Characterization of proteotoxic stress in zebrafish

A fidelidade da síntese proteica é fundamental para a estabilidade do proteoma e para a homeostasia celular. Em condições fisiológicas normais as células têm uma taxa de erro basal associada e esta muitas vezes aumenta com o envelhecimento e doença. Problemas na síntese das proteínas estão associados a várias doenças humanas e aos processos de envelhecimento. De facto, a incorporação de erros nas proteínas devido a tRNAs carregados pelas aminoacil-tRNA sintetases com o amino ácido errado causa doenças neurodegenerativas em humanos e ratos. Ainda não é claro como é que estas doenças se desenvolvem e se são uma consequência directa da disrupção do proteoma ou se são o resultado da toxicidade produzida pela acúmulação de proteínas mal traduzidas ao nível do ribossoma. Para elucidar como é que as células eucarióticas lidam com proteínas aberrantes e agregados proteicos (stress proteotóxico) desenvolvemos uma estratégia para destabilizar o proteoma. Para isso estabelecemos um sistema de erros de tradução em embriões de peixe zebra que assenta em tRNAs mutantes capazes de incorporar erradamente serina nas proteínas. As proteínas produzidas neste sistema despoletam as vias de resposta ao stress, nomeadamente a via da ubiquitina-proteassoma (UPP – “ubiquitin protesome pathway”) e a via do retículo endoplasmático (UPR – “unfolded protein response”). O stress proteotóxico gerado pelos erros de tradução altera a expressão génica e perfis de expressão de miRNAs, o desenvolvimento embrionário e viabilidade, aumenta a produção de espécies reactivas de oxigénio (ROS), leva ainda à acumulação de agregados proteicos e à disfunção mitocondrial. As malformações embrionárias e fenótipos de viabilidade que observámos foram revertidos por antioxidantes, o que sugere que os ROS desempenham papéis importantes nos fenótipos degenerativos celulares induzidos pela produção de proteínas aberrantes e agregação proteica. Estabelecemos ainda uma linha de peixe zebra transgénica para o estudo do stress proteotóxico. Este trabalho mostra que a destabilização do proteoma em embriões de peixe zebra com tRNAs mutantes é uma boa metodologia para estudar a biologia do stress proteotóxico visto que permite a agregação controlada do proteoma, mimetizando os processos de agregação de proteínas que ocorrem naturalmente durante o envelhecimento e em doenças conformacionais humanas.

SIC and PIC multiuser detection for prefix-assisted DS-CDMA systems

In this paper we present iterative frequency-domain multiuser detection (MUD) receivers for the uplink transmission of direct sequence code division multiple access systems (DS-CDMA) that combine iterative block decision feedback equalization (IB-DFE) principles with interference cancelation techniques. Both successive interference cancelation (SIC) and parallel interference cancelation (PIC) structures are considered. Our performance results show that the proposed receiver structures have excellent bit error rate (BER) performances, that can be close to the single-user matched filter bound (MFB), even for fully loaded systems and severely time-dispersive channels1.

Análise comparativa das técnicas de transmissão com modulação exterma PDSB, OSSB e OCS

Dissertação de Mestrado, Engenharia Eléctrica e Electrónica, Ramo de Tecnologias de Informação e Telecomunicações, Instituto Superior de Engenharia, Universidade do Algarve, 2009

Living and dealing with RF impairments in communication transceivers

This paper provides an overview of the sources and effects of the RF impairments limiting and rendering the performance of the future wireless communication transceivers costly as well as hindering their wide-spread use in commercial products. As transmission bandwidths and carrier frequencies increase effect of these impairments worsen. This paper studies and presents analytical evaluations of the performance degradation due to the RF impairments in terms of bit-error-rate and image rejection ratio. The paper also give highlights of the various aspects of the research carried out in mitigating the effects of these impairments primarily in the digital signal processing domain at the baseband as well as providing low-complexity hardware implementations of such algorithms incorporating a number of power and area saving techniques.

The modified Max-Log-MAP turbo decoding algorithm by extrinsic information scaling for wireless applications

The iterative nature of turbo-decoding algorithms increases their complexity compare to conventional FEC decoding algorithms. Two iterative decoding algorithms, Soft-Output-Viterbi Algorithm (SOVA) and Maximum A posteriori Probability (MAP) Algorithm require complex decoding operations over several iteration cycles. So, for real-time implementation of turbo codes, reducing the decoder complexity while preserving bit-error-rate (BER) performance is an important design consideration. In this chapter, a modification to the Max-Log-MAP algorithm is presented. This modification is to scale the extrinsic information exchange between the constituent decoders. The remainder of this chapter is organized as follows: An overview of the turbo encoding and decoding processes, the MAP algorithm and its simplified versions the Log-MAP and Max-Log-MAP algorithms are presented in section 1. The extrinsic information scaling is introduced, simulation results are presented, and the performance of different methods to choose the best scaling factor is discussed in Section 2. Section 3 discusses trends and applications of turbo coding from the perspective of wireless applications.

Parallel decoding of turbo codes using multi-point trellis termination and collision-free interleavers

The UMTS turbo encoder is composed of parallel concatenation of two Recursive Systematic Convolutional (RSC) encoders which start and end at a known state. This trellis termination directly affects the performance of turbo codes. This paper presents performance analysis of multi-point trellis termination of turbo codes which is to terminate RSC encoders at more than one point of the current frame while keeping the interleaver length the same. For long interleaver lengths, this approach provides dividing a data frame into sub-frames which can be treated as independent blocks. A novel decoding architecture using multi-point trellis termination and collision-free interleavers is presented. Collision-free interleavers are used to solve memory collision problems encountered by parallel decoding of turbo codes. The proposed parallel decoding architecture reduces the decoding delay caused by the iterative nature and forward-backward metric computations of turbo decoding algorithms. Our simulations verified that this turbo encoding and decoding scheme shows Bit Error Rate (BER) performance very close to that of the UMTS turbo coding while providing almost %50 time saving for the 2-point termination and %80 time saving for the 5-point termination.

Increasing the speed of parallel decoding of turbo codes

Turbo codes experience a significant decoding delay because of the iterative nature of the decoding algorithms, the high number of metric computations and the complexity added by the (de)interleaver. The extrinsic information is exchanged sequentially between two Soft-Input Soft-Output (SISO) decoders. Instead of this sequential process, a received frame can be divided into smaller windows to be processed in parallel. In this paper, a novel parallel processing methodology is proposed based on the previous parallel decoding techniques. A novel Contention-Free (CF) interleaver is proposed as part of the decoding architecture which allows using extrinsic Log-Likelihood Ratios (LLRs) immediately as a-priori LLRs to start the second half of the iterative turbo decoding. The simulation case studies performed in this paper show that our parallel decoding method can provide %80 time saving compared to the standard decoding and %30 time saving compared to the previous parallel decoding methods at the expense of 0.3 dB Bit Error Rate (BER) performance degradation.

Agrupamento multi-orador

Actualmente tem-se observado um aumento do volume de sinais de fala em diversas aplicações, que reforçam a necessidade de um processamento automático dos ficheiros. No campo do processamento automático destacam-se as aplicações de “diarização de orador”, que permitem catalogar os ficheiros de fala com a identidade de oradores e limites temporais de fala de cada um, através de um processo de segmentação e agrupamento. No contexto de agrupamento, este trabalho visa dar continuidade ao trabalho intitulado “Detecção do Orador”, com o desenvolvimento de um algoritmo de “agrupamento multi-orador” capaz de identificar e agrupar correctamente os oradores, sem conhecimento prévio do número ou da identidade dos oradores presentes no ficheiro de fala. O sistema utiliza os coeficientes “Mel Line Spectrum Frequencies” (MLSF) como característica acústica de fala, uma segmentação de fala baseada na energia e uma estrutura do tipo “Universal Background Model - Gaussian Mixture Model” (UBM-GMM) adaptado com o classificador “Support Vector Machine” (SVM). No trabalho foram analisadas três métricas de discriminação dos modelos SVM e a avaliação dos resultados foi feita através da taxa de erro “Speaker Error Rate” (SER), que quantifica percentualmente o número de segmentos “fala” mal classificados. O algoritmo implementado foi ajustado às características da língua portuguesa através de um corpus com 14 ficheiros de treino e 30 ficheiros de teste. Os ficheiros de treino dos modelos e classificação final, enquanto os ficheiros de foram utilizados para avaliar o desempenho do algoritmo. A interacção com o algoritmo foi dinamizada com a criação de uma interface gráfica que permite receber o ficheiro de teste, processá-lo, listar os resultados ou gerar um vídeo para o utilizador confrontar o sinal de fala com os resultados de classificação.

Acompanhamento da construção de um edifício multifuncional e de duas moradias unifamiliares

Relatório de estágio para obtenção do grau de Mestre em Engenharia Civil na Área de Especialização em Edificações

Sistema de reconhecimento de impressões digitais baseado em FPGA

Trabalho de Projeto para obtenção do grau de Mestre em Engenharia de Eletrónica e Telecomunicações

IFN stimulated gene expression in the liver is a better predictor of treatment response in chronic hepatitis c than the IL28b (IFN lambda 3) genotype

Background: Therapy of chronic hepatitis C (CHC) with pegIFNa/ribavirin achieves sustained virologic response (SVR) in ~55%. Pre-activation of the endogenous interferon system in the liver is associated non-response (NR). Recently, genome-wide association studies described associations of allelic variants near the IL28B (IFNλ3) gene with treatment response and with spontaneous clearance of the virus. We investigated if the IL28B genotype determines the constitutive expression of IFN stimulated genes (ISGs) in the liver of patients with CHC. Methods: We genotyped 93 patients with CHC for 3 IL28B single nucleotide polymorphisms (SNPs, rs12979860, rs8099917, rs12980275), extracted RNA from their liver biopsies and quantified the expression of IL28B and of 8 previously identified classifier genes which discriminate between SVR and NR (IFI44L, RSAD2, ISG15, IFI22, LAMP3, OAS3, LGALS3BP and HTATIP2). Decision tree ensembles in the form of a random forest classifier were used to calculate the relative predictive power of these different variables in a multivariate analysis. Results: The minor IL28B allele (bad risk for treatment response) was significantly associated with increased expression of ISGs, and, unexpectedly, with decreased expression of IL28B. Stratification of the patients into SVR and NR revealed that ISG expression was conditionally independent from the IL28B genotype, i.e. there was an increased expression of ISGs in NR compared to SVR irrespective of the IL28B genotype. The random forest feature score (RFFS) identified IFI27 (RFFS = 2.93), RSAD2 (1.88) and HTATIP2 (1.50) expression and the HCV genotype (1.62) as the strongest predictors of treatment response. ROC curves of the IL28B SNPs showed an AUC of 0.66 with an error rate (ERR) of 0.38. A classifier with the 3 best classifying genes showed an excellent test performance with an AUC of 0.94 and ERR of 0.15. The addition of IL28B genotype information did not improve the predictive power of the 3-gene classifier. Conclusions: IL28B genotype and hepatic ISG expression are conditionally independent predictors of treatment response in CHC. There is no direct link between altered IFNλ3 expression and pre-activation of the endogenous system in the liver. Hepatic ISG expression is by far the better predictor for treatment response than IL28B genotype.

Streamlining the medication process improves safety in the intensive care unit.

BACKGROUND: Multiple interventions were made to optimize the medication process in our intensive care unit (ICU). 1 Transcriptions from the medical order form to the administration plan were eliminated by merging both into a single document; 2 the new form was built in a logical sequence and was highly structured to promote completeness and standardization of information; 3 frequently used drug names, approved units, and fixed routes were pre-printed; 4 physicians and nurses were trained with regard to the correct use of the new form. This study was aimed at evaluating the impact of these interventions on clinically significant types of medication errors. METHODS: Eight types of medication errors were measured by a prospective chart review before and after the interventions in the ICU of a public tertiary care hospital. We used an interrupted time-series design to control the secular trends. RESULTS: Over 85 days, 9298 lines of drug prescription and/or administration to 294 patients, corresponding to 754 patient-days were collected and analysed for the three series before and three series following the intervention. Global error rate decreased from 4.95 to 2.14% (-56.8%, P < 0.001). CONCLUSIONS: The safety of the medication process in our ICU was improved by simple and inexpensive interventions. In addition to the optimization of the prescription writing process, the documentation of intravenous preparation, and the scheduling of administration, the elimination of the transcription in combination with the training of users contributed to reducing errors and carried an interesting potential to increase safety.

Frontal Lobe Function and Performance Monitoring following Total Sleep Deprivation

Imaging studies have shown reduced frontal lobe resources following total sleep deprivation (TSD). The anterior cingulate cortex (ACC) in the frontal region plays a role in performance monitoring and cognitive control; both error detection and response inhibition are impaired following sleep loss. Event-related potentials (ERPs) are an electrophysiological tool used to index the brain's response to stimuli and information processing. In the Flanker task, the error-related negativity (ERN) and error positivity (Pe) ERPs are elicited after erroneous button presses. In a Go/NoGo task, NoGo-N2 and NoGo-P3 ERPs are elicited during high conflict stimulus processing. Research investigating the impact of sleep loss on ERPs during performance monitoring is equivocal, possibly due to task differences, sample size differences and varying degrees of sleep loss. Based on the effects of sleep loss on frontal function and prior research, it was expected that the sleep deprivation group would have lower accuracy, slower reaction time and impaired remediation on performance monitoring tasks, along with attenuated and delayed stimulus- and response-locked ERPs. In the current study, 49 young adults (24 male) were screened to be healthy good sleepers and then randomly assigned to a sleep deprived (n = 24) or rested control (n = 25) group. Participants slept in the laboratory on a baseline night, followed by a second night of sleep or wake. Flanker and Go/NoGo tasks were administered in a battery at 1O:30am (i.e., 27 hours awake for the sleep deprivation group) to measure performance monitoring. On the Flanker task, the sleep deprivation group was significantly slower than controls (p's <.05), but groups did not differ on accuracy. No group differences were observed in post-error slowing, but a trend was observed for less remedial accuracy in the sleep deprived group compared to controls (p = .09), suggesting impairment in the ability to take remedial action following TSD. Delayed P300s were observed in the sleep deprived group on congruent and incongruent Flanker trials combined (p = .001). On the Go/NoGo task, the hit rate (i.e., Go accuracy) was significantly lower in the sleep deprived group compared to controls (p <.001), but no differences were found on false alarm rates (i.e., NoGo Accuracy). For the sleep deprived group, the Go-P3 was significantly smaller (p = .045) and there was a trend for a smaller NoGo-N2 compared to controls (p = .08). The ERN amplitude was reduced in the TSD group compared to controls in both the Flanker and Go/NoGo tasks. Error rate was significantly correlated with the amplitude of response-locked ERNs in control (r = -.55, p=.005) and sleep deprived groups (r = -.46, p = .021); error rate was also correlated with Pe amplitude in controls (r = .46, p=.022) and a trend was found in the sleep deprived participants (r = .39, p =. 052). An exploratory analysis showed significantly larger Pe mean amplitudes (p = .025) in the sleep deprived group compared to controls for participants who made more than 40+ errors on the Flanker task. Altered stimulus processing as indexed by delayed P3 latency during the Flanker task and smaller amplitude Go-P3s during the Go/NoGo task indicate impairment in stimulus evaluation and / or context updating during frontal lobe tasks. ERN and NoGoN2 reductions in the sleep deprived group confirm impairments in the monitoring system. These data add to a body of evidence showing that the frontal brain region is particularly vulnerable to sleep loss. Understanding the neural basis of these deficits in performance monitoring abilities is particularly important for our increasingly sleep deprived society and for safety and productivity in situations like driving and sustained operations.

Development of a Blood Antigen Molecular Profiling Panel using Genotyping Technologies for Patients Requiring Frequent Transfusions

Contexte. Les phénotypes ABO et Rh(D) des donneurs de sang ainsi que des patients transfusés sont analysés de façon routinière pour assurer une complète compatibilité. Ces analyses sont accomplies par agglutination suite à une réaction anticorps-antigènes. Cependant, pour des questions de coûts et de temps d’analyses faramineux, les dons de sang ne sont pas testés sur une base routinière pour les antigènes mineurs du sang. Cette lacune peut résulter à une allo-immunisation des patients receveurs contre un ou plusieurs antigènes mineurs et ainsi amener des sévères complications pour de futures transfusions. Plan d’étude et Méthodes. Pour ainsi aborder le problème, nous avons produit un panel génétique basé sur la technologie « GenomeLab _SNPstream» de Beckman Coulter, dans l’optique d’analyser simultanément 22 antigènes mineurs du sang. La source d’ADN provient des globules blancs des patients préalablement isolés sur papiers FTA. Résultats. Les résultats démontrent que le taux de discordance des génotypes, mesuré par la corrélation des résultats de génotypage venant des deux directions de l’ADN, ainsi que le taux d’échec de génotypage sont très bas (0,1%). Également, la corrélation entre les résultats de phénotypes prédit par génotypage et les phénotypes réels obtenus par sérologie des globules rouges et plaquettes sanguines, varient entre 97% et 100%. Les erreurs expérimentales ou encore de traitement des bases de données ainsi que de rares polymorphismes influençant la conformation des antigènes, pourraient expliquer les différences de résultats. Cependant, compte tenu du fait que les résultats de phénotypages obtenus par génotypes seront toujours co-vérifiés avant toute transfusion sanguine par les technologies standards approuvés par les instances gouvernementales, les taux de corrélation obtenus sont de loin supérieurs aux critères de succès attendus pour le projet. Conclusion. Le profilage génétique des antigènes mineurs du sang permettra de créer une banque informatique centralisée des phénotypes des donneurs, permettant ainsi aux banques de sang de rapidement retrouver les profiles compatibles entre les donneurs et les receveurs.

Redundancy gain : manifestations, causes and predictions

Les temps de réponse dans une tache de reconnaissance d’objets visuels diminuent de façon significative lorsque les cibles peuvent être distinguées à partir de deux attributs redondants. Le gain de redondance pour deux attributs est un résultat commun dans la littérature, mais un gain causé par trois attributs redondants n’a été observé que lorsque ces trois attributs venaient de trois modalités différentes (tactile, auditive et visuelle). La présente étude démontre que le gain de redondance pour trois attributs de la même modalité est effectivement possible. Elle inclut aussi une investigation plus détaillée des caractéristiques du gain de redondance. Celles-ci incluent, outre la diminution des temps de réponse, une diminution des temps de réponses minimaux particulièrement et une augmentation de la symétrie de la distribution des temps de réponse. Cette étude présente des indices que ni les modèles de course, ni les modèles de coactivation ne sont en mesure d’expliquer l’ensemble des caractéristiques du gain de redondance. Dans ce contexte, nous introduisons une nouvelle méthode pour évaluer le triple gain de redondance basée sur la performance des cibles doublement redondantes. Le modèle de cascade est présenté afin d’expliquer les résultats de cette étude. Ce modèle comporte plusieurs voies de traitement qui sont déclenchées par une cascade d’activations avant de satisfaire un seul critère de décision. Il offre une approche homogène aux recherches antérieures sur le gain de redondance. L’analyse des caractéristiques des distributions de temps de réponse, soit leur moyenne, leur symétrie, leur décalage ou leur étendue, est un outil essentiel pour cette étude. Il était important de trouver un test statistique capable de refléter les différences au niveau de toutes ces caractéristiques. Nous abordons la problématique d’analyser les temps de réponse sans perte d’information, ainsi que l’insuffisance des méthodes d’analyse communes dans ce contexte, comme grouper les temps de réponses de plusieurs participants (e. g. Vincentizing). Les tests de distributions, le plus connu étant le test de Kolmogorov- Smirnoff, constituent une meilleure alternative pour comparer des distributions, celles des temps de réponse en particulier. Un test encore inconnu en psychologie est introduit : le test d’Anderson-Darling à deux échantillons. Les deux tests sont comparés, et puis nous présentons des indices concluants démontrant la puissance du test d’Anderson-Darling : en comparant des distributions qui varient seulement au niveau de (1) leur décalage, (2) leur étendue, (3) leur symétrie, ou (4) leurs extrémités, nous pouvons affirmer que le test d’Anderson-Darling reconnait mieux les différences. De plus, le test d’Anderson-Darling a un taux d’erreur de type I qui correspond exactement à l’alpha tandis que le test de Kolmogorov-Smirnoff est trop conservateur. En conséquence, le test d’Anderson-Darling nécessite moins de données pour atteindre une puissance statistique suffisante.