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Coherent excitation of an ensemble of quantum objects underpins quantum many-body phenomena and offers the opportunity to realize a memory that stores quantum information. Thus far, a deterministic and coherent interface between a spin qubit and such an ensemble has remained elusive. In this study, we first used an electron to cool the mesoscopic nuclear spin ensemble of a semiconductor quantum dot to the nuclear sideband–resolved regime.We then implemented an all-optical approach to access individual quantized electronic-nuclear spin transitions. Lastly, we performed coherent optical rotations of a single collective nuclear spin excitation—a spin wave. These results constitute the building blocks of a dedicated local memory per quantum-dot spin qubit and promise a solid-state platform for quantum-state engineering of isolated many-body systems.

Accessing an ensemble of coherently interacting objects at the level of single quanta via a proxy qubit is transformative in the investigations of emergent quantum phenomena. An isolated nuclear spin ensemble is a remarkable platform owing to its coherence, but sensing its excitations with single spin precision has remained elusive. Here we achieve quantum sensing of a single nuclear-spin excitation (a nuclear magnon) in a dense ensemble of approximately 80,000 nuclei. A Ramsey measurement on the electron proxy qubit enables us to sense the hyperfine shift induced by a single nuclear magnon. We resolve multiple magnon modes distinguished by atomic species and spin polarity via the spectral dependence of this hyperfine shift. Finally, we observe the time-dependent shift induced by collective Rabi oscillations, revealing the competition between the buildup of quantum correlations and decoherence in the ensemble. These techniques could be extended to probe the engineered quantum states of the ensemble such as long-lived memory states.A single excitation in a semiconductor nuclear spin ensemble is detected with parts-per-million accuracy using the coupling between the ensemble and an electron-spin quantum dot.

The interaction between a confined electron and the nuclei of an optically active quantum dot provides a uniquely rich manifestation of the central spin problem. Coherent qubit control combines with an ultrafast spin–photon interface to make these confined spins attractive candidates for quantum optical networks. Reaching the full potential of spin coherence has been hindered by the lack of knowledge of the key irreversible environment dynamics. Through all-optical Hahn echo decoupling we now recover the intrinsic coherence time set by the interaction with the inhomogeneously strained nuclear bath. The high-frequency nuclear dynamics are directly imprinted on the electron spin coherence, resulting in a dramatic jump of coherence times from few tens of nanoseconds to the microsecond regime between 2 and 3 T magnetic field and an exponential decay of coherence at high fields. These results reveal spin coherence can be improved by applying large magnetic fields and reducing strain inhomogeneity. Spins confined to quantum dots are a possible qubit, but the mechanism that limits their coherence is unclear. Here, the authors use an all-optical Hahn-echo technique to determine the intrinsic coherence time of such spins set by its interaction with the inhomogeneously strained nuclear bath.

Quantum control of solid-state spin qubits typically involves pulses in the microwave domain, drawing from the well-developed toolbox of magnetic resonance spectroscopy. Driving a solid-state spin by optical means offers a high-speed alternative, which in the presence of limited spin coherence makes it the preferred approach for high-fidelity quantum control. Bringing the full versatility of magnetic spin resonance to the optical domain requires full phase and amplitude control of the optical fields. Here, we imprint a programmable microwave sequence onto a laser field and perform electron spin resonance in a semiconductor quantum dot via a two-photon Raman process. We show that this approach yields full SU(2) spin control with over \\[98 \\%\\]\\[\\pi\\]-rotation fidelity. We then demonstrate its versatility by implementing a particular multi-axis control sequence, known as spin locking. Combined with electron-nuclear Hartmann–Hahn resonances which we also report in this work, this sequence will enable efficient coherent transfer of a quantum state from the electron spin to the mesoscopic nuclear ensemble.

Background Aquagenic pruritus (AP), an intense sensation of scratching induced after water contact, is the most troublesome aspect of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). Mostly described in polycythemia vera (PV, ~ 40%), it is also present in essential thrombocythemia (ET) and primary myelofibrosis (PMF) (10%). Even if this symptom can decrease or disappear under cytoreductive treatments, 30% of treated MPN patients still persist with a real impact on the quality of life (QoL). Because its pathophysiology is poorly understood, efficient symptomatic treatments of AP are missing. The neuropeptide substance P (SP) plays a crucial role in the induction of pruritus. Several studies showed the efficacy of aprepitant, an antagonist of SP receptor (NK-1R), in the treatment of chronic pruritus but never evaluated in AP. The objectives of APHYPAP are twofold: a clinical aim with the evaluation of the efficacy of two drugs in the treatment of a persistent AP for MPN patients and a biological aim to find clues to elucidate AP pathophysiology. Methods/design A multicentric, double-blind, double-placebo, randomized study will include 80 patients with MPN (PV or ET or PMF) treated since at least 6 months for their hemopathy but suffering from a persistent AP (VAS intensity ≥6/10). Patients will be randomized between aprepitant (80 mg daily) + placebo to match to hydroxyzine OR hydroxyzine (25 mg daily) + placebo to match to aprepitant for 14 days. At D0, baseline information will be collected and drugs dispense. Outcome measures will be assessed at D15, D30, D45, and D60. The primary study endpoint will be the reduction of pruritus intensity below (or equal) at 3/10 on VAS at D15. Secondary outcome measures will include the number of patients with a reduction or cessation of AP at D15 or D60; evaluation of QoL and AP characteristics at D0, D15, D30, D45, and D60 with MPN-SAF and AP questionnaires, respectively; modification of plasmatic concentrations of cytokines and neuropeptides at D0, D15, D30, and D60; and modification of epidermal innervation density and pruriceptor expression at D0 and D15. Discussion The APHYPAP trial will examine the efficacy of aprepitant vs hydroxyzine (reference treatment for AP) to treat persistent AP in MPN patients. The primary objective is to demonstrate the superiority of aprepitant vs hydroxyzine to treat persistent AP of MPN patients. The treatment received will be considered efficient if the AP intensity will be reduced at 3/10 or below on VAS after 14 days of treatment. The results of this study may provide a new treatment option for this troublesome symptom and also give us more insights in the pathophysiology understanding of AP. Trial registration APHYPAP. NCT03808805 , first posted: January 18, 2019; last update posted: June 10, 2021. EudraCT 2018-090426-66

Background Skin, and epidermis, is innervated by sensory nerve fibres. Interactions between them and signal transduction are only partially elucidated in physiological/pathological conditions, especially in pruritus. Objectives To study the mechanisms involved in pruritus in vitro, we developed a skin explant model re‐innervated by sensory neurons. Methods This model is based on the co‐culture of human skin explants and sensory neurons from dorsal root ganglia of rats. Innervation and the expression of protease activated receptor 2 (PAR2), transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin one (TRPA1) was analysed by immunostaining. The response of the model to TRPV1, PAR2 and TRPA1 agonists was analysed by patch‐clamp, qPCR and enzyme‐linked immunosorbent assay. Results After 5 days of re‐innervating nerve fibres was evidenced in the epidermis. Re‐innervation was correlated with decrease of epidermal thickness and the number of apoptotic cells in the tissue. The major actors of non‐histaminergic itch (PAR‐2, thymic stromal lymphopoietin [TSLP], TSLP‐R, TRPA1 and TRPV1) were expressed in neurons and/or epidermal cells of skin explants. After topical exposure of TRPV1‐(Capsaicin), TRPA1‐(Polygodial) and PAR2‐agonist (SLIGKV‐NH2) activation of reinnervating neurons could be shown in patch‐clamp analysis. The release of TSLP was increased with capsaicin or SLIGKV but decreased with polygodial. Release of CGRP was increased by capsaicin and polygodial but decreased with SLIGKV. Activation by SLIGKV showed a decrease of VEGF; polygodial induced an increase of TSLP, Tumour necrosis factor (TNF) and nerve growth factor and capsaicin lead to a decrease of sema3 and TNF expression. Conclusion The present model is suitable for studying itch and neurogenic inflammation pathways in vitro. We observed that activation of TRPV1, TRPA1 and PAR‐2 leads to different response profiles in re‐innervated skin explants.

Background Pruritus is a symptom frequently associated with systemic diseases, particularly hematological disorders. Objectives The aim of this study was to evaluate the association of pruritus with morbidity in myeloproliferative neoplasms (MPN). Methods A systematic review of the literature was performed using two databases (Pubmed and Embase). Studies were included if they were published between January 2000 and August 2022 and addressed an association between pruritus and morbidity or survival in MPN patients. Results Ten articles were selected for the systematic review, 6 including patients with polycythemia vera (PV), 1 with essential thrombocythemia (ET), 2 with primary myelofibrosis (PMF) and 1 including both ET and PV. While 2 studies found no significant association between pruritus and mortality, 2 studies found a significant association between pruritus and improved survival. Three studies reported a statistically significant association between pruritus and an increase in thromboembolic events, while one study did not. One study showed an association between the presence of pruritus and sleep disturbance in PV. One study demonstrated an association between pruritus and the presence of depressive symptoms in PV. Two studies found a significant association between disease progression and the presence of pruritus, while three studies did not. Conclusions While pruritus appears to influence sleep quality and the onset of depressive symptoms, the effect of pruritus on mortality is more controversial, but the presence of pruritus might be associated with better survival. PROSPERO Number CRD42022316850. Summary This study was conducted to investigate the association of pruritus with morbidity in myeloproliferative neoplasms (MPN). Pruritus was associated with poor sleep quality and depressive symptom. The effect of pruritus on mortality is more controversial. Special attention should be paid to patients with pruritus to identify their co‐morbidities as effectively as possible.

The control of single spins in solids is a key but challenging step for any spin-based solid-state quantumcomputing device. Thanks to their expected long coherence time, localized spins on magnetic atoms in a semiconductor host could be an interesting media to store quantum information in the solid state. Optical probing and control of the spin of individual or pairs of Manganese (Mn) atoms (S = 5/2) have been obtained in II-VI and IIIV semiconductor quantum dots during the last years. In this paper, we review recently developed optical control experiments of the spin of an individual Mn atoms in II-VI semiconductor self-assembled or strain-free quantum dots (QDs).We first show that the fine structure of the Mn atom and especially a strained induced magnetic anisotropy is the main parameter controlling the spin memory of the magnetic atom at zero magnetic field. We then demonstrate that the energy of any spin state of a Mn atom or pairs of Mn atom can be independently tuned by using the optical Stark effect induced by a resonant laser field. The strong coupling with the resonant laser field modifies the Mn fine structure and consequently its dynamics.We then describe the spin dynamics of a Mn atom under this strong resonant optical excitation. In addition to standard optical pumping expected for a resonant excitation, we show that the Mn spin population can be trapped in the state which is resonantly excited. This effect is modeled considering the coherent spin dynamics of the coupled electronic and nuclear spin of the Mn atom optically dressed by a resonant laser field. Finally, we discuss the spin dynamics of a Mn atom in strain-free QDs and show that these structures should permit a fast optical coherent control of an individual Mn spin.

The long-term stability of Inconel 718 and Waspaloy forgings in the 600 °C to 850 °C temperature range and up to 10,000 hours was studied by means of mechanical tests and microstructural analyses. Hardness and tensile properties were found to decrease with increasing over-aging time and temperature. The comparative analysis of tensile results of both alloys indicates that they exhibit an equivalent stability over time if the over-aging temperature of Waspaloy is increased by 50 °C to 100 °C compared to Inconel 718. No detrimental intermetallic precipitation at grain boundaries has been detected in both alloys. Microstructure characterizations performed by scanning electron microscopy indicate that the higher stability of Waspaloy can be attributed to the slower kinetics of coarsening and dissolution of γ′ precipitates with respect to γ″ precipitates that account for the majority of hardening particles in Inconel 718. Additionally, fatigue results indicate that in both alloys over-aging promotes surface crack initiation, thus leading to shorter fatigue life.

Mutations in the serine protease inhibitor Kazal type 1 gene (SPINK1) encoding pancreatic secretory trypsin inhibitor (PSTI) have recently been found to be associated with chronic pancreatitis. Nevertheless, knowledge of severe mutations is particularly scarce, both in terms of number and in the extent of clinical information. The aim of this study was to expand the known spectrum of such mutations. 46 unrelated families, each including at least two pancreatitis patients and carrying neither cationic trypsinogen (PRSS1) mutations nor the frequent SPINK1 N34S mutation, participated in this study. The four exons and their flanking sequences of the SPINK1 gene were screened by denaturing high performance liquid chromatography analysis (DHPLC); and mutations were identified by direct sequencing. A heterozygous microdeletion mutation (c.27delC), which occurs within a symmetric element, was identified in two families. In one family, c.27delC showed segregation with the disease across two generations, with a penetrance of up to 75%. But in the other family, however, the same mutation manifested as a low‐penetrance susceptibility factor. In addition, a novel heterozygous splicing mutation, c.87+1G>A (G>A substitution at nucleotide +1 of intron 2) was found in one family with familial pancreatitis. Our results also helped to resolve the sharply differing views about PSTI's role in pancreatitis. © 2003 Wiley‐Liss, Inc.