Yuk-lan: a translation and commentary on a Chinese story of the Cultural Revolution period

One of the major functions of literature is to reveal the social and historical situation of the times. It is, however, dangerous to look at a certain type of literature and then generalize that the aspects presented there totally and truly reflect the situation of the time. The works of Ernest Hemingway and F. Scott Fitzgerald are good examples. Though Hemingway and Fitzgerald are contemporaries, their works represent two different life styles of the people who had lived through the First World War. While both of them are excellent writers, neither of their works should be read as a complete representation of the life of the Americans after the First World War. It is only by reading both their works and works by their contemporaries, such as Faulkner, that one can start to develop a general picture of\u27the time. In the case of modern Chinese literature, while the Peking Press and the Foreign Languages Press of the Chinese government have published literature in both Chinese and translations which reveals the promising side of the new society, literature which voices the disillusionment of the young people is relatively rare

Effects of class III malocclusion on young adults' vocal tract development

"A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2009."Thesis (B.Sc)--University of Hong Kong, 2009.Includes bibliographical references (p. 27-30).published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Glucocorticoids modulate CHO cell glycosylation in chemically-defined media

Product quality attributes are critical to the therapeutic activity of manufactured biologics. One key quality attribute is glycosylation, which can dramatically affect antibody activity, specificity, and/or immunogenicity. As such, a high priority during drug development is to control the glycosylation profile. Glycosylation is significantly influenced by the composition of cell culture media, including sugars, amino acids, vitamins, trace metals, and even metabolic waste products. Formulation of chemically-defined growth and feed media provides the ability to fine tune the concentrations of media components that regulate glycosylation through metabolic shifts and cell signaling. For example, some of the current strategies for modulating glycosylation involve combinations of guanosine, uridine, MnCl2, galactose, and other sugars. While these components can be adjusted to alter glycosylation, they can also negatively impact cell growth or productivity. Therefore, identifying a broad array of glycosylation control strategies is necessary for tailoring media to different cell lines. Glucocorticoids are a class of compounds commonly found in cell culture media that have demonstrated viability enhancing properties in growth of CHO cells. This class of steroid hormones regulates programmed cell death in CHO cells by triggering increased expression of the anti-apoptotic gene Tsc22d3 [Jing et al., Biotechnol Prog. 2012; 28:490496]. Using our chemically-defined media system, we demonstrate an additional property of glucocorticoids as a regulator of antibody glycosylation in CHO cell culture. Our results show reductions in fucosylated and galactosylated glycan species and a concomitant increase in mannosylated glycan species. This is notable because fucosylation and mannosylation affect potency if the mechanism of action relies on antibodydependent, cell-mediated cytotoxicity (ADCC) and galactosylation affects potency if the mechanism of action relies on complement-dependent cytotoxicity (CDC). Therefore, understanding the effect of glucocorticoids on glycosylation is important for tuning cell culture media in the pursuit of more desirable product quality attributes of biologic

Computational methods for cell culture media optimization and product quality control

Biologics development leading to approval can take decades. Acceleration of this timeline is necessary to bring safe and efficacious drugs to patients as early as possible. One research focus to reduce development time is the cell culture process development and optimization. In this study, we will present two computational strategies that cover: (1) enhancing cell culture media by amino acid optimization using Orthogonal-Partial Least Squares (OPLS) regression, and (2) modulating protein glycosylation by altering small molecule compound concentrations based on the Concentration Impact Factor. Disproportionate nutrient balance in cell culture medium can have a negative impact on cell culture performance. In our study, OPLS regression was used to explain cell growth and monoclonal antibody (mAb) production dynamics from Chinese Hamster Ovary (CHO) cells as a function of amino acid (AA) stoichiometric balances. The OPLS model was trained on metabolic data from 24 concurrent 14-day fed-batch cultures. Metabolic fluxes and respective stoichiometric balances were then generated by calculating the difference between the theoretical biomass demand of each AA and the actual AA usage towards mAb production and experimental consumption. As a result, highly weighted stoichiometric balances represented those AA that could potentially enhance the previous feed medium and aim to achieve a higher intracellular catabolic activity. Accordingly, we used our computational model to generate varied amino acid additions to either a platform feed or a low nutrient feed by means of a 16-run mixture design. The experimental results showed that addition of model generated key AA resulted in a ~55% increase in peak cell density and ~90% increase in mAb production, respectively. Appropriately glycosylated therapeutic mAb are critical for the proper molecular folding, stability, and in-vivo efficacy of the expressed proteins. Cell culture process conditions and medium compositions have been demonstrated to affect the expression of various glycosylation species. In this study, we evaluated a set of selected small compound for their potential in modifying glycosylation levels in mAb expressed in three different proprietary CHO cell lines. These small molecule compounds were first tested on one cell line to establish a baseline. To quantitate the glycosylation modifications, we have developed a mathematical correlation of a dimensionless number, termed Concentration Impact factor (Cf), to describe the degree changes in glycosylation species. Using the Cf algorithm established for the 1st cell line, we subsequently tested with other two cell lines, and were able to modulate and confirmed the level of glycan expression. This indicates that Cf correlation may serve as a tool to provide early assessment of final glycosylation profiles and levels on therapeutic proteins due to small molecule supplementations. Overall, the two computational methods presented here are aimed to enhance biologics development speed as well as ensure product quality control

The management of municipal solid waste in Hong Kong : a study of civic engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Restoring Hong Kong's landscar in the Anderson Quarry : an analysis of civic engagement strategies

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Extracellular nanomatrix-induced self-organization of neural stem cells into miniature substantia nigra-like structures with therapeutic effects on Parkinsonian rats

Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson's disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN‐like structures (mini‐SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self‐organization of mini‐SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self‐organization of the mini‐SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini‐SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self‐organization of region‐specific and functional brain‐like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD

The effects of a synthetic curcuminoid analogue,2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone on proinflammatorysignaling pathways and CLP-induced lethal sepsis in mice.

We previously showed that 2,6-bis-(4-hydroxyl-3-methoxybenzylidine)cyclohexanone (BHMC), suppressed the synthesis of various proinflammatory mediators. In this study we explain the mechanism of action of BHMC in lipopolysaccharide (LPS)-induced U937 monocytes and further show that BHMC prevents lethality of CLP-induced sepsis. BHMC showed dose-dependent inhibitory effects on p38, JNK and ERK 1/2 activity as determined by inhibition of phosphorylation of downstream transcription factors ATF-2, c-Jun and Elk-1 respectively. Inhibition of these transcription factors subsequently caused total abolishment of AP-1–DNA binding. BHMC inhibited p65 NF-κB nuclear translocation and DNA binding of p65 NF-κB only at the highest concentration used (12.5 μM) but failed to alter phosphorylation of JNK, ERK1/2 and STAT-1. Since the inhibition of p38 activity was more pronounced we evaluated the possibility that BHMC may bind to p38. Molecular docking experiments confirmed that BHMC fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We also show that BHMC was able to improve survival from lethal sepsis in a murine caecal-ligation and puncture (CLP) model

Systems biology approach in the development of chemically-defined media for production of protein therapeutics in Chinese hamster ovary cells

Cell culture medium plays a critical role on mammalian cell growth, protein expression and quality. Typical cell culture medium formulations consist of \u3e50 components which include amino acids, vitamins, trace metals, lipids and proteins. Chinese Hamster Ovary (CHO) cells that produce biotherapeutics are propagated in specific cell culture media to ensure robust productivity and product quality. Systems biology has been applied to multiple areas of biological research to gain a better understanding of disease origins and to identify potential new drug targets. Although CHO cells are simpler systems, they share similar biochemistry and cellular pathways. Therefore, leveraging the systems biology knowledge from animal systems and applying these strategic systems biological tools to bioprocess development can be valuable in gaining better understanding of CHO cell culture performance, optimizing cell culture media, and subsequently resulting in better control of the overall production processes. In this presentation, we will present several case studies of various ‘omics tools applied to (1) optimize cell culture medium formulation for improve cell growth and productivity via metabolomics, (2) understand effects of medium components on cellular gene expression via transcriptomics, and on product quality via glycomics, and (3) identify potential cellular protein targets that are affected by stress imposed during production process via proteomics. The development of a statistical model that aims to highlight key metabolites and a machine learning model that identifies significantly important genes which are involved in monoclonal antibody production will also be discussed

Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells.

NO synthesis in the RAW 264.7 murine macrophage line. The inhibition of NO synthesis was related to inhibition of p38 phosphorylation and kinase activity that led to significant inhibition of phosphorylation of ATF-2. This effect in turn caused inhibition of AP-1-DNA binding which partially explains the inhibitory effect upon the synthesis of iNOS. HMP had no effect upon phosphorylation of JNK, ERK1/2 and STAT-1. Kinase activity of JNK and ERK1/2 was also not affected by HMP as determined by levels of phosphorylated c-jun and phosphorylated elk-1. Furthermore HMP failed to block phosphorylation of IκBα, and subsequent nuclear translocation and DNA-binding activity of p65 NF-κB in IFN-γ/LPS-induced RAW 264.7 cells. Molecular docking experiments confirmed that HMP fits well in the highly conserved hydrophobic pocket of p38 MAP kinase. We conclude that the synthetic HMP is a chalcone analogue that selectively inhibits the p38/ATF-2 and AP-1 signaling pathways in the NO synthesis by the macrophage RAW 264.7