Departamento de Química

In this study, fed-batch cultures of a Pichia pastoris strain constitutively expressing a single chain antibody fragment (scFv) under the control of the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter were performed in a pilot 50 L bioreactor. Due to the very high cell density achieved within the first 75 h, typically between 140 and 160 g-DCW/L of dry cell weight (DCW), most of the scFv is produced under hard oxygen transfer limitation. To improve scFv productivity, a direct adaptive dissolved oxygen (DO)-stat feeding controller that maximizes glycerol feeding under the constraint of available oxygen transfer capacity was developed and applied to this process. The developed adaptive controller enabled to maximize glycerol feeding through the regulation of DO concentration between 3 and 5 % of saturation, thereby improving process productivity. Set-point convergence dynamics are characterized by a fast response upon large perturbations to DO, followed by a slower but very robust convergence in the vicinity of the boundary with almost imperceptible overshoot. Such control performance enabled operating closer to the 0 % boundary for longer periods of time when compared to a traditional proportional-integral-derivative algorithm, which tends to destabilize with increasing cell density.

This study correlates Holocene sedimentation with regional environmental changes for the Guadiana middle shelf, SW Iberia, based on a detailed sedimentological analysis combined with radiocarbon and amino acid racemization dating. The sedimentary record of vibrocore CRIDA16 (307 cm) from the mud patch off the Guadiana River is characterized by a transgressive signature. Terrigenous sand–gravel dominates the core base up to ca. 5,000 cal. years b.p., enriched in schist/greywackes and non-reworked quartz. The shelf area was under the direct influence of Guadiana bed load discharges, as sea level was lower than today but rising, favouring the entrapment of fines during the Guadiana estuary infilling in the early Holocene. Core upwards, fines dominate the record. Sea-level stabilization at ca. 5,700–3,700 cal. years b.p. led to estuary infilling by coarser sediments and export of suspended sediment to the middle shelf. After ca. 900–700 cal. years b.p., the formation of the Guadiana Mud Patch signifies deposition in a marine environment dominated by suspended material from the Guadiana River. Comparison with earlier publications showed that a similar evolutionary mechanism of middle shelf mud deposition occurred in other parts of the Iberian Margin, pointing to a generalized establishment of this type of sedimentary body in Iberia since the mid to late Holocene. This suggests that the formation of mud belts on the north and south Iberian Margin was to a large extent synchronous. It is likely that the evolution of the Guadiana Mud Patch on the shelf was controlled foremost by the overall climate trends identified for several parts of Iberia during the Holocene (i.e. increased aridity punctuated by significant humidity stages), and less by human occupation of the region. Enhanced humidity stages led to higher rainfall and intensified floods, with a consequent increase of discharges to the shelf which ultimately were responsible for the Guadiana Mud Patch formation. It is expected that this pattern of sedimentary dynamics has been strongly disturbed since 2002, when the closing of the Alqueva Dam (the biggest on the Iberian Peninsula) was completed in the Guadiana River basin.