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The cuprate high-temperature superconductors exhibit many unexplained electronic phases, but the superconductivity at high doping is often believed to be governed by conventional mean-field Bardeen-Cooper-Schrieffer theory1. However, it was shown that the superfluid density vanishes when the transition temperature goes to zero2,3, in contradiction to expectations from Bardeen-Cooper-Schrieffer theory. Our scanning tunnelling spectroscopy measurements in the overdoped regime of the (Pb,Bi)2Sr2CuO6+δ high-temperature superconductor show that this is due to the emergence of nanoscale superconducting puddles in a metallic matrix4,5. Our measurements further reveal that this puddling is driven by gap filling instead of gap closing. The important implication is that it is not a diminishing pairing interaction that causes the breakdown of superconductivity. Unexpectedly, the measured gap-to-filling correlation also reveals that pair breaking by disorder does not play a dominant role and that the mechanism of superconductivity in overdoped cuprate superconductors is qualitatively different from conventional mean-field theory.
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Topological metamaterials have robust properties engineered from their macroscopic arrangement, rather than their microscopic constituency. They can be designed by starting from Dirac metamaterials with either symmetry-enforced or accidental degeneracy. The latter case provides greater flexibility in the design of topological switches, waveguides, and cloaking devices, because a large number of tuning parameters can be used to break the degeneracy and induce a topological phase. However, the design of a topological logic element-a switch that can be controlled by the output of a separate switch-remains elusive. Here we numerically demonstrate a topological logic gate for ultrasound by exploiting the large phase space of accidental degeneracies in a honeycomb lattice. We find that a degeneracy can be broken by six physical parameters, and we show how to tune these parameters to create a phononic switch that transitions between a topological waveguide and a trivial insulator by ultrasonic heating. Our design scheme is directly applicable to photonic crystals and may guide the design of future electronic topological transistors.
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Helium ion beams (HIB) focused to subnanometer scales have emerged as powerful tools for high-resolution imaging as well as nanoscale lithography, ion milling, or deposition. Quantifying irradiation effects is an essential step toward reliable device fabrication, but most of the depth profiling information is provided by computer simulations rather than the experiment. Here, we demonstrate the use of atomic force microscopy (AFM) combined with scanning near-field optical microscopy (SNOM) to provide three-dimensional (3D) dielectric characterization of high-temperature superconductor devices fabricated by HIB. By imaging the infrared dielectric response obtained from light demodulation at multiple harmonics of the AFM tapping frequency, we find that amorphization caused by the nominally 0.5 nm HIB extends throughout the entire 26.5 nm thickness of the cuprate film and by â¼500 nm laterally. This unexpectedly widespread damage in morphology and electronic structure can be attributed to a helium depth distribution substantially modified by the internal device interfaces. Our study introduces AFM-SNOM as a quantitative tomographic technique for noninvasive 3D characterization of irradiation damage in a wide variety of nanoscale devices.
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New classes of drugs to treat type 2 diabetes are continually being developed and marketed. The FDA has issued guidance to the pharmaceutical industry that newer hypoglycemic agents should not be associated with unacceptable increases in cardiovascular risk. To date, five trials have assessed specific cardiovascular endpoints for these newer agents. Empagliflozin and liraglutide have been found to improve cardiovascular outcomes.
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Compuestos de Bencidrilo/farmacología , Sistema Cardiovascular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucósidos/farmacología , Hipoglucemiantes/farmacología , Liraglutida/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/fisiopatología , Angiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/etiología , Humanos , Factores de RiesgoRESUMEN
The properties of iron-based superconductors (Fe-SCs) can be varied dramatically with the introduction of dopants and atomic defects. As a pressing example, FeSe, parent phase of the highest-Tc Fe-SC, exhibits prevalent defects with atomic-scale "dumbbell" signatures as imaged by scanning tunneling microscopy (STM). These defects spoil superconductivity when their concentration exceeds 2.5%. Resolving their chemical identity is a prerequisite to applications such as nanoscale patterning of superconducting/nonsuperconducting regions in FeSe as well as fundamental questions such as the mechanism of superconductivity and the path by which the defects destroy it. We use STM and density functional theory to characterize and identify the dumbbell defects. In contrast to previous speculations about Se adsorbates or substitutions, we find that an Fe-site vacancy is the most energetically favorable defect in Se-rich conditions and reproduces our observed STM signature. Our calculations shed light more generally on the nature of Se capping, the removal of Fe vacancies via annealing, and their ordering into a â5 × â5 superstructure in FeSe and related alkali-doped compounds.
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The competition between proximate electronic phases produces a complex phenomenology in strongly correlated systems. In particular, fluctuations associated with periodic charge or spin modulations, known as density waves, may lead to exotic superconductivity in several correlated materials. However, density waves have been difficult to isolate in the presence of chemical disorder, and the suspected causal link between competing density wave orders and high-temperature superconductivity is not understood. Here we used scanning tunneling microscopy to image a previously unknown unidirectional (stripe) charge-density wave (CDW) smoothly interfacing with the familiar tridirectional (triangular) CDW on the surface of the stoichiometric superconductor NbSe(2). Our low-temperature measurements rule out thermal fluctuations and point to local strain as the tuning parameter for this quantum phase transition. We use this quantum interface to resolve two longstanding debates about the anomalous spectroscopic gap and the role of Fermi surface nesting in the CDW phase of NbSe(2). Our results highlight the importance of local strain in governing phase transitions and competing phenomena, and suggest a promising direction of inquiry for resolving similarly longstanding debates in cuprate superconductors and other strongly correlated materials.
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Niobio/química , Transición de Fase , Teoría Cuántica , Compuestos de Selenio/química , Algoritmos , Cristalización , Conductividad Eléctrica , Microscopía de Túnel de Rastreo/métodos , Modelos Químicos , Modelos Moleculares , Estructura Molecular , Temperatura de TransiciónRESUMEN
We use scanning tunneling spectroscopy to investigate the filled and empty electronic states of superconducting single-unit-cell FeSe deposited on SrTiO3(001). We map the momentum-space band structure by combining quasiparticle interference imaging with decay length spectroscopy. In addition to quantifying the filled-state bands, we discover a Γ-centered electron pocket 75 meV above the Fermi energy. Our density functional theory calculations show the orbital nature of empty states at Γ and explain how the Se height is a key tuning parameter of their energies, with broad implications for electronic properties.
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The highest-temperature superconductors are electronically inhomogeneous at the nanoscale, suggesting the existence of a local variable that could be harnessed to enhance the superconducting pairing. Here we report the relationship between local doping and local strain in the cuprate superconductor Bi(2)Sr(2)CaCu(2)O(8+x). We use scanning tunneling microscopy to discover that the crucial oxygen dopants are periodically distributed in correlation with local strain. Our picoscale investigation of the intraunit-cell positions of all oxygen dopants provides essential structural input for a complete microscopic theory.
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Cobre/química , Conductividad Eléctrica , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Modelos Químicos , Simulación por Computador , Módulo de Elasticidad , Calor , Ensayo de Materiales , Resistencia a la TracciónRESUMEN
Scanning tunneling spectroscopy has been used to reveal signatures of a bosonic mode in the local quasiparticle density of states of superconducting FeSe films. The mode appears below Tc as a "dip-hump" feature at energy Ωâ¼4.7kBTc beyond the superconducting gap Δ. Spectra on strained regions of the FeSe films reveal simultaneous decreases in Δ and Ω. This contrasts with all previous reports on other high-Tc superconductors, where Δ locally anticorrelates with Ω. A local strong coupling model is found to reconcile the discrepancy well, and to provide a unified picture of the electron-boson coupling in unconventional superconductors.
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BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2), is the primary vancomycin-induced immediate drug reaction (IDR). Clinically, distinguishing the underlying drug-induced IDR mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. OBJECTIVE: To determine if intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. METHODS: Cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose responses EC50, IDT-related local symptoms, and BAT were compared between groups. RESULTS: 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose response mean EC50 was 328 µg/mL (95% CI 296, 367) in the VIR vs. 1,166 µg/mL (95% CI 1029, 1379) in the tolerant group (p<0.0001). All VIR subjects reported IDT-related local pruritus compared to 60% of tolerant subjects (p=0.0185). The %CD63+ basophils were consistently <2%, without significant differences between groups (p < 0.54). CONCLUSIONS: Variations in skin test methodologies could help identify other IDR mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.
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A complicating factor in unravelling the theory of high-temperature (high-T(c)) superconductivity is the presence of a 'pseudogap' in the density of states, the origin of which has been debated since its discovery. Some believe the pseudogap is a broken symmetry state distinct from superconductivity, whereas others believe it arises from short-range correlations without symmetry breaking. A number of broken symmetries have been imaged and identified with the pseudogap state, but it remains crucial to disentangle any electronic symmetry breaking from the pre-existing structural symmetry of the crystal. We use scanning tunnelling microscopy to observe an orthorhombic structural distortion across the cuprate superconducting Bi(2)Sr(2)Ca(n-1)Cu(n)O(2n+4+x) (BSCCO) family tree, which breaks two-dimensional inversion symmetry in the surface BiO layer. Although this inversion-symmetry-breaking structure can impact electronic measurements, we show from its insensitivity to temperature, magnetic field and doping, that it cannot be the long-sought pseudogap state. To detect this picometre-scale variation in lattice structure, we have implemented a new algorithm that will serve as a powerful tool in the search for broken symmetry electronic states in cuprates, as well as in other materials.
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We report the SAR around a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase. 2-Aminophenethyl analogs demonstrate excellent potency but moderate kinase selectivity, while 2-aminobenzyl analogs that fill the Ala571 subpocket exhibit good inhibition activity and excellent kinase selectivity.
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Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Amidas/química , Amidas/farmacología , Animales , Humanos , Ratones , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
Optimization of the ADME properties of a series of 2,4-diaminopyrimidine-5-carboxamide inhibitors of Sky kinase resulted in the identification of highly selective compounds with properties suitable for use as in vitro and in vivo tools to probe the effects of Sky inhibition.
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Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Amidas/química , Amidas/farmacología , Animales , Humanos , Ratones , Proteínas Tirosina Quinasas Receptoras/química , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
Polo-like kinase-2 (Plk-2) is a potential therapeutic target for Parkinson's disease and this Letter describes the SAR of a series of dihydropteridinone based Plk-2 inhibitors. By optimizing both the N-8 substituent and the biaryl region of the inhibitors we obtained single digit nanomolar compounds such as 37 with excellent selectivity for Plk-2 over Plk-1. When dosed orally in rats, compound 37 demonstrated a 41-45% reduction of pS129-α-synuclein levels in the cerebral cortex.
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Diseño de Fármacos , Inhibidores de Proteínas Quinasas/síntesis química , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Administración Oral , Animales , Encéfalo/metabolismo , Proteínas de Ciclo Celular/antagonistas & inhibidores , Proteínas de Ciclo Celular/metabolismo , Células HEK293 , Semivida , Humanos , Ratones , Microsomas Hepáticos/metabolismo , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacocinética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas/metabolismo , Pteridinas/síntesis química , Pteridinas/química , Pteridinas/farmacocinética , Ratas , Relación Estructura-Actividad , Quinasa Tipo Polo 1RESUMEN
Many of today's forefront materials, such as high-Tc superconductors, doped semiconductors, and colossal magnetoresistance materials, are structurally, chemically and/or electronically inhomogeneous at the nanoscale. Although inhomogeneity can degrade the utility of some materials, defects can also be advantageous. Quite generally, defects can serve as nanoscale probes and facilitate quasiparticle scattering used to extract otherwise inaccessible electronic properties. In superconductors, non-stoichiometric dopants are typically necessary to achieve a high transition temperature, while both structural and chemical defects are used to pin vortices and increase critical current. Scanning tunneling microscopy (STM) has proven to be an ideal technique for studying these processes at the atomic scale. In this perspective, we present an overview of STM studies on chemical disorder in unconventional superconductors, and discuss how dopants, impurities and adatoms may be used to probe, pin or enhance the intrinsic electronic properties of these materials.
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PURPOSE: This study examined the impact of traumatic brain injury (TBI) on self-perceived hearing and suprathreshold binaural processing in young and middle-age adults. METHOD: Ninety-three adults with normal hearing (thresholds ≤ 25 dB HL, 250-4000 Hz) participated in one of four groups: 38 young adults, 23 young adults with TBI, 16 middle-age adults, and 16 middle-age adults with TBI. Self-perceived hearing difficulty was measured via questionnaires. Binaural processing was measured using dichotic word recognition, the Listening in Spatialized Noise-Sentences Test (LiSN-S), and the 500-Hz masking level difference (MLD). For each participant, a composite binaural processing (CBP) score was calculated to obtain a global metric of binaural processing performance. The CBP was composed of six measures from the three behavioral tests, including the S0N0 and SπN0 thresholds from the 500-Hz MLD, the low- and high-cue speech recognition thresholds from the LiSN-S, and the free and directed recall ear advantages from the dichotic word test. RESULTS: The middle-age TBI group reported significantly greater degrees of self-perceived hearing difficulty than the other groups. On average, the middle-age TBI group performed poorer on the individual binaural processing tests; however, the differences were significant for the S0N0 and SπN0 MLD thresholds only. Results for the global metric of binaural processing revealed significantly poorer CBP scores for the middle-age TBI group compared to the other groups. CONCLUSIONS: Results demonstrate that both age and a positive history of TBI contributed to deficits in suprathreshold binaural processing. Middle-age adults with a history of TBI are at risk for experiencing presenescent deficits in suprathreshold binaural processing deficits, despite having clinically normal hearing.
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Forming a hetero-interface is a materials-design strategy that can access an astronomically large phase space. However, the immense phase space necessitates a high-throughput approach for an optimal interface design. Here we introduce a high-throughput computational framework, InterMatch, for efficiently predicting charge transfer, strain, and superlattice structure of an interface by leveraging the databases of individual bulk materials. Specifically, the algorithm reads in the lattice vectors, density of states, and the stiffness tensors for each material in their isolated form from the Materials Project. From these bulk properties, InterMatch estimates the interfacial properties. We benchmark InterMatch predictions for the charge transfer against experimental measurements and supercell density-functional theory calculations. We then use InterMatch to predict promising interface candidates for doping transition metal dichalcogenide MoSe2. Finally, we explain experimental observation of factor of 10 variation in the supercell periodicity within a few microns in graphene/α-RuCl3 by exploring low energy superlattice structures as a function of twist angle using InterMatch. We anticipate our open-source InterMatch algorithm accelerating and guiding ever-growing interfacial design efforts. Moreover, the interface database resulting from the InterMatch searches presented in this paper can be readily accessed online.
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Charge modulations have been widely observed in cuprates, suggesting their centrality for understanding the high-Tc superconductivity in these materials. However, the dimensionality of these modulations remains controversial, including whether their wavevector is unidirectional or bidirectional, and also whether they extend seamlessly from the surface of the material into the bulk. Material disorder presents severe challenges to understanding the charge modulations through bulk scattering techniques. We use a local technique, scanning tunneling microscopy, to image the static charge modulations on Bi2-zPbzSr2-yLayCuO6+x. The ratio of the phase correlation length ξCDW to the orientation correlation length ξorient points to unidirectional charge modulations. By computing new critical exponents at free surfaces including that of the pair connectivity correlation function, we show that these locally 1D charge modulations are actually a bulk effect resulting from classical 3D criticality of the random field Ising model throughout the entire superconducting doping range.