Knowledge that Transforms

The anti-cancer activity of calcitriol, the active metabolite of Vitamin D, in the colon is usually attributed to its anti-proliferative and pro-differentiative actions. The levels of reactive oxygen species (ROS) are high in colon carcinomas due to increased aerobic metabolism and exposure to various anti-cancer modalities. We examined whether calcitriol modulates the response of colon cancer cells to the cytotoxic action of the common mediator of ROS injury, H2O2. Pretreatment with calcitriol (100 nM, 48 h) sensitized HT-29 colon cancer cells to cell death induced by acute exposure to H2O2 or chronic exposure to the H2O2 generating system, glucose/glucose-oxidase. Although the morphological features of H2O2-induced HT-29 cell death are consistent with apoptosis, we detected no executioner caspase activation in response to cytotoxic concentrations of H2O2 and treatment with a pan-caspase inhibitor did not affect H2O2-induced cytotoxicity nor its enhancement by calcitriol. Conversely, exposure of HT-29 cells to sub-toxic concentrations of H2O2 resulted in low executioner caspase activation that was inhibited by pretreatment with calcitriol. The sensitization of colon cancer cells to ROS-induced cytotoxicity may contribute to its assumed action as a chemopreventive agent and to its therapeutic potential alone or in combination with other anti-cancer modalities.

We study a Monte Carlo algorithm for computing marginal and stationary densities of stochastic models with the Markov property, establishing global asymptotic normality and OP(n–1/2) convergence. Asymptotic normality is used to derive error bounds in terms of the distribution of the norm deviation.

Previous research has argued that debt financing affects equity-holders' investment decisions, producing substantial inefficiency. This paper shows that the size of this inefficiency depends on the degree of investment reversibility. In a dynamic model of financing and investment, the paper provides an upper bound for the inefficiency produced by debt financing. The upper bound is decreasing in the degree of investment reversibility and is zero when investment is perfectly reversible. Copyright The Econometric Society 2008.

Much evidence suggests that people are heterogeneous with regard to their abilities to make rational, forward-looking decisions. This raises the question as to when the rational types are decisive for aggregate outcomes and when the boundedly rational types shape aggregate results. We examine this question in the context of a long-standing and important economic problem: the adjustment of nominal prices after an anticipated monetary shock. Our experiments suggest that two types of bounded rationality—money illusion and anchoring—are important behavioral forces behind nominal inertia. However, depending on the strategic environment, bounded rationality has vastly different effects on aggregate price adjustment. If agents' actions are strategic substitutes, adjustment to the new equilibrium is extremely quick, whereas under strategic complementarity, adjustment is both very slow and associated with relatively large real effects. This adjustment difference is driven by price expectations, which are very flexible and forward-looking under substitutability but adaptive and sticky under complementarity. Moreover, subjects' expectations are also considerably more rational under substitutability.

We study a model of lumpy investment wherein establishments face persistent shocks to common and plant-specific productivity, and nonconvex adjustment costs lead them to pursue generalized (S, s) investment rules. We allow persistent heterogeneity in both capital and total factor productivity alongside low-level investments exempt from adjustment costs to develop the first model consistent with the cross-sectional distribution of establishment investment rates. Examining the implications of lumpy investment for aggregate dynamics in this setting, we find that they remain substantial when factor supply considerations are ignored, but are quantitatively irrelevant in general equilibrium. The substantial implications of general equilibrium extend beyond the dynamics of aggregate series. While the presence of idiosyncratic shocks makes the time-averaged distribution of plant-level investment rates largely invariant to market-clearing movements in real wages and interest rates, we show that the dynamics of plants' investments differ sharply in their presence. Thus, model-based estimations of capital adjustment costs involving panel data may be quite sensitive to the assumption about equilibrium. Our analysis also offers new insights about how nonconvex adjustment costs influence investment at the plant. When establishments face idiosyncratic productivity shocks consistent with existing estimates, we find that nonconvex costs do not cause lumpy investments, but act to eliminate them.

We study preferences over menus which can be represented as if the agent selects an alternative from a menu and experiences regret if her choice is ex post inferior. Since regret arises from comparisons between the alternative selected and the other available alternatives, our axioms reflect the agent's desire to limit her options. We prove that our representation is essentially unique. We also introduce two measures of comparative regret attitudes and relate them to our representation. Finally, we explore the formal connection between the present work and the literature on temptation.