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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 PW facility, 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.

Laser wakefield acceleration (LWFA) using PW-class laser pulses generally requires cm-scale laser–plasma interaction Rayleigh length, which can be realized by focusing such pulses inside a long underdense plasma with a large f-number focusing optic. Here, we present a new PW-based LWFA instrument at the SG-II 5 PW laser facility, which employs f/23 focusing. The setup also adapted an online probing of the plasma density via Nomarski interferometry using a probe laser beam having 30 fs pulse duration. By focusing 1-PW, 30-fs laser pulses down to a focal spot of 230 µm, the peak laser intensity reached a mild-relativistic level of 2.6 × 1018 W/cm2, a level modest for standard LWFA experiments. Despite the large aspect ratio of >25:1 (transverse to longitudinal dimensions) of the laser pulse, electron beams were observed in our experiment only when the laser pulse experienced relativistic self-focusing at high gas-pressure thresholds, corresponding to plasma densities higher than 3 × 1018 cm−3.

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.

We propose a simple single-shot spatiotemporal measurement technique called coherent modulation imaging for the spatio-spectrum (CMISS), which reconstructs the full three-dimensional high-resolution characteristics of ultrashort pulses based on frequency-space division and coherent modulation imaging. We demonstrated it experimentally by measuring the spatiotemporal amplitude and phase of a single pulse with a spatial resolution of 44 µm and a phase accuracy of 0.04 rad. CMISS has good potential for high-power ultrashort-pulse laser facilities and can measure even spatiotemporally complicated pulses with important applications.

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.

We proposed a technique of tunable plasma narrow-band filter (PNBF) to generate high-power narrow-band pulses based on a plasma mirror and pulse chirp. PNBFs have an ultra-wide free spectral range, high damage threshold, and accurate wavelength-tunable function, and tunable sub-nanometer pulses could be achieved by controlling the pulse chirp. The feasibility of the proposed technique was verified by both simulation and experiment. Three ~0.6 nm bandwidth pulses centered at different wavelengths were obtained respectively, maintaining good near and far-field beam quality. PNBF is expected to be an effective technique for high-power tunable narrow-band pulse generation with high-power ultrafast lasers.

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.

// Ailin Guo 1,* , Pin Lu 1,* , Greg Coffey 2 , Pamela Conley 2 , Anjali Pandey 2 and Y. Lynn Wang 1 1 Department of Pathology, Lymphoma Translational Pathology, University of Chicago, Chicago, IL, USA 2 Portola Pharmaceuticals, Inc., South San Francisco, CA, USA * These authors have contributed equally to this study Correspondence to: Y. Lynn Wang, email: // Keywords : CLL, cerdulatinib, SYK, JAK-STAT, molecularly targeted therapy Received : December 21, 2016 Accepted : January 01, 2017 Published : January 10, 2017 Abstract Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases. We demonstrated that cerdulatinib delivered potent tumor inhibition in 60 primary CLL patient samples, especially in those with poor prognostic indicators. Importantly, cerdulatinib, but not ibrutinib, is able to overcome the support of microenvironment and induces CLL cell death at clinically achievable concentrations. Notably, cerdulatinib blocked proliferation of ibrutinib-resistant primary CLL cells and of BTK C481S -transfected/ibrutinib-resistant lymphoma cells. These anti-tumor effects are well correlated with the inhibition of BCR and JAK-STAT signaling and downstream inhibition of the functions of AKT, ERK and NFκB. Collectively, our results show that simultaneous targeting of BCR and JAK-STAT pathways is a more effective strategy relative to single BTK inhibition.

Plasma mirror is an effective approach to improve the temporal contrast of high power ultra-short laser system, while it might deteriorate the focal spot, which is reported in some experiments using plasma mirror. In order to investigate such far-field degradation by plasma mirror, we established a spatiotemporal multi-step focusing propagation algorithm based on the formula of plasma expansion and wave-front modulation model. The influence of plasma expansion time, amplitude and spatial frequency of wave-front error on focal spot degradation are quantitatively analyzed. The simulation results reveal that the far-field focal spot degradation by plasma mirror is caused by the non-uniform plasma expansion due to the wave-front error and the wave-front error with higher amplitude and lower spatial frequency has relatively greater effect on the focusing ability. From the perspective of high-contrast ultra-intense output capability, the requirement on the spatiotemporal quality of the pulse is put forward to avoid the far-field focal spot degradation when using plasma mirror in high power ultra-short laser system.

Rapid intracellular degradation of current drug-delivery nanocarriers presents a challenge for achieving ideal controlled drug-release kinetics. Recent in vivo studies have shown that porous hybrid metal-organic frameworks (MOFs), belonging to the Materials of Institute Lavoisier (MIL) family, display prolonged biodegradation behavior. In this study, we investigated stability of these materials in Kupffer cells, a relevant target for the treatment of several life-threatening immune-mediated liver diseases. For this aim, we selected fluorescently labeled microporous MOF particles of MIL88A and MIL88B-NH2, built from trimers of Fe(III) octahedra, as an inorganic component, and fumarate (MIL88A) or 2-amino terephthalate (MIL88B-NH2), as an organic linker. Cell uptake inhibition analysis of MOF particles by a Kupffer cell line (KUP5) has shown that phagocytosis is the major endocytic pathway involved in MIL88B-NH2 internalization. Investigation of MOF interaction with KUP5 cells by real-time microscopy indicated that the structure of MIL88B-NH2 MOFs stays intact up to 15 min after uptake, followed by MOF accumulation in acidic cell compartments and slow degradation, reaching a minimum of 10-15% decomposition over 24 h. MIL88A particles demonstrated similar degradation kinetics. Analysis of the mechanisms of MOF degradation has shown that inhibition of phagosome acidification as well as protease activity does not prevent decomposition of MIL88B-NH2 particles. Thus, our study demonstrates the relative stability of the MOF structure in the phagolysosomal environment of Kupffer cells, revealing potential use of these materials for controlled drug delivery in a case of immune-mediated liver diseases.

Intramacrophagic bacteria pose a great challenge for the treatment of infectious diseases despite many macrophage targeted drug delivery approaches explored. The use of biomimetic approaches for treating infectious diseases is promising, but not studied extensively. The study purpose is to evaluate iron-based metal-organic frameworks (MOF) as a potential bacteria-mimicking delivery system for infectious diseases. Two types of carboxylated MOFs, MIL-88A(Fe) and MIL-100(Fe) were developed as “pathogen-like” particles by surface coating with mannose. MOF morphology, cellular uptake kinetics, and endocytic mechanisms in 3D4/21 alveolar macrophages were characterized. MIL-88A(Fe) is rod-shape (aspect ratio 1:5) with a long-axis size of 3628 ± 573 nm and MIL-100(Fe) is spherical with diameter of 103.9 ± 7.2 nm. Cellular uptake kinetics of MOFs showed that MIL-100(Fe) nanoparticles were internalized at a faster rate and higher extent compared to MIL-88A(Fe) microparticles. Mannosylation did not improve the uptake of MIL-100(Fe) particles, whereas it highly increased MIL-88A(Fe) cellular uptake and number of cells involved in internalization. Cell uptake inhibition studies indicated that macropinocytosis/phagocytosis was the main endocytic pathway for internalization of MOFs. Accumulation of MOF particles in acidic compartments was clearly observed. The successfully synthesized “pathogen-like” particles provide a novel application of MOF-based particles as biomimetic delivery system for intramacrophagic-based infections.

The temporal contrast of ultrashort and ultraintense laser pulses can significantly influence the laser–plasma interactions. As the optical parametric chirped pulse amplification (OPCPA) has been widely adopted in these laser facilities, the inherent optical parametric fluorescence, exhibiting a pedestal in the time window of the pump pulse, has become a significant problem. In this paper, we investigated experimentally its influence on the contrast of the compressed pulses at 808 nm using a multistage OPCPA amplifier. Compared to the highest value of 1 0 8 ever reported in the literature for such a type of regime, by adjusting the pump energy allocation between OPCPA stages and controlling the gain of small signal regime, we for the first time, to the best of our knowledge, realized a 1 0 11 temporal contrast in a pure nanosecond OPCPA design at a gain exceeding 7 × 1 0 8 , without adopting any other noise cleaning methods, such as picosecond OPCPA, cross-polarized wave generation, etc. This indicates that the OPCPA has a very significant potential for contrast improvement and to become a candidate for the future high-energy amplifiers in ultrashort high-power laser facilities.

// Shruti Sharma 1, * , Natalie Galanina 2, * , Ailin Guo 1, * , Jimmy Lee 1 , Sabah Kadri 1, 3 , Charles Van Slambrouck 1 , Bradley Long 1 , Weige Wang 1 , Mei Ming 1 , Larissa V. Furtado 1 , Jeremy P. Segal 1 , Wendy Stock 2 , Girish Venkataraman 1 , Wei-Jen Tang 4 , Pin Lu 1 , Yue Lynn Wang 1 1 Department of Pathology, University of Chicago, Chicago, IL 60637, USA 2 Department of Medicine, University of Chicago, Chicago, IL 60637, USA 3 Center for Research Informatics, University of Chicago, Chicago, IL 60637, USA 4 Ben-May Department for Cancer Research, University of Chicago, Chicago, IL 60637, USA * These authors have contributed equally to this work Correspondence to: Yue Lynn Wang, email: ylwang@bsd.uchicago.edu Keywords: chronic lymphocytic leukemia, Richter transformation, ibrutinib resistance, BTK , molecular targeted therapy Received: June 04, 2016 Accepted: August 15, 2016 Published: September 10, 2016 ABSTRACT Ibrutinib (ibr), a first-in-class Bruton tyrosine kinase (BTK) inhibitor, has demonstrated high response rates in both relapsed/refractory and treatment naive chronic lymphocytic leukemia (CLL). However, about 25% of patients discontinue ibrutinib therapy at a median follow-up of 20 months and many patients discontinue the treatment due to leukemia progression or Richter transformation. Mutations affecting the C481 residue of BTK disrupt ibrutinib binding and have been characterized by us and others as the most common mechanism of ibrutinib resistance. Thus far, all described BTK mutations are located in its kinase domain and mutations outside this domain have never been described. Herein, we report a patient whose CLL progressed, was salvaged with ibrutinib and then relapsed. Serial analysis of samples throughout patient’s clinical course identified a structurally novel mutation ( BTK T316A ) in the SH2 domain, but not kinase domain, of Bruton tyrosine kinase which was associated with disease relapse. Functionally, cells carrying BTK T316A show resistance to ibrutinib at both cellular and molecular levels to a similar extent as BTK C481S . Our study lends further insight into the diverse mechanisms of ibrutinib resistance that has important implications for the development of next-generation BTK inhibitors as well as mutation detection in relapsed patients.

Optimizing and measuring the femtosecond pulse duration of compression are very difficult in the case of online and vacuum in a multi-petawatt laser facility. Therefore, a method is presented in this study to determine the optimum point of pulse duration by simulation calculation and experimental measurements. Using the method in the multi-petawatt laser facility, the residual dispersion is completely eliminated, and a near Fourier-transform-limited pulse duration can be attained. These results are beneficial in finding an optimized pulse duration and guarantying the repeatability of the laser physical experiment results in multi-petawatt femtosecond laser facility.

In this work, a novel electrochemical dopamine sensor was fabricated based on a composite film solely consisting of kappa-carrageenan and hierarchical porous carbon that was synthesized from alkali lignin directly. Following drop-casting onto a glassy carbon electrode and drying overnight, the film was characterized with scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, and electrochemical tests. 5 ratios by mass of hierarchical porous activated carbon: kappa-carrageenan were studied for optimizing dopamine quantification. Utilizing differential pulse voltammetry for detection, the optimized system elicited a linear range of 1 - 600 μmol L-1 and an limit of detection (LOD) of 0.4 μmol L-1(signal to noise, S/N=3) The proposed system is easy to prepare and requires no synthetic binding agents. All materials and methods utilized were cost-efficient and readily available for commercial use. Due to the simple design of the sensor, it offers great potential for further modification and optimization. Figure 1

We present a high efficiency and ultra-broadband optical parametric chirped-pulse amplification (OPCPA) system fully based on yttrium calcium oxyborate (YCOB) crystals. The OPCPA properties of YCOB at 808 nm are studied for both high gain and saturated amplification. The non-collinear angle is finely tuned to study the variation of gain spectrum at a certain phase-matching angle of YCOB crystals. After amplification by four YCOB crystals, a total signal gain of 0.9×109 is obtained and the FWHM spectral bandwidth is still over 100 nm. An amplified signal pulse of 182 mJ is achieved with pump energy of 440 mJ in the saturated amplification stage and the conversion efficiency is about 40%. After a four-grating compressor, a pulse duration of 20 fs is measured by a second-order autocorrelator.

Pulse time delay (PTD) and defocus are mainly introduced by transmitted-based large-aperture beam expander systems in ultrashort high power laser systems due to chromatic aberration, which can significantly reduce the focal-spot intensity by spatially enlarge the spot size as well as temporally distort the pulse profile. In this paper we investigate the chromatic aberration and measure how it deteriorate the focal spot size in SG-II 5PW ultrashort laser system. In addition, we propose and design a simple chromatic aberration pre-compensation scheme based on combination of aspherical lens and spherical mirrors. The simulation results indicate that both PTD and defocus dispersion can nearly be fully compensated by applying this compensation scheme with proper alignment in the system without introducing other kinds of wave-front aberrations.

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.

To meet the requirements of single shot femtosecond laser pulse diagnostic, some methods have been taken. Through carefully design and experiment, a single shot autocorrelator suit for the SGII 5PW laser facility is achieved.

Temporal contrast is one of the crucial physical determinants which guarantee the successful performance of laser–matter interaction experiments. We generally reviewed the influences on the temporal contrast in three categories of noises based on the requirement by the physical mechanisms. The spatiotemporal influences on temporal contrast at the focal region of the chromatic aberration and propagation time difference introduced by large-aperture broadband spatial filters, which were spatiotemporally coupled with compression and focusing, were calculated and discussed with a practical case in SG-II 5 PW ultrashort petawatt laser. The system-wide spatiotemporal coupling existing in large-aperture broadband ultrashort petawatt lasers was proved to be one of the possible causes of temporal contrast degradation in the focal region.

By optimization, the first two OPCPA amplifiers of SGII 5PW laser have reached the conversion efficiency of 42.8% and 41.9% respectively. These are the highest values among the ever reported OPCPA laser systems.

We present a recent progress of the SG-II 5PW facility, which designed a multi-petawatt ultrashort pulse laser based on optical parametric chirped-pulse amplification (OPCPA). The prior two optical parametric amplifiers have been accomplished and chirped pulses with an energy of 49.7 J and a full-width-at-half-maximum (FWHM) spectrum bandwidth of 85 nm have been achieved. In the PW-scale optical parametric amplification (OPA), with the pump pulse that has an energy of 118 J from the second harmonic generation of the SG-II 7th beam, the pump-to-signal conversion efficiency is up to 41.9%, which to the best of our knowledge is the highest among all of the reported values for OPCPA systems. The compressed pulse is higher than 37 J in 21 fs (1.76 PW), and the focal spot is ${\sim}10~\unicode[STIX]{x03BC}\text{m}$ after the closed-loop corrections by the adaptive optics. Limited by the repetition of the pump laser, the SG-II 5PW facility operates one shot per hour. It has successfully been employed for high energy physics experiments.

we especially improved the numerical algorithm of adaptive optics to further correct the low spatial frequency wavefront of 1ω, at 1.053μm, in this paper. The far field of the third harmonic of 3ω has been significantly enhanced from the 27 times to the 12 times diffraction limit for the SG-II Super Beamlet.

B-cell receptor (BCR) and JAK/STAT pathways play critical roles in diffuse large B-cell lymphoma (DLBCL). Herein, we investigated the anti-lymphoma activity of cerdulatinib, a novel compound that dually targets SYK and JAK/STAT pathways. On a tissue microarray of 62 primary DLBCL tumors, 58% expressed either phosphorylated SYK or STAT3 or both. SYK and STAT3 are also phosphorylated in a panel of eleven DLBCL cell lines although ABC and GCB subtypes exhibited different JAK/STAT and BCR signaling profiles. In both ABC and GCB cell lines, cerdulatinib induced apoptosis that was associated with caspase-3 and PARP cleavage. The compound also blocked G1/S transition and caused cell cycle arrest, accompanied by inhibition of RB phosphorylation and down-regulation of cyclin E. Phosphorylation of BCR components and STAT3 was sensitive to cerdulatinib in both ABC and GCB cell lines under stimulated conditions. Importantly, JAK/STAT and BCR signaling can be blocked by cerdulatinib in primary GCB and non-GCB DLBCL tumor cells that were accompanied by cell death. Our work provides mechanistic insights into the actions of cerdulatinib, suggesting that the drug has a broad anti-tumor activity in both ABC and GCB DLBCL, at least in part by inhibiting SYK and JAK pathways.

The SG II 5PW laser is designed as an open ultra-short high power laser facility that operates at the wavelength of 808nm. Three optical parametric chirped pulse amplification (OPCPA) stages are used to ensure the uncompressed pulse energy up to 260J. With a four pass zigzag compressor, the pulse width is compressed into less than 30fs and the pulse energy about 150J. By using BBO and LBO crystal, the first two OPCPA amplifiers have been accomplished this year. 35J@21fs outputs have been achieved. Since the largest size of the LBO crystal now is only about 100mm×100mm that is not enough for the needs of the third OPCPA amplifier. In our work, potassium deuterium phosphate (DKDP) as a candidate crystal has been studied theoretically and experimentally. Phase-matching parameters for various deuterium doped rate DKDP crystals are calculated. OPCPA amplifier based on 95% deuterium doped rate is designed and the output characteristics are simulated by OPA coupled wave equations. The results show that DKDP crystals with deuterium doped rate higher than 90% can be utilized in ultra-short high power laser systems that support the pulse width shorter than 30 femtoseconds. Still by estimation, when Quasi-phase-matching techniques and collinear design are used in small signal OPCPA amplification, the greatest efficiency can reach above 55%. By experiment it has proved that the output spectrum width can be more than 80nm.

A compact and multifunctional wave diagnostic system based on coherent modulation imaging with single shot diffraction pattern has been developed and the feasibility has been demonstrated on SG-II laser facility with experiments.

The Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has produced remarkable clinical response in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma. We previously reported the identification of BTK(C481S) mutation in a CLL patient who progressed following 21-month ibrutinib therapy. Initial characterization at structural and biochemical levels revealed that the mutation disrupts the covalent binding of ibrutinib to BTK, reduces its binding affinity and diminishes its ability to inhibit the BTK enzymatic activity. Herein, we further characterized the functional consequences of BTK(C481S) in terms of molecular signaling, gene expression and cellular behavior in the patient, as well as in lymphoma cells transfected with either the wild-type or the mutant BTK constructs. Further, using an in vitro CLL proliferation model, alternative kinase inhibitors that have the potential to overcome ibrutinib resistance were explored.

To ensure safe and effective amplification for the chirped pulse amplification laser facility, many factors such as pulse spectral width, pulse duration, grating parameters and incidence angle parameter are considered carefully in the design of the pulse stretcher. A compact four pass Offner stretcher design is given out. Experiment results show that the stretcher has broad spectral width, large stretching ratio and high transmission efficiency. By comparison, the calculated result of the dispersion effect on the pulse duration is completely consistent with the experiment result.

A novel chromatic aberration pre-compensation scheme for ultrashort petawatt laser systems was proposed. The pre-compensation scheme consists of a convex lens, group of concave lenses, and a spherical reflector combined with a conventional vacuum chamber. It provides a versatile method to accurately compensate the chromatic aberration of an entire laser system via controlling the amount of propagation time delay (PTD) induced by the compensator without changing the input and output beam size. A compensator, tailored based on the proposed scheme, was designed and experimentally evaluated for the Shen-Guang-II 5PW (SG-II 5PW) laser system at Shanghai Institute of Optics and Fine Mechanics (SIOM). The experimental results verified that chromatic aberration in the laser system was almost fully compensated: the size of laser beam focused by an f/2.42 off-axis parabolic mirror (OAP) was reduced tremendously from 32×18μm2to about 4×4μm2at full width at half maximum (FWHM). The proposed scheme provides the flexibility to accurately correct chromatic aberration in high-power laser systems within a wide dynamic range.

Shenguang-II 5PW laser is designed to deliver a 150J 30fs laser pulse into the target chamber. In beginning of 2016, 1PW (30J/27fs) outputs have been achieved and are used for physical experiments.

Matrix metallopeptidase 10 (MMP10) is frequently expressed and correlates closely with metastasis and poor prognosis in various human cancers. However, the significance of MMP10 expression in esophageal squamous cell carcinoma (ESCC) and its role in ESCC progression remains unclear. In this report, upregulation of MMP10 mRNA was detected in 39/60 (65.0%) of primary ESCC tissues compared with their paired nontumor esophageal tissues. Tissue microarray (TMA) study found protein overexpression of MMP10 in 188/239 (78.7%) of primary ESCC tissues but not in their corresponding nontumor esophageal tissues, suggesting that overexpression of MMP10 may play important roles in ESCC development and progression. Although the overexpression of MMP10 was not significantly associated with disease-specific survival rate (P= 0.182) for all tested ESCCs, it was significantly associated with poorer disease-specific survival (P= 0.001) in early stage of ESCCs (I-IIA). In addition, multivariate analysis found that MMP10 expression in tumor tissues was evaluated as a potential independent prognostic factor for early stage ESCC patients. These findings suggest that MMP10 plays an important role in ESCC progression in the early stage, and overexpression of MMP10 in tumor tissues could be used as a potential prognostic marker for patients with early clinical stage of ESCC.