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Table S1. Mean ({plus minus}SD) Toxicokinetic Parameters for Ipilimumab and Novolumab in Cynomolgus Monkeys Table S2 - Differentially expressed genes in the heart of ipilimumab and nivolumab treated cynos (adjusted P-value {less than or equal to} 0.05) Table S3 - Top 50 enriched pathways identified by IPA when using the data set of 882 analysis ready differentially expressed genes (adjusted P-value {less than or equal to} 0.05). Ratio: number of DE genes in a pathway divided by the number of genes comprised in the same pathway. Table S4: Top 25 networks identified based upon differentially expressed genes (adjusted P-value {less than or equal to} 0.05) in ipilimumab and nivolumab treated cynos. Table S5: Regulator effects networks generated using genes that are differentially expressed (adjusted P-value {less than or equal to} 0.05) in ipilimumab and nivolumab treated cynos. Upstream regulator and diseae& function cutoffs were each log P-value {less than or equal to} 10 and a z-score {greater than or equal to} |3| Table S6 - Differential expression of myocarditis- associated genes in the heart of ipilimumab and nivolumab treated cynos

Supplemental Figure S1. Concentration versus time profiles of ipilimumab and nivolumab following four weekly intravenous dose administrations of 15 mg/kg or 20 mg/kg, respectively. Supplementary Figure S2. Hematoxylin and eosin stained sections of tissues from control and monkeys dosed with ipilimumab and nivolumab. Supplementary Figure S3. Quantification of mononuclear cell infiltrates from IHC images of heart sections.

Purpose:Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis are poorly understood, and there is currently a lack of laboratory animal model to enhance our understanding. We aimed to develop such a model using cynomolgus monkeys.Experimental Design:Chinese-origin cynomolgus monkeys were dosed intravenously with vehicle or nivolumab 20 mg/kg plus ipilimumab 15 mg/kg once weekly and euthanized on day 29.Results:Multiple organ toxicities were observed in cynomolgus monkeys, and were characterized by loose feces, lymphadenopathy, and mononuclear cell infiltrations of varying severity in heart, colon, kidneys, liver, salivary glands, and endocrine organs. Increased proliferation of CD4+ and CD8+ T lymphocytes as well as an increase in activated T cells and central memory T cells in the blood, spleen, and lymph nodes, were observed. Transcriptomic analysis suggested increased migration and activation of T cells and increased phagocytosis and antigen presentation in the heart. Mononuclear cell infiltration in myocardium was comprised primarily of T cells, with lower numbers of macrophages and occasional B cells, and was associated with minimal cardiomyocyte degeneration as well as increases in cardiac troponin-I and NT-pro-BNP. Morphologically, cardiac lesions in our monkey model are similar to the reported ICI myocarditis in humans.Conclusions:We have developed a monkey model characterized by multiple organ toxicities including myocarditis. This model may provide insight into the immune mechanisms and facilitate biomarker identification for ICI-associated irAEs.

Topological materials hosting kagome lattices have drawn considerable attention due to the interplay between topology, magnetism, and electronic correlations. The (Fe$_{1-x}$Co$_x$)Sn system not only hosts a kagome lattice but has a tunable symmetry breaking magnetic moment with temperature and doping. In this study, angle resolved photoemission spectroscopy and first principles calculations are used to investigate the interplay between the topological electronic structure and varying magnetic moment from the planar to axial antiferromagnetic phases. A theoretically predicted gap at the Dirac point is revealed in the low temperature axial phase but no gap opening is observed across a temperature dependent magnetic phase transition. However, topological surface bands are observed to shift in energy as the surface magnetic moment is reduced or becomes disordered over time during experimental measurements. The shifting surface bands may preclude the determination of a temperature dependent bulk gap but highlights the intricate connections between magnetism and topology with a surface/bulk dichotomy that can affect material properties and their interrogation., Comment: 11 pages, 4 figures

The kagome lattice is a fertile platform to explore topological excitations with both Fermi-Dirac and Bose-Einstein statistics. While relativistic Dirac Fermions and flat-bands have been discovered in the electronic structure of kagome metals, the spin excitations have received less attention. Here we report inelastic neutron scattering studies of the prototypical kagome magnetic metal FeSn. The spectra display well-defined spin waves extending up to 120 meV. Above this energy, the spin waves become progressively broadened, reflecting interactions with the Stoner continuum. Using linear spin wave theory, we determine an effective spin Hamiltonian that reproduces the measured dispersion. This analysis indicates that the Dirac magnon at the K-point remarkably occurs on the brink of a region where well-defined spin waves become unobservable. Our results emphasize the influential role of itinerant carriers on the topological spin excitations of metallic kagome magnets., 6 pages, 4 figures

The tetragonal intermetallic compound EuAl$_{4}$ hosts an exciting variety of low temperature phases. In addition to a charge density wave below 140 K, four ordered magnetic phases are observed below 15.4 K. Recently, a skyrmion phase was proposed based on Hall effect measurements under a $c$-axis magnetic field. We present a detailed investigation of the phase transitions in EuAl$_{4}$ under $c$-axis magnetic field. Our dilatometry, heat capacity, DC magnetometry, AC magnetic susceptibility, and resonant ultrasound spectroscopy measurements reveal three magnetic phase transitions not previously reported. We discuss what our results reveal about the character of the magnetic phases. Our first key result is a detailed $H \parallel [001]$ magnetic phase diagram mapping the seven phases we observe. Second, we identify a new high-field phase, phase VII, which directly corresponds to the region were skyrmions have been suggested. Our results provide guidance for future studies exploring the complex magnetic interactions and spin structures in EuAl$_{4}$., 20 pages, 15 figures

Kagome lattices host flat bands due to their frustrated lattice geometry, which leads to destructive quantum interference of electron wave functions. Here, we report imaging of the kagome flat band localization in real-space using scanning tunneling microscopy. We identify both the Fe3Sn kagome lattice layer and the Sn2 honeycomb layer with atomic resolution in kagome antiferromagnet FeSn. On the Fe3Sn lattice, at the flat band energy determined by the angle resolved photoemission spectroscopy, tunneling spectroscopy detects an unusual state localized uniquely at the Fe kagome lattice network. We further show that the vectorial in-plane magnetic field manipulates the spatial anisotropy of the localization state within each kagome unit cell. Our results are consistent with the real-space flat band localization in the magnetic kagome lattice. We further discuss the magnetic tuning of flat band localization under the spin-orbit coupled magnetic kagome lattice model., Comment: To appear in Communications Materials

Purpose: Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis are poorly understood, and there is currently a lack of laboratory animal model to enhance our understanding. We aimed to develop such a model using cynomolgus monkeys. Experimental Design: Chinese-origin cynomolgus monkeys were dosed intravenously with vehicle or nivolumab 20 mg/kg plus ipilimumab 15 mg/kg once weekly and euthanized on day 29. Results: Multiple organ toxicities were observed in cynomolgus monkeys, and were characterized by loose feces, lymphadenopathy, and mononuclear cell infiltrations of varying severity in heart, colon, kidneys, liver, salivary glands, and endocrine organs. Increased proliferation of CD4+ and CD8+ T lymphocytes as well as an increase in activated T cells and central memory T cells in the blood, spleen, and lymph nodes, were observed. Transcriptomic analysis suggested increased migration and activation of T cells and increased phagocytosis and antigen presentation in the heart. Mononuclear cell infiltration in myocardium was comprised primarily of T cells, with lower numbers of macrophages and occasional B cells, and was associated with minimal cardiomyocyte degeneration as well as increases in cardiac troponin-I and NT-pro-BNP. Morphologically, cardiac lesions in our monkey model are similar to the reported ICI myocarditis in humans. Conclusions: We have developed a monkey model characterized by multiple organ toxicities including myocarditis. This model may provide insight into the immune mechanisms and facilitate biomarker identification for ICI-associated irAEs.

We have carried out75As nuclear magnetic resonance (NMR) measurements to investigate a new antiferromagnetic (AFM) state, the so-called hedgehog spin-vortex crystal (SVC) in CaK(Fe0.967Ni0.033)4As4. The hedgehog SVC order is clearly demonstrated by the direct observation of internal magnetic induction along the c axis at the As1 site (close to K) and a zero net internal magnetic induction at the As2 site (close to Ca) below an AFM ordering temperature of TN~ 45 K. In the superconducting (SC) state, the NMR signal intensity decreases suddenly just below Tc~ 20 K due to Meissner effect, evidencing the coexistence of the hedgehog SVC AFM and SC states from a microscopic point of view.

High critical temperature superconductivity often occurs in systems where an antiferromagnetic order is brought near $T=0$ K by slightly modifying pressure or doping. ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ is a superconducting, stoichiometric iron-pnictide compound showing optimal superconducting critical temperature with ${T}_{c}$ as large as 35 K. Doping with Ni induces a decrease in ${T}_{c}$ and the onset of spin-vortex crystal (SVC) antiferromagnetic order, which consists of spins pointing inwards to or outwards from alternating As sites on the diagonals of the in-plane square Fe lattice. Here we study the band structure of $\mathrm{CaK}{({\mathrm{Fe}}_{0.95}{\mathrm{Ni}}_{0.05})}_{4}{\mathrm{As}}_{4}$ $({T}_{c}=10 \mathrm{K},$ ${T}_{SVC}=50 \mathrm{K})$ using quasiparticle interference with a scanning tunneling microscope and show how the SVC modifies the band structure and induces a fourfold superconducting gap anisotropy.

CoSn is a Pauli paramagnet with relatively flat d-bands centered about 100 meV below the Fermi energy Ef. Single crystals of CoSn lightly doped with Fe, In, or Ni are investigated using x-ray and neutron scattering, magnetic susceptibility and magnetization, ac susceptibility, specific heat and resistivity measurements. Within the rigid band approximation, hole doping with a few percent of Fe or In should move the flat bands closer to Ef, whereas electron doping with Ni should move the flat bands further away from Ef. We provide evidence that this indeed occurs. Fe and In doping drive CoSn toward magnetism, while Ni doping suppresses CoSn's already weak magnetic response. The resulting ground state is different for Fe versus In doping. For Fe-doped crystals, Co1-xFexSn, with 0.02 < x < 0.27, the magnetic and specific heat data are consistent with the formation of a spin glass, with a glass transition temperature, Tg, ranging from 1 K for x=0.02 to 10 K for x= 0.27. Powder and single crystal neutron diffraction found no evidence of long-range magnetic order below Tg with x = 0.17. For In-doped crystals, CoSn1-yIny, both the magnetic susceptibility and the Sommerfeld coefficient, gamma, increase substantially relative to pure CoSn, but with no clear indication of a magnetic transition for 0.05 < y < 0.2. CoSn crystals doped with Ni (Co0.93Ni0.07Sn) have a significantly smaller magnetic susceptibility and gamma than pure CoSn, consistent with the flat bands further from Ef., 20 pages, 10 figures

Charge density waves (CDW) are modulations of the electron density and the atomic lattice that develop in some crystalline materials at low temperature. We report an unusual example of a CDW in BaFe$_2$Al$_9$ below 100 K. In contrast to the canonical CDW phase transition, temperature dependent physical properties of single crystals reveal a first-order phase transition. This is accompanied by a discontinuous change in the size of the crystal lattice. In fact, this large strain has catastrophic consequences for the crystals causing them to physically shatter. Single crystal x-ray diffraction reveals super-lattice peaks in the low-temperature phase signaling the development of a CDW lattice modulation. No similar low-temperature transitions are observed in BaCo$_2$Al$_9$. Electronic structure calculations provide one hint to the different behavior of these two compounds; the d-orbital states in the Fe compound are not completely filled. Iron compounds are renowned for their magnetism and partly filled d-states play a key role. It is therefore surprising that BaFe$_2$Al$_9$ develops a structural modulation instead at low temperature instead of magnetic order., 34 pages, 8 figures Edits to text as well as figures 2 and 5. Added neutron diffraction (Fig. 6)

In the nematic state of iron-based superconductors, twin formation often obscures the intrinsic, anisotropic, in-plane physical properties. Relatively high in-plane external magnetic fields ${H}_{\mathrm{ext}}$ greater than the typical laboratory-scale magnetic fields 10--15 T are usually required to completely detwin a sample. However, recently a very small in-plane ${H}_{\mathrm{ext}}\ensuremath{\sim}0.1$ T was found to be sufficient for detwinning the nematic domains in ${\mathrm{EuFe}}_{2}{\mathrm{As}}_{2}$. To explain this behavior, a microscopic theory based on biquadratic magnetic interactions between the Eu and Fe spins has been proposed. Here, using $^{153}\mathrm{Eu}$ nuclear magnetic resonance (NMR) measurements below the ${\mathrm{Eu}}^{2+}$ ordering temperature, we show experimental evidence of the detwinning under small in-plane ${H}_{\mathrm{ext}}$. Our NMR study also reveals the evolution of the angles between the Eu and Fe spins during the detwinning process, which provides experimental evidence for the existence of biquadratic coupling in the system.

The magnetic response of $\mathrm{Ca}\mathrm{K}{({\mathrm{Fe}}_{0.949}{\mathrm{Ni}}_{0.051})}_{4}{\mathrm{As}}_{4}$ was investigated by means of the muon spin rotation/relaxation. The long-range commensurate magnetic order sets in below the N\'eel temperature ${T}_{\mathrm{N}}=50.0(5)$ K. The density-functional theory calculations have identified three possible muon stopping sites. The experimental data were found to be consistent with only one type of magnetic structure, namely, the long-range magnetic spin-vortex-crystal order with the hedgehog motif within the $ab$ plane and the antiferromagnetic stacking along the $c$ direction. The value of the ordered magnetic moment at $T\ensuremath{\approx}3$ K was estimated to be ${m}_{\mathrm{Fe}}=0.38(11){\ensuremath{\mu}}_{\mathrm{B}}$ (${\ensuremath{\mu}}_{\mathrm{B}}$ is the Bohr magneton). A microscopic coexistence of magnetic and superconducting phases accompanied by a reduction of the magnetic order parameter below the superconducting transition temperature ${T}_{\mathrm{c}}\ensuremath{\simeq}9$ K is observed. Comparison with 11, 122, and 1144 families of Fe-based pnictides points to existence of correlation between the reduction of the magnetic order parameter at $T\ensuremath{\rightarrow}0$ and the ratio of the transition temperatures ${T}_{\mathrm{c}}/{T}_{\mathrm{N}}$. Such correlations were found to be described by Machida's model for coexistence of itinerant spin-density-wave magnetism and superconductivity [K. Machida, J. Phys. Soc. Jpn. 50, 2195 (1981); S. L. Bud'ko et al., Phys. Rev. B 98, 144520 (2018)].

Quantum interference on the kagome lattice generates electronic bands with narrow bandwidth, called flat bands. Crystal structures incorporating this lattice can host strong electron correlations with nonstandard ingredients, but only if these bands lie at the Fermi level. In the six compounds with the CoSn structure type (FeGe, FeSn, CoSn, NiIn, RhPb, and PtTl) the transition metals form a kagome lattice. The two iron variants are robust antiferromagnets so we focus on the latter four and investigate their thermodynamic and transport properties. We consider these results and calculated band structures to locate and characterize the flat bands in these materials. We propose that CoSn and RhPb deserve the community's attention for exploring flat-band physics.

The upper critical field of multiband superconductors is an important quantity that can reveal details about the nature of the superconducting pairing. Here we experimentally map out the complete upper-critical-field phase diagram of a stoichiometric superconductor, ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$, up to $90\phantom{\rule{0.16em}{0ex}}\mathrm{T}$ for different orientations of the magnetic field and at temperatures down to $4.2\phantom{\rule{0.16em}{0ex}}\mathrm{K}$. The upper critical fields are extremely large, reaching values close to $\ensuremath{\sim}3\phantom{\rule{0.16em}{0ex}}{T}_{\mathrm{c}}$ at the lowest temperature, and the anisotropy decreases dramatically with temperature, leading to essentially isotropic superconductivity at $4.2\phantom{\rule{0.16em}{0ex}}\mathrm{K}$. We find that the temperature dependence of the upper critical field can be well described by a two-band model in the clean limit with band-coupling parameters favoring intraband over interband interactions. The large Pauli paramagnetic effects together with the presence of the shallow bands is consistent with the stabilization of an FFLO state at low temperatures in this clean superconductor.

Magnetism is widely considered to be a key ingredient of unconventional superconductivity. In contrast to cuprate high-temperature superconductors, antiferromagnetism in Fe-based superconductors (FeSCs) is characterized by a pair of magnetic propagation vectors. Consequently, three different types of magnetic order are possible. Of theses, only stripe-type spin-density wave (SSDW) and spin-charge-density wave (SCDW) orders have been observed. A realization of the proposed spin-vortex crystal (SVC) order is noticeably absent. We report a magnetic phase consistent with the hedgehog variation of SVC order in Ni- and Co-doped CaKFe4As4 based on thermodynamic, transport, structural and local magnetic probes combined with symmetry analysis. The exotic SVC phase is stabilized by the reduced symmetry of the CaKFe4As4 structure. Our results suggest that the possible magnetic ground states in FeSCs have very similar energies, providing an enlarged configuration space for magnetic fluctuations to promote high-temperature superconductivity., Comment: Updated version including supplemental material

The compound Ag3Sn adopts the ordered orthorhombic D0a Cu3Ti-type structure. It exhibits an unusual low yield stress and high ductility for an intermetallic compound, but the reasons for these effects are not clear. Here, we report an electron microscopy study on the defects present in solution-grown Ag3Sn single crystals that have deformed during the decanting and subsequent handling processes. It is found that the crystals contain two types of lenticular deformation twins: {011}-type and {211}-type. These twins interpenetrate with no evidence of cracking at the intersections. The crystals also contain high densities of dislocations including long straight dipoles with b = ± [010] and shorter curved segments and loops with b = [ $$ 10\bar{2} $$ ] and [001]. It is inferred that the dipoles are artifacts of specimen preparation that climb in from the cross-sectional sample surfaces, whereas the shorter segments are deformation debris. If a combination of twinning and dislocation glide of the types observed here were to form concurrently during general deformation of Ag3Sn, then they could provide the necessary number of independent deformation modes to accommodate an arbitrary plastic strain, which might help to explain the unusual ductility of this compound.

In this paper we report the synthesis, magnetization, and heat capacity of the frustrated magnets $A{\mathrm{ErSe}}_{2}$($A=\mathrm{Na},\mathrm{K}$) which contain perfect triangular lattices of ${\mathrm{Er}}^{3+}$. The magnetization data suggests no long-range magnetic order exists in $A{\mathrm{ErSe}}_{2}$($A=\mathrm{Na},\mathrm{K}$), which is consistent with the heat capacity measurements. Large anisotropy is observed between the magnetization within the $ab$ plane and along the $c$ axis of both compounds. When the magnetic field is applied along the $ab$ plane, anomalies are observed at 1.8 ${\ensuremath{\mu}}_{B}$ in ${\mathrm{NaErSe}}_{2}$ at 0.2 T and 2.1 ${\ensuremath{\mu}}_{B}$ in ${\mathrm{KErSe}}_{2}$ at 0.18 T. Unlike ${\mathrm{NaErSe}}_{2}$, a plateaulike field-induced metamagnetic transition is observed for $\mathrm{H}\ensuremath{\parallel}c$ below 1 K in ${\mathrm{KErSe}}_{2}$. Two broad peaks are observed in the heat capacity below 10 K indicating possible crystal electric field (CEF) effects and magnetic entropy released under different magnetic fields. All results indicate that $A{\mathrm{ErSe}}_{2}$ are strongly anisotropic, frustrated magnets with field-induced transition at low temperature. The lack of signatures for long-range magnetic order implies that these materials are candidates for hosting a quantum spin liquid ground state.

Single crystals of the single kagome layer compound FeSn are investigated using x-ray and neutron scattering, magnetic susceptibility and magnetization, heat capacity, resistivity, Hall, Seebeck, thermal expansion, thermal conductivity measurements, and density functional theory (DFT). FeSn is a planar antiferromagnet below ${T}_{\mathrm{N}}=365\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ and exhibits ferromagnetic magnetic order within each kagome layer. The in-plane magnetic susceptibility is sensitive to synthesis conditions. Resistivity, Hall and Seebeck results indicate multiple bands near the Fermi energy. The resistivity of FeSn is \ensuremath{\approx}3 times lower for current along the stacking direction than in the plane, suggesting that transport and the bulk electronic structure of FeSn is not quasi-two-dimensional (2D). FeSn is an excellent metal with \ensuremath{\rho}(300 K)/\ensuremath{\rho}(2 K) values \ensuremath{\approx}100 in both directions. While the ordered state is antiferromagnetic, high temperature susceptibility measurements indicate a ferromagnetic Curie-Weiss temperature of 173 K, reflecting the strong in-plane ferromagnetic interactions. DFT calculations show a 3D electronic structure with the Dirac nodal lines along the K-H directions in the magnetic Brillouin zone about 0.3 eV below the Fermi energy, with the Dirac dispersions at the $K$ points gapped by spin-orbit coupling except at the $H$ point. The magnetism, however, is highly 2D with ${J}_{\mathrm{in}\text{\ensuremath{-}}\mathrm{plane}}/{J}_{\mathrm{out}\text{\ensuremath{-}}\mathrm{of}\text{\ensuremath{-}}\mathrm{plane}}\ensuremath{\approx}10$. The predicted spin-wave spectrum is presented.

FeSn is an itinerant antiferromagnet that hosts electronic Dirac states and ordered magnetic moments lying within its Fe Kagome-lattice planes. We present magnetization measurements of single crystals of $({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Co}}_{x})\text{Sn}$, revealing the evolution and suppression of this magnetic order with Co substitution. We interpret the dramatic changes in magnetic anisotropy to indicate a reorientation of the moments from perpendicular to parallel to the hexagonal $c$ axis and confirm this with neutron diffraction. It has been proposed that the Dirac nodes observed in FeSn should become gapped if the moments rotate as our data suggests. We identify Co-substituted compositions that adopt both antiferromagnetic configurations at different temperatures. This system provides a unique opportunity to study how the details of magnetic order impact Dirac electron states.

Xenobiotic-induced peripheral nerve damage is a growing concern. Identifying relative risks that a new drug may cause peripheral nerve injury over long periods of administration is gathering importance in the evaluation of animal models. Separating out age-related changes in peripheral nerves of rats caused by compression injury from drug-induced effects has been difficult. Biopsy of the sural nerve is utilized in humans for investigations of peripheral neuropathy, because it is largely removed from the effects of nerve compression. This study used transmission electron microscopy to identify incidental findings in the sural nerves and dorsal root ganglia of aged control rats over time. The goal was to establish a baseline understanding of the range of possible changes that could be noted in controls compared to rats treated with any new investigative drug. In this evaluation, most sural nerve fibers from aged control rats had few ultrastructural abnormalities of pathologic significance. However, glycogenosomes, polyglucosan bodies, swollen mitochondria, autolysosomes, split myelin, Schwann cell processes, and endoneural macrophages with phagocytosed debris (considered an indication of ongoing degenerative changes) were occasionally noted.

We report combined experimental and theoretical analysis of superconductivity in $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$ (CaK1144) for $x=0$, 0.017, and 0.034. To obtain the superfluid density $\ensuremath{\rho}={\left[1+\mathrm{\ensuremath{\Delta}}{\ensuremath{\lambda}}_{L}(T)/{\ensuremath{\lambda}}_{L}(0)\right]}^{\ensuremath{-}2}$, the temperature dependence of the London penetration depth $\mathrm{\ensuremath{\Delta}}{\ensuremath{\lambda}}_{L}(T)$ was measured by using a tunnel-diode resonator (TDR) and the results agreed with the microwave coplanar resonator (MWR) with the small differences accounted for by considering a three orders of magnitude higher frequency of MWR. The absolute value of ${\ensuremath{\lambda}}_{L}(T\ensuremath{\ll}{T}_{c})\ensuremath{\approx}{\ensuremath{\lambda}}_{L}(0)$ was measured by using MWR, ${\ensuremath{\lambda}}_{L}(5\phantom{\rule{4pt}{0ex}}\mathrm{K})\ensuremath{\approx}170\ifmmode\pm\else\textpm\fi{}20$ nm, which agreed well with the NV centers in diamond optical magnetometry that gave ${\ensuremath{\lambda}}_{L}(5\phantom{\rule{4pt}{0ex}}\mathrm{K})\ensuremath{\approx}196\ifmmode\pm\else\textpm\fi{}12$ nm. The experimental results are analyzed within the Eliashberg theory, showing that the superconductivity of CaK1144 is well described by the nodeless ${s}_{\ifmmode\pm\else\textpm\fi{}}$ order parameter and that upon Ni doping the interband interaction increases.

The nonselective cation channel TRPV1 is required for systemic inflammation to enhance aminoglycoside-induced hearing loss., Aminoglycoside antibiotics are essential for treating life-threatening bacterial infections, despite the risk of lifelong hearing loss. Infections induce inflammation and up-regulate expression of candidate aminoglycoside-permeant cation channels, including transient receptor potential vanilloid-1 (TRPV1). Heterologous expression of TRPV1 facilitated cellular uptake of (fluorescently tagged) gentamicin that was enhanced by agonists, and diminished by antagonists, of TRPV1. Cochlear TRPV1 was immunolocalized near the apical membranes of sensory hair cells, adjacent supporting cells, and marginal cells in the stria vascularis. Exposure to immunostimulatory lipopolysaccharides, to simulate of bacterial infections, increased cochlear expression of TRPV1 and hair cell uptake of gentamicin. Lipopolysaccharide exposure exacerbated aminoglycoside-induced auditory threshold shifts and loss of cochlear hair cells in wild-type, but not in heterozygous Trpv1+/− or Trpv1 knockout, mice. Thus, TRPV1 facilitates cochlear uptake of aminoglycosides, and bacteriogenic stimulation upregulates TRPV1 expression to exacerbate cochleotoxicity. Furthermore, loss-of-function polymorphisms in Trpv1 can protect against immunogenic exacerbation of aminoglycoside-induced cochleotoxicity.

The magnetic penetration depth anisotropy $\gamma_\lambda=\lambda_{c}/\lambda_{ab}$ ($\lambda_{ab}$ and $\lambda_{c}$ are the in-plane and the out-of-plane components of the magnetic penetration depth) in a CaKFe$_4$As$_4$ single crystal sample (the critical temperature $T_{\rm c}\simeq 35$ K) was studied by means of muon-spin rotation ($\mu$SR). $\gamma_\lambda$ is almost temperature independent for $T\lesssim 20$ K ($\gamma_\lambda\simeq 1.9$) and it reaches $\simeq 3.0$ by approaching $T_{\rm c}$. The change of $\gamma_\lambda$ induces the corresponding rearrangement of the flux line lattice (FLL), which is clearly detected via enhanced distortions of the FLL $\mu$SR response. Comparison of $\gamma_\lambda$ with the anisotropy of the upper critical field ($\gamma_{H_{\rm c2}}$) studied in Phys. Rev B {\bf 94}, 064501 (2016), reveals that $\gamma_\lambda$ is systematically higher than $\gamma_{H_{\rm c2}}$ at low-temperatures and approaches $\gamma_{H_{\rm c2}}$ for $T \rightarrow T_{\rm c}$. The anisotropic properties of $\lambda$ are explained by the multi-gap nature of superconductivity in CaKFe$_4$As$_4$ and are caused by anisotropic contributions of various bands to the in-plane and the out-of-plane components of the superfluid density., Comment: 6 pages, 4 figures

In condensed matter physics, knowing the lower critical magnetic field ${H}_{c1}$ is necessary to evaluate the superfluid density, which can provide insight into the gap structure gap and mechanism of superconductivity in a type-II superconductor. Measuring ${H}_{c1}$ is complicated by the distortion of a magnetic field around the sample, and by the sensitivity and spatial resolution of the chosen technique. This work demonstrates minimally invasive vector magnetometry based on optically detected magnetic resonance of N-$V$ centers in diamond, which, with the help of revised demagnetization corrections for real-world nonellipsoidal samples, provides a sensitive method to measure ${H}_{c1}$.

Fil: Haberkorn, Nestor Fabian. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche | Comision Nacional de Energia Atomica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia. Unidad Ejecutora Instituto de Nanociencia y Nanotecnologia - Nodo Bariloche; Argentina

Temperature dependent $^{57}\mathrm{Fe}$ M\"ossbauer spectroscopy and specific heat measurements for $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$ with $x=0$, 0.017, 0.033, and 0.049 are presented. No magnetic hyperfine field (i.e., no static magnetic order) down to 5.5 K was detected for $x=0$ and 0.017 in agreement with the absence of any additional feature below superconducting transition temperature ${T}_{c}$ in the specific heat data. The evolution of magnetic hyperfine field with temperature was studied for $x=0.033$ and 0.049. The long-range magnetic order in these two compounds coexists with superconductivity. The magnetic hyperfine field ${B}_{\text{hf}}$ (ordered magnetic moment) below ${T}_{c}$ in $\mathrm{CaK}{({\mathrm{Fe}}_{0.967}{\mathrm{Ni}}_{0.033})}_{4}{\mathrm{As}}_{4}$ is continuously suppressed with the developing superconducting order parameter. The ${B}_{\text{hf}}(T)$ data for $\mathrm{CaK}{({\mathrm{Fe}}_{0.967}{\mathrm{Ni}}_{0.033})}_{4}{\mathrm{As}}_{4}$ and $\mathrm{CaK}{({\mathrm{Fe}}_{0.951}{\mathrm{Ni}}_{0.049})}_{4}{\mathrm{As}}_{4}$ can be described reasonably well by Machida's model for coexistence of itinerant spin density wave magnetism and superconductivity [K. Machida, J. Phys. Soc. Jpn. 50, 2195 (1981)]. We demonstrate directly that superconductivity suppresses the spin density wave order parameter if the conditions are right, in agreement with the theoretical analysis.

We employ polarization-resolved Raman spectroscopy to study the multiband stoichiometric ${T}_{c}=35$ K superconductor ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$. We do not detect Pomeranchuk-like electronic nematic fluctuations which were universally observed in the $XY\phantom{\rule{4pt}{0ex}}({B}_{2g})$ symmetry Raman response for most families of the Fe-based superconductors. In the superconducting state we observe, consistent with a nodeless order parameter, a full spectral weight suppression at low energies and the emergence of a composite pair-breaking coherence feature at energies between 12 and 20 meV. We analyze the superconductivity-induced phonon self-energy effects and give an estimation for the electron-phonon coupling constant ${\ensuremath{\lambda}}^{\mathrm{\ensuremath{\Gamma}}}=0.0015$ which is insufficient to provide attraction for high-${T}_{c}$ pairing.

The interplay of magnetism and superconductivity (SC) has been a focus of interest in condensed matter physics for decades. $\mathrm{EuF}{\mathrm{e}}_{2}\mathrm{A}{\mathrm{s}}_{2}$ has been identified as a potential platform to investigate interactions between structural, magnetic, and electronic effects as well as the coexistence of magnetism and SC with similar transition temperatures. However, there are obvious inconsistencies in the reported phase diagrams of $\mathrm{Eu}{(\mathrm{F}{\mathrm{e}}_{1\ensuremath{-}x}\mathrm{C}{\mathrm{o}}_{x})}_{2}\mathrm{A}{\mathrm{s}}_{2}$ crystals grown by different methods. For transition metal arsenide (TMA)-flux-grown crystals, even the existence of SC is uncertain. Here we reexamine the phase diagram of single-crystalline $\mathrm{Eu}{(\mathrm{F}{\mathrm{e}}_{1\ensuremath{-}x}\mathrm{C}{\mathrm{o}}_{x})}_{2}\mathrm{A}{\mathrm{s}}_{2}$ grown by TMA flux. We found that the lattice parameter $c$ shrinks linearly with Co doping, almost twice as fast as that of the tin-flux-grown crystals. With Co doping, the spin-density-wave (SDW) order of the Fe sublattice is quickly suppressed, being detected only up to $x=0.08$. The magnetic ordering temperature of the $\mathrm{E}{\mathrm{u}}^{2+}$ sublattice (${T}_{\mathrm{Eu}}$) shows a systematic evolution with Co doping, first going down and reaching a minimum at $x=0.08$, then increasing continuously up to $x=0.24$. Over the whole composition range investigated, no signature of SC is observed above 1.8 K.

Two ordering states, antiferromagnetism and nematicity, have been observed in most iron-based superconductors (SCs). In contrast to those SCs, the newly discovered SC $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ exhibits an antiferromagnetic (AFM) state, called hedgehog spin-vortex crystal (SVC) structure, without nematic order, providing the opportunity for the investigation into the relationship between spin fluctuations and SC without any effects of nematic fluctuations. Our $^{75}\mathrm{As}$ nuclear magnetic resonance studies on $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ ($0\ensuremath{\le}x\ensuremath{\le}0.049$) revealed that ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ is located close to a hidden hedgehog SVC AFM quantum-critical point (QCP). The magnetic QCP without nematicity in $\mathrm{CaK}({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x}{)}_{4}{\mathrm{As}}_{4}$ highlights the close connection of spin fluctuations and superconductivity in iron-based SCs. The advantage of stoichiometric composition also makes ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ an ideal platform for further detailed investigation of the relationship between magnetic QCP and superconductivity in iron-based SCs without disorder effects.

Putative gain-of-function mutations in leucine-rich repeat kinase 2 (LRRK2), resulting in increased kinase activity and cellular toxicity, are a leading genetic cause of Parkinson’s disease (PD). Hence, there is strong interest in developing LRRK2 kinase inhibitors as a disease-modifying therapy. Published reports that repeat dosing with two LRRK2 kinase inhibitors (GNE-7915 and GNE-0877) induce histopathological changes in the lung of non-human primates Fuji et al. 2015 (1) raised concerns about potential safety liability of LRRK2 kinase inhibitors. In the present study, we sought to determine whether previously observed effects in the lung: (a) represent on-target pharmacology, but with the potential for margin of safety, (b) are reversible upon drug withdrawal, and (c) are associated with pulmonary function deficits. To this end, we evaluated the histopathological effects, toxicokinetics and target inhibition of three structurally diverse LRRK2 kinase inhibitors, GNE-7915 (30 mg/kg, BID, as a positive control), MLi-2 (15 and 50 mg/kg, QD) and PFE-360 (3 and 6 mg/kg, QD) following 2 weeks of dosing in non-human primates. Subsets of animals dosed with GNE-7915 or MLi-2 were evaluated after 2-week dose-free periods. All three LRRK2 kinase inhibitors induced mild cytoplasmic vacuolation of type II pneumocytes, as reported previously, confirming an on-target effect of these compounds. Interestingly, despite lower doses of both PFE-360 and MLi-2 producing nearly complete inhibition of LRRK2 kinase activity in the brain as assessed by levels of pS935-LRRK2, histopathological changes in lung were absent in animals treated with low-dose PFE-360 and observed only sporadically in the low-dose MLi-2 group. The lung effect was fully reversible at 2 weeks post-dosing of GNE-7915. In a second study of identical dosing with MLi-2 and GNE-7915, no deficits were observed in a battery of translational pulmonary functional tests. In aggregate, these results do not preclude the development of LRRK2 kinase inhibitors for clinical investigation in Parkinson’s disease.

The kinase-activating mutation G2019S in leucine-rich repeat kinase 2 (LRRK2) is one of the most common genetic causes of Parkinson's disease (PD) and has spurred development of LRRK2 inhibitors. Preclinical studies have raised concerns about the safety of LRRK2 inhibitors due to histopathological changes in the lungs of nonhuman primates treated with two of these compounds. Here, we investigated whether these lung effects represented on-target pharmacology and whether they were reversible after drug withdrawal in macaques. We also examined whether treatment was associated with pulmonary function deficits. We conducted a 2-week repeat-dose toxicology study in macaques comparing three different LRRK2 inhibitors: GNE-7915 (30 mg/kg, twice daily as a positive control), MLi-2 (15 and 50 mg/kg, once daily), and PFE-360 (3 and 6 mg/kg, once daily). Subsets of animals dosed with GNE-7915 or MLi-2 were evaluated 2 weeks after drug withdrawal for lung function. All compounds induced mild cytoplasmic vacuolation of type II lung pneumocytes without signs of lung degeneration, implicating on-target pharmacology. At low doses of PFE-360 or MLi-2, there was ~50 or 100% LRRK2 inhibition in brain tissue, respectively, but histopathological lung changes were either absent or minimal. The lung effect was reversible after dosing ceased. Lung function tests demonstrated that the histological changes in lung tissue induced by MLi-2 and GNE-7915 did not result in pulmonary deficits. Our results suggest that the observed lung effects in nonhuman primates in response to LRRK2 inhibitors should not preclude clinical testing of these compounds for PD.

We present a comprehensive study of the critical current densities and the superconducting vortex phase diagram in the stoichiometric superconductor ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ which has a critical temperature of $\ensuremath{\sim}35\phantom{\rule{0.28em}{0ex}}\mathrm{K}$. We performed detailed magnetization measurements both of high quality single crystals for different orientations in an applied magnetic field up to 16 T and for a powder sample. We find an extremely large critical current density, ${J}_{c}$, up to ${10}^{8}\phantom{\rule{0.28em}{0ex}}\mathrm{A}/{\mathrm{cm}}^{2}$ for single crystals when $H\ensuremath{\parallel}(ab)$ at $5\phantom{\rule{0.28em}{0ex}}\mathrm{K}$, which remains robust in fields up to $16\phantom{\rule{0.28em}{0ex}}\mathrm{T}$, being the largest of any other iron-based superconductor. The critical current density is reduced by a factor 10 in single crystals when $H\ensuremath{\parallel}c$ at 5 K and significantly suppressed by the presence of grain boundaries in the powder sample. We also observe the presence of the fishtail effect in the magnetic hysteresis loops of single crystals when $H\ensuremath{\parallel}c$. The flux pinning force density and the pinning parameters suggest that the large critical current could be linked to the existence of point core and surface pinning. Based on the vortex phase diagram and the large critical current densities, ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ is now established as a potential iron-based superconductor candidate for practical applications.

We report inelastic light scattering results on the stoichiometric and fully ordered superconductor ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$ as a function of temperature and light polarization. In the energy range between 10 and 315 ${\mathrm{cm}}^{\ensuremath{-}1}$ (1.24 and 39.1 meV) we observe the particle-hole continuum above and below the superconducting transition temperature ${T}_{c}$ and seven of the eight Raman active phonons. The main focus is placed on the analysis of the electronic excitations. Below ${T}_{c}$ all three symmetries projected with in-plane polarizations display a redistribution of spectral weight characteristic for superconductivity. The energies of the pair-breaking peaks in ${A}_{1g}$ and ${B}_{2g}$ symmetry are in approximate agreement with the results from photoemission studies. In ${B}_{1g}$ symmetry the difference between the normal and superconducting state is most pronounced, and the feature is shifted downwards with respect to those in ${A}_{1g}$ and ${B}_{2g}$ symmetry. The maximum peaking at 134 ${\mathrm{cm}}^{\ensuremath{-}1}$ (16.6 meV) has a substructure on the high-energy side. We interpret the peak at 134 ${\mathrm{cm}}^{\ensuremath{-}1}$ in terms of a collective Bardasis-Schrieffer (BS) mode and the substructure as a remainder of the pair-breaking feature on the electron bands. There is a very weak peak at 50 ${\mathrm{cm}}^{\ensuremath{-}1}$ (6.2 meV) which is tentatively assigned to another BS mode.

The magnetic order in CaK(Fe[1-x]Ni[x])4As4 (1144) single crystals (x = 0.051 and 0.033) has been studied by neutron diffraction. We observe magnetic Bragg peaks associated to the same propagation vectors as found for the collinear stripe antiferromagnetic (AFM) order in the related BaFe2As2 (122) compound. The AFM state in 1144 preserves tetragonal symmetry and only a commensurate, non-collinear structure with a hedgehog spin-vortex crystal (SVC) arrangement in the Fe plane and simple AFM stacking along the c direction is consistent with our observations. The SVC order is promoted by the reduced symmetry in the FeAs layer in the 1144 structure. The long-range SVC order coexists with superconductivity, however, similar to the doped 122 compounds, the ordered magnetic moment is gradually suppressed with the developing superconducting order parameter. This supports the notion that both collinear and non-collinear magnetism and superconductivity are competing for the same electrons coupled by Fermi surface nesting in iron arsenide superconductors.

The pressure dependence of the magnetic and superconducting transitions and that of the superconducting upper critical field are reported for $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$, the first example of an Fe-based superconductor with spin-vortex-crystal-type magnetic ordering. Resistance measurements were performed on single crystals with two substitution levels $(x=0.033,0.050)$ under hydrostatic pressures up to 5.12 GPa and in magnetic fields up to 9 T. Our results show that, for both compositions, magnetic transition temperatures ${T}_{\mathrm{N}}$ are suppressed upon applying pressure; the superconducting transition temperatures ${T}_{\mathrm{c}}$ are suppressed by pressure as well, except for $x=0.050$ in the pressure region where ${T}_{\mathrm{N}}$ and ${T}_{\mathrm{c}}$ cross. Furthermore, the pressure associated with the crossing of the ${T}_{\mathrm{N}}$ and ${T}_{\mathrm{c}}$ lines also coincides with a minimum in the normalized slope of the superconducting upper critical field, consistent with a likely Fermi-surface reconstruction associated with the loss of magnetic ordering. Finally, at $p\ensuremath{\sim}4$ GPa, both Ni-substituted $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$ samples likely go through a half-collapsed-tetragonal phase transition, similar to the parent compound ${\mathrm{CaKFe}}_{4}{\mathrm{As}}_{4}$.

Controlled pointlike disorder introduced by 2.5-MeV electron irradiation was used to probe the superconducting state of single crystals of $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$ superconductor at $x=0$ and 0.05 doping levels. Both compositions show an increase of the residual resistivity and a decrease of the superconducting transition temperature, ${T}_{c}$, at the rate of $d{T}_{c}/d\ensuremath{\rho}({T}_{c})\ensuremath{\approx}0.19$ K/($\ensuremath{\mu}\mathrm{\ensuremath{\Omega}}\phantom{\rule{0.16em}{0ex}}\mathrm{cm}$) for $x=0$ and 0.38 K/($\ensuremath{\mu}\mathrm{\ensuremath{\Omega}}\phantom{\rule{0.16em}{0ex}}\mathrm{cm}$) for $x=0.05$, respectively. In the Ni-doped compound ($x=0.05$), the coexisting spin-vortex crystal (SVC) magnetic phase is suppressed at the rate of $d{T}_{N}/d\ensuremath{\rho}({T}_{N})\ensuremath{\approx}$ 0.16 K/($\ensuremath{\mu}\mathrm{\ensuremath{\Omega}}\phantom{\rule{0.16em}{0ex}}\mathrm{cm}$). The low-temperature variation of London penetration depth is well approximated by the power-law function, $\mathrm{\ensuremath{\Delta}}\ensuremath{\lambda}(T)=A{T}^{n}$, with $n\ensuremath{\approx}\phantom{\rule{0.16em}{0ex}}2.5$ for $x=0$ and $n\ensuremath{\approx}\phantom{\rule{0.16em}{0ex}}1.9$ for $x=0.05$ in the pristine state. Detailed analysis of $\ensuremath{\lambda}(T)$ and ${T}_{c}$ evolution with disorder is consistent with two effective nodeless energy gaps in the density of states due to robust ${s}_{\ifmmode\pm\else\textpm\fi{}}$ pairing. Overall the behavior of $\mathrm{CaK}{({\mathrm{Fe}}_{1\ensuremath{-}x}{\mathrm{Ni}}_{x})}_{4}{\mathrm{As}}_{4}$ at $x=0$ is similar to a slightly overdoped ${\mathrm{Ba}}_{1\ensuremath{-}y}{\mathrm{K}}_{y}{\mathrm{Fe}}_{2}{\mathrm{As}}_{2}$ at $y\ensuremath{\approx}$ 0.5, and at $x=0.05$ to an underdoped composition at $y\ensuremath{\approx}$ 0.2.

The temperature dependence of the in-plane magnetic penetration depth ($\lambda_{ab}$) in an extensively characterized sample of superconducting CaKFe$_4$As$_4$ ($T_{\rm c}\simeq35$ K) was investigated using muon-spin rotation ($\mu$SR). A comparison of $\lambda_{ab}^{-2}(T)$ measured by $\mu$SR with the one inferred from ARPES data confirms the presence of multiple gaps at the Fermi level. An agreement between $\mu$SR and ARPES requires the presence of additional bands, which are not resolved by ARPES experiments. These bands are characterized by small supercondcting gaps with an average zero-temperature value of $\Delta_{0} =$ 2.4(2) meV. Our data suggest that in CaKFe$_4$As$_4$ the $s^\pm$ order parameter symmetry acquires a more sophisticated form by allowing a sign change not only between electron and hole pockets, but also within pockets of similar type., Comment: 6 pages, 4 figures. Accpeted for publication in Phys.Rev.B (Rapid)