Neutralizing BAFF/APRIL with atacicept prevents early DSA formation and AMR development in T cell depletion induced nonhuman primate AMR model.

Depletional strategies directed toward achieving tolerance induction in organ transplantation have been associated with an increased incidence and risk of antibody-mediated rejection (AMR) and graft injury. Our clinical data suggest correlation of increased serum B cell activating factor/survival factor (BAFF) with increased risk of antibody-mediated rejection in alemtuzumab treated patients. In the present study, we tested the ability of BAFF blockade (TACI-Ig) in a nonhuman primate AMR model to prevent alloantibody production and prolong allograft survival. Three animals received the AMR inducing regimen (CD3-IT/alefacept/tacrolimus) with TACI-Ig (atacicept), compared to five control animals treated with the AMR inducing regimen only. TACI-Ig treatment lead to decreased levels of DSA in treated animals at 2 and 4 weeks posttransplantation (p < 0.05). In addition, peripheral B cell numbers were significantly lower at 6 weeks posttransplantation. However, it provided only a marginal increase in graft survival (59 ± 22 vs. 102 ± 47 days; p = 0.11). Histological analysis revealed a substantial reduction in findings typically associated with humoral rejection with atacicept treatment. More T cell rejection findings were observed with increased graft T cell infiltration in atacicept treatment, likely secondary to the graft prolongation. We show that BAFF/APRIL blockade using concomitant TACI-Ig treatment reduced the humoral portion of rejection in our depletion-induced preclinical AMR model.

Safety-critical medical device development using the UPP2SF model translation tool

Software-based control of life-critical embedded systems has become increasingly complex, and to a large extent has come to determine the safety of the human being. For example, implantable cardiac pacemakers have over 80,000 lines of code which are responsible for maintaining the heart within safe operating limits. As firmware-related recalls accounted for over 41% of the 600,000 devices recalled in the last decade, there is a need for rigorous model-driven design tools to generate verified code from verified software models. To this effect, we have developed the UPP2SF model-translation tool, which facilitates automatic conversion of verified models (in UPPAAL) to models that may be simulated and tested (in Simulink/Stateflow). We describe the translation rules that ensure correct model conversion, applicable to a large class of models. We demonstrate how UPP2SF is used in themodel-driven design of a pacemaker whosemodel is (a) designed and verified in UPPAAL (using timed automata), (b) automatically translated to Stateflow for simulation-based testing, and then (c) automatically generated into modular code for hardware-level integration testing of timing-related errors. In addition, we show how UPP2SF may be used for worst-case execution time estimation early in the design stage. Using UPP2SF, we demonstrate the value of integrated end-to-end modeling, verification, code-generation and testing process for complex software-controlled embedded systems. © 2014 ACM.

The development of parallel implementation for a CFD based fire field model utilising conventional office based PCs

Parallel processing techniques have been used in the past to provide high performance computing resources for activities such as fire-field modelling. This has traditionally been achieved using specialized hardware and software, the expense of which would be difficult to justify for many fire engineering practices. In this article we demonstrate how typical office-based PCs attached to a Local Area Network has the potential to offer the benefits of parallel processing with minimal costs associated with the purchase of additional hardware or software. It was found that good speedups could be achieved on homogeneous networks of PCs, for example a problem composed of ~100,000 cells would run 9.3 times faster on a network of 12 800MHz PCs than on a single 800MHz PC. It was also found that a network of eight 3.2GHz Pentium 4 PCs would run 7.04 times faster than a single 3.2GHz Pentium computer. A dynamic load balancing scheme was also devised to allow the effective use of the software on heterogeneous PC networks. This scheme also ensured that the impact between the parallel processing task and other computer users on the network was minimized.

The Development of a Two-Dimensional Transient Catalyst Model for Direct Injection Two-Stroke Applications.

This paper describes the development of a two-dimensional transient catalyst model. Although designed primarily for two-stroke direct injection engines, the model is also applicable to four-stroke lean burn and diesel applications. The first section describes the geometries, properties and chemical processes simulated by the model and discusses the limitations and assumptions applied. A review of the modeling techniques adopted by other researchers is also included. The mathematical relationships which are used to represent the system are then described, together with the finite volume method used in the computer program. The need for a two-dimensional approach is explained and the methods used to model effects such as flow and temperature distribution are presented. The problems associated with developing surface reaction rates are discussed in detail and compared with published research. Validation and calibration of the model is achieved by comparing predictions with measurements from a flow reactor. While an extensive validation process, involving detailed measurements of gas composition and thermal gradients, has been completed, the analysis is too detailed for publication here and is the subject of a separate technical paper.

Cooperativism, entrepreneurship and economic development: a linking theoretical model

Cooperatives, as a kind of firms, are considered by many scholars as an remarkable alternative for overcoming the economic crisis started in 2008. Besides, there are other scholars which pointed out the important role that these firms play in the regional economic development. Nevertheless, when one examines the economic literature on cooperatives, it is detected that this kind of firms is mainly studied starting from the point of view of their own characteristics and particularities of participation and solidarity. In this sense, following a different analysis framework, this article proposes a theoretical model in order to explain the behavior of cooperatives based on the entrepreneurship theory with the aim of increasing the knowledge about this kind of firms and, more specifically, their contribution to regional economic development.