534 research outputs found

    Narrowing the Scope of Auditor Duties

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    (Excerpt) The tort of “deepening insolvency” refers to an action asserted by a representative of a bankruptcy estate against directors, officers, lenders, or others based on their pre-petition interactions with the debtor. 9 NORTON BANKR. L. & PRAC. 3d § 174:22. Liability under deepening insolvency has been imposed where “the defendant’s conduct, either fraudulently or even negligently, prolongs the life of a corporation, thereby increasing the corporation\u27s debt and exposure to creditors.” In re LTV Steel Co., Inc., 333 B.R. 397, 421 (Bankr. N.D. Ohio 2005). Damages under the theory are sometimes awarded to a bankrupt corporation when, by delaying liquidation, the company incurs additional debts that would not have arisen if it had filed for bankruptcy at an earlier date. Fehribach v. Ernst & Young LLP, 493 F.3d 905, 908 (7th Cir. 2007). However, recovery under deepening insolvency appears to be subject to increasing limitations. Recently, in Fehribach v. Ernst & Young LLP, 493 F.3d 905 (7th Cir. 2007), the United States Court of Appeals for the Seventh Circuit rejected the notion that a financial auditor is obligated to investigate circumstances external to a company’s records to determine whether a going-concern qualification should be included in an audit report. The Seventh Circuit opined that the auditor is required to factor into its audit report information about external matters that it is “told by the firm or otherwise leans.” Id. at 911. In so holding, the Court, though not entirely casting out the theory of deepening insolvency from future consideration, arguably sent out a warning sign for future claimants in its jurisdiction that these claims are not easy to establish. In particular, the Fehribach decision marks a victory for financial auditors who would otherwise be possible targets for creditors in bankruptcy

    Protein surface recognition with targeted fluorescent molecular probes

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    Protein surface recognition by fluorescent molecular sensors poses an immense challenge in supramolecular recognition chemistry owing to the immense difficulty of selectively targeting these large, relatively flat and non-contiguous domains. The fact that protein surfaces can exhibit different charges, topologies, and posttranslational modifications that can be found in other proteins in the mixture is an additional factor that complicates targeting and therefore, sensing specific protein surface modifications. A recent report, however, shows that the difficulty of sensing changes that occur on the surface of specific proteins could be circumvented by attaching a relatively non-specific synthetic receptor to a specific protein binder. The latter brings the receptor near the target protein and enhances its affinity toward its surface. Modifying the synthetic receptor with an environmentally sensitive fluorescent reporter along with suitable recognition elements enables such systems to target specific regions on protein surfaces and consequently, track modifications that result from conformational changes or binding interactions

    Gr\"obner Bases and Nullstellens\"atze for Graph-Coloring Ideals

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    We revisit a well-known family of polynomial ideals encoding the problem of graph-kk-colorability. Our paper describes how the inherent combinatorial structure of the ideals implies several interesting algebraic properties. Specifically, we provide lower bounds on the difficulty of computing Gr\"obner bases and Nullstellensatz certificates for the coloring ideals of general graphs. For chordal graphs, however, we explicitly describe a Gr\"obner basis for the coloring ideal, and provide a polynomial-time algorithm.Comment: 16 page

    Monoclonal Antibodies: Producing Magic Bullets by Somatic Cell Hybridization

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    Cellular expression and crystal structure of the murine cytomegalovirus MHC-Iv glycoprotein, m153

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    Mouse cytomegalovirus (MCMV), a β-herpesvirus that establishes latent and persistent infections in mice, is a valuable model for studying complex virus-host interactions. MCMV encodes the m145 family of putative immunoevasins with predicted MHC-I structure. Functions attributed to some family members include downregulation of host MHC-I (m152) and NKG2D ligands (m145, m152, m155) and interaction with inhibitory or activating NK receptors (m157). We present the cellular, biochemical and structural characterization of m153, which is a heavily glycosylated homodimer, that does not require β2m or peptide, and is expressed at the surface of MCMV-infected cells. Its 2.4 Å crystal structure confirms that this compact molecule preserves an MHC-I-like fold and reveals a novel mode of dimerization, confirmed by site-directed mutagenesis, and a distinctive disulfide-stabilized extended amino terminus. The structure provides a useful framework for comparative analysis of the divergent members of the m145 family

    Controlled release delivery of penciclovir via a silicone (MED-4750) polymer: kinetics of drug delivery and efficacy in preventing primary feline herpesvirus infection in culture

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    Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This antimetabolite was designed to have a higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS). RFC is the principal transporter for cell entrance of folates and antifolates. Once inside the cell, pralatrexate is efficiently polyglutamated by FPGS. Pralatrexate has demonstrated varying degrees of efficacy in peripheral T-cell lymphoma, with response rates differing between the multiple subtypes of the disease. While phase III studies are still to be completed, early clinical trials indicate that pralatrexate is promising new therapeutic for PTCL

    454-Pyrosequencing: A Molecular Battiscope for Freshwater Viral Ecology

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    Viruses, the most abundant biological entities on the planet, are capable of infecting organisms from all three branches of life, although the majority infect bacteria where the greatest degree of cellular diversity lies. However, the characterization and assessment of viral diversity in natural environments is only beginning to become a possibility. Through the development of a novel technique for the harvest of viral DNA and the application of 454 pyrosequencing, a snapshot of the diversity of the DNA viruses harvested from a standing pond on a cattle farm has been obtained. A high abundance of viral genotypes (785) were present within the virome. The absolute numbers of lambdoid and Shiga toxin (Stx) encoding phages detected suggested that the depth of sequencing had enabled recovery of only ca. 8% of the total virus population, numbers that agreed within less than an order of magnitude with predictions made by rarefaction analysis. The most abundant viral genotypes in the pond were bacteriophages (93.7%). The predominant viral genotypes infecting higher life forms found in association with the farm were pathogens that cause disease in cattle and humans, e.g. members of the Herpesviridae. The techniques and analysis described here provide a fresh approach to the monitoring of viral populations in the aquatic environment, with the potential to become integral to the development of risk analysis tools for monitoring the dissemination of viral agents of animal, plant and human diseases

    How the Virus Outsmarts the Host: Function and Structure of Cytomegalovirus MHC-I-Like Molecules in the Evasion of Natural Killer Cell Surveillance

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    Natural killer (NK) cells provide an initial host immune response to infection by many viral pathogens. Consequently, the viruses have evolved mechanisms to attenuate the host response, leading to improved viral fitness. One mechanism employed by members of the β-herpesvirus family, which includes the cytomegaloviruses, is to modulate the expression of cell surface ligands recognized by NK cell activation molecules. A novel set of cytomegalovirus (CMV) genes, exemplified by the mouse m145 family, encode molecules that have structural and functional features similar to those of host major histocompatibility-encoded (MHC) class I molecules, some of which are known to contribute to immune evasion. In this review, we explore the function, structure, and evolution of MHC-I-like molecules of the CMVs and speculate on the dynamic development of novel immunoevasive functions based on the MHC-I protein fold
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