O6-Methylguanine-DNA methyltransferase protein expression by immunohistochemistry in brain and non-brain systemic tumours: systematic review and meta-analysis of correlation with methylation-specific polymerase chain reaction

Background: The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) confers resistance to alkylating agents. Several methods have been applied to its analysis, with methylation-specific polymerase chain reaction (MSP) the most commonly used for promoter methylation study, while immunohistochemistry (IHC) has become the most frequently used for the detection of MGMT protein expression. Agreement on the best and most reliable technique for evaluating MGMT status remains unsettled. The aim of this study was to perform a systematic review and meta-analysis of the correlation between IHC and MSP. Methods A computer-aided search of MEDLINE (1950-October 2009), EBSCO (1966-October 2009) and EMBASE (1974-October 2009) was performed for relevant publications. Studies meeting inclusion criteria were those comparing MGMT protein expression by IHC with MGMT promoter methylation by MSP in the same cohort of patients. Methodological quality was assessed by using the QUADAS and STARD instruments. Previously published guidelines were followed for meta-analysis performance. Results Of 254 studies identified as eligible for full-text review, 52 (20.5%) met the inclusion criteria. The review showed that results of MGMT protein expression by IHC are not in close agreement with those obtained with MSP. Moreover, type of tumour (primary brain tumour vs others) was an independent covariate of accuracy estimates in the meta-regression analysis beyond the cut-off value. Conclusions Protein expression assessed by IHC alone fails to reflect the promoter methylation status of MGMT. Thus, in attempts at clinical diagnosis the two methods seem to select different groups of patients and should not be used interchangeably.

A química medicinal na próxima década

Medicinal chemistry is multi, trans and inter disciplinary on its essence. It has a great deal of challenging Brazilian chemists in the next decade. The pharmacy school is essentially attached and has an important role in the development on the field that is still in domain of big pharmaceutical industries. This work shows the challenges to face and directions to jointly follow for a myriad of researchers throughout the country. The unnamed science has to work out through specific objectives in order to diminish the problems associated with human being health. A brief history is presented where the main goal is to devise chemistry, as a natural science, and many other interfaced disciplines.

Interaktiivinen NURBS-sovelma opetuskäyttöön

Parametriset NURBS-käyrät ja -pinnat ovat yleisiä työkaluja graafisessa mallinnuksessa, tietokoneavusteisessa suunnittelussa ja muissa sovelluksissa. NURBS-mallinnus on pääosin melko intuitiivista, mutta siinä on joitakin vaikeammin ymmärrettäviä osia. Ihminen oppii parhaiten tekemällä, minkä takia päätettiin tehdä interaktiivinen NURBS-opetussovelma, joka tutustuttaa käyttäjän NURBSien toimintaan. Sovelma toimii www-selaimessa Java-liitännäisen avulla ja hyödyntää Java OpenGL -grafiikkarajapintaa kolmiulotteisen grafiikan piirtämiseen. Sovelma on helppokäyttöinen ja opastaa käyttäjää NURBS-mallinnuksen eri osa-alueissa.

Real-Time Simulation of Mobile and Industrial Machines Using the Multibody Simulation Approach

This thesis introduces a real-time simulation environment based on the multibody simulation approach. The environment consists of components that are used in conventional product development, including computer aided drawing, visualization, dynamic simulation and finite element software architecture, data transfer and haptics. These components are combined to perform as a coupled system on one platform. The environment is used to simulate mobile and industrial machines at different stages of a product life time. Consequently, the demands of the simulated scenarios vary. In this thesis, a real-time simulation environment based on the multibody approach is used to study a reel mechanism of a paper machine and a gantry crane. These case systems are used to demonstrate the usability of the real-time simulation environment for fault detection purposes and in the context of a training simulator. In order to describe the dynamical performance of a mobile or industrial machine, the nonlinear equations of motion must be defined. In this thesis, the dynamical behaviour of machines is modelled using the multibody simulation approach. A multibody system may consist of rigid and flexible bodies which are joined using kinematic joint constraints while force components are used to describe the actuators. The strength of multibody dynamics relies upon its ability to describe nonlinearities arising from wearing of the components, friction, large rotations or contact forces in a systematic manner. For this reason, the interfaces between subsystems such as mechanics, hydraulics and control systems of the mechatronic machine can be defined and analyzed in a straightforward manner.

Trolley R&D project for a small portal log yard crane

This master’s thesis was done for Andritz Inc. Atlanta Georgia. The purpose of the thesis was to develop a new trolley for a small portal log yard crane. In the beginning of the thesis the basic principles of the systematic design processes have been described, along which the design work of the trolley has proceeded. The second literature part consists of the design and dimensioning of the welded steel structures under fatigue loading. The design work of the trolley consists of the engineering and the selection of the mechanical components and the design of the load carrying structure for the trolley. The realization of the steel structure of the trolley is based on the fatigue and static dimensioning. The fatigue dimensioning is grounded in the life expectations estimated for the trolley and the static dimensioning is based on the CMAA guidelines. The computer aided element method was utilized in the design of the steel structure. The effective notch method and the hot spot method were used in the fatigue calculations. The trolley structure was carried out by using the sheet metal parts in order to manufacture the structure as effective and low cost way as possible. The corner stone of the dimensioning of the trolley structure was the utilization of the open profiles made of welded or cold formed sheet metals, which provide better weldability, weld inspection, access for repairs and corrosion protection. As a last part of the thesis a new trolley traveling system was developed. The distribution of the wheel loads of the trolley bogies on the main girder was also studied, which led to an innovative suspension arrangement between the trolley leg and the bogie. The new bogie solution increases the service life of the main girder of the crane and improves the stability of the bogies. The outcome of the thesis is an excellent trolley structure from the weight and the service life point of view.

Genetic diversity of begomovirus infecting tomato and associated weeds in Southeastern Brazil

The genetic diversity of begomovirus isolates from tomato (Lycopersicon esculentum) fields in the Southeastern region of Brazil was analyzed by direct sequencing of PCR fragments amplified by using universal oligonucleotides for the begomovirus DNA-A, and subsequent computer-aided phylogenetic analysis. Samples of tomato plants and associated weeds showing typical symptoms of virus infection were collected at seven locations in the states of Minas Gerais, Espírito Santo and Rio de Janeiro. A total of 137 out of 369 samples were infected with a begomovirus based on PCR analysis. Phylogenetic analysis indicated a high degree of genetic diversity among begomoviruses infecting tomatoes in the sampled area. One species (Tomato chlorotic mottle virus, TCMV) occurs predominantly in Minas Gerais, whereas in Rio de Janeiro and Espírito Santo a distinct species, not yet fully characterized, predominates. Phylogenetic analysis further indicates the presence of an additional four possible new species. This high degree of genetic diversity suggests a recent transfer of indigenous begomovirus from wild hosts into tomatoes. The close phylogenetic relationship verified between begomovirus infecting tomato and associated weeds favors this hypothesis.

Comparison Structure Analysis

This study presents an automatic, computer-aided analytical method called Comparison Structure Analysis (CSA), which can be applied to different dimensions of music. The aim of CSA is first and foremost practical: to produce dynamic and understandable representations of musical properties by evaluating the prevalence of a chosen musical data structure through a musical piece. Such a comparison structure may refer to a mathematical vector, a set, a matrix or another type of data structure and even a combination of data structures. CSA depends on an abstract systematic segmentation that allows for a statistical or mathematical survey of the data. To choose a comparison structure is to tune the apparatus to be sensitive to an exclusive set of musical properties. CSA settles somewhere between traditional music analysis and computer aided music information retrieval (MIR). Theoretically defined musical entities, such as pitch-class sets, set-classes and particular rhythm patterns are detected in compositions using pattern extraction and pattern comparison algorithms that are typical within the field of MIR. In principle, the idea of comparison structure analysis can be applied to any time-series type data and, in the music analytical context, to polyphonic as well as homophonic music. Tonal trends, set-class similarities, invertible counterpoints, voice-leading similarities, short-term modulations, rhythmic similarities and multiparametric changes in musical texture were studied. Since CSA allows for a highly accurate classification of compositions, its methods may be applicable to symbolic music information retrieval as well. The strength of CSA relies especially on the possibility to make comparisons between the observations concerning different musical parameters and to combine it with statistical and perhaps other music analytical methods. The results of CSA are dependent on the competence of the similarity measure. New similarity measures for tonal stability, rhythmic and set-class similarity measurements were proposed. The most advanced results were attained by employing the automated function generation – comparable with the so-called genetic programming – to search for an optimal model for set-class similarity measurements. However, the results of CSA seem to agree strongly, independent of the type of similarity function employed in the analysis.

High-speed solid-rotor induction machine – calculation program

The aim of this thesis is to utilize the technology developed at LUT and to provide an easy tool for high-speed solid-rotor induction machine preliminary design. Computer aided design tool MathCAD has been chosen as the environment for realizing the calculation program. Four versions of the design program have been made depending on the motor rotor type. The first rotor type is an axially slitted solid-rotor with steel end rings. The next one is an axially slitted solid-rotor with copper end rings. The third machine type is a solid rotor with deep, rectangular copper bars and end rings (squirrel cage). And the last one is a solid-rotor with round copper bars and end rings (squirrel cage). Each type of rotor has its own specialties but a general thread of design is common. This paper follows the structure of the calculating program and explains some features and formulas. The attention is concentrated on the difference between laminated and solid-rotor machine design principles. There is no deep analysis of the calculation ways are presented. References for all solution methods appearing during the design procedure are given for more detailed studying. This thesis pays respect to the latest innovations in solid-rotor machines theory. Rotor ends’ analytical calculation follows the latest knowledge in this field. Correction factor for adjusting the rotor impedance is implemented. The purpose of the created design program is to calculate the preliminary dimensions of the machine according to initial data. Obtained results are not recommended for exact machine development. Further more detailed design should be done in a finite element method application. Hence, this thesis is a practical tool for the prior evaluating of the high-speed machine with different solid-rotor types parameters.

A reprodutibilidade da medida do volume endometrial por meio do VOCAL: a importância do passo de rotação

OBJETIVOS: avaliar a reprodutibilidade intra-observador e interobservador da medida do volume endometrial utilizando ultra-sonografia tridimensional (3D) e o programa VOCAL® (Virtual Organ Computer-aided AnaLysis). MÉTODOS: um bloco ultra-sonográfico 3D do endométrio foi obtido de cinco pacientes inférteis voluntárias que apresentavam diferentes volumes endometriais. Para cada bloco 3D, o volume endometrial foi calculado utilizando o modo manual em quatro diferentes passos de rotação (30º, 15º, 9º e 6º) por dois diferentes observadores. Dez medidas foram obtidas para cada rotação e por cada observador. Testamos a diferença entre as médias com o one-way ANOVA e o pós-teste de Tukey e a reprodutibilidade com os coeficientes de correlação intraclasse. RESULTADOS: as medidas realizadas com passo de rotação de 30º foram associadas a médias significativamente menores em 3 das 5 pacientes. Não houve diferença entre as médias obtidas pelos passos de rotação de 15º, 9º ou 6º. Em nenhuma das avaliações foi notada diferença entre as médias obtidas pelos dois observadores. Os coeficientes de correlação intraclasse foram significativamente menores com o passo de rotação de 30º (todos abaixo de 0,984) que com os outros passos de rotação (todos acima de 0,996). CONCLUSÕES: o uso de passos de rotação de 15º ou menos apresentou medidas reprodutíveis do volume endometrial: não houve diferença significativa entre as médias obtidas pelos dois observadores, associado ao alto coeficiente de correlação intraclasse (>0,996). É recomendável o uso do passo de rotação de 15º, pois demora menos para ser obtido em comparação com 6º e 9º.

Volume do embrião estimado pela ultra-sonografia tridimensional entre a sétima e a décima semana de gestação

OBJETIVO: avaliar a evolução do volume do embrião (VE) entre a sétima e a décima semana de gestação por meio da ultra-sonografia tridimensional. MÉTODOS: realizou-se um estudo de corte transversal com 63 gestantes normais entre a sétima e a décima semana. Os exames ultra-sonográficos foram realizados por meio de um transdutor endocavitário volumétrico. Para o cálculo do VE, utilizou-se o método VOCAL (Virtual Organ Computer-aided Analysis) com ângulo de rotação de 12º, com delimitação de 15 planos seqüenciais. Para o VE foram calculadas médias, medianas, desvios padrão e valores máximo e mínimo em todas as idades gestacionais. Para se avaliar a correlação entre o VE e o comprimento cabeça-nádega (CCN) foi criado gráfico de dispersão, sendo o ajuste realizado pelo coeficiente de determinação (R²). Para se determinarem intervalos de referência do VE em função do CCN, utilizou-se a seguinte fórmula: percentil =VE+K versus dp, com K=1,96. RESULTADOS: o CCN variou de 9,0 a 39,7 mm, com média de 23,9 mm (±7,9 mm), enquanto o VE variou de 0,1 a 7,6 cm³, com média de 2,7 cm³ (±3,2 cm³). O VE foi altamente correlacionado com o CCN, sendo que o melhor ajuste foi obtido com regressão quadrática (VE=0,165 - 0,055 x CCN + 0,005 x CCN²; R²=0,853). O VE médio variou de 0,1 (-0,3 a 0,5 cm³) a 6,7 cm³ (3,8 a 9,7 cm³) no intervalo de 9 a 40 mm do CCN. Neste intervalo o VE aumentou 67 vezes, enquanto o CCN aumentou apenas 4,4 vezes. CONCLUSÕES: o VE é um parâmetro mais sensível que o CCN para avaliar o crescimento embrionário entre a sétima e a décima semana de gestação.

A feature-based object-oriented expert system to model and support product design

In this paper a computer program to model and support product design is presented. The product is represented through a hierarchical structure that allows the user to navigate across the product’s components, and it aims at facilitating each step of the detail design process. A graphical interface was also developed, which shows visually to the user the contents of the product structure. Features are used as building blocks for the parts that compose the product, and object-oriented methodology was used as a means to implement the product structure. Finally, an expert system was also implemented, whose knowledge base rules help the user design a product that meets design and manufacturing requirements.

Business intelligence viewpoint on managerial decision-making : Ill-structured problems and decision support systems

Vaikka liiketoimintatiedon hallintaa sekä johdon päätöksentekoa on tutkittu laajasti, näiden kahden käsitteen yhteisvaikutuksesta on olemassa hyvin rajallinen määrä tutkimustietoa. Tulevaisuudessa aiheen tärkeys korostuu, sillä olemassa olevan datan määrä kasvaa jatkuvasti. Yritykset tarvitsevat jatkossa yhä enemmän kyvykkyyksiä sekä resursseja, jotta sekä strukturoitua että strukturoimatonta tietoa voidaan hyödyntää lähteestä riippumatta. Nykyiset Business Intelligence -ratkaisut mahdollistavat tehokkaan liiketoimintatiedon hallinnan osana johdon päätöksentekoa. Aiemman kirjallisuuden pohjalta, tutkimuksen empiirinen osuus tunnistaa liiketoimintatiedon hyödyntämiseen liittyviä tekijöitä, jotka joko tukevat tai rajoittavat johdon päätöksentekoprosessia. Tutkimuksen teoreettinen osuus johdattaa lukijan tutkimusaiheeseen kirjallisuuskatsauksen avulla. Keskeisimmät tutkimukseen liittyvät käsitteet, kuten Business Intelligence ja johdon päätöksenteko, esitetään relevantin kirjallisuuden avulla – tämän lisäksi myös dataan liittyvät käsitteet analysoidaan tarkasti. Tutkimuksen empiirinen osuus rakentuu tutkimusteorian pohjalta. Tutkimuksen empiirisessä osuudessa paneudutaan tutkimusteemoihin käytännön esimerkein: kolmen tapaustutkimuksen avulla tutkitaan sekä kuvataan toisistaan irrallisia tapauksia. Jokainen tapaus kuvataan sekä analysoidaan teoriaan perustuvien väitteiden avulla – nämä väitteet ovat perusedellytyksiä menestyksekkäälle liiketoimintatiedon hyödyntämiseen perustuvalle päätöksenteolle. Tapaustutkimusten avulla alkuperäistä tutkimusongelmaa voidaan analysoida tarkasti huomioiden jo olemassa oleva tutkimustieto. Analyysin tulosten avulla myös yksittäisiä rajoitteita sekä mahdollistavia tekijöitä voidaan analysoida. Tulokset osoittavat, että rajoitteilla on vahvasti negatiivinen vaikutus päätöksentekoprosessin onnistumiseen. Toisaalta yritysjohto on tietoinen liiketoimintatiedon hallintaan liittyvistä positiivisista seurauksista, vaikka kaikkia mahdollisuuksia ei olisikaan hyödynnetty. Tutkimuksen merkittävin tulos esittelee viitekehyksen, jonka puitteissa johdon päätöksentekoprosesseja voidaan arvioida sekä analysoida. Despite the fact that the literature on Business Intelligence and managerial decision-making is extensive, relatively little effort has been made to research the relationship between them. This particular field of study has become important since the amount of data in the world is growing every second. Companies require capabilities and resources in order to utilize structured data and unstructured data from internal and external data sources. However, the present Business Intelligence technologies enable managers to utilize data effectively in decision-making. Based on the prior literature, the empirical part of the thesis identifies the enablers and constraints in computer-aided managerial decision-making process. In this thesis, the theoretical part provides a preliminary understanding about the research area through a literature review. The key concepts such as Business Intelligence and managerial decision-making are explored by reviewing the relevant literature. Additionally, different data sources as well as data forms are analyzed in further detail. All key concepts are taken into account when the empirical part is carried out. The empirical part obtains an understanding of the real world situation when it comes to the themes that were covered in the theoretical part. Three selected case companies are analyzed through those statements, which are considered as critical prerequisites for successful computer-aided managerial decision-making. The case study analysis, which is a part of the empirical part, enables the researcher to examine the relationship between Business Intelligence and managerial decision-making. Based on the findings of the case study analysis, the researcher identifies the enablers and constraints through the case study interviews. The findings indicate that the constraints have a highly negative influence on the decision-making process. In addition, the managers are aware of the positive implications that Business Intelligence has for decision-making, but all possibilities are not yet utilized. As a main result of this study, a data-driven framework for managerial decision-making is introduced. This framework can be used when the managerial decision-making processes are evaluated and analyzed.

Simulation of new p-type pixel strip detector with enhanced multiplication effect

This Master’s Thesis is dedicated to the simulation of new p-type pixel strip detector with enhanced multiplication effect. It is done for high-energy physics experiments upgrade such as Super Large Hadron Collider especially for Compact Muon Solenoid particle track silicon detectors. These detectors are used in very harsh radiation environment and should have good radiation hardness. The device engineering technology for developing more radiation hard particle detectors is used for minimizing the radiation degradation. New detector structure with enhanced multiplication effect is proposed in this work. There are studies of electric field and electric charge distribution of conventional and new p-type detector under reverse voltage bias and irradiation. Finally, the dependence of the anode current from the applied cathode reverse voltage bias under irradiation is obtained in this Thesis. For simulation Silvaco Technology Computer Aided Design software was used. Athena was used for creation of doping profiles and device structures and Atlas was used for getting electrical characteristics of the studied devices. The program codes for this software are represented in Appendixes.

Background for Designing an Improved Digital Musical Keyboard Instrument

Electrical keyboard instruments and computer-aided music-making generally base on the piano keyboard that was developed for a tuning system no longer used. Alternative keyboard layout offers at least easier playing, faster adopting, new ways to play and better ergonomics. This thesis explores the development of keyboard instruments and tunings, and different keyboard layouts. This work is preliminary research for an electrical keyboard instrument to be implemented later on.

Training graduate students to be teachers

Pedagogic education of graduate students, when and where it exists, is restricted to theoretical courses or to the participation of the students as teachers' assistants. This model is essentially reproductive and offers few opportunities for any significant curriculum innovation. To open an opportunity for novelty we have introduced a new approach in "Biochemistry Teaching", a course included in the Biochemistry Graduate Program of the Biochemistry Department (Universidade Estadual de Campinas and Universidade de São Paulo). The content of the course consists of a) choosing the theme, b) selecting and organizing the topics, c) preparing written material, d) establishing the methodological strategies, e) planning the evaluation tools and, finally, f) as teachers, conducting the course as an optional summer course for undergraduate students. During the first semester the graduate students establish general and specific educational objectives, select and organize contents, decide on the instructional strategies and plan evaluation tools. The contents are explored using a wide range of strategies, which include computer-aided instruction, laboratory classes, small group teaching, a few lectures and round table discussions. The graduate students also organize printed class notes to be used by the undergraduate students. Finally, as a group, they teach the summer course. In the three versions already developed, the themes chosen were Biochemistry of Exercise (UNICAMP), Biochemistry of Nutrition (UNICAMP) and Molecular Biology of Plants (USP). In all cases the number of registrations greatly exceeded the number of places and a selection had to be made. The evaluation of the experience by both graduate and undergraduate students was very positive. Graduate students considered this experience to be unique and recommended it to their schoolmates; the undergraduate students benefited from a more flexible curriculum (more options) and gave very high scores to both the courses and the teachers.