Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

Background: Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results: Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions: Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

Data-division-specific robustness and power of randomization tests for ABAB designs

This study deals with the statistical properties of a randomization test applied to an ABAB design in cases where the desirable random assignment of the points of change in phase is not possible. In order to obtain information about each possible data division we carried out a conditional Monte Carlo simulation with 100,000 samples for each systematically chosen triplet. Robustness and power are studied under several experimental conditions: different autocorrelation levels and different effect sizes, as well as different phase lengths determined by the points of change. Type I error rates were distorted by the presence of autocorrelation for the majority of data divisions. Satisfactory Type II error rates were obtained only for large treatment effects. The relationship between the lengths of the four phases appeared to be an important factor for the robustness and the power of the randomization test.

Nanocharacterization of Soft Biological Samples in Shear Mode with Quartz Tuning Fork Probes

Quartz tuning forks are extremely good resonators and their use is growing in scanning probe microscopy. Nevertheless, only a few studies on soft biological samples have been reported using these probes. In this work, we present the methodology to develop and use these nanosensors to properly work with biological samples. The working principles, fabrication and experimental setup are presented. The results in the nanocharacterization of different samples in different ambients are presented by using different working modes: amplitude modulation with and without the use of a Phase-Locked Loop (PLL) and frequency modulation. Pseudomonas aeruginosa bacteria are imaged in nitrogen using amplitude modulation. Microcontact printed antibodies are imaged in buffer using amplitude modulation with a PLL. Finally, metastatic cells are imaged in air using frequency modulation.

Histologic evaluation of thermal damage produced on soft tissues by CO2, Er,Cr:YSGG and diode lasers

Objective: The aim of this in vitro experimental study was to perform histological evaluation of the thermal effect produced on soft tissue irradiated with CO2, Er,Cr:YSGG or diode lasers. Study design: Porcine oral mucosa samples were irradiated with Er,Cr:YSGG laser at 1 W with and without water / air spray, at 2 W with and without water / air spray, and at 4 W with water / air spray, with CO2 laser at 1 W, 2 W, 10 W, 20 W continuous mode and 20 W pulsed mode and diode laser at 2W, 5W, and 10W pulsed mode. The thermal effect was evaluated measuring the width of damaged tissue adjacent to the incision, stained positively for hyalinized tissue with Hematoxylin-Eosin and Masson Trichrome stains. Besides, histological changes in the irradiated tissue were described using subjective grading scales. Results: The evaluated lasers developed a wide range of thermal damage with significant differences between groups. The samples with lowest thermal effect were those irradiated with Er,Cr:YSGG laser using water / air spray, followed by CO2 and diode lasers. Conclusions: Emission parameters of each laser system may influence the thermal damage inflicted on the soft tissue, however, the wave length of each laser determines the absorption rate characteristics of every tissue and the thermal effect

Molecular dynamics simulation of the spherical electrical double layer of a soft nanoparticle. Effect of the surface and counterion valence

Molecular dynamics simulations were performed to study the ion and water distribution around a spherical charged nanoparticle. A soft nanoparticle model was designed using a set of hydrophobic interaction sites distributed in six concentric spherical layers. In order to simulate the effect of charged functionalyzed groups on the nanoparticle surface, a set of charged sites were distributed in the outer layer. Four charged nanoparticle models, from a surface charge value of −0.035 Cm−2 to − 0.28 Cm−2, were studied in NaCl and CaCl2 salt solutions at 1 M and 0.1 M concentrations to evaluate the effect of the surface charge, counterion valence, and concentration of added salt. We obtain that Na + and Ca2 + ions enter inside the soft nanoparticle. Monovalent ions are more accumulated inside the nanoparticle surface, whereas divalent ions are more accumulated just in the plane of the nanoparticle surface sites. The increasing of the the salt concentration has little effect on the internalization of counterions, but significantly reduces the number of water molecules that enter inside the nanoparticle. The manner of distributing the surface charge in the nanoparticle (uniformly over all surface sites or discretely over a limited set of randomly selected sites) considerably affects the distribution of counterions in the proximities of the nanoparticle surface.

A broadband leptonic model for gamma-ray emitting microquasars

Observational and theoretical studies point to microquasars (MQs) as possible counterparts of a significant fraction of the unidentified gamma-ray sources detected so far. At present, a proper scenario to explain the emission beyond soft X-rays from these objects is not known, nor what the precise connection is between the radio and the high-energy radiation. We develop a new model where the MQ jet is dynamically dominated by cold protons and radiatively dominated by relativistic leptons. The matter content and power of the jet are both related with the accretion process. The magnetic field is assumed to be close to equipartition, although it is attached to and dominated by the jet matter. For the relativistic particles in the jet, their maximum energy depends on both the acceleration efficiency and the energy losses. The model takes into account the interaction of the relativistic jet particles with the magnetic field and all the photon and matter fields. Such interaction produces significant amounts of radiation from radio to very high energies through synchrotron, relativistic Bremsstrahlung, and inverse Compton (IC) processes. Variability of the emission produced by changes in the accretion process (e.g. via orbital eccentricity) is also expected. The effects of the gamma-ray absorption by the external photon fields on the gamma-ray spectrum have been taken into account, revealing clear spectral features that might be observed. This model is consistent to the accretion scenario, energy conservation laws, and current observational knowledge, and can provide deeper physical information of the source when tested against multiwavelength data.

Fiscal sustainability across government tiers: an assessment of soft budget constraints

This paper analyses how fiscal adjustment comes about when both central and sub-national governments are involved in consolidation. We test sustainability of public debt with a fiscal rule for both the federal and regional government. Results for the German Länder show that lower tier governments bear a relatively smaller part of the burden of debt consolidation, if they consolidate at all. Most of the fiscal adjustment occurs via central government debt. In contrast, both the US federal and state levels contribute to consolidation of public finances.

Improving the efficiency of PV low-power processing circuits by selecting an optimal inductor current of the DC/DC converter

In the context of autonomous sensors powered by small-size photovoltaic (PV) panels, this work analyses how the efficiency of DC/DC-converter-based power processing circuits can be improved by an appropriate selection of the inductor current that transfers the energy from the PV panel to a storage unit. Each component of power losses (fixed, conduction and switching losses) involved in the DC/DC converter specifically depends on the average inductor current so that there is an optimal value of this current that causes minimal losses and, hence, maximum efficiency. Such an idea has been tested experimentally using two commercial DC/DC converters whose average inductor current is adjustable. Experimental results show that the efficiency can be improved up to 12% by selecting an optimal value of that current, which is around 300-350 mA for such DC/DC converters.

The maximum voltage drop in an on-chip power distribution network: analysis of square, triangular and hexagonal power pad arrangements

A mathematical model of the voltage drop which arises in on-chip power distribution networks is used to compare the maximum voltage drop in the case of different geometric arrangements of the pads supplying power to the chip. These include the square or Manhattan power pad arrangement, which currently predominates, as well as equilateral triangular and hexagonal arrangements. In agreement with the findings in the literature and with physical and SPICE models, the equilateral triangular power pad arrangement is found to minimize the maximum voltage drop. This headline finding is a consequence of relatively simple formulas for the voltage drop, with explicit error bounds, which are established using complex analysis techniques, and elliptic functions in particular.

Candidate counterparts to the soft gamma-ray flare in the direction od LSI+61303

A short duration burst reminiscent of a soft gamma-ray repeater/anomalous X-ray pulsar behaviour was detected in the direction of LS I +61 303 by the Swift satellite. While the association with this well known gamma-ray binary is likely, a different origin cannot be excluded. Aims. We explore the error box of this unexpected flaring event and establish the radio, near-infrared and X-ray sources in our search for any peculiar alternative counterpart. Methods. We carried out a combined analysis of archive Very Large Array radio data of LS I +61 303 sensitive to both compact and extended emission. We also reanalysed previous near infrared observations with the 3.5 m telescope of the Centro Astronómico Hispano Alemán and X-ray observations with the Chandra satellite. Results. Our deep radio maps of the LS I +61 303 environment represent a significant advancement on previous work and 16 compact radio sources in the LS I +61 303 vicinity are detected. For some detections, we also identify near infrared and X-ray counterparts. Extended emission features in the field are also detected and confirmed. The possible connection of some of these sources with the observed flaring event is considered. Based on these data, we are unable to claim a clear association between the Swift-BAT flare and any of the sources reported here. However, this study represents the most sophisticated attempt to determine possible alternative counterparts other than LS I +61 303.