An extensible complex fast Fourier transform processor chip for real-time spectrum analysis and measurement

This paper describes in detail the design of a CMOS custom fast Fourier transform (FFT) processor for computing a 256-point complex FFT. The FFT is well-suited for real-time spectrum analysis in instrumentation and measurement applications. The FFT butterfly processor reported here consists of one parallel-parallel multiplier and two adders. It is capable of computing one butterfly computation every 100 ns thus it can compute a 256-point complex FFT in 102.4 μs excluding data input and output processes.

An integrated 256-point complex FFT processor for real-time spectrum analysis and measurement

This paper describes in detail the design of a custom CMOS Fast Fourier Transform (FFT) processor for computing 256-point complex FFT. The FFT is well suited for real-time spectrum analysis in instrumentation and measurement applications. The FFT butterfly processor consists of one parallel-parallel multiplier and two adders. It is capable of computing one butterfly computation every 100 ns thus it can compute 256-complex point FFT in 25.6 μs excluding data input and output processes.

Spectrum of Somatic Hypermutations and Implication on Antibody Function: Case of the anti HIV-1 antibody, b12

Thesis (Ph.D.)--University of Washington, 2015

Diagnostic value of H3F3A mutations in giant cell tumour of bone compared to osteoclast-rich mimics

Driver mutations in the two histone 3.3 (H3.3) genes, H3F3A and H3F3B, were recently identified by whole genome sequencing in 95% of chondroblastoma (CB) and by targeted gene sequencing in 92% of giant cell tumour of bone (GCT). Given the high prevalence of these driver mutations, it may be possible to utilise these alterations as diagnostic adjuncts in clinical practice. Here, we explored the spectrum of H3.3 mutations in a wide range and large number of bone tumours (n 5 412) to determine if these alterations could be used to distinguish GCT from other osteoclast-rich tumours such as aneurysmal bone cyst, nonossifying fibroma, giant cell granuloma, and osteoclast-rich malignant bone tumours and others. In addition, we explored the driver landscape of GCT through whole genome, exome and targeted sequencing (14 gene panel). We found that H3.3 mutations, namely mutations of glycine 34 in H3F3A, occur in 96% of GCT. We did not find additional driver mutations in GCT, including mutations in IDH1, IDH2, USP6, TP53. The genomes of GCT exhibited few somatic mutations, akin to the picture seen in CB. Overall our observations suggest that the presence of H3F3A p.Gly34 mutations does not entirely exclude malignancy in osteoclast-rich tumours. However, H3F3A p.Gly34 mutations appear to be an almost essential feature of GCT that will aid pathological evaluation of bone tumours, especially when confronted with small needle core biopsies. In the absence of H3F3A p.Gly34 mutations, a diagnosis of GCT should be made with caution.

Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20–RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response.

Práticas curriculares em jardim de infância com crianças com perturbações do espetro do autismo

Dissertação apresentada à Escola Superior de Educação de Lisboa para obtenção do grau de Mestre em Educação - Especialização em Educação Especial

Desenvolvimento de uma plataforma SIG para apoio ao estudo da sismicidade em Portugal

Trabalho Final de Mestrado elaborado no Laboratório Nacional de Engenharia Civil (LNEC) para a obtenção do grau de Mestre em Engenharia Civil pelo Instituto Superior de Engenharia de Lisboa no âmbito do protocolo de cooperação entre o ISEL e o LNEC

Thermographic and visible spectrum camera calibration for marine robotic target detection

Oceans - San Diego, 2013

Análise da sonolência na condução rodoviária a partir de sinais EEG

A Sociedade Europeia de Pesquisa do Sono realizou muito recentemente um estudo, onde mostrou que a prevalência média de adormecimento ao volante nos últimos 2 anos foi de 17%. Além disto, tem sido provado por todo o mundo que a sonolência durante a condução é uma das principais causas de acidentes de trânsito. Torna-se assim conveniente, o desenvolvimento de sistemas que analisem a suscetibilidade de um determinado condutor para adormecer no trânsito, bem como de ferramentas que monitorem em tempo real o estado físico e mental do condutor, para alertarem nos momentos críticos. Apesar do estudo do sono se ter iniciado há vários anos, a maioria das investigações focaram-se no ciclo normal do sono, estudando os indivíduos de forma relaxada e de olhos fechados. Só mais recentemente, têm surgido os estudos que se focam nas situações de sonolência em atividade, como _e o caso da condução. Uma grande parte Dos estudos da sonolência em condução têm utilizado a eletroencefalografia (EEG), de forma a perceber se existem alterações nas diferentes bandas de frequência desta, que possam indicar o estado de sonolência do condutor. Além disso, a evolução da sonolência a partir de alterações no piscar dos olhos (que podem ser vistas nos sinais EEG) também tem sido alvo de grande pesquisa, tendo vindo a revelar resultados bastante promissores. Neste contexto e em parceria com a empresa HealthyRoad, esta tese está integrada no projeto HealthyDrive, que visa o desenvolvimento de um sistema de alerta e deteção de sinais de fadiga e sonolência nos condutores de veículos automóveis. A contribuição desta tese no projeto prendeu-se com o estudo da sonolência dos indivíduos em condução a partir de sinais EEG, para desta forma investigar possíveis indicadores dos diferentes níveis desta que possam ser utilizados pela empresa no projeto. Foram recolhidos e analisados 17 sinais EEG de indivíduos em simulação de condução. Além disso foram desenvolvidos dois métodos de análise destes sinais: O primeiro para a deteção e análise dos piscar de olhos a partir de EEG, o segundo para análise do espetro de potência. Ambos os métodos foram utilizados para analisar os sinais recolhidos e investigar que tipo de relação existe entre a sonolência do condutor e as alterações nos piscares dos olhos, bem como as alterações do espetro do EEG. Os resultados mostraram uma correlação entre a duração do piscar de olhos e a sonolência do condutor. Com o aumento da sonolência velicou-se um aumento da duração do piscar, desencadeado principalmente pelo aumento na duração de fecho, que chegou aos 51.2%. Em relação ao espectro de potência, os resultados sugerem que a potência relativa de todas as bandas analisadas fornecem informações relevantes sobre a sonolência do condutor. Além disso, o parâmetro (_+_)/_ demostrou estar relacionado com variações da sonolência, diminuindo com o seu avanço e aumentando significativamente (111%) no instante em que os condutores adormeceram.

Spectrum and Frequency of GJB2 Mutations in a Cohort of 264 Portuguese Nonsyndromic Sensorineural Hearing Loss Patients

OBJECTIVE: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. DESIGN: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. STUDY SAMPLE: A cohort of 264 Portuguese NSSHL patients. RESULTS: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. CONCLUSIONS: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.

Interaction of malaria parasites with host late endocytic and autophagic pathways is essential for Plasmodium liver stage development

RESUMO: A Malária é causada por parasitas do género Plasmodium, sendo a doença parasitária mais fatal para o ser humano. Apesar de, durante o século passado, o desenvolvimento económico e a implementação de diversas medidas de controlo, tenham permitido erradicar a doença em muitos países, a Malária continua a ser um problema de saúde grave, em particular nos países em desenvolvimento. A Malária é transmitida através da picada de uma fêmea de mosquito do género Anopheles. Durante a picada, os esporozoítos são injetados na pele do hospedeiro, seguindo-se a fase hepática e obrigatória do ciclo de vida. No fígado, os esporozoítos infetam os hepatócitos onde se replicam, dentro de um vacúolo parasitário (VP) e de uma forma imunitária silenciosa, em centenas de merozoitos. Estas novas formas do parasita são as responsáveis por infetar os eritrócitos, iniciando a fase sanguínea da doença, onde se os primeiros sintomas se manifestam, tais como a característica febre cíclica. A fase hepática da doença é a menos estudada e compreendida. Mais ainda, as interações entre o VP e os organelos da células hospedeira estão ainda pouco caracterizados. Assim, neste estudo, as interações entre os organelos endocíticos e autofágicos da célula hospedeira e o VP foram dissecados, observando-se que os anfisomas, que são organelos resultantes da intersecção do dois processos de tráfego intracelular, interagem com o parasita. Descobrimos que a autofagia tem também uma importante função imunitária durante a fase hepática inicial, ao passo, que durante o desenvolvimento do parasita, já numa fase mais tardia, o parasita depende da interação com os endossomas tardios e anfisomas para crescer. Vesiculas de BSA, EGF e LC3, foram, também, observadas dentro do VP, sugerindo que os parasitas são capazes de internalizar material endocítico e autofágico do hospedeiro. Mais ainda, mostramos que esta interação depende da cinase PIKfyve, responsável pela conversão do fosfoinositidio-3-fosfato no fosfoinositidio-3,5-bifosfato, uma vez que inibindo esta cinase o parasita não é capaz de crescer normalmente. Finalmente, mostramos que a proteína TRPML1, uma proteína efetora do fosfoinositidio-3,5-bifosfato, e envolvida no processo de fusão das membranas dos organelos endocíticos e autofágicos, também é necessária para o crescimento do parasita. Desta forma, o nosso estudo sugere que a membrana do VP funde com vesiculas endocíticas e autofágicas tardias, de uma forma dependente do fositidio-3,5-bifosfato e do seu effetor TRPML1, permitindo a troca de material com a célula hospedeira. Concluindo, os nossos resultados evidenciam que o processo autofágico que ocorre na célula hospedeira tem um papel duplo durante a fase hepática da malaria. Enquanto numa fase inicial os hepatócitos usam o processo autofágico como forma de defesa contra o parasita, já durante a fase de replicação o VP funde com vesiculas autofágicas e endocíticas de forma a obter os nutrientes necessários ao seu desenvolvimento.--------- ABSTRACT: Malaria, which is caused by parasites of the genus Plasmodium, is the most deadly parasitic infection in humans. Although economic development and the implementation of control measures during the last century have erradicated the disease from many areas of the world, it remains a serious human health issue, particularly in developing countries. Malaria is transmitted by female mosquitoes of the genus Anopheles. During the mosquito blood meal, Plasmodium spp. sporozoites are injected into the skin dermis of the vertebrate host, followed by an obligatory liver stage. Upon entering the liver, Plasmodium parasites infect hepatocytes and silently replicate inside a host cell-derived parasitophorous vacuole (PV) into thousands of merozoites. These new parasite forms can infect red blood cells initiating the the blood stage of the disease which shows the characteristic febrile malaria episodes. The liver stage is the least characterized step of the malaria infection. Moreover, the interactions between the Plasmodium spp. PV and the host cell trafficking pathways are poorly understood. We dissected the interaction between Plasmodium parasites and the host cell endocytic and autophagic pathways and we found that both pathways intersect and interconnect in the close vicinity of the parasite PV, where amphisomes are formed and accumulate. Interestingly, we observed a clearance function for autophagy in hepatocytes infected with Plasmodium berghei parasites at early infection times, whereas during late liver stage development late endosomes and amphisomes are required for parasite growth. Moreover, we found the presence of internalized BSA, EGF and LC3 inside parasite vacuoles, suggesting that the parasites uptake endocytic and autophagic cargo. Furthermore, we showed that the interaction between the PV and host traffic pathways is dependent on the kinase PIKfyve, which converts the phosphoinositide PI(3)P into PI(3,5)P2, since PIKfyve inhibition caused a reduction in parasite growth. Finally, we showed that the PI(3,5)P2 effector protein TRPML1, which is involved in late endocytic and autophagic membrane fusion, is also required for parasite development. Thus, our studies suggest that the parasite parasitophorous vacuole membrane (PVM) is able to fuse with late endocytic and autophagic vesicles in a PI(3,5)P2- and TRPML1-dependent manner, allowing the exchange of material between the host cell and the parasites, necessary for the rapid development of the latter that is seen during the liver stage of infection. In conclusion, we present evidence supporting a specific and essential dual role of host autophagy during the course of Plasmodium liver infection. Whereas in the initial hours of infection the host cell uses autophagy as a cell survival mechanism to fight the infection, during the replicative phase the PV fuses with host autophagic and endocytic vesicles to obtain nutrients required for parasite growth.

Determinants of mother-baby relationship evaluated during pregnancy

ABSTRACT Background Mental health promotion is supported by a strong body of knowledge and is a matter of public health with the potential of a large impact on society. Mental health promotion programs should be implemented as soon as possible in life, preferably starting during pregnancy. Programs should focus on malleable determinants, introducing strategies to reduce risk factors or their impact on mother and child, and also on strengthening protective factors to increase resilience. The ambition of early detecting risk situations requires the development and use of tools to assess risk, and the creation of a responsive network of services based in primary health care, especially maternal consultation during pregnancy and the first months of the born child. The number of risk factors and the way they interact and are buffered by protective factors are relevant for the final impact. Maternal-fetal attachment (MFA) is not yet a totally understood and well operationalized concept. Methodological problems limit the comparison of data as many studies used small size samples, had an exploratory character or used different selection criteria and different measures. There is still a lack of studies in high risk populations evaluating the consequences of a weak MFA. Instead, the available studies are not very conclusive, but suggest that social support, anxiety and depression, self-esteem and self-control and sense of coherence are correlated with MFA. MFA is also correlated with health practices during pregnancy, that influence pregnancy and baby outcomes. MFA seems a relevant concept for the future mother baby interaction, but more studies are needed to clarify the concept and its operationalization. Attachment is a strong scientific concept with multiple implications for future child development, personality and relationship with others. Secure attachment is considered an essential basis of good mental health, and promoting mother-baby interaction offers an excellent opportunity to intervention programmes targeted at enhancing mental health and well-being. Understanding the process of attachment and intervening to improve attachment requires a comprehension of more proximal factors, but also a broader approach that assesses the impact of more distal social conditions on attachment and how this social impact is mediated by family functioning and mother-baby interaction. Finally, it is essential to understand how this knowledge could be translated in effective mental health promoting interventions and measures that could reach large populations of pregnant mothers and families. Strengthening emotional availability (EA) seems to be a relevant approach to improve the mother-baby relationship. In this review we have offered evidence suggesting a range of determinants of mother-infant relationship, including age, marital relationship, social disadvantages, migration, parental psychiatric disorders and the situations of abuse or neglect. Based on this theoretical background we constructed a theoretical model that included proximal and distal factors, risk and protective factors, including variables related to the mother, the father, their social support and mother baby interaction from early pregnancy until six months after birth. We selected the Antenatal Psychosocial Health Assessment (ALPHA) for use as an instrument to detect psychosocial risk during pregnancy. Method Ninety two pregnant women were recruited from the Maternal Health Consultation in Primary Health Care (PHC) at Amadora. They had three moments of assessment: at T1 (until 12 weeks of pregnancy) they filed out a questionnaire that included socio-demographic data, ALPHA, Edinburgh post-natal Depression Scale (EDPS), General Health Questionnaire (GHQ) and Sense of Coherence (SOC); at T2 (after the 20th weeks of pregnancy) they answered EDPS, SOC and MFA Scale (MFAS), and finally at T3 (6 months after birth), they repeated EDPS and SOC, and their interaction with their babies was videotaped and later evaluated using EA Scales. A statistical analysis has been done using descriptive statistics, correlation analysis, univariate logistic regression and multiple linear regression. Results The study has increased our knowledge on this particular population living in a multicultural, suburb community. It allow us to identify specific groups with a higher level of psychosocial risk, such as single or divorced women, young couples, mothers with a low level of education and those who are depressed or have a low SOC. The hypothesis that psychosocial risk is directly correlated with MFAS and that MFA is directly correlated with EA was not confirmed, neither the correlation between prenatal psychosocial risk and mother-baby EA. The study identified depression as a relevant risk factor in pregnancy and its higher prevalence in single or divorced women, immigrants and in those who have a higher global psychosocial risk. Depressed women have a poor MFA, and a lower structuring capacity and a higher hostility to their babies. In average, depression seems to reduce among pregnant women in the second part of their pregnancy. The children of immigrant mothers show a lower level of responsiveness to their mothers what could be transmitted through depression, as immigrant mothers have a higher risk of depression in the beginning of pregnancy and six months after birth. Young mothers have a low MFA and are more intrusive. Women who have a higher level of education are more sensitive and their babies showed to be more responsive. Women who are or have been submitted to abuse were found to have a higher level of MFA but their babies are less responsive to them. The study highlights the relevance of SOC as a potential protective factor while it is strongly and negatively related with a wide range of risk factors and mental health outcomes especially depression before, during and after pregnancy. Conclusions ALPHA proved to be a valid, feasible and reliable instrument to Primary Health Care (PHC) that can be used as a total sum score. We could not prove the association between psychosocial risk factors and MFA, neither between MFA and EA, or between psychosocial risk and EA. Depression and SOC seems to have a clear and opposite relevance on this process. Pregnancy can be considered as a maturational process and an opportunity to change, where adaptation processes occur, buffering risk, decreasing depression and increasing SOC. Further research is necessary to better understand interactions between variables and also to clarify a better operationalization of MFA. We recommend the use of ALPHA, SOC and EDPS in early pregnancy as a way of identifying more vulnerable women that will require additional interventions and support in order to decrease risk. At political level we recommend the reinforcement of Immigrant integration and the increment of education in women. We recommend more focus in health care and public health in mental health condition and psychosocial risk of specific groups at high risk. In PHC special attention should be paid to pregnant women who are single or divorced, very young, low educated and to immigrant mothers. This study provides the basis for an intervention programme for this population, that aims to reduce broad spectrum risk factors and to promote Mental Health in women who become pregnant. Health and mental health policies should facilitate the implementation of the suggested measures.

Help-seeking for 'memory loss' by older adults in India : patient, caregiver and health providers' perspectives

ABSTRACT: Background. In India, prevalence rates of dementia and prodromal amnestic Mild Cognitive Impairment (MCI) are 3.1% and 4.3% respectively. Most Indians refer to the full spectrum of cognitive disorders simply as ‘memory loss.’ Barring prevention or cure, these conditions will rise rapidly with population aging. Evidence-based policies and practices can improve the lives of affected individuals and their caregivers, but will require timely and sustained uptake. Objectives. Framed by social cognitive theories of health behavior, this study explores the knowledge, attitudes and practices concerning cognitive impairment and related service use by older adults who screen positive for MCI, their primary caregivers, and health providers. Methods. I used the Montreal Cognitive Assessment to screen for cognitive impairment in memory camps in Mumbai. To achieve sampling diversity, I used maximum variation sampling. Ten adults aged 60+ who had no significant functional impairment but screened positive for MCI and their caregivers participated in separate focus groups. Four other such dyads and six doctors/ traditional healers completed in-depth interviews. Data were translated from Hindi or Marathi to English and analyzed in Atlas.ti using Framework Analysis. Findings. Knowledge and awareness of cognitive impairment and available resources were very low. Physicians attributed the condition to disease-induced pathology while lay persons blamed brain malfunction due to normal aging. Main attitudes were that this condition is not a disease, is not serious and/or is not treatable, and that it evokes stigma toward and among impaired persons, their families and providers. Low knowledge and poor attitudes impeded help-seeking. Conclusions. Cognitive disorders of aging will take a heavy toll on private lives and public resources in developing countries. Early detection, accurate diagnosis, systematic monitoring and quality care are needed to compress the period of morbidity and promote quality of life. Key stakeholders provide essential insights into how scientific and indigenous knowledge and sociocultural attitudes affect use and provision of resources.