Controlling spin relaxation with a cavity.

Spontaneous emission of radiation is one of the fundamental mechanisms by which an excited quantum system returns to equilibrium. For spins, however, spontaneous emission is generally negligible compared to other non-radiative relaxation processes because of the weak coupling between the magnetic dipole and the electromagnetic field. In 1946, Purcell realized that the rate of spontaneous emission can be greatly enhanced by placing the quantum system in a resonant cavity. This effect has since been used extensively to control the lifetime of atoms and semiconducting heterostructures coupled to microwave or optical cavities, and is essential for the realization of high-efficiency single-photon sources. Here we report the application of this idea to spins in solids. By coupling donor spins in silicon to a superconducting microwave cavity with a high quality factor and a small mode volume, we reach the regime in which spontaneous emission constitutes the dominant mechanism of spin relaxation. The relaxation rate is increased by three orders of magnitude as the spins are tuned to the cavity resonance, demonstrating that energy relaxation can be controlled on demand. Our results provide a general way to initialize spin systems into their ground state and therefore have applications in magnetic resonance and quantum information processing. They also demonstrate that the coupling between the magnetic dipole of a spin and the electromagnetic field can be enhanced up to the point at which quantum fluctuations have a marked effect on the spin dynamics; as such, they represent an important step towards the coherent magnetic coupling of individual spins to microwave photons.

Multimode Storage of Quantum Microwave Fields in Electron Spins over 100 ms.

We report long coherence times (up to 300 ms) for near-surface bismuth donor electron spins in silicon coupled to a superconducting microresonator, biased at a clock transition. This enables us to demonstrate the partial absorption of a train of weak microwave fields in the spin ensemble, their storage for 100 ms, and their retrieval, using a Hahn-echo-like protocol. Phase coherence and quantum statistics are preserved in the storage.

Fast Gate-Based Readout of Silicon Quantum Dots Using Josephson Parametric Amplification.

Spins in silicon quantum devices are promising candidates for large-scale quantum computing. Gate-based sensing of spin qubits offers a compact and scalable readout with high fidelity, however, further improvements in sensitivity are required to meet the fidelity thresholds and measurement timescales needed for the implementation of fast feedback in error correction protocols. Here, we combine radio-frequency gate-based sensing at 622 MHz with a Josephson parametric amplifier, that operates in the 500-800 MHz band, to reduce the integration time required to read the state of a silicon double quantum dot formed in a nanowire transistor. Based on our achieved signal-to-noise ratio, we estimate that singlet-triplet single-shot readout with an average fidelity of 99.7% could be performed in 1 µs, well below the requirements for fault-tolerant readout and 30 times faster than without the Josephson parametric amplifier. Additionally, the Josephson parametric amplifier allows operation at a lower radio-frequency power while maintaining identical signal-to-noise ratio. We determine a noise temperature of 200 mK with a contribution from the Josephson parametric amplifier (25%), cryogenic amplifier (25%) and the resonator (50%), showing routes to further increase the readout speed.

Linear Hyperfine Tuning of Donor Spins in Silicon Using Hydrostatic Strain.

We experimentally study the coupling of group V donor spins in silicon to mechanical strain, and measure strain-induced frequency shifts that are linear in strain, in contrast to the quadratic dependence predicted by the valley repopulation model (VRM), and therefore orders of magnitude greater than that predicted by the VRM for small strains |ϵ|<10^{-5}. Through both tight-binding and first principles calculations we find that these shifts arise from a linear tuning of the donor hyperfine interaction term by the hydrostatic component of strain and achieve semiquantitative agreement with the experimental values. Our results provide a framework for making quantitative predictions of donor spins in silicon nanostructures, such as those being used to develop silicon-based quantum processors and memories. The strong spin-strain coupling we measure (up to 150 GHz per strain, for Bi donors in Si) offers a method for donor spin tuning-shifting Bi donor electron spins by over a linewidth with a hydrostatic strain of order 10^{-6}-as well as opportunities for coupling to mechanical resonators.

Hybrid optical-electrical detection of donor electron spins with bound excitons in silicon.

Electrical detection of spins is an essential tool for understanding the dynamics of spins, with applications ranging from optoelectronics and spintronics, to quantum information processing. For electron spins bound to donors in silicon, bulk electrically detected magnetic resonance has relied on coupling to spin readout partners such as paramagnetic defects or conduction electrons, which fundamentally limits spin coherence times. Here we demonstrate electrical detection of donor electron spin resonance in an ensemble by transport through a silicon device, using optically driven donor-bound exciton transitions. We measure electron spin Rabi oscillations, and obtain long electron spin coherence times, limited only by the donor concentration. We also experimentally address critical issues such as non-resonant excitation, strain, and electric fields, laying the foundations for realizing a single-spin readout method with relaxed magnetic field and temperature requirements compared with spin-dependent tunnelling, enabling donor-based technologies such as quantum sensing.

Electrically detected magnetic resonance of neutral donors interacting with a two-dimensional electron gas.

We have measured the electrically detected magnetic resonance of donor-doped silicon field-effect transistors in resonant X- (9.7 GHz) and W-band (94 GHz) microwave cavities. The two-dimensional electron gas resonance signal increases by 2 orders of magnitude from X to W band, while the donor resonance signals are enhanced by over 1 order of magnitude. Bolometric effects and spin-dependent scattering are inconsistent with the observations. We propose that polarization transfer from the donor to the two-dimensional electron gas is the main mechanism giving rise to the spin resonance signals.

High-cooperativity coupling of electron-spin ensembles to superconducting cavities.

Electron spins in solids are promising candidates for quantum memories for superconducting qubits because they can have long coherence times, large collective couplings, and many qubits could be encoded into spin waves of a single ensemble. We demonstrate the coupling of electron-spin ensembles to a superconducting transmission-line cavity at strengths greatly exceeding the cavity decay rates and comparable to the spin linewidths. We also perform broadband spectroscopy of ruby (Al2O3:Cr(3+)) at millikelvin temperatures and low powers, using an on-chip feedline. In addition, we observe hyperfine structure in diamond P1 centers.

Entangling remote nuclear spins linked by a chromophore.

Molecular nanostructures may constitute the fabric of future quantum technologies, if their degrees of freedom can be fully harnessed. Ideally one might use nuclear spins as low-decoherence qubits and optical excitations for fast controllable interactions. Here, we present a method for entangling two nuclear spins through their mutual coupling to a transient optically excited electron spin, and investigate its feasibility through density-functional theory and experiments on a test molecule. From our calculations we identify the specific molecular properties that permit high entangling power gates under simple optical and microwave pulses; synthesis of such molecules is possible with established techniques.

Pulsed electron spin resonance spectroscopy in the Purcell regime.

In EPR, spin relaxation is typically governed by interactions with the lattice or other spins. However, it has recently been shown that given a sufficiently strong spin-resonator coupling and high resonator quality factor, the spontaneous emission of microwave photons from the spins into the resonator can become the main relaxation mechanism, as predicted by Purcell. With increasing attention on the use of microresonators for EPR to achieve high spin-number sensitivity it is important to understand how this novel regime influences measured EPR signals, for example the amplitude and temporal shape of the spin-echo. We study this regime theoretically and experimentally, using donor spins in silicon, under different conditions of spin-linewidth and coupling homogeneity. When the spin-resonator coupling is distributed inhomogeneously, we find that the effective spin-echo relaxation time measured in a saturation recovery sequence strongly depends on the parameters for the detection echo. When the spin linewidth is larger than the resonator bandwidth, the different Fourier components of the spin echo relax with different characteristic times - due to the role of the resonator in driving relaxation - which results in the temporal shape of the echo becoming dependent on the repetition time of the experiment.

NT-proBNP does not rise on acute ascent to high altitude.

The response of brain natriuretic peptide (BNP) to acute ascent to altitude is of interest as a surrogate for ventricular function and because BNP is involved in the normal homeostasis of the pulmonary vasculature. The structurally related hormone atrial natriuretic pressure (ANP) has been demonstrated to be elevated at altitude and implicated in natriuresis. We measured plasma concentrations of ANP and NT-proBNP (a more stable BNP precursor) in 10 healthy non-HAPE-susceptible lowlanders during acute exposure to 5200 m on the Apex 2 expedition to Bolivia. Systolic pulmonary artery pressure (PASP) was measured using tricuspid regurgitant jet estimation by echocardiography. Despite a significant rise in the PASP, NT-proBNP did not rise. A small decrease in NT-pro BNP occurred after 7 days at high altitude. There was no significant change in ANP levels. The lack of any increase in NT-proBNP in healthy resting subjects supports the view that ventricular function is well preserved and suggests that BNP is not playing a significant role in altered pulmonary artery pressure.

Value of BNP to estimate cardiac risk in patients on cardioactive treatment in primary care.

UNLABELLED: Cardiac dysfunction may be suspected in patients with cardiovascular disease but identifying those with the highest risk is problematic. B-type natriuretic peptide (BNP) is a strong marker of heart failure in un-treated patients. This study evaluates a combined BNP and clinical algorithm for detecting cardiac dysfunction and the risk of death, in patients receiving cardioactive medication. METHODS: 459 stable general practice patients, who were taking typical heart failure drugs for any indication, were included. Echocardiography, ECG, and assay of NT-proANP and BNP (two methods) were performed. Regression models were used to identify items in a Risk Score to detect cardiac dysfunction. RESULTS: A Risk Score based on history of myocardial infarction (1 point), abnormal ECG (2 points), atrial fibrillation (1 point) and raised BNP (1-2 points) detected cardiac dysfunction with an AUC of ROC of 0.85. A Risk Score > or = 2 had a sensitivity of 90%, specificity of 58%, and positive and negative predictive values of 37% and 96%. Risk Score and LVEF<0.36 also predicted mortality. Abnormal BNP defined as either >100 pg/ml (Shionogi), or as age and sex related values, had similar predictive value. CONCLUSION: In patients on cardioactive medication, a structured Risk Score based on raised BNP, history of MI, atrial fibrillation and abnormal ECG was useful for identifying patients for immediate further examination and those who could be evaluated later.

Reaching the quantum limit of sensitivity in electron spin resonance.

The detection and characterization of paramagnetic species by electron spin resonance (ESR) spectroscopy is widely used throughout chemistry, biology and materials science, from in vivo imaging to distance measurements in spin-labelled proteins. ESR relies on the inductive detection of microwave signals emitted by the spins into a coupled microwave resonator during their Larmor precession. However, such signals can be very small, prohibiting the application of ESR at the nanoscale (for example, at the single-cell level or on individual nanoparticles). Here, using a Josephson parametric microwave amplifier combined with high-quality-factor superconducting microresonators cooled at millikelvin temperatures, we improve the state-of-the-art sensitivity of inductive ESR detection by nearly four orders of magnitude. We demonstrate the detection of 1,700 bismuth donor spins in silicon within a single Hahn echo with unit signal-to-noise ratio, reduced to 150 spins by averaging a single Carr-Purcell-Meiboom-Gill sequence. This unprecedented sensitivity reaches the limit set by quantum fluctuations of the electromagnetic field instead of thermal or technical noise, which constitutes a novel regime for magnetic resonance. The detection volume of our resonator is ∼ 0.02 nl, and our approach can be readily scaled down further to improve sensitivity, providing a new versatile toolbox for ESR at the nanoscale.

XactMice: humanizing mouse bone marrow enables microenvironment reconstitution in a patient-derived xenograft model of head and neck cancer.

The limitations of cancer cell lines have led to the development of direct patient-derived xenograft models. However, the interplay between the implanted human cancer cells and recruited mouse stromal and immune cells alters the tumor microenvironment and limits the value of these models. To overcome these constraints, we have developed a technique to expand human hematopoietic stem and progenitor cells (HSPCs) and use them to reconstitute the radiation-depleted bone marrow of a NOD/SCID/IL2rg(-/-) (NSG) mouse on which a patient's tumor is then transplanted (XactMice). The human HSPCs produce immune cells that home into the tumor and help replicate its natural microenvironment. Despite previous passage on nude mice, the expression of epithelial, stromal and immune genes in XactMice tumors aligns more closely to that of the patient tumor than to those grown in non-humanized mice-an effect partially facilitated by human cytokines expressed by both the HSPC progeny and the tumor cells. The human immune and stromal cells produced in the XactMice can help recapitulate the microenvironment of an implanted xenograft, reverse the initial genetic drift seen after passage on non-humanized mice and provide a more accurate tumor model to guide patient treatment.

Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat.

Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridemia, and hypertension map to a single region on rat chromosome 4. Genetic analysis of an SHR derived from a National Institutes of Health colony led to the identification of a causative mutation in the SHR Cd36. We have investigated glucose and fatty acid metabolism in the stroke-prone SHR (SHRSP). We demonstrate defects in insulin action on 2-deoxy-D-glucose transport (SHRSP 3.3 +/- 1.5 vs. 21.0 +/- 7.4 pmol x min(-1) x [20 microl packed cells](-1), SHRSP vs. WKY, respectively, P = 0.01) and inhibition of catecholamine-stimulated lipolysis (P < 0.05 at all concentrations of insulin) in adipocytes isolated from SHRSP. In contrast, basal levels of catecholamine-stimulated nonesterified free fatty acid (NEFA) release and plasma levels of NEFA are similar in SHRSP and WKY. These results are in agreement with the data on the SHR.4 congenic strain, which suggested that the QTL containing Cd36 mutations accounted for the entire defect in basal catecholamine action but only for approximately 40% of the SHR defect in insulin action. In the SHR, both abnormalities appear consequent of defective Cd36 expression. Because Cd36 sequence and expression are apparently normal in SHRSP, it is likely that the molecular mechanism for defective insulin action in this strain is caused by a gene(s) different than Cd36.

Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure.

OBJECTIVES: This study was designed to compare different proposed methods of assessing adherence with angiotensin-converting enzyme (ACE) inhibitor (ACEI) therapy in chronic heart failure. BACKGROUND: The use of ACEIs in chronic heart failure gives us a unique opportunity to assess a patient's adherence by measuring whether the expected biochemical effect of an ACEI is present in the patient's bloodstream. In fact, there are several different ways of assessing ACE in vivo: these are serum ACE activity itself, plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), urine AcSDKP, plasma angiotensin I (AI), plasma angiotensin II (AII), or the AII/AI ratio. METHODS: Patients with chronic heart failure (n = 39) were randomized to regimens of ACEI nonadherence for one week, ACEI adherence for one week or two versions of partial adherence for one week, after which the above six tests were performed. RESULTS: All six tests significantly distinguished between full nonadherence for one week and full or partial adherence. Only plasma AcSDKP produced a significantly different result between partial adherence and either full adherence or full nonadherence for one week. In terms of their ability to distinguish full nonadherence from full adherence, plasma AcSDKP was 89% sensitive and 100% specific with an area under its ROC of 0.95. Corresponding figures for urine AcSDKP were 92%, 97% and 0.95 and for serum ACE they were 86%, 95% and 0.90. CONCLUSIONS: All six tests distinguished full nonadherence from all other forms of adherence. The rank order of performance was plasma AcSDKP, urine AcSDKP, serum ACE, AII/AI ratio and plasma AII followed by plasma AI.

Endothelin B receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction.

OBJECTIVES: This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ET(A) and ET(B) agonist, with ET-3, a selective ET(B) receptor agonist. BACKGROUND: Knowledge of the functional importance of ET(B) receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ET(A) and ET(B) receptors are required to fully prevent vasoconstriction to endogenously produced ET-1. METHODS: We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. RESULTS: Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean +/- SEM 100 +/- 3 to 105 +/- 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 +/- 142 to 2,055 +/- 164 dyn/s/cm(-5), p < 0.001) and a fall in cardiac index (2.44 +/- 0.21 to 2.22 +/- 0.20 liters/min/m , p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 +/- 6 to 105 +/- 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 +/- 210 to 1,918 +/- 245 dyn/s/cm(-5), p < 0.01) and a fall in cardiac index (2.66 +/- 0.28 to 2.42 +/- 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group. CONCLUSIONS: Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ET(B) receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD.

Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria.

OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.

Haemodynamic effects of angiotensin converting enzyme inhibition after cardiopulmonary bypass in dogs.

Recent studies have suggested a possible causative relationship between elevated plasma levels of Angiotensin II (AII) and the vasoconstriction associated with conventional cardiopulmonary bypass. The haemodynamic effects of SQ14225, a specific angiotensin converting enzyme inhibitor, have been studied in a group of five dogs submitted to a 60 min period of cardiopulmonary bypass (CPB). A 20 min infusion of SQ14225 in a dose of 2 microgram .kg-1 .h-1 was administered to each dog 2 h after the end of the period of CPB. Measurements of peripheral vascular resistance index (PVRI), cardiac index (CI) and plasma levels of Angiotensin II were obtained at the start and end of the infusion period. The results in the five blocked dogs were compared with a control series of ten unblocked dogs submitted to an identical cardiopulmonary bypass regine. In the blocked dogs, PVRI fell significantly during infusion of SQ14225 from 38.27 units to 21.70 units (P <0.01). There was a simultaneous significant increase in cardiac index from 3.00 to 3.98 litre.m2 .min-1 (P <0.01). Plasma Angiotensin 11 levels fell in the blocked dogs from 57 to 11.5 pg.cm-2 during the infusion period (normal levels <15 pg.cm-3). In the control unblocked dogs, there was no corresponding fall in PVRI, no rise in cardiac index, and no fall in elevated plasma AII levels. The difference between the groups were statistically highly significant (P <0.005). These results indicate that reduction in elevated plasma AII levels after CPB using converting enzyme inhibitor SQ14225 is associated with a significant fall in peripheral vascular resistance and a significant rise in cardiac index. In addition, the study confirms the causative relationship between elevated plasma levels of Angiotensin II and the increased vasoconstriction associated with non-pulsatile CPB.

Angiotensin-induced myocardial necrosis and renal failure in the rabbit: distribution of lesions and severity in relation to plasma angiotensin II concentration and arterial pressure.

Angiotensin II was infused into conscious rabbits at various doses from 0.001 to 0.5 microgram . kg-1 . min-1 for 24 h, and caused multifocal myocardial necrosis, renal tubular necrosis and acute renal failure. The myocardial necroses were found principally in the left ventricle; only at the highest doses of angiotensin II were right ventricular lesions present. The endocardium was not involved and no arterial or arteriolar lesions were seen. Mean arterial plasma angiotensin II concentration during angiotensin infusion was closely correlated with the increase in arterial pressure, the height of the plasma urea at the end of the infusion and the severity of the induced myocardial lesions. The myocardial necroses could be a consequence of the induced hypertension, or a direct effect of angiotensin II, or a combination of effects, although their predominance in the left ventricle suggests high systemic arterial pressure is an important factor. Cardiac lesions were observed with plasma angiotensin II concentrations only some 2 to 3 fold normal values; it is therefore possible that similar myocardial abnormalities might occur as a result of rises in endogenous renin, for example, in experimental or clinical renovascular hypertension.

Endothelin-1 has haemodynamic effects at pathophysiological concentrations in patients with left ventricular dysfunction.

OBJECTIVES: Plasma levels of immunoreactive endothelin-1 (ET-1) are raised in chronic heart failure. Whether plasma ET-1 contributes to the haemodynamic derangement found in chronic heart failure is not known. We investigated the effects of exogenous ET-1 on the pulmonary and systemic vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. METHODS: ET-1 was infused at 1, 5 and 15 pmol/min into a distal pulmonary artery of ten patients with LVD to achieve plasma concentrations of ET-1 similar to those found in patients with heart failure and pulmonary hypertension. Haemodynamics were measured using a pulmonary thermodilution catheter and an arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. RESULTS: Systemic haemodynamic changes occurred with ET-1 infusion: mean arterial pressure (100 +/- 3 [standard error of the mean]) to 107 +/- 3 mmHg; p < 0.01) and systemic vascular resistance (1699 +/- 118 to 2033 +/- 135 dynes s/cm5; p < 0.001) rose, while the cardiac index fell from 2.43 +/- 0.17 to 2.20 +/- 0.16 l/min/m2 (p < 0.002). Mean pulmonary artery pressure (21 +/- 2 mmHg) and pulmonary vascular resistance (151 +/- 14 to 147 +/- 14 dynes s/cm5) did not change however. CONCLUSIONS: Exogenous ET-1, when infused to achieve plasma concentrations similar to those in severe heart failure and pulmonary hypertension, causes systemic but not pulmonary vasoconstriction.