Broadband frequency-tripling pulses with high energy are attractive for scientific research, such as inertial confinement fusion, but are difficult to scale up. Third-harmonic generation via nonlinear frequency conversion, however, remains a trade-off between bandwidth and conversion efficiency. Based on gradient deuterium deuterated potassium dihydrogen phosphate (KDxH2-xPO4, DKDP) crystal, here we report the generation of frequency-tripling pulses by rapid adiabatic passage with a low-coherence laser driver facility. The efficiency dependence on the phase-matching angle in a Type-II configuration is studied. We attained an output at 352 nm with a bandwidth of 4.4 THz and an efficiency of 36%. These results, to the best of our knowledge, represent the first experimental demonstration of gradient deuterium DKDP crystal in obtaining frequency-tripling pulses. Our research paves a new way for developing high-efficiency, large-bandwidth frequency-tripling technology.

The delay-shift of the pre-pulse may mislead the determination of its origination and cause problems for the temporal contrast improvement of high-peak-power lasers, especially when the corresponding post-pulse is beyond the time window of the measurement device. In this work, an empirical formula is proposed to predict the delay-shift of pre-pulses for the first time. The empirical formula shows that the delay-shift is proportional to the square of the post-pulse’s initial delay, and also the ratio of the third-order dispersion to the group delay dispersion’s square, which intuitively reveals the main cause for the delay-shift and may provide a convenient routing for identifying the real sources of pre-pulses in both chirped-pulse amplification (CPA) and optical parametric chirped-pulse amplification (OPCPA) systems. The empirical formula agrees well with the experimental results both in the CPA and the OPCPA systems. Besides, a numerical simulation is also carried out to further verify the empirical formula.

To meet the demands of laser-ion acceleration at a high repetition rate, we have developed a comprehensive diagnostic system for real-time and in situ monitoring of liquid sheet targets (LSTs). The spatially resolved rapid characterizations of an LST’s thickness, flatness, tilt angle and position are fulfilled by different subsystems with high accuracy. With the help of the diagnostic system, we reveal the dependence of thickness distribution on collision parameters and report the 238-nm liquid sheet generated by the collision of two liquid jets. Control methods for the flatness and tilt angle of LSTs have also been provided, which are essential for applications of laser-driven ion acceleration and others.

OBJECTIVES/GOALS: The aims of this study were to: 1) determine the involvement of each Fc gamma receptor isoform in antibody-mediated crosslinking and internalization of LILRB4 in acute monocytic leukemia and 2) elucidate the role of this crosslinking and internalization in antibody-mediated immune regulation of these malignant cells. METHODS/STUDY POPULATION: To determine the involvement of Fc gamma receptors in antibody-mediated complex internalization, we generated acute monocytic leukemia cell lines with CRISPR-Cas9 knockout of each Fc gamma receptor isoform. We tested the effects of each knockout on anti-LILRB4 antibody-mediated internalization by flow cytometry and confirmed our findings with confocal microscopy. To elucidate the role of this crosslinking and internalization in immune regulation of acute monocytic leukemia, we conducted preliminary ELISA-based studies of the inflammatory signaling and cytokine release profiles of wild-type and Fc gamma receptor knockout cells treated with the LILRB4-targeting antibody. RESULTS/ANTICIPATED RESULTS: We have concluded that Fc gamma receptor I (CD64) plays a role in LILRB4 crosslinking and internalization by our anti-LILRB4 antibody and there are also contributions from Fc gamma receptor IIA (CD32A) observed in the absence of CD64 on the cell surface. Preliminary signaling studies have demonstrated that Fc gamma receptor-mediated antibody crosslinking and internalization of LILRB4 decreases anti-inflammatory signaling downstream of LILRB4 as well as pro-inflammatory signaling downstream of Fc gamma receptors, particularly in the absence of CD64 on the cell surface. The immunomodulatory effect of antibody-mediated LILRB4 crosslinking and internalization is being confirmed in follow-up signaling, cytokine release and lymphocyte activation studies. DISCUSSION/SIGNIFICANCE: This study will improve the efficacy of LILRB4-targeting antibody therapeutics for patients suffering from acute monocytic leukemia and help characterize CD64 and CD32A as potential clinical biomarkers for patients undergoing LILRB4-targeting antibody immunotherapeutic treatment, currently in first-in-human clinical trials.

The mitochondrial genome provides important information for phylogenetic analysis and an understanding of evolutionary origin. In this study, the mitochondrial genomes of Ilisha elongata and Setipinna tenuifilis were sequenced, which are typical circular vertebrate mitochondrial genomes composed of 16,770 and 16,805 bp, respectively. The mitogenomes of I. elongata and S. tenuifilis include 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), two ribosomal RNA (rRNA) genes and one control region (CR). Both two species' genome compositions were highly A + T biased and exhibited positive AT-skews and negative GC-skews. The genetic distance and Ka/Ks ratio analyses indicated that 13 PCGs were affected by purifying selection and the selection pressures were different from certain deep-sea fishes, which were most likely due to the difference in their living environment. Results of phylogenetic analysis support close relationships among Chirocentridae, Denticipitidae, Clupeidae, Engraulidae and Pristigasteridae based on the nucleotide and amino acid sequences of 13 PCGs. Within Clupeoidei, I. elongata and S. tenuifilis were most closely related to the family Pristigasteridae and Engraulidae, respectively. These results will help to better understand the evolutionary position of Clupeiformes and provide a reference for further phylogenetic research on Clupeiformes species.

O’Grady’s generalised Franchetta conjecture (GFC) is concerned with codimension 2 algebraic cycles on universal polarised K3 surfaces. In [4], this conjecture has been studied in the Betti cohomology groups. Following a suggestion of Voisin, we investigate this problem in the Deligne-Beilinson (DB) cohomology groups. In this paper, we develop the theory of Deligne-Beilinson cohomology groups on (smooth) Deligne-Mumford stacks. Using the automorphic cohomology group and Noether-Lefschetz theory, we compute the 4th DB-cohomology group of universal oriented polarised K3 surfaces with at worst an $A_1$ -singularity and show that GFC for such family holds in DB-cohomology. In particular, this confirms O’Grady’s original conjecture in DB cohomology.

Narrowband microwave generation with tuneable frequency is demonstrated by illuminating a photoconductive semiconductor switch (PCSS) with a burst-mode fibre laser. The whole system is composed of a high-power linearly polarized burst-mode pulsed fibre laser and a linear-state PCSS. To obtain a high-performance microwave signal, a desired envelope of burst is necessary and a pulse pre-compensation technique is adopted to avoid envelope distortion induced by the gain-saturation effect. Resulting from the technique, homogenous peak power distribution in each burst is ensured. The maximum energy of the laser burst pulse reaches 200 μJ with a burst duration of 100 ns at the average power of 10 W, corresponding to a peak power of 4 kW. When the PCSS is illuminated by the burst-mode fibre laser, narrowband microwave generation with tuneable frequency (0.80–1.12 GHz) is obtained with a power up to 300 W. To the best of the authors’ knowledge, it is the first demonstration of frequency-tuneable narrowband microwave generation based on a fibre laser. The high-power burst-mode fibre laser reported here has great potential for generating high-power arbitrary microwave signals for a great deal of applicable demands such as smart adaptive radar and intelligent high-power microwave systems.

Gust/turbulence–leading edge interaction is a significant source of airfoil broadband noise. An approach often used to predict the sound is based on Amiet’s flat-plate solution. Analytical studies have been conducted to investigate the influences of airfoil geometries, non-uniform mean flows and turbulence statistics, which, however, were often too convoluted. In this work, the problem is revisited by proposing simple corrections to the standard flat-plate solution to account for the effect of non-uniform mean flows of real airfoils. A key step in the method is to use a new space–time transformation that is analogous to the Prandtl–Glauert transformation to simplify the sound governing equation with spatially varying coefficients to a classical wave equation, which is then solved using the Schwarzschild technique as in Amiet’s solution. The impacts of Mach number, wavenumber and airfoil geometry on the prediction accuracy are investigated for both single-frequency and broadband cases, and the results are compared against high-fidelity simulations. It predicts the sound reduction by the airfoil thickness, and reveals that the reduction is caused by the non-uniform streamwise velocity. The limitations of the model are discussed and the approximation errors are estimated. In general, the prediction error increases with the airfoil thickness, the sound frequency and the flow Mach number. Nevertheless, in all cases studied in this work, the proposed correction can effectively improve the prediction accuracy of the flat-plate solution much more efficiently compared to numerical solutions of the Euler equations using computational aeroacoustics.

The Qiangtang Metamorphic Belt (QMB) was considered to have either formed in situ by amalgmation of the North and South Qiangtang blocks or been underthrust from the Jinsha suture and exhumed in the interior of a single ‘Qiangtang Block’. A new Sphaeroschwagerina fusuline fauna discovered in the Raggyorcaka Lake area supports the interpretation that the North and South Qiangtang blocks were separated by a wide ocean during Asselian (Early Permian) time, indicating that the QMB was formed by the suturing of the Palaeotethys Ocean along the Longmu Co-Shuanghu suture.

The mitochondrial genome is maternally inherited in animals, despite the fact that paternal mitochondria enter oocytes during fertilization. Autophagy and ubiquitin-mediated degradation are responsible for the elimination of paternal mitochondria in Caenorhabditis elegans; however, the involvement of these two processes in the degradation of paternal mitochondria in mammals is not well understood. We investigated the localization patterns of light chain 3 (LC3) and ubiquitin in mouse and porcine embryos during preimplantation development. We found that LC3 and ubiquitin localized to the spermatozoon midpiece at 3 h post-fertilization, and that both proteins were colocalized with paternal mitochondria and removed upon fertilization during the 4-cell stage in mouse and the zygote stage in porcine embryos. Sporadic paternal mitochondria were present beyond the morula stage in the mouse, and paternal mitochondria were restricted to one blastomere of 4-cell embryos. An autophagy inhibitor, 3-methyladenine (3-MA), did not affect the distribution of paternal mitochondria compared with the positive control, while an autophagy inducer, rapamycin, accelerated the removal of paternal mitochondria compared with the control. After the intracytoplasmic injection of intact spermatozoon into mouse oocytes, LC3 and ubiquitin localized to the spermatozoon midpiece, but remnants of undegraded paternal mitochondria were retained until the blastocyst stage. Our results show that paternal mitochondria colocalize with autophagy receptors and ubiquitin and are removed after in vitro fertilization, but some remnants of sperm mitochondrial sheath may persist up to morula stage after intracytoplasmic spermatozoon injection (ICSI).

The aim of the present study was to evaluate the effects of lutein and lycopene supplementation on carotid artery intima–media thickness (CAIMT) in subjects with subclinical atherosclerosis. A total of 144 subjects aged 45–68 years were recruited from local communities. All the subjects were randomly assigned to receive 20 mg lutein/d (n 48), 20 mg lutein/d+20 mg lycopene/d (n 48) or placebo (n 48) for 12 months. CAIMT was measured using Doppler ultrasonography at baseline and after 12 months, and serum lutein and lycopene concentrations were determined using HPLC. Serum lutein concentrations increased significantly from 0·34 to 1·96 μmol/l in the lutein group (P< 0·001) and from 0·35 to 1·66 μmol/l in the combination group (P< 0·001). Similarly, serum lycopene concentrations increased significantly from 0·18 to 0·71 μmol/l in the combination group at month 12 (P< 0·001), whereas no significant change was observed in the placebo group. The mean values of CAIMT decreased significantly by 0·035 mm (P= 0·042) and 0·073 mm (P< 0·001) in the lutein and combination groups at month 12, respectively. The change in CAIMT was inversely associated with the increase in serum lutein concentrations (P< 0·05) in both the active treatment groups and with that in serum lycopene concentrations (β = − 0·342, P= 0·031) in the combination group. Lutein and lycopene supplementation significantly increased the serum concentrations of lutein and lycopene with a decrease in CAIMT being associated with both concentrations. In addition, the combination of lutein and lycopene supplementation was more effective than lutein alone for protection against the development of CAIMT in Chinese subjects with subclinical atherosclerosis, and further studies are needed to confirm whether synergistic effects of lutein and lycopene exist.

Red-emitting phosphor of Ca0.8Zn0.2TiO3:0.2 mol% Pr3+ was synthesized by the hydrothermal method with urea as a mineralizer. The crystalline structure, micromorphology, and luminescent properties of the resultant phosphor were investigated. Results show that elevated calcination temperature does not change the shape of particles that are hollow spheres with a shell thickness of 210–480 nm, and smaller particles are in the middle of the larger ones. The emission intensity at 612 nm originated from 1D2 → 3H4 transition of Pr3+ ions increases with the elevated calcination temperature due to a higher crystallinity. Excitation curves consist of two strong broad bands centered at about 330 and 380 nm and a weaker broad band range from 450 to 500 nm. The sample prepared by the hydrothermal method has better luminescent properties than that of its counterpart prepared by the solid-state method, especially the improvement of near-UV region (380 nm) excitation intensity.