Biophysical Mechanisms of Early Heart Morphogenesis

The heart is the first functioning organ in the developing embryo. Initially, the heart is a relatively straight tube created by folding and fusion of the cardiogenic fields, which lie bilaterally within the blastoderm. Shortly after formation, the primitive heart tube (HT) undergoes the morphogenetic process of c-looping as it bends and twists into a c-shaped tube. All these transformations require physical forces, which remain poorly understood. The aim of this dissertation is to elucidate some of the biophysical mechanisms that create and shape the early HT. Our work involves a combination of ex ovo experiments and computational modeling. Experiments were performed on embryonic chicken hearts, which are morphologically similar to human hearts during development. First, we explored a somewhat puzzling aspect of early heart development. Previous studies have shown that myosin-II-based cytoskeletal contraction is required for fusion of the heart fields before looping begins, but not as these tissues continue to fuse and extend the length of the HT during subsequent c-looping. To investigate this fundamental change in behavior, we focused on the tissues around the anterior intestinal portal (AIP), where fusion takes place. Our results indicate that stiffness and tangential tension decreased bilaterally with distance from the embryonic midline along the AIP. The stiffness and tension gradients increased to peaks at Hamburger-Hamilton (HH) stage 9 and decreased immediately afterward. Along with experimental results of contraction inhibition, finite-element models indicate that the measured mechanical gradients are consistent with a relatively uniform contraction of the endoderm along the AIP. Taken together, these results suggest that, before looping begins at HH10, cytoskeletal contraction pulls the bilateral cardiogenic fields toward the midline where they begin to fuse to create the HT. By HH10, however, the fusion process is far enough along to enable apposing cardiac progenitor cells to subsequently undergo filopodia-mediated “zippering” without the continuing need for contraction. Next, in light of recently published data, we examined the possible role of differential hypertrophic growth in driving the bending component of c-looping. Using cultured isolated hearts, which bend without the complicating effects of external loads, we found that myocardial growth patterns correlate with bending. We also developed finite-element models that include previously measured regional changes in myocardial growth during c-looping. The simulations show that differential growth alone can produce results that agree reasonably well with trends in our experimental data, including changes in HT morphology and tissue strains and stresses. Incorporating other mechanisms into the model, such as active changes in myocardial cell shape, provides closer agreement. These results suggest that regional difference in hypertrophic myocardial growth is the primary cause of the bending component of c-looping, with other mechanisms playing lesser roles. Finally, we extended the model of the previous study to explore the physical plausibility of a hypothesis for the entire process of c-looping. According to our hypothesis, bending is driven primarily by differential hypertrophic growth in the myocardium, torsion is mainly caused by compressive loads exerted by the overlying splanchnopleuric membrane, and looping direction is determined by asymmetric regional growth in the omphalomesenteric veins at the caudal end of the HT. Our model includes both bending and torsion of the HT, realistic 3D geometry, and loads exerted by neighboring tissues. The behavior of the model is in reasonable agreement with available experimental data from control and mechanically perturbed embryos, offering support for our hypothesis. The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed. In summary, studies of this dissertation address several important questions during early cardiac development. The results should enrich our understanding of the underlying biophysical mechanisms

How Software Startups Survive: a Model based on Resource-based View and Dynamic Capabilities

Rapid advances of IT have encouraged many software startups to enter the market place. Our research seeks to investigate the little-studied phenomenon of startup survival. The research is based on the resource-based view and on dynamic capabilities. We present a research model that investigates factors affecting software startup survival by examining how startups survive in their competitive environment. First, we categorize the resources of software startups into three areas based on socio-technical theory. Specifically, we view entrepreneurial resources as influencing both IT innovation and environmental resources. Second, we view dynamic capabilities as mediating the relationship between interactions among resources and software startup survival. Finally, we investigate the effect of competitive actions in moderating the relationship between dynamic capabilities and software startup survival. Our research seeks to contribute to extant research by proposing the first empirical study of which we are aware that addresses factors influencing software startup survival

Uncovering Digital Platform Generativity: A Systematic Literature Review

Generativity is identified as the driver for digital innovation and platform growth by engaging a large number of actors with diverse skills. Generativity is also the signal of innovation, and it enables innovative process self-reinforcement, which leads the digital platforms to evolve in unanticipated ways. However, with the proliferation of generativity in the Information Systems (IS) literature growing, we find the understanding of generativity is inconsistent. We conduct a systematic literature review to clear the understanding mist and advance the understanding of generativity. Our study shows that generativity is a social-technical system in which social actors interact with each other by employing digital technologies. Generativity is not unequivocally positive to the digital platform due to the inherent tension but requires deliberate actions by the platform owners. Our study contributes to IS research by providing a comprehensive conceptual framework of digital platform generativity

Business Analytics (BA) - powered transformation for environmental and social sustainability in organisations: A dynamic capabilities perspective

The impetus to address issues of global warming, pollution, and social inclusiveness continues to grow, forcing organisations to focus on their environmental and social sustainability. The sustainability imperative has a direct impact on how organisations operate and define their competitive advantage, this study will provide insights into the BA-powered capabilities leveraged by organisations to achieve their sustainability goals. Previous studies have explored the role of big data analytics capabilities in strengthening dynamic capabilities (DC), and the positive relationship between DC, environmental, social, and economic sustainability, yet have neglected to analyze the BA-powered capabilities that transform organisations for sustainability. This study examines how BA can facilitate the development of socio-technical capabilities to enable organisations to adapt, reconfigure and transform their internal processes to achieve sustainability and understand capabilities required to (i) unlock sustainability-related insights from analytics, and (ii) transform insights into value-creating activities that help attain sustainability goals within organisations

AF relaying with energy harvesting source and relay

In the conventional energy harvesting amplify-andforward relaying, only the relay harvests energy from the source. In this work, a new energy harvesting relaying protocol is proposed, where the source also harvests energy from the relay, in addition to the energy harvesting relay. The performances of the new protocols using two different strategies are analyzed. Numerical results show that the new protocols have certain gain over the conventional protocol

Pilot-based channel estimation for AF relaying using energy harvesting

In existing channel estimators for amplify-andforward relaying, pilots are often sent from the relay to the destination which consumes the relay’s own energy. This limits the relay’s participation in the network. In this paper, several moment-based channel estimators for amplify-and-forward relaying are proposed that harvest energy from the source and using the harvested energy to send pilots to the destination for channel estimation. Both time-switching and power-splitting strategies are considered. Numerical results show that the two schemes that perform channel estimation only at the destination have worse performances than the two schemes that perform channel estimation at both the relay and the destination. They also show that the bit error rate performances of all schemes are close to the perfect case when exact knowledge of the channel state information is available such that there is no channel estimation error in the demodulation. The assumption that the two schemes only perform channel estimation at the destination makes them simpler, as they do not require channel estimation at the relay or feed the channel estimate back to the destination