Propagation of Pericentral Necrosis During Acetaminophen-Induced Liver Injury: Evidence for Early Interhepatocyte Communication and Information Exchange.

Acetaminophen (APAP)-induced liver injury is clinically significant, and APAP overdose in mice often serves as a model for drug-induced liver injury in humans. By specifying that APAP metabolism, reactive metabolite formation, glutathione depletion, and mitigation of mitochondrial damage within individual hepatocytes are functions of intralobular location, an earlier virtual model mechanism provided the first concrete multiattribute explanation for how and why early necrosis occurs close to the central vein (CV). However, two characteristic features could not be simulated consistently: necrosis occurring first adjacent to the CV, and subsequent necrosis occurring primarily adjacent to hepatocytes that have already initiated necrosis. We sought parsimonious model mechanism enhancements that would manage spatiotemporal heterogeneity sufficiently to enable meeting two new target attributes and conducted virtual experiments to explore different ideas for model mechanism improvement at intrahepatocyte and multihepatocyte levels. For the latter, evidence supports intercellular communication via exosomes, gap junctions, and connexin hemichannels playing essential roles in the toxic effects of chemicals, including facilitating or counteracting cell death processes. Logic requiring hepatocytes to obtain current information about whether downstream and lateral neighbors have triggered necrosis enabled virtual hepatocytes to achieve both new target attributes. A virtual hepatocyte that is glutathione-depleted uses that information to determine if it will initiate necrosis. When a less-stressed hepatocyte is flanked by at least two neighbors that have triggered necrosis, it too will initiate necrosis. We hypothesize that the resulting intercellular communication-enabled model mechanism is analogous to the actual explanation for APAP-induced hepatotoxicity at comparable levels of granularity

INFORMATION TECHNOLOGY AND THE VERTICAL ORGANIZATION OF INDUSTRY

A model has been developed to study the interdependence between the choice of information technology and industry structure. Advances in information technology might provide incentives for a firm to specialize or focus on its core competence. However, the degree of specialization depends on the extent of industry-level specialization, which is, in turn, the result of the behavior of individual firms and their adoption of information technology favoring specialization. Emerging electronic markets and industries have been chosen as an application domain, as they would not exist without information technology.

Evolution of Consumers’ Preferences due to Innovation

The integration process between evolutionary approach and conventional economic analysis is very essential for the next development of economic studies, especially in the fundamental concepts of modern economics: supply and demand analysis. In this presentation, we use the concept of meme to explore evolution of demand. This study offers an evolutionary model of demand, which views utility as a function of the distance between the two types of sequences of memes (memeplex), which represent economic product and consumer preference. It is very different from the conventional approach of demand, which only views utility as a function of quantity. This modification provides an opportunity to see innovation and transformation of consumer preferences in the demand perspective. Innovation is seen as a change in sequence of memes in economic products, while the transformation of consumer behavior is defined as a change in the aligning memes of consumer preference. Demand quantity is the result of the selection process. This model produces some interesting characteristics, such as: (i) quantitative and qualitative properties of evolution of demand, (ii) relationship between consumer behavior and properties of evolution of demand that occurred and (iii) power law on the distribution of product lifetime. At the end we show the improvement of utility function, in the concept of meme, might create a new landscape for the further development of economics

Learning how to learn: an adaptive dialogue agent for incrementally learning visually grounded word meanings

We present an optimised multi-modal dialogue agent for interactive learning of visually grounded word meanings from a human tutor, trained on real human-human tutoring data. Within a life-long interactive learning period, the agent, trained using Reinforcement Learning (RL), must be able to handle natural conversations with human users and achieve good learning performance (accuracy) while minimising human effort in the learning process. We train and evaluate this system in interaction with a simulated human tutor, which is built on the BURCHAK corpus -- a Human-Human Dialogue dataset for the visual learning task. The results show that: 1) The learned policy can coherently interact with the simulated user to achieve the goal of the task (i.e. learning visual attributes of objects, e.g. colour and shape); and 2) it finds a better trade-off between classifier accuracy and tutoring costs than hand-crafted rule-based policies, including ones with dynamic policies.Comment: 10 pages, RoboNLP Workshop from ACL Conferenc

The role of technology, organisation, and demand in growth and income distribution

The paper proposes a model that explains cross-country growth divergences over time for different aspects of structural change. The model formalises the links between production technology, firm organisation (functional composition of employment) on the supply side and the endogenous evolution of income distribution and consumption patterns on the demand side. Wage distribution is the main channel between the organisation of firms and consumption patterns, and firm selection is the main trigger of investment in new capital, productivity gains and cumulative growth. The model is able to reproduce empirical stylised facts on growth and income inequality associated with different stages of growth. We use VARs to estimate the causal relations between the three aspects of structural change. We then analyse the effect of the parameters that define the structure of an economy – and the way in which this unfolds through time – on growth and income distribution via numerical simulation. Product variety, differences in consumption preferences, organisational complexity and production technology determine whether the economy experiences a take-off or a stagnating growth, and the associated distribution of income