X-ray diffraction data of tibolone Delta(4) isomer (isotibolone)

Tibolone is used for hormone reposition of postmenopause women and isotibolone is considered the major degradation product of tibolone. Isotibolone can also be present in tibolone API raw materials due to some inadequate synthesis. Its presence is then necessary to be identified and quantified in the quality control of both API and drug products. In this work we present the indexing of an isotibolone X-ray diffraction pattern measured with synchrotron light (lambda=1.2407 angstrom) in the transmission mode. The characterization of the isotibolone sample by IR spectroscopy, elemental analysis, and thermal analysis are also presented. The isotibolone crystallographic data are a=6.8066 angstrom, b=20.7350 angstrom, c=6.4489 angstrom, beta=76.428 degrees, V=884.75 angstrom(3), and space group P2(1), rho(o)= 1.187 g cm(-3), Z=2. (C) 2009 International Centre for Diffraction Data. [DOI: 10.1154/1.3257612]

Crystal structure of isotibolone: a major degradation product of tibolone

Isotibolone is frequently found as an impurity in tibolone, a drug used for hormone reposition of post-menopause women, due to some inadequate tibolone synthesis or as a result of degradation during drug storage. The presence of isotibolone impurities should be detected and quantified in active pharmaceutical ingredient products of tibolone before its use in the manufacturing of medicaments. The X-ray powder diffraction technique offers the possibility of quantifying isotibolone amounts at different stages of drug production and storage, from the chemical synthesis to the final formulation. In the course of a study involving the quantitative analysis of isotibolone by X-ray powder diffraction, the authors determined the structure of the title compound using a recently developed approach (A. Gomez and S. Kycia, J. Appl. Crystallogr. 2011, 44, 708-713). The structure is monoclinic, space group P2(1) (4), with unit cell parameters a = 6.80704(7) angstrom, b = 20.73858(18) angstrom, c = 6.44900(6) angstrom, beta = 76.4302(5)degrees, V = 884.980(15) angstrom(3) and two molecules per unit cell (Z = 2). The molecules are hydrogen bonded in the ab plane forming layers that are held together in the crystal by van der Waals interactions along the c-axis.

Polymorphisms and DNA methylation of gene TP53 associated with extra-axial brain tumors

The p53 tumor suppressor gene is the most frequently mutated gene in human cancer; this gene is mutated in up to 50% of human tumors. It has a critical role in the cell cycle, apoptosis and cell senescence, and it participates in many crucial physiological and pathological processes. Polymorphisms of p53 have been suggested to be associated with genetically determined susceptibility in various types of cancer. Another process involved with the development and progression of tumors is DNA hypermethylation. Aberrant methylation of the promoter is an alternative epigenetic change in genetic mechanisms, leading to tumor suppressor gene inactivation. In the present study, we examined the TP53 Arg72Pro and Pro47Ser polymorphisms using PCR-RFLP and the pattern of methylation of the p53 gene by methylation-specific PCR in 90 extra-axial brain tumor samples. Patients who had the allele Pro of the TP53 Arg72Pro polymorphism had an increased risk of tumor development ( odds ratio, OR = 3.23; confidence interval at 95%, 95% CI = 1.71-6.08; P = 0.003), as did the allele Ser of TP53 Pro47Ser polymorphism (OR = 1.28; 95% CI = 0.03-2.10; P = 0.01). Comparison of overall survival of patients did not show significant differences. In the analysis of DNA methylation, we observed that 37.5% of meningiomas, 30% of schwannomas and 52.6% of metastases were hypermethylated, suggesting that methylation is important for tumor progression. We suggest that TP53 Pro47Ser and Arg72Pro polymorphisms and DNA hypermethylation are involved in susceptibility for developing extra-axial brain tumors.

Allopatric speciation in ticks: genetic and reproductive divergence between geographic strains of Rhipicephalus (Boophilus) microplus

Background: The cattle tick, Rhipicephalus (Boophilus) microplus, economically impact cattle industry in tropical and subtropical regions of the world. The morphological and genetic differences among R. microplus strains have been documented in the literature, suggesting that biogeographical and ecological separation may have resulted in boophilid ticks from America/Africa and those from Australia being different species. To test the hypothesis of the presence of different boophilid species, herein we performed a series of experiments to characterize the reproductive performance of crosses between R. microplus from Australia, Africa and America and the genetic diversity of strains from Australia, Asia, Africa and America. Results: The results showed that the crosses between Australian and Argentinean or Mozambican strains of boophilid ticks are infertile while crosses between Argentinean and Mozambican strains are fertile. These results showed that tick strains from Africa (Mozambique) and America (Argentina) are the same species, while ticks from Australia may actually represent a separate species. The genetic analysis of mitochondrial 12S and 16S rDNA and microsatellite loci were not conclusive when taken separately, but provided evidence that Australian tick strains were genetically different from Asian, African and American strains. Conclusion: The results reported herein support the hypothesis that at least two different species share the name R. microplus. These species could be redefined as R. microplus (Canestrini, 1887) (for American and African strains) and probably the old R. australis Fuller, 1899 (for Australian strains), which needs to be redescribed. However, experiments with a larger number of tick strains from different geographic locations are needed to corroborate these results.

Lineage divergence detected in the malaria vector Anopheles marajoara (Diptera: Culicidae) in Amazonian Brazil

Background: Cryptic species complexes are common among anophelines. Previous phylogenetic analysis based on the complete mtDNA COI gene sequences detected paraphyly in the Neotropical malaria vector Anopheles marajoara. The ""Folmer region"" detects a single taxon using a 3% divergence threshold. Methods: To test the paraphyletic hypothesis and examine the utility of the Folmer region, genealogical trees based on a concatenated (white + 3' COI sequences) dataset and pairwise differentiation of COI fragments were examined. The population structure and demographic history were based on partial COI sequences for 294 individuals from 14 localities in Amazonian Brazil. 109 individuals from 12 localities were sequenced for the nDNA white gene, and 57 individuals from 11 localities were sequenced for the ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS2). Results: Distinct A. marajoara lineages were detected by combined genealogical analysis and were also supported among COI haplotypes using a median joining network and AMOVA, with time since divergence during the Pleistocene (< 100,000 ya). COI sequences at the 3' end were more variable, demonstrating significant pairwise differentiation (3.82%) compared to the more moderate 2.92% detected by the Folmer region. Lineage 1 was present in all localities, whereas lineage 2 was restricted mainly to the west. Mismatch distributions for both lineages were bimodal, likely due to multiple colonization events and spatial expansion (similar to 798 - 81,045 ya). There appears to be gene flow within, not between lineages, and a partial barrier was detected near Rio Jari in Amapa state, separating western and eastern populations. In contrast, both nDNA data sets (white gene sequences with or without the retention of the 4th intron, and ITS2 sequences and length) detected a single A. marajoara lineage. Conclusions: Strong support for combined data with significant differentiation detected in the COI and absent in the nDNA suggest that the divergence is recent, and detectable only by the faster evolving mtDNA. A within subgenus threshold of >2% may be more appropriate among sister taxa in cryptic anopheline complexes than the standard 3%. Differences in demographic history and climatic changes may have contributed to mtDNA lineage divergence in A. marajoara.

Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence

Background: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum. Results: Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, interpopulation differentiation, and the degree to which allele frequencies are correlated between populations. Conclusions: The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.

CHARACTERIZATION OF EXPONENTIAL DIVERGENCE OF THE KALMAN FILTER FOR TIME-VARYING SYSTEMS

This paper studies semistability of the recursive Kalman filter in the context of linear time-varying (LTV), possibly nondetectable systems with incorrect noise information. Semistability is a key property, as it ensures that the actual estimation error does not diverge exponentially. We explore structural properties of the filter to obtain a necessary and sufficient condition for the filter to be semistable. The condition does not involve limiting gains nor the solution of Riccati equations, as they can be difficult to obtain numerically and may not exist. We also compare semistability with the notions of stability and stability w.r.t. the initial error covariance, and we show that semistability in a sense makes no distinction between persistent and nonpersistent incorrect noise models, as opposed to stability. In the linear time invariant scenario we obtain algebraic, easy to test conditions for semistability and stability, which complement results available in the context of detectable systems. Illustrative examples are included.

Evaluation of the use of multiple lines for determination of metals in water by inductively coupled plasma optical emission spectrometry with axial viewing

Inductively coupled plasma optical emission spectrometers (ICP DES) allow fast simultaneous measurements of several spectral lines for multiple elements. The combination of signal intensities of two or more emission lines for each element may bring such advantages as improvement of the precision, the minimization of systematic errors caused by spectral interferences and matrix effects. In this work, signal intensities for several spectral lines were combined for the determination of Al, Cd, Co, Cr, Mn, Pb, and Zn in water. Afterwards, parameters for evaluation of the calibration model were calculated to select the combination of emission lines leading to the best accuracy (lowest values of PRESS-Predicted error sum of squares and RMSEP-Root means square error of prediction). Limits of detection (LOD) obtained using multiple lines were 7.1, 0.5, 4.4, 0.042, 3.3, 28 and 6.7 mu g L(-1) (n = 10) for Al, Cd. Co, Cr, Mn, Pb and Zn, respectively, in the presence of concomitants. On the other hand, the LOD established for the most intense emission line were 16. 0.7, 8.4, 0.074. 23, 26 and 9.6 mu g L(-1) (n = 10) for these same elements in the presence of concomitants. The accuracy of the developed procedure was demonstrated using water certified reference material. The use of multiple lines improved the sensitivity making feasible the determination of these analytes according to the target values required for the current environmental legislation for water samples and it was also demonstrated that measurements in multiple lines can also be employed as a tool to verify the accuracy of an analytical procedure in ICP DES. (C) 2009 Elsevier B.V. All rights reserved.

Influence of concrete strength and length/diameter on the axial capacity of CFT columns

This paper presents an experimental analysis of the confinement effects in steel-concrete composite columns regarding two parameters: concrete compressive strength and column slenderness. Sixteen concrete-filled steel tubular columns with circular cross section were tested under axial loading. The tested columns were filled by concrete with compressive strengths of 30, 60. 80, and 100 MPa, and had length/diameter ratios of 3, 5, 7, and 10. The experimental values of the columns` ultimate load were compared to the predictions of 4 code provisions: the Brazilian Code NBR 8800:2008, Eurocode 4 (EN 1994-1-1:2004), AINSI/AISC 360:2005, and CAN/CSA S16-01:2001. According to the results, the load capacity of the composite columns increased with increasing concrete strength and decreased with increasing length/diameter ratio. In general, the code provisions were highly accurate in the prediction of column capacity. Among them, the Brazilian Code was the most conservative, while Eurocode 4 presented the values closest to the experimental results. (C) 2009 Elsevier Ltd. All rights reserved.

Design of concrete-filled steel tubular columns under axial loading according to NBR 8800:2008 and Eurocode 4:2004: tests results and comparisons

In this paper results of tests on 32 concrete-filled steel tubular columns under axial load are reported. The test parameters were the concrete compressive strength, the column slenderness (L/D) and the wall thickness (t). The test results were compared with predictions from the codes NBR 8800:2008 and EN 1994-1-1:2004 (EC4). The columns were 3, 5, 7 and 10 length to diameter ratios (L/D) and were tested with 30MPa, 60MPa, 80MPa and 100MPa concrete compressive strengths. The results of ultimate strength predicted by codes showed good agreement with experimental results. The results of NBR 8800 code were the most conservative and the EC4 showed the best results, in mean, but it was not conservative for usual concrete-filled short columns.

Structural behaviour of three-pile caps subjected to axial compressive loading

This work presents a comparative analysis about the behaviour of pile caps supported by 3 piles subjected to axial loading. Piles with 20 cm and 30 cm diameters were analysed. The main reinforcement was maintained in all the specimens, however, the arrangement of the secondary reinforcement varied. The main reinforcement consisted of steel bars connecting the piles. The secondary reinforcement was made up of: (a) bars going through the piles and through the projection of the column, (b) bars forming a network, and (c) vertical and horizontal stirrups. The main objective was the observation of the pile cap behaviour regarding the cracks and the modes of rupture. The real scale specimens were subjected to experimental tests until failure by rupture. Instruments were placed with the aim to obtain the displacement of the bases, the strains in the main and secondary reinforcement bars, in the compression struts, in the lower and upper nodal zones and in the sides of the caps. None of the caps reached failure by rupture with a load less than 1.12 times the theoretical load. The specimens ruptured due to the cracking of the compression strut and/or the yielding of the reinforcement bars in one direction.