In and out of Madagascar : dispersal to peripheral islands, insular speciation and diversification of Indian Ocean daisy trees (Psiadia, Asteraceae)

This study was supported by the European Union’s HOTSPOTS Training Network (MEST-2005-020561)Madagascar is surrounded by archipelagos varying widely in origin, age and structure. Although small and geologically young, these archipelagos have accumulated disproportionate numbers of unique lineages in comparison to Madagascar, highlighting the role of waif-dispersal and rapid in situ diversification processes in generating endemic biodiversity. We reconstruct the evolutionary and biogeographical history of the genus Psiadia (Asteraceae), a plant genus with near equal numbers of species in Madagascar and surrounding islands. Analyzing patterns and processes of diversification, we explain species accumulation on peripheral islands and aim to offer new insights on the origin and potential causes for diversification in the Madagascar and Indian Ocean Islands biodiversity hotspot. Our results provide support for an African origin of the group, with strong support for non-monophyly. Colonization of the Mascarenes took place by two evolutionary distinct lineages from Madagascar, via two independent dispersal events, each unique for their spatial and temporal properties. Significant shifts in diversification rate followed regional expansion, resulting in co-occurring and phenotypically convergent species on high-elevation volcanic slopes. Like other endemic island lineages, Psiadia have been highly successful in dispersing to and radiating on isolated oceanic islands, typified by high habitat diversity and dynamic ecosystems fuelled by continued geological activity. Results stress the important biogeographical role for Rodrigues in serving as an outlying stepping stone from which regional colonization took place. We discuss how isolated volcanic islands contribute to regional diversity by generating substantial numbers of endemic species on short temporal scales. Factors pertaining to the mode and tempo of archipelago formation and its geographical isolation strongly govern evolutionary pathways available for species diversification, and the potential for successful diversification of dispersed lineages, therefore, appears highly dependent on the timing of arrival, as habitat and resource properties change dramatically over the course of oceanic island evolution.Publisher PDFPeer reviewe

Evolution of statistical analysis in empirical software engineering research: Current state and steps forward

Software engineering research is evolving and papers are increasingly based on empirical data from a multitude of sources, using statistical tests to determine if and to what degree empirical evidence supports their hypotheses. To investigate the practices and trends of statistical analysis in empirical software engineering (ESE), this paper presents a review of a large pool of papers from top-ranked software engineering journals. First, we manually reviewed 161 papers and in the second phase of our method, we conducted a more extensive semi-automatic classification of papers spanning the years 2001--2015 and 5,196 papers. Results from both review steps was used to: i) identify and analyze the predominant practices in ESE (e.g., using t-test or ANOVA), as well as relevant trends in usage of specific statistical methods (e.g., nonparametric tests and effect size measures) and, ii) develop a conceptual model for a statistical analysis workflow with suggestions on how to apply different statistical methods as well as guidelines to avoid pitfalls. Lastly, we confirm existing claims that current ESE practices lack a standard to report practical significance of results. We illustrate how practical significance can be discussed in terms of both the statistical analysis and in the practitioner's context.Comment: journal submission, 34 pages, 8 figure

Learning Large-Scale Bayesian Networks with the sparsebn Package

Learning graphical models from data is an important problem with wide applications, ranging from genomics to the social sciences. Nowadays datasets often have upwards of thousands---sometimes tens or hundreds of thousands---of variables and far fewer samples. To meet this challenge, we have developed a new R package called sparsebn for learning the structure of large, sparse graphical models with a focus on Bayesian networks. While there are many existing software packages for this task, this package focuses on the unique setting of learning large networks from high-dimensional data, possibly with interventions. As such, the methods provided place a premium on scalability and consistency in a high-dimensional setting. Furthermore, in the presence of interventions, the methods implemented here achieve the goal of learning a causal network from data. Additionally, the sparsebn package is fully compatible with existing software packages for network analysis.Comment: To appear in the Journal of Statistical Software, 39 pages, 7 figure

Modelling in vitro dissolution and release of sumatriptan succinate from polyvinylpyrrolidone-based microneedles aided by iontophoresis

A novel dissolving microneedle array system is developed to investigate permeation of a sumatriptan succinate formulations through the skin aided by iontophoresis. Three formulations consisting of hydrophilic, positively charged drug molecules encapsulated in a water-soluble biologically suitable polymer, polyvinylpyrrolidone (PVP), have been accepted by the U.S. Food and Drug Administration (FDA). The microneedle systems are fabricated with 600 pyramid-shaped needles, each 500 µm tall, on a 0.785-cm2 circular array. In vitro transdermal studies with minipig skin and vertical Franz diffusion cells show \u3e 68% permeation of sumatriptan over a 24-hour period. A combination of microneedle and electrical current density ranging from 100 to 500 µA/cm2 using Ag / AgCl electrodes displays increased flux with current density. At 500 µA/cm2, a dissolving array loaded with 4.3 mg sumatriptan leads to a steady-state delivery rate of 490 µg/cm2h with negligible lag time. In theory, a 9.58-cm2 microneedle-array patch loaded with 47.30 mg of sumatriptan succinate could provide the required plasma concentration, 72 ng/ml, for nearly six hours. In parallel, a mathematical model based on first principles is developed to predict the amount of drug delivered into the skin using software (e.g., Mathematica). A system of mass balance equations are derived to simulate the dissolution, diffusion, electromigration and transport of the active ingredient through the epidermis. The analytical approach allows for the evaluation and estimation of the effects of key parameters (i.e., loading dose, polymer concentration, needle height, needle pitch width and current density) on the release profile. The skin layer concentration increases significantly with either increased loading dose or elongated height of the microneedle. The percentage of sumatriptan permeating through skin increased favorably with increased electrical current applied to microneedle patch. An inverse correlation was observed between the pitch width (center to center distance of adjacent needles) and the cumulative amount of sumatriptan permeated into the dermis. Predicted cumulative release data from mathematical model simulations of each of the three formulations were successfully validated with in vitro permeation data administered with Franz cells and minipig skin

Effect of jumbo squid (Dosidicus gigas) skin extract on the microbial activity in chilled mackerel (Scomber scombrus)

6 páginas, 4 tablas, 2 figurasDuring the industrial processing of jumbo squid (Dosidicus gigas), large amounts of by-products containing biological active compounds are generated. In this study, aqueous solutions including acetic acid-ethanol extracts of jumbo squid skin (JSS) were tested at three different concentrations as icing media. The effects of the JSS extracts on the quality evolution of chilled mackerel (Scomber scombrus) were monitored. A significant inhibition (p < 0.05) of microbial activity was determined in the fish batch corresponding to the icing condition including the highest JSS concentration. Additionally, fish specimens corresponding to batches including any of the JSS concentrations tested showed lower (p < 0.05) proteolytic counts and pH values than control mackerel. Sensory analysis revealed a marked shelf life extension in chilled mackerel stored in ice including the highest JSS concentration; specimens from such batch were found to be still acceptable after 13 days of storage, while all other mackerel batches were rejectable. The marked microbial activity inhibition observed could be explained on the basis of the presence in ice of lipophilic compounds obtained by acetic acid-ethanol extraction of JSSThis work was supported by the CONACYT-Mexico grant 154046 and the Consejo Superior de Investigaciones Científicas (CSIC) through Research Project PIE 201370E001Peer reviewe

Standardization of oral mucosa barrier models, experimental conditions and use of microneedles as permeation enhancer for in vitro permeation studies

Orientadores: Michelle Franz Montan Braga Leite, Francisco Carlos GroppoTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O uso de formulações tópicas na cavidade oral apresenta baixa eficácia devido à complexidade e variabilidade da mucosa de revestimento e difícil acessibilidade aos tecidos profundos, como a polpa dental. Microagulhas têm sido relatadas como eficiente e indolor sistema transdérmico e transmucosa de fármacos para ação local e/ou sistêmica e poderia melhorar ação de fármacos tópicos em Odontologia. Visando a melhora da biodisponibilidade de formulações tópicas, estudos de permeação in vitro são muito importantes pois podem permitir a previsão do comportamento destas frente à barreira utilizada. No entanto, não existe um modelo de barreira que mimetize as condições reais da cavidade oral. Nesse contexto, este estudo teve como objetivos padronizar barreiras de tecidos espessos da cavidade oral de suínos, adaptar células de difusão e condições experimentais para realização de estudos de permeação in vitro com essas barreiras, visando o desenvolvimento de produtos tópicos em Odontologia. Além disso, avaliar a eficiência e aplicabilidade de microagulhas revestidas ou não como promotores de absorção in vitro, na metodologia desenvolvida. Artigo 1: foram padronizados os tecidos espessos de palato de porco (com e sem osso) como barreiras e condições experimentais para realização de ensaios de permeação in vitro. Em seguida, o sistema de microagulhas Dermaroller® (0,2, 0,5 e 1 mm de comprimento) foi aplicado naqueles tecidos, os quais foram montados em células de difusão vertical (Franz) adaptadas. Foram avaliados o fluxo, quantidade total permeada e o fator de promoção de permeação (EF) para os anestésicos locais lidocaína e prilocaína. Os tecidos foram padronizados com sucesso e a célula de Franz adaptada permitiu manter as condições ao longo das 12h dos experimentos de permeação. A permeação dos fármacos analisados ocorreu eventualmente, demonstrando a resistência das barreiras à difusão de fármacos. A aplicação prévia das microagulhas nos tecidos aumentou a permeação das drogas-teste em relação aos grupos-controle. Artigo 2: microagulhas de 0,7 mm foram revestidas com a droga Sulforrodamina B, aplicadas na superfície de mucosa jugal de suínos, seguida de ensaios de permeação (24h). Dois tipos de fluxo salivar (estático e dinâmico) foram simulados no compartimento doador da célula e comparados com a presença de umidade como controle negativo. Foram avaliados o tempo para início da permeação, fluxo e o EF. Ambos os tipos de fluxos salivares alteraram o perfil de permeação da droga modelo, aumentando a quantidade de droga permeada, em comparação com o controle, demonstrando a importância da saliva na realização de testes de permeação in vitro. Conclusões gerais: os tecidos foram padronizados e permitiram realizar ensaios de permeação nas células de Franz adaptadas. O uso de microagulhas foi eficaz em aumentar a permeação de fármacos nas condições avaliadas. A presença de fluxo salivar demonstrou ser importante para simular as condições reais da cavidade oral em permeação in vitro, pois pode ser fundamental na dinâmica da permeação através do tecido. O presente estudo representa um aprimoramento na realização de experimentos de permeação in vitro visando a melhora de formulações tópicas e promotores de absorção para uso em OdontologiaAbstract: The use of topical formulations in the oral cavity presents low efficiency because of the complexity and variability of the mucosal lining and hard accessibility of deep tissues, as dental pulp. Microneedles have been reported as efficient and painless transdermal and transmucosal drug systems for local and/or systemic effect and could improve action of topical drugs in Dentistry. Aiming at improving the bioavailability of topical formulations, in vitro permeation studies are very important because it may allow predicting the behavior of these formulations in front of the barrier used. However, there is no barrier model that mimics the actual conditions of the oral cavity. In this context, this study aimed to standardize thick tissue barriers of the oral cavity from pigs, adapt diffusion cells and experimental conditions for performing in vitro permeation studies with these barriers, in order to develop topical products in Dentistry. Moreover, to evaluate the efficiency and applicability of microneedles coated or not as in vitro absorption enhancers in this methodology. Article 1: pig thick palate tissues (with and without bone) and experimental conditions were standardized to carry out in vitro permeation experiment. The microneedle device Dermaroller® (0.2, 0.5 and 1 mm length) was applied in those tissues, which were mounted in adapted Franz-type vertical diffusion cells. The Flux and the permeation enhancement factor (EF) of the local anesthetics lidocaine and prilocaine were evaluated. Tissues were successfully standardized and the adapted Franz cell allowed to maintain the experimental conditions through the 12h of permeation assay. The permeation of the analyzed drugs has occurred eventually, demonstrating the effectiveness of the barriers. The microneedles pretreatment on tissues increased the permeation flux of the tested drugs, in comparison to control groups. Article 2: microneedles of 0.7 mm were coated with the drug Sulforhodamine B, and applied on the porcine buccal mucosa surface, followed by permeation tests (24h). Two types of salivary flow (static and dynamic) were simulated inside the donor chamber and were compared with a moistened gauze as a negative control. We evaluated the onset time to permeation (Lag Time), flux and EF. Either of the simulated salivary flux affected the permeation profile of the model drug, by means of increasing drug permeation, as compared to the negative control, demonstrating the importance of saliva during in vitro permeation studies. General conclusions: tissues were standardized and allowed to perform permeation assays with adapted Franz cells. The use of microneedles in those barriers was effective to increase the permeation of drugs under the conditions evaluated. The presence of salivary flow has proved to be important to simulate the real conditions of the oral cavity in in vitro permeation, which might have an essential role on permeation dynamics across the tissue. This study represents an advancement to perform in vitro permeation assays, aiming at the improvement of topical formulations and absorption enhancers for use in DentistryDoutoradoFarmacologia, Anestesiologia e TerapeuticaDoutor em Odontologia2012/02492-52012/02492-5FAPESPCAPE

Copyright issues in digital enviornment

This paper discusses about the copyright issues in the digital environment. And it also discusses the security of information over networks.it gives a brief note about Databases and multimedia technologies also.And what all are the technologies we can use for right protection that also discusses