The full Bayesian significance test for mixture models: results in gene expression clustering

Gene clustering is a useful exploratory technique to group together genes with similar expression levels under distinct cell cycle phases or distinct conditions. It helps the biologist to identify potentially meaningful relationships between genes. In this study, we propose a clustering method based on multivariate normal mixture models, where the number of clusters is predicted via sequential hypothesis tests: at each step, the method considers a mixture model of m components (m = 2 in the first step) and tests if in fact it should be m - 1. If the hypothesis is rejected, m is increased and a new test is carried out. The method continues (increasing m) until the hypothesis is accepted. The theoretical core of the method is the full Bayesian significance test, an intuitive Bayesian approach, which needs no model complexity penalization nor positive probabilities for sharp hypotheses. Numerical experiments were based on a cDNA microarray dataset consisting of expression levels of 205 genes belonging to four functional categories, for 10 distinct strains of Saccharomyces cerevisiae. To analyze the method's sensitivity to data dimension, we performed principal components analysis on the original dataset and predicted the number of classes using 2 to 10 principal components. Compared to Mclust (model-based clustering), our method shows more consistent results.

Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries

Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes. Methods: Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries. Results: Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2, MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation of BST2 and MFAP2 and the downregulation of KRT31 when samples of HNSCC were compared to tumor-free surgical margins. As expected, GNA15 presented a non-significant differential expression pattern when tumor samples were compared to normal tissues. Conclusion: To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.

No evidence for an association between the-36A > C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans.

Relationship Between Eccentric Hip Torque and Lower-Limb Kinematics: Gender Differences

The purposes of this study were to compare lower-limb kinematics between genders, and determine the relationships among eccentric hip abductor and lateral rotator torques and lower-limb kinematics. The movements of the pelvis, femur, and knee were calculated for 16 women and 16 men during the single-leg squat. Eccentric hip abductor and lateral rotator torques were measured using an isokinetic dynamometer. The results showed that women had greater contralateral pelvic depression, femur adduction, and knee abduction than men. The eccentric hip abductor and lateral rotator torques were correlated with coronal plane femur and knee movements in the overall sample. When the genders were analyzed separately, it was observed that women with greater eccentric hip abductor torque exhibited less femur adduction and femur medial rotation, and greater knee adduction excursion. No significant relationship was observed between the isokinetic and kinematic variables in the male group. The differences between the genders help to explain the greater rate of knee disorders observed in women. Moreover, the eccentric hip abduction action seemed to be more important in women to control the lower-limb movements.

Biomass Refinery as a Renewable Complement to the Petroleum Refinery

Biomass Refinery is a sequential of eleven thermochemical processes and one biological process with two initial basic treatments: prehydrolysis for lignocellulosics and low temperature conversion for biomass with medium-to-high content of lipids and proteins. The other ten processes are: effluent treatment plant, furfural plant, biodiesel plant, cellulignin dryer, calcination, fluidized bed boiler, authotermal reforming of cellulignin for syngas production, combined cycle of two-stroke low-speed engine or syngas turbine with fluidized bed boiler heat recovery, GTL technologies and ethanol from cellulose, prehydrolysate and syngas. Any kind of biomass such as wood, agricultural residues, municipal solid waste, seeds, cakes, sludges, excrements and used tires can be processed at the Biomass Refinery. Twelve basic products are generated such as cellulignin, animal feed, electric energy, fuels (ethanol, crude oil, biodiesel, char), petrochemical substitutes, some materials (ash, gypsum, fertilizers, silica, carbon black) and hydrogen. The technology is clean with recovery of energy and reuse of water, acid and effluents. Based on a holistic integration of various disciplines Biomass Refinery maximizes the simultaneous production of food, electric energy, liquid fuels and chemical products and some materials, achieving a competitive position with conventional and fossil fuel technologies, as well as payment capacity for biomass production. Biomass Refinery has a technical economical capability to complement the depletion of the conventional petroleum sources and to capture its GHGs resulting a biomass + petroleum ""green"" combination.

Geographic Information Systems (GIS) in Assessing Dental Health

The present study investigated the distribution profile of dental caries and its association with areas of social deprivation at the individual and contextual level. The cluster sample consisted of 1,002 12-year-old schoolchildren from Piracicaba, SP, Brazil. The DMFT Index was used for dental caries and the Care Index was used to determine access to dental services. On the individual level, variables were associated with a better oral status. On the contextual level, areas were not associated with oral status. However, maps enabled determining that the central districts have better social and oral conditions than the deprived outlying districts.

QTL mapping for yield components in a tropical maize population using microsatellite markers

QTL mapping provides usefull information for breeding programs since it allows the estimation of genomic locations and genetic effects of chromossomal regions related to the expression of quantitative traits. The objective of this study was to map QTL related to several agronomic important traits associated with grain yield: ear weight (EW), prolificacy (PROL), ear number (NE), ear length (EL) and diameter (ED), number of rows on the ear (NRE) and number of kernels per row on the ear (NKPR). Four hundred F-2:3 tropical maize progenies were evaluated in five environments in Piracicaba, Sao Paulo, Brazil. The genetic map was previously estimated and had 117 microssatelite loci with average distance of 14 cM. Data was analysed using Composite Interval Mapping for each trait. Thirty six QTL were mapped and related to the expression of EW (2), PROL (3), NE (2), EL (5), ED (5), NRE (10), NKPR (5). Few QTL were mapped since there was high GxE interaction. Traits EW, PROL and EN showed high genetic correlation with grain yield and several QTL mapped to similar genomic regions, which could cause the observed correlation. However, further analysis using apropriate statistical models are required to separate linked versus pleiotropic QTL. Five QTL (named Ew1, Ne1, Ed3, Nre3 and Nre10) had high genetic effects, explaining from 10.8% (Nre3) to 16.9% (Nre10) of the phenotypic variance, and could be considered in further studies.

Interceptação da chuva por duas espécies arbóreas em áreas verdes urbanas

Rainfall interception by the two most usual species in forest urban spaces was analysed by measuring of interception (I) or interception losses, through fall (PI), stem flow (Et) and gross precipitation (PT). The chosen species were Caesalpinia pluviosa DC. (Fabaceae: Caesalpinoideae) or sibipiruna, and Tipuana tipu O. Kuntze (Fabaceae: Faboideae) or tipuana. The individuals analysed were more than 50 years old, with three separate individuals and three individuals in each studied group of species at the campus of ""Luiz de Queiroz"" College of Agriculture (University of Sao Paulo), Piracicaba. The experiments were carried out from January to February 2007. Water was collected using seven-litre pails, in the edges and in the centre of the canopies. A high correlation of Th with Pg was observed on the centre of the crow of tipuana and by the edges of sibipiruna. Stand! had low correlation with Pg for both species. The average of rain interception was greater in the edges of the crow of sibipiruna individuals, 60.6%, and in the centre of tipuana crow, 59.40%. Thus, both species intercepted up to 60% of the water rainfall, which indicates a great potential of both species for arborisation in urban environments.

Deficiência em micronutrientes em mudas de sangra d'agua (Croton urucurana, Baill.)

This study had the following objectives: to induce and describe symptoms of deficiency of boron (B), copper (Cu), iron (Fe), manganese (Mn), molybdenum (Mo) and zinc (Zn), determining the effect on the mineral composition of leaves. The experiment was developed in a green house and used diagnosis technique by subtraction. The experimental design usedn was a randomized blocks, with seven treatments and three replicates. It was verified that micronutrient omission led to morphological alterations which, in turn, caused visual symptoms. The symptoms caused by the omission of Cu, Mn and Zn were the first to appear, and were followed by those of B, Fe and Mo. The omission of B, Mn and Zn was responsible for the more pronounced reduction in height and stem diameter.

Sao Paulo: globalisation and metropolitan transition

The recent transformations taking place in the city of Sao Paulo show how the global urban dimension goes hand in hand with local deprivation and segregation. Both globalisation trends and segregation dynamics orientate a social and spatial process of change which has as the main result the dissolution of the urban condition in Sao Paulo. The metropolisation dynamics currently at work in South American cities can be understood, taking into consideration evidences and facts coming from the analysis of Sao Paulo, as a transition resulting from the globalisation process which takes place in contemporary cities.

Identification of a Highly Antigenic Linear B Cell Epitope within Plasmodium vivax Apical Membrane Antigen 1 (AMA-1)

Apical membrane antigen 1 (AMA-1) is considered to be a major candidate antigen for a malaria vaccine. Previous immunoepidemiological studies of naturally acquired immunity to Plasmodium vivax AMA-1 (PvAMA-1) have shown a higher prevalence of specific antibodies to domain II (DII) of AMA-1. In the present study, we confirmed that specific antibody responses from naturally infected individuals were highly reactive to both full-length AMA-1 and DII. Also, we demonstrated a strong association between AMA-1 and DII IgG and IgG subclass responses. We analyzed the primary sequence of PvAMA-1 for B cell linear epitopes co-occurring with intrinsically unstructured/ disordered regions (IURs). The B cell epitope comprising the amino acid sequence 290-307 of PvAMA-1 (SASDQPTQYEEEMTDYQK), with the highest prediction scores, was identified in domain II and further selected for chemical synthesis and immunological testing. The antigenicity of the synthetic peptide was identified by serological analysis using sera from P. vivax-infected individuals who were knowingly reactive to the PvAMA-1 ectodomain only, domain II only, or reactive to both antigens. Although the synthetic peptide was recognized by all serum samples specific to domain II, serum with reactivity only to the full-length protein presented 58.3% positivity. Moreover, IgG reactivity against PvAMA-1 and domain II after depletion of specific synthetic peptide antibodies was reduced by 18% and 33% (P = 0.0001 for both), respectively. These results suggest that the linear epitope SASDQPTQYEEEMTDYQK is highly antigenic during natural human infections and is an important antigenic region of the domain II of PvAMA-1, suggesting its possible future use in pre-clinical studies.

The inducing NO-vasodilation by chemical reduction of coordinated nitrite ion in cis-[Ru(NO(2))L(bpy)(2)](+) complex

The synthesis of [Ru(NO(2)) L(bpy)(2)](+) (bpy = 2,2'-bipyridine and L = pyridine (py) and pyrazine (pz)) can be accomplished by addition of [Ru(NO) L(bpy) 2](PF(6))(3) to aqueous solutions of physiological pH. The electrochemical processes of [Ru(NO2) L(bpy) 2]+ in aqueous solution were studied by cyclic voltammetry and differential pulse voltammetry. The anodic scan shows a peak around 1.00 V vs. Ag/AgCl attributed to the oxidation process centered on the metal ion. However, in the cathodic scan a second peak around-0.60 V vs. Ag/AgCl was observed and attributed to the reduction process centered on the nitrite ligand. The controlled reduction potential electrolysis at-0.80 V vs. Ag/AgCl shows NO release characteristics as judged by NO measurement with a NO-sensor. This assumption was confirmed by ESI/MS(+) and spectroelectrochemical experiment where cis-[Ru(bpy)(2)L(H(2)O)](2+) was obtained as a product of the reduction of cis-[Ru(II)(NO(2)) L(bpy)(2)](+). The vasorelaxation observed in denuded aortic rings pre-contracted with 0.1 mu mol L(-1) phenylephrine responded with relaxation in the presence of cis-[RuII(NO2) L(bpy) 2]+. The potential of rat aorta cells to metabolize cis-[RuII(NO(2)) L(bpy)(2)](+) was also followed by confocal analysis. The obtained results suggest that NO release happens by reduction of cis-[RuII(NO(2)) L(bpy)(2)](+) inside the cell. The maximum vasorelaxation was achieved with 1 x 10(-5) mol L(-1) of cis-[RuII(NO(2)) L(bpy)(2)](+) complex.

Pluripotent Reprogramming of Fibroblasts by Lentiviralmediated Insertion of SOX2, C-MYC, and TCL-1A

Reprogramming of somatic cells to pluripotency promises to boost cellular therapy. Most instances of direct reprogramming have been achieved by forced expression of defined exogenous factors using multiple viral vectors. The most used 4 transcription factors, octamer-binding transcription factor 4 (OCT4), (sex determining region Y)-box 2 (SOX2), Kruppel-like factor 4 (KLF4), and v-myc myelocytomatosis viral oncogene homolog (C-MYC), can induce pluripotency in mouse and human fibroblasts. Here, we report that forced expression of a new combination of transcription factors (T-cell leukemia/lymphoma protein 1A [TCL-1A], C-MYC, and SOX2) is sufficient to promote the reprogramming of human fibroblasts into pluripotent cells. These 3-factor pluripotent cells are similar to human embryonic stem cells in morphology, in the ability to differentiate into cells of the 3 embryonic layers, and at the level of global gene expression. Induced pluripotent human cells generated by a combination of other factors will be of great help for the understanding of reprogramming pathways. This, in turn, will allow us to better control cell-fate and apply this knowledge to cell therapy.

Avaliação do Processo de Ensino e Aprendizagem em Matemática: contribuições da teoria histórico-cultural

This article presents the results of a study that investigated the meaning of evaluation in mathematics from the historical cultural perspective, focusing on activity theory. In order to develop the investigation, a collaborative group was formed from the Oficina Pedagogica de Matematica de Ribeirao Preto - Sao Paulo (Math Pedagogic Workshop of Ribeirao Preto - OPM/RP), constituted of pre-school teachers and early elementary school teachers, who were participants in this research. The main role of the collaborative group was to offer guided development to the teachers about the teaching of mathematics from the historical-cultural perspective, aiming at collecting data on the process of appropriation of mathematical knowledge by the teachers. The syntheses about the teachers' learning process have contributed to systematize the guiding elements of evaluation in mathematics from the historical-cultural perspective.

Cultivo da microalga marinha Chaetoceros calcitrans (BACILLARIOPHYCEAE) utilizando diferentes tipos de água marinha artificial

The use of microalgae as live food to a wide variety of organisms is one of the most important aspects in aquaculture. Several commercial formulations have been available in the marine aquarium market in order to prepare artificial sea water (ASW). The present study accounted microalgae Chaetoceros calcitrans performance cultured using different ASW in comparison to natural seawater(NSW). it was carried out using red Sea, Coralife and oceanic, three different ASW brands and NSW as control. nonaerated cultures were grew in 400 mL with Conwy culture medium with five replicates each under defined conditions. All cultures began with an algal inoculum of 208.000 cells/mL. a 5-mL aliquot was removed daily from each culture for cells counts. data obtained using polynomial regression test demonstrated that all ASW brands reached higher algal density rates than the one with NSW, though the three ASW brands were significantly heterogeneous. C. calcitrans raised with oceanic and red Sea brands showed similar growth rates and both were higher than Coralife brand. the results suggest that all three ASW brands studied can be used in the culture of this microalgae specie.