1,790 research outputs found
Conservation laws for invariant functionals containing compositions
The study of problems of the calculus of variations with compositions is a
quite recent subject with origin in dynamical systems governed by chaotic maps.
Available results are reduced to a generalized Euler-Lagrange equation that
contains a new term involving inverse images of the minimizing trajectories. In
this work we prove a generalization of the necessary optimality condition of
DuBois-Reymond for variational problems with compositions. With the help of the
new obtained condition, a Noether-type theorem is proved. An application of our
main result is given to a problem appearing in the chaotic setting when one
consider maps that are ergodic.Comment: Accepted for an oral presentation at the 7th IFAC Symposium on
Nonlinear Control Systems (NOLCOS 2007), to be held in Pretoria, South
Africa, 22-24 August, 200
Development of a framework for metabolic pathway analysis-driven strain optimization methods
Genome-scale metabolic models (GSMMs) have become important assets for rational design of compound overproduction using microbial cell factories. Most computational strain optimization methods (CSOM) using GSMMs, while useful in metabolic engineering, rely on the definition of questionable cell objectives, leading to some bias. Metabolic pathway analysis approaches do not require an objective function. Though their use brings immediate advantages, it has mostly been restricted to small scale models due to computational demands. Additionally, their complex parameterization and lack of intuitive tools pose an important challenge towards making these widely available to the community. Recently, MCSEnumerator has extended the scale of these methods, namely regarding enumeration of minimal cut sets, now able to handle GSMMs. This work proposes a tool implementing this method as a Java library and a plugin within the OptFlux metabolic engineering platform providing a friendly user interface. A standard enumeration problem and pipeline applicable to GSMMs is proposed, making use by the community simpler. To highlight the potential of these approaches, we devised a case study for overproduction of succinate, providing a phenotype analysis of a selected strategy and comparing robustness with a selected solution from a bi-level CSOM.The authors thank the project “DeYeastLibrary—Designer yeast strain library optimized for metabolic engineering applications”, Ref. ERA-IB-2/0003/2013, funded by national funds through “Fundação para a Ciência e Tecnologia / Ministério da Ciência, Tecnologia e Ensino Superior”.info:eu-repo/semantics/publishedVersio
Gravitational energy of a magnetized Schwarzschild black hole - a teleparallel approach
We investigate the distribution of gravitational energy on the spacetime of a
Schwarzschild black hole immersed in a cosmic magnetic field. This is done in
the context of the {\it Teleparallel Equivalent of General Relativity}, which
is an alternative geometrical formulation of General Relativity, where gravity
is describe by a spacetime endowed with torsion, rather than curvature, with
the fundamental field variables being tetrads. We calculate the energy enclosed
by a two-surface of constant radius - in particular, the energy enclosed by the
event horizon of the black hole. In this case we find that the magnetic field
has the effect of increasing the gravitational energy as compared to the vacuum
Schwarzschild case. We also compute the energy (i) in the weak magnetic field
limit, (ii) in the limit of vanishing magnetic field, and (iii) in the absence
of the black hole. In all cases our results are consistent with what should be
expected on physical grounds.Comment: version to match the one to be published on General Relativity and
Gravitatio
Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin
One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution
Cosmology of a Scalar Field Coupled to Matter and an Isotropy-Violating Maxwell Field
Motivated by the couplings of the dilaton in four-dimensional effective
actions, we investigate the cosmological consequences of a scalar field coupled
both to matter and a Maxwell-type vector field. The vector field has a
background isotropy-violating component. New anisotropic scaling solutions
which can be responsible for the matter and dark energy dominated epochs are
identified and explored. For a large parameter region the universe expands
almost isotropically. Using that the CMB quadrupole is extremely sensitive to
shear, we constrain the ratio of the matter coupling to the vector coupling to
be less than 10^(-5). Moreover, we identify a large parameter region,
corresponding to a strong vector coupling regime, yielding exciting and viable
cosmologies close to the LCDM limit.Comment: Refs. added, some clarifications. Published in JHEP10(2012)06
On a smoothed penalty-based algorithm for global optimization
This paper presents a coercive smoothed penalty framework for nonsmooth and nonconvex constrained global optimization problems. The properties of the smoothed penalty function are derived. Convergence to an ε -global minimizer is proved. At each iteration k, the framework requires the ε(k) -global minimizer of a subproblem, where ε(k)→ε . We show that the subproblem may be solved by well-known stochastic metaheuristics, as well as by the artificial fish swarm (AFS) algorithm. In the limit, the AFS algorithm convergence to an ε(k) -global minimum of the real-valued smoothed penalty function is guaranteed with probability one, using the limiting behavior of Markov chains. In this context, we show that the transition probability of the Markov chain produced by the AFS algorithm, when generating a population where the best fitness is in the ε(k)-neighborhood of the global minimum, is one when this property holds in the current population, and is strictly bounded from zero when the property does not hold. Preliminary numerical experiments show that the presented penalty algorithm based on the coercive smoothed penalty gives very competitive results when compared with other penalty-based methods.The authors would like to thank two anonymous referees for their valuable comments and
suggestions to improve the paper.
This work has been supported by COMPETE: POCI-01-0145-FEDER-007043 and FCT
- Fundac¸ao para a Ci ˜ encia e Tecnologia within the projects UID/CEC/00319/2013 and ˆ
UID/MAT/00013/2013.info:eu-repo/semantics/publishedVersio
Optimization of ex vivo hematopoietic stem cell expansion in intermittent dynamic cultures
For the ex vivo expansion of CD34+ cells, culture conditions were optimized using cytokine cocktails and media change methods. In addition, static, orbital-shake, and stirred cultures were compared. After cultivation, total cell expansion, immunophenotypes, clonogenic ability, and metabolite concentration in media were analyzed. Optimized media change methods enhanced the number of total nucleated cells (TNCs) by 600-fold (from 104 to 6 × 106 cells) in static cultures. Furthermore, intermittent orbital-shake cultures gave the highest fold increase of TNCs and CD34+/CD38− cells. These results imply that proliferation of CD34+ cells in intermittent shake cultures was more efficient than that in static cultures under optimized culture conditions
Differential regulation of NF-κB activation and function by topoisomerase II inhibitors
BACKGROUND: While many common chemotherapeutic drugs and other inducers of DNA-damage result in both NF-κB nuclear translocation and DNA-binding, we have previously observed that, depending on the precise stimulus, there is great diversity of the function of NF-κB. In particular, we found that treatment of U-2 OS osteosarcoma cells with the anthracycine daunorubicin or with ultraviolet (UV-C) light resulted in a form of NF-κB that repressed rather than induced NF-κB reporter plasmids and the expression of specific anti-apoptotic genes. Anthracyclines such as daunorubicin can induce DNA-damage though inhibiting topoisomerase II, intercalating with DNA and undergoing redox cycling to produce oxygen free radicals. In this study we have investigated other anthracyclines, doxorubicin and aclarubicin, as well as the anthracenedione mitoxantrone together with the topoisomerase II inhibitor ICRF-193, which all possess differing characteristics, to determine which of these features is specifically required to induce both NF-κB DNA-binding and transcriptional repression in U-2 OS cells. RESULTS: The use of mitoxantrone, which does not undergo redox cycling, and the reducing agent epigallocatechingallate (EGCG) demonstrated that oxygen free radical production is not required for induction of NF-κB DNA-binding and transcriptional repression by these agents and UV-C. In addition, the use of aclarubicin, which does not directly inhibit topoisomerase II and ICRF-193, which inhibits topoisomerase II but does not intercalate into DNA, demonstrated that topoisomerase II inhibition is not sufficient to induce the repressor form of NF-κB. CONCLUSION: Induction of NF-κB DNA-binding and transcriptional repression by topoisomerase II inhibitors was found to correlate with an ability to intercalate into DNA. Although data from our and other laboratories indicates that topoisomerase II inhibition and oxygen free radicals do regulate NF-κB, they are not required for the particular ability of NF-κB to repress rather than activate transcription. Together with our previous data, these results demonstrate that the nature of the NF-κB response is context dependent. In a clinical setting such effects could profoundly influence the response to chemotherapy and suggest that new methods of analyzing NF-κB function could have both diagnostic and prognostic value
On the Natural Convection in the Columnar to Equiaxed Transition in Directionally Solidified Aluminum-based Binary and Multicomponent Alloys
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