FMRI 3D registration based on Fourier space subsets using neural networks

In this work, we present a neural network (NN) based method designed for 3D rigid-body registration of FMRI time series, which relies on a limited number of Fourier coefficients of the images to be aligned. These coefficients, which are comprised in a small cubic neighborhood located at the first octant of a 3D Fourier space (including the DC component), are then fed into six NN during the learning stage. Each NN yields the estimates of a registration parameter. The proposed method was assessed for 3D rigid-body transformations, using DC neighborhoods of different sizes. The mean absolute registration errors are of approximately 0.030 mm in translations and 0.030 deg in rotations, for the typical motion amplitudes encountered in FMRI studies. The construction of the training set and the learning stage are fast requiring, respectively, 90 s and 1 to 12 s, depending on the number of input and hidden units of the NN. We believe that NN-based approaches to the problem of FMRI registration can be of great interest in the future. For instance, NN relying on limited K-space data (possibly in navigation echoes) can be a valid solution to the problem of prospective (in frame) FMRI registration.

Mutation accumulation in Tetrahymena

Background - The rate and fitness effects of mutations are key in understanding the evolution of every species. Traditionally, these parameters are estimated in mutation accumulation experiments where replicate lines are propagated in conditions that allow mutations to randomly accumulate without the purging effect of natural selection. These experiments have been performed with many model organisms but we still lack empirical estimates of the rate and effects of mutation in the protists. Results - We performed a mutation accumulation (MA) experiment in Tetrahymena thermophila, a species that can reproduce sexually and asexually in nature, and measured both the mean decline and variance increase in fitness of 20 lines. The results obtained with T. thermophila were compared with T. pyriformis that is an obligate asexual species. We show that MA lines of T. thermophila go to extinction at a rate of 1.25 clonal extinctions per bottleneck. In contrast, populations of T. pyriformis show a much higher resistance to extinction. Variation in gene copy number is likely to be a key factor in explaining these results, and indeed we show that T. pyriformis has a higher mean copy number per cell than T. thermophila. From fitness measurements during the MA experiment, we infer a rate of mutation to copy number variation of 0.0333 per haploid MAC genome of T. thermophila and a mean effect against copy number variation of 0.16. A strong effect of population size in the rate of fitness decline was also found, consistent with the increased power of natural selection. Conclusions - The rate of clonal extinction measured for T. thermophila is characteristic of a mutational degradation and suggests that this species must undergo sexual reproduction to avoid the deleterious effects detected in the laboratory experiments. We also suggest that an increase in chromosomal copy number associated with the phenotypic assortment of amitotic divisions can provide an alternative mechanism to escape the deleterious effect of random chromosomal copy number variation in species like T. pyriformis that lack the resetting mechanism of sexual reproduction. Our results are relevant to the understanding of cell line longevity and senescence in ciliates.

Besnoitia besnoiti protein disulfide isomerase (BbPDI): molecular characterization, expression and in silico modelling

Besnoitia besnoiti is an apicomplexan parasite responsible for bovine besnoitiosis, a disease with a high prevalence in tropical and subtropical regions and re-emerging in Europe. Despite the great economical losses associated with besnoitiosis, this disease has been underestimated and poorly studied, and neither an effective therapy nor an efficacious vaccine is available. Protein disulfide isomerase (PDI) is an essential enzyme for the acquisition of the correct three-dimensional structure of proteins. Current evidence suggests that in Neosporacaninum and Toxoplasmagondii, which are closely related to B. besnoiti, PDI play an important role in host cell invasion, is a relevant target for the host immune response, and represents a promising drug target and/or vaccine candidate. In this work, we present the nucleotide sequence of the B. besnoiti PDI gene. BbPDI belongs to the thioredoxin-like superfamily (cluster 00388) and is included in the PDI_a family (cluster defined cd02961) and the PDI_a_PDI_a'_c subfamily (cd02995). A 3D theoretical model was built by comparative homology using Swiss-Model server, using as a template the crystallographic deduced model of Tapasin-ERp57 (PDB code 3F8U chain C). Analysis of the phylogenetic tree for PDI within the phylum apicomplexa reinforces the close relationship among B. besnoiti, N. caninum and T. gondii. When subjected to a PDI-assay based on the polymerisation of reduced insulin, recombinant BbPDI expressed in E. coli exhibited enzymatic activity, which was inhibited by bacitracin. Antiserum directed against recombinant BbPDI reacted with PDI in Western blots and by immunofluorescence with B. besnoiti tachyzoites and bradyzoites.

Projecto suspensão formula student

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Controlo clássico vs. preditivo na regulação de frequência em sistemas de potência

Dissertação para obtenção do grau de Mestre em Engenharia Electrotécnica Ramo Automação e Electrónica Industrial

Avaliação e optimização operacional: estudo do terminal de contentores de Alcântara

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica - Ramo Manutenção e Produção

Real time manufacturing systems simulator

A área da simulação computacional teve um rápido crescimento desde o seu apareciment, sendo actualmente uma das ciências de gestão e de investigação operacional mais utilizadas. O seu princípio baseia-se na replicação da operação de processos ou sistemas ao longo de períodos de tempo, tornando-se assim uma metodologia indispensável para a resolução de variados problemas do mundo real, independentemente da sua complexidade. Das inúmeras áreas de aplicação, nos mais diversos campos, a que mais se destaca é a utilização em sistemas de produção, onde o leque de aplicações disponível é muito vasto. A sua aplicação tem vindo a ser utilizada para solucionar problemas em sistemas de produção, uma vez que permite às empresas ajustar e planear de uma maneira rápida, eficaz e ponderada as suas operações e os seus sistemas, permitindo assim uma rápida adaptação das mesmas às constantes mudanças das necessidades da economia global. As aplicações e packages de simulação têm seguindo as tendências tecnológicas pelo que é notório o recurso a tecnologias orientadas a objectos para o desenvolvimento das mesmas. Este estudo baseou-se, numa primeira fase, na recolha de informação de suporte aos conceitos de modelação e simulação, bem como a respectiva aplicação a sistemas de produção em tempo real. Posteriormente centralizou-se no desenvolvimento de um protótipo de uma aplicação de simulação de ambientes de fabrico em tempo real. O desenvolvimento desta ferramenta teve em vista eventuais fins pedagógicos e uma utilização a nível académico, sendo esta capaz de simular um modelo de um sistema de produção, estando também dotada de animação. Sem deixar de parte a possibilidade de integração de outros módulos ou, até mesmo, em outras plataformas, houve ainda a preocupação acrescida de que a sua implementação recorresse a metodologias de desenvolvimento orientadas a objectos.

Novel FGFR1 Mutations in Kallmann Syndrome and Normosmic Idiopathic Hypogonadotropic Hypogonadism: Evidence for the Involvement of an Alternatively Spliced Isoform

OBJECTIVE: To determine the prevalence of fibroblast growth factor receptor 1 (FGFR1) mutations and their predicted functional consequences in patients with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: Cross-sectional study. SETTING: Multicentric. PATIENT(S): Fifty unrelated patients with IHH (21 with Kallmann syndrome and 29 with normosmic IHH). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Patients were screened for mutations in FGFR1. The functional consequences of mutations were predicted by in silico structural and conservation analysis. RESULT(S): Heterozygous FGFR1 mutations were identified in six (12%) kindreds. These consisted of frameshift mutations (p.Pro33-Alafs*17 and p.Tyr654*) and missense mutations in the signal peptide (p.Trp4Cys), in the D1 extracellular domain (p.Ser96Cys) and in the cytoplasmic tyrosine kinase domain (p.Met719Val). A missense mutation was identified in the alternatively spliced exon 8A (p.Ala353Thr) that exclusively affects the D3 extracellular domain of FGFR1 isoform IIIb. Structure-based and sequence-based prediction methods and the absence of these variants in 200 normal controls were all consistent with a critical role for the mutations in the activity of the receptor. Oligogenic inheritance (FGFR1/CHD7/PROKR2) was found in one patient. CONCLUSION(S): Two FGFR1 isoforms, IIIb and IIIc, result from alternative splicing of exons 8A and 8B, respectively. Loss-of-function of isoform IIIc is a cause of IHH, whereas isoform IIIb is thought to be redundant. Ours is the first report of normosmic IHH associated with a mutation in the alternatively spliced exon 8A and suggests that this disorder can be caused by defects in either of the two alternatively spliced FGFR1 isoforms.

Desenvolvimento de um BMS para aplicações de mobilidade elétrica

Dissertação de mestrado integrado em Engenharia Eletrónica Industrial e de Computadores

Projeto de produção de tubo elíptico em aço avançado de elevada resistência para uma serra de arco

Dissertação de mestrado integrado em Engenharia Mecânica

Groupes diagnostiques utilisés sur SIMULIT 14

Un premier exercice avait proposé un regroupement des diagnostics pour la planification des lits. Ce regroupement avait été établi empiriquement sur une base de données provenant des hôpitaux de zone vaudois (1983-1984). Lorsqu'il s'est agi d'appliquer cette grille au Centre Hospitalier Universitaire Vaudois (CHUV), il est rapidement apparu que la structure de la clientèle d'un tel hôpital rendait indispensable le remaniement de la grille descriptive. C'est l'objet du présent cahier... [Auteurs]

Una arqueometria del canvi tecnològic: producció i consum d'àmfores durant el canvi d'era en la zona nord de la costa catalana

L’objectiu de la recerca és definir un marc teòric i metodològic per a l’estudi del canvi tecnològic en Arqueologia. Aquest model posa èmfasi en caracteritzar els compromisos que configuren una tecnologia i avaluar-los en funció dels factors de situació —tècnics, econòmics, polítics, socials i ideològics. S’ha aplicat aquest model a un cas d’estudi concret: la producció d’àmfores romanes durant el canvi d’Era en la província Tarraconensis. L’estudi tecnològic dels envasos s’ha realitzat mitjançant diverses tècniques analítiques: Fluorescència de raigs X (FRX), Difracció de raigs X (DRX), Microscòpia òptica (MO) i Microscòpia electrònica de rastreig (MER). Les dades obtingudes permeten, a més, establir els grups de referència per a cada centre productor d’àmfores i, així, identificar la provinença dels individus recuperats en els centres consumidors. Donat que les àmfores en estudi són artefactes dissenyats específicament per a ser estibats en una nau i servir com a envàs de transport, l’estudi inclou la caracterització de les propietats mecàniques de resistència a la fractura i de tenacitat. En aquest sentit, i per primera vegada, s’ha aplicat l’Anàlisi d’Elements Finits (AEF) per a conèixer el comportament dels diferents dissenys d’àmfora en ésser sotmesos a diverses forces d’ús. L’AEF permet simular per ordinador les activitats en què les àmfores haurien participat durant el seu ús i avaluar-ne el seu comportament tècnic. Els resultats mostren una gran adequació entre les formulacions teòriques i el programa analític implementat per a aquest estudi. Respecte el cas d’estudi, els resultats mostren una gran variabilitat en les eleccions tecnològiques preses pels ceramistes de diferents tallers, però també al llarg del període de funcionament d’un mateix taller. L’aplicació del model ha permès proposar una explicació al canvi de disseny de les àmfores romanes.

Comparing impact and cost-effectiveness of primary prevention strategies for lipid-lowering.

BACKGROUND: Lipid-lowering therapy is costly but effective at reducing coronary heart disease (CHD) risk. OBJECTIVE: To assess the cost-effectiveness and public health impact of Adult Treatment Panel III (ATP III) guidelines and compare with a range of risk- and age-based alternative strategies. DESIGN: The CHD Policy Model, a Markov-type cost-effectiveness model. DATA SOURCES: National surveys (1999 to 2004), vital statistics (2000), the Framingham Heart Study (1948 to 2000), other published data, and a direct survey of statin costs (2008). TARGET POPULATION: U.S. population age 35 to 85 years. Time Horizon: 2010 to 2040. PERSPECTIVE: Health care system. INTERVENTION: Lowering of low-density lipoprotein cholesterol with HMG-CoA reductase inhibitors (statins). OUTCOME MEASURE: Incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: Full adherence to ATP III primary prevention guidelines would require starting (9.7 million) or intensifying (1.4 million) statin therapy for 11.1 million adults and would prevent 20,000 myocardial infarctions and 10,000 CHD deaths per year at an annual net cost of $3.6 billion ($42,000/QALY) if low-intensity statins cost $2.11 per pill. The ATP III guidelines would be preferred over alternative strategies if society is willing to pay $50,000/QALY and statins cost $1.54 to $2.21 per pill. At higher statin costs, ATP III is not cost-effective; at lower costs, more liberal statin-prescribing strategies would be preferred; and at costs less than $0.10 per pill, treating all persons with low-density lipoprotein cholesterol levels greater than 3.4 mmol/L (>130 mg/dL) would yield net cost savings. RESULTS OF SENSITIVITY ANALYSIS: Results are sensitive to the assumptions that LDL cholesterol becomes less important as a risk factor with increasing age and that little disutility results from taking a pill every day. LIMITATION: Randomized trial evidence for statin effectiveness is not available for all subgroups. CONCLUSION: The ATP III guidelines are relatively cost-effective and would have a large public health impact if implemented fully in the United States. Alternate strategies may be preferred, however, depending on the cost of statins and how much society is willing to pay for better health outcomes. FUNDING: Flight Attendants' Medical Research Institute and the Swanson Family Fund. The Framingham Heart Study and Framingham Offspring Study are conducted and supported by the National Heart, Lung, and Blood Institute.

Modeling sequencing errors by combining Hidden Markov models.

Among the largest resources for biological sequence data is the large amount of expressed sequence tags (ESTs) available in public and proprietary databases. ESTs provide information on transcripts but for technical reasons they often contain sequencing errors. Therefore, when analyzing EST sequences computationally, such errors must be taken into account. Earlier attempts to model error prone coding regions have shown good performance in detecting and predicting these while correcting sequencing errors using codon usage frequencies. In the research presented here, we improve the detection of translation start and stop sites by integrating a more complex mRNA model with codon usage bias based error correction into one hidden Markov model (HMM), thus generalizing this error correction approach to more complex HMMs. We show that our method maintains the performance in detecting coding sequences.

Effects of selection and drift on G matrix evolution in a heterogeneous environment: a multivariate Qst-Fst Test with the freshwater snail Galba truncatula.

Unraveling the effect of selection vs. drift on the evolution of quantitative traits is commonly achieved by one of two methods. Either one contrasts population differentiation estimates for genetic markers and quantitative traits (the Q(st)-F(st) contrast) or multivariate methods are used to study the covariance between sets of traits. In particular, many studies have focused on the genetic variance-covariance matrix (the G matrix). However, both drift and selection can cause changes in G. To understand their joint effects, we recently combined the two methods into a single test (accompanying article by Martin et al.), which we apply here to a network of 16 natural populations of the freshwater snail Galba truncatula. Using this new neutrality test, extended to hierarchical population structures, we studied the multivariate equivalent of the Q(st)-F(st) contrast for several life-history traits of G. truncatula. We found strong evidence of selection acting on multivariate phenotypes. Selection was homogeneous among populations within each habitat and heterogeneous between habitats. We found that the G matrices were relatively stable within each habitat, with proportionality between the among-populations (D) and the within-populations (G) covariance matrices. The effect of habitat heterogeneity is to break this proportionality because of selection for habitat-dependent optima. Individual-based simulations mimicking our empirical system confirmed that these patterns are expected under the selective regime inferred. We show that homogenizing selection can mimic some effect of drift on the G matrix (G and D almost proportional), but that incorporating information from molecular markers (multivariate Q(st)-F(st)) allows disentangling the two effects.