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Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer’s disease, the adult neurogenesis is impaired. Our main aim was to investigate some proteins involved both in the physiopathology of Alzheimer’s disease and in the neuronal migration process using the APP/PS1 Alzheimer’s mouse model. Progenitor migrating cells are accumulated in the V-SVZ of the APP/PS1 mice. Furthermore, we find an increase of Cdh1 levels and a decrease of Cdk5/p35 and cyclin B1, indicating that these cells have an alteration of the cell cycle, which triggers a senescence state. We find less cells in the rostral migratory stream and less mature neurons in the olfactory bulbs from APP/PS1 mice, leading to an impaired odour discriminatory ability compared with WT mice. Alzheimer’s disease mice present a deficit in cell migration from V-SVZ due to a senescent phenotype. Therefore, these results can contribute to a new approach of Alzheimer’s based on senolytic compounds or pro-neurogenic factors.

Vomeronasal information is critical in mice for territorial behavior. Consequently, learning the territorial spatial structure should incorporate the vomeronasal signals indicating individual identity into the hippocampal cognitive map. In this work we show in mice that navigating a virtual environment induces synchronic activity, with causality in both directionalities, between the vomeronasal amygdala and the dorsal CA1 of the hippocampus in the theta frequency range. The detection of urine stimuli induces synaptic plasticity in the vomeronasal pathway and the dorsal hippocampus, even in animals with experimentally induced anosmia. In the dorsal hippocampus, this plasticity is associated with the overexpression of pAKT and pGSK3β. An amygdalo-entorhino-hippocampal circuit likely underlies this effect of pheromonal information on hippocampal learning. This circuit likely constitutes the neural substrate of territorial behavior in mice, and it allows the integration of social and spatial information., Male and female mice need to generate spatial maps that integrate vomeronasal signals of territory owners in the hippocampus-dependent memory. The authors show that vomeronasal information influences learning-related activity in the hippocampus via the amygdaloid PMCo, lateral entorhinal cortex, and dorsal CA1.

International audience; This article investigates new steps for the implementation and the utilization of presence indicators to identify displacement activities of a person and to model their life habits. This modeling is based on preliminary measures of displacement rate variations over a period of time. A possible time slot division of activities is highlighted by the analysis of these measures, slight variations of slot boundaries could appear from day to day, from person to person. On this basis, we show how to build three new indicators by working from time slot to time slot, in order to detect alerts or drifts from "normal" behavior as soon as possible and in a more reliable way. These indicators include start and end times of time slots, displacement rate and duration of each time slot. The algorithm we propose has been tested in real situations to show its use and relevance. Results are finally integrated in a more ambitious process of detection and automatic decision-making support through the conception of a web interface.

Oxidative stress is an early occurrence in the development of Alzheimer’s disease (AD) and one of its proposed etiologic hypotheses. There is sufficient experimental evidence supporting the theory that impaired antioxidant enzymatic activity and increased formation of reactive oxygen species (ROS) take place in this disease. However, the antioxidant treatments fail to stop its advancement. Its multifactorial condition and the diverse toxicological cascades that can be initiated by ROS could possibly explain this failure. Recently, it has been suggested that cerebral small vessel disease (CSVD) contributes to the onset of AD. Oxidative stress is a central hallmark of CSVD and is depicted as an early causative factor. Moreover, data from various epidemiological and clinicopathological studies have indicated a relationship between CSVD and AD where endothelial cells are a source of oxidative stress. These cells are also closely related to oligodendrocytes, which are, in particular, sensitive to oxidation and lead to myelination being compromised. The sleep/wake cycle is another important control in the proliferation, migration, and differentiation of oligodendrocytes, and sleep loss reduces myelin thickness. Moreover, sleep plays a crucial role in resistance against CSVD, and poor sleep quality increases the silent markers of this vascular disease. Sleep disruption is another early occurrence in AD and is related to an increase in oxidative stress. In this study, the relationship between CSVD, oligodendrocyte dysfunction, and sleep disorders is discussed while focusing on oxidative stress as a common occurrence and its possible role in the onset of AD.

We show experimentally that a dc-biased Josephson junction in series with two microwave resonators emits entangled beams of microwaves leaking out of the resonators. In the absence of a stationary phase reference for characterizing the entanglement of the outgoing beams, we measure second-order coherence functions for proving entanglement up to an emission rate of 2.5 billion photon pairs per second. The experimental results are found in quantitative agreement with theory, proving that the low frequency noise of the dc bias is the main limitation for the coherence time of the entangled beams. This agreement allows us to evaluate the entropy of entanglement of the resonators, and to identify the improvements that could bring this device closer to a useful bright source of entangled microwaves for quantum-technological applications.

In their Comment [P. Hakonen and E. B. Sonin, preceding comment, Phys. Rev. X 11, 018001 (2021)PRXHAE2160-3308], Hakonen and Sonin (HS) object to our conclusion on the absence of a dissipation-induced superconducting-to-insulating quantum phase transition (DQPT) in resistively shunted Josephson junctions (RSJJs) originally predicted by Schmid and Bulgadaev (SB). Their objections are based on the account they make of a theory explaining the DQPT in terms of Bloch bands which was developed in the 1980s and early 1990s. In this Reply, we point to several issues in the Comment which undermine the objections HS formulate against our work.

Electron spins are amongst the most coherent solid-state systems known, however, to be used in devices for quantum sensing and information processing applications, they must be typically placed near interfaces. Understanding and mitigating the impacts of such interfaces on the coherence and spectral properties of electron spins is critical to realize such applications, but is also challenging: inferring such data from single-spin studies requires many measurements to obtain meaningful results, while ensemble measurements typically give averaged results that hide critical information. Here, we report a comprehensive study of the coherence of near-surface bismuth donor spins in 28-silicon at millikelvin temperatures. In particular, we use strain-induced frequency shifts caused by a metallic electrode to make spatial maps of spin coherence as a function of depth and position relative to the electrode. By measuring magnetic-field-insensitive clock transitions we separate magnetic noise caused by surface spins from charge noise. Our results include quantitative models of the strain-split spin resonance spectra and extraction of paramagnetic impurity concentrations at the silicon surface. The interplay of these decoherence mechanisms for such near-surface electron spins is critical for their application in quantum technologies, while the combination of the strain splitting and clock transition extends the coherence lifetimes by up to two orders of magnitude, reaching up to 300 ms at a mean depth of only 100nm. The technique we introduce here to spatially map coherence in near-surface ensembles is directly applicable to other spin systems of active interest, such as defects in diamond, silicon carbide, and rare earth ions in optical crystals., Comment: 16 pages, 11 figures

Supervisory systems have become interesting solutions for monitoring the health of home-based people. Frail older people are at high risk of becoming dependent if they are not cared for quickly. Embedded devices at home or on the person are two possible options which, when coupled, allow a more precise knowledge of behaviors and a faster triggering of the alert. The idea still applied is to model the person’s activities or health parameters in a continuous and automated way to detect deviations from the usual behavior. This clinico-technical approach has been developed and tested in different places and by several research teams with a real medical interest in having a longitudinal knowledge of a patient’s behavior. However, prevention and follow-up of home prescriptions must go beyond the purely technological and medical aspects and take economical and organizational dimensions into account. We consider that three types of complementary actions must be implemented: a fundamental action on the scientific and technological level to know how to build, from the data collected, “a profile of user activity;” detecting, in real time, all kinds of deviations from the normal pattern; training and ground demonstrations actions.

The nanoscale localization of individual paramagnetic defects near an electrical circuit is an important step for realizing hybrid quantum devices with strong spin-microwave photon coupling. Here, we demonstrate the fabrication of an array of individual NV centers in diamond near a metallic nanowire deposited on top of the substrate. We determine the relative position of each NV center with $\sim$10\,nm accuracy, using it as a vector magnetometer to measure the field generated by passing a dc current through the wire., 6 pages, 5 figures

Physical systems reach thermal equilibrium through energy exchange with their environment, and for spins in solids the relevant environment is almost always their host lattice. However, recent studies1 motivated by observations by Purcell2 have shown how radiative emission into a microwave cavity can become the dominant relaxation path for spins if the spin–cavity coupling is sufficiently large (such as for small-mode-volume cavities). In this regime, the cavity electromagnetic field overrides the lattice as the dominant environment, inviting the prospect of controlling the spin temperature independently from that of the lattice, by engineering a suitable cavity field. Here, we report on precisely such control over spin temperature, illustrating a novel and universal method to increase the electron spin polarization above its thermal equilibrium value (termed hyperpolarization). By switching the cavity input between resistive loads at different temperatures we can control the electron spin polarization, cooling it below the lattice temperature. Our demonstration uses donor spins in silicon coupled to a superconducting microresonator and we observe more than a twofold increase in spin polarization. This approach provides a general route to signal enhancement in electron spin resonance, or nuclear magnetic resonance through dynamical nuclear spin polarization3,4. Electron spins in solid usually relax their energy through the coupling with phonons in the host lattice. By using the coupling to microwave photons in a cavity as an alternative relaxation path, it is demonstrated that spins can be cooled below the lattice temperature.

We report electron spin resonance measurements of donors in silicon at millikelvin temperatures using a superconducting $LC$ planar micro-resonator and a Josephson Parametric Amplifier. The resonator includes a nanowire inductor, defining a femtoliter detection volume. Due to strain in the substrate, the donor resonance lines are heavily broadened. Single-spin to photon coupling strengths up to $\sim 3~\text{kHz}$ are observed. The single shot sensitivity is $120 \pm 24~$spins/Hahn echo, corresponding to $\approx 12 \pm 3$~spins$/\sqrt{\text{Hz}}$ for repeated acquisition., 4 Figures

Biomarkers for disease diagnosis and prognosis are crucial in clinical practice. They should be objective and quantifiable and respond to specific therapeutic interventions. Optimal biomarkers should reflect the underlying process (pathological or not), be reproducible, widely available, and allow measurements repeatedly over time. Ideally, biomarkers should also be non-invasive and cost-effective. This review aims to focus on the usefulness and limitations of electroencephalography (EEG) in the search for Alzheimer’s disease (AD) biomarkers. The main aim of this article is to review the evolution of the most used biomarkers in AD and the need for new peripheral and, ideally, non-invasive biomarkers. The characteristics of the EEG as a possible source for biomarkers will be revised, highlighting its advantages compared to the molecular markers available so far.

We report measurements of electron spin echo envelope modulation (ESEEM) performed at millikelvin temperatures in a custom-built high-sensitivity spectrometer based on superconducting micro-resonators. The high quality factor and small mode volume (down to 0.2pL) of the resonator allow to probe a small number of spins, down to $5\cdot 10^2$. We measure 2-pulse ESEEM on two systems: erbium ions coupled to $^{183}$W nuclei in a natural-abundance $\text{CaWO}_4$ crystal, and bismuth donors coupled to residual $^{29}$Si nuclei in a silicon substrate that was isotopically enriched in the $^{28}$Si isotope. We also measure 3- and 5-pulse ESEEM for the bismuth donors in silicon. Quantitative agreement is obtained for both the hyperfine coupling strength of proximal nuclei, and the nuclear spin concentration., 15 pages, 11 figures

A long-lived multi-mode qubit register is an enabling technology for modular quantum computing architectures. For interfacing with superconducting qubits, such a quantum memory should be able to store incoming quantum microwave fields at the single-photon level for long periods of time, and retrieve them on-demand. Here, we demonstrate the partial absorption of a train of weak microwave fields in an ensemble of bismuth donor spins in silicon, their storage for 100 ms, and their retrieval, using a Hahn-echo-like protocol. The long storage time is obtained by biasing the bismuth donors at a clock transition. Phase coherence and quantum statistics are preserved in the storage., 11 pages including Supplementary

Obesity is known to induce leptin and insulin resistance. Leptin is a peptide hormone synthesized in adipose tissue that mainly regulates food intake. It has been shown that insulin stimulates the production of leptin when adipocytes are exposed to glucose to encourage satiety; while leptin, via a negative feedback, decreases the insulin release and enhances tissue sensitivity to it, leading to glucose uptake for energy utilization or storage. Therefore, resistance to insulin is closely related to leptin resistance. Obesity in middle age has also been related to Alzheimer’s disease (AD). In recent years, the relation between impaired leptin signaling pathway and the onset of AD has been studied. In all this context the role of the blood brain barrier (BBB) is crucial. Slow excitotoxicity happens in AD due to an excess of the neurotransmitter glutamate. Since leptin has been shown to regulate N-methyl-D-aspartate (NMDA) receptors, we want to review the link between these pathological pathways, and how they are affected by other AD triggering factors and its role in the onset of AD.

We show experimentally that a dc biased Josephson junction in series with a high-enough-impedance microwave resonator emits antibunched photons. Our resonator is made of a simple microfabricated spiral coil that resonates at 4.4 GHz and reaches a $1.97\text{ }\text{ }\mathrm{k}\mathrm{\ensuremath{\Omega}}$ characteristic impedance. The second order correlation function of the power leaking out of the resonator drops down to 0.3 at zero delay, which demonstrates the antibunching of the photons emitted by the circuit at a rate of $6\ifmmode\times\else\texttimes\fi{}{10}^{7}$ photons per second. Results are found in quantitative agreement with our theoretical predictions. This simple scheme could offer an efficient and bright single-photon source in the microwave domain.

International audience; In high sensitivity inductive electron spin resonance spectroscopy, superconducting microwave resonators with large quality factors are employed. While they enhance the sensitivity, they also distort considerably the shape of the applied rectangular microwave control pulses, which limits the degree of control over the spin ensemble. Here, we employ shaped microwave pulses compensating the signal distortion to drive the spins faster than the resonator bandwidth. This translates into a shorter echo, with enhanced signal-to-noise ratio. The shaped pulses are also useful to minimize the dead-time of our spectrometer, which allows to reduce the wait time between successive drive pulses.

Nature sets fundamental limits regarding how accurate the amplification of analog signals may be. For instance, a linear amplifier unavoidably adds some noise which amounts to half a photon at best. While for most applications much higher noise levels are acceptable, the readout of microwave quantum systems, such as spin or superconducting qubits, requires noise as close as possible to this ultimate limit. To date, it is approached only by parametric amplifiers exploiting non-linearities in superconducting circuits and driven by a strong microwave pump tone. However, this microwave drive makes them much more difficult to implement and operate than conventional DC powered amplifiers, which so far suffer from much higher noise. Here we present the first experimental proof that a simple DC-powered setup allows for amplification close to the quantum limit. Our amplification scheme is based on the stimulated microwave photon emission accompanying inelastic Cooper pair tunneling through a DC-biased Josephson junction, with the key to low noise lying in a well defined auxiliary idler mode, in analogy to parametric amplifiers., Comment: 6 pages, 4 figures

This corrects the article DOI: 10.1103/PhysRevLett.114.126801.

Vacuum fluctuations of the electromagnetic field set a fundamental limit to the sensitivity of a variety of measurements, including magnetic resonance spectroscopy. We report the use of squeezed microwave fields, which are engineered quantum states of light for which fluctuations in one field quadrature are reduced below the vacuum level, to enhance the detection sensitivity of an ensemble of electronic spins at millikelvin temperatures.} By shining a squeezed vacuum state on the input port of a microwave resonator containing the spins, we obtain a $1.2$\,dB noise reduction at the spectrometer output compared to the case of a vacuum input. This result constitutes a proof of principle of the application of quantum metrology to magnetic resonance spectroscopy., Comment: Main text : 19 pages, 6 figures. Followed by a 18-pages Supplementary Information section, which includes 6 Supplementary Figures

With the objective of water analysis, a microsystem was developed, by using Resazurin molecule as an indirect bio sensor. The detection principle consists to monitor optically the oxygen consumption of E. Coli bacteria towards their metabolism in presence of organic pollutants. Thus, aiming on Glucose detection, a concentration-dependent inhibition effect on oxygen consumption rate was evidenced in the [0–0.41 mM] range of organic pollutants.

International audience; Healthcare Systems (HCSs) throughout the world undergo important changes driven by aging populations and advances in biomedical technologies. At the same time, in the current economic climate, many Western countries are struggling to reduce public spending on all kinds of services, including healthcare. With this tension between tightening budgets and skyrocketing costs, many countries are seeking to identify ways of using Information Technology (IT) and Monitoring Technologies (MTs) to improve the efficiencies of HCSs while not reducing, or possibly even improving, the quality of healthcare and their delivery. Many experiments have been in progress since the 1990s. This paper has conducted a review evaluating such HCSs in terms of advantages and drawbacks. The objective of this review is to provide some illustrative publications and works and examples of Health Information Technology (HIT) systems to finally determine the place of biomedical MTs in the future HCS. We present the healthcare delivery system (HCDS) organization with roles of the different stakeholders, state initiatives in healthcare information delivery systems and the new relation between the hospital and the home though a new equilibrium. We mentioned the increasing role of telemedicine (TM), telecare (TLC) and telemonitoring (TLM) and expectations for monitoring the elderly. These expectations lead to preventive approaches based on monitoring technologies and pervasive healthcare (PH) which made healthcare improvements and cost reductions possible. Finally, we show the challenges and opportunities of the hospital versus home healthcare delivery.

When spin relaxation is governed by spontaneous emission of a photon into the resonator used for signal detection (the Purcell effect), the relaxation time $T_1$ depends on the spin-resonator frequency detuning $\delta$ and coupling constant $g$. We analyze the consequences of this unusual dependence for the amplitude and temporal shape of a spin-echo in a number of different experimental situations. When the coupling $g$ is distributed inhomogeneously, we find that the effective spin-echo relaxation time measured in a saturation recovery sequence strongly depends on the parameters of the detection echo. When the spin linewidth is larger than the resonator bandwidth, the Fourier components of the echo relax with different characteristic times, which implies that the temporal shape of the echo becomes dependent on the repetition time of the experiment. We provide experimental evidence of these effects with an ensemble of donor spins in silicon at millikelvin temperatures measured by a superconducting micro-resonator., Comment: 10 pages, 8 figures

Using a personnel computer, we have simulated the diffusion and agglomeration of point defects in thin foil under high energy electron irradiation. The physical model has been developed by using the Monte Carlo technique. Four types of reactions are assumed to take place: di-interstitial creation by agglomeration of two free interstitials, vacancy-interstitial annihilation, interstitial trapping by dislocation loops and interstitial annihilation on the sample surfaces. In the simulation only interstitials are mobile and extended defects are assumed to be interstitial type. We have calculated the concentration of point defects, extended defects and the size of the latter. We compared them to the results of the Chemical Reaction Rate Theory (CRRT). It has been found that the dislocation loops are distributed in the center of material leaving areas denuded close to the surface and the loops radius is also strongly dependent on the location of the defect in thin foil with respect to the results of experimental and CRRT. To explain the origin of these phenomena we have exploited the spatial distribution of vacancies close to free surfaces and around dislocation loops. These types of informations are totally missing in the CRRT and experimental.

While Alzheimer’s disease (AD) classical diagnostic criteria rely on clinical data from a stablished symptomatic disease, newer criteria aim to identify the disease in its earlier stages. For that, they incorporated the use of AD’s specific biomarkers to reach a diagnosis, including the identification of Aβ and tau depositions, glucose hypometabolism, and cerebral atrophy. These biomarkers created a new concept of the disease, in which AD’s main pathological processes have already taken place decades before we can clinically diagnose the first symptoms. Therefore, AD is now considered a dynamic disease with a gradual progression, and dementia is its final stage. With that in mind, new models were proposed, considering the orderly increment of biomarkers and the disease as a continuum, or the variable time needed for the disease’s progression. In 2011, the National Institute on Aging and the Alzheimer’s Association (NIA-AA) created separate diagnostic recommendations for each stage of the disease continuum—preclinical, mild cognitive impairment, and dementia. However, new scientific advances have led them to create a unifying research framework in 2018 that, although not intended for clinical use as of yet, is a step toward shifting the focus from the clinical symptoms to the biological alterations and toward changing the future diagnostic and treatment possibilities. This review aims to discuss the role of biomarkers in the onset of AD.

The Josephson effect describes the flow of supercurrent in a weak link, such as a tunnel junction, nanowire, or molecule, between two superconductors. It is the basis for a variety of circuits and devices, with applications ranging from medicine to quantum information. Currently, experiments using Josephson circuits that behave like artificial atoms are revolutionizing the way we probe and exploit the laws of quantum physics. Microscopically, the supercurrent is carried by Andreev pair states, which are localized at the weak link. These states come in doublets and have energies inside the superconducting gap. Existing Josephson circuits are based on properties of just the ground state of each doublet and so far the excited states have not been directly detected. Here we establish their existence through spectroscopic measurements of superconducting atomic contacts. The spectra, which depend on the atomic configuration and on the phase difference between the superconductors, are in complete agreement with theory. Andreev doublets could be exploited to encode information in novel types of superconducting qubits., Submitted to Nature

Today, the monitoring of dependent people is a real challenge. This is mainly due to the increase in the number of elderly and reduction of medical staff. However, works done in recent years in France are faced with obstacle of clinical and industrial validation. In this paper, we propose a monitoring system for dependent persons living alone at home or in an institution 24 h/24. This system is based on a presence multisensor network deployed in the living environment of the monitored person coupled with a wireless identification system. A learning algorithm is implemented in order to define a personalized behavioural model (motions deviation, nocturnal activity, falls, mobility). This model allows the nursing staff monitoring the behaviour through a web application accessed remotely, and also intervention in case of dangerous situations thanks to an alert system. In further, we describe the experiments conducted at the Caussade Local Hospital in France with Alzheimer patients and we present the results of data obtained. Finally, we propose the way for an economic model that would allow to industrialize the system with prospects of clinical validation on a larger cohort of patients.

© 2017 Author(s). We report electron spin resonance spectroscopy measurements performed at millikelvin temperatures in a custom-built spectrometer comprising a superconducting micro-resonator at 7 GHz and a Josephson parametric amplifier. Owing to the small (∼10-12λ3) magnetic resonator mode volume and to the low noise of the parametric amplifier, the spectrometer's single shot sensitivity reaches 260 ± 40 spins/echo translating into 65±10 spins/√Hz for repeated acquisition.