Hundred-watt level linearly polarized visible supercontinuum generation.

An all-fiber linearly polarized supercontinuum (SC) laser source with 93 W average output power and spectrum ranging from 520 nm to 2300 nm is experimentally demonstrated. The linearly-polarized SC is generated in a piece of 2.6 m long polarization-maintaining photonic crystal fiber (PM-PCF), pumped by a polarization-maintaining picosecond Yb-doped master oscillator power amplifier (PM-MOPA). The source exhibits a flat spectrum from 600 nm to 1880 nm at -10 dB level except for the residual pump peak. A new method is proposed to measure the polarization extinction ratio (PER) of each single wavelength of the broadband supercontinuum at a high-power level, resulting in larger than 16 dB PER from 900 nm to 1600 nm and larger than 15 dB PER from 540 nm to 650 nm. To our knowledge, this is the first demonstration of hundred-watt level linearly polarized visible SC and the first demonstration of PER measurement of each single wavelength within such a wide spectrum range.

High power LP11 mode supercontinuum generation from an all-fiber MOPA.

High power LP11 mode supercontinuum is generated from 25/250 large mode area (LMA) fiber. A mechanical long period grating (LPG) is utilized to control the transverse modes in the LMA fiber to realize the LP11 mode supercontinuum generation in a master oscillator power amplifier (MOPA) configuration. The generated LP11 mode supercontinuum covers the spectral range from ~900 nm to ~2100 nm with a -30-dB spectral width of ~1200 nm and 50% optical to optical conversion efficiency. The seed laser produces picosecond pulses with 1 MHz repetition rate at the wavelength of 1060 nm. After multi-stage amplification in ytterbium-doped fibers, the average output power is scaled to 54.51 W and 56.79 W respectively for LP11 and LP01 mode, accompanying supercontinuum generation. Obvious difference of supercontinuum generation between the LP01 and LP11 modes is experimentally observed due to the different dispersion characters.

Ultraviolet-enhanced supercontinuum generation with a mode-locked Yb-doped fiber laser operating in dissipative-soliton-resonance region.

We experimentally demonstrate an all-fiber, ultraviolet-enhanced, supercontinuum generation in a specifically designed seven-core photonic crystal fiber pumped by a picosecond Yb-doped master oscillator power amplifier (MOPA). The MOPA source is seeded by a giant-chirped Yb-doped mode-locked fiber laser operating in the dissipative-soliton-resonance (DSR) region. The DSR is achieved by using a nonlinear optical loop mirror (NOLM) with a fundamental repetition rate of 4.5 MHz and a central wavelength of 1035 nm. An extremely wide optical spectrum spanning from 350 nm to 2400 nm is obtained with a total output power of 6.86 W.

State distributions in two-dimensional parameter spaces of a nonlinear optical loop mirror-based, mode-locked, all-normal-dispersion fiber laser.

We present the results of numerical simulations of dissipative soliton generation using nonlinear Schrödinger equations in an all-normal-dispersion (ANDi) mode-locked fiber laser based on a nonlinear optical loop mirror (NOLM). Firstly, systematic and computationally intensive analysis of the pulse state distributions in two-dimensional parameter spaces of an ANDi fiber laser was conducted. In addition, we determined that unstable non-vanishing regions including pulsation and noise-like pulses are directly related to the saturable absorptions of NOLMs and that two critical filter bandwidths separate those regions from stable ones. Finally, we found that the multi-pulsing power threshold can be maximized by using an optimal optical filter bandwidth.

1016nm all fiber picosecond MOPA laser with 50W output.

This paper presents an all fiber high power picosecond laser at 1016 nm in master oscillator power amplifier (MOPA) configuration. A direct amplification of this seed source encounters obvious gain competition with amplified spontaneous emission (ASE) at ~1030 nm, leading to a seriously reduced amplification efficiency. To suppress the ASE and improve the amplification efficiency, we experimentally investigate the influence of the gain fiber length and the residual ASE on the perforemance of the 1016 nm amplifier. The optimized 1016 nm MOPA laser exhibits an average power of 50 W and an optical conversion efficiency of 53%.

Selective transverse mode operation of an all-fiber laser with a mode-selective fiber Bragg grating pair.

We propose a novel approach for achieving selective transverse mode operation of few-mode all-fiber lasers. Lasing in a specific transverse mode is enabled by employing a pair of few-mode fiber Bragg gratings as an efficient transverse mode selector. As a proof-of-principle, we have implemented a ytterbium-doped all-fiber laser operating in the second-order (LP11) transverse mode. The achieved output power is 81 mW, and the slope efficiency is as high as 54%. This simple and compact all-fiber laser is also capable of delivering cylindrical vector beams through appropriate polarization control. Furthermore, the approach has great scalability and can be applied to other working modes and spectral regimes.

80 nJ ultrafast dissipative soliton generation in dumbbell-shaped mode-locked fiber laser.

A novel all-fiberized dumbbell-shaped mode-locked fiber laser was developed to directly generate 80 nJ dissipative solitons, which can be linearly compressed from 85 to 1.2 ps externally with a diffraction grating pair. The pulse peak power reached 42 kW after compression. With the most available pump power, stable dissipative soliton bundles with up to 628 nJ bundle energy were obtained. The corresponding average output power reached 2.2 W. The employment of dual-nonlinear-optical-loop mirrors and large-mode-area fibers in the cavity played an essential role in improving structural compactness and producing high-energy ultrafast pulses. To the best of our knowledge, these are the most energetic compressible dissipative solitons generated from a strictly all-fiber cavity.

Mode-locked all-fiber dumbbell-shaped laser based on a nonlinear amplifying optical loop mirror.

We report a hybrid passively mode-locked dumbbell-shaped fiber laser based on a nonlinear optical loop mirror and a nonlinear amplifying optical fiber-loop mirror. The laser produced noise-like pulses with repetition rate of 8.85 MHz and pulse energy of 16.2 and 26.4 nJ from the two output ports, respectively. Several interesting phenomena are observed and briefly discussed in the paper.

Versatile long cavity widely tunable pulsed Yb-doped fiber laser with up to 27655th harmonic mode locking order.

We report flexible dissipative soliton generation from an all-fiberized all-normal-dispersion (ANDi) long cavity actively mode locked ytterbium doped fiber laser based on improved harmonic mode locking technique. The laser is featured with unusually wide and fine tunabilities in repetition rate and operating wavelength, meanwhile superior stability is maintained. The repetition rate of the laser can be flexibly controlled from 226 kHz to 6.25 GHz (corresponding to the highest 27655th order harmonic mode locking) in the interval of 226 kHz, while supermode suppression is confined above 50 dB and the pulse duration is retained in the range of 38 ps~80 ps. As high as 4.3 nJ pulse energy can be achieved with a low pump power of 160 mW when operating at the fundamental mode locking regime. The operating wavelength of the laser can be tuned in the wide range of 1005 nm~1100 nm. As far as we know, it is the first demonstration of up to ten thousands order stable harmonic mode locking in ANDi fiber laser, which manifests the capability of generating both high energy pulse and ultra-high repetition rate pulse in a single ANDi cavity. The destabilization of dissipative soliton under strong pump is also demonstrated.

All-fiberized synchronously pumped 1120 nm picosecond Raman laser with flexible output dynamics.

A largely simplified and highly efficient all-fiber-based synchronously pumping scheme is proposed. The synchronization between pump light and the cavity round-trip can be achieved by adjusting the repetition rate of pumping light without the requirement of altering the cavity length. Based on this scheme, we achieved generating narrow linewidth highly efficient 1120 nm pulse directly from an all-fiber Raman cavity. By pump repetition rate detuning and pump duration adjustment, the duration of the 1120 nm pulse can be widely tuned from 18 ps to ~1 ns, and the repetition rate can be adjusted from 12.41 MHz to 99.28 MHz by harmonic pumping. Up to 4.3 W high power operation is verified based on this scheme. Owing to the compact all-fiber configuration, the conversion efficiency of the 1066 nm pump light to the 1120 nm Stokes light exceeds 80% and the overall conversion efficiency (976 nm-1066 nm-1120 nm) is as high as 53.7%. The nonlinear output dynamics of the Raman laser are comprehensively explored. Two distinct operation regimes are investigated and characterized.

Ultra-compact Watt-level flat supercontinuum source pumped by noise-like pulse from an all-fiber oscillator.

We demonstrate Watt-level flat visible supercontinuum (SC) generation in photonic crystal fibers, which is directly pumped by broadband noise-like pulses from an Yb-doped all-fiber oscillator. The novel SC generator is featured with elegant all-fiber-integrated architecture, high spectral flatness and high efficiency. Wide optical spectrum spanning from 500 nm to 2300 nm with 1.02 W optical power is obtained under the pump of 1.4 W noise-like pulse. The flatness of the spectrum in the range of 700 nm~1600 nm is less than 5 dB (including the pump residue). The exceptional simplicity, economical efficiency and the comparable performances make the noise-like pulse oscillator a competitive candidate to the widely used cascade amplified coherent pulse as the pump source of broadband SC. To the best of our knowledge, this is the first demonstration of SC generation which is directly pumped by an all-fiber noise-like pulse oscillator.

Flexible rectangular wave-breaking-free pulse generation in actively mode-locked ytterbium-doped fiber laser.

We demonstrate nanosecond scale rectangular wave-breaking-free pulse generation in an actively mode locked Yb-doped fiber laser based on a combined action of active periodic cavity loss modulation and nonlinear polarization rotation effect. The pulse width of the laser can be controlled in the range of 890 ps to above 124 ns instantaneously by adjusting the electrical signal applied on the modulator. As high as 19.8 nJ wave-breaking-free pulse is achieved with maximum available pump power. The output pulse temporal dynamics exhibit various distinct characteristics under different modulation and polarization control. The laser presents unusually flexible tunabilities in pulse width, pulse energy and pulse shape.

BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.

To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.

Exploring the binding of BACE-1 inhibitors using comparative binding energy analysis (COMBINE).

BACKGROUND: The inhibition of the activity of ß-secretase (BACE-1) is a potentially important approach for the treatment of Alzheimer disease. To explore the mechanism of inhibition, we describe the use of 46 X-ray crystallographic BACE-1/inhibitor complexes to derive quantitative structure-activity relationship (QSAR) models. The inhibitors were aligned by superimposing 46 X-ray crystallographic BACE-1/inhibitor complexes, and gCOMBINE software was used to perform COMparative BINding Energy (COMBINE) analysis on these 46 minimized BACE-1/inhibitor complexes. The major advantage of the COMBINE analysis is that it can quantitatively extract key residues involved in binding the ligand and identify the nature of the interactions between the ligand and receptor. RESULTS: By considering the contributions of the protein residues to the electrostatic and van der Waals intermolecular interaction energies, two predictive and robust COMBINE models were developed: (i) the 3-PC distance-dependent dielectric constant model (built from a single X-ray crystal structure) with a q2 value of 0.74 and an SDEC value of 0.521; and (ii) the 5-PC sigmoidal electrostatic model (built from the actual complexes present in the Brookhaven Protein Data Bank) with a q2 value of 0.79 and an SDEC value of 0.41. CONCLUSIONS: These QSAR models and the information describing the inhibition provide useful insights into the design of novel inhibitors via the optimization of the interactions between ligands and those key residues of BACE-1.

Synthesis and antitumor activities of derivatives of the marine mangrove fungal metabolite deoxybostrycin.

Deoxybostrycin (1) is an anthraquinone compound derived from the marine mangrove fungus Nigrospora sp. No. 1403 and has potential to be a lead for new drugs because of its various biological properties. A series of new derivatives (2-22) of deoxybostrycin were synthesized. The in vitro cytotoxicity of all the new compounds was tested against MDA-MB-435, HepG2 and HCT-116 cancer cell lines. Most of the compounds exhibit strong cytotoxicity with IC50 values ranging from 0.62 to 10 µM. Compounds 19, 21 display comparable cytotoxicity against MDA-MB-435 to epirubicin, the positive control. The primary screening results indicate that the deoxybostrycin derivatives might be a valuable source of new potent anticancer drug candidates.

Statistical research on marine natural products based on data obtained between 1985 and 2008.

Since the 1960s, more than 20,000 compounds were discovered from marine organisms. In this paper we performed a quantitative analysis for the novel marine natural products reported between 1985 and 2008. The data was extracted mainly from the reviews of Faulkner and Blunt [1-26]. The organisms producing these marine natural products are divided into three major biological classes: marine microorganisms (including phytoplankton), marine algae and marine invertebrate. The marine natural products are divided into seven classes based on their chemical structure: terpenoids, steroids (including steroidal saponins), alkaloids, ethers (including ketals), phenols (including quinones), strigolactones, and peptides. The distribution and the temporal trend of these classes (biological classes and chemical structure classes) were investigated. We hope this article provides a comprehensive perspective on the research of marine natural products.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates II-The personalized analysis of partial pressure of oxygen and carbon dioxide difference between umbilical artery and vein at same time in same newborn].

Objective: In order to explore the mechanism of neonatal spontaneous breathing, the difference of oxygen and carbon dioxide between umbilical cord arteries and veins before the start of spontaneous breathing after birth has been analyzed among people. In this part, the related information is analyzed individually. Methods: After all fetal parents signed the informed consent before birth, and before the newborn was born and did not breathe, the umbilical cord was exposed as quickly as possible, and the heparinized arterial indwelling needle was inserted into the umbilical artery and umbilical vein in the direction of newborn and placenta, and then blood was taken continuously. Although dozens of mothers were selected,but only 3 cases were collected from Pua and Puv blood samplers at the same time for blood gas analysis and determination, and the differences and dynamic changes of umbilical vein and umbilical artery were calculated and analyzed. Results: In all 3 none spontaneous breathing newborns,PuvO2 was significantly higher than PuaO2 at the same time (P<0.01), with an average difference of (24.17±7.09) mmHg; while PuvCO2 was significantly lower than PuaCO2 (all P<0.01), with an average difference of (-7.67±3.70) mmHg.The difference of Puv-uaO2 was significantly higher than those of Puv-uaCO2 (P<0.05). Conclusion: PuaO2 decreases gradually with time (heartbeat frequency) before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates I-The group difference of partial pressure of oxygen and carbon dioxide between umbilical artery and vein in newborns].

Objective: The fetus has no actual respiration, and the newborn begins to breathe after birth. We assume that the first breath dominantly generated by hypoxia. In this study, the changes and lowest limit of blood oxygen partial pressureof umbilical artery (PuaO2) after chemoreceptor were analyzed to explore the mechanism of neonatal spontaneous breathing. Methods: With signed consent form by all fetal parents before birth, 14 newborns successfully completed the umbilical artery or vein catheterization and drawn blood according to the heartbeat. All blood samples analyzed by blood gas analyzer,calculated and analyzed the similarities and differences between umbilical vein(Puv) and umbilical artery(Pua). Results: Although we completed 14 newborns, there were only 9 cases of umbilical artery samples and 8 cases of umbilical vein samples were collected. Only 3 cases collected both Pua and Puv blood samples at the same time (see serial paper II). PuaO2 in gradually decreased with time (heartbeat frequency), until Pua contracted after spontaneous breathing produced about 8~10 heartbeats, and then could not get enough blood samples. Only 3 newborns were able to take blood samples after spontaneous breathing for 8~10 heartbeats, and their PuaO2 were jumped to 186.0, 137.0 and 93.8 mmHg respectively. The mean value of PuaO2 was (25.94±6.79, 18.04~37.51)mmHg, the highest value was (29.11±6.46, 23.00~45.90)mmHg, and the lowest value was (21.34±5.54, 14.00~33.60)mmHg. Although PuvO2 decreased gradually with time (heartbeat) too, most of them also showed the tendency of alternately rising and falling with the regularity of mother's respiration. The mean value of PuvO2 was (53.35±21.35, 32.56~100.73)mmHg, the highest value was (90.38±48.44, 43.40~153.00)mmHg, and the lowest value was (36.96±14.90, 24.80~73.80)mmHg. Although there were large individual differences, the mean, highest and lowest values of PuvO2 were significantly higher than those of PuaO2 (P<0.05); although PuvCO2 slightly lower than PuaCO2, it was no significant difference (P>0.05). Conclusion: PuaO2 decreases gradually with time before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

Smurf2 participates in human trophoblast cell invasion by inhibiting TGF-beta type I receptor.

Successful embryo implantation depends on the ability of the trophoblast cells to invade the endometrium and the receptivity of the endometrium. Unlike tumor invasion, trophoblast invasion is spatio-temporaly restricted. Transforming growth factor (TGF)-beta is a key inhibitory factor in the invasion of early trophoblast cells. Smad ubiquitination regulatory factor 2 (Smurf2), a HECT type E3 ubiquitin ligase, is an important regulator of the TGF-beta signaling pathway, targeting TGF-beta receptors and various Smads for proteasome-mediated degradation. In this context, we wished to determine whether Smurf2 has a physiological role during embryo implantation, especially in trophoblast invasion. We examined the spatio-temporal expression of Smurf2 in human placental villi and the function of Smurf2 in trophoblast cell migration and invasion in a model system involving a human extravillous trophoblast cell line, HTR-8/SVneo. Results from RT-PCR and immunohistochemical studies showed that expression of Smurf2 in placental villi was the highest during the first trimester and decreased as the pregnancy progressed. Overexpression of Smurf2 in HTR-8/SVneo cells reduced TGF-beta type I receptor levels, and enhanced cell migration and invasion. Conversely, RNA interference-mediated downregulation of Smurf2 resulted in a significant increase in TGF-beta type I receptor protein levels. However, the levels of Smad2, another potential target of Smurf2, remained unchanged. In conclusion, the present study suggests that Smurf2 promotes trophoblast cell migration and invasion, and this function may involve downregulation of TGF-beta type I receptor.

100 W all fiber picosecond MOPA laser.

A high power picosecond laser is constructed in an all fiber master oscillator power amplifier (MOPA) configuration. The seed source is an ytterbium-doped single mode fiber laser passively mode-locked by a semiconductor saturable absorber mirror (SESAM). It produces 20 mW average power with 13 ps pulse width and 59.8 MHz repetition rate. A direct amplification of this seed source encounters obvious nonlinear effects hence serious spectral broadening at only ten watt power level. To avoid these nonlinear effects, we octupled the repetition rate to about 478 MHz though a self-made all fiber device before amplification. The ultimate output laser exhibits an average power of 96 W, a pulse width of 16 ps, a beam quality M2 of less than 1.5, and an optical conversion efficiency of 61.5%.