Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections

Inflammasomes are multi-protein complexes integrating pathogen-triggered signaling leading to the generation of pro-inflammatory cytokines including interleukin-18 (IL-18). Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are associated with elevated IL-18, suggesting inflammasome activation. However, there is marked person-to-person variation in the inflammasome response to HCV and HIV. We hypothesized that host genetics may explain this variation. To test this, we analyzed the associations of plasma IL-18 levels and polymorphisms in 10 genes in the inflammasome cascade. About 1538 participants with active HIV and/or HCV infection in three ancestry groups are included. Samples were genotyped using the Illumina Omni 1-quad and Omni 2.5 arrays. Linear regression analyses were performed to test the association of variants with log IL-18 including HCV and HIV infection status, and HIV RNA in each ancestry group and then meta-analyzed. Eleven highly correlated single-nucleotide polymorphisms (r²=0.98–1) in the IL-18-BCO2 region were significantly associated with log IL-18; each T allele of rs80011693 confers a decrease of 0.06 log pg ml⁻¹ of IL-18 after adjusting for covariates (rs80011693; rs111311302 β=−0.06, P-value=2.7 × 10⁻⁴). In conclusion, genetic variation in IL-18 is associated with IL-18 production in response to HIV and HCV infection, and may explain variability in the inflammatory outcomes of chronic viral infections

Family Business Restructuring:A Review and Research Agenda

Although business restructuring occurs frequently and it is important for the prosperity of family firms across generations, research on family firms has largely evolved separately from research on business restructuring. This is a missed opportunity, since the two domains are complementary, and understanding the context, process, content, and outcome dimensions is relevant to both research streams. We address this by examining the intersection between research on business restructuring and family firms to improve our knowledge of each area and inform future research. To achieve this goal, we review and organize research across different dimensions to create an integrative framework. Building on current research, we focus on 88 studies at the intersection of family firm and business restructuring research to develop a model that identifies research needs and suggests directions for future research

Machining performance optimization of Parallel Kinematic Machines tools with regard to their anisotropic behaviour

Today, Parallel Kinematic Machines tools (PKMs) appear in automotive and aeronautic industries. These machines allow a benefit of productivity due to their higher kinematics performances than Serial Kinematic Machines tools (SKMs). However, their machining accuracy is lower. Moreover, the compensation of the defects which penalizes the machined parts quality is difficult due to their anisotropic behaviour. Thus, this article deals with the development of methods improving the machined parts quality and the productivity. In order to improve parts quality, the static behaviour of the machine structure is considered with a model taking into account joints and legs compliances. Then, it allows determining a static workspace. About the productivity, the improvement of kinematics performances is performed through an optimization work of the non productive tool path between cutting operations. The computed tool path must verify a minimum time constraint and avoid collisions between the tool and the machined part. All the methods are illustrated with the PKM Tripteor X7 developed by PCI

Cartesian Stiffness Matrix Mapping of a Translational Parallel Mechanism with Elastic Joints

This paper is devoted to calculating the Cartesian stiffness matrix of a translational parallel manipulator with elastic joints. The calculation takes into account the contribution of the Jacobian variation because of the change of manipulator configuration due to the elasticity and it covers the entire theoretical workspace of the manipulator. Three kineto-static adimensional indices are proposed to measure the response of the manipulator in terms of stiffness

Configuration-dependent modal analysis of a Cartesian parallel kinematics manipulator: numerical modeling and experimental validation

In the design optimization of a robot the configuration-dependent modal analysis can be a powerful tool to be exploited when high stiffness and high dynamic performances are concurrently required. In this paper the elastodynamics of a lower-mobility Parallel Kinematic Machine for pure translational motions is analyzed. The vibrational modes and the natural frequencies of the robot are evaluated as functions of the end effector position inside the workspace. A finite element model including kinematic joints is used to perform a series of modal analyses in a grid of points inside the workspace. A polynomial regression gives continuous volume maps of the natural frequencies distributions. The numerical model is validated by comparison with experiments: a modal analysis is conducted on a set of inertance Frequency Response Functions acquired on several points of the machine components as a result of an excitation given by an instrumented hammer. A Natural Frequency Difference analysis validates the model under certain conditions and highlights some critical issues to be focused on in future works. �� 2013 Springer Science+Business Media Dordrecht