Gene expression profiling in leiomyosarcomas and undifferentiated pleomorphic sarcomas: SRC as a new diagnostic marker

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A dimensão dialógica e a prática educativa: reflexões a partir de Paulo Freire e Humberto Maturana

Ao observarmos o cotidiano nas escolas é possível constatar que nem sempre se reconhece e se valoriza a diferença e a singularidade que caracteriza cada sujeito envolvido, pois ocorrem situações de negação mútua entre alunos, entre alunos e professores e entre outras relações do espaço escolar que ferem a dignidade humana. Uma alternativa a essa realidade é a promoção de vivências dialógicas. Nesse sentido, objetivamos com este trabalho: Refletir sobre as contribuições teórico-conceituais desenvolvidas por Paulo Freire e por Humberto Maturana acerca da vivência do diálogo, suas possibilidades e impasses nas relações sociais e na relação educativa; e identificar, a partir de um estudo de caso realizado em uma escola da Rede Pública Estadual, as concepções dos educadores sobre a prática dialógica no cotidiano escolar. Para Freire, o diálogo é o encontro e a partilha de concepções de A com B e não de A sobre B ou vice versa, sendo que nesta relação é importante que ambos se disponham à escuta mútua reconhecendo a diversidade de concepções que estimula a curiosidade epistemológica. Para Maturana, a partir da Biologia, cada ser vivo se constitui como uma organização autopoiética, ou seja, tem a tarefa de produzir-se a si próprio, estabelecendo relações com o meio. Na existência humana, essas interações com o meio e entre os humanos se estabelecem num entrelaçamento de emoções e ações, que ele nomeia de conversação. A partir das reflexões pelos autores e o diálogo estabelecido com sujeitos da pesquisa destacamos: 1) As relações sociais se mantêm quando há aceitação do outro como legítimo outro na convivência, o que implica a aceitação de si próprio; 2) O diálogo cria um clima de aceitação para com a história e a diferença do outro, o que favorece relações de partilha de ideias e de releitura coletiva do mundo. Tanto Maturana e Freire, quanto os entrevistados valorizam o ...

Caracterização funcional e estrutural das proteínas RUV-1 e RUV-2 do fungo Neurospora crassa

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Musical Training Induces Functional Plasticity in Human Hippocampus

Training can change the functional and structural organization of the brain, and animal models demonstrate that the hippocampus formation is particularly susceptible to training-related neuroplasticity. In humans, however, direct evidence for functional plasticity of the adult hippocampus induced by training is still missing. Here, we used musicians' brains as a model to test for plastic capabilities of the adult human hippocampus. By using functional magnetic resonance imaging optimized for the investigation of auditory processing, we examined brain responses induced by temporal novelty in otherwise isochronous sound patterns in musicians and musical laypersons, since the hippocampus has been suggested previously to be crucially involved in various forms of novelty detection. In the first cross-sectional experiment, we identified enhanced neural responses to temporal novelty in the anterior left hippocampus of professional musicians, pointing to expertise-related differences in hippocampal processing. In the second experiment, we evaluated neural responses to acoustic temporal novelty in a longitudinal approach to disentangle training-related changes from predispositional factors. For this purpose, we examined an independent sample of music academy students before and after two semesters of intensive aural skills training. After this training period, hippocampal responses to temporal novelty in sounds were enhanced in musical students, and statistical interaction analysis of brain activity changes over time suggests training rather than predisposition effects. Thus, our results provide direct evidence for functional changes of the adult hippocampus in humans related to musical training.

Genetic polymorphisms associated with the inflammatory response in bacterial meningitis.

BACKGROUND Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously. METHODS The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients. CONCLUSIONS In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches.

Accuracy of diagnostic testing in primary ciliary dyskinesia.

Diagnosis of primary ciliary dyskinesia (PCD) lacks a "gold standard" test and is therefore based on combinations of tests including nasal nitric oxide (nNO), high-speed video microscopy analysis (HSVMA), genotyping and transmission electron microscopy (TEM). There are few published data on the accuracy of this approach.Using prospectively collected data from 654 consecutive patients referred for PCD diagnostics we calculated sensitivity and specificity for individual and combination testing strategies. Not all patients underwent all tests.HSVMA had excellent sensitivity and specificity (100% and 93%, respectively). TEM was 100% specific, but 21% of PCD patients had normal ultrastructure. nNO (30 nL·min(-1) cut-off) had good sensitivity and specificity (91% and 96%, respectively). Simultaneous testing using HSVMA and TEM was 100% sensitive and 92% specific.In conclusion, combination testing was found to be a highly accurate approach for diagnosing PCD. HSVMA alone has excellent accuracy, but requires significant expertise, and repeated sampling or cell culture is often needed. TEM alone is specific but misses 21% of cases. nNO (≤30 nL·min(-1)) contributes well to the diagnostic process. In isolation nNO screening at this cut-off would miss ∼10% of cases, but in combination with HSVMA could reduce unnecessary further testing. Standardisation of testing between centres is a future priority.

Exploration of genetic susceptibility to pancreatic cancer: A GWAS approach

Pancreatic cancer is the 4th most common cause for cancer death in the United States, accompanied by less than 5% five-year survival rate based on current treatments, particularly because it is usually detected at a late stage. Identifying a high-risk population to launch an effective preventive strategy and intervention to control this highly lethal disease is desperately needed. The genetic etiology of pancreatic cancer has not been well profiled. We hypothesized that unidentified genetic variants by previous genome-wide association study (GWAS) for pancreatic cancer, due to stringent statistical threshold or missing interaction analysis, may be unveiled using alternative approaches. To achieve this aim, we explored genetic susceptibility to pancreatic cancer in terms of marginal associations of pathway and genes, as well as their interactions with risk factors. We conducted pathway- and gene-based analysis using GWAS data from 3141 pancreatic cancer patients and 3367 controls with European ancestry. Using the gene set ridge regression in association studies (GRASS) method, we analyzed 197 pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Using the logistic kernel machine (LKM) test, we analyzed 17906 genes defined by University of California Santa Cruz (UCSC) database. Using the likelihood ratio test (LRT) in a logistic regression model, we analyzed 177 pathways and 17906 genes for interactions with risk factors in 2028 pancreatic cancer patients and 2109 controls with European ancestry. After adjusting for multiple comparisons, six pathways were marginally associated with risk of pancreatic cancer ( P < 0.00025): Fc epsilon RI signaling, maturity onset diabetes of the young, neuroactive ligand-receptor interaction, long-term depression (Ps < 0.0002), and the olfactory transduction and vascular smooth muscle contraction pathways (P = 0.0002; Nine genes were marginally associated with pancreatic cancer risk (P < 2.62 × 10−5), including five reported genes (ABO, HNF1A, CLPTM1L, SHH and MYC), as well as four novel genes (OR13C4, OR 13C3, KCNA6 and HNF4 G); three pathways significantly interacted with risk factors on modifying the risk of pancreatic cancer (P < 2.82 × 10−4): chemokine signaling pathway with obesity ( P < 1.43 × 10−4), calcium signaling pathway (P < 2.27 × 10−4) and MAPK signaling pathway with diabetes (P < 2.77 × 10−4). However, none of the 17906 genes tested for interactions survived the multiple comparisons corrections. In summary, our current GWAS study unveiled unidentified genetic susceptibility to pancreatic cancer using alternative methods. These novel findings provide new perspectives on genetic susceptibility to and molecular mechanisms of pancreatic cancer, once confirmed, will shed promising light on the prevention and treatment of this disease. ^

The Multiple Roles of Cyk1p in the Assembly and Function of the Actomyosin Ring in Budding Yeast

The budding yeast IQGAP-like protein Cyk1p/Iqg1p localizes to the mother-bud junction during anaphase and has been shown to be required for the completion of cytokinesis. In this study, video microscopy analysis of cells expressing green fluorescent protein-tagged Cyk1p/Iqg1p demonstrates that Cyk1p/Iqg1p is a dynamic component of the contractile ring during cytokinesis. Furthermore, in the absence of Cyk1p/Iqg1p, myosin II fails to undergo the contraction-like size change at the end of mitosis. To understand the mechanistic role of Cyk1p/Iqg1p in actomyosin ring assembly and dynamics, we have investigated the role of the structural domains that Cyk1p/Iqg1p shares with IQGAPs. An amino terminal portion containing the calponin homology domain binds to actin filaments and is required for the assembly of actin filaments to the ring. This result supports the hypothesis that Cyk1p/Iqg1p plays a direct role in F-actin recruitment. Deletion of the domain harboring the eight IQ motifs abolishes the localization of Cyk1p/Iqg1p to the bud neck, suggesting that Cyk1p/Iqg1p may be localized through interactions with a calmodulin-like protein. Interestingly, deletion of the COOH-terminal GTPase-activating protein-related domain does not affect Cyk1p/Iqg1p localization or actin recruitment to the ring but prevents actomyosin ring contraction. In vitro binding experiments show that Cyk1p/Iqg1p binds to calmodulin, Cmd1p, in a calcium-dependent manner, and to Tem1p, a small GTP-binding protein previously found to be required for the completion of anaphase. These results demonstrate the critical function of Cyk1p/Iqg1p in regulating various steps of actomyosin ring assembly and cytokinesis.

Método para análise da interação fluido-estrutura em travessas do pré-distribuidor de turbinas hidráulicas.

Um dos grandes desafios enfrentados pelos fabricantes de turbinas hidráulicas é prevenir o aparecimento de vibrações induzidas pelo escoamento nas travessas do pré-distribuidor e pás do rotor. Considerando apenas as travessas, e atribuídos a tais vibrações, foram relatados 28 casos de trincas ou ruídos anormais nas últimas décadas, que acarretaram enormes prejuízos associados a reparos, atrasos e perda de geração. O estado da arte na prevenção destes problemas baseia-se na utilização de sofisticados, e caros, programas comerciais de dinâmica dos fluidos computacional para o cálculo transiente do fenômeno. Este trabalho faz uma ampla revisão bibliográfica e levantamento de eventos de trincas ou ruídos ocorridos em travessas nos últimos 50 anos. Propõe, então, um enfoque alternativo, baseado exclusivamente em ferramentas de código aberto. A partir de hipóteses simplificadoras devidamente justificadas, o problema é formulado matematicamente de forma bidimensional, no plano da seção transversal da travessa, levando em conta a interação fluido-estrutura. Nesta estratégia, as equações de Navier-Stokes são resolvidas pelo método dos elementos finitos por meio da biblioteca gratuita oomph-lib. Um código especial em C++ é desenvolvido para o problema de interação fluido-estrutura, no qual o fenômeno de turbulência é levado em consideração por meio de um algoritmo baseado no modelo de Baldwin-Lomax. O método proposto é validado por meio da comparação dos resultados obtidos com referências e medições disponíveis na literatura, que tratam de problemas de barras retangulares suportadas elasticamente. O trabalho finaliza com a aplicação do método a um estudo de caso envolvendo uma travessa particular.

Concept and measurement: the cultural borders of meaning

Paper submitted to the Sixth International Conference on Social Science Methodology, Amsterdam, The Netherlands, August 16-20, 2004.

O ambiente interagências nas operações de pacificação do Complexo da Maré

O objetivo do presente estudo foi realizar uma análise da interação do Exército Brasileiro perante os 42 (quarenta e dois) órgãos civis e militares no conjunto de favelas da Maré e de que forma estas influenciaram na doutrina das operações militares de pacificação. A Operação São Francisco - iniciada em 5 de abril de 2014 pela Força de Pacificação (F Pac), foi designada aos componentes do Ministério da Defesa para assegurar e promover a garantia da lei e da ordem (GLO) pública nas comunidades do Complexo da Maré, na cidade do Rio de Janeiro. A metodologia proposta baseou-se em uma pesquisa aplicada com técnica de abordagem mista, através da pesquisa bibliográfica, da análise dos documentos e relatórios da F Pac e da realização de entrevistas aos integrantes das forças militares e dos civis que prestaram serviços públicos na região supracitada. Para isso, foi utilizado o método indutivo por meio dos testes estatísticos, que visaram identificar relacionamentos causais entre as demandas de serviços públicos civis atendidos nas comunidades, bem como a influência destas nas operações de pacificação e nas políticas de defesa voltadas à atualização da doutrina e das operações militares. As contribuições teóricas esperadas foram a observação das mudanças no emprego operacional em um ambiente com alta criminalidade e baixo Índice de Desenvolvimento Humano (IDH) e fornecer informações para o emprego colaborativo das instituições civis sob a proteção militar (mas não sob o controle militar). Isto visou proporcionar à população o acesso aos serviços públicos básicos com segurança e minimizou o desgaste das ações de GLO através da conquista da opinião pública local. As contribuições práticas esperadas residiram no aumento do potencial militar, através da integração de políticas públicas efetivas das pastas civis. As implicações referiram-se a abordagem e a maior interação entre as pastas governamentais militares e civis através da mediação da Seção de Assuntos Civis. As pesquisas deste trabalho evidenciaram por serem restritas ao contexto da pacificação de um conjunto de favelas da capital do Estado do Rio de Janeiro no ano de 2014.

Problem solving in social interactions on the Internet: Rumor as social cognition

Rumor discourse has been conceptualized as an attempt to reduce anxiety and uncertainty via a process of social sensemaking. Fourteen rumors transmitted on various Internet discussion groups were observed and content analyzed over the life of each rumor With this (previously unavailable) more ecologically robust methodology, the intertwined threads of sensemaking and the gaining of interpretive control are clearly evident in the tapestry of rumor discourse. We propose a categorization of statements (the Rumor Interaction Analysis System) and find differences between dread rumors and wish rumors in anxiety-related content categories. Cluster analysis of these statements reveals a typology of voices (communicative postures) exhibiting sensemaking activities of the rumor discussion group, such as hypothesizing, skeptical critique, directing of activities to gain information, and presentation of evidence. These findings enrich our understanding of the long-implicated sensemaking function of rumor by clarifying the elements of communication that operate in rumor's social context.

Mathematical modelling and control of agitated extraction columns

Liquid-liquid extraction has long been known as a unit operation that plays an important role in industry. This process is well known for its complexity and sensitivity to operation conditions. This thesis presents an attempt to explore the dynamics and control of this process using a systematic approach and state of the art control system design techniques. The process was studied first experimentally under carefully selected. operation conditions, which resembles the ranges employed practically under stable and efficient conditions. Data were collected at steady state conditions using adequate sampling techniques for the dispersed and continuous phases as well as during the transients of the column with the aid of a computer-based online data logging system and online concentration analysis. A stagewise single stage backflow model was improved to mimic the dynamic operation of the column. The developed model accounts for the variation in hydrodynamics, mass transfer, and physical properties throughout the length of the column. End effects were treated by addition of stages at the column entrances. Two parameters were incorporated in the model namely; mass transfer weight factor to correct for the assumption of no mass transfer in the. settling zones at each stage and the backmixing coefficients to handle the axial dispersion phenomena encountered in the course of column operation. The parameters were estimated by minimizing the differences between the experimental and the model predicted concentration profiles at steady state conditions using non-linear optimisation technique. The estimated values were then correlated as functions of operating parameters and were incorporated in·the model equations. The model equations comprise a stiff differential~algebraic system. This system was solved using the GEAR ODE solver. The calculated concentration profiles were compared to those experimentally measured. A very good agreement of the two profiles was achieved within a percent relative error of ±2.S%. The developed rigorous dynamic model of the extraction column was used to derive linear time-invariant reduced-order models that relate the input variables (agitator speed, solvent feed flowrate and concentration, feed concentration and flowrate) to the output variables (raffinate concentration and extract concentration) using the asymptotic method of system identification. The reduced-order models were shown to be accurate in capturing the dynamic behaviour of the process with a maximum modelling prediction error of I %. The simplicity and accuracy of the derived reduced-order models allow for control system design and analysis of such complicated processes. The extraction column is a typical multivariable process with agitator speed and solvent feed flowrate considered as manipulative variables; raffinate concentration and extract concentration as controlled variables and the feeds concentration and feed flowrate as disturbance variables. The control system design of the extraction process was tackled as multi-loop decentralised SISO (Single Input Single Output) as well as centralised MIMO (Multi-Input Multi-Output) system using both conventional and model-based control techniques such as IMC (Internal Model Control) and MPC (Model Predictive Control). Control performance of each control scheme was. studied in terms of stability, speed of response, sensitivity to modelling errors (robustness), setpoint tracking capabilities and load rejection. For decentralised control, multiple loops were assigned to pair.each manipulated variable with each controlled variable according to the interaction analysis and other pairing criteria such as relative gain array (RGA), singular value analysis (SVD). Loops namely Rotor speed-Raffinate concentration and Solvent flowrate Extract concentration showed weak interaction. Multivariable MPC has shown more effective performance compared to other conventional techniques since it accounts for loops interaction, time delays, and input-output variables constraints.

Talking about depression:an analogue study of physician gender and communication style on patient disclosures

Objectives: To disentangle the effects of physician gender and patient-centered communication style on patients' oral engagement in depression care. Methods: Physician gender, physician race and communication style (high patient-centered (HPC) and low patient-centered (LPC)) were manipulated and presented as videotaped actors within a computer simulated medical visit to assess effects on analogue patient (AP) verbal responsiveness and care ratings. 307 APs (56% female; 70% African American) were randomly assigned to conditions and instructed to verbally respond to depression-related questions and indicate willingness to continue care. Disclosures were coded using Roter Interaction Analysis System (RIAS). Results: Both male and female APs talked more overall and conveyed more psychosocial and emotional talk to HPC gender discordant doctors (all p <.05). APs were more willing to continue treatment with gender-discordant HPC physicians (p <.05). No effects were evident in the LPC condition. Conclusions: Findings highlight a role for physician gender when considering active patient engagement in patient-centered depression care. This pattern suggests that there may be largely under-appreciated and consequential effects associated with patient expectations in regard to physician gender that these differ by patient gender. Practice implications: High patient-centeredness increases active patient engagement in depression care especially in gender discordant dyads. © 2014.

The role of *language in early childhood mathematics

Math literacy is imperative to succeed in society. Experience is key for acquiring math literacy. A preschooler's world is full of mathematical experiences. Children are continually counting, sorting and comparing as they play. As children are engaged in these activities they are using language as a tool to express their mathematical thinking. If teachers are aware of these teachable moments and help children bridge their daily experiences to mathematical concepts, math literacy may be enhanced. This study described the interactions between teachers and preschoolers, determining the extent to which teachers scaffold children's everyday language into expressions of mathematical concepts. Of primary concern were the teachers' responsive interactions to children's expressions of an implicit mathematical utterance made while engaged in block play. The parallel mixed methods research design consisted of two strands. Strand 1 of the study focused on preschoolers' use of everyday language and the teachers' responses after a child made a mathematical utterance. Twelve teachers and 60 students were observed and videotaped while engaged in block play. Each teacher worked with five children for 20 minutes, yielding 240 minutes of observation. Interaction analysis was used to deductively analyze the recorded observations and field notes. Using a priori codes for the five mathematical concepts, it was found children produced 2,831 mathematical utterances. Teachers ignored 60% of these utterances and responded to, but did not mediate 30% of them. Only 10% of the mathematical utterances were mediated to a mathematical concept. Strand 2 focused on the teacher's view of the role of language in early childhood mathematics. The 12 teachers who had been observed as part of the first strand of the study were interviewed. Based on a thematic analysis of these interviews three themes emerged: (a) the importance of a child's environment, (b) the importance of an education in society, and (c) the role of math in early childhood. Finally, based on a meta-inference of both strands, three themes emerged: (a) teacher conception of math, (b) teacher practice, and (c) teacher sensitivity. Implications based on the findings involve policy, curriculum, and professional development.