217 research outputs found

    IN VITRO ENZYMATIC POLYSIALYLATION OF THERAPEUTIC ANTIBODIES USING ENGINEERED GLYCOSYLTRANSFERASES

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    81 pagesAntibody-based immunotherapy is one of the most significant medical advancement of the 21st century. Monoclonal antibodies (mAb) and their conjugation variants are found to be effective in treating a myriad of conditions including autoimmune and cancer diseases. mAb is a complex biomolecule consisting of multiple polypeptides and post-translational modifications including disulfide bond and N-linked protein glycosylation. Such complexity contributes to a challenge in biomanufacturing, quality assessment, and storage of the mAb, which leads to a high cost of antibody therapy. Hence one of the major objectives of the mAb engineering is to increase its circulating half-life which will help to both reduce therapy cost and improve health care quality. In this work, we proposed using a cell-free glycoengineering strategy to enhance therapeutic antibody half-life. We employed engineered sialyltransferases derived from Campylobacter jejuni and Neisseria meningitidis to extend IgG-Fc N-glycans at the non-reducing end with the polysialic acid polymer. Using our optimized one-pot two-stage biosynthesis protocol, therapeutic antibody Herceptin modified with polysialic acid structure was efficiently produced and structurally validated. The ongoing works including a more extensive structural characterization as well as ex vivo functional assays will be discussed. Taken together, we anticipate cell-free glycoengineering technology producing polysialylated IgG will provide an attractive route for producing therapeutic mAb with enhanced stability and circulating half-life

    The Construction of Higher Education Entrepreneur Services Network System a Research Based on Ecological Systems Theory

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    AbstractThe article aims to completely, systematically and objectively analyze the current situation of Entrepreneurship Education in China with Ecological Systems Theory. From this perspective, the author discusses the structure, function and its basic features of higher education entrepreneur services network system, and puts forward the opinion that every entrepreneurship organization in higher education institution does not limited to only one platform. Different functional supporting platforms should be combined closed through composite functional organization to form an integrated network system, in which each unit would impels others’ development

    Documenting Impacts of Hydro-Meteorological Events Using Earth Observation

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    The ambition of H2020 OPERANDUM project is to develop and document Nature Based Solutions (NBS) to mitigate risks associated with hydro-meteorological (HM) hazards. NBS mitigate risks by reducing the vulnerability of a particular system. The aim of this work is to demonstrate the use of multisource remote sensing data in documenting the impact of extreme HM events to advance knowledge on vulnerability and exposure. In particular the focus is to document past impacts due to extreme events selected from a characterization of recent (3 0 years) HM events in 11 Open Air Laboratories (OALs) where co-design, co-development and deployment of NBS are taking place. The impacts were documented by applying a wide spectrum of satellite image data and other, close - range, remote sensing techniques. A better understanding of the consequences due to extreme HM events in a particular area (OALs) is essential to identify elements at risk and expected to provide a reference to evaluate the reduction of vulnerability and mitigation of risks past the completion of NBS.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Optical and Laser Remote SensingGeo-engineerin

    Luminance Adaptive Biomarker Detection in Digital Pathology Images

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    AbstractDigital pathology is set to revolutionise traditional approaches diagnosing and researching diseases. To realise the full potential of digital pathology, accurate and robust computer techniques for automatically detecting biomarkers play an important role. Traditional methods transform the colour histopathology images into a gray scale image and apply a single threshold to separate positively stained tissues from the background. In this paper, we show that the colour distribution of the positive immunohis-tochemical stains varies with the level of luminance and that a single threshold will be impossible to separate positively stained tissues from other tissues, regardless how the colour pixels are transformed. Based on this, we propose two novel luminance adaptive biomarker detection methods. We present experimental results to show that the luminance adaptive approach significantly improves biomarker detection accuracy and that random forest based techniques have the best performances

    Chinese dequity: transaction structure and two applications

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    In recent years, the financial market has been under the dual pressure of macro-economic downturn and deleveraging of industry entities. In this context, the regulating authorities have been encouraging enterprises to resort to debt replacement in order to lower financing cost. Therefore, the financing instrument characterized by "Chinese dequity" came into existence (Chen & Kensinger, 1991). As an innovative investment business, it has significantly contributed to China's economic development by making financing easier for enterprises and relieving the financial pressure on governments and banks. However, many problems have surfaced in its application in China, most notably the uneven distribution of each party’s control rights and interests, poor risk control and management, and a yet-to-be-perfected theoretical system. Further optimization is thus needed. In the above context, this thesis intends to ensure the consistency between the ultimate financing result and the expected goal by designing a transaction structure for "Chinese dequity" in construction projects. Such financing transaction structures of two projects are studied as cases, namely, the PPP Project of the Underground Utility Tunnel in HS City and XNY Private Chemical Construction Project. The author studies many theories, introduces the concept of "control rights preference", and constructs the optimal control rights allocation model by adopting stochastic cooperative games. On this basis, the designed transaction structure in infrastructure construction, allocation of control rights of participants, and existing problems are analyzed. In the end, a conclusion is made and suggestions for further research given.Nos últimos anos, o mercado financeiro tem estado sob a dupla pressão da recessão macroeconómica e da desalavancagem de entidades industriais. Neste contexto, as autoridades reguladoras vêm incentivando as empresas a recorrer à substituição de dívidas para reduzir o custo de financiamento. Portanto, surgiu o instrumento de financiamento caracterizado pela "deidade chinesa" (Chen & Kensinger, 1991). Como um negócio de investimento inovador, tem contribuído significativamente para o desenvolvimento económico da China fazendo mais fácil o financiamento para empresas e aliviando a pressão financeira sobre governos e bancos. No entanto, muitos problemas têm surgido em sua aplicação na China, principalmente a distribuição desigual dos direitos de controle e interesses de cada parte, o insatisfatório controle e gerenciamento de risco e, um sistema teórico ainda a ser aperfeiçoado. Otimização adicional é, portanto, necessária. No contexto acima, esta tese pretende garantir a consistência entre o resultado definitivo do financiamento e o objetivo esperado, projetando uma estrutura de transação para a "deidade chinesa" em projetos de construção. Tais estruturas de transação de financiamento de dois projetos são estudadas como casos, para esclarecer, o Projeto PPP do Túnel Utilitário Subterrâneo na cidade de HS e o Projeto Privado de Construção Química de XNY. O autor estuda muitas teorias, introduz o conceito de “preferência de direitos de controle” e constrói o modelo ótimo de alocação de direitos de controle adotando jogos cooperativos estocásticos. Com base nisso, a estrutura de transação projetada na construção de infraestrutura, a alocação de direitos de controle dos participantes e os problemas existentes são analisados. No final, uma conclusão é feita e sugestões para mais pesquisas são dadas

    Chinese dequity: transaction structure and two applications

    No full text
    In recent years, the financial market has been under the dual pressure of macro-economic downturn and deleveraging of industry entities. In this context, the regulating authorities have been encouraging enterprises to resort to debt replacement in order to lower financing cost. Therefore, the financing instrument characterized by "Chinese dequity" came into existence (Chen & Kensinger, 1991). As an innovative investment business, it has significantly contributed to China's economic development by making financing easier for enterprises and relieving the financial pressure on governments and banks. However, many problems have surfaced in its application in China, most notably the uneven distribution of each party’s control rights and interests, poor risk control and management, and a yet-to-be-perfected theoretical system. Further optimization is thus needed. In the above context, this thesis intends to ensure the consistency between the ultimate financing result and the expected goal by designing a transaction structure for "Chinese dequity" in construction projects. Such financing transaction structures of two projects are studied as cases, namely, the PPP Project of the Underground Utility Tunnel in HS City and XNY Private Chemical Construction Project. The author studies many theories, introduces the concept of "control rights preference", and constructs the optimal control rights allocation model by adopting stochastic cooperative games. On this basis, the designed transaction structure in infrastructure construction, allocation of control rights of participants, and existing problems are analyzed. In the end, a conclusion is made and suggestions for further research given.Nos últimos anos, o mercado financeiro tem estado sob a dupla pressão da recessão macroeconómica e da desalavancagem de entidades industriais. Neste contexto, as autoridades reguladoras vêm incentivando as empresas a recorrer à substituição de dívidas para reduzir o custo de financiamento. Portanto, surgiu o instrumento de financiamento caracterizado pela "deidade chinesa" (Chen & Kensinger, 1991). Como um negócio de investimento inovador, tem contribuído significativamente para o desenvolvimento económico da China fazendo mais fácil o financiamento para empresas e aliviando a pressão financeira sobre governos e bancos. No entanto, muitos problemas têm surgido em sua aplicação na China, principalmente a distribuição desigual dos direitos de controle e interesses de cada parte, o insatisfatório controle e gerenciamento de risco e, um sistema teórico ainda a ser aperfeiçoado. Otimização adicional é, portanto, necessária. No contexto acima, esta tese pretende garantir a consistência entre o resultado definitivo do financiamento e o objetivo esperado, projetando uma estrutura de transação para a "deidade chinesa" em projetos de construção. Tais estruturas de transação de financiamento de dois projetos são estudadas como casos, para esclarecer, o Projeto PPP do Túnel Utilitário Subterrâneo na cidade de HS e o Projeto Privado de Construção Química de XNY. O autor estuda muitas teorias, introduz o conceito de “preferência de direitos de controle” e constrói o modelo ótimo de alocação de direitos de controle adotando jogos cooperativos estocásticos. Com base nisso, a estrutura de transação projetada na construção de infraestrutura, a alocação de direitos de controle dos participantes e os problemas existentes são analisados. No final, uma conclusão é feita e sugestões para mais pesquisas são dadas

    Study on Evolution of China’s Construction Industry Based on Input-Output Analysis and Complex Network

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    Exploring the evolution of China’s construction industry is conducive to the formulation of industrial policies. The construction industry is associated with many industries. Hence, the policies formed according to internal evolution of the construction industry are easy to direct the industry toward an unfavourable direction. This study aims to analyze the evolution of construction industry based on the relationships between the construction industry and other industries. The pull coefficients and push coefficients of China’s construction industry during 2001-2015 were calculated based on the input-output table. Complex network topologies of industries were constructed, and network topologies were used to analyze the network centrality and the cohesive subgroups. The evolutionary trend of China’s construction industry in interactions with other industries was explored. Results show that the pull and push effects of China’s construction industry experience a sharp reduction. The construction industry has the inclination to be transformed from a pillar industry to an industry driven by other industries. The control of the construction industry in the network is weakened. In conclusion, using input-out analysis and complex network to study the evolution of China’s construction industry can consider interaction of different industries, and provide certain theoretical references to formulate reasonable policies
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