Interactions between cancer stem cells and their niche govern metastatic colonization.

Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps. Although dissemination of tumour cells seems to be an early and frequent event, the successful initiation of metastatic growth, a process termed 'metastatic colonization', is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites. Prevalent target sites are characteristic of many tumour entities, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.

On the Reversed Brayton Cycle with High Speed Machinery

This work was carried out in the laboratory of Fluid Dynamics, at Lappeenranta University of Technology during the years 1991-1996. The research was a part of larger high speed technology development research. First, there was the idea of making high speed machinery applications with the Brayton cycle. There was a clear need to deepen theknowledge of the cycle itself and to make a new approach in the field of the research. Also, the removal of water from the humid air seemed very interesting. The goal of this work was to study methods of designing high speed machinery to the reversed Brayton cycle, from theoretical principles to practical applications. The reversed Brayton cycle can be employed as an air dryer, a heat pump or a refrigerating machine. In this research the use of humid air as a working fluid has an environmental advantage, as well. A new calculation method for the Braytoncycle is developed. In this method especially the expansion process in the turbine is important because of the condensation of the water vapour in the humid air. This physical phenomena can have significant effects on the level of performance of the application. Also, the influence of calculating the process with actual, achievable process equipment efficiencies is essential for the development of the future machinery. The above theoretical calculations are confirmed with two different laboratory prototypes. The high speed machinery concept allows one to build an application with only one rotating shaft including all the major parts: the high speed motor, the compressor and the turbine wheel. The use of oil free bearings and high rotational speed outlines give several advantages compared to conventional machineries: light weight, compact structure, safe operation andhigher efficiency at a large operational region. There are always problems whentheory is applied to practice. The calibrations of pressure, temperature and humidity probes were made with care but still measurable errors were not negligible. Several different separators were examined and in all cases the content of the separated water was not exact. Due to the compact sizes and structures of the prototypes, the process measurement was slightly difficult. The experimental results agree well with the theoretical calculations. These experiments prove the operation of the process and lay a ground for the further development. The results of this work give very promising possibilities for the design of new, commercially competitive applications that use high speed machinery and the reversed Brayton cycle.

Entry Strategy Issues in the Ophthalmic Industry: Entry Mode, Pricing and Distribution

Maahantulostrategia asettaa yrityksen kansainvälisiä liiketoimintoja ohjaavat tavoitteet, päämäärät, resurssit ja toiminnan suuntaviivat. Tämä diplomityö käsittelee yrityksen maahantulostrategian elementeistä operaatiomuodon valintaa, hinnoittelua ja jakelua. Työssä rakennetaan teoriakehys elementteihin liittyvien päätösten tutkimiseksi lääketeollisuuden ominaispiirteet huomioiden. Lääketeollisuudella on muihin teollisuudenaloihin verrattuna useita erityispiirteitä, joihin työ perehdyttää. Lisäksi työn olennainen osa on selvittää lääketeollisuuden maakohtaisia säädöksiä ja toimintamalleja. Diplomityö on tehty silmäläkkeitä valmistavalle, kehittävälle ja markkinoivalle Santen Oy:lle, joka suunnittelee toimintansa laajentamista Keski- ja Etelä-Euroopan markkinoille. Tässä laajentumisprosessissa ensimmäisenä kohdemaana on Saksa, jonka markkinoille suuntautuvia toimenpiteitä työ tutkii. Teoriakehyksen, markkinoiden ominaispiirteiden sekä useiden erilaisten analyysien pohjalta työn tavoitteena on antaa operaatiomuotoa, tuotteiden hinnoittelua ja jakelua koskevia suosituksia.

Ydinvoimalaitoksen höyryturbiinin suorituskyvyn laskenta

Diplomityön tavoitteena on selvittää Loviisan ydinvoimalaitoksen höyryturbiinin hyötysuhteen parantamismahdollisuuksia. Työn kuvaan liittyvät oleellisesti höyryturbiinin siipivyöhykkeiden nopeuskolmioiden sekä hyötysuhteiden laskenta. Höyryturbiinien kehityskaarta sekä turbiinin häviökerrointen laskentayhtälöitä on esitetty useasta eri lähteestä ja vuosikymmeniltä. Työssä selvitettiin uusimpia ydinvoimalaitosten kostea höyryturbiinien suunnitteluperusteita lukuisista eri lähteistä. Kaikkien lähteiden mukaan kostean höyryn alueella tapahtuvaa paisuntaa on haasteellista mallintaa. Työssä on esitelty artikkeleissa tulleita eri näkökulmia höyryturbiinien suorituskyvyn parantamiseksi, sekä rakenteellisia että laskennallisia. Työssä esitellään monia turbiinin virtauksen ja suorituskyvyn laskentamenetelmiä. Esimerkiksi Baumannin säännön laskenta on yksinkertainen tapa käsitellä turbiinin suorituskykyä kostean höyryn alueella. Keskeisimpiä tehtyjä havaintoja oli se, että korkeapaineturbiinin ensimmäisestä vaiheesta löytyi mahdollista parannuspotentiaalia Loviisaan ydinvoimalaitoksen tehon lisäämiseksi. Ensimmäisessä vaiheessa on oletettu siipien olevan Laval –tyyppisiä, mutta käytännössä näin ei ole. Korkeapaineturbiinin nykyisen turbosuuttimen toimintaa voitaisiin tehostaa. Lisäksi Loviisan matalapaineturbiinin viimeisen siipivaiheen jälkeen aiheutuu suuret ulosvirtaushäviöt. Osa suurinopeuksisen virtauksen energiasta pystyttäisiin kuitenkin hyödyntämään vielä ulosvirtauskanavassa olevalla diffuusorilla.

Höyryturbiinin käytönaikaisen suorituskyvyn seuranta

Tässä diplomityössä jatkettiin Loviisan voimalaitoksen höyryturbiinien suorituskyvyn parannuspotentiaalien tutkimusta. Tavoitteena oli kehittää laitoksen höyryturbiinien suorituskyvyn käytönaikaisia on-line-mittauksia. Selvityksessä perehdyttiin norjalaisen IFE:n kehittämään stationääritilan TEMPOohjelmaan( The Thermal Performance Monitoring And Optimisation system), sen käyttöohjeisiin ja toimintaperiaatteisiin. Työssä esiteltiin laajasti tiedon yhteensovittamisen laskentateoriaa, johon TEMPOn toiminta perustuu. Työssä tarkasteltiin turbiinin todellista paisuntaprosessia, koska sen ymmärtäminen on tärkeässä osassa turbiinin suorituskyvyn valvonnassa. Tutkimuksessa esiteltiin myös turbiineille mahdollisia vikoja sekä niiden syntymisprosesseja. Työssä tarkasteltiin TEMPOn sovittamien tulostiedostojen analysointiohjelman toimivuutta havaitsemalla itse aiheutettuja poikkeamia todellisiin mittaustiedostoihin. Analysointiohjelmalla muodostettuja kuvaajia vertailtiin todellisen prosessin ajotilanteen kuvaajiin ja tarkasteltiin, kuinka poikkeamia on mahdollista havaita kuvaajien avulla. TEMPO-ohjelmalle löydettiin tutkimuksen edetessä kehittämisehdotuksia. Näillä muutoksilla ohjelma saadaan mallintamaan Loviisan voimalaitoksen turbiiniprosessia tarkemmin ja tuloksista saadaan hyödyllisempiä.

Incursión a mercados internacionales en el sector de las consultoras a petroleras

Lo que se pretende con esta investigación es determinar la viabilidad de Digitoil Ltda. para iniciar un proceso de internacionalización en Latinoamérica en el corto plazo, y en el largo plazo en países de medio oriente. Para realizar este trabajo, en primer lugar se realizará un diagnostico general de la empresa que permita determinar aspectos fundamentales como lo son sus fortalezas y debilidades en las áreas de mercadeo, operaciones, finanzas y talento humano. Con este diagnóstico se evaluará la situación actual en la que se encuentra la empresa, se identificaran las oportunidades de mejora (problemas) y se desarrollará un plan de mejora para explotar las restricciones con las que cuente actualmente la empresa. Este diagnóstico también nos permitirá ver en qué posición se encuentra actualmente la empresa para iniciar un proceso de internacionalización. Un apoyo que permitirá a la organización evaluar alternativas de países para iniciar su proceso de expansión, será una matriz de mercados en donde se evaluarán 8 países objetivos, de entre los cuales se escogerán los tres países más atractivos de acuerdo al análisis de algunas variables que nos permiten identificar la viabilidad de iniciar procesos de expansión en dichos países. Una vez escogido los tres países, a saber, objetivo, alterno y contingente; se procederá a analizar otra serie de aspectos como lo son barreras de entrada y salida; fortalezas, oportunidades, debilidades y amenazas; potenciales clientes y segmentación del mercado y competencia; y el plan logístico para entrar en el país objetivo. Al final de esta investigación se tomarán las acciones necesarias y recomendaciones para fortalecer la empresa y empezar el proceso de internacionalización.

Caso exitoso de internacionalización de la compañía de galletas Noel S.A.S y panificadora el Country

Por medio de en un estudio realizado a dos empresas de mercado colombiano, una de ellas con visión expansiva (Pan el Country) y otra presentada como caso de éxito de internacionalización (Compañía de Galletas Noel S.A.S) y basados en diferentes teorías administrativas. Se logro percibir los diferentes medios con que Noel alcanzo su posicionamiento tanto a nivel nacional e internacional y a su vez dar estrategias comparativas y competitivas para el desarrollo productivo de Pan el Country. De este modo se identifico que Pan el country con sus estrategia expansiva y por medio de una red de comercialización que lo llevo a realizar exportaciones ocasionales a Estados Unidos, cumple de manera progresiva los estándares con las que las empresas inician sus procesos de internacionalización y avanzan notablemente en la medida que haya reconocimiento de marca, y posicionamiento en el país o región determinada. Sin duda alguna las características más sobresalientes que llevan a Noel al éxito nacional, van ligadas a la innovación de productos y las grandes investigaciones que promueven a definir estrategias para penetrar en diferentes segmentos del mercado, pasos que le dan empuje a redefinir las metas y objetivos a Pan el Country en busca de un desarrollo continuo y un futuro exitoso.

Juan Valdez: Resurgimiento de una marca

La Federación Nacional de Cafeteros fue fundada en el año 1927 con el objetivo de elevar el nivel de vida de los caficultores y dar a conocer la calidad del café Colombiano en el mundo. Parte del trabajo de la federación ha sido el posicionamiento a nivel mundial del café Colombiano, para lo cual ha utilizado varias campañas publicitarias entre las cuales se destaca la creación en el año 1959 del icono Juan Valdez con su mula Conchita. Así mismo, en noviembre del año 2002 la Federación Nacional de Cafeteros creó la empresa Procafecol S.A. con el objetivo de generar negocios de valor agregado para los cafeteros y desarrollar las actividades empresariales bajo la marca Juan Valdez Café. En el año 2005 Procafecol S.A. inició el proceso de expansión internacional, para el año 2013 la compañía reportaba utilidades alrededor de los cuatro mil millones de pesos colombianos y excelentes cifras de expansión. Sin embargo, desde la apertura de la primera tienda Juan Valdez en el año 2002 la marca generaba pérdidas, que alcanzaron aproximadamente diecinueve mil millones de pesos colombianos en el año 2012. (Procafecol S.A., 2013) Teniendo en cuenta que es necesario tener herramientas que permitan generar estrategias desde la dirección y gerencia para asegurar la perdurabilidad en las empresas, adscrito al GIPE (Grupo de Investigación en Perdurabilidad Empresarial), se realizó este estudio de caso como parte de la línea de investigación de Realidad empresarial. Con el fin de analizar el caso de Procafecol S.A. y su marca Juan Valdez, e ilustrar el resurgimiento de la compañía después de 9 años de presentar pérdidas en el ejercicio financiero. (Escuela de administración Universidad del Rosario, 2013)

Chinese multinationals and public policy

Purpose – The purpose of this paper is to examine the interaction between large Chinese firms as they internationalize and their home and host governments. Design/methodology/approach – The approach taken is that of an analysis of relevant literature and the application of a popular theoretical framework by Rugman and Verbeke to the case of Chinese firms as they expand abroad. Findings – First, the paper adapts a well-known business-government framework to analyze emerging economy issues, all in a Chinese context. Then the paper relates this analysis to the existing literature on the international expansion process of Chinese firms. The paper finds that in their attempt to seek strategic assets, Chinese multinational enterprises (MNEs) face conflicts with host countries and Western firms in which host government support for international competitiveness can be used as quasi protectionist defense mechanisms. Using the public policy and MNE framework, the paper examines several recent disputes and finds that Chinese MNEs have complementary goals with the Chinese state, but they have conflicting goals with Western governments. Originality/value – These findings have important academic research, managerial, and public policy implications.

Does Gibrat’s Law hold for Swedish energy firms?

Gibrat's law predicts that firm growth is purely random and should be independent of firm size. We use a random effects-random coefficient model to test whether Gibrat's law holds on average in the studied sample as well as at the individual firm level in the Swedish energy market. No study has yet investigated whether Gibrat's law holds for individual firms, previous studies having instead estimated whether the law holds on average in the samples studied. The present results support the claim that Gibrat's law is more likely to be rejected ex ante when an entire firm population is considered, but more likely to be confirmed ex post after market selection has "cleaned" the original population of firms or when the analysis treats more disaggregated data. From a theoretical perspective, the results are consistent with models based on passive and active learning, indicating a steady state in the firm expansion process and that Gibrat's law is violated in the short term but holds in the long term once firms have reached a steady state. These results indicate that approximately 70 % of firms in the Swedish energy sector are in steady state, with only random fluctuations in size around that level over the 15 studied years.

Três ensaios sobre política monetária e crédito

In the first essay, "Determinants of Credit Expansion in Brazil", analyzes the determinants of credit using an extensive bank level panel dataset. Brazilian economy has experienced a major boost in leverage in the first decade of 2000 as a result of a set factors ranging from macroeconomic stability to the abundant liquidity in international financial markets before 2008 and a set of deliberate decisions taken by President Lula's to expand credit, boost consumption and gain political support from the lower social strata. As relevant conclusions to our investigation we verify that: credit expansion relied on the reduction of the monetary policy rate, international financial markets are an important source of funds, payroll-guaranteed credit and investment grade status affected positively credit supply. We were not able to confirm the importance of financial inclusion efforts. The importance of financial sector sanity indicators of credit conditions cannot be underestimated. These results raise questions over the sustainability of this expansion process and financial stability in the future. The second essay, “Public Credit, Monetary Policy and Financial Stability”, discusses the role of public credit. The supply of public credit in Brazil has successfully served to relaunch the economy after the Lehman-Brothers demise. It was later transformed into a driver for economic growth as well as a regulation device to force private banks to reduce interest rates. We argue that the use of public funds to finance economic growth has three important drawbacks: it generates inflation, induces higher loan rates and may induce financial instability. An additional effect is the prevention of market credit solutions. This study contributes to the understanding of the costs and benefits of credit as a fiscal policy tool. The third essay, “Bayesian Forecasting of Interest Rates: Do Priors Matter?”, discusses the choice of priors when forecasting short-term interest rates. Central Banks that commit to an Inflation Target monetary regime are bound to respond to inflation expectation spikes and product hiatus widening in a clear and transparent way by abiding to a Taylor rule. There are various reports of central banks being more responsive to inflationary than to deflationary shocks rendering the monetary policy response to be indeed non-linear. Besides that there is no guarantee that coefficients remain stable during time. Central Banks may switch to a dual target regime to consider deviations from inflation and the output gap. The estimation of a Taylor rule may therefore have to consider a non-linear model with time varying parameters. This paper uses Bayesian forecasting methods to predict short-term interest rates. We take two different approaches: from a theoretic perspective we focus on an augmented version of the Taylor rule and include the Real Exchange Rate, the Credit-to-GDP and the Net Public Debt-to-GDP ratios. We also take an ”atheoretic” approach based on the Expectations Theory of the Term Structure to model short-term interest. The selection of priors is particularly relevant for predictive accuracy yet, ideally, forecasting models should require as little a priori expert insight as possible. We present recent developments in prior selection, in particular we propose the use of hierarchical hyper-g priors for better forecasting in a framework that can be easily extended to other key macroeconomic indicators.

Entre o mar e estrela, um lugar para se bem viver : a problemática da expansão urbana da Cidade de Baía Formosa/RN

The urban expansion problem of Baía Formosa, a southern edge city of de Rio Grande do Norte eastern coast, which has been presented in other coast Brazilian towns, specially on those with tourist activities increase. Therefore, this situation brings huge concerns to their inhabitants, to their technical /scientific community and to the governments, because of the conflicts of interest and of the growth of urban problems that this has been created. At Baía Formosa, the situation is aggravated because the city is confined, once around it, there are large private proprieties, environmental preservation area and the sea, at the eastern edge. The objectives of this study are the analyses of this city expansion process in order to obtain adequate alternatives and defining methodology to apply in other urban nucleus that are subjected to similar situations. Of course, presents social relations, environmental conditions and promoting local population insertion should be considered in order that enjoin this process and contributing to a better social balance. This case study has used bibliography research, field data, maps and soil occupation recorders and photographs of the area, besides the primary data gathering by surveys carried out with many social actors. The present analysis shows that the urban expansion observed today is featured by a recent unsustainable model, which attacks the environment and brings either farm conflicts. On the other hand, the ecological tourism can represent an alternative in order to achieve an adequate expansion form, without forgetting the several structural parameters necessary to support the sustainable activities

O processo de urbanização de Mossorò: dos processos históricos à estrutura urbana atual

The general objective of this academic work is to analyze the relationship between the territorial division and the urban expansion process of Mossoró city, understood here as the production and occupation of space. The urban expansion in Mossoró, since its formation as settlement in 1772 until current days, identifies with the Brazilian urbanization process whose growth is determined by the capitalist development. Thus, the expansion was determined by several economical specializations imposed by the territorial division of work which occurs at an interregional level, and, sometimes at an international level. Then, each specialization determined a moment of the urban expansion of the city, as follows: a) The cattle farmer specialization, between 1772 and 1857, when the urban expansion was shy, is summarized to a commercial square that received goods from Aracati aiming to cover a wide rural area; b) The commercial emporium specialization, between 1857 and 1930, when the urban expansion took an important impulse with the concentration of public and private capitals; c) The salt industry and the agricultural-industrial exporter specialization inside a state of development policy, between 1930 and 1970, when the urban expansion, joined to the settlement of the working class in the urban soil, developed along an important axis -the railway; d) The render of services specialization inside a state of intervention policy, between 1970 and 1990, when the urban expansion was characterized by the accelerated growth rhythm, by the reuse of some spaces, and by space segregation of demanding people; e) The render of services policy inside a neoliberal state policy, since 1990 until current days, when the urban expansion reduced its rhythm abruptly, when only small alterations occurred in the existing spaces. It focused on social policies and on several slums eradication programs. Finally, the territorial structure is deeply articulated with others, no territorial, but economical, social and political, which happens at a national, regional and local rate. Only within a historical and conceptual panorama, it was possible to explain the urban expansion in Mossoró from its formation in 1772 until current days. Therefore, this work is a several discipline analysis of the urbanization process existing in Mossoró

Avaliação do impacto do plano de expansão da rede federal na qualidade dos institutos federais de educação segundo indicadores de desempenho

The Expansion Plan of the Federal Network of Vocational Education foresees the construction of 860 new units of instruction until 2020, representing a strong growth against the 140 existing units prior to its disclosure by Federal Government of Brazil, in 2005. The Federal Institutes of Education, Science and Technology have been performing the expansion while experiencing the shortcomings and challenges of units still in development, created in previous phases of the Plan. The quality of the services of these institutions has been evaluated by the control bodies, which require the submission of performance indicators in annual management reports of institutions under their jurisdiction. In this context of expansion process, particularly, is desirable to identify possible changes in quality standards. Thus, this research was motivated by the following problem: there was difference in the performance of the Federal Institutes of Education, Science and Technology after the inauguration of the first units of phase II of the Expansion Plan of the Federal Network of Vocational Education? This is an exploratory-descriptive, ex-post-facto, quantitative approach research, which aims to contribute to the knowledge of the impact of the expansion of the Federal Network. The data were collected from 12 indicators presented in management reports of 38 Federal Institutes through years 2007 to 2011 to evaluate the performances using descriptive statistical techniques. The indicators were analyzed in both consolidated and open manners by the following perspectives: country region, growth of instruction units and institutions origin. Was also performed a multivariate analysis of clusters in order to identify excellence groups of Institutes. The results showed differences in the expansion plan s development among Brazilian regions, both in terms of infrastructure and academic indicators, with better results in the Midwest and South, and that there are differentiated profiles of institutes as its origin, where the best quality indicators occur in those originated by integration of different educational institutions. Still, were identified two excellence groups, with emphasis on academic management, human resources and expansion

Inundações urbanas no semiarido nordestino: o caso da cidade de Pau dos Ferros - RN

The Apodi river basin, particularly within the snippet that crosses Pau dos Ferros - RN city, place anthropogenic actions that interfere in the dynamic environment by modifying the local landscape. The reflection of these actions can be seen in the floods that occur in rainy periods (February to may) virtually every year in the city. It is important to stress that the project of integration of the waters of the San Francisco basin with the northern basin of Northeastern will perennial the main channel of the river basin, and generate greater impacts in the region. This work sought to define a methodology able to delimit areas susceptible to flooding in cities of semiarid Northeast based on the Pau dos Ferros RN city. The dissertation is divided into two chapters and introduction. The introduction presents a theoretical frame based on discussion of the concept of risk, their main characteristics and subdivisions; floods; geotecnologies; Apodi River basin; municipal data Pau dos Ferros RN and design integration of Francisco basin with the northern basins Northeast. The first chapter evaluates the urban expansion process between 1987 and 2008, delimiting the flood areas and analyzes the relationship between urban growth and retention areas. The second chapter identifies the flood risk areas in the Pau dos Ferros city. The methodology used was based on tools of geographic information system GIS from software SPRING/INPE 5.1, as well as bibliographical, satellite images, aerial photographs and field activities. The results obtained enabled view the rapid expansion of the urban area of Pau dos Ferros, which has doubled in a period of 22 years. The population density checks with greater intensity in South-central portion of the city, in flood areas and not flood (Cap. 01). It was noted also that some neighborhoods along the River Apodi are susceptible to more instances of flooding ranging from minimum to maximum, while in neighborhoods near the Riacho Cajazeiras floods occur to a lesser extent because of altimetry higher and lower water volume. (Cap. 02). It is expected that this work will help in the preparation of flood risk municipal map subsidising managers in implementing public policies targeted to the softening of urban flood-related issues in Pau dos Ferros RN and serve as a model for mapping of other cities with similar characteristics analyzed in this work