Desintegración vertical en la industria del automóvil en España: un caso de estudio = Vertical disintegration in the automotive industry in Spain: a case study

En los años recientes se ha producido un rápido crecimiento del comercio internacional en productos semielaborados que son diseñados, producidos y ensamblados en diferentes localizaciones a lo largo de diferentes países, debido principalmente a los siguientes motivos: el desarrollo de las tecnologías de la información, la reducción de los costes de transporte, la liberalización de los mercados de capitales, la armonización de factores institucionales, la integración económica regional que implica la reducción y la eliminación de las barreras al comercio, el desarrollo económico de los países emergentes, el uso de economías de escala, así como una desregulación del comercio internacional. Todo ello ha incrementado la competencia a nivel mundial en los mercados y ha posibilitado a las compañías tener más facilidad de acceso a potenciales mercados, así como a la adquisición de capacidades y conocimientos en otros países y a la realización de alianzas estratégicas internacionales con terceros, creando un entorno con mayor incertidumbre y más exigente para las compañías que componen una industria, y que tiene consecuencias directas en las operaciones de las compañías y en la organización de su producción. Las compañías, para adaptarse, ser competitivas y beneficiarse de este nuevo escenario globalizado y más competitivo, han externalizado partes del proceso productivo hacia proveedores especializados, creando un nuevo mercado intermedio que divide el proceso productivo, anteriormente integrado en las compañías que conforman una industria, entre dos conjuntos de empresas especializadas en esa industria. Dicho proceso suele ocurrir conservando la industria en que tiene lugar, los mismos servicios y productos, la tecnología empleada y las compañías originales que la conformaban previamente a la desintegración vertical. Todo ello es así debido a que es beneficioso tanto para las compañías originales de la industria como para las nuevas compañías de este mercado intermedio por diversos motivos. La desintegración vertical en una industria tiene unas consecuencias que la transforman completamente, así como la forma de operar de las compañías que la integran, incluso para aquellas que permanecen verticalmente integradas. Una de las características más importantes de esta desintegración vertical en una industria es la posibilidad que tiene una compañía de adquirir a una tercera la primera parte del proceso productivo o un bien semielaborado, que posteriormente será finalizado por la compañía adquiriente con la práctica del outsourcing; así mismo, una compañía puede realizar la primera parte del proceso productivo o un bien semielaborado, que posteriormente será finalizado por una tercera compañía con la práctica de la fragmentación. El principal objetivo de la presente investigación es el estudio de los motivos, los facilitadores, los efectos, las consecuencias y los principales factores significativos, microeconómicos y macroeconómicos, que desencadenan o incrementan la práctica de la desintegración vertical en una industria; para ello, la investigación se divide en dos líneas completamente diferenciadas: el estudio de la práctica del outsourcing y, por otro lado, el estudio de la fragmentación por parte de las compañías que componen la industria del automóvil en España, puesto que se trata de una de las industrias más desintegradas verticalmente y fragmentadas, y este sector posee una gran importancia en la economía del país. En primer lugar, se hace una revisión de la literatura existente relativa a los siguientes aspectos: desintegración vertical, outsourcing, fragmentación, teoría del comercio internacional, historia de la industria del automóvil en España y el uso de las aglomeraciones geográficas y las tecnologías de la información en el sector del automóvil. La metodología empleada en cada uno de ellos ha sido diferente en función de la disponibilidad de los datos y del enfoque de investigación: los factores microeconómicos, utilizando el outsourcing, y los factores macroeconómicos, empleando la fragmentación. En el estudio del outsourcing, se usa un índice basado en las compras externas sobre el valor total de la producción. Así mismo, se estudia su correlación y significación con las variables económicas más importantes que definen a una compañía del sector del automóvil, utilizando la técnica estadística de regresión lineal. Aquellas variables relacionadas con la competencia en el mercado, la externalización de las actividades de menor valor añadido y el incremento de la modularización de las actividades de la cadena de valor, han resultado significativas con la práctica del outsourcing. En el estudio de la fragmentación se seleccionan un conjunto de factores macroeconómicos, comúnmente usados en este tipo de investigaciones, relacionados con las principales magnitudes económicas de un país, y un conjunto de factores macroeconómicos, no comúnmente usados en este tipo de investigaciones, relacionados con la libertad económica y el comercio internacional de un país. Se emplea un modelo de regresión logística para identificar qué factores son significativos en la práctica de la fragmentación. De entre todos los factores usados en el modelo, los relacionados con las economías de escala y los costes de servicio han resultado significativos. Los resultados obtenidos de los test estadísticos realizados en el modelo de regresión logística han resultado satisfactorios; por ello, el modelo propuesto de regresión logística puede ser considerado sólido, fiable y versátil; además, acorde con la realidad. De los resultados obtenidos en el estudio del outsourcing y de la fragmentación, combinados conjuntamente con el estado del arte, se concluye que el principal factor que desencadena la desintegración vertical en la industria del automóvil es la competencia en el mercado de vehículos. Cuanto mayor es la demanda de vehículos, más se reducen los beneficios y la rentabilidad para sus fabricantes. Estos, para ser competitivos, diferencian sus productos de la competencia centrándose en las actividades que mayor valor añadido aportan al producto final, externalizando las actividades de menor valor añadido a proveedores especializados, e incrementando la modularidad de las actividades de la cadena de valor. Las compañías de la industria del automóvil se especializan en alguna o varias de estas actividades modularizadas que, combinadas con el uso de factores facilitadores como las economías de escala, las tecnologías de la información, las ventajas de la globalización económica y la aglomeración geográfica de una industria, incrementan y motivan la desintegración vertical en la industria del automóvil, desencadenando la coespecialización en dos sectores claramente diferenciados: el sector de fabricantes de vehículos y el sector de proveedores especializados. Cada uno de ellos se especializa en unas actividades y en unos productos o servicios específicos de la cadena de valor, lo cual genera las siguientes consecuencias en la industria del automóvil: se reducen los costes de transacción en los productos o servicios intercambiados; se incrementan la relación de dependencia entre fabricantes de vehículos y proveedores especializados, provocando un aumento en la cooperación y la coordinación, acelerando el proceso de aprendizaje, posibilitando a ambos adquirir nuevas capacidades, conocimientos y recursos, y creando nuevas ventajas competitivas para ambos; por último, las barreras de entrada a la industria del automóvil y el número de compañías se ven alteradas cambiando su estructura. Como futura línea de investigación, los fabricantes de vehículos tenderán a centrarse en investigar, diseñar y comercializar el producto o servicio, delegando el ensamblaje en manos de nuevos especialistas en la materia, el contract manufacturer; por ello, sería conveniente investigar qué factores motivantes o facilitadores existen y qué consecuencias tendría la implantación de los contract manufacturer en la industria del automóvil. 1.1. ABSTRACT In recent years there has been a rapid growth of international trade in semi-finished products designed, produced and assembled in different locations across different countries, mainly due to the following reasons: development of information technologies, reduction of transportation costs, liberalisation of capital markets, harmonisation of institutional factors, regional economic integration, which involves the reduction and elimination of trade barriers, economic development of emerging countries, use of economies of scale and deregulation of international trade. All these factors have increased competition in markets at a global level and have allowed companies to gain easier access to potential markets and to the acquisition of skills and knowledge in other countries, as well as to the completion of international strategic alliances with third parties, thus creating a more demanding and uncertain environment for these companies constituting an industry, which has a direct impact on the companies' operations and the organization of their production. In order to adapt, be competitive and benefit from this new and more competitive global scenario, companies have outsourced some parts of their production process to specialist suppliers, generating a new intermediate market which divides the production process, previously integrated in the companies that made up the industry, into two sets of companies specialized in that industry. This process often occurs while preserving the industry where it takes place, its same services and products, the technology used and the original companies that formed it prior to vertical disintegration. This is because it is beneficial for both the industry's original companies and the companies belonging to this new intermediate market, for various reasons. Vertical disintegration has consequences which completely transform the industry where it takes place as well as the modus operandi of the companies that are part of it, even of those who remain vertically integrated. One of the most important features of vertical disintegration of an industry is the possibility for a company to acquire from a third one the first part of the production process or a semi-finished product, which will then be finished by the acquiring company through the practice of outsourcing; also, a company can perform the first part of the production process or a semi-finish product, which will then be completed by a third company through the practice of fragmentation. The main objective of this research is to study the motives, facilitators, effects, consequences and major significant microeconomic and macroeconomic factors that trigger or increase the practice of vertical disintegration in a certain industry; in order to do so, research is divided into two completely differentiated lines: on the one hand, the study of the practise of outsourcing and, on the other, the study of fragmentation by companies constituting the automotive industry in Spain, since this is one of the most vertically disintegrated and fragmented industries and this particular sector is of major significance in this country's economy. First, a review is made of the existing literature, on the following aspects: vertical disintegration, outsourcing, fragmentation, international trade theory, history of the automobile industry in Spain and the use of geographical agglomeration and information technologies in the automotive sector. The methodology used for each of these aspects has been different depending on the availability of data and the research approach: the microeconomic factors, using outsourcing, and the macroeconomic factors, using fragmentation. In the study on outsourcing, an index is used based on external purchases in relation to the total value of production. Likewise, their significance and correlation with the major economic variables that define an automotive company are studied, using the statistical technique of linear regression. Variables related to market competition, outsourcing of lowest value-added activities and increased modularisation of the activities of the value chain have turned out to be significant with the practice of outsourcing. In the study of fragmentation, a set of macroeconomic factors commonly used for this type of research, is selected, related to the main economic indicators of a country, as well as a set of macroeconomic factors, not commonly used for this type of research, which are related to economic freedom and the international trade of a certain country. A logistic regression model is used to identify which factors are significant in the practice of fragmentation. Amongst all factors used in the model, those related to economies of scale and service costs have turned out to be significant. The results obtained from the statistical tests performed on the logistic regression model have been successful; hence, the suggested logistic regression model can be considered to be solid, reliable and versatile; likewise, it is in line with reality. From the results obtained in the study of outsourcing and fragmentation, combined with the state of the art, it is concluded that the main factor that triggers vertical disintegration in the automotive industry is competition within the vehicle market. The greater the vehicle demand, the lower the earnings and profitability for manufacturers. These, in order to be competitive, differentiate their products from the competition by focusing on those activities that contribute with the highest added value to the final product, outsourcing the lower valueadded activities to specialist suppliers, and increasing the modularity of the activities of the value chain. Companies in the automotive industry specialize in one or more of these modularised activities which, combined with the use of enabling factors such as economies of scale, information technologies, the advantages of economic globalisation and the geographical agglomeration of an industry, increase and encourage vertical disintegration in the automotive industry, triggering co-specialization in two clearly distinct sectors: the sector of vehicle manufacturers and the specialist suppliers sector. Each of them specializes in certain activities and specific products or services of the value chain, generating the following consequences in the automotive industry: reduction of transaction costs of the goods or services exchanged; growth of the relationship of dependency between vehicle manufacturers and specialist suppliers, which causes an increase in cooperation and coordination, accelerates the learning process, enables both to acquire new skills, knowledge and resources, and creates new competitive advantages for both; finally, barriers to entry the automotive industry and the number of companies are altered, changing their structure. As a future line of research, vehicle manufacturers will tend to focus on researching, designing and marketing the product or service, delegating the assembly in the hands of new specialists in the field, the contract manufacturer; for this reason, it would be useful to investigate what motivating or facilitating factors exist in this respect and what consequences would the implementation of contract manufacturers have in the automotive industry.

Proposal for redesigning the financial system: lessons learned from the crisis

this paper analyzes the singularities inherent to the financial industry, in relation to other businesses, and its implications to financial crises throughout history. The efficient markets hypothesis is questioned, and its impact on the deregulation of the financial system is analyzed. Finally, the causes of the current crisis are investigated, and the general lines to be addressed for the redesign of a financial system to achieve an efficient and equitable capitalism are suggested.

Propuesta de una metodología para gestión de proyectos de outsourcing de TI para proveedores

Los avances tecnológicos actuales que han llevado a una economía globalmente conectada, junto con la creciente tendencia hacia la privatización, globalización y desregulación están dando lugar a nuevos modelos organizativos y a un aumento de la colaboración entre proveedores y clientes, compartiendo información y flujos de proceso. Todo ello ha contribuido directamente a la gran expansión del outsourcing y a que se considere como una herramienta estratégica para las organizaciones. En este entorno y dada la creciente complejidad organizativa, el uso de una metodología para ayudar a la implantación de proyectos de outsourcing se ha convertido en algo casi necesario. En los últimos años se han propuesto algunas metodologías, especialmente para apoyo de las organizaciones cliente de outsourcing, pero no consideramos que sean completas en cuanto a contemplar todos los aspectos necesarios para guiar un proyecto de outsourcing. Es por ello que, en este artículo, proponemos una metodología para gestión de proyectos de outsourcing de TI desde el punto de vista del proveedor que sea completa y fácil de aplicar. Abstract -. Current technological advances that have led to a globally connected economy, together with the increasing trend towards privatization and deregulation, are leading to new organizational models and increased collaboration between suppliers and customers, sharing information and process flows. This has directly contributed to the great expansion of outsourcing, considering it as a strategic tool for organizations. In this environment, and given the increasing organizational complexity, the use of a methodology to assist the implementation of outsourcing projects has become almost necessary. In recent years several methodologies and models have been proposed, especially for supporting client outsourcing organizations, but we do not consider them to be complete, they do not cover all necessary aspects to manage an outsourcing project. That is the reason because we, in this paper, propose a methodology for outsourcing project management from the point of view of the suppliers that was complete and easy to apply.

La aplicación de métodos estadísticos en la valoración masiva de inmuebles: una propuesta de regulación en el marco normativo del Banco de España

Las valoraciones automatizadas (AVM según sus siglas en inglés) son modelos matemáticos de valoración que permiten estimar el valor de un inmueble o una cartera de inmuebles mediante la utilización de información de mercado previamente recogida y analizada. Las principales ventajas de los modelos AVM respecto a las valoraciones tradicionales son su objetividad, rapidez y economía. Existe regulación al respecto y estándares profesionales en otros países, no obstante en España los criterios de valoración mediante modelos AVM siguen siendo excesivamente básicos, al no establecer procesos concretos ni distinguir entre los diversos métodos estadísticos existentes y la aplicación adecuada de los mismos. Por otra parte, desde la publicación de la Circular 3/2008 del Banco de España se ha extendido el uso de este tipo de valoraciones en España para la actualización de valor de inmuebles en garantía de préstamos hipotecarios. La actual desregularización en nuestro país en cuanto a normativa de valoraciones automatizadas nos permite plantear propuestas y metodologías con el fin de aportar un punto de vista nuevo desde la investigación, la experiencia en otros países y la práctica empresarial más reciente. Este trabajo de investigación trata de sentar las bases de una futura regulación en España en materia de valoraciones masivas adaptadas al marco hipotecario español. ABSTRACT The Automated Valuation Models (AVM) are mathematically based valuation models that allow to estimate the value of a property or portfolio of properties by using market information previously collected and analyzed. The main advantages of the AVMs in comparison to traditional valuations are the objectivity, speed and economy. In other countries there is regulation and standards regarding the use of AVMs. However, in Spain the norms that apply to AVM valuations are still too basic, since these norms do not define specific processes and do not distinguish between the different statistical approaches available and their correct use. On the other hand, following the ratification of the 3/2008 Bank of Spain Circular the use of AVM models in Spain for the value update of mortgaged properties has increased. The current deregulation in Spain regarding Automated Valuation Models allows to provide propositions and methodologies in order to offer a new point of view based on the research, experience in other countries and the most recent professional practice. The present research thesis aims to provide basic principles and criteria for a future Spanish regulation on massive valuation in the context of the Spanish mortgage framework.

ESCOLHAS E DECISÕES: ESTUDO DO PROCESSO PARTICIPATIVO EM ORGANIZAÇÕES DA ECONOMIA SOLIDÁRIA

As últimas décadas, no caso brasileiro, foram marcadas pela predominância da estabilidade econômica e desregulamentação estatal no campo da economia, desconsiderando o impacto na vida das pessoas. Quebras e falências são constatadas como resultado desse processo. Aos trabalhadores surge a oportunidade, com muito esforço, de modelos alternativos nas relações de trabalho. Aparece nesse contexto, o novo discurso da Economia Solidária que preza por práticas autogestionadas. As Empresas Recuperadas são enquadradas dentro desse novo discurso. Entretanto, nas Empresas Recuperadas e nos empreendimentos da Economia Solidária, o espaço fértil proporcionado no campo da subjetividade enfrenta um dilema objetivo. Em sua batalha pela sobrevivência e sustentação, a organização deverá adotar práticas burocráticas e poderá desencantar o espaço da participação. Resulta disso, um dilema entre a objetividade, que a gestão demanda, e a subjetividade que o discurso da Economia Solidária exige. Nessa dissertação, propõe-se que a participação permite um efeito psicológico na medida em que assegura uma inter-relação contínua entre o funcionamento das instituições e as qualidades e atitudes das pessoas que atuam em seu interior. Escolhas e decisões, dessa forma, se colocam como processo que compõe a categoria da participação. Como os trabalhadores das Organizações da Economia Solidária participam do processo de escolhas e decisões em um sistema coletivo e cooperativo de trabalho? Essa é a pergunta central desta pesquisa, que tem por objetivo analisar o processo de escolhas e decisões em organizações da Economia Solidária. Nesse intuito realizou-se um estudo de caso por meio da metodologia da pesquisa-ação de uma empresa recuperada no interior de São Paulo. A pesquisa-ação é um tipo de pesquisa social, com base empírica, que é concebida e realizada em estreita associação com uma ação ou resolução de um problema. Esse problema, no contexto do estudo de caso, foi a concepção de um processo de formação de funcionários para futuros cooperados. A trajetória da discussão foi realizada com acompanhamento de um Grupo Tarefa composto por membros (celetistas e cooperados) da organização. A análise dos resultados foi construída a partir da fundamentação teórica convergindo em três categorias, que compõe o processo de participação, dentro de uma organização da Economia Solidária: Eu comigo (EUCMG), Eu com o(s) outro(s) (EUCOU) e Eu na Organização (EUORG). Os resultados mostram que a Empresa estudada não pode ser considerada como autogestionada e está fundamentada em práticas elitizadas. Há poucas práticas coletivas e se divide em classes internas (chão-defábrica e staff). Contudo, reconhece-se um grande esforço para chegar a uma nova prática de gestão coletiva. A participação se dá dentro de aspectos formais (assembléia) com predominância de assuntos burocráticos que não passaram por apropriação coletiva em sua construção. A educatividade ilumina o caminho processual, rompendo com visões finalísticas e alcançando uma sustentabilidade para a organização.(AU)

ESCOLHAS E DECISÕES: ESTUDO DO PROCESSO PARTICIPATIVO EM ORGANIZAÇÕES DA ECONOMIA SOLIDÁRIA

As últimas décadas, no caso brasileiro, foram marcadas pela predominância da estabilidade econômica e desregulamentação estatal no campo da economia, desconsiderando o impacto na vida das pessoas. Quebras e falências são constatadas como resultado desse processo. Aos trabalhadores surge a oportunidade, com muito esforço, de modelos alternativos nas relações de trabalho. Aparece nesse contexto, o novo discurso da Economia Solidária que preza por práticas autogestionadas. As Empresas Recuperadas são enquadradas dentro desse novo discurso. Entretanto, nas Empresas Recuperadas e nos empreendimentos da Economia Solidária, o espaço fértil proporcionado no campo da subjetividade enfrenta um dilema objetivo. Em sua batalha pela sobrevivência e sustentação, a organização deverá adotar práticas burocráticas e poderá desencantar o espaço da participação. Resulta disso, um dilema entre a objetividade, que a gestão demanda, e a subjetividade que o discurso da Economia Solidária exige. Nessa dissertação, propõe-se que a participação permite um efeito psicológico na medida em que assegura uma inter-relação contínua entre o funcionamento das instituições e as qualidades e atitudes das pessoas que atuam em seu interior. Escolhas e decisões, dessa forma, se colocam como processo que compõe a categoria da participação. Como os trabalhadores das Organizações da Economia Solidária participam do processo de escolhas e decisões em um sistema coletivo e cooperativo de trabalho? Essa é a pergunta central desta pesquisa, que tem por objetivo analisar o processo de escolhas e decisões em organizações da Economia Solidária. Nesse intuito realizou-se um estudo de caso por meio da metodologia da pesquisa-ação de uma empresa recuperada no interior de São Paulo. A pesquisa-ação é um tipo de pesquisa social, com base empírica, que é concebida e realizada em estreita associação com uma ação ou resolução de um problema. Esse problema, no contexto do estudo de caso, foi a concepção de um processo de formação de funcionários para futuros cooperados. A trajetória da discussão foi realizada com acompanhamento de um Grupo Tarefa composto por membros (celetistas e cooperados) da organização. A análise dos resultados foi construída a partir da fundamentação teórica convergindo em três categorias, que compõe o processo de participação, dentro de uma organização da Economia Solidária: Eu comigo (EUCMG), Eu com o(s) outro(s) (EUCOU) e Eu na Organização (EUORG). Os resultados mostram que a Empresa estudada não pode ser considerada como autogestionada e está fundamentada em práticas elitizadas. Há poucas práticas coletivas e se divide em classes internas (chão-defábrica e staff). Contudo, reconhece-se um grande esforço para chegar a uma nova prática de gestão coletiva. A participação se dá dentro de aspectos formais (assembléia) com predominância de assuntos burocráticos que não passaram por apropriação coletiva em sua construção. A educatividade ilumina o caminho processual, rompendo com visões finalísticas e alcançando uma sustentabilidade para a organização.(AU)

MLL is fused to CBP, a histone acetyltransferase, in therapy-related acute myeloid leukemia with a t(11;16)(q23;p13.3)

The recurring translocation t(11;16)(q23;p13.3) has been documented only in cases of acute leukemia or myelodysplasia secondary to therapy with drugs targeting DNA topoisomerase II. We show that the MLL gene is fused to the gene that codes for CBP (CREB-binding protein), the protein that binds specifically to the DNA-binding protein CREB (cAMP response element-binding protein) in this translocation. MLL is fused in-frame to a different exon of CBP in two patients producing chimeric proteins containing the AT-hooks, methyltransferase homology domain, and transcriptional repression domain of MLL fused to the CREB binding domain or to the bromodomain of CBP. Both fusion products retain the histone acetyltransferase domain of CBP and may lead to leukemia by promoting histone acetylation of genomic regions targeted by the MLL AT-hooks, leading to transcriptional deregulation via aberrant chromatin organization. CBP is the first partner gene of MLL containing well defined structural and functional motifs that provide unique insights into the potential mechanisms by which these translocations contribute to leukemogenesis.

Plo1 Kinase Recruitment to the Spindle Pole Body and Its Role in Cell Division in Schizosaccharomyces pombe

Polo kinases execute multiple roles during cell division. The fission yeast polo related kinase Plo1 is required to assemble the mitotic spindle, the prophase actin ring that predicts the site for cytokinesis and for septation after the completion of mitosis (Ohkura et al., 1995; Bahler et al., 1998). We show that Plo1 associates with the mitotic but not interphase spindle pole body (SPB). SPB association of Plo1 is the earliest fission yeast mitotic event recorded to date. SPB association is strong from mitotic commitment to early anaphase B, after which the Plo1 signal becomes very weak and finally disappears upon spindle breakdown. SPB association of Plo1 requires mitosis-promoting factor (MPF) activity, whereas its disassociation requires the activity of the anaphase-promoting complex. The stf1.1 mutation bypasses the usual requirement for the MPF activator Cdc25 (Hudson et al., 1990). Significantly, Plo1 associates inappropriately with the interphase SPB of stf1.1 cells. These data are consistent with the emerging theme from many systems that polo kinases participate in the regulation of MPF to determine the timing of commitment to mitosis and may indicate that pole association is a key aspect of Plo1 function. Plo1 does not associate with the SPB when septation is inappropriately driven by deregulation of the Spg1 pathway and remains SPB associated if septation occurs in the presence of a spindle. Thus, neither Plo1 recruitment to nor its departure from the SPB are required for septation; however, overexpression of plo1+ activates the Spg1 pathway and causes transient Cdc7 recruitment to the SPB and multiple rounds of septation.

Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression

The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome.

Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis

Telomeres are essential for preserving chromosome integrity during the cell cycle and have been specifically implicated in mitotic progression, but little is known about the signaling molecule(s) involved. The human telomeric repeat binding factor protein (TRF1) is shown to be important in regulating telomere length. However, nothing is known about its function and regulation during the cell cycle. The sequence of PIN2, one of three human genes (PIN1-3) we previously cloned whose products interact with the Aspergillus NIMA cell cycle regulatory protein kinase, reveals that it encodes a protein that is identical in sequence to TRF1 apart from an internal deletion of 20 amino acids; Pin2 and TRF1 may be derived from the same gene, PIN2/TRF1. However, in the cell Pin2 was found to be the major expressed product and to form homo- and heterodimers with TRF1; both dimers were localized at telomeres. Pin2 directly bound the human telomeric repeat DNA in vitro, and was localized to all telomeres uniformly in telomerase-positive cells. In contrast, in several cell lines that contain barely detectable telomerase activity, Pin2 was highly concentrated at only a few telomeres. Interestingly, the protein level of Pin2 was highly regulated during the cell cycle, being strikingly increased in G2+M and decreased in G1 cells. Moreover, overexpression of Pin2 resulted in an accumulation of HeLa cells in G2+M. These results indicate that Pin2 is the major human telomeric protein and is highly regulated during the cell cycle, with a possible role in mitosis. The results also suggest that Pin2/TRF1 may connect mitotic control to the telomere regulatory machinery whose deregulation has been implicated in cancer and aging.

Expressão dos genes da via mTORC1 e seu envolvimento nas Neoplasias Mieloproliferativas

As Neoplasias Mieloproliferativas (NMPs) se caracterizam por apresentarem acúmulo de eritrócitos, leucócitos e plaquetas morfologicamente normais e seus precursores. Nos últimos anos vários estudos buscaram conhecer os mecanismos celulares e moleculares envolvidos na fisiopatologia e evolução dessas desordens, com o intuito de encontrar marcadores de diagnóstico, prognóstico e terapias eficazes. A mutação pontual no gene que codifica a enzima Janus Kinase 2 (JAK2 V617F), presente em aproximadamente 90% dos pacientes com PV e em 50% dos pacientes com TE e MF, foi o principal achado genético anormal associado a essas doenças. Essa mutação resulta na ativação constitutiva da enzima JAK2 e na desregulação da proliferação celular e resistência à apoptose. Nosso grupo de pesquisa descreveu em PV, TE e MF a expressão alterada de genes reguladores da apoptose e dados da literatura indicam que a desregulação do ciclo celular contribui para a fisiopatologia das NMPs. Nesse projeto o intuito foi investigar a associação da via de sinalização m-TOR com as alterações do ciclo celular e via JAK/STAT nas NMPs. A via de sinalização m-TOR participa dos processos celulares de sobrevivência e proliferação. A estratégia experimental foi avaliar a expressão de genes e proteínas, reguladores da via m-TOR, em leucócitos de pacientes com NPMC e linhagens celulares JAK2+ tratadas com inibidores de JAK2 e AKT. Para determinar a relação da via m-TOR nas NMPs foi escolhido o gene eIF4E, alterado nessas doenças, para observar sua modulação diante da inibição farmacológica nas linhagens celulares JAK2 positivas. Os resultados desse estudo contribuem para a descrição de novos alvos terapêuticos dependentes e indepentendes da atividade quinase JAK2 e para o melhor conhecimento da participação da via de sinalização m-TOR na fisiopatologia das NMPs.

Social Inequity and Globalization: Understanding Violent and Nonviolent Responses

Globalization generates economic growth that is dominated by the free market dynamics of liberalization, deregulation, and privatization. The benefits of this growth are not distributed equally. The resulting inequities cause poverty, marginalization, exclusion, and instability. People respond to these inequities in both positive/nonviolent and negative/violent ways. This capstone project investigates the reasons for divergent responses to globalization by contrasting the underlying social factors in two case studies: peace communities in Colombia and piracy in Somalia. By measuring the level of vulnerability, considering security in a variety of domains, and examining stress on socio-cultural norms, this project develops a social factors framework for understanding the reasons for negative/violent versus positive/nonviolent responses to globalization.

Asymmetric rivalry within and between strategic groups

Our study examines asymmetric rivalry within and between strategic groups defined according to the size of their members. We hypothesize that, owing to several forms of group-level effects, including switching costs and efficiency, strategic groups comprising large firms expect to experience a large amount of retaliation from firms within their group and accommodation from the group comprising smaller firms. Small firms, on the other hand, expect to experience a small amount of retaliation from the group comprising large firms and no reaction from the other firms in their group. We estimate the effect of group-level strategic interactions on firm performance. Our analysis reveals that the rivalry behavior within and between groups is asymmetric, which supports the dominant-fringe relation between firms, as described in our hypothesis.

Who performs a stronger response to whom? Detecting individual competitive actions and reactions

This study analyzes the degree of competition through individual actions and reactions. Empirical support for this analysis has derived mainly from structural econometric models describing the nature of competition. This analysis extends the existing literature by empirically considering a direct measurement of competition through the analysis of the competitive actions and responses, and describing how firms compete within and between strategic groups. We estimate the firms’ conduct in the Spanish deposits market with 146 firms and 18,888 observations. This is a specially compelling context for the banking industry, in which a deregulation process gives rise to the adoption of aggressive strategies seeking to increase the market shares of deposit accounts; thus, producing a turbulent situation of increasing rivalry. Our results offer a deeper understanding of the firms’ competitive behavior, since we identify different patterns of actions and reactions depending upon the strategic group the firm belongs to.

Revisiting the Measurement of Anomie

Sociologists coined the term "anomie" to describe societies that are characterized by disintegration and deregulation. Extending beyond conceptualizations of anomie that conflate the measurements of anomie as 'a state of society' and as a 'state of mind', we disentangle these conceptualizations and develop an analysis and measure of this phenomenon focusing on anomie as a perception of the 'state of society'. We propose that anomie encompasses two dimensions: a perceived breakdown in social fabric (i.e., disintegration as lack of trust and erosion of moral standards) and a perceived breakdown in leadership (i.e., deregulation as lack of legitimacy and effectiveness of leadership). Across six studies we present evidence for the validity of the new measure, the Perception of Anomie Scale (PAS). Studies 1a and 1b provide evidence for the proposed factor structure and internal consistency of PAS. Studies 2a-c provide evidence of convergent and discriminant validity. Finally, assessing PAS in 28 countries, we show that PAS correlates with national indicators of societal functioning and that PAS predicts national identification and well-being (Studies 3a & 3b). The broader implications of the anomie construct for the study of group processes are discussed.