Estructura computacional i aplicacions de la semblança molecular quàntica

La tesis tracta diferents aspectes relacionats amb el càlcul de la semblança quàntica, així com la seva aplicació en la racionalització i predicció de l'activitat de fàrmacs. Es poden destacar dos progressos importants en el desenvolupament de noves metodologies que faciliten el càlcul de les mesures de semblança quàntica. En primer lloc, la descripció de les molècules mitjançant les funciones densitat aproximades PASA (Promolecular Atomic Shell Approximation) ha permès descriure amb suficient precisió la densitat electrònica dels sistemes moleculars analitzats, reduint substancialment el temps de càlcul de les mesures de semblança. En segon lloc, el desenvolupament de tècniques de superposició molecular específiques de les mesures de semblança quàntica ha permès resoldre el problema de l'alineament en l'espai dels compostos comparats. El perfeccionament d'aquests nous procediments i algoritmes matemàtics associats a les mesures de semblança molecular quàntica, ha estat essencial per poder progressar en diferents disciplines de la química computacional, sobretot les relacionades amb les anàlisis quantitatives entre les estructures moleculars i les seves activitats biològiques, conegudes amb les sigles angleses QSAR (Quantitative Structure-Activity Relationships). Precisament en l'àrea de les relacions estructura-activitat s'han presentat dues aproximacions fonamentades en la semblança molecular quàntica que s'originen a partir de dues representacions diferents de les molècules. La primera descripció considera la densitat electrònica global de les molècules i és important, entre altres, la disposició dels objectes comparats en l'espai i la seva conformació tridimensional. El resultat és una matriu de semblança amb les mesures de semblança de tots els parells de compostos que formen el conjunt estudiat. La segona descripció es fonamenta en la partició de la densitat global de les molècules en fragments. S'utilitzen mesures d'autosemblança per analitzar els requeriments bàsics d'una determinada activitat des del punt de vista de la semblança quàntica. El procés permet la detecció de les regions moleculars que són responsables d'una alta resposta biològica. Això permet obtenir un patró amb les regions actives que és d'evident interès per als propòsits del disseny de fàrmacs. En definitiva, s'ha comprovat que mitjançant la simulació i manipulació informàtica de les molècules en tres dimensions es pot obtenir una informació essencial en l'estudi de la interacció entre els fàrmacs i els seus receptors macromoleculars.

Development, implementation and application of electronic structural descriptors to the analysis of the chemical bonding, aromaticity and chemical reactivity

En la literatura sobre mecànica quàntica és freqüent trobar descriptors basats en la densitat de parells o la densitat electrònica, amb un èxit divers segons les aplicacions que atenyin. Per tal de que tingui sentit químic un descriptor ha de donar la definició d'un àtom en una molècula, o ésser capaç d'identificar regions de l'espai molecular associades amb algun concepte químic (com pot ser un parell solitari o zona d'enllaç, entre d'altres). En aquesta línia, s'han proposat diversos esquemes de partició: la teoria d'àtoms en molècules (AIM), la funció de localització electrònica (ELF), les cel·les de Voroni, els àtoms de Hirshfeld, els àtoms difusos, etc. L'objectiu d'aquesta tesi és explorar descriptors de la densitat basats en particions de l'espai molecular del tipus AIM, ELF o àtoms difusos, analitzar els descriptors existents amb diferents nivells de teoria, proposar nous descriptors d'aromaticitat, així com estudiar l'habilitat de totes aquestes eines per discernir entre diferents mecanismes de reacció.

Implementation and application of basis set superposition error-correction schemes to the theoretical modeling of weak intermolecular interactions

This thesis deals with the so-called Basis Set Superposition Error (BSSE) from both a methodological and a practical point of view. The purpose of the present thesis is twofold: (a) to contribute step ahead in the correct characterization of weakly bound complexes and, (b) to shed light the understanding of the actual implications of the basis set extension effects in the ab intio calculations and contribute to the BSSE debate. The existing BSSE-correction procedures are deeply analyzed, compared, validated and, if necessary, improved. A new interpretation of the counterpoise (CP) method is used in order to define counterpoise-corrected descriptions of the molecular complexes. This novel point of view allows for a study of the BSSE-effects not only in the interaction energy but also on the potential energy surface and, in general, in any property derived from the molecular energy and its derivatives A program has been developed for the calculation of CP-corrected geometry optimizations and vibrational frequencies, also using several counterpoise schemes for the case of molecular clusters. The method has also been implemented in Gaussian98 revA10 package. The Chemical Hamiltonian Approach (CHA) methodology has been also implemented at the RHF and UHF levels of theory for an arbitrary number interacting systems using an algorithm based on block-diagonal matrices. Along with the methodological development, the effects of the BSSE on the properties of molecular complexes have been discussed in detail. The CP and CHA methodologies are used for the determination of BSSE-corrected molecular complexes properties related to the Potential Energy Surfaces and molecular wavefunction, respectively. First, the behaviour of both BSSE-correction schemes are systematically compared at different levels of theory and basis sets for a number of hydrogen-bonded complexes. The Complete Basis Set (CBS) limit of both uncorrected and CP-corrected molecular properties like stabilization energies and intermolecular distances has also been determined, showing the capital importance of the BSSE correction. Several controversial topics of the BSSE correction are addressed as well. The application of the counterpoise method is applied to internal rotational barriers. The importance of the nuclear relaxation term is also pointed out. The viability of the CP method for dealing with charged complexes and the BSSE effects on the double-well PES blue-shifted hydrogen bonds is also studied in detail. In the case of the molecular clusters the effect of high-order BSSE effects introduced with the hierarchical counterpoise scheme is also determined. The effect of the BSSE on the electron density-related properties is also addressed. The first-order electron density obtained with the CHA/F and CHA/DFT methodologies was used to assess, both graphically and numerically, the redistribution of the charge density upon BSSE-correction. Several tools like the Atoms in Molecules topologycal analysis, density difference maps, Quantum Molecular Similarity, and Chemical Energy Component Analysis were used to deeply analyze, for the first time, the BSSE effects on the electron density of several hydrogen bonded complexes of increasing size. The indirect effect of the BSSE on intermolecular perturbation theory results is also pointed out It is shown that for a BSSE-free SAPT study of hydrogen fluoride clusters, the use of a counterpoise-corrected PES is essential in order to determine the proper molecular geometry to perform the SAPT analysis.

Enhanced convolution approach for CAC in ATM networks, an analytical study and implementation

The characteristics of service independence and flexibility of ATM networks make the control problems of such networks very critical. One of the main challenges in ATM networks is to design traffic control mechanisms that enable both economically efficient use of the network resources and desired quality of service to higher layer applications. Window flow control mechanisms of traditional packet switched networks are not well suited to real time services, at the speeds envisaged for the future networks. In this work, the utilisation of the Probability of Congestion (PC) as a bandwidth decision parameter is presented. The validity of PC utilisation is compared with QOS parameters in buffer-less environments when only the cell loss ratio (CLR) parameter is relevant. The convolution algorithm is a good solution for CAC in ATM networks with small buffers. If the source characteristics are known, the actual CLR can be very well estimated. Furthermore, this estimation is always conservative, allowing the retention of the network performance guarantees. Several experiments have been carried out and investigated to explain the deviation between the proposed method and the simulation. Time parameters for burst length and different buffer sizes have been considered. Experiments to confine the limits of the burst length with respect to the buffer size conclude that a minimum buffer size is necessary to achieve adequate cell contention. Note that propagation delay is a no dismiss limit for long distance and interactive communications, then small buffer must be used in order to minimise delay. Under previous premises, the convolution approach is the most accurate method used in bandwidth allocation. This method gives enough accuracy in both homogeneous and heterogeneous networks. But, the convolution approach has a considerable computation cost and a high number of accumulated calculations. To overcome this drawbacks, a new method of evaluation is analysed: the Enhanced Convolution Approach (ECA). In ECA, traffic is grouped in classes of identical parameters. By using the multinomial distribution function instead of the formula-based convolution, a partial state corresponding to each class of traffic is obtained. Finally, the global state probabilities are evaluated by multi-convolution of the partial results. This method avoids accumulated calculations and saves storage requirements, specially in complex scenarios. Sorting is the dominant factor for the formula-based convolution, whereas cost evaluation is the dominant factor for the enhanced convolution. A set of cut-off mechanisms are introduced to reduce the complexity of the ECA evaluation. The ECA also computes the CLR for each j-class of traffic (CLRj), an expression for the CLRj evaluation is also presented. We can conclude that by combining the ECA method with cut-off mechanisms, utilisation of ECA in real-time CAC environments as a single level scheme is always possible.

O banco mundial e a política educacional no Estado da Bahia a partir de 1996, o programa Educar para vencer : fortalecimento da gestão educacional

RESUMO: A gestão do sistema educacional brasileiro foi significativamente descentralizada pela Constituição Federal de 1988 (CF/88) ao reconhecer a autonomia entre os três níveis federativos e ao introduzir o princípio da gestão democrática da Educação. Assim motivado, o sistema educacional baiano iniciou sua reforma em 1999, através do Programa Educar para Vencer, tendo como referencial oferecer maiores níveis de autonomia e capacidade local de gestão para as unidades escolares públicas no Estado da Bahia. Para fortalecer a gestão educacional, o Governo, através do Projeto Fortalecimento da Gestão e Autonomia Educacional (PFGAE), introduziu o planejamento estratégico para melhorar a qualidade de ensino como ferramenta de gestão das escolas públicas estaduais baianas, apoiado em um amplo programa de financiamento para a sua implementação. ABSTRACT: The administration of Brazil’s educational system was significantly decentralized by the Federal Constitution of 1988 (CF/88) when it recognized the autonomy between the three federative levels and introduced the education’s democratic management principle. Motivated by that, Bahia’s educational system started its reform in 1999, through the “Educar para Vencer” (Educate to Win) program, having as its aim to offer bigger levels of autonomy and administrative local capacity for public schools in the State of Bahia. To strengthen the educational administration, the government, via the Administration Strengthening and Educational Autonomy Project (PFGAE), introduced the strategic planning to improve the quality of education as a management tool of the state schools of Bahia, supported by a wide financing program for its implementation.

Los tributos medioambientales: estudio comparado Andino

El desarrollo de la presente tesis es hacer un estudio comparativo de la implementación de los tributos Medioambientales en nuestro país, a partir de la experiencia de la Comunidad Europea quienes desarrollaron y siguen desarrollando la protección y conservación del Medio Ambiente a través de la imposición tributaria. En ese sentido partimos definiendo y precisando el término Medio Ambiente y ecología a fin de delimitar el tema de estudio, ya que el objetivo de la tesis es identificar las formas o mecanismos de protección del Medio Ambiente, enfatizando en la imposición Medioambiental que pueden ser a través de los impuestos, tasas o contribuciones; además de la consideración por nuestra Constitución del medio ambiente como un derecho humano fundamental de los seres humanos. Durante el desarrollo de la tesis, exponemos los instrumentos nacionales e internacionales, cuya finalidad busca garantizar la protección y conservación del Medio Ambiente, bajo el principio “quien contamina paga”, que no es otra cosa que la el criterio objetivo en la que el sujeto que deteriora o contamina el Medio Ambiente debe ser el responsable de reparar el daño causado. Finalmente analizamos la viabilidad de la protección del Medio Ambiente en los países andinos y en nuestro texto constitucional.

What kind of European Banking Union? Bruegel Policy Contribution [2012/12?]June 25, 2012

This paper discusses the creation of a European Banking Union. First, we discuss questions of design. We highlight seven fundamental choices that decision makers will need to make: Which EU countries should participate in the banking union? To which categories of banks should it apply? Which institution should be tasked with supervision? Which one should deal with resolution? How centralised should the deposit insurance system be? What kind of fiscal backing would be required? What governance framework and political institutions would be needed? In terms of geographical scope, we see the coverage of the banking union of the euro area as necessary and of additional countries as desirable, even though this would entail important additional economic difficulties. The system should ideally cover all banks within the countries included, in order to prevent major competitive and distributional distortions. Supervisory authority should be granted either to both the ECB and a new agency, or to a new agency alone. National supervisors, acting under the authority of the European supervisor, would be tasked with the supervision of smaller banks in accordance with the subsidiarity principle. A European resolution authority should be established, with the possibility of drawing on ESM resources. A fully centralized deposit insurance system would eventually be desirable, but a system of partial reinsurance may also be envisaged at least in a first phase. A banking union would require at least implicit European fiscal backing, with significant political authority and legitimacy. Thus, banking union cannot be considered entirely separately from fiscal union and political union. The most difficult challenge of creating a European banking union lies with the short-term steps towards its eventual implementation. Many banks in the euro area, and especially in the crisis countries, are currently under stress and the move towards banking union almost certainly has significant distributional implications. Yet it is precisely because banks are under such stress that early and concrete action is needed. An overarching principle for such action is to minimize the cost to the tax payers. The first step should be to create a European supervisor that will anchor the development of the future banking union. In parallel, a capability to quickly assess the true capital position of the system’s most important banks should be created, for which we suggest establishing a temporary European Banking Sector Task Force working together with the European supervisor and other authorities. Ideally, problems identified by this process should be resolved by national authorities; in case fiscal capacities would prove insufficient, the European level would take over in the country concerned with some national financial participation, or in an even less likely adverse scenario, in all participating countries at once. This approach would require the passing of emergency legislation in the concerned countries that would give the Task Force the required access to information and, if necessary, further intervention rights. Thus, the principle of fiscal responsibility of respective member states for legacy costs would be preserved to the maximum extent possible, and at the same time, market participants and the public would be reassured that adequate tools are in place to address any eventuality.