Competition, Technology Licensing-in, and Innovation

This is the author accepted manuscript. The final version is available from INFORMS via the DOI in this recordAlthough the relationship between competition and firm innovation has long been of scholarly interest, prior research has predominantly considered changes in internal research and development (R&D) as a strategic response to competitors’ actions. In this study, we focus on one of the most important and commonly observed contractual mechanisms used to acquire external technologies: technology licensing. Surprisingly, licensing has been mostly overlooked by prior studies examining the effect of competition on firms’ allocation of R&D. We take into account the unique properties of licensing and systematically link them to the demands arising from the competitive pressure caused by rivals’ launches of new products. Furthermore, we discuss how licensing-in decisions ultimately shape a firm’s subsequent innovation in areas where they are threatened by competitors and how such innovation depends on the cumulative R&D investments inside the organization into which licensed knowledge is added. We test our theoretical model through a longitudinal design that tracks the licensing-in and innovation outcomes of firms in the global biopharmaceutical industry. Accounting for the endogenous selection of firms into licensing, our findings illustrate that licensing-in is motivated by competitive pressures. We also find that licensing-in increases a firm’s capacity to innovate in areas where competitors have exerted pressure, particularly in the presence of cumulative R&D investments. In so doing, the paper anchors technology licensing as a key organizational action that helps increase our understanding of the important relationship between competition and innovation

Cross-reactive LTP sensitization in food-dependent exercise-induced urticaria/anaphylaxis: a pilot study of a component-resolved and in vitro depletion approach

Background: Challenge tests for food-dependent exercise-induced anaphylaxis (FDEIA) carry some risk and have a high rate of false negatives. Our aim was to explore the usefulness of an in vitro immunodepletion assay and an allergen microarray test in the identification of IgE-mediated cross-reactive food allergens in patients with suspected FDEIA or food-dependent exercise-induced urticaria and panallergen sensitization. Methods: Three patients with a history of food dependent exercise induced urticaria/anaphylaxis and food panallergen sensitization in whom a food-exercise challenge was not feasible were selected: a 25-year-old man with cholinergic urticaria who experienced generalized urticaria and angioedema during a soccer match after drinking a peach-based soft drink; a 19-year-old woman with allergic rhinitis and controlled asthma who experienced anaphylactic shock while playing soccer, having eaten walnuts in the previous 90 min; and a 57-year-old man with baker’s asthma who experienced four episodes of anaphylaxis during exercise after ingesting wheat-containing food. All individuals underwent a diagnostic work-up with skin prick tests, specific IgE (sIgE) and ImmunoCAP ISAC test. For the in vitro immunodepletion procedure, patients’ serum was pre-incubated with the suspected native allergen (peach, walnut, or wheat) in solid phase (ImmunoCAP). The eluted serum, containing unbound IgE, was collected and samples were re-tested using Immunocap ISAC 112 and compared with baseline results. Results: All individuals were sensitized to lipid transfer proteins. The first patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; after pre-incubation with peach there was 100% depletion of sIgE to all components. The second patient was sensitized to Pru p 3, Cor a 8, Jug r 3, and Ara h 9; immunodepletion with walnut depleted sIgE to Ara h 9 by 67%, Pru p 3 and Pla a 3 (60%), Art v 3 (75%), Jug r 3 (88%), and Cor a 8 (100%). The third patient was sensitized to Pru p 3, Jug r 3, Ara h 9, and Tri a 14; immunodepletion with wheat depleted Tri a 14 only (100%). Conclusions: In vitro immunodepletion might be a useful diagnostic tool in food dependent exercise induced urticaria/anaphylaxis with panallergen sensitization, particularly for identifying the culprit allergen and guiding dietary elimination recommendations

Informational Gene Phylogenies Do Not Support a Fourth Domain of Life for Nucleocytoplasmic Large DNA Viruses

Mimivirus is a nucleocytoplasmic large DNA virus (NCLDV) with a genome size (1.2 Mb) and coding capacity ( 1000 genes) comparable to that of some cellular organisms. Unlike other viruses, Mimivirus and its NCLDV relatives encode homologs of broadly conserved informational genes found in Bacteria, Archaea, and Eukaryotes, raising the possibility that they could be placed on the tree of life. A recent phylogenetic analysis of these genes showed the NCLDVs emerging as a monophyletic group branching between Eukaryotes and Archaea. These trees were interpreted as evidence for an independent “fourth domain” of life that may have contributed DNA processing genes to the ancestral eukaryote. However, the analysis of ancient evolutionary events is challenging, and tree reconstruction is susceptible to bias resulting from non-phylogenetic signals in the data. These include compositional heterogeneity and homoplasy, which can lead to the spurious grouping of compositionally-similar or fast-evolving sequences. Here, we show that these informational gene alignments contain both significant compositional heterogeneity and homoplasy, which were not adequately modelled in the original analysis. When we use more realistic evolutionary models that better fit the data, the resulting trees are unable to reject a simple null hypothesis in which these informational genes, like many other NCLDV genes, were acquired by horizontal transfer from eukaryotic hosts. Our results suggest that a fourth domain is not required to explain the available sequence data

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Fixed-time artificial insemination in beef cattle

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background: The study was designed to test the effect of fixed-time artificial insemination (fixed-AI) after the slightly modified Ovsynch protocol on the pregnancy rate in beef cattle in Finnish field conditions. The modification was aimed to optimize the number of offsprings per AI dose. Methods: Ninety Charolais cows and heifers were entered into the program an average of 1.8 times. Thus, 164 animal cases were included. Animals were administered 10-12 μg of buserelin. Seven days later animals without a corpus luteum (CL) were rejected (20.7%) while the remaining 130 cases with a CL were administered prostaglandin F2α, followed 48 h later with a second injection of buserelin (8-10 μg). Fixed-AI was performed 16-20 hours after the last injection. Results: The pregnancy rate was 51.5 % (67/130). The pregnancy rate after a short interval (50-70 d) from calving to entering the program was significantly higher than that after a long interval (>70 d). Conclusion: This protocol seems to give acceptable pregnancy results in beef herds and its effect on saving labour is notable

Altering micro-environments to change population health behaviour: towards an evidence base for choice architecture interventions.

BACKGROUND: The idea that behaviour can be influenced at population level by altering the environments within which people make choices (choice architecture) has gained traction in policy circles. However, empirical evidence to support this idea is limited, especially its application to changing health behaviour. We propose an evidence-based definition and typology of choice architecture interventions that have been implemented within small-scale micro-environments and evaluated for their effects on four key sets of health behaviours: diet, physical activity, alcohol and tobacco use. DISCUSSION: We argue that the limitations of the evidence base are due not simply to an absence of evidence, but also to a prior lack of definitional and conceptual clarity concerning applications of choice architecture to public health intervention. This has hampered the potential for systematic assessment of existing evidence. By seeking to address this issue, we demonstrate how our definition and typology have enabled systematic identification and preliminary mapping of a large body of available evidence for the effects of choice architecture interventions. We discuss key implications for further primary research, evidence synthesis and conceptual development to support the design and evaluation of such interventions. SUMMARY: This conceptual groundwork provides a foundation for future research to investigate the effectiveness of choice architecture interventions within micro-environments for changing health behaviour. The approach we used may also serve as a template for mapping other under-explored fields of enquiry

Long-Term Monitoring of Fecal Steroid Hormones in Female Snow Leopards (Panthera uncia) during Pregnancy or Pseudopregnancy

Knowledge of the basic reproductive physiology of snow leopards is required urgently in order to develop a suitable management conditions under captivity. In this study, the long-term monitoring of concentrations of three steroid hormones in fecal matter of three female snow leopards was performed using enzyme immunoassays: (1) estradiol-17β, (2) progesterone and (3) cortisol metabolite. Two of the female animals were housed with a male during the winter breeding season, and copulated around the day the estradiol-17β metabolite peaked subsequently becoming pregnant. The other female was treated in two different ways: (1) first housed with a male in all year round and then (2) in the winter season only. She did not mate with him on the first occasion, but did so latter around when estradiol-17β metabolite peaked, and became pseudopregnant. During pregnancy, progesterone metabolite concentrations increased for 92 or 94 days, with this period being approximately twice as long as in the pseudopregnant case (31, 42, 49 and 53 days). The levels of cortisol metabolite in the pseudopregnant female (1.35 µg/g) were significantly higher than in the pregnant females (0.33 and 0.24 µg/g) (P<0.05). Similarly, during the breeding season, the levels of estradiol-17β metabolite in the pseudopregnant female (2.18 µg/g) were significantly higher than those in the pregnant females (0.81 and 0.85 µg/g) (P<0.05). Unlike cortisol the average levels of estradiol-17β during the breeding season were independent of reproductive success

Fires can benefit plants by disrupting antagonistic interactions

Fire has a key role in the ecology and evolution of many ecosystems, yet its effects on plant–insect interactions are poorly understood. Because interacting species are likely to respond to fire differently, disruptions of the interactions are expected. We hypothesized that plants that regenerate after fire can benefit through the disruption of their antagonistic interactions. We expected stronger effects on interactions with specialist predators than with generalists. We studied two interactions between two Mediterranean plants (Ulex parviflorus, Asphodelus ramosus) and their specialist seed predators after large wildfires. In A. ramosus we also studied the generalist herbivores. We sampled the interactions in burned and adjacent unburned areas during 2 years by estimating seed predation, number of herbivores and fruit set. To assess the effect of the distance to unburned vegetation we sampled plots at two distance classes from the fire perimeter. Even 3 years after the fires, Ulex plants experienced lower seed damage by specialists in burned sites. The presence of herbivores on Asphodelus decreased in burned locations, and the variability in their presence was significantly related to fruit set. Generalist herbivores were unaffected. We show that plants can benefit from fire through the disruption of their antagonistic interactions with specialist seed predators for at least a few years. In environments with a long fire history, this effect might be one additional mechanism underlying the success of fire-adapted plants