Pivotal role of the carbohydrate recognition domain in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory function in murine conventional dendritic cells in vitro.

C-type lectin receptors (CLRs), pattern recognition receptors (PRRs) with a characteristic carbohydrate recognition domain (CRD) in the extracellular portion, mediate crucial cellular functions upon recognition of glycosylated pathogens and self-glycoproteins. CLEC4A is the only classical CLR that possesses an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM), which possibly transduces negative signals. However, how CLEC4A exerts cellular inhibition remains unclear. Here, we report that the self-interaction of CLEC4A through the CRD is required for the ITIM-mediated suppressive function in conventional dendritic cells (cDCs). Human type 2 cDCs (cDC2) and monocytes display a higher expression of CLEC4A than cDC1 and plasmacytoid DCs (pDCs) as well as B cells. The extracellular portion of CLEC4A specifically binds to a murine cDC cell line expressing CLEC4A, while its extracellular portion lacking the N-glycosylation site or the EPS motif within the CRD reduces their association. Furthermore, the deletion of the EPS motif within the CRD or ITIM in CLEC4A almost completely impairs its suppressive effect on the activation of the murine cDC cell line, whereas the absence of the N-glycosylation site within the CRD exhibits partial inhibition on their activation. On the other hand, antagonistic monoclonal antibody (mAb) to CLEC4A, which inhibits the self-interaction of CLEC4A and its downstream signaling in murine transfectants, enhances the activation of monocytes and monocyte-derived immature DCs upon stimulation with a Toll-like receptor (TLR) ligand. Thus, our findings suggest a pivotal role of the CRD in self-interaction of CLEC4A to elicit the ITIM-mediated inhibitory signal for the control of the function of cDCs.

Fast pulse train control using filled-aperture coherent beam combining for high-average-power laser systems.

This study demonstrates fast pulse train switching using a coherent polarization beam combiner with a phase difference detection (PDD) algorithm. Based on the highly stable feedback control obtained with the PDD algorithm, stable burst-mode extraction with an arbitrary duty cycle was achieved with a contrast ratio of 800:1 for a third-harmonic light (347 nm) of a 5 MHz pulsed Yb-doped fiber laser. The proposed method can be effectively used for high-speed switching in high-average-power pulsed laser systems.

Critical role of plasmacytoid dendritic cells in induction of oral tolerance.

BACKGROUND: Exposure to dietary constituents through the mucosal surface of the gastrointestinal tract generates oral tolerance that prevents deleterious T cell-mediated immunity. Although oral tolerance is an active process that involves emergence of CD4+ forkhead box p3 (Foxp3)+ regulatory T (Treg) cells in gut-associated lymphoid tissues (GALTs) for suppression of effector T (Teff) cells, how antigen-presenting cells initiate this process remains unclear. OBJECTIVE: We sought to determine the role of plasmacytoid dendritic cells (pDCs), which are known as unconventional antigen-presenting cells, in establishment of oral tolerance. METHODS: GALT-associated pDCs in wild-type mice were examined for their ability to induce differentiation of CD4+ Teff cells and CD4+Foxp3+ Treg cells in vitro. Wild-type and pDC-ablated mice were fed oral antigen to compare their intestinal generation of CD4+Foxp3+ Treg cells and induction of oral tolerance to protect against Teff cell-mediated allergic inflammation. RESULTS: GALT-associated pDCs preferentially generate CD4+Foxp3+ Treg cells rather than CD4+ Teff cells, and such generation requires an autocrine loop of TGF-ß for its robust production. A deficiency of pDCs abrogates antigen-specific de novo generation of CD4+Foxp3+ Treg cells occurring in GALT after antigenic feeding. Furthermore, the absence of pDCs impairs development of oral tolerance, which ameliorates the progression of delayed-type hypersensitivity and systemic anaphylaxis, as well as allergic asthma, accompanied by an enhanced antigen-specific CD4+ Teff cell response and antibody production. CONCLUSION: pDCs are required for establishing oral tolerance to prevent undesirable allergic responses, and they might serve a key role in maintaining gastrointestinal immune homeostasis.

Simulating ultra-intense femtosecond lasers in the 3-dimensional space-time domain.

Femtosecond petawatt (fs-PW) lasers, with femtosecond pulses and sub-meter-sized beams, could be easily distorted by spatiotemporal coupling (STC). In 2016, a femtosecond terawatt pulsed beam was experimentally reconstructed in the 3-dimensional (3D) space-time domain for the first time, and showing STC induced distortions. Referring to recently developed laser techniques, traditional first-order STCs can be controlled and then removed. However, the complex STC induced by wavefront errors in a meter-sized grating compressor, where the spatial and spectral coordinates of beams and pulses are coupled, would introduce a non-negligible and complicated distortion. Herein, we theoretically simulated this complex STC in the 3D space-time/spectrum domain and presented its evolution with various factors, which opens a new perspective to analyze CPA lasers in the 3D domain.

Stable ultra-broadband gain spectrum with wide-angle non-collinear optical parametric amplification.

Comparing with the non-collinear optical parametric amplification (NOPA), the gain bandwidth could be significantly enhanced by the wide-angle NOPA (WNOPA), i.e., with a divergent signal (WNOPA-S) or pump (WNOPA-P). In a uniaxial crystal, the spectral symmetry/asymmetry of WNOPA is introduced. In WNOPA-S, the ultra-broadband gain spectrum can be obtained in two phase-matching directions at both sides of the pump, however, the output is heavily angularly dispersed. In WNOPA-P, although the gain bandwidth enhancement is only achieved in one phase-matching direction, i.e., on the opposite side of the crystal axis, it is free of angular dispersion. The stabilities of the gain spectrum in NOPA and in WNOPA-P are experimentally compared and theoretically analyzed. Compared with NOPA, WNOPA-P supports an even broader and more stable gain spectrum, and compared with WNOPA-S, WNOPA-P is angular-dispersion-free. The conversation efficiency of WNOPA-P is the same as NOPA. We suppose WNOPA-P is ideally suitable for the amplification of stable ultra-broadband few-cycle pulse lasers.

Single-shot real-time detection technique for pulse-front tilt and curvature of femtosecond pulsed beams with multiple-slit spatiotemporal interferometry.

Spatiotemporal coupling (STC) of femtosecond pulsed beams could significantly reduce the focal-spot intensity of ultra-intense lasers. We theoretically present a very simple method for single-shot real-time detecting pulse-front tilt, curvature, or tilt and curvature (PFT, PFC or PFT&PFC) by using multiple-slit spatiotemporal interferometry (MSTI). An unknown input pulsed beam is spatially cut by a high-density multiple-slit and changed into a series of spatially separated sub-pulses. By only measuring the spatial distribution of the interference pattern in the far-field, PFT, PFC, or PFT&PFC can be detected. Comparing with recent methods, no reference pulses or beams, no temporal or spatial scanning, and no temporal or spectral measurement is required. The single-shot and spatial-only measurement will greatly simplify the real-time detection of PFT and PFC.

PCSEL pumped coupling optics free Yb:YAG/Cr:YAG microchip laser.

The passively Q-switched operation of a cryogenically cooled Yb:YAG/Cr:YAG microchip laser was demonstrated with end pumping by a photonic crystal surface emitting laser (PCSEL). This laser generated 70 µJ/1.7 ns/3.2 kHz pulses with near diffraction limited beam quality (M2=1.1) at 1029.4 nm. There were no coupling optics between the microchip laser crystal and PCSEL, which made the system simple and compact.

Scattering pulse-induced temporal contrast degradation in chirped-pulse amplification lasers.

Herein, a theory for modeling the problem of scattering pulse-induced temporal contrast degradation in chirped-pulse amplification (CPA) lasers is introduced. Using this model, the temporal evolutions of the scattering and signal pulses were simulated, the temporal contrasts for different cases were compared, and finally the theoretical prediction was verified by an experimental demonstration. The result shows that the picosecond and the nanosecond temporal contrast is mainly determined by the scattering pulses generated in the stretcher and the compressor, respectively. In addition, the B-integral accumulation will further degrade the temporal contrast, especially the picosecond temporal contrast. We believe it is helpful for solving the problem of the picosecond pedestal contrast (i.e., noise limit). With reference to these results, some suggestions for the temporal contrast improvement are presented.

Spatial asymmetry of optical parametric fluorescence with a divergent pump beam and potential applications.

The spatial distribution of the optical parametric fluorescence generated in a negative uniaxial nonlinear crystal is asymmetric with respect to the pump when the pump beam has a slight divergence angle. The formation mechanism of this phenomenon and the influence of parameters were analyzed and discussed from a theoretical standpoint. Moreover, two potential applications of this phenomenon were experimentally demonstrated, showing the temporal contrast improvement of ultra-intense lasers and the intensity enhancement of special light sources induced by the optical parametric generation.

600 W green and 300 W UV light generated from an eight-beam, sub-nanosecond fiber laser system.

We describe a sub-nanosecond pulse laser system that delivers high-average-power green and ultraviolet (UV) light. This system includes a front end, two modules each of which has four photonic crystal fiber main amplifiers, two sets of coherent beam combiners with efficiencies of 83 and 90%, and two sets of harmonic converters. A single beam was ultimately produced through polarization-beam combining. The maximum average output power was 955 W at the fundamental wavelength (1040 nm) with a 10 MHz repetition rate and 285 ps pulse duration. The M-square of the UV was 1.3. The average power of each of its harmonics is 600 W in green (520 nm) and 300 W in UV (347 nm). The nonlinear crystals were longitudinally cooled by Peltier devices for efficient harmonic conversion.

Direction-dependent waist-shift-difference of Gaussian beam in a multiple-pass zigzag slab amplifier and geometrical optics compensation method.

Zigzag and non-zigzag beam waist shifts in a multiple-pass zigzag slab amplifier are investigated based on the propagation of a Gaussian beam. Different incident angles in the zigzag and non-zigzag planes would introduce a direction-dependent waist-shift-difference, which distorts the beam quality in both the near- and far-fields. The theoretical model and analytical expressions of this phenomenon are presented, and intensity distributions in the two orthogonal planes are simulated and compared. A geometrical optics compensation method by a beam with 90° rotation is proposed, which not only could correct the direction-dependent waist-shift-difference but also possibly average the traditional thermally induced wavefront-distortion-difference between the horizontal and vertical beam directions.

High-average-power green laser using Nd:YAG amplifier with stimulated Brillouin scattering phase-conjugate pulse-cleaning mirror.

We present a high-average-power green laser based on second harmonic conversion of a laser diode-pumped master oscillator Nd:YAG power amplifier system. The power amplifier chain includes a stimulated Brillouin scattering (SBS) cell that was used a phase-conjugate mirror to double-pass scheme. That suppresses the thermal phase distortion and compresses the pulse duration. The fundamental beam output power was 670 W with a pulse width of 7.9 ns. A second harmonic power of 335 W with a 4.8-ns pulse width and 80-mJ pulse energy was produced using a LiB3O5 (LBO) crystal.

Demonstration of a photonic crystal surface-emitting laser pumped Yb:YAG laser.

We developed a cryogenically cooled Yb:YAG continuous wave oscillator directly pumped with a photonic crystal surface-emitting laser (PCSEL). A high slope efficiency of 65.7% was obtained at an output power of 208 mW. The beam quality was close to the diffraction limit, with M2<1.2 in both directions. To the best of our knowledge, this is the first PCSEL pumped solid state laser to be developed.

Amplification characteristics of a cryogenic Yb³âº:YAG total-reflection active-mirror laser.

We have studied the amplification characteristics of a cryogenically cooled Yb³âº:YAG total-reflection active-mirror (TRAM) ceramic laser including wavefront distortion, birefringence loss, small signal gain (SSG), and temperature rise for developing high-performance master oscillator power amplifier (MOPA) systems. A 0.6 mm thick Yb³âº:YAG ceramic sample was used, and maximum pump intensity ~10 kW/cm² was reached. The transmitted wavefront was measured by using a Shack-Hartmann wavefront sensor, and we evaluated the thermal lens focal length and Strehl ratio for different pump conditions. We have also observed a butterfly-like leakage profile of thermally induced birefringence loss at the maximum pump intensity. From SSG measurements, we obtained moderate laser gain of G=3 for one bounce with a near aberration-free wavefront. Gain calculations, which included also temperature dependence of the emission cross section and reabsorption of Yb³âº:YAG, were in good agreement with the experiments. These experimental results will be useful as benchmark data for numerical simulations of temperature distribution in TRAM and for designing multikilowatt-class high-performance MOPA systems.

ASE and parasitic lasing in thin disk laser with anti-ASE cap.

The amplified spontaneous emission (ASE) and parasitic lasing (PL) effects in thin disk laser with an anti-ASE cap have been investigated in detail by measuring both time-resolved radiated intensity at longer axis of elliptical pump profile (dominant ASE direction) and small signal gain (SSG) in laser amplifier. A cryogenically-cooled total-reflection active-mirror laser consisting of 9.8 at.% doped, 0.6-mm thick Yb:YAG and un-doped YAG trapezoidal ceramics cap was used as a sample. The phased transitions from spontaneous emission (SE) to ASE and from ASE to PL have been unambiguously observed. For several pump beam diameters, the ASE gain parameter g(0)l(ASE) at ASE threshold was about 3, and the SSG coefficient was down to about 65% until PL started. To the best of our knowledge, this is the first quantitative characterization of the ASE/PL effects in the thin disk laser with an anti-ASE cap.

High efficiency 12.5 J second-harmonic generation from CsLiB6O10 nonlinear crystal by diode-pumped Nd:glass laser.

A 12.5 J second-harmonic generation with 71.5% conversion efficiency at 0.6 Hz repetition rate from a diode-pumped Nd:glass laser system has been demonstrated by using a CsLiB(6)O(10) (CLBO) nonlinear optical crystal as a frequency doubler. The CLBO has aperture of 40 mm x 40 mm and thickness of 14 mm with Type-II phase matching. The CLBO is mounted into a housing which flows dry nitrogen gas on the CLBO's face. There is no significant reduction of conversion efficiency by exposing of over 600,000 shots for intermissive experiment during 3 years. In our knowledge, these experimental results of output energy and conversion efficiency are highest performance as second-harmonic generation of a diode-pumped solid state laser by using one CLBO nonlinear crystal. In this paper, potential of the CLBO as a frequency converter for repetitive kJ class laser is discussed.

Interferometric phase shift compensation technique for high-power, tiled-aperture coherent beam combination.

We propose a simple coherent beam combining technique for applications in high-power multichannel laser amplifier systems with tiled aperture design. Using a photodiode pair coupled with piezo-actuator mirrors, we demonstrated robust beam combining bandwidth (~1 KHz) and root mean-square deviation (~λ/25) for two beam channels. We estimate that the performance of this technique can be further enhanced in terms of operational bandwidth and phase locking accuracy. It is not limited by single beam power or channel number restrictions, does not require optical phase retrieval algorithms, or calibrations, and can be integrated into various master oscillator power amplifier architectures.

Output characteristics of high power cryogenic Yb:YAG TRAM laser oscillator.

We analyzed the output power characteristics of a cryogenically cooled Yb:YAG total-reflection active-mirror (TRAM) laser oscillator including the temperature dependence of the emission cross section and the reabsorption loss of the Yb:YAG TRAM. A CW multi-transverse mode oscillation of a 9.8 at.% doped 0.6 mm thick Yb:YAG ceramic TRAM was investigated for various pump spot sizes and compared with theoretical results. The Yb:YAG temperatures were inferred from the ratio between fluorescence intensities at 1022 nm and 1027 nm which varied significantly with temperature below 200 K. Output power calculations using evaluated temperatures were in good agreement with the experimental data measured between 77 and 200 K, and the output power suppression due to the temperature rise observed above ~140 K. To the best of our knowledge, this is the first evaluation of output power for a cryogenically cooled Yb:YAG TRAM laser.

Generation of sub-7-cycle optical pulses from a mode-locked ytterbium-doped single-mode fiber oscillator pumped by polarization-combined 915 nm laser diodes.

We report on a passively mode-locked ytterbium-doped fiber oscillator pumped by polarization-combined diodes emitting at a wavelength of 915 nm instead of 976 nm. Stable mode-locked operation based on nonlinear polarization evolution generated a broad spectrum of 140 nm, spanning from 950 to 1090 nm. The output power was 16.3 mW at a repetition rate of 93.1 MHz. External compression using a pair of transmission gratings resulted in pulse durations as short as 21.6 fs, which is equivalent to 6.6 cycle optical pulses at a wavelength of around 1000 nm.