Tumor slices as a model to evaluate doxorubicin in vitro treatment and expression of trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 in canine mammary gland cancer

Background: In women with breast cancer submitted to neoadjuvant chemotherapy based in doxorubicin, tumor expression of groups of three genes (PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2) have classified them as responsive or resistant. We have investigated whether expression of these trios of genes could predict mammary carcinoma response in dogs and whether tumor slices, which maintain epithelial-mesenchymal interactions, could be used to evaluate drug response in vitro. Methods: Tumors from 38 dogs were sliced and cultured with or without doxorubicin 1 mu M for 24 h. Tumor cells were counted by two observers to establish a percentage variation in cell number, between slices. Based on these results, a reduction in cell number between treated and control samples >= 21.7%, arbitrarily classified samples, as drug responsive. Tumor expression of PRSS11, MTSS1, CLPTM1 and SMYD2, was evaluated by real time PCR. Relative expression results were then transformed to their natural logarithm values, which were spatially disposed according to the expression of trios of genes, comprising PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. Fisher linear discrimination test was used to generate a separation plane between responsive and non-responsive tumors. Results: Culture of tumor slices for 24 h was feasible. Nine samples were considered responsive and 29 non-responsive to doxorubicin, considering the pre-established cut-off value of cell number reduction = 21.7%, between doxorubicin treated and control samples. Relative gene expression was evaluated and tumor samples were then spatially distributed according to the expression of the trios of genes: PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2. A separation plane was generated. However, no clear separation between responsive and non-responsive samples could be observed. Conclusion: Three-dimensional distribution of samples according to the expression of the trios of genes PRSS11, MTSS1, CLPTM1 and PRSS11, MTSS1, SMYD2 could not predict doxorubicin in vitro responsiveness. Short term culture of mammary gland cancer slices may be an interesting model to evaluate chemotherapy activity.

Ablation Rate and Morphology of Superficial and Deep Dentin Irradiated with Different Er:YAG Laser Energy Levels

Objective: In this study we evaluated the ablation rate of superficial and deep dentin irradiated with different Er:YAG laser energy levels, and observed the micromorphological aspects of the lased substrates with a scanning electron microscope (SEM). Background Data: Little is known about the effect of Er: YAG laser irradiation on different dentin depths. Materials and Methods: Sixty molar crowns were bisected, providing 120 specimens, which were randomly assigned into two groups ( superficial or deep dentin), and later into five subgroups (160, 200, 260, 300, or 360 mJ). Initial masses of the specimens were obtained. After laser irradiation, the final masses were obtained and mass losses were calculated followed by the preparation of specimens for SEM examination. Mass-loss values were subjected to two-way ANOVA and Fisher's least significant difference multiple-comparison tests (p < 0.05). Results: There was no difference between superficial and deep dentin. A significant and gradual increase in the mass-loss values was reached when energies were raised, regardless of the dentin depth. The energy level of 360 mJ showed the highest values and was statistically significantly different from the other energy levels. The SEM images showed that deep dentin was more selectively ablated, especially intertubular dentin, promoting tubule protrusion. At 360 mJ the micromorphological features were similar for both dentin depths. Conclusion: The ablation rate did not depend on the depth of the dentin, and an energy level lower than 360 mJ is recommended to ablate both superficial and deep dentin effectively without causing tissue damage.

Kinematics of galaxies in compact groups Studying the B-band Tully-Fischer relation

We obtained new Fabry-Perot data cubes and derived velocity fields, monochromatic, and velocity dispersion maps for 28 galaxies in the Hickson compact groups 37, 40, 47, 49, 54, 56, 68, 79, and 93. We also derived rotation curves for 9 of the studied galaxies, 6 of which are strongly asymmetric. Combining these new data with previously published 2D kinematic maps of compact group galaxies, we investigated the differences between the kinematic and morphological position angles for a sample of 46 galaxies. We find that one third of the unbarred compact group galaxies have position angle misalignments between the stellar and gaseous components. This and the asymmetric rotation curves are clear signatures of kinematic perturbations, probably because of interactions among compact group galaxies. A comparison between the B-band Tully-Fisher relation for compact group galaxies and for the GHASP field-galaxy sample shows that, despite the high fraction of compact group galaxies with asymmetric rotation curves, these lay on the TF relation defined by galaxies in less dense environments, although with more scatter. This agrees with previous results, but now confirmed for a larger sample of 41 galaxies. We confirm the tendency for compact group galaxies at the low-mass end of the Tully-Fisher relation (HCG 49b, 89d, 96c, 96d, and 100c) to have either a magnitude that is too bright for its mass (suggesting brightening by star formation) and/or a low maximum rotational velocity for its luminosity (suggesting tidal stripping). These galaxies are outside the Tully Fisher relation at the 1 sigma level, even when the minimum acceptable values of inclinations are used to compute their maximum velocities. Including such galaxies with nu < 100 km s(-1) in the determination of the zero point and slope of the compact group B-band Tully-Fisher relation would strongly change the fit, making it different from the relation for field galaxies, which has to be kept in mind when studying scaling relations of interacting galaxies, especially at high redshifts.

Hubble parameter reconstruction from a principal component analysis: minimizing the bias

Aims. A model-independent reconstruction of the cosmic expansion rate is essential to a robust analysis of cosmological observations. Our goal is to demonstrate that current data are able to provide reasonable constraints on the behavior of the Hubble parameter with redshift, independently of any cosmological model or underlying gravity theory. Methods. Using type Ia supernova data, we show that it is possible to analytically calculate the Fisher matrix components in a Hubble parameter analysis without assumptions about the energy content of the Universe. We used a principal component analysis to reconstruct the Hubble parameter as a linear combination of the Fisher matrix eigenvectors (principal components). To suppress the bias introduced by the high redshift behavior of the components, we considered the value of the Hubble parameter at high redshift as a free parameter. We first tested our procedure using a mock sample of type Ia supernova observations, we then applied it to the real data compiled by the Sloan Digital Sky Survey (SDSS) group. Results. In the mock sample analysis, we demonstrate that it is possible to drastically suppress the bias introduced by the high redshift behavior of the principal components. Applying our procedure to the real data, we show that it allows us to determine the behavior of the Hubble parameter with reasonable uncertainty, without introducing any ad-hoc parameterizations. Beyond that, our reconstruction agrees with completely independent measurements of the Hubble parameter obtained from red-envelope galaxies.

Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

Background: Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability. Methods: We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis. Results: European ( E), Asian-American ( AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 ( adjusted odds ratio [ OR] = 0.66; 95% confidence interval [CI]: 0.39-1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers ( OR = 0.27; 95% CI: 0.10-0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases ( p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E ( OR = 2.99; 95% CI: 1.13-7.86) or AA variants ( OR = 2.34; 95% CI: 1.00-5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene ( OR = 0.27; 95% CI: 0.08-0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found ( OR = 0.37; 95% CI: 0.15-0.89). Conclusion: Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants.

Use of Hyaluronidase to Prevent Perineal Trauma During Spontaneous Births: A Randomized, Placebo-Controlled, Double-blind, Clinical Trial

Introduction: The purpose of this study was to compare the frequency and severity of perineal trauma during spontaneous birth with or without perineal injections of hyaluronidase (HAase). Methods: A randomized, placebo-controlled, double-blind clinical trial was conducted in a midwife-led, in-hospital birth center in Sao Paulo, Brazil. Primiparous women (N = 160) were randomly assigned to an experimental (n = 80) or control (n = 80) group. During the second stage of labor, women in the experimental group received an injection of 20.000 turbidity-reducing units of HAase in the posterior region of the perineum, and those in the control group received a placebo injection. The assessment of perineal outcome was performed by 2 independent nurse-midwives. A 1-tailed Fisher exact test was performed, and a P value < .025 was considered statistically significant. Results: Perineal integrity occurred in 34.2% of the experimental group and in 32.5% of the control group, which was not a statistically significant difference (P = .477). First-degree laceration was the most common trauma in the posterior region of the perineum in women in both groups (experimental = 56%, control = 42.6%). Severe perineal trauma occurred in 28.9% of the experimental group and 38.8% of the control group, which also was not a statistically significant difference (P =. 131). The depth of second-degree perineal lacerations in the experimental and control groups, measured by the Peri-Rule, was 1.9 cm and 2.3 cm, respectively. An episiotomy was performed in 11 women (experimental group = 3, control group = 8), and 4 (all in control group) had third-degree lacerations. Discussion: The use of injectable HAase did not increase the proportion of intact perineum and did not reduce the proportion of severe perineal trauma in our sample. J Midwifery Womens Health 2011; 56: 436-445 (C) 2011 by the American College of Nurse-Midwives.

The Poisson-exponential lifetime distribution

In this paper we proposed a new two-parameters lifetime distribution with increasing failure rate. The new distribution arises on a latent complementary risk problem base. The properties of the proposed distribution are discussed, including a formal proof of its probability density function and explicit algebraic formulae for its reliability and failure rate functions, quantiles and moments, including the mean and variance. A simple EM-type algorithm for iteratively computing maximum likelihood estimates is presented. The Fisher information matrix is derived analytically in order to obtaining the asymptotic covariance matrix. The methodology is illustrated on a real data set. (C) 2010 Elsevier B.V. All rights reserved.

General results for the beta-modified Weibull distribution

We study in detail the so-called beta-modified Weibull distribution, motivated by the wide use of the Weibull distribution in practice, and also for the fact that the generalization provides a continuous crossover towards cases with different shapes. The new distribution is important since it contains as special sub-models some widely-known distributions, such as the generalized modified Weibull, beta Weibull, exponentiated Weibull, beta exponential, modified Weibull and Weibull distributions, among several others. It also provides more flexibility to analyse complex real data. Various mathematical properties of this distribution are derived, including its moments and moment generating function. We examine the asymptotic distributions of the extreme values. Explicit expressions are also derived for the chf, mean deviations, Bonferroni and Lorenz curves, reliability and entropies. The estimation of parameters is approached by two methods: moments and maximum likelihood. We compare by simulation the performances of the estimates from these methods. We obtain the expected information matrix. Two applications are presented to illustrate the proposed distribution.

Characterization of the electrocardiographic pattern of individuals with cerebral palsy

Background: Dentists of Lar Sao Francisco observed during dental treatment that children with cerebral palsy (CP) had increased heart rate (HR) and lower production of saliva. Despite the high prevalence of CP found in the literature (2.08-3.6/1000 individuals), little is known about the electrocardiographic (ECG) characteristics, especially HR, of individuals with CP. Objective: This study aimed to investigate the hypothesis that individuals with CP have a higher HR and to define other ECG characteristics of this population. Methods: Ninety children with CP underwent clinical examination and 12-lead rest ECG. Electrocardiographic data on rhythm, HR, PR interval, QRS duration, P/QRS/T axis, and QT, QTc and T(peak-end) intervals (minimum, mean, maximum, and dispersion) were measured and analyzed then compared with data from a control group with 35 normal children. Fisher and Mann-Whitney U tests were used, respectively, to compare categorical and continuous data. Results: Groups cerebral palsy and control did not significantly differ in age (9 +/- 3 x 9 +/- 4 years) and male gender (65% x 49%). Children with CP had a higher HR (104.0 +/- 20.6 x 84.2 +/- 13.3 beats per minute; P < .0001), shorter PR interval (128.8 +/- 15.0 x 138.1 +/- 15.1 milliseconds; P = .0018), shorter QRS duration (77.4 +/- 8.6 x 82.0 +/- 8.7 milliseconds; P = .0180), QRS axis (46.0 degrees +/- 26.3 degrees x 59.7 degrees +/- 24.8 degrees; P = .0024) and T-wave axis (34.3 degrees +/- 28.9 degrees x 42.9 degrees +/- 17.1 degrees; P = .034) more horizontally positioned, and greater mean QTc (418.1 +/- 18.4 x 408.5 +/- 19.4 milliseconds; P = .0110). All the electrocardiogram variables were within the reference range for the age group including those with significant differences. Conclusion: Children with CP showed increased HR and other abnormal ECG findings in the setting of this investigation. Further studies are needed to explain our findings and to correlate the increased HR with situations such as dehydration, stress, and autonomic nervous disorders. (C) 2011 Elsevier Inc. All rights reserved.

Natural regeneration of Atlantic Forest species in the understory of Eucalyptus saligna Smith. in a former forest production unit at the Parque das Neblinas, Bertioga, SP

This study aimed at characterizing the potential for natural regeneration of native vegetation in the under-story of an earlier Eucalyptus saligna Smith production stand. The study was carried out at the Parque das Neblinas, Bertioga municipality, SP, in a 45 ha third rotation stand; which had been abandoned 15 years ago for natural regeneration to occur. The sampling was done in 24 plots of 20 x 40 m. The sampled area was of 19,200 m(2), with inventory made of 100% of the eucalyptus trees. All regeneration trees with a height >= 1.30 m and DBH >= 5.0 cm were measured, as well as adult individuals with DBH >= 5.0 cm; surveyed in two size classes. 1,417 individuals of E. saligna were measured, with a density of 738,02 individuals/ha and a basal area of 22.69 m(2)/ha. Among 2,763 natural regeneration individuals, 111 species belonged to 66 genera and 34 botanical families. The species represented 43.7% of the tree richness of neighboring native forest fragments. The total estimated density and the basal area were respectively 1,052.6 individuals/ha and 6.4 m(2)/ha of autochthonous trees with DBH >= 5.0 cm (Class 1); while for regeneration there were 3,864.58 individuals/ha, and 2.76 m(2)/ha of individuals with a height >= 1.30 m and DBH <5.0 cm (Class 2). Shannon diversity (H`) was 2.83 and 3.68, respectively, for Classes 1 and 2, and the corrected species richness for a 1000-individual sample (R(1000)) were 75.6 and 87.29 (Fisher`s a index) for the same classes. The majority of the species (34.84%) was typical from the understory of wet tropical forest and had zoochoric fruit dispersal (67.57%). The results indicate that, under these conditions, a eucalyptus forest is able to provide adequate regeneration niches for native vegetation, and may represent a sink habitat for local populations.

Quercetin inhibits UV irradiation-induced inflammatory cytokine production in primary human keratinocytes by suppressing NF-kappa B pathway

Background: Topical flavonoids, such as quercetin, have been shown to reduce ultraviolet (UV) irradiation-mediated skin damage. However, the mechanisms and signaling pathways involved in this protective effect are not clear. UV irradiation leads to activation of two major signaling pathways, namely nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) pathways. Activation of NF-kappa B pathway by UV irradiation stimulates inflammatory cytokine expression, whereas activation of AP-1 pathway by UV irradiation promotes matrix metalloproteinase (MMP) production. Both pathways contribute to UV irradiation-induced skin damage, such as photoaging and skin tumor formation. Objective: To elucidate the underlying mechanism, we examined the effect of quercetin on UV irradiation induced activation of NF-kappa B and AP-1 pathways. Methods: Primary human keratinocytes, the major skin cell type subjected to physiological solar UV irradiation, were used to study the effects of quercetin on UV irradiation-induced signal transduction pathways. Results: Quercetin decreased UV irradiation-induced NF-kappa B DNA-binding by 80%. Consequently, quercetin suppressed UV irradiation-induced expression of inflammatory cytokines IL-1 beta (similar to 60%), IL-6 (similar to 80%), IL-8 (similar to 76%) and TNF-alpha (similar to 69%). In contrast, quercetin had no effect on UV irradiation activation of three MAP kinases, ERK, JNK, or p38. Accordingly, induction of AP-1 target genes such as MMP-1 and MMP-3 by UV irradiation was not suppressed by quercetin. Conclusion: Our data indicate that the ability of quercetin to block UV irradiation-induced skin inflammation is mediated, at least in part, by its inhibitory effect on NF-kappa B activation and inflammatory cytokine production. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

The 2008 update of the Aspergillus nidulans genome annotation: A community effort

The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.

A class of compact dwarf galaxies from disruptive processes in galaxy clusters

Dwarf galaxies have attracted increased attention in recent years, because of their susceptibility to galaxy transformation processes within rich galaxy clusters. Direct evidence for these processes, however, has been difficult to obtain, with a small number of diffuse light trails and intra-cluster stars, being the only signs of galaxy disruption. Furthermore, our current knowledge of dwarf galaxy populations may be very incomplete, because traditional galaxy surveys are insensitive to extremely diffuse or compact galaxies. Aware of these concerns, we recently undertook an all-object survey of the Fornax galaxy cluster. This revealed a new population of compact members, overlooked in previous conventional surveys. Here we demonstrate that these 'ultra-compact' dwarf galaxies are structurally and dynamically distinct from both globular star clusters and known types of dwarf galaxy, and thus represent a new class of dwarf galaxy. Our data are consistent with the interpretation that these are the remnant nuclei of disrupted dwarf galaxies, making them an easily observed tracer of galaxy disruption.

Hydraulic engineering in the 21st century: Where to?

For centuries, hydraulic engineers were at the forefront of science. The last forty years marked a change of perception in our society with a focus on environmental sustainability and management, particularly in developed countries. Herein, the writer illustrates his strong belief that the future of hydraulic engineering lies upon a combination of innovative engineering, research excellence and higher education of quality. This drive continues a long tradition established by eminent scholars like Arthur Thomas IPPEN, John Fisher KENNEDY and Hunter ROUSE.