Engineering controllable, strongly interacting many-body quantum systems is at the frontier of quantum simulation and quantum information processing. Arrays of laser-cooled neutral atoms in optical ...tweezers have emerged as a promising platform because of their flexibility and the potential for strong interactions via Rydberg states. Existing neutral atom array experiments utilize alkali atoms, but alkaline-earth atoms offer many advantages in terms of coherence and control, and also open the door to new applications in precision measurement and time keeping. In this Letter, we present a technique to trap individual alkaline-earth-like ytterbium (Yb) atoms in optical tweezer arrays. The narrow ^{1}S_{0}-^{3}P_{1} intercombination line is used for both cooling and imaging in a magic-wavelength optical tweezer at 532 nm. The low Doppler temperature allows for imaging near the saturation intensity, resulting in a very high atom detection fidelity. We demonstrate the imaging fidelity concretely by observing rare (<1 in 10^{4} images) spontaneous quantum jumps into and out of a metastable state. We also demonstrate stochastic loading of atoms into a two-dimensional, 144-site tweezer array. This platform will enable advances in quantum information processing, quantum simulation, and precision measurement. The demonstrated narrow-line Doppler imaging may also be applied in tweezer arrays or quantum gas microscopes using other atoms with similar transitions, such as erbium and dysprosium.
Neutral atom qubits with Rydberg-mediated interactions are a leading platform for developing large-scale coherent quantum systems. In the majority of experiments to date, the Rydberg states are not ...trapped by the same potential that confines ground state atoms, resulting in atom loss and constraints on the achievable interaction time. In this Letter, we demonstrate that the Rydberg states of an alkaline earth atom, ytterbium, can be stably trapped by the same red-detuned optical tweezer that also confines the ground state, by leveraging the polarizability of the Yb^{+} ion core. Using the previously unobserved ^{3}S_{1} series, we demonstrate trapped Rydberg atom lifetimes exceeding 100 μs, and observe no evidence of auto- or photoionization from the trap light for these states. We measure a coherence time of T_{2}=59 μs between two Rydberg levels, exceeding the 28 μs lifetime of untrapped Rydberg atoms under the same conditions. These results are promising for extending the interaction time of Rydberg atom arrays for quantum simulation and computing, and are vital to capitalize on the extended Rydberg lifetimes in circular states or cryogenic environments.
Elastic strain engineering for ultralow mechanical dissipation Ghadimi, A H; Fedorov, S A; Engelsen, N J ...
Science (American Association for the Advancement of Science),
2018-May-18, 2018-05-18, 20180518, Letnik:
360, Številka:
6390
Journal Article
Recenzirano
Extreme stresses can be produced in nanoscale structures; this feature has been used to realize enhanced materials properties, such as the high mobility of silicon in modern transistors. We show how ...nanoscale stress can be used to realize exceptionally low mechanical dissipation when combined with "soft-clamping"-a form of phononic engineering. Specifically, using a nonuniform phononic crystal pattern, we colocalize the strain and flexural motion of a free-standing silicon nitride nanobeam. Ringdown measurements at room temperature reveal string-like vibrational modes with quality (
) factors as high as 800 million and
× frequency exceeding 10
hertz. These results illustrate a promising route for engineering ultracoherent nanomechanical devices.
Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of ...the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver. We identify a scar-associated TREM2
CD9
subpopulation of macrophages, which expands in liver fibrosis, differentiates from circulating monocytes and is pro-fibrogenic. We also define ACKR1
and PLVAP
endothelial cells that expand in cirrhosis, are topographically restricted to the fibrotic niche and enhance the transmigration of leucocytes. Multi-lineage modelling of ligand and receptor interactions between the scar-associated macrophages, endothelial cells and PDGFRα
collagen-producing mesenchymal cells reveals intra-scar activity of several pro-fibrogenic pathways including TNFRSF12A, PDGFR and NOTCH signalling. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides a conceptual framework for the discovery of rational therapeutic targets in liver cirrhosis.
In real-time quantum feedback protocols, the record of a continuous measurement is used to stabilize a desired quantum state. Recent years have seen successful applications of these protocols in a ...variety of well-isolated micro-systems, including microwave photons and superconducting qubits. However, stabilizing the quantum state of a tangibly massive object, such as a mechanical oscillator, remains very challenging: the main obstacle is environmental decoherence, which places stringent requirements on the timescale in which the state must be measured. Here we describe a position sensor that is capable of resolving the zero-point motion of a solid-state, 4.3-megahertz nanomechanical oscillator in the timescale of its thermal decoherence, a basic requirement for real-time (Markovian) quantum feedback control tasks, such as ground-state preparation. The sensor is based on evanescent optomechanical coupling to a high-Q microcavity, and achieves an imprecision four orders of magnitude below that at the standard quantum limit for a weak continuous position measurement--a 100-fold improvement over previous reports--while maintaining an imprecision-back-action product that is within a factor of five of the Heisenberg uncertainty limit. As a demonstration of its utility, we use the measurement as an error signal with which to feedback cool the oscillator. Using radiation pressure as an actuator, the oscillator is cold damped with high efficiency: from a cryogenic-bath temperature of 4.4 kelvin to an effective value of 1.1 ± 0.1 millikelvin, corresponding to a mean phonon number of 5.3 ± 0.6 (that is, a ground-state probability of 16 per cent). Our results set a new benchmark for the performance of a linear position sensor, and signal the emergence of mechanical oscillators as practical subjects for measurement-based quantum control.
Elemental compositions of organic aerosol (OA) particles provide useful constraints on OA sources, chemical evolution, and effects. The Aerodyne high-resolution time-of-flight aerosol mass ...spectrometer (HR-ToF-AMS) is widely used to measure OA elemental composition. This study evaluates AMS measurements of atomic oxygen-to-carbon (O : C), hydrogen-to-carbon (H : C), and organic mass-to-organic carbon (OM : OC) ratios, and of carbon oxidation state (OS C) for a vastly expanded laboratory data set of multifunctional oxidized OA standards. For the expanded standard data set, the method introduced by Aiken et al. (2008), which uses experimentally measured ion intensities at all ions to determine elemental ratios (referred to here as "Aiken-Explicit"), reproduces known O : C and H : C ratio values within 20% (average absolute value of relative errors) and 12%, respectively. The more commonly used method, which uses empirically estimated H2O+ and CO+ ion intensities to avoid gas phase air interferences at these ions (referred to here as "Aiken-Ambient"), reproduces O : C and H : C of multifunctional oxidized species within 28 and 14% of known values. The values from the latter method are systematically biased low, however, with larger biases observed for alcohols and simple diacids. A detailed examination of the H2O+, CO+, and CO2+ fragments in the high-resolution mass spectra of the standard compounds indicates that the Aiken-Ambient method underestimates the CO+ and especially H2O+ produced from many oxidized species. Combined AMS-vacuum ultraviolet (VUV) ionization measurements indicate that these ions are produced by dehydration and decarboxylation on the AMS vaporizer (usually operated at 600 degree C). Thermal decomposition is observed to be efficient at vaporizer temperatures down to 200 degree C. These results are used together to develop an "Improved-Ambient" elemental analysis method for AMS spectra measured in air. The Improved-Ambient method uses specific ion fragments as markers to correct for molecular functionality-dependent systematic biases and reproduces known O : C (H : C) ratios of individual oxidized standards within 28% (13%) of the known molecular values. The error in Improved-Ambient O : C (H : C) values is smaller for theoretical standard mixtures of the oxidized organic standards, which are more representative of the complex mix of species present in ambient OA. For ambient OA, the Improved-Ambient method produces O : C (H : C) values that are 27% (11%) larger than previously published Aiken-Ambient values; a corresponding increase of 9% is observed for OM : OC values. These results imply that ambient OA has a higher relative oxygen content than previously estimated. The OS C values calculated for ambient OA by the two methods agree well, however (average relative difference of 0.06 OS C units). This indicates that OS C is a more robust metric of oxidation than O : C, likely since OS C is not affected by hydration or dehydration, either in the atmosphere or during analysis.
Recent studies suggest that most cases of myelodysplastic syndrome (MDS) are clonally heterogeneous, with a founding clone and multiple subclones. It is not known whether specific gene mutations ...typically occur in founding clones or subclones. We screened a panel of 94 candidate genes in a cohort of 157 patients with MDS or secondary acute myeloid leukemia (sAML). This included 150 cases with samples obtained at MDS diagnosis and 15 cases with samples obtained at sAML transformation (8 were also analyzed at the MDS stage). We performed whole-genome sequencing (WGS) to define the clonal architecture in eight sAML genomes and identified the range of variant allele frequencies (VAFs) for founding clone mutations. At least one mutation or cytogenetic abnormality was detected in 83% of the 150 MDS patients and 17 genes were significantly mutated (false discovery rate ≤0.05). Individual genes and patient samples displayed a wide range of VAFs for recurrently mutated genes, indicating that no single gene is exclusively mutated in the founding clone. The VAFs of recurrently mutated genes did not fully recapitulate the clonal architecture defined by WGS, suggesting that comprehensive sequencing may be required to accurately assess the clonal status of recurrently mutated genes in MDS.
Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that ...inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.
Alterations in DNA methylation have been implicated in the pathogenesis of myelodysplastic syndromes (MDS), although the underlying mechanism remains largely unknown. Methylation of CpG dinucleotides ...is mediated by DNA methyltransferases, including DNMT1, DNMT3A and DNMT3B. DNMT3A mutations have recently been reported in patients with de novo acute myeloid leukemia (AML), providing a rationale for examining the status of DNMT3A in MDS samples. In this study, we report the frequency of DNMT3A mutations in patients with de novo MDS, and their association with secondary AML. We sequenced all coding exons of DNMT3A using DNA from bone marrow and paired normal cells from 150 patients with MDS and identified 13 heterozygous mutations with predicted translational consequences in 12/150 patients (8.0%). Amino acid R882, located in the methyltransferase domain of DNMT3A, was the most common mutation site, accounting for 4/13 mutations. DNMT3A mutations were expressed in the majority of cells in all tested mutant samples regardless of myeloblast counts, suggesting that DNMT3A mutations occur early in the course of MDS. Patients with DNMT3A mutations had worse overall survival compared with patients without DNMT3A mutations (P=0.005) and more rapid progression to AML (P=0.007), suggesting that DNMT3A mutation status may have prognostic value in de novo MDS.
When an optical field is reflected from a compliant mirror, its intensity and phase become quantum-correlated due to radiation pressure. These correlations form a valuable resource: the mirror may be ...viewed as an effective Kerr medium generating squeezed states of light, or the correlations may be used to erase backaction from an interferometric measurement of the mirror’s position. To date, optomechanical quantum correlations have been observed in only a handful of cryogenic experiments, owing to the challenge of distilling them from thermomechanical noise. Accessing them at room temperature, however, would significantly extend their practical impact, with applications ranging from gravitational wave detection to chip-scale accelerometry. Here, we observe broadband quantum correlations developed in an optical field due to its interaction with a room-temperature nanomechanical oscillator, taking advantage of its high-cooperativity near-field coupling to an optical microcavity. The correlations manifest as a reduction in the fluctuations of a rotated quadrature of the field, in a frequency window spanning more than an octave below mechanical resonance. This is due to coherent cancellation of the two sources of quantum noise contaminating the measured quadrature—backaction and imprecision. Supplanting the backaction force with an off-resonant test force, we demonstrate the working principle behind a quantum-enhanced “variational” force measurement.