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Control of the crystalline orientation of nitrogen-vacancy (NV) defects in diamond is here demonstrated by tuning the temperature of chemical vapor deposition (CVD) growth on a (113)-oriented diamond substrate. We show that preferential alignment of NV defects along the [111] axis is improved when the CVD growth temperature is decreased, leading to 79% preferential orientation at 800∘C, as compared to only 47.5% at 1000∘C. This effect is then combined with temperature-dependent incorporation of NV defects during the CVD growth to obtain preferential alignment over dense ensembles of NV defects spatially localized in thin diamond layers. These results demonstrate that growth temperature can be exploited as an additional degree of freedom to engineer optimized diamond samples for quantum sensing applications. Unlabelled Image • Preferential orientation of NVs for (113) growth is improved by decreasing deposition temperature. • Up to 79% of NVs are aligned along a single direction. • Dense ensembles of aligned NVs are created in 300 nm thin diamond layers at low growth temperature. • Long spin coherence properties of such oriented and localized NVs are preserved. [ABSTRACT FROM AUTHOR]

The loading-rate mechanical response of the mode I delamination in composites and adhesively bonded joints was investigated. The tests were carried out using a recently developed Guided Double Cantilever Beam test method. Three different data reduction methods were proposed and assessed: a displacement-based formulation, a near-crack-tip displacement formulation, and a numerical assessment using the Virtual Crack-Closure Technique method. The methods account for the dynamic effects which may be present. While small differences between the three different methods can be seen, no rate-dependency higher than the uncertainty for the materials and the loading rates considered have been evidenced. [Display omitted] • Study of the loading-rate mechanical response of the mode I delamination. • Different data reduction methods to determine G Ic for the GDCB test method proposed. • The methods account for the dynamic effects which may be present in the testing. • Assessment of the data reduction methods including their advantages and limitations. [ABSTRACT FROM AUTHOR]

We report on sliding charge density waves (CDWs) in the quasi-two-dimensional TbTe3 system probed by coherent x-ray diffraction combined with in situ transport measurements. We show that the non-Ohmic conductivity in TbTe3 is made possible thanks to a strong distortion of the CDW. Our diffraction experiment versus current shows first that the CDW remains undeformed below the threshold current IS and then suddenly rotates and reorders by motion above threshold. Contrary to quasi-one-dimensional systems, the CDW in TbTe3 does not display any phase shifts below IS and tolerates only slow spatial variations of the phase above. This is the first observation of CDW behavior in the bulk in a quasi-two-dimensional system allowing collective transport of charges at room temperature. [ABSTRACT FROM AUTHOR]

We present a novel technique based on an ensemble of Nitrogen-Vacancy (NV) centers of diamond to perform Magnetic Current Imaging (MCI) on an Integrated Circuit (IC). NV centers of diamond permit to measure the three components of the magnetic fields generated by mA range current in an IC structure over a field of 50 × 200 μm with sub-micrometric resolution. Vector measurements allow the use of a more robust algorithm than those used for MCI using GMR or SQUID sensors and it is opening new current reconstruction prospects. Calculated MCI from these measurements shows a very good agreement with theoretical current path. Acquisition time is around 10 s, which is much faster than scanning measurements using Superconducting Quantum Interference Device (SQUID) or Giant Magneto Resistance (GMR). The experimental set-up relies on a standard optical microscope, and the measurements can be performed at room temperature and atmospheric pressure. These early experiences, not optimized for IC, show that NV centers in diamond could become a real alternative for MCI in IC. [ABSTRACT FROM AUTHOR]

Thick CVD diamond layers were successfully grown on (113)-oriented substrates. They exhibited smooth surface morphologies and a crystalline quality comparable to (100) electronic grade material, and much better than (111)-grown layers. High growth rates (15–50 μm/h) were obtained while nitrogen doping could be achieved in a fairly wide range without seriously imparting crystalline quality. Electron spin resonance measurements were carried out to determine NV centers orientation and concluded that one specific orientation has an occurrence probability of 73% when (100)-grown layers show an equal distribution in the 4 possible directions. A spin coherence time of around 270 μs was measured which is equivalent to that reported for material with similar isotopic purity. Although a higher degree of preferential orientation was achieved with (111)-grown layers (almost 100%), the ease of growth and post-processing of the (113) orientation make it a potentially useful material for magnetometry or other quantum mechanical applications. [ABSTRACT FROM AUTHOR]

The control of domain walls in magnetic wires underpins an emerging class of spintronic devices. Propagation of these walls in imperfect media requires defects that pin them to be characterized on the nanoscale. Using a magnetic microscope based on a single nitrogen-vacancy (NV) center in diamond, we report domain-wall imaging on a 1-nanometer-thick ferromagnetic nanowire and directly observe Barkhausen jumps between two pinning sites spaced 50 nanometers apart. We further demonstrate in situ laser control of these jumps, which allows us to drag the domain wall along the wire and map the pinning landscape. Our work demonstrates the potential of NV microscopy to study magnetic nano-objects in complex media, whereas controlling domain walls with laser light may find an application in spintronic devices. [ABSTRACT FROM AUTHOR]

We report a systematic study of the hyperfine interaction between the electron spin of a single nitrogen-vacancy (NV) defect in diamond and nearby 13C nuclear spins, by using pulsed electron-spin resonance spectroscopy. We isolate a set of discrete values of the hyperfine coupling strength ranging from 14 MHz to 400 kHz and corresponding to 13C nuclear spins placed at different lattice sites of the diamond matrix. For each lattice site, the hyperfine interaction is further investigated through nuclear-spin polarization measurements and by studying the magnetic field dependence of the hyperfine splitting. This work provides information that is relevant for the development of nuclear-spin-based quantum register in diamond. [ABSTRACT FROM AUTHOR]

We report a systematic study of the magnetic field sensitivity of a magnetic sensor consisting of a single nitrogen-vacancy (NV) defect in diamond, by using continuous optically detected electron spin resonance (ESR) spectroscopy. We first investigate the behavior of the ESR contrast and linewidth as a function of the microwave and optical pumping power. The experimental results are in good agreement with a simplified model of the NV defect spin dynamics, leading to an optimized sensitivity around 2 μT/√H-z for a single NV defect in a high-purity diamond crystal grown by chemical vapor deposition. We then demonstrate an enhancement of the magnetic sensitivity by one order of magnitude by using a simple pulsed-ESR scheme. This technique is based on repetitive excitation of the NV defect with a resonant microwave π pulse followed by an optimized readout laser pulse, allowing to fully eliminate power broadening of the ESR linewidth. The achieved sensitivity is similar to that obtained by using Ramsey-type sequences, which is the optimal magnetic field sensitivity for the detection of a dc magnetic field. [ABSTRACT FROM AUTHOR]

We report the detection of individual emitters in silicon belonging to seven different families of optically active point defects. These fluorescent centers are created by carbon implantation of a commercial silicon-on-insulator wafer usually employed for integrated photonics. Single photon emission is demonstrated over the 1.1-1.55  μm range, spanning the O and C telecom bands. We analyze their photoluminescence spectra, dipolar emissions, and optical relaxation dynamics at 10 K. For a specific family, we show a constant emission intensity at saturation from 10 K to temperatures well above the 77 K liquid nitrogen temperature. Given the advanced control over nanofabrication and integration in silicon, these individual artificial atoms are promising systems to investigate for Si-based quantum technologies. [ABSTRACT FROM AUTHOR]

The therapeutic potential of bone marrow mesenchymal stromal cells (bmMSCs) to address heart failure needs improvement for better engraftment and survival. This study explores the role of metabolic sorting for human bmMSCs in coculture in vitro and on doxorubicin-induced heart failure mice models. Using functional, epigenetic, and gene expression approaches on cells sorted for mitochondrial membrane potential in terms of their metabolic status, we demonstrated that bmMSCs selected for their glycolytic metabolism presented proliferative advantage and resistance to oxidative stress thereby favoring cell engraftment. Therapeutic use of glycolytic bmMSCs rescued left ventricular ejection fraction and decreased fibrosis in mice models of acute heart failure. Metabolic changes were also related to epigenetic histone modifications such as lysine methylation. By targeting LSD1 (lysine-specific demethylase 1) as a conditioning agent to enhance the metabolic profile of bmMSCs, we deciphered the interplay between glycolysis and bmMSC functionality. Our study elucidates novel strategies for optimizing bmMSC-based treatments for heart failure, highlighting the metabolic properties of bmMSCs as a promising target for more effective cardiovascular regenerative therapies., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Among a broad diversity of color centers hosted in layered van der Waals materials, the negatively charged boron vacancy (V B ) center in hexagonal boron nitride (hBN) is garnering considerable attention for the development of quantum sensing units on a two-dimensional platform. In this work, we investigate how the optical response of an ensemble of V - centers evolves with the hBN thickness in a range of a few to hundreds of nanometers. We show that the photoluminescence intensity features a nontrivial evolution with thickness, which is quantitatively reproduced by numerical calculations taking into account thickness-dependent variations of the absorption, radiative lifetime, and radiation pattern of V B centers. Besides providing an important resource to optimize the performances of quantum sensing units based on V - centers evolves with the hBN thickness in a range of a few to hundreds of nanometers. We show that the photoluminescence intensity features a nontrivial evolution with thickness, which is quantitatively reproduced by numerical calculations taking into account thickness-dependent variations of the absorption, radiative lifetime, and radiation pattern of V B - centers. Besides providing an important resource to optimize the performances of quantum sensing units based on V B - centers in hBN, the thickness-dependent nanophotonic effects discussed in this work generally apply to any type of color center embedded in a van der Waals material.

Topologically protected spin whirls in ferromagnets are foreseen as the cart-horse of solitonic information technologies. Nevertheless, the future of skyrmionics may rely on antiferromagnets due to their immunity to dipolar fields, straight motion along the driving force and ultrafast dynamics. While complex topological objects were recently discovered in intrinsic antiferromagnets, mastering their nucleation, stabilization and manipulation with energy-efficient means remains an outstanding challenge. Designing topological polar states in magnetoelectric antiferromagnetic multiferroics would allow one to electrically write, detect and erase topological antiferromagnetic entities. Here we stabilize ferroelectric centre states using a radial electric field in multiferroic BiFeO 3 thin films. We show that such polar textures contain flux closures of antiferromagnetic spin cycloids, with distinct antiferromagnetic entities at their cores depending on the electric field polarity. By tuning the epitaxial strain, quadrants of canted antiferromagnetic domains can also be electrically designed. These results open the path to reconfigurable topological states in multiferroic antiferromagnets., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: 177 Lu-oxodotreotide peptide receptor therapy (LuPRRT) is an efficient treatment for midgut neuroendocrine tumors (NETs) of variable radiological response. Several clinical, biological, and imaging parameters may be used to establish a relative disease prognosis but none is able to predict early efficacy or toxicities. We investigated expression levels for mRNA and miRNA involved in radiosensitivity and tumor progression searching for correlations related to patient outcome during LuPRRT therapy., Methods: Thirty-five patients received LuPRRT for G1/G2 midgut NETs between May 2019 and September 2021. Peripheral blood samples were collected prior to irradiation, before and 48 h after the second and the fourth LuPRRT, and at 6-month follow-up. Multiple regression analyses and Pearson correlations were performed to identify the miRNA/mRNA signature that will best predict response to LuPRRT., Results: Focusing on four mRNAs and three miRNAs, we identified a miRNA/mRNA signature enabling the early identification of responders to LuPRRT with significant reduced miRNA/mRNA expression after the first LuPRRT administration for patients with progressive disease at 1 year ( p < 0.001). The relevance of this signature was reinforced by studying its evolution up to 6 months post-LuPRRT. Moreover, nadir absolute lymphocyte count within the first 2 months after the first LuPRRT administration was significantly related to low miRNA/mRNA expression level ( p < 0.05) for patients with progressive disease., Conclusion: We present a pilot study exploring a miRNA/mRNA signature that correlates with early hematologic toxicity and therapeutic response 12 months following LuPRRT. This signature will be tested prospectively in a larger series of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Jacques, Dierickx, Texier, Brillouet, Courbon, Guimbaud, Vija and Savagner.)

Since the late 1990s, and Henrik Kehlet's hypothesis that a reduction of the body's stress response to major surgeries could decrease postoperative morbidity, "Enhanced Recovery After Surgery" (ERAS) care pathways have been streamlined. They are now well accepted and considered standard in many surgical disciplines. Yet, to this day, there is no specific ERAS protocol for chest wall resections (CWRs), the removal of a full-thickness portion of the chest wall, including muscle, bone and possibly skin. This is most unfortunate because these are high-risk surgeries, which carry high morbidity rates. In this review, we propose an overview of the current key elements of the ERAS guidelines for thoracic surgery that might apply to CWRs. A successful ERAS pathway for CWR patients would entail, as is the standard approach, three parts: pre-, peri- and postoperative elements. Preoperative items would include specific information, targeted patient education, involvement of all members of the team, including the plastic surgeons, smoking cessation, dedicated nutrition and carbohydrate loading. Perioperative items would likely be standard for thoracotomy patients, namely carefully selective pre-anesthesia sedative medication only in some rare instances, low-molecular-weight heparin throughout, antibiotic prophylaxis, minimization of postoperative nausea and vomiting, avoidance of fluid overload and of urinary drainage. Postoperative elements would include early mobilization and feeding, swift discontinuation of intravenous fluid supply and chest tube removal as soon as safe. Optimal pain management throughout also appears to be critical to minimize the risk of respiratory complications. Together, all these items are achievable and may hold the key to successful introduction of ERAS pathways to the benefit of CWR patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-911/coif). The series “Chest Wall Resections and Reconstructions” was commissioned by the editorial office without any funding or sponsorship. M.G. serves as an unpaid editorial board member of Journal of Thoracic Disease from February 2023 to January 2025. The authors have no other conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

The precise arrangement and nature of atoms drive electronic phase transitions in condensed matter. To explore this tenuous link, we developed a true biaxial mechanical deformation device working at cryogenic temperatures, compatible with x-ray diffraction and transport measurements, well adapted to layered samples. Here we show that a slight deformation of TbTe 3 can have a dramatic influence on its Charge Density Wave (CDW), with an orientational transition from c to a driven by the a/c parameter, a tiny coexistence region near a = c, and without space group change. The CDW transition temperature T c displays a linear dependence with a / c - 1 while the gap saturates out of the coexistence region. This behaviour is well accounted for within a tight-binding model. Our results question the relationship between gap and T c in RTe 3 systems. This method opens a new route towards the study of coexisting or competing electronic orders in condensed matter., (© 2024. The Author(s).)

Magnetic skyrmions are topological magnetic textures that hold great promise as nanoscale bits of information in memory and logic devices. Although room-temperature ferromagnetic skyrmions and their current-induced manipulation have been demonstrated, their velocity has been limited to about 100 meters per second. In addition, their dynamics are perturbed by the skyrmion Hall effect, a motion transverse to the current direction caused by the skyrmion topological charge. Here, we show that skyrmions in compensated synthetic antiferromagnets can be moved by current along the current direction at velocities of up to 900 meters per second. This can be explained by the cancellation of the net topological charge leading to a vanishing skyrmion Hall effect. Our results open an important path toward the realization of logic and memory devices based on the fast manipulation of skyrmions in tracks.

The unique physical, mechanical, chemical, optical, and electronic properties of hexagonal boron nitride (hBN) make it a promising 2D material for electronic, optoelectronic, nanophotonic, and quantum devices. Here, the changes in hBN's properties induced by isotopic purification in both boron and nitrogen are reported. Previous studies on isotopically pure hBN have focused on purifying the boron isotope concentration in hBN from its natural concentration (≈20 at% 10 B, 80 at% 11 B) while using naturally abundant nitrogen (99.6 at% 14 N, 0.4 at% 15 N), that is, almost pure 14 N. In this study, the class of isotopically purified hBN crystals to 15 N is extended. Crystals in the four configurations, namely h 10 B 14 N, h 11 B 14 N, h 10 B 15 N, and h 11 B 15 N, are grown by the metal flux method using boron and nitrogen single isotope (> 99%) enriched sources, with nickel plus chromium as the solvent. In-depth Raman and photoluminescence spectroscopies demonstrate the high quality of the monoisotopic hBN crystals with vibrational and optical properties of the 15 N-purified crystals at the state-of-the-art of currently available 14 N-purified hBN. The growth of high-quality h 10 B 14 N, h 11 B 14 N, h 10 B 15 N, and h 11 B 15 N opens exciting perspectives for thermal conductivity control in heat management, as well as for advanced functionalities in quantum technologies., (© 2023 Wiley-VCH GmbH.)

In the room-temperature magnetoelectric multiferroic BiFeO 3 , the noncollinear antiferromagnetic state is coupled to the ferroelectric order, opening applications for low-power electric-field-controlled magnetic devices. While several strategies have been explored to simplify the ferroelectric landscape, here we directly stabilize a single-domain ferroelectric and spin cycloid state in epitaxial BiFeO 3 (111) thin films grown on orthorhombic DyScO 3 (011). Comparing them with films grown on SrTiO 3 (111), we identify anisotropic in-plane strain as a powerful handle for tailoring the single antiferromagnetic state. In this single-domain multiferroic state, we establish the thickness limit of the coexisting electric and magnetic orders and directly visualize the suppression of the spin cycloid induced by the magnetoelectric interaction below the ultrathin limit of 1.4 nm. This as-grown single-domain multiferroic configuration in BiFeO 3 thin films opens an avenue both for fundamental investigations and for electrically controlled noncollinear antiferromagnetic spintronics.

We report on electron spin resonance (ESR) spectroscopy of boron-vacancy (V&#95;{B}^{-}) centers hosted in isotopically engineered hexagonal boron nitride (hBN) crystals. We first show that isotopic purification of hBN with ^{15}N yields a simplified and well-resolved hyperfine structure of V&#95;{B}^{-} centers, while purification with ^{10}B leads to narrower ESR linewidths. These results establish isotopically purified h^{10}B^{15}N crystals as the optimal host material for future use of V&#95;{B}^{-} spin defects in quantum technologies. Capitalizing on these findings, we then demonstrate optically induced polarization of ^{15}N nuclei in h^{10}B^{15}N, whose mechanism relies on electron-nuclear spin mixing in the V&#95;{B}^{-} ground state. This work opens up new prospects for future developments of spin-based quantum sensors and simulators on a two-dimensional material platform.

Optically active spin defects in hexagonal boron nitride (hBN) are promising quantum systems for the design of two-dimensional quantum sensing units offering optimal proximity to the sample being probed. In this Letter, we first demonstrate that the electron spin resonance frequencies of boron vacancy centers (V&#95;{B}^{-}) can be detected optically in the limit of few-atomic-layer thick hBN flakes despite the nanoscale proximity of the crystal surface that often leads to a degradation of the stability of solid-state spin defects. We then analyze the variations of the electronic spin properties of V&#95;{B}^{-} centers with the hBN thickness with a focus on (i) the zero-field splitting parameters, (ii) the optically induced spin polarization rate and (iii) the longitudinal spin relaxation time. This Letter provides important insights into the properties of V&#95;{B}^{-} centers embedded in ultrathin hBN flakes, which are valuable for future developments of foil-based quantum sensing technologies.

Congenital iodide transport defect is an uncommon autosomal recessive disorder caused by loss-of-function variants in the sodium iodide symporter (NIS)-coding SLC5A5 gene and leading to dyshormonogenic congenital hypothyroidism. Here, we conducted a targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients suspected of having a congenital iodide transport defect based on the absence of 99mTc-pertechnetate accumulation in a eutopic thyroid gland. Although, unexpectedly, we could not detect pathogenic SLC5A5 gene variants, we identified two novel compound heterozygous TG gene variants (p.Q29* and c.177-2A>C), three novel heterozygous TG gene variants (p.F1542Vfs*20, p.Y2563C, and p.S523P), and a novel heterozygous DUOX2 gene variant (p.E1496Dfs*51). Splicing minigene reporter-based in vitro assays revealed that the variant c.177-2A>C affected normal TG pre-mRNA splicing, leading to the frameshift variant p.T59Sfs*17. The frameshift TG variants p.T59Sfs*17 and p.F1542Vfs*20, but not the DUOX2 variant p.E1496Dfs*51, were predicted to undergo nonsense-mediated decay. Moreover, functional in vitro expression assays revealed that the variant p.Y2563C reduced the secretion of the TG protein. Our investigation revealed unexpected findings regarding the genetics of congenital iodide transport defects, supporting the existence of yet to be discovered mechanisms involved in thyroid hormonogenesis.

Spin defects in hexagonal boron nitride (hBN) are promising quantum systems for the design of flexible two-dimensional quantum sensing platforms. Here we rely on hBN crystals isotopically enriched with either 10 B or 11 B to investigate the isotope-dependent properties of a spin defect featuring a broadband photoluminescence signal in the near infrared. By analyzing the hyperfine structure of the spin defect while changing the boron isotope, we first confirm that it corresponds to the negatively charged boron-vacancy center ([Formula: see text]). We then show that its spin coherence properties are slightly improved in 10 B-enriched samples. This is supported by numerical simulations employing cluster correlation expansion methods, which reveal the importance of the hyperfine Fermi contact term for calculating the coherence time of point defects in hBN. Using cross-relaxation spectroscopy, we finally identify dark electron spin impurities as an additional source of decoherence. This work provides new insights into the properties of [Formula: see text] spin defects, which are valuable for the future development of hBN-based quantum sensing foils., (© 2022. The Author(s).)

X-linked adrenoleukodystrophy (ALD) results from ABCD1 gene mutations which impair Very Long Chain Fatty Acids (VLCFA; C26:0 and C24:0) peroxisomal import and β-oxidation, leading to accumulation in plasma and tissues. Excess VLCFA drives impaired cellular functions (e.g. disrupted mitochondrial function), inflammation, and neurodegeneration. Major disease phenotypes include: adrenomyeloneuropathy (AMN), progressive spinal cord axonal degeneration, and cerebral ALD (C-ALD), inflammatory white matter demyelination and degeneration. No pharmacological treatment is available to-date for ALD. Pioglitazone, an anti-diabetic thiazolidinedione, exerts potential benefits in ALD models. Its mechanisms are genomic (PPARγ agonism) and nongenomic (mitochondrial pyruvate carrier-MPC, long-chain acyl-CoA synthetase 4-ACSL4, inhibition). However, its use is limited by PPARγ-driven side effects (e.g. weight gain, edema). PXL065 is a clinical-stage deuterium-stabilized (R)-enantiomer of pioglitazone which lacks PPARγ agonism but retains MPC activity. Here, we show that incubation of ALD patient-derived cells (both AMN and C-ALD) and glial cells from Abcd1-null mice with PXL065 resulted in: normalization of elevated VLCFA, improved mitochondrial function, and attenuated indices of inflammation. Compensatory peroxisomal transporter gene expression was also induced. Additionally, chronic treatment of Abcd1-null mice lowered VLCFA in plasma, brain and spinal cord and improved both neural histology (sciatic nerve) and neurobehavioral test performance. Several in vivo effects of PXL065 exceeded those achieved with pioglitazone. PXL065 was confirmed to lack PPARγ agonism but retained ACSL4 activity of pioglitazone. PXL065 has novel actions and mechanisms and exhibits a range of potential benefits in ALD models; further testing of this molecule in ALD patients is warranted., (© 2022 Poxel SA. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

We report on the formation of topological defects emerging from the cycloidal antiferromagnetic order at the surface of bulk BiFeO&#95;{3} crystals. Combining reciprocal and real-space magnetic imaging techniques, we first observe, in a single ferroelectric domain, the coexistence of antiferromagnetic domains in which the antiferromagnetic cycloid propagates along different wave vectors. We then show that the direction of these wave vectors is not strictly locked to the preferred crystallographic axes as continuous rotations bridge different wave vectors. At the junctions between the magnetic domains, we observe topological line defects identical to those found in a broad variety of lamellar physical systems with rotational symmetries. Our work establishes the presence of these magnetic objects at room temperature in the multiferroic antiferromagnet BiFeO&#95;{3}, offering new possibilities for their use in spintronics.

We investigate the magnetic field dependent photophysics of individual nitrogen-vacancy (NV) color centers in diamond under cryogenic conditions. At distinct magnetic fields, we observe significant reductions in the NV photoluminescence rate, which indicate a marked decrease in the optical readout efficiency of the NV's ground state spin. We assign these dips to excited state level anticrossings, which occur at magnetic fields that strongly depend on the effective, local strain environment of the NV center. Our results offer new insights into the structure of the NVs' excited states and a new tool for their effective characterization. Using this tool, we observe strong indications for strain-dependent variations of the NV's orbital g factor, obtain new insights into NV charge state dynamics, and draw important conclusions regarding the applicability of NV centers for low-temperature quantum sensing.

The release of excessive amounts of catecholamine by pheochromocytoma-paragangliomas (PPGL) can lead to life-threatening catecholamine-induced cardiomyopathy (CIC). Single-nucleotide polymorphisms of the beta1 and alpha-2c adrenergic receptors alter myocyte receptor function and enhanced norepinephrine release. We tested the hypothesis that such genetic variations may impact the risk of developing CIC in the context of PPGL. Thirty-one patients with PPGL, including nine with a history of CIC, were analyzed for alpha-2-adrenergic receptors: ADRA2C, beta-1 and beta-2 adrenergic receptors: ADRB1 and ADRB2 genotyping. CIC was defined either by a history of heart failure or cardiogenic shock associated with dilated or Takotsubo cardiomyopathy. Subjects were genotyped for ADRA2C (rs61767072 for del322&#95;325), ADRB1 (rs1801252 for Ser49Gly and rs1801253 for Arg389Gly) and ADRB2 (rs1042713 for Arg16Gly and rs1042714 for Gln27Glu). Single-locus analysis revealed that variant in ADRA2C (alpha 2CDel322-325) was more common among patients with CIC than among controls (allele frequency, 0.44 vs 0.05; P< 0.001). The lack of alpha 2CDel322-325 polymorphism has a negative predictive value of 95% for the onset of CIC. In a replication cohort including 26 patients with PPGL whom eight have developed a CIC, the association between Alpha 2CDel322-325 and CIC was confirmed (allele frequency, 0.33 vs 0.; P= 0.0001). In conclusion, Alpha 2CDel322-325 through the identification of patients at low risk of developing CIC can help physicians to better determine the most appropriate therapeutic approach, notably in patients at high risk of surgical complications.

We use ultrafast electron diffraction to study the out-of-equilibrium dynamics of the charge density wave (CDW) phase transition in GdTe 3 , a quasi-two-dimensional compound displaying a unidirectional CDW state. Experiments were conducted at different incident fluences and different initial sample temperatures below T c . We find that following photo-excitation, the system undergoes a non-thermal ultrafast phase transition that occurs in out-of-equilibrium conditions. The intrinsic crystal temperature was estimated at each time delay from the atomic thermal motion, which affects each Bragg peak intensity via the Debye Waller factor. We find that the crystal temperature stabilizes with a 6 ps timescale in a quasi-equilibrium state at temperature T q . e . . We then relate the recovery time of the CDW and its correlation lengths as a function of T q . e . . The charge density wave is suppressed in less than a picosecond while its recovery time increases linearly with incident fluence and initial temperature. Our results highlight that the dynamics is strongly determined by the initial sample temperature. In addition, the transient CDW phase recently observed along the transverse direction in LaTe 3 and CeTe 3 is not observed in GdTe 3 ., Competing Interests: The authors have no conflicts to disclose., (© 2022 Author(s).)

Context: Congenital hypothyroidism (CH) is related to dyshormonogenesis in 15% to 40% of the world population and associated with homozygous or heterozygous variants in the main genes of the hormone synthesis pathway. Emerging diagnostic tools, such as next-generation sequencing (NGS), have been used to efficiently explore panels of genes and identify complex mechanisms of pathogenesis., Objective: We explored 19 candidate genes known to be causative for permanent or transient CH to evaluate the role of complex gene variations in CH phenotype., Patients Design and Setting: Using the NGS approach, we studied 65 newborns with thyroid dyshormonogenesis (TDH). New variants were assessed in silico for pathogenicity., Results: Among the 65 infants, 56.9% presented a variant in one or more genes of the thyroid hormone synthesis axis. We identified homozygous or compound heterozygous variants in the TG , DUOX2 , TPO , or SLC5A5 genes in 10 infants and heterozygous variants in DUOX2 , TG , TPO , and TSHR in 19 others. In seven cases, a heterozygous variant in the TG gene was the unique anomaly detected, but related to disturbed hormonal balance. Oligogenic variants were found in eight infants associated with severe CH and goiter in five of them., Conclusion: The systematic exploration of genes involved in thyroid hormone synthesis by NGS in TDH showed high diagnostic relevance. Oligogenic inheritance could be related to phenotypic heterogeneity and a high frequency of goiter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oliver-Petit, Edouard, Jacques, Bournez, Cartault, Grunenwald and Savagner.)

The antidiabetic drug pioglitazone is, to date, the most efficacious oral drug recommended off-label for the treatment of nondiabetic or diabetic patients with biopsy-proven nonalcoholic steatohepatitis (NASH). However, weight gain and edema side effects have limited its use for NASH. Pioglitazone is a mixture of two stereoisomers (( R )-pioglitazone and ( S )-pioglitazone) that interconvert in vitro and in vivo . We aimed to characterize their individual pharmacology to develop a safer and potentially more potent drug for NASH. We stabilized the stereoisomers of pioglitazone with deuterium at the chiral center. Preclinical studies with deuterium-stabilized ( R )-pioglitazone (PXL065) and ( S )-pioglitazone demonstrated that ( R )-pioglitazone retains the efficacy of pioglitazone in NASH, including reduced hepatic triglycerides, free fatty acids, cholesterol, steatosis, inflammation, hepatocyte enlargement, and fibrosis. Although both stereoisomers inhibit the mitochondrial pyruvate carrier, PXL065 shows limited to no peroxisome proliferator-activated receptor gamma (PPARγ) activity, whereas ( S )-pioglitazone appears responsible for the PPARγ activity and associated weight gain. Nonetheless, in preclinical models, both stereoisomers reduce plasma glucose and hepatic fibrosis to the same extent as pioglitazone, suggesting that these benefits may also be mediated by altered mitochondrial metabolism. In a phase 1a clinical study, we demonstrated safety and tolerability of single 7.5-mg, 22.5-mg, and 30-mg doses of PXL065 as well as preferential exposure to the ( R )-stereoisomer in comparison to 45-mg pioglitazone. Conclusion : PXL065 at a dose lower than 22.5 mg is predicted to exhibit efficacy for NASH equal to, or greater than, 45-mg pioglitazone without the potentially detrimental weight gain and edema. The development of PXL065 for NASH represents a unique opportunity to leverage the therapeutic benefits of pioglitazone, while reducing or eliminating PPARγ-related side effects., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Antiferromagnetic materials are promising platforms for next-generation spintronics owing to their fast dynamics and high robustness against parasitic magnetic fields. However, nanoscale imaging of the magnetic order in such materials with zero net magnetization remains a major experimental challenge. Here we show that non-collinear antiferromagnetic spin textures can be imaged by probing the magnetic noise they locally produce via thermal populations of magnons. To this end, we perform nanoscale, all-optical relaxometry with a scanning quantum sensor based on a single nitrogen-vacancy (NV) defect in diamond. Magnetic noise is detected through an increase of the spin relaxation rate of the NV defect, which results in an overall reduction of its photoluminescence signal under continuous laser illumination. As a proof-of-concept, the efficiency of the method is demonstrated by imaging various spin textures in synthetic antiferromagnets, including domain walls, spin spirals and antiferromagnetic skyrmions. This imaging procedure could be extended to a large class of intrinsic antiferromagnets and opens up new opportunities for studying the physics of localized spin wave modes for magnonics.

Antiferromagnetic thin films are currently generating considerable excitement for low dissipation magnonics and spintronics. However, while tuneable antiferromagnetic textures form the backbone of functional devices, they are virtually unknown at the submicron scale. Here we image a wide variety of antiferromagnetic spin textures in multiferroic BiFeO 3 thin films that can be tuned by strain and manipulated by electric fields through room-temperature magnetoelectric coupling. Using piezoresponse force microscopy and scanning NV magnetometry in self-organized ferroelectric patterns of BiFeO 3 , we reveal how strain stabilizes different types of non-collinear antiferromagnetic states (bulk-like and exotic spin cycloids) as well as collinear antiferromagnetic textures. Beyond these local-scale observations, resonant elastic X-ray scattering confirms the existence of both types of spin cycloids. Finally, we show that electric-field control of the ferroelectric landscape induces transitions either between collinear and non-collinear states or between different cycloids, offering perspectives for the design of reconfigurable antiferromagnetic spin textures on demand.

Chirality, a foundational concept throughout science, may arise at ferromagnetic domain walls 1 and in related objects such as skyrmions 2 . However, chiral textures should also exist in other types of ferroic materials, such as antiferromagnets, for which theory predicts that they should move faster for lower power 3 , and ferroelectrics, where they should be extremely small and possess unusual topologies 4,5 . Here, we report the concomitant observation of antiferromagnetic and electric chiral textures at domain walls in the room-temperature ferroelectric antiferromagnet BiFeO 3 . Combining reciprocal and real-space characterization techniques, we reveal the presence of periodic chiral antiferromagnetic objects along the domain walls as well as a priori energetically unfavourable chiral ferroelectric domain walls. We discuss the mechanisms underlying their formation and their relevance for electrically controlled topological oxide electronics and spintronics.

Separation of the preferred enantiomer from racemic mixtures, i.e. "chiral switching," often improves efficacy and reduces toxicity. However, this strategy is not applicable for all chiral compounds-particularly for molecules with hydrogen-containing chiral centers, which can be prone to rapid stereoisomerization. Deuterium incorporation can stabilize such chiral centers while retaining the pharmacologic characteristics of the parent racemic mixture, thereby enabling their "chiral switching", changing the drug from a racemate to a single enantiomer. We describe "deuterium-enabled chiral switching" (DECS) as a means of improving on the therapeutic promise of chemically unstable racemic drugs and demonstrate its utility with the isolation and characterization of stable preferred enantiomers of thalidomide and thiazolidinedione (TZD) analogs., Competing Interests: The authors declare the following competing financial interest(s): SDW and VJ are employees and unit holders of DeuteRx, LLC. AWC is a unit holder of DeuteRx, LLC.

Magnetic skyrmions are quasiparticle-like textures which are topologically different from other states. Their discovery in systems with broken inversion symmetry sparked the search for materials containing such magnetic phase at room temperature. Their topological properties combined with the chirality-related spin-orbit torques make them interesting objects to control the magnetization at nanoscale. Here we show that a pair of coupled skyrmions of opposite chiralities can be stabilized in a symmetric magnetic bilayer system by combining Dzyaloshinskii-Moriya interaction (DMI) and dipolar coupling effects. This opens a path for skyrmion stabilization with lower DMI. We demonstrate in a device with asymmetric electrodes that such skyrmions can be independently written and shifted by electric current at large velocities. The skyrmionic nature of the observed quasiparticles is confirmed by the gyrotropic force. These results set the ground for emerging spintronic technologies where issues concerning skyrmion stability, nucleation and propagation are paramount.

An important epigenetic modification in Huntington's disease (HD) research is histone acetylation, which is regulated by histone acetyltransferase and histone deacetylase (HDAC) enzymes. HDAC inhibitors have proven effective in HD model systems, and recent work is now focused on functional dissection of the individual HDAC enzymes in these effects. Histone deacetylase 3 (HDAC3), a member of the class I subfamily of HDACs, has previously been implicated in neuronal toxicity and huntingtin-induced cell death. Hence, we tested the effects of RGFP966 ((E)-N-(2-amino-4-fluorophenyl)-3-(1-cinnamyl-1H-pyrazol-4-yl)acrylamide), a benzamide-type HDAC inhibitor that selectively targets HDAC3, in the N171-82Q transgenic mouse model of HD. We found that RGFP966 at doses of 10 and 25 mg/kg improves motor deficits on rotarod and in open field exploration, accompanied by neuroprotective effects on striatal volume. In light of previous studies implicating HDAC3 in immune function, we measured gene expression changes for 84 immune-related genes elicited by RGFP966 using quantitative PCR arrays. RGFP966 treatment did not cause widespread changes in cytokine/chemokine gene expression patterns, but did significantly alter the striatal expression of macrophage migration inhibitory factor (Mif), a hormone immune modulator associated with glial cell activation, in N171-82Q transgenic mice, but not WT mice. Accordingly, RGFP966-treated mice showed decreased glial fibrillary acidic protein (GFAP) immunoreactivity, a marker of astrocyte activation, in the striatum of N171-82Q transgenic mice compared to vehicle-treated mice. These findings suggest that the beneficial actions of HDAC3 inhibition could be related, in part, with lowered Mif levels and its associated downstream effects.

Research over the past decade indicates a novel role for epigenetic mechanisms in memory formation. Of particular interest is chromatin modification by histone deacetylases (HDACs), which, in general, negatively regulate transcription. HDAC deletion or inhibition facilitates transcription during memory consolidation and enhances long-lasting forms of synaptic plasticity and long-term memory. A key open question remains: How does blocking HDAC activity lead to memory enhancements? To address this question, we tested whether a normal function of HDACs is to gate information processing during memory formation. We used a class I HDAC inhibitor, RGFP966 (C21H19FN4O), to test the role of HDAC inhibition for information processing in an auditory memory model of learning-induced cortical plasticity. HDAC inhibition may act beyond memory enhancement per se to instead regulate information in ways that lead to encoding more vivid sensory details into memory. Indeed, we found that RGFP966 controls memory induction for acoustic details of sound-to-reward learning. Rats treated with RGFP966 while learning to associate sound with reward had stronger memory and additional information encoded into memory for highly specific features of sounds associated with reward. Moreover, behavioral effects occurred with unusually specific plasticity in primary auditory cortex (A1). Class I HDAC inhibition appears to engage A1 plasticity that enables additional acoustic features to become encoded in memory. Thus, epigenetic mechanisms act to regulate sensory cortical plasticity, which offers an information processing mechanism for gating what and how much is encoded to produce exceptionally persistent and vivid memories. Significance statement: Here we provide evidence of an epigenetic mechanism for information processing. The study reveals that a class I HDAC inhibitor (Malvaez et al., 2013; Rumbaugh et al., 2015; RGFP966, chemical formula C21H19FN4O) alters the formation of auditory memory by enabling more acoustic information to become encoded into memory. Moreover, RGFP966 appears to affect cortical plasticity: the primary auditory cortex reorganized in a manner that was unusually "tuned-in" to the specific sound cues and acoustic features that were related to reward and subsequently remembered. We propose that HDACs control "informational capture" at a systems level for what and how much information is encoded by gating sensory cortical plasticity that underlies the sensory richness of newly formed memories., (Copyright © 2015 the authors 0270-6474/15/3513125-09$15.00/0.)

Introduction: Microarray studies have shown elevated transcript levels of endothelial and natural killer (NK) cell-associated genes during antibody-mediated rejection (AMR) of the renal allograft. This study aimed to assess the use of quantitative real-time polymerase chain reaction as an alternative to microarray analysis on a subset of these elevated genes., Methods: Thirty-nine renal transplant biopsies from patients with de novo donor-specific antibodies and eighteen 1-year surveillance biopsies with no histological evidence of rejection were analyzed for expression of 11 genes previously identified as elevated in AMR., Results: Expression levels of natural killer markers were correlated to microcirculation inflammation and graft outcomes to a greater extent than endothelial markers. Creating a predictive model reduced the number of gene transcripts to be assessed to 2, SH2D1b and MYBL1, resulting in 66.7% sensitivity and 89.7% specificity for graft loss., Discussion: This work demonstrates that elevated gene expression levels, proposed to be associated with AMR, can be detected by established quantitative real-time polymerase chain reaction technology, making transition to the clinical setting feasible. Transcript analysis provides additional diagnostic information to the classification schema for AMR diagnosis but it remains to be determined whether significant numbers of centres will validate transcript analysis in their laboratories and put such analysis into clinical use.

The capacity to propagate magnetic domain walls with spin-polarized currents underpins several schemes for information storage and processing using spintronic devices. A key question involves the internal structure of the domain walls, which governs their response to certain current-driven torques such as the spin Hall effect. Here we show that magnetic microscopy based on a single nitrogen-vacancy defect in diamond can provide a direct determination of the internal wall structure in ultrathin ferromagnetic films under ambient conditions. We find pure Bloch walls in Ta/CoFeB(1 nm)/MgO, while left-handed Néel walls are observed in Pt/Co(0.6 nm)/AlOx. The latter indicates the presence of a sizable interfacial Dzyaloshinskii-Moriya interaction, which has strong bearing on the feasibility of exploiting novel chiral states such as skyrmions for information technologies.

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using "deuterium-enabled chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics.

The objective of this study is to describe the superior canal dehiscence syndrome (SCDS) and its vestibule-cochlear manifestations, while analyzing dehiscence size, audiogram and vestibular-evoked myogenic potential (VEMP) changes following dehiscence obliteration. We conducted a prospective study in a tertiary referral center. All Patients diagnosed and surgically treated for SCDS were operated through a middle fossa craniotomy (MFC). Clinical and radiological data were collected. The main outcome measures were Air-bone gaps, Pure-tone average (PTA), speech discrimination scores (SDS) and VEMP thresholds and were correlated to dehiscence size. 28 patients were included in this study with a mean dehiscence size of 4.68 mm. Phonophobia and imbalance were the most debilitating cochlear and vestibular symptoms, respectively. At 2 months postoperatively, low-frequency air-bone gaps showed a statistically significant improvement (p < 0.001). SDS and PTA did not show any statistically significant changes 2 months postoperatively (p = 0.282 and p = 0.295, respectively). VEMP threshold differences between operated and contralateral ears were statistically significant preoperatively (p < 0.001) and non-significant 2 months postoperatively (p = 0.173). Dehiscence size only showed a statistically significant correlation with preoperative total cochlear symptoms, while remaining insignificant with all other variables measured. Air-bone gaps, VEMP and computerized tomography remain essential tools in diagnosing and following SCDS. Dehiscence size is an independent factor in the analysis of SCDS, with cochlear symptomatology being associated to dehiscence sizes. Finally, it is shown that overall symptomatology, audiometric results and VEMP thresholds return to normal values post-obliteration, confirming the continuing success of the MFC approach for SCDS obliteration.

Using fast electron spin resonance spectroscopy of a single nitrogen-vacancy defect in diamond, we demonstrate real-time readout of the Overhauser field produced by its nuclear spin environment under ambient conditions. These measurements enable narrowing the Overhauser field distribution by postselection, corresponding to a conditional preparation of the nuclear spin bath. Correlations of the Overhauser field fluctuations are quantitatively inferred by analyzing the Allan deviation over consecutive measurements. This method allows us to extract the dynamics of weakly coupled nuclear spins of the reservoir.