The Rose of Rietfontein A South African Pastoral Romance

https://commons.und.edu/settler-literature/1184/thumbnail.jp

Modelling of industrial biopharmaceutical multicomponent chromatography

The development and validation of a chromatography rate model for an industrial multicomponent chromatographicbioseparation is presented. The model is intended for use in a process scenario to allow specific variables critical toproduct quality to be studied. The chromatography provides impurity clearance whilst producing a complex productcomposed of six closely related variants of a dimer protein therapeutic (∼30 kDa), with their monomer subunits in aspecific ratio. Impurity removal is well understood, however, achieving the correct monomer subunit ratio can posea purification challenge. We utilise a stepwise approach to develop a model for studying the effect of feed materialvariability on product quality. Scale down experiments are completed to quickly generate data for estimating modelparameters, before an iterative procedure is employed where the industrial process is used to refine parameters ina sequential manner, until model predictions exhibit satisfactory agreement with experimental data. Final modelpredictions were in good agreement with experimental product quality (within 3%). The results demonstrate howgood understanding of an industrial process can help facilitate model development when an exhaustive descrip-tion is not required, despite considering a chromatographic bioseparation with crude feed material and challengingpurification objectives

The Assessment of Total Energy Expenditure During a 14-Day In-Season Period of Professional Rugby League Players Using the Doubly Labelled Water Method

Rugby League is a high-intensity collision sport competed over 80 min. Training loads are monitored to maximize recovery and assist in the design of nutritional strategies although no data are available on the total energy expenditure (TEE) of players. We therefore assessed resting metabolic rate (RMR) and TEE in six Super League players over 2 consecutive weeks in-season including one game per week. Fasted RMR was assessed followed by a baseline urine sample before oral administration of a bolus dose of hydrogen (deuterium 2H) and oxygen (18O) stable isotopes in the form of water (2H218O). Every 24 hr thereafter, players provided urine for analysis of TEE via DLW method. Individual training load was quantified using session rating of perceived exertion (sRPE) and data were analyzed using magnitude-based inferences. There were unclear differences in RMR between forwards and backs (7.7 ± 0.5 cf. 8.0 ± 0.3 MJ, respectively). Indirect calorimetry produced RMR values most likely lower than predictive equations (7.9 ± 0.4 cf. 9.2 ± 0.4 MJ, respectively). A most likely increase in TEE from Week 1 to 2 was observed (17.9 ± 2.1 cf. 24.2 ± 3.4 MJ) explained by a most likelyincrease in weekly sRPE (432 ± 19 cf. 555 ± 22 AU), respectively. The difference in TEE between forward and backs was unclear (21.6 ± 4.2 cf. 20.5 ± 4.9 MJ, respectively). We report greater TEE than previously reported in rugby that could be explained by the ability of DLW to account for all match and training-related activities that contributes to TEE

A model based approach for identifying robust operating conditions for industrial chromatography with process variability

A model based approach has been developed and used to identify robust operating conditions for an industrial hydrophobic interaction chromatography where resin lot variability, combined with feed stream variability, was resulting in serious performance issues during the purification of a multi component therapeutic protein from crude feed material. An equilibrium dispersive model was formulated which successfully predicted the key product critical quality attribute during validation studies. The model was then used to identify operating parameter ranges that assured product quality despite the process variability. Probabilistic design spaces were generated using stochastic simulations that showed the probability that each resin lot would meet product quality specifications, over a range of possible operating conditions, accounting for the historical variability experienced in the load material composition and concentration. No operating condition was found with normal process variability where quality assurance remained >0.95 for resins that gave the highest and lowest product recoveries during process development. The lowest risk of batch failure found was 16%, and operating conditions were not robust. We then extended the stochastic methodology used to generate probabilistic design spaces, to identify the level of control required on the load material composition and concentration to bring process robustness to an acceptable level, which is not possible using DOE experimental methods due to the impractical amount of resources that would be required. Although reducing inlet variability resulted in an increase in the assurance of product quality, the results indicated that changing operating conditions according to which resin lot is in use is the favorable option

Fouling of an anion exchange chromatography operation in a monoclonal antibody process: Visualization and kinetic studies

Fouling of chromatographic resins over their operational lifetimes can be a significant problem for commercial bioseparations. In this article, scanning electron microscopy (SEM), batch uptake experiments, confocal laser scanning microscopy (CLSM) and small-scale column studies were applied to characterize a case study where fouling had been observed during process development. The fouling was found to occur on an anion exchange (AEX) polishing step following a protein A affinity capture step in a process for the purification of a monoclonal antibody. Fouled resin samples analyzed by SEM and batch uptake experiments indicated that after successive batch cycles, significant blockage of the pores at the resin surface occurred, thereby decreasing the protein uptake rate. Further studies were performed using CLSM to allow temporal and spatial measurements of protein adsorption within the resin, for clean, partially fouled and extensively fouled resin samples. These samples were packed within a miniaturized flowcell and challenged with fluorescently labeled albumin that enabled in situ measurements. The results indicated that the foulant has a significant impact on the kinetics of adsorption, severely decreasing the protein uptake rate, but only results in a minimal decrease in saturation capacity. The impact of the foulant on the kinetics of adsorption was further investigated by loading BSA onto fouled resin over an extended range of flow rates. By decreasing the flow rate during BSA loading, the capacity of the resin was recovered. These data support the hypothesis that the foulant is located on the particle surface, only penetrating the particle to a limited degree. The increased understanding into the nature of the fouling can help in the continued process development of this industrial example

Photo-production of Nucleon Resonances and Nucleon Spin Structure Function in the Resonance Region

The photo-production of nucleon resonances is calculated based on a chiral constituent quark model including both relativistic corrections H{rel} and two-body exchange currents, and it is shown that these effects play an important role. We also calculate the first moment of the nucleon spin structure function g1 (x,Q^2) in the resonance region, and obtain a sign-changing point around Q^2 ~ 0.27 {GeV}^2 for the proton.Comment: 23 pages, 5 figure

Energy expenditure in professional flat jockeys using doubly labelled water during the racing season: Implications for body weight management.

To formulate individualized dietary strategies for jockeys, it is vital that energy requirements are quantified. We measured total energy expenditure (TEE) over two separate weeks in spring and summer using doubly labelled water in a group of male flat jockeys (n = 8, 36.9 ± 5.7 years, 164 ± 8 cm, 54.6 ± 2.5 kg). Total energy intake (TEI) was self-recorded, as were all riding and structured exercise activity. Mean daily TEE was 10.83 (±2.3) and 10.66 (±1.76) MJ, (p = .61) respectively. Self-reported TEI were 6.03 (±1.7) and 5.37 (±1.1) MJ (p = .40), respectively, and were significantly lower than TEE (p = .01). Mean race rides were 17 (±6) and 13 (±3; p = 0.37) and horses ridden at morning exercise were 8 (±6) and 7 (±4; p = .77) respectively. Additional structured exercise was 76.25 (±95.1) and 52.5 (±80.9) min per week (p = .35), respectively. At the individual level, TEE was related to body mass and the level of non-racing physical activity, but not riding. Physical activity levels for TEE were 1.76 (±0.37) and 1.69 (±0.27; p = .59) and appear modest when compared with other athletes, and similar to age-matched non-athletes, suggesting that conventional sport-specific nutritional recommendations do not appear applicable. The large discrepancy between TEE and TEI suggests significant under reporting of dietary intake. These data now provide an appropriate framework from which to formulate jockey nutritional guidelines to promote the ability to achieve the daily weight target and improve athlete welfare

On the Energy Dependence of the Dipole-Proton Cross Section in Deep Inelastic Scattering

We study the dipole picture of high-energy virtual-photon-proton scattering. It is shown that different choices for the energy variable in the dipole cross section used in the literature are not related to each other by simple arguments equating the typical dipole size and the inverse photon virtuality, contrary to what is often stated. We argue that the good quality of fits to structure functions that use Bjorken-x as the energy variable - which is strictly speaking not justified in the dipole picture - can instead be understood as a consequence of the sign of scaling violations that occur for increasing Q^2 at fixed small x. We show that the dipole formula for massless quarks has the structure of a convolution. From this we obtain derivative relations between the structure function F_2 at large and small Q^2 and the dipole-proton cross section at small and large dipole size r, respectively.Comment: 27 page

Accreting Protoplanets in the LkCa 15 Transition Disk

Exoplanet detections have revolutionized astronomy, offering new insights into solar system architecture and planet demographics. While nearly 1900 exoplanets have now been discovered and confirmed, none are still in the process of formation. Transition discs, protoplanetary disks with inner clearings best explained by the influence of accreting planets, are natural laboratories for the study of planet formation. Some transition discs show evidence for the presence of young planets in the form of disc asymmetries or infrared sources detected within their clearings, as in the case of LkCa 15. Attempts to observe directly signatures of accretion onto protoplanets have hitherto proven unsuccessful. Here we report adaptive optics observations of LkCa 15 that probe within the disc clearing. With accurate source positions over multiple epochs spanning 2009 - 2015, we infer the presence of multiple companions on Keplerian orbits. We directly detect H{\alpha} emission from the innermost companion, LkCa 15 b, evincing hot (~10,000 K) gas falling deep into the potential well of an accreting protoplanet.Comment: 35 pages, 3 figures, 1 table, 9 extended data item