Study of the Antibacterial Capacity of a Biomaterial of Zeolites Saturated with Copper Ions (Cu2+) and Supported with Copper Oxide (CuO) Nanoparticles.

In this work, copper (II) ions were saturated and copper oxide nanoparticles (CuO NPs) were supported in natural zeolite from Chile; this was achieved by making the adsorbent material come into contact with a copper ion precursor solution and using mechanical agitation, respectively. The kinetic and physicochemical process of the adsorption of copper ions in the zeolite was studied, as well as the effect of the addition of CuO NPs on the antibacterial properties. The results showed that the saturation of copper (II) ions in the zeolite is an efficient process, obtaining a 27 g L-1 concentration of copper ions in a time of 30 min. The TEM images showed that a good dispersion of the CuO NPs was obtained via mechanical stirring. The material effectively inhibited the growth of Gram-negative and Gram-positive bacteria that have shown resistance to methicillin and carbapenem. Furthermore, the zeolite saturated with copper at the same concentration had a better bactericidal effect than the zeolite supported with CuO NPs. The results suggested that the ease of processing and low cost of copper (II) ion-saturated zeolitic material could potentially be used for dental biomedical applications, either directly or as a bactericidal additive for 3D printing filaments.

Electrical properties of tissues from a microscopic model of confined electrolytes.

Objective. In the presence of oscillatory electric fields, the motion of electrolyte ions in biological tissues is often limited by the confinement created by cell and organelle walls. This confinement induces the organization of the ions into dynamic double layers. This work determines the contribution of these double layers to the bulk conductivity and permittivity of tissues.Approach. Tissues are modeled as repeated units of electrolyte regions separated by dielectric walls. Within the electrolyte regions, a coarse-grained model is used to describe the associated ionic charge distribution. The model emphasizes the role of the displacement current in addition to the ionic current and enables the evaluation of macroscopic conductivities and permittivities.Main results. We obtain analytical expressions for the bulk conductivity and permittivity as a function of the frequency of the oscillatory electric field. These expressions explicitly include the geometric information of the repeated structure and the contribution of the dynamic double layers. The low-frequency limit of the conductivity expression yields a result predicted by the Debye permittivity form. The model also provides a microscopic interpretation of the Maxwell-Wagner effect.Significance. The results obtained contribute to the interpretation of the macroscopic measurements of electrical properties of tissues in terms of their microscopic structure. The model enables a critical assessment of the justification for the use of macroscopic models to analyze the transmission of electrical signals through tissues.

Antigen receptor therapy in bone metastasis via optimal control for different human life stages.

In this work we propose a bone metastasis model using power law growth functions in order to describe the biochemical interactions between bone cells and cancer cells. Experimental studies indicate that bone remodeling cycles are different for human life stages: childhood, young adulthood, and adulthood. In order to include such differences in our study, we estimate the model parameter values for each human life stage via bifurcation analysis. Results reveal an intrinsic relationship between the active period of remodeling cycles and the proliferation of cancer cells. Subsequently, using optimal control theory we analyze a possible antigen receptor therapy as a new treatment for bone metastasis. Theoretical results such as existence of optimal solutions are proved. Numerical simulations for late stages of bone metastasis are presented and a discussion of our results is carried out.

Pimples reduce and dimples enhance flat dielectric surface image repulsion.

In solid-liquid, or liquid-liquid, interfaces with dielectric contrast, charged particles interact with the induced polarization charge of the interface. These interactions contribute to an effective self-energy of the bulk ions and mediate ion-ion interactions. For flat interfaces, the self-energy and the mediated interactions are neatly constructed by the image charge method. For other geometries, explicit results are scarce and the problem must be treated via approximations or direct computation. The case of interfaces with roughness is of great practical importance. This article provides analytical results, valid to first-order in perturbation theory, for the self-energy of particles near rough substrates. Explicit formulas are provided for the case of a sinusoidal deformation of a flat surface. Generic deformations can be treated by superposition. In addition to results for the self-energy, the surface polarization charge is presented as a quadrature. The interaction between an ion and the deformed surface is modified by the change in relative distance as well as by the local curvature of the surface. Solid walls, with a lower dielectric constant than the liquid, repel all ions. We show that the repulsion is reduced by local convexity and enhanced by concavity; dimples are more repulsive than pimples.

Strange attractors in discrete slow power-law models of bone remodeling.

Recently, a family of nonlinear mathematical discrete systems to describe biological interactions was considered. Such interactions are modeled by power-law functions where the exponents involve regulation processes. Considering exponent values giving rise to hyperbolic equilibria, we show that the systems exhibit irregular behavior characterized by strange attractors. The systems are numerically analyzed for different parameter values. Depending on the initial conditions, the orbits of each system either diverge to infinity or approach a periodic orbit or a strange attractor. Such dynamical behavior is identified by their Lyapunov exponents and local dimension. Finally, an application to the biochemical process of bone remodeling is presented. The existence of deterministic chaos in this process reveals a possible explanation of reproducibility failure and variation of effects in clinical experiments.

A simple model of immune and muscle cell crosstalk during muscle regeneration.

Muscle injury during aging predisposes skeletal muscles to increased damage due to reduced regenerative capacity. Some of the common causes of muscle injury are strains, while other causes are more complex muscle myopathies and other illnesses, and even excessive exercise can lead to muscle damage. We develop a new mathematical model based on ordinary differential equations of muscle regeneration. It includes the interactions between the immune system, healthy and damaged myonuclei as well as satellite cells. Our new mathematical model expands beyond previous ones by accounting for 21 specific parameters, including those parameters that deal with the interactions between the damaged and dead myonuclei, the immune system, and the satellite cells. An important assumption of our model is the replacement of only damaged parts of the muscle fibers and the dead myonuclei. We conduce systematic sensitivity analysis to determine which parameters have larger effects on the model and therefore are more influential for the muscle regeneration process. We propose additional validation for these parameters. We further demonstrate that these simulations are species-, muscle-, and age-dependent. In addition, the knowledge of these parameters and their interactions, may suggest targeting or selecting these interactions for treatments that accelerate the muscle regeneration process.

Gonadotropin-inhibitory hormone (GnIH) distribution in the brain of the ancient fish Atractosteus tropicus (Holostei, Lepisosteiformes).

The Holostei group occupies a critical phylogenetic position as the sister group of the Teleostei. However, little is known about holostean pituitary anatomy or brain distribution of important reproductive neuropeptides, such as the gonadotropin-inhibitory hormone (GnIH). Thus, the present study set out to characterize the structure of the pituitary and to localize GnIH-immunoreactive cells in the brain of Atractosteus tropicus from the viewpoint of comparative neuroanatomy. Juveniles of both sexes were processed for general histology and immunohistochemistry. Based on the differences in cell organization, morphology, and staining properties, the neurohypophysis and three regions in the adenohypophysis were identified: the rostral and proximal pars distalis (PPD) and the pars intermedia. This last region was found to be innervated by the neurohypophysis. This organization, together with the presence of a saccus vasculosus, resembles the general teleost pituitary organization. A vast number of blood vessels were also recognized between the infundibulum floor of the hypothalamus and the PPD, evidencing the characteristic presence of a median eminence and a portal system. However, this well-developed pituitary portal system resembles that of tetrapods. As regards the immunohistochemical localization of GnIH, we found four GnIH-immunoreactive (GnIH-ir) populations in three hypothalamic nuclei (suprachiasmatic, retrotuberal, and tuberal nuclei) and one in the diencephalon (prethalamic nucleus), as well as a few scattered neurons throughout the olfactory bulbs, the telencephalon, and the intersection between them. GnIH-ir fibers showed a widespread distribution over almost all brain regions, suggesting that GnIH function is not restricted to reproduction only. In conclusion, the present study describes, for the first time, the pituitary of A. tropicus and the neuroanatomical localization of GnIH in a holostean fish that exhibits a similar distribution pattern to that of teleosts and other vertebrates, suggesting a high degree of phylogenetic conservation of this system.

Power Dissipation and Surface Charge in EEG: Application to Eigenvalue Structure of Integral Operators.

OBJECTIVE: To demonstrate the role of surface charge and power dissipation in the analysis of EEG measurements. METHODS: The forward EEG problem is formulated in terms of surface charge density. Using bounds based on power dissipation, the integral equations for forward solutions are shown to satisfy bounds on their eigenvalue structure. RESULTS: We show that two physical variables, dissipated power and the accumulated charge at interfaces, can be used in formulating the forward problem. We derive the boundary integral equations satisfied by the charge and show their connection to the integral equations for the potential that are known from other approaches. We show how the dissipated power determines bounds on the range of eigenvalues of the integral operators that appear in EEG boundary element methods. Using the eigenvalue structure, we propose a new method for the solution of the forward problem, where the integral kernels are regularized by the exclusion of eigenvectors associated to a finite range of eigenvalues. We demonstrate the method on a head model with realistic shape. CONCLUSION: The eigenvalue analysis of the EEG forward problem is given a clear interpretation in terms of power dissipation and surface charge density. SIGNIFICANCE: The use of these variables enhances our understanding of the structure of EEG, makes connection with other techniques and contributes to the development of new analysis algorithms.

Asymmetric electrolytes near structured dielectric interfaces.

The ion distribution of electrolytes near interfaces with dielectric contrast has important consequences for electrochemical processes and many other applications. To date, most studies of such systems have focused on geometrically simple interfaces, for which dielectric effects are analytically solvable or computationally tractable. However, all real surfaces display nontrivial structure at the nanoscale and have, in particular, a nonuniform local curvature. Using a recently developed, highly efficient computational method, we investigate the effect of surface geometry on ion distribution and interface polarization. We consider an asymmetric 2:1 electrolyte bounded by a sinusoidally deformed solid surface. We demonstrate that even when the surface is neutral, the electrolyte acquires a nonuniform ion density profile near the surface. This profile is asymmetric and leads to an effective charging of the surface. We furthermore show that the induced charge is modulated by the local curvature. The effective charge is opposite in sign to the multivalent ions and is larger in concave regions of the surface.

Ontogeny of Gonadotropin-Inhibitory Hormone (GnIH) in the cichlid fish Cichlasoma dimerus.

RFamide peptides are expressed in the early stages of development in most vertebrates. Gonadotropin-inhibitory hormone (GnIH) belongs to the RFamide family, and its role in reproduction has been widely studied in adult vertebrates, ranging from fish to mammals. As only three reports evaluated GnIH during development, the aim of this study was to characterise the ontogeny of GnIH in a fish model, Cichlasoma dimerus. We detected the presence of two GnIH-immunoreactive (GnIH-ir) cell clusters with spatial and temporal differences. One cluster was observed by 3 days post-hatching (dph) in the nucleus olfacto-retinalis (NOR) and the other in the nucleus posterioris periventricularis by 14 dph. The number of GnIH-ir neurons increased in both nuclei, whereas their size increased only in the NOR from hatchling to juvenile stages. These changes occurred from the moment larvae started feeding exogenously and during development and differentiation of gonadal primordia. We showed by double-label immunofluorescence that only GnIH-ir neurons in the NOR co-expressed GnRH3 associated peptide. In addition, GnIH-ir fibre density increased in all brain regions from 5 dph. GnIH-ir fibres were also detected in the retina, optic tract and optic tectum, suggesting that GnIH acts as a neuromodulator of photoreception and the integration of different sensory modalities. Also, there were GnIH-ir fibres in the pituitary from 14 dph, which were in close association with somatotropes. Moreover, GnIH-ir fibres were observed in the saccus vasculosus from 30 dph, suggesting a potential role of GnIH in the modulation of its function. Finally, we found that gnih was expressed from 1 dph, and that the pattern of variation of its transcript levels was in accordance with that of cell number. Present results are the starting point for the study of new GnIH roles during development. This article is protected by copyright. All rights reserved.

Bifurcations and limit cycles in cytosolic yeast calcium.

Calcium homeostasis is a fundamental cellular process in yeast. The regulation of the cytosolic calcium concentration is required for volume preservation and to regulate many vital calcium dependent processes such as mating and response to stress. The homeostatic mechanism is often studied by applying calcium pulses: sharply changing the calcium concentration in the yeast environment and observing the cellular response. To address these experimental investigations, several mathematical models have been proposed to describe this response. In this article we demonstrate that a previously studied model for this response predicts the presence of limit point instabilities and limit cycles in the dynamics of the calcium homeostasis system. We discuss the ways in which such dynamic characteristics can be observed with luminometric techniques. We contrast these predictions with experimentally observed responses and find that the experiments reveal a number of features that are consistent with modeling predictions. In particular, we find that equilibrium cytosolic concentrations have a sharp change in behavior as pulse size changes in the micromolar range. We show that such change is consistent with the presence of limit point instabilities. Additionally, we find that the response of synchronized yeast cells to millimolar range pulses is non-monotonic in its late stages. This response has characteristics similar to those associated with limit cycles.

Control of Selective Ion Transfer across Liquid-Liquid Interfaces: A Rectifying Heterojunction Based on Immiscible Electrolytes.

The current rectification displayed by solid-state p-n semiconductor diodes relies on the abundance of electrons and holes near the interface between the p-n junction. In analogy to this electronic device, we propose here the construction of a purely ionic liquid-state electric rectifying heterojunction displaying an excess of monovalent cations and anions near the interface between two immiscible solvents with different dielectric properties. This system does not need any physical membrane or material barrier to show preferential ion transfer but relies on the ionic solvation energy between the two immiscible solvents. We construct a simple device, based on an oil/water interface, displaying an asymmetric behavior of the electric current as a function of the polarity of an applied electric field. This device also exhibits a region of negative differential conductivity, analogous to that observed in brain and heart cells via voltage clamp techniques. Computer simulations and mean field theory calculations for a model of this system show that the application of an external electric field is able to control the bulk concentrations of the ionic species in the immiscible liquids in a manner that is asymmetric with respect to the polarity or direction of the applied electric field. These properties make possible to enhance or suppress selective ion transport at liquid-liquid interfaces with the application of an external electric field or electrostatic potential, mimicking the function of biological ion channels, thus creating opportunities for varied applications.

Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Dynamics of coarsening in multicomponent lipid vesicles with non-uniform mechanical properties.

Multicomponent lipid vesicles are commonly used as a model system for the complex plasma membrane. One phenomenon that is studied using such model systems is phase separation. Vesicles composed of simple lipid mixtures can phase-separate into liquid-ordered and liquid-disordered phases, and since these phases can have different mechanical properties, this separation can lead to changes in the shape of the vesicle. In this work, we investigate the dynamics of phase separation in multicomponent lipid vesicles, using a model that couples composition to mechanical properties such as bending rigidity and spontaneous curvature. The model allows the vesicle surface to deform while conserving surface area and composition. For vesicles initialized as spheres, we study the effects of phase fraction and spontaneous curvature. We additionally initialize two systems with elongated, spheroidal shapes. Dynamic behavior is contrasted in systems where only one phase has a spontaneous curvature similar to the overall vesicle surface curvature and systems where the spontaneous curvatures of both phases are similar to the overall curvature. The bending energy contribution is typically found to slow the dynamics by stabilizing configurations with multiple domains. Such multiple-domain configurations are found more often in vesicles with spheroidal shapes than in nearly spherical vesicles.

Generating true minima in constrained variational formulations via modified Lagrange multipliers.

Variational principles are important in the investigation of large classes of physical systems. They can be used both as analytical methods as well as starting points for the formulation of powerful computational techniques such as dynamical optimization methods. Systems with charged objects in dielectric media and systems with magnetically active particles are important examples. In these examples and other important cases, the variational principles describing the system are required to obey a number of constraints. These constraints are implemented within the variational formulation by means of Lagrange multipliers. Such constrained variational formulations are in general not unique. For the application of efficient simulation methods, one must find specific formulations that satisfy a number of important conditions. An often required condition is that the functional be positive-definite, in other words, its extrema be actual minima. In this article, we present a general approach to attack the problem of finding, among equivalent variational functionals, those that generate true minima. The method is based on the modification of the Lagrange multiplier which allows us to generate large families of effective variational formulations associated with a single original constrained variational principle. We demonstrate its application to different examples and, in particular, to the important cases of Poisson and Poisson-Boltzmann equations. We show how to obtain variational formulations for these systems with extrema that are always minima.

Free-energy functionals of the electrostatic potential for Poisson-Boltzmann theory.

In simulating charged systems, it is often useful to treat some ionic components of the system at the mean-field level and solve the Poisson-Boltzmann (PB) equation to get their respective density profiles. The numerically intensive task of solving the PB equation at each step of the simulation can be bypassed using variational methods that treat the electrostatic potential as a dynamic variable. But such approaches require the access to a true free-energy functional: a functional that not only provides the correct solution of the PB equation upon extremization, but also evaluates to the true free energy of the system at its minimum. Moreover, the numerical efficiency of such procedures is further enhanced if the free-energy functional is local and is expressed in terms of the electrostatic potential. Existing PB functionals of the electrostatic potential, while possessing the local structure, are not free-energy functionals. We present a variational formulation with a local free-energy functional of the potential. In addition, we also construct a nonlocal free-energy functional of the electrostatic potential. These functionals are suited for employment in simulation schemes based on the ideas of dynamical optimization.

A variational formulation of electrostatics in a medium with spatially varying dielectric permittivity.

In biological and synthetic materials, many important processes involve charges that are present in a medium with spatially varying dielectric permittivity. To accurately understand the role of electrostatic interactions in such systems, it is important to take into account the spatial dependence of the permittivity of the medium. However, due to the ensuing theoretical and computational challenges, this inhomogeneous dielectric response of the medium is often ignored or excessively simplified. We develop a variational formulation of electrostatics to accurately investigate systems that exhibit this inhomogeneous dielectric response. Our formulation is based on a true energy functional of the polarization charge density. The defining characteristic of a true energy functional is that at its minimum it evaluates to the actual value of the energy; this is a feature not found in many commonly used electrostatic functionals. We explore in detail the charged systems that exhibit sharp discontinuous change in dielectric permittivity, and we show that for this case our functional reduces to a functional of only the surface polarization charge density. We apply this reduced functional to study model problems for which analytical solutions are well known. We demonstrate, in addition, that the functional has many properties that make it ideal for use in molecular dynamics simulations.

Effects of interleaflet coupling on the morphologies of multicomponent lipid bilayer membranes.

We investigate dynamical and stationary compositional and surface morphologies in macroscopically phase-separating multicomponent lipid bilayer membranes using a computational model. We employ a phase-field method for the description of the coexisting phases and treat the two leaflets individually while including interleaflet interactions. The compositional evolution of the two leaflets is coupled to the shape evolution of the membrane via a Helfrich free energy with a composition-dependent spontaneous curvature. We investigate the effects of the interleaflet interaction on the dynamics and stationary states of a system favoring nonzero spontaneous curvatures. Morphological phase diagrams are mapped in composition space using three different interleaflet coupling strengths. We find that characteristics sensitive to the coupling strength include the time required to develop regions of fully separated phases, the prevalence of a stripe morphology, and the shifting of phase compositions to accommodate energetically favorable interactions across leaflets. Characteristics found to be robust with respect to coupling strength include (1) the stripe morphology is favored at nearly equal mixtures and (2) phase separation is prevented in systems where a pair of phases that preferentially interact across leaflets together occupy nearly all or none of the membrane.

Nematic liquid crystals on spherical surfaces: control of defect configurations by temperature, density, and rod shape.

Recent experiments have shown that defect conformations in spherical nematic liquid crystals can be controlled through variations of temperature, shell thickness, and other environmental parameters. These modifications can be understood as a result of the induced changes in the effective elastic constants of the system. To characterize the relation between defect conformations and elastic anisotropy, we carry out Monte Carlo simulations of a nematic on a spherical surface. As the anisotropy is increased, the defects flow from a tetrahedral arrangement to two coalescing pairs and then to a great circle configuration. We also analyze this flow using a variational method based on harmonic configurations.

Simulation of charged systems in heterogeneous dielectric media via a true energy functional.

For charged systems in heterogeneous dielectric media, a key obstacle for molecular dynamics (MD) simulations is the need to solve the Poisson equation in the media. This obstacle can be bypassed using MD methods that treat the local polarization charge density as a dynamic variable, but such approaches require access to a true free energy functional, one that evaluates to the equilibrium electrostatic energy at its minimum. In this Letter, we derive the needed functional. As an application, we develop a Car-Parrinello MD method for the simulation of free charges present near a spherical emulsion droplet separating two immiscible liquids with different dielectric constants. Our results show the presence of nonmonotonic ionic profiles in the dielectric with a lower dielectric constant.