Theoretical Analysis and Experimental Investigation of Simulated Moving Bed Chromatography for the Purification of Protein Mixtures

Stepwise-Elution Simulated Moving Bed Chromatography (SE-SMB) is a promising method for ‘intensification’ of polishing chromatographic processes in downstream bioprocessing. This is because SE-SMB systems are continuous, capable of high-resolution separations, efficient in their utilization of chromatographic resins, well-suited to non-isocratic proteinaceous separation problems operated under high feed-loading conditions, and highly productive. However, there are a number of theoretical and practical problems which have impeded industrial interest in the adoption of SE-SMB separations into downstream processes. Fundamental phenomena, such as the modulator dynamics of SE-SMB systems, have yet to be theoretically analysed. Consequently, important practical questions – such as how productive and high-resolution separations may be best achieved through SE-SMB systems – remain unanswered. Furthermore, the complexity and operational fragility of SE-SMB systems require much improvement in their ‘robustness’ before any consideration of their application to industrial purification of therapeutic proteins may be entertained. This thesis constitutes an initial investigation of the theoretical and practical issues which arise concerning the application of SE-SMB to industrial bioseparations. Regarding the theoretical issues, an analysis of modulator dynamics in SE-SMB systems is presented. This provides new insights into how such systems – both for binary and ternary separations - should be designed for productive and robust operations. Furthermore, the behaviour of SE-SMB systems under high feedloading conditions is also investigated. Regarding practical issues, experimental SMB separations of a challenging proteinaceous mixture are demonstrated, and simulated comparisons are used to investigate the comparative performance of various intensified processes. Finally, an exploration of SE-SMB fault detection and diagnosis methods is undertaken. The results suggest that SE-SMB chromatography may be ‘de-risked’ to such an extent that, with future development, it becomes an attractive option for incorporation into industrial bioprocesses

Salmonine Consumption and Competition for Endemic Prey Fishes in Bear Lake, Utah-Idaho

Two principal sport fish—the indigenous Bonneville cutthroat trout Oncorhynchus clarki utah and the introduced lake trout Salvelinus namaycush—are the dominant piscivores in Bear Lake, a 282-km^2 oligotrophic system. These piscivores rely predominantly on four endemic prey fish species that make up a major portion of the unique Bear Lake fish assemblage. We estimated the annual biomass of pelagic and benthic prey fish by using hydroacoustic and trawling techniques. We also estimated the lakewide abundance of piscivores with a multiple mark–recapture survey and used a bioenergetics model to compare the population-level consumption of prey fish with prey fish production. Prey fish biomass declined to a minimum during 1991 and 1992 but subsequently recovered to reach maximum levels during 1994 and 1995. The proportion of maximum ration estimates from model simulations indicated that the piscivores were consuming well below maximum rations during a period when predation exceeded prey fish production, thereby providing the potential for a predator–prey imbalance. Predation impacts by lake trout cohorts were prolonged because of high survivorship and long life expectancy. Although cutthroat trout outnumbered lake trout, the larger, more piscivorous size-classes of cutthroat trout accounted for only 12.5% of their population. This information, combined with overlapping diets and declining condition factors at increased piscivore biomass, also indicates that lake trout may be competing with cutthroat trout during periods of low prey fish resources. Lake trout predation on juvenile cutthroat trout, combined with competition with other age-classes, also contributes to the poor survival of cutthroat trout. Although prey fish abundance appears to be largely influenced by bottom-up factors related to water elevation, lake trout exert a decoupled predatory threat to the endemic prey fish populations and have the potential to suppress endemic fishes during unpredictable periods of poor prey fish production

Quantifying Inter- and Intra-Population Niche Variability Using Hierarchical Bayesian Stable Isotope Mixing Models

Variability in resource use defines the width of a trophic niche occupied by a population. Intra-population variability in resource use may occur across hierarchical levels of population structure from individuals to subpopulations. Understanding how levels of population organization contribute to population niche width is critical to ecology and evolution. Here we describe a hierarchical stable isotope mixing model that can simultaneously estimate both the prey composition of a consumer diet and the diet variability among individuals and across levels of population organization. By explicitly estimating variance components for multiple scales, the model can deconstruct the niche width of a consumer population into relevant levels of population structure. We apply this new approach to stable isotope data from a population of gray wolves from coastal British Columbia, and show support for extensive intra-population niche variability among individuals, social groups, and geographically isolated subpopulations. The analytic method we describe improves mixing models by accounting for diet variability, and improves isotope niche width analysis by quantitatively assessing the contribution of levels of organization to the niche width of a population

Corrosion risk assessment of structural concrete with coarse crushed concrete aggregate

Crushed concrete aggregates (CCA) are an increasingly popular replacement for natural aggregates (NA) in structural concrete due to industry demands for more recycled, low carbon footprint and responsibly sourced materials. There is uncertainty regarding chloride-ion ingress, which can ultimately cause deterioration of reinforced concrete. This is reflected in European and British concrete design standards, which currently exclude CCA in chloride environments. Structural concretes with up to 60% coarse CCA (and CEM I, CEM II/B-V and CEM III/A binders) were exposed to aggressive chloride environments and monitored with electrochemical techniques and subsequent destructive testing to determine their risk of corrosion initiation. The results showed that CEM II/B-V and CEM III/A concretes with up to 60% coarse CCA outperformed the control CEM I concrete with 100% NA, and had a lower risk of corrosion initiation. It is recommended that further monitoring is required over longer periods to determine the corrosion-initiation risk. Supplementary cementitious materials had a beneficial effect on the chloride-ion ingress resistance, significantly increased the predicted time to corrosion initiation beyond the 50-year design life and largely outweighed any observed detrimental effects from an increased coarse CCA content, suggesting that limitations imposed by existing design standards are conservative

Chloride ion ingress and chloride-induced corrosion initiation of coarse CCA structural concrete

The specification of crushed concrete aggregates (CCA) is increasing, with the construction industry still seeking new ways to improve the quality and performance. In higher value applications, such as structural concrete, further research is required to understand the effect of coarse CCAs, particularly on durability. This 4 year research programme investigated the effect of coarse CCA on transport mechanisms within CEM I and CEM III/A structural concretes, with particular emphasis on chloride ion ingress and corrosion initiation. CEM III/A concretes with up to 100% coarse CCA outperformed control CEM I concrete with 100% natural aggregates in durability performance tests, irrespective of the source of CCA. The results indicate that coarse CCA can be incorporated up to 60% replacement of natural aggregates if the criterion for compressive strength compliance at 28 days is relaxed for CEM III/A concretes. Water absorption, chemical and petrographic analysis, of the sources of coarse CCA with known compositions, had a good correlation with durability performance. This type of testing is recommended on future construction projects to mitigate potential risks

Should durability be a barrier to the use of crushed concrete aggregate in structural concrete?

Applications involving crushed concrete aggregate (CCA), or recycled concrete aggregate (RCA), are growing, as interest continues to increase in the sustainable sourcing of materials. For CCA to be fully used in structural concrete however, it’s influence on the mechanical and durability properties of the resultant concrete is required. The electrical resistivity and water absorption by capillary action of CEM I and CEM III/A concretes were hence investigated to determine the effects on concrete microstructure and water ingress. Findings show that incorporating coarse CCA has generally a detrimental effect on the microstructure and water ingress of structural concrete. However, this can be mostly overcome through the inclusion of GGBS, hence allowing higher proportions of coarse CCA to be incorporated. Limiting the GGBS and coarse CCA content to 50% and 60% respectively is advised, hence minimising the risk of any significant deterioration of mechanical and durability performance. Results suggest that CCA CEM III/A concrete cou

The Dark Energy Survey Data Management System

The Dark Energy Survey collaboration will study cosmic acceleration with a 5000 deg2 griZY survey in the southern sky over 525 nights from 2011-2016. The DES data management (DESDM) system will be used to process and archive these data and the resulting science ready data products. The DESDM system consists of an integrated archive, a processing framework, an ensemble of astronomy codes and a data access framework. We are developing the DESDM system for operation in the high performance computing (HPC) environments at NCSA and Fermilab. Operating the DESDM system in an HPC environment offers both speed and flexibility. We will employ it for our regular nightly processing needs, and for more compute-intensive tasks such as large scale image coaddition campaigns, extraction of weak lensing shear from the full survey dataset, and massive seasonal reprocessing of the DES data. Data products will be available to the Collaboration and later to the public through a virtual-observatory compatible web portal. Our approach leverages investments in publicly available HPC systems, greatly reducing hardware and maintenance costs to the project, which must deploy and maintain only the storage, database platforms and orchestration and web portal nodes that are specific to DESDM. In Fall 2007, we tested the current DESDM system on both simulated and real survey data. We used Teragrid to process 10 simulated DES nights (3TB of raw data), ingesting and calibrating approximately 250 million objects into the DES Archive database. We also used DESDM to process and calibrate over 50 nights of survey data acquired with the Mosaic2 camera. Comparison to truth tables in the case of the simulated data and internal crosschecks in the case of the real data indicate that astrometric and photometric data quality is excellent.Comment: To be published in the proceedings of the SPIE conference on Astronomical Instrumentation (held in Marseille in June 2008). This preprint is made available with the permission of SPIE. Further information together with preprint containing full quality images is available at http://desweb.cosmology.uiuc.edu/wik

Clinical and budget impacts of changes in oral anticoagulation prescribing for atrial fibrillation

OBJECTIVE: To assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England. METHODS: Data on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011-June 2014 and July 2014-December 2017. RESULTS: Between 2011-2014 and 2014-2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI -11.5% to -11.1%) from 86 467 in 2011-2014 to 76 730 in 2014-2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289. CONCLUSIONS: Despite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level

Galaxy Zoo and SPARCFIRE: constraints on spiral arm formation mechanisms from spiral arm number and pitch angles

In this paper, we study the morphological properties of spiral galaxies, including measurements of spiral arm number and pitch angle. Using Galaxy Zoo 2, a stellar mass-complete sample of 6222 SDSS spiral galaxies is selected. We use the machine vision algorithm sparcfire to identify spiral arm features and measure their associated geometries. A support vector machine classifier is employed to identify reliable spiral features, with which we are able to estimate pitch angles for half of our sample. We use these machine measurements to calibrate visual estimates of arm tightness, and hence estimate pitch angles for our entire sample. The properties of spiral arms are compared with respect to various galaxy properties. The star formation properties of galaxies vary significantly with arm number, but not pitch angle. We find that galaxies hosting strong bars have spiral arms substantially (4°-6°) looser than unbarred galaxies. Accounting for this, spiral arms associated with many-armed structures are looser (by 2°) than those in two-armed galaxies. In contrast to this average trend, galaxies with greater bulge-to-total stellar mass ratios display both fewer and looser spiral arms. This effect is primarily driven by the galaxy disc, such that galaxies with more massive discs contain more spiral arms with tighter pitch angles. This implies that galaxy central mass concentration is not the dominant cause of pitch angle and arm number variations between galaxies, which in turn suggests that not all spiral arms are governed by classical density waves or modal theories