5,920 research outputs found

    Are Bond Covenants Priced?

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    In this paper we ask the empirical question are bond covenants priced? Consistent with the Costly Contracting Hypothesis (CCH) developed by Smith and Warner (1979), we find that they are. We document a negative relation between the promised yield on corporate debt issues and the presence of covenants. We also find that loans made to high-growth firms are more likely to include restrictive covenants than loans made to low-growth firms. We show that the inclusion of a covenant varies systematically with macroeconomic factors as well as with supply-side factors, especially the identity of the lending institution. Finally, we show that consistent with the CCH, firms that elect to issue private rather than public debt are smaller, have greater growth opportunities, less long term debt, fewer tangible assets, and include more covenants in their debt agreements. An important byproduct of our analysis is to demonstrate empirically that the decision to include a covenant and the corresponding promised yield are determined simultaneously. Consequently, statistical models that ignore this simultaneity in analyzing the effects of covenants, like single-equation probit models, are misspecified and generate unreliable statisticsAgency Costs, Costly Contracting, Debt Covenants

    Regulation of Arabidopsis 14-3-3 gene expression by GABA.

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    The function in plants of the non-protein amino acid, gamma-aminobutyric acid (GABA) is poorly understood. In this study, we show that GABA down-regulates the expression of a large sub-set of 14-3-3 gene family members in Arabidopsis thaliana seedlings in a calcium, ethylene and abscisic acid-dependent manner. Gene expression is not affected when seedlings are supplied with glutamate, a precursor of GABA. The repression of 14-3-3 gene expression by GABA is dependent on functional ethylene and abscisic acid signalling pathways, since the response is lost in the etr1-1, abi1-1 and abi2-1 mutants. Calcium measurements show that in contrast to glutamate, GABA does not elicit a cytoplasmic calcium elevation, suggesting that the GABA response is unlikely to be mediated by glutamate receptors, as has been suggested previously. We suggest that in addition to its role as a stress-related metabolite, GABA may regulate gene expression in Arabidopsis, including members of the 14-3-3 gene family

    Developmental genetics

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    The culture of enthesopathies: Differences in musculoskeletal stress markers between samples in a historic population

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    Information Agents for Pervasive Sensor Networks

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    In this paper, we describe an information agent, that resides on a mobile computer or personal digital assistant (PDA), that can autonomously acquire sensor readings from pervasive sensor networks (deciding when and which sensor to acquire readings from at any time). Moreover, it can perform a range of information processing tasks including modelling the accuracy of the sensor readings, predicting the value of missing sensor readings, and predicting how the monitored environmental parameters will evolve into the future. Our motivating scenario is the need to provide situational awareness support to first responders at the scene of a large scale incident, and we describe how we use an iterative formulation of a multi-output Gaussian process to build a probabilistic model of the environmental parameters being measured by local sensors, and the correlations and delays that exist between them. We validate our approach using data collected from a network of weather sensors located on the south coast of England

    Ets-2 and C/EBP-beta are important mediators of ovine trophoblast Kunitz domain protein-1 gene expression in trophoblast

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    BACKGROUND: The trophoblast Kunitz domain proteins (TKDPs) constitute a highly expressed, placenta-specific, multigene family restricted to ruminant ungulates and characterized by a C-terminal "Kunitz" domain, preceded by one or more unique N-terminal domains. TKDP-1 shares an almost identical expression pattern with interferon-tau, the "maternal recognition of pregnancy protein" in ruminants. Our goal here has been to determine whether the ovine (ov) Tkdp-1 and IFNT genes possess a similar transcriptional code. RESULTS: The ovTkdp-1 promoter has been cloned and characterized. As with the IFNT promoter, the Tkdp-1 promoter is responsive to Ets-2, and promoter-driven reporter activity can be increased over 700-fold in response to over-expression of Ets-2 and a constitutively active form of protein Kinase A (PKA). Unexpectedly, the promoter element of Tkdp-1 responsible for this up-regulation, unlike that of the IFNT, does not bind Ets-2. However, mutation of a CCAAT/enhancer binding element within this control region not only reduced basal transcriptional activity, but prevented Ets-2 as well as cyclic adenosine 5'-monophosphate (cAMP)/PKA and Ras/mitogen-activated protein kinase (MAPK) responsiveness. In vitro binding experiments and in vivo protein-protein interaction assays implicated CCAAT/enhancer binding protein-beta (C/EBP-β) as involved in up-regulating the Tkdp-1 promoter activity. A combination of Ets-2 and C/EBP-β can up-regulate expression of the minimal Tkdp-1 promoter as much as 930-fold in presence of a cAMP analog. An AP-1-like element adjacent to the CCAAT enhancer, which binds Jun family members, is required for basal and cAMP/ C/EBP-β-dependent activation of the gene, but not for Ets-2-dependent activity. CONCLUSION: This paper demonstrates how Ets-2, a key transcription factor for trophoblast differentiation and function, can control expression of two genes (Tkdp-1 and IFNT) having similar spatial and temporal expression patterns via very different mechanisms

    Effects of a Three-day Period of Intense, Intermittent Exercise on Oxidative Stress and Inflammation

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    It is documented that strenuous and prolonged exercise induces oxidative stress and inflammation, with the associated muscle damage and fatigue compromising performance. Little is known about the oxidant effects of intense, intermittent exercise, as performed daily by elite athletes competing in team sports. PURPOSE: To assess the short-term effects of a 3-day period of intense, intermittent exercise on biomarkers of oxidative stress and inflammation in trained athletes. METHODS: Ten trained athletes (age: 32.11±1.91yrs; mass: 66.33±1.95kg; maximal oxygen uptake (VO2max): 51.44±1.59mL·kg·minˉ1) completed a high-intensity, intermittent exercise protocol (90-minute intermittent treadmill run, ~70% VO2max) on three consecutive days and were compared to a control group (N=10). Blood samples were collected immediately pre (T1) and post (T2) the 3-day exercise protocol, then 21h- (T3) and 42h-post-exercise (T4); and assayed for Total Antioxidant Status (TAS), Thiobarbituric Acid Reactive Substances (TBARS), Interleukins (IL-6, IL-8 and IL-10), C-Reactive Protein (C-RP) and Lactate Dehydrogenase (LDH). Data were corrected for plasma volume change; results presented as M±SE. RESULTS: No significant differences were observed between the exercise and control group at T1 (TAS: 1.20±0.14mmol.L-1 vs. 1.18±0.11mmol.L-1; LDH: 302.14±16.24U/L vs. 295.27±31.26U/L; TBARS: 6.21±1.09μM vs. 5.88±1.00μM; and IL-6: 0.67±0.70pg/ml vs. 1.12±0.28pg/ml). The 3-day exercise period caused a significant increase in LDH (413.24±35.27U/L, P = 0.029), IL-6 (2.54±0.35pg/ml, P = 0.037) and TBARS (7.00±0.61μM, P = 0.042) at T2, with the effects of TBARS remaining above baseline at T4 (6.43±0.79μM, P = 0.043). TAS increased post-exercise with a significant difference observed between groups at T2 (1.86±0.21mmol.L-1 vs. 1.20±0.13mmol.L-1, P = 0.006), T3 (1.86±0.28mmol.L-1 vs. 1.30±0.14mmol.L-1, P = 0.010) and T4 (1.71±0.22mmol.L-1 vs. 1.17±0.13mmol.L-1, P = 0.014). IL-8, IL-10, and C-RP did not differ between groups. CONCLUSIONS: A 3-day period of intense, intermittent exercise increased oxidative stress and upregulated antioxidants in trained athletes, confirming the current model that exercise-induced oxidants play an important role in intracellular signaling pathways of endogenous antioxidants

    The evolution of the Sin1 gene product, a little known protein implicated in stress responses and type I interferon signaling in vertebrates

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    BACKGROUND: In yeast, birds and mammals, the SAPK-interacting protein 1 (Sin1) gene product has been implicated as a component of the stress-activated protein kinase (SAPK) signal transduction pathway. Recently, Sin1 has also been shown to interact with the carboxyl terminal end of the cytoplasmic domain of the ovine type I interferon receptor subunit 2 (IFNAR2). However, the function of Sin1 remains unknown. Since SAPK pathways are ancient and the IFN system is confined to vertebrates, the organization of the Sin1 gene and the sequences of the Sin1 protein have been compared across a wide taxonomic range of species. RESULTS: Sin1 is represented, apparently as a single gene, in all metazoan species and fungi but is not detectable in protozoa, prokaryotes, or plants. Sin1 is highly conserved in vertebrates (79–99% identity at amino acid level), which possess an interferon system, suggesting that it has been subjected to powerful evolutionary constraint that has limited its diversification. Sin1 possesses at least two unique sequences in its IFNAR2-interacting region that are not represented in insects and other invertebrates. Sequence alignment between vertebrates and insects revealed five Sin1 strongly conserved domains (SCDs I-V), but an analysis of any of these domains failed to identify known functional protein motifs. SCD III, which is approximately 129 amino acids in length, is particularly highly conserved and is present in all the species examined, suggesting a conserved function from fungi to mammals. The coding region of the vertebrate Sin1 gene encompasses 11 exon and 10 introns, while in C. elegans the gene consists of 10 exons and 9 introns organized distinctly from those of vertebrates. In yeast and insects, Sin1 is intronless. CONCLUSIONS: The study reveals the phylogeny of a little studied gene which has recently been implicated in two important signal transduction pathways, one ancient (stress response), one relatively new (interferon signaling)
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