Extent and patterns of MGMT promoter methylation in glioblastoma- and respective glioblastoma-derived spheres.

Purpose: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. Experimental Design: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), cultured under stem cell conditions, were analyzed for the degree and pattern of MGMT promoter methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin status, and respective effects on MGMT expression and MGMT activity. Results: In glioblastoma, MGMT-methylated alleles ranged from 10% to 90%. In contrast, methylated alleles were highly enriched (100% of clones) in respective GS, even when 2 MGMT alleles were present, with 1 exception (<50%). The CpG methylation patterns were characteristic for each glioblastoma exhibiting 25% to 90% methylated CpGs of 28 sites interrogated. Furthermore, MGMT promoter methylation was associated with a nonpermissive chromatin status in accordance with very low MGMT transcript levels and undetectable MGMT activity. Conclusions: In MGMT-methylated glioblastoma, MGMT promoter methylation is highly enriched in GS that supposedly comprise glioma-initiating cells. Thus, even a low percentage of MGMT methylation measured in a glioblastoma sample may be relevant and predict benefit from an alkylating agent therapy. Clin Cancer Res; 17(2); 255-66. (C)2010 AACR.

Executive Order Number Twenty-Five, August 6, 2010

July 24, 2010, the breach of the Lake Delhi dam caused flash floods and massive damage to persons and businesses and public infrastructure in Delaware and Jones counties and surrounding areas, including Jackson County, resulting in gubernatorial declarations of emergency and applications for federal disaster assistance for these areas.

Modelos matemáticos para a estimativa do potencial de mineralização anaeróbia do nitrogênio em solos de Várzea do Rio Grande do Sul

Diferentes modelos matemáticos são utilizados para estimar o potencial de mineralização de N no solo, e os parâmetros estimados com a decomposição anaeróbia podem ser empregados na predição da disponibilidade do N para a cultura do arroz irrigado. Os objetivos deste trabalho foram estimar, a partir de cinco modelos matemáticos, os parâmetros "N potencialmente mineralizável" (N0) e "taxa de mineralização" (k) de diferentes solos de várzea do Rio Grande do Sul (RS) e correlacionar os valores de N0 dos modelos com o N acumulado por plantas de arroz irrigado. O trabalho foi desenvolvido a partir de amostras de solos de várzea coletadas em 15 locais do RS, utilizadas em um experimento de incubação anaeróbia em laboratório, onde foram determinados valores de N mineral da solução do solo ao longo de 24 semanas. A partir dos resultados, foram estimados os parâmetros de acordo com cinco modelos matemáticos. Posteriormente, amostras dos solos foram utilizadas em dois cultivos sucessivos de arroz irrigado, em casa de vegetação, obtendo-se valores da quantidade de N acumulado pelas plantas. O modelo mais bem ajustado na estimativa do N0 e k para a média dos 15 solos de várzea do RS foi o de Jones. Entretanto, o N0 do modelo de Stanford & Smith foi o que melhor se correlacionou com a quantidade de N acumulado pelas plantas de arroz irrigado no primeiro cultivo, enquanto o N0 do modelo de Jones foi o que melhor se correlacionou com o N acumulado pelas plantas no segundo cultivo.

Extent and Patterns of MGMT Promoter Methylation in Glioblastoma- and Respective Glioblastoma-Derived Spheres.

PURPOSE: Quantitative methylation-specific tests suggest that not all cells in a glioblastoma with detectable promoter methylation of the O6-methylguanine DNA methyltransferase (MGMT) gene carry a methylated MGMT allele. This observation may indicate cell subpopulations with distinct MGMT status, raising the question of the clinically relevant cutoff of MGMT methylation therapy. Epigenetic silencing of the MGMT gene by promoter methylation blunts repair of O6-methyl guanine and has been shown to be a predictive factor for benefit from alkylating agent therapy in glioblastoma. EXPERIMENTAL DESIGN: Ten paired samples of glioblastoma and respective glioblastoma-derived spheres (GS), cultured under stem cell conditions, were analyzed for the degree and pattern of MGMT promoter methylation by methylation-specific clone sequencing, MGMT gene dosage, chromatin status, and respective effects on MGMT expression and MGMT activity. RESULTS: In glioblastoma, MGMT-methylated alleles ranged from 10% to 90%. In contrast, methylated alleles were highly enriched (100% of clones) in respective GS, even when 2 MGMT alleles were present, with 1 exception (<50%). The CpG methylation patterns were characteristic for each glioblastoma exhibiting 25% to 90% methylated CpGs of 28 sites interrogated. Furthermore, MGMT promoter methylation was associated with a nonpermissive chromatin status in accordance with very low MGMT transcript levels and undetectable MGMT activity. CONCLUSIONS: In MGMT-methylated glioblastoma, MGMT promoter methylation is highly enriched in GS that supposedly comprise glioma-initiating cells. Thus, even a low percentage of MGMT methylation measured in a glioblastoma sample may be relevant and predict benefit from an alkylating agent therapy. Clin Cancer Res; 17(2); 255-66. ©2010 AACR.

Tax reforms and inequality: theoretical and empirical implications

In this paper we examine the effect of tax policy on the relationship between inequality and growth in a two-sector non-scale model. With non-scale models, the longrun equilibrium growth rate is determined by technological parameters and it is independent of macroeconomic policy instruments. However, this fact does not imply that fiscal policy is unimportant for long-run economic performance. It indeed has important effects on the different levels of key economic variables such as per capita stock of capital and output. Hence, although the economy grows at the same rate across steady states, the bases for economic growth may be different.The model has three essential features. First, we explicitly model skill accumulation, second, we introduce government finance into the production function, and we introduce an income tax to mirror the fiscal events of the 1980¿s and 1990¿s in the US. The fact that the non-scale model is associated with higher order dynamics enables it to replicate the distinctly non-linear nature of inequality in the US with relative ease. The results derived in this paper attract attention to the fact that the non-scale growth model does not only fit the US data well for the long-run (Jones, 1995b) but also that it possesses unique abilities in explaining short term fluctuations of the economy. It is shown that during transition the response of the relative simulated wage to changes in the tax code is rather non-monotonic, quite in accordance to the US inequality pattern in the 1980¿s and early 1990¿s.More specifically, we have analyzed in detail the dynamics following the simulation of an isolated tax decrease and an isolated tax increase. So, after a tax decrease the skill premium follows a lower trajectory than the one it would follow without a tax decrease. Hence we are able to reduce inequality for several periods after the fiscal shock. On the contrary, following a tax increase, the evolution of the skill premium remains above the trajectory carried on by the skill premium under a situation with no tax increase. Consequently, a tax increase would imply a higher level of inequality in the economy

AMADEUS: advanced manipulation for deep underwater sampling

AMADEUS is a dexterous subsea robot hand incorporating force and slip contact sensing, using fluid filled tentacles for fingers. Hydraulic pressure variations in each of three flexible tubes (bellows) in each finger create a bending moment, and consequent motion or increase in contact force during grasping. Such fingers have inherent passive compliance, no moving parts, and are naturally depth pressure-compensated, making them ideal for reliable use in the deep ocean. In addition to the mechanical design, development of the hand has also considered closed loop finger position and force control, coordinated finger motion for grasping, force and slip sensor development/signal processing, and reactive world modeling/planning for supervisory `blind grasping¿. Initially, the application focus is for marine science tasks, but broader roles in offshore oil and gas, salvage, and military use are foreseen. Phase I of the project is complete, with the construction of a first prototype. Phase I1 is now underway, to deploy the hand from an underwater robot arm, and carry out wet trials with users.

Tax reforms and inequality: theoretical and empirical implications

In this paper we examine the effect of tax policy on the relationship between inequality and growth in a two-sector non-scale model. With non-scale models, the longrun equilibrium growth rate is determined by technological parameters and it is independent of macroeconomic policy instruments. However, this fact does not imply that fiscal policy is unimportant for long-run economic performance. It indeed has important effects on the different levels of key economic variables such as per capita stock of capital and output. Hence, although the economy grows at the same rate across steady states, the bases for economic growth may be different.The model has three essential features. First, we explicitly model skill accumulation, second, we introduce government finance into the production function, and we introduce an income tax to mirror the fiscal events of the 1980¿s and 1990¿s in the US. The fact that the non-scale model is associated with higher order dynamics enables it to replicate the distinctly non-linear nature of inequality in the US with relative ease. The results derived in this paper attract attention to the fact that the non-scale growth model does not only fit the US data well for the long-run (Jones, 1995b) but also that it possesses unique abilities in explaining short term fluctuations of the economy. It is shown that during transition the response of the relative simulated wage to changes in the tax code is rather non-monotonic, quite in accordance to the US inequality pattern in the 1980¿s and early 1990¿s.More specifically, we have analyzed in detail the dynamics following the simulation of an isolated tax decrease and an isolated tax increase. So, after a tax decrease the skill premium follows a lower trajectory than the one it would follow without a tax decrease. Hence we are able to reduce inequality for several periods after the fiscal shock. On the contrary, following a tax increase, the evolution of the skill premium remains above the trajectory carried on by the skill premium under a situation with no tax increase. Consequently, a tax increase would imply a higher level of inequality in the economy

Quantification of human adenoviruses in European recreational waters

The presence of human adenoviruses in recreational water might cause disease in the population upon exposure. Human adenoviruses detected by PCR could also serve as indicators of the virological water quality. In order to assess the applicability of human adenoviruses to the evaluation of the faecal contamination in European bathing waters, a real-time quantitative PCR assay was developed for the quantification of human adenoviruses in 132 samples collected from 24 different recreational marine and freshwater sites in nine European countries.Selected samples presenting positive nested-PCR results for human adenoviruses were analyzed using quantitative PCR and 80 samples from a total of 132 produced quantitative results with mean values of 3.2x102 10 per 100 ml of water, human adenovirus 41 being the most prevalent serotype. Human adenoviruses were quantified in samples from all 15 surveillance laboratories. Statistical analysis showed no homogeneous linear relation between humanadenoviruses and E. coli, intestinal enterococci or somatic coliphages concentrations in the tested samples when considering all the data together. Significant correlations between human adenoviruses and at least one of the other indicators were observed only when data from individual Laboratories were considered. The quantification of human adenoviruses may provide complementary information in relation to the use of bacterial standards in the control of water quality in bathing water.

AMADEUS: advanced manipulation for deep underwater sampling

AMADEUS is a dexterous subsea robot hand incorporating force and slip contact sensing, using fluid filled tentacles for fingers. Hydraulic pressure variations in each of three flexible tubes (bellows) in each finger create a bending moment, and consequent motion or increase in contact force during grasping. Such fingers have inherent passive compliance, no moving parts, and are naturally depth pressure-compensated, making them ideal for reliable use in the deep ocean. In addition to the mechanical design, development of the hand has also considered closed loop finger position and force control, coordinated finger motion for grasping, force and slip sensor development/signal processing, and reactive world modeling/planning for supervisory `blind grasping¿. Initially, the application focus is for marine science tasks, but broader roles in offshore oil and gas, salvage, and military use are foreseen. Phase I of the project is complete, with the construction of a first prototype. Phase I1 is now underway, to deploy the hand from an underwater robot arm, and carry out wet trials with users.

Genomics and the origin of species.

Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics.

DRIS formulas for evaluation of nutritional status of cupuaçu trees

DRIS, an Diagnosis and Recommendation Integrated System, is a tool to evaluate the nutritional status of plants. Different DRIS formulas have been proposed to improve the efficiency of the crop nutrition diagnoses. The objective of this study was to compare the nutritional diagnosis of the formulas of Beaufils (1973), of Jones (1981) and of Elwali and Gascho (1984), based on the degree of agreement in commercial orchards of Theobrama grandiflorum trees. Leaf samples of 5 to 18 year-old cupuaçu trees were collected from 153 commercial orchards in agroforestry and monoculture systems in the state of Rondonia, Brazil. Bivariate relationships between nutrition concentrations in healthy trees were used to calculate DRIS norms. DRIS indices were calculated based on the different formulas and interpreted by the Potential Fertilizer Response method, in five categories. The DRIS norms, DRIS index calculations and their interpretations were developed using the DRIS Cupuaçu computer program (www.dris.com.br). The different DRIS formulas resulted in similar diagnoses with a degree of agreement of > 90% for the nutrients N, P, K, Ca, and Mg.

Interpretação de índices dris para a cultura do cupuaçu

A produtividade dos pomares de cupuaçu na Amazônia tem experimentado lento declínio, provavelmente devido à diminuição da fertilidade do solo, requerendo adubações. Na ausência de recomendações técnicas para quantificar a demanda por nutrientes por essa cultura, o uso do Sistema Integrado de Diagnose e Recomendação (DRIS) pode representar uma alternativa para suprir essa necessidade. O objetivo deste trabalho foi avaliar os diagnósticos produzidos por diferentes fórmulas e critérios de interpretação dos índices DRIS em pomares de cupuaçu. Amostras foliares de 153 pomares foram analisadas para os nutrientes N, P, K, Ca, Mg, Zn, Mn, Cu e Fe e diagnosticadas por três fórmulas DRIS: Beaufils, Jones e Wadt e colaboradores. Na interpretação dos índices DRIS, utilizaram-se: o método DRIS Matéria Seca (M-DRIS), que separa os nutrientes em limitantes ou não limitantes, e o método do Potencial de Resposta à Adubação, o qual separa os nutrientes no estado nutricional de insuficientes, equilibrados ou em excesso. Foram também adotados níveis críticos para os teores dos nutrientes foliares em cupuaçueiros, oriundos da literatura. Os diagnósticos produzidos pelos diferentes critérios de interpretação dos índices DRIS não foram consistentes entre si ou em comparação com o método do nível crítico. A exceção foi a fórmula de Wadt e colaboradores que mostrou maior consistência entre os diagnósticos, independentemente do critério utilizado para sua interpretação. Os valores sugeridos para avaliação do estado nutricional pelo método do nível crítico não foram satisfatórios.

Fertilization response likelihood for the interpretation of leaf analyses

Leaf analysis is the chemical evaluation of the nutritional status where the nutrient concentrations found in the tissue reflect the nutritional status of the plants. Thus, a correct interpretation of the results of leaf analysis is fundamental for an effective use of this tool. The purpose of this study was to propose and compare the method of Fertilization Response Likelihood (FRL) for interpretation of leaf analysis with that of the Diagnosis and Recommendation Integrated System (DRIS). The database consisted of 157 analyses of the N, P, K, Ca, Mg, S, Cu, Fe, Mn, Zn, and B concentrations in coffee leaves, which were divided into two groups: low yield (< 30 bags ha-1) and high yield (> 30 bags ha-1). The DRIS indices were calculated using the method proposed by Jones (1981). The fertilization response likelihood was computed based on the approximation of normal distribution. It was found that the Fertilization Response Likelihood (FRL) allowed an evaluation of the nutritional status of coffee trees, coinciding with the DRIS-based diagnoses in 84.96 % of the crops.