Research on bearing fault diagnosis based on improved genetic algorithm and BP neural network.

Health monitoring and fault diagnosis of rolling bearings are crucial for the continuous and effective operation of mechanical equipment. In order to improve the accuracy of BP neural network in fault diagnosis of rolling bearings, a feature model is established from the vibration signals of rolling bearings, and an improved genetic algorithm is used to optimize the initial weights, biases, and hyperparameters of the BP neural network. This overcomes the shortcomings of BP neural network, such as being prone to local minima, slow convergence speed, and sample dependence. The improved genetic algorithm fully considers the degree of concentration and dispersion of population fitness in genetic algorithms, and adaptively adjusts the crossover and mutation probabilities of genetic algorithms in a non-linear manner. At the same time, in order to accelerate the optimization efficiency of the selection operator, the elite retention strategy is combined with the hierarchical proportional selection operation. Using the rolling bearing dataset from Case Western Reserve University in the United States as experimental data, the proposed algorithm was used for simulation and prediction. The experimental results show that compared with the other seven models, the proposed IGA-BPNN exhibit superior performance in both convergence speed and predictive performance.

Study on aluminum nitride/addition-cure liquid silicone rubber composite for high-voltage power encapsulation.

In view of the development direction of high power and miniaturization of high-voltage power supply, higher requirements are put forward for the breakdown strength, thermal conductivity of packaging materials for its high voltage output module. An electric-insulated heat-conducted material with aluminium nitride as heat conducting filler and addition-cure liquid silicone rubber (ALSR) as matrix for high voltage power encapsulation has been studied. Initially, the thermal conductivity and breakdown strength of composites were explored at different filler fractions. With increase of filler fraction, the thermal conductivity increased and the breakdown strength decreased. Then, with the packaging module volume as the optimization objective and the working temperature as the optimization condition, the temperature distribution of high voltage power supply was studied by using the finite element method, and 40wt% filling fraction was selected as the optimal ratio. Finally, the actual packaging experiment of the high voltage module is carried out. and the variation of the output voltage and temperature with the working time is obtained. According to the experimental results, the output voltage of the high voltage module is basically stable, and the maximum surface temperature is 40.4°C. The practicability of the electric-insulated heat-conducted material has been proved.

Research on the thermal conductivity and dielectric properties of AlN and BN co-filled addition-cure liquid silicone rubber composites.

The present work aims at studying the thermal and dielectric properties of addition-cure liquid silicone rubber (ALSR) matrix composites using boron nitride (BN) and aluminum nitride (AlN) as a hybrid thermal conductive filler. Composite samples with different filler contents were fabricated, and the density, thermal conductivity, thermal stability, dielectric properties, and volume resistivity of the samples were measured. According to the experimental results, the density, thermal conductivity, dielectric constant and dielectric loss tangent values all increased with the increasing addition of filler. When the weight fraction of hBN filler was 50 wt%, the thermal conductivity of composites was 0.554 W (m-1 K-1), which is 3.4 times higher than that of pure ALSR. The corresponding relative permittivity and dielectric loss were 3.98 and 0.0085 at 1 MHz, respectively. Furthermore, TGA results revealed that the AlN/BN hybrid filler could also improve the thermal stability of ALSR. The volume resistivity of ALSR composites was higher than that of pure ALSR. The addition of fillers improved the thermal properties of ALSR and had little effect on its insulation properties. This characteristic makes ALSR composites attractive in the field of insulating materials.

Synthesis and biological assays of 9-(acylamino) homocamptothecins as DNA topoisomerase I inhibitors.

In an effort to improve the stability of homocamptothecin and reduce the toxicity, novel homocamptothecin analogs with acylamino groups at C(9) were designed and synthesized. The cytotoxic activities of all the synthetic compounds against three cancer cell lines were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, and irinotecan was used as reference compound. Compound 7c with a piperidinylacetamido group and 10a with phenylacetamido group at C(9) showed potent activities both in vitro and in vivo. In addition, they also revealed remarkable topoisomerase I inhibitions which were exhibited with well-established bonds with amino acid residues Arg364 and Asp533 in the active pocket. On the basis of the biological activities, 7c and 10a would be potential candidates for further studies.

A new strategy to improve the metabolic stability of lactone: discovery of (20S,21S)-21-fluorocamptothecins as novel, hydrolytically stable topoisomerase I inhibitors.

Lactone is a common structural motif in biologically active natural products. However, the metabolic instability of lactone significantly reduces their in vivo potency. In the present investigation, a new strategy to improve the metabolic stability of lactone was provided by the design of α-fluoro ether as a novel bioisostere of lactone. The effectiveness of the α-fluoro ether/lactone replacement was validated by the discovery of (20S,21S)-21-fluorocamptothecins as hydrolytically stable topoisomerase I inhibitors. A highly potent camptothecin derivative, 8l, was successfully identified, which showed excellent in vitro and in vivo antitumor activities and represents a promising lead for the discovery of novel antitumor agents. Interestingly, this study also provided a new structure-activity relationship for the C21-carbonyl group of camptothecin, which has been regarded as an essential pharmacophore. Our results revealed that the conserved C21-carbonyl group can be replaced by a fluorine substituent. α-Fluoro ether may have general application in improving the metabolic stability of lactone.

Synthesis and preliminary bioevaluation of novel E-ring modified acetal analog of camptothecin as cytotoxic agents.

In an effort to improve the metabolic stability of the E-ring and decrease the toxicity of camptothecin (CPT), a novel cytotoxic acetal analog with 21-alkoxy groups was designed and synthesized. The preliminary results revealed that this class of compounds showed superior antiproliferative activity in vitro and moderate in vivo activity, while their topoisomerase I (Topo I) inhibitory activity was weakened significantly. The implications of these results within the current understanding of the structure-activity relationship of camptothecin are analyzed in detail. The obtained information provides insight into the role of the 21-carbonyl group in the binding of CPT to Topo I-DNA complex.

Discovery, synthesis, and biological evaluation of orally active pyrrolidone derivatives as novel inhibitors of p53-MDM2 protein-protein interaction.

The p53-MDM2 interaction has been proved to be a valuable target to develop effective antitumor agents. Novel p53-MDM2 inhibitors bearing pyrrolidone scaffolds were successfully identified by structure-based design. The nanomolar inhibitor 5 possessed good p53-MDM2 inhibitory activity (K(i) = 780 nM) due to its hydrophobic and hydrogen bonding interactions with MDM2. Further hit optimization led to the discovery of a number of highly potent pyrrolidone derivatives with improved p53-MDM2 inhibitory activity and in vitro antiproliferative potency. Compounds 41 (K(i) = 260.0 nM) and 60a (K(i) = 150.0 nM) showed good and selective activity against tumor cells with deleted p53. In addition, these two compounds also effectively inhibited the tumor growth in the A549 xenograft model. Interestingly, compound 41 was proved to be a potent MDM2/MDMX dual inhibitor. The novel pyrrolidone p53-MDM2 inhibitors represent promising lead structures for the development of novel antitumor agents.

Structure-activity relationship and antitumor activity of thio-benzodiazepines as p53-MDM2 protein-protein interaction inhibitors.

In order to discuss the structure-activity relationship (SAR) of the thio-benzodiazepine compounds which showed excellent activity against p53-MDM2 protein-protein interaction, we designed and synthesized twenty compounds with electrophilic and nucleophilic groups on the benzene ring. Among them, compounds 8i (K(i) = 91 nM) and 8n (K(i) = 89 nM) showed better binding activity than that of the reference drug Nutlin-3a (K(i) = 121 nM). In addition, in vitro antitumor activity against Saos-2, U-2 OS, A549 and NCI-H1299 cell-lines were assayed by the MTT method. Especially, compounds 8i and 8n possessed excellent biological activity and good selectivity comparable to Nutlin-3a, which were promising candidates for further evaluation.

Synthesis and biological evaluation of 7-alkenyl homocamptothecins as potent topoisomerase I inhibitors.

Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered ß-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.

[Determination of sodium by near infrared spectroscopy].

The research on near infrared spectroscopy of sodium in biological and medicine is significant. Sodion is the main component of electrolytes in human blood and electrolytes help maintain the body's acid-base balance. In the present paper the concentration of sodium was determined with the use of NIR spectra. On the basis of NIR spectroscopic measurement mechanism of sodion, prediction models of the concentration of sodium were developed with linear regression using the absorbance at selected wavelengths. In order to reduce temperature perturbations to water bands with the measurement of sodium, Partial least squares regression (PLS) was adopted using select spectra area. The result shows that the determination coefficients (R2) = 99.82%, the root mean square error of cross validation (RMSECV) = 14.5, and the residual prediction deviation (RPD) = 23.7, for the calibration model. It meets the daily requirements of biochemical detection accuracy. This technique can be applied to quantitative analysis of sodion in the hospital laboratory.

Design, synthesis and structure-activity relationships of new triazole derivatives containing N-substituted phenoxypropylamino side chains.

The incidence of invasive fungal infections and resistance to antifungal agents is increasing dramatically. It is highly desirable to develop novel azoles with improved biological profiles. The structure-activity relationship (SAR) of the N-substitutions was investigated in this study. In vitro antifungal activities revealed that sterically large groups were not favored for the N-substitutions. The removal of the N-substitutions had little effect on the antifungal activity. Two compounds with free amine group (i.e.9a and 10a) showed excellent activity with broad antifungal spectrum. The SAR results were supported by molecular docking and the N-substitutions were found to be important for the conformation of the side chains. The SAR and binding mode of the azoles are useful for further lead optimization.

Synthesis of novel benzoxanthone analogues as non-Camptothecin topoisomerase I inhibitors.

Structure modification of the side chain of the lead compound benzoxanthone provided a series of benzoxanthone analogues and 12 of them were first reported. The results showed that most of these compounds had moderate cytotoxicity against tumour cells with the 50% inhibition concentration in the micromolar range. Furthermore, benzoxanthone derivatives 5, 6c, 7a and 7e, showed potent topoisomerase I (Topo I) inhibitory effect and the results indicated that some compounds had potential for development as non-Camptothecin (CPT) topoisomerase I inhibitors.

Synthesis and biological evaluation of thio-benzodiazepines as novel small molecule inhibitors of the p53-MDM2 protein-protein interaction.

A series of thio-benzodiazepine p53-MDM2 inhibitors were designed and synthesized based on the principle of bioisosterism. Most of the thio-benzodiazepines had nanomolar to micromolar affinity toward MDM2. Particularly, compounds 8a (K(i) = 0.52µM) and 8f (K(i) = 0.32 µM) showed binding activity comparable to the positive drug nutlin-3a (K(i) = 0.23 µM). Meanwhile, compound 8j exhibited excellent antitumor activity against the U-2 OS human osteosarcoma cell line with an IC(50) value of 1.06 µM, which was about 23 times higher than that of nutlin-3a. The docking model also successfully predicted that this class of compounds mimicked three p53 critical residues binding to MDM2. The thio-benzodiazepines represent a promising class of non-peptide inhibitors of the p53-MDM2 interaction.

Synthesis and biological evaluation of novel homocamptothecins conjugating with dihydropyrimidine derivatives as potent topoisomerase I inhibitors.

Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH2) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7-formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435 and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.

Synthesis of 9-(heteroarylmethylidene)amino derivatives of homocamptothecin with biological activities.

Six 9-(heteroarylmethylidene)amino derivatives, 2a-2f, of homocamptothecin were synthesized for the first time by total synthesis in 22 steps and biologically evaluated as inhibitors of topoisomerase I. Moreover, the antitumor activities of 2a-2f against three human tumor cell lines, i.e., A-549, MDA-MB-435, and HCT-116, were determined and the results showed that compound 2c was the most active homocamptothecin derivative against the A-549 (IC(50) =0.046 µM) and HTC-116 tumor cells (IC(50) =3.67 µM), with a ca. 50 times higher activity than the reference drug topotecan (TPT) against the lung cancer cell line A-549.

Synthesis and biological evaluation of novel 7-acyl homocamptothecins as Topoisomerase I inhibitors.

A series of novel 7-acyl derivatives of homocamptothecin (hCPT) were designed and synthesized with the purpose to improve antitumor activity of hCPT, via Minisci free-radical reaction from 10-methoxyhomocamptothecin. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, MDA-MB-435 and HCT116). For MDA-MB-435 cell line, compounds, 6a, 6b, 6k and all of 7-alkylcabonyl homocamptothecin derivatives showed higher in vitro inhibitory activities than topotecan (TPT). Furthermore, compounds 6d, 6e, and 6k showed highly potent inhibitory activities with the IC50 values from less than 1 nM to 2.2 nM. In Topoisomerase I (Topo I)-induced DNA cleavage assay, compounds 6a, 6d, and 6k, as compared to CPT, revealed higher Topo I inhibitory activity.

[A method for quantitative analysis system of alkane gaseous mixture with near infrared spectroscopy].

A method for online quantitative analysis system of alkane gaseous mixture with near infrared spectroscopy is described in the present paper. A single plane diffraction grating is used as the principal device in the monochromatic spectrum system. The key parameters of the monochromator were deduced and calculated in detail. A quantitative analysis system was designed and constructed according to the parameters. The narrow-band beam testing experiments and spectral scanning experiments of seven kinds of single-component alkane gases were accomplished on the above hardware system platform. The narrow-beam experiments show that a 10 nm narrow-band beam spectra was successfully obtained by the monochromatic system when the entrance slit width is 2 mm. And a step-scanning resolution of the outgoing beam's center wavelength with 0.1 nm can be realized within the spectra of 1.2-1.8 microm. The spectral scanning experiments indicate that there was some stronger characteristi absorption spectrum existing between the spectra of 1.6-1.8 microm, which is consistent with the HITRAN spectral database. And there is serious cross-aliasing phenomenon existing among the absorption spectra. These experiments demonstrate that this method has a successful application in mixed gas monitoring and on-line analysis with the characteristics of simple structure and low cost. And it also provides further technical reserves and opens a path way to spectral analysis in the follow-up studies.

[On-line and in-situ spectral analysis of multicomponent gas mixture with same molecular group].

Aimed at the problem that Fourier transform infrared (FTIR) spectral analysis can't be used solely to analyze complex gas mxiture, in which there are many gas compositions, some compositions have same molecular group, and the concentrations of some compositions range greatly, in the present paper, a new spectral analysis method is proposed. For this method, the effects of gas temperature and gas pressure on the analysis result are taken into account, and feature variable extraction, recognition and correction of spectral disorder, robust modeling and multi-layer modeling with neural network (NN) are used to build gas mixture analysis models. At the end of this paper, on-line analysis of five alkane gases is taken as example to test the performance of the analysis method. CH4, C2 H6, Ca3 Ha8, iso-C4 H10 and n-C4 H10 are taken as object gases while iso-C5 H12 and n-C5 H12 are looked as disturbing gases. The comparison results that analysis result curves of FTIR overlap that of gas chromatograph indicate that FTIR can be solely used in on-line and in-situ analysis of multicomponent gas mixture with same molecular group if the analysis method presented in this paper is used.

Synthesis and evaluation of 9-benzylideneamino derivatives of homocamptothecin as potent inhibitors of DNA topoisomerase I.

A series of novel 9-benzylideneamino derivatives of homocamptothecin were synthesized via Friedlaender cyclization from our obtained intermediate 5. All the compounds were evaluated for in vitro cytotoxicity against three cancer cell lines (A549, LOVO and MDA-MB-435). Most of these derivatives possessed potent growth inhibitory effect on all the tested cell lines and four compounds (6d, 6f, 6i, 6k) showed higher inhibitory activities with the IC50 values of 2.3 nM-9.8 nM against breast cancer cell than topotecan. As compared to CPT, compound 6f revealed higher topoisomerase I inhibitory activity.

Trifluoromethyl-promoted homocamptothecins: synthesis and biological activity.

The homocamptothecin (hCPT) represents a new class of topoisomerase inhibitor which combines enhanced plasma stability and strong antitumor activity. Fluorine imparts desirable characteristics to drugs by modulating both the pharmacokinetics and pharmacodynamic properties of a drug. Therefore, in an attempt to improve the antitumor activity of homocamptothecins, seven new 7-trifluoromethylated homocamptothecin derivatives were prepared by proline-catalyzed Friedlander annulation. The antitumor activity in vitro and in vivo on cancer cell lines, and inhibitory properties of topoisomerase I-mediated DNA cleavage of compounds 6c and 8b were evaluated. Several of these trifluoromethylated hCPT derivatives (such as 6a, 6b and 6c) possessed higher in vitro antitumor activity than topotecan (TPT). Especially, the compound 6c showed effective in vivo antitumor activity comparable to that of TPT.