Antecedents and consequences of effectuation and causation in the international new venture creation process

The selection of the entry mode in an international market is of key importance for the venture. A process-based perspective on entry mode selection can add to the International Business and International Entrepreneurship literature. Framing the international market entry as an entrepreneurial process, this paper analyzes the antecedents and consequences of causation and effectuation in the entry mode selection. For the analysis, regression-based techniques were used on a sample of 65 gazelles. The results indicate that experienced entrepreneurs tend to apply effectuation rather than causation, while uncertainty does not have a systematic influence. Entrepreneurs using causation-based international new venture creation processes tend to engage in export-type entry modes, while effectuation-based international new venture creation processes do not predetermine the entry mod

Functional genomics reveals serine synthesis is essential in PHGDH-amplified breast cancer

Cancer cells adapt their metabolic processes to drive macromolecular biosynthesis for rapid cell growth and proliferation[superscript 1, 2]. RNA interference (RNAi)-based loss-of-function screening has proven powerful for the identification of new and interesting cancer targets, and recent studies have used this technology in vivo to identify novel tumour suppressor genes[superscript 3]. Here we developed a method for identifying novel cancer targets via negative-selection RNAi screening using a human breast cancer xenograft model at an orthotopic site in the mouse. Using this method, we screened a set of metabolic genes associated with aggressive breast cancer and stemness to identify those required for in vivo tumorigenesis. Among the genes identified, phosphoglycerate dehydrogenase (PHGDH) is in a genomic region of recurrent copy number gain in breast cancer and PHGDH protein levels are elevated in 70% of oestrogen receptor (ER)-negative breast cancers. PHGDH catalyses the first step in the serine biosynthesis pathway, and breast cancer cells with high PHGDH expression have increased serine synthesis flux. Suppression of PHGDH in cell lines with elevated PHGDH expression, but not in those without, causes a strong decrease in cell proliferation and a reduction in serine synthesis. We find that PHGDH suppression does not affect intracellular serine levels, but causes a drop in the levels of α-ketoglutarate, another output of the pathway and a tricarboxylic acid (TCA) cycle intermediate. In cells with high PHGDH expression, the serine synthesis pathway contributes approximately 50% of the total anaplerotic flux of glutamine into the TCA cycle. These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH overexpression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer targets.Susan G. Komen Breast Cancer Foundation (Fellowship)Life Sciences Research Foundation (Fellowship)W. M. Keck FoundationDavid H. Koch Cancer Research FundAlexander and Margaret Stewart TrustNational Institutes of Health (U.S.) (Grant CA103866

A Conceptualization of e-Risk Perceptions and the Offline-Online Risk Trade-Off for Small Firm Internationalization

A sound conceptualization of international e-risks has grown in demand, because of the increasing penetration of the Internet, and specifically the enabling-facility of the Internet technology for small firms. Yet, to date, there has been no study explicitly attempting to build an international business risk framework for the online environment, nor to explain online internationalization decisions. The purpose of the present paper is threefold, (1) to combine and complement the existing traditional international risk constructs and the emerging views on e-business risks into a comprehensive and unified international risk framework for the online context; (2) to develop propositions regarding SMEs’ active online internationalization decisions by drawing on Dunning's OLI framework; and (3) to explore the online–offline risk trade-off inherent in online internationalization decisions by integrating the e-risk framework into the eclectic paradigm

Towards a Unified Theory of Health-Disease: I. Health as a complex model-object

Este trabalho apresenta uma abordagem sistemática para a modelagem de várias classes de enfermidade-moléstia-doença, designada como Holopatogênese. Holopatogênese é definido como um processo de sobre determinação de doenças e condições relacionadas, tomadas como um integral, compreendendo facetas selecionadas da saúde enquanto objeto complexo. Em primeiro lugar, o marco conceitual da Holopatogênese é apresentado como uma série de três interfaces significativas: biomolecular- imunológica, fisiopatológico-clínica e epidemiológico-ecossocial. Em segundo lugar, proposições derivadas da Holopatogênese são introduzidas a fim de permitir o desenho do complexo doença-enfermidade como uma rede hierárquica de redes. Em terceiro lugar, propõe-se uma formalização de correspondências intra e inter nível, processos de sobredeterminação, efeitos e laços componentes da Holopatogênese. Finalmente, o modelo Holopatogênese é avaliado como uma patologia teórica compreensiva tomada como passo preliminar para uma teoria unificada de saúde-doença