The role of Notch signaling in cervical cancer is seemingly controversial. To confirm the function of Notch signaling in this type of cancer, we established a stable Notch1-activated cervical cancer HeLa cell line. We found that Notch1 activation resulted in apoptosis, cell cycle arrest, and tumor suppression. At the molecular level, we found that a variety of genes associated with cyclic AMP, G protein-coupled receptor, and cancer signaling pathways contributed to Notch1-mediated tumor suppression. We observed that the expression of somatostatin (SST) was dramatically induced by Notch1 signaling activation, which was accompanied by enhanced expression of the cognate SST receptor subtype 1 (SSTR1) and SSTR2. Certain genes, such as tumor protein 63 (TP63, p63), were upregulated, whereas others, such as B-cell lymphoma 2 (BCL-2), Myc, Akt, and STAT3, were downregulated. Subsequently, knockdown of Notch1-induced SST reversed Notch1-induced decrease of BCL-2 and increase of p63, indicating that Notch1-induced tumor suppression may be partly through upregulating SST signaling. Our findings support a possible crosstalk between Notch signaling and SST signaling. Moreover, Notch-induced SSTR activation could enhance SSTRtargeted cancer chemotherapy. Valproic acid (VPA), a histone deacetylase inhibitor, suppressed cell growth and upregulated the expression of Notch1 and SSTR2. A combination therapy with VPA and the SSTR2-targeting cytotoxic conjugate CPT-SST strongly led to greater suppression, as compared to each alone. Our findings thus provide us with a promising clinical opportunity for enhanced cancer therapy using combinations of Notch1-activating agents and SSTR2-targeting agents. The Oncologist 2012;17:220 -232

In this paper, we first achieve nanosecond-scale dissipative soliton resonance (DSR) generation in a thulium-doped double-clad fiber (TDF) laser with all-anomalous-dispersion regime, and also first scale the average power up to 100.4 W by employing only two stage TDF amplifiers, corresponding to gains of 19.3 and 14.4 dB, respectively. It is noted that both the fiber laser oscillator and the amplification system employ double-clad fiber as the gain medium for utilizing the advantages in high-gain-availability, high-power-handling and good-mode-quality-maintaining. DSR mode-locking of the TDF oscillator is realized by using a nonlinear optical loop mirror (NOLM), which exhibits all-fiber-format, high nonlinear and passive saturable absorption properties. The TDF oscillator can deliver rectangular-shape pulses with duration ranging from ~3.74 to ~72.19 ns while maintaining a nearly equal output peak power level of ~0.56 W, namely peak power clamping (PPC) effect. Comparatively, the two stage amplifiers can scale the seeding pulses to similar average power levels, but to dramatically different peak powers ranging from ~0.94 to ~18.1 kW depending on the durations. Our TDF master-oscillator-power-amplifier (MOPA) system can provide a high power 2-μm band all-fiber-format laser source both tunable in pulse duration and peak power.

Membrane fouling and membrane deterioration are two major concerns since they greatly worsen membrane performance in pressure retarded osmosis (PRO) and shorten the membrane lifetime.

We demonstrate an integrated all-fiber mid-infrared (mid-IR) supercontinuum (SC) source generated by a 1.95 μm master oscillator power amplifier system and a single-mode ZBLAN (ZrF 4 -BaF 2 -LaF 3 -AlF 3 -NaF) fiber. The maximum average output power is 10.67 W with spectral bandwidth covering from ∼1.9 to 4.1 μm. The single-mode ZBLAN fiber and silica fiber are thermal-spliced to enhance the robustness and practicability of the system. It is, to the best of our knowledge, the first high-power integrated compacted all-fiber mid-IR SC source based on thermal-spliced silica fiber and ZBLAN fiber. ©

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