An optical tweezer array of ultracold polyatomic molecules.

Polyatomic molecules have rich structural features that make them uniquely suited to applications in quantum information science1-3, quantum simulation4-6, ultracold chemistry7 and searches for physics beyond the standard model8-10. However, a key challenge is fully controlling both the internal quantum state and the motional degrees of freedom of the molecules. Here we demonstrate the creation of an optical tweezer array of individual polyatomic molecules, CaOH, with quantum control of their internal quantum state. The complex quantum structure of CaOH results in a non-trivial dependence of the molecules' behaviour on the tweezer light wavelength. We control this interaction and directly and non-destructively image individual molecules in the tweezer array with a fidelity greater than 90%. The molecules are manipulated at the single internal quantum state level, thus demonstrating coherent state control in a tweezer array. The platform demonstrated here will enable a variety of experiments using individual polyatomic molecules with arbitrary spatial arrangement.

Magneto-optical trapping and sub-Doppler cooling of a polyatomic molecule.

Laser cooling and trapping1,2, and magneto-optical trapping methods in particular2, have enabled groundbreaking advances in science, including Bose-Einstein condensation3-5, quantum computation with neutral atoms6,7 and high-precision optical clocks8. Recently, magneto-optical traps (MOTs) of diatomic molecules have been demonstrated9-12, providing access to research in quantum simulation13 and searches for physics beyond the standard model14. Compared with diatomic molecules, polyatomic molecules have distinct rotational and vibrational degrees of freedom that promise a variety of transformational possibilities. For example, ultracold polyatomic molecules would be uniquely suited to applications in quantum computation and simulation15-17, ultracold collisions18, quantum chemistry19 and beyond-the-standard-model searches20,21. However, the complexity of these molecules has so far precluded the realization of MOTs for polyatomic species. Here we demonstrate magneto-optical trapping of a polyatomic molecule, calcium monohydroxide (CaOH). After trapping, the molecules are laser cooled in a blue-detuned optical molasses to a temperature of 110 µK, which is below the Doppler cooling limit. The temperatures and densities achieved here make CaOH a viable candidate for a wide variety of quantum science applications, including quantum simulation and computation using optical tweezer arrays15,17,22,23. This work also suggests that laser cooling and magneto-optical trapping of many other polyatomic species24-27 will be both feasible and practical.

Internal feedback in the cortical perception-action loop enables fast and accurate behavior.

Animals move smoothly and reliably in unpredictable environments. Models of sensorimotor control, drawing on control theory, have assumed that sensory information from the environment leads to actions, which then act back on the environment, creating a single, unidirectional perception-action loop. However, the sensorimotor loop contains internal delays in sensory and motor pathways, which can lead to unstable control. We show here that these delays can be compensated by internal feedback signals that flow backward, from motor toward sensory areas. This internal feedback is ubiquitous in neural sensorimotor systems, and we show how internal feedback compensates internal delays. This is accomplished by filtering out self-generated and other predictable changes so that unpredicted, actionable information can be rapidly transmitted toward action by the fastest components, effectively compressing the sensory input to more efficiently use feedforward pathways: Tracts of fast, giant neurons necessarily convey less accurate signals than tracts with many smaller neurons, but they are crucial for fast and accurate behavior. We use a mathematically tractable control model to show that internal feedback has an indispensable role in achieving state estimation, localization of function (how different parts of the cortex control different parts of the body), and attention, all of which are crucial for effective sensorimotor control. This control model can explain anatomical, physiological, and behavioral observations, including motor signals in the visual cortex, heterogeneous kinetics of sensory receptors, and the presence of giant cells in the cortex of humans as well as internal feedback patterns and unexplained heterogeneity in neural systems.

Diversity-enabled sweet spots in layered architectures and speed-accuracy trade-offs in sensorimotor control.

Nervous systems sense, communicate, compute, and actuate movement using distributed components with severe trade-offs in speed, accuracy, sparsity, noise, and saturation. Nevertheless, brains achieve remarkably fast, accurate, and robust control performance due to a highly effective layered control architecture. Here, we introduce a driving task to study how a mountain biker mitigates the immediate disturbance of trail bumps and responds to changes in trail direction. We manipulated the time delays and accuracy of the control input from the wheel as a surrogate for manipulating the characteristics of neurons in the control loop. The observed speed-accuracy trade-offs motivated a theoretical framework consisting of two layers of control loops-a fast, but inaccurate, reflexive layer that corrects for bumps and a slow, but accurate, planning layer that computes the trajectory to follow-each with components having diverse speeds and accuracies within each physical level, such as nerve bundles containing axons with a wide range of sizes. Our model explains why the errors from two control loops are additive and shows how the errors in each control loop can be decomposed into the errors caused by the limited speeds and accuracies of the components. These results demonstrate that an appropriate diversity in the properties of neurons across layers helps to create "diversity-enabled sweet spots," so that both fast and accurate control is achieved using slow or inaccurate components.

Comparison of circulating and excreted metals and of autoimmunity between two Great Plains Tribal communities.

Metals contaminants of the environment from mine waste have been implicated as contributing agents in autoimmune disease. The current study compares metals and autoimmunity in two Tribal communities residing in the Black Hills and the Bighorn Mountains geographical regions that are scattered with extant hard rock mines. With documented drinking water contamination in both communities, in vivo levels of more than half of the measured serum and urine metals differed between the two communities and were substantially different from their national median values. Serum autoantibodies associated with systemic autoimmune disease were rare or at low-level, but antibodies to denatured (single-stranded) DNA and thyroid-specific autoantibodies were commonly elevated, especially in women. A three-tier statistical modeling process was carried out to examine individual metals exposure as predictors of autoantibody levels. For the most part only weak positive associations between individual metals and systemic autoantibodies were found, although univariate quantile regression analysis showed positive statistical associations of serum lead and antimony with anti-chromatin and anti-histone autoantibodies. Using age and gender-adjusted multivariable statistical models, metals did not predict anti-thyroglobulin or -thyroid peroxidase significantly and metals were generally negative predictors of the other autoantibodies. Overall these results suggest that elevated levels of environmental metals and metalloids in these communities may result in suppression of autoantibodies associated with systemic autoimmune disease.

High-sensitivity low-noise photodetector using a large-area silicon photomultiplier.

The application of silicon photomultiplier (SiPM) technology for weak-light detection at a single photon level has expanded thanks to its better photon detection efficiency in comparison to a conventional photomultiplier tube (PMT). SiPMs with large detection area have recently become commercially available, enabling applications where the photon flux is low both temporarily and spatially. On the other hand, several drawbacks exist in the usage of SiPMs such as a higher dark count rate, many readout channels, slow response time, and optical crosstalk; therefore, users need to carefully consider the trade-offs. This work presents a SiPM-embedded compact large-area photon detection module. Various techniques are adopted to overcome the disadvantages of SiPMs so that it can be generally utilized as an upgrade from a PMT. A simple cooling component and recently developed optical crosstalk suppression method are adopted to reduce the noise which is more serious for larger-area SiPMs. A dedicated readout circuit increases the response frequency and reduces the number of readout channels. We favorably compare this design with a conventional PMT and obtain both higher photon detection efficiency and larger-area acceptance.

Optical Trapping of a Polyatomic Molecule in an ℓ-Type Parity Doublet State.

We report optical trapping of a polyatomic molecule, calcium monohydroxide (CaOH). CaOH molecules from a magneto-optical trap are sub-Doppler laser cooled to 20(3) µK in free space and loaded into an optical dipole trap. We attain an in-trap molecule number density of 3(1)×10^{9} cm^{-3} at a temperature of 57(8) µK. Trapped CaOH molecules are optically pumped into an excited vibrational bending mode, whose ℓ-type parity doublet structure is a potential resource for a wide range of proposed quantum science applications with polyatomic molecules. We measure the spontaneous, radiative lifetime of this bending mode state to be ∼0.7 s.

The Structural and Functional Correlates of Frailty in Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with HIV (PWH) are at increased risk of frailty, a clinically recognizable state of increased vulnerability resulting from aging-associated decline in multiple physiologic systems. Frailty is often defined by the Fried criteria, which includes subjective and objective standards concerning health resiliency. However, these frailty metrics do not incorporate cognitive performance or neuroimaging measures. METHODS: We compared structural (diffusion tensor imaging [DTI]) and functional (cerebral blood flow [CBF]) neuroimaging markers in PWH with frailty and cognitive performance. Virologically controlled PWH were dichotomized as either frail (≥3) or nonfrail (<3) using the Fried criteria. Cognitive Z-scores, both domain (executive, psychomotor speed, language, and memory) and global, were derived from a battery of tests. We identified three regions of reduced CBF, based on a voxel-wise comparison of frail PWH compared with nonfrail PWH. These clusters (bilateral frontal and posterior cingulate) were subsequently used as seed regions of interest (ROIs) for DTI probabilistic white matter tractography. RESULTS: White matter integrity connecting the ROIs was significantly decreased in frail compared with nonfrail PWH. No differences in cognition were observed between frail and nonfrail PWH. However, reductions in white matter integrity among these ROIs was significantly associated with worse psychomotor speed and executive function across the entire cohort. CONCLUSIONS: We conclude that frailty in PWH can lead to structural and functional brain changes, including subtle changes that are not detectable by standard neuropsychological tests. Multimodal neuroimaging in conjunction with frailty assessment could identify pathological brain changes observed in PWH.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

Body mass index and additional risk factors for cancer in adults with cystic fibrosis.

BACKGROUND: Adults with cystic fibrosis (CF) have an increased risk of a variety of cancers, notably gastrointestinal cancers. In CF higher body mass index (BMI) is associated with improved long-term outcomes, yet in the general population high BMI is associated with increased cancer risk. We aimed to delineate associations between BMI and other factors with cancer risk in adults with CF. METHODS: This was a retrospective cohort study using CF Foundation Patient Registry data from 1992 to 2015. Data were collected on age, sex, CFTR mutation class, pancreatic insufficiency, and annualized data on BMI and FEV1. The primary analysis was the association between BMI and cancer, with secondary analyses focused on BMI trajectory. Multivariable logistic regression was performed, with analyses stratified by history of transplant. RESULTS: Of 26,199 adults with CF, 446 (1.7%) had cancer diagnosed by histology at a mean age of 40.0 years (SD 12.2), with a higher proportion of transplanted patients developing cancer (137 (3.8%) v 309(1.4%), p < 0.001). Among non-transplanted patients, there was no association between BMI and cancer (p for trend = 0.43). Pancreatic insufficiency (p < 0.01) and higher FEV1 (p < 0.01) were associated with increased cancer risk. In transplanted patients, higher BMI was associated with reduced risk of cancer (p for trend = 0.04). Older age was associated with increased risk in both groups (p < 0.001). BMI trajectories were not associated with cancer risk in either group. CONCLUSION: Higher BMI is associated with a reduced risk of cancer in transplanted adults with CF. Pancreatic insufficiency is a risk factor for cancer in non-transplanted CF patients.

Tunable VUV frequency comb for 229mTh nuclear spectroscopy.

Laser spectroscopy of the 229mTh nuclear clock transition is necessary for the future construction of a nuclear-based optical clock. Precision laser sources with broad spectral coverage in the vacuum ultraviolet are needed for this task. Here, we present a tunable vacuum-ultraviolet frequency comb based on cavity-enhanced seventh-harmonic generation. Its tunable spectrum covers the current uncertainty range of the 229mTh nuclear clock transition.

Continuous probing of cold complex molecules with infrared frequency comb spectroscopy.

For more than half a century, high-resolution infrared spectroscopy has played a crucial role in probing molecular structure and dynamics. Such studies have so far been largely restricted to relatively small and simple systems, because at room temperature even molecules of modest size already occupy many millions of rotational/vibrational states, yielding highly congested spectra that are difficult to assign. Targeting more complex molecules requires methods that can record broadband infrared spectra (that is, spanning multiple vibrational bands) with both high resolution and high sensitivity. However, infrared spectroscopic techniques have hitherto been limited either by narrow bandwidth and long acquisition time, or by low sensitivity and resolution. Cavity-enhanced direct frequency comb spectroscopy (CE-DFCS) combines the inherent broad bandwidth and high resolution of an optical frequency comb with the high detection sensitivity provided by a high-finesse enhancement cavity, but it still suffers from spectral congestion. Here we show that this problem can be overcome by using buffer gas cooling to produce continuous, cold samples of molecules that are then subjected to CE-DFCS. This integration allows us to acquire a rotationally resolved direct absorption spectrum in the C-H stretching region of nitromethane, a model system that challenges our understanding of large-amplitude vibrational motion. We have also used this technique on several large organic molecules that are of fundamental spectroscopic and astrochemical relevance, including naphthalene, adamantane and hexamethylenetetramine. These findings establish the value of our approach for studying much larger and more complex molecules than have been probed so far, enabling complex molecules and their kinetics to be studied with orders-of-magnitude improvements in efficiency, spectral resolution and specificity.

Prevalence of Adenomas on Surveillance Colonoscopies for Patients with a History of Colonic Polyps of Unknown Histology.

BACKGROUND: Guidelines for surveillance colonoscopy depend on polyp histology. When patients present to a new healthcare system and report a personal history of "colon polyps," however, information on polyp histology is frequently unavailable. AIMS: To assess adenoma prevalence in patients with a history of colonic polyps of unknown histology and to compare it to patients undergoing either screening colonoscopy or surveillance colonoscopy for known adenomatous polyps. METHODS: This cohort study evaluated colonoscopies of patients ≥ 50 years of age over a 14-year period at a single institution. The exposure of interest was colonoscopy indication, categorized into three groups: screening colonoscopy, surveillance colonoscopy for history of colonic polyp(s) of unknown histology, and surveillance colonoscopy for history of adenoma(s). The primary outcome was adenoma detection rate. Multivariable logistic regression was used to assess the association between colonoscopy indication and adenoma detection rate. RESULTS: Of 31,856 colonoscopies, the adenoma prevalence was 26.1% for patients undergoing screening colonoscopy, 32.9% for patients with a history of polyps of unknown histology, and 41.9% for patients with a history of known adenomatous polyps. Relative to screening colonoscopies, there were higher odds of adenoma detection in surveillance colonoscopies for polyps of unknown histology (aOR compared to screening 1.42, 95% CI 1.30-1.55) and even higher odds among surveillance colonoscopies for a history of adenoma (aOR compared to screening 1.89, 95% CI 1.75-2.05). CONCLUSION: The adenoma prevalence on surveillance colonoscopy for patients with polyps of unknown histology was higher than that of screening colonoscopies but lower than that of surveillance colonoscopies for patients with adenomatous polyps.

Collateral damage: Impact of SARS-CoV-2 pandemic in people living with HIV.

People living with HIV (PLWH) may be at higher risk for adverse outcomes indirectly associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2). When comparing responses to questionnaires administered when social distancing and quarantine guidelines were first implemented, we found that PLWH were more likely to have restricted access to medical care, increased financial stress, increased symptoms of anxiety and depression, and increased substance use compared to demographically-similar people without HIV.

Suppression of the optical crosstalk in a multi-channel silicon photomultiplier array.

We propose and study a method of optical crosstalk suppression for silicon photomultipliers (SiPMs) using optical filters. We demonstrate that attaching absorptive visible bandpass filters to the SiPM can substantially reduce the optical crosstalk. Measurements suggest that the absorption of near infrared light is important to achieve this suppression. The proposed technique can be easily applied to suppress the optical crosstalk in SiPMs in cases where filtering near infrared light is compatible with the application.

Rotational Coherence Times of Polar Molecules in Optical Tweezers.

Qubit coherence times are critical to the performance of any robust quantum computing platform. For quantum information processing using arrays of polar molecules, a key performance parameter is the molecular rotational coherence time. We report a 93(7) ms coherence time for rotational state qubits of laser cooled CaF molecules in optical tweezer traps, over an order of magnitude longer than previous systems. Inhomogeneous broadening due to the differential polarizability between the qubit states is suppressed by tuning the tweezer polarization and applied magnetic field to a "magic" angle. The coherence time is limited by the residual differential polarizability, implying improvement with further cooling. A single spin-echo pulse is able to extend the coherence time to nearly half a second. The measured coherence times demonstrate the potential of polar molecules as high fidelity qubits.

Zeeman-Sisyphus Deceleration of Molecular Beams.

We present a robust, continuous molecular decelerator that employs high magnetic fields and few optical pumping steps. CaOH molecules are slowed, accumulating at low velocities in a range sufficient for loading both magnetic and magneto-optical traps. During the slowing, the molecules scatter only seven photons, removing around 8 K of energy. Because large energies can be removed with only a few spontaneous radiative decays, this method can in principle be applied to nearly any paramagnetic atomic or molecular species, opening a general path to trapping of complex molecules.

Accurate prediction and measurement of vibronic branching ratios for laser cooling linear polyatomic molecules.

We report a generally applicable computational and experimental approach to determine vibronic branching ratios in linear polyatomic molecules to the 10-5 level, including for nominally symmetry-forbidden transitions. These methods are demonstrated in CaOH and YbOH, showing approximately two orders of magnitude improved sensitivity compared with the previous state of the art. Knowledge of branching ratios at this level is needed for the successful deep laser cooling of a broad range of molecular species.

Observation of Collisions between Two Ultracold Ground-State CaF Molecules.

We measure inelastic collisions between ultracold CaF molecules by combining two optical tweezers, each containing a single molecule. We observe collisions between ^{2}Σ CaF molecules in the absolute ground state |X,v=0,N=0,F=0⟩, and in excited hyperfine and rotational states. In the absolute ground state, we find a two-body loss rate of 7(4)×10^{-11} cm^{3}/s, which is below, but close to, the predicted universal loss rate.

1D Magneto-Optical Trap of Polyatomic Molecules.

We demonstrate a 1D magneto-optical trap of the polar free radical calcium monohydroxide (CaOH). A quasiclosed cycling transition is established to scatter ∼10^{3} photons per molecule, predominantly limited by interaction time. This enables radiative laser cooling of CaOH while compressing the molecular beam, leading to a significant increase in on axis beam brightness and reduction in temperature from 8.4 to 1.4 mK.