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Epidermal growth factor receptor (EGFR) exon 19 deletion (E19del) is the most common activating mutation in advanced non–small cell lung cancer (NSCLC) and associates with the sensitivity of EGFR tyrosine kinase inhibitors (TKIs) treatment. However, not all mutant patterns of E19del have been well studied for the limited coverage of regular EGFR mutation testing. Here, we performed a retrospective cohort study of the C-helix E19del in advanced NSCLC patients based on the screening data by the next-generation sequencing (NGS) platform. From May 2012 to December 2019, clinical information and specimen from 7544 consecutive advanced (IIIB/IV) NSCLC patients were collected and screened for EGFR gene mutations by NGS from multicenters in China. The molecular characteristics and responsiveness to first-line EGFR TKIs therapy in NSCLC patients with C-helix E19del were analyzed. The clinical characteristics were also compared between patients with classical E19del and C-helix E19del. Thirty-eight (2.6%) patients with C-helix E19del and 1400 (97.4%) patients with classical E19dels were identified from 1438 patients with E19del. No significant difference in clinical characteristics was observed between the C-helix E19del and classical E19del groups (P > .05), except for histology (P < .001). All 22 patients with C-helix E19del as p.S752_I759del, p.A750_E758del, p.A750_E758delinsP, p.T751_A755delinsNY, p.T751_I759delinsG, p.T751_I759delinsLD, p.T751_I759delinsN, p.T751_L760delinsNL, and p.T751_D761delinsLY reached the best response as partial response rate (72.7%), and the progression-free survival (PFS) was 12.0 months. The PFS after EGFR TKIs in patients with C-helix E19del tended to be longer than patients with classical E19del but has no statistical significance (12.0 months vs 8.5 months, P = .06). The C-helix E19del could be a positive biomarker for predicting response to EGFR TKIs in advanced NSCLC patients. NGS should be the appropriate platform to identify this rare population, especially when patients harbor no actionable driver mutation initially and are reluctant to accept chemotherapy as first-line therapy.

Abstract Background ALK rearrangement-advanced NSCLC patients respond to crizotinib. ALK rearrangement is currently determined with RT-PCR. VENTANA IHC is a standard method to identify ALK protein overexpression in NSCLC; however, VENTANA IHC has rarely been used to determine the response to crizotinib in Chinese patients with NSCLC and ALK overexpression. To better clarify the clinical implication of VENTANA IHC to detect ALK rearrangements, we conducted this study to analyze VENTANA IHC and RT-PCR in a large cohort of Chinese patients with NSCLC undergoing screening for ALK rearrangements. Methods A total of 1720 patients with NSCLC who had ALK rearrangements detected by VENTANA IHC and/or RT-PCR were included in this analysis. We compared the efficacy and survival of ALK-positive patients detected by VENTANA IHC and RT-PCR. We used NGS to identify patients in whom the two methods were inconsistent. Results Among 1720 patients, 187 (10.87%) were shown to be ALK-positive by VENTANA IHC and/or RT-PCR, and 66 received crizotinib treatment. We identified 10.27% (172/1674) of patients as ALK-positive by the VENTANA IHC method, and 12.73% (41/322) of patients had ALK rearrangements by the RT-PCR method. Twenty-nine of 276 (10.51%) ALK-positive patients were simultaneously analyzed using VENTANA IHC and RT-PCR. The overall response rates were 65.90% (29/44) by VENTANA IHC and 55.88% (19/34) by RT-PCR. The disease control rates were 86.36% (38/44) by VENTANA IHC and 76.47% (26/34) by RT-PCR. In contrast, the median progression-free survival for VENTANA IHC and RT-PCR was 8.5 and 9.2 months, respectively. The VENTANA IHC and RT-PCR results obtained for 6 of 17 ALK-positive patients were inconsistent based on NGS; specifically, 4 patients had EML4-ALK fusions, 2 patients had non EML4-ALK fusions, 1 patient had a KCL1-ALK fusion, and one patient had a FBXO36-ALK fusion. Conclusions VENTANA IHC is a reliable and rapid screening tool used in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy. VENTANA IHC has moderate sensitivity and a slightly higher association with response to therapy with ALK inhibitors, and some VENTANA IHC-positive, but RT-PCR-negative cases may benefit from crizotinib.

The efficient and compact representation of images is a fundamental problem in computer vision. In this paper, we propose methods that use Haar- like binary box functions to represent a single image or a set of images. A desirable property of these box functions is that their inner product operation with an image can be computed very efficiently. We propose two closely related novel subspace methods to model images: The nonorthogonal binary subspace ( NBS) method and the binary principal component analysis ( B-PCA) algorithm. NBS is spanned directly by binary box functions and can be used for image representation, fast template matching, and many other vision applications. B- PCA is a structure subspace that inherits the merits of both NBS ( fast computation) and PCA ( modeling data structure information). B- PCA base vectors are obtained by a novel PCA- guided NBS method. We also show that B- PCA base vectors are nearly orthogonal to each other. As a result, in the nonorthogonal vector decomposition process, the computationally intensive pseudoinverse projection operator can be approximated by the direct dot product without causing significant distance distortion. Experiments on real image data sets show a promising performance in image matching, reconstruction, and recognition tasks with significant speed improvement.

Linear Discriminant Analysis (LDA) is a widely used technique for pattern classification. It seeks the linear projection of the data to a low dimensional subspace where the data features can be modelled with maximal discriminative power. The main computation in LDA is the dot product between LDA base vector and the data point which involves costly element-wise floating point multiplications. In this paper, we present a fast linear discriminant analysis method called binary LDA (B-LDA), which possesses the desirable property that the subspace projection operation can be computed very efficiently. We investigate the LDA guided non-orthogonal binary subspace method to find the binary LDA bases, each of which is a linear combination of, a small number of Haar-like box functions. We also show that B-LDA base vectors are nearly orthogonal to each other. As a result, in the non-orthogonal vector decomposition process, the computationally intensive pseudo-inverse projection operator can be approximated by the direct dot product without causing significant distance distortion. This direct dot product projection can be computed as a linear combination of the dot products with a small number of Haar-like box functions which can be efficiently evaluated using the integral image. The proposed approach is applied to face recognition on ORL and FERET dataset. Experiments show that the discriminative power of binary LDA is preserved and the projection computation is significantly reduced. (c) 2007 Elsevier B.V. All rights reserved.

We report the fabrication, microstructure, thermal property, and piezoelectric performance of flexible waterborne polyurethane (WPU) nanocomposite films reinforced with barium titanate (BT) nanoparticles with ~50 nm diameter. An anionic segmented WPU was synthesized via bulk polymerization, and its nanocomposite films containing 10–40 wt% BT were fabricated via aqueous dispersion casting and hot pressing. Although the BT nanoparticles interacted with the urethane groups of the WPU hard segment by inducing the separation of the semicrystalline soft segment, they were aggregated in the WPU matrix. Accordingly, the glass transition temperature of the WPU matrix decreased with BT content, but the melting temperature increased. As the BT content increased in the nanocomposite films, the thermal decomposition temperature of the WPU soft segment showed a slight decrease, while the decomposition temperature of the hard segment increased. Additionally, the residue at 600°C increased significantly from 2.0% for neat WPU film to 36.3% for the nanocomposite film containing 40 wt% BT. The piezoelectric outputs attained by the nanocomposite films increased with BT content. Under compressive stress of 23 kPa, the nanocomposite film containing 40 wt% BT was able to achieve the highest piezoelectric voltage of ~0.51 V, a current of ~43.0 nA, and an electric power of ~21.9 nW. For the nanocomposite film, a linear relationship between the piezoelectric out voltage and the applied compressive stress with a slope of ~0.0253 was also observed. Highlights: Anionic waterborne polyurethane (WPU) with hard/soft segments is synthesized.Barium titanate (BT) nanoparticles are adopted as a piezoelectric nanofiller.WPU/BT nanocomposites are manufactured by dispersion casting and hot pressing.Specific interactions between BT nanoparticles and WPU hard segments exist.Piezoelectric outputs of nanocomposites increase with BT content and stress. [ABSTRACT FROM AUTHOR]

A small molecular phenanthroline derivative Phen‐NaDPO (3‐[6‐(diphenylphosphinyl)‐2‐naphthalenyl]‐1,10‐Phenanthroline) to modify tin oxide (SnO2) electron‐transport layer (ETL) in organic solar cells is employed. Quantum chemistry calculations and experimental results show that Phen‐NaDPO can interact with SnO2, thereby effectively passivating the surface defects, reducing the work function and improving the electrical conductivity of SnO2, leading to more efficient electron extraction and transport in the organic solar cells (OSCs). Moreover, upon the Phen‐NaDPO modification, the decreased surface energy of SnO2 ETL accounts for enhanced exciton dissociation and charge transport, due to the more ordered molecular organizations of the active layers. Consequently, the inverted OSCs involving Phen‐NaDPO/SnO2 ETLs exhibit an enhanced power conversion efficiency of 17.06% (PM6:Y6) and 18.31% (PM6:L8‐BO), which is the highest efficiency for SnO2 ETL‐based binary solar cells to date. Furthermore, the devices based on Phen‐NaDPO/SnO2 ETL show better device stability (storage stability, photostability and humid stability), with T80 exceeding 200 h encapsulated under light irradiation and 400 h without encapsulation in high‐humidity ambient condition. These results demonstrate that the modification of SnO2 using wide‐band highly stable conjugated small molecules is very promising for simultaneously improve the efficiencies and device stability of OSCs. [ABSTRACT FROM AUTHOR]

To achieve high‐accuracy urine specific gravity discrimination and guide the design of four‐waveband multispectral sensors. A modified combination strategy was attempted to be proposed based on the successive projections algorithm (SPA) and the spectral index (SI) in the present study. First, the SPA was used to select four spectral variables in the full spectra. Second, the four spectral variables were mathematically transformed by SI to obtain SI values. Then, SPA gradually fusions the SI values and establishes models to identify USG. The results showed that the SPA can screen out the four characteristic wavelengths related to the measured sample attributes. SIs can be used to improve the performance of constructed prediction models. The best model only involves four spectral variables and 1 SI value, with high accuracy (91.62%), sensitivity (0.9051), and specificity (0.9667). The results reveal that m‐SPA‐SI can effectively distinguish USG and provide design guidance for 4‐wavelength multispectral sensors. [ABSTRACT FROM AUTHOR]

This study prepares composite panels with three Polylactic acid (PLA)-based materials via the multi-material fused filament fabrication method. The influences of four processing parameters on the mechanical properties of 3D-printed samples are investigated employing the Taguchi method. These parameters include the relative volume ratio, material printing order, filling pattern, and filling density. A "larger is better" signal-to-noise analysis is performed to identify the optimal combination of printing parameters that yield maximum bending strength and bending modulus of elasticity. The results reveal that the optimal combination of printing parameters that maximizes the bending strength involves a volume ratio of 1:1:2, a material sequence of PLA/foam-agent-modified eco-friendly PLA (ePLA-LW)/glass fiber-reinforced eco-friendly PLA (ePLA-GF), a Gyroid filling pattern, and a filling density of 80%, and the optimal combination of printing parameters for maximum bending modulus involves a volume ratio of 1:2:1 with a material sequence of PLA/ePLA-LW/ePLA-GF, a Grid filling pattern, and 80% filling density. The Taguchi prediction method is utilized to determine an optimal combination of processing parameters for achieving optimal flexural performances, and predicted outcomes are validated through related experiments. The experimental values of strength and modulus are 43.91 MPa and 1.23 GPa, respectively, both very close to the predicted values of 46.87 MPa and 1.2 GPa for strength and modulus. The Taguchi experiments indicate that the material sequence is the most crucial factor influencing the flexural strength of the composite panels. The experiment result demonstrates that the flexural strength and modulus of the first material sequence are 67.72 MPa and 1.53 GPa, while the flexural strength and modulus of the third material sequence are reduced to 27.09 MPa and 0.72 GPa, respectively, only 42% and 47% of the first material sequence. The above findings provide an important reference for improving the performance of multi-material 3D-printed products. [ABSTRACT FROM AUTHOR]

The hydrophilic polysaccharides (PS) were isolated and purified from the tuberous roots of Pseudostellaria heterophylla. The extraction process of PS from Pesudostellariae radix was optimized by single–factor experiments and orthogonal design. The extract was purified by DEAE cellulose column to obtain the pure polysaccharide PHP. Then PHP was treated with different intensities of sonication to study the effect of sonication on PHP's characteristics and its biological activity in vitro and in vivo. The results of this study revealed that ultrasound treatment did not significantly change the properties of PHP. Further, with the increase of ultrasound intensity, PHP enhanced the proliferation and phagocytosis of macrophage RAW264.7. Meanwhile, it could also significantly improve the body's antioxidant activity and immune function. The results of this study demonstrated that PHP has the potential as a food additive with enhanced antioxidant and immune functions, and its biological activities could be enhanced by sonication. [ABSTRACT FROM AUTHOR]

Microsatellite repeat expansions within genes contribute to a number of neurological diseases1,2. The accumulation of toxic proteins and RNA molecules with repetitive sequences, and/or sequestration of RNA-binding proteins by RNA molecules containing expanded repeats are thought to be important contributors to disease aetiology3–9. Here we reveal that the adenosine in CAG repeat RNA can be methylated to N1-methyladenosine (m1A) by TRMT61A, and that m1A can be demethylated by ALKBH3. We also observed that the m1A/adenosine ratio in CAG repeat RNA increases with repeat length, which is attributed to diminished expression of ALKBH3 elicited by the repeat RNA. Additionally, TDP-43 binds directly and strongly with m1A in RNA, which stimulates the cytoplasmic mis-localization and formation of gel-like aggregates of TDP-43, resembling the observations made for the protein in neurological diseases. Moreover, m1A in CAG repeat RNA contributes to CAG repeat expansion-induced neurodegeneration in Caenorhabditis elegans and Drosophila. In sum, our study offers a new paradigm of the mechanism through which nucleotide repeat expansion contributes to neurological diseases and reveals a novel pathological function of m1A in RNA. These findings may provide an important mechanistic basis for therapeutic intervention in neurodegenerative diseases emanating from CAG repeat expansion.TDP-43 binds to N1-methyladenosine on CAG repeat RNA, resulting in the formation of gel-like TDP-43 aggregates in the cytoplasm that resemble those observed in neurological disease pathology. [ABSTRACT FROM AUTHOR]

The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation. Specific modification or functionalization of proteins at the C-terminus is of interest but remains challenging. Here, the authors report an approach for the efficient modification of C-terminus by fusion of the cysteine protease domain (CPD) on the C-terminus of the protein of interest, and subsequent functionalization with amine-containing molecules triggered by InsP6-mediated CPD self-cleavage. [ABSTRACT FROM AUTHOR]

The oxidation behavior of a nanostructured CoNiCrA1Y bond coat dispersed nano-sized alumina particles was compared to that of a conventional coarse-grained CoNiCrA1Y bond coat. It was found that after a 1000ºC/24 h oxidation a protective alumina layer was developed on the nanostructured coating, whereas a mixed and less protective oxide layer was observed on the conventional coating. Correspondingly, spallation of the oxide layer was not observed with the nanostructured coating but did occur with the conventional coating. The improvement in oxidation behavior observed in the nanostructured coating was suggested to be due to its fine-grained structure, which provides rapid pathways (grain boundaries) for A1 diffusion to form a protective scale of pure alumina. Furthermore, the dispersion of the nano-sized alumina particles was effective in suppressing grain growth and in promoting the rapid formation of a protective alumina scale and thus significantly improving the oxidation resistance of the bond coat.

Thermal barrier coating (TBC) systems protect turbine blades against high-temperature corrosion and oxidation. They consist of a metal bond coat (MCrAIY, M = Ni, Co) and a ceramic top layer (ZrO2/Y2O3). In this work the oxidation behavior of conventional and nanostructured HVOF NiCrAIY coatings has been compared. Commercially available NiCrAIY powder was mechanically cryomilled and HVOF sprayed on a nickel alloy foil to form a nanocrystalline coating. Free-standing bodies of conventional and nanostructured HVOF NiCrAIY coatings were oxidized at a 1000ºC for different time periods in order to form the thermally grown oxide (TGO) layer. The experimants show an improvement in oxidation resistance in the nanostructured coating when compared to that of the conventional one. This behavior is a result of the formation of a continuous AI2O3 layer on the top surface of the nanostructured HVOF NiCrAIY coating. This layer protects the coating from further oxide protrusions present in the conventional coating.