A novel set of ss-N-biaryl ether sulfonamide hydroxamates as potential MMPs inhibitors: Molecular dynamics simulations and molecular properties evaluation

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent proteases involved in the extracellular matrix degradation. MMP-2 and MMP9 are overexpressed in several human cancer types, including melanoma, thus the development of new compounds to inhibit MMPs' activity is desirable. Molecular dynamic simulation and molecular properties calculations were performed on a set of novel beta-N-biaryl ether sulfonamide-based hydroxamates, reported as MMP-2 and MMP-9 inhibitors, for providing data to develop an exploratory analysis. Thermodynamic, electronic, and steric descriptors have significantly discriminated highly active from moderately and less active inhibitors of MMP-2 whereas apparent partition coefficient at pH 1.5 was also significant for the MMP-9 data set. Compound 47 was considered an outlier in all analysis, indicating the presence of a bulky substituent group in R3 is crucial to this set of inhibitors for the establishment of molecular interactions with the S1 subsite of both enzymes, but there is a limit. (C) 2012 Wiley Periodicals, Inc.

Electrostatic potentials and polarization effects in proton-molecule interactions by means of multipoles from the quantum theory of atoms in molecules

Some atomic multipoles (charges, dipoles and quadrupoles) from the Quantum Theory of Atoms in Molecules (QTAIM) and CHELPG charges are used to investigate interactions between a proton and a molecule (F2, Cl2, BF, AlF, BeO, MgO, LiH, H2CO, NH3, PH3, BF3, and CO2). Calculations were done at the B3LYP/6-311G(3d,3p) level. The main aspect of this work is the investigation of polarization effects over electrostatic potentials and atomic multipoles along a medium to long range of interaction distances. Large electronic charge fluxes and polarization changes are induced by a proton mainly when this positive particle approaches the least electronegative atom of diatomic heteronuclear molecules. The search for simple equations to describe polarization on electrostatic potentials from QTAIM quantities resulted in linear relations with r-4 (r is the interaction distance) for many cases. Moreover, the contribution from atomic dipoles to these potentials is usually the most affected contribution by polarization what reinforces the need for these dipoles to a minimal description of purely electrostatic interactions. Finally, CHELPG charges provide a description of polarization effects on electrostatic potentials that is in disagreement with physical arguments for certain of these molecules. (c) 2012 Wiley Periodicals, Inc.

Interactions between 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid and gamma-Al2O3 (100) surface calculated by density functional theory

The main aim of this work is to investigate the 1-butyl-3-methylimidazolium tetrafluoroborate ([C4C1Im]+[BF4]-) ionic liquid (IL) adsorption on the gamma-Al2O3 (100) by density functional theory calculations to try to rationalize the adsorption as an electrostatic phenomenon. Optimized geometries and interaction energies of IL one-monolayer on the gamma-Al2O3 were obtained on high surface coverage (one cationanion pair per 94.96 nm2). A study of dispersion force was made to estimate its contribution to the adsorption. Overall, the process is ruled by electrostatic interaction between ions and surface. Adsorption of the anion [BF4]- and cation [C4C1Im]+ was also studied by Bader charge analysis and charge density difference for supported and unsupported situations. It is suggested that the IL ions have their charges maintained with significant anion cloud polarization inward to the acid aluminum sites. (c) 2012 Wiley Periodicals, Inc.

Density Functional Theory (DFT) Study of Edaravone Derivatives as Antioxidants

Quantum chemical calculations at the B3LYP/6-31G* level of theory were employed for the structure-activity relationship and prediction of the antioxidant activity of edaravone and structurally related derivatives using energy (E), ionization potential (IP), bond dissociation energy (BDE), and stabilization energies(Delta E-iso). Spin density calculations were also performed for the proposed antioxidant activity mechanism. The electron abstraction is related to electron-donating groups (EDG) at position 3, decreasing the IP when compared to substitution at position 4. The hydrogen abstraction is related to electron-withdrawing groups (EDG) at position 4, decreasing the BDECH when compared to other substitutions, resulting in a better antioxidant activity. The unpaired electron formed by the hydrogen abstraction from the C-H group of the pyrazole ring is localized at 2, 4, and 6 positions. The highest scavenging activity prediction is related to the lowest contribution at the carbon atom. The likely mechanism is related to hydrogen transfer. It was found that antioxidant activity depends on the presence of EDG at the C-2 and C-4 positions and there is a correlation between IP and BDE. Our results identified three different classes of new derivatives more potent than edaravone.

Rare-earth impurities in gallium nitride: The role of the Hubbard potential

We performed a first principles investigation on the electronic properties of 4f-rare earth substitutional impurities in zincblende gallium nitride (GaN:REGa, with RE=Eu, Gd, Tb, Dy, Ho, Er and Tm). The calculations were performed within the all electron methodology and the density functional theory. We investigated how the introduction of the on-site Hubbard U potential (GGA + U) corrects the electronic properties of those impurities. We showed that a self-consistent procedure to compute the Hubbard potential provides a reliable description on the position of the 4f-related energy levels with respect of the GaN valence band top. The results were compared to available data coming from a recent phenomenological model. (C) 2012 Elsevier B.V. All rights reserved.

A critical analysis on "Active Learning" in the light of Cultural-Historical Activity Theory (CHAT): Implications to Physics Education and to experimental activities as a particular case.

This is a research paper in which we discuss “active learning” in the light of Cultural-Historical Activity Theory (CHAT), a powerful framework to analyze human activity, including teaching and learning process and the relations between education and wider human dimensions as politics, development, emancipation etc. This framework has its origin in Vygotsky's works in the psychology, supported by a Marxist perspective, but nowadays is a interdisciplinary field encompassing History, Anthropology, Psychology, Education for example.

Structural and vibrational study of 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone: a potential metal-protein attenuating compound (MPAC) for the treatment of Alzheimer's disease

A comprehensive structural and vibrational study of the potential metal-protein attenuating compound 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone is reported. X-ray diffraction data, as well as FT-IR and Raman frequencies, were compared with the respective theoretical values obtained from DFT calculations. Theory agrees well with experiment. In this context, an attempt of total assignment concerning the FT-IR and Raman spectra of the title compound was performed, shedding new light on previous partial assignments published elsewhere.

Potential respiration is a better respiratory predictor than biomass in young Artemia salina

[EN] These experiments test whether respiration can be predicted better from biomass or from potential respiration, a measurement of the mitochondrial and microsomal respiratory electron transport systems. For nearly a century Kleiber's law or a similar precursor have argued the importance of biomass in predicting respiration. In the last decade, a version of the Metabolic Theory of Ecology has elaborated on Kleiber's Law adding emphasis to the importance of biomass in predicting respiration. We argue that Kleiber's law works because biomass packages mitochondria and microsomal electron transport complexes. On a scale of five orders of magnitude we have shown previously that potential respiration predicts respiration aswell as biomass inmarine zooplankton. Here, using cultures of the branchiopod, Artemia salina and on a scale of less than 2 orders of magnitude,we investigated the power of biomass and potential respiration in predicting respiration.We measured biomass, respiration and potential respiration in Artemia grown in different ways and found that potential respiration (Ф) could predict respiration (R), both in μlO2h−1 (R=0.924Φ+0.062, r2=0.976), but biomass (as mg dry mass) could not (R=27.02DM+8.857, r2=0.128). Furthermore the R/Ф ratio appeared independent of age and differences in the food source.

The Dynamics of a Small Model Glass Former as Viewed from Its Potential Energy Landscape

Despite intensive research during the last decades, thetheoreticalunderstanding of supercooled liquids and the glasstransition is stillfar from being complete. Besides analytical investigations,theso-called energy-landscape approach has turned out to beveryfruitful. In the literature, many numerical studies havedemonstratedthat, at sufficiently low temperatures, all thermodynamicquantities can be predicted with the help of the propertiesof localminima in the potential-energy-landscape (PEL). The main purpose of this thesis is to strive for anunderstanding ofdynamics in terms of the potential energy landscape. Incontrast to the study of static quantities, this requirestheknowledge of barriers separating the minima.Up to now, it has been the general viewpoint that thermallyactivatedprocesses ('hopping') determine the dynamics only belowTc(the critical temperature of mode-coupling theory), in thesense that relaxation rates follow from local energybarriers.As we show here, this viewpoint should be revisedsince the temperature dependence of dynamics is governed byhoppingprocesses already below 1.5Tc.At the example of a binary mixture of Lennard-Jonesparticles (BMLJ),we establish a quantitative link from the diffusioncoefficient,D(T), to the PEL topology. This is achieved in three steps:First, we show that it is essential to consider wholesuperstructuresof many PEL minima, called metabasins, rather than singleminima. Thisis a consequence of strong correlations within groups of PELminima.Second, we show that D(T) is inversely proportional to theaverageresidence time in these metabasins. Third, the temperaturedependenceof the residence times is related to the depths of themetabasins, asgiven by the surrounding energy barriers. We further discuss that the study of small (but not toosmall) systemsis essential, in that one deals with a less complex energylandscapethan in large systems. In a detailed analysis of differentsystemsizes, we show that the small BMLJ system consideredthroughout thethesis is free of major finite-size-related artifacts.

Hypersurfaces with many singularities

1. Teil: Bekannte Konstruktionen. Die vorliegende Arbeit gibt zunächst einen ausführlichen Überblick über die bisherigen Entwicklungen auf dem klassischen Gebiet der Hyperflächen mit vielen Singularitäten. Die maximale Anzahl mu^n(d) von Singularitäten auf einer Hyperfläche vom Grad d im P^n(C) ist nur in sehr wenigen Fällen bekannt, im P^3(C) beispielsweise nur für d<=6. Abgesehen von solchen Ausnahmen existieren nur obere und untere Schranken. 2. Teil: Neue Konstruktionen. Für kleine Grade d ist es oft möglich, bessere Resultate zu erhalten als jene, die durch allgemeine Schranken gegeben sind. In dieser Arbeit beschreiben wir einige algorithmische Ansätze hierfür, von denen einer Computer Algebra in Charakteristik 0 benutzt. Unsere anderen algorithmischen Methoden basieren auf einer Suche über endlichen Körpern. Das Liften der so experimentell gefundenen Hyperflächen durch Ausnutzung ihrer Geometrie oder Arithmetik liefert beispielsweise eine Fläche vom Grad 7 mit $99$ reellen gewöhnlichen Doppelpunkten und eine Fläche vom Grad 9 mit 226 gewöhnlichen Doppelpunkten. Diese Konstruktionen liefern die ersten unteren Schranken für mu^3(d) für ungeraden Grad d>5, die die allgemeine Schranke übertreffen. Unser Algorithmus hat außerdem das Potential, auf viele weitere Probleme der algebraischen Geometrie angewendet zu werden. Neben diesen algorithmischen Methoden beschreiben wir eine Konstruktion von Hyperflächen vom Grad d im P^n mit vielen A_j-Singularitäten, j>=2. Diese Beispiele, deren Existenz wir mit Hilfe der Theorie der Dessins d'Enfants beweisen, übertreffen die bekannten unteren Schranken in den meisten Fällen und ergeben insbesondere neue asymptotische untere Schranken für j>=2, n>=3. 3. Teil: Visualisierung. Wir beschließen unsere Arbeit mit einer Anwendung unserer neuen Visualisierungs-Software surfex, die die Stärken mehrerer existierender Programme bündelt, auf die Konstruktion affiner Gleichungen aller 45 topologischen Typen reeller kubischer Flächen.

Pseudodifferential analysis in Psi*-algebras on transmission spaces, infinite solving ideal chains and K-theory for conformally compact spaces

The present thesis is a contribution to the theory of algebras of pseudodifferential operators on singular settings. In particular, we focus on the $b$-calculus and the calculus on conformally compact spaces in the sense of Mazzeo and Melrose in connection with the notion of spectral invariant transmission operator algebras. We summarize results given by Gramsch et. al. on the construction of $Psi_0$-and $Psi*$-algebras and the corresponding scales of generalized Sobolev spaces using commutators of certain closed operators and derivations. In the case of a manifold with corners $Z$ we construct a $Psi*$-completion $A_b(Z,{}^bOmega^{1/2})$ of the algebra of zero order $b$-pseudodifferential operators $Psi_{b,cl}(Z, {}^bOmega^{1/2})$ in the corresponding $C*$-closure $B(Z,{}^bOmega^{12})hookrightarrow L(L^2(Z,{}^bOmega^{1/2}))$. The construction will also provide that localised to the (smooth) interior of Z the operators in the $A_b(Z, {}^bOmega^{1/2})$ can be represented as ordinary pseudodifferential operators. In connection with the notion of solvable $C*$-algebras - introduced by Dynin - we calculate the length of the $C*$-closure of $Psi_{b,cl}^0(F,{}^bOmega^{1/2},R^{E(F)})$ in $B(F,{}^bOmega^{1/2}),R^{E(F)})$ by localizing $B(Z, {}^bOmega^{1/2})$ along the boundary face $F$ using the (extended) indical familiy $I^B_{FZ}$. Moreover, we discuss how one can localise a certain solving ideal chain of $B(Z, {}^bOmega^{1/2})$ in neighbourhoods $U_p$ of arbitrary points $pin Z$. This localisation process will recover the singular structure of $U_p$; further, the induced length function $l_p$ is shown to be upper semi-continuous. We give construction methods for $Psi*$- and $C*$-algebras admitting only infinite long solving ideal chains. These algebras will first be realized as unconnected direct sums of (solvable) $C*$-algebras and then refined such that the resulting algebras have arcwise connected spaces of one dimensional representations. In addition, we recall the notion of transmission algebras on manifolds with corners $(Z_i)_{iin N}$ following an idea of Ali Mehmeti, Gramsch et. al. Thereby, we connect the underlying $C^infty$-function spaces using point evaluations in the smooth parts of the $Z_i$ and use generalized Laplacians to generate an appropriate scale of Sobolev spaces. Moreover, it is possible to associate generalized (solving) ideal chains to these algebras, such that to every $ninN$ there exists an ideal chain of length $n$ within the algebra. Finally, we discuss the $K$-theory for algebras of pseudodifferential operators on conformally compact manifolds $X$ and give an index theorem for these operators. In addition, we prove that the Dirac-operator associated to the metric of a conformally compact manifold $X$ is not a Fredholm operator.

Noble-metal nanoparticles produced with colloidal lithography: fabrication, optical properties and applications

In this work, metal nanoparticles produced by nanosphere lithography were studied in terms of their optical properties (in connection to their plasmon resonances), their potential application in sensing platforms - for thin layer sensing and bio-recognition events -, and for a particular case (the nanocrescents), for enhanced spectroscopy studies. The general preparation procedures introduced early in 2005 by Shumaker-Parry et al. to produce metallic nanocrescents were extended to give rise to more complex (isolated) structures, and also, by combining colloidal monolayer fabrication and plasma etching techniques, to arrays of them. The fabrication methods presented in this work were extended not only to new shapes or arrangements of particles, but included also a targeted surface tailoring of the substrates and the structures, using different thiol and silane compounds as linkers for further attachment of, i.e. polyelectrolyte layers, which allow for a controlled tailoring of their nanoenvironment. The optical properties of the nanocrescents were studied with conventional transmission spectroscopy; a simple multipole model was adapted to explain their behaviour qualitatively. In terms of applications, the results on thin film sensing using these particles show that the crescents present an interesting mode-dependent sensitivity and spatial extension. Parallel to this, the penetrations depths were modeled with two simplified schemes, obtaining good agreement with theory. The multiple modes of the particles with their characteristic decay lengths and sensitivities represent a major improvement for particle-sensing platforms compared to previous single resonance systems. The nanocrescents were also used to alter the emission properties of fluorophores placed close to them. In this work, green emitting dyes were placed at controlled distances from the structures and excited using a pulsed laser emitting in the near infrared. The fluorescence signal obtained in this manner should be connected to a two-photon processes triggered by these structures; obtaining first insight into plasmon-mediated enhancement phenomena. An even simpler and faster approach to produce plasmonic structures than that for the crescents was tested. Metallic nanodiscs and nanoellipses were produced by means of nanosphere lithography, extending a procedure reported in the literature to new shapes and optical properties. The optical properties of these particles were characterized by extinction spectroscopy and compared to results from the literature. Their major advantage is that they present a polarization-dependent response, like the nanocrescents, but are much simpler to fabricate, and the resonances can be tailored in the visible with relative ease. The sensing capabilities of the metallic nanodiscs were explored in the same manner as for the nanocrescents, meaning their response to thin layers and to bio-recognition events on their surface. The sensitivity of these nanostructures to thin films proved to be lower than that of the crescents, though in the same order of magnitude. Experimental information about the near field extension for the Au nanodiscs of different sizes was also extracted from these measurements. Further resonance-tailoring approaches based on electrochemical deposition of metals on the nanodiscs were explored, as a means of modifying plasmon resonances by changing surface properties of the nanoparticles. First results on these experiments would indicate that the deposition of Ag on Au on a submonolayer coverage level can lead to important blue-shifts in the resonances, which would open a simple way to tailor resonances by changing material properties in a local manner.

Statistical problems related to excitation threshold and reset value of membrane potentials

Die vorliegende Arbeit ist motiviert durch biologische Fragestellungen bezüglich des Verhaltens von Membranpotentialen in Neuronen. Ein vielfach betrachtetes Modell für spikende Neuronen ist das Folgende. Zwischen den Spikes verhält sich das Membranpotential wie ein Diffusionsprozess X der durch die SDGL dX_t= beta(X_t) dt+ sigma(X_t) dB_t gegeben ist, wobei (B_t) eine Standard-Brown'sche Bewegung bezeichnet. Spikes erklärt man wie folgt. Sobald das Potential X eine gewisse Exzitationsschwelle S überschreitet entsteht ein Spike. Danach wird das Potential wieder auf einen bestimmten Wert x_0 zurückgesetzt. In Anwendungen ist es manchmal möglich, einen Diffusionsprozess X zwischen den Spikes zu beobachten und die Koeffizienten der SDGL beta() und sigma() zu schätzen. Dennoch ist es nötig, die Schwellen x_0 und S zu bestimmen um das Modell festzulegen. Eine Möglichkeit, dieses Problem anzugehen, ist x_0 und S als Parameter eines statistischen Modells aufzufassen und diese zu schätzen. In der vorliegenden Arbeit werden vier verschiedene Fälle diskutiert, in denen wir jeweils annehmen, dass das Membranpotential X zwischen den Spikes eine Brown'sche Bewegung mit Drift, eine geometrische Brown'sche Bewegung, ein Ornstein-Uhlenbeck Prozess oder ein Cox-Ingersoll-Ross Prozess ist. Darüber hinaus beobachten wir die Zeiten zwischen aufeinander folgenden Spikes, die wir als iid Treffzeiten der Schwelle S von X gestartet in x_0 auffassen. Die ersten beiden Fälle ähneln sich sehr und man kann jeweils den Maximum-Likelihood-Schätzer explizit angeben. Darüber hinaus wird, unter Verwendung der LAN-Theorie, die Optimalität dieser Schätzer gezeigt. In den Fällen OU- und CIR-Prozess wählen wir eine Minimum-Distanz-Methode, die auf dem Vergleich von empirischer und wahrer Laplace-Transformation bezüglich einer Hilbertraumnorm beruht. Wir werden beweisen, dass alle Schätzer stark konsistent und asymptotisch normalverteilt sind. Im letzten Kapitel werden wir die Effizienz der Minimum-Distanz-Schätzer anhand simulierter Daten überprüfen. Ferner, werden Anwendungen auf reale Datensätze und deren Resultate ausführlich diskutiert.

Adiabatic and local approximations for the kohn-sham potential in the hubbard model

We obtain the exact time-dependent Kohn-Sham potentials Vks for 1D Hubbard chains, driven by a d.c. external field, using the time-dependent electron density and current density obtained from exact many-body time-evolution. The exact Vxc is compared to the adiabatically-exact Vad-xc and the “instantaneous ground state” Vigs-xc. The effectiveness of these two approximations is analyzed. Approximations for the exchange-correlation potential Vxc and its gradient, based on the local density and on the local current density, are also considered and both physical quantities are observed to be far outside the reach of any possible local approximation. Insight into the respective roles of ground-state and excited-state correlation in the time-dependent system, as reflected in the potentials, is provided by the pair correlation function.