2,083 research outputs found

    The Rise of 144A Market for Convertible Debt

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    We document and study the migration of convertible debt offerings from the public to the 144A market during 1991-2004. Over 88% of the 144A convertible debt issues are subsequently registered. An analysis of financing costs (gross spreads, yields, and stock price announcements) and issue characteristics indicates that convertible debt issues in these two markets are essentially the same. We find evidence that the 144A market allows firms to better time equity market conditions. Our findings are consistent with the hypothesis that the 144A market is attractive because it allows firms to issue convertible debt more quickly

    Information Opacity, Credit Risk, and the Design of Loan Contracts for Private Firms

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    This paper examines the structure and cost of a large sample of bank loans to private firms. Compared to public firms, private firms are more informationally opaque and riskier. The results suggest that the design of a loan to a private firm is significantly different from that to a public firm. Bank loans to private firms are more likely to be by a sole lender, collateralized, and have sweep covenants than loans to public firms. The cost of borrowing is higher for a private firm than for a public firm, even after holding constant firm and loan characteristics

    Effects of Boson Dispersion in Fermion-Boson Coupled Systems

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    We study the nonlinear feedback in a fermion-boson system using an extension of dynamical mean-field theory and the quantum Monte Carlo method. In the perturbative regimes (weak-coupling and atomic limits) the effective interaction among fermions increases as the width of the boson dispersion increases. In the strong coupling regime away from the anti-adiabatic limit, the effective interaction decreases as we increase the width of the boson dispersion. This behavior is closely related with complete softening of the boson field. We elucidate the parameters that control this nonperturbative region where fluctuations of the dispersive bosons enhance the delocalization of fermions.Comment: 14 pages RevTeX including 12 PS figure

    Quantification of unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples

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    Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings

    Dynamic and wear study of an extremely bidisperse magnetorheological fluid

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    Acceso a la versión publicada en Smart Mater. Struct. 24(12) 127001 (http://iopscience.iop.org/0964-1726/24/12/127001)"This is an author-created, un-copyedited version of an article accepted for publication/published in Smart Materials and Structures. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://dx.doi.org/10.1088/0964-1726/24/12/127001."In this work the friction and wear properties of five magnetorheologicalfluids (MRFs)with varying compositions are investigated. Considering that many of the proposed applications for these fluids involve lubricated contact between mobile metal –metal or polymer– metal parts, the relationship between MR response and wear behavior appears to be of fundamental importance. One of the fluids(MR#1)contains only the iron microparticles and base oil; the second and third ones(MR#2 and MR#3) contain an anti-wear additive as well. The fourth one(MR#4)is a well known commercial MRF. Finally, MR#5 is stabilized by dispersing the iron particles in a magnetite ferrofluid. The MR response of the latter fluid is better(higher yield stress and post-yield viscosity)than that of the others. More importantly, it remains(and even improves)after the wear test: the pressure applied in the four-ball apparatus produces a compaction of the magnetite layer around the iron microparticles. Additionally, the friction coefficient is larger, which seems paradoxical in principle, but can be explained by considering the stability of MR#5 in comparison to the other four MRs, which appear to undergo partial phase separation during the test. In fact, electron and optical microscope observations confirm a milder wear effect of MR#5, with almost complete absence of scars from the steel test spheres and homogeneous and shallow grooves on them. Comparatively, MR#2, MR#3 and, particularly, MR#1 produce a much more significant wear.MINECO Ramón y Cajal Programme (RYC-2014-16901)MINECO FIS 2013-07666-C3-1-RCEI Biotic BS27.2015Junta de Andalucía, PE2012-FQM-069

    Timescales of transformational climate change adaptation in sub-Saharan African agriculture

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    Climate change is projected to constitute a significant threat to food security if no adaptation actions are taken. Transformation of agricultural systems, for example switching crop types or moving out of agriculture, is projected to be necessary in some cases. However, little attention has been paid to the timing of these transformations. Here, we develop a temporal uncertainty framework using the CMIP5 ensemble to assess when and where cultivation of key crops in sub-Saharan Africa becomes unviable. We report potential transformational changes for all major crops during the twenty-first century, as climates shift and areas become unsuitable. For most crops, however, transformation is limited to small pockets (<15% of area), and only for beans, maize and banana is transformation more widespread (â 1/430% area for maize and banana, 60% for beans). We envisage three overlapping adaptation phases to enable projected transformational changes: an incremental adaptation phase focused on improvements to crops and management, a preparatory phase that establishes appropriate policies and enabling environments, and a transformational adaptation phase in which farmers substitute crops, explore alternative livelihoods strategies, or relocate. To best align policies with production triggers for no-regret actions, monitoring capacities to track farming systems as well as climate are needed

    Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration

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    Mutations in the gene coding for Sequestosome 1 (SQSTM1) have been genetically associated with amyotrophic lateral sclerosis (ALS) and Paget disease of bone. In the present study, we analyzed the SQSTM1 coding sequence for mutations in an extended cohort of 1,808 patients with frontotemporal lobar degeneration (FTLD), ascertained within the European Early-Onset Dementia consortium. As control dataset, we sequenced 1,625 European control individuals and analyzed whole-exome sequence data of 2,274 German individuals (total n = 3,899). Association of rare SQSTM1 mutations was calculated in a meta-analysis of 4,332 FTLD and 10,240 control alleles. We identified 25 coding variants in FTLD patients of which 10 have not been described. Fifteen mutations were absent in the control individuals (carrier frequency < 0.00026) whilst the others were rare in both patients and control individuals. When pooling all variants with a minor allele frequency < 0.01, an overall frequency of 3.2 % was calculated in patients. Rare variant association analysis between patients and controls showed no difference over the whole protein, but suggested that rare mutations clustering in the UBA domain of SQSTM1 may influence disease susceptibility by doubling the risk for FTLD (RR = 2.18 [95 % CI 1.24-3.85]; corrected p value = 0.042). Detailed histopathology demonstrated that mutations in SQSTM1 associate with widespread neuronal and glial phospho-TDP-43 pathology. With this study, we provide further evidence for a putative role of rare mutations in SQSTM1 in the genetic etiology of FTLD and showed that, comparable to other FTLD/ALS genes, SQSTM1 mutations are associated with TDP-43 pathology

    Functional electrical stimulation therapy controlled by a P300-based brain–computer interface, as a therapeutic alternative for upper limb motor function recovery in chronic post-stroke patients. A non-randomized pilot study

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    IntroductionUp to 80% of post-stroke patients present upper-limb motor impairment (ULMI), causing functional limitations in daily activities and loss of independence. UMLI is seldom fully recovered after stroke when using conventional therapeutic approaches. Functional Electrical Stimulation Therapy (FEST) controlled by Brain–Computer Interface (BCI) is an alternative that may induce neuroplastic changes, even in chronic post-stroke patients. The purpose of this work was to evaluate the effects of a P300-based BCI-controlled FEST intervention, for ULMI recovery of chronic post-stroke patients.MethodsA non-randomized pilot study was conducted, including 14 patients divided into 2 groups: BCI-FEST, and Conventional Therapy. Assessments of Upper limb functionality with Action Research Arm Test (ARAT), performance impairment with Fugl–Meyer assessment (FMA), Functional Independence Measure (FIM) and spasticity through Modified Ashworth Scale (MAS) were performed at baseline and after carrying out 20 therapy sessions, and the obtained scores compared using Chi square and Mann–Whitney U statistical tests ( = 0.05).ResultsAfter training, we found statistically significant differences between groups for FMA (p = 0.012), ARAT (p &lt; 0.001), and FIM (p = 0.025) scales.DiscussionIt has been shown that FEST controlled by a P300-based BCI, may be more effective than conventional therapy to improve ULMI after stroke, regardless of chronicity.ConclusionThe results of the proposed BCI-FEST intervention are promising, even for the most chronic post-stroke patients often relegated from novel interventions, whose expected recovery with conventional therapy is very low. It is necessary to carry out a randomized controlled trial in the future with a larger sample of patients

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types
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