PRISMA: Model-driven development of aspect-oriented software architectures

This summary presents a methodology for supporting the development of AOSAs following the MDD paradigm. This new methodology is called PRISMA and allows the code generation from models which specify functional and non-functional requirements.

Histograms of oriented gradients for fast on-board vehicle verification

Histograms of Oriented Gradients (HoGs) provide excellent results in object detection and verification. However, their demanding processing requirements bound their applicability in some critical real-time scenarios, such as for video-based on-board vehicle detection systems. In this work, an efficient HOG configuration for pose-based on-board vehicle verification is proposed, which alleviates both the processing requirements and required feature vector length without reducing classification performance. The impact on classification of some critical configuration and processing parameters is in depth analyzed to propose a baseline efficient descriptor. Based on the analysis of its cells contribution to classification, new view-dependent cell-configuration patterns are proposed, resulting in reduced descriptors which provide an excellent balance between performance and computational requirements, rendering higher verification rates than other works in the literature.

Proposal of a trust and reputation model to provide recommendation in open quality oriented environments

El auge y penetración de las nuevas tecnologías junto con la llamada Web Social están cambiando la forma en la que accedemos a la medicina. Cada vez más pacientes y profesionales de la medicina están creando y consumiendo recursos digitales de contenido clínico a través de Internet, surgiendo el problema de cómo asegurar la fiabilidad de estos recursos. Además, un nuevo concepto está apareciendo, el de pervasive healthcare o sanidad ubicua, motivado por pacientes que demandan un acceso a los servicios sanitarios en todo momento y en todo lugar. Este nuevo escenario lleva aparejado un problema de confianza en los proveedores de servicios sanitarios. Las plataformas de eLearning se están erigiendo como paradigma de esta nueva Medicina 2.0 ya que proveen un servicio abierto a la vez que controlado/supervisado a recursos digitales, y facilitan las interacciones y consultas entre usuarios, suponiendo una buena aproximación para esta sanidad ubicua. En estos entornos los problemas de fiabilidad y confianza pueden ser solventados mediante la implementación de mecanismos de recomendación de recursos y personas de manera confiable. Tradicionalmente las plataformas de eLearning ya cuentan con mecanismos de recomendación, si bien están más enfocados a la recomendación de recursos. Para la recomendación de usuarios es necesario acudir a mecanismos más elaborados como son los sistemas de confianza y reputación (trust and reputation) En ambos casos, tanto la recomendación de recursos como el cálculo de la reputación de los usuarios se realiza teniendo en cuenta criterios principalmente subjetivos como son las opiniones de los usuarios. En esta tesis doctoral proponemos un nuevo modelo de confianza y reputación que combina evaluaciones automáticas de los recursos digitales en una plataforma de eLearning, con las opiniones vertidas por los usuarios como resultado de las interacciones con otros usuarios o después de consumir un recurso. El enfoque seguido presenta la novedad de la combinación de una parte objetiva con otra subjetiva, persiguiendo mitigar el efecto de posibles castigos subjetivos por parte de usuarios malintencionados, a la vez que enriquecer las evaluaciones objetivas con información adicional acerca de la capacidad pedagógica del recurso o de la persona. El resultado son recomendaciones siempre adaptadas a los requisitos de los usuarios, y de la máxima calidad tanto técnica como educativa. Esta nueva aproximación requiere una nueva herramienta para su validación in-silico, al no existir ninguna aplicación que permita la simulación de plataformas de eLearning con mecanismos de recomendación de recursos y personas, donde además los recursos sean evaluados objetivamente. Este trabajo de investigación propone pues una nueva herramienta, basada en el paradigma de programación orientada a agentes inteligentes para el modelado de comportamientos complejos de usuarios en plataformas de eLearning. Además, la herramienta permite también la simulación del funcionamiento de este tipo de entornos dedicados al intercambio de conocimiento. La evaluación del trabajo propuesto en este documento de tesis se ha realizado de manera iterativa a lo largo de diferentes escenarios en los que se ha situado al sistema frente a una amplia gama de comportamientos de usuarios. Se ha comparado el rendimiento del modelo de confianza y reputación propuesto frente a dos modos de recomendación tradicionales: a) utilizando sólo las opiniones subjetivas de los usuarios para el cálculo de la reputación y por extensión la recomendación; y b) teniendo en cuenta sólo la calidad objetiva del recurso sin hacer ningún cálculo de reputación. Los resultados obtenidos nos permiten afirmar que el modelo desarrollado mejora la recomendación ofrecida por las aproximaciones tradicionales, mostrando una mayor flexibilidad y capacidad de adaptación a diferentes situaciones. Además, el modelo propuesto es capaz de asegurar la recomendación de nuevos usuarios entrando al sistema frente a la nula recomendación para estos usuarios presentada por el modo de recomendación predominante en otras plataformas que basan la recomendación sólo en las opiniones de otros usuarios. Por último, el paradigma de agentes inteligentes ha probado su valía a la hora de modelar plataformas virtuales complejas orientadas al intercambio de conocimiento, especialmente a la hora de modelar y simular el comportamiento de los usuarios de estos entornos. La herramienta de simulación desarrollada ha permitido la evaluación del modelo de confianza y reputación propuesto en esta tesis en una amplia gama de situaciones diferentes. ABSTRACT Internet is changing everything, and this revolution is especially present in traditionally offline spaces such as medicine. In recent years health consumers and health service providers are actively creating and consuming Web contents stimulated by the emergence of the Social Web. Reliability stands out as the main concern when accessing the overwhelming amount of information available online. Along with this new way of accessing the medicine, new concepts like ubiquitous or pervasive healthcare are appearing. Trustworthiness assessment is gaining relevance: open health provisioning systems require mechanisms that help evaluating individuals’ reputation in pursuit of introducing safety to these open and dynamic environments. Technical Enhanced Learning (TEL) -commonly known as eLearning- platforms arise as a paradigm of this Medicine 2.0. They provide an open while controlled/supervised access to resources generated and shared by users, enhancing what it is being called informal learning. TEL systems also facilitate direct interactions amongst users for consultation, resulting in a good approach to ubiquitous healthcare. The aforementioned reliability and trustworthiness problems can be faced by the implementation of mechanisms for the trusted recommendation of both resources and healthcare services providers. Traditionally, eLearning platforms already integrate recommendation mechanisms, although this recommendations are basically focused on providing an ordered classifications of resources. For users’ recommendation, the implementation of trust and reputation systems appears as the best solution. Nevertheless, both approaches base the recommendation on the information from the subjective opinions of other users of the platform regarding the resources or the users. In this PhD work a novel approach is presented for the recommendation of both resources and users within open environments focused on knowledge exchange, as it is the case of TEL systems for ubiquitous healthcare. The proposed solution adds the objective evaluation of the resources to the traditional subjective personal opinions to estimate the reputation of the resources and of the users of the system. This combined measure, along with the reliability of that calculation, is used to provide trusted recommendations. The integration of opinions and evaluations, subjective and objective, allows the model to defend itself against misbehaviours. Furthermore, it also allows ‘colouring’ cold evaluation values by providing additional quality information such as the educational capacities of a digital resource in an eLearning system. As a result, the recommendations are always adapted to user requirements, and of the maximum technical and educational quality. To our knowledge, the combination of objective assessments and subjective opinions to provide recommendation has not been considered before in the literature. Therefore, for the evaluation of the trust and reputation model defined in this PhD thesis, a new simulation tool will be developed following the agent-oriented programming paradigm. The multi-agent approach allows an easy modelling of independent and proactive behaviours for the simulation of users of the system, conforming a faithful resemblance of real users of TEL platforms. For the evaluation of the proposed work, an iterative approach have been followed, testing the performance of the trust and reputation model while providing recommendation in a varied range of scenarios. A comparison with two traditional recommendation mechanisms was performed: a) using only users’ past opinions about a resource and/or other users; and b) not using any reputation assessment and providing the recommendation considering directly the objective quality of the resources. The results show that the developed model improves traditional approaches at providing recommendations in Technology Enhanced Learning (TEL) platforms, presenting a higher adaptability to different situations, whereas traditional approaches only have good results under favourable conditions. Furthermore the promotion period mechanism implemented successfully helps new users in the system to be recommended for direct interactions as well as the resources created by them. On the contrary OnlyOpinions fails completely and new users are never recommended, while traditional approaches only work partially. Finally, the agent-oriented programming (AOP) paradigm has proven its validity at modelling users’ behaviours in TEL platforms. Intelligent software agents’ characteristics matched the main requirements of the simulation tool. The proactivity, sociability and adaptability of the developed agents allowed reproducing real users’ actions and attitudes through the diverse situations defined in the evaluation framework. The result were independent users, accessing to different resources and communicating amongst them to fulfil their needs, basing these interactions on the recommendations provided by the reputation engine.

In situ atomic force microscopy study of Alzheimer’s β-amyloid peptide on different substrates: New insights into mechanism of β-sheet formation

We have applied in situ atomic force microscopy to directly observe the aggregation of Alzheimer’s β-amyloid peptide (Aβ) in contact with two model solid surfaces: hydrophilic mica and hydrophobic graphite. The time course of aggregation was followed by continuous imaging of surfaces remaining in contact with 10–500 μM solutions of Aβ in PBS (pH 7.4). Visualization of fragile nanoscale aggregates of Aβ was made possible by the application of a tapping mode of imaging, which minimizes the lateral forces between the probe tip and the sample. The size and the shape of Aβ aggregates, as well as the kinetics of their formation, exhibited pronounced dependence on the physicochemical nature of the surface. On hydrophilic mica, Aβ formed particulate, pseudomicellar aggregates, which at higher Aβ concentration had the tendency to form linear assemblies, reminiscent of protofibrillar species described recently in the literature. In contrast, on hydrophobic graphite Aβ formed uniform, elongated sheets. The dimensions of those sheets were consistent with the dimensions of β-sheets with extended peptide chains perpendicular to the long axis of the aggregate. The sheets of Aβ were oriented along three directions at 120° to each other, resembling the crystallographic symmetry of a graphite surface. Such substrate-templated self-assembly may be the distinguishing feature of β-sheets in comparison with α-helices. These studies show that in situ atomic force microscopy enables direct assessment of amyloid aggregation in physiological fluids and suggest that Aβ fibril formation may be driven by interactions at the interface of aqueous solutions and hydrophobic substrates, as occurs in membranes and lipoprotein particles in vivo.

The structural basis for the oriented assembly of a TBP/TFB/promoter complex

Recently the definition of the metazoan RNA polymerase II and archaeal core promoters has been expanded to include a region immediately upstream of the TATA box called the B recognition element (BRE), so named because eukaryal transcription factor TFIIB and its archaeal orthologue TFB interact with the element in a sequence-specific manner. Here we present the 2.4-Å crystal structure of archaeal TBP and the C-terminal core of TFB (TFBc) in a complex with an extended TATA-box-containing promoter that provides a detailed picture of the stereospecific interactions between the BRE and a helix–turn–helix motif in the C-terminal cyclin repeat of TFBc. This interaction is important in determining the level of basal transcription and explicitly defines the direction of transcription.

Structural basis of DNA bending and oriented heterodimer binding by the basic leucine zipper domains of Fos and Jun

Interactions among transcription factors that bind to separate sequence elements require bending of the intervening DNA and juxtaposition of interacting molecular surfaces in an appropriate orientation. Here, we examine the effects of single amino acid substitutions adjacent to the basic regions of Fos and Jun as well as changes in sequences flanking the AP-1 site on DNA bending. Substitution of charged amino acid residues at positions adjacent to the basic DNA-binding domains of Fos and Jun altered DNA bending. The change in DNA bending was directly proportional to the change in net charge for all heterodimeric combinations between these proteins. Fos and Jun induced distinct DNA bends at different binding sites. Exchange of a single base pair outside of the region contacted in the x-ray crystal structure altered DNA bending. Substitution of base pairs flanking the AP-1 site had converse effects on the opposite directions of DNA bending induced by homodimers and heterodimers. These results suggest that Fos and Jun induce DNA bending in part through electrostatic interactions between amino acid residues adjacent to the basic region and base pairs flanking the AP-1 site. DNA bending by Fos and Jun at inverted binding sites indicated that heterodimers bind to the AP-1 site in a preferred orientation. Mutation of a conserved arginine within the basic regions of Fos and transversion of the central C:G base pair in the AP-1 site to G:C had complementary effects on the orientation of heterodimer binding and DNA bending. The conformational variability of the Fos–Jun–AP-1 complex may contribute to its functional versatility at different promoters.

Nanoscale imaging of chemical interactions: Fluorine on graphite

Using C60-functionalized scanning tunneling microscope tips, we have investigated the adsorption of fluorine on graphite. Based on characteristics of the accompanying electron standing waves, we are able to distinguish the fluorine adatoms that have bonded ionically to the graphite surface from those that have formed covalent bonds with the surface. This result permits determination of the ratio of ionic to covalent C–F bonds on graphite obtained by gas phase fluorination, which seems to be temperatureindependent between 200 and 300°C under the reaction conditions used.

Internal molecular motions of bacteriorhodopsin: hydration-induced flexibility studied by quasielastic incoherent neutron scattering using oriented purple membranes.

Quasielastic incoherent neutron scattering from hydrogen atoms, which are distributed nearly homogeneously in biological molecules, allows the investigation of diffusive motions occurring on the pico- to nanosecond time scale. A quasielastic incoherent neutron scattering study was performed on the integral membrane protein bacteriorhodopsin (BR), which is a light-driven proton pump in Halobacterium salinarium. BR is embedded in lipids, forming patches in the cell membrane of the organism, which are the so called purple membranes (PMs). Measurements were carried out at room temperature on oriented PM-stacks hydrated at two different levels (low hydration, h = 0.03 g of D2O per g of PM; high hydration, h = 0.28 g of D2O per g of PM) using time-of-flight spectrometers. From the measured spectra, different diffusive components were identified and analyzed with respect to the influence of hydration. This study supports the idea that a decrease in hydration results in an appreciable decrease in internal molecular flexibility of the protein structure. Because it is known from studies on the function of BR that the pump activity is reduced if the hydration level of the protein is insufficient, we conclude that the observed diffusive motions are essential for the function of this protein. A detailed analysis and classification of the different kinds of diffusive motions, predominantly occurring in PMs under physiological conditions, is presented.

Nuclear magnetic dipole interactions in field-oriented proteins: information for structure determination in solution.

The measurement of dipolar contributions to the splitting of 15N resonances of 1H-15N amide pairs in multidimensional high-field NMR spectra of field-oriented cyanometmyoglobin is reported. The splittings appear as small field-dependent perturbations of normal scalar couplings. Assignment of more than 90 resonances to specific sequential sites in the protein allows correlation of the dipolar contributions with predictions based on the known susceptibility and known structure of the protein. Implications as an additional source of information for protein structure determination in solution are discussed.

Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups. Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds. To develop this novel methodology further and explore its generality, we directed our attention to the Diels-Alder adducts based on various chromones. We discovered that the Diels-Alder adducts of chromones are capable of photoinduced alkene-arene [2+2] cycloaddition producing different dienes, which can either dimerize or be introduced into a double-tandem [4π+2π]·[2π+2π]·[4π+2π]·[2π+2π] synthetic sequence, followed by an acid-catalyzed oxametathesis, leading to a rapid expansion of molecular complexity over a few experimentally simple steps. In view of the fact that oxametathesis previously was primarily observed in aromatic oxetanes, we decided to prepare model aliphatic oxetanes with a conformationally unconstrained or "flexible" methyl group based on the Diels-Alder adducts of cyclohexadiene or cyclopentadiene with methyl vinyl ketone. Upon addition of an acid, the expected oxametathesis occurred with results similar to those observed in the aromatic series proving the generality of this approach. Also we synthesized polycyclic oxetanes resulting from the Diels-Alder adducts of cyclic ketones. This not only gave us access to remarkably strained oxetane systems, but also the mechanism for their protolytic ring opening provided a great deal of insight to how the strain affects the reactivity. Additionally, we discovered that although the model Hetero-Diels-Alder adducts did not undergo [2+2] cycloaddition, both exo- and endo-Sulfa-Diels-Alder products, nonetheless, were photochemically active and various products with defined stereochemistry could be produced upon photolysis. In conclusion, we have developed an approach to the encoding and screening of solution phase libraries based on the photorelease of externally sensitized photolabile tags. The encoding tags can be released into solution only when a binding event occurs between the ligand and the receptor, equipped with an electron transfer sensitizer. The released tags are analyzed in solution revealing the identity of the lead ligand or narrowing the range of potential leads.

The Impact of Transit Oriented Development on the Travel Behaviors of Workers in Denver, Colorado

To combat unsustainable transportation systems characterized by reliance on petroleum, polluting emissions, traffic congestion and suburban sprawl, planners encourage mixed use, densely populated areas that provide individuals with opportunities to live, work, eat and shop without necessarily having to drive private automobiles to accommodate their needs. Despite these attempts, the frequency and duration of automobile trips has consistently increased in the United States throughout past decades. While many studies have focused on how residential proximity to transit influences travel behavior, the effect of workplace location has largely been ignored. This paper asks, does working near a TOD influence the travel behaviors of workers differently than workers living near a TOD? We examine the non-work travel behaviors of workers based upon their commuting mode and proximity to TODs. The data came from a 2009 travel behavior survey by the Denver Regional Council of Governments, which contains 8,000 households, 16,000 individuals, and nearly 80,000 trips. We measure sustainable travel behaviors as reduced mileage, reduced number of trips, and increased use of non-automobile transportation. The results of this study indicate that closer proximity of both households and workplaces to TODs decrease levels of car commuting and that non-car commuting leads to more sustainable personal travel behaviors characterized by more trips made with alternative modes.

Architecture of a multi-modal dialogue system oriented to multilingual question-answering

In this paper, a proposal of a multi-modal dialogue system oriented to multilingual question-answering is presented. This system includes the following ways of access: voice, text, avatar, gestures and signs language. The proposal is oriented to the question-answering task as a user interaction mechanism. The proposal here presented is in the first stages of its development phase and the architecture is presented for the first time on the base of the experiences in question-answering and dialogues previously developed. The main objective of this research work is the development of a solid platform that will permit the modular integration of the proposed architecture.

Corn stover thermal decomposition in pyrolytic and oxidant atmosphere

The pyrolysis and combustion of corn stover were studied by dynamic thermogravimetry and derivate thermogravimetry (TG-DTG) at heating rates of 5, 10, 20 and 50 K min−1 at atmospheric pressure. For the simulation of pyrolysis and combustion processes a kinetic model based on the distribution of activation energies was used, with three pools of reactants (three pseudocomponents) because of the complexity of the biomass samples of agricultural origin. The experimental thermogravimetric data of pyrolysis and combustion processes were simultaneously fitted to determine a single set of kinetic parameters able to describe both processes at the different heating rates. The model proposed achieves a good correlation between the experimental and calculated curves, with an error of less than 4% for fitting four heating rates simultaneously. The experimental results and kinetic parameters may provide useful data for the design of thermo decomposition processing system using corn stover as feedstock. On the other hand, analysis of the main compounds in the evolved gas is given by means of a microcromatograph.

Specific and reversible immobilization of proteins tagged to the affinity polypeptide C-LytA on functionalized graphite electrodes

We have developed a general method for the specific and reversible immobilization of proteins fused to the choline-binding module C-LytA on functionalized graphite electrodes. Graphite electrode surfaces were modified by diazonium chemistry to introduce carboxylic groups that were subsequently used to anchor mixed self-assembled monolayers consisting of N,N-diethylethylenediamine groups, acting as choline analogs, and ethanolamine groups as spacers. The ability of the prepared electrodes to specifically bind C-LytA-tagged recombinant proteins was tested with a C-LytA-β-galactosidase fusion protein. The binding, activity and stability of the immobilized protein was evaluated by electrochemically monitoring the formation of an electroactive product in the enzymatic hydrolysis of the synthetic substrate 4-aminophenyl β-D-galactopyranoside. The hybrid protein was immobilized in an specific and reversible way, while retaining the catalytic activity. Moreover, these functionalized electrodes were shown to be highly stable and reusable. The method developed here can be envisaged as a general, immobilization procedure on the protein biosensor field.