We consider a model for driven particulate matter in which absorbing states can be reached both by particle isolation and by particle caging. The model predicts a non-equilibrium phase diagram in which analogues of hydrodynamic and elastic reversibility emerge at low and high volume fractions respectively, partially separated by a diffusive, non-absorbing region. We thus find a single phase boundary that spans the onset of chaos in sheared suspensions to the onset of yielding in jammed packings. This boundary has the properties of a non-equilibrium second order phase transition, leading us to write a Manna-like mean-field description that captures the model predictions. Dependent on contact details, jamming marks either a direct transition between the two absorbing states, or occurs within the diffusive region.

Although the study of non-radiating anapoles has long been part of fundamental physics, the dynamic anapole at optical frequencies was only recently experimentally demonstrated in a specialized silicon nanodisk structure. We report excitation of the electrodynamic anapole mode in isotropic silicon nanospheres using radially polarized beam illumination. The superposition of equal and out-of-phase amplitudes of the Cartesian electric and toroidal dipoles produces by a pronounced dip in the scattering spectra with the scattering intensity almost reaching zero - a signature of anapole excitation. The total scattering intensity associated with the anapole excitation is found to be more than 25 times weaker for illumination with radially vs. linearly polarized beams. Our approach provides a simple, straightforward alternative path to realize electrodynamic anapole mode at the optical frequencies.

Perturbative corrections to General Relativity alter the expressions for both the entropy of black holes and their extremality bounds. We prove a universal relation between the leading corrections to these quantities. The derivation is purely thermodynamic and the result also applies beyond the realm of gravitational systems. In scenarios where the correction to the entropy is positive, our result proves that the perturbations decrease the mass of extremal black holes, when holding all other extensive variables fixed in the comparison. This implies that the extremality relations of a wide class of black holes display Weak Gravity Conjecture-like behavior.

We study the temperature dependence of the magnetic penetration depth in a 3D topological superconductor (TSC), incorporating the paramagnetic current due to the surface states. A TSC is predicted to host a gapless 2D surface Majorana fluid. In addition to the bulk-dominated London response, we identify a T3 power-law-in-temperature contribution from the surface, valid in the low-temperature limit. Our system is fully gapped in the bulk, and should be compared to bulk nodal superconductivity, which also exhibits power-law behavior. Power-law temperature dependence of the penetration depth can be one indicator of topological superconductivity.

A challenge in biology is to associate molecular differences among progenitor cells with their capacity to generate mature cell types. Here, we use expressed DNA barcodes to clonally trace transcriptomes over time and applied this to study fate determination in hematopoiesis. We identify states of primed fate potential and locate them on a continuous transcriptional landscape. We identify two routes of monocyte differentiation that leave an imprint on mature cells. Yet analysis of sister cells also reveals cells to have intrinsic fate biases not detectable by single-cell RNA sequencing. Finally, we benchmark computational methods of dynamic inference from single-cell snapshots, showing that fate choice occurs earlier than is detected by state-of the-art algorithms, and that cells progress steadily through pseudotime with precise and consistent dynamics.

The parity of the number of elementary excitations present in a quantum system provides important insights into its physical properties. Parity measurements are used, for example, to tomographically reconstruct quantum states or to determine if a decay of an excitation has occurred, information which can be used for quantum error correction in computation or communication protocols. Here we demonstrate a versatile parity detector for propagating microwaves, which distinguishes between radiation fields containing an even or odd number n of photons, both in a single-shot measurement and without perturbing the parity of the detected field. We showcase applications of the detector for direct Wigner tomography of propagating microwaves and heralded generation of Schr{"o}dinger cat states. This parity detection scheme is applicable over a broad frequency range and may prove useful, for example, for heralded or fault-tolerant quantum communication protocols.

Predicting the Bs0−B‾s0 width difference ΔΓs relies on the heavy quark expansion and on hadronic matrix elements of ΔB=2 operators. We present the first lattice QCD results for matrix elements of the dimension-7 operators R2,3 and linear combinations R̃2,3 using nonrelativistic QCD for the bottom quark and a highly improved staggered quark (HISQ) action for the strange quark. Computations use MILC ensembles of gauge field configuations with 2+1+1 flavors of sea quarks with the HISQ discretization, including lattices with physically light up/down quark masses. We discuss features unique to calculating matrix elements of these operators and analyze uncertainties from series truncation, discretization, and quark mass dependence. Finally we report the first Standard Model determination of ΔΓs using lattice QCD results for all hadronic matrix elements through 𝒪(1/mb). The main result of our calculations yields the 1/mb contribution ΔΓ1/mb=−0.022(10)ps−1. Adding this to the leading order contribution, the Standard Model prediction is ΔΓs=0.092(14)ps−1.

In 1935, in a paper~ entitled ``Can quantum-mechanical description of reality be considered complete?", Einstein, Podolsky, and Rosen (EPR) formulated an apparent paradox of quantum theory. They considered two quantum systems that were initially allowed to interact, and were then later separated. A measurement of a physical observable performed on one system then had to have an immediate effect on the conjugate observable in the other system – even if the systems were causally disconnected! The authors viewed this as a clear indication of the inconsistency of quantum mechanics. In the parton model~ of the nucleon formulated by Bjorken, Feynman, and Gribov, the partons (quarks and gluons) are viewed by an external hard probe as independent. The standard argument is that, inside the nucleon boosted to an infinite-momentum frame, the parton probed by a virtual photon with virtuality Q is causally disconnected from the rest of the nucleon during the hard interaction. Yet, the parton and the rest of the nucleon have to form a colour-singlet state due to colour confinement, and so have to be in strongly correlated quantum states – we thus encounter the EPR paradox at the sub-nucleonic scale. In this paper, we propose a resolution of this paradox based on the quantum entanglement of partons. We devise an experimental test of entanglement, and carry it out using data on proton-proton collisions from the Large Hadron Collider (LHC). Our results provide a strong direct indication of quantum entanglement at sub-nucleonic scales.

Three hidden-charm pentaquark Pc states, Pc(4312), Pc(4440) and Pc(4457) were revealed in the Λb0→J/ψpK− process measured by LHCb using both Run I and Run II data. Their nature is under lively discussion, and their quantum numbers have not been determined. We analyze the $\jp$ invariant mass distributions under the assumption that the crossed-channel effects provide a smooth background. For the first time, such an analysis is performed employing a coupled-channel formalism with the scattering potential involving both one-pion exchange as well as short-range operators constrained by heavy quark spin symmetry. We find that the data can be well described in the hadronic molecular picture, which predicts seven Σc(*)D‾(*) molecular states in two spin multiplets, such that the Pc(4312) is mainly a ΣcD‾ bound state with JP=1/2−, while Pc(4440) and Pc(4457) are ΣcD‾* bound states with quantum numbers 3/2− and 1/2−, respectively. We also show that there is evidence for a narrow Σc*D‾ bound state in the data which we call Pc(4380), different from the broad one reported by LHCb in 2015. With this state included, all predicted ΣcD‾, Σc*D‾, and ΣcD‾* hadronic molecules are seen in the data, while the missing three Σc*D‾* states are expected to be found in future runs of the LHC or in photoproduction experiments.

We study the phonon dynamics in lattices of optomechanical resonators where the mutually coupled photonic modes are coherently driven and the mechanical resonators are uncoupled and connected to independent thermal baths. We present a general procedure to obtain the effective Lindblad dynamics of the phononic modes for an arbitrary lattice geometry, where the light modes play the role of an effective reservoir that mediates the phonon nonequilibrium dynamics. We show how to stabilize stationary states exhibiting directional heat currents over arbitrary distance, despite the absence of thermal gradient and of direct coupling between the mechanical resonators.

The existence of ideal quantum measurements is one of the fundamental predictions of quantum mechanics. In theory, an ideal measurement projects a quantum state onto the eigenbasis of the measurement observable while preserving coherences between eigenstates which have the same eigenvalue. The question arises whether there are processes in nature that correspond to such ideal quantum measurements and how such processes are dynamically implemented in nature. Here we address this question and present experimental results monitoring the dynamics of a naturally occurring measurement process: the coupling of a trapped ion qutrit to the photon environment. By taking tomographic snapshots during the detection process, we show that the process develops in agreement with the model of an ideal quantum measurement with an average fidelity of 94% .

Among aspects of agricultural intensification that have been criticized for negative impacts on biodiversity (1, 2), pesticides have been linked to declines in insects, birds, and biodiversity in aquatic systems (3–5). If pesticide use is to blame, even partially, then this raises questions both about pesticide use and the regulatory procedures that are used to protect the environment (4). Environmental risk assessment (ERA) of pesticides does not account for many stressors that have intensified in recent years, such as climate change, habitat destruction, and increasing landscape homogeneity, the combination of which can aggravate effects of pesticides in nature. We describe how several assumptions underlying ERA may not hold in modern intensive agricultural landscapes, and the interaction among assumption violations may account for observed declines in biodiversity. Using European contexts to exemplify these global concerns, we review how regulatory ERA for pesticides has fallen out of step with scientific knowledge (4) and societal demands for sustainable food production and suggest systematic and recently feasible changes for regulation.

Scientists have long marveled at the ability of complex patterns to emerge from seemingly chaotic origins. In biology, each cell must circumvent the stochastic nature, or noise, inherent to chemical reactions and molecular diffusion. This noise introduces large fluctuations in messenger RNA (mRNA) and protein concentrations, which might be deleterious to processes such as biosynthesis, macroscale organization, and self-replication. Noise may be decreased through compartmentalization, including liquid-liquid phase separation (LLPS), a process underlying the formation of membraneless compartments (1, 2). On page 464 of this issue, Klosin et al. (3) provide evidence that LLPS can buffer noise in cells and may play a role in stabilizing various biological circuits.

Aging is a multifaceted process that results in organismal decay. At the cellular level, protein homeostasis is a key system that becomes dysregulated with age, causing the accumulation of aberrant or unfolded proteins. In a youthful individual, unfolded proteins normally trigger the unfolded protein response (UPR), which upregulates the protein clearance machinery and returns cells to a homeostatic state. The UPR is typically induced in a cell-autonomous manner. But some cells communicate protein folding stress to distal cells. For example, neurons communicate activation of the UPR to peripheral tissues to promote longevity in the worm Caenorhabditis elegans (1). On page 436 of this issue, Frakes et al. (2) show that support cells in the brain called glial cells (3) can also initiate long-range activation of the endoplasmic reticulum UPR (UPRER) in distal cells to coordinate stress resistance and longevity in C. elegans and that this occurs through neuropeptide secretion.

The ultimate goal of any nanotechnology is to resolve and control elementary processes in matter. In general, although many spectroscopies can achieve high temporal resolution and many microscopies can achieve high spatial resolution, achieving both is difficult. On page 411 of this issue, Garg and Kern (1) improve the limits of concomitant spatial and temporal resolutions by combining scanning tunneling microscopy (STM) (2) with an ingenious phase-locking train of ultrafast optical pulses. The authors go on to demonstrate that their instrument can deconvolve femtosecond electron dynamics with nanoscale resolution. These feats are only made more interesting because the phase-locking scheme enables an imprint of the laser's (coherent) phase onto the tunneling electrons. This demonstration of “light-wave electronics” at atomic scales is unprecedented.

Drawing from new sources and scholarship, historian David Marwell has written a compelling work that dispels many of the myths obscuring the identity of the infamous physician, Josef Mengele. Mengele: Unmasking the "Angel of Death" is at once a compact biography of the notorious war criminal, a detailed account of Mengele's flight to South America, and an absorbing narrative of the quest to bring him to justice.

Sexual Citizens is one of the products of a 5-year study of undergraduates at Columbia University called the Sexual Health Initiative to Foster Transformation (SHIFT). The goal of SHIFT was to identify the social causes of campus sexual assault in order to develop more effective prevention strategies. This mixed-methods project, involving nearly 30 researchers from multiple disciplines, included a population-based survey, a 60-day daily diary study, 17 focus groups, multihour interviews, and hundreds of hours of ethnographic field observation of students socializing in various settings.

Knowledge of the hazards and associated risks from chemicals discharged to the environment has grown considerably over the past 40 years. This improving awareness stems from advances in our ability to measure chemicals at low environmental concentrations, recognition of a range of effects on organisms, and a worldwide growth in expertise. Environmental scientists and companies have learned from the experiences of the past; in theory, the next generation of chemicals will cause less acute toxicity and be less environmentally persistent and bioaccumulative. However, researchers still struggle to establish whether the nonlethal effects associated with some modern chemicals and substances will have serious consequences for wildlife. Obtaining the resources to address issues associated with chemicals in the environment remains a challenge.

Chemicals have improved our quality of life, but the resulting environmental pollution has the potential to cause detrimental effects on humans and the environment. People and biota are chronically exposed to thousands of chemicals from various environmental sources through multiple pathways. Environmental chemists and toxicologists have moved beyond detecting and quantifying single chemicals to characterizing complex mixtures of chemicals in indoor and outdoor environments and biological matrices. We highlight analytical and bioanalytical approaches to isolating, characterizing, and tracking groups of chemicals of concern in complex matrices. Techniques that combine chemical analysis and bioassays have the potential to facilitate the identification of mixtures of chemicals that pose a combined risk.

Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The “exposome” concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.

The material basis of a sustainable society will depend on chemical products and processes that are designed following principles that make them conducive to life. Important inherent properties of molecules need to be considered from the earliest stage—the design stage—to address whether compounds and processes are depleting versus renewable, toxic versus benign, and persistent versus readily degradable. Products, feedstocks, and manufacturing processes will need to integrate the principles of green chemistry and green engineering under an expanded definition of performance that includes sustainability considerations. This transformation will require the best of the traditions of science and innovation coupled with new emerging systems thinking and systems design that begins at the molecular level and results in a positive impact on the global scale.

Single-cell RNA sequencing (scRNA-seq) is a powerful approach for reconstructing cellular differentiation trajectories. However, inferring both the state and direction of differentiation is challenging. Here, we demonstrate a simple, yet robust, determinant of developmental potential—the number of expressed genes per cell—and leverage this measure of transcriptional diversity to develop a computational framework (CytoTRACE) for predicting differentiation states from scRNA-seq data. When applied to diverse tissue types and organisms, CytoTRACE outperformed previous methods and nearly 19,000 annotated gene sets for resolving 52 experimentally determined developmental trajectories. Additionally, it facilitated the identification of quiescent stem cells and revealed genes that contribute to breast tumorigenesis. This study thus establishes a key RNA-based feature of developmental potential and a platform for delineation of cellular hierarchies.

Nanoelectronic devices operating in the quantum regime require coherent manipulation and control over electrons at atomic length and time scales. We demonstrate coherent control over electrons in a tunnel junction of a scanning tunneling microscope by means of precise tuning of the carrier-envelope phase of two-cycle long (<6-femtosecond) optical pulses. We explore photon and field-driven tunneling, two different regimes of interaction of optical pulses with the tunnel junction, and demonstrate a transition from one regime to the other. Our results show that it is possible to induce, track, and control electronic current at atomic scales with subfemtosecond resolution, providing a route to develop petahertz coherent nanoelectronics and microscopy.

Superluminous supernovae radiate up to 100 times more energy than normal supernovae. The origin of this energy and the nature of the stellar progenitors of these transients are poorly understood. We identify neutral iron lines in the spectrum of one such supernova, SN 2006gy, and show that they require a large mass of iron (≳0.3 solar masses) expanding at 1500 kilometers per second. By modeling a standard type Ia supernova hitting a shell of circumstellar material, we produce a light curve and late-time iron-dominated spectrum that match the observations of SN 2006gy. In such a scenario, common envelope evolution of a progenitor binary system can synchronize envelope ejection and supernova explosion and may explain these bright transients.

Integrating multiple materials in arbitrary arrangements within nanoparticles is a prerequisite for advancing many applications. Strategies to synthesize heterostructured nanoparticles are emerging, but they are limited in complexity, scope, and scalability. We introduce two design guidelines, based on interfacial reactivity and crystal structure relations, that enable the rational synthesis of a heterostructured nanorod megalibrary. We define synthetically feasible pathways to 65,520 distinct multicomponent metal sulfide nanorods having as many as 6 materials, 8 segments, and 11 internal interfaces by applying up to seven sequential cation-exchange reactions to copper sulfide nanorod precursors. We experimentally observe 113 individual heterostructured nanorods and demonstrate the scalable production of three samples. Previously unimaginable complexity in heterostructured nanorods is now routinely achievable with simple benchtop chemistry and standard laboratory glassware.

The recent development of hybrid systems based on superconducting circuits provides the possibility of engineering quantum sensors that exploit different degrees of freedom. Quantum magnonics, which aims to control and read out quanta of collective spin excitations in magnetically ordered systems, provides opportunities for advances in both the study of magnetism and the development of quantum technologies. Using a superconducting qubit as a quantum sensor, we report the detection of a single magnon in a millimeter-sized ferrimagnetic crystal with a quantum efficiency of up to 0.71. The detection is based on the entanglement between a magnetostatic mode and the qubit, followed by a single-shot measurement of the qubit state. This proof-of-principle experiment establishes the single-photon detector counterpart for magnonics.

Imaging a reaction taking place at the molecular level could provide direct information for understanding the catalytic reaction mechanism. We used in situ environmental transmission electron microscopy and a nanocrystalline anatase titanium dioxide (001) surface with (1 × 4) reconstruction as a catalyst, which provided highly ordered four-coordinated titanium “active rows” to realize real-time monitoring of water molecules dissociating and reacting on the catalyst surface. The twin-protrusion configuration of adsorbed water was observed. During the water–gas shift reaction, dynamic changes in these structures were visualized on these active rows at the molecular level.

The plant embryonic cuticle is a hydrophobic barrier deposited de novo by the embryo during seed development. At germination, it protects the seedling from water loss and is, thus, critical for survival. Embryonic cuticle formation is controlled by a signaling pathway involving the ABNORMAL LEAF SHAPE1 subtilase and the two GASSHO receptor-like kinases. We show that a sulfated peptide, TWISTED SEED1 (TWS1), acts as a GASSHO ligand. Cuticle surveillance depends on the action of the subtilase, which, unlike the TWS1 precursor and the GASSHO receptors, is not produced in the embryo but in the neighboring endosperm. Subtilase-mediated processing of the embryo-derived TWS1 precursor releases the active peptide, triggering GASSHO-dependent cuticle reinforcement in the embryo. Thus, a bidirectional molecular dialogue between embryo and endosperm safeguards cuticle integrity before germination.

The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRER transcription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in Caenorhabditis elegans. Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRER in distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRER and life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity.

The arousal state of the brain covaries with the motor state of the animal. How these state changes are coordinated remains unclear. We discovered that sleep–wake brain states and motor behaviors are coregulated by shared neurons in the substantia nigra pars reticulata (SNr). Analysis of mouse home-cage behavior identified four states with different levels of brain arousal and motor activity: locomotion, nonlocomotor movement, quiet wakefulness, and sleep; transitions occurred not randomly but primarily between neighboring states. The glutamic acid decarboxylase 2 but not the parvalbumin subset of SNr γ-aminobutyric acid (GABA)–releasing (GABAergic) neurons was preferentially active in states of low motor activity and arousal. Their activation or inactivation biased the direction of natural behavioral transitions and promoted or suppressed sleep, respectively. These GABAergic neurons integrate wide-ranging inputs and innervate multiple arousal-promoting and motor-control circuits through extensive collateral projections.

Chimeric antigen receptor (CAR)–T cells have shown efficacy in patients with B cell malignancies. Yet, their application for solid tumors has challenges that include limited cancer-specific targets and nonpersistence of adoptively transferred CAR-T cells. Here, we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident antigen-presenting cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at subtherapeutic CAR-T cell doses.

Tissue morphogenesis is driven by local cellular deformations that are powered by contractile actomyosin networks. How localized forces are transmitted across tissues to shape them at a mesoscopic scale is still unclear. Analyzing gastrulation in entire avian embryos, we show that it is driven by the graded contraction of a large-scale supracellular actomyosin ring at the margin between the embryonic and extraembryonic territories. The propagation of these forces is enabled by a fluid-like response of the epithelial embryonic disk, which depends on cell division. A simple model of fluid motion entrained by a tensile ring quantitatively captures the vortex-like “polonaise” movements that accompany the formation of the primitive streak. The geometry of the early embryo thus arises from the transmission of active forces generated along its boundary.

Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers—shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions—form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonidentical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguous shapes. Using total synthesis, we found that the peptidic alkaloid tryptorubin A can be one of two noncanonical atropisomers. We then devised a synthetic strategy that drives the atropospecific synthesis of a noncanonical atrop-defined small molecule.

Expression of proteins inside cells is noisy, causing variability in protein concentration among identical cells. A central problem in cellular control is how cells cope with this inherent noise. Compartmentalization of proteins through phase separation has been suggested as a potential mechanism to reduce noise, but systematic studies to support this idea have been missing. In this study, we used a physical model that links noise in protein concentration to theory of phase separation to show that liquid droplets can effectively reduce noise. We provide experimental support for noise reduction by phase separation using engineered proteins that form liquid-like compartments in mammalian cells. Thus, phase separation can play an important role in biological signal processing and control.

Forebrain development is characterized by highly synchronized cellular processes, which, if perturbed, can cause disease. To chart the regulatory activity underlying these events, we generated a map of accessible chromatin in human three-dimensional forebrain organoids. To capture corticogenesis, we sampled glial and neuronal lineages from dorsal or ventral forebrain organoids over 20 months in vitro. Active chromatin regions identified in human primary brain tissue were observed in organoids at different developmental stages. We used this resource to map genetic risk for disease and to explore evolutionary conservation. Moreover, we integrated chromatin accessibility with transcriptomics to identify putative enhancer-gene linkages and transcription factors that regulate human corticogenesis. Overall, this platform brings insights into gene-regulatory dynamics at previously inaccessible stages of human forebrain development, including signatures of neuropsychiatric disorders.

In a magnetic topological insulator, nontrivial band topology conspires with magnetic order to produce exotic states of matter such as quantum anomalous Hall (QAH) insulators and axion insulators. Here, we probe quantum transport in MnBi2Te4 thin flake—a topological insulator with intrinsic magnetic order. In this layered van der Waals crystal, the ferromagnetic layers couple anti-parallel to each other; atomically thin MnBi2Te4, however, becomes ferromagnetic when the sample has an odd number of septuple layers. We observe zero-field QAH effect in a five-septuple-layer specimen at 1.4 Kelvin; an external magnetic field further raises the quantization temperature up to 6.5 Kelvin by aligning all layers ferromagnetically. The results establish MnBi2Te4 as an ideal arena for further exploring various topological phenomena with a spontaneously broken time-reversal symmetry.