Self-organised transients in a neural mass model of epileptogenic tissue dynamics

Stimulation of human epileptic tissue can induce rhythmic, self-terminating responses on the EEG or ECoG. These responses play a potentially important role in localising tissue involved in the generation of seizure activity, yet the underlying mechanisms are unknown. However, in vitro evidence suggests that self-terminating oscillations in nervous tissue are underpinned by non-trivial spatio-temporal dynamics in an excitable medium. In this study, we investigate this hypothesis in spatial extensions to a neural mass model for epileptiform dynamics. We demonstrate that spatial extensions to this model in one and two dimensions display propagating travelling waves but also more complex transient dynamics in response to local perturbations. The neural mass formulation with local excitatory and inhibitory circuits, allows the direct incorporation of spatially distributed, functional heterogeneities into the model. We show that such heterogeneities can lead to prolonged reverberating responses to a single pulse perturbation, depending upon the location at which the stimulus is delivered. This leads to the hypothesis that prolonged rhythmic responses to local stimulation in epileptogenic tissue result from repeated self-excitation of regions of tissue with diminished inhibitory capabilities. Combined with previous models of the dynamics of focal seizures this macroscopic framework is a first step towards an explicit spatial formulation of the concept of the epileptogenic zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of the epileptogenic zone will help to improve diagnostic and therapeutic measures for treating epilepsy.

Estudo de formulação de massa para aplicação em placas cerâmicas

The sector of civil construction is strongly related to the red ceramic industry. This sector uses clay as raw material for manufacturing of various products such as ceramic plates. In this study, two types of clay called clay 1 and clay 2 were collected on deposit in Ielmo Marinho city (RN) and then characterized by thermogravimetric analysis (TG/DTG), differential thermal analysis (DTA), X-ray diffraction (XRD), X-ray fluorescence (XRF), rational analysis and particle size distribution and dilatometric analyses. Ceramic plates were manufactured by uniaxial pressing and by extrusion. The plates obtained by pressing were produced from the four formulations called 1, 2, 3 and 4, which presented, respectively, the following proportions by mass: 66.5% clay 1 and 33.5% clay 2, 50% clay 1 and 50% clay 2, 33.5% clay 1 and 66.5% clay 2, 25% clay 1 and 75% clay 2. After firing at 850, 950 and 1050 °C with heating rate of 10 °C/min and soaking time of 30 minutes, the following technological properties were determined: linear firing shrinkage, water absorption, apparent porosity, apparent specific mass and tensile strength (3 points). The formulation containing 25% clay 1 produced plates with most satisfactory results of water absorption and mechanical resistance, because of that it was chosen for manufacturing plates by extrusion. A single firing cycle was established for these plates, which took place as follow: heating rate of 2 °C/min up to 600 ºC with soaking time of 60 minutes, followed by heating using the same rate up to 1050 ºC with soaking time of 30 minutes. After this cycle, the same technological properties investigated in the plates obtained by pressing were determined. The results indicate (according to NRB 13818/1997) that the plates obtained by pressing from the mixture containing 25 wt% clay 1, after firing at 1050 °C, reach the specifications for semi-porous coating (BIIb). On the other hand, the plates obtained by extrusion were classified as semi-stoneware (group AIIa)

Stabilization of a (3+1)-dimensional soliton in a Kerr medium by a rapidly oscillating dispersion coefficient

Using the numerical solution of the nonlinear Schrodinger equation and a variational method it is shown that (3 + 1)-dimensional spatiotemporal optical solitons can be stabilized by a rapidly oscillating dispersion coefficient in a Kerr medium with cubic nonlinearity. This has immediate consequence in generating dispersion-managed robust optical soliton in communication as well as possible stabilized Bose-Einstein condensates in periodic optical-lattice potential via an effective-mass formulation. We also critically compare the present stabilization with that obtained by a rapid sinusoidal oscillation of the Kerr nonlinearity parameter.

Estudo de formulação de massas através do controle da mistura: argilas aluvionares do pólo cerâmico de Russas-Ceará

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Separação do calcário e do folhelho pirobetuminoso da formação irati para utilização como corretivo e como aditivo na indústria cerâmica

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The forced oscillations of submerged bodies

The increasing use of very light structures in aerospace applications are given rise to the need of taking into account the effects of the surrounding media in the motion of a structure (as for instance, in modal testing of solar panels or antennae) as it is usually performed in the motion of bodies submerged in water in marine applications. New methods are in development aiming at to determine rigid-body properties (the center of mass position and inertia properties) from the results of oscillations tests (at low frequencies during modal testing, by exciting the rigid-body modes only) by using the equations of the rigid-body dynamics. As it is shown in this paper, the effect of the surrounding media significantly modifies the oscillation dynamics in the case of light structures and therefore this effect should be taken into account in the development of the above-mentioned methods. The aim of the paper is to show that, if a central point exists for the aerodynamic forces acting on the body, the motion equations for the small amplitude rotational and translational oscillations can be expressed in a form which is a generalization of the motion equations for a body in vacuum, thus allowing to obtain a physical idea of the motion and aerodynamic effects and also significantly simplifying the calculation of the solutions and the interpretation of the results. In the formulation developed here the translational oscillations and the rotational motion around the center of mass are decoupled, as is the case for the rigid-body motion in vacuum, whereas in the classical added mass formulation the six motion equations are coupled. Also in this paper the nonsteady motion of small amplitude of a rigid body submerged in an ideal, incompressible fluid is considered in order to define the conditions for the existence of the central point in the case of a three-dimensional body. The results here presented are also of interest in marine applications.

Propylthiouracil Quantification In Human Plasma By High-performance Liquid Chromatography Coupled With Electrospray Tandem Mass Spectrometry: Application In A Bioequivalence Study.

A rapid, sensitive and specific method for quantifying propylthiouracil in human plasma using methylthiouracil as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (ethyl acetate). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS) in negative mode (ES-). Chromatography was performed using a Phenomenex Gemini C18 5μm analytical column (4.6mm×150mm i.d.) and a mobile phase consisting of methanol/water/acetonitrile (40/40/20, v/v/v)+0.1% of formic acid. For propylthiouracil and I.S., the optimized parameters of the declustering potential, collision energy and collision exit potential were -60 (V), -26 (eV) and -5 (V), respectively. The method had a chromatographic run time of 2.5min and a linear calibration curve over the range 20-5000ng/mL. The limit of quantification was 20ng/mL. The stability tests indicated no significant degradation. This HPLC-MS/MS procedure was used to assess the bioequivalence of two propylthiouracil 100mg tablet formulations in healthy volunteers of both sexes in fasted and fed state. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 109.28% (103.63-115.25%) and 115.60% (109.03-122.58%) for Cmax, 103.31% (100.74-105.96%) and 103.40% (101.03-105.84) for AUClast. This method offers advantages over those previously reported, in terms of both a simple liquid-liquid extraction without clean-up procedures, as well as a faster run time (2.5min). The LOQ of 20ng/mL is well suited for pharmacokinetic studies. The assay performance results indicate that the method is precise and accurate enough for the routine determination of the propylthiouracil in human plasma. The test formulation with and without food was bioequivalent to reference formulation. Food administration increased the Tmax and decreased the bioavailability (Cmax and AUC).

Pharmacokinetic And Pharmacodynamic Evaluation Of A Nanotechnological Topical Formulation Of Lidocaine/prilocaine (nanorap) In Healthy Volunteers.

Nanorap is a new nanotechnological formulation for topical anesthesia composed of lidocaine (2.5%) and prilocaine (2.5%). The present study evaluated the pharmacokinetics (PK) of Nanorap. For the determination of lidocaine and prilocaine in human plasma a new method using high-performance liquid-chromatography coupled to tandem mass spectrometry was developed. Nanorap pharmacodynamic (PD) and its physical proprieties were also evaluated. Nanorap was administered by topical application of 2g to healthy volunteers and blood samples were collected for the PK analysis. The drugs were extracted from plasma by liquid-liquid extraction with ether/hexane (80/20, v/v). The chromatography separation was performed on a Genesis C18 analytical column 4 µm (100 x 2.1 mm i.d.) with a mobile phase of methanol/acetonitrile/water (40/30/30, for lidocaine, and 50/30/20, for prilocaine, v/v/v) + 2 mM of ammonium acetate and ropivacaine as internal standard. The drugs were quantified using a mass spectrometer with an electrospray source in the ESI positive mode (ES+) configured for multiple reaction monitoring. The PD of Nanorap was evaluated with the use of a visual analogue scale. Nanorap was characterized by cryofracture. The chromatography run time was 5.5 min for lidocaine and 3.3 min for prilocaine and the lower limit of quantification was 0.05 ng/mL for both drugs. Mean Cmax was 6.62 and 1.72 ng/mL for lidocaine and prilocaine, respectively. Median Tmax was 6.5 hours for both drugs. Nanocapsules had a mean size of 88nm and mean drug association of 92.5% and 89% for lidocaine and prilocaine, respectively. The PD study showed that Nanorap has a sufficient analgesic effect (>30% reduction in pain) after 10 minutes of application. A new simple, selective and sensitive method for determination of lidocaine and prilocaine in human plasma was developed. Nanorap generated safe plasma levels of the drugs and satisfactory analgesic effect.

In Vitro Evaluation Of Sun Protection Factor And Stability Of Commercial Sunscreens Using Mass Spectrometry.

Sunlight exposure causes several types of injury to humans, especially on the skin; among the most common harmful effects due to ultraviolet (UV) exposure are erythema, pigmentation and lesions in DNA, which may lead to cancer. These long-term effects are minimized with the use of sunscreens, a class of cosmetic products that contains UV filters as the main component in the formulation; such molecules can absorb, reflect or diffuse UV rays, and can be used alone or as a combination to broaden the protection on different wavelengths. Currently, worldwide regulatory agencies define which ingredients and what quantities must be used in each country, and enforce companies to conduct tests that confirm the Sun Protection Factor (SPF) and the UVA (Ultraviolet A) factor. Standard SPF determination tests are currently conducted in vivo, using human subjects. In an industrial mindset, apart from economic and ethical reasons, the introduction of an in vitro method emerges as an interesting alternative by reducing risks associated to UV exposure on tests, as well as providing assertive analytical results. The present work aims to describe a novel methodology for SPF determination directly from sunscreen formulations using the previously described cosmetomics platform and mass spectrometry as the analytical methods of choice.

Impact Of Drug Formulation And Free Platinum/cisplatin Ratio On Hypersensitivity Reactions To Cisplatin: Formulation Matters.

Use of cisplatin can induce type I hypersensitivity reactions that may also be linked to the quality of the drug utilized. We observed cases of hypersensitivity that appeared to be associated with the brand of cisplatin used. The aim of this study was to compare two different brands of cisplatin in relation to type I hypersensitivity reactions. Brand A was used in a tertiary care teaching hospital until 2012, and use of brand B started from January 2013, when the first hypersensitivity cases were observed. Patients were categorized based on symptom. Cisplatin of both brands was analysed by high-performance liquid chromatography (HPLC) and high-resolution electrospray ionization mass spectrometry (ESI-(+)-MS) and characterized according to US Pharmacopeia. There were no cases of hypersensitivity associated with the use of cisplatin brand A, whereas four of 127 outpatients that used cisplatin brand B were affected. The two brands were in accordance with the US Pharmacopeia parameters, and there was no significant difference in the total platinum levels between the two brands when analysed by HPLC. However, high-resolution ESI-(+)-MS analyses show that brand B contains approximately 2.7 times more hydrolysed cisplatin than brand A. The increase in the hydrolysed form of cisplatin found in brand B may be the cause of the hypersensitivity reaction observed in a subset of patients. We present the first study of the quality of drugs by high-resolution ESI-(+)-MS. Drug regulatory agencies and manufacturers should consider including measurement of hydrolysed cisplatin as a quality criterion for cisplatin formulations.

A sensor array based on mass and capacitance transducers for the detection of adulterated gasolines

The simultaneous use of different sensors technologies is an efficient method to increase the performance of chemical sensors systems. Among the available technologies, mass and capacitance transducers are particularly interesting because they can take advantage also from non-conductive sensing layers, such as most of the more interesting molecular recognition systems. In this paper, an array of quartz microbalance sensors is complemented by an array of capacitors obtained from a commercial biometrics fingerprints detector. The two sets of transducers, properly functionalized by sensitive molecular and polymeric films, are utilized for the estimation of adulteration in gasolines, and in particular to quantify the content of ethanol in gasolines, an application of importance for Brazilian market. Results indicate that the hybrid system outperforms the individual sensor arrays even if the quantification of ethanol in gasoline, due to the variability of gasolines formulation, is affected by a barely acceptable error. (C) 2009 Elsevier B.V. All rights reserved.

MASS CONSERVATION ENHANCEMENT OF FREE BOUNDARY FLOWS IN COMPOSITES MANUFACTURING

Undesirable void formation during the injection phase of the liquid composite molding process can be understood as a consequence of the non-uniformity of the flow front progression, caused by the dual porosity of the fiber perform. Therefore the best examination of the void formation physics can be provided by a mesolevel analysis, where the characteristic dimension is given by the fiber tow diameter. In mesolevel analysis, liquid impregnation along two different scales; inside fiber tows and within the spaces between them; must be considered and the coupling between these flow regimes must be addressed. In such case, it is extremely important to account correctly for the surface tension effects, which can be modeled as capillary pressure applied at the flow front. When continues Galerkin method is used, exploiting elements with velocity components and pressure as nodal variables, strong numerical implementation of such boundary conditions leads to ill-posing of the problem, in terms of the weak classical as well as stabilized formulation. As a consequence, there is an error in mass conservation accumulated especially along the free flow front. This article presents a numerical procedure, which was formulated and implemented in the existing Free Boundary Program in order to significantly reduce this error.

Mass Conservation Enhancement of Free Boundary Mesolevel Flows during LCM Processes of Composites Manufacturing

Undesirable void formation during the injection phase of the liquid composite moulding process can be understood as a consequence of the non-uniformity of the flow front progression, caused by the dual porosity of the fibre perform. Therefore the best examination of the void formation physics can be provided by a mesolevel analysis, where the characteristic dimension is given by the fibre tow diameter. In mesolevel analysis, liquid impregnation along two different scales; inside fibre tows and within the open spaces between them; must be considered and the coupling between these flow regimes must be addressed. In such case, it is extremely important to account correctly for the surface tension effects, which can be modelled as capillary pressure applied at the flow front. Numerical implementation of such boundary conditions leads to ill-posing of the problem, in terms of the weak classical as well as stabilized formulation. As a consequence, there is an error in mass conservation accumulated especially along the free flow front. This contribution presents a numerical procedure, which was formulated and implemented in the existing Free Boundary Program in order to significantly reduce this error.

Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

An operator formulation of the multiscale finite-volume method with correction function

The multiscale finite-volume (MSFV) method has been derived to efficiently solve large problems with spatially varying coefficients. The fine-scale problem is subdivided into local problems that can be solved separately and are coupled by a global problem. This algorithm, in consequence, shares some characteristics with two-level domain decomposition (DD) methods. However, the MSFV algorithm is different in that it incorporates a flux reconstruction step, which delivers a fine-scale mass conservative flux field without the need for iterating. This is achieved by the use of two overlapping coarse grids. The recently introduced correction function allows for a consistent handling of source terms, which makes the MSFV method a flexible algorithm that is applicable to a wide spectrum of problems. It is demonstrated that the MSFV operator, used to compute an approximate pressure solution, can be equivalently constructed by writing the Schur complement with a tangential approximation of a single-cell overlapping grid and incorporation of appropriate coarse-scale mass-balance equations.