Modelagem hidrológica da bacia hidrográfica do rio Bengalas, Nova Friburgo, RJ, utilizando o potencial de geotecnologias na definição de áreas de risco de inundação.

A presente pesquisa concentra-se no estudo hidrológico utilizando o potencial das geotecnologias na modelagem do escoamento na bacia do rio Bengalas, cujo rio principal de mesmo nome, corta o município de Nova Friburgo, RJ, no sentido Sul-Norte. Esse município, um dos mais importantes da região serrana, sofre frequentemente com inundações e deslizamentos, onde, dados históricos e acontecimentos recentes mostram que a ocupação inadequada de encostas e calhas dos rios são as áreas destacada e negativamente afetadas. A metodologia tem suporte no uso de um SIG, extraindo informações, que por sua vez, serão entrada de dados na fase de modelagem, e reforçando a apresentação dos resultados das simulações através de mapas. Ela está divida basicamente em três etapas: "SIG", "Modelagem" e "Suporte à Tomada de Decisão/Simulação". Esse primeiro estudo permitiu compor um banco de dados geográfico com as características fisiográficas da bacia; a seleção criteriosa de uma modelagem matemática e encadeamento de seus parâmetros com os componentes do ciclo hidrológico; realizar a calibração do modelo de transformação chuva-vazão, Soil Conservation Service (CN); e simular a passagem dos volumes gerados pela precipitação efetiva na calha do rio Bengalas, com o objetivo de identificar e analisar as áreas suscetíveis a inundações na porção central da cidade de Nova Friburgo. Modelagem dessa natureza vem sendo empregada, principalmente, no gerenciamento de recursos hídricos, onde a tomada de decisões embasada nos resultados de simulações computacionais, contribuem para evitar prejuízos materiais e financeiros, e ainda, perdas de vidas humanas em áreas de risco, neste caso, aquelas suscetíveis a inundações. Analisando os resultados encontrados temos que a área suscetível à inundação para uma chuva com tempo de recorrência de 50 anos, o mais crítico estudado, seja de aproximadamente 1,0 km, distribuídos nos seus 8,5km na região central de Nova Friburgo-RJ, sendo está, ora delimitada, prioritariamente edificada.

Privacy invasive geo-mashups : privacy 2.0 and the limits of first generation information privacy laws

Online technological advances are pioneering the wider distribution of geospatial information for general mapping purposes. The use of popular web-based applications, such as Google Maps, is ensuring that mapping based applications are becoming commonplace amongst Internet users which has facilitated the rapid growth of geo-mashups. These user generated creations enable Internet users to aggregate and publish information over specific geographical points. This article identifies privacy invasive geo-mashups that involve the unauthorized use of personal information, the inadvertent disclosure of personal information and invasion of privacy issues. Building on Zittrain’s Privacy 2.0, the author contends that first generation information privacy laws, founded on the notions of fair information practices or information privacy principles, may have a limited impact regarding the resolution of privacy problems arising from privacy invasive geo-mashups. Principally because geo-mashups have different patterns of personal information provision, collection, storage and use that reflect fundamental changes in the Web 2.0 environment. The author concludes by recommending embedded technical and social solutions to minimize the risks arising from privacy invasive geo-mashups that could lead to the establishment of guidelines for the general protection of privacy in geo-mashups.

PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Inequitable Provision of Optimal Services for Patients with Chronic Heart failure: A National Geo-Mapping Study

Objective: To compare the location and accessibility of current Australian chronic heart failure (CHF) management programs and general practice services with the probable distribution of the population with CHF. Design and setting: Data on the prevalence and distribution of the CHF population throughout Australia, and the locations of CHF management programs and general practice services from 1 January 2004 to 31 December 2005 were analysed using geographic information systems (GIS) technology. Outcome measures: Distance of populations with CHF to CHF management programs and general practice services. Results: The highest prevalence of CHF (20.3–79.8 per 1000 population) occurred in areas with high concentrations of people over 65 years of age and in areas with higher proportions of Indigenous people. Five thousand CHF patients (8%) discharged from hospital in 2004–2005 were managed in one of the 62 identified CHF management programs. There were no CHF management programs in the Northern Territory or Tasmania. Only four CHF management programs were located outside major cities, with a total case load of 80 patients (0.7%). The mean distance from any Australian population centre to the nearest CHF management program was 332 km (median, 163 km; range, 0.15–3246 km). In rural areas, where the burden of CHF management falls upon general practitioners, the mean distance to general practice services was 37 km (median, 20 km; range, 0–656 km). Conclusion: There is an inequity in the provision of CHF management programs to rural Australians.

Study of a geo-multicast framework for efficient message dissemination at unmanned level crossings

Collisions among trains and cars at road/rail level crossings (LXs) can have severe consequences such as high level of fatalities, injuries and significant financial losses. As communication and positioning technologies have significantly advanced, implementing vehicular ad hoc networks (VANETs) in the vicinity of unmanned LXs, generally LXs without barriers, is seen as an efficient and effective approach to mitigate or even eliminate collisions without imposing huge infrastructure costs. VANETs necessitate unique communication strategies, in which routing protocols take a prominent part in their scalability and overall performance, through finding optimised routes quickly and with low bandwidth overheads. This article studies a novel geo-multicast framework that incorporates a set of models for communication, message flow and geo-determination of endangered vehicles with a reliable receiver-based geo-multicast protocol to support cooperative level crossings (CLXs), which provide collision warnings to the endangered motorists facing road/rail LXs without barriers. This framework is designed and studied as part of a $5.5 m Government and industry funded project, entitled 'Intelligent-Transport-Systems to improve safety at road/rail crossings'. Combined simulation and experimental studies of the proposed geo-multicast framework have demonstrated promising outcomes as cooperative awareness messages provide actionable critical information to endangered drivers who are identified by CLXs.

Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

Geo-locked photo sharing on mobile devices

We introduce the idea of geo-locking through a mobile phone based photo sharing application called Picalilly (figure 1). Using its geo-locking feature, Picalilly allows its users to manually define geographical boundaries for sharing photos -- limiting sharing within user-defined boundaries as well as facilitating open sharing between strangers within such boundaries. To explore the potential of geo-locking, we carried out a small scale field trial of Picalilly involving two groups of students, who were part of a two-week long introduction program at a university. Our preliminary results show that Picalilly facilitated 1) sharing of 'places' and 2) localized explorations.

Invasive and metastatic properties of MCF-7 cells and ras(H)-transfected MCF-7 cell lines

In vitro invasion and in vivo metastasis assays were performed with a panel of MCF-7 cells transfected with isogenic constructs of mutated ras(H) genes. Both increased levels of ras(H) expression and ras(H) oncogene activation increased activity of derivative cell lines in in vitro invasion assays. In vivo formation of spontaneous metastases was assessed after intradermal inoculation of MCF-7 cells in the vicinity of the mammary fat pads of ovariectomized nude mice. No metastases were seen in the absence of estradiol treatment of the mice. With estradiol supplementation of the mice both the ras(H)-transfected and control transfected cell lines gave a higher incidence of metastases than parental MCF-7 cells. Prolonged treatment of mice with exogenous estradiol (60 days vs. 21 days) resulted in more frequent metastases to liver and lung at the end of the 90-day observation period. In contrast to activated ras(H)-gene enhancement of metastatic capacity of rodent fibroblast and epithelial cell lines, there was no correlation of ras(H) expression with in vivo metastatic capacity of a human mammary carcinoma cell line.

Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes

Infection with erbB-2 (E) of Ha-ras (H) oncogene-transfected cells has been previously shown to cooperatively induce anchorage-independent growth of the MCF10A human mammary epithelial cell line in vitro, but not to induce nude mouse tumorigenicity. Here we show that oncogene-transformed MCF10A are able to halt in the lungs of nude mice, a sign of organ colonization potential. We have therefore studied the transformants for in vitro migratory and invasive properties known to correlate with the metastatic potential of human mammary carcinoma cells in nude mice. MCF10A transfected with Ha-ras, infected with a recombinant retroviral vector containing the human c-erB-2 proto-oncogene (MCF10A-HE cells), show a higher invasive index than either the single transfectant (MCF10A-H) or MCF10A-erB-2(MCF10A-E) cells in the Boyden chamber chemotaxis and chemoinvasion assays. The MCF10A-HE cells also adopted an invasive stellate growth pattern when plated or embedded in Matrigel, in contrast to the spherical colonies formed by the single transformants MCF10A-H, MCF10A-E, and the parental cells. Dot-blot analysis of gelatinase A and TIMP-2 mRNA levels revealed increasing gelatinase A mRNA levels (HE > E > H > MCF10A) and reduced TIMP-2 expression in both single and double transformants. Furthermore, MCF10A-HE cells show more MMP-2 activity than parental MCF10A cells or the single transformants. CD44 analysis revealed differential isoform banding for the MCF10A-HE cells compared to parental cells, MCF10A-H and MCF10A-E, accompanied by increased binding of hyaluronan by the double transformants. Our results indicate that erB-2 and Ha-ras co-expression can induce a more aggressive phenotype in vitro, representative of the malignancy of mammary carcinomas.

MicroRNAs targeting mutant K-ras by electrotransfer inhibit human colorectal adenocarcinoma cell growth in vitro and in vivo

Mutations of K-ras have been found in 30-60% of colorectal carcinomas and are believed to be associated with tumor initiation, tumor progression and metastasis formation. Therefore, silencing of mutant K-ras expression has become an attractive therapeutic strategy for colorectal cancer treatment. The aim of our study was to investigate the effect of microRNA (miRNA) molecules directed against K-ras (miRNA-K-ras) on K-ras expression level and the growth of colorectal carcinoma cell line LoVo in vitro and in vivo. In addition, we evaluated electroporation as a gene delivery method for transfection of LoVo cells and tumors with plasmid DNA encoding miRNA-K-ras (pmiRNA-K-ras). Results of our study indicated that miRNAs targeting K-ras efficiently reduced K-ras expression and cell survival after in vitro electrotransfection of LoVo cells with pmiRNA-K-ras. In vivo, electroporation has proven to be a simple and efficient delivery method for local administration of pmiRNA-K-ras molecules into LoVo tumors. This therapy shows pronounced antitumor effectiveness and has no side effects. The obtained results demonstrate that electrogene therapy with miRNA-K-ras molecules can be potential therapeutic strategy for treatment of colorectal cancers harboring K-ras mutations. © 2010 Nature Publishing Group All rights reserved.

Kirsten ras mutations in patients with colorectal cancer : the ‘RASCAL II’ study

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes’ C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes’ B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.