Immune cell early activation, apoptotic kinetic, and T-cell functional impairment in domestic pigs after ASFV CADC_HN09 strain infection

African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV

Optimisation of the Logistics System in an Electric Motor Assembly Flowshop by Integrating the Taguchi Approach and Discrete Event Simulation

An electric motor assembly flowshop (EMAF) is a type of classical mixed-product assembly line that uses automatic guided vehicle (AGV) systems for material handling. To optimise the logistics system configuration and alleviate the impact of the AGV parameters on the efficiency of the EMAF, a modelling and optimisation method based on discrete event simulation (DES) combined with Taguchi orthogonal experimental design was proposed. A DES model of the entire production process for the EMAF was constructed using the Tecnomatix Plant Simulation software package. After optimisation of the principal layout in the DES model, the number of assembly stations was decreased from 13 to 9, and the balance ratio was increased from 65.08% to 84.65%. In addition, the combination of the Taguchi method with the DES model was further developed to achieve the optimal parameter combination of the AGVs in order to allow the AGVs to operate more efficiently under various states. The final overall theoretical throughput was increased from 134 to 295 units within the seven-hour observation period

Optimisation of the Logistics System in an Electric Motor Assembly Flowshop by Integrating the Taguchi Approach and Discrete Event Simulation

An electric motor assembly flowshop (EMAF) is a type of classical mixed-product assembly line that uses automatic guided vehicle (AGV) systems for material handling. To optimise the logistics system configuration and alleviate the impact of the AGV parameters on the efficiency of the EMAF, a modelling and optimisation method based on discrete event simulation (DES) combined with Taguchi orthogonal experimental design was proposed. A DES model of the entire production process for the EMAF was constructed using the Tecnomatix Plant Simulation software package. After optimisation of the principal layout in the DES model, the number of assembly stations was decreased from 13 to 9, and the balance ratio was increased from 65.08% to 84.65%. In addition, the combination of the Taguchi method with the DES model was further developed to achieve the optimal parameter combination of the AGVs in order to allow the AGVs to operate more efficiently under various states. The final overall theoretical throughput was increased from 134 to 295 units within the seven-hour observation period

Deficits of cognitive restructuring in major depressive disorder: Measured by textual micro-counseling dialogues

Cognitive restructuring is an important strategy in cognitive behavioral therapy (CBT). The present study aimed to observe cognitive restructuring in major depressive disorder (MDD) patients using textual micro-counseling dialogue situations. A set of textual micro-counseling dialogues was used to trigger cognitive restructuring in 25 MDD patients and 27 healthy adults. The participants read descriptions ("problems") and explanations ("solutions") for psychologically distressing situations. High-, low-, and zero-restructuring solutions were randomly matched to the problems. The participants evaluated the adaptability and emotional valence of the problems and the insightfulness, adaptability, novelty, and emotional valence of the solutions. Insightfulness ratings for high-restructuring solutions were significantly higher relative to those of low-restructuring solutions in healthy adults, while adaptability ratings for low-restructuring solutions were significantly higher relative to those of high-restructuring solutions in MDD patients. Insightfulness ratings for the solutions were significantly predicted by novelty and adaptability in healthy adults and emotional valence in MDD patients. Lower insightfulness in high restructuring solutions and higher adaptability in low-restructuring solutions in MDD patients may reflect deficits in cognitive control. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Use of Geographically Weighted Regression (GWR) to Reveal Spatially Varying Relationships between Cd Accumulation and Soil Properties at Field Scale

The spatial variation of correlation between Cd accumulation and its impact factors plays an important role in precise management of Cd contaminated farmland. Samples of topsoils (n = 247) were collected from suburban farmland located at the junction of the Yellow River Basin and the Huaihe River Basin in China using a 200 m × 200 m grid system. The total and available contents of Cd (T-Cd and A-Cd) in topsoils were analyzed by ICP-MS, and their spatial distribution was analyzed using kriging interpolation with the GIS technique. Geographically weighted regression (GWR) models were applied to explore the spatial variation and their influencing mechanisms of relationships between major environmental factors (pH, organic matter, available phosphorus (A-P)) and Cd accumulation. Spatial distribution showed that T-Cd, A-Cd and their influencing factors had obvious spatial variability, and high value areas primarily cluster near industrial agglomeration areas and irrigation canals. GWR analysis revealed that relationships between T-Cd, A-Cd and their environmental factors presented obvious spatial heterogeneity. Notably, there was a significant negative correlation between soil pH and T-Cd, A-Cd, but with the increase of pH in soil the correlation decreased. A novel finding of a positive correlation between OM and T-Cd, A-Cd was observed, but significant positive correlation only occurred in the high anthropogenic input area due to the complex effects of organic matter on Cd activity. The influence intensity of pH and OM on T-Cd and A-Cd increases under the strong influence of anthropogenic sources. Additionally, T-Cd and A-Cd were totally positively related to soil A-P, but mostly not significantly, which was attributed to the complexity of the available phosphorus source and the differences in Cd contents in chemical fertilizer. Furthermore, clay content might be an important factor affecting the correlation between Cd and soil properties, considering that the correlation between Cd and pH, SOM, A-P was significantly lower in areas with lower clay particles. This study suggested that GWR was an effective tool to reveal spatially varying relationships at field scale, which provided a new idea to further explore the related influencing factors on spatial distribution of contaminants and to realize precise management of a farmland environment

Monte Carlo Optimization for Sliding Window Size in Dixon Quality Control of Environmental Monitoring Time Series Data

Outliers are often present in large datasets of water quality monitoring time series data. A method of combining the sliding window technique with Dixon detection criterion for the automatic detection of outliers in time series data is limited by the empirical determination of sliding window sizes. The scientific determination of the optimal sliding window size is very meaningful research work. This paper presents a new Monte Carlo Search Method (MCSM) based on random sampling to optimize the size of the sliding window, which fully takes advantage of computers and statistics. The MCSM was applied in a case study to automatic monitoring data of water quality factors in order to test its validity and usefulness. The results of comparing the accuracy and efficiency of the MCSM show that the new method in this paper is scientific and effective. The experimental results show that, at different sample sizes, the average accuracy is between 58.70% and 75.75%, and the average computation time increase is between 17.09% and 45.53%. In the era of big data in environmental monitoring, the proposed new methods can meet the required accuracy of outlier detection and improve the efficiency of calculation

Correlations between Ape1/Ref-1, ICAM-1 and IL-17A Levels in Serum and Radiation Pneumonitis for Local Advanced Non-small Cell Lung Cancer Patients

Background and objective The main manifestations of radiation pneumonitis are injury of alveolar epithelial and endothelial cells, abnormal expression of cytokines, abnormal proliferation of fibroblasts and synthesis of fibrous matrix. The occurrence of radiation pneumonitis is associated with multiplecytokine level abnormality. These cytokines can also be used as bio-markers to predict the occurrence of radiation pneumonitis. This study was to evaluate the correlation between the change of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1), intercellular adhesion molecules 1 (ICAM-1) and interleukin-17A (IL-17A) before and after radiotherapy and radiation pneumonitis for local advanced non-small cell lung cancer (NSCLC) patients with concurrent chemoradiotherapy. Methods NSCLC patients (68 cases) were treated with concurrent radiotherapy and chemotherapy, every patient’s normal tissue were controlled with a same radation dose. 68 local advanced NSCLC patients with concurrent chemoradiotherapy were detected the levels of Ape1/Ref-1, ICAM-1 and IL-17A in serum by ELISA before radiotherapy and in the 14th week after radiotherapy. Acute and advanced radiation pulmonary injury was graded according to Radiation Therapy Oncology Group/European Organization For Research and Treatment (RTOG/EORTC) diagnostic and grading criteria. Grade 2 or more radiation pneumonitis was taken as the main end point. Results Eighteen cases out of 68 developed radiation pneumonitis, 50 of 68 cases have no radiation pneumonia development. There was no significant change of Ape1/Ref-1 levels before and after radiotherapy in radiation pneumonitis group (P>0.05). There was no significant change of Ape1/Ref-1 concentration in serum after radiotherapy between radiation pneumonitis group and non-radiation pneumonitis group (P>0.05). Compared with before radiotherapy, upregulation degree of ICAM-1 levels in radiation pneumonitis group was significantly higher than that in non- radiation pneumonitis group (P<0.05). There was no significant change of IL-17A concentration before and after radiotherapy in radiation pneumonitis group, but after radiotherapy IL-17A concentration in serum were remarkably higher than that in non-radiation pneumonitis group (P<0.05). Correlation analysis found that the change of ICAM-1 before and after radiotherapy has no obvious correlation with the incidence of radiation pneumonitis, and IL-17A change has obvious correlation with the incidence of radiation pneumonitis. Conclusion On the basis of strictly controlling radiation dose on normal tissue, IL-17A in serum could be the predictive factors of radiation pneumonitis for local advanced NSCLC patients with concurrent chemoradiotherapy

Discovery and development of natural heat shock protein 90 inhibitors in cancer treatment

Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone that plays a vital role in the signal transduction of cancers. Hsp90 inhibitors are able to inhibit Hsp90 or the complex of Hsp90 and co-chaperones resulting in the degradation of Hsp90-dependent client proteins through the ubiquitination-proteasome pathway, thereby leading to the growth inhibition of tumor cells. This review will briefly discuss the molecular structure and biological function of Hsp90, and focus on a summary of recent progress in the development and testing of natural Hsp90 inhibitors and their different means by which they interact with Hsp90