Design, synthesis and biologival evaluation of novel isoniazid derivatives with potente antitubercular activity

The disturbing emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has been driving the scientific community to urgently search for new and efficient antitubercular drugs. Despite the various drugs currently under evaluation, isoniazid is still the key and most effective component in all multi-therapeutic regimens recommended by the WHO. This paper describes the QSAR-oriented design, synthesis and in vitro antitubercular activity of several potent isoniazid derivatives (isonicotinoyl hydrazones and isonicotinoyl hydrazides) against H37Rv and two resistant Mtb strains. QSAR studies entailed RFs and ASNNs classification models, as well as MLR models. Strict validation procedures were used to guarantee the models' robustness and predictive ability. Lipophilicity was shown not to be relevant to explain the activity of these derivatives, whereas shorter N-N distances and lengthy substituents lead to more active compounds. Compounds I, 2, 4, 5 and 6, showed measured activities against H37Rv higher than INH (i.e., MIC <= 0.28 mu M), while compound 9 exhibited a six fold decrease in MIC against the katG (S315T) mutated strain, by comparison with INH (Le., 6.9 vs. 43.8 mu M). All compounds were ineffective against H37Rv(INH) (Delta katG), a strain with a full deletion of the katG gene, thus corroborating the importance of KatG in the activation of INH-based compounds. The most potent compounds were also shown not to be cytotoxic up to a concentration 500 times higher than MIC. (C) 2014 Elsevier Masson SAS. All rights reserved.

Dynamic network data envelopment analysis for university hospitals evaluation

ABSTRACT OBJECTIVE To develop an assessment tool to evaluate the efficiency of federal university general hospitals. METHODS Data envelopment analysis, a linear programming technique, creates a best practice frontier by comparing observed production given the amount of resources used. The model is output-oriented and considers variable returns to scale. Network data envelopment analysis considers link variables belonging to more than one dimension (in the model, medical residents, adjusted admissions, and research projects). Dynamic network data envelopment analysis uses carry-over variables (in the model, financing budget) to analyze frontier shift in subsequent years. Data were gathered from the information system of the Brazilian Ministry of Education (MEC), 2010-2013. RESULTS The mean scores for health care, teaching and research over the period were 58.0%, 86.0%, and 61.0%, respectively. In 2012, the best performance year, for all units to reach the frontier it would be necessary to have a mean increase of 65.0% in outpatient visits; 34.0% in admissions; 12.0% in undergraduate students; 13.0% in multi-professional residents; 48.0% in graduate students; 7.0% in research projects; besides a decrease of 9.0% in medical residents. In the same year, an increase of 0.9% in financing budget would be necessary to improve the care output frontier. In the dynamic evaluation, there was progress in teaching efficiency, oscillation in medical care and no variation in research. CONCLUSIONS The proposed model generates public health planning and programming parameters by estimating efficiency scores and making projections to reach the best practice frontier.

On the analysis of compensation correctness

One fundamental idea of service-oriented computing is that applications should be developed by composing already available services. Due to the long running nature of service interactions, a main challenge in service composition is ensuring correctness of transaction recovery. In this paper, we use a process calculus suitable for modelling long running transactions with a recovery mechanism based on compensations. Within this setting, we discuss and formally state correctness criteria for compensable processes compositions, assuming that each process is correct with respect to transaction recovery. Under our theory, we formally interpret self-healing compositions, that can detect and recover from faults, as correct compositions of compensable processes. Moreover, we develop an automated verification approach and we apply it to an illustrative case study.

Land use / land cover change detection: an object oriented approach, Münster, Germany

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

A stochastic programming approach for the development of offering strategies for a wind power producer

A stochastic programming approach is proposed in this paper for the development of offering strategies for a wind power producer. The optimization model is characterized by making the analysis of several scenarios and treating simultaneously two kinds of uncertainty: wind power and electricity market prices. The approach developed allows evaluating alternative production and offers strategies to submit to the electricity market with the ultimate goal of maximizing profits. An innovative comparative study is provided, where the imbalances are treated differently. Also, an application to two new realistic case studies is presented. Finally, conclusions are duly drawn.

Extending the learning object definition to represent programming problems

The present generation of eLearning platforms values the interchange of learning objects standards. Nevertheless, for specialized domains these standards are insufficient to fully describe all the assets, especially when they are used as input for other eLearning services. To address this issue we extended an existing learning objects standard to the particular requirements of a specialized domain, namely the automatic evaluation of programming problems. The focus of this paper is the definition of programming problems as learning objects. We introduce a new schema to represent metadata related to automatic evaluation that cannot be conveniently represented using existing standards, such as: the type of automatic evaluation; the requirements of the evaluation engine; or the roles of different assets - tests cases, program solutions, etc. This new schema is being used in an interoperable repository of learning objects, called crimsonHex.

Defining programming problems as learning objects

Standards for learning objects focus primarily on content presentation. They were already extended to support automatic evaluation but it is limited to exercises with a predefined set of answers. The existing standards lack the metadata required by specialized evaluators to handle types of exercises with an indefinite set of solutions. To address this issue we extended existing learning object standards to the particular requirements of a specialized domain. We present a definition of programming problems as learning objects that is compatible both with Learning Management Systems and with systems performing automatic evaluation of programs. The proposed definition includes metadata that cannot be conveniently represented using existing standards, such as: the type of automatic evaluation; the requirements of the valuation engine; and the roles of different assets - tests cases, program solutions, etc. We present also the EduJudge project and its main services as a case study on the use of the proposed definition of programming problems as learning objects.

Trypanosoma cruzi: expression of antigenic component 5 among 35 laboratory clones obtained from 18 different isozymic variants

Two monoclonal antibodies anti-component 5 of Trypanosoma cruzi (I-35/115 and II-190/30) were tested in IFA and ELISA respectively against 35 T. cruzi laboratory clones. Among the 35 clones tested, 18 different isozyme patterns were detected. All clones were recognized by both monoclonal antibodies except one clone which did not react with II-190/30. These results support the universal expression of specific component 5 within the taxon T. cruzi.

From e-learning systems to specialised e-learning services

Learning systems are evolving from component based and centralized architectures towards service oriented and decentralized architectures. The standardization of e-learning content and interoperability is a powerful force in this evolution. In this chapter we put in perspective the evolution of e-learning systems and standards, and argue that specialized services will play an important role in future learning systems, especially in those targeted for competitive learning.

A contribution to the e-framework: a specification of a programming exercise evaluation service

This work is a contribution to the e-Framework, arguably the most prominent e-learning framework today, and consists of the definition of a service for the automatic evaluation of programming exercises. This evaluation domain differs from trivial evaluations modelled by languages such as the IMS Question & Test Interoperability (QTI) specification. Complex evaluation domains justify the development of specialized evaluators that participate in several business processes. These business processes can combine other type of systems such as Programming Contest Management Systems, Learning Management Systems, Integrated Development Environments and Learning Object Repositories where programming exercises are stored as Learning Objects. This contribution describes the implementation approaches used, more precisely, behaviours & requests, use & interactions, applicable standards, interface definition and usage scenarios.

Visual programming of XSLT from examples

Vishnu is a tool for XSLT visual programming in Eclipse - a popular and extensible integrated development environment. Rather than writing the XSLT transformations, the programmer loads or edits two document instances, a source document and its corresponding target document, and pairs texts between then by drawing lines over the documents. This form of XSLT programming is intended for simple transformations between related document types, such as HTML formatting or conversion among similar formats. Complex XSLT programs involving, for instance, recursive templates or second order transformations are out of the scope of Vishnu. We present the architecture of Vishnu composed by a graphical editor and a programming engine. The editor is an Eclipse plug-in where the programmer loads and edits document examples and pairs their content using graphical primitives. The programming engine receives the data collected by the editor and produces an XSLT program. The design of the engine and the process of creation of an XSLT program from examples are also detailed. It starts with the generation of an initial transformation that maps source document to the target document. This transformation is fed to a rewrite process where each step produces a refined version of the transformation. Finally, the transformation is simplified before being presented to the programmer for further editing.

Specifying a programming exercises evaluation service on the e-Framework

The e-Framework is arguably the most prominent e-learning framework currently in use. For this reason it was selected as basis for modelling a programming exercises evaluation service. The purpose of this type of evaluator is to mark and grade exercises in computer programming courses and in programming contests. By exposing its functions as services a programming exercise evaluator is able to participate in business processes integrating different system types, such as Programming Contest Management Systems, Learning Management Systems, Integrated Development Environments and Learning Object Repositories. This paper formalizes the approaches to be used in the implementation of a programming exercise evaluator as a service on the e-Framework.

Modelling an e-learning environment for learning programming languages

It is widely accepted that solving programming exercises is fundamental to learn how to program. Nevertheless, solving exercises is only effective if students receive an assessment on their work. An exercise solved wrong will consolidate a false belief, and without feedback many students will not be able to overcome their difficulties. However, creating, managing and accessing a large number of exercises, covering all the points in the curricula of a programming course, in classes with large number of students, can be a daunting task without the appropriated tools working in unison. This involves a diversity of tools, from the environments where programs are coded, to automatic program evaluators providing feedback on the attempts of students, passing through the authoring, management and sequencing of programming exercises as learning objects. We believe that the integration of these tools will have a great impact in acquiring programming skills. Our research objective is to manage and coordinate a network of eLearning systems where students can solve computer programming exercises. Networks of this kind include systems such as learning management systems (LMS), evaluation engines (EE), learning objects repositories (LOR) and exercise resolution environments (ERE). Our strategy to achieve the interoperability among these tools is based on a shared definition of programming exercise as a Learning Object (LO).