Runx2 is necessary and sufficient for osteoblast differentiation, yet its expression precedes the appearance of osteoblasts by 4 days. Here we show that Twist proteins transiently inhibit Runx2 function during skeletogenesis. Twist-1 and -2 are expressed in Runx2-expressing cells throughout the skeleton early during development, and osteoblast-specific gene expression occurs only after their expression decreases. Double heterozygotes for Twist-1 and Runx2 deletion have none of the skull abnormalities observed in Runx2(+/-) mice, a Twist-2 null background rescues the clavicle phenotype of Runx2(+/-) mice, and Twist-1 or -2 deficiency leads to premature osteoblast differentiation. Furthermore, Twist-1 overexpression inhibits osteoblast differentiation without affecting Runx2 expression. Twist proteins' antiosteogenic function is mediated by a novel domain, the Twist box, which interacts with the Runx2 DNA binding domain to inhibit its function. In vivo mutagenesis confirms the antiosteogenic function of the Twist box. Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation.

Electron spins in solids are promising candidates for quantum memories for superconducting qubits because they can have long coherence times, large collective couplings, and many quantum bits can be encoded into the spin-waves of a single ensemble. We demonstrate the coupling of electron spin ensembles to a superconducting transmission-line resonator at coupling strengths greatly exceeding the cavity decay rate and comparable to spin linewidth. We also use the enhanced coupling afforded by the small cross-section of the transmission line to perform broadband spectroscopy of ruby at millikelvin temperatures at low powers. In addition, we observe hyperfine structure in diamond P1 centers and time domain saturation-relaxation of the spins.An eventual quantum computer, like its classical analog, will make use of a variety of physical systems specialized for different tasks. Just as a classical computer uses charge-based transistors for fast processing and magnetic hard drives for long term information storage, a quantum computer might use superconducting qubits for processing [1] and ensembles of electron spins as quantum memories [2,3], linked by single microwave photons. Although other microscopic systems have been proposed for use in a hybrid architecture [4][5][6][7], electron spins complement superconducting qubits particularly well. They feature similar transition frequencies, do not require trapping, and can be packed densely. Furthermore, a single ensemble could be used to store many qubits using holographic encoding techniques [3] demonstrated classically for nuclear [8] and electron [9] spins.In this Letter, we demonstrate the first step toward realizing a solid-state quantum memory: coupling an electron spin ensemble to an on-chip superconducting cavity at powers corresponding to a single cavity photon. We observe megahertz spin-photon interaction strengths in both ruby Cr 3+ spins and N substitution (P1) centers in diamond. A parallel effort by Kubo, et. al.[? ] sees similar coupling to nitrogen vacancy (NV) centers in diamond. In doing so we develop a platform for the study of electron spin resonance (ESR) physics in picoliter mode volumes, millikelvin temperatures, and attowatt powers. Finally, we perform time-resolved saturation/relaxation measurements of the P1 centers, a precursor to full pulsed control of the system. ESR studies the microwave response of electron spins at their resonant frequency in a magnetic field. Samples are conventionally placed inside a 3D high quality-factor (Q) cavity which enhances the sensitivity by confining photons with the spins and extending the interaction time [10]. In this work, several 1D cavities are capacitively coupled to a common feedline on a sapphire chip. We place the spins within the mode volume by fabricating the device on doped sapphire (ruby - Fig. 1a), attaching a substrate on top of an existing device (diamond - Fig. 1b), or simply spin-coating the surface (DPPHnot shown). The single spin-photon coupling is given by g s /2π = m 0 (µ 0 ω/2hV c ) 1/2 ,...

Electron and nuclear spins have good coherence times and an ensemble of spins is a promising candidate for a quantum memory. By employing holographic techniques via field gradients a single ensemble may be used to store many bits of information. Here we present a coherent memory using a pulsed magnetic field gradient, and demonstrate the storage and retrieval of up to 100 weak 10 GHz coherent excitations in collective states of an electron spin ensemble. We further show that such collective excitations in the electron spin can then be stored in nuclear spin states, which offer coherence times in excess of seconds.Instead of storing information in specific locations as in photography and in conventional computer memory, information can be stored in distributed collective modes, as in holography. Advantages include obviating the need for local manipulations and measurements, enhanced coupling to electromagnetic fields, and robustness against decoherence of individual members of the ensemble. This principle has been applied to different light-matter interfaces such as atoms [1][2][3][4], ion-doped crystals [5][6][7][8][9], polar molecules [10-13], or spins [14,15]. Controlled reversible inhomogeneous broadening (CRIB) [8], or gradient echo memory (GEM) [7] schemes which apply external field gradients to address different storage modes have been proposed and observed in gaseous atomic samples [1,2] and in ion-doped solids [6,7].In this Letter, we demonstrate the storage of multiple microwave excitations in an electron spin ensemble. The spin ensembles used as the storage medium are the electron spin of nitrogen atoms in fullerene cages ( 14 N@C 60 ) and phosphorous donors in silicon. The microwave excitations are phase encoded using a static or pulsed field gradient, with the latter allowing for recall in arbitrary order. We have stored up to 100 weak excitations in a spin ensemble and recalled them sequentially. We also demonstrate the coherent transfer of the stored multiple excitations between electron spin and nuclear spin, which will allow much longer storage times [16]. The multimode storage achieved in this way offers prospects of constructing a long-lived quantum memory which could be used for a hybrid quantum computing architecture with superconducting qubits.A quasistatic magnetic field along the z-axis causes the members of the spin ensemble to precess at an angular frequency B(z, t)µg e / , where µ is the Bohr magneton and g e is the electron gyromagnetic ratio. Applying a magnetic gradient of strength G = ∂B(z, t)/∂z for a time τ consequently leads to a difference in precession angle of δθ = (µg e / )Gτ · δz between two spins with separation δz along the z-axis. A gradient pulse thus maps a spin state with a coherent transverse magnetization (such as that generated by a global resonant microwave tipping pulse) to a spin-wave excitation associated with a wave number k = (µg e / )Gτ · z. Each further application of G for duration τ generates a change in the wavevector of the global spin wave mode, by an a...

We demonstrate the strong coupling between an electron spin ensemble and a three-dimensional cavity in a reflection geometry. We also find that an anticrossing in the cavity/spin spectrum can be observed under conditions that the collective coupling strength g c is smaller than the spin linewidth γ s or the cavity linewidth. We identify a ratio of g c to γ s (g c /γ s > 0.64) as a condition to observe a splitting in the cavity frequency. Finally, we confirm that g c scales with √ N , where N is the number of polarized spins.When two oscillators couple strongly, their otherwise degenerate modes repel each other to develop an anticrossing in the spectrum. A canonical example is the interaction between a single photon and a single atom, and this phenomenon is called the vacuum Rabi splitting. 1 The strong light-matter coupling has been a central subject in cavity quantum electrodynamics (QED), and has attracted increasing attention as a means to coherently transfer information between a flying (photonic) and stationary (atomic) qubits in the field of quantum information processing. So far, the strong coupling regime has been realized in various systems. 2-5 Even when the cavity-atom coupling strength g s is small, as in the case of natural spins, the interaction can be collectively enhanced, by utilizing an ensemble of N identical two-level systems, to replace g s with a new parameter g c = g s √ N . Such a collective enhancement has been observed in a wide variety of systems, such as Bose-Einstein condensates, 6,7 trapped ions, 8 and circuit QED with superconductors. 9 More recently, the strong coupling between an electron spin ensemble and a superconducting coplanar waveguide resonator has been demonstrated for impurity spins in ruby and diamond. 10,11 A rough estimation of g s in the spin system is given as g s ≈ m 0 µ 0 ω c /2 V c , where m 0 is the magnetic dipole moment of the spin, ω c is the cavity frequency, and V c is the cavity mode volume. There, the small V c of the order of 10 −12 m 3 helped to enhance the cavity-spin coupling. These experiments are motivated by the goal of using an electron spin ensemble as a medium for quantum memory, which will potentially benefit from the capability of storing multiple qubits in different modes of the ensemble. 12 In this Letter, we study the coupling between an electron spin ensemble and a microwave resonator with much larger V c , a three-dimensional cavity that is commonly used for bulk electron paramagnetic resonance (EPR), and demonstrate that by increasing the number of spins a) Electronic mail: eisuke.abe@materials.ox.ac.uk the spectrum experiences the transition from the weak to strong coupling regimes. Our result provides an opportunity for studying the strong coupling effect with readily accessible setups and wider tunabilities in the experimental parameters. In addition, it has been recently observed that such a three-dimensional cavity allows a superconducting qubit to preserve its coherence longer than the case of a two-dimensional counterpart. 13 Toge...

Acute respiratory distress syndrome/acute lung injury (ALI) was described in 1967. The uncontrolled inflammation is a central issue of the syndrome. The regulatory T cells (Tregs), formerly known as suppressor T cells, are a subpopulation of T cells. Tregs indirectly limits immune inflammation-inflicted tissue damage by employing multiple mechanisms and creating the appropriate immune environment for successful tissue repair. And it plays a central role in the resolution of ALI. Accordingly, for this review, we will focus on Treg populations which are critical for inflammatory immunity of ALI, and the effect of interaction between Treg subsets and cytokines on ALI. And then explore the possibility of cytokines as beneficial factors in inflammation resolution of ALI.

Inflammatory mediators and G protein-coupled signaling were associated with the pathogenesis of synovitis in CIA rats. Pae, as a new monomer, had anti-inflammatory effects on the animal model of CIA in rats, but also had regulatory effects on FLS from CIA rats in vitro. These results highlight Pae as a good candidate for therapeutic intervention in RA.

Simultaneous Multi-Slice (SMS) magnetic resonance imaging (MRI) is a rapidly evolving technique for increasing imaging speed. Controlled aliasing techniques utilize periodic undersampling patterns to help mitigate the loss in signal-to-noise ratio (SNR) in SMS MRI. To evaluate the performance of different undersampling patterns, a quantitative description of the image SNR loss is needed. Additionally, eddy current effects in echo planar imaging (EPI) lead to slice-specific Nyquist ghosting artifacts. These artifacts cannot be accurately corrected for each individual slice before or after slice-unaliasing. In this work, we propose a hybrid-space sensitivity encoding (SENSE) reconstruction framework for SMS MRI by adopting a three-dimensional representation of the SMS acquisition. Analytical SNR loss maps are derived for SMS acquisitions with arbitrary phase encoding undersampling patterns. Moreover, we propose a matrix-decoding correction method that corrects the slice-specific Nyquist ghosting artifacts in SMS EPI acquisitions. Brain images demonstrate that the proposed hybrid-space SENSE reconstruction generates images with comparable quality to commonly used split-slice-generalized autocalibrating partially parallel acquisition reconstruction. The analytical SNR loss maps agree with those calculated by a Monte Carlo based method, but require less computation time for high quality maps. The analytical maps enable a fair comparison between the performances of coherent and incoherent SMS undersampling patterns. Phantom and brain SMS EPI images show that the matrix-decoding method performs better than the single-slice and slice-averaged Nyquist ghosting correction methods under the hybrid-space SENSE reconstruction framework.

Development of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of longitudinal relaxation rate (R1) of white matter in 0, 3 and 6 months-old human infants, and developed an automated method to identify white matter bundles and quantify their properties in each infant’s brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and development rate increases along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy.