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Browsing by Issue Date, starting with "2014-04-01"

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  • Inflation in a two 3-form fields scenario
    Publication . Kumar, K. Sravan; Marto, João; Nunes, Nelson J.; Moniz, Paulo
    A setting constituted by N 3-form fields, without any direct interaction between them, minimally coupled to gravity, is introduced in this paper as a framework to study the early evolution of the universe. We focus particularly on the two 3-forms case. An inflationary scenario is found, emerging from the coupling to gravity. More concretely, the fields coupled in this manner exhibit a complex interaction, mediated by the time derivative of the Hubble parameter. Our investigation is supported by means of a suitable choice of potentials, employing numerical methods and analytical approximations. In more detail, the oscillations on the small field limit become correlated, and one field is intertwined with the other. In this type of solution, a varying sound speed is present, together with the generation of isocurvature perturbations. The mentioned features allow to consider an interesting model, to test against observation. It is subsequently shown how our results are consistent with current CMB data (viz.Planck and BICEP2).
    2014-04-01Journal article Restricted access Show more
  • Improved Minicircle DNA Biosynthesis for Gene Therapy Applications
    Publication . Gaspar, V. M.; Maia, C J; Queiroz, João; Pichon, Chantal; Correia, Ilídio; Sousa, Fani
    Minicircular DNA (mcDNA) biopharmaceuticals have recently risen as a valuable alternative for the development of a next generation of bioactive therapeutics because they are more efficient and safer than standard plasmid DNA (pDNA). To date, the relatively insufficient knowledge regarding mcDNA biosynthesis is currently hindering its manufacture in suitable amounts for clinical trial evaluations. Addressing this limitation is therefore mandatory to bring forth the full therapeutic potential of this cutting-edge technology. Herein, we describe for the first time new processing parameters that improve the overall yield of mcDNA obtained from bacterial fermentations. We provide details for further in-line monitoring and optimization in view of the current good manufacturing guidelines. Our results show that by rising growth temperature to 42°C, an increase in the overall minicircle producer plasmid yield is attained, while biomass amounts are reduced. Moreover, by monitoring in real time the dynamic recombination of parental plasmids to mcDNA, we found that this event is more efficient at specific time points, regardless of the growth temperature and inductor concentration used. These are important findings since mcDNA can be recovered with higher yields at these determined key stages. Indeed, the manipulation of these parameters resulted in a 2.21-fold increase in mcDNA production compared with the established growth temperatures for this technology. Overall, our findings highlight that to achieve maximum productivity while attaining pharmaceutical-grade mcDNA preparations, process design and biosynthesis optimization must take into account key parameters such as temperature, inductor concentration, and recovery time.
    2014-04-01Journal article Restricted access Show more