1,053 research outputs found

    Competitive Lending with Partial Knowledge of Loan Repayment

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    We study a competitive credit market in which lenders with partial knowledge of loan repayment use one of three decision criteria – maximization of expected utility, maximin, or minimax regret – to make lending decisions. Lenders allocate endowments between loans and a safe asset, while borrowers demand loans to undertake investments. Borrowers may incompletely repay their loans when investment productivity turns out to be low ex post. We characterize market equilibrium, the contracted repayment rate being the price variable that equilibrates loan supply and demand. Supposing that a public Authority wants to maximize the net social return to borrowing, we study two interventions in the credit market to achieve this objective. One intervention manipulates the return on the safe asset and the other guarantees a minimum loan return to lenders. In a simple scenario, we find that manipulation of the return on the safe asset can be an effective way to achieve the socially desired outcome if lender beliefs about the return to lending are not too pessimistic relative to the beliefs of the Authority. Contrariwise, guaranteeing a minimum loan return can be effective if lender beliefs are not too optimistic relative to the beliefs of the Authority.

    Do Gamma-Ray Burst Sources Repeat?

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    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb 1993; Wang and Lingenfelter 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al. 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.Comment: ApJ Letters, in press, 13 pages, including three embedded figures. uuencoded Unix-compressed PostScrip

    Particle number concentrations and size distributions in the stratosphere : implications of nucleation mechanisms and particle microphysics

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    While formation and growth of particles in the troposphere have been extensively studied in the past two decades, very limited efforts have been devoted to understanding these in the stratosphere. Here we use both Cosmics Leaving OUtdoor Droplets (CLOUD) laboratory measurements taken under very low temperatures (205-223 K) and Atmospheric Tomography Mission (ATom) in situ observations of particle number size distributions (PNSDs) down to 3 nm to constrain nucleation mechanisms and to evaluate model-simulated particle size distributions in the lowermost stratosphere (LMS). We show that the binary homogenous nucleation (BHN) scheme used in most of the existing stratospheric aerosol injection (a proposed method of solar radiation modification) modeling studies overpredicts the nucleation rates by 3-4 orders of magnitude (when compared to CLOUD data) and particle number concentrations in the background LMS by a factor similar to 2-4 (when compared to ATom data). Based on a recently developed kinetic nucleation model, which gives rates of both ion-mediated nucleation (IMN) and BHN at low temperatures in good agreement with CLOUD measurements, both BHN and IMN occur in the stratosphere. However, IMN rates are generally more than 1 order of magnitude higher than BHN rates and thus dominate nucleation in the background stratosphere. In the Southern Hemisphere (SH) LMS with minimum influence of anthropogenic emissions, our analysis shows that ATom-measured PNSDs generally have four apparent modes. The model captures reasonably well the two modes (Aitken mode and the first accumulation mode) with the highest number concentrations and size-dependent standard deviations. However, the model misses an apparent second accumulation mode peaking around 300-400 nm, which is in the size range important for aerosol direct radiative forcing. The bimodal structure of accumulation mode particles has also been observed in the stratosphere well above tropopause and in the volcano-perturbed stratosphere. We suggest that this bimodal structure may be caused by the effect of charges on coagulation and growth, which is not yet considered in any existing models and may be important in the stratosphere due to high ionization rates and the long lifetime of aerosols. Considering the importance of accurate PNSDs for projecting a realistic radiation forcing response to stratospheric aerosol injection (SAI), it is essential to understand and incorporate such potentially important processes in SAI model simulations and to carry out further research to find out what other processes the present models might have missed.Peer reviewe

    Development and evaluation of a diagnostic cytokine-release assay for Mycobacterium suricattae infection in meerkats (Suricata suricatta)

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    CITATION: Clarke, C., et al. 2017. Development and evaluation of a diagnostic cytokine-release assay for mycobacterium suricattae infection in meerkats (Suricata suricatta). BMC Veterinary Research, 13:2, doi:10.1186/s12917-016-0927-x.The original publication is available at http://bmcvetres.biomedcentral.comBackground: Sensitive diagnostic tools are necessary for the detection of Mycobacterium suricattae infection in meerkats (Suricata suricatta) in order to more clearly understand the epidemiology of tuberculosis and the ecological consequences of the disease in this species. We therefore aimed to develop a cytokine release assay to measure antigen-specific cell-mediated immune responses of meerkats. Results: Enzyme-linked immunosorbent assays (ELISAs) were evaluated for the detection of interferon-gamma (IFN-γ) and IFN-γ inducible protein 10 (IP-10) in meerkat plasma. An IP-10 ELISA was selected to measure the release of this cytokine in whole blood in response to Bovigam® PC-HP Stimulating Antigen, a commercial peptide pool of M. bovis antigens. Using this protocol, captive meerkats with no known M. suricattae exposure (n = 10) were tested and results were used to define a diagnostic cut off value (mean plus 2 standard deviations). This IP-10 release assay (IPRA) was then evaluated in free-living meerkats with known M. suricattae exposure, categorized as having either a low, moderate or high risk of infection with this pathogen. In each category, respectively, 24.7%, 27.3% and 82.4% of animals tested IPRA-positive. The odds of an animal testing positive was 14.0 times greater for animals with a high risk of M. suricattae infection compared to animals with a low risk. Conclusion: These results support the use of this assay as a measure of M. suricattae exposure in meerkat populations. Ongoing longitudinal studies aim to evaluate the value of the IPRA as a diagnostic test of M. suricattae infection in individual animals.http://bmcvetres.biomedcentral.com/articles/10.1186/s12917-016-0927-xPublisher's versio

    Alterations of immune response of non-small lung cancer with azacytidine

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    Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

    Identification of Key Elements in Prostate Cancer for Ontology Building via a Multidisciplinary Consensus Agreement

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    BACKGROUND: Clinical data collection related to prostate cancer (PCa) care is often unstructured or heterogeneous among providers, resulting in a high risk for ambiguity in its meaning when sharing or analyzing data. Ontologies, which are shareable formal (i.e., computable) representations of knowledge, can address these challenges by enabling machine-readable semantic interoperability. The purpose of this study was to identify PCa-specific key data elements (KDEs) for standardization in clinic and research. METHODS: A modified Delphi method using iterative online surveys was performed to report a consensus agreement on KDEs by a multidisciplinary panel of 39 PCa specialists. Data elements were divided into three themes in PCa and included (1) treatment-related toxicities (TRT), (2) patient-reported outcome measures (PROM), and (3) disease control metrics (DCM). RESULTS: The panel reached consensus on a thirty-item, two-tiered list of KDEs focusing mainly on urinary and rectal symptoms. The Expanded Prostate Cancer Index Composite (EPIC-26) questionnaire was considered most robust for PROM multi-domain monitoring, and granular KDEs were defined for DCM. CONCLUSIONS: This expert consensus on PCa-specific KDEs has served as a foundation for a professional society-endorsed, publicly available operational ontology developed by the American Association of Physicists in Medicine (AAPM) Big Data Sub Committee (BDSC)
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