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Transmission of a compressed video signal over a lossy communication network exposes the information to losses and errors, which leads to significant visible errors in the reconstructed frames at the decoder side. In this paper we present a new hybrid error concealment algorithm for compressed video sequences, based on temporal and spatial concealment methods. We describe spatial and temporal techniques for the recovery of lost blocks. In particular, we develop postprocessing techniques for the reconstruction of missing or damaged macroblocks. A new decision support tree is developed to efficiently choose the best appropriate error concealment method, according to the spatial and temporal characteristics of the sequence. The proposed algorithm is compared to three error concealment methods: spatial, temporal, and a previous hybrid approach using different noise levels. The results are evaluated using four quality measures. We show that our error concealment scheme outperforms all the other three methods for all the tested video sequences.

Holistic consideration of the human and the robot is necessary to overcome hurdles in human-robot interaction.

Manganese complexes exhibit a rich redox chemistry, usually accompanied by structural reorganization during the redox processes often followed by ligand dissociation or association. The push-pull ligand 2,6-diguanidylpyridine (dgpy) stabilizes manganese in the oxidation states +II, +III, and + IV in the complexes [Mn(dgpy) 2 ] n + ( n = 2-4) without change in the coordination sphere in the condensed phase [Heinze et al. , Inorganic Chemistry , 2022 , 61, 14616]. In the condensed phase, the manganese(IV) complex is a very strong oxidant. In the present work, we investigate the stability and redox activity of the Mn IV complex and its counterion (PF 6 - ) adducts in the gas phase, using two modified 3D Paul ion trap mass spectrometers. Six different cationic species of the type [Mn x (dgpy) 2 (PF 6 ) y ] n + ( x = II, III, IV, y = 0-3, n = 1-3) could be observed for the three oxidation states Mn IV , Mn III , and Mn II , of which one observed complex also contains a reduced dgpy ligand. Mn II species showed the highest relative stability in collision induced dissociation and UV/vis photo dissociation experiments. The lowest stability is observed in the presence of one or more counterions, which correlates to a lower total charge n +. Gas phase UV/vis spectra show similar features as the condensed phase spectra only differing in relative band intensities. The strongly oxidizing Mn IV complex reacts with triethylamine (NEt 3 ) in the gas phase to give Mn III , while Mn III species show little reactivity toward NEt 3 .

Orbital magnetization provides a sensitive probe of topology and interactions, with particularly rich phenomenology in Chern insulators in which the topological edge states carry large equilibrium currents. Here we use a nanoscale superconducting sensor 1,2 to map the magnetic fringe fields in twisted bilayers of MoTe 2 , in which transport 3,4 and optical sensing 5,6 experiments have revealed the formation of fractional Chern insulator (FCI) states at zero magnetic field. We observe oscillations in the local magnetic field associated with fillings ν = -1, -2/3, -3/5, -4/7 and -5/9 of the first moiré hole band, consistent with the formation of FCIs at these fillings. We determine the local thermodynamic gaps of the most robust FCI state at ν = -2/3, finding -2/3 Δ as large as 7 meV. We also characterize sample spatial disorder, which is dominated by both inhomogeneity in the effective unit cell area 7 as well as inhomogeneity in the band edge offset and bound dipole moment. Our results highlight both the challenges posed by structural disorder in the study of twisted homobilayer moiré systems and the opportunities afforded by the robust nature of the underlying correlated topological states., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The coercivity of single-domain magnetic nanoparticles typically decreases with the nanoparticle size and reaches zero when thermal fluctuations overcome the magnetic anisotropy. Here, we used SQUID-on-tip microscopy to investigate the coercivity of square-shaped CrGeTe 3 nanoislands with a wide range of sizes and width-to-thickness aspect ratios. The results reveal an anomalous size-dependent coercivity, with smaller islands exhibiting higher coercivity. The nonconventional scaling of the coercivity in CrGeTe 3 nanoislands was found to be inversely proportional to the island width and thickness (1/ wd ). This scaling implies that the nanoisland magnetic anisotropy is proportional to the perimeter rather than the volume, suggesting a magnetic edge state. In addition, we observe that 1600 nm wide islands display multi-domain structures with zero net remnant field, corresponding to the magnetic properties of pristine CrGeTe 3 flakes. Our findings highlight the significant influence of edge states on the magnetic properties of CrGeTe 3 and deepen our understanding of low-dimensional magnetic systems.

A conserved intracellular allosteric binding site (IABS) was recently identified at several G protein-coupled receptors (GPCRs). This target site allows the binding of allosteric modulators and enables a new mode of GPCR inhibition. Herein, we report the development of a NanoBRET-based assay platform based on the fluorescent ligand LT221 (5), to detect intracellular binding to CCR6 and CXCR1, two chemokine receptors that have been pursued as promising drug targets in inflammation and immuno-oncology. Our assay platform enables cell-free as well as cellular NanoBRET-based binding studies in a nonisotopic and straightforward manner. By combining this screening platform with a previously reported CXCR2 assay, we investigated CXCR1/CXCR2/CCR6 selectivity profiles for both known and novel squaramide analogues derived from navarixin, a known intracellular CXCR1/CXCR2 antagonist and phase II clinical candidate for the treatment of pulmonary diseases. By means of these studies we identified compound 10, a previously reported tert-butyl analogue of navarixin, as a low nanomolar intracellular CCR6 antagonist. Further, our assay platform clearly indicated intracellular binding of the CCR6 antagonist PF-07054894, currently evaluated in phase I clinical trials for the treatment of ulcerative colitis, thereby providing profound evidence for the existence and the pharmacological relevance of a druggable IABS at CCR6., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks 1-5 . The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities 6-8 or interacting with a stellar object in a close orbit 9-11 . It has been suggested that this disk could be created when the SMBH disrupts a passing star 8,11 , implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs 4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions 13,14 . TDEs and QPEs also occur preferentially in similar galaxies 15 . However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE 16 . We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs., (© 2024. The Author(s).)

The controlled activation of methane has drawn significant attention throughout various disciplines over the last few decades. In gas-phase experiments, the use of model systems with reduced complexity compared to condensed-phase catalytic systems allows us to investigate the intrinsic reactivity of elementary reactions down to the atomic level. Methane is rather inert in chemical reactions, as the weakening or cleavage of a C-H bond is required to make use of methane as C 1 -building block. The simplest model system for transition-metal-based catalysts is a mono-atomic metal ion. Only a few atomic transition-metal cations activate methane at room temperature. One of the most efficient elements is tantalum, which forms a carbene and releases molecular hydrogen in the reaction with methane: Ta + + CH 4 → TaCH 2 + + H 2 . The reaction takes place at room temperature due to efficient intersystem crossing from the quintet to the triplet surface, i.e. , from the electronic ground state of the tantalum cation to the triplet ground state of the tantalum carbene. This multi-state reactivity is often seen for reactions involving transition-metal centres, but leads to their theoretical treatment being a challenge even today. Chemical reactions, or to be precise reactive collisions, are dynamic processes making their description even more of a challenge to experiment and theory alike. Experimental energy- and angle-differential cross sections allow us to probe the rearrangement of atoms during a reactive collision. By interpreting the scattering signatures, we gain insight into the atomistic mechanisms and can move beyond stationary descriptions. Here, we present a study combining collision energy dependent experimentally measured differential cross sections with ab initio calculations of the minimum energy pathway. Product ion velocity distributions were recorded using our crossed-beam velocity map imaging experiment dedicated to studying transition-metal ion molecule reactions. TaCH 2 + velocity distributions reveal a significant degree of indirect dynamics. However, the scattering distributions also show signatures of rebound dynamics. We compare the present results to the oxygen transfer reaction between Ta + and carbon dioxide, which we recently studied.

In this study, we describe the structure-based development of the first fluorescent ligands targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor type 1 (CCR1), a G protein-coupled receptor (GPCR) that has been pursued as a drug target in inflammation and immune diseases. Starting from previously reported intracellular allosteric modulators of CCR1, tetramethylrhodamine (TAMRA)-labeled ligands were designed, synthesized, and tested for their suitability as fluorescent tracers to probe binding to the IABS of CCR1. In the course of these studies, we developed LT166 ( 12 ) as a highly versatile fluorescent CCR1 ligand, enabling cell-free as well as cellular NanoBRET-based binding studies in a nonradioactive and high-throughput manner. Besides the detection of intracellular allosteric ligands by direct competition with 12 , we were also able to monitor the binding of extracellular antagonists due to their positive cooperative binding with 12 . Thereby, we provide a straightforward and nonradioactive method to easily distinguish between ligands binding to the IABS of CCR1 and extracellular negative modulators. Further, we applied 12 for the identification of novel chemotypes for intracellular CCR1 inhibition that feature high binding selectivity for CCR1 over CCR2. For one of the newly identified intracellular CCR1 ligands ( i.e. , 23 ), we were able to show CCR1 over CCR2 selectivity also on a functional level and demonstrated that this compound inhibits basal β-arrestin recruitment to CCR1, thereby acting as an inverse agonist. Thus, our fluorescent CCR1 ligand 12 represents a highly promising tool for future studies of CCR1-targeted pharmacology and drug discovery., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

The interleukin-8 receptor beta (CXCR2) is a highly promising target for molecular imaging of inflammation and inflammatory diseases. This is due to its almost exclusive expression on neutrophils. Modified fluorinated ligands were designed based on a squaramide template, with different modification sites and synthetic strategies explored. Promising candidates were then tested for affinity to CXCR2 in a NanoBRET competition assay, resulting in tracer candidate 16b . As direct 18 F-labeling using established tosyl chemistry did not yield the expected radiotracer, an indirect labeling approach was developed. The radiotracer [ 18 F] 16b was obtained with a radiochemical yield of 15% using tert -butyl ( S )-3-(tosyloxy)pyrrolidine carboxylate and a pentafluorophenol ester. The subsequent time-dependent uptake of [ 18 F] 16b in CXCR2-negative and CXCR2-overexpressing human embryonic kidney cells confirmed the radiotracer's specificity. Further studies with human neutrophils revealed its diagnostic potential for functional imaging of neutrophils.

The membrane protein family of G protein-coupled receptors (GPCRs) represents a major class of drug targets. Over the last years, the presence of additional intracellular binding sites besides the canonical orthosteric binding pocket has been demonstrated for an increasing number of GPCRs. Allosteric modulators harnessing these pockets may represent valuable alternatives when targeting the orthosteric pocket is not successful for drug development. Starting from SBI-553, a recently discovered intracellular allosteric modulator for neurotensin receptor subtype 1 (NTSR1), we developed the fluorescent molecular probe 14 . Compound 14 binds to NTSR1 with an affinity of 0.68 μM in the presence of the agonist NT(8-13). NanoBRET-based ligand binding assays with 14 were established to derive the affinity and structure-activity relationships for allosteric NTSR1 modulators in a direct and nonisotopic manner, thereby facilitating the search for and optimization of novel allosteric NTSR1 ligands. As a consequence of cooperativity between the ligands binding to the allosteric and orthosteric pocket, compound 14 can also be used to investigate orthosteric NTSR1 agonists and antagonists. Moreover, employing 14 as a probe in a drug library screening, we identified novel chemotypes as binders for the intracellular allosteric SBI-553 binding pocket of NTSR1 with single-digit micromolar affinity. These hits may serve as interesting starting points for the development of novel intracellular allosteric ligands for NTSR1 as a highly interesting yet unexploited drug target in the fields of pain and addiction disorder therapy., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

The reactions of Ta + and Nb + with CO 2 proceed only by a highly efficient oxygen atom transfer reaction to the respective oxide at room temperature in the gas phase. Although the product spin states are not determined, thermochemistry dictates that they must be different from ground state quintet Ta + and Nb + , implying that intersystem crossing (ISC) has occurred. Recent reactive scattering experiments found dominant indirect dynamics for the reaction with Ta + hinting at a bottleneck along the reaction path. The question on the nature of the bottleneck, whether it involves a crossing point or a transition state, could not be finally answered because theory located both close to each other. Here, we aim at shedding further light onto the impact of intersystem crossing on the reaction dynamics and ultimately the reactivity of transition metal ion reactions in the gas phase. We employ a combination of thermal kinetics for Ta + and Nb + with CO 2 using a selected-ion flow tube (SIFT) apparatus and differential scattering cross sections for Nb + + CO 2 from crossed-beam velocity map imaging. The reaction with niobium again shows dominant indirect dynamics and in general very similar dynamics compared to Ta + + CO 2 . At thermal energies, both reactions show sub-collisional rate constants with small negative temperature dependencies. Experiments are complemented by high level quantum chemical calculations of the minimum energy pathway. Statistical modelling well-reproduces the experimental thermal rate constants, and suggests that the Nb + reaction is rate-limited by the intersystem crossing at thermal energies.

MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 antigen presentation pathways. To investigate ligand exchange pathways for MR1, we used MR1 monomers and tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) to deliver the antigen. Using MR1-deficient cells reconstituted with wild-type MR1 or MR1 molecules that cannot bind 5-OP-RU, we show that presentation of monomer-delivered 5-OP-RU is dependent on cellular MR1 and requires the transfer of ligand from the soluble molecule onto MR1 expressed by the antigen presenting cell. This mode of antigen delivery strengthens the evidence for post-ER ligand exchange pathways for MR1, which could represent an important avenue by which MR1 acquires antigens derived from endocytosed pathogens., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Addressing the wide range of marine pollution problems facing the global ocean requires a continual transfer of credible, relevant and timely scientific information to policy and decision makers in coastal and ocean management. The United Nations GESAMP (Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection) is a long-standing scientific advisory group providing such information on a wide range of marine topics and emerging issues of concern to ten UN Sponsoring Organizations. This paper presents an overview of GESAMPs operation and examples of its current work. The group's scientific output is often cited by national governments, inter-governmental groups, and a range of non-governmental groups. Given the growing concerns about ocean health and the impacts of many stressors in an era of climate change, the development of timely and effective ocean policy and decision making would benefit from wider recognition and application of GESAMPs work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantum oscillations originating from the quantization of electron cyclotron orbits provide sensitive diagnostics of electron bands and interactions. We report on nanoscale imaging of the thermodynamic magnetization oscillations caused by the de Haas-van Alphen effect in moiré graphene. Scanning by means of superconducting quantum interference device (SQUID)-on-tip in Bernal bilayer graphene crystal axis-aligned to hexagonal boron nitride reveals large magnetization oscillations with amplitudes reaching 500 Bohr magneton per electron in weak magnetic fields, unexpectedly low frequencies, and high sensitivity to superlattice filling fraction. The oscillations allow us to reconstruct the complex band structure, revealing narrow moiré bands with multiple overlapping Fermi surfaces separated by unusually small momentum gaps. We identified sets of oscillations that violate the textbook Onsager Fermi surface sum rule, signaling formation of broad-band particle-hole superposition states induced by coherent magnetic breakdown.

Attaining viable thermoelectric cooling at cryogenic temperatures is of considerable fundamental and technological interest for electronics and quantum materials applications. In-device temperature control can provide more efficient and precise thermal environment management compared with conventional global cooling. The application of a current and perpendicular magnetic field gives rise to cooling by generating electron-hole pairs on one side of the sample and to heating due to their recombination on the opposite side, which is known as the Ettingshausen effect. Here we develop nanoscale cryogenic imaging of the magneto-thermoelectric effect and demonstrate absolute cooling and an Ettingshausen effect in exfoliated WTe 2 Weyl semimetal flakes at liquid He temperatures. In contrast to bulk materials, the cooling is non-monotonic with respect to the magnetic field and device size. Our model of magneto-thermoelectricity in mesoscopic semimetal devices shows that the cooling efficiency and the induced temperature profiles are governed by the interplay between sample geometry, electron-hole recombination length, magnetic field, and flake and substrate heat conductivities. The observations open the way for the direct integration of microscopic thermoelectric cooling and for temperature landscape engineering in van der Waals devices., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Wearable exoskeletons show significant potential for improving gait impairments, such as interlimb asymmetry. However, a more profound understanding of whether exoskeletons are capable of eliciting neural adaptation is needed. This study aimed to characterize how individuals adapt to bilateral asymmetric joint stiffness applied by a hip exoskeleton, similar to split-belt treadmill training. Thirteen unimpaired individuals performed a walking trial on the treadmill while wearing the exoskeleton. The right side of the exoskeleton acted as a positive stiffness torsional spring, pulling the thigh towards the neutral standing position, while the left acted as a negative stiffness spring pulling the thigh away from the neutral standing position. The results showed that this intervention applied by a hip exoskeleton elicited adaptation in spatiotemporal and kinetic gait measures similar to split-belt treadmill training. These results demonstrate the potential of the proposed intervention for retraining symmetric gait.

The exceptional control of the electronic energy bands in atomically thin quantum materials has led to the discovery of several emergent phenomena 1 . However, at present there is no versatile method for mapping the local band structure in advanced two-dimensional materials devices in which the active layer is commonly embedded in the insulating layers and metallic gates. Using a scanning superconducting quantum interference device, here we image the de Haas-van Alphen quantum oscillations in a model system, the Bernal-stacked trilayer graphene with dual gates, which shows several highly tunable bands 2-4 . By resolving thermodynamic quantum oscillations spanning more than 100 Landau levels in low magnetic fields, we reconstruct the band structure and its evolution with the displacement field with excellent precision and nanoscale spatial resolution. Moreover, by developing Landau-level interferometry, we show shear-strain-induced pseudomagnetic fields and map their spatial dependence. In contrast to artificially induced large strain, which leads to pseudomagnetic fields of hundreds of tesla 5-7 , we detect naturally occurring pseudomagnetic fields as low as 1 mT corresponding to graphene twisting by 1 millidegree, two orders of magnitude lower than the typical angle disorder in twisted bilayer graphene 8-11 . This ability to resolve the local band structure and strain at the nanoscale level enables the characterization and use of tunable band engineering in practical van der Waals devices., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Recent advancements in 2D materials have revealed the potential of van der Waals magnets, and specifically of their magnetic anisotropy that allows applications down to the 2D limit. Among these materials, CrSBr has emerged as a promising candidate, because its intriguing magnetic and electronic properties have appeal for both fundamental and applied research in spintronics or magnonics. In this work, nano-SQUID-on-tip (SOT) microscopy is used to obtain direct magnetic imaging of CrSBr flakes with thicknesses ranging from monolayer (N = 1) to few-layer (N = 5). The ferromagnetic order is preserved down to the monolayer, while the antiferromagnetic coupling of the layers starts from the bilayer case. For odd layers, at zero applied magnetic field, the stray field resulting from the uncompensated layer is directly imaged. The progressive spin reorientation along the out-of-plane direction (hard axis) is also measured with a finite applied magnetic field, allowing evaluation of the anisotropy constant, which remains stable down to the monolayer and is close to the bulk value. Finally, by selecting the applied magnetic field protocol, the formation of Néel magnetic domain walls is observed down to the single-layer limit., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

We investigate small tantalum clusters Tan+, n = 2-4, for their capability to cleave N2 adsorption spontaneously. We utilize infrared photon dissociation (IR-PD) spectroscopy of isolated and size selected clusters under cryogenic conditions within a buffer gas filled ion trap, and we augment our experiments by quantum chemical simulations (at DFT level). All Tan+ clusters, n = 2-4, seem to cleave N2 efficiently. We confirm and extend a previous study under ambient conditions on Ta2+ cluster [Geng et al., Proc. Natl. Acad. Sci. U. S. A. 115, 11680-11687 (2018)]. Our cryo studies and the concomitant DFT simulations of the tantalum trimer Ta3+ suggest cleavage of the first and activation of the second and third N2 molecule across surmountable barriers and along much-involved multidimensional reaction paths. We unravel the underlying reaction processes and the intermediates involved. The study of the N2 adsorbate complexes of Ta4+ presented here extends our earlier study and previously published spectra from (4,m), m = 1-5 [Fries et al., Phys. Chem. Chem. Phys. 23(19), 11345-11354 (2021)], up to m = 12. We confirm the priory published double activation and nitride formation, succeeded by single side-on N2 coordination. Significant red shifts of IR-PD bands from these side-on coordinated μ2-κN:κN,N N2 ligands correlate with the degree of tilting towards the second coordinating Ta center. All subsequently attaching N2 adsorbates onto Ta4+ coordinate in an end-on fashion, and we find clear evidence for co-existence of end-on coordination isomers. The study of stepwise N2 adsorption revealed adsorption limits m(max) of [Tan(N2)m]+ which increase with n, and kinetic fits revealed significant N2 desorption rates upon higher N2 loads. The enhanced absolute rate constants of the very first adsorbate steps kabs(n,0) of the small Ta3+ and Ta4+ clusters independently suggest dissociative N2 adsorption and likely N2 cleavage into Ta nitrides., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

We present an IR-PD study of tantalum cluster adsorbate complexes [Tan(N2)m]+, abbreviated (n,m), n = 5-8. We utilize infrared spectroscopy of isolated and size selected clusters as prepared and characterized by a cryogenic tandem ion trap setup, and we augment our experiments with quantum chemical simulations at the level of density functional theory. The cluster adsorbate complexes (n,m) reveal vibrational bands above 2000 cm-1, which indicate end-on coordinated μ1-N2 oscillators, and bands below 2000 cm-1, which indicate side-on μ2-κN:κN,N coordinated ones. We observe a general increase in spectral complexity and an inhomogeneous broadening, mainly towards the red, at certain points of N2 loading m, which originates from an increasingly higher amount of double and triple N2 coordination at Ta sites, eventually at all of them. Other than the small tantalum clusters Tan+, n = 2-4, the IR-PD spectra of the initial N2 adsorbate species (n,1), n = 5-8, provide strong evidence for a lack of spontaneous N2 cleavage. Spontaneous N2 cleavage by Tan+, n = 5-8, seems suppressed. Therefore, the ability of a small Ta cluster to cleave dinitrogen disappears with one more tantalum core atom. The study of stepwise N2 adsorption on size selected Tan+, n = 5-8 clusters revealed adsorption limits m(max) of [Tan(N2)m]+ that are independent of cluster size within this size range. Cryo-adsorption kinetics at 26 K allowed for kinetic fits to consecutive N2 adsorption steps, and the fits revealed significant N2 desorption rates upon higher N2 loads, and the cluster adsorbate complexes eventually reached equilibrium. Some enhanced N2 desorption rates point towards likely adsorbate shell reorganization, and there is also some evidence for the coexistence of isomeric cluster adsorbate complexes., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

We measured the nuclear-recoil ionization yield in silicon with a cryogenic phonon-sensitive gram-scale detector. Neutrons from a monoenergetic beam scatter off of the silicon nuclei at angles corresponding to energy depositions from 4 keV down to 100 eV, the lowest energy probed so far. The results show no sign of an ionization production threshold above 100 eV. These results call for further investigation of the ionization yield theory and a comprehensive determination of the detector response function at energies below the keV scale.

Herein, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric binding site (IABS) of CXC chemokine receptor 2 (CXCR2), a G protein-coupled receptor (GPCR) that has been pursued as a drug target in oncology and inflammation. Starting from the cocrystallized intracellular CXCR2 antagonist 00767013 ( 1 ), tetramethylrhodamine (TAMRA)-labeled CXCR2 ligands were designed, synthesized, and tested for their suitability as fluorescent reporters to probe binding to the IABS of CXCR2. By means of these studies, we developed Mz438 ( 9a ) as a high-affinity and selective fluorescent CXCR2 ligand, enabling cell-free as well as cellular NanoBRET-based binding studies in a nonisotopic and high-throughput manner. Further, we show that 9a can be used as a tool to visualize intracellular target engagement for CXCR2 via fluorescence microscopy. Thus, our small-molecule-based fluorescent CXCR2 ligand 9a represents a promising tool for future studies of CXCR2 pharmacology.

The understanding of fundamental atomic-level processes often requires well-defined model systems. The oxygen atom transfer from CO 2 to a transition metal cation in the gas phase presents such a model system. We investigate the reaction of Ta + + CO 2 for which the formation of TaO + is highly efficient and attributed to multistate reactivity. Here, we study the atomistic dynamics of the oxygen atom transfer reaction by recording experimental energy and angle differential cross sections by crossed beam velocity map imaging supported by ab initio quantum chemical calculations. Product ion velocity distributions are dominated by signatures for indirect dynamics, despite the reaction being highly exothermic. Product kinetic energy distributions show little dependence on additional collision energy even with only four atoms involved, which hints at dynamical trapping behind a submerged barrier.

The synthesis of two-dimensional van der Waals magnets has paved the way for both technological applications and fundamental research on magnetism confined to ultra-small length scales. Edge magnetic moments in ferromagnets are expected to be less magnetized than in the sample interior because of the reduced amount of neighboring ferromagnetic spins at the sample edge. We recently demonstrated that CrGeTe 3 (CGT) flakes thinner than 10 nm are hard ferromagnets; i.e., they exhibit an open hysteresis loop. In contrast, thicker flakes exhibit zero net remnant field in the interior, with hard ferromagnetism present only at the cleaved edges. This experimental observation suggests that a nontrivial interaction exists between the sample edge and the interior. Here, we demonstrate that artificial edges fabricated by focus ion beam etching also display hard ferromagnetism. This enables us to write magnetic nanowires in CGT directly and use this method to characterize the magnetic interaction between the interior and edge. The results indicate that the interior saturation and depolarization fields depend on the lateral dimensions of the sample. Most notably, the interior region between the edges of a sample narrower than 300 nm becomes a hard ferromagnet, suggesting an enhancement of the magnetic exchange induced by the proximity of the edges. Last, we find that the CGT regions amorphized by the gallium beam are nonmagnetic, which introduces a novel method to tune the local magnetic properties of CGT films, potentially enabling integration into spintronic devices., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The scanning superconducting quantum interference device (SQUID) fabricated on the tip of a sharp quartz pipette (SQUID-on-tip) has emerged as a versatile tool for the nanoscale imaging of magnetic, thermal, and transport properties of microscopic devices of quantum materials. We present the design and performance of a scanning SQUID-on-tip microscope in a top-loading probe of a cryogen-free dilution refrigerator. The microscope is enclosed in a custom-made vacuum-tight cell mounted at the bottom of the probe and is suspended by springs to suppress vibrations caused by the pulse tube cryocooler. Two capillaries allow for the in situ control of helium exchange gas pressure in the cell that is required for thermal imaging. A nanoscale heater is used to create local temperature gradients in the sample, which enables quantitative characterization of relative vibrations between the tip and the sample. The spectrum of the vibrations shows distinct resonant peaks with a maximal power density of about 27 nm/Hz1/2 in the in-plane direction. The performance of the SQUID-on-tip microscope is demonstrated by magnetic imaging of the MnBi2Te4 magnetic topological insulator, magnetization and current distribution imaging in a SrRuO3 ferromagnetic oxide thin film, and thermal imaging of dissipation in graphene., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

In this report, we present the dinuclear copper(II) dimethylglyoxime (H 2 dmg) complex [Cu 2 (H 2 dmg)(Hdmg)(dmg)] + (1), which, in contrast to its mononuclear analogue [Cu(Hdmg) 2 ] (2), is subject to a cooperativity-driven hydrolysis. The combined Lewis acidity of both copper centers increases the electrophilicity of the carbon atom in the bridging μ 2 -O-N=C-group of H 2 dmg and thus, facilitates the nucleophilic attack of H 2 O. This hydrolysis yields butane-2,3-dione monoxime (3) and NH 2 OH that, depending on the solvent, is then either oxidized or reduced. In ethanol, NH 2 OH is reduced to NH 4 + , yielding acetaldehyde as the oxidation product. In contrast, in CH 3 CN, NH 2 OH is oxidized by Cu II to form N 2 O and [Cu(CH 3 CN) 4 ] + . Herein are presented the combined synthetic, theoretical, spectroscopic and spectrometric methods that indicate and establish the reaction pathway of this solvent-dependent reaction., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Walking on a split-belt treadmill elicits an adaptation response that changes baseline step length asymmetry. The underlying causes of this adaptation, however, are difficult to determine. It has been proposed that effort minimization may drive this adaptation, based on the idea that adopting longer steps on the fast belt, or positive step length asymmetry (SLA), can cause the treadmill to exert net-positive mechanical work on a bipedal walker. However, humans walking on split-belt treadmills have not been observed to reproduce this behavior when allowed to freely adapt. To determine if an effort-minimization motor control strategy would result in experimentally observed adaptation patterns, we conducted simulations of walking on different combinations of belt speeds with a human musculoskeletal model that minimized muscle excitations and metabolic rate. The model adopted increasing amounts of positive SLA and decreased its net metabolic rate with increasing belt speed difference, reaching +42.4% SLA and -5.7% metabolic rate relative to tied-belt walking at our maximum belt speed ratio of 3:1. These gains were primarily enabled by an increase in braking work and a reduction in propulsion work on the fast belt. The results suggest that a purely effort minimization driven split-belt walking strategy would involve substantial positive SLA, and that the lack of this characteristic in human behavior points to additional factors influencing the motor control strategy, such as aversion to excessive joint loads, asymmetry, or instability. NEW & NOTEWORTHY Behavioral observations of split-belt treadmill adaptation have been inconclusive toward its underlying causes. To estimate gait patterns when driven exclusively by one of these possible underlying causes, we simulated split-belt treadmill walking with a musculoskeletal model that minimized its summed muscle excitations. Our model took significantly longer steps on the fast belt and reduced its metabolic rate below tied-belt walking, unlike experimental observations. This suggests that asymmetry is energetically optimal, but human adaptation involves additional factors.

A conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs). Ligands targeting the IABS, so-called intracellular allosteric antagonists, are highly promising compounds for pharmaceutical intervention and currently evaluated in several clinical trials. Beside co-crystal structures that laid the foundation for the structure-based development of intracellular allosteric GPCR antagonists, small molecule tools that enable an unambiguous identification and characterization of intracellular allosteric GPCR ligands are of utmost importance for drug discovery campaigns in this field. Herein, we discuss recent approaches that leverage cellular target engagement studies for the IABS and thus play a critical role in the evaluation of IABS-targeted ligands as potential therapeutic agents., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Chronic obstructive pulmonary disease (COPD) is associated with airway inflammation, increased infiltration by CD8 + T lymphocytes, and infection-driven exacerbations. Although cigarette smoke is the leading risk factor for COPD, the mechanisms driving the development of COPD in only a subset of smokers are incompletely understood. Lung-resident mucosal-associated invariant T (MAIT) cells play a role in microbial infections and inflammatory diseases. The role of MAIT cells in COPD pathology is unknown. Here, we examined MAIT cell activation in response to cigarette smoke-exposed primary human bronchial epithelial cells (BECs) from healthy, COPD, or smoker donors. We observed significantly higher baseline MAIT cell responses to COPD BECs than healthy BECs. However, infected COPD BECs stimulated a smaller fold increase in MAIT cell response despite increased microbial infection. For all donor groups, cigarette smoke-exposed BECs elicited reduced MAIT cell responses; conversely, cigarette smoke exposure increased ligand-mediated MR1 surface translocation in healthy and COPD BECs. Our data demonstrate that MAIT cell activation is dysregulated in the context of cigarette smoke and COPD. MAIT cells could contribute to cigarette smoke- and COPD-associated inflammation through inappropriate activation and reduced early recognition of bacterial infection, contributing to microbial persistence and COPD exacerbations.

Humans have an astonishing ability to extract hidden information from the movement of others. In previous work, subjects observed the motion of a simulated stick-figure, two-link planar arm and estimated its stiffness. Fundamentally, stiffness is the relation between force and displacement. Given that subjects were unable to physically interact with the simulated arm, they were forced to make their estimates solely based on observed kinematic information. Remarkably, subjects were able to correctly correlate their stiffness estimates with changes in the simulated stiffness, despite the lack of force information. We hypothesized that subjects were only able to do this because the controller used to produce the simulated arm's movement, composed of oscillatory motions driving mechanical impedances, resembled the controller humans use to produce their own movement. However, it is still unknown what motion features subjects used to estimate stiffness. Human motion exhibits systematic velocity-curvature patterns, and it has previously been shown that these patterns play an important role in perceiving and interpreting motion. Thus, we hypothesized that manipulating the velocity profile should affect subjects' ability to estimate stiffness. To test this, we changed the velocity profile of the simulated two-link planar arm while keeping the simulated joint paths the same. Even with manipulated velocity signals, subjects were still able to estimate changes in simulated joint stiffness. However, when subjects were shown the same simulated path with different velocity profiles, they perceived motions that followed a veridical velocity profile to be less stiff than that of a non-veridical profile. These results suggest that path information (displacement) predominates over temporal information (velocity) when humans use visual observation to estimate stiffness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 West et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays. Here, we report the structure-based development of fluorescent ligands targeting the intracellular allosteric binding site (IABS) of the CC chemokine receptor 2 (CCR2), a class A GPCR that has been pursued as a drug target in oncology and inflammation. Starting from previously reported intracellular CCR2 antagonists, several tetramethylrhodamine (TAMRA)-labeled CCR2 ligands were designed, synthesized, and tested for their suitability as fluorescent reporters to probe binding to the IABS of CCR2. By means of these studies, we developed 14 as a fluorescent CCR2 ligand, enabling cell-free as well as cellular NanoBRET-based binding studies in a non-isotopic and high-throughput manner. Further, we show that 14 can be used as a tool for fragment-based screening approaches. Thus, our small-molecule-based fluorescent CCR2 ligand 14 represents a promising tool for future studies of CCR2 pharmacology.

Vortices are the hallmarks of hydrodynamic flow. Strongly interacting electrons in ultrapure conductors can display signatures of hydrodynamic behaviour, including negative non-local resistance 1-4 , higher-than-ballistic conduction 5-7 , Poiseuille flow in narrow channels 8-10 and violation of the Wiedemann-Franz law 11 . Here we provide a visualization of whirlpools in an electron fluid. By using a nanoscale scanning superconducting quantum interference device on a tip 12 , we image the current distribution in a circular chamber connected through a small aperture to a current-carrying strip in the high-purity type II Weyl semimetal WTe 2 . In this geometry, the Gurzhi momentum diffusion length and the size of the aperture determine the vortex stability phase diagram. We find that vortices are present for only small apertures, whereas the flow is laminar (non-vortical) for larger apertures. Near the vortical-to-laminar transition, we observe the single vortex in the chamber splitting into two vortices; this behaviour is expected only in the hydrodynamic regime and is not anticipated for ballistic transport. These findings suggest a new mechanism of hydrodynamic flow in thin pure crystals such that the spatial diffusion of electron momenta is enabled by small-angle scattering at the surfaces instead of the routinely invoked electron-electron scattering, which becomes extremely weak at low temperatures. This surface-induced para-hydrodynamics, which mimics many aspects of conventional hydrodynamics including vortices, opens new possibilities for exploring and using electron fluidics in high-mobility electron systems., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

CrGeTe 3 (CGT) is a semiconducting vdW ferromagnet shown to possess magnetism down to a two-layer thick sample. Although CGT is one of the leading candidates for spintronics devices, a comprehensive analysis of CGT thickness dependent magnetization is currently lacking. In this work, we employ scanning SQUID-on-tip (SOT) microscopy to resolve the magnetic properties of exfoliated CGT flakes at 4.2 K. Combining transport measurements of CGT/NbSe 2 samples with SOT images, we present the magnetic texture and hysteretic magnetism of CGT, thereby matching the global behavior of CGT to the domain structure extracted from local SOT magnetic imaging. Using this method, we provide a thickness dependent magnetization state diagram of bare CGT films. No zero-field magnetic memory was found for films thicker than 10 nm, and hard ferromagnetism was found below that critical thickness. Using scanning SOT microscopy, we identify a unique edge magnetism, contrasting the results attained in the CGT interior.

Humans excel at physical interaction despite long feedback delays and low-bandwidth actuators. Yet little is known about how humans manage physical interaction. A quantitative understanding of how they do is critical for designing machines that can safely and effectively interact with humans, e.g. amputation prostheses, assistive exoskeletons, therapeutic rehabilitation robots, and physical human-robot collaboration. To facilitate applications, this understanding should be in the form of a simple mathematical model that not only describes humans' capabilities but also their limitations. In robotics, hybrid control allows simultaneous, independent control of both motion and force and it is often assumed that humans can modulate force independent of motion as well. This paper experimentally tested that assumption. Participants were asked to apply a constant 5N force on a robot manipulandum that moved along an elliptical path. After initial improvement, force errors quickly plateaued, despite practice and visual feedback. Within-trial analyses revealed that force errors varied with position on the ellipse, rejecting the hypothesis that humans have independent control of force and motion. The findings are consistent with a feed-forward motion command composed of two primitive oscillations acting through mechanical impedance to evoke force.