349 resultados para 1235
Resumo:
Economic models of crime and punishment implicitly assume that the government can credibly commit to the fines, sentences, and apprehension rates it has chosen. We study the government's problem when credibility is an issue. We find that several of the standard predictions of the economic model of crime and punishment are robust to commitment, but that credibility may in some cases result in lower apprehension rates, and hence a higher crime rate, compared to the static version of the model.
Resumo:
Growth factor signaling promotes anabolic processes via activation of the PI3K-Akt kinase cascade. Deregulation of the growth factor-dependent PI3K-Akt pathway was implicated in tumorigenesis. Akt is an essential serine/threonine protein kinase that controls multiple physiological functions such as cell growth, proliferation, and survival to maintain cellular homeostasis. Recently, the mammalian Target of Rapamycin Complex 2 (mTORC2) was identified as the main Akt Ser-473 kinase, and Ser-473 phosphorylation is required for Akt hyperactivation. However, the detailed mechanism of mTORC2 regulation in response to growth factor stimulation or cellular stresses is not well understood. In the first project, we studied the regulation of the mTORC2-Akt signaling under ER stress. We identified the inactivation of mTORC2 by glycogen synthase kinase-3β (GSK-3β). Under ER stress, the essential mTORC2 component, rictor, is phosphorylated by GSK-3β at Ser-1235. This phosphorylation event results in the inhibition of mTORC2 kinase activity by interrupting Akt binding to mTORC2. Blocking rictor Ser-1235 phosphorylation can attenuate the negative impacts of GSK-3β on mTORC2/Akt signaling and tumor growth. Thus, our work demonstrated that GSK-3β-mediated rictor Ser-1235 phosphorylation in response to ER stress interferes with Akt signaling by inhibiting mTORC2 kinase activity. In the second project, I investigated the regulation of the mTORC2 integrity. We found that basal mTOR kinase activity depends on ATP level, which is tightly regulated by cell metabolism. The ATP-sensitive mTOR kinase is required for SIN1 protein phosphorylation and stabilization. SIN1 is an indispensable subunit of mTORC2 and is required for the complex assembly and mTORC2 kinase activity. Our findings reveal that mTOR-mediated phosphorylation of SIN1 is critical for maintaining complex integrity by preventing SIN1 from lysosomal degradation. In sum, our findings verify two distinct mTORC2 regulatory mechanisms via its components rictor and SIN1. First, GSK-3β-mediated rictor Ser-1235 phosphorylation results in mTORC2 inactivation by interfering its substrate binding ability. Second, mTOR-mediated Ser-260 phosphorylation of SIN1 preserves its complex integrity. Thus, these two projects provide novel insights into the regulation of mTORC2.
Resumo:
Fil: Castro, Edgardo. Universidad Nacional de Cuyo. Facultad de Artes y Diseño
Resumo:
Since studies on deep-sea cores were carried out in the early 1990s it has been known that ambient temperature may have a marked affect on apatite fission track annealing. Due to sluggish annealing kinetics, this effect cannot be quantified by laboratory annealing experiments. The unknown amount of low-temperature annealing remains one of the main uncertainties for extracting thermal histories from fission track data, particularly for samples which experienced slow cooling in shallow crustal levels. To further elucidate these uncertainties, we studied volcanogenic sediments from five deep-sea drill cores, that were exposed to maximum temperatures between ~10° and 70°C over geological time scales of ~15-120 Ma. Mean track lengths (MTL) and etch pit diameters (Dpar) of all samples were measured, and the chemical composition of each grain analyzed for age and track length measurements was determined by electron microprobe analysis. Thermal histories of the sampled sites were independently reconstructed, based on vitrinite reflectance measurements and/or 1D numerical modelling. These reconstructions were used to test the most widely used annealing models for their ability to predict low-temperature annealing. Our results show that long-term exposure to temperatures below the temperature range of the nominal apatite fission track partial annealing zone results in track shortening ranging between 4 and 11%. Both chlorine content and Dpar values explain the downhole annealing patterns equally well. Low chlorine apatite from one drill core revealed a systematic relation between Si-content and Dpar value. The question whether Si-substitution in apatite has direct and systematic effects on annealing properties however, cannot be addressed by our data. For samples, which remained at temperatures <30°C, and which are low in chlorine, the Laslett et al. [Laslett G., Green P., Duddy I. and Gleadow A. (1987) Thermal annealing of fission tracks in apatite. Chem. Geol. 65, 1-13] annealing model predicts MTL up to 0.6 µm longer than those actually measured, whereas for apatites with intermediate to high chlorine content, which experienced temperatures >30°C, the predictions of the Laslett et al. (1987) model agree with the measured MTL data within error levels. With few exceptions, predictions by the Ketcham et al. [Ketcham R., Donelick R. and Carlson W. (1999) Variability of apatite fission-track annealing kinetics. III: Extrapolation to geological time scales. Am. Mineral. 84/9, 1235-1255] annealing model are consistent with the measured data for samples which remained at temperatures below ~30°C. For samples which experienced maximum temperatures between ~30 and 70°C, and which are rich in chlorine, the Ketcham et al. (1999) model overestimates track annealing.
Resumo:
An integrated instrument package for measuring and understanding the surface radiation budget of sea ice is presented, along with results from its first deployment. The setup simultaneously measures broadband fluxes of upwelling and downwelling terrestrial and solar radiation (four components separately), spectral fluxes of incident and reflected solar radiation, and supporting data such as air temperature and humidity, surface temperature, and location (GPS), in addition to photographing the sky and observed surface during each measurement. The instruments are mounted on a small sled, allowing measurements of the radiation budget to be made at many locations in the study area to see the effect of small-scale surface processes on the large-scale radiation budget. Such observations have many applications, from calibration and validation of remote sensing products to improving our understanding of surface processes that affect atmosphere-snow-ice interactions and drive feedbacks, ultimately leading to the potential to improve climate modelling of ice-covered regions of the ocean. The photographs, spectral data, and other observations allow for improved analysis of the broadband data. An example of this is shown by using the observations made during a partly cloudy day, which show erratic variations due to passing clouds, and creating a careful estimate of what the radiation budget along the observed line would have been under uniform sky conditions, clear or overcast. Other data from the setup's first deployment, in June 2011 on fast ice near Point Barrow, Alaska, are also shown; these illustrate the rapid changes of the radiation budget during a cold period that led to refreezing and new snow well into the melt season.
Meteorological observations during BUITENZORG cruise from Batavia to Rotterdam started at 1848-11-10
Resumo:
Investigar 'el lado B' de la Historia proporciona otras respuestas y perspectivas para comprender un hecho traumático ocurrido el 29 de octubre de 1949 en Arauca, Caldas; cuando 49 personas perdieron su vida en el contexto histórico de lo que la Violentología denomina en Colombia 'La violencia'. Las indagaciones se circunscriben en el orden de ¿Qué pasó?, ¿Cómo pasó? y ¿Qué se ha narrado? Ya que las respuestas difieren, esencialmente, dependiendo de si las versiones provienen del diario manizalita 'La Patria' y la historia oficial, donde la autoría de los asesinatos fue atribuida a los liberales gaitanistas; o de fuentes tales como: el diario 'El Tiempo', los archivos judiciales, los testimonios orales de las víctimas sobrevivientes, los álbumes fotográficos y la asistencia de los estudios de memoria, donde se evidencia que la masacre fue ejecutada por la Policía, las fuerzas paramilitares de la época, conocidos como "los pájaros", y civiles conservadores que a su vez fueron la pieza procesal para iniciar la investigación judicial tendiente a "esclarecer" los hechos
Resumo:
Investigar 'el lado B' de la Historia proporciona otras respuestas y perspectivas para comprender un hecho traumático ocurrido el 29 de octubre de 1949 en Arauca, Caldas; cuando 49 personas perdieron su vida en el contexto histórico de lo que la Violentología denomina en Colombia 'La violencia'. Las indagaciones se circunscriben en el orden de ¿Qué pasó?, ¿Cómo pasó? y ¿Qué se ha narrado? Ya que las respuestas difieren, esencialmente, dependiendo de si las versiones provienen del diario manizalita 'La Patria' y la historia oficial, donde la autoría de los asesinatos fue atribuida a los liberales gaitanistas; o de fuentes tales como: el diario 'El Tiempo', los archivos judiciales, los testimonios orales de las víctimas sobrevivientes, los álbumes fotográficos y la asistencia de los estudios de memoria, donde se evidencia que la masacre fue ejecutada por la Policía, las fuerzas paramilitares de la época, conocidos como "los pájaros", y civiles conservadores que a su vez fueron la pieza procesal para iniciar la investigación judicial tendiente a "esclarecer" los hechos