Real-time bioprocess and automated feed control with in-line Raman sensor

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Therapeutic effect of Cerebrolysin on reducing impaired cerebral endothelial cell permeability

Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and fibrin significantly increased proinflammatory and procoagulation proteins of intercellular adhesion molecule 1, high mobility group box 1, tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced tight junction proteins zonular 1, occludin and claudin. However, Cerebrolysin significantly diminished and reversed tPA- and fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and fibrin-augmented proinflammatory and procoagulation proteins and significant elevations of tPA- and fibrin-decreased tight junction proteins. The beneficial effect of Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct peptide composition, failed to show the reduction of tPA- and fibrin-impaired permeability. These data indicate that cererbrolysin has a therapeutic effect on tPA- and fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation proteins and by elevating tight junction proteins

消化内科护理风险及管理对策分析

Objective: To explore the common nursing risk in department of gastroenterology and clinical nursing management strategies, in order to provide the basis for nursing in the department of gastroenterology. Methods: Analyze and discuss of the common characteristics of nursing risk in our hospital department of gastroenterology, and summarize the countermeasure and method of correlation of risk management. The implementation of risk management as the observation group and the other as the control group, and clinical nursing effect between the two groups would be compared. Moreover, nursing ability improvement circumstance for the nursing staff was compared before and after the implementation of risk management. Results: The observation group after the risk management of nursing errors, medical disputes and the patients' satisfaction were better than the control group, there is statistical significance (P< 0.05). After the risk management in Department of gastroenterology, nursing work of nursing staff in various digestive operation is proficient, medical record documents writing norms, communication ability, the emergency ability is superior before the implementation of risk management, there is statistical significance (P<0.05). Conclusion: In the nursing management in the Department of gastroenterology, the implementation of risk management is helpful to improve the ability of nursing and the nursing quality, reduce nursing risk in Department of gastroenterology, and improve hospital patient satisfaction.目的  探讨消化内科中常见的护理风险以及临床护理管理对策，为消化内科的安全护理提供依据。方法  对本院消化内科常见的护理风险特点进行分析讨论，总结相关风险管理的对策与方法。将未实施风险管理作为对照组，实施风险管理为观察组，比较两组临床护理效果，并对护理人员实施风险管理前、后护理能力改善情况进行对比研究。结果  观察组实施风险管理后护理差错、医疗纠纷以及患者护理满意度方面均优于对照组，比较差异有显著性（P<0.05），具有统计学意义。实施风险管理后护理人员对消化内科各种护理工作操作熟练程度，病历文书书写规范性，沟通能力，应急能力等方面均优于实施风险管理前，比较差异有显著性（P<0.05），具有统计学意义。结论  在消化内科的护理管理中，实施风险管理有助于提高护理能力和护理质量，降低消化内科的护理风险，提高患者的满意度

Development of a high-density CHO-C system enables rapid protein production in 10 days

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Pityriasis lichenoid-like mycosis fungoides in a 9-year-old boy: A case report

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Taiwan Oscillation Network

The Taiwan Oscillation Network (TON) is a ground-based network to measure solar intensity oscillations to study the internal structure of the Sun. K-line full-disk images of 1000 pixels diameter are taken at a rate of one image per minute. Such data would provide information onp-modes withl as high as 1000. The TON will consist of six identical telescope systems at proper longitudes around the world. Three telescope systems have been installed at Teide Observatory (Tenerife), Huairou Solar Observing Station (near Beijing), and Big Bear Solar Observatory (California). The telescopes at these three sites have been taking data simultaneously since October of 1994. Anl – v diagram derived from 512 images is included to show the quality of the data

Omics approach for generating a high-yield CHO cell line producing monoclonal antibodies

Chinese hamster ovary (CHO) cells are extensively used for the industrial manufacture of therapeutic antibodies. Generating high producing cell lines for secretory protein production requires knowing the bottleneck in the cellular machinery for protein expression. Integration site of gene of interest (GOI) is one of the important factors that influence the protein productivity. Even though screening of cells randomly integrated GOI can select high producing cells, the selected cell might not stable due to the chromosome instability. Here, we would like to look for host integration sites where GOI is high yield and stable by screening a single copy integration system. We developed several methods to identify integration sites including PCR based, whole genome sequencing based, and a platform to integrate a single copy of GOI into host genome. By determining the integration sites of the high producing clones, we can elucidate the major high yield sites for target gene expression. We have also employed the genome-editing tool, TALEN and CRISPR/cas9 to specifically integrate the vector with an antibody gene into two integration sites of CHO genome. Our data showed, IS1 and IS2 integration sites can be actively edited and specifically integrated an antibody expression vector of 15kb by either TALEN or CRISPR/Cas9. We successfully established site specifically integrated cell pools and expanded the FACS-sorted single cell into a cell line. Each single cell derived cell lines was confirmed by junction-PCR and sequence analysis. Furthermore, these single cells derived CHO cell lines are shown to express antibody gene with high titer. With the combination of omics knowledge and toolbox, including CHO genomics, transcriptomics and CHO specific microarray, GOI can be stably and highly produced

High-yield antibody production using targeted integration and engineering CHO host

To identify the high expression sites in the CHO cells, we employed NGS to analyze the integration sites of a high producing cell line (titer \u3e 3g/L). The pair-end reads with one read mapped to the vector and the other read mapped to the CHO reference genome are extracted to identify the integration sites. To test the expression activity of the integration sites, we employed CRISPR/Cas9 to specifically integrate the antibody gene into CHO genome for expression. Our data showed 4 integration sites are in the high producing cell line. Among the 4 integration site, one integration site was tested by CRISPR/Cas9 for target integration of antibody gene for expression. The target integrated cell pool present higher expression level (130 mg/L/copy) and less copy number when compared other integration sites. Through single-copy integration method, we can also achieve 60-150 mg/L/copy in a batch culture. About 80% of the single-copy cell clones were stable at generation 60. We have also applied the CHO-specific microarray transcriptomics technology to identify genes that contribute to high productivity. Transfection of our proprietary dual promoter vector J 1.0 resulting in 1.65 to 2.4 fold increase in the expression in engineered CHO DXB11 host. Through fed-batch process development, 3 – 5 g/L mAb productivity can be achieved through targeted integration and engineered CHO host