Caracterização do “warpage” e sua variabilidade no processo produtivo de encapsulamento de circuitos integrados

Nos últimos anos a indústria de semicondutores, nomeadamente a produção de memórias, tem sofrido uma grande evolução. A necessidade de baixar custos de produção, assim como de produzir sistemas mais complexos e com maior capacidade, levou à criação da tecnologia WLP (Wafer Level Packaging). Esta tecnologia permite a produção de sistemas mais pequenos, simplificar o fluxo do processo e providenciar uma redução significativa do custo final do produto. A WLP é uma tecnologia de encapsulamento de circuitos integrados quando ainda fazem parte de wafers (bolachas de silício), em contraste com o método tradicional em que os sistemas são individualizados previamente antes de serem encapsulados. Com o desenvolvimento desta tecnologia, surgiu a necessidade de melhor compreender o comportamento mecânico do mold compound (MC - polímero encapsulante) mais especificamente do warpage (empeno) de wafers moldadas. O warpage é uma característica deste produto e deve-se à diferença do coeficiente de expansão térmica entre o silício e o mold compound. Este problema é observável no produto através do arqueamento das wafers moldadas. O warpage de wafers moldadas tem grande impacto na manufatura. Dependendo da quantidade e orientação do warpage, o transporte, manipulação, bem como, a processamento das wafers podem tornar-se complicados ou mesmo impossíveis, o que se traduz numa redução de volume de produção e diminuição da qualidade do produto. Esta dissertação foi desenvolvida na Nanium S.A., empresa portuguesa líder mundial na tecnologia de WLP em wafers de 300mm e aborda a utilização da metodologia Taguchi, no estudo da variabilidade do processo de debond para o produto X. A escolha do processo e produto baseou-se numa análise estatística da variação e do impacto do warpage ao longo doprocesso produtivo. A metodologia Taguchi é uma metodologia de controlo de qualidade e permite uma aproximação sistemática num dado processo, combinando gráficos de controlo, controlo do processo/produto, e desenho do processo para alcançar um processo robusto. Os resultados deste método e a sua correta implementação permitem obter poupanças significativas nos processos com um impacto financeiro significativo. A realização deste projeto permitiu estudar e quantificar o warpage ao longo da linha de produção e minorar o impacto desta característica no processo de debond. Este projecto permitiu ainda a discussão e o alinhamento entre as diferentes áreas de produção no que toca ao controlo e a melhoria de processos. Conseguiu–se demonstrar que o método Taguchi é um método eficiente no que toca ao estudo da variabilidade de um processo e otimização de parâmetros. A sua aplicação ao processo de debond permitiu melhorar ou a fiabilidade do processo em termos de garantia da qualidade do produto, como ao nível do aumento de produção.

Epidemiological analysis of bacterial strains involved in hospital infection in a University Hospital from Brazil

Hospital infections cause an increase in morbidity and mortality of hospitalized patients with significant rise in hospital costs. The aim of this work was an epidemiological analysis of hospital infection cases occurred in a public University Hospital in Rio de Janeiro. Hence, 238 strains were isolated from 14 different clinical materials of 166 patients hospitalized in the period between August 1995 and July 1997. The average age of the patients was 33.4 years, 72.9% used antimicrobials before having a positive culture. The most common risk conditions were surgery (19.3%), positive HIV or AIDS (18.1%) and lung disease (16.9%). 24 different bacterial species were identified, S. aureus (21%) and P. aeruginosa (18.5%) were predominant. Among 50 S. aureus isolated strains 36% were classified as MRSA (Methicillin Resistant S. aureus). The Gram negative bacteria presented high resistance to aminoglycosides and cephalosporins. A diarrhea outbreak, detected in high-risk neonatology ward, was caused by Salmonella serovar Infantis strain, with high antimicrobial resistance and a plasmid of high molecular weight (98Mda) containing virulence genes and positive for R factor.

Characterization and regulation of a bacterial sugar phosphatase of the haloalkanoate dehalogenase superfamily, AraL, from Bacillus subtilis

FEBS journal, Volume 278, Issue 14, pages 2511-2524, July 2011

Bacterial inter-species communication mediated by the autoinducer-2 signal

Dissertation presented to obtain the Ph.D degree in Biology by Universidade Nova de Lisboa, Instituto de Tecnologia Química e Biológica, Instituto Gulbenkian de Ciência.

Pyogenic abscesses and parasitic diseases

Parasitic diseases which during their course in the host switch the immune system from a T helper 1 to a T helper 2 response may be detrimental to the host, contributing to granuloma formation, eosinophilia, hyper-IgE, and increased susceptibility to bacterial and fungal infections. Patients and animals with acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S. mansoni association has also been well documented. The association of tropical pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara infection has recently been described in the same context. In tropical countries that may be an interesting explanation for the great morbidity of bacterial diseases. If the association of parasitic infections and pyogenic abscesses and/or fungal diseases are confirmed, there will be a strong case in favor of universal treatment for parasitic diseases to prevent or decrease the morbidity of superinfection with bacteria and fungi.

The role of ribonuclease R in bacterial adaptation to cold shock

RESUMO:Os microrganismos reagem à súbita descida de temperatura através de uma resposta adaptativa específica que assegura a sua sobrevivência em condições desfavoráveis. Esta adaptação inclui alterações na composição da membrana, na maquinaria de tradução e transcrição. A resposta ao choque térmico pelo frio induz uma repressão da transcrição. No entanto, a descida de temperatura induz a produção de um grupo de proteínas específicas que ajudam a ajustar/re-ajustar o metabolismo celular às novas condições ambientais. Em E. coli o processo de adaptação demora apenas quatro horas, no qual um grupo de proteínas específicas são induzidas. Depois desde período recomeça lentamente a produção de proteínas.A ribonuclease R, uma das proteínas induzidas durante o choque térmico pelo frio, é uma das principais ribonucleases em E. coli envolvidas na degradação do RNA. É uma exoribonuclease que degrada RNA de cadeia dupla, possui funções importantes na maturação e “turnover” do RNA, libertação de ribossomas e controlo de qualidade de proteínas e RNAs. O nível celular desta enzima aumenta até dez vezes após exposição ao frio e estabiliza em células na fase estacionária. A capacidade de degradar RNA de dupla cadeia é importante a baixas temperaturas quando as estruturas de RNA estão mais estáveis. No entanto, este mecanismo é desconhecido. Embora a resposta específica ao “cold shock” tenha sido descoberta há mais de duas décadas e o número de proteínas envolvidas sugerirem que esta adaptação é rápida e simples, continuamos longe de compreender este processo. No nosso trabalho pretendemos descobrir proteínas que interactuem com a RNase R em condições ambientais diferentes através do método “TAP-tag” e espectrometria de massa. A informação obtida pode ser utilizada para deduzir algumas das novas funções da RNase R durante a adaptação bacteriana ao frio e durante a fase estacionária. Mais importante ainda, RNase R poderá ser recrutada para um complexo de proteínas de elevado peso molecular durante o “cold-shock”.------------ABSTRACT:Microorganisms react to the rapid temperature downshift with a specific adaptative response that ensures their survival in unfavorable conditions. Adaptation includes changes in membrane composition, in translation and transcription machinery. Cold shock response leads to overall repression of translation. However, temperature downshift induces production of a set of specific proteins that help to tune cell metabolism and readjust it to the new environmental conditions. For Escherichia coli the adaptation process takes only about four hours with a relatively small set of specifically induced proteins involved. After this time, protein production resumes, although at a slower rate. One of the cold inducible proteins is RNase R, one of the main E. coli ribonucleases involved in RNA degradation. RNase R is an exoribonuclease that digest double stranded RNA, serves important functions in RNA maturation and turnover, release of stalled ribosomes by trans-translation, and RNA and protein quality control. The level of this enzyme increases about ten-fold after cold induction, and it is also stabilised in cells growing in stationary phase. The RNase R ability to digest structured RNA is important at low temperatures where RNA structures are stabilized but the exact role of this mechanism remains unclear. Although specific bacterial cold shock response was discovered over two decades ago and the number of proteins involved suggests that this adaptation is fast and simple, we are still far from understanding this process. In our work we aimed to discover the proteins interacting with RNase R in different environmental conditions using TAP tag method and mass spectrometry analysis. The information obtained can be used to deduce some of the new functions of RNase R during adaptation of bacteria to cold and in stationary growth phase. Most importantly RNase R can be recruited into a high molecular mass complex of protein in cold shock.

Recycling old screen-printed electrodes with newly designed plastic antibodies on the wall of carbon nanotubes as sensory element for in situ detection of bacterial toxins in water

Using low cost portable devices that enable a single analytical step for screening environmental contaminants is today a demanding issue. This concept is here tried out by recycling screen-printed electrodes that were to be disposed of and by choosing as sensory element a low cost material offering specific response for an environmental contaminant. Microcystins (MCs) were used as target analyte, for being dangerous toxins produced by cyanobacteria released into water bodies. The sensory element was a plastic antibody designed by surface imprinting with carefully selected monomers to ensure a specific response. These were designed on the wall of carbon nanotubes, taking advantage of their exceptional electrical properties. The stereochemical ability of the sensory material to detect MCs was checked by preparing blank materials where the imprinting stage was made without the template molecule. The novel sensory material for MCs was introduced in a polymeric matrix and evaluated against potentiometric measurements. Nernstian response was observed from 7.24 × 10−10 to 1.28 × 10−9 M in buffer solution (10 mM HEPES, 150 mM NaCl, pH 6.6), with average slopes of −62 mVdecade−1 and detection capabilities below 1 nM. The blank materials were unable to provide a linear response against log(concentration), showing only a slight potential change towards more positive potentials with increasing concentrations (while that ofthe plastic antibodies moved to more negative values), with a maximum rate of +33 mVdecade−1. The sensors presented good selectivity towards sulphate, iron and ammonium ions, and also chloroform and tetrachloroethylene (TCE) and fast response (<20 s). This concept was successfully tested on the analysis of spiked environmental water samples. The sensors were further applied onto recycled chips, comprehending one site for the reference electrode and two sites for different selective membranes, in a biparametric approach for “in situ” analysis.

Failure of nitric oxide production by macrophages and decrease in CD4+ T cells in oral paracoccidioidomycosis: possible mechanisms that permit local fungal multiplication

Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO), a product of the inducible nitric oxide synthase enzyme (iNOS), as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP), we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm². Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN) cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues). Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.

Seroprevalence of selected viral, bacterial and parasitic infections among inpatients of a public psychiatric hospital of Mexico

We sought to determine the frequency of serological markers of selected infections in a population of psychiatric patients in Durango City, Mexico, and to determine whether there are any epidemiological characteristics of the subjects associated with the infections. One hundred and five inpatients of a public psychiatric hospital of Durango were examined for HBsAg, anti-HCV antibodies, anti-HIV antibodies, anti-Brucella antibodies, rapid plasma reagin and anti-Cysticercus antibodies by commercially available assays. Anti-Cysticercus antibodies were confirmed by Western blot and HBsAg by neutralization assay. Epidemiological data from each participant were also obtained. Seroprevalences of HBsAg, anti-HCV, anti-HIV, anti-Brucella, rapid plasma reagin and anti-Cysticercus antibodies found were 0.0%, 4.8%, 0.9%, 0.0%, 1.9%, and 0.9%, respectively. Overall, 9 (8.6%) inpatients showed seropositivity to any infection marker. We concluded that our psychiatric inpatients have serological evidence of a number of infections. HCV is an important pathogen among our psychiatric inpatients. Health care strategies for prevention and control of infections in Mexican psychiatric patients should be considered.

Rat muscle opacity decrease due to the osmosis of a simple mixture

It is known that the fibrous structure of muscle causes light scattering. This phenomenon occurs due to the refractive index discontinuities located between muscle fibers and interstitial fluid. To study the possibility of reducing light scattering inside muscle, we consider its spectral transmittance evolution during an immersion treatment with an optical clearing solution containing ethanol, glycerol, and distilled water. Our methodology consists of registering spectral transmittance of muscle samples while immersed in that solution. With the spectral data collected, we represent the transmittance evolution for some wavelengths during the treatment applied. Additionally, we study the variations that the treatment has caused on the samples regarding tissue refractive index and mass. By analyzing microscopic photographs of tissue cross section, we can also verify changes in the internal arrangement of muscle fibers caused by the immersion treatment. Due to a mathematical model that we develop, we can explain the variations observed in the studied parameters and estimate the amount of optical clearing agent that has diffused into the tissue samples during the immersion treatment. At the end of the study, we observe and explain the improvement in tissue spectral transmittance, which is approximately 65% after 20 min.

Muscular strength decrease in Rattus norvegicus experimentally infected by Toxocara canis

The muscular strength of experimental infected Rattus norvegicus with 3rd. stage Toxocara canis larvae was investigated. Fifty Wistar rats, divided in three groups (G1 - 20 rats infected by 300 eggs of T. canis; G2 - 20 rats infected by 2,000 eggs of T. canis and G3 - 10 rats without infection) had been used. Ten and 30 days after infection the muscular strength in the fore-feet of the rats was checked; at the same time, the body weight was determined. No significative differences in the body weight were noted among the infected and control rats in both occasions. Otherwise, an impairment on the muscular strength was observed in rats infected with T. canis 30 days after inoculation.

Perinatal Bacterial Infection: Screenning of Vertical Transmitted Infections

Perinatal bacterial infection may be caused by any microorganism colonizing the vaginal tract. Neonatologists and paediatricians are especially concerned about group B Stretpococcus (GBS). However, Enterobactereacea, mainly E.coli and Proteus, are also responsible for infection. GBS screening may be accomplished in over 90% of pregnant women. In our maternity in 2007-2008, 85% of the mothers had been screened. Screening and prophylaxis were responsible for a decreasing incidence of neonatal infection - from 0.6/1000 to 0.15/1000 live births in Portugal, from 2002 to 2007. However there are some difficulties related to screening. In the second Portuguese study 16/57 NB with early-onset infection (28%) were born to “negative” mothers. Several factors illustrate how difficult is to draw national screening policies: a wide range of carrier’s state rate throughout a country - in Portugal from 12% to 30%. The success of any screening policy may also be affected by additional technical and organizational problems. In countries where home delivery is a tradition or a trend intrapartum GBS prophylaxis requires a very well organized assistance.. Moreover factors usually accepted as protective are not so effective. In the Portuguese study 24/57 infected newborns (42%) were delivery by caesarean section. Another subject deals with the workload in the postnatal ward generated by deficient compliance to the guidelines a problem not confirm by a study of our group. Decreasing the importance of GBS, highlight the importance of E. coli in perinatal infection. From the 16 340 registrations of the National Registry 1676 were newborns with mother-related infection. Applying the same reasoning to E.coli as to GBS and Listeria monocytogenes – that is considering all of them are of maternal origin - 6.7% of these infections were due to E. coli, 4.6% to SGB and 0.5% to Listeria monocytogenes. In conclusion screening and prophylaxis may be not the best way to prevent all GBS neonatal infections but by now it is the only available procedure. The other bacteria continue to demand a high suspicion level and immediate intervention.

Mobilidade funcional, risco de queda, nível de actividade física e percepção de saúde em indivíduos com 65 ou mais anos

RESUMO:O objectivo deste estudo foi analisar a relação entre mobilidade funcional, risco de queda, nível de actividade física e percepção de saúde de 34 indivíduos praticantes (n=18) e não praticantes (n=16) de exercício físico duas ou mais vezes por semana durante pelo menos 45 minutos, residentes na comunidade e ambulatórios. Tipo de estudo: transversal exploratório-descritivo. Metodologia: foi feito um levantamento das variáveis de caracterização (idade, sexo, habilitações literárias, situação sócio-económica, situação familiar) e do estado cognitivo e estado emocional/depressão (Mini-Mental State Examination e Geriatric Depression Scale). As variáveis em análise foram: a mobilidade funcional avaliada através do Timed up and GoTest, o risco de queda medido com o Funtional Reach Test, o nível de actividade física avaliado através do Questionário Internacional de Actividade Física (IPAQ) e a percepção de saúde medida através do SF-6D. Foi também questionada a prática de alguma modalidade de exercício físico, da sua frequência e duração. Os dados foram analisados através de estatística descritiva, foi realizada uma regressão linear múltipla e uma análise bivariada das correlações, utilizando o coeficiente de correlação linear de Pearson (p ≤ 0,05).Resultados: verificou-se que, na amostra global, a maioria dos indivíduos apresentou uma mobilidade funcional considerada normal (TUG<10 segundos), e um risco de queda moderado (FRT entre 15,24 e 25,40 cm), embora sem diferenças entre os grupos em análise. A actividade física apresentou uma duração média de 685,88±540,16 minutos por semana, sendo que 18 indivíduos praticavam exercício físico pelo menos 45 minutos e duas ou mais vezes por semana.A percepção do estado de saúde foi bastante satisfatória, sendo a pontuação média do SF-6D de 0,915±0,067. A análise entre grupos demonstrou que o grupo que praticava exercício físico apresentava um maior número de indivíduos na faixa etária dos 65-74 anos, tinha mais escolarização e melhor estado cognitivo. Estes indivíduos eram fisicamente mais activos e faziam-o, na sua maioria, com uma frequência bissemanal, apenas um desempenhando uma modalidade de intensidade vigorosa. A análise estatística demonstrou que: a mobilidade funcional e o risco de queda eram mais desfavoráveis nos indivíduos com mais idade; o estado cognitivo estava associado a maior mobilidade funcional; uma boa mobilidade funcional correspondeu a um risco de queda reduzido, a mais prática de actividade física, a melhor percepção do estado de saúde e a manutenção do estado cognitivo. Os indivíduos com menor risco de queda apresentaram melhor estado cognitivo e emocional. E este último correspondeu a uma melhor percepção do estado de saúde e a um melhor estado cognitivo. Conclusão: a manutenção da mobilidade funcional reduz o risco de queda aumenta a prática de actividade física e melhora a percepção de saúde de indivíduos com 65 ou mais anos residentes na comunidade.--------- ABSTRACT: Objective: the aim of this study was to analyze the relationship between functional mobility, falls risk, level of physical activity and health perception in a sample of 34 subjects, 18 that practice exercise two or more times a week for at least 45 minutes and 16 that don’t practice exercise, residents and community. Designs: cross-sectional exploratory-descriptive survey. Methods: descriptive variables are age, sex, education, socio-economic level, family status, cognitive status (Mini-Mental State Examination) and emotional status/depression (Geriatric Depression Scale). We analyze the functional mobility with the Timed up and Go Test, the falls risk with Functional Reach Test, the level of physical activity with the International Physical Activity Questionnaire (IPAQ) and health perception with SF-6D. We also questioned the practice of exercise, their frequency and duration. Data were analyzed using descriptive statistics, a multiple linear regression analysis and bivariate correlations, using the linear correlation coefficient of Pearson (p ≤ 0.05). Results: we found that, in the total sample, most individuals had considered a normal functional mobility (TUG <10 seconds), and a moderate falls risk (FRT between 15.24 and 25.40 cm), but no difference between groups. Physical activity showed an mean of 685.88 ± 540.16 minutes per week, with 18 individuals pratice physical exercise at least 45 minutes and two or more times per week. The mean score of the SF-6D was 0.915 ± 0.067 and the perception of health was satisfactory. The analysis between groups showed that the group that practice physical exercise had a greater number of individuals aged 65-74 years, had more schooling and better cognitive status. These subjects were more physically active and mostly did it two times a weak and only one playing a kind of vigorous intensity. The multiple linear regression and correlations, using the linear correlation coefficient of Pearson (p≤0.05) showed that: functional mobility and fall risk decrease with age increase. The cognitive status was associated with greater functional mobility, a good functional mobility corresponded to a reduced falls risk, more physical activity, a better perception of health status and maintenance of cognitive status. Subjects with lower falls risk had better cognitive and emotional state. And subjects with a better emotional status have a better health perception and better cognitive status. Conclusion: the maintenance of functional mobility reduces falls risk, increase physical activity and improves health perception of individuals with 65 years or older living in the community.

Edible coatings based on chitosan-beeswax emulsions

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica