Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1β-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of connective tissue mast cell depletion (Mcpt5-Cre:Rosa26-Stopfl/fl-DTa) was crossed with CMO mice and the resulting mice (referred to as CMO/MC–) showed a significant delay in disease onset compared with age-matched CMO mice. At 5-6 months of age, CMO/MC– mice had fewer bone lesions and immune infiltration in the popliteal lymph nodes that drain the affected tissues. In bone marrow-derived mast cell cultures from CMO mice, cytokine production in response to the alarmin IL-33 was elevated compared with wild-type cultures. To test the relevance of mast cells to human CRMO, we tested serum samples from a cohort of healthy controls and from CRMO patients at diagnosis. Interestingly, mast cell chymase was elevated in CRMO patients as well as in patients with oligoarticular juvenile arthritis. Tryptase-positive mast cells were also detected in bone lesions from CRMO patients and patients with bacterial osteomyelitis. Together, our results identify mast cells as cellular contributors to bone inflammation in CMO/CRMO and provide rationale for further study of mast cells as therapeutic targets

Interferometric Single-Shot Parity Measurement in an InAs-Al Hybrid Device

The fusion of non-Abelian anyons or topological defects is a fundamental operation in measurement-only topological quantum computation. In topological superconductors, this operation amounts to a determination of the shared fermion parity of Majorana zero modes. As a step towards this, we implement a single-shot interferometric measurement of fermion parity in indium arsenide-aluminum heterostructures with a gate-defined nanowire. The interferometer is formed by tunnel-coupling the proximitized nanowire to quantum dots. The nanowire causes a state-dependent shift of these quantum dots' quantum capacitance of up to 1 fF. Our quantum capacitance measurements show flux h/2e-periodic bimodality with a signal-to-noise ratio of 1 in 3.7 $\mu$s at optimal flux values. From the time traces of the quantum capacitance measurements, we extract a dwell time in the two associated states that is longer than 1 ms at in-plane magnetic fields of approximately 2 T. These results are consistent with a measurement of the fermion parity encoded in a pair of Majorana zero modes that are separated by approximately 3 $\mu$m and subjected to a low rate of poisoning by non-equilibrium quasiparticles. The large capacitance shift and long poisoning time enable a parity measurement error probability of 1%.Comment: Added data on a second measurement of device A and a measurement of device B, expanded discussion of a trivial scenario. Refs added, author list update

InAs-Al Hybrid Devices Passing the Topological Gap Protocol

We present measurements and simulations of semiconductor-superconductor heterostructure devices that are consistent with the observation of topological superconductivity and Majorana zero modes. The devices are fabricated from high-mobility two-dimensional electron gases in which quasi-one-dimensional wires are defined by electrostatic gates. These devices enable measurements of local and non-local transport properties and have been optimized via extensive simulations for robustness against non-uniformity and disorder. Our main result is that several devices, fabricated according to the design's engineering specifications, have passed the topological gap protocol defined in Pikulin {\it et al.}\ [arXiv:2103.12217]. This protocol is a stringent test composed of a sequence of three-terminal local and non-local transport measurements performed while varying the magnetic field, semiconductor electron density, and junction transparencies. Passing the protocol indicates a high probability of detection of a topological phase hosting Majorana zero modes. Our experimental results are consistent with a quantum phase transition into a topological superconducting phase that extends over several hundred millitesla in magnetic field and several millivolts in gate voltage, corresponding to approximately one hundred micro-electron-volts in Zeeman energy and chemical potential in the semiconducting wire. These regions feature a closing and re-opening of the bulk gap, with simultaneous zero-bias conductance peaks at {\it both} ends of the devices that withstand changes in the junction transparencies. The measured maximum topological gaps in our devices are 20-$30\,\mu$eV. This demonstration is a prerequisite for experiments involving fusion and braiding of Majorana zero modes.Comment: Fixed typos. Fig. 3 is now readable by Adobe Reade