Neural network analysis identifies scaffold properties necessary for in vitro chondrogenesis in elastin-like polypeptide biopolymer scaffolds.

The successful design of biomaterial scaffolds for articular cartilage tissue engineering requires an understanding of the impact of combinations of material formulation parameters on diverse and competing functional outcomes of biomaterial performance. This study sought to explore the use of a type of unsupervised artificial network, a self-organizing map, to identify relationships between scaffold formulation parameters (crosslink density, molecular weight, and concentration) and 11 such outcomes (including mechanical properties, matrix accumulation, metabolite usage and production, and histological appearance) for scaffolds formed from crosslinked elastin-like polypeptide (ELP) hydrogels. The artificial neural network recognized patterns in functional outcomes and provided a set of relationships between ELP formulation parameters and measured outcomes. Mapping resulted in the best mean separation amongst neurons for mechanical properties and pointed to crosslink density as the strongest predictor of most outcomes, followed by ELP concentration. The map also grouped formulations together that simultaneously resulted in the highest values for matrix production, greatest changes in metabolite consumption or production, and highest histological scores, indicating that the network was able to recognize patterns amongst diverse measurement outcomes. These results demonstrated the utility of artificial neural network tools for recognizing relationships in systems with competing parameters, toward the goal of optimizing and accelerating the design of biomaterial scaffolds for articular cartilage tissue engineering.

Competing manufacturers in a retail supply chain: On contractual form and coordination

It is common for a retailer to sell products from competing manufacturers. How then should the firms manage their contract negotiations? The supply chain coordination literature focuses either on a single manufacturer selling to a single retailer or one manufacturer selling to many (possibly competing) retailers. We find that some key conclusions from those market structures do not apply in our setting, where multiple manufacturers sell through a single retailer. We allow the manufacturers to compete for the retailer's business using one of three types of contracts: a wholesale-price contract, a quantity-discount contract, or a two-part tariff. It is well known that the latter two, more sophisticated contracts enable the manufacturer to coordinate the supply chain, thereby maximizing the profits available to the firms. More importantly, they allow the manufacturer to extract rents from the retailer, in theory allowing the manufacturer to leave the retailer with only her reservation profit. However, we show that in our market structure these two sophisticated contracts force the manufacturers to compete more aggressively relative to when they only offer wholesale-price contracts, and this may leave them worse off and the retailer substantially better off. In other words, although in a serial supply chain a retailer may have just cause to fear quantity discounts and two-part tariffs, a retailer may actually prefer those contracts when offered by competing manufacturers. We conclude that the properties a contractual form exhibits in a one-manufacturer supply chain may not carry over to the realistic setting in which multiple manufacturers must compete to sell their goods through the same retailer. © 2010 INFORMS.

The Golden Rule Ethic, its Measurement, and Relationships with Well-Being and Prosocial Values Across Four Religions in India

As a psychological principle, the golden rule represents an ethic of universal empathic concern. It is, surprisingly, present in the sacred texts of virtually all religions, and in philosophical works across eras and continents. Building on the literature demonstrating a positive impact of prosocial behavior on well-being, the present study investigates the psychological function of universal empathic concern in Indian Hindus, Christians, Muslims and Sikhs.

I develop a measure of the centrality of the golden rule-based ethic, within an individual’s understanding of his or her religion, that is applicable to all theistic religions. I then explore the consistency of its relationships with psychological well-being and other variables across religious groups.

Results indicate that this construct, named Moral Concern Religious Focus, can be reliably measured in disparate religious groups, and consistently predicts well-being across them. With measures of Intrinsic, Extrinsic and Quest religious orientations in the model, only Moral Concern and religiosity predict well-being. Moral Concern alone mediates the relationship between religiosity and well-being, and explains more variance in well-being than religiosity alone. The relationship between Moral Concern and well-being is mediated by increased preference for prosocial values, more satisfying interpersonal relationships, and greater meaning in life. In addition, across religious groups Moral Concern is associated with better self-reported physical and mental health, and more compassionate attitudes toward oneself and others.

Two additional types of religious focus are identified: Personal Gain, representing the motive to use religion to improve one’s life, and Relationship with God. Personal Gain is found to predict reduced preference for prosocial values, less meaning in life, and lower quality of relationships. It is associated with greater interference of pain and physical or mental health problems with daily activities, and lower self-compassion. Relationship with God is found to be associated primarily with religious variables and greater meaning in life.

I conclude that individual differences in the centrality of the golden rule and its associated ethic of universal empathic concern may play an important role in explaining the variability in associations between religion, prosocial behavior and well-being noted in the literature.

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity.