primary feature of our mental lives. Nowadays, consciousness science encompasses a rich interdisciplinary mixture drawing together philosophical, theoretical, computational, experimental, and clinical perspectives, with neuroscience its central discipline. Researchers have learned a great deal about the neural mechanisms underlying global states of consciousness, distinctions between conscious and unconscious perception, and self-consciousness. Further progress will depend on specifying closer explanatory mappings between (first-person subjective) phenomenological descriptions and (third-person objective) descriptions of (embodied and embedded) neuronal mechanisms. Such progress will help reframe our understanding of our place in nature and accelerate clinical approaches to a wide range of psychiatric and neurological disorders

Searching for outflows in ultraluminous X-ray sources through high-resolution X-ray spectroscopy

Ultraluminous X-ray sources (ULXs) are non-nuclear point sources exceeding the Eddington luminosity of a 10 M⊙ black hole. Modern consensus for a majority of the ULX population is that they are powered by stellar-mass black holes or neutron stars accreting well above the Eddington limit. Theoretical models of super-Eddington accretion predict existence of powerful outflows of moderately ionized gas at mildly relativistic velocities. So far, these winds have been found in three systems: NGC 1313 X-1, NGC 5408 X-1 and NGC 55 ULX. In this work, we create a sample of all ULXs with usable archival high-resolution X-ray data, with 10 sources in total, in which we aim to find more signatures of outflows. We perform Gaussian line scans to find any narrow spectral signatures, and physical wind model scans where possible. We tentatively identify an outflow in NGC 5204 X-1, blueshifted to 0.34c, which produces emission features with a total significance of at least 3σ. Next we compare ULXs with similar hardness ratios. Holmberg IX X-1 shows absorption features that could be associated with a photoionized outflowing absorber, similar to that seen in NGC 1313 X-1. The spectrum of Holmberg II X-1 possesses features similar to NGC 5408 X-1 and NGC 6946 X-1 shows O VIII rest-frame emission. All other sources from the sample also show tentative evidence of spectral features in their high-resolution spectra. Further observations with the XMM–Newton and Chandra gratings will place stronger constraints. Future missions like XARM and Athena will be able to detect them at larger distances and increase our sample

Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor

Apixaban (BMS-562247; 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide), a direct inhibitor of activated factor X (FXa), is in development for the prevention and treatment of various thromboembolic diseases. With an inhibitory constant of 0.08 nM for human FXa, apixaban has greater than 30,000-fold selectivity for FXa over other human coagulation proteases. It produces a rapid onset of inhibition of FXa with association rate constant of 20 μM−1/s approximately and inhibits free as well as prothrombinase- and clot-bound FXa activity in vitro. Apixaban also inhibits FXa from rabbits, rats and dogs, an activity which parallels its antithrombotic potency in these species. Although apixaban has no direct effects on platelet aggregation, it indirectly inhibits this process by reducing thrombin generation. Pre-clinical studies of apixaban in animal models have demonstrated dose-dependent antithrombotic efficacy at doses that preserved hemostasis. Apixaban improves pre-clinical antithrombotic activity, without excessive increases in bleeding times, when added on top of aspirin or aspirin plus clopidogrel at their clinically relevant doses. Apixaban has good bioavailability, low clearance and a small volume of distribution in animals and humans, and a low potential for drug–drug interactions. Elimination pathways for apixaban include renal excretion, metabolism and biliary/intestinal excretion. Although a sulfate conjugate of Ο-demethyl apixaban (O-demethyl apixaban sulfate) has been identified as the major circulating metabolite of apixaban in humans, it is inactive against human FXa. Together, these non-clinical findings have established the favorable pharmacological profile of apixaban, and support the potential use of apixaban in the clinic for the prevention and treatment of various thromboembolic diseases

Constraining the mass of accreting black holes in ultraluminous X-ray sources with ultrafast outflows

The nature of ultraluminous X-ray sources (ULXs) – off-nuclear extragalactic sources with luminosity, assumed isotropic, ≳1039 erg s−1 – is still debated. One possibility is that ULXs are stellar black holes (BHs) accreting beyond the Eddington limit. This view has been recently reinforced by the discovery of ultrafast outflows at ∼0.1–0.2c in the high-resolution spectra of a handful of ULXs, as predicted by models of supercritical accretion discs. Under the assumption that ULXs are powered by super-Eddington accretion on to BHs, we use the properties of the observed outflows to self-consistently constrain their masses and accretion rates. We find masses ≲100 M⊙ and typical accretion rates ∼10−5 M⊙ yr−1, i.e. ≈10 times larger than the Eddington limit calculated with a radiative efficiency of 0.1. However, the emitted luminosity is only ≈10 per cent beyond the Eddington luminosity, because most of the energy released in the inner part of the accretion disc is used to accelerate the wind, which implies radiative efficiency ∼0.01. Our results are consistent with a formation model where ULXs are BH remnants of massive stars evolved in low-metallicity environments.DF acknowledges support by European Research Council (ERC) Starting Grant 638707 ‘Black holes and their host galaxies: coevolution across cosmic time’. CP and ACF acknowledge support by ERC Advanced Grant 340442 ‘Accreting black holes and cosmic feedback’

Response of the North Atlantic storm track to climate change shaped by ocean–atmosphere coupling

A poleward shift of the mid-latitude storm tracks in response to anthropogenic greenhouse-gas forcing has been diagnosed in climate model simulations1, 2. Explanations of this effect have focused on atmospheric dynamics3, 4, 5, 6, 7. However, in contrast to storm tracks in other regions, the North Atlantic storm track responds by strengthening and extending farther east, in particular on its southern flank8. These adjustments are associated with an intensification and extension of the eddy-driven jet towards western Europe9 and are expected to have considerable societal impacts related to a rise in storminess in Europe10, 11, 12. Here, we apply a regression analysis to an ensemble of coupled climate model simulations to show that the coupling between ocean and atmosphere shapes the distinct storm-track response to greenhouse-gas forcing in the North Atlantic region. In the ensemble of simulations we analyse, at least half of the differences between the storm-track responses of different models are associated with uncertainties in ocean circulation changes. We compare the fully coupled simulations with both the associated slab model simulations and an ocean-forced experiment with one climate model to establish causality. We conclude that uncertainties in the response of the North Atlantic storm track to anthropogenic emissions could be reduced through tighter constraints on the future ocean circulation

Studies on the interaction of the carbohydrate binding module 3 from the Clostridium thermocellum CipA scaffolding protein with cellulose and paper fibres

The adsorption of a carbohydrate binding module (CBM3) from the Clostridium thermocellum scaffolding protein (CipA) to cellulose was analysed in this work. The effect of CBM-PEG on the drainability of E. globulus and P. sylvestris pulps and on the physical properties of the respective papersheets was also studied. The CBM binding to cellulose is often described as “irreversible”, but this classification does not fully characterize this interaction. Indeed, the results obtained demonstrate that, although the adsorption on cellulose is rather stable, CBM inter-fibre mobility may be observed. The results also showed that the CBM-PEG conjugate improves the drainability of E. globulus and P. sylvestris pulps without affecting the physical properties of the papersheets.This research was supported by Fundacao para a Ciencia e a Tecnologia under grant POCTI/BIO/45356/2002

Ultrafast outflows disappear in high-radiation fields

Ultrafast outflows (UFOs) are the most extreme winds launched by active galactic nuclei (AGN) due to their mildly-relativistic speeds (~0.1-0.3c) and are thought to significantly contribute to galactic evolution via AGN feedback. Their nature and launching mechanism are however not well understood. Recently, we have discovered the presence of a variable UFO in the narrow-line Seyfert 1 IRAS 13224-3809. The UFO varies in response to the brightness of the source. In this work we perform flux-resolved X-ray spectroscopy to study the variability of the UFO and found that the ionisation parameter is correlated with the luminosity. In the brightest states the gas is almost completely ionised by the powerful radiation field and the UFO is hardly detected. This agrees with our recent results obtained with principal component analysis. We might have found the tip of the iceberg: the high ionisation of the outflowing gas may explain why it is commonly difficult to detect UFOs in AGN and possibly suggest that we may underestimate their actual feedback. We have also found a tentative correlation between the outflow velocity and the luminosity, which is expected from theoretical predictions of radiation-pressure driven winds. This trend is rather marginal due to the Fe XXV-XXVI degeneracy. Further work is needed to break such degeneracy through time-resolved spectroscopy

Analysis of symmetries in models of multi-strain infections

In mathematical studies of the dynamics of multi-strain diseases caused by antigenically diverse pathogens, there is a substantial interest in analytical insights. Using the example of a generic model of multi-strain diseases with cross-immunity between strains, we show that a significant understanding of the stability of steady states and possible dynamical behaviours can be achieved when the symmetry of interactions between strains is taken into account. Techniques of equivariant bifurcation theory allow one to identify the type of possible symmetry-breaking Hopf bifurcation, as well as to classify different periodic solutions in terms of their spatial and temporal symmetries. The approach is also illustrated on other models of multi-strain diseases, where the same methodology provides a systematic understanding of bifurcation scenarios and periodic behaviours. The results of the analysis are quite generic, and have wider implications for understanding the dynamics of a large class of models of multi-strain diseases

XMM–Newton campaign on ultraluminous X-ray source NGC 1313 X-1: wind versus state variability

Most ultraluminous X-ray sources (ULXs) are thought to be powered by neutron stars and black holes accreting beyond the Eddington limit. If the compact object is a black hole or a neutron star with a magnetic field ≲1012 G, the accretion disc is expected to thicken and launch powerful winds driven by radiation pressure. Evidence of such winds has been found in ULXs through the high-resolution spectrometers onboardXMM–Newton, but several unknowns remain, such as the geometry and launching mechanism of these winds. In order to better understand ULX winds and their link to the accretion regime, we have undertaken a major campaign with XMM–Newton to study the ULX NGC 1313 X-1, which is known to exhibit strong emission and absorption features from a mildly relativistic wind. The new observations show clear changes in the wind with a significantly weakened fast component (0.2c) and the rise of a new wind phase which is cooler and slower (0.06–0.08c). We also detect for the first time variability in the emission lines which indicates an origin within the accretion disc or in the wind. We describe the variability of the wind in the framework of variable super-Eddington accretion rate and discuss a possible geometry for the accretion disc