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1.
Nat Genet ; 54(5): 593-602, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35501419

RESUMO

Improved understanding of genetic regulation of the proteome can facilitate identification of the causal mechanisms for complex traits. We analyzed data on 4,657 plasma proteins from 7,213 European American (EA) and 1,871 African American (AA) individuals from the Atherosclerosis Risk in Communities study, and further replicated findings on 467 AA individuals from the African American Study of Kidney Disease and Hypertension study. Here, we identified 2,004 proteins in EA and 1,618 in AA, with most overlapping, which showed associations with common variants in cis-regions. Availability of AA samples led to smaller credible sets and notable number of population-specific cis-protein quantitative trait loci. Elastic Net produced powerful models for protein prediction in both populations. An application of proteome-wide association studies to serum urate and gout implicated several proteins, including IL1RN, revealing the promise of the drug anakinra to treat acute gout flares. Our study demonstrates the value of large and diverse ancestry study to investigate the genetic mechanisms of molecular phenotypes and their relationship with complex traits.


Assuntos
Gota , Proteoma , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Gota/genética , Humanos , Polimorfismo de Nucleotídeo Único , Proteoma/genética
2.
Kidney Int ; 101(4): 814-823, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35120996

RESUMO

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m2 in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations was unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.


Assuntos
Estudo de Associação Genômica Ampla , Insuficiência Renal Crônica , Estudos de Coortes , Feminino , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/genética
3.
Sci Adv ; 8(6): eabk1660, 2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35138888

RESUMO

Quantum measurements cannot be thought of as revealing preexisting results, even when they do not disturb any other measurement in the same trial. This feature is called contextuality and is crucial for the quantum advantage in computing. Here, we report the observation of quantum contextuality simultaneously free of the detection, sharpness, and compatibility loopholes. The detection and sharpness loopholes are closed by adopting a hybrid two-ion system and highly efficient fluorescence measurements offering a detection efficiency of 100% and a measurement repeatability of >98%. The compatibility loophole is closed by targeting correlations between observables for two different ions in a Paul trap, a 171Yb+ ion and a 138Ba+ ion, chosen so measurements on each ion use different operation laser wavelengths, fluorescence wavelengths, and detectors. The experimental results show a violation of the bound for the most adversarial noncontextual models and open a way to certify quantum systems.

4.
J Am Soc Nephrol ; 32(9): 2291-2302, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34465608

RESUMO

BACKGROUND: Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression of CKD. METHODS: We quantified the association between 4877 plasma proteins and a composite outcome of ESKD or decline in eGFR by ≥50% among 9406 participants in the Atherosclerosis Risk in Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for a median of 14.4 years. We performed separate analyses for these proteins in a subset of 4378 participants (visit 5), who were followed at a later time point, for a median of 4.4 years. For validation, we evaluated proteins with significant associations (false discovery rate <5%) in both time periods in 3249 participants in the Chronic Renal Insufficiency Cohort (CRIC) and 703 participants in the African American Study of Kidney Disease and Hypertension (AASK). We also compared the genetic determinants of protein levels with those from a meta-analysis genome-wide association study of eGFR. RESULTS: In models adjusted for multiple covariates, including baseline eGFR and albuminuria, we identified 13 distinct proteins that were significantly associated with the composite end point in both time periods, including TNF receptor superfamily members 1A and 1B, trefoil factor 3, and ß-trace protein. Of these proteins, 12 were also significantly associated in CRIC, and nine were significantly associated in AASK. Higher levels of each protein associated with higher risk of 50% eGFR decline or ESKD. We found genetic evidence for a causal role for one protein, lectin mannose-binding 2 protein (LMAN2). CONCLUSIONS: Large-scale proteomic analysis identified both known and novel proteomic risk factors for eGFR decline.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Proteômica , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Fatores Etários , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco
5.
Nat Commun ; 12(1): 233, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431845

RESUMO

Realizing a long coherence time quantum memory is a major challenge of current quantum technology. Until now, the longest coherence-time of a single qubit was reported as 660 s in a single 171Yb+ ion-qubit through the technical developments of sympathetic cooling and dynamical decoupling pulses, which addressed heating-induced detection inefficiency and magnetic field fluctuations. However, it was not clear what prohibited further enhancement. Here, we identify and suppress the limiting factors, which are the remaining magnetic-field fluctuations, frequency instability and leakage of the microwave reference-oscillator. Then, we observe the coherence time of around 5500 s for the 171Yb+ ion-qubit, which is the time constant of the exponential decay fit from the measurements up to 960 s. We also systematically study the decoherence process of the quantum memory by using quantum process tomography and analyze the results by applying recently developed resource theories of quantum memory and coherence. Our experimental demonstration will accelerate practical applications of quantum memories for various quantum information processing, especially in the noisy-intermediate-scale quantum regime.

6.
J Chem Phys ; 152(8): 084106, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32113342

RESUMO

On the basis of the screened 29 hybrid halide compounds from our prior study [Y. Li and K. Yang, Energy Environ. Sci. 12, 2233-2243 (2019)], here, we reported a systematic computational study of the stability diagram, defect tolerance, and optical absorption coefficients for these candidate materials using high-throughput first-principles calculations. We took two exemplary compounds, MA2SnI4 and MA3Sb2I9, as examples to show the computational process, and they are discussed in detail. This work is expected to provide a detailed guide for further experimental synthesis and characterization, with the potential to develop novel lead-free optoelectronic devices.

7.
Nat Commun ; 11(1): 587, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32001680

RESUMO

Various quantum applications can be reduced to estimating expectation values, which are inevitably deviated by operational and environmental errors. Although errors can be tackled by quantum error correction, the overheads are far from being affordable for near-term technologies. To alleviate the detrimental effects of errors on the estimation of expectation values, quantum error mitigation techniques have been proposed, which require no additional qubit resources. Here we benchmark the performance of a quantum error mitigation technique based on probabilistic error cancellation in a trapped-ion system. Our results clearly show that effective gate fidelities exceed physical fidelities, i.e., we surpass the break-even point of eliminating gate errors, by programming quantum circuits. The error rates are effectively reduced from (1.10 ± 0.12) × 10-3 to (1.44 ± 5.28) × 10-5 and from (0.99 ± 0.06) × 10-2 to (0.96 ± 0.10) × 10-3 for single- and two-qubit gates, respectively. Our demonstration opens up the possibility of implementing high-fidelity computations on a near-term noisy quantum device.

8.
Nature ; 572(7769): 363-367, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31341282

RESUMO

Quantum computers can efficiently solve classically intractable problems, such as the factorization of a large number1 and the simulation of quantum many-body systems2,3. Universal quantum computation can be simplified by decomposing circuits into single- and two-qubit entangling gates4, but such decomposition is not necessarily efficient. It has been suggested that polynomial or exponential speedups can be obtained with global N-qubit (N greater than two) entangling gates5-9. Such global gates involve all-to-all connectivity, which emerges among trapped-ion qubits when using laser-driven collective motional modes10-14, and have been implemented for a single motional mode15,16. However, the single-mode approach is difficult to scale up because isolating single modes becomes challenging as the number of ions increases in a single crystal, and multi-mode schemes are scalable17,18 but limited to pairwise gates19-23. Here we propose and implement a scalable scheme for realizing global entangling gates on multiple 171Yb+ ion qubits by coupling to multiple motional modes through modulated laser fields. Because such global gates require decoupling multiple modes and balancing all pairwise coupling strengths during the gate, we develop a system with fully independent control capability on each ion14. To demonstrate the usefulness and flexibility of these global gates, we generate a Greenberger-Horne-Zeilinger state with up to four qubits using a single global operation. Our approach realizes global entangling gates as scalable building blocks for universal quantum computation, motivating future research in scalable global methods for quantum information processing.

9.
Phys Rev Lett ; 121(16): 160502, 2018 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-30387619

RESUMO

We develop a deterministic method to generate and verify arbitrarily high NOON states of quantized vibrations (phonons), through the coupling to the internal state. We experimentally create the entangled states up to N=9 phonons in two vibrational modes of a single trapped ^{171}Yb^{+} ion. We observe an increasing phase sensitivity of the generated NOON state as the number of phonons N increases and obtain the fidelity from the contrast of the phase interference and the population of the phonon states through the two-mode projective measurement, which are significantly above the classical bound. We also measure the quantum Fisher information of the generated state and observe Heisenberg scaling in the lower bounds of phase sensitivity as N increases. Our scheme is generic and applicable to other photonic or phononic systems such as circuit QED systems or nanomechanical oscillators, which have Jaynes-Cummings-type of interactions.

10.
Phys Rev E ; 97(5-1): 052136, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29906912

RESUMO

We extend the well-known static duality [M. Girardeau, J. Math. Phys. 1, 516 (1960)JMAPAQ0022-248810.1063/1.1703687; T. Cheon and T. Shigehara, Phys. Rev. Lett. 82, 2536 (1999)PRLTAO0031-900710.1103/PhysRevLett.82.2536] between one-dimensional (1D) bosons and 1D fermions to the dynamical version. By utilizing this dynamical duality, we find the duality of nonequilibrium work distributions between interacting 1D bosonic (Lieb-Liniger model) and 1D fermionic (Cheon-Shigehara model) systems with dual contact interactions. As a special case, the work distribution of the Tonks-Girardeau gas is identical to that of 1D noninteracting fermionic system even though their momentum distributions are significantly different. In the classical limit, the work distributions of Lieb-Liniger models (Cheon-Shigehara models) with arbitrary coupling strength converge to that of the 1D noninteracting distinguishable particles, although their elementary excitations (quasiparticles) obey different statistics, e.g., the Bose-Einstein, the Fermi-Dirac, and the fractional statistics. We also present numerical results of the work distributions of Lieb-Liniger model with various coupling strengths, which demonstrate the convergence of work distributions in the classical limit.

11.
Nat Commun ; 9(1): 195, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29335446

RESUMO

Quantum field theories describe a variety of fundamental phenomena in physics. However, their study often involves cumbersome numerical simulations. Quantum simulators, on the other hand, may outperform classical computational capacities due to their potential scalability. Here we report an experimental realization of a quantum simulation of fermion-antifermion scattering mediated by bosonic modes, using a multilevel trapped ion, which is a simplified model of fermion scattering in both perturbative and non-perturbative quantum electrodynamics. The simulated model exhibits prototypical features in quantum field theory including particle pair creation and annihilation, as well as self-energy interactions. These are experimentally observed by manipulating four internal levels of a 171Yb+ trapped ion, where we encode the fermionic modes, and two motional degrees of freedom that simulate the bosonic modes. Our experiment establishes an avenue towards the efficient implementation of field modes, which may prove useful in studies of quantum field theories including non-perturbative regimes.

12.
Cell Mol Neurobiol ; 38(2): 421-430, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28321604

RESUMO

Glioblastoma, one of the common malignant brain tumors, results in the highly death, but its underlying molecular mechanisms remain unclear. Smurf1, a member of Nedd4 family of HECT-type ligases, has been reported to contribute to tumorigenicity through several important biological pathways. Recently, it was also found to participate in modulate cellular processes, including morphogenesis, autophagy, growth, and cell migration. In this research, we reported the clinical guiding significance of the expression of Smurf1 in human glioma tissues and cell lines. Western blotting analysis discovered that the expression of Smurf1 was increased with WHO grade. Immunohistochemistry levels discovered that high expression of Smurf1 is closely consistent with poor prognosis of glioma. In addition, suppression of Smurf1 can reduce cell invasion and increase the E-cadherin expression, which is a marker of invasion. Our study firstly demonstrated that Smurf1 may promote glioma cell invasion and suppression of the Smurf1 may provide a novel treatment strategy for glioma.


Assuntos
Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Ubiquitina-Proteína Ligases/genética , Adulto , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Feminino , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Ubiquitina-Proteína Ligases/biossíntese
13.
Phys Rev Lett ; 118(10): 100602, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-28339228

RESUMO

Counterdiabatic driving (CD) exploits auxiliary control fields to tailor the nonequilibrium dynamics of a quantum system, making possible the suppression of dissipated work in finite-time thermodynamics and the engineering of optimal thermal machines with no friction. We show that while the mean work done by the auxiliary controls vanishes, CD leads to a broadening of the work distribution. We derive a fundamental inequality that relates nonequilibrium work fluctuations to the operation time and quantifies the thermodynamic cost of CD in both critical and noncritical systems.

14.
Nat Commun ; 7: 11410, 2016 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-27097897

RESUMO

Single-quantum level operations are important tools to manipulate a quantum state. Annihilation or creation of single particles translates a quantum state to another by adding or subtracting a particle, depending on how many are already in the given state. The operations are probabilistic and the success rate has yet been low in their experimental realization. Here we experimentally demonstrate (near) deterministic addition and subtraction of a bosonic particle, in particular a phonon of ionic motion in a harmonic potential. We realize the operations by coupling phonons to an auxiliary two-level system and applying transitionless adiabatic passage. We show handy repetition of the operations on various initial states and demonstrate by the reconstruction of the density matrices that the operations preserve coherences. We observe the transformation of a classical state to a highly non-classical one and a Gaussian state to a non-Gaussian one by applying a sequence of operations deterministically.

15.
Nat Commun ; 6: 7917, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26239028

RESUMO

A quantum simulator is an important device that may soon outperform current classical computations. A basic arithmetic operation, the complex conjugate, however, is considered to be impossible to be implemented in such a quantum system due to the linear character of quantum mechanics. Here, we present the experimental quantum simulation of such an unphysical operation beyond the regime of unitary and dissipative evolutions through the embedding of a quantum dynamics in the electronic multilevels of a (171)Yb(+) ion. We perform time reversal and charge conjugation, which are paradigmatic examples of antiunitary symmetry operators, in the evolution of a Majorana equation without the tomographic knowledge of the evolving state. Thus, these operations can be applied regardless of the system size. Our approach offers the possibility to add unphysical operations to the toolbox of quantum simulation, and provides a route to efficiently compute otherwise intractable quantities, such as entanglement monotones.

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