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Inflammation is inseparable part of different diseases especially cancer and autoimmunity. During inflammation process toll like receptor 4(TLR4) responds to lipopolysaccharide (LPS), one of the bacterial components, and TLR4 signaling leads to interleukine-1 receptor associated kinase-1 (IRAK1) and tumor necrosis factor (TNF) receptor associated factor6 (TRAF6) activation which ultimately results in nuclear factor- ĸB (NF-ĸB) activation as the main transcription factor of inflammatory cytokines. Conversely, NF-ĸB over activation induces miR-146a in innate immune cells which can consequently reduce TRAF6, IRAK1, and NF-ĸB activation in a negative feedback. G2013 is a novel designed non-steroidal anti-inflammatory drug (NSAID) which was recently shown to be effective in experimental autoimmune encephalomyelitis (EAE) mouse model. The aim of this study was to evaluate G2013 effects on inflammatory (IRAK1 and TRAF6) and anti-inflammatory (miR-146a) factors of TLR4 signaling pathway. For this purpose, cytotoxicity of G2013 has been evaluated by MTT assay. Expression level of miR-146a in PBMCs and IRAK1 along with TRAF6 in HEK-293 TLR4 cells have been determined using real time PCR. Our results showed that IC50 of G2013 was 25µg/ml, thus 5 and 25 µg/ml concentrations used for further treatments as low dose and high dose concentrations. Our results showed that IRAK1 expression reduced between 5 to 8 fold after treatment by G2013 in a dose dependent manner (p<0.001). In parallel TRAF6 expression declined between 3 to 10 fold dose dependently (p<0.05). However, miR-146a expression was not affected after treatment with low dose and high dose of G2013. In conclusion our data showed that G2013 can regulate TLR4 signaling pathway during inflammation by reducing downstream signaling molecules, IRAK1 and TRAF6 without altering miR-146a expression.
Asunto(s)
Ácidos Hexurónicos/farmacología , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , MicroARNs/metabolismo , Transducción de Señal/efectos de los fármacos , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/metabolismo , Ácidos Urónicos/farmacología , Proliferación Celular/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/genética , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , MicroARNs/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor 6 Asociado a Receptor de TNF/genética , Factores de Tiempo , Receptor Toll-Like 4/genéticaRESUMEN
Femtosecond laser-based generation of radio frequency signals has produced astonishing improvements in achievable spectral purity, one of the basic features characterizing the performance of an radio frequency oscillator. Kerr frequency combs hold promise for transforming these lab-scale oscillators to chip-scale level. In this work we demonstrate a miniature 10 GHz radio frequency photonic oscillator characterized with phase noise better than -60 dBc Hz(-1) at 10 Hz, -90 dBc Hz(-1) at 100 Hz and -170 dBc Hz(-1) at 10 MHz. The frequency stability of this device, as represented by Allan deviation measurements, is at the level of 10(-10) at 1-100 s integration time-orders of magnitude better than existing radio frequency photonic devices of similar size, weight and power consumption.
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Advanced applications in optical metrology demand improved lasers with high spectral purity, in form factors that are small and insensitive to environmental perturbations. While laboratory-scale lasers with extraordinarily high stability and low noise have been reported, all-integrated chip-scale devices with sub-100 Hz linewidth have not been previously demonstrated. Lasers integrated with optical microresonators as external cavities have the potential for substantial reduction of noise. However, stability and spectral purity improvements of these lasers have only been validated with rack-mounted support equipment, assembled with fibre lasers to marginally improve their noise performance. In this work we report on a realization of a heterogeneously integrated, chip-scale semiconductor laser featuring 30-Hz integral linewidth as well as sub-Hz instantaneous linewidth.
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We describe generation of stable mode-locked pulse trains from on-chip normal dispersion microresonators. The excitation of hyperparametric oscillation is facilitated by the local dispersion disruptions induced by mode interactions. The system is then driven from hyperparametric oscillation to the mode-locked state with over 200 nm spectral width by controlled pump power and detuning. With the continuous-wave-driven nonlinearity, the pulses sit on a pedestal, akin to a cavity soliton. We identify the importance of pump detuning and wavelength-dependent quality factors in stabilizing and shaping the pulse structure, to achieve a single pulse inside the cavity. We examine the mode-locking dynamics by numerically solving the master equation and provide analytic solutions under appropriate approximations.
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We demonstrate a nearly spherical diamond whispering gallery mode resonator with quality factor (Q factor) Q=2.4×10(7) limited by material loss approaching α=4×10(-3) cm(-1). The Q factor does not depend on the wavelength: it is approximately the same at 1319 and 1550 nm. Resonators with this range of Q (<10 MHz at 1550 nm wavelength) are attractive for laser locking and stabilization. Applications such as stable compact optical comb generators as well as Raman optical frequency shifters will be feasible with further improvement of the material.
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We study stability and spectral purity of a microresonator-based Kerr frequency comb oscillator experimentally and observe a correlation between the frequency of the continuous wave laser pumping the nonlinear resonator and the repetition frequency of the comb. This correlation is used in a proof-of-principle demonstration of a Kerr frequency comb stabilized with an optical transition of 87Rb.
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We theoretically and experimentally investigate the chaotic regime of optical frequency combs generated in nonlinear ring microresonators pumped with continuous wave light. We show that the chaotic regime reveals itself by a flat top symmetric envelope of the frequency spectrum, when observed by means of an optical spectrum analyzer. The comb, demodulated on a fast photodiode, produces a noisy radio frequency signal with spectral width significantly exceeding the linear bandwidth of the microresonator mode. We discuss practical ways of excitation of a coherent frequency comb and avoiding the chaotic regime.
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We theoretically investigate mode-locked regimes of optical-frequency combs generated in a nonlinear ring microresonator pumped with continuous-wave light. We find that breather solitons can be formed in the resonator for certain values of frequency and power of the pump. We argue that relatively slow modulation of the comb-frequency harmonics observed in several recent experiments can be attributed to soliton formation.
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We show that scattering-based interaction among nearly degenerate optical modes is the key factor in low threshold generation of Kerr frequency combs in nonlinear optical resonators with small group velocity dispersion (GVD). Mode interaction is capable of producing drastic changes in the local GVD, resulting in either a significant reduction, or an increase, in the oscillation threshold. Furthermore, we show that mode interaction is also responsible for majority of observed optical frequency combs in resonators characterized with large normal GVD. We present results of our numerical simulations together with supporting experimental data.
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Simulación por Computador , Modelos Teóricos , Dispositivos Ópticos , Transductores , Diseño Asistido por Computadora , Diseño de Equipo , Dinámicas no LinealesRESUMEN
We show via numerical simulation that Kerr frequency combs can be generated in a nonlinear resonator characterized with normal group-velocity dispersion. We find the spectral shape of the comb and temporal envelope of the corresponding optical pulses formed in the resonator.
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An optical technique based on stability transfer among modes of a monolithic optical microresonator is proposed for long term frequency stabilization of a radio frequency (RF) oscillator. We show that locking the frequency difference of two microresonator modes with dissimilar sensitivity to an applied forcing function to a master RF oscillator improves the long term stability of a slave RF oscillator locked to the frequency difference of another pair of modes with nearly identical sensitivity to the same forcing function. For instance, the stability of a 10 MHz master oscillator with Allan deviation of 10(-7) at 10(3) s can be improved and transferred to a slave oscillator with identical free running stability performance, so that the resultant Allan deviation of the slave oscillator becomes equal to 10(-13) at 10(3) s. The suggested method does not require absolute frequency references.
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We report on realization of an efficient triply resonant coupling between two long lived optical modes and a high frequency surface acoustic wave (SAW) mode of the same monolithic crystalline whispering gallery mode resonator. The coupling results in an opto-mechanical oscillation and generation of a monochromatic SAW. A strong nonlinear interaction of this mechanical mode with other equidistant SAW modes leads to mechanical hyperparametric oscillation and generation of a SAW pulse train and associated frequency comb in the resonator. We visualized the comb by observing the modulation of the light escaping the resonator.
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We analyze a mode-locked regime in Kerr frequency combs generated in nonlinear microresonators. Using damped driven nonlinear Schrödinger equations we show that the combs can produce subpicosecond optical pulses when the resonators are characterized with a small enough anomalous group velocity dispersion. We provide an analytical solution of the problem for the case of small damping.
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We report on generation of a 20 nm wide, 35 GHz repetition rate optical frequency comb in a magnesium fluoride whispering gallery mode resonator pumped with 2 mW of 1543 nm light. The high efficiency of comb generation is associated with the small anomalous group velocity dispersion of the resonator. Growth dynamics of the comb is studied and compared with earlier theoretical predictions.
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We demonstrate a miniature self-injection locked distributed-feedback laser using resonant optical feedback from a high-Q crystalline whispering-gallery-mode resonator. The linewidth reduction factor is greater than 10,000, with resultant instantaneous linewidth of less than 200 Hz. The minimal value of the Allan deviation for the laser-frequency stability is 3 x 10(-12) at the integration time of 20 micros. The laser possesses excellent spectral purity and good long-term stability.
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Rayos Láser , Semiconductores , Electrodos , LuzRESUMEN
We demonstrate a second-order bandpass filter using a single gradient index lens (GRIN) coated with mirrors. The filter becomes possible because of the residual and externally introduced small birefringence of the GRIN lens material. We show that the filter function can be trimmed by mechanical strain of the lens. Applications of the filter in microwave photonics are discussed.
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We report the development and demonstration of an X-band voltage-controlled photonic oscillator based on a whispering gallery mode resonator made of an electro-optic crystalline material. The oscillator has good spectral purity and wide, agile, linear tunability. We have modified the existing theoretical model of the opto-electronic oscillator to describe the performance of our tunable oscillator and have found a good agreement between the theoretical predictions and the measurement results. We show that the device is promising for higher-frequency applications where high-performance tunable oscillators with wide tunability do not exist.
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We report on the observation of a mode-locked laser generated with a crystalline whispering gallery mode resonator pumped with a continuous wave laser. Optical pumping of the resonator generates an optical frequency comb with phase locked components at the Raman offset of the resonator host material. Phase locking of the modes is confirmed via measurement of the radio-frequency beat note produced by the comb on a fast photodiode. Neither the conventional Kerr comb nor hyperparametric oscillation is observed when the comb is present. We present a theoretical explanation of the effect.
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We show that a linear chain of circular macroscopic resonators coupled in parallel demonstrates the phenomena of "superabsorption" and superradiance. Both the frequency spectrum of the transmitted light through the resonator chain and the decay rate of the resonator chain being prepared in a proper initial state are proportional to the number of resonators in the chain, N, and the intensity of the emitted radiation grows as N(2). The spectral bandwidth, the growth of the decay rate, and the intensity are restricted by the dispersion of the waveguides connecting the resonators.
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We report on the development of a new class of widely tunable resonant single-sideband electro-optical modulators based on interaction of different mode families of a crystalline whispering gallery mode resonator with an externally applied rf field. The tunability comes from the different response of mode families to either the temperature change or the voltage applied to the resonator.