DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Copy number variations of colorectal cancer by whole exome sequencing data

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death worldwide. About 85% of the cases of CRC are known to have chromosomal instability, an allelic imbalance at several chromosomal loci, and chromosome amplification and translocation. The aim of this study is to determine the recurrent copy number variant (CNV) regions present in stage II of CRC through whole exome sequencing, a rapidly developing targeted next-generation sequencing (NGS) technology that provides an accurate alternative approach for accessing genomic variations. 42 normal-tumor paired samples were sequenced by Illumina Genome Analyzer. Data was analyzed with Varscan2 and segmentation was performed with R package R-GADA. Summary of the segments across all samples was performed and the result was overlapped with DEG data of the same samples from a previous study in the group1. Major and more recurrent segments of CNV were: gain of chromosome 7pq(13%), 13q(31%) and 20q(75%) and loss of 8p(25%), 17p(23%), and 18pq(27%). This results are coincident with the known literature of CNV in CRC or other cancers, but our methodology should be validated by array comparative genomic hybridisation (aCGH) profiling, which is currently the gold standard for genetic diagnosis of CNV.

A Case-based reasoning approach to validate grammatical gender and number agreement in Spanish language

Across Latin America 420 indigenous languages are spoken. Spanish is considered a second language in indigenous communities and is progressively introduced in education. However, most of the tools to support teaching processes of a second language have been developed for the most common languages such as English, French, German, Italian, etc. As a result, only a small amount of learning objects and authoring tools have been developed for indigenous people considering the specific needs of their population. This paper introduces Multilingual–Tiny as a web authoring tool to support the virtual experience of indigenous students and teachers when they are creating learning objects in indigenous languages or in Spanish language, in particular, when they have to deal with the grammatical structures of Spanish. Multilingual–Tiny has a module based on the Case-based Reasoning technique to provide recommendations in real time when teachers and students write texts in Spanish. An experiment was performed in order to compare some local similarity functions to retrieve cases from the case library taking into account the grammatical structures. As a result we found the similarity function with the best performance

Minimum number of assessment times to compare chemical control treatments for papaya fruit anthracnose

The chemical treatment evaluation in the field to control post-harvest fruit anthracnose (Colletotrichum gloeosporioides) requires a suitable disease incidence assessment on harvested papaya (Carica papaya) fruits. The minimum number of papaya fruit harvests was determined for valid treatment comparison in field trials for anthracnose chemical control. Repeatability analysis was done using previously published data. The coefficient determination (R²) estimate range, using four methods, and based on means of 12 assessment times, was 92.58 < R² < 94.45%. The number of assessment times required for R²=90% varied from seven to nine. The R² values of 85.1 < R² < 91.3% estimated by ANOVA suggested that any seven successive assessment times were sufficient for treatment comparison.

THE FORMAL AND THE FORMALIZED: THE CASES OF SYLLOGISTIC AND SUPPOSITION THEORY

As a discipline, logic is arguably constituted of two main sub-projects: formal theories of argument validity on the basis of a small number of patterns, and theories of how to reduce the multiplicity of arguments in non-logical, informal contexts to the small number of patterns whose validity is systematically studied (i.e. theories of formalization). Regrettably, we now tend to view logic 'proper' exclusively as what falls under the first sub-project, to the neglect of the second, equally important sub-project. In this paper, I discuss two historical theories of argument formalization: Aristotle's syllogistic theory as presented in the "Prior Analytics", and medieval theories of supposition. They both illustrate this two-fold nature of logic, containing in particular illuminating reflections on how to formalize arguments (i.e. the second sub-project). In both cases, the formal methods employed differ from the usual modern technique of translating an argument in ordinary language into a specially designed symbolism, a formal language. The upshot is thus a plea for a broader conceptualization of what it means to formalize.

Influence of distance, geometry and number of control stations on quality of local geodetic networks for the purpose of georeferencing of rural properties

The implementation of local geodetic networks for georeferencing of rural properties has become a requirement after publication of the Georeferencing Technical Standard by INCRA. According to this standard, the maximum distance of baselines to GNSS L1 receivers is of 20 km. Besides the length of the baseline, the geometry and the number of geodetic control stations are other factors to be considered in the implementation of geodetic networks. Thus, this research aimed to examine the influence of baseline lengths higher than the regulated limit of 20 km, the geometry and the number of control stations on quality of local geodetic networks for georeferencing, and also to demonstrate the importance of using specific tests to evaluate the solution of ambiguities and on the quality of the adjustment. The results indicated that the increasing number of control stations has improved the quality of the network, the geometry has not influenced on the quality and the baseline length has influenced on the quality; however, lengths higher than 20 km has not interrupted the implementation, with GPS L1 receiver, of the local geodetic network for the purpose of georeferencing. Also, the use of different statistical tests, both for the evaluation of the resolution of ambiguities and for the adjustment, have enabled greater clearness in analyzing the results, which allow that unsuitable observations may be eliminated.

The number and profile of reactive NADH-d and NADPH-d neurons of myenteric plexus of six-month-old rats are different in the cecum portions

Whole-mount preparations were prepared and submitted to NADH-diaphorase and NADPH-diaphorase histochemistry techniques. The myenteric plexus arrangement and the number of neurons were comparatively evaluated among the different portions of the cecum. The neurons from the apical and basal regions were distributed in classes at intervals of 100µm², the means of the corresponding intervals being compared. The ganglia, in both techniques, were often connected by fine bundles, which became thicker in the mesenteric region and in the region next to the cecal ampulla. The number of positive NADH-d neurons was higher than that of NADPH-d neurons in all portions, from both regions. The numbers of reactive NADH-d e NADPH-d neurons were significantly different among the different portions of the cecum, except for the antimesenteric basal and intermediate basal regions, considering the NADH-d neurons. The profile area for the reactive NADH-d e NADPH-d neurons was higher in the apical region than in the basal area. Differences in arrangement, distribution and size of positive NADH-d e NADPH-d neurons in the different cecum portions evidenced the importance of the subdivision of the analyzed organ.

Spontaneous Focusing on Quantitative Relations and the Development of Rational Number Conceptual Knowledge

The aim of the present set of studies was to explore primary school children’s Spontaneous Focusing On quantitative Relations (SFOR) and its role in the development of rational number conceptual knowledge. The specific goals were to determine if it was possible to identify a spontaneous quantitative focusing tendency that indexes children’s tendency to recognize and utilize quantitative relations in non-explicitly mathematical situations and to determine if this tendency has an impact on the development of rational number conceptual knowledge in late primary school. To this end, we report on six original empirical studies that measure SFOR in children ages five to thirteen years and the development of rational number conceptual knowledge in ten- to thirteen-year-olds. SFOR measures were developed to determine if there are substantial differences in SFOR that are not explained by the ability to use quantitative relations. A measure of children’s conceptual knowledge of the magnitude representations of rational numbers and the density of rational numbers is utilized to capture the process of conceptual change with rational numbers in late primary school students. Finally, SFOR tendency was examined in relation to the development of rational number conceptual knowledge in these students. Study I concerned the first attempts to measure individual differences in children’s spontaneous recognition and use of quantitative relations in 86 Finnish children from the ages of five to seven years. Results revealed that there were substantial inter-individual differences in the spontaneous recognition and use of quantitative relations in these tasks. This was particularly true for the oldest group of participants, who were in grade one (roughly seven years old). However, the study did not control for ability to solve the tasks using quantitative relations, so it was not clear if these differences were due to ability or SFOR. Study II more deeply investigated the nature of the two tasks reported in Study I, through the use of a stimulated-recall procedure examining children’s verbalizations of how they interpreted the tasks. Results reveal that participants were able to verbalize reasoning about their quantitative relational responses, but not their responses based on exact number. Furthermore, participants’ non-mathematical responses revealed a variety of other aspects, beyond quantitative relations and exact number, which participants focused on in completing the tasks. These results suggest that exact number may be more easily perceived than quantitative relations. As well, these tasks were revealed to contain both mathematical and non-mathematical aspects which were interpreted by the participants as relevant. Study III investigated individual differences in SFOR 84 children, ages five to nine, from the US and is the first to report on the connection between SFOR and other mathematical abilities. The cross-sectional data revealed that there were individual differences in SFOR. Importantly, these differences were not entirely explained by the ability to solve the tasks using quantitative relations, suggesting that SFOR is partially independent from the ability to use quantitative relations. In other words, the lack of use of quantitative relations on the SFOR tasks was not solely due to participants being unable to solve the tasks using quantitative relations, but due to a lack of the spontaneous attention to the quantitative relations in the tasks. Furthermore, SFOR tendency was found to be related to arithmetic fluency among these participants. This is the first evidence to suggest that SFOR may be a partially distinct aspect of children’s existing mathematical competences. Study IV presented a follow-up study of the first graders who participated in Studies I and II, examining SFOR tendency as a predictor of their conceptual knowledge of fraction magnitudes in fourth grade. Results revealed that first graders’ SFOR tendency was a unique predictor of fraction conceptual knowledge in fourth grade, even after controlling for general mathematical skills. These results are the first to suggest that SFOR tendency may play a role in the development of rational number conceptual knowledge. Study V presents a longitudinal study of the development of 263 Finnish students’ rational number conceptual knowledge over a one year period. During this time participants completed a measure of conceptual knowledge of the magnitude representations and the density of rational numbers at three time points. First, a Latent Profile Analysis indicated that a four-class model, differentiating between those participants with high magnitude comparison and density knowledge, was the most appropriate. A Latent Transition Analysis reveal that few students display sustained conceptual change with density concepts, though conceptual change with magnitude representations is present in this group. Overall, this study indicated that there were severe deficiencies in conceptual knowledge of rational numbers, especially concepts of density. The longitudinal Study VI presented a synthesis of the previous studies in order to specifically detail the role of SFOR tendency in the development of rational number conceptual knowledge. Thus, the same participants from Study V completed a measure of SFOR, along with the rational number test, including a fourth time point. Results reveal that SFOR tendency was a predictor of rational number conceptual knowledge after two school years, even after taking into consideration prior rational number knowledge (through the use of residualized SFOR scores), arithmetic fluency, and non-verbal intelligence. Furthermore, those participants with higher-than-expected SFOR scores improved significantly more on magnitude representation and density concepts over the four time points. These results indicate that SFOR tendency is a strong predictor of rational number conceptual development in late primary school children. The results of the six studies reveal that within children’s existing mathematical competences there can be identified a spontaneous quantitative focusing tendency named spontaneous focusing on quantitative relations. Furthermore, this tendency is found to play a role in the development of rational number conceptual knowledge in primary school children. Results suggest that conceptual change with the magnitude representations and density of rational numbers is rare among this group of students. However, those children who are more likely to notice and use quantitative relations in situations that are not explicitly mathematical seem to have an advantage in the development of rational number conceptual knowledge. It may be that these students gain quantitative more and qualitatively better self-initiated deliberate practice with quantitative relations in everyday situations due to an increased SFOR tendency. This suggests that it may be important to promote this type of mathematical activity in teaching rational numbers. Furthermore, these results suggest that there may be a series of spontaneous quantitative focusing tendencies that have an impact on mathematical development throughout the learning trajectory.

Interaction between the mineral content and the occurrence number of aquatic fungi in leaves submerged in a stream in the Atlantic rainforest, São Paulo, Brazil

Leaves of Ficus microcarpa L. f., Quercus robur L., and Alchornea triplinervia (Spreng.) Muell. Arg., submerged in a stream of the Atlantic rainforest in the "Reserva Biológica do Alto da Serra de Paranapiacaba", State of São Paulo, Brazil, were collected monthly, from April to November 1990, in order to determine the number of fungal occurrences (zoosporic fungi and aquatic Hyphomycetes), and the content of total N (%), total P (%), K+ (%), Ca+2 (%), Mg+2 (%), S+3 (%), Fe+3 (ppm), Cu+3 (ppm), Mn+2 (ppm), Zn+2 (ppm), Bo (ppm), Na+2 (ppm) and Al+3 (ppm). According to the tests of Kruskal-Wallis, Mann-Whitney and Wilcoxon, the means of the mineral content of the three types of leaves were significantly different, except for Mg+2 (%), Mn+2 (ppm), Zn+2 (ppm) and Na+2 (ppm). On comparing the mineral content with the number of fungal occurrence, an independence test showed a positive correlation between the presence of zoosporic fungi on the leaves of A. triplinervia and the total nitrogen, phosphorus and S+3 content, whereas the aquatic Hyphomycetes depended on the amount of Ca+2 available. Regarding leaves of F. microcarpa, the occurrence of zoosporic fungi was linked to the S+3 level, and the presence of aquatic Hyphomycetes, to the content of K+, Ca+2, S+3 and Bo. On Q. robur leaves, zoosporic fungi showed a positive correlation with the Ca+2 content, but a negative one with Fe+3 and Al+3 levels, while the occurrence of aquatic Hyphomycetes was influenced by the content of Ca+2, Mg+2, Fe+3, Al+3, Mn+2, Zn+2 and Na+2. The correlation between the occurrence number of aquatic Hyphomycetes and a high mineral content indicates that their nutritional requirements may be more complex than those of zoosporic fungi. Further studies are still required to understand the implications of this tendency on the diversity of aquatic native mycota.

Number of buried seeds and seedlings emergence in cerradão, cerrado and gallery forest soils at Pedregulho, Itirapina (SP), Brazil

This study was carried out at the site named Pedregulho in the "Estação Experimental de Itirapina", Itirapina, state of São Paulo, Brazil. Soil samples were collected in the rainy and in the dry season at three depths in the gallery forest, cerrado and cerradão. The total number of seeds was counted after being separated from the soil by wet sieving and the number of viable seeds was determined by emergence of seedlings in soil samples in a greenhouse. The number of seeds and of emerged seedlings decreases as soil samples become deeper. The number of seeds was much larger in the cerrado in the dry season than in the rainy season, but it was lower in the dry than in the rainy season in the gallery forest. The number of seeds in the cerradão was similar in both seasons. There was a heavy discrepancy between the total number of seeds and that of emerged seedlings.

Intrapopulational chromosome number variation in Zephyranthes sylvatica Baker (Amaryllidaceae: Hippeastreae) from Northeast Brazil

Zephyranthes Herb. is a taxonomically complex and cytologically variable group, with about 65 species of Neotropical distribution. Chromosome number variability in 32 individuals of a Zephyranthes sylvatica population from Northeast Brazil was investigated. Three cytotypes were found: 2n = 12 (one metacentric, four submetacentric and one acrocentric pairs), in 24 individuals; 2n = 12 + 1B, in five and three individuals with 2n = 18, a triploid cytotype. All diploid individuals showed chromosomes with polymorphism in pair one and two, while in triploids this polymorphism was observed in all chromosome triplets, generally with two homomorphic chromosomes and a higher or lower heteromorphic chromosome. All individuals had reticulated interfasic nucleus and a slightly asymmetric chromosome complement, with one metacentric chromosome pair and the others more submetacentric to acrocentric. These data confirm the cytological variability previously registered for the genus. Mechanisms involved in karyotypic evolution in this population are discussed.

Chromosome number in germplasm accessions of Paspalum notatum (Gramineae)

Chromosome numbers are reported for 127 germplasm accessions of Paspalum notatum maintained by EMBRAPA (Empresa Brasileira de Pesquisa Agropecuária) in two research centers in Brazil. Most accessions were collected in their natural habitats in Southern Brazil. Tetraploidy (2n = 40 chromosomes) was predominant (91% of the accessions studied), confirming previous reports for the species. Eleven accessions with 2n = 20 chromosomes, although collected in the wild, are possibly derived from 'Pensacola' bahiagrass, commonly cultivated in the area since its introduction from the United States in the 60's, for the establishment of permanent pastures.

Chromosome number and secondary constriction variation in 51 accessions of a citrus germplasm bank

The mitotic chromosomes of 51 citrus accessions from the Centro Nacional de Pesquisa em Mandioca e Fruticultura Tropical, Cruz das Almas, BA, Brazil, were analyzed. The sample included representatives of 20 Citrus species, one of Poncirus and seven hybrids. All accessions showed 2n = 18 without any evidence of numerical variation. The most clearly variable karyotype feature was the number and position of secondary constrictions (SECs). In 19 accessions the SECs were not identified, mainly due to the degree of chromatin condensation. In the remainder they varied in number from one to three per karyotype. They were found in the proximal region of one of the three largest chromosome pairs, in the terminal/subterminal region of a smaller chromosome or, more seldom, terminally in a larger chromosome. Only in a few cases were such constrictions observed simultaneously in both homologues of the same chromosome pair. The high variability of this karyotype feature may be due to the activation of this region in the previous interphase but may also indicate a high structural variability and heterozygosity of citrus germplasms