The size of silicon transistors used in microelectronic devices is shrinking to the level where quantum effects become important 1 . While this presents a significant challenge for the further scaling of microprocessors, it provides the potential for radical innovations in the form of spin-based quantum computers 2-4 and spintronic devices 5 . An electron spin in Si can represent a well-isolated quantum bit with long coherence times 6 because of the weak spin-orbit coupling 7 and the possibility to eliminate nuclear spins from the bulk crystal 8 . However, the control of single electrons in Si has proved challenging, and has so far hindered the observation and manipulation of a single spin. Here we report the first demonstration of single-shot, time-resolved readout of an electron spin in Si. This has been performed in a device consisting of implanted phosphorus donors 9 coupled to a metal-oxide-semiconductor single-electron transistor 10,11 -compatible with current microelectronic technology. We observed a spin lifetime approaching 1 second at magnetic fields below 2 T, and achieved spin readout fidelity better than 90%. High-fidelity single-shot spin readout in Si opens the path to the development of a new generation of quantum computing and spintronic devices, built using the most important material in the semiconductor industry.The projective, single-shot readout of a qubit is a crucial step in both circuit-based and measurement-based quantum computers 12 . For electron spins in solid state, this has only been achieved in GaAs/AlGaAs quantum dots coupled to charge detectors 13-15 . The spin readout was achieved utilizing spin-dependent tunnelling, in which the electron was displaced to a different location depending on its spin state. The charge detector, electrostatically coupled to the electron site, sensed whether the charge had been displaced, thereby determining the spin state. Here we apply a novel approach to charge sensing, where the detector is not only electrostatically coupled, but also tunnel-coupled to the electron site 11 , as shown in Fig. 1a. As a charge detector we employ here the silicon single-electron transistor 10 (SET), a nonlinear nanoelectronic device consisting of a small island of electrons tunnel-coupled to source and drain reservoirs, electrostatically induced beneath an insulating SiO 2 layer. A current can flow from source to drain only when the electrochemical potential of the island assumes specific values 16 , resulting in a characteristic pattern of sharp current peaks as a function of gate voltage (Fig. 1e). The shift in electrochemical potential arising from the tunnelling of a single electron from a nearby charge centre into the SET island is large enough to switch the current from zero to its maximum value. This tunnelling event becomes spin-dependent in the presence of a large magnetic field, when the spin-up state | ↑ has a higher energy than the spin-down state | ↓ , by an amount larger than the thermal and electromagnetic broadening of electron states in the SET isla...

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC.nasopharyngeal carcinoma | somatic mutation landscape | NF-κB signaling | whole-exome sequencing | APOBEC-mediated signature

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We have developed nanoscale double-gated field-effect-transistors for the study of electron states and transport properties of single deliberately implanted phosphorus donors. The devices provide a high-level of control of key parameters required for potential applications in nanoelectronics. For the donors, we resolve transitions corresponding to two charge states successively occupied by spin down and spin up electrons. The charging energies and the Lande g-factors are consistent with expectations for donors in gated nanostructures.

Silicon quantum dots are considered an excellent platform for spin qubits, partly due to their weak spin-orbit interaction. However, the sharp interfaces in the heterostructures induce a small but significant spin-orbit interaction which degrade the performance of the qubits or, when understood and controlled, could be used as a powerful resource. To understand how to control this interaction we build a detailed profile of the spin-orbit interaction of a silicon metal-oxide-semiconductor double quantum dot system. We probe the derivative of the Stark shift, g-factor and g-factor difference for two single-electron quantum dot qubits as a function of external magnetic field and find that they are dominated by spin-orbit interactions originating from the vector potential, consistent with recent theoretical predictions. Conversely, by populating the double dot with two electrons we probe the mixing of singlet and spin-polarized triplet states during electron tunneling, which we conclude is dominated by momentum-term spin-orbit interactions that varies from 1.85 MHz up to 27.5 MHz depending on the magnetic field orientation. Finally, we exploit the tunability of the derivative of the Stark shift of one of the dots to reduce its sensitivity to electric noise and observe an 80 % increase in T * 2 . We conclude that the tuning of the spin-orbit interaction will be crucial for scalable quantum computing in silicon and that the optimal setting will depend on the exact mode of qubit operations used.Silicon-based spin qubits have attracted attention as candidates for large scale quantum computing thanks to their long coherence times, excellent controllability and fabrication techniques that are well established in the semiconductor industry [1][2][3][4][5][6][7][8][9][10][11][12][13]. Even though being weak compared, for instance, to GaAs, the spin-orbit interaction (SOI) significantly affects the behaviour of silicon spin qubits, especially through the dependency of the SOI on the valley state [12,14,15]. SOI is responsible for effects such as the Stark shift of the electron spin resonance (ESR) frequency, variation of Lande gfactors, and mixing between singlet (S) and polarized triplet (T − ) states [15][16][17][18]. These effects can be harnessed, for instance, to drive the ESR transition electrically via Stark shift or by exploiting the variation in the g-factors to address qubits individually with a global microwave (MW) field [14,[19][20][21]. In contrast, spin-orbit effects such as spin-flip tunneling and strong Stark shift can cause state leakage or increased sensitivity to electric noise [14,16,22]. Hence, understanding and controlling the SOI will be important for spin qubit control in larger arrays of dots in the future [23][24][25].Here, we fully characterize the SOI and demonstrate how we can tune it in a silicon metal-oxide-semiconductor * current address: Microsoft Quantum, (SiMOS) double quantum dot (QD) structure. The structure studied here is shown in Fig. 1b and described in Ref. [24]. We vary the directio...

The objective of this qualitative study of patients with osteoarthritis (OA) of the knee was to evaluate the influence of different pain patterns on their quality of life and to investigate their interpretation and coping strategies for the disease using patient interviews. Patients were recruited by convenience sampling in a private general practice clinic in Hong Kong. Those screened positive for OA of the knee were asked to self-evaluate their average pain score and classify the severity of their OA before attending a semi-structured interview by a research assistant. Twenty patients were interviewed and 98 codes were identified. The content was analyzed independently by two researchers who were not doing the interviews. Codes and themes generated were analyzed based on the grounded theory. A wide range of symptoms was described by patients with OA of the knee, in which pain was the most prominent symptom. Most patients (80%) described two different types of pain, mechanical and inflammatory pain, each presenting with a different pain quality and onset pattern. Most patients self-graded their OA severity at a level higher than their corresponding pain score, indicating that there may be other variables that patients would consider during self-evaluation of severity. More than half of the participants seek medical assistance late because their health-seeking behavior was affected by their perception of the problem, concern, and expectation from treatment. The study findings can help healthcare providers to understand and be aware of the existence of two pain patterns, mechanical and inflammatory pain in knee OA, as well as to appreciate the great variations of symptoms, the different perspectives, and the different coping and health-seeking behaviors among knee OA patients during their management. Finally, this study also provides a useful basis for further research on topics like factors that affect patients' self-evaluated disease severity and efficacy of interventions specific for the two different pain patterns associated with knee OA.

Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

Purpose: Previously, FTY720 was found to possess potent anticancer effects on various types of cancer. In the present study, we aimed to first verify the role of Runx2 in prostate cancer progression and metastasis, and, subsequently, assessed if FTY720 could modulate Runx2 expression, thus interfering downstream events regulated by this protein.Experimental Design: First, the association between Runx2 and prostate cancer progression was assessed using localized prostate cancer specimens and mechanistic investigation of Runx2-induced cancer aggressiveness was then carried out. Subsequently, the effect of FTY720 on Runx2 expression and transcriptional activity was investigated using PC-3 cells, which highly expressed Runx2 protein. Last, the involvement of Runx2 in FTY720-induced anticancer effects was evaluated by modulating Runx2 expression in various prostate cancer cell lines. Results: Runx2 nuclear expression was found to be up-regulated in prostate cancer and its expression could be used as a predictor of metastasis in prostate cancer. Further mechanistic studies indicated that Runx2 accelerated prostate cancer aggressiveness through promotion of cadherin switching, invasion toward collagen I, and Akt activation. Subsequently, we found that FTY720 treatment down-regulated Runx2 expression and its transcriptional activity, as well as inhibited its regulated downstream events. More importantly, silencing Runx2 in PC-3 enhanced FTY720-induced anticancer effects as well as cell viability inhibition, whereas overexpressing Runx2 in 22Rv1that expressed very low endogenous Runx2 protein conferred resistance in the same events. Conclusion: This study provided a novel mechanism for the anticancer effect of FTY720 on advanced prostate cancer, thus highlighting the therapeutic potential of this drug in treating this disease.