Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro

Reproducing the characteristics and the functional responses of the blood-brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.

Impact of a program for the prevention of traffic accidents in a Southern Brazilian city: a model for implementation in a developing country

Background: Traffic accidents constitute the main cause of death in the first decades of life. Traumatic brain injury is the event most responsible for the severity of these accidents. The SBN started an educational program for the prevention of traffic accidents, adapted from the American model ""Think First"" to the Brazilian environment, since 1995, with special effort devoted to the prevention of TBI by using seat belts and motorcycle helmets. The objective of the present study was to set up a traffic accident prevention program based on the adapted Think First and to evaluate its impact by comparing epidemiological variables before and after the beginning of the program. Methods: The program was executed in Maringa city, from September 2004 to August 2005, with educational actions targeting the entire population, especially teenagers and young adults. The program was implemented by building a network of information facilitators and multipliers inside the organized civil society, with widespread population dissemination. To measure the impact of the program, a specific software was developed for the storage and processing of the epidemiological variables. Results: The results showed a reduction of trauma severity due to traffic accidents after the execution of the program, mainly TBI. Conclusions: The adapted Think First was systematically implemented and its impact measured for the first time in Brazil, revealing the usefulness of the program for reducing trauma and TBI severity in traffic accidents through public education and representing a standardized model of implementation in a developing country. (C) 2009 Elsevier Inc. All rights reserved.

A modified rat model of neonatal anoxia: Development and evaluation by pulseoximetry, arterial gasometry and Fos immunoreactivity

Neonatal anoxia is a worldwide clinical problem that has serious and lasting consequences. The diversity of models does not allow complete reproducibility, so a standardized model is needed. In this study, we developed a rat model of neonatal anoxia that utilizes a semi-hermetic system suitable for oxygen deprivation. The validity of this model was confirmed using pulse oximetry, arterial gasometry, observation of skin color and behavior and analysis of Fos immunoreactivity in brain regions that function in respiratory control. For these experiments, 87 male albino neonate rats (Rattus norvegicus, lineage Wistar) aged approximate 30 postnatal hours were divided into anoxia and control groups. The pups were kept in an euthanasia polycarbonate chamber at 36 +/- 1 degrees C, with continuous 100% nitrogen gas flow at 3 L/min and 101.7 kPa for 25 min. The peripheral arterial oxygen saturation of the anoxia group decreased 75% from its initial value. Decreased pH and partial pressure of oxygen and increased partial pressure of carbon dioxide were observed in this group, indicating metabolic acidosis, hypoxia and hypercapnia. respectively. Analysis of neuronal activation showed Fos immunoreactivity in the solitary tract nucleus, the lateral reticular nucleus and the area postrema, confirming that those conditions activated areas related to respiratory control in the nervous system. Therefore, the proposed model of neonatal anoxia allows standardization and precise control of the anoxic condition, which should be of great value in indentifying both the mechanisms underlying neonatal anoxia and novel therapeutic strategies to combat or prevent this widespread public health problem. (C) 2011 Elsevier B.V. All rights reserved.

Standardization of project management processes

Software development is a discipline that is almost as old as the history of computers. With the advent of the Internet and all of its related technologies, software development has been on high demand. But, and especially in SME (small and medium enterprise), this was not accompanied with a comparable effort to develop a set of sustainable and standardized activities of project management, which lead to increasing inefficiencies and costs. Given the actual economic situation, it makes sense to engage in an effort to reduce said inefficiencies and rising costs. For that end, this work will analyze the current state of software development’s project management processes on a Portuguese SME, along with its problems and inefficiencies in an effort to create a standardized model to manage software development, with special attention given to critical success factors in an agile software development environment, while using the best practices in process modeling. This work also aims to create guidelines to correctly integrate these changes in the existing IS structure of a company.

Market risk charge of the trading book: a comparison of the Basel II and Basel III

This paper aims to investigate if the market capital charge of the trading book increased in Basel III compared to Basel II. I showed that the capital charge rises by 232% and 182% under the standardized and internal model, respectively. The varying liquidity horizons, the calibration to a stress period, the introduction of credit spread risk, the restrictions on correlations across risk categories and the incremental default charge boost Basel III requirements. Nevertheless, the impact of Expected shortfall at 97.5% is low and long term shocks decrease the charge. The standardized approach presents advantages and disadvantages relative to internal models.

Innovaatioprosessin alkupään toimintamalli ja päätöksenteko

Työn tavoitteena oli tutkia innovaatioita ja organisaation innovaatiokyvykkyyttä, innovaatiokyvykkyyden taustatekijöitä sekä innovaatioprosessin alkupään (Fuzzy Front End, FFE) sekä siinä tapahtuvan päätöksenteon johtamista. Lisäksi tavoitteena oli suunnitella innovaatioprosessin alkupään toimintamalli selkeyttämään toimintaa prosessin alkupäässä sekä antaa toimenpide-ehdotuksia ja suosituksia. Tutkimuksen teoriaosuus tehtiin kirjallisuustutkimuksena. Tutkimuksen empiirinen osuus suoritettiin case -analyysinä yrityksen henkilöhaastattelu- ja toimintatutkimuksen muodossa. Innovaatioprosessin alkupäähän on tunnistettu toimintamalleja, joilla selkeytetään ja tehostetaan prosessin alkupään vaiheita. Vaiheet ovat mahdollisuuksien tunnistaminen, mahdollisuuksien analysointi, ideointi, ideoiden valitseminen ja konsepti- ja teknologiakehitys. Innovaatioprosessin rinnalla kulkee päätöksenteon prosessi, jonka suhteen tunnistetaan selkeät päätöksentekokohdat ja kriteerit prosessissa etenemiselle. Innovaatio- ja päätöksentekoprosessiin osallistuu eri vaiheissa sekä yrityksen sisäiset, kuten henkilöstö, että ulkoiset, kuten asiakkaat, toimittajat ja verkostokumppanit, sidosryhmät. Lisäksi innovaatioprosessin toimintaan vaikuttavat johdon tuki ja sitoutuminen, osallistujien kyky luovuuteen sekä muut innovaatiokyvykkyyden taustatekijät. Kaikki nämä tekijät tulee huomioida innovaatioprosessin alkupään mallia suunniteltaessa. Tutkimus tehtiin tietoliikennealan yrityksen tarpeisiin. Yrityksessä on käytössä aloitetoimintaa, mutta sen ei koeta tarjoavan riittävästi ideoita yrityksen tuotekehityksen tarpeisiin. Yrityksen henkilöstön innovaatiopotentiaali on suuri, mikä halutaan hyödyntää paremmin suunnittelemalla yrityksen käyttöön soveltuva, innovaatioprosessin alkupään toimintaan ohjaava, vakioitu ja henkilöstöä ja muita yhteistyötahoja, kuten asiakkaita, osallistava toimintamalli. Toimenpide-ehdotuksina ja suosituksina esitetään innovaatioprosessin alkupään johtamisen toimintamallia. Esitetyssä mallissa määritellään vaiheet, menetelmät, päätöksenteko ja vastuut. Toimintamalli esitetään soveltuen yhdistettäväksi yrityksessä käytössä olevaan innovaatioprosessin loppupään, tuotekehitysprojektien läpiviemisen, malliin.

Vigilancia médica para los trabajadores expuestos a benceno, tolueno y xileno

En este estudio se revisaron recomendaciones nacionales e internacionales donde se evidencio que no hay un modelo estándar que permita establecer un seguimiento de las condiciones de trabajo y las condiciones de salud que afectan los trabajadores expuestos a hidrocarburos aromáticos BTX. Para este propósito este estudio señalara las directrices a seguir para implementar el programa de vigilancia médica incorporando los aspectos clínicos y de diagnóstico de laboratorio para generar estrategias oportunas que conllevan al mantenimiento de adecuadas condiciones de salud de los trabajadores y que permitirá detectar las alteraciones producidas por los mismos en un estadio reversible; esta vigilancia médica debe ajustarse a las distintas necesidades y los recursos de las industrias en cuyos procesos se utilizan los hidrocarburos aromáticos. (Benceno, tolueno y xileno).

Uncertainty in simulating wheat yields under climate change

Projections of climate change impacts on crop yields are inherently uncertain1. Uncertainty is often quantified when projecting future greenhouse gas emissions and their influence on climate2. However, multi-model uncertainty analysis of crop responses to climate change is rare because systematic and objective comparisons among process-based crop simulation models1, 3 are difficult4. Here we present the largest standardized model intercomparison for climate change impacts so far. We found that individual crop models are able to simulate measured wheat grain yields accurately under a range of environments, particularly if the input information is sufficient. However, simulated climate change impacts vary across models owing to differences in model structures and parameter values. A greater proportion of the uncertainty in climate change impact projections was due to variations among crop models than to variations among downscaled general circulation models. Uncertainties in simulated impacts increased with CO2 concentrations and associated warming. These impact uncertainties can be reduced by improving temperature and CO2 relationships in models and better quantified through use of multi-model ensembles. Less uncertainty in describing how climate change may affect agricultural productivity will aid adaptation strategy development andpolicymaking.

Procedimentos para a formulação da estratégia competitiva de empresas

Pós-graduação em Engenharia Mecânica - FEG

Do fracasso à reforma das operações de paz das Nações Unidas (2000-2010)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

POSTDATA – Towards publishing European poetry as linked open data

POSTDATA is a 5 year's European Research Council (ERC) Starting Grant Project that started in May 2016 and is hosted by the Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain. The context of the project is the corpora of European Poetry (EP), with a special focus on poetic materials from different languages and literary traditions. POSTDATA aims to offer a standardized model in the philological field and a metadata application profile (MAP) for EP in order to build a common classification of all these poetic materials. The information of Spanish, Italian and French repertoires will be published in the Linked Open Data (LOD) ecosystem. Later we expect to extend the model to include additional corpora. There are a number of Web Based Information Systems in Europe with repertoires of poems available to human consumption but not in an appropriate condition to be accessible and reusable by the Semantic Web. These systems are not interoperable; they are in fact locked in their databases and proprietary software, not suitable to be linked in the Semantic Web. A way to make this data interoperable is to develop a MAP in order to be able to publish this data available in the LOD ecosystem, and also to publish new data that will be created and modeled based on this MAP. To create a common data model for EP is not simple since the existent data models are based on conceptualizations and terminology belonging to their own poetical traditions and each tradition has developed an idiosyncratic analytical terminology in a different and independent way for years. The result of this uncoordinated evolution is a set of varied terminologies to explain analogous metrical phenomena through the different poetic systems whose correspondences have been hardly studied – see examples in González-Blanco & Rodríguez (2014a and b). This work has to be done by domain experts before the modeling actually starts. On the other hand, the development of a MAP is a complex task though it is imperative to follow a method for this development. The last years Curado Malta & Baptista (2012, 2013a, 2013b) have been studying the development of MAP's in a Design Science Research (DSR) methodological process in order to define a method for the development of MAPs (see Curado Malta (2014)). The output of this DSR process was a first version of a method for the development of Metadata Application Profiles (Me4MAP) (paper to be published). The DSR process is now in the validation phase of the Relevance Cycle to validate Me4MAP. The development of this MAP for poetry will follow the guidelines of Me4MAP and this development will be used to do the validation of Me4MAP. The final goal of the POSTDATA project is: i) to be able to publish all the data locked in the WIS, in LOD, where any agent interested will be able to build applications over the data in order to serve final users; ii) to build a Web platform where: a) researchers, students and other final users interested in EP will be able to access poems (and their analyses) of all databases; b) researchers, students and other final users will be able to upload poems, the digitalized images of manuscripts, and fill in the information concerning the analysis of the poem, collaboratively contributing to a LOD dataset of poetry.

Bay 41-2272, A Soluble Guanylate Cyclase Stimulator, Relaxes Isolated Human Ureter In A Standardized In Vitro Model.

To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 ± 3.2 years, male/female ratio 2:1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 μM) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 ± 0.14 and 84% ± 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 ± 0.10, P <.05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. BAY 41-2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved.

Experimental model of tooth movement in mice: A standardized protocol for studying bone remodeling under compression and tensile strains

During orthodontic tooth movement (OTM), alveolar bone is resorbed by osteoclasts in compression sites (CS) and is deposited by osteoblasts in tension sites (TS). The aim of this study was to develop a standardized OTM protocol in mice and to investigate the expression of bone resorption and deposition markers in CS and TS. An orthodontic appliance was placed in C57BL6/J mice. To define the ideal orthodontic force, the molars of the mice were subjected to forces of 0.1 N, 0.25 N, 0.35 N and 0.5 N. The expression of mediators that are involved in bone remodeling at CS and TS was analyzed using a Real-Time PCR. The data revealed that a force of 0.35 N promoted optimal OTM and osteoclast recruitment without root resorption. The levels of TNF-alpha, RANKL, MMP13 and OPG were all altered in CS and TS. Whereas TNF-a and Cathepsin K exhibited elevated levels in CS. RUNX2 and OCN levels were higher in TS. Our results suggest that 0.35 N is the ideal force for OTM in mice and has no side effects. Moreover, the expression of bone remodeling markers differed between the compression and the tension areas, potentially explaining the distinct cellular migration and differentiation patterns in each of these sites. (C) 2012 Elsevier Ltd. All rights reserved.

Histologic Study of Acute Vocal Fold Wound Healing After Corticosteroid Injection in a Rabbit Model

Objectives: Injectable corticosteroids have been used in phonosurgery to prevent scarring of the vocal fold because of their effects of wound healing, and to ensure better voice quality. We histologically evaluated the effects of dexamethasone sodium phosphate infiltration on acute vocal fold wound healing in rabbits 3 and 7 days after surgically induced injury by quantification of the inflammatory reaction and collagen deposition. Methods: A standardized surgical incision was made in the vocal folds of 12 rabbits, and 0.1 mL dexamethasone sodium phosphate (4 mg/mL) was injected into the left vocal fold. The right vocal fold was not injected and served as the control. The larynges were collected 3 and 7 days after surgery. For histologic analysis, the vocal folds were stained with hematoxylin-eosin for quantification of the inflammatory response and with picrosirius red for qunatification of collagen depostion. Results: There was no quantitative difference in the inflammatory response between vocal folds injected with the corticosteroid and control vocal folds. However, the rate of collage deposition was significantly lower in the corticosteroid-treated group at 3 and 7 days after injury (p = 0.002). Conclusions: The present results suggest that dexamethasone reduces collagen depostion during acute vocal fold wound healing.

Evaluating a model of parental influence on youth physical activity

Objective: To test a conceptual model linking parental physical activity orientations, parental support for physical activity, and children's self-efficacy perceptions with physical activity participation. Participants and Setting: The sample consisted of 380 students in grades 7 through 12 (mean age, 14.0 +/- 1.6 years) and their parents. Data collection took place during the fall of 1996. Main Outcome Measures: Parents completed a questionnaire assessing their physical activity habits, enjoyment of physical activity, beliefs regarding the importance of physical activity, and supportive behaviors for their child's physical activity. Students completed a 46-item inventory assessing physical activity during the previous 7 days and a 5-item physical activity self-efficacy scale. The model was tested via observed variable path analysis using structural equation modeling techniques (AMOS 4.0). Results: An initial model, in which parent physical activity orientations predicted child physical activity via parental support and child self-efficacy, did not provide an acceptable fit to the data. Inclusion of a direct path from parental support to child physical activity and deletion of a nonsignificant path from parental physical activity to child physical activity significantly improved model fit. Standardized path coefficients for the revised model ranged from 0.17 to 0.24, and all were significant at the p < 0.0001 level. Conclusions: Parental support was an important correlate of youth physical activity, acting directly or indirectly through its influence on self-efficacy. Physical activity interventions targeted at youth should include and evaluate the efficacy of individual-level and community-level strategies to increase parents' capacity to provide instrumental and motivational support for their children's physical activity.