Incumbent Responses to an Entrant with a New Business Model: Resource Co-Deployment and Resource Re-Deployment Strategies

The constructs of re-deployment and co-deployment have been central to discussions of scope economies in diversified firms. We argue however that these constructs are also significant in the context of single business firms. Increasingly, changes in technology and demand preferences have provided opportunities for entrants to attack incumbents with a different business model, one that may neutralize the incumbent’s advantage for at least some set of customers (e.g. Netflix versus Blockbuster). In such a context incumbents often respond by modifying their business model. We note that several of the business model-altering responses of the incumbent can be characterized in terms of co-deployment and re-deployment benefits and costs, where co-deployment benefits/cost apply to the scope economies/diseconomies in running multiple business-models within the same firm and re-deployment benefits/costs apply to the implications of moving assets from one business model to another. We then examine the set of strategic choices faced by the incumbent in competing with an entrant with a different business model. We identify five set of factors that are likely to influence the decision to choose between these alternatives – uncertainty spawned by the new business model, market segment targeted by the new model, the within-business-across-business-model co-deployment and re-deployment benefits and costs, the across-business co-deployment and re-deployment benefits and costs, and the incumbent’s prior performance history. Although some of these choices have seen some work, most remain relatively underexplored in the strategy literature. We highlight the potential for research in this area with a set of propositions that identify key conditions that should hold true for a particular strategic choice to be picked by an incumbent

From Business Model to Business Modelling: Modularity and Manipulation

The concept of modularity has gained considerable traction in technology studies as a way to conceive, describe and innovate complex systems, such as product design or organizational structures. In the recent literature, technological modularity has often been intertwined with business model innovation, and scholarship has started investigating how modularity in technology affects changes in business models, both at the cognitive and activity system levels. Yet we still lack a theoretical definition of what modularity is in the business model domain. Business model innovation also encompasses different possibilities of modeling businesses, which are not clearly understood nor classified. We ask when, how and if modularity theory can be extended to business models in order to enable effective and efficient modeling. We distinguish theoretically between modularity for technology and for business models, and investigate the key processes of modularization and manipulation. We introduce the basic operations of business modeling via modular operators adapted from the technological modularity domain, using iconic examples to develop an analogical reasoning between modularity in technology and in business models. Finally, we discuss opportunities for using modularity theory to foster the understanding of business models and modeling, and develop a challenging research agenda for future investigations

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

The role of oxidative stress in the pathogenesis of Alzheimer's disease

[ES]: La presencia de estrés oxidativo es la característica más temprana de la Enfermedad de Alzheimer (EA), lo cual proporciona un atractivo objetivo para intervenciones terapéuticas. Entre los mayores retos que se presentan actualmente están el establecimiento de la fuente de estrés oxidativo y la determinación de cómo este proceso puede influir en la etiología de la Enfermedad de Alzheimer. Este es un tema complejo, pues varios procesos, enzimáticos y no-enzimáticos, están implicados en la formación de oxígeno reactivo y otras moléculas tóxicas. En este artículo discutimos el progreso en el entendimiento de estos procesos[EN]: Oxidative stress is the earliest feature of Alzheimer disease and an attractive therapeutic target. One of the major challenges today is to establish the source of the reactive oxygen and to determine the role of oxidative stress in the etiology of Alzheimer disease. This is a complex issue since a variety of enzymatic and non-enzymatic processes are involved in the formation of reactive oxygen and other toxic molecules. In this review, we discuss progress in the understanding of these processes.Peer reviewe

How to Develop Strategic Management Competency: Reconsidering the Learning Goals and Knowledge Requirements of the Core Strategy Course

The dominance of theory-based approaches to strategy teaching has not displaced the need for core courses in strategic management to cultivate broader management skills. Yet, limited attention has been given to explicating, first, why we need to teach these skills, second, which skills we need to teach, and third how they can to be developed in the classroom. To help answer these three questions we need to understand the linkages between theory-based and skills-based approaches to strategy teaching. We begin with the proposition that the purpose of the core strategic management is to develop the strategic management competency of our students. We then adopt a systematic approach to identifying the why, what, and how components of strategic management competency. We show why analytical tools need to be complemented by judgment, insight, intuition, creativity, and social and communicative skills. We outline what these skills are and where they come from. Finally, we derive implications for how we should design and deliver of the core strategic management course

Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G>C Variant in SMN2

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype-phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype-phenotype correlations and improve prognostic outcomes

Hsmar1 transposition is sensitive to the topology of the transposon donor and the target

Hsmar1 is a member of the Tc1-mariner superfamily of DNA transposons. These elements mobilize within the genome of their host by a cut-and-paste mechanism. We have exploited the in vitro reaction provided by Hsmar1 to investigate the effect of DNA supercoiling on transposon integration. We found that the topology of both the transposon and the target affect integration. Relaxed transposons have an integration defect that can be partially restored in the presence of elevated levels of negatively supercoiled target DNA. Negatively supercoiled DNA is a better target than nicked or positively supercoiled DNA, suggesting that underwinding of the DNA helix promotes target interactions. Like other Tc1-mariner elements, Hsmar1 integrates into 5′-TA dinucleotides. The direct vicinity of the target TA provides little sequence specificity for target interactions. However, transposition within a plasmid substrate was not random and some TA dinucleotides were targeted preferentially. The distribution of intramolecular target sites was not affected by DNA topology

Adaptation and Preadaptation of Salmonella enterica to Bile

Bile possesses antibacterial activity because bile salts disrupt membranes, denature proteins, and damage DNA. This study describes mechanisms employed by the bacterium Salmonella enterica to survive bile. Sublethal concentrations of the bile salt sodium deoxycholate (DOC) adapt Salmonella to survive lethal concentrations of bile. Adaptation seems to be associated to multiple changes in gene expression, which include upregulation of the RpoS-dependent general stress response and other stress responses. The crucial role of the general stress response in adaptation to bile is supported by the observation that RpoS− mutants are bile-sensitive. While adaptation to bile involves a response by the bacterial population, individual cells can become bile-resistant without adaptation: plating of a non-adapted S. enterica culture on medium containing a lethal concentration of bile yields bile-resistant colonies at frequencies between 10−6 and 10−7 per cell and generation. Fluctuation analysis indicates that such colonies derive from bile-resistant cells present in the previous culture. A fraction of such isolates are stable, indicating that bile resistance can be acquired by mutation. Full genome sequencing of bile-resistant mutants shows that alteration of the lipopolysaccharide transport machinery is a frequent cause of mutational bile resistance. However, selection on lethal concentrations of bile also provides bile-resistant isolates that are not mutants. We propose that such isolates derive from rare cells whose physiological state permitted survival upon encountering bile. This view is supported by single cell analysis of gene expression using a microscope fluidic system: batch cultures of Salmonella contain cells that activate stress response genes in the absence of DOC. This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations

Fluoxetine Counteracts the Cognitive and Cellular Effects of 5-Fluorouracil in the Rat Hippocampus by a Mechanism of Prevention Rather than Recovery

5-Fluorouracil (5-FU) is a cytostatic drug associated with chemotherapy-induced cognitive impairments that many cancer patients experience after treatment. Previous work in rodents has shown that 5-FU reduces hippocampal cell proliferation, a possible mechanism for the observed cognitive impairment, and that both effects can be reversed by co-administration of the antidepressant, fluoxetine. In the present study we investigate the optimum time for administration of fluoxetine to reverse or prevent the cognitive and cellular effects of 5-FU