Uncovering compounds by synergy of cluster expansion and high-throughput methods.

Predicting from first-principles calculations whether mixed metallic elements phase-separate or form ordered structures is a major challenge of current materials research. It can be partially addressed in cases where experiments suggest the underlying lattice is conserved, using cluster expansion (CE) and a variety of exhaustive evaluation or genetic search algorithms. Evolutionary algorithms have been recently introduced to search for stable off-lattice structures at fixed mixture compositions. The general off-lattice problem is still unsolved. We present an integrated approach of CE and high-throughput ab initio calculations (HT) applicable to the full range of compositions in binary systems where the constituent elements or the intermediate ordered structures have different lattice types. The HT method replaces the search algorithms by direct calculation of a moderate number of naturally occurring prototypes representing all crystal systems and guides CE calculations of derivative structures. This synergy achieves the precision of the CE and the guiding strengths of the HT. Its application to poorly characterized binary Hf systems, believed to be phase-separating, defines three classes of alloys where CE and HT complement each other to uncover new ordered structures.

Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage.

Diarthrodial joints are essential for load bearing and locomotion. Physiologically, articular cartilage sustains millions of cycles of mechanical loading. Chondrocytes, the cells in cartilage, regulate their metabolic activities in response to mechanical loading. Pathological mechanical stress can lead to maladaptive cellular responses and subsequent cartilage degeneration. We sought to deconstruct chondrocyte mechanotransduction by identifying mechanosensitive ion channels functioning at injurious levels of strain. We detected robust expression of the recently identified mechanosensitive channels, PIEZO1 and PIEZO2. Combined directed expression of Piezo1 and -2 sustained potentiated mechanically induced Ca(2+) signals and electrical currents compared with single-Piezo expression. In primary articular chondrocytes, mechanically evoked Ca(2+) transients produced by atomic force microscopy were inhibited by GsMTx4, a PIEZO-blocking peptide, and by Piezo1- or Piezo2-specific siRNA. We complemented the cellular approach with an explant-cartilage injury model. GsMTx4 reduced chondrocyte death after mechanical injury, suggesting a possible therapy for reducing cartilage injury and posttraumatic osteoarthritis by attenuating Piezo-mediated cartilage mechanotransduction of injurious strains.

The ranking of alternative tariff and quota policies in the presence of domestic monopoly

Bhagwati demonstrated the nonequivalence between tariffs and quotas in the presence of monopoly. This paper also assumes domestic production to be monopolized and shows that giving import licenses or tariff revenues to the domestic producer may raise or lower the welfare cost of protection and the price paid by consumers from the price under other tariff and quota arrangements which maintain the same market share for the domestic producer. However, if the monopolist realizes that commercial policy is an instrument used to maximize the policymaker's welfare function, instead of being a goal in itself, the equivalence of tariffs and quotas re-emerges. © 1977.

Beyond signaling and human capital: Education and the revelation of ability

We provide evidence that college graduation plays a direct role in revealing ability to the labor market. Using the NLSY79, our results suggest that ability is observed nearly perfectly for college graduates, but is revealed to the labor market more gradually for high school graduates. Consequently, from the beginning of their careers, college graduates are paid in accordance with their own ability, while the wages of high school graduates are initially unrelated to their own ability. This view of ability revelation in the labor market has considerable power in explaining racial differences in wages, education, and returns to ability.

Real-Time Decision Making and Aggressive Behavior in Youth: A Heuristic Model of Response Evaluation and Decision (RED).

Considerable scientific and intervention attention has been paid to judgment and decision-making systems associated with aggressive behavior in youth. However, most empirical studies have investigated social-cognitive correlates of stable child and adolescent aggressiveness, and less is known about real-time decision making to engage in aggressive behavior. A model of real-time decision making must incorporate both impulsive actions and rational thought. The present paper advances a process model (response evaluation and decision; RED) of real-time behavioral judgments and decision making in aggressive youths with mathematic representations that may be used to quantify response strength. These components are a heuristic to describe decision making, though it is doubtful that individuals always mentally complete these steps. RED represents an organization of social-cognitive operations believed to be active during the response decision step of social information processing. The model posits that RED processes can be circumvented through impulsive responding. This article provides a description and integration of thoughtful, rational decision making and nonrational impulsivity in aggressive behavioral interactions.

Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure.

Chronic human heart failure is characterized by abnormalities in beta-adrenergic receptor (betaAR) signaling, including increased levels of betaAR kinase 1 (betaARK1), which seems critical to the pathogenesis of the disease. To determine whether inhibition of betaARK1 is sufficient to rescue a model of severe heart failure, we mated transgenic mice overexpressing a peptide inhibitor of betaARK1 (betaARKct) with transgenic mice overexpressing the sarcoplasmic reticulum Ca(2+)-binding protein, calsequestrin (CSQ). CSQ mice have a severe cardiomyopathy and markedly shortened survival (9 +/- 1 weeks). In contrast, CSQ/betaARKct mice exhibited a significant increase in mean survival age (15 +/- 1 weeks; P < 0.0001) and showed less cardiac dilation, and cardiac function was significantly improved (CSQ vs. CSQ/betaARKct, left ventricular end diastolic dimension 5.60 +/- 0.17 mm vs. 4.19 +/- 0.09 mm, P < 0.005; % fractional shortening, 15 +/- 2 vs. 36 +/- 2, P < 0.005). The enhancement of the survival rate in CSQ/betaARKct mice was substantially potentiated by chronic treatment with the betaAR antagonist metoprolol (CSQ/betaARKct nontreated vs. CSQ/betaARKct metoprolol treated, 15 +/- 1 weeks vs. 25 +/- 2 weeks, P < 0.0001). Thus, overexpression of the betaARKct resulted in a marked prolongation in survival and improved cardiac function in a mouse model of severe cardiomyopathy that can be potentiated with beta-blocker therapy. These data demonstrate a significant synergy between an established heart-failure treatment and the strategy of betaARK1 inhibition.

HPV clearance and the neglected role of stochasticity.

Clearance of anogenital and oropharyngeal HPV infections is attributed primarily to a successful adaptive immune response. To date, little attention has been paid to the potential role of stochastic cell dynamics in the time it takes to clear an HPV infection. In this study, we combine mechanistic mathematical models at the cellular level with epidemiological data at the population level to disentangle the respective roles of immune capacity and cell dynamics in the clearing mechanism. Our results suggest that chance-in form of the stochastic dynamics of basal stem cells-plays a critical role in the elimination of HPV-infected cell clones. In particular, we find that in immunocompetent adolescents with cervical HPV infections, the immune response may contribute less than 20% to virus clearance-the rest is taken care of by the stochastic proliferation dynamics in the basal layer. In HIV-negative individuals, the contribution of the immune response may be negligible.

Introduction: The apparel industry and North American economic integration

The economic and social consequences of international trade agreements have become a major area of inquiry in development studies in recent years. As evidenced by the energetic protests surrounding the Seattle meeting of the World Trade Organization (WTO) in December 1999 and the controversy about China's admission to the WTO, such agreements have also become a focus of political conflict in both the developed and developing countries. At issue are questions of job gains and job losses in different regions, prices paid by consumers, acceptable standards for wages and working conditions in transnational manufacturing industries, and the quality of the environment. All these concerns have arisen with regard to the North American Free Trade Agreement (NAFTA) and can be addressed through an examination of changes in the dynamics of the apparel industry in the post-NAFTA period.1 In this book, we examine the evolution of the apparel industry in North America in order to address some of these questions as they pertain to North America, with an eye toward the broader implications of our findings. We also consider the countries of the Caribbean Basin and Central America, whose textile and apparel goods are now allowed to enter the U.S. market on the same basis as those from Canada and Mexico (Odessey 2000). © 2009 by Temple University Press. All rights reserved.