Structure- and ligand-based drug design approaches for neglected tropical diseases

Drug discovery has moved toward more rational strategies based on our increasing understanding of the fundamental principles of protein-ligand interactions. Structure( SBDD) and ligand-based drug design (LBDD) approaches bring together the most powerful concepts in modern chemistry and biology, linking medicinal chemistry with structural biology. The definition and assessment of both chemical and biological space have revitalized the importance of exploring the intrinsic complementary nature of experimental and computational methods in drug design. Major challenges in this field include the identification of promising hits and the development of high-quality leads for further development into clinical candidates. It becomes particularly important in the case of neglected tropical diseases (NTDs) that affect disproportionately poor people living in rural and remote regions worldwide, and for which there is an insufficient number of new chemical entities being evaluated owing to the lack of innovation and R&D investment by the pharmaceutical industry. This perspective paper outlines the utility and applications of SBDD and LBDD approaches for the identification and design of new small-molecule agents for NTDs.

A representação gráfica na Revista Projeto & Design.

Esta pesquisa inicia-se pelo estudo das diferentes maneiras de representação de um projeto arquitetônico: desenhos analógicos e digitais, desenhos naturais e técnicos, desenhos auxiliados por computador, maquetes físicas e modelos digitais. Teve como objetivo analisar a representação gráfica utilizada nas publicações de obras arquitetônicas em mídias impressas especializadas, tendo sido selecionada a Revista Projeto & Design como estudo de caso. Com este estudo foi possível, por meio de bibliometria gráfica, verificar as contribuições das representações na compreensão e leitura dos projetos arquitetônicos, elencando-se e exemplificando-se as tipologias de imagens utilizadas nas últimas décadas, bem como relacionar os resultados com o momento histórico em que foram projetadas ou publicadas.

A navigation system for percutaneous needle interventions based on PET/CT images: design, workflow and error analysis of soft tissue and bone punctures

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Influence of Abutment Design on Stiffness, Strength, and Failure of Implant-Supported Monolithic Resin Nano Ceramic (RNC) Crowns

BACKGROUND Recent technical development allows the digital manufacturing of monolithic reconstructions with high-performance materials. For implant-supported crowns, the fixation requires an abutment design onto which the reconstruction can be bonded. PURPOSE The aim of this laboratory investigation was to analyze stiffness, strength, and failure modes of implant-supported, computer-assisted design and computer-aided manufacturing (CAD/CAM)-generated resin nano ceramic (RNC) crowns bonded to three different titanium abutments. MATERIALS AND METHODS Eighteen monolithic RNC crowns were produced and loaded in a universal testing machine under quasi-static condition according to DIN ISO 14801. With regard to the type of titanium abutment, three groups were defined: (1) prefabricated cementable standard; (2) CAD/CAM-constructed individualized; and (3) novel prefabricated bonding base. Stiffness and strength were measured and analyzed statistically with Wilcoxon rank sum test. Sections of the specimens were examined microscopically. RESULTS Stiffness demonstrated high stability for all specimens loaded in the physiological loading range with means and standard deviations of 1,579 ± 120 N/mm (group A), 1,733 ± 89 N/mm (group B), and 1,704 ± 162 N/mm (group C). Mean strength of the novel prefabricated bonding base (group C) was 17% lower than of the two other groups. Plastic deformations were detectable for all implant-abutment crown connections. CONCLUSIONS Monolithic implant crowns made of RNC seem to represent a feasible and stable prosthetic construction under laboratory testing conditions with strength higher than the average occlusal force, independent of the different abutment designs used in this investigation.

Design of in-building wireless networks deployments using evolutionary algorithms

In this article, a novel approach to deal with the design of in-building wireless networks deployments is proposed. This approach known as MOQZEA (Multiobjective Quality Zone Based Evolutionary Algorithm) is a hybr id evolutionary algorithm adapted to use a novel fitness function, based on the definition of quality zones for the different objective functions considered. This approach is conceived to solve wireless network design problems without previous information of the required number of transmitters, considering simultaneously a high number of objective functions and optimizing multiple configuration parameters of the transmitters.

A novel hybrid simulation-optimization approach for the optimal design of multicomponent distillation columns

Póster presentado en Escape 22, European Symposium on Computer Aided Process Engineering, University College London, UK, 17-20 June 2012.

Handling of Uncertainty in Life Cycle Inventory by Correlated Multivariate Lognormal Distributions: Application to the Design of Supply Chain Networks

Poster presented in the 24th European Symposium on Computer Aided Process Engineering (ESCAPE 24), Budapest, Hungary, June 15-18, 2014.

Logic-Based Outer Approximation for the Design of Discrete-Continuous Dynamic Systems with Implicit Discontinuities

We address the optimization of discrete-continuous dynamic optimization problems using a disjunctive multistage modeling framework, with implicit discontinuities, which increases the problem complexity since the number of continuous phases and discrete events is not known a-priori. After setting a fixed alternative sequence of modes, we convert the infinite-dimensional continuous mixed-logic dynamic (MLDO) problem into a finite dimensional discretized GDP problem by orthogonal collocation on finite elements. We use the Logic-based Outer Approximation algorithm to fully exploit the structure of the GDP representation of the problem. This modelling framework is illustrated with an optimization problem with implicit discontinuities (diver problem).

Optimal Design of a Hybrid Membrane System Combining Reverse and Forward Osmosis for Seawater Desalination

In this work we study Forward Osmosis (FO) as an emerging desalination technology, and its capability to replace totally or partially Reverse Osmosis (RO) in order to reduce the great amount of energy required in the current desalination plants. For this purpose, we propose a superstructure that includes both membrane based desalination technologies, allowing the selection of only one of the technologies or a combination of both of them seeking for the optimal configuration of the network. The optimization problem is solved for a seawater desalination plant with a given fresh water production. The results obtained show that the optimal solution combines both desalination technologies to reduce not only the energy consumption but also the total cost of the desalination process in comparison with the same plant but operating only with RO.

Handling of Uncertainty in Life Cycle Inventory by Correlated Multivariate Lognormal Distributions: Application to the Design of Supply Chain Networks

In this work, we analyze the effect of incorporating life cycle inventory (LCI) uncertainty on the multi-objective optimization of chemical supply chains (SC) considering simultaneously their economic and environmental performance. To this end, we present a stochastic multi-scenario mixed-integer linear programming (MILP) coupled with a two-step transformation scenario generation algorithm with the unique feature of providing scenarios where the LCI random variables are correlated and each one of them has the desired lognormal marginal distribution. The environmental performance is quantified following life cycle assessment (LCA) principles, which are represented in the model formulation through standard algebraic equations. The capabilities of our approach are illustrated through a case study of a petrochemical supply chain. We show that the stochastic solution improves the economic performance of the SC in comparison with the deterministic one at any level of the environmental impact, and moreover the correlation among environmental burdens provides more realistic scenarios for the decision making process.

A Sequential Algorithm for the Rigorous Design of Thermally Coupled Distillation Sequences

A sequential design method is presented for the design of thermally coupled distillation sequences. The algorithm starts by selecting a set of sequences in the space of basic configurations in which the internal structure of condensers and reboilers is explicitly taken into account and extended with the possibility of including divided wall columns (DWC). This first stage is based on separation tasks (except by the DWCs) and therefore it does not provide an actual sequence of columns. In the second stage the best arrangement in N-1 actual columns is performed taking into account operability and mechanical constraints. Finally, for a set of candidate sequences the algorithm try to reduce the number of total columns by considering Kaibel columns, elimination of transfer blocks or columns with vertical partitions. An example illustrate the different steps of the sequential algorithm.

Design alternatives for computer network security /

Includes bibliographical references (p. 154-159).

The design and evaluation of distributed virtual environment to support learning in global operations management

The primary goal of this research is to design and develop an education technology to support learning in global operations management. The research implements a series of studies to determine the right balance among user requirements, learning methods and applied technologies, on a view of student-centred learning. This research is multidisciplinary by nature, involving topics from various disciplines such as global operations management, curriculum and contemporary learning theory, and computer aided learning. Innovative learning models that emphasise on technological implementation are employed and discussed throughout this research.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.