Strategic targeting of the PI3K–NFκB axis in cisplatin-resistant NSCLC

Chemoresistance is a major therapeutic challenge to overcome in NSCLC, in order to improve the current survival rates of <15% at 5 years. We and others have shown increased PI3K signaling in NSCLC to be associated with a more aggressive disease, and a poorer prognosis. In this study, targeted inhibition of three strategic points of the PI3K–NFκB axis was performed with the aim of exploiting vulnerabilities in cisplatin-resistant NSCLC cells. Cisplatin-resistant cell lines were previously generated through prolonged exposure to the drug. Expression of PI3K and NFκB pathway-related genes were compared between cisplatin-resistant cells and their matched parent cells using a gene expression array, qRT-PCR, DNA sequencing, western blot, and immunofluorescence. Targeted inhibition was performed using GDC-0980, a dual PI3K–mTOR inhibitor currently in Phase II clinical trials in NSCLC, and DHMEQ, an inhibitor of NFκB translocation which has been used extensively both in vitro and in vivo. Effects of the two inhibitors were assessed by BrdU proliferation assay and multiparameter viability assay. NFKBIA was shown to be 12-fold overexpressed in cisplatin-resistant cells, with no mutations present in exons 3, 4, or 5 of the gene. Corresponding overexpression of IκBα was also observed. Treatment with DHMEQ (but not GDC-0980) led to significantly enhanced effects on viability and proliferation in cisplatin-resistant cells compared with parent cells. We conclude that NFκB inhibition represents a more promising strategy than PI3K–mTOR inhibition for treatment in the chemoresistance setting in NSCLC.

A brush with the real world : the future of inertial motion capture in live performance

3D Motion capture is a medium that plots motion, typically human motion, converting it into a form that can be represented digitally. It is a fast evolving field and recent inertial technology may provide new artistic possibilities for its use in live performance. Although not often used in this context, motion capture has a combination of attributes that can provide unique forms of collaboration with performance arts. The inertial motion capture suit used for this study has orientation sensors placed at strategic points on the body to map body motion. Its portability, real-time performance, ease of use, and its immunity from line-of-sight problems inherent in optical systems suggest it would work well as a live performance technology. Many animation techniques can be used in real-time. This research examines a broad cross-section of these techniques using four practice-led cases to assess the suitability of inertial motion capture to live performance. Although each case explores different visual possibilities, all make use of the performativity of the medium, using either an improvisational format or interactivity among stage, audience and screen that would be difficult to emulate any other way. A real-time environment is not capable of reproducing the depth and sophistication of animation people have come to expect through media. These environments take many hours to render. In time the combination of what can be produced in real-time and the tools available in a 3D environment will no doubt create their own tree of aesthetic directions in live performance. The case study looks at the potential of interactivity that this technology offers.

From the guest editors: Urban acupuncture

The term urban acupuncture refers to a concept where a localised intervention or treatment is used for the revitalisation and (re)creation of cities by targeting strategic points, poking or activating networks into action. These actions impart stimuli for further responses and opportunity through small projects rather than large developments. Urban Acupuncture activates dynamic transformative forces of the place and focuses on the maintenance of a healthy situation rather than on the cure of problems, and thus metaphorically resonates with the principles of the practice of acupuncture in traditional Chinese medicine...

Abuso sexual infantil intrafamiliar: a subnotificação e os serviços de saúde

A pesquisa investigou aspectos referentes ao diagnóstico e à notificação de abuso sexual infantil intrafamiliar pelos serviços básicos de saúde do Município de Maringá-PR. O abuso sexual contra crianças é um problema de saúde pública, devido à alta incidência epidemiológica e às graves conseqüências dele decorrentes. Apesar de iniciativas municipais recentes para enfrentamento do problema, poucos são os casos denunciados oficialmente, o que dificulta o dimensionamento do problema e a criação de políticas adequadas. As instituições de saúde são espaços privilegiados para a detecção precoce e a notificação dos casos, porém é essencial que, na medida em que os profissionais de saúde consigam identificar a ocorrência da violência, sintam-se seguros para notificar. Dificuldades em relação à detecção, à notificação e ao funcionamento da rede de apoio às vítimas foram levantadas, possibilitando inferir pontos estratégicos para desenvolvimento de programas de capacitação necessários para o estabelecimento de ações de combate ao abuso sexual infantil. Os resultados apontam dificuldades importantes no que se refere ao diagnóstico precoce e insuficiente informação sobre o processo de notificação e de encaminhamento dos casos. Essas dificuldades podem ser minimizadas mediante a adoção de uma política de educação continuada, bem como do fortalecimento da rede de proteção à criança e ao denunciante.

A proximidade de ecopontos e o comportamento ambiental

Dissertação de Mestrado em Gestão Integrada da Qualidade Ambiente e Segurança

Dilemmas in Regards to the Restitution of Lands in Colombia

The text argues that, even if different sectors of society have some strategic points of agreement on the issue of land, which converge on the specific issue of restitution, they strongly disagree on various other points. On one side are some who advocate “pure restitution” and consequently support a restitution policy that focuses on correcting the illegal dispossession and clarifying land titles and individual rights to property, which would serve to boost the land market and allow for rural development policies that modernize agricultural production, fundamentally based on large, corporate ownership. On the other end of the spectrum are advocates of what we call “comprehensive restitution,” who promote adopting a restitution policy that meets the requirements not only of corrective justice but also of recognition and redistribution, advancing the interest of peasant, indigenous, and afro-Colombian communities.

A capacitação de gestão estratégica como um instrumento na avaliação do crédito de curto prazo

Esta dissertação busca introduzir no Modelo de Análise de Crédito dos Bancos Comerciais alguns fatores estratégicos fundamentais para boa avaliação e defElrimento de uma operação de crédito de curto prazo. Para este fim foi elaborado um modelo Rating que tem como objetivo levar em consideração além da análise cadastral, econômico-financeira e das garantias, uma visão de todo o conjunto da empresa, dando um peso fundamental na estratégia de atuélção analisando \a competitividade , o ambiente interno e externo para que se possa chegar a um número que irá determinar o deferimento ou não da operação, dentro de parâmetros de risco definido pela instituição financeira detontora do recurso, cumprindo as normas do Sistema Financeiro Nacional.

Arquitetura da (in)segurança: estudando relações entre configuração espacial, artifícios de segurança e violência urbana no bairro Manaíra, João Pessoa, Paraíba

João Pessoa, the capital city of the state of Paraíba (Northeast Brazil), is reputed throughout the country as a quiet place, although it has been acquiring, over the past years, an urban character with social implications similar to those of major metropolitan Brazilian areas. The new situation is evident by the social inequalities, with the creation of confined spaces, which segregate and cause enclosure of the inhabitants, leading to death the public space. This study correlates accessibility in spatial structure with two types of crime data, burglary and robbery, recorded in 2008 and 2009, by the Secretaria de Segurança da Paraíba (The government agency public in charge of safety), in the district of Manaíra, an upper middle class neighborhood, which has, in recent times, been considered one of the most violent areas in João Pessoa. Sought to understand connections between these events and morpho-social aspects of the built environment, where examined the spatial properties, such as accessibility of the urban net, the presence of control measures, the safety of buildings and their uses. Spatial properties were also validated by the observation of pedestrian flows at strategic points of the study area. It was concluded that the presence of intense flows helps to attract potential thieves, physical security and control offers little protection

Análise de desempenho de um refrigerador de pequeno porte com drop in de refrigerantes hidrocarbonetos

From what was stated in the Montreal Protocol, the researchers and refrigeration industry seek substitutes for synthetic refrigerants -chlorofluorocarbons (CFCs) and HCFCs (HCFC) - that contribute to the depletion of the ozone layer. The phase-out of these substances was started using as one of the replacement alternatives the synthetic fluids based on hydro fluorocarbons (HFCs) that have zero potential depletion of the ozone layer. However, contribute to the process of global warming. HFC refrigerants are greenhouse gases and are part of the group of gases whose emissions must be reduced as the Kyoto Protocol says. The hydrocarbons (HC's), for not contribute to the depletion of the ozone layer, because they have very low global warming potential, and are found abundantly in nature, has been presented as an alternative, and therefore, are being used in new home refrigeration equipment in several countries. In Brazil, due to incipient production of domestic refrigerators using HC's, the transition refrigerants remain on the scene for some years. This dissertation deals with an experimental evaluation of the conduct of a drinking fountain designed to work with HFC (R-134a), operating with a mixture of HC's or isobutane (R-600a) without any modification to the system or the lubricating oil. In the refrigeration laboratory of Federal University of Rio Grande do Norte were installed, in a drinking fountain, temperature and pressure sensors at strategic points in the refrigeration cycle, connected to an acquisition system of computerized data, to enable the mapping and thermodynamics analysis of the device operating with R-134a or with a mixture of HC's or with R-600a. The refrigerator-test operating with the natural fluids (mixture of HC's or R-600a) had a coefficient of performance (COP) lower than the R-134a

Estudo do equilíbrio líquido-vapor do sistema água+etanol+líquido iônico visando a separação do álcool anidro

Anhydrous ethanol is used in chemical, pharmaceutical and fuel industries. However, current processes for obtaining it involve high cost, high energy demand and use of toxic and pollutant solvents. This problem occurs due to the formation of an azeotropic mixture of ethanol + water, which does not allow the complete separation by conventional methods such as simple distillation. As an alternative to currently used processes, this study proposes the use of ionic liquids as solvents in extractive distillation. These are organic salts which are liquids at low temperatures (under 373,15 K). They exhibit characteristics such as low volatility (almost zero/ low vapor ), thermal stability and low corrosiveness, which make them interesting for applications such as catalysts and as entrainers. In this work, experimental data for the vapor pressure of pure ethanol and water in the pressure range of 20 to 101 kPa were obtained as well as for vapor-liquid equilibrium (VLE) of the system ethanol + water at atmospheric pressure; and equilibrium data of ethanol + water + 2-HDEAA (2- hydroxydiethanolamine acetate) at strategic points in the diagram. The device used for these experiments was the Fischer ebulliometer, together with density measurements to determine phase compositions. The experimental data were consistent with literature data and presented thermodynamic consistency, thus the methodology was properly validated. The results were favorable, with the increase of ethanol concentration in the vapor phase, but the increase was not shown to be pronounced. The predictive model COSMO-SAC (COnductor-like Screening MOdels Segment Activity Coefficient) proposed by Lin & Sandler (2002) was studied for calculations to predict vapor-liquid equilibrium of systems ethanol + water + ionic liquids at atmospheric pressure. This is an alternative for predicting phase equilibrium, especially for substances of recent interest, such as ionic liquids. This is so because no experimental data nor any parameters of functional groups (as in the UNIFAC method) are needed

Allocation of protective devices in distribution circuits using nonlinear programming models and genetic algorithms

The optimized allocation of protective devices in strategic points of the circuit improves the quality of the energy supply and the system reliability index. This paper presents a nonlinear integer programming (NLIP) model with binary variables, to deal with the problem of protective device allocation in the main feeder and all branches of an overhead distribution circuit, to improve the reliability index and to provide customers with service of high quality and reliability. The constraints considered in the problem take into account technical and economical limitations, such as coordination problems of serial protective devices, available equipment, the importance of the feeder and the circuit topology. The use of genetic algorithms (GAs) is proposed to solve this problem, using a binary representation that does (1) or does not (0) show allocation of protective devices (reclosers, sectionalizers and fuses) in predefined points of the circuit. Results are presented for a real circuit (134 busses), with the possibility of protective device allocation in 29 points. Also the ability of the algorithm in finding good solutions while improving significantly the indicators of reliability is shown. (C) 2003 Elsevier B.V. All rights reserved.

Optimized allocation of sectionalizing switches and control and protection devices for reliability indices improvement in distribution systems

Reliability of power supply is related, among other factors, to the control and protection devices allocation in feeders of distribution systems. In this way, optimized allocation of sectionalizing switches and protection devices in strategic points of distribution circuits, improves the quality of power supply and the system reliability indices. In this work, it is presented a mixed integer non-linear programming (MINLP) model, with real and binary variables, for the sectionalizing switches and protection devices allocation problem, in strategic sectors, aimed at improving reliability indices, increasing the utilities billing and fulfilling exigencies of regulatory agencies for the power supply. Optimized allocation of protection devices and switches for restoration, allows that those faulted sectors of the system can be isolated and repaired, re-managing loads of the analyzed feeder into the set of neighbor feeders. Proposed solution technique is a Genetic Algorithm (GA) developed exploiting the physical characteristics of the problem. Results obtained through simulations for a real-life circuit, are presented. © 2004 IEEE.

Development of a prototype for measuring plantar forces

Studies on the distribution of plantar pressure between the sole of the foot and the ground were developed before the 19th century. Currently, the most often employed plantar pressure measurement systems are Pedar® and FScan®, which have restrictions such as operational difficulty and high cost. In the present study, a device was constructed from two pressure plates capable of measuring plantar forces in discreet areas of the feet at a low cost, using strain-gages attached to sixteen strategic points of the mechanical elements. Sixteen prismatic beams were soldered to each frame, for which the free extremity of each beam represented a specific point of the foot. Two strain gauges were attached to each beam - one near the upper fixed extremity and the other near the lower fixed extremity. Using a Wheatstone bridge electric circuit, the gauges were used to measure the force acting on the extremity of the beam. Precision and accuracy of the prototype was about 10%. In some measurements, accuracy was 2%. The low precision and accuracy were mainly due to the restrictions of the available equipment, which only permitted four measurements at a time. Thus, it was necessary for participants to stand on the plates four separate times, which signified possible changes in the position of the feet on the pressure plates. Despite some limitations, the aim was achieved. The prototype has been used in some studies and represents a contribution to biomechanics, demonstrating the viability of using strain gauges.

Alocação otimizada de dispositivos de proteção em sistema de distribuição de energia elétrica

Pós-graduação em Engenharia Elétrica - FEIS