High-fidelity operation and algorithmic initialisation of spin qubits above one kelvin

The encoding of qubits in semiconductor spin carriers has been recognised as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale. However, the operation of the large number of qubits required for advantageous quantum applications will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 kelvin, where the cooling power is orders of magnitude higher. Here, we tune up and operate spin qubits in silicon above 1 kelvin, with fidelities in the range required for fault-tolerant operation at such temperatures. We design an algorithmic initialisation protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies, and incorporate high-fidelity radio-frequency readout to achieve an initialisation fidelity of 99.34 per cent. Importantly, we demonstrate a single-qubit Clifford gate fidelity of 99.85 per cent, and a two-qubit gate fidelity of 98.92 per cent. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for high-fidelity operation to be possible, surmounting a major obstacle in the pathway to scalable and fault-tolerant quantum computation

High-fidelity spin qubit operation and algorithmic initialization above 1 K

The encoding of qubits in semiconductor spin carriers has been recognized as a promising approach to a commercial quantum computer that can be lithographically produced and integrated at scale. However, the operation of the large number of qubits required for advantageous quantum applications will produce a thermal load exceeding the available cooling power of cryostats at millikelvin temperatures. As the scale-up accelerates, it becomes imperative to establish fault-tolerant operation above 1 K, at which the cooling power is orders of magnitude higher. Here we tune up and operate spin qubits in silicon above 1 K, with fidelities in the range required for fault-tolerant operations at these temperatures. We design an algorithmic initialization protocol to prepare a pure two-qubit state even when the thermal energy is substantially above the qubit energies and incorporate radiofrequency readout to achieve fidelities up to 99.34% for both readout and initialization. We also demonstrate single-qubit Clifford gate fidelities up to 99.85% and a two-qubit gate fidelity of 98.92%. These advances overcome the fundamental limitation that the thermal energy must be well below the qubit energies for the high-fidelity operation to be possible, surmounting a main obstacle in the pathway to scalable and fault-tolerant quantum computation

Consistency of high-fidelity two-qubit operations in silicon

The consistency of entangling operations between qubits is essential for the performance of multi-qubit systems, and is a crucial factor in achieving fault-tolerant quantum processors. Solid-state platforms are particularly exposed to inconsistency due to the materials-induced variability of performance between qubits and the instability of gate fidelities over time. Here we quantify this consistency for spin qubits, tying it to its physical origins, while demonstrating sustained and repeatable operation of two-qubit gates with fidelities above 99% in the technologically important silicon metal-oxide-semiconductor (SiMOS) quantum dot platform. We undertake a detailed study of the stability of these operations by analysing errors and fidelities in multiple devices through numerous trials and extended periods of operation. Adopting three different characterisation methods, we measure entangling gate fidelities ranging from 96.8% to 99.8%. Our analysis tools also identify physical causes of qubit degradation and offer ways to maintain performance within tolerance. Furthermore, we investigate the impact of qubit design, feedback systems, and robust gates on implementing scalable, high-fidelity control strategies. These results highlight both the capabilities and challenges for the scaling up of spin-based qubits into full-scale quantum processors

Cytochrome P450 1A2 Metabolizes 17β-Estradiol to Suppress Hepatocellular Carcinoma

<div><p>Hepatocellular carcinoma (HCC) occurs more frequently in men than in women. It is commonly agreed that estrogen plays important roles in suppressing HCC development, however, the underlying mechanism remains largely unknown. Since estrogen is mainly metabolized in liver and its metabolites affect cell proliferation, we sought to investigate if the liver-specific cytochrome P450 1A2 (CYP1A2) mediated the inhibitory effect of estrogen on HCC. In this study, the expression of estrogen-metabolizing enzyme CYP1A2 was determined in HCC tissues and cell lines. Cell proliferation and apoptosis were assessed in cells with or without <i>CYP1A2</i> overexpression. The levels of 17β-estradiol (E2) and its metabolite 2-methoxyestradiol (2-ME) were determined. A xenograft tumor model in mice was established to confirm the findings. It was found that <i>CYP1A2</i> expression was greatly repressed in HCC. E2 suppressed HCC cell proliferation and xenograft tumor development by inducing apoptosis. The inhibitory effect was significantly enhanced in cells with <i>CYP1A2</i> overexpression, which effectively conversed E2 to the cytotoxic 2-ME. E2 in combination with sorafenib showed an additive effect on HCC. The anti-HCC effect of E2 was not associated with estrogen receptors ERα and ERβ as well as tumor suppressor P53 but enhanced by the approved anti-HCC drug sorafenib. In addition, HDAC inhibitors greatly induced <i>CYP1A2</i> promoter activities in cancer cells, especially liver cancer cells, but not in non-tumorigenic cells. Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy.</p></div

Effects of gene overexpression on E2-mediated inhibition of cell proliferation.

<p><b>(A)</b> Growth rate of the transfected cells. Hep3B cells were transfected with vector control or <i>ERα</i>, <i>ERβ</i>, <i>GPR30</i>, <i>CYP1A2</i>, <i>CYP3A4</i>, <i>COMT</i> plasmid DNAs, respectively, and grown for 24 hours. Then the cells were seeded at 5x10³ cells/per well of 96-well plates and grown for 24 hours, at which time MTT was performed with one set of the cells (Day0). MTT for another set of the cells was performed 48 hours later (Day2). The growth ratios of the cells are expressed as the value of Day2 cells versus that of the Day0 cells of the same transfection (= 100%). <b>(B)</b> Hep3B cells were transfected and reseeded as mentioned in (A). Afterwards the cells were treated as indicated for 48 hours and analyzed for proliferation rate by MTT. The proliferation rate is expressed as the value of treated cells versus that of the untreated cells of same transfection (= 100%). Each column represents mean±s.d. of data obtained from four replicate wells. Consistent results were obtained in three independent experiments. <b>(C)</b> CYP1A2 mediates E2-inhibition of cell proliferation in 293T cells. The proliferation rate is expressed as the value of treated cells versus that of the untreated cells of same transfection (= 100%) Consistent results were obtained in three independent experiments. <b>(D)</b> CYP1A2 stable Hep3B cells migrated slowly under E2 treatment. Hep3B stable cells overexpressing CYP1A2 or empty vector were grown to confluence and a 2mm-thin wound gap was generated by scratching with a rubber policeman (Day0). The cells were then grown in medium supplemented with or without 1 μM E2 for 10 days (Day10) before microscopic images were taken. The lines indicate the wound edges. Consistent results were obtained in three independent experiments. (<b>E</b>) Hep3B cells were co-transfected with siRNA against <i>CYP1A2</i> (siCYP1A2) or <i>COMT</i> (siCOMT) and <i>CYP1A2</i>-expressing plasmids and grown for 24 hours. Then the cells were seeded at 5x10³ cells/per well of 96-well plates and grown for 24 hours. Afterwards the cells were treated as indicated for 48 hours and analyzed for proliferation rate by MTT. The proliferation rate is expressed as the value of treated cells versus that of the untreated cells of same transfection (= 100%). Each column represents mean±s.d. of data obtained from four replicate wells. Consistent results were obtained in three independent experiments. <b>(E)</b> Hep3B cells were transfected with <i>CYP1A2</i> and grown for 24 hours. Then the cells were grown in 10μM E2 supplemented medium for another 24 hours. Afterwards the cells were harvested and lysed in PBS by sonication. Concentrations of E2 and 2-ME were measured with respective EIA kits mentioned in Materials and Methods. The values represent the relative concentrations normalized against the protein concentration in the same sample. Each column represents mean±s.d. of data obtained from three independent assays.</p

CYP1A2 enhanced the inhibitory effect of E2 on xenograft tumors.

<p>Empty vector control and <i>CYP1A2</i>-overexpressing Hep3B stable cells were generated and nine clones of each cell line were combined in culture and used <i>in vivo</i> animal experiments. 1 x 10⁷ Hep3B cells with <i>CYP1A2</i> or empty vector were subcutaneously injected into 4-week old male BALB/c nude mice. Two days later, the mice were intraperitoneally injected with E2 (50 μg/kg) or vehicle control (0.02% DMSO in PBS) once daily for 10 days. Afterwards the mice were maintained for about four weeks before the tumors were collected for analysis. Weights of the tumors were indicated under the tumor images. Three independent xenograft assays were performed. <b>(A)</b> Xenograft tumor-carrying mice and the tumors in each experiment. <b>(B)</b> E2 suppressed the growth of <i>CYP1A2</i>-overexpressing tumors more potently. Mass ratio is expressed as the value of the weight of E2-treated tumors versus the vehicle-treated tumors of each stable cell line (vector or <i>CYP1A2</i>). Each column represents mean±s.d. of data obtained from the three independent xenograft assays. *p<0.05 when compared to vector stable cells.</p

The expression of <i>CYP1A2</i> was regulated by HDAC inhibitors.

<p><b>(A)</b><i>CYP1A2</i> promoter is activated by HDAC inhibitors. Hep3B cells were transfected with luciferase reporter plasmids and then treated for 24 hours with the drugs of the following concentrations before being harvested for Luc assays: 2μM SAHA, 1μM TSA, 5mM sodium butyrate (NaB), 5mM VPA, 0.2μg/ml doxorubicin, 2μM camptothecin, 5μM decitabine, 5μM zebularine, and 10μM etoposide. The concentrations were determined in preliminary cell proliferation assays in which the drugs caused obvious changes in cell growth. The data are expressed as fold changes of luc reading relative to that of vehicle-treated cells of same transfection (control). Each column represents the mean ± s.d. of three independent experiments. <b>(B)</b> Inductive effect of HDAC inhibitor on <i>CYP1A2</i> promoter is higher in cancer cells. Tumorigenic (Hep3B, PCL/PRF/5, Huh7, H1299, MCF7) or non-tumorigenic (MIHA, LO2, 293T) cells were transfected with <i>CYP1A2</i> promoter-luciferase reporter plasmids and treated with 2μM SAHA for 24 hours before being harvested for Luc assays. The data are expressed as fold changes of luc reading relative to that of vehicle-treated cells (control). Each column represents the mean ± s.d. of three independent experiments. <b>(C)</b> Different HDAC inhibitors exert different effects on <i>CYP1A2</i> promoter activity. The data are expressed as fold changes of luc reading relative to that of vehicle-treated cells (control). Concentrations of the drugs were determined by referring to the reported Half Maximal Inhibitory Concentrations (IC50) of the inhibitors against various HDAC proteins. <b>(D)</b> Expression levels of “classical” <i>HDAC</i> genes in HCC cells and non-tumorigenic cells. The expression levels were normalized with β-Actin mRNA levels. Each column represents the mean ± s.d. of four technical replicates. <b>(E)</b> Hypothesis on how E2 contributes to the clearance of carcinogen-damaged cells and consequently suppresses carcinogenesis.</p