Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement characterizes a subgroup of patients who show sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients. Methods: We retrospectively analyzed 96 patients with NSCLC with ALK detected by immunohistochemical staining (VENTANA anti-ALK(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of ALK fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed. Results: Among the 96 patients with immunohistochemically identified ALK fusions, 80 (83%) were confirmed by next-generation sequencing. TP53 mutation was the most commonly co-occurring mutation with ALK rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog (KRAS) G12, 1 epidermal growth factor receptor (EGFR) 19del, and 1 MET exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions were identified in 95% of ALK-rearranged patients, with 16.2% of them also harboring additional non-EML4- ALK fusions. Nineteen non-EML4 translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring PIK3R2 alterations showed a trend toward shorter progression-free survival (6 vs. 13 months, P=0.064) and significantly shorter overall survival (11 vs. 32 months, P=0.004) than did PIK3R2-wild-type patients. Patients with concomitant alterations in PI3K the signaling pathway also had a shorter median overall survival than those without such alterations (23 vs. 32 months, P=0.014), whereas progression-free survival did not differ significantly. Conclusions: The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy

Construction and Evaluation of the Brucella Double Gene Knock-out Vaccine Strain MB6 Δbp26ΔwboA (RM6)

Brucellosis is a serious zoonotic infection worldwide. To date, vaccination is the most effective measure against brucellosis. This study was aimed at obtaining a vaccine strain that has high protective efficacy and low toxicity, and allows vaccination to be differentiated from infection. Using homologous recombination, we constructed a double gene-deletion Brucella strain MB6 Δbp26ΔwboA (RM6) and evaluated its characteristics, safety and efficacy. The RM6 strain had good proliferative ability and stable biological characteristics in vivo and in vitro. Moreover, it had a favorable safety profile and elicited specific immune responses in mice and sheep. The RM6 strain may have substantial practical application value

Development and Efficacy Evaluation of an SP01-adjuvanted Inactivated Escherichia Coli Mutant Vaccine Against Bovine Coliform Mastitis

Escherichia coli ( E. coli ) is one of the most common pathogens causing clinical mastitis in cattle, but no vaccine is available to prevent this disease in China. Therefore, development of an E. coli vaccine against bovine clinical mastitis is urgently needed. The candidate vaccine (Ch-O111-1) and challenge (LZ06) strains were screened from milk samples of cows with clinical mastitis. To extend the cross-protection of the Ch-O111-1 strain, we deleted the galE gene fragment of the Ch-O111-1 strain through homologous recombination between the Ch-O111-1 strain and pCVD442/ΔgalE plasmid, which was identified through conventional methods, including PCR, SDS-PAGE and sequencing. The Ch-O111-1/ΔgalE (Z9) strain was characterized by extensive cross-reactivity and attenuated virulence. We prepared inactivated Z9 vaccines with different adjuvants. Immunization of inactivated Z9 antigen induced adjuvant-, dosage- and inoculation time-dependent antibody titers in cows and mice. Furthermore, immunization with SP01-adjuvanted inactivated Z9 vaccine protected cows against severe clinical mastitis caused by LZ06 and protected mice against death due to LZ06. An SP01-adjuvanted inactivated Z9 vaccine was successfully developed and found to protect cows against severe mastitis caused by Escherichia coli

Innovative Deep Neural Network Modeling for Fine-Grained Chinese Entity Recognition

Named entity recognition (NER) is a basic but crucial task in the field of natural language processing (NLP) and big data analysis. The recognition of named entities based on Chinese is more complicated and difficult than English, which makes the task of NER in Chinese more challenging. In particular, fine-grained named entity recognition is more challenging than traditional named entity recognition tasks, mainly because fine-grained tasks have higher requirements for the ability of automatic feature extraction and information representation of deep neural models. In this paper, we propose an innovative neural network model named En2BiLSTM-CRF to improve the effect of fine-grained Chinese entity recognition tasks. This proposed model including the initial encoding layer, the enhanced encoding layer, and the decoding layer combines the advantages of pre-training model encoding, dual bidirectional long short-term memory (BiLSTM) networks, and a residual connection mechanism. Hence, it can encode information multiple times and extract contextual features hierarchically. We conducted sufficient experiments on two representative datasets using multiple important metrics and compared them with other advanced baselines. We present promising results showing that our proposed En2BiLSTM-CRF has better performance as well as better generalization ability in both fine-grained and coarse-grained Chinese entity recognition tasks

Improved Dyna-Q: A Reinforcement Learning Method Focused via Heuristic Graph for AGV Path Planning in Dynamic Environments

Dyna-Q is a reinforcement learning method widely used in AGV path planning. However, in large complex dynamic environments, due to the sparse reward function of Dyna-Q and the large searching space, this method has the problems of low search efficiency, slow convergence speed, and even inability to converge, which seriously reduces the performance and practicability of it. To solve these problems, this paper proposes an Improved Dyna-Q algorithm for AGV path planning in large complex dynamic environments. First, to solve the problem of the large search space, this paper proposes a global path guidance mechanism based on heuristic graph, which can effectively reduce the path search space and, thus, improve the efficiency of obtaining the optimal path. Second, to solve the problem of the sparse reward function in Dyna-Q, this paper proposes a novel dynamic reward function and an action selection method based on the heuristic graph, which can provide more intensive feedback and more efficient action decision for AGV path planning, effectively improving the convergence of the algorithm. We evaluated our approach in scenarios with static obstacles and dynamic obstacles. The experimental results show that the proposed algorithm can obtain better paths more efficiently than other reinforcement-learning-based methods including the classical Q-Learning and the Dyna-Q algorithms

Improved Dyna-Q: A Reinforcement Learning Method Focused via Heuristic Graph for AGV Path Planning in Dynamic Environments

Dyna-Q is a reinforcement learning method widely used in AGV path planning. However, in large complex dynamic environments, due to the sparse reward function of Dyna-Q and the large searching space, this method has the problems of low search efficiency, slow convergence speed, and even inability to converge, which seriously reduces the performance and practicability of it. To solve these problems, this paper proposes an Improved Dyna-Q algorithm for AGV path planning in large complex dynamic environments. First, to solve the problem of the large search space, this paper proposes a global path guidance mechanism based on heuristic graph, which can effectively reduce the path search space and, thus, improve the efficiency of obtaining the optimal path. Second, to solve the problem of the sparse reward function in Dyna-Q, this paper proposes a novel dynamic reward function and an action selection method based on the heuristic graph, which can provide more intensive feedback and more efficient action decision for AGV path planning, effectively improving the convergence of the algorithm. We evaluated our approach in scenarios with static obstacles and dynamic obstacles. The experimental results show that the proposed algorithm can obtain better paths more efficiently than other reinforcement-learning-based methods including the classical Q-Learning and the Dyna-Q algorithms

A Novel Hierarchical Coding Progressive Transmission Method for WMSN Wildlife Images

In the wild, wireless multimedia sensor network (WMSN) communication has limited bandwidth and the transmission of wildlife monitoring images always suffers signal interference, which is time-consuming, or sometimes even causes failure. Generally, only part of each wildlife image is valuable, therefore, if we could transmit the images according to the importance of the content, the above issues can be avoided. Inspired by the progressive transmission strategy, we propose a hierarchical coding progressive transmission method in this paper, which can transmit the saliency object region (i.e. the animal) and its background with different coding strategies and priorities. Specifically, we firstly construct a convolution neural network via the MobileNet model for the detection of the saliency object region and obtaining the mask on wildlife. Then, according to the importance of wavelet coefficients, set partitioned in hierarchical tree (SPIHT) lossless coding is utilized to transmit the saliency image which ensures the transmission accuracy of the wildlife region. After that, the background region left over is transmitted via the Embedded Zerotree Wavelets (EZW) lossy coding strategy, to improve the transmission efficiency. To verify the efficiency of our algorithm, a demonstration of the transmission of field-captured wildlife images is presented. Further, comparison of results with existing EZW and discrete cosine transform (DCT) algorithms shows that the proposed algorithm improves the peak signal to noise ratio (PSNR) and structural similarity index (SSIM) by 21.11%, 14.72% and 9.47%, 6.25%, respectively

A Sampling-Based Algorithm with the Metropolis Acceptance Criterion for Robot Motion Planning

Motion planning is one of the important research topics of robotics. As an improvement of Rapidly exploring Random Tree (RRT), the RRT* motion planning algorithm is widely used because of its asymptotic optimality. However, the running time of RRT* increases rapidly with the number of potential path vertices, resulting in slow convergence or even an inability to converge, which seriously reduces the performance and practical value of RRT*. To solve this issue, this paper proposes a two-phase motion planning algorithm named Metropolis RRT* (M-RRT*) based on the Metropolis acceptance criterion. First, to efficiently obtain the initial path and start the optimal path search phase earlier, an asymptotic vertex acceptance criterion is defined in the initial path estimation phase of M-RRT*. Second, to improve the convergence rate of the algorithm, a nonlinear dynamic vertex acceptance criterion is defined in the optimal path search phase, which preferentially accepts vertices that may improve the current path. The effectiveness of M-RRT* is verified by comparing it with existing algorithms through the simulation results in three test environments

A Novel Saliency Detection Method for Wild Animal Monitoring Images with WMSN

We proposed a novel saliency detection method based on histogram contrast algorithm and images captured with WMSN (wireless multimedia sensor network) for practical wild animal monitoring purpose. Current studies on wild animal monitoring mainly focus on analyzing images with high resolution, complex background, and nonuniform illumination features. Most current visual saliency detection methods are not capable of completing the processing work. In this algorithm, we firstly smoothed the image texture and reduced the noise with the help of structure extraction method based on image total variation. After that, the saliency target edge information was obtained by Canny operator edge detection method, which will be further improved by position saliency map according to the Hanning window. In order to verify the efficiency of the proposed algorithm, field-captured wild animal images were tested by using our algorithm in terms of visual effect and detection efficiency. Compared with histogram contrast algorithm, the result shows that the rate of average precision, recall and F-measure improved by 18.38%, 19.53%, 19.06%, respectively, when processing the captured animal images