Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity

This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow theological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20%(w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and mucoadhesive properties (at body temperature) render the formulations composed of 20% (w/w) P407 and C934P as potentially useful platforms for mucoadhesive, controlled topical drug delivery within the oral cavity. (c) 2009 Published by Elsevier B.V.

Surface miscibility of EPC/DOTAP/DOPE in binary and ternary mixed monolayers

Surface pressure (pi)-molecular area (A) curves were used to characterize the packing of pseudo-ternary mixed Langmuir monolayers of egg phosphatidylcholine (EPC), 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and L-alpha-dioleoyl phosphatidylethanolamine (DOPE). This pseudo-ternary mixture EPC/DOPE/DOTAP has been successfully employed in liposome formulations designed for DNA non-viral vectors. Pseudo-binary mixtures were also studied as a control. Miscibility behavior was inferred from pi-A curves applying the additivity rule by calculating the excess free energy of mixture (Delta G(Exc)). The interaction between the lipids was also deduced from the surface compressional modulus (C(s)(-1)). The deviation from ideality shows dependence on the lipid polar head type and monolayer composition. For lower DOPE concentrations, the forces are predominantly attractive. However, if the monolayer is DOPE rich, the DOTAP presence disturbs the PE-PE intermolecular interaction and the net interaction is then repulsive. The ternary monolayer EPC/DOPE/DOTAP presented itself in two configurations, modulated by the DOPE content, in a similar behavior to the DOPE/DOTAP monolayers. These results contribute to the understanding of the lipid interactions and packing in self-assembled systems associated with the in vitro and in vivo stability of liposomes. (C) 2010 Elsevier B.V. All rights reserved.

Hyperplane navigation: A method to set individual scores in fMRI group datasets

Recent studies have demonstrated that spatial patterns of fMRI BOLD activity distribution over the brain may be used to classify different groups or mental states. These studies are based on the application of advanced pattern recognition approaches and multivariate statistical classifiers. Most published articles in this field are focused on improving the accuracy rates and many approaches have been proposed to accomplish this task. Nevertheless, a point inherent to most machine learning methods (and still relatively unexplored in neuroimaging) is how the discriminative information can be used to characterize groups and their differences. In this work, we introduce the Maximum Uncertainty Linear Discrimination Analysis (MLDA) and show how it can be applied to infer groups` patterns by discriminant hyperplane navigation. In addition, we show that it naturally defines a behavioral score, i.e., an index quantifying the distance between the states of a subject from predefined groups. We validate and illustrate this approach using a motor block design fMRI experiment data with 35 subjects. (C) 2008 Elsevier Inc. All rights reserved.

Precession and nutation in the eta Carinae binary system: evidence from the X-ray light curve

It is believed that eta Carinae is actually a massive binary system, with the wind-wind interaction responsible for the strong X-ray emission. Although the overall shape of the X-ray light curve can be explained by the high eccentricity of the binary orbit, other features like the asymmetry near periastron passage and the short quasi-periodic oscillations seen at those epochs have not yet been accounted for. In this paper we explain these features assuming that the rotation axis of eta Carinae is not perpendicular to the orbital plane of the binary system. As a consequence, the companion star will face eta Carinae on the orbital plane at different latitudes for different orbital phases and, since both the mass-loss rate and the wind velocity are latitude dependent, they would produce the observed asymmetries in the X-ray flux. We were able to reproduce the main features of the X-ray light curve assuming that the rotation axis of eta Carinae forms an angle of 29 degrees +/- 4 degrees with the axis of the binary orbit. We also explained the short quasi-periodic oscillations by assuming nutation of the rotation axis, with an amplitude of about 5 degrees and a period of about 22 days. The nutation parameters, as well as the precession of the apsis, with a period of about 274 years, are consistent with what is expected from the torques induced by the companion star.

Building binary-tree-based multiclass classifiers using separability measures

Various popular machine learning techniques, like support vector machines, are originally conceived for the solution of two-class (binary) classification problems. However, a large number of real problems present more than two classes. A common approach to generalize binary learning techniques to solve problems with more than two classes, also known as multiclass classification problems, consists of hierarchically decomposing the multiclass problem into multiple binary sub-problems, whose outputs are combined to define the predicted class. This strategy results in a tree of binary classifiers, where each internal node corresponds to a binary classifier distinguishing two groups of classes and the leaf nodes correspond to the problem classes. This paper investigates how measures of the separability between classes can be employed in the construction of binary-tree-based multiclass classifiers, adapting the decompositions performed to each particular multiclass problem. (C) 2010 Elsevier B.V. All rights reserved.

A review on the combination of binary classifiers in multiclass problems

Several real problems involve the classification of data into categories or classes. Given a data set containing data whose classes are known, Machine Learning algorithms can be employed for the induction of a classifier able to predict the class of new data from the same domain, performing the desired discrimination. Some learning techniques are originally conceived for the solution of problems with only two classes, also named binary classification problems. However, many problems require the discrimination of examples into more than two categories or classes. This paper presents a survey on the main strategies for the generalization of binary classifiers to problems with more than two classes, known as multiclass classification problems. The focus is on strategies that decompose the original multiclass problem into multiple binary subtasks, whose outputs are combined to obtain the final prediction.

Invariants of binary differential equations

In this paper, we study binary differential equations a(x, y)dy (2) + 2b(x, y) dx dy + c(x, y)dx (2) = 0, where a, b, and c are real analytic functions. Following the geometric approach of Bruce and Tari in their work on multiplicity of implicit differential equations, we introduce a definition of the index for this class of equations that coincides with the classical Hopf`s definition for positive binary differential equations. Our results also apply to implicit differential equations F(x, y, p) = 0, where F is an analytic function, p = dy/dx, F (p) = 0, and F (pp) not equal aEuro parts per thousand 0 at the singular point. For these equations, we relate the index of the equation at the singular point with the index of the gradient of F and index of the 1-form omega = dy -aEuro parts per thousand pdx defined on the singular surface F = 0.

Structural Characterization of Photopolymerizable Binary Liposomes Containing Diacetylenic and Saturated Phospholipids

The use of liposomes to encapsulate materials has received widespread attention for drug delivery, transfection, diagnostic reagent, and as immunoadjuvants. Phospholipid polymers form a new class of biomaterials with many potential applications in medicine and research. Of interest are polymeric phospholipids containing a diacetylene moiety along their acyl chain since these kinds of lipids can be polymerized by Ultra-Violet (UV) irradiation to form chains of covalently linked lipids in the bilayer. In particular the diacetylenic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)- sn-glycero-3-phosphocholine (DC8,9PC) can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer. As knowledge of liposome structures is certainly fundamental for system design improvement for new and better applications, this work focuses on the structural properties of polymerized DC8,9PC:1,2-dimyristoyl-sn-glycero-3-phusphocholine (DMPC) liposomes. Liposomes containing mixtures of DC8,9PC and DMPC, at different molar ratios, and exposed to different polymerization cycles, were studied through the analysis of the electron spin resonance (ESR) spectra of a spin label incorporated into the bilayer, and the calorimetric data obtained from differential scanning calorimetry (DSC) studies. Upon irradiation, if all lipids had been polymerized, no gel-fluid transition would be expected. However, even samples that went through 20 cycles of UV irradiation presented a DSC band, showing that around 80% of the DC8,9PC molecules were not polymerized. Both DSC and ESR indicated that the two different lipids scarcely mix at low temperatures, however few molecules of DMPC are present in DC8,9PC rich domains and vice versa. UV irradiation was found to affect the gel fluid transition of both DMPC and DC8,9PC rich regions, indicating the presence of polymeric units of DC8,9PC in both areas, A model explaining lipids rearrangement is proposed for this partially polymerized system.

An Information Theory framework for two-stage binary image operator design

The design of translation invariant and locally defined binary image operators over large windows is made difficult by decreased statistical precision and increased training time. We present a complete framework for the application of stacked design, a recently proposed technique to create two-stage operators that circumvents that difficulty. We propose a novel algorithm, based on Information Theory, to find groups of pixels that should be used together to predict the Output Value. We employ this algorithm to automate the process of creating a set of first-level operators that are later combined in a global operator. We also propose a principled way to guide this combination, by using feature selection and model comparison. Experimental results Show that the proposed framework leads to better results than single stage design. (C) 2009 Elsevier B.V. All rights reserved.

Multilevel Training of Binary Morphological Operators

The design of binary morphological operators that are translation-invariant and locally defined by a finite neighborhood window corresponds to the problem of designing Boolean functions. As in any supervised classification problem, morphological operators designed from a training sample also suffer from overfitting. Large neighborhood tends to lead to performance degradation of the designed operator. This work proposes a multilevel design approach to deal with the issue of designing large neighborhood-based operators. The main idea is inspired by stacked generalization (a multilevel classifier design approach) and consists of, at each training level, combining the outcomes of the previous level operators. The final operator is a multilevel operator that ultimately depends on a larger neighborhood than of the individual operators that have been combined. Experimental results show that two-level operators obtained by combining operators designed on subwindows of a large window consistently outperform the single-level operators designed on the full window. They also show that iterating two-level operators is an effective multilevel approach to obtain better results.

Perfect Simulation of a Coupling Achieving the (d)over-bar-distance Between Ordered Pairs of Binary Chains of Infinite Order

We explicitly construct a stationary coupling attaining Ornstein`s (d) over bar -distance between ordered pairs of binary chains of infinite order. Our main tool is a representation of the transition probabilities of the coupled bivariate chain of infinite order as a countable mixture of Markov transition probabilities of increasing order. Under suitable conditions on the loss of memory of the chains, this representation implies that the coupled chain can be represented as a concatenation of i.i.d. sequences of bivariate finite random strings of symbols. The perfect simulation algorithm is based on the fact that we can identify the first regeneration point to the left of the origin almost surely.

Framework for Skew-Probit Links in Binary Regression

We review several asymmetrical links for binary regression models and present a unified approach for two skew-probit links proposed in the literature. Moreover, under skew-probit link, conditions for the existence of the ML estimators and the posterior distribution under improper priors are established. The framework proposed here considers two sets of latent variables which are helpful to implement the Bayesian MCMC approach. A simulation study to criteria for models comparison is conducted and two applications are made. Using different Bayesian criteria we show that, for these data sets, the skew-probit links are better than alternative links proposed in the literature.

Automorphism Groups of Generalized (Binary) Icosahedral, Tetrahedral and Octahedral Groups

Let G be any of the (binary) icosahedral, generalized octahedral (tetrahedral) groups or their quotients by the center. We calculate the automorphism group Aut(G).

ON SPECIALITY OF BINARY-LIE ALGEBRAS

In the present work, binary-Lie, assocyclic, and binary (-1,1) algebras are studied. We prove that, for every assocyclic algebra A, the algebra A(-) is binary-Lie. We find a simple non-Malcev binary-Lie superalgebra T that cannot be embedded in A(-s) for an assocyclic superalgebra A. We use the Grassmann envelope of T to prove the similar result for algebras. This solve negatively a problem by Filippov (see [1, Problem 2.108]). Finally, we prove that the superalgebra T is isomorphic to the commutator superalgebra A(-s) for a simple binary (-1,1) superalgebra A.

Solvatochromism in Binary Mixtures: First Report on a Solvation Free Energy Relationship between Solvent Exchange Equilibrium Constants and the Properties of the Medium

We have employed UV-vis spectroscopy in order to investigate details of the solvation of six solvatochromic indicators, hereafter designated as ""probes"", namely, 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl) phenolate (RB); 4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePM; 1-methylquinolinium-8-olate, QB; 2-bromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr, 2,6-dichloro-4-(2,4,6-triphenylpyridinium-1-yl) phenolate (WB); and 2,6-dibromo-4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl] phenolate, MePMBr,, respectively. These can be divided into three pairs, each includes two probes of similar pK(a) in water and different lipophilicity. Solvation has been studied in binary mixtures, BMs, of water, W, with 12 protic organic solvents, S, including mono- and bifunctional alcohols (2-alkoxyethanoles, unsaturated and chlorinated alcohols). Each medium was treated as a mixture of S, W, and a complex solvent, S-W, formed by hydrogen bonding. Values of lambda(max) (of the probe intramolecular charge transfer) were converted into empirical polarity scales, E(T)(probe) in kcal/mol, whose values were correlated with the effective mole fraction of water in the medium, chi w(effective). This correlation furnished three equilibrium constants for the exchange of solvents in the probe solvation shell; phi(W/S) (W substitutes S): phi(S-W/W) (S-W substitutes W), and phi(S-W/S) (S-W substitutes S), respectively. The values of these constants depend on the physicochemical properties of the probe and the medium. We tested, for the first time, the applicability of a new solvation free energy relationship: phi = constant + a alpha(BM) + b beta(BM) + s(pi*(BM) + d delta) + p log P(BM), where a, b, s, and p are regression coefficients alpha(BM), beta(BM), and pi*(BM) are solvatochromic parameters of the BM, delta is a correction term for pi*, and log P is an empirical scale of lipophilicity. Correlations were carried out with two-, three-, and four-medium descriptors. In all cases, three descriptors gave satisfactory correlations; use of four parameters gave only a marginal increase of the goodness of fit. For phi(W/S), the most important descriptor was found to be the lipophilicity of the medium; for phi(S-W/W) and phi(S-W/S), solvent basicity is either statistically relevant or is the most important descriptor. These responses are different from those of E(T)(probe) of many solvatochromic indicators in pure solvents, where the importance of solvent basicity is usually marginal, and can be neglected.