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.

Pulsatile Blood Flow Simulations in Computed Tomography(CT) Scan-Based and Idealized Geometries of Human Aorta

Blood flow in human aorta is an unsteady and complex phenomenon. The complex patterns are related to the geometrical features like curvature, bends, and branching and pulsatile nature of flow from left ventricle of heart. The aim of this work was to understand the effect of aorta geometry on the flow dynamics. To achieve this, 3D realistic and idealized models of descending aorta were reconstructed from Computed Tomography (CT) images of a female patient. The geometries were reconstructed using medical image processing code. The blood flow in aorta was assumed to be laminar and incompressible and the blood was assumed to be Newtonian fluid. A time dependent pulsatile and parabolic boundary condition was deployed at inlet. Steady and unsteady blood flow simulations were performed in real and idealized geometries of descending aorta using a Finite Volume Method (FVM) code. Analysis of Wall Shear Stress (WSS) distribution, pressure distribution, and axial velocity profiles were carried out in both geometries at steady and unsteady state conditions. The results obtained in thesis work reveal that the idealization of geometry underestimates the values of WSS especially near the region with sudden change of diameter. However, the resultant pressure and velocity in idealized geometry are close to those in real geometry

CT and PET/CT Hybrid Imaging of Coronary Artery Disease

Coronary artery disease (CAD) is a chronic process that evolves over decades and may culminate in myocardial infarction (MI). While invasive coronary angiography (ICA) is still considered the gold standard of imaging CAD, non-invasive assessment of both the vascular anatomy and myocardial perfusion has become an intriguing alternative. In particular, computed tomography (CT) and positron emission tomography (PET) form an attractive combination for such studies. Increased radiation dose is, however, a concern. Our aim in the current thesis was to test novel CT and PET techniques alone and in hybrid setting in the detection and assessment of CAD in clinical patients. Along with diagnostic accuracy, methods for the reduction of the radiation dose was an important target. The study investigating the coronary arteries of patients with atrial fibrillation (AF) showed that CAD may be an important etiology of AF because a high prevalence of CAD was demonstrated within AF patients. In patients with suspected CAD, we demonstrated that a sequential, prospectively ECG-triggered CT technique was applicable to nearly 9/10 clinical patients and the radiation dose was over 60% lower than with spiral CT. To detect the functional significance of obstructive CAD, a novel software for perfusion quantification, CarimasTM, showed high reproducibility with 15O-labelled water in PET, supporting feasibility and good clinical accuracy. In a larger cohort of 107 patients with moderate 30-70% pre-test probability of CAD, hybrid PET/CT was shown to be a powerful diagnostic method in the assessment of CAD with diagnostic accuracy comparable to that of invasive angiography and fractional flow reserve (FFR) measurements. A hybrid study may be performed with a reasonable radiation dose in a vast majority of the cases, improving the performance of stand-alone PET and CT angiography, particularly when the absolute quantification of the perfusion is employed. These results can be applied into clinical practice and will be useful for daily clinical diagnosis of CAD.

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.

Detection of beetle damage in forests by X-ray CT image processing

Some beetle species can have devastating economic impacts on forest and nursery industries. A recent example is Anophophora glabripennis, a species of beetle known in the United States as the ''Asian Longhorrned beetle'', which has damaged many American forests, and is a threat which can unintentionally reach south American countries, including Brazil. This work presents a new method based on X-ray computerized tomography (CT) and image processing for beetle injury detection in forests. Its results show a set of images with correct identification of the location of beetles in living trees as well as damage evaluation with time.

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%.

Lipotoxicity in Obesity and Coronary Artery Disease. Studies by PET, CT and MR

Lipotoxicity is a condition in which fatty acids (FAs) are not efficiently stored in adipose tissue and overflow to non-adipose tissue, causing organ damages. A defect of adipose tissue FA storage capability can be the primary culprit in the insulin resistance condition that characterizes many of the severe metabolic diseases that affect people nowadays. Obesity, in this regard, constitutes the gateway and risk factor of the major killers of modern society, such as cardiovascular disease and cancer. A deep understanding of the pathogenetic mechanisms that underlie obesity and the insulin resistance syndrome is a challenge for modern medicine. In the last twenty years of scientific research, FA metabolism and dysregulations have been the object of numerous studies. Development of more targeted and quantitative methodologies is required on one hand, to investigate and dissect organ metabolism, on the other hand to test the efficacy and mechanisms of action of novel drugs. The combination of functional and anatomical imaging is an answer to this need, since it provides more understanding and more information than we have ever had. The first purpose of this study was to investigate abnormalities of substrate organ metabolism, with special reference to the FA metabolism in obese drug-naïve subjects at an early stage of disease. Secondly, trimetazidine (TMZ), a metabolic drug supposed to inhibit FA oxidation (FAO), has been for the first time evaluated in obese subjects to test a whole body and organ metabolism improvement based on the hypothesis that FAO is increased at an early stage of the disease. A third objective was to investigate the relationship between ectopic fat accumulation surrounding heart and coronaries, and impaired myocardial perfusion in patients with risk of coronary artery disease (CAD). In the current study a new methodology has been developed with PET imaging with 11C-palmitate and compartmental modelling for the non-invasive in vivo study of liver FA metabolism, and a similar approach has been used to study FA metabolism in the skeletal muscle, the adipose tissue and the heart. The results of the different substudies point in the same direction. Obesity, at the an early stage, is associated with an impairment in the esterification of FAs in adipose tissue and skeletal muscle, which is accompanied by the upregulation in skeletal muscle, liver and heart FAO. The inability to store fat may initiate a cascade of events leading to FA oversupply to lean tissue, overload of the oxidative pathway, and accumulation of toxic lipid species and triglycerides, and it was paralleled by a proportional growth in insulin resistance. In subjects with CAD, the accumulation of ectopic fat inside the pericardium is associated with impaired myocardial perfusion, presumably via a paracrine/vasocrine effect. At the beginning of the disease, TMZ is not detrimental to health; on the contrary at the single organ level (heart, skeletal muscle and liver) it seems beneficial, while no relevant effects were found on adipose tissue function. Taken altogether these findings suggest that adipose tissue storage capability should be preserved, if it is not possible to prevent excessive fat intake in the first place.

Mucocele do apêndice

A case of benign appendiceal mucocele treated by appendectomy tony is reported. Appendiceal mucocele is a rare lesion of the appendix, characterized by a gross enlargement of the appendix from luminal accumulation of mucoid substance. It is a rare condition, detected in only 0.1-0.4% of all appendicectomies, with a female predominance and an average age at the time of diagnosis over 50 years. The possibility of a pre-operative diagnosis is examined. Abdominal ultrasound and CT scan of the abdomen or colonoscopy may suggest the diagnosis. However the diagnosis is often incidental. The pathogenesis and the different surgical strategies are discussed.

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.