Language impairment in a case of a complex chromosomal rearrangement with a breakpoint downstream of FOXP2

BACKGROUND: We report on a young female, who presents with a severe speech and language disorder and a balanced de novo complex chromosomal rearrangement, likely to have resulted from a chromosome 7 pericentromeric inversion, followed by a chromosome 7 and 11 translocation. RESULTS: Using molecular cytogenetics, we mapped the four breakpoints to 7p21.1-15.3 (chromosome position: 20,954,043-21,001,537, hg19), 7q31 (chromosome position: 114,528,369-114,556,605, hg19), 7q21.3 (chromosome position: 93,884,065-93,933,453, hg19) and 11p12 (chromosome position: 38,601,145-38,621,572, hg19). These regions contain only non-coding transcripts (ENSG00000232790 on 7p21.1 and TCONS_00013886, TCONS_00013887, TCONS_00014353, TCONS_00013888 on 7q21) indicating that no coding sequences are directly disrupted. The breakpoint on 7q31 mapped 200 kb downstream of FOXP2, a well-known language gene. No splice site or non-synonymous coding variants were found in the FOXP2 coding sequence. We were unable to detect any changes in the expression level of FOXP2 in fibroblast cells derived from the proband, although this may be the result of the low expression level of FOXP2 in these cells. CONCLUSIONS: We conclude that the phenotype observed in this patient either arises from a subtle change in FOXP2 regulation due to the disruption of a downstream element controlling its expression, or from the direct disruption of non-coding RNAs.

Influência do tipo de chuteira em variáveis preditoras do risco de entorse lateral do tornozelo

Introdução: No futebol, a entorse lateral do tornozelo (ELT) destaca-se como sendo a lesão mais prevalente. Potenciada pela variedade de chuteiras disponíveis no mercado e pela crescente utilização de relvados sintéticos, a interação entre o terreno e o calçado tem assumido elevada relevância como fator de risco para a ELT. A maior incidência de lesões na 2ª parte do jogo traduz a necessidade do estudo dessa interação durante tarefas que envolvam fadiga. Objetivo: Estudar a influência das chuteiras em variáveis preditoras do risco de ELT em relvado sintético sob duas condições: sem e com fadiga dos músculos eversores do tornozelo Métodos: Foi utilizada uma amostra de atletas saudáveis. Todos os indivíduos realizaram 3 séries de 5 saltos médio-laterais uni-podálicos, cada uma com 1 de 3 modelos de chuteiras (Turf, Hard e Firm ground) em duas condições: sem e com fadiga induzida pelo dinamómetro isocinético. Durante a tarefa, a atividade eletromiográfica do longo e curto peroniais, o valor das forças de reação do solo e o movimento do retro-pé (plano frontal), foram recolhidos e usados para calcular variáveis cinemáticas (eversão/inversão do tornozelo, o deslocamento e velocidade do centro de pressão), cinéticas (taxa de crescimento das forças de reação do solo) e neuromusculares (tempo de ativação muscular dos peroniais). Resultados: À exceção do tempo de ativação do curto peronial com o modelo Hard ground (sem fadiga vs com fadiga (p=0,050), não foram identificadas diferenças estatisticamente significativas nas variáveis preditoras de lesão, entre chuteiras, nem entre as duas condições avaliadas. Conclusão: Para o teste funcional escolhido e executado por atletas saudáveis em sintético de 3ª geração, nenhuma das chuteiras apresenta maior risco de lesão (com e sem fadiga), tendo em conta as variáveis em estudo.

Representations of Portugal in Herman Hesse

The aim of my research is to answer the question: How is Portugal seen by non-Portuguese fictionists? The main reason why I chose this research line is the following: Portuguese essayists like Eduardo Lourenço and José Gil (2005) focus their attention on the image or representation of Portugal as conceived by the Portuguese; indeed there is a tendency in Portuguese cultural studies (and, to a certain extent, also in Portuguese philosophical studies) to focus on studying the so-called ‗portugalidade‘ (portugueseness), i.e., the essence of being Portuguese. In my view, the problem with the studies I have been referring to is that everything is self-referential, and if ‗portugueseness‘ is an issue, then it might be useful, when dealing with it, to separate subject from object of observation. That is the reason why we, in the CEI (Centro de Estudos Interculturais), decided to start this research line, which is an inversion in the current tendency of the studies about ‗portugueseness‘: instead of studying the image or representation of Portugal by the Portuguese, my task is to study the image or representation of Portugal by the non-Portuguese, in this case, in non-Portuguese fiction. For the present paper I selected three writers of the 20th century: the German Hermann Hesse and the North-Americans Philip Roth and Paul Auster

Some reflections on acquisition, processing and analysis of statistical data in forest soils

Beyond the classical statistical approaches (determination of basic statistics, regression analysis, ANOVA, etc.) a new set of applications of different statistical techniques has increasingly gained relevance in the analysis, processing and interpretation of data concerning the characteristics of forest soils. This is possible to be seen in some of the recent publications in the context of Multivariate Statistics. These new methods require additional care that is not always included or refered in some approaches. In the particular case of geostatistical data applications it is necessary, besides to geo-reference all the data acquisition, to collect the samples in regular grids and in sufficient quantity so that the variograms can reflect the spatial distribution of soil properties in a representative manner. In the case of the great majority of Multivariate Statistics techniques (Principal Component Analysis, Correspondence Analysis, Cluster Analysis, etc.) despite the fact they do not require in most cases the assumption of normal distribution, they however need a proper and rigorous strategy for its utilization. In this work, some reflections about these methodologies and, in particular, about the main constraints that often occur during the information collecting process and about the various linking possibilities of these different techniques will be presented. At the end, illustrations of some particular cases of the applications of these statistical methods will also be presented.

Radioactivity studies in Porto urban area: gamma radiation of Paranhos sector

A set of radiation measurements were carried out in several public and private institutions. These were selected with basis on the people affluence and passage to these sites. These measurements were registration formed either indoor, outdoor or underground and were compiled in three Case Studies. Radiation doses measurements were also made, surface and underground locations, and compiled in other two Case Studies. There were sampled, at the same time, humidity, temperature, atmospheric pressure and relevant construction materials at sampling locations. They were collected and registration formed to analyse if there is any relation or contribution for the measured value in each specific place. Geostatistical models were used to elaborate maps of the results both for radiation values and for doses. Preliminary relations were established among the measured parameters.

Groundwater quality, vulnerability and potential assessment in Kobo Valley development project, Ethiopia

This study deals with investigating the groundwater quality for irrigation purpose, the vulnerability of the aquifer system to pollution and also the aquifer potential for sustainable water resources development in Kobo Valley development project. The groundwater quality is evaluated up on predicting the best possible distribution of hydrogeochemicals using geostatistical method and comparing them with the water quality guidelines given for the purpose of irrigation. The hydro geochemical parameters considered are SAR, EC, TDS, Cl-, Na+, Ca++, SO4 2- and HCO3 -. The spatial variability map reveals that these parameters falls under safe, moderate and severe or increasing problems. In order to present it clearly, the aggregated Water Quality Index (WQI) map is constructed using Weighted Arithmetic Mean method. It is found that Kobo-Gerbi sub basin is suffered from bad water quality for the irrigation purpose. Waja Golesha sub-basin has moderate and Hormat Golena is the better sub basin in terms of water quality. The groundwater vulnerability assessment of the study area is made using the GOD rating system. It is found that the whole area is experiencing moderate to high risk of vulnerability and it is a good warning for proper management of the resource. The high risks of vulnerability are noticed in Hormat Golena and Waja Golesha sub basins. The aquifer potential of the study area is obtained using weighted overlay analysis and 73.3% of the total area is a good site for future water well development. The rest 26.7% of the area is not considered as a good site for spotting groundwater wells. Most of this area fall under Kobo-Gerbi sub basin.

Trading the changes of stock market index composition: Evidence from European markets

This paper studies the changes in European stock market indexes composition from 1995 to 2015. It was found that there are mixed price effects producing abnormal returns around the effective replacement of added and deleted stocks. The price pressure hypothesis seems to hold for added stocks in some indexes but not for deleted stocks as there is not a clear inversion of behaviour after the replacement. Finally, the building and back testing of a trading strategy aiming to capture some of those abnormal returns shows it yields a Sharpe Ratio of 1.4 and generates an annualised alpha of 11%.

Metodologias de Sistemas de Informação Geográfica em sistemas de produção florestal : uma aplicação geoestatística

As florestas são uma fonte importante de recursos naturais, desempenhando um papel fulcral na sustentabilidade ambiental. A sua gestão quer territorial quer económica, conduz a uma maximização da produção, sem alteração da qualidade da matéria-prima. Portugal apresenta mais de um terço do seu território coberto por floresta, apresentando uma possibilidade de aplicação de sistemas de gestão, territorial e económica que maximizem a sua produção. Os Sistemas de Informação Geográfica (SIG) são modelos da realidade em que é possível integrar toda a informação disponível sobre um assunto tendo por base um campo comum a todos as variáveis, a localização geográfica. Os SIG podem contribuir de diversas formas para um maior desenvolvimento das rotinas e ferramentas de planeamento e gestão florestal. A sua integração com modelos quantitativos para planeamento e gestão de florestas é uma mais-valia nesta área. Nesta dissertação apresentam-se modelos geoestatísticos, com recurso a Sistemas de Informação Geográfica, de apoio e suporte à produção de pinha em Pinheiro-manso (Pinus pinea L.). Procurando estimar as áreas com melhor propensão à produção, a partir de dados amostrais. Estes foram previamente estudados tendo sido selecionadas quatro variáveis: largura da copa, área basal, altura da árvore e produção de pinha. A geoestatística aplicada, inclui modelos de correlação espacial: kriging, onde são atribuídos pesos às amostras a partir de uma análise espacial baseada no variograma experimental. Foi utilizada a extensão Geostatistical Analyst do ArcGis da ESRI, para realizar 96 krigings para as quatro variáveis em estudo, com diferentes parametrizações, destes foram selecionados 8 krigings. Com base nos critérios de adequação dos modelos e da análise de resultados da predição dos erros - cross validation. O resultado deste estudo é apresentado através de mapas de previsão para a produção de pinha em Pinheiro manso, em que foram analisadas áreas com maior e menor probabilidade de produção tendo-se realizado análises de comparação de variáveis. Através da interseção de todas as variáveis com a produção, podemos concluir que os concelhos com maiores áreas de probabilidade de produção de pinha em Pinheiro manso, da área de estudo, são Alcácer do Sal, Montemor-o-Novo, Vendas Novas, Coruche e Chamusca. Com a realização de um cruzamento de dados entre os resultados obtidos dos krigings, e a Carta de Uso e Ocupação do Solo de Portugal Continental para 2007 (COS2007), realizaram-se mapas de previsão para a expansão do Pinheiro manso. Nas áreas de expansão conseguimos atingir aumentos mínimos na ordem dos 11% e máximo na ordem dos 61%. No total consegue-se atingir aproximadamente 128 mil ha para área de expansão do Pinheiro manso. Superando, os valores esperados pelos Planos Regionais de Ordenamento Florestal, abrangidos pela área da amostra em estudo, em que é esperado um incremento de cerca de 130 mil hectares de área de Pinheiro manso para 2030.

Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas.

Pediatric follicular lymphoma is a rare disease that differs genetically and clinically from its adult counterpart. With the exception of pediatric follicular lymphoma with IRF4-translocation, the genetic events associated with these lymphomas have not yet been defined. We applied array-comparative genomic hybridization and molecular inversion probe assay analyses to formalin-fixed paraffin-embedded tissues from 18 patients aged 18 years and under with IRF4 translocation negative follicular lymphoma. All evaluable cases lacked t(14;18). Only 6 of 16 evaluable cases displayed chromosomal imbalances with gains or amplifications of 6pter-p24.3 (including IRF4) and deletion and copy number neutral-loss of heterozygosity in 1p36 (including TNFRSF14) being most frequent. Sequencing of TNFRSF14 located in the minimal region of loss in 1p36.32 showed nine mutations in 7 cases from our series. Two subsets of pediatric follicular lymphoma were delineated according to the presence of molecular alterations, one with genomic aberrations associated with higher grade and/or diffuse large B-cell lymphoma component and more widespread disease, and another one lacking genetic alterations associated with more limited disease.

Simple method for detection of MYH11 DNA rearrangements in patients with inv(16)(p13q22) and acute myeloid leukemia.

The pericentric inversion on chromosome 16 [inv(16)(p13q22)] and related t(16;16)(p13;q22) are recurrent aberrations associated with acute myeloid leukemia (AML) M4 Eo. Both abberations result in a fusion of the core binding factor beta (CBFB) and smooth muscle myosin heavy chain gene (MYH11). A selected genomic 6.9-kb BamHl probe detects MYH11 DNA rearrangements in 18 of 19 inv(16)/t(16;16) patients tested using HindIII digested DNA. The rearranged fragments were not detectable after remission in two cases tested, while they were present after relapse in one of these two cases tested.

Adaptive MCMC methods with applications in environmental and geophysical models

This work presents new, efficient Markov chain Monte Carlo (MCMC) simulation methods for statistical analysis in various modelling applications. When using MCMC methods, the model is simulated repeatedly to explore the probability distribution describing the uncertainties in model parameters and predictions. In adaptive MCMC methods based on the Metropolis-Hastings algorithm, the proposal distribution needed by the algorithm learns from the target distribution as the simulation proceeds. Adaptive MCMC methods have been subject of intensive research lately, as they open a way for essentially easier use of the methodology. The lack of user-friendly computer programs has been a main obstacle for wider acceptance of the methods. This work provides two new adaptive MCMC methods: DRAM and AARJ. The DRAM method has been built especially to work in high dimensional and non-linear problems. The AARJ method is an extension to DRAM for model selection problems, where the mathematical formulation of the model is uncertain and we want simultaneously to fit several different models to the same observations. The methods were developed while keeping in mind the needs of modelling applications typical in environmental sciences. The development work has been pursued while working with several application projects. The applications presented in this work are: a winter time oxygen concentration model for Lake Tuusulanjärvi and adaptive control of the aerator; a nutrition model for Lake Pyhäjärvi and lake management planning; validation of the algorithms of the GOMOS ozone remote sensing instrument on board the Envisat satellite of European Space Agency and the study of the effects of aerosol model selection on the GOMOS algorithm.

Large amplitude motions in the S1 state of formic acid /

A detailed theoretical investigation of the large amplitude motions in the S, excited electronic state of formic acid (HCOOH) was done. This study focussed on the the S, «- So electronic band system of formic acid (HCOOH). The torsion and wagging large amplitude motions of the S, were considered in detail. The potential surfaces were simulated using RHF/UHF ab-initio calculations for the two electronic states. The energy levels were evaluated by the variational method using free rotor basis functions for the torsional coordinates and harmonic oscillator basis functions for the wagging coordinates. The simulated spectrum was compared to the slit-jet-cooled fluorescence excitation spectrum allowing for the assignment of several vibronic bands. A rotational analysis of certain bands predicted that the individual bands are a mixture of rotational a, b and c-type components.The electronically allowed transition results in the c-type or Franck-Condon band and the electronically forbidden, but vibronically allowed transition creates the a/b-type or Herzberg-Teller components. The inversion splitting between these two band types differs for each band. The analysis was able to predict the ratio of the a, b and c-type components of each band.

Enantiodivergent chemoenzymatic synthesis of codeine

The present thesis describes our latest results in the chemistry of morphine alkaloids. An enantiodivergent synthesis of codeine utilizing a cis-cyclohexadiene diol derived from microbial whole cell oxidation of ~-bromoethylbenzene,as starting material is discussed. The total synthesis of (+)-codeine in 14 steps featuring a Mitsunobu inversion and two intramolecular Heck cyclizations is presented. Investigation of a regioselective nucleophilic opening of a homochiral vinyl oxirane, which led to a total synthesis of the natural isomer of codeine, is detailed. Furthermore, described herein are novel methodologies designed for the transformation of naturally occurring opiates into medicinally relevant derivatives. Two studies on the conversion of thebaine into the commercially available analgesic hydrocodone, two novel ·transition metal catalyzed N-demethylation procedures for opioids, and the development of a catalytic protocol for N-demethylation and Nacylation of morphine and tropane alkaloids are presented. In addition, reactions of a menthol-based version of the Burgess reagent with epoxides are discussed. The synthetic utility of this novel chiral derivative of the Burgess reagent was demonstrated by an enantiodivergent formal total synthesis of balanol. ii