‘Next generation’ chromatographic media for biopharmaceutical manufacturing

Novel ways to produce bilayered chromatography adsorbent media featuring a functionalised core surrounded by an inert size exclusion layer for nanoplex purification were explored. Surface functionalisation of anion exchange chromatography media via cold atmospheric pressure plasma etching and oxidation was investigated. Both, a dielectric barrier discharge plasma generation system and a fluidised bed underwater reactor produced bead samples with significantly reduced surface binding, while maintaining their core binding capacities. A 3D visualisation method, allowing the study of the binding topography of the spatial distribution of pDNA and BSA adhered to Q ligands within particles was developed. This CLSM method revealed imperfections on the surface of adsorbents, providing additional binding sites for pDNA due to micro crevices. Implementing beads with a more homogenous surface, restricted access media were produced via an AGE activation-partial bromination method. The thickness and homogeneity of the size exclusion layer was controlled via viscosity enhanced reaction diffusion balancing, yielding a distinct layer devoid of ligands. The particles did not show residual pDNA binding and selectivity of core vs surface binding increased by 100-fold cf. previous studies. The commercial adsorbent Capto Core 700 was successfully implemented as a first capture step for pDNA purification from crude E.coli lysates

Economic and legal aspects of international environmental agreements: The case of enforcing and stabilising an international CO 2 agreement

The protection of the global environment is impeded by multilateral externalities which the international community attempts to bring under control by entering into international agreements. International agreements, however, can suffer from non-compliance and free-riding behaviour by sovereign states and must therefore be enforced and stabilised internationally. This paper describes instruments for the enforcement and stabilisation of an international CO2 agreement and evaluates them in the light of economic and legal theory. Economic instruments build on repetition and use utility transfers, economic sanctions and flexible treaty adjustments. Important legal instruments are reciprocal obligations and cooperation duties, international funding and transfer rules, treaty suspension, retorsions and reprisals, treaty revision, and monitoring. The paper shows that economic and legal instruments are compatible to a considerable extent. It develops proposals for the enforcement and stabilisation of a global CO2 agreement and other multilateral treaties.International environmental agreements,international cooperation,non-compliance,enforcement,global warming,international law

Fabrication of highly resistive NiO thin films for nanoelectronic applications

Thin films of the prototypical charge transfer insulator NiO appear to be a promising material for novel nanoelectronic devices. The fabrication of the material is challenging however, and mostly a p-type semiconducting phase is reported. Here, the results of a factorial experiment are presented that allow optimization of the film properties of thin films deposited using sputtering. A cluster analysis is performed, and four main types of films are found. Among them, the desired insulating phase is identified. From this material, nanoscale devices are fabricated, which demonstrate that the results carry over to relevant length scales. Initial switching results are reported

Separation of the systems for color and spatial manipulation in working memory revealed by a dual-task procedure

The manipulation of different kinds of content is fundamental to working memory. It has been suggested that the mere maintenance of color and spatial information occurs in parallel, but little is known about whether this holds true for manipulation as well. Using a dual-task delayed-response paradigm that required the manipulation of color and angles, this study finds that the two functions do not interfere. Conversely, interference did occur when both components of a dual-task tapped into the spatial system. Thus, color and spatial information are manipulated in parallel. A concurrent phonological task did not interfere with either maintenance or manipulation, whereas a task requiring central executive processes interfered with manipulation only. We speculate that the ventral–dorsal dissociation of visual processing is conserved for manipulation processes and that manipulation differs from maintenance in the extent to which is relies on central executive resources

Enantioseparation of Dansylated Amino Acids by Ligand-exchange Capillary Electrophoresis Using L-phenylalaninamide, L-lysine or L-threonine as Chiral Selector

In recent years enantioseparation of both active pharmaceutical ingredients and bio molecules such as amino acids became more and more necessary because in most cases the two stereo forms exhibit different pharmacological effects. This article deals with the chiral separation of dansylated amino acids by ligand-exchange capillary electrophoresis using L-phenylalaninamide, L-lysine and L-threonine as chiral selectors. Experiments with different central metal ions such as Cu(II), Co(II), Cd(II), Ni(II) and Zn(II) were carried out. Optimal conditions were found out by studying the effect of the pH and the selector molarity on the chiral resolution. Best separation was obtained for the Cu(II)/L-lysine complex, showing a chiral resolution up to 17 for Dns-DL-Met. (doi: 10.5562/cca1762

Umweltpolitik mit handelbaren Emissionsrechten : Möglichkeiten zur Verringerung der Kohlendioxid- und Stickoxidemissionen.

Emissionsrechte; Luftverunreinigung; Kohlendioxid; Stickoxid; Klimaveränderung; Deutschland; EU-Staaten;

miR-34a is upregulated inAIP-mutated somatotropinomas and promotes octreotide resistance

Pituitary adenomas (PAs) are intracranial tumors associated with significant morbidity due to hormonal dysregulation, mass effects and have a heavy treatment burden. Growth hormone (GH)-secreting PAs (somatotropinomas) cause acromegaly-gigantism. Genetic forms of somatotropinomas due to germlineAIPmutations (AIPmut+) have an early onset and are aggressive and resistant to treatment with somatostatin analogs (SSAs), including octreotide. The molecular underpinnings of these clinical features remain unclear. We investigated the role of miRNA dysregulation inAIPmut+ vsAIPmut- PA samples by array analysis. miR-34a and miR-145 were highly expressed inAIPmut+ vsAIPmut- somatotropinomas. Ectopic expression ofAIPmut (p.R271W) inAip(-/-)mouse embryonic fibroblasts (MEFs) upregulated miR-34a and miR-145, establishing a causal link betweenAIPmut and miRNA expression. In PA cells (GH3), miR-34a overexpression promoted proliferation, clonogenicity, migration and suppressed apoptosis, whereas miR-145 moderately affected proliferation and apoptosis. Moreover, high miR-34a expression increased intracellular cAMP, a critical mitogenic factor in PAs. Crucially, high miR-34a expression significantly blunted octreotide-mediated GH inhibition and antiproliferative effects. miR-34a directly targetsGnai2encoding G alpha i2, a G protein subunit inhibiting cAMP production. Accordingly, G alpha i2 levels were significantly lower inAIPmut+ vsAIPmut- PA. Taken together, somatotropinomas withAIPmutations overexpress miR-34a, which in turn downregulates G alpha i2 expression, increases cAMP concentration and ultimately promotes cell growth. Upregulation of miR-34a also impairs the hormonal and antiproliferative response of PA cells to octreotide. Thus, miR-34a is a novel downstream target of mutantAIPthat promotes a cellular phenotype mirroring the aggressive clinical features ofAIPmut+ acromegaly.Peer reviewe