MECHANISMS OF DISEASE Acute Oxygen-Sensing Mechanisms

JOSEPH PRIESTLEY, ONE OF THE THREE SCIENTISTS CREDITED WITH THE discovery of oxygen, described the death of mice that were deprived of oxygen. However, he was also well aware of the toxicity of too much oxygen, stating, “For as a candle burns much faster in dephlogisticated [oxygen enriched] than in common air, so we might live out too fast, and the animal powers be too soon exhausted in this pure kind of air. A moralist, at least, may say, that the air which nature has provided for us is as good as we deserve.”1 In this review we examine the remarkable mechanisms by which different organs detect and respond to acute changes in oxygen tension. Specialized tissues that sense the local oxygen tension include glomus cells of the carotid body, neuroepithelial bodies in the lungs, chromaffin cells of the fetal adrenal medulla, and smooth-muscle cells of the resistance pulmonary arteries, fetoplacental arteries, systemic arteries, and the ductus arteriosus. Together, they constitute a specialized homeostatic oxygen-sensing system. Although all tissues are sensitive to severe hypoxia, these specialized tissues respond rapidly to moderate changes in oxygen tension within the physiologic range (roughly 40 to 100 mm Hg in an adult and 20 to 40 mm Hg in a fetus)Junta de Andalucí

Characterisation of damage mechanisms in oxide ceramics indented at dynamic and quasi-static strain rates

Ceramic materials are known to display rate dependent behaviour under impact. Tests to establish the strain-rate dependent variations in damage mechanisms have been carried out on debased alumina, an alumina-zirconia composite, and 3Y-TZP. Materials were indented dynamically and quasi-statically using identical sharp hardened steel projectiles while recording the load profile. Characteristics typical of both sharp and blunt indentation types were observed using scanning electron microscopy and piezospectroscopic mapping. At dynamic strain rates both the depth of the indentation and the residual stress in the material were lower than for quasi-static tests. This was attributed to temperature-induced softening of the projectile. Unusual behaviour was observed in the 3Y-TZP samples due to the reversible transformation from tetragonal to monoclinic crystal structures during mechanical loading. These effects and the observed superior mechanical strength against impact suggest that zirconia or zirconia-composite materials may have advantages over debased alumina for application as ceramic armour materials

Reallocation Mechanisms

We consider reallocation problems in settings where the initial endowment of each agent consists of a subset of the resources. The private information of the players is their value for every possible subset of the resources. The goal is to redistribute resources among agents to maximize efficiency. Monetary transfers are allowed, but participation is voluntary. We develop incentive-compatible, individually-rational and budget balanced mechanisms for several classic settings, including bilateral trade, partnership dissolving, Arrow-Debreu markets, and combinatorial exchanges. All our mechanisms (except one) provide a constant approximation to the optimal efficiency in these settings, even in ones where the preferences of the agents are complex multi-parameter functions

Undominated Groves Mechanisms

The family of Groves mechanisms, which includes the well-known VCG mechanism (also known as the Clarke mechanism), is a family of efficient and strategy-proof mechanisms. Unfortunately, the Groves mechanisms are generally not budget balanced. That is, under such mechanisms, payments may flow into or out of the system of the agents, resulting in deficits or reduced utilities for the agents. We consider the following problem: within the family of Groves mechanisms, we want to identify mechanisms that give the agents the highest utilities, under the constraint that these mechanisms must never incur deficits. We adopt a prior-free approach. We introduce two general measures for comparing mechanisms in prior-free settings. We say that a non-deficit Groves mechanism $M$ {\em individually dominates} another non-deficit Groves mechanism $M'$ if for every type profile, every agent's utility under $M$ is no less than that under $M'$, and this holds with strict inequality for at least one type profile and one agent. We say that a non-deficit Groves mechanism $M$ {\em collectively dominates} another non-deficit Groves mechanism $M'$ if for every type profile, the agents' total utility under $M$ is no less than that under $M'$, and this holds with strict inequality for at least one type profile. The above definitions induce two partial orders on non-deficit Groves mechanisms. We study the maximal elements corresponding to these two partial orders, which we call the {\em individually undominated} mechanisms and the {\em collectively undominated} mechanisms, respectively.Comment: 34 pages. To appear in Journal of AI Research (JAIR

Exotic mitotic mechanisms

The emergence of eukaryotes around two billion years ago provided new challenges for the chromosome segregation machineries: the physical separation of multiple large and linear chromosomes from the microtubule-organizing centres by the nuclear envelope. In this review, we set out the diverse solutions that eukaryotic cells use to solve this problem, and show how stepping away from ‘mainstream’ mitosis can teach us much about the mechanisms and mechanics that can drive chromosome segregation. We discuss the evidence for a close functional and physical relationship between membranes, nuclear pores and kinetochores in generating the forces necessary for chromosome segregation during mitosis

Budget Feasible Mechanisms

We study a novel class of mechanism design problems in which the outcomes are constrained by the payments. This basic class of mechanism design problems captures many common economic situations, and yet it has not been studied, to our knowledge, in the past. We focus on the case of procurement auctions in which sellers have private costs, and the auctioneer aims to maximize a utility function on subsets of items, under the constraint that the sum of the payments provided by the mechanism does not exceed a given budget. Standard mechanism design ideas such as the VCG mechanism and its variants are not applicable here. We show that, for general functions, the budget constraint can render mechanisms arbitrarily bad in terms of the utility of the buyer. However, our main result shows that for the important class of submodular functions, a bounded approximation ratio is achievable. Better approximation results are obtained for subclasses of the submodular functions. We explore the space of budget feasible mechanisms in other domains and give a characterization under more restricted conditions

Mechanisms in ecology

New mechanistic philosophy has not examined explanations in ecology although they are based extensively on describing mechanisms responsible for phenomena under scrutiny. This chapter uses the example of research on the shrub Lonicera maackii (Amur honeysuckle) to scrutinize individual-level mechanisms that are generally accepted and used in ecology and confronts them with the minimal account of mechanisms. Individual-level mechanisms are for a phenomenon, are hierarchical, and absent entities play a role in their functioning. They are distinguished by the role played by properties in determining activities and organization. The chapter also considers the experimental methods for discovery of individual-level mechanisms, the possibility of group-level mechanisms in ecology, and suggests further research problems