CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells.

BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells

Knowledge protection in firms: A conceptual framework and evidence from HP Labs

This paper proposes a simple framework to examine organizational methods of knowledge protection. The framework highlights a basic trade‐off between improving decision‐making and innovation through communication and mitigating security risks by imposing restrictions on communication flows. The trade‐off is mediated by factors such as the sensitivity of information, the degree to which employees can be trusted to handle sensitive information appropriately, and firms’ investments in legal protection mechanisms. Evidence from HP Labs supports the basic predictions of the model, in particular the importance of employee trustworthiness and internalized codes of behavior in promoting open communication. Our interviews also suggest a potential conflict between two of the most important appropriability mechanisms: secrecy and lead‐time advantage

Towards the Prediction of User Actions on Exercises with Hints Based on Survey Results

Proceedings of: 6th European Conference of Technology Enhanced Learning, EC-TEL 2011, Palermo, Italy, September 20-23, 2011.The actions a user performs on exercises depending on the different hinting techniques applied, can be used to adapt future exercises. In this paper, we propose a survey for users in order to know their different actions depending on different conditions. The analysis of preliminary results for some questions of the model shows that there is a correlation between some survey questions and the real student actions, but there is a case in which there is not such correlation. For the cases where that correlation exists, this correlation leads to think that some prediction of users actions based on survey results is possible.Work partially funded by the Learn3 project TIN2008-05163/TSI within the Spanish “Plan Nacional de I+D+I”, and the Madrid regional community project eMadrid S2009/TIC-1650

PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.

Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS

Inside Organizations: Pricing, Politics, and Path Dependence

When economists have considered organizations, much attention has focused on the boundary of the firm, rather than its internal structures and processes. In contrast, this review sketches three approaches to the economic theory of internal organization—one substantially developed, another rapidly emerging, and a third on the horizon. The first approach (pricing) applies Pigou's prescription: If markets get prices wrong, then the economist's job is to fix the prices. The second approach (politics) considers environments where important actions inside organizations simply cannot be priced, so power and control become central. Finally, the third approach (path dependence) complements the first two by shifting attention from the between variance to the within. That is, rather than asking how organizations confronting different circumstances should choose different structures and processes, the focus here is on how path dependence can cause persistent performance differences among seemingly similar enterprises

The medicine selection process in four large university hospitals in Brazil: Does the DTC have a role?

Knowledge about evidence-based medicine selection and the role of the Drug and Therapeutics Committee (DTC) is an important topic in the literature but is scarcely discussed in Brazil. Our objective, using a qualitative design, was to analyze the medicine selection process performed in four large university hospitals in the state of Rio de Janeiro. Information was collected from documents, interviews with key informants and direct observations. Two dimensions were analyzed: the structural and organizational aspects of the selection process and the criteria and methods used in medicine selection. The findings showed that the DTC was active in two hospitals. The structure for decision-making was weak. DTC members had little experience in evidence-based selection, and their everyday functions did not influence their participation in DTC activities. The methods used to evaluate evidence were inadequate. The uncritical adoption of new medicines in these complex hospital facilities may be hampering pharmaceutical services, with consequences for the entire health system. Although the qualitative approach considerably limits the extent to which the results can be extrapolated, we believe that our findings may be relevant to other university hospitals in the country

The wisdom of the crowd playing The Price Is Right

In The Price Is Right game show, players compete to win a prize, by placing bids on its price. We ask whether it is possible to achieve a “wisdom of the crowd” effect, by combining the bids to produce an aggregate price estimate that is superior to the estimates of individual players. Using data from the game show, we show that a wisdom of the crowd effect is possible, especially by using models of the decision-making processes involved in bidding. The key insight is that, because of the competitive nature of the game, what people bid is not necessarily the same as what they know. This means better estimates are formed by aggregating latent knowledge than by aggregating observed bids. We use our results to highlight the usefulness of models of cognition and decision-making in studying the wisdom of the crowd, which are often approached only from non-psychological statistical perspectives