Ixazomib enhances parathyroid hormone-induced β-catenin/T-cell factor signaling by dissociating β-catenin from the parathyroid hormone receptor.

The anabolic action of PTH in bone is mostly mediated by cAMP/PKA and Wnt-independent activation of β-catenin/T-cell factor (TCF) signaling. β-Catenin switches the PTH receptor (PTHR) signaling from cAMP/PKA to PLC/PKC activation by binding to the PTHR. Ixazomib (Izb) was recently approved as the first orally administered proteasome inhibitor for the treatment of multiple myeloma; it acts in part by inhibition of pathological bone destruction. Proteasome inhibitors were reported to stabilize β-catenin by the ubiquitin-proteasome pathway. However, how Izb affects PTHR activation to regulate β-catenin/TCF signaling is poorly understood. In the present study, using CRISPR/Cas9 genome-editing technology, we show that Izb reverses β-catenin-mediated PTHR signaling switch and enhances PTH-induced cAMP generation and cAMP response element-luciferase activity in osteoblasts. Izb increases active forms of β-catenin and promotes β-catenin translocation, thereby dissociating β-catenin from the PTHR at the plasma membrane. Furthermore, Izb facilitates PTH-stimulated GSK3β phosphorylation and β-catenin phosphorylation. Thus Izb enhances PTH stimulation of β-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating β-catenin from the PTHR. These findings provide evidence that Izb may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases

Terahertz Wave Guiding by Femtosecond Laser Filament in Air

Femtosecond laser filament generates strong terahertz (THz) pulse in air. In this paper, THz pulse waveform generated by femtosecond laser filament has been experimentally investigated as a function of the length of the filament. Superluminal propagation of THz pulse has been uncovered, indicating that the filament creates a THz waveguide in air. Numerical simulation has confirmed that the waveguide is formed because of the radially non-uniform refractive index distribution inside the filament. The underlying physical mechanisms and the control techniques of this type THz pulse generation method might be revisited based on our findings. It might also potentially open a new approach for long-distance propagation of THz wave in air.Comment: 5 pages, 6 figure

Investigating Online Service Alliance in A Signaling Game

This research uses the concept of service blueprinting to separate the online platform into several individual services. This research uses signaling game theory to investigate if service providers should cooperate with Yahoo according to information asymmetry. By using the concept of game theory, service providers can judge the decision of cooperation. This research uses signaling game theory to investigate the interaction of online service providers and decide if the cooperation is the best strategy. In particular, the payoffs under cooperation will be further evaluated by Shapley value. Shapley value is used to measure the fairness of profit after cooperation

_In vivo_ photoacoustic molecular imaging with simultaneous multiple selective targeting using antibody-conjugated gold nanorods

The use of gold nanorods for photoacoustic molecular imaging in vivo with simultaneous multiple selective targeting is reported. The extravasation of multiple molecular probes is demonstrated, and used to probe molecular information of cancer cells. This technique allows molecular profiles representing tumor characteristics to be obtained and a heterogeneous population of cancer cells in a lesion to be determined. The results also show that the image contrast can be enhanced by using a mixture of different molecular probes. In this study, HER2, EGFR, and CXCR4 were chosen as the primary target molecules for examining two types of cancer cells, OECM1 and Cal27. OECM1 cells overexpressed HER2 but exhibited a low expression of EGFR, while Cal27 cells showed the opposite expression profile. Single and double targeting resulted in signal enhancements of up to 3 dB and up to 5 dB, respectively, and hence has potential in improving cancer diagnoses

A COMPUTER SIMULATION OF KINETICS IN LANDING OF GYMNASTICS VAULTING

Gymnasts suffer from high impact loadings during landing and/or dismounts, and injuries are not unusual. The aims of this work were to develop a method for measuring or calculating the landing GRFs, which can be applied in practice and/or competitions, and to get loadings upon lower limbs during vaulting landings. A multi-body model with 19 segments and 52 freedoms was developed on the biomechanical simulation platform, software MSC.ADAMS / LifeMod. In order to test the validity of the model, the kinematics and simulation upon a university student’s drop jump were studied. The differences of maximum GRFs obtained from simulation studies and a force plate were less than 2.0% of the maximum GRF got by the force platform. After that, a vault performed by an elite gymnast was simulated and GRFs and net joint reaction forces and torques at ankle, knee, and hip were obtained

Impulsive rotational Raman scattering of N2 by a remote "air laser" in femtosecond laser filament

We report on experimental realization of impulsive rotational Raman scattering from neutral nitrogen molecules in a femtosecond laser filament using an intense self-induced white-light seeding "air laser" generated during the filamentation of an 800 nm Ti: Sapphire laser in nitrogen gas. The impulsive rotational Raman fingerprint signals are observed with a maximum conversion efficiency of ~0.8%. Our observation provides a promising way of remote identification and location of chemical species in atmosphere by rotational Raman scattering of molecules.Comment: 4 pages, 4 figure