525 research outputs found

    What is the value of recourse to asset backed securities? A clinical study of credit card banks

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    The present paper uses data from revolving credit card securitizations to show that, conditional on being in a position where implicit recourse has become necessary and actually providing that recourse, recourse to securitized debt may benefit short- and long-term stock returns, and long-term operating performance of sponsors. The paper suggests that this result may come about because those sponsors providing the recourse do not seem to be extreme default or insolvency risks. However, sponsors providing recourse do experience an abnormal delay in their normal issuance cycle around the event. Hence, it appears that the asset-backed securities market is like the commercial paper market, where a firm's ability to issue is directly correlated with credit quality. Therefore, although in violation of regulatory guidelines and FASB140, recourse may have beneficial effects for sponsors by revealing that the shocks that made recourse necessary are transitory. ; Also issued as Payment Cards Center Discussion Paper No. 03-04Asset-backed financing ; Credit cards

    The Information Content of the 1999 Announcement of Funds from Operations (FFO) Changes for Real Estate Investment Trusts

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    This study examines the market response to the 1999 announcement of a change in accounting for Funds from Operations (FFO) for Real Estate Investment Trusts (REITs). This change provides an increase in transparency in the accounting statements of REITs regarding the calculation of FFO. An analysis of this announcement finds that shareholder wealth increases but the significance of that increase is questionable. Additionally, an analysis of the adverse selection component of the bid-ask spread finds weak evidence to support the conjecture that the amount of information asymmetry in REIT prices declines after the announcement of the FFO accounting change.

    NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity

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    <p>Abstract</p> <p>Background</p> <p>The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. Because the pathway may not be completely inhibited after blockade of PI3K itself, due to feedback through mammalian target of rapamycin (mTOR), more effective inhibition might be expected by targeting both PI3K and mTOR inhibition.</p> <p>Materials and methods</p> <p>We investigated the effect of two dual PI3K/mTOR (both mTORC1 and mTORC2) inhibitors, NVP-BEZ235 and NVP-BGT226, on SQ20B laryngeal and FaDu hypopharyngeal cancer cells characterised by EGFR overexpression, on T24 bladder tumor cell lines with H-Ras mutation and on endothelial cells. Analysis of target protein phosphorylation, clonogenic survival, number of residual γH2AX foci, cell cycle and apoptosis after radiation was performed in both tumor and endothelial cells. In vitro angiogenesis assays were conducted as well.</p> <p>Results</p> <p>Both compounds effectively inhibited phosphorylation of Akt, mTOR and S6 target proteins and reduced clonogenic survival in irradiated tumor cells. Persistence of DNA damage, as evidenced by increased number of γH2AX foci, was detected after irradiation in the presence of PI3K/mTOR inhibition, together with enhanced G2 cell cycle delay. Treatment with one of the inhibitors, NVP-BEZ235, also resulted in decreased clonogenicity after irradiation of tumor cells under hypoxic conditions. In addition, NVP-BEZ235 blocked VEGF- and IR-induced Akt phosphorylation and increased radiation killing in human umbilical venous endothelial cells (HUVEC) and human dermal microvascular dermal cells (HDMVC). NVP-BEZ235 inhibited VEGF-induced cell migration and capillary tube formation in vitro and enhanced the antivascular effect of irradiation. Treatment with NVP-BEZ235 moderately increased apoptosis in SQ20B and HUVEC cells but not in FaDu cells, and increased necrosis in both tumor and endothelial all cells tumor.</p> <p>Conclusions</p> <p>The results of this study demonstrate that PI3K/mTOR inhibitors can enhance radiation-induced killing in tumor and endothelial cells and may be of benefit when combined with radiotherapy.</p

    Ethnic differences in the prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian prenatal population

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    Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity (p < 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity (p < 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity (p < 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women (p < 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population

    The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense

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    Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense

    Assessment of F/HN-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy

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    RATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES: To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved. METHODS: F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air-liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices. MEASUREMENTS AND MAIN RESULTS: A single dose produces lung expression for the lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS: The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials

    The structure of haplotype blocks in the human genome

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    Haplotype-based methods offer a powerful approach to disease gene mapping, based on the association between causal mutations and the ancestral haplotypes on which they arose. As part of The SNP Consortium Allele Frequency Projects, we characterized haplotype patterns across 51 autosomal regions (spanning 13 megabases of the human genome) in samples from Africa, Europe, and Asia. We show that the human genome can be parsed objectively into haplotype blocks; sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed. The boundaries of blocks and specific haplotypes they contain are highly correlated across populations. We demonstrate that such haplotype frameworks provide substantial statistical power in association studies of common genetic variation across each region. Our results provide a foundation for the construction of a haplotype map of the human genome, facilitating comprehensive genetic association studies of human disease

    Freshwater ecoregions of the world: A new map of biogeographic units for freshwater biodiversity conservation

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    We present a new map depicting the first global biogeographic regionalization of Earth's freshwater systems. This map of freshwater ecoregions is based on the distributions and compositions of freshwater fish species and incorporates major ecological and evolutionary patterns. Covering virtually all freshwater habitats on Earth, this ecoregion map, together with associated species data, is a useful tool for underpinning global and regional conservation planning efforts (particularly to identify outstanding and imperiled freshwater systems); for serving as a logical framework for large-scale conservation strategies; and for providing a global-scale knowledge base for increasing freshwater biogeographic literacy. Preliminary data for fish species compiled by ecoregion reveal some previously unrecognized areas of high biodiversity, highlighting the benefit of looking at the world's freshwaters through a new framework.La lista completa de autores que integran el documento puede consultarse en el archivo.Facultad de Ciencias Naturales y Muse
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