BEING AGILE TO THRIVE AMIDST DISRUPTIVE DIGITAL INNOVATIONS

Firms around the world have been experiencing disruptive digital innovation. Such disruptionsaffect their business operations and models over time and geography. In this paper, we adopt Lucas and Goh’s (2009) framework of disruption responseto examine how do firms achieve agility in responding to disruptive digital innovation. The framework draws on dynamic capability theory, disruptive innovation concept, organizational agility concept and organizational core rigidity concept. This research-in-progress paper aims to conduct an in-depth case studyto understand how firms can be agile in responding to disruptive digital innovation. As a case study, this study adds to the growing corpus of literature on disruptive digital innovation. Theoretically, this study extends Lucas and Goh’s (2009) framework of disruption response, underpinning the advancement of knowledge in this area. The managerialinsights gleaned from this study can also guide firmsin being agile and thrive amidst disruptive digital innovations

Agility in responding to disruptive digital innovation: Case study of an SME

Disruptive digital innovation (DDI) often creates hypercompetitive market environment that forces firms to be agile to survive and remain competitive. Whereas most studies have focused on larger firms' effort to be agile, few have looked at how small‐ and medium‐sized enterprises (SMEs) respond to DDI. The study attempts to answer the research question of how SMEs achieve agility to respond to DDI. Drawing on a case study of an innovative SME, our study develops a framework on agility based on the processes of mitigating organizational rigidity, developing innovative capabilities, and balancing the tension of organizational ambidexterity. Specifically, our findings show that for SMEs, mitigating organizational rigidity is enabled by the mechanism of achieving boundary openness while developing innovative capability is enabled by the mechanism of achieving organizational adaptability. At the same time, given the inherent challenges of resource constraints, SMEs also need to balance the tension of organizational ambidexterity

Conflicts in Knowledge Management: Vistiting the Hidden Partner

As knowledge gains a reputation for being a critical resource in the information-intensive economy, organizations have doubled their efforts in trying to extract value from knowledge management policies. One particular aspect of knowledge management, which has gone unnoticed in academic research, is the presence of conflicts in knowledge activities. By adopting a conflict perspective of knowledge activities, this study arrives at a two-dimensional framework that defines knowledge conflicts in terms of its type and nature. Central to this paper is the fundamental idea that conflicts form an integral part of knowledge management and depending on how they are managed; conflicts may be formidable partners or dangerous adversaries in the corporate quest for knowledge-derived competitiveness

The Genetic Architecture of Noise-Induced Hearing Loss: Evidence for a Gene-by-Environment Interaction.

The discovery of environmentally specific genetic effects is crucial to the understanding of complex traits, such as susceptibility to noise-induced hearing loss (NIHL). We describe the first genome-wide association study (GWAS) for NIHL in a large and well-characterized population of inbred mouse strains, known as the Hybrid Mouse Diversity Panel (HMDP). We recorded auditory brainstem response (ABR) thresholds both pre and post 2-hr exposure to 10-kHz octave band noise at 108 dB sound pressure level in 5-6-wk-old female mice from the HMDP (4-5 mice/strain). From the observation that NIHL susceptibility varied among the strains, we performed a GWAS with correction for population structure and mapped a locus on chromosome 6 that was statistically significantly associated with two adjacent frequencies. We then used a "genetical genomics" approach that included the analysis of cochlear eQTLs to identify candidate genes within the GWAS QTL. In order to validate the gene-by-environment interaction, we compared the effects of the postnoise exposure locus with that from the same unexposed strains. The most significant SNP at chromosome 6 (rs37517079) was associated with noise susceptibility, but was not significant at the same frequencies in our unexposed study. These findings demonstrate that the genetic architecture of NIHL is distinct from that of unexposed hearing levels and provide strong evidence for gene-by-environment interactions in NIHL

Genetic regulation of mouse liver metabolite levels.

We profiled and analyzed 283 metabolites representing eight major classes of molecules including Lipids, Carbohydrates, Amino Acids, Peptides, Xenobiotics, Vitamins and Cofactors, Energy Metabolism, and Nucleotides in mouse liver of 104 inbred and recombinant inbred strains. We find that metabolites exhibit a wide range of variation, as has been previously observed with metabolites in blood serum. Using genome-wide association analysis, we mapped 40% of the quantified metabolites to at least one locus in the genome and for 75% of the loci mapped we identified at least one candidate gene by local expression QTL analysis of the transcripts. Moreover, we validated 2 of 3 of the significant loci examined by adenoviral overexpression of the genes in mice. In our GWAS results, we find that at significant loci the peak markers explained on average between 20 and 40% of variation in the metabolites. Moreover, 39% of loci found to be regulating liver metabolites in mice were also found in human GWAS results for serum metabolites, providing support for similarity in genetic regulation of metabolites between mice and human. We also integrated the metabolomic data with transcriptomic and clinical phenotypic data to evaluate the extent of co-variation across various biological scales

Intestinal cell type-specific communication networks underlie homeostasis and response to Western diet

The small intestine plays a key role in immunity and mediates inflammatory responses to high fat diets. We have used single-cell RNA-sequencing (scRNA-seq) and statistical modeling to examine gaps in our understanding of the dynamic properties of intestinal cells and underlying cellular mechanisms. Our scRNA-seq and flow cytometry studies of different layers of intestinal cells revealed new cell subsets and modeled developmental trajectories of intestinal intraepithelial lymphocytes, lamina propria lymphocytes, conventional dendritic cells, and enterocytes. As compared to chow-fed mice, a high-fat high-sucrose (HFHS) "Western" diet resulted in the accumulation of specific immune cell populations and marked changes to enterocytes nutrient absorption function. Utilizing ligand-receptor analysis, we profiled high-resolution intestine interaction networks across all immune cell and epithelial structural cell types in mice fed chow or HFHS diets. These results revealed novel interactions and communication hubs among intestinal cells, and their potential roles in local as well as systemic inflammation

Collaborative interactions of heterogenous ribonucleoproteins contribute to transcriptional regulation of sterol metabolism in mice.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of functionally versatile proteins that play critical roles in the biogenesis, cellular localization and transport of RNA. Here, we outline a role for hnRNPs in gene regulatory circuits controlling sterol homeostasis. Specifically, we find that tissue-selective loss of the conserved hnRNP RALY enriches for metabolic pathways. Liver-specific deletion of RALY alters hepatic lipid content and serum cholesterol level. In vivo interrogation of chromatin architecture and genome-wide RALY-binding pattern reveal insights into its cooperative interactions and mode of action in regulating cholesterogenesis. Interestingly, we find that RALY binds the promoter region of the master metabolic regulator Srebp2 and show that it directly interacts with coactivator Nuclear Transcription Factor Y (NFY) to influence cholesterogenic gene expression. Our work offers insights into mechanisms orchestrating selective promoter activation in metabolic control and a model by which hnRNPs can impact health and disease states