102 resultados para Dynamic dispatch
Resumo:
The three essays constituting this thesis focus on financing and cash management policy. The first essay aims to shed light on why firms issue debt so conservatively. In particular, it examines the effects of shareholder and creditor protection on capital structure choices. It starts by building a contingent claims model where financing policy results from a trade-off between tax benefits, contracting costs and agency costs. In this setup, controlling shareholders can divert part of the firms' cash ows as private benefits at the expense of minority share- holders. In addition, shareholders as a class can behave strategically at the time of default leading to deviations from the absolute priority rule. The analysis demonstrates that investor protection is a first order determinant of firms' financing choices and that conflicts of interests between firm claimholders may help explain the level and cross-sectional variation of observed leverage ratios. The second essay focuses on the practical relevance of agency conflicts. De- spite the theoretical development of the literature on agency conflicts and firm policy choices, the magnitude of manager-shareholder conflicts is still an open question. This essay proposes a methodology for quantifying these agency conflicts. To do so, it examines the impact of managerial entrenchment on corporate financing decisions. It builds a dynamic contingent claims model in which managers do not act in the best interest of shareholders, but rather pursue private benefits at the expense of shareholders. Managers have discretion over financing and dividend policies. However, shareholders can remove the manager at a cost. The analysis demonstrates that entrenched managers restructure less frequently and issue less debt than optimal for shareholders. I take the model to the data and use observed financing choices to provide firm-specific estimates of the degree of managerial entrenchment. Using structural econometrics, I find costs of control challenges of 2-7% on average (.8-5% at median). The estimates of the agency costs vary with variables that one expects to determine managerial incentives. In addition, these costs are sufficient to resolve the low- and zero-leverage puzzles and explain the time series of observed leverage ratios. Finally, the analysis shows that governance mechanisms significantly affect the value of control and firms' financing decisions. The third essay is concerned with the documented time trend in corporate cash holdings by Bates, Kahle and Stulz (BKS,2003). BKS find that firms' cash holdings double from 10% to 20% over the 1980 to 2005 period. This essay provides an explanation of this phenomenon by examining the effects of product market competition on firms' cash holdings in the presence of financial constraints. It develops a real options model in which cash holdings may be used to cover unexpected operating losses and avoid inefficient closure. The model generates new predictions relating cash holdings to firm and industry characteristics such as the intensity of competition, cash flow volatility, or financing constraints. The empirical examination of the model shows strong support of model's predictions. In addition, it shows that the time trend in cash holdings documented by BKS can be at least partly attributed to a competition effect.
Resumo:
Vegetation has a profound effect on flow and sediment transport processes in natural rivers, by increasing both skin friction and form drag. The increase in drag introduces a drag discontinuity between the in-canopy flow and the flow above, which leads to the development of an inflection point in the velocity profile, resembling a free shear layer. Therefore, drag acts as the primary driver for the entire canopy system. Most current numerical hydraulic models which incorporate vegetation rely either on simple, static plant forms, or canopy-scaled drag terms. However, it is suggested that these are insufficient as vegetation canopies represent complex, dynamic, porous blockages within the flow, which are subject to spatially and temporally dynamic drag forces. Here we present a dynamic drag methodology within a CFD framework. Preliminary results for a benchmark cylinder case highlight the accuracy of the method, and suggest its applicability to more complex cases.
Resumo:
Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-specific expression of genes involved in biological processes such as cell cycle regulation, metabolism and energy production, retinoic acid synthesis, and blood-testis barrier biogenesis. Finally, regulatory network analysis identified the transcription factors endothelial PAS domain-containing protein 1 (EPAS1/Hif2α), aryl hydrocarbon receptor nuclear translocator (ARNT/Hif1β), and signal transducer and activator of transcription 1 (STAT1) as potential master regulators driving the SC transcriptional program. Our results highlight the plastic transcriptional landscape of SCs during the progression of spermatogenesis and provide valuable resources to better understand SC function and spermatogenesis and its related disorders, such as male infertility.
Resumo:
Literature on medical dispatch is growing, focusing mainly on efficiency (under and overtriage) and dispatch-assisted CPR. But the issue of population catchment size, functional costs and rationalization is rarely addressed. If we can observe a trend toward a decreasing number of dispatch centres in many European countries, there is today no evidence on what is the right catchment size to reach the best balance between quality of services and costs.
Resumo:
The current challenge in a context of major environmental changes is to anticipate the responses of species to future landscape and climate scenarios. In the Mediterranean basin, climate change is one the most powerful driving forces of fire dynamics, with fire frequency and impact having markedly increased in recent years. Species distribution modelling plays a fundamental role in this challenge, but better integration of available ecological knowledge is needed to adequately guide conservation efforts. Here, we quantified changes in habitat suitability of an early-succession bird in Catalonia, the Dartford Warbler (Sylvia undata) ― globally evaluated as Near Threatened in the IUCN Red List. We assessed potential changes in species distributions between 2000 and 2050 under different fire management and climate change scenarios and described landscape dynamics using a spatially-explicit fire-succession model that simulates fire impacts in the landscape and post-fire regeneration (MEDFIRE model). Dartford Warbler occurrence data were acquired at two different spatial scales from: 1) the Atlas of European Breeding Birds (EBCC) and 2) Catalan Breeding Bird Atlas (CBBA). Habitat suitability was modelled using five widely-used modelling techniques in an ensemble forecasting framework. Our results indicated considerable habitat suitability losses (ranging between 47% and 57% in baseline scenarios), which were modulated to a large extent by fire regime changes derived from fire management policies and climate changes. Such result highlighted the need for taking the spatial interaction between climate changes, fire-mediated landscape dynamics and fire management policies into account for coherently anticipating habitat suitability changes of early succession bird species. We conclude that fire management programs need to be integrated into conservation plans to effectively preserve sparsely forested and early succession habitats and their associated species in the face of global environmental change.
Dynamic single cell measurements of kinase activity by synthetic kinase activity relocation sensors.
Resumo:
BACKGROUND: Mitogen activated protein kinases (MAPK) play an essential role in integrating extra-cellular signals and intra-cellular cues to allow cells to grow, adapt to stresses, or undergo apoptosis. Budding yeast serves as a powerful system to understand the fundamental regulatory mechanisms that allow these pathways to combine multiple signals and deliver an appropriate response. To fully comprehend the variability and dynamics of these signaling cascades, dynamic and quantitative single cell measurements are required. Microscopy is an ideal technique to obtain these data; however, novel assays have to be developed to measure the activity of these cascades. RESULTS: We have generated fluorescent biosensors that allow the real-time measurement of kinase activity at the single cell level. Here, synthetic MAPK substrates were engineered to undergo nuclear-to-cytoplasmic relocation upon phosphorylation of a nuclear localization sequence. Combination of fluorescence microscopy and automated image analysis allows the quantification of the dynamics of kinase activity in hundreds of single cells. A large heterogeneity in the dynamics of MAPK activity between individual cells was measured. The variability in the mating pathway can be accounted for by differences in cell cycle stage, while, in the cell wall integrity pathway, the response to cell wall stress is independent of cell cycle stage. CONCLUSIONS: These synthetic kinase activity relocation sensors allow the quantification of kinase activity in live single cells. The modularity of the architecture of these reporters will allow their application in many other signaling cascades. These measurements will allow to uncover new dynamic behaviour that previously could not be observed in population level measurements.
Resumo:
INTRODUCTION: Dispatch-assisted cardiopulmonary resuscitation (DA-CPR) plays a key role in out-of-hospital cardiac arrests. We sought to measure dispatchers' performances in a criteria-based system in recognizing cardiac arrest and delivering DA-CPR. Our secondary purpose was to identify the factors that hampered dispatchers' identification of cardiac arrests, the factors that prevented them from proposing DA-CPR, and the factors that prevented bystanders from performing CPR. METHODS AND RESULTS: We reviewed dispatch recordings for 1254 out-of-hospital cardiac arrests occurring between January 1, 2011 and December 31, 2013. Dispatchers correctly identified cardiac arrests in 71% of the reviewed cases and 84% of the cases in which they were able to assess for patient consciousness and breathing. The median time to recognition of the arrest was 60s. The median time to start chest compression was 220s. CONCLUSIONS: This study demonstrates that performances from a criteria-based dispatch system can be similar to those from a medical-priority dispatch system regarding out-of-hospital cardiac arrest (OHCA) time recognition and DA-CPR delivery. Agonal breathing recognition remains the weakest link in this sensitive task in both systems. It is of prime importance that all dispatch centers tend not only to implement DA-CPR but also to have tools to help them reach this objective, as today it should be mandatory to offer this service to the community. In order to improve benchmarking opportunities, we completed previously proposed performance standards as propositions.
Resumo:
PURPOSE: This study aims to identify which aspects of the pupil light reflex are most influenced by rods and cones independently by analyzing pupil recordings from different mouse models of photoreceptor deficiency. METHODS: One-month-old wild type (WT), rodless (Rho-/-), coneless (Cnga3-/-), or photoreceptor less (Cnga3-/-; Rho-/- or Gnat1-/-) mice were subjected to brief red and blue light stimuli of increasing intensity. To describe the initial dynamic response to light, the maximal pupillary constriction amplitudes and the derivative curve of the first 3 seconds were determined. To estimate the postillumination phase, the constriction amplitude at 9.5 seconds after light termination was related to the maximal constriction amplitude. RESULTS: Rho-/- mice showed decreased constriction amplitude but more prolonged pupilloconstriction to all blue and red light stimuli compared to wild type mice. Cnga3-/- mice had constriction amplitudes similar to WT however following maximal constriction, the early and rapid dilation to low intensity blue light was decreased. To high intensity blue light, the Cnga3-/- mice demonstrated marked prolongation of the pupillary constriction. Cnga3-/-; Rho-/- mice had no pupil response to red light of low and medium intensity. CONCLUSIONS: From specific gene defective mouse models which selectively voided the rod or cone function, we determined that mouse rod photoreceptors are highly contributing to the pupil response to blue light stimuli but also to low and medium red stimuli. We also observed that cone cells mainly drive the partial rapid dilation of the initial response to low blue light stimuli. Thus photoreceptor dysfunction can be derived from chromatic pupillometry in mouse models.