38 resultados para Alexander the Great, 356-323 B.C.
Resumo:
This article examines changes that occurred in English contract law as a result of the demands made upon Great Britain by the Great War. The focus is on the development of the doctrine of frustration in English law. In particular, it is argued that the development of the doctrine of frustration was fashioned from internal legal forces in the form of both existing case law and emergency legislation in response to the demands placed upon the nation by a global war. The way in which the doctrine of frustration developed during the Great War arose as a direct result of the way in which Britain chose to meet the logistical demands created by the way it fought the Great War.
Resumo:
The L-glutamate transporter GLT-1 is an abundant CNS membrane protein of the excitatory amino acid transporter (EAAT) family which controls extracellular L-glutamate levels and is important in limiting excitotoxic neuronal death. Using RT-PCR, we have determined that four mRNAs encoding GLT-1 exist in mouse brain, with the potential to encode four GLT-1 isoforms that differ in their N- and C-termini. We expressed all four isoforms (termed MAST-KREK, MPK-KREK, MAST-DIETCI and MPK-DIETCI according to amino acid sequence) in a range of cell lines and primary astrocytes and show that each isoform can reach the cell surface. In transfected HEK-293 or COS-7 cells, all four isoforms support high-affinity sodium-dependent L-glutamate uptake with identical pharmacological and kinetic properties. Inserting a viral epitope (V5, HA or FLAG) into the second extracellular domain of each isoform allowed co-immunoprecipitation and tr-FRET studies using transfected HEK-293 cells. Here we show for the first time that each of the four isoforms are able to combine to form homomeric and heteromeric assemblies, each of which are expressed at the cell surface of primary astrocytes. After activation of protein kinase C by phorbol ester, V5-tagged GLT-1 is rapidly removed from the cell surface of HEK-293 cells and degraded. This study provides direct biochemical evidence for oligomeric assembly of GLT-1 and reports the development of novel tools to provide insight into the trafficking of GLT-1.
Resumo:
Sediments play a fundamental role in the behaviour of contaminants in aquatic systems. Various processes in sediments, eg adsorption-desorption, oxidation-reduction, ion exchange or biological activities, can cause accumulation or release of metals and anions from the bottom of reservoirs, and have been recently studied in Polish waters [1-3]. Sediment samples from layer A: (1 divided by 6 cm depth in direct contact with bottom water); layer B: (7 divided by 12 cm depth moderate contact); and layer C: (12+ cm depth, in theory an inactive layer) were collected in September 2007 from six sites representing different types of hydrological conditions along the Dobczyce Reservoir (Fig. l). Water depths at the sampling points varied from 3.5 to 21 m. We have focused on studying the distribution and accumulation of several heavy metals (Cr, Pb, Cd, Cu and Zn) in the sediments. The surface, bottom and pore water (extracted from sediments by centrifugation) samples were also collected. Possible relationships between the heavy-metal distribution in sediments and the sediment characteristics (mineralogy, organic matter) as well as the Fe, Mn and Ca content of sediments, have been studied. The 02 concentrations in water samples were also measured. The heavy metals in sediments ranged from 19.0 to 226.3 mg/kg of dry mass (ppm). The results show considerable variations in heavy-metal concentrations between the 6 stations, but not in the individual layers (A, B, C). These variations are related to the mineralogy and chemical composition of the sediments and their pore waters.
Resumo:
Radiocarbon (carbon-14) data from the Aegean Bronze Age 1700-1400 B.C. show that the Santorini (Thera) eruption must have occurred in the late 17th century B.C. By using carbon-14 dates from the surrounding region, cultural phases, and Bayesian statistical analysis, we established a chronology for the initial Aegean Late Bronze Age cultural phases (Late Minoan IA, IB, and II). This chronology contrasts with conventional archaeological dates and cultural synthesis: stretching out the Late Minoan IA, IB, and II phases by similar to 100 years and requiring reassessment of standard interpretations of associations between the Egyptian and Near Eastern historical dates and phases and those in the Aegean and Cyprus in the mid-second millennium B.C.
Resumo:
Homologous desensitization of beta(2)-adrenergic and other G-protein-coupled receptors is a two-step process. After phosphorylation of agonist-occupied receptors by G-protein-coupled receptor kinases, they bind beta-arrestins, which triggers desensitization and internalization of the receptors. Because it is not known which regions of the receptor are recognized by beta-arrestins, we have investigated beta-arrestin interaction and internalization of a set of mutants of the human beta(2)-adrenergic receptor. Mutation of the four serine/threonine residues between residues 355 and 364 led to the loss of agonist-induced receptor-beta-arrestin2 interaction as revealed by fluorescence resonance energy transfer (FRET), translocation of beta-arrestin2 to the plasma membrane, and receptor internalization. Mutation of all seven serine/threonine residues distal to residue 381 did not affect agonist-induced receptor internalization and beta-arrestin2 translocation. A beta(2)-adrenergic receptor truncated distal to residue 381 interacted normally with beta-arrestin2, whereas its ability to internalize in an agonist-dependent manner was compromised. A similar impairment of internalization was observed when only the last eight residues of the C terminus were deleted. Our experiments show that the C terminus distal to residue 381 does not affect the initial interaction between receptor and beta-arrestin, but its last eight amino acids facilitate receptor internalization in concert with beta-arrestin2.
Resumo:
By employing Moody’s corporate default and rating transition data spanning the last 90 years we explore how much capital banks should hold against their corporate loan portfolios to withstand historical stress scenarios. Specifically, we will focus on the worst case scenario over the observation period, the Great Depression. We find that migration risk and the length of the investment horizon are critical factors when determining bank capital needs in a crisis. We show that capital may need to rise more than three times when the horizon is increased from 1 year, as required by current and future regulation, to 3 years. Increases are still important but of a lower magnitude when migration risk is introduced in the analysis. Further, we find that the new bank capital requirements under the so-called Basel 3 agreement would enable banks to absorb Great Depression-style losses. But, such losses would dent regulatory capital considerably and far beyond the capital buffers that have been proposed to ensure that banks survive crisis periods without government support.