Muscle signaling in exercise intolerance: Insights from the McArdle mouse model

We recently generated a knock-in mouse model (PYGM p.R50X/p.R50X) of McArdle disease (myophosphorylase deficiency). One mechanistic approach to unveil the molecular alterations caused by myophosphorylase deficiency, which is arguably the paradigm of 'exercise intolerance', is to compare the skeletal-muscle tissue of McArdle, heterozygous, and healthy (wild type (wt)) mice. We analyzed in quadriceps muscle of p.R50X/p.R50X (n=4), p.R50X/wt (n=6) and wt/wt mice (n=5) (all male, 8 wk-old) molecular markers of energy-sensing pathways, oxidative phosphorylation (OXPHOS) and autophagy/proteasome systems, oxidative damage and sarcoplamic reticulum (SR) Ca handling. We found a significant group effect for total AMPK (tAMPK) and ratio of phosphorylated (pAMPK)/tAMPK (P=0.012 and 0.033), with higher mean values in p.R50X/p.R50X mice vs. the other two groups. The absence of massive accumulation of ubiquitinated proteins, autophagosomes or lysosomes in p.R50X/p.R50X mice suggested no major alterations in autophagy/proteasome systems. Citrate synthase activity was lower in p.R50X/p.R50X mice vs. the other two groups (P=0.036) but no statistical effect existed for respiratory chain complexes. We found higher levels of 4-hydroxy-2-nonenal-modified proteins in p.R50X/p.R50X and p.R50X/wt mice compared with the wt/wt group (P=0.011). Sarco(endo)plasmic reticulum ATPase 1 (SERCA1) levels detected at 110kDa tended to be higher in p.R50X/p.R50X and p.R50X/wt mice compared with wt/wt animals (P=0.076), but their enzyme activity was normal. We also found an accumulation of phosphorylated SERCA1 in p.R50X/p.R50X animals. Myophosphorylase deficiency causes alterations in sensory energetic pathways together with some evidence of oxidative damage and alterations in Ca handling but with no major alterations in OXPHOS capacity or autophagy/ubiquitination pathways, which suggests that the muscle tissue of patients is likely to adapt overall favorably to exercise training interventions.

Kontakty społeczności Europy środkowej i strefy egejskiej w drugim tysiącleciu przed Chr. Próba analizy archeologiczno-chronometrycznej

Wydział Historyczny: Instytut Prahistorii

L’équivalence des clitiques français en et y en espagnol: problèmes de traduction

info:eu-repo/semantics/published

Art as an educative and social tool

Since remote times, certain sectors of society have been exposed to inequality and vulnerability, where adequate intervention processes have become conspicuous because of their absence. Nowadays, current societies have the responsibility of contributing, based on their experience and knowledge, with more efficient policies and programs that improve the life quality of the most disadvantaged. It is here where art and its different tools play a very important role, not only on a physical level, but also as an education tool that allows the development of emotional, mental and communicative skills. The aim of this paper is to make clear the potential of art as an instrument of social and educational intervention. It starts by showing worldwide-collected experience related to education and arts, and then, it acquaints the reader with two parallel intervention projects that worked with youths under social vulnerability conditions. These interventions were developed based on a qualitative research (Grounded theory), using as methodology “The Artistic Mediation” with emphasis on body language. This methodology helped researchers to get close to the participants and to know their experiences and emotions. At the same time, it was possible to evidence the positive effects of educative interventions through art. These workshops were based on an artistic methodology especially focused on body language. Data in this work is qualitative, and as such, it permits a special approach to the personal and emotional experiences of the participants; clearly showing the positive effects of the referenced practice on them.

The in-service teacher trainer: profile, career path and duties

This article is the result of a doctoral thesis that aims to understand the reality of teacher trainers at a given moment, when their professional role changes from being a managing training advisor to a role that is more centred on process counselling. Using in-depth interviews, we defined the personal and professional profile of training counsellors in the Balearic Islands, their career path, the process for their inclusion in Teacher Centres (CEP) and, finally, the duties and skills that they perform as teacher trainers. The data that has been collected shows the coexistence of different professional roles in the group of education advisors. Moreover, it also indicates a lack of definition of the profile needed to access an advisor's position. There are indeed some coincidences determining the access route to such a position when it comes to the teaching profession since their leadership qualities and group dynamics expertise are a common indicator in most cases. The research also shows that they are subjected not only to a wide range of roles and tasks but also to a vast array of competences required to tackle the education advisor's tasks.

Pattern Switching Compact Patch Antenna for On-body and Off-body Communications at 2.45 GHz

The ability to switch between propagating modes is important for body-centric applications such as medical body area networks where a single node may need to be able to optimise communications for either on-body sensor links or off-body links to the wider network. Therefore, we present a compact 2.45 GHz active mode-switching wearable antenna for both on-body and off-body wireless communications. The single-layer patch antenna was pattern-switched using shorting pins and had an impedance bandwidth of 253 MHz and 217 MHz for the on-body and off-body radiating modes, respectively. An efficiency of 57 % and 56.8 % was obtained for on-body and off-body mode respectively when placed in close proximity to a phantom that represents a muscle issue at 2.45 GHz.

Image processing chip for small object detection

A new, front-end image processing chip is presented for real-time small object detection. It has been implemented using a 0.6 µ, 3.3 V CMOS technology and operates on 10-bit input data at 54 megasamples per second. It occupies an area of 12.9 mm×13.6 mm (including pads), dissipates 1.5 W, has 92 I/O pins and is to be housed in a 160-pin ceramic quarter flat-pack. It performs both one- and two-dimensional FIR filtering and a multilayer perceptron (MLP) neural network function using a reconfigurable array of 21 multiplication-accumulation cells which corresponds to a window size of 7×3. The chip can cope with images of 2047 pixels per line and can be cascaded to cope with larger window sizes. The chip performs two billion fixed point multiplications and additions per second.

64-point Fourier transform chip for digital television applications

A 64-point Fourier transform chip is described that performs a forward or inverse, 64-point Fourier transform on complex two's complement data supplied at a rate of 13.5MHz and can operate at clock rates of up to 40MHz, under worst-case conditions. It uses a 0.6µm double-level metal CMOS technology, contains 535k transistors and uses an internal 3.3V power supply. It has an area of 7.8×8mm, dissipates 0.9W, has 48 pins and is housed in a 84 pin PLCC plastic package. The chip is based on a FFT architecture developed from first principles through a detailed investigation of the structure of the relevant DFT matrix and through mapping repetitive blocks within this matrix onto a regular silicon structure.

PROSTATIC INTRAEPITHELIAL NEOPLASIA (PIN) - PERFORMANCE OF BAYESIAN BELIEF NETWORK FOR DIAGNOSIS AND GRADING

Prostatic intraepithelial neoplasia (PIN) diagnosis and grading are affected by uncertainties which arise from the fact that almost all knowledge of PIN histopathology is expressed in concepts, descriptive linguistic terms, and words. A Bayesian belief network (BBN) was therefore used to reduce the problem of uncertainty in diagnostic clue assessment, while still considering the dependences between elements in the reasoning sequence. A shallow network was used with an open-tree topology, with eight first-level descendant nodes for the diagnostic clues (evidence nodes), each independently linked by a conditional probability matrix to a root node containing the diagnostic alternatives (decision node). One of the evidence nodes was based on the tissue architecture and the others were based on cell features. The system was designed to be interactive, in that the histopathologist entered evidence into the network in the form of likelihood ratios for outcomes at each evidence node. The efficiency of the network was tested on a series of 110 prostate specimens, subdivided as follows: 22 cases of non-neoplastic prostate or benign prostatic tissue (NP), 22 PINs of low grade (PINlow), 22 PINs of high grade (PINhigh), 22 prostatic adenocarcinomas with cribriform pattern (PACcri), and 22 prostatic adenocarcinomas with large acinar pattern (PAClgac). The results obtained in the benign and malignant categories showed that the belief for the diagnostic alternatives is very high, the values being in general more than 0.8 and often close to 1.0. When considering the PIN lesions, the network classified and graded most of the cases with high certainty. However, there were some cases which showed values less than 0.8 (13 cases out of 44), thus indicating that there are situations in which the feature changes are intermediate between contiguous categories or grades. Discrepancy between morphological grading and the BBN results was observed in four out of 44 PIN cases: one PINlow was classified as PINhigh and three PINhigh were classified as PINlow. In conclusion, the network can grade PlN lesions and differentiate them from other prostate lesions with certainty. In particular, it offers a descriptive classifier which is readily implemented and which allows the use of linguistic, fuzzy variables.

Papel da assessoria na auto-avaliação das escolas

Esta tese apresenta uma investigação que procura problematizar o papel da assessoria na auto-avaliação das escolas. Reflecte-se sobre o contributo de assessores externos nas unidades de gestão para encontrar fórmulas que permitam a construção e sustentabilidade da sua auto-avaliação através da concepção, monitorização e avaliação de planos de acção. A investigação consubstanciou-se na análise dos relatórios das 100 unidades orgânicas que participaram na avaliação externa em 2006/2007 promovida pela Inspecção-Geral de Educação (IGE) especificamente no domínio da Capacidade de Auto-Regulação e Melhoria da Escola (CARME), no Questionário a 90 participantes em equipas de auto-avaliação e ainda em todo o trabalho de campo realizado numa escola secundária através de observação participante. Durante a investigação percebeu-se a adaptação de alguns modelos de auto-avaliação de carácter gerencialista à realidade das unidades orgânicas, identificam-se alguns obstáculos que se apresentam à aplicação dos referidos modelos, as dificuldades que as referidas unidades de gestão sentem quando autonomamente se querem auto-avaliar e identificam-se mecanismos utilizados para a concretização da auto-avaliação e sua manutenção ao longo do tempo. Por fim, constata-se que a assessoria externa é um pilar que pode contribuir para a introdução efectiva dos referidos mecanismos de auto-avaliação e sua sustentabilidade.

Behavioral modeling optimization and enhancement for high-speed analog mixed-signal I/O interfaces

A integridade do sinal em sistemas digitais interligados de alta velocidade, e avaliada através da simulação de modelos físicos (de nível de transístor) é custosa de ponto vista computacional (por exemplo, em tempo de execução de CPU e armazenamento de memória), e exige a disponibilização de detalhes físicos da estrutura interna do dispositivo. Esse cenário aumenta o interesse pela alternativa de modelação comportamental que descreve as características de operação do equipamento a partir da observação dos sinais eléctrico de entrada/saída (E/S). Os interfaces de E/S em chips de memória, que mais contribuem em carga computacional, desempenham funções complexas e incluem, por isso, um elevado número de pinos. Particularmente, os buffers de saída são obrigados a distorcer os sinais devido à sua dinâmica e não linearidade. Portanto, constituem o ponto crítico nos de circuitos integrados (CI) para a garantia da transmissão confiável em comunicações digitais de alta velocidade. Neste trabalho de doutoramento, os efeitos dinâmicos não-lineares anteriormente negligenciados do buffer de saída são estudados e modulados de forma eficiente para reduzir a complexidade da modelação do tipo caixa-negra paramétrica, melhorando assim o modelo standard IBIS. Isto é conseguido seguindo a abordagem semi-física que combina as características de formulação do modelo caixa-negra, a análise dos sinais eléctricos observados na E/S e propriedades na estrutura física do buffer em condições de operação práticas. Esta abordagem leva a um processo de construção do modelo comportamental fisicamente inspirado que supera os problemas das abordagens anteriores, optimizando os recursos utilizados em diferentes etapas de geração do modelo (ou seja, caracterização, formulação, extracção e implementação) para simular o comportamento dinâmico não-linear do buffer. Em consequência, contributo mais significativo desta tese é o desenvolvimento de um novo modelo comportamental analógico de duas portas adequado à simulação em overclocking que reveste de um particular interesse nas mais recentes usos de interfaces de E/S para memória de elevadas taxas de transmissão. A eficácia e a precisão dos modelos comportamentais desenvolvidos e implementados são qualitativa e quantitativamente avaliados comparando os resultados numéricos de extracção das suas funções e de simulação transitória com o correspondente modelo de referência do estado-da-arte, IBIS.