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We present a new scheme of picosecond optical parametric chirped pulse amplification (OPCPA) in which a Fourier-transform-limit 5.0 ps pulse is optically sheared from a single-longitudinal-mode 1064 nm CW laser. The pulse is amplified and frequency-doubled as the pump in order to maintain the pump narrow bandwidth and picosecond duration simultaneously, which is very important to ensure the high temporal contrast for an OPCPA amplifier. Combined with the cross-polarized wave generation (XPW), a compound frontend for the high-power femtosecond laser system that delivers a 1 Hz chirped pulse train is established. The experiments provide an output pulse energy of 17.1 mJ, a spectrum bandwidth 71 nm (FWHM), and a pulse duration 16.4 fs. The pulse contrast reaches 1:10−12 several picoseconds before the peak of the main pulse, which is the best value of the available measuring instruments.

We report on comprehensive research regarding the potential of phase-conjugate wave (PCW) generation via backward degenerate four-wave mixing process as a pulse cleaner in femtosecond high-power laser systems. We analyzed the performance of this technique by investigating the contrast enhancement capability, gain bandwidth, and energy conversion efficiency. All of these parameters are important in pulse cleaning. The numerical calculations verified that a considerably large efficiency bandwidth product and an excellent contrast enhancement capability can be realized by finding a balance between each physical effect. The simulation results based on this study provide guidance for the application of this technique in laser systems with different bandwidths. The method, which is based on PCW generation, provides new insights for femtosecond petawatt laser systems as pulse cleaners.

Abstract: The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in mantle cell lymphoma (MCL). However, approximately one-third of patients do not respond to the drug initially. To identify the mechanisms underlying primary ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib-sensitive and ibrutinib-resistant cell lines on ibrutinib treatment. We found that MYC gene signature was suppressed by ibrutinib in sensitive but not resistant cell lines. We demonstrated that MYC gene was structurally abnormal and MYC protein was overexpressed in MCL cells. Further, MYC knockdown with RNA interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib-resistant cells. We explored the possibility of inhibiting MYC through HSP90 inhibition. The chaperon protein is overexpressed in both cell lines and primary MCL cells from the patients. We demonstrated that MYC is a bona fide client of HSP90 in the context of MCL by both immunoprecipitation and chemical precipitation. Furthermore, inhibition of HSP90 using PU-H71 induced apoptosis and caused cell cycle arrest. PU-H71 also demonstrates strong and relatively specific inhibition of the MYC transcriptional program compared with other oncogenic pathways. In a MCL patient-derived xenograft model, the HSP90 inhibitor retards tumor growth and prolongs survival. Last, we showed that PU-H71 induced apoptosis and downregulated MYC protein in MCL cells derived from patients who were clinically resistant to ibrutinib. In conclusion, MYC activity underlies intrinsic resistance to ibrutinib in MCL. As a client protein of HSP90, MYC can be inhibited via PU-H71 to overcome primary ibrutinib resistance.

We focused on a single-shot method for directly measuring the temporal contrast enhancement of a single plasma mirror by analyzing the spectrum of a chirped pulse spatiotemporally overlapped with the igniting laser used for generating a plasma mirror. Experimentally, temporal contrast enhancement of 102 by one plasma mirror was successfully measured in a hundred picosecond timescale and was consistent with the theory. This single-shot measurement method caused no degradation on the performance of the plasma mirror, which was proved by monitoring the efficiency and far-field pattern of the igniting laser after the plasma mirror. Combined with calorimeters and CCD cameras, this method is expected to realize the single-shot online diagnosis of plasma mirrors. This method is expected to be an efficient approach for measuring the temporal contrast enhancement of the plasma mirrors.

Abstract: Ibrutinib has generated remarkable responses in patients with chronic lymphocytic leukemia (CLL), including those with an unfavorable cytogenetic profile. However, patients develop resistance, with poor outcomes and no established treatment options. Mutations in BTK and PLCG2 have emerged as main mechanisms of drug resistance, but not all patients carry these mutations. Further understanding of mechanisms of resistance is urgently needed and will support rational development of new therapeutic strategies. To that end, we characterized the genomic profiles of serial samples from 9 patients with ibrutinib-relapsed disease, including 6 who had Richter transformation. Mutations, indels, copy-number aberrations, and loss of heterozygosity were assessed using next-generation sequencing and single-nucleotide polymorphism array. We found that 18p deletion (del(18p)), together with del(17p)/TP53 mutations, was present in 5 of 9 patients before ibrutinib therapy. In addition to BTKC481, we identified BTKT316A, a structurally novel mutation located in the SH2 domain of BTK. Minor BTK clones with low allele frequencies were captured in addition to major BTK clones. Although TP53 loss predisposes patients for relapse, clone size of TP53 loss may diminish during disease progression while mutant BTK clone expands. In patients who had Richter transformation, we found that the transformed cells were clonal descendants of circulating leukemia cells but continued to undergo evolution and drifts. Surprisingly, transformed lymphoma cells in tissue may acquire a different BTK mutation from that in the CLL leukemia cells. Collectively, these results provide insights into clonal evolution underlying ibrutinib relapse and prompt further investigation on genomic abnormalities that have clinical application potential.

As optical parametric chirped pulse amplification has been widely adopted for the generation of extreme intensity laser sources, nonlinear crystals of large aperture are demanded for high-energy amplifiers. Yttrium calcium oxyborate (YCa4O(BO3)3, YCOB) is capable of being grown with apertures exceeding 100 mm, which makes it possible for application in systems of petawatt scale. In this paper, we experimentally demonstrated for the first time to our knowledge, an ultra-broadband non-collinear optical parametric amplifier with YCOB for petawatt-scale compressed pulse generation at 800 nm. Based on the SG-II 5 PWfacility, amplified signal energy of approximately 40 J was achieved and pump-to-signal conversion efficiency was up to 42.3%. A gain bandwidth of 87 nm was realized and supported a compressed pulse duration of 22.3 fs. The near-field and wavefront aberration represented excellent characteristics, which were comparable with those achieved in lithium triborate-based amplifiers. These results verified the great potential for YCOB utilization in the future. [ABSTRACT FROM AUTHOR]

Flexible piezoresistive sensors with viscoelastic conductive freestanding films have attracted tremendous interest for the great practical applications of human motion and health monitoring, and intelligent electronic skins. However, it is still a challenge to achieve stable and strong adhesion between the viscoelastic conductive films and two electrodes due to mismatched Young's modulus. Herein, the as-prepared Ni nanowires were mixed with PDMS to form viscoelastic conductive composites, which were strongly contacted on and partly permeated into Ni foam electrodes for flexible strain sensors. Importantly, the binding between the viscoelastic conductive composites and Ni foams is strong and stable, which can be remained after a thousand forward and backward bent. The fabricated flexible piezoresistive sensors were utilized to monitor human motion including clicking mouse, finger bending, elbow bending, eye blinking and wrist bending. The typical respond and recovery times are fast to about 0.1 s. Thus, this sensor will have great potential for future real applications in smart wearable devices. [ABSTRACT FROM AUTHOR]

A model is presented to analyze the effect of chromatic aberration of the spatial filter lenses on the compressed pulse duration. The parameters of the SHENGUANG (SG) II 5 PW laser system are demonstrated as examples. The numerical simulation results show that the compressed pulse duration with full aperture is increased by 3 times compared with the ideal compressed pulse duration in the case of chromatic aberration of the lenses. The result of full-aperture measurement at the SG II 5 PW laser system is in good agreement with the theoretical calculation. In the case of full-aperture measurement, the shortest compressed pulse duration is obtained by adjusting the compressor to compensate for the phase aberration introduced by the chromatic aberration of the spatial filter lenses at the SG II 5 PW laser facility. These results are helpful in finding an optimized pulse duration, considering the chromatic aberration of lenses in the femtosecond laser facility, and in obtaining a deep understanding of the effect of chromatic aberration of lenses on the pulse contrast ratio and pulse duration in ultrashort laser systems. [ABSTRACT FROM AUTHOR]