The in vivo and in vitro formation of sticky DNA and the GAA.TTC trinucleotide repeat associated with Friedreich's ataxia

Friedreich's ataxia is caused by the expansion of the GAA•TTC trinucleotide repeat sequence located in intron 1 of the frataxin gene. The long GAA•TTC repeats are known to form several non-B DNA structures including hairpins, triplexes, parallel DNA and sticky DNA. Therefore it is believed that alternative DNA structures play a role in the loss of mRNA transcript and functional frataxin protein in FRDA patients. We wanted to further elucidate the characteristics for formation and stability of sticky DNA by evaluating the structure in a plasmid based system in vitro and in vivo in Escherichia coli. The negative supercoil density of plasmids harboring different lengths of GAA•TTC repeats, as well as either one or two repeat tracts were studied in E. coli to determine if plasmids containing two long tracts (≥60 repeats) in a direct repeat orientation would have a different topological effect in vivo compared to plasmids that harbored only one GAA•TTC tract or two tracts of < 60 repeats. The experiments revealed that, in fact, sticky DNA forming plasmids had a lower average negative supercoil density (-σ) compared to all other control plasmids used that had the potential to form other non-B DNA structures such as triplexes or Z-DNA. Also, the requirements for in vitro dissociation and reconstitution of the DNA•DNA associated region of sticky DNA were evaluated. Results conclude that the two repeat tracts associate in the presence of negative supercoiling and MgCl 2 or MnCl2 in a time and concentration-dependent manner. Interaction of the repeat sequences was not observed in the absence of negative supercoiling and/or MgCl2 or in the presence of other monovalent or divalent cations, indicating that supercoiling and quite specific cations are needed for the association of sticky DNA. These are the first experiments studying a more specific role of supercoiling and cation influence on this DNA conformation. To support our model of the topological effects of sticky DNA in plasmids, changes in sticky DNA band migration was measured with reference to the linear DNA after treatment with increasing concentrations of ethidium bromide (EtBr). The presence of independent negative supercoil domains was confirmed by this method and found to be segregated by the DNA-DNA associated region. Sequence-specific polyamide molecules were used to test the effect of binding of the ligands to the GAA•TTC repeats on the inhibition of sticky DNA. The destabilization of the sticky DNA conformation in vitro through this binding of the polyamides demonstrated the first conceptual therapeutic approach for the treatment of FRDA at the DNA molecular level. ^ Thus, examining the properties of sticky DNA formed by these long repeat tracts is important in the elucidation of the possible role of sticky DNA in Friedreich's ataxia. ^

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression By Ali K. Naji B.S. Advisor: Dr. Melvin E. Klegerman PhD Background and significance: Echogenic liposomes can be used as drug and cell delivery vehicles that reduce atheroma progression. Vascular endothelial growth factor (VEGF) is a signal protein that induces vasculogenesis and angiogenesis. VEGF functionally induces migration and proliferation of endothelial cells and increases intracellular vascular permeability. VEGF activates angiogenic transduction factors through VEGF tyrosine kinase domains in high-affinity receptors of endothelial cells. Bevacizumab is a humanized monoclonal antibody specific for VEGF-A which was developed as an anti-tumor agent. Often, anti-VEGF agents result in regression of existing microvessels, inhibiting tumor growth and possibly causing tumor shrinkage with time. During atheroma progression neovasculation in the arterial adventitia is mediated by VEGF. Therefore, bevacizumab may be effective in inhibiting atheroma progression. Stem cells show an ability to inhibit atheroma progression. We have previously demonstrated that monocyte derived CD-34+ stem cells that can be delivered to atheroma by bifunctional-ELIP ( BF-ELIP) targeted to Intercellular Adhesion Molecule-1 (ICAM-1) and CD-34. Adhesion molecules such as ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) are expressed by endothelial cells under inflammatory conditions. Ultrasound enhanced liposomal targeting provides a method for stem cell delivery into atheroma and encapsulated drug release. This project is designed to examine the ability of echogenic liposomes to deliver bevacizumab and stem cells to inhibit atheroma progression and neovasculation with and without ultrasound in vitro and optimize the ultrasound parameters for delivery of bevacizumab and stem cells to atheroma. V Hypotheses: Previous studies showed that endothelial cell VEGF expression may relate to atherosclerosis progression and atheroma formation in the cardiovascular system. Bevacizumab-loaded ELIP will inhibit endothelial cell VEGF expression in vitro. Bevacizumab activity can be enhanced by pulsed Doppler ultrasound treatment of BEV-ELIP. I will also test the hypothesis that the transwell culture system can serve as an in vitro model for study of US-enhanced targeted delivery of stem cells to atheroma. Monocyte preparations will serve as a source of CD34+ stem cells. Specific Aims: Induce VEGF expression using PKA and PKC activation factors to endothelial cell cultures and use western blot and ELISA techniques to detect the expressed VEGF.  Characterize the relationship between endothelial cell proliferation and VEGF expression to develop a specific EC culture based system to demonstrate BEV-ELIP activity as an anti-VEGF agent. Design a cell-based assay for in vitro assessment of ultrasound-enhanced bevacizumab release from echogenic liposomes.  Demonstrate ultrasound delivery enhancement of stem cells by applying different types of liposomes on transwell EC culture using fluorescently labeled monocytes and detect the effect on migration and attachment rate of these echogenic liposomes with and without ultrasound in vitro.

La economía del conocimiento : perspectivas urbano - regionales

El conocimiento y su aplicación en la economía, ha sido siempre un factor importante del desarrollo socio-económico. El conocimiento toma relevancia en la economía contemporánea al invertirse la jerarquización de los factores del desarrollo, cobrando mayor importancia los factores intangibles, como el conocimiento, el cual se convierte en el recurso fundamental para los procesos productivos. En este contexto, surgieron los estudios relacionados con la Economía Regional del Conocimiento (ERC) así como los estudios relativos al Desarrollo basado en el Conocimiento (DBC). Ambas perspectivas teóricas han establecido indicadores para explicar el fenómeno de la economía del conocimiento desde su base territorial, sea a nivel regional (ERC) o desde la ciudad (DBC). A manera exploratoria consideramos que los indicadores de los sistemas regionales de innovación pueden complementarse con los indicadores del desarrollo basado en el conocimiento, sobre todo por la dimensión meta-cultural a la que hacen referencia estos estudios.

La gestión del conocimiento en las Bibliotecas Universitarias : ¿El qué, cómo y para qué?

El presente artículo tiene como propósito proponer la incorporación de la teoría administrativa denominada Gestión del Conocimiento (GC), en Bibliotecas Universitarias (BU). ¿El qué, el cómo y el para qué? Representa un reto de gestión que conlleva a la implementación de diversas estrategias para el cambio y la innovación (ECI). Hipotéticamente, el diseño de estrategias de gestión posibilita que la BU en los escenarios competitivos de la sociedad de conocimiento y el tercer entorno desarrolle nuevas competencias y directrices para el aprovechamiento de sus diversos recursos con eficiencia y logren alcanzar sus objetivos con eficacia. La innovación es otra de las variables que posibilita la transformación de los servicios que son ofertados a los usuarios, también denominados "socios estratégicos", bajo la visión de creatividad, sustentabilidad y bienestar

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

La gestión del conocimiento en las Bibliotecas Universitarias : ¿El qué, cómo y para qué?

El presente artículo tiene como propósito proponer la incorporación de la teoría administrativa denominada Gestión del Conocimiento (GC), en Bibliotecas Universitarias (BU). ¿El qué, el cómo y el para qué? Representa un reto de gestión que conlleva a la implementación de diversas estrategias para el cambio y la innovación (ECI). Hipotéticamente, el diseño de estrategias de gestión posibilita que la BU en los escenarios competitivos de la sociedad de conocimiento y el tercer entorno desarrolle nuevas competencias y directrices para el aprovechamiento de sus diversos recursos con eficiencia y logren alcanzar sus objetivos con eficacia. La innovación es otra de las variables que posibilita la transformación de los servicios que son ofertados a los usuarios, también denominados "socios estratégicos", bajo la visión de creatividad, sustentabilidad y bienestar

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

La gestión del conocimiento en las Bibliotecas Universitarias : ¿El qué, cómo y para qué?

El presente artículo tiene como propósito proponer la incorporación de la teoría administrativa denominada Gestión del Conocimiento (GC), en Bibliotecas Universitarias (BU). ¿El qué, el cómo y el para qué? Representa un reto de gestión que conlleva a la implementación de diversas estrategias para el cambio y la innovación (ECI). Hipotéticamente, el diseño de estrategias de gestión posibilita que la BU en los escenarios competitivos de la sociedad de conocimiento y el tercer entorno desarrolle nuevas competencias y directrices para el aprovechamiento de sus diversos recursos con eficiencia y logren alcanzar sus objetivos con eficacia. La innovación es otra de las variables que posibilita la transformación de los servicios que son ofertados a los usuarios, también denominados "socios estratégicos", bajo la visión de creatividad, sustentabilidad y bienestar

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

Asian Industrial Development from the Perspective of the Motorcycle Industry

This paper discusses the diversity of industrial development among Asian countries that emerges through an investigation of the motorcycle industry despite its uniform industrial attributes. The paper then explores factors that generate diversity, focusing attention on the differences in knowledge-based assets accumulated in each country. It finds that diversity is brought about through the differences in domestic industrial resources and the capabilities of local firms. The analysis underscores each country’s intrinsic logic in industrial development, contrary to the current trend of stressing assimilation through the global production networks of multinational corporations.

How Blended Learning Reduce Underachievement in Higher Education: An Experience in Teaching Computer Sciences.

This paper presents a blended learning approach and a study evaluating instruction in a software engineering-related course unit as part of an undergraduate engineering degree program in computing. In the past, the course unit had a lecture-based format. In view of student underachievement and the high course unit dropout rate, a distance-learning system was deployed, where students were allowed to choose between a distance-learning approach driven by a moderate constructivist instructional model or a blended-learning approach. The results of this experience are presented, with the aim of showing the effectiveness of the teaching/learning system deployed compared to the lecture-based system previously in place. The grades earned by students under the new system, following the distance-learning and blended-learning courses, are compared statistically to the grades attained in earlier years in the traditional face-to-face classroom (lecture-based) learning.

Automatic Categorization for Improving Spanish into Spanish Sign Language Machine Translation

This paper describes a preprocessing module for improving the performance of a Spanish into Spanish Sign Language (Lengua de Signos Espanola: LSE) translation system when dealing with sparse training data. This preprocessing module replaces Spanish words with associated tags. The list with Spanish words (vocabulary) and associated tags used by this module is computed automatically considering those signs that show the highest probability of being the translation of every Spanish word. This automatic tag extraction has been compared to a manual strategy achieving almost the same improvement. In this analysis, several alternatives for dealing with non-relevant words have been studied. Non-relevant words are Spanish words not assigned to any sign. The preprocessing module has been incorporated into two well-known statistical translation architectures: a phrase-based system and a Statistical Finite State Transducer (SFST). This system has been developed for a specific application domain: the renewal of Identity Documents and Driver's License. In order to evaluate the system a parallel corpus made up of 4080 Spanish sentences and their LSE translation has been used. The evaluation results revealed a significant performance improvement when including this preprocessing module. In the phrase-based system, the proposed module has given rise to an increase in BLEU (Bilingual Evaluation Understudy) from 73.8% to 81.0% and an increase in the human evaluation score from 0.64 to 0.83. In the case of SFST, BLEU increased from 70.6% to 78.4% and the human evaluation score from 0.65 to 0.82.

La telefonía móvil : el impacto social

El objetivo de este proyecto ha sido el de realizar un análisis del importante desarrollo que han sufrido las telecomunicaciones, haciendo un especial hincapié en la telefonía móvil y el impacto y repercusión que ha causado actualmente en nuestra sociedad. Para ello se hará un repaso evolutivo de las tecnologías de la información y las telecomunicaciones, y se establecerá una relación entre la gran difusión de éstas y su efecto sobre los usos, y cambios percibidos por los consumidores del nuevo siglo. Ciertamente la historia de la tecnología, nos enseña que la gente y las organizaciones acaban utilizándola para unos propósitos muy diferentes de aquellos que inicialmente fueron concebidas. Además cuanto más interactiva sea una tecnología, tanto más probable será que los usuarios se conviertan en productores o modificadores de la misma. Por tanto, la sociedad necesita resolver las incógnitas que pueda suscitar el rápido y continúo cambio de las comunicaciones. Este proyecto trata de ayudar a responder alguna de las cuestiones que actualmente se están planteando. ¿Son los teléfonos móviles una expresión de identidad, artilugios de moda, herramientas de la vida cotidiana, o todo lo anterior? ¿Existen nuevos modelos de comportamiento y conducta social? ¿La comunicación móvil está favoreciendo la aparición de una nueva cultura joven con un lenguaje propio basado en la comunicación textual y multimodal? ¿Tienen los teléfonos móviles efectos nocivos en la salud? La respuesta a estas preguntas afecta a nuestras vidas y también condiciona las políticas públicas y las estrategias de negocio, por eso requiere adquirir un conocimiento cimentado en la información, y la recopilación de datos de diversas fuentes, tanto de estadísticas provenientes de diferentes estudios e investigaciones, como de empresas consultoras, siempre basada en una perspectiva global. En conjunto, se espera dentro de los límites del conocimiento actual, contribuir a establecer las bases para el análisis y valoración de la relación existente entre comunicación, tecnología y sociedad en todo el mundo. Abstract The purpose of this project has been to analyse the significant development undergone by telecommunications, putting a special emphasis on mobile phones and the impact it has caused in society. We will go over the evolution of IT technologies and telecommunications as well as establish a relationship between its spread and effect of its uses and changes understood by the new century consumers. Technology history shows us that people and organizations use it for very different purposes from those originally thought. Furthermore, the more interactive technologies are, the more users will modify or produce it. Therefore, society needs to solve the mysteries of the quick and continuous change of communications. This project tries to help and answer some of the questions considered these days. Are mobile phones an expression of identity, fashionable devices, tools for everyday life or all at once? Are there any new models of performance and social behaviour? Is mobile communication favouring the existence of a new young culture with a typical language based on textual and multimodal communication? Are mobile phones bad for our health? The answer to these questions affects us all and conditions public politics and business strategies so it is required to get firm knowledge based on information. It is also important to compile data from various sources, from statistics of research and studies, based on a global perspective. As a whole, we hope to contribute to establish the bases for the future analysis and assessment of a fundamental trend that is redefining the relationship between communication, technology and society worldwide by transforming the wireless networks that make our lives.

An intelligent sales assistant for configurable products

Some of the recent proposals of web-based applications are oriented to provide advanced search services through virtual shops. Within this context, this paper proposes an advanced type of software application that simulates how a sales assistant dialogues with a consumer to dynamically configure a product according to particular needs. The paper presents the general knowl- edge model that uses artificial intelligence and knowledge-based techniques to simulate the configuration process. Finally, the paper illustrates the description with an example of an application in the field of photography equipment.

Context-sensitive multivariant assertion checking in modular programs

We propose a modular, assertion-based system for verification and debugging of large logic programs, together with several interesting models for checking assertions statically in modular programs, each with different characteristics and representing different trade-offs. Our proposal is a modular and multivariant extensión of our previously proposed abstract assertion checking model and we also report on its implementation in the CiaoPP system. In our approach, the specification of the program, given by a set of assertions, may be partial, instead of the complete specification required by raditional verification systems. Also, the system can deal with properties which cannot always be determined at compile-time. As a result, the proposed system needs to work with safe approximations: all assertions proved correct are guaranteed to be valid and all errors actual errors. The use of modular, context-sensitive static analyzers also allows us to introduce a new distinction between assertions checked in a particular context or checked in general.