72 research outputs found

    Ecological expected utility and the mythical neural code

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    Neural spikes are an evolutionarily ancient innovation that remains nature’s unique mechanism for rapid, long distance information transfer. It is now known that neural spikes sub serve a wide variety of functions and essentially all of the basic questions about the communication role of spikes have been answered. Current efforts focus on the neural communication of probabilities and utility values involved in decision making. Significant progress is being made, but many framing issues remain. One basic problem is that the metaphor of a neural code suggests a communication network rather than a recurrent computational system like the real brain. We propose studying the various manifestations of neural spike signaling as adaptations that optimize a utility function called ecological expected utility

    Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19

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    Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19

    Context Matters: The Illusive Simplicity of Macaque V1 Receptive Fields

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    Even in V1, where neurons have well characterized classical receptive fields (CRFs), it has been difficult to deduce which features of natural scenes stimuli they actually respond to. Forward models based upon CRF stimuli have had limited success in predicting the response of V1 neurons to natural scenes. As natural scenes exhibit complex spatial and temporal correlations, this could be due to surround effects that modulate the sensitivity of the CRF. Here, instead of attempting a forward model, we quantify the importance of the natural scenes surround for awake macaque monkeys by modeling it non-parametrically. We also quantify the influence of two forms of trial to trial variability. The first is related to the neuron’s own spike history. The second is related to ongoing mean field population activity reflected by the local field potential (LFP). We find that the surround produces strong temporal modulations in the firing rate that can be both suppressive and facilitative. Further, the LFP is found to induce a precise timing in spikes, which tend to be temporally localized on sharp LFP transients in the gamma frequency range. Using the pseudo R[superscript 2] as a measure of model fit, we find that during natural scene viewing the CRF dominates, accounting for 60% of the fit, but that taken collectively the surround, spike history and LFP are almost as important, accounting for 40%. However, overall only a small proportion of V1 spiking statistics could be explained (R[superscript 2]~5%), even when the full stimulus, spike history and LFP were taken into account. This suggests that under natural scene conditions, the dominant influence on V1 neurons is not the stimulus, nor the mean field dynamics of the LFP, but the complex, incoherent dynamics of the network in which neurons are embedded.National Institutes of Health (U.S.) (K25 NS052422-02)National Institutes of Health (U.S.) (DP1 ODOO3646

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    The contributions of image content and behavioral relevancy to overt attention

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    During free-viewing of natural scenes, eye movements are guided by bottom-up factors inherent to the stimulus, as well as top-down factors inherent to the observer. The question of how these two different sources of information interact and contribute to fixation behavior has recently received a lot of attention. Here, a battery of 15 visual stimulus features was used to quantify the contribution of stimulus properties during free-viewing of 4 different categories of images (Natural, Urban, Fractal and Pink Noise). Behaviorally relevant information was estimated in the form of topographical interestingness maps by asking an independent set of subjects to click at image regions that they subjectively found most interesting. Using a Bayesian scheme, we computed saliency functions that described the probability of a given feature to be fixated. In the case of stimulus features, the precise shape of the saliency functions was strongly dependent upon image category and overall the saliency associated with these features was generally weak. When testing multiple features jointly, a linear additive integration model of individual saliencies performed satisfactorily. We found that the saliency associated with interesting locations was much higher than any low-level image feature and any pair-wise combination thereof. Furthermore, the low-level image features were found to be maximally salient at those locations that had already high interestingness ratings. Temporal analysis showed that regions with high interestingness ratings were fixated as early as the third fixation following stimulus onset. Paralleling these findings, fixation durations were found to be dependent mainly on interestingness ratings and to a lesser extent on the low-level image features. Our results suggest that both low- and high-level sources of information play a significant role during exploration of complex scenes with behaviorally relevant information being more effective compared to stimulus features.publisher versio

    A many-analysts approach to the relation between religiosity and well-being

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    The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

    Instabilities in the oscillatory flow of a complex fluid.

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    The dynamics of a fluid in a vertical tube, subjected to an oscillatory pressure gradient, is studied experimentally for both a Newtonian and a viscoelastic shear-thinning fluid. Particle image velocimetry is used to determine the two-dimensional velocity fields in the vertical plane of the tube axis, in a range of driving amplitudes from 0.8 to 2.5 mm and of driving frequencies from 2.0 to 11.5 Hz. The Newtonian fluid exhibits a laminar flow regime, independent of the axial position, in the whole range of drivings. For the complex fluid, instead, the parallel shear flow regime exhibited at low amplitudes [Torralba, Phys. Rev. E 72, 016308 (2005)] becomes unstable at higher drivings against the formation of symmetric vortices, equally spaced along the tube. At even higher drivings the vortex structure itself becomes unstable, and complex nonsymmetric structures develop. Given that inertial effects remain negligible even at the hardest drivings (Re < 10(-1)), it is the complex rheology of the fluid that is responsible for the instabilities observed. The system studied represents an interesting example of the development of shear-induced instabilities in nonlinear complex fluids in purely parallel shear flow
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