This paper reviews the literature on audit committees in order to evaluate the extent to which committees are effective in terms of strengthening financial reporting. The paper aims to achieve two goals: first. to provide updated information about the effectiveness of the audit committee, and second to identify research opportunities. Compared with other reviews on the matter, we cover a broader spectrum of theoretical perspectives from various fields, methods, and countries. In particular, our review investigates from a meta-perspective the results reported in studies which examine the relationship between certain audit committee characteristics and measures of audit committee effectiveness. It is hoped that this work will sensitize accounting researchers about the appropriateness of extending the boundaries of research on audit committees, from methodological, theoretical, and geographical points of view.

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Crystal structures of the RNA-dependent RNA polymerase genotype 2a of hepatitis C virus (HCV) from two crystal forms have been determined. Similar to the three-dimensional structures of HCV polymerase genotype 1b and other known polymerases, the structures of the HCV polymerase genotype 2a in both crystal forms can be depicted in the classical right-hand arrangement with fingers, palm, and thumb domains. The main structural differences between the molecules in the two crystal forms lie at the interface of the fingers and thumb domains. The relative orientation of the thumb domain with respect to the fingers and palm domains and the ␤-flap region is altered. Structural analysis reveals that the NS5B polymerase in crystal form I adopts a "closed" conformation that is believed to be the active form, whereas NS5B in crystal form II adopts an "open" conformation and is thus in the inactive form. In addition, we have determined the structures of two NS5B polymerase/non-nucleoside inhibitor complexes. Both inhibitors bind at a common binding site, which is nearly 35 Å away from the polymerase active site and is located in the thumb domain. The binding pocket is predominantly hydrophobic in nature, and the enzyme inhibitor complexes are stabilized by hydrogen bonding and van der Waals interactions. Inhibitors can only be soaked in crystal form I and not in form II; examination of the enzyme-inhibitor complex reveals that the enzyme has undergone a dramatic conformational change from the form I (active) complex to the form II (inactive).

X-ray crystal structures of two non-nucleoside analogue inhibitors bound to hepatitis C virus NS5B RNAdependent RNA polymerase have been determined to 2.0 and 2.9 Å resolution. These noncompetitive inhibitors bind to the same site on the protein, ϳ35 Å from the active site. The common features of binding include a large hydrophobic region and two hydrogen bonds between both oxygen atoms of a carboxylate group on the inhibitor and two main chain amide nitrogen atoms of Ser 476 and Tyr 477 on NS5B. The inhibitor-binding site lies at the base of the thumb domain, near its interface with the C-terminal extension of NS5B. The location of this inhibitor-binding site suggests that the binding of these inhibitors interferes with a conformational change essential for the activity of the polymerase. Hepatitis C virus (HCV)1 infects about 3% of the world's human population. HCV infection can develop into chronic hepatitis, which, in some cases, causes cirrhosis of the liver, eventually leading to hepatocellular carcinoma (1). There is no vaccine against HCV currently, and no generally effective therapy for all genotypes of HCV is available. At the present time, the use of recombinant interferon ␣-2a, ␣-2b, "consensus" interferon, and pegylated interferon ␣-2b either in monotherapy or in combination with ribavirin is the only approved therapy available (2). However, limited efficacy and some adverse side effects are associated with these therapies (3). Therefore, the development of HCV-specific antiviral agents is needed urgently.Extensive studies have been done to understand the structures and functions of the individual components of the HCVencoded polyprotein (structural proteins C, E1, and E2 and nonstructural proteins NS2, NS3, NS4A, NS4B, NS5A, and NS5B) (4 -6). Among them, NS2, NS3 protease and helicase, and NS5B RNA-dependent RNA polymerase are essential enzymes for the replication of HCV. The high resolution crystal structures of NS3 protease (7-9) and helicase domains (10, 11) and NS5B polymerase (12-14) have been determined by crystallographic methods in the past 5 years. These enzymes are potential targets for structure-based drug design. The inhibitors of NS3 protease and, in some cases, corresponding structures of NS3 protease/inhibitor complexes have been reported recently (15). In the case of HCV NS5B polymerase, both nucleoside and non-nucleoside inhibitors have been discovered in recent years (16). 3TC (2Ј-deoxy-3Ј-thiacytidine proprietary compound lamivudine) triphosphate has been reported to have a weak inhibitory effect with a 50% inhibitory concentration (IC 50 ) of 180 M (17), whereas numerous non-nucleoside compounds have been documented to possess relatively potent anti-NS5B activity. Examples include specific rhodanines and barbituric acid derivatives, many of which were found to exhibit anti-NS5B activity with IC 50 values below 1 M (18, 19). Classes of dihydroxypyrimidine carboxylic acids and diketoacid derivatives were claimed as well with IC 50 values within the submicromolar range for the latt...

SUMMARY This research synthesis evaluates relevant research concerning the audit report. For too long, there has been a significant “expectations gap” between what financial statement users expect an audit is delivering and what the audit profession believes it is providing. This gap becomes particularly problematic for auditors when there is a “business crisis” and attention is directed to the role of the auditor. Two related gaps are considered in this synthesis, a communications gap, and an information gap. All of these gaps relate to the demand for, understanding of, and use of auditor communications, which is the focus of this synthesis. Our synthesis is driven by two primary research questions: What do financial statement users perceive as information that should be communicated, and what does research show to be the effects on users of existing and other auditor communications currently being considered? As we discuss in detail, prior research does address many aspects of these two questions, but many of the findings are mixed and some important aspects have not been studied. Further research, particularly in areas regarding changes to the audit reporting model currently being considered, could lead to the improvement of the value relevance of auditor services, disclosures, and assurances. The clear interest by regulators and standard setters in such applied research should serve as a strong incentive for academics to conduct such research and for the practicing profession to support it.