Kullback-Leibler and Renormalized Entropy: Applications to EEGs of Epilepsy Patients

Recently, renormalized entropy was proposed as a novel measure of relative entropy (P. Saparin et al., Chaos, Solitons & Fractals 4, 1907 (1994)) and applied to several physiological time sequences, including EEGs of patients with epilepsy. We show here that this measure is just a modified Kullback-Leibler (K-L) relative entropy, and it gives similar numerical results to the standard K-L entropy. The latter better distinguishes frequency contents of e.g. seizure and background EEGs than renormalized entropy. We thus propose that renormalized entropy might not be as useful as claimed by its proponents. In passing we also make some critical remarks about the implementation of these methods.Comment: 15 pages, 4 Postscript figures. Submitted to Phys. Rev. E, 199

Prediction of genotypic values of maize for the agricultural frontier region in northeastern Maranhão, Brazil.

Agricultural research, mainly focused on the evaluation of maize cultivars along agricultural frontiers, are scarce. This study assessed 128 maize genotypes in the agricultural frontier region of the State of Maranhão, between 2008 and 2009. The experiment was arranged in a lattice design with two replications. The genotypes were evaluated for grain yield in a mixed model, with fixed intercept and experimental effects. The random effects were genotype, genetic class (single-, double or triple-cross hybrid and variety), and incomplete block/replication/ environment. The genotype effect was significant by the likelihood ratio test in all models, highlighting the genotypic values of the single-cross hybrids DKB177, AG8088 and DKB390, the triple-cross PL6882, the double-cross BM502 and of the open-pollinated variety SHS3031Nota técnica

Produtividade de híbridos de milho na região de fronteira agrícola no nordeste do Maranhão.

O Maranhão é um estado onde a agricultura tecnificada está em rápida expansão e que possui excelente potencial para desenvolvimento do agronegócio e para a exportação de produtos agrícolas. No entanto, ainda é escassa a realização de pesquisas na região, incluindo pesquisas com a cultura do milho. Esse fato levou à realização deste trabalho, visando avaliar a produtividade de híbridos modernos de milho. Assim, 42 híbridos foram avaliados no ano de 2008 em dois locais (Anapurus e Brejo), em região de fronteira agrícola no nordeste do Estado do Maranhão. O rendimento médio foi de 5.593 kg ha-1 na análise conjunta, 5.097 kg ha-1 em Anapurus e 6.089 kg ha -1 em Brejo, demonstrando excelente potencial regional para o cultivo do milho. Foram significativas as diferenças entre híbridos e entre locais, sendo possível encontrar híbridos com rendimento acima de 8.000 kg ha-1, quando maximizadas as variáveis ambiente e cultivar. No entanto, não ocorreu interação significativa entre híbridos e locais. Na média, os híbridos simples são superiores aos triplos e duplos e os híbridos triplos, superiores aos duplos, apesar de a diferença nem sempre ser estatisticamente significativ

Measuring Information Transfer

An information theoretic measure is derived that quantifies the statistical coherence between systems evolving in time. The standard time delayed mutual information fails to distinguish information that is actually exchanged from shared information due to common history and input signals. In our new approach, these influences are excluded by appropriate conditioning of transition probabilities. The resulting transfer entropy is able to distinguish driving and responding elements and to detect asymmetry in the coupling of subsystems.Comment: 4 pages, 4 Figures, Revte

Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity

The PROP1 2-Base Pair Deletion Is a Common Cause of Combined Pituitary Hormone Deficiency

Combined pituitary hormone deficiency (CPHD) has an incidence of approximately 1 in 8000 births. Although the proportion of familial CPHD cases is unknown, about 10% have an affected first degree relative. We have recently reported three mutations in the PROP1 gene that cause CPHD in human subjects. We report here the frequency of one of these mutations, a 301–302delAG deletion in exon 2 of PROP1, in 10 independently ascertained CPHD kindreds and 21 sporadic cases of CPHD from 8 different countries. Our results show that 55% (11 of 20) of PROP1 alleles have the 301–302delAG deletion in familial CPHD cases. Interestingly, although only 12% (5 of 42) of the PROP1 alleles of our 21 sporadic cases were 301–302delAG, the frequency of this allele (in 20 of 21 of the sporadic subjects given TRH stimulation tests) was 50% (3 of 6) and 0% (0 of 34) in the CPHD cases with pituitary and hypothalamic defects, respectively. Using whole genome radiation hybrid analysis, we localized the PROP1 gene to the distal end of chromosome 5q and identified a tightly linked polymorphic marker, D5S408, which can be used in segregation studies. Analysis of this marker in affected subjects with the 301–302delAG deletion suggests that rather than being inherited from a common founder, the 301–302delAG may be a recurring mutation

Oxidative Activity of Human Polymorphonuclear Leukocytes Stimulated by the Long-Chain Phosphatidic Acids

Summary It has already been suggested that phosphatidic acids (PAs) play an important role in the regulation of signaling pathways involved in the production of reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs). The present study was performed to elucidate the effects of extracellularly added PAs -1,2-distearoyl-(DSPA) and 1-stearoyl-2-arachidonoyl-sn-glycero-phosphate (SAPA) -on the ROS production and on the elastase release by human PMNs. ROS production was monitored by luminol-amplified chemiluminescence and the elastase activity was measured in the supernatant of the PA-stimulated human PMNs by colorimetric assay. Obtained effects were compared with those of cells stimulated by either a chemotactic tripeptide, phorbol ester or calcium ionophore. Our results show that long-chain PAs at concentrations higher than 3 × 10 -5 mol/l stimulate the ROS production by human PMNs, whereas they were ineffective in promoting the elastase release. The chemiluminescence pattern of the SAPA-stimulated cells exhibited a biphasic curve, whereas cell stimulation with DSPA resulted in a monophasic chemiluminescence curve. Stimulation of the ROS production by PAs in dependence of the fatty acid composition required the activity of protein kinases

Nova mutação nonsense (p.Y113X) no gene do receptor do hormônio do crescimento em um paciente brasileiro com síndrome de Laron

BACKGROUND: To date, about sixty different mutations within GH receptor (GHR) gene have been described in patients with GH insensitivity syndrome (GHI). In this report, we described a novel nonsense mutation of GHR. METHODS: The patient was evaluated at the age of 6 yr, for short stature associated to clinical phenotype of GHI. GH, IGF-1, and GHBP levels were determined. The PCR products from exons 2-10 were sequenced. RESULTS: The patient had high GH (26 µg/L), low IGF-1 (22.5 ng/ml) and undetectable GHBP levels. The sequencing of GHR exon 5 disclosed adenine duplication at nucleotide 338 of GHR coding sequence (c.338dupA) in homozygous state. CONCLUSION: We described a novel mutation that causes a truncated GHR and a loss of receptor function due to the lack of amino acids comprising the transmembrane and intracellular regions of GHR protein, leading to GHI.INTRODUÇÃO: Até o momento, aproximadamente 60 diferentes mutações envolvendo o gene do receptor do GH (GHR) foram descritas em pacientes com a síndrome de insensibilidade ao GH (GHI). Neste artigo, descrevemos uma nova mutação nonsense do GHR. MÉTODOS: O paciente foi avaliado aos 6 anos de idade para baixa estatura associada ao fenótipo clínico da GHI. Níveis de GH, IGF-1 e GHBP foram determinados. Os produtos de PCR dos éxons 2-10 foram seqüenciados. RESULTADOS: O paciente apresentou níveis elevados de GH (26 µg/L), baixos de IGF-1 (22.5 ng/ml) e indetectáveis de GHBP. O seqüenciamento do éxon 5 do GHR revelou uma duplicação da adenina no nucleotídeo 338 da sequência de codificação do GHR (c.338dupA) em homozigose. CONCLUSÃO: Descrevemos uma nova mutação que causa um GHR truncado e uma perda da função do receptor devido à perda de aminoácidos compreendendo as regiões transmembrana e intracelular do receptor, levando a GHI.Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq