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In order to make a good compromise of cost and safety with small data in the early structural design stage, a practical decoupled credibility-based design optimization method is developed in the presence of fuzzy uncertainty. In the proposed approach, failure credibility is constructed as optimization constraints estimated by fuzzy advanced first-order second-moment method. By approximating the fuzzy credibility constraint by the adaptive Kriging surrogate model, a fuzzy credibility-based design is decoupled to a common deterministic optimization so that various existing optimization algorithms can be easily applied. Compared to the traditional double-loop approach, the newly proposed method is more efficient and strongly practical for complicated engineering problems. Design results of three structural engineering examples also show advantages in accuracy and computation speed of the proposed method over the traditional double-loop approach.

Fuzzy uncertainty (FU) exists widely in engineering applications, but there lack design optimization methods under FU, thus a credibility-based design optimization (CBDO) is focused to obtain the safety design under FU in this paper. Firstly, the concepts of credibility index and most credible point (MCP) are presented to measure the safety degree under FU, where the credibility index and the MCP, respectively, show similar properties as the reliability index and the most probable point under random uncertainty. Secondly, the inverse MCP (IMCP) is defined with respect to the required credibility, and the detailed method is established for searching IMCP, on which the performance measure approach (PMA) can be combined to solve the CBDO. Since the PMA combined with the IMCP includes a time-consuming double-loop strategy, the sequential optimization and credibility assessment (SOCA) is proposed to decouple the double-loop strategy thirdly. In the SOCA, a shifting vector constructed by the IMCP is used to transform the credibility constraint into an equivalent deterministic one, on which the double-loop strategy can be avoided to reduce the computational cost for solving the CBDO. One numerical example and two engineering examples fully illustrate the efficiency and accuracy of the SOCA.

Abstract cDNA display is an in vitro display technology based on a covalent linkage between a protein and its corresponding mRNA/cDNA, widely used for the selection of proteins and peptides from large libraries (10 12 ) in a high throughput manner, based on their binding affinity. Here, we developed a platform using cDNA display and next-generation sequencing (NGS) for rapid and comprehensive substrate profiling of transglutaminase 2 (TG2), an enzyme crosslinking glutamine and lysine residues in proteins. After screening and selection of the control peptide library randomized at the reactive glutamine, a combinatorial library of displayed peptides randomized at positions − 1, + 1, + 2, and + 3 from the reactive glutamine was screened followed by NGS and bioinformatic analysis, which indicated a strong preference of TG2 towards peptides with glutamine at position − 1 (Gln-Gln motif), and isoleucine or valine at position + 3. The highly enriched peptides indeed contained the indicated sequence and showed a higher reactivity as TG2 substrates than the peptide previously selected by phage display, thus representing the novel candidate peptide probes for TG2 research. Furthermore, the obtained information on substrate profiling can be used to identify potential TG2 protein targets. This platform will be further used for the substrate profiling of other TG isozymes, as well as for the selection and evolution of larger biomolecules.

Based on the road surface (bridge deck) temperature, relative humidity, air temperature, wind speed and precipitation observed at two road surface meteorological stations and two bridge deck meteorological stations, as well as subsurface temperature at different depths observed at Hefei meteorological station, the independent variables are selected to establish the relationship between these factors and road surface temperature, using random forest and stepwise regression. The performance of these two methods was compared, and the importance of each factor was analyzed. Results show that the road surface (bridge deck) temperature linearly correlates with air temperature. In the case of low air temperature conditions (air temperature ≤ 8 °C), the road surface temperature is mainly higher than air temperature observed at the same station, and the bridge deck temperature is mainly lower than air temperature. In the retrieving of road surface temperature and bridge deck temperature, the random forest algorithm has lower mean absolute error (MAE) and root mean square error (RMSE) than the stepwise regression algorithm, especially in the retrieving of road surface temperature. MAE of road surface temperature retrieved by random forest on two bridge deck stations is reduced by 0.19 °C and 0.26 °C compared with the stepwise regression, and RMSE is reduced by 0.33 °C and 0.49 °C, respectively. The bias in the retrievals can be originated from the model itself and the error in the observations. Among the factors in the random forest model, air temperature is the most important. Meanwhile, there are differences in the importance of each factor in the retrieval of road surface temperature and bridge deck temperature. The subsurface temperature is more important in retrieving road surface temperature, while humidity and wind speed are generally more important to bridge deck temperature. It should be noted that due to the limitation of the observations, this study did not consider the net radiative flux, and the influence of net radiative flux on bridge deck and road surface temperature may be different.

In order to measure structural safety with fuzzy uncertainty, a new root finding method of failure credibility is presented by taking advantage of the simple relation on input and output credibility inverse distributions. A brief introduction is given of the fuzzy credibility measure and the credibility inverse distribution at first. As the theoretical basis of root finding method, principles of transformation from failure credibility solving into a root finding process through credibility inverse distribution functions, are fully explained from the standpoint of root screening conditions as well as computing features. After organizing the fuzzy root finding algorithm for both explicit and implicit performance functions, arithmetical differences of fuzzy safety are meanwhile compared to random reliability to reveal the essence of their different type of uncertainty. Finally the applicability and effectiveness of fuzzy root finding method are testified by several engineering cases.

A regional fully coupled meteorology–chemistry model, Weather Research and Forecasting model with Chemistry (WRF-Chem), was employed to study the seasonality of ozone (O3) pollution and its sources in both China and India. Observations and model results suggest that O3 in the North China Plain (NCP), Yangtze River Delta (YRD), Pearl River Delta (PRD), and India exhibit distinctive seasonal features, which are linked to the influence of summer monsoons. Through a factor separation approach, we examined the sensitivity of O3 to individual anthropogenic, biogenic, and biomass burning emissions. We found that summer O3 formation in China is more sensitive to industrial and biogenic sources than to other source sectors, while the transportation and biogenic sources are more important in all seasons for India. Tagged simulations suggest that local sources play an important role in the formation of the summer O3 peak in the NCP, but sources from Northwest China should not be neglected to control summer O3 in the NCP. For the YRD region, prevailing winds and cleaner air from the ocean in summer lead to reduced transport from polluted regions, and the major source region in addition to local sources is Southeast China. For the PRD region, the upwind region is replaced by contributions from polluted PRD as autumn approaches, leading to an autumn peak. The major upwind regions in autumn for the PRD are YRD (11 %) and Southeast China (10 %). For India, sources in North India are more important than sources in the south. These analyses emphasize the relative importance of source sectors and regions as they change with seasons, providing important implications for O3 control strategies.

The Bermuda High (BH) quasi-permanent pressure system is the key large-scale circulation pattern influencing summertime weather over the eastern and southern US. Here we developed a multiple linear regression (MLR) model to characterize the effect of the BH on year-to-year changes in monthly-mean maximum daily 8 h average (MDA8) ozone in the Houston–Galveston–Brazoria (HGB) metropolitan region during June, July, and August (JJA). The BH indicators include the longitude of the BH western edge (BH-Lon) and the BH intensity index (BHI) defined as the pressure gradient along its western edge. Both BH-Lon and BHI are selected by MLR as significant predictors (p < 0.05) of the interannual (1990–2015) variability of the HGB-mean ozone throughout JJA, while local-scale meridional wind speed is selected as an additional predictor for August only. Local-scale temperature and zonal wind speed are not identified as important factors for any summer month. The best-fit MLR model can explain 61–72 % of the interannual variability of the HGB-mean summertime ozone over 1990–2015 and shows good performance in cross-validation (R2 higher than 0.48). The BH-Lon is the most important factor, which alone explains 38–48 % of such variability. The location and strength of the Bermuda High appears to control whether or not low-ozone maritime air from the Gulf of Mexico can enter southeastern Texas and affect air quality. This mechanism also applies to other coastal urban regions along the Gulf Coast (e.g., New Orleans, LA, Mobile, AL, and Pensacola, FL), suggesting that the BH circulation pattern can affect surface ozone variability through a large portion of the Gulf Coast.

The medicine has ihe efficacy of promoting flow of qi and blood circulation, dispelling the wind anti activating collaterals, dissipating blood stasis and relieving pain, so it can be used to cure rheumatoid arthralgia, cirrhosis with ascites, epigastric pain, acute and chronic nephritis, acute gastroenteritis, dysmenorrhea, postpartum abdominalgia with blood stasis, traumatic injury, fracture, etc 3 . In this study, based on the adjuvant arthritis (AA) model of rats, the therapeutic effect of K. coccinea on AA rats was studied, and its possible mechanism was explored at the cellular level to provide theoretical basis for the treatment of rheumatoid arthritis ( RA) by Yao medicine Dazuan. 2Materials and methods 2.1 Materials 2.1.1 Drugs and reagents. An outside micrometer was from Radio Shack; an electronic analytical balance tvas from Mcttler Toledo (Shanghai) Instrument Co. Ltd. ; an electronic balance was from Changshu Shttangjie Test Inslrumenl Factory; a centrifuge was from Shanghai Anting Scientific Instrument Factory; an automatic microplale reader was from Thermo Fisher (Shanghai) Inslrumenl Co. Ltd. 2.2Methods 2.2.1 Establishment of AA rat model anti administration. According to the experimental results, KCTE had significant effects on the reduction of primary and secondary articular swelling of AA rats and the improvement of their arthritic symptoms, showing that KCTF had significant inhibitory effects on the primary and secondary lesions of AA rats.

cDNA display is an in vitro display technology based on a covalent linkage between a protein and its corresponding mRNA/cDNA, where a stable complex is formed suitable for a wide range of selection conditions. A great advantage of cDNA display is the ability to handle enormous library size (1012) in a microtube scale, in a matter of days. To harness its benefits, we aimed at developing a platform which combines the advantages of cDNA display with high-throughput and accuracy of next-generation sequencing (NGS) for the selection of preferred substrate peptides of transglutaminase 2 (TG2), a protein cross-linking enzyme. After the optimization of the platform by the repeated screening of binary model libraries consisting of substrate and non-substrate peptides at different ratios, screening and selection of combinatorial peptide library randomized at positions -1, +1, +2, and +3 from the glutamine residue was carried out. Enriched cDNA complexes were analyzed by NGS and bioinformatics, revealing the comprehensive amino acid preference of the TG2 at targeted positions of the peptide backbone. This is the first report on cDNA display/NGS screening system to yield comprehensive data on TG substrate preference. Although some issues remain to be solved, this platform can be applied to selection of other TGs and easily adjusted for the selection of other peptide substrates and even larger biomolecules. Competing Interest Statement The authors have declared no competing interest.

We have reported a high expression of IGF-I in pancreatic islet β-cells of transgenic mice under the metallothionein promoter. cDNA microarray analysis of the islets revealed that the expression of 82 genes was significantly altered compared to wild-type mice. Of these, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which is responsible for the conversion of inert cortisone (11-dehydrocorticosterone, DHC in rodents) to active cortisol (corticosterone) in the liver and adipose tissues, has not been identified previously as an IGF-I target in pancreatic islets. We characterized the changes in its protein level, enzyme activity and glucose-stimulated insulin secretion. In freshly isolated islets, the level of 11β-HSD1 protein was significantly lower in MT-IGF mice. Using dual-labeled immunofluorescence, 11β-HSD1 was observed exclusively in glucagon-producing, islet α-cells but at a lower level in transgenic vs. wild-type animals. MT-IGF islets also exhibited reduced enzymatic activities. Dexamethasone (DEX) and DHC inhibited glucose-stimulated insulin secretion from freshly isolated islets of wild-type mice. In the islets of MT-IGF mice, 48-h pre-incubation of DEX caused a significant decrease in insulin release, while the effect of DHC was largely blunted consistent with diminished 11β-HSD1 activity. In order to establish the function of intracrine glucocorticoids, we overexpressed 11β-HSD1 cDNA in MIN6 insulinoma cells, which together with DHC caused apoptosis and a significant decrease in proliferation. Both effects were abolished with the treatment of an 11β-HSD1 inhibitor. Our results demonstrate an inhibitory effect of IGF-I on 11β-HSD1 expression and activity within the pancreatic islets, which may mediate part of the IGF-I effects on cell proliferation, survival and insulin secretion.