Study of ligand-based virtual screening tools in computer-aided drug design

Virtual screening is a central technique in drug discovery today. Millions of molecules can be tested in silico with the aim to only select the most promising and test them experimentally. The topic of this thesis is ligand-based virtual screening tools which take existing active molecules as starting point for finding new drug candidates. One goal of this thesis was to build a model that gives the probability that two molecules are biologically similar as function of one or more chemical similarity scores. Another important goal was to evaluate how well different ligand-based virtual screening tools are able to distinguish active molecules from inactives. One more criterion set for the virtual screening tools was their applicability in scaffold-hopping, i.e. finding new active chemotypes. In the first part of the work, a link was defined between the abstract chemical similarity score given by a screening tool and the probability that the two molecules are biologically similar. These results help to decide objectively which virtual screening hits to test experimentally. The work also resulted in a new type of data fusion method when using two or more tools. In the second part, five ligand-based virtual screening tools were evaluated and their performance was found to be generally poor. Three reasons for this were proposed: false negatives in the benchmark sets, active molecules that do not share the binding mode, and activity cliffs. In the third part of the study, a novel visualization and quantification method is presented for evaluation of the scaffold-hopping ability of virtual screening tools.

The relationship between a virtual leader’s communication practices and a virtual team’s performance

A lot of research has been carried out into virtual teams and virtual leadership, yet there is hardly any research available on the communication behaviour of virtual leaders within a real business context. This research assessed the communication practices of virtual leaders and analysed the relationship between these practices and the performance of virtual teams. The objective of this research was to examine the distinctions of virtual teams, to study the leader’s role in a virtual team and its performance, and to examine the leader’s communication practices within virtual teams. The research involves a case study in which interviews have been carried out within an international technology company headquartered in Finland. Qualitative research methods were applied in the research. Based on the results of the study it can be said that there is a strong relationship between a virtual leader’s communication practices and a virtual team member’s job satisfaction. Through their communication practices, activities and message contents, leaders can affect the job satisfaction of virtual team members. In virtual leadership the focus is not in virtual but in leadership. It does not matter if the context is virtual or face-to-face; similar communication practices are good in both cases. As the global economic crisis strongly affected the sales results of the between a leader’s communication practices and a virtual team’s objective performance cannot be made.

Self-assembly of supermolecular species directed by hydrogen bonding and aromatic π-π stacking interactions

A new Cu(II) trimers, [Cu3(dcp)2(H2O)8]. 4DMF, with the ligand 3,5-pyrazoledicarboxylic acid monohydrate (H3dcp) has been prepared by solvent method. Its solid-state structure has been characterized by elemental analysis, thermal analysis (TGA and DSC), and single crystal X-ray diffraction. X-ray crystallographic studies reveal that this complex has extended 1-D,2-D and 3-D supramolecular architectures directed by weak interactions (hydrogen bond and aromatic π-π stacking interaction) leading to a sandwich solid-state structure.

Functional characterization of proteins required for mitotic progression and the spindle assembly checkpoint

During mitotic cell division, the genetic material packed into chromosomes is divided equally between two daughter cells. Before the separation of the two copies of a chromosome (sister chromatids), each chromosome has to be properly connected with microtubules of the mitotic spindle apparatus and aligned to the centre of the cell. The spindle assembly checkpoint (SAC) monitors connections between microtubules and chromosomes as well as tension applied across the centromere. Microtubules connect to a chromosome via kinetochores, which are proteinaceous organelles assembled onto the centromeric region of the sister chromatids. Improper kinetochore-microtubule attachments activate the SAC and block chromosome segregation until errors are corrected and all chromosomes are connected to the mitotic spindle in a bipolar manner. The purpose of this surveillance mechanism is to prevent loss or gain of chromosomes in daughter cells that according to current understanding contributes to cancer formation. Numerous proteins participate in the regulation of mitotic progression. In this thesis, the mitotic tasks of three kinetochore proteins, Shugoshin 1 (Sgo1), INCENP, and p38 MAP kinase (p38 MAPK), were investigated. Sgo1 is a protector of centromeric cohesion. It is also described in the tension-sensing mechanism of the SAC and in the regulation of kinetochore-microtubule connections. Our results revealed a central role for Sgo1 in a novel branch of kinetochore assembly. INCENP constitutes part of the chromosomal passenger complex (CPC). The other members of the core complex are the Aurora B kinase, Survivin and Borealin. CPC is an important regulatory element of cell division having several roles at various stages of mitosis. Our results indicated that INCENP and Aurora B are highly dynamic proteins at the mitotic centromeres and suggested a new role for CPC in regulation of chromosome movements and spindle structure during late mitosis. The p38 MAPK has been implicated in G1 and G2 checkpoints during the cell cycle. However, its role in mitotic progression and control of SAC signaling has been controversial. In this thesis, we discovered a novel function for p38γ MAPK in chromosome orientation and spindle structure as well as in promotion of viability of mitotic cells.

Virtual Professional Network as a Value Creator in the Dental Business

The research of virtual professional networks has been enormous but the lack of research in the dental field was obvious. This study focuses on those uses and gratifications, and motives of participants that a virtual pro-fessional network should fulfil. The aim of this study is to understand the factors behind the successful virtual professional network, and motives of participants that support a particular business network’s building up for contributing its further success. In this study the focus is on particular mo-tives, needs and benefits of participants that are significant for the net-work’s further development. The study will explore relevant scientific research and theory that is char-acteristic in networking, and theories of user’s needs and motives. Empiri-cal data was collected from dental professionals by net based question-naire that was sent by e-mail. Data analysis was done by quantitative fac-tor analysis. The findings of this study were obvious that virtual knowledge of implantology is inadequate and knowledge is rather difficult to find in the Internet. Sharing of virtual knowledge, net-learning and communication were seen to improve the quality of impolantological professionalism and also the development of these areas was experienced essential. On the grounds of this study a host of a virtual professional network can focus on those aspects that serve the users at best, can develop professionalism in implantology and can profit in its own business operations.

Serious games baseados em realidade virtual para educação médica

A evolução tecnológica tem permitido utilizar novas abordagens no processo de ensino-aprendizagem. Os serious games se relacionam com uma categoria especial de jogos, voltados a conteúdos e finalidades específicos, nos quais o jogador utiliza seus conhecimentos para resolver problemas, conhecer novas problemáticas e treinar tarefas. Uma das tecnologias propícias à construção de serious games é a Realidade Virtual, que oferece ambientes computacionais tridimensionais com formas avançadas de interação capazes de prover maior motivação ao processo de aprendizagem. No contexto da educação médica, tais aplicações apresentam um nicho ainda pouco explorado, se observados sua relevância e impactos na sociedade. Este artigo apresenta os serious games baseados em Realidade Virtual como uma proposta para o ensino de conteúdos específicos da área médica. Para isso, categoriza-os e apresenta o que tem sido desenvolvido nos últimos anos, seus componentes, características de desenvolvimento e suas potencialidades como oportunidades de pesquisa, desenvolvimento e negócios.

Tecnologia educacional no contexto do ensino de histologia: pesquisa e desenvolvimento de um ambiente virtual de ensino e aprendizagem

Discutem-se as mudanças constatadas no ensino da Histologia, como a tecnologia tem sido empregada nos contextos de aprendizagem, os aspectos pedagógicos inerentes à utilização de recursos, tais como atlas digitais e microscópios virtuais, e apresenta-se pesquisa sobre o desenvolvimento de um ambiente virtual de ensino-aprendizagem de Histologia, que contou com a participação de alunos e professores em sua construção. Verificou-se que os ambientes virtuais e outros recursos didáticos baseados nas Tecnologias da Informação e da Comunicação (TICs) procuram atender à atual tendência de complementar a educação presencial com ferramentas de educação a distância, que podem ser utilizadas facultativamente no estudo extraclasse continuado. Concluiu-se que, embora as novas tecnologias possam contribuir para o ensino de Histologia, os materiais didáticos baseados em TICs devem se adequar às expectativas docentes e discentes e aos aspectos pedagógicos e ergonômicos, e precisam ser adotados pelos professores não como ferramentas isoladas, mas integrados às estratégias de ensino-aprendizagem.

Desenvolvimento de um ambiente virtual de ensino em histologia para estudantes da saúde

As tecnologias da informação e da comunicação (TICs) têm sido amplamente utilizadas no ensino da saúde. As plataformas usadas para o desenvolvimento do ambiente virtual de ensino (AVE) geralmente apresentam uma linguagem de informática complexa. O objetivo deste trabalho foi desenvolver um AVE em Histologia voltado para estudantes da área da saúde, disponibilizado na internet com o uso de uma plataforma de uso gratuito e livre. O material elaborado utilizou diferentes TICs, como: animações, vídeos, atlas virtual, aulas virtuais, simulados online e chat. Foi desenvolvido um AVE com uso da plataforma online wordpress.org, que apresentou as seguintes vantagens: fácil manipulação, gerenciamento e atualização do site; interface simples; ampla quantidade de plugins disponíveis, que supriram as necessidades primárias do AVE; e utilização gratuita e livre. Embora esse recurso possa facilitar o aprendizado em Histologia, é preciso avaliar sua efetividade.

Ambiente Virtual de Avaliação de Competências no Manejo do Diabetes Mellitus

RESUMO O diabetes mellitus apresenta inúmeras lacunas na efetividade do seu tratamento, e a avaliação em serviço necessita ser contínua, sistemática e com dimensão orientadora de seus elementos intrínsecos: processo formativo e avaliação de competências profissional. Objetivo Apresentar o desenho didático de construção de ferramenta de avaliação de competências que o médico possui sobre o manejo do diabetes mellitus, com base em sua fisiopatologia. Métodos Estruturada como uma pesquisa participativa, o Ambiente Virtual de Avaliação de Competências, por meio de casos clínicos virtuais simulados, propõe um desenho aberto que vai sendo construído, avaliado, corrigido e melhorado durante sua execução. Resultados Com Tecnologias de Informação e Comunicação (TIC), o instrumento foi desenvolvido no âmbito de uma pesquisa de mestrado vinculada à Telessaúde da Faculdade de Medicina da Universidade Federal de Goiás. Validado o instrumento, viabilizou-se sua utilização por discentes e profissionais. Considerações As ações interativas propostas pelo ambiente virtual possibilitarão avaliar conhecimentos e identificar padrões que poderão melhorar conteúdos para manejo do DM. Propõe-se sua utilização na rede básica de saúde para confirmar sua validação, a fim de alcançar seus objetivos.

Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Avaliação do treinamento de operadores de harvester com uso de simulador de realidade virtual

Este trabalho teve por objetivo avaliar os potenciais ganhos de operadores de harvester no treinamento com uso de simuladores de realidade virtual. Foram coletados dados durante o treinamento de 39 operadores, avaliando-se os seus desempenhos nas variáveis: tempo de execução no corte da árvore, direção de queda, altura de corte, eficiência no processamento, eficiência no empilhamento e produtividade. Os resultados permitiram a conclusão de que o simulador de realidade virtual é uma ferramenta viável do ponto de vista técnico e essencial no apoio ao treinamento de operadores de máquinas florestais, possibilitando a obtenção de elevados ganhos de qualidade e produtividade. O melhor desempenho dos operadores ocorreu com a variável produtividade, cujo ganho médio foi de 41,3% em relação ao início do treinamento, seguido pelo tempo de execução, com 38,8%; e pela direção de queda, com ganho médio de 36,1%.

Virtual Battlespace 2 Panssarikoulun opetuksessa : tapaustutkimus sotilaspedagogiikan näkökulmasta

Tutkielmani tavoitteena oli tutkia tapauksena Bohemia Interactive Simulationsin valmistaman Virtual Battlespace 2 (VBS2) -tietokonepelisimulaattorin käyttöönottoa Panssariprikaatin Panssarikoulun varusmieskoulutuksessa. Tutkimuskysymysten avulla oli tarkoituksena selvittää, mitkä tekijät ja tapahtumat vaikuttivat siihen, että VBS2 otettiin käyttöön, minkälaisin perustein koulutus suunniteltiin ja järjestelmän käyttö varusmieskoulutuksessa käynnistettiin. Lisäksi ajatuksena oli aineiston mahdollistamissa puitteissa tutkia VBS2:n käytöstä tähän mennessä kertyneitä kokemuksia kouluttajien näkökulmasta, tavoitteena tuottaa myös perustietoa tulevaisuuden VBS2-koulutuksen suunnittelua ja toteuttamista varten. Tutkimusmenetelmänä oli tapaustutkimus, jonka aineisto kerättiin toteuttamalla teemahaastatteluita. Tutkimusta varten haastateltiin kahta VBS2-järjestelmää ensimmäisenä varusmieskoulutuksessa käyttänyttä kouluttajaa. Haastatteluaineisto käsiteltiin aineistolähtöisen sisällönanalyysin menetelmin. Tuloksia tarkasteltiin sotilaspedagogiikan näkökulmasta ja suhteessa oppimisympäristöjen sekä oppimisprosessin suunnittelun teorioihin. Tutkielma rakentuu johdannosta, menetelmäluvusta, yhdistetystä teoria- ja tulosluvusta sekä johtopäätös- ja pohdintaluvusta. Tutkimuksen tuloksina ilmeni, että Virtual Battlespace 2:n käyttöönotto Panssarikoulussa oli aktiivisten ja innovatiivisten henkilöiden aikaansaannosta, jossa spontaanin, ennakkoluulottoman ja opetuksen laadun kehittämiseen tähtäävän kokeilun myötä otettiin käyttöön uudenlainen koulutusväline. Samalla saatiin aikaan myönteisiä oppimistuloksia ja kiinnostavia muutoksia yhden joukkoyksikön koulutuskulttuuriin ja totunnaisiin koulutuksen käytäntöihin. VBS2:n käyttöön liittyviä keskeisiä teemoja ovat oppimisprosessin kokonaisvaltainen hallinta, eli VBS2-koulutuksen huolellinen suunnittelu ja integrointi osaksi muuta koulutusta, koulutustapahtumien valmistelujen ja kouluttajien ammattitaidon merkitys, koulutustapahtumien johtamisen paikoin muusta sotilaskoulutuksesta poikkeavat käytännöt sekä VBS2:n aikaansaaman oppimisen ymmärtäminen. Kouluttajien kokemusten perusteella VBS2 on avoin oppimisympäristö, joka ei korvaa mitään olemassa olevista koulutusmuodoista, mutta täydentää niitä tehokkaasti tarjoten uudenlaisia ulottuvuuksia sotilaskoulutukseen. Sen avulla voidaan tehokkaasti kehittää erityisesti sotilaan henkistä ja sosiaalista toimintakykyä sekä siirtää koulutuksen painopistettä soveltaviin maastoharjoituksiin. Tutkielma avaa näkökulmia VBS2:n ja muiden virtuaalisten oppimisympäristöjen pedagogiselle pohtimiselle ja tuleville aiheeseen syventyville tutkimuksille. Lisäksi se herättää keskustelua varusmieskoulutuksemme parhaista käytänteistä ja kehitystrendeistä.