RESUMEN
B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent apoptosis. To address this cancer hallmark, a concerted effort has been made to induce apoptosis by inhibiting BCL-2 family proteins. A series of highly selective BCL-2 homology 3 (BH3) domain mimetics are in clinical use and in ongoing clinical trials for acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). These inhibitors serve as promising candidates, both as single agents or in combination therapy to improve patient outcomes. In other diseases such as follicular lymphoma, efficacy has been notably limited. There are also clinical problems with BCL-2 family inhibition, including drug resistance, disease relapse, tumour lysis syndrome, and clinically relevant cytopenias. Here, we provide a balanced view on both the clinical benefits of BCL-2 inhibition as well as the associated challenges.
Asunto(s)
Antineoplásicos , Neoplasias Hematológicas , Leucemia Linfocítica Crónica de Células B , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Hematológicas/metabolismo , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Apoptosis , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoAsunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Células Madre Hematopoyéticas , Interleucina-3 , Leucemia Mieloide Aguda , Proteínas Proto-Oncogénicas c-bcl-2 , Sulfonamidas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Citopenia , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/efectos de los fármacos , Interleucina-3/metabolismo , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Sulfonamidas/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Neutral silicon vacancy centers (SiV^{0}) in diamond are promising candidates for quantum applications; however, stabilizing SiV^{0} requires high-purity, boron-doped diamond, which is not a readily available material. Here, we demonstrate an alternative approach via chemical control of the diamond surface. We use low-damage chemical processing and annealing in a hydrogen environment to realize reversible and highly stable charge state tuning in undoped diamond. The resulting SiV^{0} centers display optically detected magnetic resonance and bulklike optical properties. Controlling the charge state tuning via surface termination offers a route for scalable technologies based on SiV^{0} centers, as well as charge state engineering of other defects.
RESUMEN
Color centers in diamond are promising platforms for quantum technologies. Most color centers in diamond discovered thus far emit in the visible or near-infrared wavelength range, which are incompatible with long-distance fiber communication and unfavorable for imaging in biological tissues. Here, we report the experimental observation of a new color center that emits in the telecom O-band, which we observe in silicon-doped bulk single crystal diamonds and microdiamonds. Combining absorption and photoluminescence measurements, we identify a zero-phonon line at 1221 nm and phonon replicas separated by 42 meV. Using transient absorption spectroscopy, we measure an excited state lifetime of around 270 ps and observe a long-lived baseline that may arise from intersystem crossing to another spin manifold.
RESUMEN
Neutral silicon vacancy (SiV^{0}) centers in diamond are promising candidates for quantum networks because of their excellent optical properties and long spin coherence times. However, spin-dependent fluorescence in such defects has been elusive due to poor understanding of the excited state fine structure and limited off-resonant spin polarization. Here we report the realization of optically detected magnetic resonance and coherent control of SiV^{0} centers at cryogenic temperatures, enabled by efficient optical spin polarization via previously unreported higher-lying excited states. We assign these states as bound exciton states using group theory and density functional theory. These bound exciton states enable new control schemes for SiV^{0} as well as other emerging defect systems.
RESUMEN
Matrix metalloproteinases (MMPs) and the related families of disintegrin metalloproteinases (ADAMs) and ADAMs with thrombospondin repeats (ADAMTSs) play a crucial role in extracellular matrix (ECM) turnover and shedding of cell-surface molecules. The proteolytic activity of metalloproteinases is post-translationally regulated by their endogenous inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs). Several MMPs, ADAMTSs and TIMPs have been reported to be endocytosed by the low-density lipoprotein receptor-related protein-1 (LRP-1). Different binding affinities of these proteins for the endocytic receptor correlate with different turnover rates which, together with differences in their mRNA expression, determines their nett extracellular levels. In this study, we used surface plasmon resonance to evaluate the affinity between LRP-1 and a number of MMPs, ADAMs, ADAMTSs, TIMPs and metalloproteinase/TIMP complexes. This identified MMP-1 as a new LRP-1 ligand. Among the proteins analyzed, TIMP-3 bound to LRP-1 with highest affinity (KD = 1.68 nM). Additionally, we found that TIMP-3 can facilitate the clearance of its target metalloproteinases by bridging their binding to LRP-1. For example, the free form of MMP-1 was found to have a KD of 34.6 nM for LRP-1, while the MMP-1/TIMP-3 complex had a sevenfold higher affinity (KD = 4.96 nM) for the receptor. TIMP-3 similarly bridged binding of MMP-13 and MMP-14 to LRP-1. TIMP-1 and TIMP-2 were also found to increase the affinity of target metalloproteinases for LRP-1, albeit to a lesser extent. This suggests that LRP-1 scavenging of TIMP/metalloproteinase complexes may be a general mechanism by which inhibited metalloproteinases are removed from the extracellular environment.
Asunto(s)
Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/metabolismo , Endocitosis , Humanos , Cinética , Complejos Multiproteicos/metabolismo , Unión Proteica , Inhibidor Tisular de Metaloproteinasa-3/antagonistas & inhibidores , Inhibidor Tisular de Metaloproteinasa-3/genéticaRESUMEN
Engineering coherent systems is a central goal of quantum science. Color centers in diamond are a promising approach, with the potential to combine the coherence of atoms with the scalability of a solid-state platform. We report a color center that shows insensitivity to environmental decoherence caused by phonons and electric field noise: the neutral charge state of silicon vacancy (SiV0). Through careful materials engineering, we achieved >80% conversion of implanted silicon to SiV0 SiV0 exhibits spin-lattice relaxation times approaching 1 minute and coherence times approaching 1 second. Its optical properties are very favorable, with ~90% of its emission into the zero-phonon line and near-transform-limited optical linewidths. These combined properties make SiV0 a promising defect for quantum network applications.
RESUMEN
Change history: In this Letter, the received date should be 20 December 2017, instead of 27 April 2018. This has been corrected online.
RESUMEN
Large-scale quantum networks promise to enable secure communication, distributed quantum computing, enhanced sensing and fundamental tests of quantum mechanics through the distribution of entanglement across nodes1-7. Moving beyond current two-node networks8-13 requires the rate of entanglement generation between nodes to exceed the decoherence (loss) rate of the entanglement. If this criterion is met, intrinsically probabilistic entangling protocols can be used to provide deterministic remote entanglement at pre-specified times. Here we demonstrate this using diamond spin qubit nodes separated by two metres. We realize a fully heralded single-photon entanglement protocol that achieves entangling rates of up to 39 hertz, three orders of magnitude higher than previously demonstrated two-photon protocols on this platform 14 . At the same time, we suppress the decoherence rate of remote-entangled states to five hertz through dynamical decoupling. By combining these results with efficient charge-state control and mitigation of spectral diffusion, we deterministically deliver a fresh remote state with an average entanglement fidelity of more than 0.5 at every clock cycle of about 100 milliseconds without any pre- or post-selection. These results demonstrate a key building block for extended quantum networks and open the door to entanglement distribution across multiple remote nodes.
RESUMEN
The silicon-vacancy center in diamond offers attractive opportunities in quantum photonics due to its favorable optical properties and optically addressable electronic spin. Here, we combine both to achieve all-optical coherent control of its spin states. We utilize this method to explore spin dephasing effects in an impurity-rich sample beyond the limit of phonon-induced decoherence: Employing Ramsey and Hahn-echo techniques at temperatures down to 40 mK we identify resonant coupling to a substitutional nitrogen spin bath as limiting decoherence source for the electron spin.
RESUMEN
Using a high-Q diamond microresonator (Q>300,000) interfaced with high-power-handling directly-written doped-glass waveguides, we demonstrate a Raman laser in an integrated platform pumped in the near-visible. Both TM-to-TE and TE-to-TE lasing is observed, with a Raman lasing threshold as low as 20 mW and Stokes power of over 1 mW at 120 mW pump power. Stokes emission is tuned over a 150 nm (60 THz) bandwidth of approximately 875 nm wavelength, corresponding to 17.5% of the center frequency.
RESUMEN
Spin impurities in diamond have emerged as a promising building block in a wide range of solid-state-based quantum technologies. The negatively charged silicon-vacancy centre combines the advantages of its high-quality photonic properties with a ground-state electronic spin, which can be read out optically. However, for this spin to be operational as a quantum bit, full quantum control is essential. Here we report the measurement of optically detected magnetic resonance and the demonstration of coherent control of a single silicon-vacancy centre spin with a microwave field. Using Ramsey interferometry, we directly measure a spin coherence time, T2*, of 115±9 ns at 3.6 K. The temperature dependence of coherence times indicates that dephasing and decay of the spin arise from single-phonon-mediated excitation between orbital branches of the ground state. Our results enable the silicon-vacancy centre spin to become a controllable resource to establish spin-photon quantum interfaces.
RESUMEN
Precise timekeeping is critical to metrology, forming the basis by which standards of time, length, and fundamental constants are determined. Stable clocks are particularly valuable in spectroscopy because they define the ultimate frequency precision that can be reached. In quantum metrology, the qubit coherence time defines the clock stability, from which the spectral linewidth and frequency precision are determined. We demonstrate a quantum sensing protocol in which the spectral precision goes beyond the sensor coherence time and is limited by the stability of a classical clock. Using this technique, we observed a precision in frequency estimation scaling in time T as T-3/2 for classical oscillating fields. The narrow linewidth magnetometer based on single spins in diamond is used to sense nanoscale magnetic fields with an intrinsic frequency resolution of 607 microhertz, which is eight orders of magnitude narrower than the qubit coherence time.
RESUMEN
The generation and control of fast switchable magnetic fields with large gradients on the nanoscale is of fundamental interest in material science and for a wide range of applications. However, it has not yet been possible to characterize those fields at high bandwidth with arbitrary orientations. Here, we measure the magnetic field generated by a hard-disk-drive write head with high spatial resolution and large bandwidth by coherent control of single electron and nuclear spins. We are able to derive field profiles from coherent spin Rabi oscillations close to the gigahertz range, measure magnetic field gradients on the order of 1â mTâ nm-1 and quantify axial and radial components of a static and dynamic magnetic field independent of its orientation. Our method paves the way for precision measurement of the magnetic fields of nanoscale write heads, which is important for future miniaturization of these devices.
RESUMEN
Complete control of the state of a quantum bit (qubit) is a fundamental requirement for any quantum information processing (QIP) system. In this context, all-optical control techniques offer the advantage of a well-localized and potentially ultrafast manipulation of individual qubits in multi-qubit systems. Recently, the negatively charged silicon vacancy centre (SiV-) in diamond has emerged as a novel promising system for QIP due to its superior spectral properties and advantageous electronic structure, offering an optically accessible Λ-type level system with large orbital splittings. Here, we report on all-optical resonant as well as Raman-based coherent control of a single SiV- using ultrafast pulses as short as 1 ps, significantly faster than the centre's phonon-limited ground state coherence time of about 40 ns. These measurements prove the accessibility of a complete set of single-qubit operations relying solely on optical fields and pave the way for high-speed QIP applications using SiV- centres.
RESUMEN
We experimentally demonstrate the protection of a room-temperature hybrid spin register against environmental decoherence by performing repeated quantum error correction whilst maintaining sensitivity to signal fields. We use a long-lived nuclear spin to correct multiple phase errors on a sensitive electron spin in diamond and realize magnetic field sensing beyond the time scales set by natural decoherence. The universal extension of sensing time, robust to noise at any frequency, demonstrates the definitive advantage entangled multiqubit systems provide for quantum sensing and offers an important complement to quantum control techniques.
RESUMEN
Efficient collection of the broadband fluorescence from the diamond nitrogen vacancy (NV) center is essential for a range of applications in sensing, on-demand single photon generation, and quantum information processing. Here, we introduce a circular "bullseye" diamond grating which enables a collected photon rate of (2.7 ± 0.09) × 10(6) counts per second from a single NV with a spin coherence time of 1.7 ± 0.1 ms. Back-focal-plane studies indicate efficient redistribution of the NV photoluminescence into low-NA modes by the bullseye grating.
RESUMEN
A central aim of quantum information processing is the efficient entanglement of multiple stationary quantum memories via photons. Among solid-state systems, the nitrogen-vacancy centre in diamond has emerged as an excellent optically addressable memory with second-scale electron spin coherence times. Recently, quantum entanglement and teleportation have been shown between two nitrogen-vacancy memories, but scaling to larger networks requires more efficient spin-photon interfaces such as optical resonators. Here we report such nitrogen-vacancy-nanocavity systems in the strong Purcell regime with optical quality factors approaching 10,000 and electron spin coherence times exceeding 200 µs using a silicon hard-mask fabrication process. This spin-photon interface is integrated with on-chip microwave striplines for coherent spin control, providing an efficient quantum memory for quantum networks.
RESUMEN
Spin impurities in diamond can be versatile tools for a wide range of solid-state-based quantum technologies, but finding spin impurities that offer sufficient quality in both photonic and spin properties remains a challenge for this pursuit. The silicon-vacancy center has recently attracted much interest because of its spin-accessible optical transitions and the quality of its optical spectrum. Complementing these properties, spin coherence is essential for the suitability of this center as a spin-photon quantum interface. Here, we report all-optical generation of coherent superpositions of spin states in the ground state of a negatively charged silicon-vacancy center using coherent population trapping. Our measurements reveal a characteristic spin coherence time, T2*, exceeding 45 nanoseconds at 4 K. We further investigate the role of phonon-mediated coupling between orbital states as a source of irreversible decoherence. Our results indicate the feasibility of all-optical coherent control of silicon-vacancy spins using ultrafast laser pulses.
RESUMEN
One of the most striking features of quantum mechanics is the profound effect exerted by measurements alone. Sophisticated quantum control is now available in several experimental systems, exposing discrepancies between quantum and classical mechanics whenever measurement induces disturbance of the interrogated system. In practice, such discrepancies may frequently be explained as the back-action required by quantum mechanics adding quantum noise to a classical signal. Here, we implement the "three-box" quantum game [Aharonov Y, et al. (1991) J Phys A Math Gen 24(10):2315-2328] by using state-of-the-art control and measurement of the nitrogen vacancy center in diamond. In this protocol, the back-action of quantum measurements adds no detectable disturbance to the classical description of the game. Quantum and classical mechanics then make contradictory predictions for the same experimental procedure; however, classical observers are unable to invoke measurement-induced disturbance to explain the discrepancy. We quantify the residual disturbance of our measurements and obtain data that rule out any classical model by â³7.8 standard deviations, allowing us to exclude the property of macroscopic state definiteness from our system. Our experiment is then equivalent to the test of quantum noncontextuality [Kochen S, Specker E (1967) J Math Mech 17(1):59-87] that successfully addresses the measurement detectability loophole.