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Ultrasonic-assisted grinding technology can significantly improve the processing quality of hard and brittle materials, with the continuous improvement of machining accuracy, and the three-dimensional roughness characterization of ultra-precision machined surfaces has gradually become a research hotspot. However, it is necessary to develop a reliable three-dimensional roughness prediction model because the experimental measurement of three-dimensional roughness is time-consuming and laborious. In this study, the probabilistic analysis of the two-dimensional ultrasonic-assisted grinding (TUAG) process of nano-ZrO2 ceramics was carried out, and the influence of the random distribution, random prominence height, and unique motion trajectory of abrasive particles on the material removal mechanism of workpiece surface was explored. On that basis, a probabilistic calculation method for the height of residual material on the surface of nano-ZrO2 ceramics under TUAG was further proposed to obtain the more accurate height value which accords with the characteristics of three-dimensional roughness sampling. According to the obtained height value, the three-dimensional roughness prediction model of nano-ZrO2 ceramic under TUAG was developed. The accuracy and reliability of the theoretical model have been verified by the simulation analysis and the TUAG experiment of nano-ZrO2 ceramics, and this study can provide a new theoretical reference to evaluate and predict the quality of the ultra-precision machined surface of hard and brittle materials.

Being an active scaffold in bone tissue engineering, hydrogel self-assembled from biomimetic peptide amphiphile (PA) has excellent ability to induce osteogenic differentiation and osteogenesis. Here, a multifunctional scaffold based on bone morphogenetic protein-2 (BMP-2) mimicking peptide, RGDS, and phosphoserine has been developed to enhance osteogenesis. Cell experiments in vitro displayed that the hydrogel could effectively promote rat messenchymal stem cells (rMSCs) proliferation and induce them differentiation into oesteblasts. The up-regulated RNA expression of osteogenic marker genes, like BMP-2, osteopontin (OPN), osteocalcin (OCN) and runt-related transcription factor 2 (Runx2) revealed that the scaffold could accelerate rMSCs differentiation at RNA level. Further studies on rat skull defect model demonstrated that the multifunctional scaffold exhibited excellent repair ability due to a potential synergistic effect of biomimetic peptide and phosphoserine. Histochemical/immunohistochemical staining results showed that expressions of alkaline phosphatase (ALP) and OCN was significantly up-regulated, indicating that the hydrogel could accelerate maturation of osteoblast precursors during the whole repairing process and be a promising bioactive scaffold for bone repairing.

In order to accurately and quickly perform transient stability assessment (TSA), this paper introduces extreme learning machine (ELM) into TSA, and proposes a power system transient evaluation method based on improved adaptive differential evolution algorithm and ELM. First, a set of original features are constructed and set as the input of the ELM model, deep-level relationship between the grid steady state and the key feature are established. Then, an improved adaptive differential evolution algorithm (JADE) is presented to optimize the parameters of extreme learning. By adopting an improved mutation strategy and introducing an optimal particle local optimization mechanism, the global optimization ability is improved. Finally, simulation verification was performed on a provincial power grid. The results show that the proposed method shows better classification performance than the other traditional stability evaluation methods.

The aim of the present study was to identify key genes and signaling pathways associated with the pathogenesis of juvenile spondyloarthritis (JSA). The gene expression profile dataset {"type":"entrez-geo","attrs":{"text":"GSE58667","term_id":"58667"}}GSE58667, including data from 15 human whole blood samples collected from 11 patients with JSA and four healthy controls, was analyzed to identify differentially expressed genes (DEGs) associated with disease characteristics. Additionally, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the DEGs were performed. Protein-protein, microRNA-transcription factor and chemical-gene interaction networks were constructed. A total of 326 DEGs, 196 upregulated and 130 downregulated, were identified. DEGs, including C-X-C motif chemokine ligand 5 (CXCL5), BCL2 interacting protein 3 like (BNIP3L), dual specificity phosphatase 5 (DUSP5) and tumor protein p53 (TP53) were enriched in functions associated with apoptosis, the cell cycle and immune responses. KEGG pathway enrichment analysis revealed that pathways associated with inflammation and the mitogen-activated protein kinase 1 (MAPK) signaling pathway were the most enriched by DEGs. The results of the present study indicated that the MAPK signaling pathway and four genes, including CXCL5, BNIP3L, DUSP5 and TP53, may be implicated in the pathogenesis of JSA.

A range-reduced static definition-use (def-use) fault detection framework is proposed to improve the scalability, but still retain its accuracy, when applied to large application programs. It casts common faults, such as null pointer dereferences, undefined references, buffer overflows, and memory leaks into a common def-use fault pattern, and uses a two-level path-insensitive approach to classify variable uses that can trigger faults into must-trigger, must-not-trigger, and may-trigger categories depending on whether the unsafe uses can actually be, never be, or may be executed. For those must-trigger unsafe uses, faults are immediately reported, and those must-not-trigger uses are dropped from further analysis. The already reduced program range that is relevant to the may-trigger unsafe uses is further reduced by using a binary decision diagram encoded path extraction scheme for more accurate, but more expensive, path-sensitive analysis. A prototype has been built using this approach, and a set of large realistic applications (a total of more than 4.8 MLOC) was tested for such common types of def-use faults. Compared with existing popular path-sensitive detection tools such as Clang Static Analyzer, we find our approach incurs less analysis time, but achieves good accuracy with a low false positive rate and no false negative.

P(AM-DMDAAC) (PDA) was synthesized by ultrasound assisted polymerization with dimethyl diallyl ammonium chloride (DMDAAC) and acrylamide (AM) as the monomers. The reaction conditions of polymerization were investigated by single factor approach and L 16 (4 5 ) orthogonal array. Results showed that the intrinsic viscosity of PDA could reach 14.6 dL/g with the optimum polymerization conditions as following: monomer concentration of 30%, temperature of 30 °C, ultrasound time of 1 h, monomer mass ratio (m (DMDAAC) :m (AM) ) of 2:8, initiator concentration of 0.4‰, sodium benzoate concentration of 0.5‰, ethylene diamine tetraacetic acid (EDTA) concentration of 0.5‰, solution pH value of 6 and urea concentration of 0.3‰. The self-made PDA was characterized by several instruments. The results of FTIR and 1 HNMR indicated that PDA was successfully polymerized by AM and DMDAAC. DTA-TGA showed that PDA was very stable at room temperature. And SEM proved the porous and mushroom shaped structure of PDA. For PDA used as flocculant in sludge dewatering experiment, the results showed that the filter cake moisture content and the supernatant turbidity could be reduced to 66.3% and 24.1 NTU, respectively. Comparing with other four cationic polyacrylamides, the filter cake moisture content could be reduced by 2.0-7.4% and the supernatant turbidity could be reduced by 18.3-32.1% via using self-made PDA, that was to say, the dewatering efficiency of self-made PDA was the best. Besides, the optimal dosage of self-made PDA was the least, and the cost analysis showed that it was also favorable, a 14.6-39.3% cost could be saved by using self-made PDA.

pH-triggered conformational change and subsequent re-assembly of nanostructures provide a new strategy in nanomedicine for controlled drug release and enhanced therapy. Here, we reported the development of a novel pH-responsive nano-assembly as a drug carrier from peptide amphiphile (PA) consisting of mimicking peptide and stearic acid moieties. The mimicking peptide is a basic 17-amino acid peptide derived from antennapedia homeodomain, and undergoes a conformational transition of the secondary structure from β-sheet at pH7.4 to α-helix at pH5.0. Such transition therefore leads to simultaneous evolution of the self-assembled structure of PA from nanosphere to nanofiber, promotes assemblies retention and then release drugs in the cytoplasm of tumor cell. In vitro studies showed that the doxorubicin (Dox)-loaded PA nanoparticle (PA@Dox) could be uptaken efficiently by the cell due to the membrane penetrating capability of the mimicking peptide and subsequently the released Dox further induce apoptosis of murine colon carcinoma CT26 (MCCC) cell. In a mouse xenograft model of MCCC, administration of PA@Dox via lateral tail vein injection could remarkably retard the tumor growth. The overall results suggested that the PA-based nanocarriers adopting the novel strategy of pH-triggered secondary structural change could enhance therapeutic efficacy and be used as a promising platform for potential development of new generation of drug carriers for cancer therapy.

Bone morphogenetic protein-2 biomimetic peptide (BMPBP) is a potent osteoinductive cytokine and plays a critical role during bone regeneration. Efforts to prepare hydrogels with surface modification or physical absorption of bioactive molecules do not provide sufficient bioactivity to meet the requirements of clinical application. The goal of this study was to form a three-dimensional hydrogel comprised of BMP-2 core sequence oligopeptide, phosphoserine, a synthetic cell adhesion peptide (RGDS), and polyaspartic acid to synergistically promote osteogenesis. Experiments performed in vitro revealed that the peptide gel was conducive to adhesion and proliferation of rat marrow mesenchymal stem cells (rMSCs). In addition, RT-PCR analysis indicated that rMSCs allowed better expression of osteogenesis-related genes such as BMP-2, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Use of the rat cranial bone defects model with micro-CT 3D reconstruction showed that bone regeneration patterns occurred from one side edge toward the center of the area implanted with the prepared biomimetic peptide hydrogels, demonstrating significantly accelerated bone regeneration. This work will provide a basis to explore the further application potential of this bioactive scaffold.

Effective Protein A column regeneration is important in therapeutic monoclonal antibody (mAb) production for product quality and process economics. To design a robust and effective regeneration strategy, resin compatibility, microbial inactivation efficiency and cleaning effectiveness are three major considerations. Regenerating Protein A column using acidic (e.g. acetic acid) and/or caustic (e.g. NaOH) solutions is a common approach. However, it is challenging to balance between resin performance decline and adequate microbial control in choosing the right caustic solution concentration, even for resin with enhanced caustic tolerance such as MabSelect SuRe. This report introduces an enhanced regeneration strategy for MabSelect SuRe resin. The approach applies benzyl alcohol in low concentration acetic acid and NaOH (100 mM) solutions in sequential steps to regenerate MabSelect SuRe resin for reuse. Such solutions demonstrated good resin compatibility in resin functional test after extended solution incubation time, and demonstrated superior microbial control using eight test microorganisms. The cleaning effectiveness of the proposed strategy is demonstrated by carryover study, where product and impurity carryover was below detection limit. Finally, during a resin lifetime study, consistent step yields and product quality attributes were demonstrated, and no carryover was observed, up to 150 purification cycles. A viral clearance study further demonstrated that aged resin at the end of the resin lifetime had comparable viral clearance performance compared to new resin. No active virus was detected in the elution pool of the subsequent blank runs. These studies further verified the robustness of the proposed regeneration strategy for MabSelect SuRe resin.

To investigate the distribution of statin therapy correlated gene polymorphism allele CYP2D6*10 (C188T) in Ningxia Hui nationality and to discuss the relationship between the gene polymorphism allele CYP2D6*10 (C188T) and the lipid-lowering efficacy of simvastatin and hyperlipidemia.One hundred and fifty healthy people (80 males and 70 females) and 200 hyperlipidemia patients (105 males and 95 females) were recruited at Ningxia People's Hospital. Genotypes were determined by using allele-specific amplification (ASA-PCR) in 150 healthy controls and 200 patients with hyperlipidemia. Relationships between genotypes and lipid levels and the lipid-lowering efficacy of simvastatin were analyzed.The distribution frequency of the CYP2D6*10 allele was 47.6% in the Ningxia Hui nationality. There was no significant correlation between the CYP2D6*10 allele and hyperlipidemia. At 8 weeks after treatment with simvastatin, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were more obviously decreased with the CC genotype than the CT and TT genotypes, with significant differences.Distribution of the gene polymorphism of CYP2D6*10 is ethnically and geographical different. The allele T of CYP2D6*10 is not related to hyperlipidemia. CC expression seemed to increase the lipid-lowering effects of simvastatin. The hyperlipidemia patients with CC genotype should take lower doses of simvastatin than those with CT/TT genotype in the Ningxia Hui population.

Based on the field-survey prototype hydrology data in typical years, the effect during the running periods of different dispatch modes of the Three Gorges Reservoir on the water regimes in Dongting Lake area is comparatively analyzed. The results are shown as follows. (1) The influence periods are from 25 May to 10 June, from 1 July to 31 August, from 15 September to 31 October and from December to the next April, among which the influence of the water-supplement dispatch in the dry season is not very sensitive. (2) During the period under the pre-discharge dispatch, the runoff volume slightly increases as well as both the average water level and the highest water level rise in the usual year. While in the wet and dry years, the average increase in the runoff volume is 40.25×108 m3 and the average rises of the average water level and the highest water level are both 1.06 m. (3) As for the flood-storage dispatch, the flood volume increases slightly, in the dry and wet years, the flood volume, the average water level and the highest water level averagely reduce by 444.02×108 m3, 2.64 m and 1.42 m respectively. (4) Under the water-storage dispatch, the runoff volume slightly increases and the water level heightens in a sort in the usual year. And in the dry and wet years, the average decreases in the runoff volume, the average water level and the highest water levels are respectively 185.27×108 m3, 3.13 m and 2.14 m. (5) During the period under the water-supplement dispatch, the runoff volume, the average water level and the highest water levels averagely decline by 337.7×108 m3, 1.89 m and 2.39 m respectively in the usual and wet years. However, in the dry year, the runoff volume increases as well as the average and highest water levels slightly go up.

Rad51 and Rad54 play crucial roles during homologous recombination. The biochemical activities of human Rad51 (hRad51) and human Rad54 (hRad54) and their interactions with each other are well documented. However, it is not known how these two proteins work together to bypass heterologous sequences; i.e. mismatched base pairs, during homologous recombination. In this study, we used a fluorescence resonance energy transfer assay to monitor homologous recombination processes in real time so that the interactions between hRad54 and hRad51 during DNA strand exchange and branch migration, which are two core steps of homologous recombination, could be characterized. Our results indicate that hRad54 can facilitate hRad51-promoted strand exchange through various degrees of mismatching. We propose that the main roles of hRad51 in homologous recombination is to initiate the homology recognition and strand-exchange steps and those of hRad54 are to promote efficient branch migration, bypass potential mismatches and facilitate long-range strand exchanges through branch migration of Holliday junctions.

Human RAD51 and RAD54 are key players in homologous recombination, a process that requires homology recognition and strand invasion by a RAD51-single-stranded DNA (ssDNA) nucleoprotein filament and chromatin remodeling by RAD54. Here we use in vitro chromatin reconstitution systems to show that RAD51-ssDNA stimulates RAD54-dependent chromatin remodeling in a homology-dependent, polarity-independent manner. This stimulation was not seen with RAD54B or other remodelers. Chromatin remodeling by RAD54 enabled strand invasion by RAD51-ssDNA on nucleosomal templates, which was homology- and polarity-dependent. Three natural RAD54 mutants found in primary cancer cells showed specific defects in remodeling or in the RAD54-RAD51 interaction. We propose that RAD54 is recruited by RAD51-ssDNA filament to the chromatin of the intact chromosome and that it remodels that chromatin to facilitate accessibility for strand exchange.