The ‘Who’ and ‘How’ of Operational Alignment for Digital Innovation (Units)

To harness the value of digital technologies, incumbents establish digital innovation units (DIU). In pursuing digital innovation outcomes, DIUs follow activities along the innovation process that are carried out in collaboration with other organizational units. Collaboration has been identified as a specific DIU challenge. However, prior studies do not go beyond DIU-centric research on their setup, objectives, and challenges. In practice, DIUs become increasingly integrated with the organization as news and bad press about their performance up to discontinuance appears. The lack of knowledge on integrating DIUs with other organizational units, coupled with the practical relevance of realizing value from digital innovation, calls for an investigation into the operational alignment of DIUs. Rooted in digital innovation and business-IT alignment research, we analyze the digital innovation process, involved units, and corresponding aligning actions based on a multiple case study. We show that aligning for digital innovation happens in two modes depending on the DIU\u27s structural positioning and innovation orientation: a triangle (business-IT-DIU) and a dual mode (business-DIU). First, we go beyond a DIU-centric perspective and shed light on the interaction of multiple units pursuing digital innovation from initiation to exploitation. Second, we contribute to research on business-IT alignment by expanding it with the perspective of digital units and outlining operational aligning activities, enhancing our understanding of how organizations can exploit their explorative digital innovation activities

Exploiting Exploration: Reintegrating Digital Innovations from Digital Innovation Units

In digital transformation, incumbents are pressured to exploit their core business and simultaneously explore opportunities for digital innovation. When pursuing ambidexterity, organizations establish digital innovation units (DIUs) dedicated to digital innovation. Due to the novelty of the phenomenon, prior studies targeted DIUs' design, objectives, and challenges. However, their value lies in reintegrating digital innovations back into the operational organization for use and commercialization, which has been neglected so far. Thus, we analyze the reintegration based on a single-embedded case study of four heterogeneous DIUs. We identify three phases of reintegration activities and trace differences to the contextual factors: innovation orientation, number of involved entities, and ownership. Our contribution is twofold. First, we shed light on the reintegration of DIUs' innovation outcomes for the first time. Second, we extend research on digital innovation and ambidexterity by outlining drivers and inhibitors of reintegration, enhancing our understanding of how organizations can exploit exploration

Variability in cTBS Aftereffects Attributed to the Interaction of Stimulus Intensity With BDNF Val66Met Polymorphism

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts

Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression

Publisher Copyright: © 2022, The Author(s).Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies.Peer reviewe

Dynamic partitioning of branched-chain amino acids-derived nitrogen supports renal cancer progression.

Metabolic reprogramming is critical for tumor initiation and progression. However, the exact impact of specific metabolic changes on cancer progression is poorly understood. Here, we integrate multimodal analyses of primary and metastatic clonally-related clear cell renal cancer cells (ccRCC) grown in physiological media to identify key stage-specific metabolic vulnerabilities. We show that a VHL loss-dependent reprogramming of branched-chain amino acid catabolism sustains the de novo biosynthesis of aspartate and arginine enabling tumor cells with the flexibility of partitioning the nitrogen of the amino acids depending on their needs. Importantly, we identify the epigenetic reactivation of argininosuccinate synthase (ASS1), a urea cycle enzyme suppressed in primary ccRCC, as a crucial event for metastatic renal cancer cells to acquire the capability to generate arginine, invade in vitro and metastasize in vivo. Overall, our study uncovers a mechanism of metabolic flexibility occurring during ccRCC progression, paving the way for the development of novel stage-specific therapies

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.</p

A Taxonomy for Digital Process Innovation

Digital process innovation (DPI) is anchored to the continuous optimization and redefinition of business processes based on digital technologies. DPI is central for digital transformation as it enables organizations to maintain competitiveness and operational excellence in a world shaped by short innovation cycles and boundary-spanning forces of change. Knowledge on DPI stems from separate communities: digital innovation and business process management (BPM). Consequently, DPI currently lacks an integrated perspective at the junction of operational processes and digital innovation. To address this gap, we characterize DPI and develop a taxonomy, drawing on the theoretical lens of sociotechnical systems and empirical data from 26 expert interviews. We provide a comprehensive overview of DPI characteristics and derive four interrelated tensions across its sociotechnical components. Our contribution is twofold. First, we add to contemporary discussions on how digital innovation challenges traditional BPM. Second, we expand research on digital innovation with respect to organizational processe

Introducing (Machine) Learning Ability as Antecedent of Trust in Intelligent Systems

Artificial intelligence enables the emergence of novel intelligent decision support systems (IDSSs). Despite the potential for increased efficiency, mixed evidence on user aversion to or appreciation for such intelligent systems prevails, questioning user trust in algorithmic decision support. Recent advances in machine learning facilitate the incorporation of a promising driver of trust into the systems: the systems’ ability to learn. In this study, we conduct an experiment, manipulating the type of decision support (human vs. automated) and their learning ability in the context of a clinical decision support system. Results indicate increased trust in automated decision support with the ability to learn. Our findings contribute to theory and practice, identifying (machine) learning as an antecedent of trust, thereby enhancing our understanding of user perceptions of IDSSs. Furthermore, we add to literature on algorithm aversion by showing that people readily rely on algorithmic support in the context of clinical decision making