Challenges with in vitro and in vivo experimental models of urinary bladder cancer for novel drug discovery

Urinary bladder cancer (UBC) is the second most frequent malignancy of the urinary system and the ninth most common cancer worldwide, affecting individuals over the age of 65. Several investigations have embarked on advancing knowledge of the mechanisms underlying urothelial carcinogenesis, understanding the mechanisms of antineoplastic drugs resistance and discovering new antineoplastic drugs. In vitro and in vivo models are crucial for providing additional insights into the mechanisms of urothelial carcinogenesis. With these models, various molecular pathways involved in urothelial carcinogenesis have been discovered, allowing therapeutic manipulation.

Deficit of quantal release of GABA in experimental models of temporal lobe epilepsy

Because GABA (gamma-aminobutyric acid) receptor-mediated inhibition controls the excitability of principal neurons in the brain, deficits in GABAergic inhibition have long been favored to explain seizures. In an experimental model of temporal lobe epilepsy, we have identified a deficit of inhibition in presynaptic GABAergic terminals characterized by decreased GABA quantal activity associated with reduced synaptic vesicle density. This decrease in vesicle number primarily seems to affect the reserve pool, rather than the docked or the readily releasable pool.

Occurrence and abundance models of threatened plant species: Applications to mitigate the impact of hydroelectric power dams

Species occurrence and abundance models are important tools that can be used in biodiversity conservation, and can be applied to predict or plan actions needed to mitigate the environmental impacts of hydropower dams. In this study our objectives were: (i) to model the occurrence and abundance of threatened plant species, (ii) to verify the relationship between predicted occurrence and true abundance, and (iii) to assess whether models based on abundance are more effective in predicting species occurrence than those based on presence–absence data. Individual representatives of nine species were counted within 388 randomly georeferenced plots (10 m × 50 m) around the Barra Grande hydropower dam reservoir in southern Brazil. We modelled their relationship with 15 environmental variables using both occurrence (Generalised Linear Models) and abundance data (Hurdle and Zero-Inflated models). Overall, occurrence models were more accurate than abundance models. For all species, observed abundance was significantly, although not strongly, correlated with the probability of occurrence. This correlation lost significance when zero-abundance (absence) sites were excluded from analysis, but only when this entailed a substantial drop in sample size. The same occurred when analysing relationships between abundance and probability of occurrence from previously published studies on a range of different species, suggesting that future studies could potentially use probability of occurrence as an approximate indicator of abundance when the latter is not possible to obtain. This possibility might, however, depend on life history traits of the species in question, with some traits favouring a relationship between occurrence and abundance. Reconstructing species abundance patterns from occurrence could be an important tool for conservation planning and the management of threatened species, allowing scientists to indicate the best areas for collection and reintroduction of plant germplasm or choose conservation areas most likely to maintain viable populations.

Use of Coarse-resolution models of species' distributions to guide local conservation inferences

Distribution models are used increasingly for species conservation assessments over extensive areas, but the spatial resolution of the modeled data and, consequently, of the predictions generated directly from these models are usually too coarse for local conservation applications. Comprehensive distribution data at finer spatial resolution, however, require a level of sampling that is impractical for most species and regions. Models can be downscaled to predict distribution at finer resolutions, but this increases uncertainty because the predictive ability of models is not necessarily consistent beyond their original scale. We analyzed the performance of downscaled, previously published models of environmental favorability (a generalized linear modeling technique) for a restricted endemic insectivore, the Iberian desman (Galemys pyrenaicus), and a more widespread carnivore, the Eurasian otter ( Lutra lutra), in the Iberian Peninsula. The models, built from presence–absence data at 10 × 10 km resolution, were extrapolated to a resolution 100 times finer (1 × 1 km). We compared downscaled predictions of environmental quality for the two species with published data on local observations and on important conservation sites proposed by experts. Predictions were significantly related to observed presence or absence of species and to expert selection of sampling sites and important conservation sites. Our results suggest the potential usefulness of downscaled projections of environmental quality as a proxy for expensive and time-consuming field studies when the field studies are not feasible. This method may be valid for other similar species if coarse-resolution distribution data are available to define high-quality areas at a scale that is practical for the application of concrete conservation measures

Inversion of ambient seismic noise HVSR to evaluate velocity and structural models of the Lower Tagus Basin, Portugal

During its history, several significant earthquakes have shaken the Lower Tagus Valley (Portugal). These earthquakes were destructive; some strong earthquakes were produced by large ruptures in offshore structures located southwest of the Portuguese coastline, and other moderate earthquakes were produced by local faults. In recent years, several studies have successfully obtained strong-ground motion syntheses for the Lower Tagus Valley using the finite difference method. To confirm the velocity model of this sedimentary basin obtained from geophysical and geological data, we analysed the ambient seismic noise measurements by applying the horizontal to vertical spectral ratio (HVSR) method. This study reveals the dependence of the frequency and amplitude of the low-frequency (HVSR) peaks (0.2–2 Hz) on the sediment thickness. We have obtained the depth of the Cenozoic basement along a profile transversal to the basin by the inversion of these ratios, imposing constraints from seismic reflection, boreholes, seismic sounding and gravimetric and magnetic potentials. This technique enables us to improve the existing three-dimensional model of the Lower Tagus Valley structure. The improved model will be decisive for the improvement of strong motion predictions in the earthquake hazard analysis of this highly populated basin. The methodology discussed can be applied to any other sedimentary basin.

Internacionalización de empresas colombianas caso exitoso: Grupo Nutresa

A través de un estudio realizado tanto a los modelos de internacionalización de las empresas y como a una empresa colombiana exitosa a nivel internacional llamada Grupo Nutresa, se identificaron implementaciones que la empresa había tenido a través de estos años dentro de su proceso de internacionalización, acordes (unos más que otros) con los modelos de internacionalización existentes. Gracias a este análisis se pudieron determinar varias conclusiones dentro de las cuales se encuentra la continua innovación que una empresa debe tener para ser exitosa, asimismo un cierto grado de flexibilidad frente a las estrategias implementadas por la empresa dentro de los países a los cuales se está llegando, debido a que no siempre las mismas estrategias implementadas en un país y en otro son las mismas, teniendo siempre en cuenta no cambiar la esencia que tiene la compañía, entre otras conclusiones.

Internacionalización de empresas colombianas, caso exitoso: Súper de Alimentos S.A.

Partiendo de un estudio previamente realizado a una de las empresas colombianas con mayor éxito en el mercado confitero llamada Súper de Alimentos S.A., y cimentado en las diferentes teorías desarrolladas sobre los procesos de internacionalización en Colombia, se logró identificar un patrón integral de uso esencial y general para los empresarios del sector confitero colombiano que decidan aventurarse a enfrentar el mercado internacional. Se comprobó que las empresas vinculadas al sector confitero en Colombia tienen necesidades sumamente similares en materia de internacionalización. En efecto, se evidenció el compromiso que poseen la mayoría de estas empresas con sus clientes, aportando así un alto grado de innovación, calidad y experiencias al paladar de sus consumidores. La rentabilidad demostrada por estas empresas ha sido producto de un arduo análisis de los mercados, costos, riesgos, entre otros, que se planearon afrontar. Teniendo en cuenta figuras como alianzas, licitaciones, joint ventures, etc., y al estar sujetos a un plan estratégico claro, basado en los modelos de internacionalización lo cual da paso a trazar la ruta de internacionalización deseada, permitió a la empresa Súper de Alimentos S.A. irse posicionando no solo en los mercados naciones sino también internacionales.

Análisis comparativo del sector ecoturismo entre Costa Rica y Colombia para generar estrategias de internacionalización

Por medio de la realización de un análisis comparativo de las mejores prácticas y la situación actual del sector ecoturismo en Costa Rica y Colombia y teniendo como referente las diversas teorías de internacionalización, se generaron numerosas estrategias de internacionalización para poder posicionar al turismo de naturaleza en Colombia como un sector de talla mundial. A partir del análisis general del sector ecoturismo a nivel mundial y profundizando después en Costa Rica y Colombia, se identificó el comportamiento del sector en Costa Rica para posicionarse como un país líder en ecoturismo, para así concluir con las estrategias de internacionalización comúnmente usadas en ese país y llevarlas al contexto colombiano. El indiscutible éxito del sector ecoturismo de Costa Rica en el mundo, es el motivo por el cual se tomó como patrón y base para dicho análisis comparativo. Sus prácticas y estrategias pueden ser utilizadas por el sector colombiano para realizar su proceso de internacionalización y de ésta manera mejorar su productividad, proyectarse internacionalmente y generar empleo para así contribuir con el desarrollo económico del país y la calidad de vida de sus habitantes.

Análisis de factores que intervienen en la internacionalización de las Pymes en Colombia

La comprensión de los factores que interviene en la internacionalización de las Pymes en Colombia, conlleva toda una compleja estructura, fundamentación, estrategias, teorías, modelos y metodología organizacional, en el contexto dinámico del mundo comercial y financiero. Por consiguiente, se realizó un análisis de las teorías, modelos de internacionalización y de los factores que allí se reflejan y que interviene en el desarrollo de las pequeñas y medianas empresas, se comparó con las Pymes en Colombia y se apoyó en datos estadísticos de entidades gubernamentales y bases de datos.

A vállalatok nemzetköziesedésének dinamikája – egy kutatási modell (Dynamics of firm internationalization – a research model)

A tanulmány a nemzetköziesedés elméleti modelljeinek hiányosságaival szembesülve amellett érvel, hogy ahhoz, hogy megértsük a nemzetköziesedés időben zajló folyamatát, a vállalatok nemzetközi evolúcióját a kontextussal összefüggésben kell vizsgálni. A tanulmány a vállalatok nemzetköziesedésének folyamatát vizsgáló elméleti szakirodalomra építve egy olyan kutatási modellt vázol fel, amely alkalmas lehet a nemzetköziesedés dinamikájának empirikus vizsgálatához. A modell a belépés, diverzitás, ütem és szakasz koncepciók mentén operacionalizált nemzetköziesedés mintázata és a kontextus (környezet, vállalat, menedzsment) közötti kapcsolatot teremti meg. A vázolt kutatási modell empirikus alkalmazásával lehetővé válik a nemzetközivé válás folyamata során kialakuló komplex kapcsolatrendszer feltárása és megértése. ________ Addressing some of the limitations of the theoretical models of firm internationalization this paper argues that in order to understand the process of firm internationalization along time one should observe firms and their contextual environments as complex interacting processes. Drawing on the theoretical models of firm internationalization process this study proposes a research model that may be suitable for the empirical examination of the dynamics of internationalization. The proposed model builds a relationship between the pattern of firm internationalization operationalized via concepts such as entry, diversity, pace, phases and the context (environment, firm, management) of it. By analyzing the interaction between the multi-level processes that shape internationalization, one can explore the reasons behind the dynamic profile of firm internationalization.

Assessing the impact of business group diversification on the internationalization of their affiliates: The case of Latin American firms

This dissertation explored the capacity of business group diversification to generate value to their affiliates in an institutional environment characterized by the adoption of structural pro-market reforms. In particular, the three empirical essays explored the impact of business group diversification on the internationalization process of their affiliates. ^ The first essay examined the direct effect of business group diversification on firm performance and its moderating effect on the multinationality-performance relationship. It further explored whether such moderating effect varies depending upon whether the focal affiliate is a manufacturing or service firm. The findings suggested that the benefits of business group diversification on firm performance have a threshold, that those benefits are significant at earlier stages of internationalization and that these benefits are stronger for service firms. ^ The second essay studied the capacity of business group diversification to ameliorate the negative effects of the added complexity faced by its affiliates when they internationalized. The essay explored this capacity in different dimensions of international complexity. The results indicated that business group diversification effectively ameliorated the effects of the added international complexity. This positive effect is stronger in the institutional voids rather than the societal complexity dimension. In the former dimension, diversified business groups can use both their non-market resources and previous experience to ameliorate the effects of complexity on firm performance. ^ The last essay explored whether the benefits of business group diversification on the scope-performance relationship varies depending on the level of development of the network of subsidiaries and the region of operation of the focal firm. The results suggested that the benefits of business group diversification are location bound within the region but that they are not related to the level of development of the targeted countries. ^ The three essays use longitudinal analyses on a sample of Latin American firms to test the hypotheses. While the first essay used multilevel models and fix effects models, the last two essays used exclusively fix effects models to assess the impact of business group diversification. In conclusion, this dissertation aimed to explain the capacity of business group diversification to generate value under conditions of institutional change.^

From conceptual process models to running systems: A holistic approach for the configuration of enterprise system processes

This paper proposes a method which aims at increasing the efficiency of enterprise system implementations. First, we argue that existing process modeling languages that feature different degrees of abstraction for different user groups exist and are used for different purposes which makes it necessary to integrate them. We describe how to do this using the meta models of the involved languages. Second, we argue that an integrated process model based on the integrated meta model needs to be configurable and elaborate on the enabling mechanisms. We introduce a business example using SAP modeling techniques to illustrate the proposed method.

Typical accuracy and quality control of a process for creating CT-Based virtual bone models

A pragmatic method for assessing the accuracy and precision of a given processing pipeline required for converting computed tomography (CT) image data of bones into representative three dimensional (3D) models of bone shapes is proposed. The method is based on coprocessing a control object with known geometry which enables the assessment of the quality of resulting 3D models. At three stages of the conversion process, distance measurements were obtained and statistically evaluated. For this study, 31 CT datasets were processed. The final 3D model of the control object contained an average deviation from reference values of −1.07±0.52 mm standard deviation (SD) for edge distances and −0.647±0.43 mm SD for parallel side distances of the control object. Coprocessing a reference object enables the assessment of the accuracy and precision of a given processing pipeline for creating CTbased 3D bone models and is suitable for detecting most systematic or human errors when processing a CT-scan. Typical errors have about the same size as the scan resolution.

Explaining usage of process modeling grammars : comparing three theoretical models in the study of two grammars

Our objective was to determine the factors that lead users to continue working with process modeling grammars after their initial adoption. We examined the explanatory power of three theoretical models of IT usage by applying them to two popular process modeling grammars. We found that a hybrid model of technology acceptance and expectation-confirmation best explained user intentions to continue using the grammars. We examined differences in the model results, and used them to provide three contributions. First, the study confirmed the applicability of IT usage models to the domain of process modeling. Second, we discovered that differences in continued usage intentions depended on the grammar type instead of the user characteristics. Third, we suggest implications and practice.