Expression and functional changes in the organic anion transporting polypeptide (OATP)multidrug resistance associated protein (MRP) axis of transporters are well reported in nonalcoholic steatohepatitis (NASH) patients. These changes can impact plasma and tissue disposition of endo-and exogenous compounds. The transporter alterations are often assessed by administration of a xenobiotic, or by transporter proteomic analysis from liver biopsies. Using gene expression, proteomics and endogenous biomarkers, we show that the gene expression and activity of OATP and MRP transporters are associated with disease progression and recovery in humans and in preclinical animal models of NASH. Decreased OATP and increased MRP3/4 gene expression in two steatosis and NASH patient cohorts, as well as gene and protein expression in multiple NASH rodent models have been established. Coproporphyrin I and III (CP I and III) were established as substrates of MRP4. CP I plasma concentration increased significantly in four animal models of NASH, indicating the transporter changes. Upto a 60-fold increase in CP I plasma concentration was observed in the mouse bile duct ligated model compared to sham controls. In the choline deficient high This article has not been copyedited and formatted. The final version may differ from this version.
Current authentication schemes suffer from many weaknesses. Textual passwords are widely used; however users tend to choose meaningful words from dictionaries. This makes textual passwords easy to break and vulnerable to dictionary or brute force attacks. Many available graphical passwords face lack of space. Smart cards or tokens can be lost or are prone to theft. Many biometric authentications have been proposed but users tend to resist using them because of their intrusiveness on their privacy. The three-dimensional (3-D) password is a multifactor authentication scheme i.e. it combines most of the existing authentication schemes such as textual passwords, graphical passwords, and biometrics into a single virtual three-dimensional environment. Users navigate through this virtual environment and interact with the objects placed in it. The combination of all the actions and inputs towards the virtual three-dimensional environment constructs the user's 3D password. Simple approach for a secure authentication is to use one or more of the above mentioned authentication techniques in combination for multi-level authentication, so that, the probability of breaking such a password is reduced to a large extent. Hence multi-level authentication technique can be used for ensuring a more stringent authentication.
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