Attenuation of WNT signaling by DKK-1 and -2 regulates BMP2-induced osteoblast differentiation and expression of OPG, RANKL and M-CSF

Abstract Background Enhanced osteoblast-dependent osteoclastogenesis due to inhibition of Wnt/β-catenin signaling in bone morphogenic protein (BMP)-driven osteoprogenitors has been repeatedly implicated in the natural history of cancer-associated osteolytic lesions, but the mechanism of this bone loss is poorly understood. Methods We examined the impact of secreted Wnt inhibitors from the Dickkopf (Dkk) family on pluripotent mesenchymal cells undergoing BMP2-induced osteoblastic differentiation. Results We found that Dkk1 and -2 restored the Wnt3a-dependent reduction of alkaline phosphatase (ALP), Osterix and p53, indicating that mitigated Wnt/β-catenin signaling promotes certain aspects of early osteoblastogenesis through the BMP-p53-Osterix-ALP axis. Dkk1 and -2 increased the expression of the osteoclast differentiation factors, receptor activator of NF-κB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF), upon stimulation with Wnt3a/1,25-dihydroxyvitamine D3 and Wnt3a/BMP2, respectively. The decoy receptor of RANKL, osteoprotegerin (OPG), was down regulated under the latter conditions. These findings indicated that Dkk1 and -2 facilitate osteoclastogenesis by enhancing RANKL/RANK and M-CSF/c-Fms interactions. Dkk4 weakly shared activities of Dkk-1 and -2, whereas Dkk3 was ineffective. Conclusion Our results suggest that inhibited Wnt/β-catenin signaling in BMP2-induced osteoprogenitors in vivo promotes, on balance, the heightened formation of osteoclasts. Focally increased Dkk1 production by tumor cells in the bone may thus lead to focal bone loss.</p

All-optical switching using nonlinear subwavelength Mach-Zehnder on silicon

We report on the experimental demonstration of ultrafast all-optical switching and wavelength down-conversion based on a novel nonlinear Mach-Zehnder interferometer with subwavelength grating and wire waveguides. Unlike other periodic waveguides such as line-defects in a 2D photonic crystal lattice, a subwavelength grating waveguide confines the light as a conventional index-guided structure and does not exhibit optically resonant behaviour. Since the device had no dedicated port to input optical signal to control switching a new approach was also implemented for all-optical switching control

Multiaperture planar waveguide spectrometer formed by arrayed Mach-Zehnder interferometers

Concept, theory and simulations of a new type of waveguide device, a multiaperture Fourier-transform planar waveguide spectrometer, are presented. The spectrometer is formed by an array of Mach-Zehnder interferometers generating a wavelength dependent spatial fringe pattern at the array output. The input light spectrum is calculated using a discrete Fourier transformation of the output spatial fringes. The multiaperture input significantly increases the optical throughput (étendue) compared to conventional single input spectrometers. Design rules for the arrayed spectrometer are deduced from performance specifications such as wavelength range and spectral resolution. A design example with spectral resolution 0.025 nm and range 2.5 nm is presented, where the optical throughput is increased by a factor of 200 compared to a single input device

A general approach for robust integrated polarization rotators

Integrated polarization rotators suffer from very high sensitivity to fabrication errors. A polarization rotator scheme that substantially increases fabrication tolerances is proposed. In the proposed scheme, two tunable polarization phase shifters are used to connect three rotator waveguide sections. By means of properly setting the polarization phase shifters, fabrication errors are compensated and perfect polarization rotation is achieved. Analytical conditions are shown that determine the maximum deviation that can be corrected with the proposed scheme. A design example is discussed, where the thermo-optic effect is used to provide the required tunable polarization phase shifting. Calculated 40dB extinction ratio is shown in presence of fabrication errors that would yield a 4dB extinction ratio in the conventional approach. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.The authors want to aknowledge Universidad de Málaga alaga, Campus de Excelencia Internacional Andalucia Tech for their support

Fabrication tolerant and broadband polarization splitter and rotator based on a taper-etched directional coupler.

We propose a fabrication tolerant polarization splitter and rotator (PSR) on the silicon-on-insulator platform based on the mode-coupling mechanism. The PSR consists of a silicon wire waveguide coupled to a taper-etched waveguide. Compared to previously reported PSRs based on directional couplers which are sensitive to fabrication variations, the partially etched taper structure can compensate for fabrication inaccuracies. In addition, the taper-etched geometry breaks both the horizontal and vertical symmetries of the waveguide, introducing an additional degree of design freedom to accommodate different upper cladding layers. The proposed PSR can be readily integrated in a planar waveguide circuit using e.g. SiO(2) cladding, making it compatible with typical metal back-end-of-line processes. Our simulation results show that the PSR has a low TM-to-TE polarization conversion loss of -0.09 dB in the C-band (or a conversion efficiency of 98%). A low TE-to-TE through insertion loss (-0.07 dB) and a very low polarization crosstalk (-30 dB) over a wide wavelength range exceeding 160 nm with a large fabrication tolerance (50 nm) are numerically demonstrated

Measurement Accuracy in Silicon Photonic Ring Resonator Thermometers: Identifying and Mitigating Intrinsic Impairments

Silicon photonic ring resonator thermometers have been shown to provide temperature measurements with a 10 mK accuracy. In this work we identify and quantify the intrinsic on-chip impairments that may limit further improvement in temperature measurement accuracy. The impairments arise from optically induced changes in the waveguide effective index, and from back-reflections and scattering at defects and interfaces inside the ring cavity and along the path between light source and detector. These impairments are characterized for 220 x 500 nm Si waveguide rings by experimental measurement in a calibrated temperature bath and by phenomenological models of ring response. At different optical power levels both positive and negative light induced resonance shifts are observed. For a ring with L = 100 um cavity length, the self-heating induced resonance red shift can alter the temperature reading by 200 mK at 1 mW incident power, while a small blue shift is observed below 100 uW. The effect of self-heating is shown to be effectively suppressed by choosing longer ring cavities. Scattering and back-reflections often produce split and distorted resonance line shapes. Although these distortions can vary with resonance order, they are almost completely invariant with temperature for a given resonance and do not lead to measurement errors in themselves. The effect of line shape distortions can largely be mitigated by tracking only selected resonance orders with negligible shape distortion, and by measuring the resonance minimum wavelength directly, rather than attempting to fit the entire resonance line shape. The results demonstrate the temperature error due to these impairments can be limited to below the 3 mK level through appropriate design choices and measurement procedures

Silicon waveguide modulator based on carrier depletion in periodically interleaved PN junctions

We present the design and numerical simulation results for a silicon waveguide modulator based on carrier depletion in a linear array of periodically interleaved PN junctions that are oriented perpendicular to the light propagation direction. In this geometry the overlap of the optical waveguide mode with the depletion region is much larger than in designs using a single PN junction aligned parallel to the waveguide propagation direction. Simulations predict that an optimized modulator will have a high modulation efficiency of 0.56 V.cm for a 3V bias, with a 3 dB frequency bandwidth of over 40 GHz. This device has a length of 1.86 mm with a maximum intrinsic loss of 4.3 dB at 0V bias, due to free carrier absorption. (C) 2009 Optical Society of Americ

Optical wavefront phase-tilt measurement using Si-photonic waveguide grating couplers

Silicon photonic wavefront phase-tilt sensors for wavefront monitoring using surface coupling grating arrays are demonstrated. The first design employs the intrinsic angle dependence of the grating coupling efficiency to determine local wavefront tilt, with a measured sensitivity of 7 dB/degree. A second design connects four gratings in an interferometric waveguide circuit to determine incident wavefront phase variation across the sensor area. In this device, one fringe spacing corresponds to approximately 2 degree wavefront tilt change. These sensor elements can sample a wavefront incident on the chip surface without the use of bulk optic elements, fiber arrays, or imaging arrays. Both sensor elements are less than 60 um across, and can be combined into larger arrays to monitor wavefront tilt and distortion across an image or pupil plane in adaptive optics systems for free space optical communications, astronomy and beam pointing applications