TNA4OptFlux : a software tool for the analysis of strain optimization strategies

BACKGROUND:Rational approaches for Metabolic Engineering (ME) deal with the identification of modifications that improve the microbes' production capabilities of target compounds. One of the major challenges created by strain optimization algorithms used in these ME problems is the interpretation of the changes that lead to a given overproduction. Often, a single gene knockout induces changes in the fluxes of several reactions, as compared with the wild-type, and it is therefore difficult to evaluate the physiological differences of the in silico mutant. This is aggravated by the fact that genome-scale models per se are difficult to visualize, given the high number of reactions and metabolites involved.FINDINGS:We introduce a software tool, the Topological Network Analysis for OptFlux (TNA4OptFlux), a plug-in which adds to the open-source ME platform OptFlux the capability of creating and performing topological analysis over metabolic networks. One of the tool's major advantages is the possibility of using these tools in the analysis and comparison of simulated phenotypes, namely those coming from the results of strain optimization algorithms. We illustrate the capabilities of the tool by using it to aid the interpretation of two E. coli strains designed in OptFlux for the overproduction of succinate and glycine.CONCLUSIONS:Besides adding new functionalities to the OptFlux software tool regarding topological analysis, TNA4OptFlux methods greatly facilitate the interpretation of non-intuitive ME strategies by automating the comparison between perturbed and non-perturbed metabolic networks. The plug-in is available on the web site http://www.optflux.org webcite, together with extensive documentation.This work is funded by ERDF - European Regional Development Fund through the COMPETE Programme (operational programme for competitiveness) and by National Funds through the FCT (Portuguese Foundation for Science and Technology) within projects ref. COMPETE FCOMP-01-0124-FEDER-015079 and PEst-OE/EEI/UI0752/2011. JPP and RP work is funded by PhD grants from the Portuguese FCT (ref. SFRH/BD/41763/ 2007 and SFRH/BD/51111/2010)

Strong controlled-invariance of behavioural nD systems

In this paper we give a stronger version of the notion of behavioral controlled invariance introduced in (Pereira & Rocha, 2017) in the context of regular partial interconnections. In such interconnections, the variables are divided into two sets: the variables to-be-controlled and the variables on which it is allowed to enforce restrictions (control variables); moreover, regularity means that the restrictions of the controller do not overlap with the ones already implied by the laws of the original behavior. A complete characterization of strong controlled invariance for nD behaviors is derived making use of a special controller behavior known as the canonical controller.publishe

A computationally efficient method for calculating the maximum conductance of disordered networks: Application to 1-dimensional conductors

Random networks of carbon nanotubes and metallic nanowires have shown to be very useful in the production of transparent, conducting films. The electronic transport on the film depends considerably on the network properties, and on the inter-wire coupling. Here we present a simple, computationally efficient method for the calculation of conductance on random nanostructured networks. The method is implemented on metallic nanowire networks, which are described within a single-orbital tight binding Hamiltonian, and the conductance is calculated with the Kubo formula. We show how the network conductance depends on the average number of connections per wire, and on the number of wires connected to the electrodes. We also show the effect of the inter-/intra-wire hopping ratio on the conductance through the network. Furthermore, we argue that this type of calculation is easily extendable to account for the upper conductivity of realistic films spanned by tunneling networks. When compared to experimental measurements, this quantity provides a clear indication of how much room is available for improving the film conductivity.Comment: 7 pages, 5 figure

Microlenses for stereoscopic image formation

This paper presents microlenses for integration on a stereoscopic image sensor in CMOS technology for use in biomedical devices. It is intended to provide an image sensor with a stereoscopic vision. An array of microlenses potentiates stereoscopic vision and maximizes the color fidelity. An array of optical filters tuned at the primary colors will enable a multicolor usage. The material selected for fabricating the microlens was the AZ4562 positive photoresist. The reflow method applied to the photoresist allowing the fabrication of microlenses with high reproducibility.This work was fully supported by the Portuguese Foundation for Science and Technology under the project FCT/PTDC/EEA-ELC/109936/2009

Discovery and implementation of a novel pathway for n-butanol production via 2-oxoglutarate

Background: One of the European Union directives indicates that 10% of all fuels must be bio-synthesized by 2020. In this regard, biobutanol - natively produced by clostridial strains - poses as a promising alternative biofuel. One possible approach to overcome the difficulties of the industrial exploration of the native producers is the expression of more suitable pathways in robust microorganisms such as Escherichia coli. The enumeration of novel pathways is a powerful tool, allowing to identify non-obvious combinations of enzymes to produce a target compound. Results: This work describes the in silico driven design of E. coli strains able to produce butanol via 2-oxoglutarate by a novel pathway. This butanol pathway was generated by a hypergraph algorithm and selected from an initial set of 105,954 different routes by successively applying different filters, such as stoichiometric feasibility, size and novelty. The implementation of this pathway involved seven catalytic steps and required the insertion of nine heterologous genes from various sources in E. coli distributed in three plasmids. Expressing butanol genes in E. coli K12 and cultivation in High-Density Medium formulation seem to favor butanol accumulation via the 2-oxoglutarate pathway. The maximum butanol titer obtained was 85 \ub1 1 mg L-1 by cultivating the cells in bioreactors. Conclusions: In this work, we were able to successfully translate the computational analysis into in vivo applications, designing novel strains of E. coli able to produce n-butanol via an innovative pathway. Our results demonstrate that enumeration algorithms can broad the spectrum of butanol producing pathways. This validation encourages further research to other target compounds

The quadratic spinor Lagrangian, axial torsion current, and generalizations

We show that the Einstein-Hilbert, the Einstein-Palatini, and the Holst actions can be derived from the Quadratic Spinor Lagrangian (QSL), when the three classes of Dirac spinor fields, under Lounesto spinor field classification, are considered. To each one of these classes, there corresponds a unique kind of action for a covariant gravity theory. In other words, it is shown to exist a one-to-one correspondence between the three classes of non-equivalent solutions of the Dirac equation, and Einstein-Hilbert, Einstein-Palatini, and Holst actions. Furthermore, it arises naturally, from Lounesto spinor field classification, that any other class of spinor field (Weyl, Majorana, flagpole, or flag-dipole spinor fields) yields a trivial (zero) QSL, up to a boundary term. To investigate this boundary term we do not impose any constraint on the Dirac spinor field, and consequently we obtain new terms in the boundary component of the QSL. In the particular case of a teleparallel connection, an axial torsion 1-form current density is obtained. New terms are also obtained in the corresponding Hamiltonian formalism. We then discuss how these new terms could shed new light on more general investigations.Comment: 9 pages, RevTeX, to be published in Int.J.Mod.Phys.D (2007

Combining high-value biotechnological processes: from wastewaters bioremediation to bacterial bioenergy feedstock production

Book of Abstracts of CEB Annual Meeting 2017[Excerpt] The significant increase of global industrialization has been promoting the generation of large amounts of residues and wastewaters. In particular, oily wastewaters (contaminated with hydrocarbons) must be considered, since their disposal into the surrounding environments can represent a serious threat to several types of environmental resources. Simultaneously, the drastic depletion of fossil fuel resources demands for search of alternative feedstocks with environmental and economic advantages. Therefore, the production of bacterial lipids using inexpensive substrates, as wastes, has attracted much attention. Hydrocarbonoclastic bacteria are important players in bioremediation of hydrocarbon contaminated wastewaters with additional capacity for the accumulation of storage lipids such as triacylglycerols and wax esters [1, 2]. These compounds are relevant raw materials for biofuels and oleochemicals production. [...]info:eu-repo/semantics/publishedVersio

Polichromatic image sensor with microlenses for stereoscopic acquisition

This paper presents the fabrication of microlenses for integration on a stereoscopic image sensor in CMOS technology and a low-cost technology for fabricating optical filters arrays tuned for the primary colors. The material selected for fabricating the microlens was the AZ4562 positive photoresist and the fabrication process explained. Moreover, the fabrication process presented in this paper is for directly printing the optical filters into a transparent flexible substrate (acetate).This work was fully supported by the Portuguese Foundation for Science and Technology under the project FCT/PTDC/EEA-ELC/109936/2009 and R. P. Rocha is supported by the Foundation for Science and Technology financial grant SFRH/BD/33733/2009