Mechanical objects have important practical applications in the fields of quantum information and metrology as quantum memories or transducers for measuring and connecting different types of quantum systems. The field of electromechanics is in pursuit of a robust and highly coherent device that couples motion to nonlinear quantum objects such as superconducting qubits. Here, we experimentally demonstrate a high-frequency bulk acoustic wave resonator that is strongly coupled to a superconducting qubit using piezoelectric transduction with a cooperativity of 260. We measure qubit and mechanical coherence times on the order of 10 microseconds. Our device requires only simple fabrication methods and provides controllable access to a multitude of phonon modes. We demonstrate quantum control and measurement on gigahertz phonons at the single-quantum level.

Nano- and micromechanical solid-state quantum devices have become a focus of attention. Reliably generating nonclassical states of their motion is of interest both for addressing fundamental questions about macroscopic quantum phenomena and for developing quantum technologies in the domains of sensing and transduction. We used quantum optical control techniques to conditionally generate single-phonon Fock states of a nanomechanical resonator. We performed a Hanbury Brown and Twiss–type experiment that verified the nonclassical nature of the phonon state without requiring full state reconstruction. Our result establishes purely optical quantum control of a mechanical oscillator at the single-phonon level.

Halogens are among the most electronegative elements, and the variations in size and polarizability of halogens require different descriptions of the intermolecular bonds they form. Here we use the inelastic tunneling probe (itProbe) to acquire real-space imaging of intermolecular-bonding structures in the two-dimensional self-assembly of halogenbenzene molecules on a metal surface. Direct visualization is obtained for the intermolecular attraction and the "windmill" pattern of bonding among the fully halogenated molecules. Our results provide a hitherto missing understanding of the nature of the halogen bond.

Technologies that use stretchable materials are increasingly important, yet we are unable to control how they stretch with much more sophistication than inflating balloons. Nature, however, demonstrates remarkable control of stretchable surfaces; for example, cephalopods can project hierarchical structures from their skin in milliseconds for a wide range of textural camouflage. Inspired by cephalopod muscular morphology, we developed synthetic tissue groupings that allowed programmable transformation of two-dimensional (2D) stretchable surfaces into target 3D shapes. The synthetic tissue groupings consisted of elastomeric membranes embedded with inextensible textile mesh that inflated to within 10% of their target shapes by using a simple fabrication method and modeling approach. These stretchable surfaces transform from flat sheets to 3D textures that imitate natural stone and plant shapes and camouflage into their background environments.

Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering of a cytochrome P450 enzyme by directed evolution to catalyze metal-oxo–mediated anti-Markovnikov oxidation of styrenes with high efficiency. The enzyme uses dioxygen as the terminal oxidant and achieves selectivity for anti-Markovnikov oxidation over the kinetically favored alkene epoxidation by trapping high-energy intermediates and catalyzing an oxo transfer, including an enantioselective 1,2-hydride migration. The anti-Markovnikov oxygenase can be combined with other catalysts in synthetic metabolic pathways to access a variety of challenging anti-Markovnikov functionalization reactions.

Bryostatin 1 is an exceedingly scarce marine-derived natural product that is in clinical development directed at HIV/AIDS eradication, cancer immunotherapy, and the treatment of Alzheimer’s disease. Despite this unique portfolio of indications, its availability has been limited and variable, thus impeding research and clinical studies. Here, we report a total synthesis of bryostatin 1 that proceeds in 29 total steps (19 in the longest linear sequence, >80% average yield per step), collectively produces grams of material, and can be scaled to meet clinical needs (~20 grams per year). This practical solution to the bryostatin supply problem also opens broad, facile, and efficient access to derivatives and potentially superior analogs.

The selective oxidation of methane, the primary component of natural gas, remains an important challenge in catalysis. We used colloidal gold-palladium nanoparticles, rather than the same nanoparticles supported on titanium oxide, to oxidize methane to methanol with high selectivity (92%) in aqueous solution at mild temperatures. Then, using isotopically labeled oxygen (O₂) as an oxidant in the presence of hydrogen peroxide (H₂O₂)_, we demonstrated that the resulting methanol incorporated a substantial fraction (70%) of gas-phase O₂. More oxygenated products were formed than the amount of H₂O₂ consumed, suggesting that the controlled breakdown of H₂O₂ activates methane, which subsequently incorporates molecular oxygen through a radical process. If a source of methyl radicals can be established, then the selective oxidation of methane to methanol using molecular oxygen is possible.

Little is known about the portion of the Milky Way lying beyond the Galactic center at distances of more than 9 kiloparsec from the Sun. These regions are opaque at optical wavelengths because of absorption by interstellar dust, and distances are very large and hard to measure. We report a direct trigonometric parallax distance of 20.4–2.2+2.8 kiloparsec obtained with the Very Long Baseline Array to a water maser source in a region of active star formation. These measurements allow us to shed light on Galactic spiral structure by locating the Scutum-Centaurus spiral arm as it passes through the far side of the Milky Way and to validate a kinematic method for determining distances in this region on the basis of transverse motions.

The carbon balance of tropical ecosystems remains uncertain, with top-down atmospheric studies suggesting an overall sink and bottom-up ecological approaches indicating a modest net source. Here we use 12 years (2003 to 2014) of MODIS pantropical satellite data to quantify net annual changes in the aboveground carbon density of tropical woody live vegetation, providing direct, measurement-based evidence that the world’s tropical forests are a net carbon source of 425.2 ± 92.0 teragrams of carbon per year (Tg C year^–1). This net release of carbon consists of losses of 861.7 ± 80.2 Tg C year^–1 and gains of 436.5 ± 31.0 Tg C year^–1. Gains result from forest growth; losses result from deforestation and from reductions in carbon density within standing forests (degradation or disturbance), with the latter accounting for 68.9% of overall losses.

Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology and could hold diagnostic and prognostic value. We developed a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR-Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed subcloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair–deficient colorectal cancers. Application of this strategy to the cancer predisposition gene NTHL1, which encodes a base excision repair protein, revealed a mutational footprint (signature 30) previously observed in a breast cancer cohort. We show that signature 30 can arise from germline NTHL1 mutations.

A substantial fraction of the proteome is intrinsically disordered, and even well-folded proteins adopt non-native geometries during synthesis, folding, transport, and turnover. Characterization of intrinsically disordered proteins (IDPs) is challenging, in part because of a lack of accurate physical models and the difficulty of interpreting experimental results. We have developed a general method to extract the dimensions and solvent quality (self-interactions) of IDPs from a single small-angle x-ray scattering measurement. We applied this procedure to a variety of IDPs and found that even IDPs with low net charge and high hydrophobicity remain highly expanded in water, contrary to the general expectation that protein-like sequences collapse in water. Our results suggest that the unfolded state of most foldable sequences is expanded; we conjecture that this property was selected by evolution to minimize misfolding and aggregation.

B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase.

The 2015–2016 El Niño led to historically high temperatures and low precipitation over the tropics, while the growth rate of atmospheric carbon dioxide (CO₂) was the largest on record. Here we quantify the response of tropical net biosphere exchange, gross primary production, biomass burning, and respiration to these climate anomalies by assimilating column CO₂, solar-induced chlorophyll fluorescence, and carbon monoxide observations from multiple satellites. Relative to the 2011 La Niña, the pantropical biosphere released 2.5 ± 0.34 gigatons more carbon into the atmosphere in 2015, consisting of approximately even contributions from three tropical continents but dominated by diverse carbon exchange processes. The heterogeneity of the carbon-exchange processes indicated here challenges previous studies that suggested that a single dominant process determines carbon cycle interannual variability.

NASA’s Orbiting Carbon Observatory-2 (OCO-2) mission was motivated by the need to diagnose how the increasing concentration of atmospheric carbon dioxide (CO₂) is altering the productivity of the biosphere and the uptake of CO₂ by the oceans. Launched on 2 July 2014, OCO-2 provides retrievals of the column-averaged CO₂ dry-air mole fraction (XCO2) as well as the fluorescence from chlorophyll in terrestrial plants. The seasonal pattern of uptake by the terrestrial biosphere is recorded in fluorescence and the drawdown of XCO2 during summer. Launched just before one of the most intense El Niños of the past century, OCO-2 measurements of XCO2 and fluorescence record the impact of the large change in ocean temperature and rainfall on uptake and release of CO₂ by the oceans and biosphere.

Quantifying gross primary production (GPP) remains a major challenge in global carbon cycle research. Spaceborne monitoring of solar-induced chlorophyll fluorescence (SIF), an integrative photosynthetic signal of molecular origin, can assist in terrestrial GPP monitoring. However, the extent to which SIF tracks spatiotemporal variations in GPP remains unresolved. Orbiting Carbon Observatory-2 (OCO-2)’s SIF data acquisition and fine spatial resolution permit direct validation against ground and airborne observations. Empirical orthogonal function analysis shows consistent spatiotemporal correspondence between OCO-2 SIF and GPP globally. A linear SIF-GPP relationship is also obtained at eddy-flux sites covering diverse biomes, setting the stage for future investigations of the robustness of such a relationship across more biomes. Our findings support the central importance of high-quality satellite SIF for studying terrestrial carbon cycle dynamics.

Spaceborne observations of carbon dioxide (CO₂) from the Orbiting Carbon Observatory-2 are used to characterize the response of tropical atmospheric CO₂ concentrations to the strong El Niño event of 2015–2016. Although correlations between the growth rate of atmospheric CO₂ concentrations and the El Niño–Southern Oscillation are well known, the magnitude of the correlation and the timing of the responses of oceanic and terrestrial carbon cycle remain poorly constrained in space and time. We used space-based CO₂ observations to confirm that the tropical Pacific Ocean does play an early and important role in modulating the changes in atmospheric CO₂ concentrations during El Niño events—a phenomenon inferred but not previously observed because of insufficient high-density, broad-scale CO₂ observations over the tropics.

Spaceborne measurements by NASA’s Orbiting Carbon Observatory-2 (OCO-2) at the kilometer scale reveal distinct structures of atmospheric carbon dioxide (CO₂) caused by known anthropogenic and natural point sources. OCO-2 transects across the Los Angeles megacity (USA) show that anthropogenic CO₂ enhancements peak over the urban core and decrease through suburban areas to rural background values more than ~100 kilometers away, varying seasonally from ~4.4 to 6.1 parts per million. A transect passing directly downwind of the persistent isolated natural CO₂ plume from Yasur volcano (Vanuatu) shows a narrow filament of enhanced CO₂ values (~3.4 parts per million), consistent with a CO₂ point source emitting 41.6 kilotons per day. These examples highlight the potential of the OCO-2 sensor, with its unprecedented resolution and sensitivity, to detect localized natural and anthropogenic CO₂ sources.

Sushkevich et al. (Reports, 5 May 2017, p. 523) report on the use of water to oxidize methane to methanol. This seems problematic because the reaction of CH₄ and water to generate methanol and H₂ is highly unfavorable at any temperature (G of reaction +28 kcal/mol at 200°C, equilibrium constant K 10^–13). Consequently, even if the reaction is separated into two steps, it seems inconceivable to carry out such a net reaction in a practical manner.

Periana argues that the stepwise reaction of methane with water is thermodynamically unfavorable and therefore impractical. We reply by presenting an in-depth thermodynamic analysis of each step in the process and show that the surface concentrations of the reactants and products as well as the stabilizing effect of additional water molecules, as discussed in the original paper, fully support the feasibility of the proposed reaction.

The immune system varies in cell types, states, and locations. The complex networks, interactions, and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity, and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as massively parallel single-cell RNA sequencing and sophisticated computational methods are catalyzing a revolution in our understanding of immunology. Here we provide an overview of the state of single-cell genomics methods and an outlook on the use of single-cell techniques to decipher the adaptive and innate components of immunity.

The stereotyped spatial architecture of the brain is both beautiful and fundamentally related to its function, extending from gross morphology to individual neuron types, where soma position, dendritic architecture, and axonal projections determine their roles in functional circuitry. Our understanding of the cell types that make up the brain is rapidly accelerating, driven in particular by recent advances in single-cell transcriptomics. However, understanding brain function, development, and disease will require linking molecular cell types to morphological, physiological, and behavioral correlates. Emerging spatially resolved transcriptomic methods promise to fill this gap by localizing molecularly defined cell types in tissues, with simultaneous detection of morphology, activity, or connectivity. Here, we review the requirements for spatial transcriptomic methods toward these goals, consider the challenges ahead, and describe promising applications.

Single-cell multi-omics has recently emerged as a powerful technology by which different layers of genomic output—and hence cell identity and function—can be recorded simultaneously. Integrating various components of the epigenome into multi-omics measurements allows for studying cellular heterogeneity at different time scales and for discovering new layers of molecular connectivity between the genome and its functional output. Measurements that are increasingly available range from those that identify transcription factor occupancy and initiation of transcription to long-lasting and heritable epigenetic marks such as DNA methylation. Together with techniques in which cell lineage is recorded, this multilayered information will provide insights into a cell’s past history and its future potential. This will allow new levels of understanding of cell fate decisions, identity, and function in normal development, physiology, and disease.

At the core of the "proton radius puzzle" is a four–standard deviation discrepancy between the proton root-mean-square charge radii (r_p) determined from the regular hydrogen (H) and the muonic hydrogen (µp) atoms. Using a cryogenic beam of H atoms, we measured the 2S-4P transition frequency in H, yielding the values of the Rydberg constant R = 10973731.568076(96) per meterand r_p = 0.8335(95) femtometer. Our r_p value is 3.3 combined standard deviations smaller than the previous H world data, but in good agreement with the µp value. We motivate an asymmetric fit function, which eliminates line shifts from quantum interference of neighboring atomic resonances.

The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.

Strontium optical lattice clocks have the potential to simultaneously interrogate millions of atoms with a high spectroscopic quality factor of 4 x 10¹⁷. Previously, atomic interactions have forced a compromise between clock stability, which benefits from a large number of atoms, and accuracy, which suffers from density-dependent frequency shifts. Here we demonstrate a scalable solution that takes advantage of the high, correlated density of a degenerate Fermi gas in a three-dimensional (3D) optical lattice to guard against on-site interaction shifts. We show that contact interactions are resolved so that their contribution to clock shifts is orders of magnitude lower than in previous experiments. A synchronous clock comparison between two regions of the 3D lattice yields a measurement precision of 5 x 10^–19 in 1 hour of averaging time.

A laser is based on the electromagnetic modes of its resonator, which provides the feedback required for oscillation. Enormous progress has been made toward controlling the interactions of longitudinal modes in lasers with a single transverse mode. For example, the field of ultrafast science has been built on lasers that lock many longitudinal modes together to form ultrashort light pulses. However, coherent superposition of longitudinal and transverse modes in a laser has received little attention. We show that modal and chromatic dispersions in fiber lasers can be counteracted by strong spatial and spectral filtering. This allows locking of multiple transverse and longitudinal modes to create ultrashort pulses with a variety of spatiotemporal profiles. Multimode fiber lasers thus open new directions in studies of nonlinear wave propagation and capabilities for applications.

The properties of materials change, sometimes catastrophically, as alloying elements and impurities accumulate preferentially at grain boundaries. Studies of bicrystals show that regular atomic patterns often arise as a result of this solute segregation at high-symmetry boundaries, but it is not known whether superstructures exist at general grain boundaries in polycrystals. In bismuth-doped polycrystalline nickel, we found that ordered, segregation-induced grain boundary superstructures occur at randomly selected general grain boundaries, and that these reconstructions are driven by the orientation of the terminating grain surfaces rather than by lattice matching between grains. This discovery shows that adsorbate-induced superstructures are not limited to special grain boundaries but may exist at a variety of general grain boundaries, and hence they can affect the performance of polycrystalline engineering alloys.

In a 26-year soil warming experiment in a mid-latitude hardwood forest, we documented changes in soil carbon cycling to investigate the potential consequences for the climate system. We found that soil warming results in a four-phase pattern of soil organic matter decay and carbon dioxide fluxes to the atmosphere, with phases of substantial soil carbon loss alternating with phases of no detectable loss. Several factors combine to affect the timing, magnitude, and thermal acclimation of soil carbon loss. These include depletion of microbially accessible carbon pools, reductions in microbial biomass, a shift in microbial carbon use efficiency, and changes in microbial community composition. Our results support projections of a long-term, self-reinforcing carbon feedback from mid-latitude forests to the climate system as the world warms.

Value information about a drug, such as the price tag, can strongly affect its therapeutic effect. We discovered that value information influences adverse treatment outcomes in humans even in the absence of an active substance. Labeling an inert treatment as expensive medication led to stronger nocebo hyperalgesia than labeling it as cheap medication. This effect was mediated by neural interactions between cortex, brainstem, and spinal cord. In particular, activity in the prefrontal cortex mediated the effect of value on nocebo hyperalgesia. Value furthermore modulated coupling between prefrontal areas, brainstem, and spinal cord, which might represent a flexible mechanism through which higher-cognitive representations, such as value, can modulate early pain processing.

Growing evidence for global pollinator decline is causing concern for biodiversity conservation and ecosystem services maintenance. Neonicotinoid pesticides have been identified or suspected as a key factor responsible for this decline. We assessed the global exposure of pollinators to neonicotinoids by analyzing 198 honey samples from across the world. We found at least one of five tested compounds (acetamiprid, clothianidin, imidacloprid, thiacloprid, and thiamethoxam) in 75% of all samples, 45% of samples contained two or more of these compounds, and 10% contained four or five. Our results confirm the exposure of bees to neonicotinoids in their food throughout the world. The coexistence of neonicotinoids and other pesticides may increase harm to pollinators. However, the concentrations detected are below the maximum residue level authorized for human consumption (average ± standard error for positive samples: 1.8 ± 0.56 nanograms per gram).