How employees experience digital transformation: a dynamic and multi-layered sensemaking perspective.

The capacity to deal with digital transformation is a valuable asset for established organizations, and employees play a crucial role in this process. This study contributes to the understanding of employees’ sensemaking of digital transformation in the tour operating industry. Using prior digital transformation research, construal-level theory (CLT), and dynamic change perspectives, our scholarly work focuses on the complexities of organizational change in a digital transformation context. Although employees generally support digital transformation, our findings show that their perceptions change over time across a range of specific challenges experienced during the employee change journey. Our findings stress the importance of adopting a social exchange lens in digital transformation knowledge as this represents deep structure change that might cause well-designed transformation processes to fail. Implications for hospitality and tourism management are discussed

The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

Keystone symposium: The role of microenvironment in tumor induction and progression, Banff, Canada, 5–10 February 2005

The first Keystone symposium on the role of microenvironment in tumor induction and progression attracted 274 delegates from 13 countries to Banff in the heart of the Canadian Rockies. The meeting was organized by Mina Bissell, Ronald DePinho and Luis Parada, and was held concurrently with the Keystone symposium on cancer and development, chaired by Matthew Scott and Roeland Nusse. The 30 oral presentations and over 130 posters provided an excellent forum for discussing emerging data in this rapidly advancing field

An Excursion-Theoretic Approach to Stability of Discrete-Time Stochastic Hybrid Systems

We address stability of a class of Markovian discrete-time stochastic hybrid systems. This class of systems is characterized by the state-space of the system being partitioned into a safe or target set and its exterior, and the dynamics of the system being different in each domain. We give conditions for $L_1$-boundedness of Lyapunov functions based on certain negative drift conditions outside the target set, together with some more minor assumptions. We then apply our results to a wide class of randomly switched systems (or iterated function systems), for which we give conditions for global asymptotic stability almost surely and in $L_1$. The systems need not be time-homogeneous, and our results apply to certain systems for which functional-analytic or martingale-based estimates are difficult or impossible to get.Comment: Revised. 17 pages. To appear in Applied Mathematics & Optimizatio

High density of peritumoral lymphatic vessels is a potential prognostic marker of endometrial carcinoma: a clinical immunohistochemical method study

<p>Abstract</p> <p>Background</p> <p>The lymphatic system is a major route for cancer cell dissemination and also a potential target for antitumor therapy. To investigate whether increased lymphatic vessel density (LVD) is a prognostic factor for nodal metastasis and survival, we studied peritumoral LVD (P-LVD) and intratumoral LVD (I-LVD) in samples from 102 patients with endometrial carcinoma;</p> <p>Methods</p> <p>Endometrial carcinoma tissues were analyzed for lymphatic vessels by immunohistochemical staining with an antibody against LYVE-1. Univariate analysis was performed with Kaplan-Meier life-table curves to estimate survival, and was compared using the log rank test. Prognostic models used multivariate Cox regression analysis for multivariate analyses of survival;</p> <p>Results</p> <p>Our study showed that P-LVD, but not I-LVD, was significantly correlated with lymph vascular space invasion (LVSI), lymph node metastasis, tumor stage, and CD44 expression in endometrial carcinoma. Moreover, P-LVD was an independent prognostic factor for progression-free survival and overall survival of endometrial carcinoma;</p> <p>Conclusions</p> <p>P-LVD may serve as a prognostic factor for endometrial carcinoma. The peritumoral lymphatics might play an important role in lymphatic vessel metastasis.</p

Modeling Time in Computing: A Taxonomy and a Comparative Survey

The increasing relevance of areas such as real-time and embedded systems, pervasive computing, hybrid systems control, and biological and social systems modeling is bringing a growing attention to the temporal aspects of computing, not only in the computer science domain, but also in more traditional fields of engineering. This article surveys various approaches to the formal modeling and analysis of the temporal features of computer-based systems, with a level of detail that is suitable also for non-specialists. In doing so, it provides a unifying framework, rather than just a comprehensive list of formalisms. The paper first lays out some key dimensions along which the various formalisms can be evaluated and compared. Then, a significant sample of formalisms for time modeling in computing are presented and discussed according to these dimensions. The adopted perspective is, to some extent, historical, going from "traditional" models and formalisms to more modern ones.Comment: More typos fixe

The clinical potential of antiangiogenic fragments of extracellular matrix proteins

Neovasculature development is a crucial step in the natural history of a cancer. While much emphasis has been placed on proangiogenic growth factors such as VEGF, it is clear that endogenous angiogenesis inhibitors also have critical roles in the regulation of this process. Recent research has identified several cryptic fragments of extracellular matrix/vascular basement membrane proteins that have potent antiangiogenic properties in vivo. It has become apparent that many of these fragments signal via interactions with endothelial integrins, although multiple downstream effector pathways have been implicated and endostatin, the first non-collagenous domain of collagen XVIII, influences an intricate signalling network. The activity of these molecules in animal models suggests that they may have significant clinical activity; however, results of phase I/II trials with endostatin were disappointing. Many possible reasons can be found for the failure of these studies. Weaknesses in trial design, endostatin administration regimen and patient selection are identifiable, and importantly the lack of a clearly defined antiangiogenic mechanism for endostatin hindered assessment of biologically effective dose. Additionally, in vivo immunological and proteolytic function-neutralising mechanisms may have negated endostatin's actions. Lessons learned from these studies will aid the future clinical development of other antiangiogenic extracellular matrix protein fragments