In silico dynamic optimisation studies for batch/fed-batch mammalian cell suspension cultures producing biopharmaceuticals

Mammalian cell cultures are valuable for synthesis of therapeutic proteins and antibodies. They are commonly cultivated in bioindustry in form of large-scale suspension fed-batch cultures. The structure and regulatory responses of mammalian cells are complex, making it challenging to model them for practical process optimisation. The adjustable degrees of freedom in the cell cultures can be continuous variables as well as binary-type variables. The binary-type variables may be irreversible in cases such as cell-cycle arrest. The main aim of this study was to develop a general model for mammalian cell cultures using extracellular variables and capturing major changes in cellular responses between batch and fed-batch cultures. The model development started with a simple model for a hybridoma cell culture using first-principle equations. The growth kinetics was only linked to glucose and glutamine and the cell population was divided into three cell-cycle phases to study the phenomenon of cell-cycle arrest. But there were certain deficiencies in predicting growth rates in the death phase in fed-batch cultures although it was successful to simultaneously optimise a combination of continuous and binary-irreversible degrees of freedom. Thus, the growth kinetics was further related to amino acids concentration and cellular responses to high versus low concentration of glutamine and glucose based on a Chinese hamster ovary cell-line where amino acids data were available. The model contained 192 parameters with 26 measured cell culture variables. Most of the sensitive parameters were able to be identified using the Sobol' method of Global Sensitivity Analysis. The model could capture the main trends of key variables and be used to search for the optimal working range of the controllable variables. But uncertainties in the sensitive model parameters caused non-negligible variations in the model-based optimisation results. It is recommended to couple such off-line optimisation with on-line measurements of a few major variables to tackle the real-time uncertain nature of the complex cell culture system.Open acces

The Examination Of Entertainment Product Performance In Macau

Macau surpassed Las Vegas as the top gaming destination many years ago. Entertainment is a crucial element in many gambling destinations. Associating entertainment and gambling helped create a more appealing image and package of gambling destination. This study investigated the performance of entertainment products in Macau. This study used convenience sampling to collect 300 usable questionnaires from three tourists’ departure spots. Respondents were asked to evaluate the importance and performance of seven categories of entertainment products. The most important entertainment products were Family Fun and Show. Most people did not think Beauty and Wellness, or Sports and Recreation were important. Many people have the impression that Gambling is one of the most important entertainment products in Macau; however, in our sample, Gambling was ranked as the second most important entertainment product. Government and entertainment providers should continue their effort to provide more Family Fun and Shows to fulfill the needs of visitors

A Comparative Study of Routine Laparoscopic Versus Open Appendectomy

Scientific PapersOBJECTIVE: We evaluated the outcomes of routine laparoscopy and laparoscopic appendectomy (LA) in patients with suspected appendicitis. This is a retrospective study of the outcomes of patients undergoing laparoscopic appendectomy compared with outcomes for patients undergoing open appendectomy (OA) during the time that LA came into use. METHOD: Results of patients managed with routine laparoscopy and LA for suspected acute appendicitis were reviewed and analyzed. The preoperative and intraoperative findings were recorded. The clinical outcomes were compared with those of patients undergoing OA in the preceding 10 months. RESULTS: During the LA study period, 97 patients (47 men) with the median age of 34 years (range, 18 to 79) presented with clinical features of acute appendicitis. With the exclusion of 5 patients with open operations and 10 patients with other pathologies, 82 patients underwent laparoscopic appendectomy (Group A) for appendicitis. Thirty-one (37.8%) patients had complicated appendicitis (perforated or gangrenous appendicitis). Conversions were required in 6 patients (7.3%). During the OA period, 125 patients (57 men) with the median age of 42 (range, 19 to 79) years were operated on. With the exclusion of 6 patients with other pathologies, 119 underwent OA for acute appendicitis (Group B). Fifty-one (42.9%) had either perforated or gangrenous appendicitis. The median durations of surgery in Group A and Group B were 80 minutes (range, 40 to 195) and 60 minutes (range, 25 to 260), respectively (P < 0.005). Postoperative complication rates were comparable between the 2 groups (13.4% in Group A versus 15.8% in Group B). The median hospital stay for patients in Group A and Group B were 3.0 days (range, 1 to 47) and 4.0 days (range, 1 to 47), respectively (P = 0.037). CONCLUSIONS: We conclude that routine laparoscopy and LA for suspected acute appendicitis is safe and is associated with a significantly shorter hospital stay. Other intra-abdominal pathologies can also be diagnosed more accurately with the laparoscopic approach.link_to_OA_fulltex

Delayed diagnosis of 22q11.2 deletion syndrome in an adult Chinese lady

We report a 32 year-old Chinese lady with history of tetralogy of Fallot, presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism. With her dysmorphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study. Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease, facial dysmorphism, intellectual disability and primary hypoparathyroidism.published_or_final_versio

Understanding Potential Cyber-Armies in Elections: A Study of Taiwan

Currently, online social networks are essential platforms for political organizations to monitor public opinion, disseminate information, argue with the opposition, and even achieve spin control. However, once such purposeful/aggressive articles flood social sites, it would be more difficult for users to distinguish which messages to read or to trust. In this paper, we aim to address this issue by identifying potential “cyber-armies/professional users” during election campaigns on social platforms. We focus on human-operated accounts who try to influence public discussions, for instance, by publishing hundreds/thousands of comments to show their support or rejection of particular candidates. To achieve our objectives, we collected activity data over six months from a prominent Taiwan-based social forum before the 2018 national election and applied a series of statistical analyses to screen out potential targets. From the results, we successfully identified several accounts according to distinctive characteristics that corresponded to professional users. According to the findings, users and platforms could realize potential information manipulation and increase the transparency of the online society

BASE: a practical de novo assembler for large genomes using long NGS reads

© 2016 The Author(s). Background: De novo genome assembly using NGS data remains a computation-intensive task especially for large genomes. In practice, efficiency is often a primary concern and favors using a more efficient assembler like SOAPdenovo2. Yet SOAPdenovo2, based on de Bruijn graph, fails to take full advantage of longer NGS reads (say, 150 bp to 250 bp from Illumina HiSeq and MiSeq). Assemblers that are based on string graphs (e.g., SGA), though less popular and also very slow, are more favorable for longer reads. Methods: This paper shows a new de novo assembler called BASE. It enhances the classic seed-extension approach by indexing the reads efficiently to generate adaptive seeds that have high probability to appear uniquely in the genome. Such seeds form the basis for BASE to build extension trees and then to use reverse validation to remove the branches based on read coverage and paired-end information, resulting in high-quality consensus sequences of reads sharing the seeds. Such consensus sequences are then extended to contigs. Results: Experiments on two bacteria and four human datasets shows the advantage of BASE in both contig quality and speed in dealing with longer reads. In the experiment on bacteria, two datasets with read length of 100 bp and 250 bp were used. Especially for the 250 bp dataset, BASE gives much better quality than SOAPdenovo2 and SGA and is simlilar to SPAdes. Regarding speed, BASE is consistently a few times faster than SPAdes and SGA, but still slower than SOAPdenovo2. BASE and Soapdenov2 are further compared using human datasets with read length 100 bp, 150 bp and 250 bp. BASE shows a higher N50 for all datasets, while the improvement becomes more significant when read length reaches 250 bp. Besides, BASE is more-meory efficent than SOAPdenovo2 when sequencing data with error rate. Conclusions: BASE is a practically efficient tool for constructing contig, with significant improvement in quality for long NGS reads. It is relatively easy to extend BASE to include scaffolding.published_or_final_versio

Age composition and survival of public housing stock in Hong Kong

Emerging notably in more developed regions, building stock ageing which is characterised by shrinking new completions and falling “mortality” has been posing challenges to various stakeholders in built environment. To find way out of this transition, we need to know how long buildings will last these days and the factors leading to their “mortality”. By using data from 1950s till to date, a comprehensive investigation is conducted to analyse the age composition and life expectancy of public housing stock in Hong Kong. What comes after are survival analysis and empirical analysis of those demolished to identify the key factors leading to demolition. Presented in this paper are the preliminary findings as well as the research agenda on the theme to model age composition and survival of both private and public building stocks in Hong Kong and other similar cities in Asia Pacific Rim such as Adelaide and Singapore, together with research activities to formulate policies for sustainable urban management

Automated Long-Term Monitoring of Parallel Microfluidic Operations Applying a Machine Vision-Assisted Positioning Method

As microfluidics has been applied extensively in many cell and biochemical applications, monitoring the related processes is an important requirement. In this work, we design and fabricate a high-throughput microfluidic device which contains 32 microchambers to perform automated parallel microfluidic operations and monitoring on an automated stage of a microscope. Images are captured at multiple spots on the device during the operations for monitoring samples in microchambers in parallel; yet the device positions may vary at different time points throughout operations as the device moves back and forth on a motorized microscopic stage. Here, we report an image-based positioning strategy to realign the chamber position before every recording of microscopic image. We fabricate alignment marks at defined locations next to the chambers in the microfluidic device as reference positions. We also develop image processing algorithms to recognize the chamber positions in real-time, followed by realigning the chambers to their preset positions in the captured images. We perform experiments to validate and characterize the device functionality and the automated realignment operation. Together, this microfluidic realignment strategy can be a platform technology to achieve precise positioning of multiple chambers for general microfluidic applications requiring long-term parallel monitoring of cell and biochemical activities

SOAP3-dp: Fast, Accurate and Sensitive GPU-based Short Read Aligner

To tackle the exponentially increasing throughput of Next-Generation Sequencing (NGS), most of the existing short-read aligners can be configured to favor speed in trade of accuracy and sensitivity. SOAP3-dp, through leveraging the computational power of both CPU and GPU with optimized algorithms, delivers high speed and sensitivity simultaneously. Compared with widely adopted aligners including BWA, Bowtie2, SeqAlto, GEM and GPU-based aligners including BarraCUDA and CUSHAW, SOAP3-dp is two to tens of times faster, while maintaining the highest sensitivity and lowest false discovery rate (FDR) on Illumina reads with different lengths. Transcending its predecessor SOAP3, which does not allow gapped alignment, SOAP3-dp by default tolerates alignment similarity as low as 60 percent. Real data evaluation using human genome demonstrates SOAP3-dp's power to enable more authentic variants and longer Indels to be discovered. Fosmid sequencing shows a 9.1 percent FDR on newly discovered deletions. SOAP3-dp natively supports BAM file format and provides a scoring scheme same as BWA, which enables it to be integrated into existing analysis pipelines. SOAP3-dp has been deployed on Amazon-EC2, NIH-Biowulf and Tianhe-1A.Comment: 21 pages, 6 figures, submitted to PLoS ONE, additional files available at "https://www.dropbox.com/sh/bhclhxpoiubh371/O5CO_CkXQE". Comments most welcom