Parametric Copula-GP model for analyzing multidimensional neuronal and behavioral relationships

One of the main goals of current systems neuroscience is to understand how neuronal populations integrate sensory information to inform behavior. However, estimating stimulus or behavioral information that is encoded in high-dimensional neuronal populations is challenging. We propose a method based on parametric copulas which allows modeling joint distributions of neuronal and behavioral variables characterized by different statistics and timescales. To account for temporal or spatial changes in dependencies between variables, we model varying copula parameters by means of Gaussian Processes (GP). We validate the resulting Copula-GP framework on synthetic data and on neuronal and behavioral recordings obtained in awake mice. We show that the use of a parametric description of the high-dimensional dependence structure in our method provides better accuracy in mutual information estimation in higher dimensions compared to other non-parametric methods. Moreover, by quantifying the redundancy between neuronal and behavioral variables, our model exposed the location of the reward zone in an unsupervised manner (i.e., without using any explicit cues about the task structure). These results demonstrate that the Copula-GP framework is particularly useful for the analysis of complex multidimensional relationships between neuronal, sensory and behavioral variables

V1T: large-scale mouse V1 response prediction using a Vision Transformer

Accurate predictive models of the visual cortex neural response to natural visual stimuli remain a challenge in computational neuroscience. In this work, we introduce V1T, a novel Vision Transformer based architecture that learns a shared visual and behavioral representation across animals. We evaluate our model on two large datasets recorded from mouse primary visual cortex and outperform previous convolution-based models by more than 12.7% in prediction performance. Moreover, we show that the self-attention weights learned by the Transformer correlate with the population receptive fields. Our model thus sets a new benchmark for neural response prediction and can be used jointly with behavioral and neural recordings to reveal meaningful characteristic features of the visual cortex.Comment: updated references and added link to code repository; add analysis on generalization and visualize aRF

NASA's Ares I and Ares V Launch Vehicles--Effective Space Operations Through Efficient Ground Operations

The United States (U.S.) is charting a renewed course for lunar exploration, with the fielding of a new human-rated space transportation system to replace the venerable Space Shuttle, which will be retired after it completes its missions of building the International Space Station (ISS) and servicing the Hubble Space Telescope. Powering the future of space-based scientific exploration will be the Ares I Crew Launch Vehicle, which will transport the Orion Crew Exploration Vehicle to orbit where it will rendezvous with the Altair Lunar Lander, which will be delivered by the Ares V Cargo Launch Vehicle (fig. 1). This configuration will empower rekindled investigation of Earth's natural satellite in the not too distant future. This new exploration infrastructure, developed by the National Aeronautics and Space Administration (NASA), will allow astronauts to leave low-Earth orbit (LEO) for extended lunar missions and preparation for the first long-distance journeys to Mars. All space-based operations - to LEO and beyond - are controlled from Earth. NASA's philosophy is to deliver safe, reliable, and cost-effective architecture solutions to sustain this multi-billion-dollar program across several decades. Leveraging SO years of lessons learned, NASA is partnering with private industry and academia, while building on proven hardware experience. This paper outlines a few ways that the Engineering Directorate at NASA's Marshall Space Flight Center is working with the Constellation Program and its project offices to streamline ground operations concepts by designing for operability, which reduces lifecycle costs and promotes sustainable space exploration

Evolutionary Tracks of Individual Quasars in the Mass-Luminosity Plane

Previous work on the quasar mass-luminosity plane indicates the possibility that quasars of the same central black hole mass might follow a common evolutionary track, independent of the properties of the host galaxy. We consider two simple models for the evolution of individual quasars. Requiring these tracks to lie within the observed quasar locus at all redshifts strongly constrains the model parameters, but does allow some solutions. These solutions include a family of tracks with similar shape but different initial masses that might match the observed quasar distributions at all redshifts z < 2.0. This family of solutions is characterized by short (1-2 Gyr) lifetimes, a duty cycle in which the quasar is on at least 25% of the time, and a rapid decline in Eddington ratio, perhaps with L/L_Edd ~ t^-6 or steeper.Comment: Accepted by MNRA

Predictive MGMT status in a homogeneous cohort of IDH wildtype glioblastoma patients

Methylation of the O(6)-Methylguanine-DNA methyltransferase (MGMT) promoter is predictive for treatment response in glioblastoma patients. However, precise predictive cutoff values to distinguish "MGMT methylated" from "MGMT unmethylated" patients remain highly debated in terms of pyrosequencing (PSQ) analysis. We retrospectively analyzed a clinically and molecularly very well-characterized cohort of 111 IDH wildtype glioblastoma patients, who underwent gross total tumor resection and received standard Stupp treatment. Detailed clinical parameters were obtained. Predictive cutoff values for MGMT promoter methylation were determined using ROC curve analysis and survival curve comparison using Log-rank (Mantel-Cox) test. MGMT status was analyzed using pyrosequencing (PSQ), semi-quantitative methylation specific PCR (sqMSP) and direct bisulfite sequencing (dBiSeq). Highly methylated (> 20%) MGMT correlated with significantly improved progression-free survival (PFS) and overall survival (OS) in our cohort. Median PFS was 7.2 months in the unmethylated group (UM, 20% mean methylation). Median OS was 13.4 months for UM, 17.9 months for LM and 29.93 months for HM. Within the LM group, correlation of PSQ and sqMSP or dBiSeq was only conclusive in 51.5% of our cases. ROC curve analysis revealed superior test precision for survival if additional sqMSP results were considered (AUC = 0.76) compared to PSQ (cutoff 10%) alone (AUC = 0.67). We therefore challenge the widely used, strict PSQ cutoff at 10% which might not fully reflect the clinical response to alkylating agents and suggest applying a second method for MGMT testing (e.g. MSP) to confirm PSQ results for patients with LM MGMT levels if therapeutically relevant

A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans

In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins

Effects of Biases in Virial Mass Estimation on Cosmic Synchronization of Quasar Accretion

Recent work using virial mass estimates and the quasar mass-luminosity plane has yielded several new puzzles regarding quasar accretion, including a sub-Eddington boundary on most quasar accretion, near-independence of the accretion rate from properties of the host galaxy, and a cosmic synchronization of accretion among black holes of a common mass. We consider how these puzzles might change if virial mass estimation turns out to have a systematic bias. As examples, we consider two recent claims of mass-dependent biases in MgII masses. Under any such correction, the surprising cosmic synchronization of quasar accretion rates and independence from the host galaxy remain. The slope and location of the sub-Eddington boundary are very sensitive to biases in virial mass estimation, and various mass calibrations appear to favor different possible physical explanations for feedback between the central black hole and its environment. The alternative mass estimators considered do not simply remove puzzling quasar behavior, but rather replace it with new puzzles that may be more difficult to solve than those using current virial mass estimators and the Shen et al. (2008) catalog.Comment: 8 pages, 4 figure

The Quasar Mass-Luminosity Plane III: Smaller Errors on Virial Mass Estimates

We use 62185 quasars from the Sloan Digital Sky Survey (SDSS) DR5 sample to explore the quasar mass-luminosity plane view of virial mass estimation. Previous work shows deviations of ~0.4 dex between virial and reverberation masses. The decline in quasar number density for the highest Eddington ratio quasars at each redshift provides an upper bound of between 0.13 and 0.29 dex for virial mass estimate statistical uncertainties. Across different redshift bins, the maximum possible MgII mass uncertainties average 0.15 dex, while H{\beta} uncertainties average 0.21 dex and CIV uncertainties average 0.27 dex. Any physical spread near the high-Eddington-ratio boundary will produce a more restrictive bound. A comparison of the sub-Eddington boundary slope using H{\beta} and MgII masses finds better agreement with uncorrected MgII masses than with recently proposed corrections. The best agreement for these bright objects is produced by a multiplicative correction by a factor of 1.19, smaller than the factor of 1.8 previously reported as producing the best agreement for the entire SDSS sample.Comment: 5 pages, MNRAS letter

The Quasar Mass-Luminosity Plane II: High Mass Turnoff Evolution and a Synchronization Puzzle

We use 62,185 quasars from the Sloan Digital Sky Survey DR5 sample and standard virial mass scaling laws based on the widths of H beta, Mg II, and C IV lines and adjacent continuum luminosities to explore the maximum mass of quasars as a function of redshift, which we find to be sharp and evolving. This evolution is in the sense that high-mass black holes cease their luminous accretion at higher redshift than lower-mass black holes. Further, turnoff for quasars at any given mass is more highly synchronized than would be expected given the dynamics of their host galaxies. We investigate potential signatures of the quasar turnoff mechanism, including a dearth of high-mass quasars at low Eddington ratio. These new results allow a closer examination of several common assumptions used in modeling quasar accretion and turnoff.Comment: 10 pages, submitted to MNRA