684 research outputs found
The role of Computer Aided Process Engineering in physiology and clinical medicine
This paper discusses the potential role for Computer Aided Process Engineering (CAPE) in developing engineering analysis and design approaches to biological systems across multiple levels—cell signalling networks, gene, protein and metabolic networks, cellular systems, through to physiological systems. The 21st Century challenge in the Life Sciences is to bring together widely dispersed models and knowledge in order to enable a system-wide understanding of these complex systems. This systems level understanding should have broad clinical benefits. Computer Aided Process Engineering can bring systems approaches to (i) improving understanding of these complex chemical and physical (particularly molecular transport in complex flow regimes) interactions at multiple scales in living systems, (ii) analysis of these models to help to identify critical missing information and to explore the consequences on major output variables resulting from disturbances to the system, and (iii) ‘design’ potential interventions in in vivo systems which can have significant beneficial, or potentially harmful, effects which need to be understood. This paper develops these three themes drawing on recent projects at UCL. The first project has modeled the effects of blood flow on endothelial cells lining arteries, taking into account cell shape change resulting in changes in the cell skeleton which cause consequent chemical changes. A second is a project which is building an in silico model of the human liver, tieing together models from the molecular level to the liver. The composite model models glucose regulation in the liver and associated organs. Both projects involve molecular transport, chemical reactions, and complex multiscale systems, tackled by approaches from CAPE.
Chemical Engineers solve multiple scale problems in manufacturing processes – from molecular scale through unit operations scale to plant-wide and enterprise wide systems – so have an appropriate skill set for tackling problems in physiology and clinical medicine, in collaboration with life and clinical scientists
Economic Benefits of Waste Pickling Solution Valorization
An integrated hybrid membrane process, composed of a diffusion dialysis (DD), a membrane distillation (MD) and a reactive precipitation unit (CSTR), is proposed as a promising solution for the valorization and onsite recycling of pickling waste streams. An economic analysis was performed aiming to demonstrate the feasibility of the developed process with a NPV of about EUR 40,000 and a DPBP of 4 years. The investment and operating costs, as well as the avoided costs and the benefits for the company operating the plant, were analyzed with an extensive cost tracking exercise and through face-to-face contact with manufacturers and sector leaders. A mathematical model was implemented using the gPROMS modelling platform. It is able to simulate steady state operations and run optimization analysis of the process performance. The impact of key operating and design parameters, such as the set-point bath concentration and the DD and MD membrane areas, respectively, was investigated and the optimal arrangement was identified. Finally, operating variables and design parameters were optimized simultaneously in a nonlinear framework as a tradeoff between profitability and environmental impact. We show how the integration of new technologies into the traditional pickling industry could provide a significant benefit for the issues of process sustainability, which are currently pressing
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Actinide Behavior in a Freshwater Pond
Long-term investigations of solution chemistry in an alkaline freshwater pond have revealed that actinide oxidation state behavior, particularly that of plutonium, is complex. The Pu(V,VI) fraction was predominant in solution, but it varied over the entire range reported from other natural aquatic environments, in this case, as a result of intrinsic biological and chemical cycles (redox and pH-dependent phenomena). A strong positive correlation between plutonium (Pu), but not uranium (U), and hydroxyl ion over the observation period, especially when both were known to be in higher oxidation states, was particularly notable. Coupled with other examples of divergent U and Pu behavior, this result suggests that Pu(V), or perhaps a mixture of Pu(V,VI), was the prevalent oxidation state in solution. Observations of trivalent actinide sorption behavior during an algal bloom, coupled with the association with a high-molecular weight (nominally 6000 to 10,000 mol wt) organic fraction in solution, indicate that solution-detritus cycling of organic carbon, in turn, may be the primary mechanism in amercium-curium (Am-Cm) cycling. Sorption by sedimentary materials appears to predominate over other factors controlling effective actinide solubility and may explain, at least partially, the absence of an expected strong positive correlation between carbonate and dissolved U. 49 references, 6 figures, 12 tables
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Plugging and Abandonment Plan for Wells and Coreholes at Oak Ridge National Laboratory, Oak Ridge, Tennessee
Site environmental characterization and remediation require data obtained from the installation and sampling of wells and coreholes. When these wells and coreholes are no longer needed, are not producing reliable information, or are damaged and can act as conduits for contaminant migration, they should be identified and properly decommissioned. This is most important for wells of sufficient depth to create the potential for exchange of fluids between different hydrologic units. This plan presents the strategy and detailed approach for the well and corehole P A plan for most of the areas for which ORNL has responsibility. Although wells in Waste Area Grouping (WAG) 5 and WAG 10 are not specifically addressed in this plan, these wells will be incorporated into the decommissioning program in FY 1993
Effects of citric acid and fibronectin and laminin application in treating periodontitis
. To determine the effect on new connective tissue attachment of citric acid conditioning and fibronectin-laminin application in treating naturally occurring periodontitis, all 4 quadrants in each of 2 Beagle dogs were used. Each quadrant included: P 2 , P 3 , P 4 , and M 1 teeth. 2 treatment modalities were employed and comparatively analyzed for differences in histological healing respponses at 120 days after surgery. The treatments were: (1) surgery (mucoperiosteal flaps) plus citric acid; (2) surgery plus citric acid followed by fibronectin-laminin application. After scaling and root planing, coronal and root surface reference notches were placed for histometric measurements. Following each of the randomly assigned treatments, flaps were sutured. After sacrifice, tissue blocks of treated areas were decalcified and serially cut, obtaining bucco-lingual and mesiodistal sections. Using a Filar micrometer. 5 distances were masured on the buccal aspect: (1) from root surface notch to alveolar bone crest; (2) from root surface notch to coronal extent of the cementum; (3) from root surface notch to apical extent of the junctional epithelium; 84) from free gingival margin to apical extent of junctional epithelium; (5) from the coronal notch to the alveolar bone crest. Results showed no differences among the 5 measurements between the 2 treatments tested. On mesiodistal sections, surface area determinations were made in the furcations, evaluating the space occupied by new connective tissue, with or without bone, or by epithelium. For this, images were digitized using a Zeiss IBAS Image analysis system with a 4mB of array processor memory coupled to a Newvicon TV camera and a microcomputer. Significant differences were found, with increased values for both regenerative connective tissue and bone when surgery plus citric acid was followed by fibronectin-laminin application. Often, these tissues filled completely furcation areas above root surface reference notches.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73686/1/j.1600-051X.1987.tb01543.x.pd
Spiking of intracellular calcium ion concentration in single cultured pig aortic endothelial cells stimulated with ATP or bradykinin
Bystander Effects of Hypoxia-Activated Prodrugs: Agent-Based Modeling Using Three Dimensional Cell Cultures
Intra-tumor heterogeneity represents a major barrier to anti-cancer therapies. One strategy to minimize this limitation relies on bystander effects via diffusion of cytotoxins from targeted cells. Hypoxia-activated prodrugs (HAPs) have the potential to exploit hypoxia in this way, but robust methods for measuring bystander effects are lacking. The objective of this study is to develop experimental models (monolayer, multilayer, and multicellular spheroid co-cultures) comprising ‘activator’ cells with high expression of prodrug-activating reductases and reductase-deficient ‘target’ cells, and to couple these with agent-based models (ABMs) that describe diffusion and reaction of prodrugs and their active metabolites, and killing probability for each cell. HCT116 cells were engineered as activators by overexpressing P450 oxidoreductase (POR) and as targets by knockout of POR, with fluorescent protein and antibiotic resistance markers to enable their quantitation in co-cultures. We investigated two HAPs with very different pharmacology: SN30000 is metabolized to DNA-breaking free radicals under hypoxia, while the dinitrobenzamide PR104A generates DNA-crosslinking nitrogen mustard metabolites. In anoxic spheroid co-cultures, increasing the proportion of activator cells decreased killing of both activators and targets by SN30000. An ABM parameterized by measuring SN30000 cytotoxicity in monolayers and diffusion-reaction in multilayers accurately predicted SN30000 activity in spheroids, demonstrating the lack of bystander effects and that rapid metabolic consumption of SN30000 inhibited prodrug penetration. In contrast, killing of targets by PR104A in anoxic spheroids was markedly increased by activators, demonstrating that a bystander effect more than compensates any penetration limitation. However, the ABM based on the well-studied hydroxylamine and amine metabolites of PR104A did not fit the cell survival data, indicating a need to reassess its cellular pharmacology. Characterization of extracellular metabolites of PR104A in anoxic cultures identified more stable, lipophilic, activated dichloro mustards with greater tissue diffusion distances. Including these metabolites explicitly in the ABM provided a good description of activator and target cell killing by PR104A in spheroids. This study represents the most direct demonstration of a hypoxic bystander effect for PR104A to date, and demonstrates the power of combining mathematical modeling of pharmacokinetics/pharmacodynamics with multicellular culture models to dissect bystander effects of targeted drug carriers
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Comparative food-chain behavior and distribution of actinide elements in and around a contaminated fresh-water pond
The bioaccumulation of /sup 233/ /sup 234/U, /sup 238/U, /sup 238/Pu, /sup 239/ /sup 240/Pu, /sup 241/Am, and /sup 244/Cm in both native and introduced biota was studied at Pond 3513, a former low-level radioactive waste settling basin at Oak Ridge National Laboratory. This system, which was decommissioned in 1976 after more than 30 years use, contains approximately 5 Ci of /sup 239/ /sup 240/Pu; inventories of other actinide isotopes are considerably less. Significantly higher concentrations of actinides in fish that were allowed access to sediments indicated that sedimentary particulates may be the primary source of transuranics to biota in shallow fresh-water ecosystems. Our study determined habitat, in particular the degree of association of an organism with the sediment-water interface, to be the primary factor in controlling transuranic concentrations in aquatic biota. In most of the biological samples analyzed, excluding samples suspected of being contaminated by sediment, /sup 241/Am//sup 239/Pu, /sup 244/Cm//sup 239/Pu, and /sup 238/U//sup 239/Pu ratios were greater than the respective ratio in sediment while /sup 233/ /sup 234/U//sup 238/U, and /sup 239/ /sup 240/Pu//sup 238/Pu ratios were not different from the respective ratios in sediment. The relative uptake of actinides from contaminated sediment by aquatic and terrestrial biota at this site was U > Cm greater than or equal to Am > Pu. The relative extractability of actinides from shoreline sediment was U > Cm approx. = Am > Pu; we also observed the same relative ranking for sediment-water exchange in situ. Concentrations of transuranics in water, terrestrial vegetation, and vertebrate carcasses were less than 10% of the recommended public exposure maximum permissible concentration (MPC) of the ICRP
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