Scaling-up vaccine production: implementation aspects of a biomass growth observer and controller

Abstract This study considers two aspects of the implementation of a biomass growth observer and specific growth rate controller in scale-up from small- to pilot-scale bioreactors towards a feasible bulk production process for whole-cell vaccine against whooping cough. The first is the calculation of the oxygen uptake rate, the starting point for online monitoring and control of biomass growth, taking into account the dynamics in the gas-phase. Mixing effects and delays are caused by amongst others the headspace and tubing to the analyzer. These gas phase dynamics are modelled using knowledge of the system in order to reconstruct oxygen consumption. The second aspect is to evaluate performance of the monitoring and control system with the required modifications of the oxygen consumption calculation on pilot-scale. In pilot-scale fed-batch cultivation good monitoring and control performance is obtained enabling a doubled concentration of bulk vaccine compared to standard batch productio

Dispersal of Plants by Waterbirds

The widespread distribution of fresh-water plants and of the lower animals, whether retaining the same identical form or in some degree modified, I believe mainly depends on the wide dispersal of their seeds and eggs by animals, more especially by fresh-water birds, which have large powers of flight, and naturally travel from one to another and often distant piece of water. — Charles Darwin (1859)Peer reviewe

Seed dispersal by dabbling ducks: an overlooked dispersal pathway for a broad spectrum of plant species

1. Dabbling ducks (Anatinae) are omnivorous birds that are widespread, numerous, highly mobile and often migratory, and therefore have great potential for (long distance) dispersal of other organisms, including plants. However, their ability to act as plant dispersal vectors has received little attention compared to frugivores and is often assumed to be relevant only for wetland species. 2. To evaluate the potential for plant dispersal by dabbling ducks, we collated and analysed existing data. We identified all plant species whose seeds have been recorded in the diets of the seven dabbling duck (Anas) species in the Western Palaearctic, as reported from gut content analyses. We then analysed the habitats and traits of these plant species to identify general patterns, and related these to data on gut passage survival and duck movements. 3. A large number of plant species (> 445 species of 189 genera and 57 families) have been recorded in the diet of dabbling ducks. These plant species represent a very wide range of habitats, including almost the full range of site fertility, moisture and light conditions, excluding only very dry and deeply shaded habitats. The ducks prefer seeds of intermediate sizes (1–10 mm3), which have good chances to survive gut passage, but also ingest smaller and larger seeds. Ingested seeds represent a wide range of dispersal syndromes, including fleshy fruits. Many species (62%) were not previously considered animal- dispersed in plant data bases, and 66% were not identified as bird-dispersed. Rarefaction analyses suggest that our analysis still greatly underestimates the total number of plant species ingested. 4. Synthesis. Dabbling ducks do not exclusively ingest seeds of wetland plants, which make up only 40% of the ingested species. Rather, they feed opportunistically on a wide cross-section of plant species available across the landscapes they inhabit. Given the millions of ducks, the hundreds to thousands of seeds ingested per individual on a daily basis, and known gut passage survival rates, this results in vast numbers of seeds dispersed by ducks per day. Internal seed dispersal by dabbling ducks appears to be a major dispersal pathway for a far broader spectrum of plant species than previously consideredPeer reviewe

Criticism of the Use of Coomassie Brilliant Blue G-250 for the Quantitative Determination of Proteins

Peer Reviewe

Online automatic tuning and control for fed-batch cultivation

Performance of controllers applied in biotechnological production is often below expectation. Online automatic tuning has the capability to improve control performance by adjusting control parameters. This work presents automatic tuning approaches for model reference specific growth rate control during fed-batch cultivation. The approaches are direct methods that use the error between observed specific growth rate and its set point; systematic perturbations of the cultivation are not necessary. Two automatic tuning methods proved to be efficient, in which the adaptation rate is based on a combination of the error, squared error and integral error. These methods are relatively simple and robust against disturbances, parameter uncertainties, and initialization errors. Application of the specific growth rate controller yields a stable system. The controller and automatic tuning methods are qualified by simulations and laboratory experiments with Bordetella pertussis

Darwin’s wind hypothesis: does it work for plant dispersal in fragmented habitats?

Using the wind-dispersed plant Mycelis muralis, we examined how landscape fragmentation affects variation in seed traits contributing to dispersal. Inverse terminal velocity (Vt−1) of field-collected achenes was used as a proxy for individual seed dispersal ability. We related this measure to different metrics of landscape connectivity, at two spatial scales: in a detailed analysis of eight landscapes in Spain and along a latitudinal gradient using 29 landscapes across three European regions. In the highly patchy Spanish landscapes, seed Vt−1 increased significantly with increasing connectivity. A common garden experiment suggested that differences in Vt−1 may be in part genetically based. The Vt−1 was also found to increase with landscape occupancy, a coarser measure of connectivity, on a much broader (European) scale. Finally, Vt−1 was found to increase along a south–north latitudinal gradient. Our results for M. muralis are consistent with ‘Darwin’s wind dispersal hypothesis’ that high cost of dispersal may select for lower dispersal ability in fragmented landscapes, as well as with the ‘leading edge hypothesis’ that most recently colonized populations harbour more dispersive phenotypes.

Effect of Terbinafine on the Pharmacokinetics of Cyclosporin in Humans

Cyclosporin is largely metabolized by hepatic cytochrome P450 enzymes, and azole drugs that inhibit cytochrome P450 may precipitate cyclosporin toxicity. The allylamine terbinafine binds to a small subfraction of hepatic cytochrome P450 in type I fashion, and has no effect upon hepatic metabolism of cyclosporin in vitro. The purpose of this study was to determine whether oral terbinafine alters the pharmacokinetics of oral cyclosporin in vivo.Twenty male volunteers (age 19–44 years), were randomly allocated to two groups. The first group received three single oral doses of cyclosporin 300mg at intervals of 21 d. The second and third doses of cyclosporin were preceded by a 6-d course of oral terbinafine 250mg each morning. A further 250mg of terbinafine was taken with the second and third doses of cyclosporin. Blood levels of cyclosporin and terbinafine were monitored for 36h after each dose. The second group received a 7-d course of terbinafine 250mg each morning. On the seventh day a single dose of cyclosporin 300mg was taken together with the terbinafine. Blood levels of both cyclosporin and terbinafine were monitored for 36kh. Two further single doses of cyclosporin 300mg were given at intervals of 2 weeks and the cyclosporin levels again monitored. In both groups each cyclosporin dose was preceded by an 8-h fast.The mean peak blood concentration of cyclosporin when taken alone was 958 μg/I, and 822 when taken with terbinafine. The mean area under the curve for cyclosporin was 4207 μg/l/h when taken alone and 3665 when taken with terbinafine. The mean absorption half-life for cyclosporin when taken alone was 0.29 h, and 0.33 when taken with terbinafine. The mean time of maximum concentration and elimination half-life of cyclosporin were unaltered by terbinafine. The results suggest that terbinafine is likely to prove a safe systemic anti-fungal treatment for patients who are taking cyclosporin

Micro-CT-scanning as a valuable source of data for musculoskeletal studies in biology

Over time, so-called classic biological studies (such as anatomical studies) have evolved into modern, highly integrated strategies tackling important questions in evolutionary biology. Where early morphologists limited themselves to descriptions based on dissections, non-invasive imaging techniques nowadays allow to uncover details of anatomy in a way that morphologists can go far beyond basic and descriptive anatomy, e.g. through modelling. In this presentation, an overview is presented on some on-going research projects that rely on X-ray tomography data, which focus on the adaptive evolution of musculoskeletal systems in different vertebrate lineages. Cases discussed are (1) a study on the cranial anatomical diversity and functional implications in the feeding apparatus in seahorses, (2) as well as multi-body modelling of the tail system in these fishes; and (3) structural diversity in Darwin’s finches in relation to high performance seed cracking. These cases clearly show the (still not fully explored) potential for testing specific hypotheses with respect to adaptive evolution, where X-ray tomography provides the tools to model experimental conditions that are impossible to achieve with live specimens (e.g. perfect control of specific parameters)