Broussardvestergaard9392
How dynamic activity in neural circuits gives rise to behavior is a major area of interest in neuroscience. A key experimental approach for addressing this question involves measuring extracellular neuronal activity in awake, behaving animals. Recently developed Neuropixels probes have provided a step change in recording neural activity in large tissue volumes with high spatiotemporal resolution. This protocol describes the chronic implantation of Neuropixels probes in mice and rats using compact and reusable 3D-printed fixtures. The fixtures facilitate stable chronic in vivo recordings in freely behaving rats and mice. They consist of two parts a covered main body and a skull connector. Single-, dual- and movable-probe fixture variants are available. After completing an experiment, probes are safely recovered for reimplantation by a dedicated retrieval mechanism. Fixture assembly and surgical implantation typically take 4-5 h, and probe retrieval takes ~30 min, followed by 12 h of incubation in probe cleaning agent. The duration of data acquisition depends on the type of behavioral experiment. Since our protocol enables stable, chronic recordings over weeks, it enables longitudinal large-scale single-unit data to be routinely obtained in a cost-efficient manner, which will facilitate many studies in systems neuroscience.More than 90% of the human genome is transcribed into noncoding RNAs, but their functional characterization has lagged behind. A major bottleneck in the understanding of their functions and mechanisms has been a dearth of systematic methods for identifying interacting protein partners. There now exist several methods, including identification of direct RNA interacting proteins (iDRiP), chromatin isolation by RNA purification (ChIRP), and RNA antisense purification, each previously applied towards identifying a proteome for the prototype noncoding RNA, Xist. iDRiP has recently been modified to successfully identify proteomes for two additional noncoding RNAs of interest, TERRA and U1 RNA. Here we describe the modified protocol in detail, highlighting technical differences that facilitate capture of various noncoding RNAs. The protocol can be applied to short and long RNAs in both cultured cells and tissues, and requires ~1 week from start to finish. Here we also perform a comparative analysis between iDRiP and ChIRP. We obtain partially overlapping profiles, but find that iDRiP yields a greater number of specific proteins and fewer mitochondrial contaminants. With an increasing number of essential long noncoding RNAs being described, robust RNA-centric protein capture methods are critical for the probing of noncoding RNA function and mechanism.The effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey-a large community-based survey of individuals living in randomly selected private households across the United Kingdom-to assess the effectiveness of the BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value ( less then 30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54-68%) versus 66% (95% CI = 60-71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65-88%) versus 80% (95% CI = 73-85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines.Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.Chip floorplanning is the engineering task of designing the physical layout of a computer chip. Despite five decades of research1, chip floorplanning has defied automation, requiring months of intense effort by physical design engineers to produce manufacturable layouts. Here we present a deep reinforcement learning approach to chip floorplanning. In under six hours, our method automatically generates chip floorplans that are superior or comparable to those produced by humans in all key metrics, including power consumption, performance and chip area. To achieve this, we pose chip floorplanning as a reinforcement learning problem, and develop an edge-based graph convolutional neural network architecture capable of learning rich and transferable representations of the chip. As a result, our method utilizes past experience to become better and faster at solving new instances of the problem, allowing chip design to be performed by artificial agents with more experience than any human designer. Our method was used to design the next generation of Google's artificial intelligence (AI) accelerators, and has the potential to save thousands of hours of human effort for each new generation. Finally, we believe that more powerful AI-designed hardware will fuel advances in AI, creating a symbiotic relationship between the two fields.The electrification of heavy-duty transport and aviation will require new strategies to increase the energy density of electrode materials1,2. The use of anionic redox represents one possible approach to meeting this ambitious target. However, questions remain regarding the validity of the O2-/O- oxygen redox paradigm, and alternative explanations for the origin of the anionic capacity have been proposed3, because the electronic orbitals associated with redox reactions cannot be measured by standard experiments. Here, using high-energy X-ray Compton measurements together with first-principles modelling, we show how the electronic orbital that lies at the heart of the reversible and stable anionic redox activity can be imaged and visualized, and its character and symmetry determined. We find that differential changes in the Compton profile with lithium-ion concentration are sensitive to the phase of the electronic wave function, and carry signatures of electrostatic and covalent bonding effects4. Our study not only provides a picture of the workings of a lithium-rich battery at the atomic scale, but also suggests pathways to improving existing battery materials and designing new ones.In the last few decades, topological phase1-11 has emerged as a new classification of matter states beyond the Ginzburg-Landau symmetry-breaking paradigm. The underlying global invariant is usually well characterized by integers, such as Chern numbers or winding numbers-the Abelian charges12-15. Very recently, researchers proposed the notion of non-Abelian topological charges16-19, which possess non-commutative and fruitful braiding structures with multiple (more than one) bandgaps tangled together. Here we experimentally observe the non-Abelian topological charges in a time-reversal and inversion-symmetric transmission line network. The quaternion-valued non-Abelian topological charges are clearly mapped onto an eigenstate-frame sphere. Moreover, we find a non-Abelian quotient relation that provides a global perspective on the distribution of edge/domain-wall states. Our work opens the door towards characterization and manipulation of non-Abelian topological charges, which may lead to interesting observables such as trajectory-dependent Dirac/Weyl node collisions in two-dimensional systems16,17,20, admissible nodal line configurations in three dimensions16,19,20, and may provide insight into certain strongly correlated phases of twisted bilayer graphene21.Superfluidity in its various forms has been of interest since the observation of frictionless flow in liquid helium II1,2. In three spatial dimensions it is conceptually associated with the emergence of long-range order at a critical temperature. One of the hallmarks of superfluidity, as predicted by the two-fluid model3,4 and observed in both liquid helium5 and in ultracold atomic gases6,7, is the existence of two kinds of sound excitation-the first and second sound. In two-dimensional systems, thermal fluctuations preclude long-range order8,9; however, superfluidity nevertheless emerges at a non-zero critical temperature through the infinite-order Berezinskii-Kosterlitz-Thouless (BKT) transition10,11, which is associated with a universal jump12 in the superfluid density without any discontinuities in the thermodynamic properties of the fluid. BKT superfluids are also predicted to support two sounds, but so far this has not been observed experimentally. Here we observe first and second sound in a homogeneous two-dimensional atomic Bose gas, and use the two temperature-dependent sound speeds to determine the superfluid density of the gas13-16. Our results agree with the predictions of BKT theory, including the prediction of a universal jump in the superfluid density at the critical temperature.The evolution of satellite galaxies is shaped by their constant interaction with the circumgalactic medium surrounding central galaxies, which in turn may be affected by gas and energy ejected from the central supermassive black hole1-6. The nature of such a coupling between black holes and galaxies is, however, much debated7-9 and observational evidence remains scarce10,11. this website Here we report an analysis of archival data on 124,163 satellite galaxies in the potential wells of 29,631 dark matter halos with masses between 1012 and 1014 solar masses. We find that quenched satellite galaxies are relatively less frequent along the minor axis of their central galaxies. This observation might appear counterintuitive given that black hole activity is expected to eject mass and energy preferentially in the direction of the minor axis of the host galaxy. We show, however, that the observed anisotropic signal results precisely from the ejective nature of black hole feedback in massive halos, as outflows powered by active galactic nuclei clear out the circumgalactic medium, reducing the ram pressure and thus preserving star formation in satellite galaxies.