FGF-receptor substrate 2 functions as a molecular sensor ntegrating external regulatory signals into the FGF pathway

Fibroblast growth factor （FGF） receptor substrate 2a （FRS2α） is the main mediator of signaling in the FGF pathway. Recent studies have shown that mitogen-activated protein kinase （MAPK） phosphorylates serine and threonine residues in FRS2, negatively affecting FGF-induced tyrosine phosphorylation （PY） of FRS2. Several kinds of stimuli can induce serine/threonine phosphorylation （PS/T） of FRS2, indicating that FRS2 may be useful for studying crosstalk between growth factor signaling pathways. Here, we report that FGF-induced PY of FRS2 can be attenuated by EGF co-stimulation in PC12cells; this inhibitory effect could be completely reversed by U0126, an inhibitor of MEK. We further identified the ERK1/2-binding motif in FRS2 and generated FRS2-3KL, a mutant lacking MAPK binding and PT upon FGF and/or EGF stimulation. Unlike wild-type （WT） FRS2, FGF-induced PY of FRS2-3KL could not be inhibited by EGF co-stimulation, and FRS2-3KL-expressing PC12 cells exhibited more differentiating potential than FRS2-WT-expressing cells in response to FGF treatment. These results suggest that PS/T of FRS2 mediated by the FRS2-MAPK negative regulatory loop may function as a molecular switch integrating negative regulatory signals from other pathways into FGFR-generated signal transduction.

Soliton frequency comb generation in CMOS-compatible silicon nitride microresonators

The monolithic integration of soliton microcomb devices with active photonic components and high-frequency electronics is highly desirable for practical applications. Among many materials, silicon nitride(SiN_(x)) waveguide layers prepared by low-pressure chemical vapor deposition(LPCVD) have been the main platform for on-chip optical frequency comb generation. However, the high temperatures involved in LPCVD render it incompatible as a back-end process with complementary metal oxide semiconductor(CMOS) or active Ⅲ-Ⅴ compound semiconductor fabrication flows. We report the generation of coherent soliton frequency combs in micro-ring resonators fabricated in deuterated silicon nitride(SiN_(x):D) waveguides with a loss of 0.09 d B/cm. Deposited at 270℃ by an inductance-coupled plasma chemical vapor deposition(ICP-CVD) process, the material preparation and fabrication flow are fully CMOS-compatible. These results enable the integration of silicon-nitride-based optical combs and photonic integrated circuits(PICs) on prefabricated CMOS and/or Ⅲ-Ⅴ substrates, therefore marking a major step forward in Si Nxphotonic technologies.

THEORETICAL INVESTIGATION ON THE DYNAMIC PERFORMANCE OF CMUT FOR DESIGN OPTIMIZATION

Although many modeling approaches exist for analyzing the behavior of capacitive micro-machined ultrasonic transducers （CMUTs）, the relation equation between the design pa- rameters with input and output is still lacking. What there is can only be used to analyze the dynamic performance of CMUT indirectly and qualitatively, such as stiffness and sound pressure. A lumped-parameter theoretical model based on the dynamic theory is proposed in this paper. The relation equations between the design parameters with inputs and outputs are given. The results obtained by the proposed model agree well with those by finite element method （FEM） simulation. The dynamic and static behavior of CMUT can be clearly depicted, which is helpful for design and optimization iterations. This shows that the proposed model makes it easier to optimize the parameters of a CMUT with respect to output and bandwidth directly and to better understand the influence of each parameter.