Metabolic engineering with multi-objective optimization of kinetic models

Kinetic models have a great potential for metabolic engineering applications. They can be used for testing which genetic and regulatory modifications can increase the production of metabolites of interest, while simultaneously monitoring other key functions of the host organism. This work presents a methodology for increasing productivity in biotechnological processes exploiting dynamic models. It uses multi-objective dynamic optimization to identify the combination of targets (enzymatic modifications) and the degree of up- or down-regulation that must be performed in order to optimize a set of pre-defined performance metrics subject to process constraints. The capabilities of the approach are demonstrated on a realistic and computationally challenging application: a large-scale metabolic model of Chinese Hamster Ovary cells (CHO), which are used for antibody production in a fed-batch process. The proposed methodology manages to provide a sustained and robust growth in CHO cells, increasing productivity while simultaneously increasing biomass production, product titer, and keeping the concentrations of lactate and ammonia at low values. The approach presented here can be used for optimizing metabolic models by finding the best combination of targets and their optimal level of up/down-regulation. Furthermore, it can accommodate additional trade-offs and constraints with great flexibility.

Combining data mining and evolutionary computation for multi-criteria optimization of earthworks

Earthworks tasks aim at levelling the ground surface at a target construction area and precede any kind of structural construction (e.g., road and railway construction). It is comprised of sequential tasks, such as excavation, transportation, spreading and compaction, and it is strongly based on heavy mechanical equipment and repetitive processes. Under this context, it is essential to optimize the usage of all available resources under two key criteria: the costs and duration of earthwork projects. In this paper, we present an integrated system that uses two artificial intelligence based techniques: data mining and evolutionary multi-objective optimization. The former is used to build data-driven models capable of providing realistic estimates of resource productivity, while the latter is used to optimize resource allocation considering the two main earthwork objectives (duration and cost). Experiments held using real-world data, from a construction site, have shown that the proposed system is competitive when compared with current manual earthwork design.

Search for a CP-odd Higgs boson decaying to Zh in pp collisions at s=8TeV with the ATLAS detector

A search for a heavy, CP-odd Higgs boson, A, decaying into a Z boson and a 125 GeV Higgs boson, h, with the ATLAS detector at the LHC is presented. The search uses proton–proton collision data at a centre-of-mass energy of 8 TeV corresponding to an integrated luminosity of 20.3 fb−1. Decays of CP-even h bosons to ττ or bb pairs with the Z boson decaying to electron or muon pairs are considered, as well as h→bbh→bb decays with the Z boson decaying to neutrinos. No evidence for the production of an A boson in these channels is found and the 95% confidence level upper limits derived for View the MathML sourceσ(gg→A)×BR(A→Zh)×BR(h→ff¯) are 0.098–0.013 pb for f=τf=τ and 0.57–0.014 pb for f=bf=b in a range of mA=220–1000 GeVmA=220–1000 GeV. The results are combined and interpreted in the context of two-Higgs-doublet models.

Search for low-scale gravity signatures in multi-jet final states with the ATLAS detector at s√ = 8 TeV

We search for evidence of physics beyond the Standard Model in the production of final states with multiple high transverse momentum jets, using 20.3 fb−1 of proton-proton collision data recorded by the ATLAS detector at s√ = 8 TeV. No excess of events beyond Standard Model expectations is observed, and upper limits on the visible cross-section for non-Standard Model production of multi-jet final states are set. Using a wide variety of models for black hole and string ball production and decay, the limit on the cross-section times acceptance is as low as 0.16 fb at the 95% CL for a minimum scalar sum of jet transverse momentum in the event of about 4.3 TeV. Using models for black hole and string ball production and decay, exclusion contours are determined as a function of the production mass threshold and the gravity scale. These limits can be interpreted in terms of lower-mass limits on black hole and string ball production that range from 4.6 to 6.2 TeV.

Constraints on new phenomena via Higgs boson couplings and invisible decays with the ATLAS detector

The ATLAS experiment at the LHC has measured the Higgs boson couplings and mass, and searched for invisible Higgs boson decays, using multiple production and decay channels with up to 4.7 fb−1 of pp collision data at √s=7 TeV and 20.3 fb−1 at √s=8 TeV. In the current study, the measured production and decay rates of the observed Higgs boson in the γγ, ZZ, W W , Zγ, bb, τ τ , and μμ decay channels, along with results from the associated production of a Higgs boson with a top-quark pair, are used to probe the scaling of the couplings with mass. Limits are set on parameters in extensions of the Standard Model including a composite Higgs boson, an additional electroweak singlet, and two-Higgs-doublet models. Together with the measured mass of the scalar Higgs boson in the γγ and ZZ decay modes, a lower limit is set on the pseudoscalar Higgs boson mass of m A > 370 GeV in the “hMSSM” simplified Minimal Supersymmetric Standard Model. Results from direct searches for heavy Higgs bosons are also interpreted in the hMSSM. Direct searches for invisible Higgs boson decays in the vector-boson fusion and associated production of a Higgs boson with W/Z (Z → ℓℓ, W/Z → jj) modes are statistically combined to set an upper limit on the Higgs boson invisible branching ratio of 0.25. The use of the measured visible decay rates in a more general coupling fit improves the upper limit to 0.23, constraining a Higgs portal model of dark matter.

Study of the spin and parity of the Higgs boson in diboson decays with the ATLAS detector

Studies of the spin, parity and tensor couplings of the Higgs boson in the H→ZZ∗→4ℓ , H→WW∗→eνμν and H→γγ decay processes at the LHC are presented. The investigations are based on 25 fb−1 of pp collision data collected by the ATLAS experiment at s√=7 TeV and s√=8 TeV. The Standard Model (SM) Higgs boson hypothesis, corresponding to the quantum numbers JP=0+, is tested against several alternative spin scenarios, including non-SM spin-0 and spin-2 models with universal and non-universal couplings to fermions and vector bosons. All tested alternative models are excluded in favour of the SM Higgs boson hypothesis at more than 99.9% confidence level. Using the H→ZZ∗→4ℓ and H→WW∗→eνμν decays, the tensor structure of the HVV interaction in the spin-0 hypothesis is also investigated. The observed distributions of variables sensitive to the non-SM tensor couplings are compatible with the SM predictions and constraints on the non-SM couplings are derived.

Search for Dark Matter in Events with Missing Transverse Momentum and a Higgs Boson Decaying to Two Photons in pp Collisions at root s=8 TeV with the ATLAS Detector

Results of a search for new phenomena in events with large missing transverse momentum and a Higgs boson decaying to two photons are reported. Data from proton--proton collisions at a center-of-mass energy of 8 TeV and corresponding to an integrated luminosity of 20.3 fb−1 have been collected with the ATLAS detector at the LHC. The observed data are well described by the expected Standard Model backgrounds. Upper limits on the cross section of events with large missing transverse momentum and a Higgs boson candidate are also placed. Exclusion limits are presented for models of physics beyond the Standard Model featuring dark-matter candidates.

Behavior-based price discrimination in a multi-dimensional preferences market

NIPE WP 04/ 2016

Optimização do processo de recolha de resíduos: desenvolvimento de ferramentas de investigação operacional para o problema de orientação de equipas com multi-restrições

Tese de Doutoramento em Engenharia Industrial e de Sistemas.