Multi-objective optimization of genome-scale metabolic models: the case of ethanol production

Ethanol is among the largest fermentation product used worldwide, accounting for more than 90% of all biofuel produced in the last decade. However current production methods of ethanol are unable to meet the requirements of increasing global demand, because of low yields on glucose sources. In this work, we present an in silico multi-objective optimization and analyses of eight genome-scale metabolic networks for the overproduction of ethanol within the engineered cell. We introduce MOME (multi-objective metabolic engineering) algorithm, that models both gene knockouts and enzymes up and down regulation using the Redirector framework. In a multi-step approach, MOME tackles the multi-objective optimization of biomass and ethanol production in the engineered strain; and performs genetic design and clustering analyses on the optimization results. We find in silico E. coli Pareto optimal strains with a knockout cost of 14 characterized by an ethanol production up to 19.74mmolgDW−1h−1 (+832.88% with respect to wild-type) and biomass production of 0.02h−1 (−98.06% ). The analyses on E. coli highlighted a single knockout strategy producing 16.49mmolgDW−1h−1 (+679.29% ) ethanol, with biomass equals to 0.23h−1 (−77.45% ). We also discuss results obtained by applying MOME to metabolic models of: (i) S. aureus; (ii) S. enterica; (iii) Y. pestis; (iv) S. cerevisiae; (v) C. reinhardtii; (vi) Y. lipolytica. We finally present a set of simulations in which constrains over essential genes and minimum allowable biomass were included. A bound over the maximum allowable biomass was also added, along with other settings representing rich media compositions. In the same conditions the maximum improvement in ethanol production is +195.24%

A combined analysis technique for the search for fast magnetic monopoles with the MACRO detector

We describe a search method for fast moving ($\beta > 5 \times 10^{-3}$) magnetic monopoles using simultaneously the scintillator, streamer tube and track-etch subdetectors of the MACRO apparatus. The first two subdetectors are used primarily for the identification of candidates while the track-etch one is used as the final tool for their rejection or confirmation. Using this technique, a first sample of more than two years of data has been analyzed without any evidence of a magnetic monopole. We set a 90% CL upper limit to the local monopole flux of $1.5 \times 10^{-15} cm^{-2} s^{-1} sr^{-1}$ in the velocity range $5 \times 10^{-3} \le \beta \le 0.99$ and for nucleon decay catalysis cross section smaller than $\sim 1 mb$.Comment: 29 pages (12 figures). Accepted by Astroparticle Physic

Final results of magnetic monopole searches with the MACRO experiment

We present the final results obtained by the MACRO experiment in the search for GUT magnetic monopoles in the penetrating cosmic radiation, for the range $4\times 10^{-5}< \beta < 1$. Several searches with all the MACRO sub-detectors (i.e. scintillation counters, limited streamer tubes and nuclear track detectors) were performed, both in stand alone and combined ways. No candidates were detected and a 90% Confidence Level (C.L.) upper limit to the local magnetic monopole flux was set at the level of $1.4\times 10^{-16}$ cm$^{-2}$ s$^{-1}$ sr$^{-1}$. This result is the first experimental limit obtained in direct searches which is well below the Parker bound in the whole $\beta$ range in which GUT magnetic monopoles are expected.Comment: 12 pages, Latex, 9 figures and 2 Table

Income Attainment among Victims of Violence: Results From a Preliminary Study

Violent victimisation may have many short-term psychological and physical outcomes. Occasionally, the negative aftermath of violence persists over time or induces other and more far-reaching consequences. Income attainment after victimisation is one of these outcomes. To date, previous studies have focussed on the income effects of violent victimisation during childhood and adolescence. Violence exposure during the early stages of the life course may frustrate processes of educational and occupational attainment and consequentially result in lower income levels. However, in addition or alternatively, many other and age-independent pathways between violent victimisation and income may be suggested. Prior studies appear to have paid little attention to this issue. Therefore, the purpose of the current study was to explore whether violent victimisation is associated with income levels several years after victimisation, irrespective of the age at which victimisation occurs. Victims of violence were recruited through the Dutch Victim Compensation Fund. To preliminary estimate the effect of violent victimisation on income, a comparable control group of non-victims was composed. The study sample contained 206 victims and 173 non-victims. Both bivariate correlational and multivariate statistical techniques suggested that violent victimisation is a significant predictor of income. Implications of the presented results were discussed with regard to future research and policy practice

The Observation of Up-going Charged Particles Produced by High Energy Muons in Underground Detectors

An experimental study of the production of up-going charged particles in inelastic interactions of down-going underground muons is reported, using data obtained from the MACRO detector at the Gran Sasso Laboratory. In a sample of 12.2 10^6 single muons, corresponding to a detector livetime of 1.55 y, 243 events are observed having an up-going particle associated with a down-going muon. These events are analysed to determine the range and emission angle distributions of the up-going particle, corrected for detection and reconstruction efficiency. Measurements of the muon neutrino flux by underground detectors are often based on the observation of through-going and stopping muons produced in $\nu_\mu$ interactions in the rock below the detector. Up-going particles produced by an undetected down-going muon are a potential background source in these measurements. The implications of this background for neutrino studies using MACRO are discussed.Comment: 18 pages, 9 figures. Accepted by Astrop. Physic

Nuclearite search with the MACRO detector at Gran Sasso

In this paper we present the results of a search for nuclearites in the penetrating cosmic radiation using the scintillator and track-etch subdetectors of the MACRO apparatus. The analyses cover the beta =v/c range at the detector depth (3700 hg/cm^2) 10^-5 < beta < 1; for beta = 2 x 10^-3 the flux limit is 2.7 x 10^-16 cm^-2 s^-1 sr^-1 for an isotropic flux of nuclearites, and twice this value for a flux of downgoing nuclearites.Comment: 16 pages, 4 Encapsulated Postscript figures, uses article.sty. Submitted to The European Physical Journal

Atmospheric neutrino induced muons in the MACRO detector

A measurement of the flux of neutrino-induced muons using the MACRO detector is presented. Different event topologies, corresponding to different neutrino parent energies can be detected. The upward throughgoing muon sample is the larger event sample. The observed upward-throughgoing muons are 26% fewer than expected and the zenith angle distribution does not fit with the expected one. Assuming neutrino oscillations, both measurements suggest maximum mixing and Dm2 of a few times 10-3 eV2. The other samples are due to the internally produced events and to upward-going stopping muons. These data show a regular deficit of observed events in each angular bin, as expected assuming neutrino oscillations with maximum mixing, in agreement with the analysis of the upward-throughgoing muon sample.Comment: 7 pages 6 figures to appear in the proceedings of XVIII International Conference on Neutrino Physics and Astrophysics (Neutrino'98), Takayama, Japan 4-9 June, 199

Fitness Cost of Resistance to Bt Cotton Linked with Increased Gossypol Content in Pink Bollworm Larvae

Fitness costs of resistance to Bacillus thuringiensis (Bt) crops occur in the absence of Bt toxins, when individuals with resistance alleles are less fit than individuals without resistance alleles. As costs of Bt resistance are common, refuges of non-Bt host plants can delay resistance not only by providing susceptible individuals to mate with resistant individuals, but also by selecting against resistance. Because costs typically vary across host plants, refuges with host plants that magnify costs or make them less recessive could enhance resistance management. Limited understanding of the physiological mechanisms causing fitness costs, however, hampers attempts to increase costs. In several major cotton pests including pink bollworm (Pectinophora gossypiella), resistance to Cry1Ac cotton is associated with mutations altering cadherin proteins that bind this toxin in susceptible larvae. Here we report that the concentration of gossypol, a cotton defensive chemical, was higher in pink bollworm larvae with cadherin resistance alleles than in larvae lacking such alleles. Adding gossypol to the larval diet decreased larval weight and survival, and increased the fitness cost affecting larval growth, but not survival. Across cadherin genotypes, the cost affecting larval growth increased as the gossypol concentration of larvae increased. These results suggest that increased accumulation of plant defensive chemicals may contribute to fitness costs associated with resistance to Bt toxins

New MACRO results on atmospheric neutrino oscillations

The final results of the MACRO experiment on atmospheric neutrino oscillations are presented and discussed. The data concern different event topologies with average neutrino energies of ~3 and ~50 GeV. Multiple Coulomb Scattering of the high energy muons in absorbers was used to estimate the neutrino energy of each event. The angular distributions, the L/E_nu distribution, the particle ratios and the absolute fluxes all favour nu_mu --> nu_tau oscillations with maximal mixing and Delta m^2 =0.0023 eV^2. A discussion is made on the Monte Carlos used for the atmospheric neutrino flux. Some results on neutrino astrophysics are also briefly discussed.Comment: Invited Paper at the NANP03 Int. Conf., Dubna, 200