103 research outputs found

    A Metric Framework for quantifying Data Concentration

    Get PDF
    Poor performance of artificial neural nets when applied to credit-related classification problems is investigated and contrasted with logistic regression classification. We propose that artificial neural nets are less successful because of the inherent structure of credit data rather than any particular aspect of the neural net structure. Three metrics are developed to rationalise the result with such data. The metrics exploit the distributional properties of the data to rationalise neural net results. They are used in conjunction with a variant of an established concentration measure that differentiates between class characteristics. The results are contrasted with those obtained using random data, and are compared with results obtained using logistic regression. We find, in general agreement with previous studies, that logistic regressions out-perform neural nets in the majority of cases. An approximate decision criterion is developed in order to explain adverse results

    Sources of pro-cyclicality in east Asian financial systems

    Get PDF
    Procyclicality is a normal feature of economic systems, but financial sector weaknesses can exacerbate it sufficiently to pose a threat to macroeconomic and financial stability. These include shortcomings in bank risk management and governance, in supervision and in terms of dependence on volatile sources of funds. The paper tests econometrically for the importance of such features leading to pro-cyclicality in the financial systems of 11 East Asian countries. This analysis makes it possible to identify specific policy measures for East Asian countries that could limit the extent to which financial systems exacerbate pro-cyclicality

    Is the MENA banking sector competitive?

    Get PDF
    The purpose of this paper is to investigate the competitive conditions and revenue drivers of commercial banks in the MENA region in the context of Panzar–Rosse model. It is the first study of its kind that examines a large sample of MENA banks for an extensive period (1999–2012) during an era of political and economic unrest and transformation that includes the the global financial crisis (2007–2009). Panel data analysis using fixed effects was employed in order to examine whether the competitive conditions in MENA banks is explained by monopoly, monopolistic competition or perfect competition. Findings show that MENA banks operate under monopolistic competition, and bank-specific variables show a positive impact on revenue. These findings indicate that policymakers should relax capital adequacy requirements to guarantee the stability of the financial system. They also raise a concern that commercial banks in the MENA economies tend to concentrate on traditional lending activities, where their competitive position may be eroded in the long run by the decreasing state role of Islamic banks and by mergers that are not empirically justified for MENA banks during this period

    Lung volume calculated from electrical impedance tomography in ICU patients at different PEEP levels

    Get PDF
    Purpose: To study and compare the relationship between end-expiratory lung volume (EELV) and changes in end-expiratory lung impedance (EELI) measured with electrical impedance tomography (EIT) at the basal part of the lung at different PEEP levels in a mixed ICU population. Methods: End-expiratory lung volume, EELI and tidal impedance variation were determined at four PEEP levels (15-10-5-0 cm H2O) in 25 ventilated ICU patients. The tidal impedance variation and tidal volume at 5 cm H2O PEEP were used to calculate change in impedance per ml; this ratio was then used to calculate change in lung volume from change in EELI. To evaluate repeatability, EELV was measured in quadruplicate in five additional patients. Results: There was a significant but relatively low correlation (r = 0.79; R2= 0.62) and moderate agreement (bias 194 ml, SD 323 ml) between ΔEELV and change in lung volume calculated from the ΔEELI. The ratio of tidal impedance variation and tidal volume differed between patients and also varied at different PEEP levels. Good agreement was found between repeated EELV measurements and washin/washout of a simulated nitrogen washout technique. Conclusion: During a PEEP trial, the assumption of a linear relationship between change in global tidal impedance and tidal volume cannot be used to calculate EELV when impedance is measured at only one thoracic level just above the diaphragm

    Structure-guided selection of specificity determining positions in the human kinome

    Get PDF
    Background: The human kinome contains many important drug targets. It is well-known that inhibitors of protein kinases bind with very different selectivity profiles. This is also the case for inhibitors of many other protein families. The increased availability of protein 3D structures has provided much information on the structural variation within a given protein family. However, the relationship between structural variations and binding specificity is complex and incompletely understood. We have developed a structural bioinformatics approach which provides an analysis of key determinants of binding selectivity as a tool to enhance the rational design of drugs with a specific selectivity profile. Results: We propose a greedy algorithm that computes a subset of residue positions in a multiple sequence alignment such that structural and chemical variation in those positions helps explain known binding affinities. By providing this information, the main purpose of the algorithm is to provide experimentalists with possible insights into how the selectivity profile of certain inhibitors is achieved, which is useful for lead optimization. In addition, the algorithm can also be used to predict binding affinities for structures whose affinity for a given inhibitor is unknown. The algorithm’s performance is demonstrated using an extensive dataset for the human kinome. Conclusion: We show that the binding affinity of 38 different kinase inhibitors can be explained with consistently high precision and accuracy using the variation of at most six residue positions in the kinome binding site. We show for several inhibitors that we are able to identify residues that are known to be functionally important

    Combinatorial Clustering of Residue Position Subsets Predicts Inhibitor Affinity across the Human Kinome

    Get PDF
    The protein kinases are a large family of enzymes that play fundamental roles in propagating signals within the cell. Because of the high degree of binding site similarity shared among protein kinases, designing drug compounds with high specificity among the kinases has proven difficult. However, computational approaches to comparing the 3-dimensional geometry and physicochemical properties of key binding site residue positions have been shown to be informative of inhibitor selectivity. The Combinatorial Clustering Of Residue Position Subsets (CCORPS) method, introduced here, provides a semi-supervised learning approach for identifying structural features that are correlated with a given set of annotation labels. Here, CCORPS is applied to the problem of identifying structural features of the kinase ATP binding site that are informative of inhibitor binding. CCORPS is demonstrated to make perfect or near-perfect predictions for the binding affinity profile of 8 of the 38 kinase inhibitors studied, while only having overall poor predictive ability for 1 of the 38 compounds. Additionally, CCORPS is shown to identify shared structural features across phylogenetically diverse groups of kinases that are correlated with binding affinity for particular inhibitors; such instances of structural similarity among phylogenetically diverse kinases are also shown to not be rare among kinases. Finally, these function-specific structural features may serve as potential starting points for the development of highly specific kinase inhibitors

    How local is local? Evidence from bank competition and corporate innovation in U.S.

    Get PDF
    This paper aims to fill in a research gap in the effects of bank competition on corporate innovation. In addition to the evidence on the favorable effects of bank competition on corporate innovation, we show novel evidence on the substitution effects of bank competition in a wider region and neighbor-state to local bank competition in financing corporate innovation activities. In banking market, we show ‘how local is local’ depends on the operating scope and information transparency of firms. Local banks have an information advantage over distant banks in financing local businesses and informationally opaque corporate innovation activities

    A Survival Analysis of Islamic and Conventional Banks

    Get PDF
    Are Islamic banks inherently more stable than conventional banks? We address this question by applying a survival analysis based on the Cox proportional hazard model to a comprehensive sample of 421 banks in 20 Middle and Far Eastern countries from 1995 to 2010. By comparing the failure risk for both bank types, we find that Islamic banks have a significantly lower risk of failure than that of their conventional peers. This lower risk is based both unconditionally and conditionally on bank-specific (microeconomic) variables as well as macroeconomic and market structure variables. Our findings indicate that the design and implementation of early warning systems for bank failure should recognize the distinct risk profiles of the two bank types

    Administration of intrapulmonary sodium polyacrylate to induce lung injury for the development of a porcine model of early acute respiratory distress syndrome.

    Get PDF
    BACKGROUND: The loss of alveolar epithelial and endothelial integrity is a central component in acute respiratory distress syndrome (ARDS); however, experimental models investigating the mechanisms of epithelial injury are lacking. The purpose of the present study was to design and develop an experimental porcine model of ARDS by inducing lung injury with intrapulmonary administration of sodium polyacrylate (SPA). METHODS: The present study was performed at the Centre for Comparative Medicine, University of British Columbia, Vancouver, British Columbia. Human alveolar epithelial cells were cultured with several different concentrations of SPA; a bioluminescence technique was used to assess cell death associated with each concentration. In the anesthetized pig model (female Yorkshire X pigs (n = 14)), lung injury was caused in 11 animals (SPA group) by injecting sequential aliquots (5 mL) of 1% SPA gel in aqueous solution into the distal airway via a rubber catheter through an endotracheal tube. The SPA was dispersed throughout the lungs by manual bag ventilation. Three control animals (CON group) underwent all experimental procedures and measurements with the exception of SPA administration. RESULTS: The mean (± SD) ATP concentration after incubation of human alveolar epithelial cells with 0.1% SPA (0.92 ± 0.27 μM/well) was approximately 15% of the value found for the background control (6.30 ± 0.37 μM/well; p < 0.001). Elastance of the respiratory system (E RS) and the lung (E L) increased in SPA-treated animals after injury (p = 0.003 and p < 0.001, respectively). Chest wall elastance (E CW) did not change in SPA-treated animals. There were no differences in E RS, E L, or E CW in the CON group when pre- and post-injury values were compared. Analysis of bronchoalveolar lavage fluid showed a significant shift toward neutrophil predominance from before to after injury in SPA-treated animals (p < 0.001) but not in the CON group (p = 0.38). Necropsy revealed marked consolidation and congestion of the dorsal lung lobes in SPA-treated animals, with light-microscopy evidence of bronchiolar and alveolar spaces filled with neutrophilic infiltrate, proteinaceous debris, and fibrin deposition. These findings were absent in animals in the CON group. Electron microscopy of lung tissue from SPA-treated animals revealed injury to the alveolar epithelium and basement membranes, including intra-alveolar neutrophils and fibrin on the alveolar surface and intravascular fibrin (microthrombosis). CONCLUSIONS: In this particular porcine model, the nonimmunogenic polymer SPA caused a rapid exudative lung injury. This model may be useful to study ARDS caused by epithelial injury and inflammation

    Analysis of copy number variation at DMBT1 and age-related macular degeneration

    Get PDF
    BACKGROUND: DMBT1 is a gene that shows extensive copy number variation (CNV) that alters the number of bacteria-binding domains in the protein and has been shown to activate the complement pathway. It lies next to the ARMS2/HTRA1 genes in a region of chromosome 10q26, where single nucleotide variants have been strongly associated with age-related macular degeneration (AMD), the commonest cause of blindness in Western populations. Complement activation is thought to be a key factor in the pathogenesis of this condition. We sought to investigate whether DMBT1 CNV plays any role in the susceptibility to AMD. METHODS: We analysed long-range linkage disequilibrium of DMBT1 CNV1 and CNV2 with flanking single nucleotide polymorphisms (SNPs) using our previously published CNV and HapMap Phase 3 SNP data in the CEPH Europeans from Utah (CEU). We then typed a large cohort of 860 AMD patients and 419 examined age-matched controls for copy number at DMBT1 CNV1 and CNV2 and combined these data with copy numbers from a further 480 unexamined controls. RESULTS: We found weak linkage disequilibrium between DMBT1 CNV1 and CNV2 with the SNPs rs1474526 and rs714816 in the HTRA1/ARMS2 region. By directly analysing copy number variation, we found no evidence of association of CNV1 or CNV2 with AMD. CONCLUSIONS: We have shown that copy number variation at DMBT1 does not affect risk of developing age-related macular degeneration and can therefore be ruled out from future studies investigating the association of structural variation at 10q26 with AMD
    corecore