Processes2014, 2(4), 867-900; doi:10.3390/pr2040867 - published 25 November 2014 Show/Hide Abstract
Abstract: Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR) and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1) SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2) CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3) elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs), is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.
Processes2014, 2(4), 795-866; doi:10.3390/pr2040795 - published 20 October 2014 Show/Hide Abstract
Abstract: Membrane fouling is one of the most important considerations in the design and operation of membrane systems as it affects pretreatment needs, cleaning requirements, operating conditions, cost and performance. Given that membrane fouling represents the main limitation to membrane process operation, it is unsurprising that the majority of membrane material and process research and development conducted is dedicated to its characterization and amelioration. This work presents the fundamentals of fouling issues in membrane separations, with specific regard to membrane fouling in Membrane Bioreactors (MBRs) and the most frequently applied preventive-control strategies. Feed pretreatment, physical and chemical cleaning protocols, optimal operation of MBR process and membrane surface modification are presented and discussed in detail. Membrane fouling is the major obstacle to the widespread application of the MBR technology and, therefore, fouling preventive-control strategies is a hot issue that strongly concerns not only the scientific community, but industry as well.
Processes2014, 2(4), 773-794; doi:10.3390/pr2040773 - published 17 October 2014 Show/Hide Abstract
Abstract: Activation and deactivation of hepatic stellate cells (HSCs) is an important mechanism contributing to both healthy liver function and development of liver diseases, which relies on the interplay between numerous signaling pathways. There is accumulating evidence for the regulatory role of microRNAs that are downstream from these pathways in HSC activation. However, the relative contribution of these pathways and interacting microRNA regulators to the activation process is unknown. We pursued a computational modeling approach to explore the timing and regulatory balances that are critical to HSC activation and quiescence. We developed an integrated model incorporating three signaling pathways with crosstalk (NF-κB, STAT3 and TGF-β) and two microRNAs (miR-146a, miR-21) that are differentially regulated by these pathways. Simulations demonstrated that TGF-β-mediated regulation of microRNAs is critical to drive the HSC phenotypic switch from quiescence (miR-146ahigh miR-21low) to an activated state (miR-146alow miR-21high). We found that the relative timing between peak NF-κB and STAT3 activation plays a key role driving the initial dynamics of miR-146a. We observed re-quiescence from the activated HSC state upon termination of cytokine stimuli. Our integrated model of signaling and microRNA regulation provides a new computational platform for investigating the mechanisms driving HSC molecular state phenotypes in normal and pathological liver physiology.
Processes2014, 2(4), 753-772; doi:10.3390/pr2040753 - published 17 October 2014 Show/Hide Abstract
Abstract: The spinner flask bioreactor has been widely used in in vitro cell culturing processes due to its superiority in providing a homogeneous culture environment compared to traditional culturing methods. However, there is limited understanding of the flow fields in these bioreactors, and optimum culture conditions are yet to be determined. This article presents the experimental characterization of the flow field within a spinner flask at varying speeds (10 RPM to 80 RPM) and impeller positions. An optical, non-invasive measurement technique, Particle Image Velocimetry (PIV), was employed to illustrate the fluid flow and calculate the stresses and vorticity associated with the flow within the flask. The largest recirculation structure was observed in the meridional plane at the highest impeller position while the highest shear stress region was observed at the base of the spinner flask. The study provides an overview of the fluid structure within the spinner flask in the meridional and azimuthal planes. Furthermore, the results presented in this study give an accurate quantification of the range of stresses for the given impeller speeds. These results provide estimates of the biomechanical properties within the type of spinner flask used in many published cell studies.
Processes2014, 2(4), 711-752; doi:10.3390/pr2040711 - published 17 October 2014 Show/Hide Abstract
Abstract: Microorganisms in nature form diverse communities that dynamically change in structure and function in response to environmental variations. As a complex adaptive system, microbial communities show higher-order properties that are not present in individual microbes, but arise from their interactions. Predictive mathematical models not only help to understand the underlying principles of the dynamics and emergent properties of natural and synthetic microbial communities, but also provide key knowledge required for engineering them. In this article, we provide an overview of mathematical tools that include not only current mainstream approaches, but also less traditional approaches that, in our opinion, can be potentially useful. We discuss a broad range of methods ranging from low-resolution supra-organismal to high-resolution individual-based modeling. Particularly, we highlight the integrative approaches that synergistically combine disparate methods. In conclusion, we provide our outlook for the key aspects that should be further developed to move microbial community modeling towards greater predictive power.
Processes2014, 2(4), 694-710; doi:10.3390/pr2040694 - published 26 September 2014 Show/Hide Abstract
Abstract: In a time of increasing concerns about the immense energy consumption and poor environmental performance of contemporary processes in the chemical industry, there is great need to develop novel sustainable technologies that enhance energy efficiency. There is abundant chemical literature on process innovations (laboratory-scale) around the plasma reactor itself, which, naturally, is the essential part to be intensified to achieve a satisfactory process. In essence, a plasma process needs attention beyond reaction engineering towards the process integration side and also with strong electrical engineering focus. In this mini-review, we have detailed our future focus on the process and energy intensification of plasma-based N-fixation. Three focal points are mainly stressed throughout the review: (I) the integration of renewable energy; (II) the power supply system of plasma reactors and (III) process design of industrial plasma-assisted nitrogen fixation. These different enabling strategies will be set in a holistic and synergetic picture so as to improve process performance.