Affordable Loss in Entrepreneurial Internationalisation: A Focus on Finnish Biotechnology Firms

This paper develops the concept of affordable loss in the context of decision-making in entrepreneurial internationalisation and offers both an in-depth conceptual analysis and practical application in the biotechnology sector. Based on our findings, affordable loss seems to be connected to short-term, operative decisions, but is less applicable for long-term, strategic decisions. Furthermore, the use of the affordable loss principle appears to be more common in decisions involving a single decision-maker than in shared decision-making. However, we also challenge the premise of effectuation theory, as affordable loss and expected reward do not seem to present alternative elements when viewing decision-making in the context of entrepreneurial internationalisation. Instead, they are used in parallel, indicating that making a single decision may include the use of both causation and effectuation-based logic

A New Acoustic Portal into the Odontocete Ear and Vibrational Analysis of the Tympanoperiotic Complex

Global concern over the possible deleterious effects of noise on marine organisms was catalyzed when toothed whales stranded and died in the presence of high intensity sound. The lack of knowledge about mechanisms of hearing in toothed whales prompted our group to study the anatomy and build a finite element model to simulate sound reception in odontocetes. The primary auditory pathway in toothed whales is an evolutionary novelty, compensating for the impedance mismatch experienced by whale ancestors as they moved from hearing in air to hearing in water. The mechanism by which high-frequency vibrations pass from the low density fats of the lower jaw into the dense bones of the auditory apparatus is a key to understanding odontocete hearing. Here we identify a new acoustic portal into the ear complex, the tympanoperiotic complex (TPC) and a plausible mechanism by which sound is transduced into the bony components. We reveal the intact anatomic geometry using CT scanning, and test functional preconceptions using finite element modeling and vibrational analysis. We show that the mandibular fat bodies bifurcate posteriorly, attaching to the TPC in two distinct locations. The smaller branch is an inconspicuous, previously undescribed channel, a cone-shaped fat body that fits into a thin-walled bony funnel just anterior to the sigmoid process of the TPC. The TPC also contains regions of thin translucent bone that define zones of differential flexibility, enabling the TPC to bend in response to sound pressure, thus providing a mechanism for vibrations to pass through the ossicular chain. The techniques used to discover the new acoustic portal in toothed whales, provide a means to decipher auditory filtering, beam formation, impedance matching, and transduction. These tools can also be used to address concerns about the potential deleterious effects of high-intensity sound in a broad spectrum of marine organisms, from whales to fish

Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers

Gene fusions can act as oncogenic drivers and offer targets for cancer therapy. Since fusions are rare in colorectal cancer (CRC), their universal screening seems impractical. Our aim was to investigate gene fusions in 62 CRC cases with deficient MLH1 (dMLH1) and BRAFV600E wild-type (wt) status from a consecutive real-life series of 2079 CRCs. First, gene fusions were analysed using a novel FusionPlex Lung v2 RNA-based next-generation sequencing (NGS) panel, and these results were compared to a novel Idylla GeneFusion assay and pan-TRK immunohistochemistry (IHC). NGS detected seven (7/62, 11%) NTRK1 fusions (TPM3::NTRK1, PLEKHA6::NTRK1 and LMNA::NTRK1, each in two cases, and IRF2BP2::NTRK1 in one case). In addition, two ALK, four RET and seven BRAF fusions were identified. Idylla detected seven NTRK1 expression imbalances, in line with the NGS results (overall agreement 100%). Furthermore, Idylla detected the two NGS-identified ALK rearrangements as one specific ALK fusion and one ALK expression imbalance, whilst only two of the four RET fusions were discovered. However, Idylla detected several expression imbalances of ALK (n = 7) and RET (n = 1) that were found to be fusion negative with the NGS. Pan-TRK IHC showed clearly detectable, fusion partner-dependent staining patterns in the seven NTRK1 fusion cases. Overall agreement for pan-TRK antibody clone EPR17341 was 98% and for A7H6R 100% when compared to the NGS. Of the 62 CRCs, 43 were MLH1 promoter hypermethylated (MLH1ph) and 39 were RASwt. All fusion cases were both MLH1ph and RASwt. Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS

Analysis of X chromosome inactivation in autism spectrum disorders.

International audienceAutism spectrum disorders (ASD) are complex genetic disorders more frequently observed in males. Skewed X chromosome inactivation (XCI) is observed in heterozygous females carrying gene mutations involved in several X-linked syndromes. In this study, we aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 163 affected girls. The XCI pattern was also determined in two control groups (144 adult females and 40 young females) with a similar age distribution to the mothers sample and affected girls sample, respectively. We observed no significant excess of skewed XCI in families with ASD. Interestingly, two mothers and one girl carrying known mutations in X-linked genes (NLGN3, ATRX, MECP2) showed highly skewed XCI, suggesting that ascertainment of XCI could reveal families with X-linked mutations. Linkage analysis was carried out in the subgroup of multiplex families with skewed XCI (> or = 80:20) and a modest increased allele sharing was obtained in the Xq27-Xq28 region, with a peak Z-score of 1.75 close to rs719489. In summary, our results suggest that there is no major X-linked gene subject to XCI and expressed in blood cells conferring susceptibility to ASD. However, the possibility that rare mutations in X-linked genes could contribute to ASD cannot be excluded. We propose that the XCI profile could be a useful criteria to prioritize families for mutation screening of X-linked candidate genes

Fetal and Early Post-Natal Mineralization of the Tympanic Bulla in Fin Whales May Reveal a Hitherto Undiscovered Evolutionary Trait

The evolution of the cetacean skeleton followed a path that differentiated this group from other terrestrial mammals about 50 million years ago [1], and debate is still going on about the relationships between Cetacea and Artiodactyla [2], [3], [4]. Some skeletal traits of the basilosaurids (the more advanced forms of Archaeocetes), such as the expansion of the peribullary air sinuses, dental modification and vertebral size uniformity [5] are maintained and further emphasized also in contemporary odontocetes and mysticetes. Using Dual-Energy X-Ray Absorptiometry here we report that the deposition of bone mineral in fetal and newborn specimens of the fin whale Balaenoptera physalus is remarkably higher in the bulla tympanica than in the adjacent basal skull or in the rest of the skeleton. Ossification of the tympanic bulla in fetal Artiodactyla (bovine, hippopotamus) is minimal, becomes sensible after birth and then progresses during growth, contrarily to the precocious mineralization that we observed in fin whales. Given the importance of the ear bones for the precise identification of phylogenetic relationship in therian evolution [6], this feature may indicate a specific evolutionary trait of fin whales and possibly other cetacean species or families. Early mineralization of the tympanic bulla allows immediate sound conduction in the aquatic medium and consequently holds potential importance for mother-calf relationship and postnatal survival

Analysis of the FGF gene family provides insights into aquatic adaptation in cetaceans

Cetacean body structure and physiology exhibit dramatic adaptations to their aquatic environment. Fibroblast growth factors (FGFs) are a family of essential factors that regulate animal development and physiology; however, their role in cetacean evolution is not clearly understood. Here, we sequenced the fin whale genome and analysed FGFs from 8 cetaceans. FGF22, a hair follicle-enriched gene, exhibited pseudogenization, indicating that the function of this gene is no longer necessary in cetaceans that have lost most of their body hair. An evolutionary analysis revealed signatures of positive selection for FGF3 and FGF11, genes related to ear and tooth development and hypoxia, respectively. We found a D203G substitution in cetacean FGF9, which was predicted to affect FGF9 homodimerization, suggesting that this gene plays a role in the acquisition of rigid flippers for efficient manoeuvring. Cetaceans utilize low bone density as a buoyancy control mechanism, but the underlying genes are not known. We found that the expression of FGF23, a gene associated with reduced bone density, is greatly increased in the cetacean liver under hypoxic conditions, thus implicating FGF23 in low bone density in cetaceans. Altogether, our results provide novel insights into the roles of FGFs in cetacean adaptation to the aquatic environment.ope

Accelerated FoxP2 Evolution in Echolocating Bats

FOXP2 is a transcription factor implicated in the development and neural control of orofacial coordination, particularly with respect to vocalisation. Observations that orthologues show almost no variation across vertebrates yet differ by two amino acids between humans and chimpanzees have led to speculation that recent evolutionary changes might relate to the emergence of language. Echolocating bats face especially challenging sensorimotor demands, using vocal signals for orientation and often for prey capture. To determine whether mutations in the FoxP2 gene could be associated with echolocation, we sequenced FoxP2 from echolocating and non-echolocating bats as well as a range of other mammal species. We found that contrary to previous reports, FoxP2 is not highly conserved across all nonhuman mammals but is extremely diverse in echolocating bats. We detected divergent selection (a change in selective pressure) at FoxP2 between bats with contrasting sonar systems, suggesting the intriguing possibility of a role for FoxP2 in the evolution and development of echolocation. We speculate that observed accelerated evolution of FoxP2 in bats supports a previously proposed function in sensorimotor coordination

Once bitten, not necessarily shy? Determinants of foreign market re-entry commitment strategies

We investigate foreign market re-entry commitment strategies, namely the changes in the modes of operation (commitment) undertaken by multinational enterprises (MNEs) as they return to foreign markets from which they had previously exited. We combine organisational learning theory with the institutional change literature to examine the antecedents of re-entry commitment strategies. From an analysis of 1,020 re-entry events between 1980 and 2016, we find that operation mode prior to exit is a strong predictor of subsequent re-entry mode. Contrary to the predictions of learning theory, we did not find support for the effect of experience accumulated during the initial market endeavour on the re-entry commitment strategies of MNEs. In turn, exit motives significantly impact on the re-entrants' decision to re-enter via a different mode of operation, by either increasing or decreasing their commitment to the market. We show that re-entrants do not replicate unsuccessful operation mode strategies if they had previously underperformed in the market. When favourable host institutional changes occur during the time-out period re-entrants tend to increase commitment in the host market irrespective of the degree of prior experience accumulated in the market

Association between sporting event attendance and self-rated health: an analysis of multiyear cross-sectional national data in Japan

Background This study examined the extent to which sporting event attendance is associated with self-rated health. Drawing from an economic model of health production and psychological research on the health benefits of psychosocial resources, sporting event attendance was hypothesized to have a positive relationship with self-rated health. Methods A two-level multilevel ordered logistic regression was used to analyze multiyear cross-sectional data collected from national surveys in Japan. Results The results demonstrate that, controlling for the effects of personal and environmental characteristics, sporting event attendance positively correlates with self-rated health over a 12-year period. Specifically, when compared to individuals who did not attend any sporting event during the past year, those who attended a sporting event were 33% more likely to indicate a higher level of self-rated health. Conclusions These findings provide evidence for a positive association between sport spectatorship and the perception of general health and contribute to the literature examining the relationship between sport spectatorship and health outcomes