Endothelin-Converting Enzyme-1 (ECE-1) Is Post-Transcriptionally Regulated by Alternative Polyadenylation

Endothelin-converting enzyme-1 (ECE-1) is the enzyme predominantly responsible for producing active endothelin-1 (ET-1), a mitogenic peptide implicated in the aetiology of a number of diseases, including cancer. Elevated levels of ECE-1 have been observed in a range of malignancies, with high expression conferring poor prognosis and aiding the acquisition of androgen independence in prostate cancer. The mechanisms regulating the expression of ECE-1 in cancer cells are poorly understood, hampering the development of novel therapies targeting the endothelin axis. Here we provide evidence that the expression of ECE-1 is markedly inhibited by its 3′UTR, and that alternative polyadenylation (APA) results in the production of ECE-1 transcripts with truncated 3′UTRs which promote elevated protein expression. Abolition of the ECE-1 APA sites reduced protein expression from a reporter vector in prostate cancer cells, suggesting these sites are functional. This is the first study to identify ECE-1 as a target for APA, a regulatory mechanism aberrantly activated in cancer cells, and provides novel information about the mechanisms leading to ECE-1 overexpression in malignant cells

Generalized exponential and logarithmic functions

AbstractGeneralizations of the exponential and logarithmic functions are defined and an investigation is made of two possible versions of these functions. Some applications are described, including computer arithmetic, properties of very large and very small numbers, and the determination of functional roots

An automotive engine charge-air intake conditioner system: analysis of fuel economy benefits in a gasoline engine application

A combination of analytical techniques has been used to quantify the potential fuel economy benefits of an automotive engine charge-air intake conditioner system applied to a spark-ignited gasoline engine. This system employs a compressor, intercooler, and expander to provide increased charge density with the possibility of reducing charge-air temperature below sink temperature. This reduction in charge-air temperature provides the potential for improved knock resistance at full load; thereby allowing the possibility of increasing compression ratio with corresponding benefits in thermodynamic cycle efficiency and part-load fuel economy. The four linked and interfaced models comprised a first-law thermodynamic model of the charge-air conditioner system, a one-dimensional engine cycle simulation, a two-zone combustion model, and a knock criterion model. An analysis was carried out under full load at 3000 r/min and showed that a charge-air conditioner system - with compressor, intercooler, and expander efficiencies of 0.8 - allowed the compression ratio to be increased by approximately half a ratio, which gave up to 1.5 per cent reduction in brake specific fuel consumption at 2000 r/min 2 bar brake mean effective pressure when compared with a conventional pressure charger intercooler system with no expander

An automotive engine charge-air intake conditioner system: thermodynamic analysis of performance characteristics

A first law thermodynamic model has been developed and used to characterize the performance of an automotive engine charge-air intake conditioner system. This system employs a compressor, intercooler, and expander to provide increased charge density with the possibility of reducing, the charge-air temperature below the sink temperature. The model was validated against experimental measurements. The variation of system effectiveness with compressor, intercooler, and expander efficiency was quantified and system operating limits were identified. While the expander was found to have a greater effect than the compressor, the performance of the system was shown to be most dependent upon intercooler effectiveness

Renal pericytes: regulators of medullary blood flow

Regulation of medullary blood flow (MBF) is essential in maintaining normal kidney function. Blood flow to the medulla is supplied by the descending vasa recta (DVR), which arise from the efferent arterioles of juxtamedullary glomeruli. DVR are composed of a continuous endothelium, intercalated with smooth muscle-like cells called pericytes. Pericytes have been shown to alter the diameter of isolated and in situ DVR in response to vasoactive stimuli that are transmitted via a network of autocrine and paracrine signalling pathways. Vasoactive stimuli can be released by neighbouring tubular epithelial, endothelial, red blood cells and neuronal cells in response to changes in NaCl transport and oxygen tension. The experimentally described sensitivity of pericytes to these stimuli strongly suggests their leading role in the phenomenon of MBF autoregulation. Because the debate on autoregulation of MBF fervently continues, we discuss the evidence favouring a physiological role for pericytes in the regulation of MBF and describe their potential role in tubulo-vascular cross-talk in this region of the kidney. Our review also considers current methods used to explore pericyte activity and function in the renal medulla

Dynamic instabilities induced by asymmetric influence: Prisoners' dilemma game on small-world networks

A two-dimensional small-world type network, subject to spatial prisoners' dilemma dynamics and containing an influential node defined as a special node with a finite density of directed random links to the other nodes in the network, is numerically investigated. It is shown that the degree of cooperation does not remain at a steady state level but displays a punctuated equilibrium type behavior manifested by the existence of sudden breakdowns of cooperation. The breakdown of cooperation is linked to an imitation of a successful selfish strategy of the influential node. It is also found that while the breakdown of cooperation occurs suddenly, the recovery of it requires longer time. This recovery time may, depending on the degree of steady state cooperation, either increase or decrease with an increasing number of long range connections.Comment: 5 pages, 6 figure

Model- and calibration-independent test of cosmic acceleration

We present a calibration-independent test of the accelerated expansion of the universe using supernova type Ia data. The test is also model-independent in the sense that no assumptions about the content of the universe or about the parameterization of the deceleration parameter are made and that it does not assume any dynamical equations of motion. Yet, the test assumes the universe and the distribution of supernovae to be statistically homogeneous and isotropic. A significant reduction of systematic effects, as compared to our previous, calibration-dependent test, is achieved. Accelerated expansion is detected at significant level (4.3 sigma in the 2007 Gold sample, 7.2 sigma in the 2008 Union sample) if the universe is spatially flat. This result depends, however, crucially on supernovae with a redshift smaller than 0.1, for which the assumption of statistical isotropy and homogeneity is less well established.Comment: 13 pages, 2 figures, major change

A complete 3D numerical study of the effects of pseudoscalar-photon mixing on quasar polarizations

We present the results of three-dimensional simulations of quasar polarizations in the presence of pseudoscalar-photon mixing in the intergalactic medium. The intergalactic magnetic field is assumed to be uncorrelated in wave vector space but correlated in real space. Such a field may be obtained if its origin is primordial. Furthermore we assume that the quasars, located at cosmological distances, have negligible initial polarization. In the presence of pseudoscalar-photon mixing we show, through a direct comparison with observations, that this may explain the observed large scale alignments in quasar polarizations within the framework of big bang cosmology. We find that the simulation results give a reasonably good fit to the observed data.Comment: 15 pages, 8 figures, significant changes, to appear in EPJ

Applications of scalar attractor solutions to Cosmology

We develop a framework to study the phase space of a system consisting of a scalar field rolling down an arbitrary potential with varying slope and a background fluid, in a cosmological setting. We give analytical approximate solutions of the field evolution and discuss applications of its features to the issues of quintessence, moduli stabilisation and quintessential inflation.Comment: 9 pages, 7 figures. Accepted for publication in PR

A mathematical analysis of the evolution of perturbations in a modified Chaplygin gas model

One approach in modern cosmology consists in supposing that dark matter and dark energy are different manifestations of a single `quartessential' fluid. Following such idea, this work presents a study of the evolution of perturbations of density in a flat cosmological model with a modified Chaplygin gas acting as a single component. Our goal is to obtain properties of the model which can be used to distinguish it from another cosmological models which have the same solutions for the general evolution of the scale factor of the universe, without the construction of the power spectrum. Our analytical results, which alone can be used to uniquely characterize the specific model studied in our work, show that the evolution of the density contrast can be seen, at least in one particular case, as composed by a spheroidal wave function. We also present a numerical analysis which clearly indicates as one interesting feature of the model the appearence of peaks in the evolution of the density constrast.Comment: 21 pages, accepted for publication in General Relativity and Gravitatio