International Entrepreneurship in Bottom of the Pyramid Markets – Overcoming institutional constraints

Bottom of the pyramid (BoP) markets are an underserved market of approximately four billion people living on under $5 a day in four regional areas: Africa, Asia, Eastern Europe and Latin America. According to estimations, the BoP market forms a $5 trillion global consumer market. Despite the potential of BoP markets, companies have traditionally focused on serving the markets of developed countries and ignored the large customer group at the bottom of the pyramid. The BoP approach as first developed by Prahalad and Hart in 2002 has focused on multinational corporations (MNCs), which were thought of as the ones who should take responsibility in serving the customers at the bottom of the pyramid. This study challenges this proposition and gives evidence that also smaller international new ventures – entrepreneurial firms that are international from their birth, can be successful in BoP markets. BoP markets are characterized by a number of deficiencies in the institutional environment such as strong reliance on informal sector, lack of infrastructure and lack of skilled labor. The purpose of this study is to increase the understanding of international entrepreneurship in BoP markets by analyzing how international new ventures overcome institutional constraints in BoP markets and how institutional uncertainty can be exploited by solving institutional problems. The main objective is divided into four sub objectives. • To describe the opportunities and challenges BoP markets present • To analyze the internationalization of INVs to BoP markets • To examine what kinds of strategies international entrepreneurs use to overcome institutional constraints • To explore the opportunities institutional uncertainty offers for INVs Qualitative approach was used to conduct this study and multiple-case study was chosen as a research strategy in order to allow cross-case analysis. The empirical data was collected through four interviews with the companies Fuzu, Mifuko, Palmroth Consulting and Sibesonke. The results indicated that understanding of the wider institutional environment improves the survival prospects of INVs in BoP markets and that it is indeed possible to exploit institutional uncertainty by solving institutional problems. The main findings were that first-hand experience of the markets and grassroots levels of information are the best assets in internationalization to BoP markets. This study highlights that international entrepreneurs with limited resources can improve the lives of people at the BoP with their business operations and act as small-scale institutional entrepreneurs contributing to the development of the institutional environment of BoP markets.

Capacidades dinámicas que influyen en la operación de la Red de Turismo de La Candelaria

El desarrollo de la presente investigación, centra su atención en las capacidades dinámicas que influyen en la operación de la Red de Turismo de La Candelaria de Bogotá. Para este fin, se realizó una encuesta a 100 directivos o dueños de las empresas que conforman dicha red, y que es una muestra significativa para los propósitos de la investigación, puesto que permite describir a nivel de la empresa y a nivel de la red, la influencia de las capacidades dinámicas de absorción, adaptación e innovación. Como resultados, se obtuvieron que al nivel de empresas las tres capacidades dinámicas influyen en la operación de la misma, encontrándose una mayor relación entre las capacidades de “Innovación – Adaptación"; a nivel de red empresarial ocurre lo contrario, puesto que la relación de las capacidades dinámicas de “Innovación – Adaptación” es nula, mientras que las relaciones entre “Absorción – Innovación” y “Absorción – Adaptación” poseen una alta relación para la operación de la red. Lo anterior, se deriva del análisis realizado de los datos tabulados de la encuesta aplicada a las empresas de la red de turismo, con los estudios empíricos hallados que proponen escalas de medición para las capacidades dinámicas de absorción, adaptación e innovación, y el marco teórico elaborado como soporte para la presente investigación.

Utilidad de la relación estratégica comunitaria y el marketing en los mercados internacionales

Dentro de este trabajo de investigación se quiere profundizar en la teoría que abarca la relación estratégica comunitaria en los mercados internacionales donde se quiere resaltar si ha habido investigaciones alrededor de este tema y si el aporte que se está dando en esta investigación realmente si es información nueva que se está investigando. Se quiere enfocar la investigación hacia como las empresas están realizando la penetración de mercados internacionales pensando en la comunidad en la que están ingresando, sus costumbres, creencias y aspectos sociales.

Análisis del modelo de Internacionalización de e-Tech Simulation según la teoría de redes

La teoría de redes de Johanson y Mattson (1988) explica como las pequeñas empresas, también conocidas como PyMes, utilizan las redes de negocio para desarrollar sus procesos de internacionalización. Es así que a través de las redes pueden superar sus limitaciones de tamaño para encontrar cierto tipo de fluidez y dinamismo en su gestión, con el fin de aprovechar los beneficios de la internacionalización. A partir del desarrollo y fortalecimiento de las relaciones dentro de la red la organización puede posicionarse en una instancia competitiva cada vez más fuerte (Jarillo, 1988). Según Forsgren y Johanson (1992), para los gerentes es importante coordinar la interacción entre los diferentes actores de la red, ya que a través de estas su posición dentro de la red mejora y así mismo el flujo de recursos será mayor. El propósito de este trabajo es analizar el modelo de internacionalización según la teoría de redes, desde una perspectiva cultural, de e-Tech Simulation una PyME “Born to be global” norteamericana. Esta empresa ha minimizado su riesgo de internacionalización, a través del desarrollo de acuerdos entre los diferentes actores. Al mejorar su posición dentro de la red, es decir al fortalecer aún más los lazos existentes y crear nuevas relaciones, la empresa ha obtenido mayores beneficios de la misma y ha logrado ser aún más flexible con sus clientes. Es por esto que a partir de este análisis se planteó una serie de recomendaciones para mejorar los procesos de negociación dentro de la red, bajo un contexto cultural. De igual forma se evidencio la importancia del papel del emprendimiento del gerente en los procesos de internacionalización, así como su habilidad para mezclar los recursos obtenidos de diferentes mercados internacionales para satisfacer las necesidades de los clientes.

Resampling Strategies for Deforming MLS Surfaces

Moving-least-squares (MLS) surfaces undergoing large deformations need periodic regeneration of the point set (point-set resampling) so as to keep the point-set density quasi-uniform. Previous work by the authors dealt with algebraic MLS surfaces, and proposed a resampling strategy based on defining the new points at the intersections of the MLS surface with a suitable set of rays. That strategy has very low memory requirements and is easy to parallelize. In this article new resampling strategies with reduced CPU-time cost are explored. The basic idea is to choose as set of rays the lines of a regular, Cartesian grid, and to fully exploit this grid: as data structure for search queries, as spatial structure for traversing the surface in a continuation-like algorithm, and also as approximation grid for an interpolated version of the MLS surface. It is shown that in this way a very simple and compact resampling technique is obtained, which cuts the resampling cost by half with affordable memory requirements.

Preclinical neuroblastoma models for a pharmacological study of a new MYCN oncogene inhibitor

Background. Neuroblastoma is the most deadly solid tumor of childhood. In the 25% of cases it is associated with MYCN amplification (MA), resulting in the disregulation of several genes involved in cancer progression, chemotherapy resistance and poor prognosis causing the disregulation of several genes involved in cancer progression and chemotherapy resistance and resulting in a poor prognosis. Moreover, in this contest, therapy-related p53 mutations are frequently found in relapsed cases conferring an even stronger aggressiveness. For this reason, the actual therapy requires new antitumor molecules. Therefore, rapid, accurate, and reproducible preclinical models are needed to evaluate the evolution of the different subtypes and the efficacy of new pharmacological strategies. Procedures. We report the real-time tumorigenesis of MA Neuroblastoma mouse models: transgenic TH-MYCN mice and orthotopic xenograft models with either p53wt or p53mut, by non-invasive micro PET and bioluminescent imaging, respectively. Characterization of MYCN amplification and expression was performed on every collected sample. We tested the efficacy of a new MYCN inhibitor in vitro and in vivo. Results. MicroPET in TH-MYCN mice permitted the identification of Neuroblastoma at an early stage and offered a sensitive method to follow metabolic progression of tumors. The MA orthotopic model harboring multitherapy-related p53 mutations showed a shorter latency and progression and a stronger aggressiveness respect to the p53wt model. The presence of MA and overexpression was confirmed in each model and we saw a better survival in the TH-MYCN homozigous mice treated with the inhibitor. Conclusions. The mouse models obtained show characteristics of non-invasiveness, rapidity and sensitivity that make them suitable for the in vivo preclinical study of MA-NB. In particular, our firstly reported p53mut BLI xenograft orthotopic mouse model offers the possibility to evaluate the role of multitherapy-related p53 mutations and to validate new p53 independent therapies for this highly aggressive Neuroblastoma subtype. Moreover, we have shown potential clinical suitability of an antigene strategy through its cellular and molecular activity, ability to specifically inhibit transcription and in vivo efficacy with no evidence of toxicity.

Innovative Strategies for the Synthesis of Biologically Active Small Molecules

The post genomic era, set the challenge to develop drugs that target an ever-growing list of proteins associated with diseases. However, an increase in the number of drugs approved every year is nowadays still not observed. To overcome this gap, innovative approaches should be applied in drug discovery for target validation, and at the same time organic synthetic chemistry has to find new fruitful strategies to obtain biologically active small molecules not only as therapeutic agents, but also as diagnostic tools to identify possible cellular targets. In this context, in view of the multifactorial mechanistic nature of cancer, new chimeric molecules, which can be either antitumor lead candidates, or valuable chemical tools to study molecular pathways in cancer cells, were developed using a multitarget-directed drug design strategy. According to this approach, the desired hybrid compounds were obtained by combining in a single chemical entity SAHA analogues, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives able to block cell cycle, to induce apoptosis and cell differentiation and with Sorafenib derivative, a multikinase inhibitor. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on leukemia Bcr-Abl-expressing K562 cell lines, as well as their HDACs inhibition. Preliminary results confirmed that one of the hybrid compounds has the desired chimeric profile. A distinct project was developed in the laboratory of Dr Spring, regarding the synthesis of a diversity-oriented synthesis (DOS) library of macrocyclic peptidomimetics. From a biological point of view, this class of molecules is extremely interesting but underrepresented in drug discovery due to the poor synthetic accessibility. Therefore it represents a valid challenge for DOS to take on. A build/couple/pair (B/C/P) approach provided, in an efficient manner and in few steps, the structural diversity and complexity required for such compounds.

Generation and characterization of mouse models of Small cell lung cancer and Basal cell carcinoma for the preclinical evaluation of new therapies

Background. Human small cell lung cancer (SCLC) accounting for approximately 15-20% of all lung cancers, is an aggressive tumor with high propensity for early regional and distant metastases. Although the initial tumor rate response to chemotherapy is very high, SCLC relapses after approximately 4 months in ED and 12 months in LD. Basal cell carcinoma (BCC) is the most prevalent cancer in the western world, and its incidence is increasing worldwide. This type of cancer rarely metastasizes and the death rate is extraordinary low. Surgery is curative for most of the patients, but for those that develop locally advanced or metastatic BCC there is currently no effective treatment. Both types of cancer have been deeply investigated and genetic alterations, MYCN amplification (MA) among the most interesting, have been found. These could become targets of new pharmacological therapies. Procedures. We created and characterized novel BLI xenograft orthotopic mouse models of SCLC to evaluate the tumor onset and progression and the efficacy of new pharmacological strategies. We compared an in vitro model with a transgenic mouse model of BCC, to investigate and delineate the canonical HH signalling pathway and its connections with other molecular pathways. Results and conclusions. The orthotopic models showed latency and progression patterns similar to human disease. Chemotherapy treatments improved survival rates and validated the in vivo model. The presence of MA and overexpression were confirmed in each model and we tested the efficacy of a new MYCN inhibitor in vitro. Preliminar data of BCC models highlighted Hedgehog pathway role and underlined the importance of both in vitro and in vivo strategies to achieve a better understanding of the pathology and to evaluate the applicability of new therapeutic compounds

The Impact Of Inward Licensing On New Venture’s Performance. Is inward licensing a winning strategy?

The original idea of the thesis draws on interrelated assumptions: 1) among the tools used, in the markets for technology, for the acquisition of external knowledge, the licensing agreements are acknowledged as one of the most important contractual mechanisms; 2) the liabilities of newness and the liabilities of smallness force new venture to strongly rely on external knowledge sources. Albeit the relevance of this topic, little attention has been paid so far to its investigation, especially in the licensing context; 3) nowadays there is an increasing trend in licensing practices, but the literature on markets for technology focuses almost exclusively on the incentives and rationales that foster firms’ decisions to trade their technologies, under-investigating the role of the acquiring firm, the licensee, overlooking the demand side of the market. Therefore, the thesis investigates the inward licensing phenomenon within the context of new ventures. The main questions that new venture licensee has to address if it decides to undertake an inward licensing strategy, can be summarized as follows: 1) Is convenient for a new venture to choose, as initial technology strategy, the implementation of an inward licensing ? 2) Does this decision affect its survival probabilities? 3) Does the age, at which a new venture becomes a licensee, affect its innovative capabilities? Is it better to undertake a licensing-in strategy soon after founding or to postpone this strategy until the new venture has accumulated significant resources? The findings suggest that new ventures licensees survive less than their non-licensee counterparts; the survival rates are directly connected to the time taken by firms to reach the market;being engaged in licensing-in deals some years after its inception allows a new venture licensee to increase its subsequent capacity to produce innovations.

The impact of intraclonal heterogeneity on the outcomes of Multiple Myeloma patients treated with new drugs

Understanding the biology of Multiple Myeloma (MM) is of primary importance in the struggle to achieve a cure for this yet incurable neoplasm. A better knowledge of the mechanism underlying the development of MM can guide us in the development of new treatment strategies. Studies both on solid and haematological tumours have shown that cancer comprises a collection of related but subtly different clones, a feature that has been termed “intra-clonal heterogeneity”. This intra-clonal heterogeneity is likely, from a “Darwinian” natural selection perspective, to be the essential substrate for cancer evolution, disease progression and relapse. In this context the critical mechanism for tumour progression is competition between individual clones (and cancer stem cells) for the same microenvironmental “niche”, combined with the process of adaptation and natural selection. The Darwinian behavioural characteristics of cancer stem cells are applicable to MM. The knowledge that intra-clonal heterogeneity is an important feature of tumours’ biology has changed our way to addressing cancer, now considered as a composite mixture of clones and not as a linear evolving disease. In this variable therapeutic landscape it is important for clinicians and researchers to consider the impact that evolutionary biology and intra-clonal heterogeneity have on the treatment of myeloma and the emergence of treatment resistance. It is clear that if we want to effectively cure myeloma it is of primarily importance to understand disease biology and evolution. Only by doing so will we be able to effectively use all of the new tools we have at our disposal to cure myeloma and to use treatment in the most effective way possible. The aim of the present research project was to investigate at different levels the presence of intra-clonal heterogeneity in MM patients, and to evaluate the impact of treatment on clonal evolution and on patients’ outcomes.

Strategies to prevent neuronal damage in paediatric bacterial meningitis

PURPOSE OF REVIEW: The mortality of bacterial meningitis can reach 30%, and up to 50% of survivors suffer from persisting neurological deficits as a consequence of the disease. The incidence of neurological sequelae of bacterial meningitis has not improved over the last decade. Adjunctive therapeutic options are limited, and ongoing research into the pathophysiology of brain damage in bacterial meningitis aims at providing the scientific basis for future development of more efficient adjunctive options. RECENT FINDINGS: In a population with good access to health care, dexamethasone given before or at the time of initiation of antibiotic therapy acts beneficially in paediatric pneumococcal meningitis, but not in meningococcal meningitis. In experimental animal models, brain-derived neurotrophic factor protected against brain injury and improved hearing while melatonin, which has antioxidant properties among other effects, reduced neuronal death. Transgene technology can be used to provide new insights into the pathophysiology of the disease and to identify potential therapeutic targets. SUMMARY: Although dexamethasone improves outcome of bacterial meningitis under defined circumstances, the morbidity of bacterial meningitis still remains unacceptably high. Experimental models may help to identify new therapeutic strategies to further improve the neurological outcome in young children suffering from bacterial meningitis.

Epidermal growth factor receptor inhibitors plus chemotherapy in non-small-cell lung cancer: biologic rationale for combination strategies

Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.

Ceramic foam plates: a new tool for processing fresh radical prostatectomy specimens

Procurement of fresh tissue of prostate cancer is critical for biobanking and generation of xenograft models as an important preclinical step towards new therapeutic strategies in advanced prostate cancer. However, handling of fresh radical prostatectomy specimens has been notoriously challenging given the distinctive physical properties of prostate tissue and the difficulty to identify cancer foci on gross examination. Here, we have developed a novel approach using ceramic foam plates for processing freshly cut whole mount sections from radical prostatectomy specimens without compromising further diagnostic assessment. Forty-nine radical prostatectomy specimens were processed and sectioned from the apex to the base in whole mount slices. Putative carcinoma foci were morphologically verified by frozen section analysis. The fresh whole mount slices were then laid between two ceramic foam plates and fixed overnight. To test tissue preservation after this procedure, formalin-fixed and paraffin-embedded whole mount sections were stained with hematoxylin and eosin (H&E) and analyzed by immunohistochemistry, fluorescence, and silver in situ hybridization (FISH and SISH, respectively). There were no morphological artifacts on H&E stained whole mount sections from slices that had been fixed between two plates of ceramic foam, and the histological architecture was fully retained. The quality of immunohistochemistry, FISH, and SISH was excellent. Fixing whole mount tissue slices between ceramic foam plates after frozen section examination is an excellent method for processing fresh radical prostatectomy specimens, allowing for a precise identification and collection of fresh tumor tissue without compromising further diagnostic analysis.

Linking livelihood strategies with a regional level landscape mosaic to explore trade-offs between forest conservation and human wellbeing in a Madagascar biodiversity hotspot

The north-eastern escarpment of Madagascar contains the island’s last remaining large-scale humid forest massifs surrounded by diverse small-scale agricultural mosaics. There is high deforestation mainly caused by shifting cultivation practiced by local land users to produce upland rice for subsistence. Today, large protected areas restrict land users’ access to forests to collect wood and other forest products. Moreover, they are no more able to expand their cultivated land, which leads to shorter shifting cultivation cycles and decreasing plot sizes for irrigated rice and cash crop cultivation. Cash crop production of clove and vanilla is exposed to risks such as extreme inter-annual price fluctuations, pests and cyclones. In the absence of work opportunities, agricultural extension services and micro-finance schemes people are stuck in a poverty trap. New development strategies are needed to mitigate the trade-offs between forest conservation and human well-being. As landscape composition and livelihood strategies vary across the region, these strategies need to be spatially differentiated to avoid implementing generic solutions, which do not fit the local context. However, up to date, little is known about the spatial patterns of shifting cultivation and other land use systems at the regional level. This is mainly due to the high spatial and temporal dynamics inherent to shifting cultivation, which makes it difficult to monitor the dynamics of this land use system with remote sensing methods. Furthermore, knowledge about land users’ livelihood strategies and the risks and opportunities they face stems from very few local case studies. To overcome this challenge, firstly, we used remote sensing data and a landscape mosaic approach to delineate the main landscape types at the regional level. Secondly, we developed a land user typology based on socio-ecological data from household surveys in 45 villages spread throughout the region. Combining the land user typology with the landscape mosaic map allowed us to reveal spatial patterns of the interaction between landscapes and people and to better understand the trade-offs between forest conservation and local wellbeing. While shifting cultivation systems are being transformed into more intensive permanent agricultural systems in many countries around the globe, Madagascar seems to be an exception to this trend. Linking land cover information to human-environmental interactions over large areas is crucial to designing policies and to inform decision making for a more sustainable development of this resource-rich but poverty-prone context.

Growth strategies in a greener world

Two new developments in the global landscape - growing concerns towards global warming and the rising prices of commodities – require countries to craft new growth strategies. These recent developments in the global market offer fresh industrial opportunities as well as difficulties for developing countries embarking on industrialization. In this paper, we examine current developments in global market that would affect industrialization prospects in East Asia and explores development strategies that are suitable for development based on export oriented manufacturing industries in a green world.