An integrated genomic analysis of human glioblastoma Multiforme

Glioblastoma multiforme ( GBM) is the most common and lethal type of brain cancer. To identify the genetic alterations in GBMs, we sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high- density oligonucleotide arrays, and performed gene expression analyses using next- generation sequencing technologies in 22 human tumor samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs. Most notably, we found recurrent mutations in the active site of isocitrate dehydrogenase 1 ( IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. These studies demonstrate the value of unbiased genomic analyses in the characterization of human brain cancer and identify a potentially useful genetic alteration for the classification and targeted therapy of GBMs.

Integrated multivariate analysis to evaluate effects of pre-slaughter handling on pork quality

The aim of this study was to investigate the effect of pre-slaughter handling on the occurrence of PSE (Pale, Soft, and Exudative) meat in swine slaughtered at a commercial slaughterhouse located in the metropolitan region of Dourados, Mato Grosso do Sul, Brazil. Based on the database (n=1,832 carcasses), it was possible to apply the integrated multivariate analysis for the purpose of identifying, among the selected variables, those of greatest relevance to this study. Results of the Principal Component Analysis showed that the first five components explained 89.28% of total variance. In the Factor Analysis, the first factor represented the thermal stress and fatiguing conditions for swine during pre-slaughter handling. In general, this study indicated the importance of the pre-slaughter handling stages, evidencing those of greatest stress and threat to animal welfare and pork quality, which are transport time, resting period, lairage time before unloading, unloading time, and ambience.

Field report from sediment coring in peat for landscape analysis in Hjaltadalur, Skagafjörður, north Iceland 2010 : Sediment drilling in Hólar, Vidvik and Kolkuós, Hjaltadalur

This field report presents fieldwork undertaken in Hjaltadalur, Skagafjördur, northern Iceland during summer 2010. The main aim was to initiate coring in selected mires in order to determine the composition of organic material and sediments in the mires, sub-sample for sedimentological and palaeoecological analyses, and initiate advanced landscape analysis of Hjaltadalur. Three mires were selected for sediments coring in Hjaltadalur: Ástunga close to Kolkóus, Hólakot at Viðvik, and Hólar. All three represented a landscape transect in NW to SE direction, from close to the coast to valley interior, i.e. close to the old settlement at Hólar.

Mapping surface deformation in open pit iron mines of Carajas Province (Amazon Region) using an integrated SAR analysis

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

Microfabricated structures for integrated DNA analysis.

Photolithographic micromachining of silicon is a candidate technology for the construction of high-throughput DNA analysis devices. However, the development of complex silicon microfabricated systems has been hindered in part by the lack of a simple, versatile pumping method for integrating individual components. Here we describe a surface-tension-based pump able to move discrete nanoliter drops through enclosed channels using only local heating. This thermocapillary pump can accurately mix, measure, and divide drops by simple electronic control. In addition, we have constructed thermal-cycling chambers, gel electrophoresis channels, and radiolabeled DNA detectors that are compatible with the fabrication of thermocapillary pump channels. Since all of the components are made by conventional photolithographic techniques, they can be assembled into more complex integrated systems. The combination of pump and components into self-contained miniaturized devices may provide significant improvements in DNA analysis speed, portability, and cost. The potential of microfabricated systems lies in the low unit cost of silicon-based construction and in the efficient sample handling afforded by component integration.

Environmental consequences of CO² climate interactions : the need for integrated resource analysis /

Mode of access: Internet.

Integrated sensitivity analysis, calibration, and uncertainty propagation analysis approaches for supporting hydrological modeling

The successful performance of a hydrological model is usually challenged by the quality of the sensitivity analysis, calibration and uncertainty analysis carried out in the modeling exercise and subsequent simulation results. This is especially important under changing climatic conditions where there are more uncertainties associated with climate models and downscaling processes that increase the complexities of the hydrological modeling system. In response to these challenges and to improve the performance of the hydrological models under changing climatic conditions, this research proposed five new methods for supporting hydrological modeling. First, a design of experiment aided sensitivity analysis and parameterization (DOE-SAP) method was proposed to investigate the significant parameters and provide more reliable sensitivity analysis for improving parameterization during hydrological modeling. The better calibration results along with the advanced sensitivity analysis for significant parameters and their interactions were achieved in the case study. Second, a comprehensive uncertainty evaluation scheme was developed to evaluate three uncertainty analysis methods, the sequential uncertainty fitting version 2 (SUFI-2), generalized likelihood uncertainty estimation (GLUE) and Parameter solution (ParaSol) methods. The results showed that the SUFI-2 performed better than the other two methods based on calibration and uncertainty analysis results. The proposed evaluation scheme demonstrated that it is capable of selecting the most suitable uncertainty method for case studies. Third, a novel sequential multi-criteria based calibration and uncertainty analysis (SMC-CUA) method was proposed to improve the efficiency of calibration and uncertainty analysis and control the phenomenon of equifinality. The results showed that the SMC-CUA method was able to provide better uncertainty analysis results with high computational efficiency compared to the SUFI-2 and GLUE methods and control parameter uncertainty and the equifinality effect without sacrificing simulation performance. Fourth, an innovative response based statistical evaluation method (RESEM) was proposed for estimating the uncertainty propagated effects and providing long-term prediction for hydrological responses under changing climatic conditions. By using RESEM, the uncertainty propagated from statistical downscaling to hydrological modeling can be evaluated. Fifth, an integrated simulation-based evaluation system for uncertainty propagation analysis (ISES-UPA) was proposed for investigating the effects and contributions of different uncertainty components to the total propagated uncertainty from statistical downscaling. Using ISES-UPA, the uncertainty from statistical downscaling, uncertainty from hydrological modeling, and the total uncertainty from two uncertainty sources can be compared and quantified. The feasibility of all the methods has been tested using hypothetical and real-world case studies. The proposed methods can also be integrated as a hydrological modeling system to better support hydrological studies under changing climatic conditions. The results from the proposed integrated hydrological modeling system can be used as scientific references for decision makers to reduce the potential risk of damages caused by extreme events for long-term water resource management and planning.

Integrated molecular analysis of endometrial carcinoma: translation of biomarker profiles into the clinical practice

The Cancer Genome Atlas (TCGA) collaborative project identified four distinct prognostic groups of endometrial carcinoma (EC) based on molecular alterations: (i) the ultramutated subtype that encompassed POLE mutated (POLE) cases; (ii) the hypermutated subtype, characterized by MisMatch Repair deficiency (MMRd); (iii) the copy-number high subtype, with p53 abnormal/mutated features (p53abn); (iv) the copy-number low subtype, known as No Specific Molecular Profile (NSMP). Although the prognostic value of TCGA molecular classification, NSMP tumors present a wide variability in molecular alterations and biological aggressiveness. This study aims to investigate the impact of ARID1A and CTNNB1/β-catenin alterations by targeted Next-generation sequencing (NGS) and immunohistochemistry (IHC) in a consecutive series of 125 molecularly classified ECs. NGS and IHC were used to assign surrogate TCGA groups and to identify molecular alterations of multiple target genes including POLE, PTEN, ARID1A, CTNNB1, TP53. Associations with clinicopathologic parameters, molecular subtypes, and outcomes identified NSMP category as the most heterogeneous group in terms of clinicopathologic features and outcome. Integration of surrogate TCGA molecular classification with ARID1A and β-catenin analysis showed NSMP cases with ARID1A mutation characterized by the worst outcome with early recurrence, while NSMP tumors with ARID1A wild-type and β-catenin alteration had indolent clinicopathologic features and no recurrence. This study indicates how the identification of ARID1A and β-catenin alterations in EC represents a simple and effective way to characterize NSMP tumor aggressiveness and metastatic potential.

Modelo de análise espacial em sistemas de informação geográfica para requalificação biofísica de explorações mineiras

Dissertação apresentada como requisito parcial para obtenção do grau de Mestre em Ciência e Sistemas de Informação Geográfica

Proposta de critérios adicionais para definição de Área Prioritária para Conservação no Semiárido brasileiro

Environmental changes and their consequences on the global level have challenged the different fields of study to integrate towards effective solutions to minimize and /or equate the negative impacts of these changes in different types of environments. In this context, the Environmental Perception has been a widely used and relevant in studies that consider the relationship between the environment and human actions, by allowing analysis of perceptions, attitudes and values, key influencers of topophilia that resonates in conservation tool. Allied to Environmental Perception, Integrated Analysis of the Landscape is relevant because it allows to analyze in a systematic way the geographical space where all its elements are interrelated in a way that supports needed to understand the complex physical and human environment of a given environment. In this perspective, we have studied the João do Vale Serrano Complex, located in semiarid of Rio Grande do Norte state, which features a set of landscapes with different faces, which are being replaced by various economic activities and disordered population growth, with consequent exploitation the potential of natural resources. This thesis main goal was to combine the Environmental Perception of rural communities to the of Serrano Complex Landscape Analysis as additional criteria for the definition of Priority Areas for Conservation. The perception data were collected through direct observation, questioning, interviews and application forms to 240 people (100 % of occupied households in the mountain community) during the months of february and august 2011, with theoretical and methodological basis Environmental Perception. Integrated Landscape Analysis was performed by GTP (Geosystem - Territory - Landscape) method, using the Geographic Information System (GIS), using the technique of GIS for mapping the landscape. The results showed that respondents have a sense of topophilia by where they live, hold a vast knowledge of the natural resources in this Serrano Complex, and responded positively regarding the choice of an exclusive area for conservation. The Integrated Analysis of Landscape possible to identify the different forms of existing uses and occupations in Serrano Complex, have caused significant changes in space, especially on the plateau where vegetation was virtually replaced by human dwellings and cashew plantations. Through the maps of slope and environmental vulnerability was identified that areas with high slopes (gullies) are limiting factor for occupation by communities and therefore relevant and amenable to conservation, including by being Permanent Preservation Areas. These results, together, made possible to define a map of Priority Areas for Conservation in Serrano Complex, with three priority categories: low, medium and high. Therefore, the use of these additional criteria are relevant for the definition /designation of Priority Areas for Conservation

An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P<0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.