Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

The actual status of the development of a Danish/Swedish system concept of a solar combisystem

At the beginning of 2003 the four year long research project REBUS on education, research, development and demonstration of competitive solar combisystems was launched. Research groups in Norway, Denmark, Sweden and Latvia are working together with partners from industry on innovative solutions for solar heating in the Nordic countries. Existing system concepts have been analyzed and based on the results new system designs have been developed. The proposed solutions have to fulfill country specific technical, sociological and cost requirements. Due to the similar demands on the systems in Denmark and Sweden it has been decided to develop a common system concept for both countries, which increases the market potential for the manufacturer. The focus of the development is on systems for the large number of rather well insulated existing single family houses. In close collaboration with the industrial partners a system concept has been developed that is characterized by its high compactness and flexibility. It allows the use of different types of boilers, heating distribution systems and a variable store and collector size. Two prototypes have been built, one for the Danish market with a gas boiler, and one for the Swedish market with a pellet boiler as auxiliary heater. After intensive testing and eventual further improvements at least two systems will be installed and monitored in demonstration houses. The systems have been modeled in TRNSYS and the simulation results will be used to further improve the system and evaluate the system performance.

The concept of e-service from a social interaction perspective

Today’s e-services are complex phenomenon consisting of several different e-services linked together. The e-services are provided by IT systems and presented to customers through user interfaces. Within web design research criteria are laid out for the design of good user interfaces, but one problem is that these analyses are performed without a service focus. This lack of service focus can result in the designed user interfaces providing indistinct service concepts, especially where several e-services are intertwined with each other.In order to design IT system interfaces, we have to be clear about which e-services are provided by the IT system and how these e-services are related to each other. This paper presents a framework for the analysis of user interfaces in terms of focused e-service, service environment and two types of intertwined e-services; related e-services and interrelating e-services. The analyses are exemplified by an Internet based e-marketplace. The paper discusses how the framework can be combined with ordinary web design criteria and how it can be used for e-service development.

Security Issues in a SOA-based Provenance System

Recent work has begun exploring the characterization and utilization of provenance in systems based on the Service Oriented Architecture (such as Web Services and Grid based environments). One of the salient issues related to provenance use within any given system is its security. In a broad sense, security requirements arise within any data archival and retrieval system, however provenance presents unique requirements of its own. These requirements are additionally dependent on the architectural and environmental context that a provenance system operates in. We seek to analyze the security considerations pertaining to a Service Oriented Architecture based provenance system. Towards this end, we describe the components of such a system and illustrate the security considerations that arise within it. Concurrently, we outline possible approaches to address them.

A Framework for Monitoring Agent-Based Normative Systems

The behaviours of autonomous agents may deviate from those deemed to be for the good of the societal systems of which they are a part. Norms have therefore been proposed as a means to regulate agent behaviours in open and dynamic systems, where these norms specify the obliged, permitted and prohibited behaviours of agents. Regulation can effectively be achieved through use of enforcement mechanisms that result in a net loss of utility for an agent in cases where the agent's behaviour fails to comply with the norms. Recognition of compliance is thus crucial for achieving regulation. In this paper we propose a generic architecture for observation of agent behaviours, and recognition of these behaviours as constituting, or counting as, compliance or violation. The architecture deploys monitors that receive inputs from observers, and processes these inputs together with transition network representations of individual norms. In this way, monitors determine the fulfillment or violation status of norms. The paper also describes a proof of concept implementation and deployment of monitors in electronic contracting environments.

A Framework for Monitoring Agent-Based Normative Systems

The behaviours of autonomous agents may deviate from those deemed to be for the good of the societal systems of which they are a part. Norms have therefore been proposed as a means to regulate agent behaviours in open and dynamic systems, where these norms specify the obliged, permitted and prohibited behaviours of agents. Regulation can effectively be achieved through use of enforcement mechanisms that result in a net loss of utility for an agent in cases where the agent’s behaviour fails to comply with the norms. Recognition of compliance is thus crucial for achieving regulation. In this paper we propose a generic architecture for observation of agent behaviours, and recognition of these behaviours as constituting, or counting as, compliance or violation. The architecture deploys monitors that receive inputs from observers, and processes these inputs together with transition network representations of individual norms. In this way, monitors determine the fulfillment or violation status of norms. The paper also describes a proof of concept implementation and deployment of monitors in electronic contracting environments.

From Smart Meters To Smart Decisions: Web-Based Support For The Water Efficient Household

Smart water metering technologies for residential buildings offer, in principle, great opportunities for sustainable urban water management. However, much of this potential is as yet unrealized. Despite that several ICT solutions have already been deployed aiming at optimum operations on the water utilities side (e.g. real time control for water networks, dynamic pump scheduling etc.), little work has been done to date on the consumer side. This paper presents a web-based platform targeting primarily the household end user. The platform enables consumers to monitor, on a real-time basis, the water demand of their household, providing feedback not only on the total water consumption and relevant costs but also on the efficiency (or otherwise) of specific indoor and outdoor uses. Targeting the reduction of consumption, the provided feedback is combined with notifications about possible leakages\bursts, and customised suggestions to improve the efficiency of existing household uses. It also enables various comparisons, with past consumption or even with that of similar households, aiming to motivate further the householder to become an active player in the water efficiency challenge. The issue of enhancing the platform’s functionality with energy timeseries is also discussed in view of recent advances in smart metering and the concept of “smart cities”. The paper presents a prototype of this web-based application and critically discusses first testing results and insights. It also presents the way in which the platform communicates with central databases, at the water utility level. It is suggested that such developments are closing the gap between technology availability and usefulness to end users and could help both the uptake of smart metering and awareness raising leading, potentially, to significant reductions of urban water consumption. The work has received funding from the European Union FP7 Programme through the iWIDGET Project, under grant agreement no318272.

Performance Evaluation Of SMOS Soil Moisture Retrieval Parameters For Hydrological Application

Microwave remote sensing has high potential for soil moisture retrieval. However, the efficient retrieval of soil moisture depends on optimally choosing the soil moisture retrieval parameters. In this study first the initial evaluation of SMOS L2 product is performed and then four approaches regarding soil moisture retrieval from SMOS brightness temperature are reported. The radiative transfer equation based tau-omega rationale is used in this study for the soil moisture retrievals. The single channel algorithms (SCA) using H polarisation is implemented with modifications, which includes the effective temperatures simulated from ECMWF (downscaled using WRF-NOAH Land Surface Model (LSM)) and MODIS. The retrieved soil moisture is then utilized for soil moisture deficit (SMD) estimation using empirical relationships with Probability Distributed Model based SMD as a benchmark. The square of correlation during the calibration indicates a value of R2 =0.359 for approach 4 (WRF-NOAH LSM based LST with optimized roughness parameters) followed by the approach 2 (optimized roughness parameters and MODIS based LST) (R2 =0.293), approach 3 (WRF-NOAH LSM based LST with no optimization) (R2 =0.267) and approach 1(MODIS based LST with no optimization) (R2 =0.163). Similarly, during the validation a highest performance is reported by approach 4. The other approaches are also following a similar trend as calibration. All the performances are depicted through Taylor diagram which indicates that the H polarisation using ECMWF based LST is giving a better performance for SMD estimation than the original SMOS L2 products at a catchment scale.

A BDI-based approach for the assessment of driver's decision-making in commuter scenarios

The rapid growth of urban areas has a significant impact on traffic and transportation systems. New management policies and planning strategies are clearly necessary to cope with the more than ever limited capacity of existing road networks. The concept of Intelligent Transportation System (ITS) arises in this scenario; rather than attempting to increase road capacity by means of physical modifications to the infrastructure, the premise of ITS relies on the use of advanced communication and computer technologies to handle today’s traffic and transportation facilities. Influencing users’ behaviour patterns is a challenge that has stimulated much research in the ITS field, where human factors start gaining great importance to modelling, simulating, and assessing such an innovative approach. This work is aimed at using Multi-agent Systems (MAS) to represent the traffic and transportation systems in the light of the new performance measures brought about by ITS technologies. Agent features have good potentialities to represent those components of a system that are geographically and functionally distributed, such as most components in traffic and transportation. A BDI (beliefs, desires, and intentions) architecture is presented as an alternative to traditional models used to represent the driver behaviour within microscopic simulation allowing for an explicit representation of users’ mental states. Basic concepts of ITS and MAS are presented, as well as some application examples related to the subject. This has motivated the extension of an existing microscopic simulation framework to incorporate MAS features to enhance the representation of drivers. This way demand is generated from a population of agents as the result of their decisions on route and departure time, on a daily basis. The extended simulation model that now supports the interaction of BDI driver agents was effectively implemented, and different experiments were performed to test this approach in commuter scenarios. MAS provides a process-driven approach that fosters the easy construction of modular, robust, and scalable models, characteristics that lack in former result-driven approaches. Its abstraction premises allow for a closer association between the model and its practical implementation. Uncertainty and variability are addressed in a straightforward manner, as an easier representation of humanlike behaviours within the driver structure is provided by cognitive architectures, such as the BDI approach used in this work. This way MAS extends microscopic simulation of traffic to better address the complexity inherent in ITS technologies.

A Modular and digitally programmable interface based on band-pass sigma-delta modulator for mixed-signal systems-on-chip

The focus of this thesis is to discuss the development and modeling of an interface architecture to be employed for interfacing analog signals in mixed-signal SOC. We claim that the approach that is going to be presented is able to achieve wide frequency range, and covers a large range of applications with constant performance, allied to digital configuration compatibility. Our primary assumptions are to use a fixed analog block and to promote application configurability in the digital domain, which leads to a mixed-signal interface. The use of a fixed analog block avoids the performance loss common to configurable analog blocks. The usage of configurability on the digital domain makes possible the use of all existing tools for high level design, simulation and synthesis to implement the target application, with very good performance prediction. The proposed approach utilizes the concept of frequency translation (mixing) of the input signal followed by its conversion to the ΣΔ domain, which makes possible the use of a fairly constant analog block, and also, a uniform treatment of input signal from DC to high frequencies. The programmability is performed in the ΣΔ digital domain where performance can be closely achieved according to application specification. The interface performance theoretical and simulation model are developed for design space exploration and for physical design support. Two prototypes are built and characterized to validate the proposed model and to implement some application examples. The usage of this interface as a multi-band parametric ADC and as a two channels analog multiplier and adder are shown. The multi-channel analog interface architecture is also presented. The characterization measurements support the main advantages of the approach proposed.

Sports administration: an examination of the competitive balance concept through european and brazilian domestic soccer leagues comparison

A questão do Equilíbrio Competitivo é um tema importante da economia dos esportes profissionais nos Estados Unidos e na Europa. Muitas pesquisas foram feitas para estabelecer os critérios mais relevantes para avaliar a competitividade das ligas profissionais de futebol. Esta pesquisa analisou a relevância do Equilíbrio Competitivo como determinante da competitividade comparando o Brasileirão Série A com as nove principais ligas na Europa (Bélgica, Inglaterra, Alemanha, Holanda, França, Itália, Portugal, Escócia e Espanha). A competitividade é a capacidade de uma empresa (um clube) ou de uma indústria de enfrentar a concorrência efetiva ou potencial. A medida da competitividade deve levar em consideração uma série de fatores importantes como a qualidade e a relação qualidade/preço, a gestão de recursos humanos e a organização empresarial. Esse trabalho visa demonstrar que, apesar da incerteza do resultado ter sido considerado por muito tempo como um fator positivo de atratividade/interesse dos fãs nos esportes, um campeonato equilibrado poderia ter um efeito insignificante, para não dizer desprezível sobre a competitividade das ligas de futebol a longo prazo. Os resultados mostraram que o aumento do Equilíbrio Competitivo pode ser relevante para os campeonatos mais fracos (Bélgica, Holanda, Portugal, Escócia), mas nao dos cincos melhores (Alemanha, Espanha, França, Inglaterra, Itália). Consequentemente, o Equilíbrio Competitivo deve ser contemplado como uma variável desprezível quanto à competitividade das ligas de futebol, apesar do interesse crescente pelo conceito na literatura. Baseado principalmente em pesquisas de Dell'Osso e Symanski (1991) e de Oughton e Michie (2004), o índice HHI (Herfindahl-Hirschman) tem sido utilizado para determinar o nível de concentração de 11 ligas de futebol estudadas. Uma revisão da literatura sobre administração de futebol e esportes foi realizada.

Simulation -based smoothing and filtering in factor stochastic volatility models : two econometric applications (July-2001)

The past decade has wítenessed a series of (well accepted and defined) financial crises periods in the world economy. Most of these events aI,"e country specific and eventually spreaded out across neighbor countries, with the concept of vicinity extrapolating the geographic maps and entering the contagion maps. Unfortunately, what contagion represents and how to measure it are still unanswered questions. In this article we measure the transmission of shocks by cross-market correlation\ coefficients following Forbes and Rigobon's (2000) notion of shift-contagion,. Our main contribution relies upon the use of traditional factor model techniques combined with stochastic volatility mo deIs to study the dependence among Latin American stock price indexes and the North American indexo More specifically, we concentrate on situations where the factor variances are modeled by a multivariate stochastic volatility structure. From a theoretical perspective, we improve currently available methodology by allowing the factor loadings, in the factor model structure, to have a time-varying structure and to capture changes in the series' weights over time. By doing this, we believe that changes and interventions experienced by those five countries are well accommodated by our models which learns and adapts reasonably fast to those economic and idiosyncratic shocks. We empirically show that the time varying covariance structure can be modeled by one or two common factors and that some sort of contagion is present in most of the series' covariances during periods of economical instability, or crisis. Open issues on real time implementation and natural model comparisons are thoroughly discussed.

Three applications of the marginal cost of public funds concept

This paper illustrates the use of the marginal cost of public funds concept in three contexts. First, we extend Parry’s (2003) analysis of the efficiency effects excise taxes in the U.K., primarily by incorporating the distortion caused by imperfect competition in the cigarette market and distinguishing between the MCFs for per unit and ad valorem taxes on cigarettes. Our computations show, contrary to the standard result in the literature, that the per unit tax on cigarettes has a slightly lower MCF than the ad valorem tax on cigarettes. Second, we calculate the MCF for a payroll tax in a labour market with involuntary unemployment, using the Shapiro and Stiglitz (1984) efficiency wage model as our framework. Our computations, based on Canadian labour market data, indicate that incorporating the distortion caused by involuntary unemployment raises the MCF by 25 to 50 percent. Third, we derive expressions for the distributionally-weighted MCFs for the exemption level and the marginal tax rate for a “flat tax”, such as the one that has been adopted by the province of Alberta. This allows us to develop a restricted, but tractable, version of the optimal income tax problem. Computations indicate that the optimal marginal tax rate may be quite high, even with relatively modest pro-poor distributional preferences.

Neww challenges in the luxury universe: an exploratory study of the concept of luxury experience in the Brazilian market from the perspective of brands and consumers: a case study of Pati Piva.

Luxury has evolved over the centuries; new challenges have created questions of appropriate strategies for brands. Experience and authenticity became important aspects in the field: consumers are enjoying more material comfort and there is a trend of a cultural shift for personal fulfillment and aspiration through experience. The biggest challenge for today's luxury marketers is to not only talk to the target, but to understand how the target is shifting, while not alienating consumers and damaging the brand´s image. Considering managers and consumers perspectives separately, it would be possible to conclude that their perceptions are congruent, as many studies have presented. However, if perspectives are put together and compared, different realities could emerge. This exploratory research is based on a case study that describes both perspectives of their perception on luxury experience, consumer behavior and consumption motivations, and luxury retailing. It was developed interviews with the brand owner and 10 brand´s consumers, and also indirect observations in the brands distribution formats. In the brand perspective, the case study has shown that luxury experience involves the construction of brand experience strategy based on products, multiple retail channels, consumer engagement, personal activity, exploration of five senses and other forms. In the consumer´s perspective, results revealed that brand consumers interviwed have different luxury experience perceptions and expectations; however, what is common is that service and quality must be maintained and they reflected the overall experience. Additionally, luxury retailing influences directly the consumer´s perception that must integrate multiple channels to fulfill personal demands. The research makes contributions for both actors - brand and consumer, in the sense that translates theoretical concepts of the experience itself and tries to clarify aspects that are still unknown and explored through the exploration of ways to detect the alignment between brand and consumer expectations of the experience.

JML- Based formal development of a Java card application for managing medical appointments

Although formal methods can dramatically increase the quality of software systems, they have not widely been adopted in software industry. Many software companies have the perception that formal methods are not cost-effective cause they are plenty of mathematical symbols that are difficult for non-experts to assimilate. The Java Modelling Language (short for JML) Section 3.3 is an academic initiative towards the development of a common formal specification language for Java programs, and the implementation of tools to check program correctness. This master thesis work shows how JML based formal methods can be used to formally develop a privacy sensitive Java application. This is a smart card application for managing medical appointments. The application is named HealthCard. We follow the software development strategy introduced by João Pestana, presented in Section 3.4. Our work influenced the development of this strategy by providing hands-on insight on challenges related to development of a privacy sensitive application in Java. Pestana’s strategy is based on a three-step evolution strategy of software specifications, from informal ones, through semiformal ones, to JML formal specifications. We further prove that this strategy can be automated by implementing a tool that generates JML formal specifications from a welldefined subset of informal software specifications. Hence, our work proves that JML-based formal methods techniques are cost-effective, and that they can be made popular in software industry. Although formal methods are not popular in many software development companies, we endeavour to integrate formal methods to general software practices. We hope our work can contribute to a better acceptance of mathematical based formalisms and tools used by software engineers. The structure of this document is as follows. In Section 2, we describe the preliminaries of this thesis work. We make an introduction to the application for managing medical applications we have implemented. We also describe the technologies used in the development of the application. This section further illustrates the Java Card Remote Method Invocation communication model used in the medical application for the client and server applications. Section 3 introduces software correctness, including the design by contract and the concept of contract in JML. Section 4 presents the design structure of the application. Section 5 shows the implementation of the HealthCard. Section 6 describes how the HealthCard is verified and validated using JML formal methods tools. Section 7 includes some metrics of the HealthCard implementation and specification. Section 8 presents a short example of how a client-side of a smart card application can be implemented while respecting formal specifications. Section 9 describes a prototype tools to generate JML formal specifications from informal specifications automatically. Section 10 describes some challenges and main ideas came acrorss during the development of the HealthCard. The full formal specification and implementation of the HealthCard smart card application presented in this document can be reached at https://sourceforge.net/projects/healthcard/.