Twist1 Inactivation in Dmp1-Expressing Cells Increases Bone Mass but Does Not Affect the Anabolic Response to Sclerostin Neutralization

Wnt signaling plays a major role in bone metabolism. Advances in our understanding of secreted regulators of Wnt have yielded several therapeutic targets to stimulate osteoanabolism—the most promising of which is the Wnt inhibitor sclerostin. Sclerostin antibody recently gained approval for clinical use to treat osteoporosis, but the biology surrounding sclerostin antagonism is still incompletely understood. Numerous factors regulate the efficacy of sclerostin inhibition on bone formation, a process known as self-regulation. In previous communications we reported that the basic helix-loop-helix transcription factor Twist1—a gene know to regulate skeletal development—is highly upregulated among the osteocyte cell population in mice treated with sclerostin antibody. In this communication, we tested the hypothesis that preventing Twist1 upregulation by deletion of Twist1 from late-stage osteoblasts and osteocytes would increase the efficacy of sclerostin antibody treatment, since Twist1 is known to restrain osteoblast activity in many models. Twist1-floxed loss-of-function mice were crossed to the Dmp1-Cre driver to delete Twist1 in Dmp1-expressing cells. Conditional Twist1 deletion was associated with a mild but significant increase in bone mass, as assessed by dual energy x-ray absorptiometry (DXA) and microCT (µCT) for many endpoints in both male and female mice. Biomechanical properties of the femur were not affected by conditional mutation of Twist1. Sclerostin antibody improved all bone properties significantly, regardless of Twist1 status, sex, or endpoint examined. No interactions were detected when Twist1 status and antibody treatment were examined together, suggesting that Twist1 upregulation in the osteocyte population is not an endogenous mechanism that restrains the osteoanabolic effect of sclerostin antibody treatment. In summary, Twist1 inhibition in the late-stage osteoblast/osteocyte increases bone mass but does not affect the anabolic response to sclerostin neutralization

Deep learning for synthetic microstructure generation in a materials-by-design framework for heterogeneous energetic materials

The sensitivity of heterogeneous energetic (HE) materials (propellants, explosives, and pyrotechnics) is critically dependent on their microstructure. Initiation of chemical reactions occurs at hot spots due to energy localization at sites of porosities and other defects. Emerging multi-scale predictive models of HE response to loads account for the physics at the meso-scale, i.e. at the scale of statistically representative clusters of particles and other features in the microstructure. Meso-scale physics is infused in machine-learned closure models informed by resolved meso-scale simulations. Since microstructures are stochastic, ensembles of meso-scale simulations are required to quantify hot spot ignition and growth and to develop models for microstructure-dependent energy deposition rates. We propose utilizing generative adversarial networks (GAN) to spawn ensembles of synthetic heterogeneous energetic material microstructures. The method generates qualitatively and quantitatively realistic microstructures by learning from images of HE microstructures. We show that the proposed GAN method also permits the generation of new morphologies, where the porosity distribution can be controlled and spatially manipulated. Such control paves the way for the design of novel microstructures to engineer HE materials for targeted performance in a materials-by-design framework

Train Small, Model Big: Scalable Physics Simulators via Reduced Order Modeling and Domain Decomposition

Numerous cutting-edge scientific technologies originate at the laboratory scale, but transitioning them to practical industry applications is a formidable challenge. Traditional pilot projects at intermediate scales are costly and time-consuming. An alternative, the E-pilot, relies on high-fidelity numerical simulations, but even these simulations can be computationally prohibitive at larger scales. To overcome these limitations, we propose a scalable, physics-constrained reduced order model (ROM) method. ROM identifies critical physics modes from small-scale unit components, projecting governing equations onto these modes to create a reduced model that retains essential physics details. We also employ Discontinuous Galerkin Domain Decomposition (DG-DD) to apply ROM to unit components and interfaces, enabling the construction of large-scale global systems without data at such large scales. This method is demonstrated on the Poisson and Stokes flow equations, showing that it can solve equations about $15 - 40$ times faster with only $\sim$ $1\%$ relative error. Furthermore, ROM takes one order of magnitude less memory than the full order model, enabling larger scale predictions at a given memory limitation.Comment: 40 pages, 12 figures. Submitted to Computer Methods in Applied Mechanics and Engineerin

Neutrino Oscillations and R-parity Violating Collider Signals

R-parity and L violation in the MSSM would be the origin of the neutrino oscillation observed in Super-Kamiokande. A distinctive feature of this framework is that it can be tested in colliders by observing decay products of the destabilized LSP. We examine all the possible decay processes of the neutralino LSP assuming the bilinear contribution to neutrino masses dominates over the trilinear one which gives rise to the solar neutrino mass. We find that it is possible to probe neutrino oscillations through colliders in most of the R-parity conserving MSSM parameter space.Comment: 23 pages, 8 figures, to appear in Phys. Rev.

New scalar resonances from sneutrino-Higgs mixing in supersymmetry with small lepton number (R-parity) violation

We consider new s-channel scalar exchanges in top quark and massive gauge-bosons pair production in e+e- collisions, in supersymmetry with a small lepton number violation. We show that a soft bilinear lepton number violating term in the scalar potential which mixes the Higgs and the slepton fields can give rise to a significant scalar resonance enhancement in e+e- -> ZZ, W+W- and in e+e- -> t t(bar). The sneutrino-Higgs mixed state couples to the incoming light leptons through its sneutrino component and to either the top quark or the massive gauge bosons through its Higgs component. Such a scalar resonance in these specific production channels cannot result from trilinear Yukawa-like R-parity violation alone, and may, therefore, stand as strong evidence for the existence of R-parity violating bilinears in the supersymmetric scalar potential. We use the LEP2 measurements of the WW and ZZ cross-sections to place useful constrains on this scenario, and investigate the expectations for the sensitivity of a future linear collider to these signals. We find that signals of these scalar resonances, in particular in top-pair production, are well within the reach of linear colliders in the small lepton number violation scenario.Comment: 22 pages in revtex, 10 figures embadded in the text using epsfi

Interaction-based quantum metrology showing scaling beyond the Heisenberg limit

Quantum metrology studies the use of entanglement and other quantum resources to improve precision measurement. An interferometer using N independent particles to measure a parameter X can achieve at best the "standard quantum limit" (SQL) of sensitivity {\delta}X \propto N^{-1/2}. The same interferometer using N entangled particles can achieve in principle the "Heisenberg limit" {\delta}X \propto N^{-1}, using exotic states. Recent theoretical work argues that interactions among particles may be a valuable resource for quantum metrology, allowing scaling beyond the Heisenberg limit. Specifically, a k-particle interaction will produce sensitivity {\delta}X \propto N^{-k} with appropriate entangled states and {\delta}X \propto N^{-(k-1/2)} even without entanglement. Here we demonstrate this "super-Heisenberg" scaling in a nonlinear, non-destructive measurement of the magnetisation of an atomic ensemble. We use fast optical nonlinearities to generate a pairwise photon-photon interaction (k = 2) while preserving quantum-noise-limited performance, to produce {\delta}X \propto N^{-3/2}. We observe super-Heisenberg scaling over two orders of magnitude in N, limited at large N by higher-order nonlinear effects, in good agreement with theory. For a measurement of limited duration, super-Heisenberg scaling allows the nonlinear measurement to overtake in sensitivity a comparable linear measurement with the same number of photons. In other scenarios, however, higher-order nonlinearities prevent this crossover from occurring, reflecting the subtle relationship of scaling to sensitivity in nonlinear systems. This work shows that inter-particle interactions can improve sensitivity in a quantum-limited measurement, and introduces a fundamentally new resource for quantum metrology

Collider Signatures of Neutrino Masses and Mixing from R-parity Violation

R-parity violation in the supersymmetric standard model can be the source of neutrino masses and mixing. We analyze the neutrino mass matrix coming from either bilinear or trilinear R-parity violation and its collider signatures, assuming that the atmospheric and solar neutrino data are explained by three active neutrino oscillations. Taking the gauge mediated supersymmetry breaking mechanism, we show that the lightest neutralino decays well inside the detector and the model could be tested by observing its branching ratios in the future colliders. In the bilinear model where only the small solar neutrino mixing angle can be accommodated, the relation, $10^3$ BR($\nu e^\pm \tau^\mp$) $\sim$ BR($\nu \mu^\pm \tau^\mp$) $\approx$ BR($\nu \tau^\pm \tau^\mp$), serves as a robust test of the model. The large mixing angle solution can be realized in the trilinear model which predicts BR($\nu e^\pm \tau^\mp$) $\sim$ BR($\nu \mu^\pm \tau^\mp$) $\sim$ BR($\nu \tau^\pm \tau^\mp$). In either case, the relation, BR($e jj$) $\ll$ BR($\mu jj$) $\sim$ BR($\tau jj$), should hold to be consistent with the atmospheric neutrino and CHOOZ experiments.Comment: 24pages, Late

Constraining an R-parity violating supersymmetric theory from the SuperKamiokande data on atmospheric neutrinos

The constraints on an R-parity violating supersymmetric theory arising from the recent SuperKamiokande results on atmospheric neutrinos are studied, with special reference to a scenario with bilinear R-parity violating terms. Considering both the fermionic and scalar sectors, we find that a large area of the parameter space is allowed, in terms of both the lepton-number violating entries in the superpotential and the soft R-violating terms in the scalar potential, and that no fine-tuning is required. However, the need to avoid flavour changing neutral currents puts additional restrictions on the theory, requiring either the R-violating terms in the superpotential to be smaller than the R-conserving ones, or a hierarchy in the R-violating parameters for different lepton flavours in the superpotential.Comment: 18 pages, LaTex including postscript figure

The K^*_0(800) scalar resonance from Roy-Steiner representations of pi K scattering

We discuss the existence of the light scalar meson K^*_0(800) (also called kappa) in a rigorous way, by showing the presence of a pole in the pi K --> pi K amplitude on the second Riemann sheet. For this purpose, we study the domain of validity of two classes of Roy-Steiner representations in the complex energy plane. We prove that one of them is valid in a region sufficiently broad in the imaginary direction. From this representation, we compute the l=0 partial wave in the complex plane with neither additional approximation nor model dependence, relying only on experimental data. A scalar resonance with strangeness S=1 is found with the following mass and width: E_kappa = 658 \pm 13 MeV and Gamma_kappa = 557 \pm 24 MeV.Comment: 16 pages, 8 figures. Domain of validity of a Roy-Steiner representation corrected and enlarged, and features of the K^*_0(800) pole discussed in more details. Conclusions unchange

Implication of Super-Kamiokande Data on R-parity Violation

R-parity violating bilinear (soft) terms in the supersymmetric standard model would be the leading source for nonzero neutrino masses and mixing. We point out that the mixing between neutralinos (charginos) and neutrinos (charged leptons) driven by the bilinear terms take factorized forms, which may enable us to probe the neutrino mixing parameters in a collider. It is then shown that the Super-Kamiokande data on atmospheric neutrinos require all the baryon number violating couplings to be substantially suppressed: $\lambda''_{\rm any} <10^{-9}$.Comment: 11 pages, LaTeX, to appear in Phys. Rev.