34 research outputs found
Intensification of viral vector production and clarification by integration of perfusion platforms
Gene Therapies represent an important new frontier in therapeutic development as they have the potential to treat diseases that have previously been difficult to manage. The new gene therapies currently being developed will address larger patient population and/or using higher dosage needed for global clinical and commercialization. Manufacturing improvement is therefore needed to realize the full potential of gene therapy. We will present two case studies which illustrate the next generation viral vector manufacturing process. The first case study will demonstrate how integration of perfusion platforms, alternating tangential flow (ATF) and the tangential flow depth filtration (TFDF) to bioreactor led to 2-4-fold increase of total rAAV8 yield comparing to the current bioreactor process. The second case study will show how the perfusion TFDF platform used in clarification mode was applied to increase lentivirus (LV) yield through multiple harvests. The cell retention filters enabled the continuous harvest clarification of LV particles present in the media during the virus production, demonstrating the potential for continuous upstream-downstream processing of secreted LV vectors. The implementation of the TFDF in a continuous clarification strategy during the harvest led to a total yield of more than 200% potent LV compared to the depth filtration process.
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Testing in the incremental design and development of complex products
Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested
Interaction between the microbiome and TP53 in human lung cancer.
BACKGROUND: Lung cancer is the leading cancer diagnosis worldwide and the number one cause of cancer deaths. Exposure to cigarette smoke, the primary risk factor in lung cancer, reduces epithelial barrier integrity and increases susceptibility to infections. Herein, we hypothesize that somatic mutations together with cigarette smoke generate a dysbiotic microbiota that is associated with lung carcinogenesis. Using lung tissue from 33 controls and 143 cancer cases, we conduct 16S ribosomal RNA (rRNA) bacterial gene sequencing, with RNA-sequencing data from lung cancer cases in The Cancer Genome Atlas serving as the validation cohort.
RESULTS: Overall, we demonstrate a lower alpha diversity in normal lung as compared to non-tumor adjacent or tumor tissue. In squamous cell carcinoma specifically, a separate group of taxa are identified, in which Acidovorax is enriched in smokers. Acidovorax temporans is identified within tumor sections by fluorescent in situ hybridization and confirmed by two separate 16S rRNA strategies. Further, these taxa, including Acidovorax, exhibit higher abundance among the subset of squamous cell carcinoma cases with TP53 mutations, an association not seen in adenocarcinomas.
CONCLUSIONS: The results of this comprehensive study show both microbiome-gene and microbiome-exposure interactions in squamous cell carcinoma lung cancer tissue. Specifically, tumors harboring TP53 mutations, which can impair epithelial function, have a unique bacterial consortium that is higher in relative abundance in smoking-associated tumors of this type. Given the significant need for clinical diagnostic tools in lung cancer, this study may provide novel biomarkers for early detection
A descriptive study: SERVQUAL dimensions in customer service
This study determines the applicability of the five-service dimension present in the SERVQUAL instrument in a customer service environment making use of e-mail namely: service dimensions tangible, reliability, responsiveness, assurance, and empathy. Three hundred ninety-nine randomly selected Internet service provider subscribers who sent an e-mail requesting for customer service within a three-month period from January to March 2000 were used in the study. The study used a descriptive research design, and employed the following statistical tools: frequency distribution, percentage allocation, and z-tests large-sample test concerning difference between two means. The results showed that four of the five-service dimensions, reliability, assurance, responsiveness and empathy are applicable in a customer service environment. The study showed that service dimension tangible is not applicable in a customer service environment making use of e-mail. The study also highlighted the key service dimension at work in the said environment. The study answered the call for a service specific instrument, to measure service quality for the customer service environment making use of e-mail known as CUSTQUAL online
Bahala na: An experimental study
The study seeks to find if there is a significant difference in the perception of De La Salle University college students given the conditions of bahala na and procrastination. Significant differences are hypothesized to be determined through the perception of the characteristics of the person and situation across the varied procrastination stories. A semantic differential questionnaire was constructed to measure the perceived characteristics of the stimulus person in a procrastination situation. Convenience sampling was used to gather a total of 36 subjects treated in a repeated measures design to find out if bahala na response will affect student\u27s perception. The subjects were asked to answer 3 sets of questionnaire with stimulus situation characterizing three variations of bahala na namely: (a) the procrastination only, (6) procrastination with positive bahala na, and (c) procrastination with negative bahala na. Complete counterbalancing was employed to balance any sequence effect. A focus group discussion was conducted to determine the participant\u27s perceptions in relation to the characteristics in the three procrastination stories. The results of data gathered were analyzed using one-way ANOVA. A post hoc test with repeated measures was further used to see which among the three variation of bahala na had a significant difference in each characteristic. Significant difference found in time management, focus, determination, fear and anxiety, responsibility and motivation characteristics were supported. The theory of Lagmay about bipolarity of bahala na was empirically validated. Positive bahala na was found to be a mindset when procrastination occurs. Focus and motivation characteristics have no significant difference in procrastination therefore perceived as similar to negative bahala na. Procrastination was perceived more negative compared to positive bahala na in time management, focus, fear and anxiety
The Impact of Vacuum-Drying on Efficiency of Hardwood Products Manufacturing
Many wood product manufacturers are trying to increase competitiveness by implementing continuous improvement programs such as lean manufacturing. However, the lumber drying process can significantly affect manufacturing time and inventory size, thus limiting how “lean” the entire process can become. The goal of this research was to determine how vacuum drying technology could support lean manufacturing concepts relative to conventional drying technology in hardwood manufacturing. Two flooring manufacturers with drying operations were modeled, and simulations were used to determine differences in cycle time and work-in-process inventory. The total cycle time of vacuum drying was 78% and 90% less than conventional drying. Work-in-process inventory was reduced by 57% and 52%. The reduction of work-in-process inventory in the drying process represents a potential cost savings of 13.6 million per year for each manufacturer, respectively. The reduction in inventory carrying costs, faster drying rates, and reduced cycle time demonstrate that vacuum drying could significantly improve the competitiveness of hardwood flooring manufacturers