Partial inhibition and bilevel optimization in flux balance analysis

Motivation: Within Flux Balance Analysis, the investigation of complex subtasks, such as finding the optimal perturbation of the network or finding an optimal combination of drugs, often requires to set up a bilevel optimization problem. In order to keep the linearity and convexity of these nested optimization problems, an ON/OFF description of the effect of the perturbation (i.e. Boolean variable) is normally used. This restriction may not be realistic when one wants, for instance, to describe the partial inhibition of a reaction induced by a drug.Results: In this paper we present a formulation of the bilevel optimization which overcomes the oversimplified ON/OFF modeling while preserving the linear nature of the problem. A case study is considered: the search of the best multi-drug treatment which modulates an objective reaction and has the minimal perturbation on the whole network. The drug inhibition is described and modulated through a convex combination of a fixed number of Boolean variables. The results obtained from the application of the algorithm to the core metabolism of E.coli highlight the possibility of finding a broader spectrum of drug combinations compared to a simple ON/OFF modeling.Conclusions: The method we have presented is capable of treating partial inhibition inside a bilevel optimization, without loosing the linearity property, and with reasonable computational performances also on large metabolic networks. The more fine-graded representation of the perturbation allows to enlarge the repertoire of synergistic combination of drugs for tasks such as selective perturbation of cellular metabolism. This may encourage the use of the approach also for other cases in which a more realistic modeling is required. \ua9 2013 Facchetti and Altafini; licensee BioMed Central Ltd

A Split-step Method to Include Electron-electron Collisions via Monte Carlo in Multiple Rate Equation Simulations

A split-step numerical method for calculating ultrafast free-electron dynamics in dielectrics is introduced. The two split steps, independently programmed in C++11 andFORTRAN 2003, are interfaced via the presented open source wrapper. The first step solves a deterministic extended multi-rate equation for the ionization, electron–phonon collisions, and single photon absorption by free-carriers. The second step is stochastic and models electron–electron collisions using Monte-Carlo techniques. This combination of deterministic and stochastic approaches is a unique and efficient method of calculating the nonlinear dynamics of 3D materials exposed to high intensity ultrashort pulses. Results from simulations solving the proposed model demonstrate how electron–electron scattering relaxes the non-equilibrium electron distribution on the femtosecond time scale

Entwurf eines Datenbankrechners auf der Basis eines Multi-Mikrorechnersystems Schlussbericht

With 55 refs., 6 figs.SIGLECopy held by FIZ Karlsruhe; available from UB/TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Strategy to sequence the genome of Corynebacterium glutamicum ATCC 13032: use of a cosmid and a bacterial artificial chromosome library

Tauch A, Homann I, Mormann S, et al. Strategy to sequence the genome of Corynebacterium glutamicum ATCC 13032: use of a cosmid and a bacterial artificial chromosome library. JOURNAL OF BIOTECHNOLOGY. 2002;95(1):25-38.The initial strategy of the Corynebacterium glutamicum genome project was to sequence overlapping inserts of an ordered cosmid library. High-density colony grids of approximately 28 genome equivalents were used for the identification of overlapping clones by Southern hybridization. Altogether 18 contiguous genomic segments comprising 95 overlapping cosmids were assembled. Systematic shotgun sequencing of the assembled cosmid set revealed that only 2.84 Mb (86.6%) of the C glutamicum genome were represented by the cosmid library. To obtain a complete genome coverage, a bacterial artificial chromosome (BAC) library of the C. glutamicum chromosome was constructed in pBeloBAC11 and used for genome mapping. The BAC library consists of 3168 BACs and represents a theoretical 63-fold coverage of the C. glutamicum genome (3.28 Mb). Southern screening of 2304 BAC clones with PCR-amplified chromosomal markers and subsequent insert terminal sequencing allowed the identification of 119 BACs covering the entire chromosome of C. glutamicum. The minimal set representing a 100% genome coverage contains 44 unique BAC clones with an average overlap of 22 kb. A total of 21 BACs represented linking clones between previously sequenced cosmid contigs and provided a valuable tool for completing the genome sequence of C. glutamicum. (C) 2002 Elsevier Science B.V. All rights reserved