744 research outputs found
Dan River, Inc. v. Icahn: Disclosure Violations - Relief for Subject Management?
The heightened level of takeover activity during recent years has provoked many innovative responses from the management of subject companies that wish to remain independent. Since successful acquisition of a company usually involves the termination of its existing management, that management will often seek to mobilize the resources of the subject corporation to oppose the takeover attempt. As a result, litigation initiated by management now plays a part in virtually every takeover contest. The case of Dan River, Inc. v. Icahn, a recent Fourth Circuit decision, illustrates the use of litigation to forestall a takeover attempt
Carbon monoxide concentrations evaluated by traffic noise data in urban areas
It is shown that variations in carbon monoxide concentrations can be evaluated by measuring environmental noise, wind velocity and vertical Thermal stability. The results can be justified on the basis of the theory of the street canyon effect. The methodology proposed was verified in two Italian cities with different characteristics: Milan and Ravenna
Discovery of a Novel Small Molecule Inhibitor Targeting the Frataxin/Ubiquitin Interaction via Structure-Based Virtual Screening and Bioassays
Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardiodegenerative disorder for which there are no proven effective treatments. FRDA is caused by decreased expression and/or function of the mitochondrial protein frataxin. Here, we report findings that frataxin is degraded via the ubiquitin-proteasomal pathway and that it is ubiquitinated at residue K147 in Calu-6 cells. A theoretical model of the frataxin-K147/Ub complex, constructed by combining bioinformatics interface predictions with information-driven docking, revealed a hitherto unnoticed, potential ubiquitin-binding domain in frataxin. Through structure-based virtual screening and cell-based assays, we discovered a novel small molecule (compound (+)-11) able to prevent frataxin ubiquitination and degradation. (+)-11 was synthesized and tested for specific binding to frataxin by an UF-LC/MS based ligand-binding assay. Follow-up scaffold-based searches resulted in the identification of a lead series with micromolar activity in disrupting the frataxin/Ub interaction. This study also suggests that frataxin could be a potential target for FRDA drug development
Comparative Genomics Suggests a Taxonomic Revision of the Staphylococcus cohnii Species Complex
Staphylococcus cohnii (SC), a coagulase-negative bacterium, was first isolated in 1975 from human skin. Early phenotypic analyses led to the delineation of two subspecies (subsp.), Staphylococcus cohnii subsp. cohnii (SCC) and Staphylococcus cohnii subsp. urealyticus (SCU). SCC was considered to be specific to humans, whereas SCU apparently demonstrated a wider host range, from lower primates to humans. The type strains ATCC 29974 and ATCC 49330 have been designated for SCC and SCU, respectively. Comparative analysis of 66 complete genome sequences-including a novel SC isolate-revealed unexpected patterns within the SC complex, both in terms of genomic sequence identity and gene content, highlighting the presence of 3 phylogenetically distinct groups. Based on our observations, and on the current guidelines for taxonomic classification for bacterial species, we propose a revision of the SC species complex. We suggest that SCC and SCU should be regarded as two distinct species: SC and SU (Staphylococcus urealyticus), and that two distinct subspecies, SCC and SCB (SC subsp. barensis, represented by the novel strain isolated in Bari) should be recognized within SC. Furthermore, since large-scale comparative genomics studies recurrently suggest inconsistencies or conflicts in taxonomic assignments of bacterial species, we believe that the approach proposed here might be considered for more general application
Link Mining for Kernel-based Compound-Protein Interaction Predictions Using a Chemogenomics Approach
Virtual screening (VS) is widely used during computational drug discovery to
reduce costs. Chemogenomics-based virtual screening (CGBVS) can be used to
predict new compound-protein interactions (CPIs) from known CPI network data
using several methods, including machine learning and data mining. Although
CGBVS facilitates highly efficient and accurate CPI prediction, it has poor
performance for prediction of new compounds for which CPIs are unknown. The
pairwise kernel method (PKM) is a state-of-the-art CGBVS method and shows high
accuracy for prediction of new compounds. In this study, on the basis of link
mining, we improved the PKM by combining link indicator kernel (LIK) and
chemical similarity and evaluated the accuracy of these methods. The proposed
method obtained an average area under the precision-recall curve (AUPR) value
of 0.562, which was higher than that achieved by the conventional Gaussian
interaction profile (GIP) method (0.425), and the calculation time was only
increased by a few percent
Extracellular soil DNA (eDNA): a driving force of microbial life in initial stages of soil development?
Draft Genome Sequences of Three Novel Staphylococcus arlettae Strains Isolated from a Disused Biological Safety Cabinet
The genome sequences of three new strains of Staphylococcus arlettae named Bari1, Bari2, and Bari3 are presented. The strains exhibited tolerance to hexavalent chromium ions. An sprC gene encoding a putative chromium transporter was present in each of the three draft genome sequences
Surface modification of flax yarns by enzymatic treatment and their interfacial adhesion with thermoset matrices
The aim of this study was to assess the effects of commercially available and relatively inexpensive enzyme preparations based on endo 1,4-β-xylanase, pectinase and xyloglucanase on the thermal (TGA), morphological (SEM), chemical (FT-IR) and mechanical (single yarn tensile tests) properties of flax yarns. The preparation based on pectinase and xyloglucanase provided the best results, resulting in the effective removal of hydrophilic components such as hemicellulose and pectin, the individualization of yarns and increased thermal stability at the expense of a reduction in mechanical properties, depending on the treatment parameters. Single yarn fragmentation tests pointed out an improved interfacial adhesion after enzymatic treatment, with reduced debonding length values of 18% for an epoxy matrix and up to 36% for a vinylester resin compared to untreated flax yarns
Geodetic model of the 2016 Central Italy earthquake sequence inferred from InSAR and GPS data
We investigate a large geodetic data set of interferometric synthetic aperture radar (InSAR)and GPS measurements to determine the source parameters for the three main shocks of the 2016Central Italy earthquake sequence on 24 August and 26 and 30 October (Mw6.1, 5.9, and 6.5,respectively). Our preferred model is consistent with the activation of four main coseismic asperitiesbelonging to the SW dipping normal fault system associated with the Mount Gorzano-Mount Vettore-Mount Bove alignment. Additional slip, equivalent to aMw~ 6.1–6.2 earthquake, on a secondary (1) NEdipping antithetic fault and/or (2) on a WNW dipping low-angle fault in the hanging wall of the mainsystem is required to better reproduce the complex deformation pattern associated with the greatestseismic event (theMw6.5 earthquake). The recognition of ancillary faults involved in the sequencesuggests a complex interaction in the activated crustal volume between the main normal faults and thesecondary structures and a partitioning of strain releas
Development and experimental validation of a dynamic numerical model for human articular cartilage
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