Coherent spin qubit transport in silicon.

A fault-tolerant quantum processor may be configured using stationary qubits interacting only with their nearest neighbours, but at the cost of significant overheads in physical qubits per logical qubit. Such overheads could be reduced by coherently transporting qubits across the chip, allowing connectivity beyond immediate neighbours. Here we demonstrate high-fidelity coherent transport of an electron spin qubit between quantum dots in isotopically-enriched silicon. We observe qubit precession in the inter-site tunnelling regime and assess the impact of qubit transport using Ramsey interferometry and quantum state tomography techniques. We report a polarization transfer fidelity of 99.97% and an average coherent transfer fidelity of 99.4%. Our results provide key elements for high-fidelity, on-chip quantum information distribution, as long envisaged, reinforcing the scaling prospects of silicon-based spin qubits.

Bolometer operating at the threshold for circuit quantum electrodynamics.

Radiation sensors based on the heating effect of absorbed radiation are typically simple to operate and flexible in terms of input frequency, so they are widely used in gas detection1, security2, terahertz imaging3, astrophysical observations4 and medical applications5. Several important applications are currently emerging from quantum technology and especially from electrical circuits that behave quantum mechanically, that is, circuit quantum electrodynamics6. This field has given rise to single-photon microwave detectors7-9 and a quantum computer that is superior to classical supercomputers for certain tasks10. Thermal sensors hold potential for enhancing such devices because they do not add quantum noise and they are smaller, simpler and consume about six orders of magnitude less power than the frequently used travelling-wave parametric amplifiers11. However, despite great progress in the speed12 and noise levels13 of thermal sensors, no bolometer has previously met the threshold for circuit quantum electrodynamics, which lies at a time constant of a few hundred nanoseconds and a simultaneous energy resolution of the order of 10h gigahertz (where h is the Planck constant). Here we experimentally demonstrate a bolometer that operates at this threshold, with a noise-equivalent power of 30 zeptowatts per square-root hertz, comparable to the lowest value reported so far13, at a thermal time constant two orders of magnitude shorter, at 500 nanoseconds. Both of these values are measured directly on the same device, giving an accurate estimation of 30h gigahertz for the calorimetric energy resolution. These improvements stem from the use of a graphene monolayer with extremely low specific heat14 as the active material. The minimum observed time constant of 200 nanoseconds is well below the dephasing times of roughly 100 microseconds reported for superconducting qubits15 and matches the timescales of currently used readout schemes16,17, thus enabling circuit quantum electrodynamics applications for bolometers.

Label-free sensing of exosomal MCT1 and CD147 for tracking metabolic reprogramming and malignant progression in glioma.

Malignant glioma is a fatal brain tumor whose pathological progression is closely associated with glycolytic reprogramming, leading to the high expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein, cluster of differentiation 147 (CD147) for enhancing lactate efflux. In particular, malignant glioma cells (GMs) release tremendous number of exosomes, nanovesicles of 30 to 200 nm in size, promoting tumor progression by the transport of pro-oncogenic molecules to neighboring cells. In the present study, we found that hypoxia-induced malignant GMs strongly enhanced MCT1 and CD147 expression, playing a crucial role in promoting calcium-dependent exosome release. Furthermore, it was first identified that hypoxic GMs-derived exosomes contained significantly high levels of MCT1 and CD147, which could be quantitatively detected by noninvasive localized surface plasmon resonance and atomic force microscopy biosensors, demonstrating that they could be precise surrogate biomarkers for tracking parent GMs' metabolic reprogramming and malignant progression as liquid biopsies.

Operation of a silicon quantum processor unit cell above one kelvin.

Quantum computers are expected to outperform conventional computers in several important applications, from molecular simulation to search algorithms, once they can be scaled up to large numbers-typically millions-of quantum bits (qubits)1-3. For most solid-state qubit technologies-for example, those using superconducting circuits or semiconductor spins-scaling poses a considerable challenge because every additional qubit increases the heat generated, whereas the cooling power of dilution refrigerators is severely limited at their operating temperature (less than 100 millikelvin)4-6. Here we demonstrate the operation of a scalable silicon quantum processor unit cell comprising two qubits confined to quantum dots at about 1.5 kelvin. We achieve this by isolating the quantum dots from the electron reservoir, and then initializing and reading the qubits solely via tunnelling of electrons between the two quantum dots7-9. We coherently control the qubits using electrically driven spin resonance10,11 in isotopically enriched silicon12 28Si, attaining single-qubit gate fidelities of 98.6 per cent and a coherence time of 2 microseconds during 'hot' operation, comparable to those of spin qubits in natural silicon at millikelvin temperatures13-16. Furthermore, we show that the unit cell can be operated at magnetic fields as low as 0.1 tesla, corresponding to a qubit control frequency of 3.5 gigahertz, where the qubit energy is well below the thermal energy. The unit cell constitutes the core building block of a full-scale silicon quantum computer and satisfies layout constraints required by error-correction architectures8,17. Our work indicates that a spin-based quantum computer could be operated at increased temperatures in a simple pumped 4He system (which provides cooling power orders of magnitude higher than that of dilution refrigerators), thus potentially enabling the integration of classical control electronics with the qubit array18,19.

Coherent spin control of s-, p-, d- and f-electrons in a silicon quantum dot.

Once the periodic properties of elements were unveiled, chemical behaviour could be understood in terms of the valence of atoms. Ideally, this rationale would extend to quantum dots, and quantum computation could be performed by merely controlling the outer-shell electrons of dot-based qubits. Imperfections in semiconductor materials disrupt this analogy, so real devices seldom display a systematic many-electron arrangement. We demonstrate here an electrostatically confined quantum dot that reveals a well defined shell structure. We observe four shells (31 electrons) with multiplicities given by spin and valley degrees of freedom. Various fillings containing a single valence electron-namely 1, 5, 13 and 25 electrons-are found to be potential qubits. An integrated micromagnet allows us to perform electrically-driven spin resonance (EDSR), leading to faster Rabi rotations and higher fidelity single qubit gates at higher shell states. We investigate the impact of orbital excitations on single qubits as a function of the dot deformation and exploit it for faster qubit control.

A clinical prediction score using age at diagnosis and saline infusion test parameters can predict aldosterone-producing adenoma from idiopathic adrenal hyperplasia.

PURPOSE: Accurate subtyping of the primary aldosteronism into aldosterone-producing adenoma (APA) and idiopathic adrenal hyperplasia (IAH) is important to direct for specific treatment modalities. The objective of the study was to compare the clinical and biochemical parameters of APA and IAH patients to derive a Clinical Prediction Score reliably predicting APA from IAH. METHODS: This was a retrospective multi-centre study recruiting 38 APA patients and 42 IAH patients from four major hospitals in Hong Kong using database from Surgical Outcomes Monitoring and Improvement Programme and Clinical Data Analysis and Reporting System. Their clinical and biochemical parameters were evaluated. RESULTS: Patients in APA group were younger than IAH group (mean age 48.6 ± 9.2 vs. 57.1 ± 7.3 years old, p < 0.001), had more suppressed renin before saline infusion in saline infusion test (SIT) (median 0.19 [IQR 0.15-0.37] vs. 0.39 [IQR 0.19-0.69] ng/mL/h, p = 0.01), and higher aldosterone level after saline infusion in SIT (median 674 [IQR 498-1000] vs. 327 [IQR 242-483] pmol/L, p < 0.001). A clinical prediction score using three parameters was devised, comprising age at diagnosis < 50 years, PRA before saline infusion in SIT ≤ 0.26 ng/mL/h, and aldosterone level after saline infusion in SIT ≥ 424 pmol/L. A score of 2 would predict APA with a sensitivity of 84.2% and specificity of 88.1%, and a score of 3 would predict APA with a sensitivity of 31.6% and specificity of 100%. CONCLUSIONS: Clinical Prediction Score based on the combination of age at diagnosis, PRA, and aldosterone level in the saline infusion tests could reliably predict APA from IAH.

Single-spin qubits in isotopically enriched silicon at low magnetic field.

Single-electron spin qubits employ magnetic fields on the order of 1 Tesla or above to enable quantum state readout via spin-dependent-tunnelling. This requires demanding microwave engineering for coherent spin resonance control, which limits the prospects for large scale multi-qubit systems. Alternatively, singlet-triplet readout enables high-fidelity spin-state measurements in much lower magnetic fields, without the need for reservoirs. Here, we demonstrate low-field operation of metal-oxide-silicon quantum dot qubits by combining coherent single-spin control with high-fidelity, single-shot, Pauli-spin-blockade-based ST readout. We discover that the qubits decohere faster at low magnetic fields with [Formula: see text] µs and [Formula: see text] µs at 150 mT. Their coherence is limited by spin flips of residual 29Si nuclei in the isotopically enriched 28Si host material, which occur more frequently at lower fields. Our finding indicates that new trade-offs will be required to ensure the frequency stabilization of spin qubits, and highlights the importance of isotopic enrichment of device substrates for the realization of a scalable silicon-based quantum processor.

Cost-utility analysis of 21-gene assay for node-positive early breast cancer.

Background: For women with lymph node (ln)-positive, estrogen receptor-positive, and her2 (human epidermal growth factor receptor 2)-negative breast cancer (bca), current guidelines recommend treatment with both hormonal therapy and chemotherapy. The 21-gene Recurrence Score (rs) assay might be helpful in selecting patients with bca who can be spared chemotherapy when they have 1-3 positive lns and a lower risk of recurrence. In the present study, we performed a cost-utility analysis comparing use of the 21-gene rs assay with current practice from the perspective of a Canadian health care payer. Methods: A Markov model was developed to determine costs and quality-adjusted life-years (qalys) over a patient's lifetime. Patient outcomes in both study groups were examined based on published clinical trials. Costs were derived primarily from published Canadian sources. Costs and outcomes were discounted at 1.5% annually, and costs are reported in 2016 Canadian dollars. A probabilistic analysis was used, and the model parameters were varied in a sensitivity analysis. Results: The results indicate that use of the 21-gene rs assay was less costly ($432 less) and more effective (0.22 qalys) than current practice. The probabilistic analysis revealed that 70% of the 10,000 simulated incremental cost-effectiveness ratios were in the southeast quadrant. The results were sensitive to the probability of a low rs and to the probability of receiving chemotherapy in the low-risk rs category and in current practice. Conclusions: Use of the 21-gene rs assay could be a cost-effective strategy for Ontario patients with estrogen receptor-positive, her2-negative early bca and 1-3 positive lns.

Fidelity benchmarks for two-qubit gates in silicon.

Universal quantum computation will require qubit technology based on a scalable platform1, together with quantum error correction protocols that place strict limits on the maximum infidelities for one- and two-qubit gate operations2,3. Although various qubit systems have shown high fidelities at the one-qubit level4-10, the only solid-state qubits manufactured using standard lithographic techniques that have demonstrated two-qubit fidelities near the fault-tolerance threshold6 have been in superconductor systems. Silicon-based quantum dot qubits are also amenable to large-scale fabrication and can achieve high single-qubit gate fidelities (exceeding 99.9 per cent) using isotopically enriched silicon11,12. Two-qubit gates have now been demonstrated in a number of systems13-15, but as yet an accurate assessment of their fidelities using Clifford-based randomized benchmarking, which uses sequences of randomly chosen gates to measure the error, has not been achieved. Here, for qubits encoded on the electron spin states of gate-defined quantum dots, we demonstrate Bell state tomography with fidelities ranging from 80 to 89 per cent, and two-qubit randomized benchmarking with an average Clifford gate fidelity of 94.7 per cent and an average controlled-rotation fidelity of 98 per cent. These fidelities are found to be limited by the relatively long gate times used here compared with the decoherence times of the qubits. Silicon qubit designs employing fast gate operations with high Rabi frequencies16,17, together with advanced pulsing techniques18, should therefore enable much higher fidelities in the near future.

Integrated silicon qubit platform with single-spin addressability, exchange control and single-shot singlet-triplet readout.

Silicon quantum dot spin qubits provide a promising platform for large-scale quantum computation because of their compatibility with conventional CMOS manufacturing and the long coherence times accessible using 28Si enriched material. A scalable error-corrected quantum processor, however, will require control of many qubits in parallel, while performing error detection across the constituent qubits. Spin resonance techniques are a convenient path to parallel two-axis control, while Pauli spin blockade can be used to realize local parity measurements for error detection. Despite this, silicon qubit implementations have so far focused on either single-spin resonance control, or control and measurement via voltage-pulse detuning in the two-spin singlet-triplet basis, but not both simultaneously. Here, we demonstrate an integrated device platform incorporating a silicon metal-oxide-semiconductor double quantum dot that is capable of single-spin addressing and control via electron spin resonance, combined with high-fidelity spin readout in the singlet-triplet basis.

Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.

This corrects the article DOI: 10.1038/hdy.2015.89.

Clinical heterogeneity in children with gonadal dysgenesis associated with non-mosaic 46,XY karyotype.

INTRODUCTION: Gonadal dysgenesis is unique in disorders of sex development (DSD), in that it can be associated with 46,XX, 46,XY or mosaic 45,X/46,XY karyotypes. Gonadal dysgenesis can be partial or complete. Gonadal dysgenesis associated with the Y-chromosome has increased risk of gonadal germ cell neoplasms. Most of the literature focus on 45,X/46,XY gonadal dysgenesis, while there are scanty data on the condition when the karyotype is non-mosaic 46,XY. OBJECTIVE: To investigate the diversity of clinical pictures of children presenting with 46,XY DSD due to gonadal dysgenesis. METHODS: A retrospective study on consecutive patients diagnosed with 46,XY gonadal dysgenesis at age ≤18 years in a tertiary center from 1985 to 2015. The clinical presentations, phenotypes, gonadal features and associated anomalies were investigated. RESULTS: Twenty-eight patients with Y-chromosome gonadal dysgenesis were identified during the study period and six (21.4%) had non-mosaic 46,XY karyotype. Three had complete gonadal dysgenesis (CGD) with normal female phenotype, while the other three had partial gonadal dysgenesis (PGD). Of the three patients with CGD, two presented with the classical Swyer syndrome at adolescence, while the third presented at birth with multiple congenital anomalies. The three PGD patients presented with ambiguous genitalia at birth (n = 2), and isolated hypospadias (n = 1), which was associated with Frasier syndrome. Three patients had germ cell neoplasms: bilateral gonadoblastoma (n = 1), bilateral intratubular germ cell neoplasia unclassified (n = 1), and dysgerminoma + gonadoblastoma (n = 1). Two patients had global developmental delay with other congenital anomalies, and another patient had learning difficulties with borderline intelligence (Table). DISCUSSION: The findings suggest that 46,XY gonadal dysgenesis is much rarer than 45,X/46,XY gonadal dysgenesis. Patients differed in their clinical presentations and well-established syndromes happened in half of them. Overall, the risk of germ cell neoplasms and the association with other somatic anomalies appeared to be high. The study was limited by: its small number, single-center experience, and the possibility of missing the diagnosis in some male patients with mild undervirilization. CONCLUSION: Heterogeneity was noted in the clinical, phenotypic and gonadal features among pediatric patients with 46,XY gonadal dysgenesis.

MicroRNA-377 suppresses initiation and progression of esophageal cancer by inhibiting CD133 and VEGF.

Esophageal cancer is one of the most lethal cancers worldwide with poor survival and limited therapeutic options. The discovery of microRNAs created a new milestone in cancer research. miR-377 is located in chromosome region 14q32, which is frequently deleted in esophageal squamous cell carcinoma (ESCC), but the biological functions, clinical significance and therapeutic implication of miR-377 in ESCC are largely unknown. In this study, we found that miR-377 expression was significantly downregulated in tumor tissue and serum of patients with ESCC. Both tumor tissue and serum miR-377 expression levels were positively correlated with patient survival. Higher serum miR-377 expression was inversely associated with pathologic tumor stage, distant metastasis, residual tumor status and chemoradiotherapy resistance. The roles of miR-377 in suppressing tumor initiation and progression, and the underlying molecular mechanisms were investigated. Results of in vitro and in vivo experiments showed that miR-377 overexpression inhibited the initiation, growth and angiogenesis of ESCC tumors as well as metastatic colonization of ESCC cells, whereas silencing of miR-377 had opposite effects. Mechanistically, miR-377 regulated CD133 and VEGF by directly binding to their 3' untranslated region. Moreover, systemic delivery of formulated miR-377 mimic not only suppressed tumor growth in nude mice but also blocked tumor angiogenesis and metastasis of ESCC cells to the lungs without overt toxicity to mice. Collectively, our study established that miR-377 plays a functional and significant role in suppressing tumor initiation and progression, and may represent a promising non-invasive diagnostic and prognostic biomarker and therapeutic strategy for patients with ESCC.

Antiangiogenic activity of 2-formyl-8-hydroxy-quinolinium chloride.

Tumour growth is closely related to the development of new blood vessels to supply oxygen and nutrients to cancer cells. Without the neovascular formation, tumour volumes cannot increase and undergo metastasis. Antiangiogenesis is one of the most promising approaches for antitumour therapy. The exploration of new antiangiogenic agents would be helpful in antitumour therapy. Quinoline is an aromatic nitrogen compound characterized by a double-ring structure which exhibits a benzene ring fused to pyridine at two adjacent carbon atoms. The high stability of quinoline makes it preferable in a variety of therapeutic and pharmaceutical applications, including antitumour treatment. This work is to examine the potential antiangiogenic activity of the synthetic compound 2-Formyl-8-hydroxy-quinolinium chloride. We found that 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of human umbilical vein endothelial cells in vitro. Using the diethylnitrosamine-induced hepatocarcinogenesis model, 2-Formyl-8-hydroxy-quinolinium chloride showed strong antiangiogenic activity. Furthermore, 2-Formyl-8-hydroxy-quinolinium chloride could inhibit the growth of large Hep3B xenografted tumour from the nude mice. We assume that 2-Formyl-8-hydroxy-quinolinium chloride could be a potential antiangiogenic and antitumour agent and it is worthwhile to further study its underlying working mechanism.

Downregulation of renal tubular Wnt/ß-catenin signaling by Dickkopf-3 induces tubular cell death in proteinuric nephropathy.

Studies on the role of Wnt/ß-catenin signaling in different forms of kidney disease have yielded discrepant results. Here, we report the biphasic change of renal ß-catenin expression in mice with overload proteinuria in which ß-catenin was upregulated at the early stage (4 weeks after disease induction) but abrogated at the late phase (8 weeks). Acute albuminuria was observed at 1 week after bovine serum albumin injection, followed by partial remission at 4 weeks that coincided with overexpression of renal tubular ß-catenin. Interestingly, a rebound in albuminuria at 8 weeks was accompanied by downregulated tubular ß-catenin expression and heightened tubular apoptosis. In addition, there was an inverse relationship between Dickkopf-3 (Dkk-3) and renal tubular ß-catenin expression at these time points. In vitro, a similar trend in ß-catenin expression was observed in human kidney-2 (HK-2) cells with acute (upregulation) and prolonged (downregulation) exposure to albumin. Induction of a proapoptotic phenotype by albumin was significantly enhanced by silencing ß-catenin in HK-2 cells. Finally, Dkk-3 expression and secretion was increased after prolonged exposure to albumin, leading to the suppression of intracellular ß-catenin signaling pathway. The effect of Dkk-3 on ß-catenin signaling was confirmed by incubation with exogenous Dkk-3 in HK-2 cells. Taken together, these data suggest that downregulation of tubular ß-catenin signaling induced by Dkk-3 has a detrimental role in chronic proteinuria, partially through the increase in apoptosis.