De Marco A.,University of Nova Gorica
Critical Reviews in Biotechnology | Year: 2013
The availability of binders to different functional domains of the same protein or to physiologically co-operating proteins allows for the simultaneous inhibition of independent downstream signaling pathways. This multi-target approach represents a promising therapeutic strategy, as demonstrated in the case of the synergistic effect of anti-Her2 treatment based on the combined use of the trastuzumab and pertuzumab monoclonal antibodies that induce cellular cytotoxicity and impair the receptor dimerization, respectively. Therefore, a reliable selection method for the recovery of epitope-specific antibodies is highly needed. Animal immunization with short peptides resembling the epitope sequence for raising conventional antibodies represents an alternative. Panning phage displayed libraries of recombinant antibodies such as scFvs and nanobodies or of other peptide collections is another option. Although recombinant antibodies can provide the same specificity as conventional antibodies, they offer at least two further advantages: i) the protocols for the selection of epitope-specific antibodies can be rationally designed, and ii) their expression as multivalent, bispecific and biparatopic molecules is feasible. This review will analyze the recent literature concerning technical aspects related to the isolation, the expression as multivalent molecules, and the therapeutic applications of binders able to interfere with antigen functional domains. The term binder will be preferred when possible to include those molecules, such as peptides or affibodies, with at least some proven practical uses. © 2013 Informa Healthcare USA, Inc.
de Marco A.,University of Nova Gorica
Microbial Cell Factories | Year: 2015
Background: Antibodies have been a pillar of basic research, while their relevance in clinical diagnostics and therapy is constantly growing. Consequently, the production of both conventional and fragment antibodies constantly faces more demanding challenges for the improvement of their quantity and quality. The answer to such an increasing need has been the development of a wide array of formats and alternative production platforms. This review offers a critical comparison and evaluation of the different options to help the researchers interested in expressing recombinant antibodies in their choice. Results: Rather than the compilation of an exhaustive list of the recent publications in the field, this review intendeds to analyze the development of the most innovative or fast-growing strategies. These have been illustrated with some significant examples and, when possible, compared with the existing alternatives. Space has also been given to those solutions that might represent interesting opportunities or that investigate critical aspects of the production optimization but for which the available data as yet do not allow for a definitive judgment. Conclusions: The take-home message is that there is a clear process of progressive diversification concerning the antibody expression platforms and an effort to yield directly application-adapted immune-reagents rather than generic naked antibodies that need further in vitro modification steps before becoming usable. © 2015 de Marco.
Di Mitri S.,Elettra - Sincrotrone Trieste |
Cornacchia M.,Elettra - Sincrotrone Trieste |
Spampinati S.,University of Nova Gorica
Physical Review Letters | Year: 2013
Minimizing transverse emittance is essential in linear accelerators designed to deliver very high brightness electron beams. Emission of coherent synchrotron radiation (CSR), as a contributing factor to emittance degradation, is an important phenomenon to this respect. A manner in which to cancel this perturbation by imposing certain symmetric conditions on the electron transport system has been suggested.We first expand on this idea by quantitatively relating the beam Courant-Snyder parameters to the emittance growth and by providing a general scheme of CSR suppression with asymmetric optics, provided it is properly balanced along the line. We present the first experimental evidence of this cancellation with the resultant optics balance of multiple CSR kicks: the transverse emittance of a 500 pC, sub-picosecond, high brightness electron beam is being preserved after the passage through the achromatic transfer line of the FERMI@Elettra free electron laser, and emittance growth is observed when the optics balance is intentionally broken. We finally show the agreement between the theoretical model and the experimental results. This study holds the promise of compact dispersive lines with relatively large bending angles, thus reducing costs for future electron facilities. © 2013 American Physical Society.
Blau M.,University of Bern |
O'Loughlin M.,University of Nova Gorica
Journal of High Energy Physics | Year: 2016
We revisit the theory of null shells in general relativity, with a particular emphasis on null shells placed at horizons of black holes. We study in detail the considerable freedom that is available in the case that one solders two metrics together across null hypersurfaces (such as Killing horizons) for which the induced metric is invariant under translations along the null generators. In this case the group of soldering transformations turns out to be infinite dimensional, and these solderings create non-trivial horizon shells containing both massless matter and impulsive gravitational wave components. We also rephrase this result in the language of Carrollian symmetry groups. To illustrate this phenomenon we discuss in detail the example of shells on the horizon of the Schwarzschild black hole (with equal interior and exterior mass), uncovering a rich classical structure at the horizon and deriving an explicit expression for the general horizon shell energy-momentum tensor. In the special case of BMS-like soldering supertranslations we find a conserved shell-energy that is strikingly similar to the standard expression for asymptotic BMS supertranslation charges, suggesting a direct relation between the physical properties of these horizon shells and the recently proposed BMS supertranslation hair of a black hole. © 2016, The Author(s).
de Marco A.,University of Nova Gorica
Microbial Cell Factories | Year: 2011
Background: Single-domain antibody fragments possess structural features, such as a small dimension, an elevated stability, and the singularity of recognizing epitopes non-accessible for conventional antibodies that make them interesting for several research and biotechnological applications.Results: The discovery of the single-domain antibody's potentials has stimulated their use in an increasing variety of fields. The rapid accumulation of articles describing new applications and further developments of established approaches has made it, therefore, necessary to update the previous reviews with a new and more complete summary of the topic.Conclusions: Beside the necessary task of updating, this work analyses in detail some applicative aspects of the single-domain antibodies that have been overseen in the past, such as their efficacy in affinity chromatography, as co-crystallization chaperones, protein aggregation controllers, enzyme activity tuners, and the specificities of the unconventional single-domain fragments. © 2011 de Marco; licensee BioMed Central Ltd.