Analysis of Genetic Interaction Maps Reveals Functional Pleiotropy

Epistatic or genetic interactions, representing the effects of mutations on the phenotypes caused by other mutations, can be very helpful for uncovering functional relationships between genes. Recently, the Epistasis Miniarray Profile (E-MAP) method has emerged as a powerful approach for identifying such interactions systematically. As part of this approach, hierarchical clustering is used to partition genes into groups on the basis of the similarity between their global interaction profiles. Here we present an original biclustering algorithm for identifying groups of functionally related genes from E-MAP data in a manner that allows individual genes to be assigned to more than one functional group. This enables investigation of the pleiotropic nature of gene function, a goal that cannot be achieved with hierarchical clustering. The performance of our algorithm is illustrated by applying it to two E-MAP datasets and an E-MAP-like in silico dataset for the yeast S. cerevisiae. In addition to identifying the majority of the functional modules reported in these studies, our algorithm uncovers many recently documented and novel multi-functional relationships between genes and gene groups

CD81/CD9 tetraspanins aid plasmacytoid dendritic cells in recognition of HCV-infected cells and induction of IFNα

Recognition of hepatitis C virus (HCV)-infected hepatocyes and interferon (IFN) induction are critical in antiviral immune response. We hypothesized that cell-cell contact between pDCs and HCV-infected cells was required for IFNα induction via involvement of cell surface molecules. Co-culture of human peripheral blood mononuclear cells (PBMCs) with genotype 1a full length HCV genomic replicon cells (FL) or genotype 2a JFH-1 virus infected hepatoma cells (JFH-1), not with uninfected hepatoma cells (Huh7.5), induced IFNα production. Depletion of pDCs from PBMCs attenuated IFNα release and purified pDCs produced high levels of IFNα after co-culture with FL replicons or JFH-1 infected cells. IFNα induction by HCV-containing hepatoma cells required viral replication, direct cell-cell contact with pDCs, and receptor-mediated endocytosis. We determined that the tetraspanin proteins, CD81 and CD9 and not other HCV entry receptors were required for IFNα induction in pDCs by HCV infected hepatoma cells. Disruption of cholesterol-rich membrane microdomains, the localization site of CD81 or inhibition of CD81 downstream molecule, Rac GTPase, inhibited IFNα production from co-cultures. IFNα production by HCV infected hepatoma cells was decreased in pDCs from HCV infected patients compared to normal controls. We found that pre-exposure of normal PBMCs to HCV viral particles attenuated IFNα induction by HCV infected hepatoma cells or TLR ligands and this inhibitory effect could be prevented by an anti-HCV E2 blocking antibody. In conclusion, our novel data show that recognition of HCV-infected hepatoma cells by pDCs involves CD81/CD9-associated membrane microdomains and induces potent IFNα production

The Use of Loan Loss Provisions for Capital Management, Earnings Management, and Procyclicality of Banks from UK and HK

The loan loss provisions is an important account which deals with the credit risks of the banks, and could be related to the accounting issues, capital management , earnings management and the economic recessions. Since the several financial crisis happened, there comes out more attention to the loan loss provisions study in the banking industry. In this dissertation, it detects whether UK banks and HK banks have used the loan loss provisions being the tool to do the capital management and the earnings management and also to find out the procyclicality pattern of them in the case of loan loss provisions. For doing so, it selects different variables to stand for different functions by using the GMM model. The results here show that the bank managers in UK and HK don not use the LLPs as the tool to do the capital management and the earnings management, however the procyclicality patter do exist in both UK and HK. And by the comparison, it gets out more issues related to agency theory, compensation policies and incentives mechamism of bank managers in UK and HK

A Review: Solder Joint Cracks at Sn-Bi58 Solder ACFs Joints

In this chapter, solder joint cracks at Sn-Bi58 solder ACF joints were investigated in conventional thermal compression bonding and ultrasonic bonding. It was found that resin storage modulus is the crucial for solder joint morphology regardless of bonding pressures. At high temperature, polymer resin tends to rebound above Tg and break the molten solder morphology. We proposed two useful methods to keep off solder joints cracks during bonding process. One is to remain bonding pressure until room temperature, the other is to use fillers to increase resin thermal mechanical property. The thermal cycling reliability was significantly enhanced when solder joint morphology was modified using 10 wt% 0.2 μm SiO2 fillers in acrylic based Sn-Bi58 solder ACF joints