Envisioning Entrepreneurship’s Future:Introducing Me-Search and Research Agendas

The future of the field of entrepreneurship is bright primarily because of the many research opportunities to make a difference. However, as scholars how can we find these opportunities and choose the ones most likely to contribute to the literature? This essay introduces me-search and a special issue of research-agenda papers from leading scholars as tools for blazing new trails in entrepreneurship research. Me-search and the agenda papers point to the importance of solving a practical problem; problematizing, contextualizing, and abstracting entrepreneurship research; and using empirical theorizing to explore entrepreneurial phenomena.</p

The impact of entrepreneurship research on other academic fields

The remarkable ascent of entrepreneurship witnessed as a scientific field over the last 4 decades has been made possible by entrepreneurship’s ability to absorb theories, paradigms, and methods from other fields such as economics, psychology, sociology, geography, and even biology. The respectability of entrepreneurship as an academic discipline is now evidenced by many other fields starting to borrow from the entrepreneurship view. In the present paper, seven examples are given from this “pay back” development. These examples were first presented during a seminar at the Erasmus Entrepreneurship Event called what has the entrepreneurship view to offer to other academic fields? This article elaborates on the core ideas of these presentations and focuses on the overarching question of how entrepreneurship research impacts the development of other academic fields. We found that entrepreneurship research questions the core assumptions of other academic fields and provides new insights into the antecedents, mechanisms, and consequences of their respective core phenomena. Moreover, entrepreneurship research helps to legitimize other academic fields both practically and academically.</p

Multivariate paired data analysis: multilevel PLSDA versus OPLSDA

Metabolomics data obtained from (human) nutritional intervention studies can have a rather complex structure that depends on the underlying experimental design. In this paper we discuss the complex structure in data caused by a cross-over designed experiment. In such a design, each subject in the study population acts as his or her own control and makes the data paired. For a single univariate response a paired t-test or repeated measures ANOVA can be used to test the differences between the paired observations. The same principle holds for multivariate data. In the current paper we compare a method that exploits the paired data structure in cross-over multivariate data (multilevel PLSDA) with a method that is often used by default but that ignores the paired structure (OPLSDA). The results from both methods have been evaluated in a small simulated example as well as in a genuine data set from a cross-over designed nutritional metabolomics study. It is shown that exploiting the paired data structure underlying the cross-over design considerably improves the power and the interpretability of the multivariate solution. Furthermore, the multilevel approach provides complementary information about (I) the diversity and abundance of the treatment effects within the different (subsets of) subjects across the study population, and (II) the intrinsic differences between these study subjects

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Imaging Immune Surveillance of Individual Natural Killer Cells Confined in Microwell Arrays

New markers are constantly emerging that identify smaller and smaller subpopulations of immune cells. However, there is a growing awareness that even within very small populations, there is a marked functional heterogeneity and that measurements at the population level only gives an average estimate of the behaviour of that pool of cells. New techniques to analyze single immune cells over time are needed to overcome this limitation. For that purpose, we have designed and evaluated microwell array systems made from two materials, polydimethylsiloxane (PDMS) and silicon, for high-resolution imaging of individual natural killer (NK) cell responses. Both materials were suitable for short-term studies (<4 hours) but only silicon wells allowed long-term studies (several days). Time-lapse imaging of NK cell cytotoxicity in these microwell arrays revealed that roughly 30% of the target cells died much more rapidly than the rest upon NK cell encounter. This unexpected heterogeneity may reflect either separate mechanisms of killing or different killing efficiency by individual NK cells. Furthermore, we show that high-resolution imaging of inhibitory synapse formation, defined by clustering of MHC class I at the interface between NK and target cells, is possible in these microwells. We conclude that live cell imaging of NK-target cell interactions in multi-well microstructures are possible. The technique enables novel types of assays and allow data collection at a level of resolution not previously obtained. Furthermore, due to the large number of wells that can be simultaneously imaged, new statistical information is obtained that will lead to a better understanding of the function and regulation of the immune system at the single cell level

Act or wait-and-see? Adversity, agility, and entrepreneur wellbeing across countries during the Covid-19 pandemic

How can entrepreneurs protect their wellbeing during a crisis? Does engaging agility (namely, opportunity agility and planning agility) in response to adversity help entrepreneurs safeguard their wellbeing? Activated by adversity, agility may function as a specific resilience mechanism enabling positive adaption to crisis. We studied 3,162 entrepreneurs from 20 countries during the COVID-19 pandemic and found that more severe national lockdowns enhanced firm-level adversity for entrepreneurs and diminished their wellbeing. Moreover, entrepreneurs who combined opportunity agility with planning agility experienced higher wellbeing but planning agility alone lowered wellbeing. Entrepreneur agility offers a new agentic perspective to research on entrepreneur wellbeing

Gender gaps and reentry into entrepreneurial ecosystems after business failure

Despite the significant role played by serial entrepreneurs in the entrepreneurial process, we know little about group differences in reentry decisions after business failure. Using an ecosystems framework and stigma theory, we investigate the variance in gender gaps related to the reentry decisions of 8,171 entrepreneurs from 35 countries who experienced business failures. We find evidence of persisting gender gaps that vary across ecosystem framework conditions of public stigma of business failure and public fear of business failure. Our findings shed new light on ecosystem inefficiencies that arise from multiple interactions between entrepreneurs and institutions

Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia

NF-κB is constitutively activated in chronic lymphocytic leukemia (CLL); however, the implicated molecular mechanisms remain largely unknown. Thus, we performed targeted deep sequencing of 18 core complex genes within the NF-κB pathway in a discovery and validation CLL cohort totaling 315 cases. The most frequently mutated gene was NFKBIE (21/315 cases; 7%), which encodes IκBε, a negative regulator of NF-κB in normal B cells. Strikingly, 13 of these cases carried an identical 4-bp frameshift deletion, resulting in a truncated protein. Screening of an additional 377 CLL cases revealed that NFKBIE aberrations predominated in poor-prognostic patients and were associated with inferior outcome. Minor subclones and/or clonal evolution were also observed, thus potentially linking this recurrent event to disease progression. Compared with wild-type patients, NFKBIE-deleted cases showed reduced IκBε protein levels and decreased p65 inhibition, along with increased phosphorylation and nuclear translocation of p65. Considering the central role of B cell receptor (BcR) signaling in CLL pathobiology, it is notable that IκBε loss was enriched in aggressive cases with distinctive stereotyped BcR, likely contributing to their poor prognosis, and leading to an altered response to BcR inhibitors. Because NFKBIE deletions were observed in several other B cell lymphomas, our findings suggest a novel common mechanism of NF-κB deregulation during lymphomagenesis