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In recent years, deep learning has made a breakthrough in the field of speech recognition, and pushes forward the wide application of speech recognition technology in people's daily lives. Further optimization of the speech recognition model needs to be supported by a larger scale calibrated data. However, the scale of the current open source audio data set is still too small, and corpus is mostly written language of news-based long texts. This paper, by talking about the popular speech recognition applications like human-computer interaction and intelligent customer service, builds and opens the largest ever Chinese Mandarin speech corpus DTZH1505 through crowdsourcing. Data set records natural speech of 6 408 speakers from 8 major Chinese dialect regions and 33 provinces, up to 1 505 hours and on various scenes like social networking, human-computer interaction, intelligent customer service and on-board commands. It can be widely used in the researches of corpus linguistics, conversation analysis, speech recognition, as well as speaker recognition. This paper implements a series benchmark speech recognition experiments, and the results show that: compared to the same scale Chinese speech corpus aishell2, the speech recognition model based on this data set has better performance. [ABSTRACT FROM AUTHOR]

Background: To study the clinical manifestations and advantages of open-heart surgery and echocardiographic transthoracic or percutaneous closure with secundum atrial septal defect (ASD). The surgeon's learning curve was also analyzed.Methods: In all, 115 consecutive patients with ASD from May 2013 to May 2019 were enrolled. According to the operative procedure, patients were divided into three groups: group one (open repair group) (n = 24), where patients underwent ASD repair (ASDR) under cardiopulmonary bypass (CPB); group two (closed surgical device closure group) (n = 69), where patients (six patients ≤1 y and sixteen ≤10 kg) underwent transthoracic ASD occlusion under transesophageal echocardiographic (TEE) guidance; and group three (transcatheter occlusion group) (n = 22), where patients underwent percutaneous ASD occlusion under echocardiography. The clinical features and results of each group were analyzed. All patients were telephonically followed-up after 3 months.Results: All the three methods treating ASD were successfully performed in our hospital. It was also a typical developing history of congenital heart disease (CHD) surgery in China. One patient in the group two was transferred to emergency surgery for occluder retrieval and CPB-ASDR. Eight patients experienced failed transthoracic or percutaneous occlusion, two of whom underwent unsuccessful percutaneous closure at another hospital. Two patients each in the groups two and three were intraoperatively converted to CPB-ASDR. Two patient in the group three was converted to transthoracic occlusion surgery. All patients were discharged without any residual shunt. The three-month follow-up also did not show any residual shunt and occluder displacement.Conclusion: In low-weight, infants, or huge ASDs with suitable rim for device occlusion, transthoracic ASD closure was successfully performed. Based on knowledge of ASD anatomy and skilled transthoracic occlusion of ASD, surgeons can perform percutaneous occlusion of ASD under echocardiographic guidance. [ABSTRACT FROM AUTHOR]

A new series of nonlinear optical crystals LaxY1−xCa4O(BO3)3 (LaxY1−xCOB) with multiple components were grown by using the traditional Czochralski pulling method. X-ray powder diffraction and single-crystal X-ray diffraction experimental results proved that all these crystals formed in the LaxY1−xCOB solid solution state with a monoclinic structure of space group Cm. The optical birefringence was found to be adjustable by changing the compositional parameter x for the LaxY1−xCOB crystals. Taking advantage of the optical parametric oscillator laser, the non-critical phase-matching (NCPM) second-harmonic-generation (SHG) and third-harmonic-generation (THG) wavelengths along the Y-axis were determined at ambient temperature. In addition, the relationships between and among the optical birefringence, NCPM wavelength and crystal structure were discussed, and the NCPM SHG and THG of the 1064 nm laser were further achieved from the La0.120Y0.880COB and La0.140Y0.860COB crystals by adjusting the temperature, respectively. Using a 1064 nm Nd:YAG laser as the fundamental light source, the angular acceptance, temperature acceptance, and optical conversion efficiencies were determined and found to be on the order of 107.6 mrad, 18.3 °C and 48.8% for SHG of the La0.120Y0.880COB crystal, respectively, and 126.8 mrad, 68.6 mrad, 10.6 °C and 32.4% for THG of the La0.140Y0.860COB crystal, respectively. It is demonstrated that LaxY1−xCOB is a promising NLO crystal for NCPM frequency conversion applications in the visible and ultraviolet spectral regions. [ABSTRACT FROM AUTHOR]

In the field of nonlinear optics, cascaded frequency conversion is an effective method to obtain a solid-state laser source in the short wavelength region. By far, the most famous and popular frequency conversion approach is cascaded third-harmonic-generation (THG), which is composed of two steps: a phase-matching (PM) second-harmonic-generation, followed by a PM sum-frequency-generation. Correspondingly, two nonlinear optical (NLO) crystals are required. Theoretically, THG could be realized by utilizing only one crystal, as long as the frequency conversion processes occur at similar PM orientations and the polarization matching problem is solved. In this paper, we realized this approach by using one GdxY1-xCOB crystal; an ultrawide angular acceptance was observed because the SHG process was noncritical phase matching, thereby providing the advantages of large angular acceptance and freedom from beam walk-off as the optimum PM approach in the NLO domain. Compared to the traditional cascaded THG configuration that requires two crystals, this configuration possesses the advantages of small volume, compactness, and low cost, all of which are favorable for practical applications. [ABSTRACT FROM PUBLISHER]

A new series of nonlinear optical crystals LaxY1−xCa4O(BO3)3 (LaxY1−xCOB) with multiple components were grown by using the traditional Czochralski pulling method. X-ray powder diffraction and single-crystal X-ray diffraction experimental results proved that all these crystals formed in the LaxY1−xCOB solid solution state with a monoclinic structure of space group Cm. The optical birefringence was found to be adjustable by changing the compositional parameter x for the LaxY1−xCOB crystals. Taking advantage of the optical parametric oscillator laser, the non-critical phase-matching (NCPM) second-harmonic-generation (SHG) and third-harmonic-generation (THG) wavelengths along the Y-axis were determined at ambient temperature. In addition, the relationships between and among the optical birefringence, NCPM wavelength and crystal structure were discussed, and the NCPM SHG and THG of the 1064 nm laser were further achieved from the La0.120Y0.880COB and La0.140Y0.860COB crystals by adjusting the temperature, respectively. Using a 1064 nm Nd:YAG laser as the fundamental light source, the angular acceptance, temperature acceptance, and optical conversion efficiencies were determined and found to be on the order of 107.6 mrad, 18.3 °C and 48.8% for SHG of the La0.120Y0.880COB crystal, respectively, and 126.8 mrad, 68.6 mrad, 10.6 °C and 32.4% for THG of the La0.140Y0.860COB crystal, respectively. It is demonstrated that LaxY1−xCOB is a promising NLO crystal for NCPM frequency conversion applications in the visible and ultraviolet spectral regions. [ABSTRACT FROM AUTHOR]

Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in acute myeloid leukemia (AML) and other cancers. We report the development of new allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants. Treatment of IDH1 mutant primary AML cells uniformly led to a decrease in intracellular 2-HG, abrogation of the myeloid differentiation block and induction of granulocytic differentiation at the level of leukemic blasts and more immature stem-like cells, in vitro and in vivo. Molecularly, treatment with the inhibitors led to a reversal of the DNA cytosine hypermethylation patterns caused by mutant IDH1 in the cells of individuals with AML. Our study provides proof of concept for the molecular and biological activity of novel allosteric inhibitors for targeting different mutant forms of IDH1 in leukemia. [ABSTRACT FROM AUTHOR]

The protein Keap1 is central to the regulation of the Nrf2-mediated cytoprotective response, and is increasingly recognized as an important target for therapeutic intervention in a range of diseases involving excessive oxidative stress and inflammation. The BTB domain of Keap1 plays key roles in sensing environmental electrophiles and in mediating interactions with the Cul3/Rbx1 E3 ubiquitin ligase system, and is believed to be the target for several small molecule covalent activators of the Nrf2 pathway. However, despite structural information being available for several BTB domains from related proteins, there have been no reported crystal structures of Keap1 BTB, and this has precluded a detailed understanding of its mechanism of action and interaction with antagonists. We report here the first structure of the BTB domain of Keap1, which is thought to contain the key cysteine residue responsible for interaction with electrophiles, as well as structures of the covalent complex with the antagonist CDDO/bardoxolone, and of the constitutively inactive C151W BTB mutant. In addition to providing the first structural confirmation of antagonist binding to Keap1 BTB, we also present biochemical evidence that adduction of Cys 151 by CDDO is capable of inhibiting the binding of Cul3 to Keap1, and discuss how this class of compound might exert Nrf2 activation through disruption of the BTB-Cul3 interface. [ABSTRACT FROM AUTHOR]

Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor. [ABSTRACT FROM AUTHOR]

The angular non-critical phase-matching (A-NCPM) second-harmonic-generation (SHG) properties of RE1xRE21−xCOB (RE1, RE2 = Y, Gd, La, Tm, Sm, and Nd) type mixed crystals including NCPM wavelength and conversion efficiency were detailedly investigated. Theoretical calculations manifest that the A-NCPM SHG scope of these crystals is 0.72~1.42 µm, and in experiments, the A-NCPM SHG waveband of 0.72~1.25 µm has been realized, by changing the ratio of the rare-earth elements RE1 and RE2 in RE1xRE21−xCOB crystals. Comparing to the temperature-dependent A-NCPM SHG of 0.95~1.34 µm in LiB3O5 (LBO) crystal, the composition-dependent A-NCPM SHG of 0.72~0.95 µm in RE1xRE21−xCOB type crystals is unique and has special significance for the frequency conversion of Ti:Sapphire lasers. Relationships between the birefringence and radius of rare-earth ion RE3+ in RE1xRE21−xCOB mixed crystals were discussed. Aiming for the A-NCPM SHG of 0.72~1.42 µm, we supply a clear, completed, and optimized solution on how to select the compositions of RE1xRE21−xCOB mixed crystals. Under focusing light beam conditions, high efficient A-NCPM SHG for both OPO and Ti:sapphire lasers were realized experimentally by using long Y- and Z-cut RE1xRE21−xCOB crystal samples. [ABSTRACT FROM AUTHOR]