405 research outputs found

    Executive compensation and the susceptibility of firms to hostile takeovers : An empirical investigation of the U.S. oil industry

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    We investigate the suggested substitutive relation between executive compensation and the disciplinary threat of takeover imposed by the market for corporate control. We complement other empirical studies on managerial compensation and corporate control mechanisms in three distinct ways. First, we concentrate on firms in the oil industry for which agency problems were especially severe in the 1980s. Due to the extensive generation of excess cash flow, product and factor market discipline was ineffective. Second, we obtain a unique data set drawn directly from proxy statements which accounts not only for salary and bonus but for the value of all stock-market based compensation held in the portfolio of a CEO. Our data set consists of 51 firms in the U.S. oil industry from 1977 to 1994. Third, we employ ex ante measures of the threat of takeover at the individual firm level which are superior to ex post measures like actual takeover occurrence or past incidence of takeovers in an industry. Results show that annual compensation and, to a much higher degree, stock-based managerial compensation increase after a firm becomes protected from a hostile takeover. However, clear-cut evidence that CEOs of protected firms receive higher compensation than those of firms considered susceptible to a takeover cannot be found

    Epidermal Langerhans Cells Rapidly Capture and Present Antigens from C-Type Lectin-Targeting Antibodies Deposited in the Dermis

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    Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin− CD103− mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions

    PManalyzer: A Software Facilitating the Study of Sensorimotor Control of Whole-Body Movements

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    Motion analysis is used to study the functionality or dysfunctionality of the neuromuscular system, as human movements are the direct outcome of neuromuscular control. However, motion analysis often relies on measures that quantify simplified aspects of a motion, such as specific joint angles, despite the well-known complexity of segment interactions. In contrast, analyzing whole-body movement patterns may offer a new understanding of movement coordination and movement performance. Clinical research and sports technique evaluations suggest that principal component analysis (PCA) provides novel and valuable insights into control aspects of the neuromuscular system and how they relate to coordinative patterns. However, the implementation of PCA computations are time consuming, and require mathematical knowledge and programming skills, drastically limiting its application in current research. Therefore, the aim of this study is to present the Matlab software tool “PManalyzer” to facilitate and encourage the application of state-of-the-art PCA concepts in human movement science. The generalized PCA concepts implemented in the PManalyzer allow users to apply a variety of marker set independent PCA-variables on any kinematic data and to visualize the results with customizable plots. In addition, the extracted movement patterns can be explored with video options that may help testing hypotheses related to the interplay of segments. Furthermore, the software can be easily modified and adapted to any specific application

    Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

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    Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs

    Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

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    Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

    Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting

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    Dexamethasone (20 mg) or its equivalent in combination with 5-HT3 antagonists appears to be the gold-standard dose for antiemetic prophylaxis. Additional to concerns about the use of corticosteroids with respect to enhanced tumour growth or impaired killing of the tumour cells, there is evidence that high-dosage dexamethasone impairs the control of delayed nausea and emesis, whereas lower doses appear more beneficial. To come closer to the most adequate dose, we started a prospective, single-blind, randomized trial investigating additional dosage of 8 or 20 mg dexamethasone to tropisetron (Navoban), a 5-HT3 receptor antagonist, in cis-platinum-containing chemotherapy. After an interim analysis of 121 courses of chemotherapy in 69 patients, we have been unable to detect major differences between both treatment alternatives. High-dose dexamethasone (20 mg) had no advantage over medium-dose dexamethasone with respect to objective and subjective parameters of acute and delayed nausea and vomiting. In relation to concerns about the use of corticosteroids in non-haematological cancer chemotherapy, we suggest that 8 mg or its equivalent should be used in combination with 5-HT3 antagonists until further research proves otherwise. © 1999 Cancer Research Campaig

    Development of Mouse Hepatocyte Lines Permissive for Hepatitis C Virus (HCV)

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    The lack of a suitable small animal model for the analysis of hepatitis C virus (HCV) infection has hampered elucidation of the HCV life cycle and the development of both protective and therapeutic strategies against HCV infection. Human and mouse harbor a comparable system for antiviral type I interferon (IFN) induction and amplification, which regulates viral infection and replication. Using hepatocytes from knockout (ko) mice, we determined the critical step of the IFN-inducing/amplification pathways regulating HCV replication in mouse. The results infer that interferon-beta promoter stimulator (IPS-1) or interferon A receptor (IFNAR) were a crucial barrier to HCV replication in mouse hepatocytes. Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or IFNAR through immortalization with SV40T antigen. Expression of human (h)CD81 on these hepatocyte lines rendered both lines HCVcc-permissive. We also found that the chimeric J6JFH1 construct, having the structure region from J6 isolate enhanced HCV replication in mouse hepatocytes rather than the full length original JFH1 construct, a new finding that suggests the possible role of the HCV structural region in HCV replication. This is the first report on the entry and replication of HCV infectious particles in mouse hepatocytes. These mouse hepatocyte lines will facilitate establishing a mouse HCV infection model with multifarious applications
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