SERPINC1 c.1247dupC: a novel SERPINC1 gene mutation associated with familial thrombosis results in a secretion defect and quantitative antithrombin deficiency.

BACKGROUND: Antithrombin (AT) is an important anticoagulant in hemostasis. We describe here the characterization of a novel AT mutation associated with clinically relevant thrombosis. A pair of sisters with confirmed type I AT protein deficiency was genetically analyzed on suspicion of an inherited SERPINC1 mutation. A frameshift mutation, c.1247dupC, was identified and the effect of this mutation was examined on the cellular and molecular level. METHODS: Plasmids for the expression of wild-type (WT) and mutated SERPINC1 coding sequence (CDS) fused to green fluorescent protein (GFP) or hemagglutinin (HA) tag were transfected into HEK293T cells. Subcellular localization and secretion of the respective fusion proteins were analyzed by confocal laser scanning microscopy and Western blot. RESULTS: The c.1247dupC mutation results in a frameshift in the CDS of the SERPINC1 gene and a subsequently altered amino acid sequence (p.Ser417LysfsTer48). This alteration affects the C-terminus of the AT antigen and results in impaired secretion as confirmed by GFP- and HA-tagged mutant AT analyzed in HEK293T cells. CONCLUSION: The p.Ser417LysfsTer48 mutation leads to impaired secretion, thus resulting in a quantitative AT deficiency. This is in line with the type I AT deficiency observed in the patients.

Directional Excitation of a High-Density Magnon Gas Using Coherently Driven Spin Waves.

Controlling magnon densities in magnetic materials enables driving spin transport in magnonic devices. We demonstrate the creation of large, out-of-equilibrium magnon densities in a thin-film magnetic insulator via microwave excitation of coherent spin waves and subsequent multimagnon scattering. We image both the coherent spin waves and the resulting incoherent magnon gas using scanning-probe magnetometry based on electron spins in diamond. We find that the gas extends unidirectionally over hundreds of micrometers from the excitation stripline. Surprisingly, the gas density far exceeds that expected for a boson system following a Bose-Einstein distribution with a maximum value of the chemical potential. We characterize the momentum distribution of the gas by measuring the nanoscale spatial decay of the magnetic stray fields. Our results show that driving coherent spin waves leads to a strong out-of-equilibrium occupation of the spin-wave band, opening new possibilities for controlling spin transport and magnetic dynamics in target directions.

Flexure-tuned membrane-at-the-edge optomechanical system.

We introduce a passively-aligned, flexure-tuned cavity optomechanical system in which a membrane is positioned microns from one end mirror of a Fabry-Perot optical cavity. By displacing the membrane through gentle flexure of its silicon supporting frame (i.e., to ∼80 m radius of curvature (ROC)), we gain access to the full range of available optomechanical couplings, finding also that the optical spectrum exhibits none of the abrupt discontinuities normally found in "membrane-in-the-middle" (MIM) systems. More aggressive flexure (3 m ROC) enables >15 µm membrane travel, milliradian tilt tuning, and a wavelength-scale (1.64 ± 0.78 µm) membrane-mirror separation. We also provide a complete set of analytical expressions for this system's leading-order dispersive and dissipative optomechanical couplings. Notably, this system can potentially generate orders of magnitude larger linear dissipative or quadratic dispersive strong coupling parameters than is possible with a MIM system. Additionally, it can generate the same purely quadratic dispersive coupling as a MIM system, but with significantly suppressed linear dissipative back-action (and force noise).

Optically Coherent Nitrogen-Vacancy Centers in Micrometer-Thin Etched Diamond Membranes.

Diamond membrane devices containing optically coherent nitrogen-vacancy (NV) centers are key to enable novel cryogenic experiments such as optical ground-state cooling of hybrid spin-mechanical systems and efficient entanglement distribution in quantum networks. Here, we report on the fabrication of a (3.4 ± 0.2) µm thin, smooth (surface roughness rq < 0.4 nm over an area of 20 µm by 30 µm) diamond membrane containing individually resolvable, narrow linewidth (< 100 MHz) NV centers. We fabricate this sample via a combination of high-energy electron irradiation, high-temperature annealing, and an optimized etching sequence found via a systematic study of the diamond surface evolution on the microscopic level in different etch chemistries. Although our particular device dimensions are optimized for cavity-enhanced entanglement generation between distant NV centers in open, tunable microcavities, our results have implications for a broad range of quantum experiments that require the combination of narrow optical transitions and micrometer-scale device geometry.

High mechanical bandwidth fiber-coupled Fabry-Perot cavity.

Fiber-based optical microcavities exhibit high quality factor and low mode volume resonances that make them attractive for coupling light to individual atoms or other microscopic systems. Moreover, their low mass should lead to excellent mechanical response up to high frequencies, opening the possibility for high bandwidth stabilization of the cavity length. Here, we demonstrate a locking bandwidth of 44 kHz achieved using a simple, compact design that exploits these properties. Owing to the simplicity of fiber feedthroughs and lack of free-space alignment, this design is inherently compatible with vacuum and cryogenic environments. We measure the transfer function of the feedback circuit (closed-loop) and the cavity mount itself (open-loop), which, combined with simulations of the mechanical response of our device, provide insight into underlying limitations of the design as well as further improvements that can be made.