Maximizing efficacy of the hypomethylating drug 5-aza-2'-deoxycytidine in human leukemia

5-aza-2'-deoxycytidine (DAC) is a cytidine analogue that strongly inhibits DNA methylation, and was recently approved for the treatment of myelodysplastic syndromes (MDS). To maximize clinical results with DAC, we investigated its use as an anti-cancer drug. We also investigated mechanisms of resistance to DAC in vitro in cancer cell lines and in vivo in MDS patients after relapse. We found DAC sensitized cells to the effect of 1-β-D-Arabinofuranosylcytosine (Ara-C). The combination of DAC and Ara-C or Ara-C following DAC showed additive or synergistic effects on cell death in four human leukemia cell lines in vitro, but antagonism in terms of global methylation. RIL gene activation and H3 lys-9 acetylation of short interspersed elements (Alu). One possible explanation is that hypomethylated cells are sensitized to cell killing by Ara-C. Turning to resistance, we found that the IC50 of DAC differed 1000 fold among and was correlated with the dose of DAC that induced peak hypomethylation of long interspersed nuclear elements (LINE) (r=0.94, P<0.001), but not with LINE methylation at baseline (r=0.05, P=0.97). Sensitivity to DAC did not significantly correlate with sensitivity to another hypomethylating agent 5-azacytidine (AZA) (r=0.44, P=0.11). The cell lines most resistant to DAC had low dCK, hENT1, and hENT2 transporters and high cytosine deaminase (CDA). In an HL60 leukemia cell line, resistance to DAC could be rapidly induced by drug exposure, and was related to a switch from monoallelic to biallelic mutation of dCK or a loss of wild type DCK allele. Furthermore, we showed that DAC induced DNA breaks evidenced by histone H2AX phosphorylation and increased homologous recombination rates 7-10 folds. Finally, we found there were no dCK mutations in MDS patients after relapse. Cytogenetics showed that three of the patients acquired new abnormalities at relapse. These data suggest that in vitro spontaneous and acquired resistance to DAC can be explained by insufficient incorporation of drug into DNA. In vivo resistance to DAC is likely due to methylation-independent pathways such as chromosome changes. The lack of cross resistance between DAC and AZA is of potential clinical relevance, as is the combination of DAC and Ara-C. ^

Documental : Estampas de la crisis

El documental se complementa con un CD interactivo, con ellos se ha profundizado y generado una reflexión sobre su contenido y sobre el papel de las TICs en nuestra sociedad actual y definiendo estrategias que mejoren el acceso y la producción de información en forma masiva, plural, democrática y con altos niveles de participación ciudadana. El objetivo del proyecto es el relevamiento teórico, la producción audiovisual digital y la difusión masiva por redes y medios telemáticos de la problemática cotidiana social y cultural con que se expresa LA CRISIS que vive nuestro país, región y provincia, con el fin de plasmar imágenes y contenidos de gran perdurabilidad por su registro digital, orientados a la generación de espacios para la reflexión y el replanteo teórico crítico acerca de lo que nos sucedió y sucede, sobre todo dentro de espacios educativos, culturales y de la sociedad civil, con el fin de aportar ideas, escenarios posibles y proyectos a la sociedad y el momento que nos toca vivir. Es parte de una hipótesis que remite al mundo de las imágenes y al desarrollo de las TICs como modo de registro y difusión esencial para testimoniar y reflexionar sobre la crisis actual y el papel progresista y democratizador que pueden jugar las nuevas tecnologías en la promoción de espacios físicos y virtuales para el reforzamiento de la ciudadanía plena. La metodología se establece a través de tres momentos diferentes: 1- Relevamiento teórico, a través de encuestas cuanti-cualitativas, entrevistas, análisis de casos y seguimiento de la información económica, política, social y cultural de los últimos años. 2- El tratamiento de la información audiovisual, en soportes digitiales, seguirá los pasos metodológicos propio del proceso de pre-producción, producción y post-producción específico de realización audiovisual. 3- La difusión a través de redes y medios telemáticos de los productos obtenidos y el seguimiento de los procesos dinámicos (sincrónicos y asincrónicos) de participación, intercambio de ideas, reflexiones y propuestas a través de internet y sus herramientas (foros y chats), videoconferencias, aulas virtuales, etc.

Derechos de consumidor : ciudadanía en acción

El video se complementa con el objeto digital en soporte textual titulado de igual manera publicado en esta Biblioteca Digital que propone una mediación pedagógica de la temática para ser utilizado junto al video en instancias educativas no formales diseñadas con modalidad a distancia.Los objetivos que se propone el proyecto son: trabajar articuladamente en la formación de los consumidores contribuyendo así al ejercicio de una ciudadanía activa y contribuir al conocimiento de los derechos de los consumidores, el desarrollo de una actitud crítica en la evaluación, toma de decisiones para la adquisición de bienes y servicios.

Participación ciudadana

El video es parte del programa " INICIATIVAS para el fortalecimiento democrático y social "creado por el Centro de Estudios Legales y Sociales (CELS), la Universidad de San Andrés (EDESA) y la Facultad Latinoamericana de Ciencias Sociales (FLACSO) con Fondos donados por la Fundación FORD. OIKOS presenta este video con el objetivo de promocionar la participación ciudadana, el libre acceso a la información y la resolución de conflictos ambientales en Mendoza. Desarrolla en el mismo los conceptos de participación representativa y ciudadana ante una temática puntual: defensa del medio ambiente. El acceso a la información, la posibilidad de ejercer como ciudadanos nuestros derechos, la función del estado, la reforma constitucional, la audiencia pública como una herramienta del ciudadano.

Compañeros del alma

"Compañeros del alma" es una obra de teatro que formó parte del ciclo "Teatro por la memoria" organizado por el Instituto Nacional del Teatro en el año 2009. Se desarrolla en el ámbito de una familia trabajadora que vivió en la época del último gobierno de Juan Domingo Perón hasta la dictadura militar de 1976. La dramatización, representa la historia de los muchos argentinos que desaparecieron quedando las familias quebradas, en la incansable búsqueda de la verdad y la justicia. La obra ha sido segmentada en 14 bloques. En su edición para la Biblioteca Digital se utilizaron imágenes de archivo para reforzar el contenido de la obra . La filmación completa de la puesta en escena se puede consultar en el CDA-Centro de Documentación Audiovisual UNCuyo.

Sulfur and carbon in mIcrobial processes in waters and sediments of the Kara Sea in September 2007

Results of microbiological, biogeochemical and isotope geochemical studies in the Kara Sea are described. Samples for these studies were obtained during Cruise 54 of R/V Akademik Mstislav Keldysh in September 2007. The studied area covered the northern, central, and southwestern parts of the Kara Sea and the Obskaya Guba (Ob River estuary). Quantitative characteristics of total bacterial population and activity of microbial processes in the water column and bottom sediments were obtained. Total abundance of bacterioplankton (BP) varied from 250000 cells/ml in the northern Kara Sea to 3000000 cells/ml in the Obskaya Guba. BP abundance depended on concentration of suspensded matter. Net BP production was minimal in the central Kara Sea (up to 0.15-0.2 µg C/l/day) and maximal (0.5-0.75 µg C/l/day) in the Obskaya Guba. Organic material at the majority of stations at the Ob transect predominantly contained light carbon isotopes (-28.0 to -30.18 per mil) of terrigenous origin. Methane concentration in the surface water layer varied from 0.18 to 2.0 µl CH4/l, and methane oxidation rate varied from 0.1 to 100 nl CH4/l/day. Methane concentration in the upper sediment layer varied from 30 to 300 µl CH4/dm**3; rate of methane formation was varied from 44 to 500 nl CH4/dm**3/day and rate of methane oxidation - from 30 to 2000 nl CH4/dm**3/day. Rate of sulfate reduction varied from 4 to 184 µg S/dm**3/day.

Results of biogeochemical studies in the Russian Arctic seas: isotope and radioisotope data

Comprehensive biogeochemical studies including determination of isotopic composition of organic carbon in both suspended matter and surface layer (0-1 cm) bottom sediments (more than 260 determinations of d13C-Corg) were carried out for five Arctic shelf seas: White, Barents, Kara, East Siberian, and Chukchi Seas. The aim of this study is to elucidate causes that change isotopic composition of particulate organic carbon at the water-sediment boundary. It is shown that isotopic composition of organic carbon in sediments from seas with high river run-off (White, Kara, and East Siberian Seas) does not inherit isotopic composition of organic carbon in particles precipitating from the water column, but is enriched in 13C. Seas with low river run-off (Barents and Chukchi Seas) show insignificant difference between d13C-Corg values in both suspended load and sediments because of low content of isotopically light allochthonous organic matter in suspended matter. Biogeochemical studies with radioisotope tracers (14CO2, 35S, and 14CH4) revealed existence of specific microbial filter formed from heterotrophic and autotrophic organisms at the water-sediment boundary. This filter prevents mass influx of products of organic matter decomposition into the water column, as well as reduces influx of OM contained in suspended matter from water into sediments.

Biogeochemistry and microbiology of groundwater during acetate and bicarbonate amendment to an alluvial aquifer

These data are from a field experiment conducted in a shallow alluvial aquifer along the Colorado River in Rifle, Colorado, USA. In this experiment, bicarbonate-promoted uranium desorption and acetate amendment were combined and compared to an acetate amendment-only experiment in the same experimental plot. Data include names and location data for boreholes, geochemical data for all the boreholes between June 1, 2010 and January 1, 2011, microarray data provided as signal to noise ratio (SNR) for individual microarray probes, microarray data provided as signal to noise ratio (SNR) by Genus.

CDAPubMed: a browser extension to retrieve EHR-based biomedical literature

Over the last few decades, the ever-increasing output of scientific publications has led to new challenges to keep up to date with the literature. In the biomedical area, this growth has introduced new requirements for professionals, e.g., physicians, who have to locate the exact papers that they need for their clinical and research work amongst a huge number of publications. Against this backdrop, novel information retrieval methods are even more necessary. While web search engines are widespread in many areas, facilitating access to all kinds of information, additional tools are required to automatically link information retrieved from these engines to specific biomedical applications. In the case of clinical environments, this also means considering aspects such as patient data security and confidentiality or structured contents, e.g., electronic health records (EHRs). In this scenario, we have developed a new tool to facilitate query building to retrieve scientific literature related to EHRs. Results: We have developed CDAPubMed, an open-source web browser extension to integrate EHR features in biomedical literature retrieval approaches. Clinical users can use CDAPubMed to: (i) load patient clinical documents, i.e., EHRs based on the Health Level 7-Clinical Document Architecture Standard (HL7-CDA), (ii) identify relevant terms for scientific literature search in these documents, i.e., Medical Subject Headings (MeSH), automatically driven by the CDAPubMed configuration, which advanced users can optimize to adapt to each specific situation, and (iii) generate and launch literature search queries to a major search engine, i.e., PubMed, to retrieve citations related to the EHR under examination. Conclusions: CDAPubMed is a platform-independent tool designed to facilitate literature searching using keywords contained in specific EHRs. CDAPubMed is visually integrated, as an extension of a widespread web browser, within the standard PubMed interface. It has been tested on a public dataset of HL7-CDA documents, returning significantly fewer citations since queries are focused on characteristics identified within the EHR. For instance, compared with more than 200,000 citations retrieved by breast neoplasm, fewer than ten citations were retrieved when ten patient features were added using CDAPubMed. This is an open source tool that can be freely used for non-profit purposes and integrated with other existing systems.

Software tool for simulation of aircraft trajectories

New concepts in air navigation have been introduced recently. Among others, are the concepts of trajectory optimization, 4D trajectories, RBT (Reference Business Trajectory), TBO (trajectory based operations), CDA (Continuous Descent Approach) and ACDA (Advanced CDA), conflict resolution, arrival time (AMAN), introduction of new aircraft (UAVs, UASs) in air space, etc. Although some of these concepts are new, the future Air Traffic Management will maintain the four ATM key performance areas such as Safety, Capacity, Efficiency, and Environmental impact. So much, the performance of the ATM system is directly related to the accuracy with which the future evolution of the traffic can be predicted. In this sense, future air traffic management will require a variety of support tools to provide suitable help to users and engineers involved in the air space management. Most of these tools are based on an appropriate trajectory prediction module as main component. Therefore, the purposes of these tools are related with testing and evaluation of any air navigation concept before they become fully operative. The aim of this paper is to provide an overview to the design of a software tool useful to estimate aircraft trajectories adapted to air navigation concepts. Other usage of the tool, like controller design, vertical navigation assessment, procedures validation and hardware and software in the loop are available in the software tool. The paper will show the process followed to design the tool, the software modules needed to perform accurately and the process followed to validate the output data.

Discriminating Crop, Weeds and Soil Surface with a Terrestrial LIDAR Sensor

In this study, the evaluation of the accuracy and performance of a light detection and ranging (LIDAR) sensor for vegetation using distance and reflection measurements aiming to detect and discriminate maize plants and weeds from soil surface was done. The study continues a previous work carried out in a maize field in Spain with a LIDAR sensor using exclusively one index, the height profile. The current system uses a combination of the two mentioned indexes. The experiment was carried out in a maize field at growth stage 12–14, at 16 different locations selected to represent the widest possible density of three weeds: Echinochloa crus-galli (L.) P.Beauv., Lamium purpureum L., Galium aparine L.and Veronica persica Poir.. A terrestrial LIDAR sensor was mounted on a tripod pointing to the inter-row area, with its horizontal axis and the field of view pointing vertically downwards to the ground, scanning a vertical plane with the potential presence of vegetation. Immediately after the LIDAR data acquisition (distances and reflection measurements), actual heights of plants were estimated using an appropriate methodology. For that purpose, digital images were taken of each sampled area. Data showed a high correlation between LIDAR measured height and actual plant heights (R 2 = 0.75). Binary logistic regression between weed presence/absence and the sensor readings (LIDAR height and reflection values) was used to validate the accuracy of the sensor. This permitted the discrimination of vegetation from the ground with an accuracy of up to 95%. In addition, a Canonical Discrimination Analysis (CDA) was able to discriminate mostly between soil and vegetation and, to a far lesser extent, between crop and weeds. The studied methodology arises as a good system for weed detection, which in combination with other principles, such as vision-based technologies, could improve the efficiency and accuracy of herbicide spraying.

Analysis of the geometric altimetry to support aircraft optimal trajectories within the future 4d trajectory management

Over the past few years, the common practice within air traffic management has been that commercial aircraft fly by following a set of predefined routes to reach their destination. Currently, aircraft operators are requesting more flexibility to fly according to their prefer- ences, in order to achieve their business objectives. Due to this reason, much research effort is being invested in developing different techniques which evaluate aircraft optimal trajectory and traffic synchronisation. Also, the inefficient use of the airspace using barometric altitude overall in the landing and takeoff phases or in Continuous Descent Approach (CDA) trajectories where currently it is necessary introduce the necessary reference setting (QNH or QFE). To solve this problem and to permit a better airspace management born the interest of this research. Where the main goals will be to evaluate the impact, weakness and strength of the use of geometrical altitude instead of the use of barometric altitude. Moreover, this dissertation propose the design a simplified trajectory simulator which is able to predict aircraft trajectories. The model is based on a three degrees of freedom aircraft point mass model that can adapt aircraft performance data from Base of Aircraft Data, and meteorological information. A feature of this trajectory simulator is to support the improvement of the strategic and pre-tactical trajectory planning in the future Air Traffic Management. To this end, the error of the tool (aircraft Trajectory Simulator) is measured by comparing its performance variables with actual flown trajectories obtained from Flight Data Recorder information. The trajectory simulator is validated by analysing the performance of different type of aircraft and considering different routes. A fuel consumption estimation error was identified and a correction is proposed for each type of aircraft model. In the future Air Traffic Management (ATM) system, the trajectory becomes the fundamental element of a new set of operating procedures collectively referred to as Trajectory-Based Operations (TBO). Thus, governmental institutions, academia, and industry have shown a renewed interest for the application of trajectory optimisation techniques in com- mercial aviation. The trajectory optimisation problem can be solved using optimal control methods. In this research we present and discuss the existing methods for solving optimal control problems focusing on direct collocation, which has received recent attention by the scientific community. In particular, two families of collocation methods are analysed, i.e., Hermite-Legendre-Gauss-Lobatto collocation and the pseudospectral collocation. They are first compared based on a benchmark case study: the minimum fuel trajectory problem with fixed arrival time. For the sake of scalability to more realistic problems, the different meth- ods are also tested based on a real Airbus 319 El Cairo-Madrid flight. Results show that pseudospectral collocation, which has shown to be numerically more accurate and computa- tionally much faster, is suitable for the type of problems arising in trajectory optimisation with application to ATM. Fast and accurate optimal trajectory can contribute properly to achieve the new challenges of the future ATM. As atmosphere uncertainties are one of the most important issues in the trajectory plan- ning, the final objective of this dissertation is to have a magnitude order of how different is the fuel consumption under different atmosphere condition. Is important to note that in the strategic phase planning the optimal trajectories are determined by meteorological predictions which differ from the moment of the flight. The optimal trajectories have shown savings of at least 500 [kg] in the majority of the atmosphere condition (different pressure, and temperature at Mean Sea Level, and different lapse rate temperature) with respect to the conventional procedure simulated at the same atmosphere condition.This results show that the implementation of optimal profiles are beneficial under the current Air traffic Management (ATM).

O MOVIMENTO DIRETAS JÁ PELA ÓTICA DE JANIO DE FREITAS NA FOLHA DE S.PAULO

O presente trabalho verificou como o jornalismo pode ser parceiro e fonte para a história por meio da reprodução e análise dos fatos político-econômicos brasileiros nas páginas dos jornais impressos diários. Nessa perspectiva, as colunas escritas nos últimos 25 anos (1983-2009) por Janio de Freitas, no jornal Folha de S.Paulo, significam interpretação e análise dessa história. Trata-se, portanto, de uma pesquisa qualitativa e está ancorada nos Estudos Culturais. O corpus desta pesquisa é composto de um recorte de 47 comentários sobre as Diretas Já , de janeiro até abril de 1984, período em que ocorreram as principais mobilizações da sociedade civil pela eleição direta para a Presidência da República e culminou com a votação e a rejeição da emenda Dante de Oliveira pelo Congresso Nacional. No desenvolvimento do trabalho foram utilizadas as ferramentas da Análise de Conteúdo a partir das categorias analíticas criadas Personagens, Votação da Emenda Dante de Oliveira e Movimento Diretas Já nas ruas , para descrever o conteúdo textual das colunas. Para que se pudesse efetuar uma análise aprofundada do corpus da pesquisa foi utilizado o referencial teórico da ACD Análise Crítica do Discurso em nove das 47 colunas selecionadas. O critério de escolha para essas colunas foi a identificação daquelas que no título já traziam uma referência explícita à Campanha pelas Diretas Já , Às mobilizações nas ruas , A votação da emenda Dante de Oliveira , Ao processo de sucessão presidencial ou as que tinham o seu conteúdo integral sobre um dos temas. Este estudo constata a hipótese de que o jornalista é um historiador do cotidiano e que é possível fazer uma leitura da história da Campanha das Diretas Já por meio das colunas de Janio de Freitas. Ao tecer em suas colunas o cenário da época, desnuda para a história e para os historiadores o xadrez político personagens, acordos políticos, votação da emenda e a campanha nas ruas que envolveu o processo. Dessa forma, a partir de suas lentes, oferece elementos para a construção da memória coletiva sobre esse período da história brasileira.(AU)

O MOVIMENTO DIRETAS JÁ PELA ÓTICA DE JANIO DE FREITAS NA FOLHA DE S.PAULO

O presente trabalho verificou como o jornalismo pode ser parceiro e fonte para a história por meio da reprodução e análise dos fatos político-econômicos brasileiros nas páginas dos jornais impressos diários. Nessa perspectiva, as colunas escritas nos últimos 25 anos (1983-2009) por Janio de Freitas, no jornal Folha de S.Paulo, significam interpretação e análise dessa história. Trata-se, portanto, de uma pesquisa qualitativa e está ancorada nos Estudos Culturais. O corpus desta pesquisa é composto de um recorte de 47 comentários sobre as Diretas Já , de janeiro até abril de 1984, período em que ocorreram as principais mobilizações da sociedade civil pela eleição direta para a Presidência da República e culminou com a votação e a rejeição da emenda Dante de Oliveira pelo Congresso Nacional. No desenvolvimento do trabalho foram utilizadas as ferramentas da Análise de Conteúdo a partir das categorias analíticas criadas Personagens, Votação da Emenda Dante de Oliveira e Movimento Diretas Já nas ruas , para descrever o conteúdo textual das colunas. Para que se pudesse efetuar uma análise aprofundada do corpus da pesquisa foi utilizado o referencial teórico da ACD Análise Crítica do Discurso em nove das 47 colunas selecionadas. O critério de escolha para essas colunas foi a identificação daquelas que no título já traziam uma referência explícita à Campanha pelas Diretas Já , Às mobilizações nas ruas , A votação da emenda Dante de Oliveira , Ao processo de sucessão presidencial ou as que tinham o seu conteúdo integral sobre um dos temas. Este estudo constata a hipótese de que o jornalista é um historiador do cotidiano e que é possível fazer uma leitura da história da Campanha das Diretas Já por meio das colunas de Janio de Freitas. Ao tecer em suas colunas o cenário da época, desnuda para a história e para os historiadores o xadrez político personagens, acordos políticos, votação da emenda e a campanha nas ruas que envolveu o processo. Dessa forma, a partir de suas lentes, oferece elementos para a construção da memória coletiva sobre esse período da história brasileira.(AU)

La representación de las mujeres inmigrantes en una muestra de la prensa española: deconstruyendo la invisibilidad

Esta investigación tiene como objetivo principal estudiar la representación de las mujeres inmigrantes en una muestra de la prensa española. Para ello, se recopiló un corpus de noticias sobre mujeres inmigrantes desde febrero de 2012 hasta julio de 2014, lo que suma un total de dos años y medio, de los tres principales periódicos españoles: El País, El Mundo y ABC. El número total de noticias recopiladas es de 56. En este estudio se analizarán los principales temas que se tratan en las noticias seleccionadas y las principales características lingüísticas y visuales empleadas para hablar sobre las mujeres inmigrantes. El análisis crítico del discurso (ACD) se empleará en este trabajo por su interés en la dimensión social del discurso al estudiar la lengua unida a temas sociales y por permitir profundizar en la ideología. En este sentido, el ACD puede ayudar a desentrañar problemas relacionados con las desigualdades de género al observar el modo en que las mujeres inmigrantes aparecen representadas en los textos objeto de estudio. Además, se empleará el modelo de gramática visual propuesto por Kress y van Leeuwen (2006) con el fin de analizar las principales características de las fotografías. Los principales resultados obtenidos del estudio señalan que la representación de las mujeres inmigrantes en la prensa española es escasa y que cuando éstas aparecen como protagonistas de noticias suelen representarse como víctima y se las relaciona fundamentalmente con la prostitución.