Rapid screening of 4000 individuals for germ-line variations in the BRAF gene

Background: The BRAF gene is frequently somatically altered in malignant melanoma. A majority of variations are at the valine 600 residue leading to a V600E substitution that constitutively activates the kinase. We screened 4000 patient and control DNAs for germ-line variations at the valine 600 residue. Methods: We developed a novel assay by adapting single-base variation assays and software for MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry to screen for all 5 reported variants at codon 600 of the BRAF gene. We screened a case-control collection comprising samples from 1082 melanoma patients and 154 of their unaffected relatives from 1278 families and from 2744 individuals from 659 unselected twin families with no history of melanoma. A panel of 66 melanoma cell lines was used for variation-positive controls. Results: All melanoma cell lines that we had found previously to carry a codon 600 variation were verified in this study. Three of the 4 possible variants (V600E n = 47, V600K n = 2, V600R n = 1) were detected, but no case of V600D was available. No germ-line variants were found in the samples from the 3980 melanoma patients or from the control individuals. Conclusions: This new assay is a high-throughput, automated alternative to standard sequencing and can be used as a rapid initial screen for somatic variants associated with melanoma. Germ-line variants at valine 600 are unlikely to exist and do not contribute to the reported role of the BRAF gene in melanoma predisposition. (c) 2006 American Association for Clinical Chemistry.

Sistemas de cálculo, análise e operação virtual: interferências de campos elétricos e magnéticos produzidas por estações radio base de acesso múltiplo por divisão de código em banda larga - WCDMA

In this work it was developed mathematical resolutions taking as parameter maximum intensity values for the interference analysis of electric and magnetic fields and was given two virtual computer system that supports families of CDMA and WCDMA technologies. The first family were developed computational resources to solve electric and magnetic field calculations and power densities in Radio Base stations , with the use of CDMA technology in the 800 MHz band , taking into account the permissible values referenced by the Commission International Protection on non-Ionizing Radiation . The first family is divided into two segments of calculation carried out in virtual operation. In the first segment to compute the interference field radiated by the base station with input information such as radio channel power; Gain antenna; Radio channel number; Operating frequency; Losses in the cable; Attenuation of direction; Minimum Distance; Reflections. Said computing system allows to quickly and without the need of implementing instruments for measurements, meet the following calculated values: Effective Radiated Power; Sector Power Density; Electric field in the sector; Magnetic field in the sector; Magnetic flux density; point of maximum permissible exposure of electric field and power density. The results are shown in charts for clarity of view of power density in the industry, as well as the coverage area definition. The computer module also includes folders specifications antennas, cables and towers used in cellular telephony, the following manufacturers: RFS World, Andrew, Karthein and BRASILSAT. Many are presented "links" network access "Internet" to supplement the cable specifications, antennas, etc. . In the second segment of the first family work with more variables , seeking to perform calculations quickly and safely assisting in obtaining results of radio signal loss produced by ERB . This module displays screens representing propagation systems denominated "A" and "B". By propagating "A" are obtained radio signal attenuation calculations in areas of urban models , dense urban , suburban , and rural open . In reflection calculations are present the reflection coefficients , the standing wave ratio , return loss , the reflected power ratio , as well as the loss of the signal by mismatch impedance. With the spread " B" seek radio signal losses in the survey line and not targeted , the effective area , the power density , the received power , the coverage radius , the conversion levels and the gain conversion systems radiant . The second family of virtual computing system consists of 7 modules of which 5 are geared towards the design of WCDMA and 2 technology for calculation of telephone traffic serving CDMA and WCDMA . It includes a portfolio of radiant systems used on the site. In the virtual operation of the module 1 is compute-: distance frequency reuse, channel capacity with noise and without noise, Doppler frequency, modulation rate and channel efficiency; Module 2 includes computes the cell area, thermal noise, noise power (dB), noise figure, signal to noise ratio, bit of power (dBm); with the module 3 reaches the calculation: breakpoint, processing gain (dB) loss in the space of BTS, noise power (w), chip period and frequency reuse factor. Module 4 scales effective radiated power, sectorization gain, voice activity and load effect. The module 5 performs the calculation processing gain (Hz / bps) bit time, bit energy (Ws). Module 6 deals with the telephone traffic and scales 1: traffic volume, occupancy intensity, average time of occupancy, traffic intensity, calls completed, congestion. Module 7 deals with two telephone traffic and allows calculating call completion and not completed in HMM. Tests were performed on the mobile network performance field for the calculation of data relating to: CINP , CPI , RSRP , RSRQ , EARFCN , Drop Call , Block Call , Pilot , Data Bler , RSCP , Short Call, Long Call and Data Call ; ECIO - Short Call and Long Call , Data Call Troughput . As survey were conducted surveys of electric and magnetic field in an ERB , trying to observe the degree of exposure to non-ionizing radiation they are exposed to the general public and occupational element. The results were compared to permissible values for health endorsed by the ICNIRP and the CENELEC .

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

As unidades de alojamento de 5 estrelas no concelho de lisboa - a evolução e comparação dos preços on-line em duas épocas distintas

A utilização da internet para efetuar reservas on-line de alojamento no setor hoteleiro, tem um peso cada vez maior no conjunto das reservas efetuadas. É por isso, necessário que sejam elaborados estudos que permitam perceber a evolução dos preços oferecidos ao cliente, ao longo do tempo, nos diversos sites de reserva on-line e no site do próprio hotel, para que quer os clientes quer os gestores possuam informação rigorosa que lhes permita tomar decisões e elaborar estratégias eficazes. Nesta investigação, apresentar-se-á a evolução dos preços médios dos hotéis em estudo, obtida a partir da consulta de um conjunto de sites de reserva on-line que previamente se definiram e do site institucional, consulta efetuada ao longo dos dois períodos de doze dias que antecederam a época festiva da Páscoa e uma época não festiva. A investigação empírica efetuada, neste trabalho, foi realizada com base num estudo de caso exploratório, tendo como objeto de estudo os hotéis de 5 estrelas do concelho de Lisboa, tendo em conta os dados secundários disponíveis. O recurso ao estudo de caso permitiu delimitar de modo preciso o contexto desta investigação. A opção pelo tipo de pesquisa exploratória teve em conta o facto de se conhecer pouca bibliografia científica disponível sobre a temática em estudo. Os resultados obtidos permitiram perceber qual foi a evolução dos preços ao longo do período de consulta para a época festiva da Páscoa e para a época não festiva, possibilitando depois fazer a comparação da evolução dos preços entre as duas épocas. Da análise dos dados pôde ainda perceber-se se havia concertação entre os vários meios de reserva consultados, ou seja, entre os sites de reserve on-line considerados e o site institucional. Tomando por base os hotéis que durante os períodos de consulta foram esgotando pode, ainda, observar-se o comportamento dos preços médios em relação à variação da oferta disponível.

Design rationnel de nanothermomètres programmables à base d’ADN

Développer de nouveaux nanomatériaux, interrupteurs et machines nanométriques sensibles à de petites variations de température spécifiques devrait être de grande utilité pour une multitude de domaines œuvrant dans la nanotechnologie. De plus, l’objectif est de convaincre le lecteur que les nanotechnologies à base d’ADN offrent d’énormes possibilités pour la surveillance de température en temps réel à l’échelle nanométrique. Dans la section Résultats, nous exploitons les propriétés de l’ADN pour créer des thermomètres versatiles, robustes et faciles à employer. En utilisant une série de nouvelles stratégies inspirées par la nature, nous sommes en mesure de créer des nanothermomètres d’ADN capables de mesurer des températures de 25 à 95°C avec une précision de <0.1°C. En créant de nouveaux complexes d’ADN multimériques, nous arrivons à développer des thermomètres ultrasensibles pouvant augmenter leur fluorescence 20 fois sur un intervalle de 7°C. En combinant plusieurs brins d’ADN avec des plages dynamiques différentes, nous pouvons former des thermomètres montrant une transition de phase linéaire sur 50°C. Finalement, la vitesse de réponse et la précision des thermomètres développés et leur réversibilité sont illustrées à l’aide d’une expérience de surveillance de température à l’intérieur d’un unique puits d’un appareil de qPCR. En conclusion, les applications potentielles de tels nanothermomètres en biologie synthétique, imagerie thermique cellulaire, nanomachines d’ADN et livraison contrôlée seront considérées.

Stability of Granular Base Course Materials Containing Bituminous Admixtures

This report concerns the stabilization of three crushed limestones by an ss-1 asphalt emulsion and an asphalt cement, 120-150 penetration. Stabilization is evaluated by marshall stability and triaxial shear tests. Test specimens were compacted by the marshall, standard proctor and vibratory methods. Stabilization is evaluated primarily by triaxial shear tests in which confining pressures of 0 to 80 psi were used. Data were obtained on the angle of internal friction, cohesion, volume change, pore water pressure and strain characteristics of the treated and untreated aggregates. The MOHR envelope, bureau of reclamation and modified stress path methods were used to determine shear strength parameters at failure. Several significant conclusions developed by the authors are as follows: (1) the values for effective angle of internal friction and effective cohesion were substantially independent of asphalt content, (2) straight line MOHR envelopes of failure were observed for all treated stones, (3) bituminous admixtures did little to improve volume change (deformation due to load) characteristics of the three crushed limestones, (4) with respect to pore water characteristics (pore pressures and suctions due to lateral loading), bituminous treatment notably improved only the bedford stone, and (5) at low lateral pressures bituminous treatments increased stability by limiting axial strain. This would reduce rutting of highway bases. At high lateral pressures treated stone was less stable than untreated stone.

Measurement and Simulation of Suppression Effects in a Buoyant Turbulent Line Fire

An experimental and numerical study of turbulent fire suppression is presented. For this work, a novel and canonical facility has been developed, featuring a buoyant, turbulent, methane or propane-fueled diffusion flame suppressed via either nitrogen dilution of the oxidizer or application of a fine water mist. Flames are stabilized on a slot burner surrounded by a co-flowing oxidizer, which allows controlled delivery of either suppressant to achieve a range of conditions from complete combustion through partial and total flame quenching. A minimal supply of pure oxygen is optionally applied along the burner to provide a strengthened flame base that resists liftoff extinction and permits the study of substantially weakened turbulent flames. The carefully designed facility features well-characterized inlet and boundary conditions that are especially amenable to numerical simulation. Non-intrusive diagnostics provide detailed measurements of suppression behavior, yielding insight into the governing suppression processes, and aiding the development and validation of advanced suppression models. Diagnostics include oxidizer composition analysis to determine suppression potential, flame imaging to quantify visible flame structure, luminous and radiative emissions measurements to assess sooting propensity and heat losses, and species-based calorimetry to evaluate global heat release and combustion efficiency. The studied flames experience notable suppression effects, including transition in color from bright yellow to dim blue, expansion in flame height and structural intermittency, and reduction in radiative heat emissions. Still, measurements indicate that the combustion efficiency remains close to unity, and only near the extinction limit do the flames experience an abrupt transition from nearly complete combustion to total extinguishment. Measurements are compared with large eddy simulation results obtained using the Fire Dynamics Simulator, an open-source computational fluid dynamics software package. Comparisons of experimental and simulated results are used to evaluate the performance of available models in predicting fire suppression. Simulations in the present configuration highlight the issue of spurious reignition that is permitted by the classical eddy-dissipation concept for modeling turbulent combustion. To address this issue, simple treatments to prevent spurious reignition are developed and implemented. Simulations incorporating these treatments are shown to produce excellent agreement with the experimentally measured data, including the global combustion efficiency.

CHALLENGES OF EDUCATION IN LINE FOR CHALLENGES TO EDUCATION BIBLIOTECÓLOGOS-DOCENTES/ONLINE-TEACHERS LIBRARIANS

This article tries to reflect about skills that librarian or information specialists should develop to design an online course. Define distance education, online education, and collaborative learning. Establish the importance of community sense. Describe the process to design online courses. Finally, compare the Mexican Librarianship and Information Sciences Schools graduate profiles with the skills required to design online courses.

Avaliação de hábitos de consumo e adequação nutricional de refeições rápidas cuja base é o pão

As rápidas alterações sociais, económicas, culturais e ambientais determinaram mudanças significativas nos estilos de vida e contribuíram para o crescimento e generalização do consumo de alimentos e refeições fora de casa. Portugal acompanha a tendência de aumento do consumo alimentar fora de casa, assim, as refeições fora de casa, que há uns anos eram um acontecimento fortuito, são hoje uma prática habitual das famílias portuguesas, não só durante a semana de trabalho, mas também nos fins-de-semana. As, visitas aos centros comerciais que se tornaram um hábito no nosso país incluem uma paragem nas Praças de Alimentação, espaços de excelência pela diversidade alimentar onde predominam as refeições de fast-food. Porém é fundamental a escolha adequada/equilibrada dos alimentos que se vão consumir. O presente trabalho procurou avaliar os hábitos e percepção dos consumidores de refeições rápidas com base numa ementa específica cujo alimento principal é o pão. Posteriormente e de acordo com as preferências de consumo procedeu-se à avaliação nutricional das escolhas. Neste estudo participaram 150 indivíduos que frequentaram as instalações de um restaurante de comida rápida situada na praça de alimentação de um centro comercial situado em Viseu. Foi aplicado um questionário de autopreenchimento, por nós elaborado dividido em 4 partes: caracterização sociodemográfica; hábitos de consumo dos inquiridos; produtos escolhidos pelos inquiridos; grau de satisfação face aos produtos escolhidos. As análises estatísticas foram efectuadas com recurso ao Programa informático Statistical Package for the Social Sciences - SPSS® for Windows, versão 22. Realizam-se testes de Qui-quadrado com simulação de Monte Carlo, considerando o nível de significância de 0,05. Com base nas escolhas mais frequentes feitas pelos inquiridos procedeu-se à avaliação nutricional dos menus recorrendo ao programa DIAL 1.19 versão 1 e quando não se encontrou informação neste utilizou-se a tabela de composição de alimentos portugueses on line (INSA, 2010). Compararam-se os valores obtidos para o Valor Calórico Total, os macronutrientes, a fibra, o colesterol e o sódio com as Doses Diárias Recomendadas. A amostra era composta por 68,7% mulheres e 31,3% homens, com uma média de idades de 29,9 ± 3 anos e, maioritariamente empregados (64,7%). O grau de instrução da maioria dos inquiridos (54,7%) era o ensino superior. Grande parte da amostra não se considera consumidora habitual de fast-food,referindo ainda efectuar frequentemente uma alimentação equilibrada. Sendo que apenas 5 % frequenta as instalações mais de uma vez por semana. De entre os produtos disponíveis, a preferência fez-se pela sandes e batata-frita, sendo o momento de maior consumo o almoçoA avaliação nutricional das escolhas preferenciais dos inquiridos mostrou que o VCT do menu que inclui água como bebida está dentro dos limites calóricos preconizados para o almoço excepção feita ao menu que inclui sandes quente de frango em pão de orégãos e sandes fria de queijo fresco que se destacam por apresentar um valor inferior ao limite mínimo recomendado. Pelo contrário, a inclusão no menu do refrigerante faz com que haja um aumento do VCT, independentemente da sandes considerada, em 18%. Uma análise detalhada mostra que estas ementas são desequilibradas, apresentando 33,3% delas valores de proteínas superiores à DDR enquanto que os valores de HC e lípidos se encontram maioritariamente dentro dos limites havendo apenas 13,3% das ementas fora desses valores. Relativamente ao aporte de fibra e de sódio 86,7% das ementas aparecem desenquadradas com valores excessivos de sódio e valores de fibra 33% abaixo do limite mínimo recomendado. Tratando-se de um estudo de caso em que apenas se inclui um único restaurante de uma praça de alimentação, que fornece ementas à base de pão (sandes) os resultados são interpretados de forma cautelosa e sem generalização. Podemos no entanto concluir, face aos resultados obtidos a necessidade de redução do teor de sal das ementas. Para além disso parece-nos fundamental, para que o consumidor possa comparar opções alimentares e tomar decisões informadas, a disponibilização da informação nutricional das ementas propostas.

Papel da proteína de reparo XPC na regulação das proteínas de reparo APE1, OGG1 e PARP-1 em células humanas e de camundongos

studies using UV as a source of DNA damage. However, even though unrepaired UV-induced DNA damages are related to mutagenesis, cell death and tumorigenesis, they do not explain phenotypes such as neurodegeneration and internal tumors observed in patients with syndromes like Xeroderma Pigmentosum (XP) and Cockayne Syndrome (CS) that are associated with NER deficiency. Recent evidences point to a role of NER in the repair of 8-oxodG, a typical substrate of Base Excision Repair (BER). Since deficiencies in BER result in genomic instability, neurodegenerative diseases and cancer, it was investigated in this research the impact of XPC deficiency on BER functions in human cells. It was analyzed both the expression and the cellular localization of APE1, OGG1 e PARP-1, the mainly BER enzymes, in different NER-deficient human fibroblasts. The endogenous levels of these enzymes are reduced in XPC deficient cells. Surprisingly, XP-C fibroblasts were more resistant to oxidative agents than the other NER deficient fibroblasts, despite presenting the highest of 8-oxodG. Furthermore, subtle changes in the nuclear and mitochondrial localization of APE1 were detected in XP-C fibroblasts. To confirm the impact of XPC deficiency in the regulation of APE1 and OGG1 expression and activity, we constructed a XPC-complemented cell line. Although the XPC complementation was only partial, we found that XPC-complemented cells presented increased levels of OGG1 than XPC-deficient cells. The extracts from XPC-complemented cells also presented an elevated OGG1 enzimatic activity. However, it was not observed changes in APE1 expression and activity in the XPCcomplemented cells. In addition, we found that full-length APE1 (37 kDa) and OGG1- α are in the mitochondria of XPC-deficient fibroblasts and XPC-complemented fibroblasts before and after induction of oxidative stress. On the other hand, the expression of APE1 and PARP-1 are not altered in brain and liver of XPC knockout mice. However, XPC deficiency changed the APE1 localization in hypoccampus and hypothalamus. We also observed a physical interaction between XPC and APE1 proteins in human cells. In conclusion, the data suggest that XPC protein has a role in the regulation of OGG1 expression and activity in human cells and is involved mainly in the regulation of APE1 localization in mice. Aditionally, the response of NER deficient cells under oxidative stress may not be only associated to the NER deficiency per se, but it may include the new functions of NER enzymes in regulation of expression and cell localization of BER proteins

Evaluación de Nutrire®: una herramienta on-line para realizar estudios de evaluación del estado nutricional

Introducción: Nutrire® es un programa informático, fruto de tres proyectos de innovación docente de la Universidad de Granada (España), que permite la valoración del estado nutricional mediante a partir de parámetros antropométricos, dietéticos y bioquímicos. Objetivo: El objetivo de este trabajo es presentar los resultados obtenidos de la evaluación global del programa por alumnos y egresados para poder analizar sus puntos fuertes y débiles que sirvan con posterioridad para realizar las modificaciones oportunas. Material y Métodos: Se ha realizado una encuesta anónima a 128 alumnos de 3 titulaciones de grado y 1 de postgrado de la Universidad de Granada. Se incluye 6 preguntas sobre navegabilidad y diseño y 5 sobre contenidos académicos del programa. Asimismo, se han entrevistado a 20 egresados que lo han utilizado en su actividad profesional. Resultados: La puntuación media obtenida en los alumnos fue de 4,1 sobre 5. Como aspectos positivos destacan: facilidad de uso, incorporación de fotografías de alimentos para elegir el tamaño de ración/porción. Como aspectos de mejora señalan: incorporar más fotos de alimentos, el poder instalar el programa para su uso en un ordenador. Según los egresados, el principal punto fuerte es tener reunido en un solo programa los tres aspectos de la evaluación del estado nutricional. Como puntos débiles señalan la falta de algún nutriente, como los azucares, en la base de datos nutricional. Conclusión: Nutrire® es un programa de fácil utilización, muy bien valorada por los alumnos y por los egresados para realizar estudios de evaluación del estado nutricional.

Radiotórax.es: una herramienta para la evaluación on-line de las capacidades interpretativas en radiografía de tórax.

Introducción La radiografía de tórax es una de las técnicas diagnósticas más importantes ya que aporta gran cantidad de información para el diagnóstico de enfermedades respiratorias y cardíacas. Es la prueba radiológica más usada en urgencias, ampliamente utilizada por especialistas de radiología, por médicos de familia y otras especialidades (intensivistas, neumólogos, anestesistas, internistas, pediatras y cardiólogos). Su correcta interpretación es fundamental, pues con frecuencia influye en la toma de decisión para el manejo del paciente. La autoevaluación, metodología poco explorada en nuestro entorno, es una parte del proceso educativo que fomenta la reflexión sobre las competencias adquiridas del individuo en formación, donde el alumno se evalúa para progresar en su formación y no para superar una nota, eliminar una materia o establecer un orden de prelación con sus compañeros. Justificación y objetivos Los objetivos de este trabajo son: 1) desarrollar una aplicación informática que permita autoevaluar las habilidades interpretativas de la radiografía de tórax emulando una sesión de trabajo de 20 casos; 2) evaluar el funcionamiento e introducir mejoras en fases preliminares, y 3) analizar los hábitos de uso y las posibilidades formativas de la misma. Material y métodos Radiotórax.es es una herramienta Web de libre acceso por toda la comunidad, ubicada en la URL www.radiotorax.es. El sistema pretende emular una sesión de trabajo, informando 20 casos radiológicos , seleccionados aleatoriamente de una base de datos de 400, con una o dos proyecciones de tórax que debe informar disponiendo de una hora. Los informes y resultados se archivan en una base de datos y el usuario dispone de un documento pdf detallado de cada ronda de evaluación que realice. Resultados Se analizan los resultados del global de usuarios registrados en la fase beta de desarrollo de la aplicación ( 30/05/2011 - 31/08/2011) y durante el período comprendido entre el 01/09/2011 hasta el 31/12/2013 de la fase definitiva de la aplicación, que sigue vigente en la actualidad. La autoevaluación en Radiotorax.es guarda correlación con el grado de experiencia y nivel de aprendizaje del usuario, obteniéndose mejores resultados los grupos con mayor experiencia y formación. Además el 75.7% de los usuarios mejoró en evaluaciones sucesivas. Conclusiones Radiotorax.es es un proyecto educativo de interés en pregrado y en la formación continuada de postgrado que persigue como objetivo facilitar la autoevaluación en habilidades interpretativas de radiología de tórax. Es una aplicación gratuita, de acceso libre, que se puede utilizar con cualquier sistema operativo y cualquier navegador Web y permite realizar autoevaluaciones sucesivas, modificando los casos y manteniendo la misma proporción de dificultad. Proporciona un documento pdf con toda la información de cada evaluación completada accesible por el usuario, lo que le permite controlar su evolución en el aprendizaje. Los estudios sobre la interpretación de radiografías de tórax por diferentes colectivos subrayan que la formación es esencial para disminuir el número de errores en la interpretación de radiografías de tórax y resaltan la necesidad de disponer de herramientas formativas de tipo práctico para mejorar la habilidad interpretando radiografías torácicas, como Radiotorax.es.