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Assessment of fed-batch cultivation strategies for an inducible CHO cell line
No full textIn order to maximize cell growth and productivity for an inducible CHO cell line expressing rituximab, various fed-batch culture strategies were investigated. In each case, the performance was evaluated for cultures induced at moderate and high cell density conditions (4\u2009
7\u2009106 and 10\u2009
7\u2009106 cells/mL) to assess the impact of the timing of induction. We first demonstrate the importance of starting the feeding process during the growth phase, as this translated into significantly improved integral of viable cells and antibody concentration, when compared to post-induction feeding only. Secondly, we investigated the impact of the feed rate by maintaining different levels of glucose (25, 35 and 50\u2009mM) via a dynamic feeding strategy. The highest antibody concentrations were achieved under a moderate feeding regime for both cell densities at induction, highlighting the risks of under- or over-feeding the cultures. We then evaluated the impact of performing a temperature shift at induction by testing different mild hypothermia conditions. At small-scale, the highest production yields (1.2\u2009g/L) were achieved when the temperature was reduced from 37 to 30\u2009\ub0C during the production phase of a culture induced at high cell density. When the strategy was applied in bioreactor, the better controlled conditions led to even greater product concentrations (1.8\u2009g/L). Furthermore, this production protocol was shown to promote a more galactosylated glycan profile than a bioreactor culture initiated at 34\u2009\ub0C during growth and downshifted to 30\u2009\ub0C during the production phase.Peer reviewed: YesNRC publication: Ye
Characterization and mechanical testing on novel (\u3b3\u202f+\u202f\u3b12) \u2013 TiAl/Ti3Al/Al2O3 cermet
No full textThis study investigates the micro/nanostructural features and mechanical responses of a novel TiAl/Ti3Al/Al2O3 cermet fabricated by self-propagation high-temperature synthesis. The microscopic diagnosis was used to examine the material composition, phase distribution, and elemental concentration of the cermet. Three phases were identified in the cermet, including \u3b3-TiAl, \u3b12-TiAl, and Al2O3. The material exhibited ultrafine microstructure with the size of alumina particles between 0.5\u202f\ub5m and 1.5\u202f\ub5m occupying 65\u202f\ub1\u202f1% areal fraction of the material. Transmission electron microscopy (TEM) was employed to examine the \u201ccoral\u201d network of alumina particles with the titanium aluminide matrix, which was believed to be contributing to the failure of the material. Iron/nickel-based nano-precipitates were found through TEM as well, and these were believed to be contributing to the mechanical properties of the material. The rate-dependency on the compressive strength and failure mechanisms were studied by quasi-static and dynamic uniaxial compression, and it was found that the quasi-static and dynamic compressive strengths were 2400\u202f\ub1\u202f120\u202fMPa and 3370\u202f\ub1\u202f450\u202fMPa, respectively. The results are compared with those for alumina AD995 to highlight differences in mechanical properties, such as compressive strength and failure strains. These findings serve as the preliminary dataset for material design, manufacturing, and modeling of advanced cermets.Peer reviewed: YesNRC publication: Ye
Intermediate strain rate material characterization with digital image correlation
No full textThe mechanical response of a material under dynamic load is typically different than its behavior under static conditions; therefore, the common quasistatic equipment and procedures used for material characterization are not applicable for materials under dynamic loads. The dynamic response of a material depends on its deformation rate and is broadly categorized into high (i.e., greater than 200/s), intermediate (i.e., 10 12200/s) and low strain rate regimes (i.e., below 10/s). Each of these regimes calls for specific facilities and testing protocols to ensure the reliability of the acquired data. Due to the limited access to high-speed servo-hydraulic facilities and validated testing protocols, there is a noticeable gap in the results at the intermediate strain rate. The current manuscript presents a validated protocol for the characterization of different materials at these intermediate strain rates. Strain gauge instrumentation and digital image correlation protocols are also included as complimentary modules to extract the utmost level of detailed data from every single test. Examples of raw data, obtained from a variety of materials and test setups (e.g., tensile and shear) is presented and the analysis procedure used to process the output data is described. Finally, the challenges of dynamic characterization using the current protocol, along with the limitations of the facility and methods of overcoming potential problems are discussed.Peer reviewed: YesNRC publication: Ye
The effect of viscosity on free surface flow inside an angularly oscillating rectangular tank
No full textThis paper presents a three-dimensional solution algorithm for solving free surface flows including the effect of near wall viscous dissipation. Slip boundary conditions that could take into account the viscous shear at the boundary are proposed in a context that is well suited to free surface flow applications. The proposed finite element method uses a Level-Set formulation on fixed meshes and, consequently, the liquid/gas interface is generally located inside mesh elements. Standard interpolation of flow variables inside partially filled elements leads to an inappropriate treatment of gravity forces, pressure gradient and inertia which can generate spurious oscillations. To alleviate these issues, we use enriched shape functions for the pressure that introduce a discontinuity in the normal pressure gradient at the interface. The additional pressure degree of freedom is eliminated at the elementary system level by static condensation thus having no impact on the structure of the linear system matrix. This approach is well-suited for gravity-driven free surface problems such as violent sloshing inside tanks. The algorithm is first verified and validated on simpler problems for which analytical or experimental results are available. Then it is applied to the study of sloshing where it is validated against a robust set of experiment from Delorme et al. [1] and Souto-Iglesias et al. [2, 3] for the water and oil flow inside an angularly oscillating rectangular tank. The proposed approach to include viscous dissipation at the wall proves to be very effective in capturing the significant differences in flow dynamics between the two liquids having different viscosities. Moreover, the enriched pressure shape functions results in stable, oscillation free solution thus representing an efficient way to accurately solve complex gravity-driven free surface problems without requiring re-meshing or mesh refinement.Peer reviewed: YesNRC publication: Ye
Apparent sound insulation in precast concrete buildings
No full textThis Report presents the results from experimental studies of airborne sound transmission, together with an explanation of calculation procedures to predict the apparent airborne sound transmission class (ASTC) rating between adjacent spaces in a building with walls and floors of precast concrete.
This Report was developed in a project established by the National Research Council of Canada and The Canadian Precast/ Prestressed Concrete Institute to support the transition of construction industry practice to using the ASTC rating rather than STC for sound control objectives in the National Building Code of Canada (NBCC). However, the potential range of application goes beyond the minimum requirements of the NBCC. The Report also facilitates design to provide enhanced levels of sound insulation, and should be generally applicable to buildings with precast concrete walls and floors in both Canada and the USA.
Buildings assembled from precast concrete elements commonly have floors of hollowcore precast concrete slabs combined with wall panels of solid reinforced concrete. The building may also include linings on the precast concrete wall, ceiling, or floor surfaces, but this Report focusses primarily on performance of the base constructions of precast concrete.Peer reviewed: NoNRC publication: Ye
Unveiling integrated functional pathways leading to enhanced respiratory disease associated with inactivated respiratory syncytial viral vaccine
No full textRespiratory syncytial virus (RSV) infection is a severe threat to young children and the elderly. Despite decades of research, no vaccine has been approved. Notably, instead of affording protection, a formalin-inactivated RSV vaccine induced severe respiratory disease including deaths in vaccinated children in a 1960s clinical trial; however, recent studies indicate that other forms of experimental vaccines can also induce pulmonary pathology in pre-clinical studies. These findings suggest that multiple factors/pathways could be involved in the development of enhanced respiratory diseases. Clearly, a better understanding of the mechanisms underlying such adverse reactions is critically important for the development of safe and efficacious vaccines against RSV infection, given the exponential growth of RSV vaccine clinical trials in recent years. By employing an integrated systems biology approach in a pre-clinical cotton rat model, we unraveled a complex network of pulmonary canonical pathways leading to disease development in vaccinated animals upon subsequent RSV infections. Cytokines including IL-1, IL-6 GRO/IL-8, and IL-17 in conjunction with mobilized pulmonary inflammatory cells could play important roles in disease development, which involved a wide range of host responses including exacerbated pulmonary inflammation, oxidative stress, hyperreactivity, and homeostatic imbalance between coagulation and fibrinolysis. Moreover, the observed elevated levels of MyD88 implicate the involvement of this critical signal transduction module as the central node of the inflammatory pathways leading to exacerbated pulmonary pathology. Finally, the immunopathological consequences of inactivated vaccine immunization and subsequent RSV exposure were further substantiated by histological analyses of these key proteins along with inflammatory cytokines, while hypercoagulation was supported by increased pulmonary fibrinogen/fibrin accompanied by reduced levels of plasma D-dimers. Enhanced respiratory disease associated with inactivated RSV vaccine involves a complex network of host responses, resulting in significant pulmonary lesions and clinical manifestations such as tachypnea and airway obstruction. The mechanistic insight into the convergence of different signal pathways and identification of biomarkers could help facilitate the development of safe and effective RSV vaccine and formulation of new targeted interventions.Peer reviewed: YesNRC publication: Ye
Extraction of nucleic acids from blood: unveiling the potential of active pneumatic pumping in centrifugal microfluidics for integration and automation of sample preparation processes
No full textThis paper describes the development of an on-chip nucleic acid (NA) extraction assay from whole blood using a centrifugal microfluidic platform that allows for pneumatic actuation of liquids during rotation. The combination of pneumatic and centrifugal forces makes it possible to perform fluidic operations without the need for integrating active control elements on the microfluidic cartridge. The cartridge is fabricated from thermoplastic polymers (e.g., Zeonor 1060R) and features a simple design that is compatible with injection molding. In addition, the cartridge is interfaced with two external vials for off-chip storage of the blood sample and retrieval of the eluted NA solution, respectively. On-chip capture of NAs is performed using an embedded solid-phase extraction matrix composed of commercial glass microfiber filters (Whatman GF/D and GF/F). The yield of the automated, on-chip extraction protocol, determined by measuring absorbance at 260 nm, is comparable to some of the best manually operated kits (e.g., Qiagen QIAamp DNA Mini Kit) while providing low assay-to-assay variability due to the high level of control provided by the platform for each processing step. The A260/A280 and A260/A230 ratios of the absorbance spectra also reveal that protein contamination of the sample is negligible. The capability of the pneumatic platform to circulate air flux through the microfluidic conduit was used to dry leftover ethanol residues retained in the capture matrix during washing. This method, applied in combination with localized heating, proved effective for reducing ethanol contamination in eluted samples from ~12% to 1% (v/v).Peer reviewed: YesNRC publication: Ye