967 resultados para Alternative system


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For the functional role of the ribosomal tRNA exit (E) site, two different models have been proposed. It has been suggested that transient E-site binding of the tRNA leaving the peptidyl (P) site promotes elongation factor G (EF-G)-dependent translocation by lowering the energetic barrier of tRNA release [Lill, R., Robertson, J. M. & Wintermeyer, W. (1989) EMBO J. 8, 3933-3938]. The alternative "allosteric three-site model" [Nierhaus, K.H. (1990) Biochemistry 29, 4997-5008] features stable, codon-dependent tRNA binding to the E site and postulates a coupling between E and aminoacyl (A) sites that regulates the tRNA binding affinity of the two sites in an anticooperative manner. Extending our testing of the two conflicting models, we have performed translocation experiments with fully active ribosomes programmed with heteropolymeric mRNA. The results confirm that the deacylated tRNA released from the P site is bound to the E site in a kinetically labile fashion, and that the affinity of binding, i.e., the occupancy of the E site, is increased by Mg2+ or polyamines. At conditions of high E-site occupancy in the posttranslocation complex, filling the A site with aminoacyl-tRNA had no influence on the E site, i.e., there was no detectable anticooperative coupling between the two sites, provided that second-round translocation was avoided by removing EF-G. On the basis of these results, which are entirely consistent with our previous results, we consider the allosteric three-site model of elongation untenable. Rather, as proposed earlier, the E site-bound state of the leaving tRNA is a transient intermediate and, as such, is a mechanistic feature of the classic two-state model of the elongating ribosome.

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Various compounds that affect signal transduction regulate the relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.

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More than ever alternative energy solutions are being discussed including potential legislative action. With the use of fossil fuels being the most abundant and most controversial sources of energy, new solutions must be found. This paper looks at the economic and technical feasibility of different types of alternative energy and cogeneration applications within a steel mill. This paper examines alternative energy systems. The systems examined include Solar systems, thermal electric materials, and an Organic Rankine Cycle cogeneration project. None of the projects has limiting technical feasibility issues however each of the projects face economically limiting factors. Taking into account tangible and non-tangible factors the solar system and Organic Rankine Cycle cogeneration project are recommended for further study and potential installation.

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The ubiquitin–proteasome system (UPS) is the main intracellular pathway for modulated protein turnover, playing an important role in the maintenance of cellular homeostasis. It also exerts a protein quality control through degradation of oxidized, mutant, denatured, or misfolded proteins and is involved in many biological processes where protein level regulation is necessary. This system allows the cell to modulate its protein expression pattern in response to changing physiological conditions and provides a critical protective role in health and disease. Impairments of UPS function in the central nervous system (CNS) underlie an increasing number of genetic and idiopathic diseases, many of which affect the retina. Current knowledge on the UPS composition and function in this tissue, however, is scarce and dispersed. This review focuses on UPS elements reported in the retina, including ubiquitinating and deubiquitinating enzymes (DUBs), and alternative proteasome assemblies. Known and inferred roles of protein ubiquitination, and of the related, SUMO conjugation (SUMOylation) process, in normal retinal development and adult homeostasis are addressed, including modulation of the visual cycle and response to retinal stress and injury. Additionally, the relationship between UPS dysfunction and human neurodegenerative disorders affecting the retina, including Alzheimer's, Parkinson's, and Huntington's diseases, are dealt with, together with numerous instances of retina-specific illnesses with UPS involvement, such as retinitis pigmentosa, macular degenerations, glaucoma, diabetic retinopathy (DR), and aging-related impairments. This information, though still basic and limited, constitutes a suitable framework to be expanded in incoming years and should prove orientative toward future therapy design targeting sight-affecting diseases with a UPS underlying basis.

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Resumen de la comunicación presentada en PIC2015 – the 14th International Congress on Combustion By-Products and Their Health Effects, Umeå, Sweden, 14-17 June 2015.

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Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2016

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Stefano Micossi argues in this paper that the Basel framework for bank prudential requirements is deeply flawed and that the Basel III revision has failed to correct these flaws, making the system even more complicated, opaque and open to manipulation. In practice, he finds that the present system does not offer regulators and financial markets a reliable capital standard for banks and its divergent implementation in the main jurisdictions of the European Union and the United States has broken the market into special fiefdoms governed by national regulators in response to untoward special interests. The time is ripe to stop tinkering with minor adjustment and revisions in order to rescue the system, because the system cannot be rescued. In response to the current situation, Micossi calls for abandoning reference to risk-weighted assets calculated by banks with their internal risk management models for the determination of banks’ prudential capital, together with the preoccupation with the asset side of banks in correcting for risk exposure. He suggests that the alternative may be provided by a combination of a straight capital ratio and a properly designed deposit insurance system. It is a logical, complete and much less distortive alternative; it would serve better the cause of financial stability as well as the interest of the banks in clear, transparent and level playing field.

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EDITED VERSION TO BE PUBLISHED SOON. The aim of this paper is to contribute to the estimation of the potential effects of the CAP reform on propensity to transaction, particularly comparing the effect of different new instruments/policy settings with the current policy (CAP health check) used as a baseline. The work is focused on three of new policy instruments within the post 2013 CAP reform proposal: regionalization, greening and capping. The first and second are analysed in more detail. The analysis will be based on a survey of farmers in the Province of Bologna, Emilia Romagna, Italy. The questionnaire focuses on mechanism of access to land and related incentives towards different land use/economic behaviour. The survey includes information about respondent characteristics (farm, farmer, household and payments received) and stated intention about potential changes in land operated under alternative agricultural policy scenarios (particularly the post-2013 reform proposals).

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This study examines the workings of the Common European Asylum System (CEAS), in order to assess the need and potential for new approaches to ensure access to protection for people seeking it in the EU, including joint processing and distribution of asylum seekers. Rather than advocating the addition of further complexity and coercion to the CEAS, the study proposes a focus on front-line reception and streamlined refugee status determination, in order to mitigate the asylum challenges facing Member States, and vindicate the rights of asylum seekers and refugees according to the EU acquis and international legal standards. Joint processing could contribute to front-line reception and processing capacity, but is no substitute for proper investment in national systems. The Dublin system as currently configured leads inexorably to increasing coercion and detention, and must thus be reconfigured to remove coercion as a principle and ensure consistency with human rights and other fundamental values of the EU.

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Competition law seeks to protect competition on the market as a means of enhancing consumer welfare and of ensuring an efficient allocation of resources. In order to be successful, therefore, competition authorities should be adequately equipped and have at their disposal all necessary enforcement tools. However, at the EU level the current enforcement system of competition rules allows only for the imposition of administrative fines by the European Commission to liable undertakings. The main objectives, in turn, of an enforcement policy based on financial penalties are two fold: to impose sanctions on infringing undertakings which reflect the seriousness of the violation, and to ensure that the risk of penalties will deter both the infringing undertakings (often referred to as 'specific deterrence') and other undertakings that may be considering anti-competitive activities from engaging in them (often referred to as 'general deterrence'). In all circumstances, it is important to ensure that pecuniary sanctions imposed on infringing undertakings are proportionate and not excessive. Although pecuniary sanctions against infringing undertakings are a crucial part of the arsenal needed to deter competition law violations, they may not be sufficient. One alternative option in that regard is the strategic use of sanctions against the individuals involved in, or responsible for, the infringements. Sanctions against individuals are documented to focus the minds of directors and employees to comply with competition rules as they themselves, in addition to the undertakings in which they are employed, are at risk of infringements. Individual criminal penalties, including custodial sanctions, have been in fact adopted by almost half of the EU Member States. This is a powerful tool but is also limited in scope and hard to implement in practice mostly due to the high standards of proof required and the political consensus that needs first to be built. Administrative sanctions for individuals, on the other hand, promise to deliver up to a certain extent the same beneficial results as criminal sanctions whilst at the same time their adoption is not likely to meet strong opposition and their implementation in practice can be both efficient and effective. Directors’ disqualification, in particular, provides a strong individual incentive for each member, or prospective member, of the Board as well as other senior executives, to take compliance with competition law seriously. It is a flexible and promising tool that if added to the arsenal of the European Commission could bring balance to the current sanctioning system and that, in turn, would in all likelihood make the enforcement of EU competition rules more effective. Therefore, it is submitted that a competition law regime in order to be effective should be able to deliver policy objectives through a variety of tools, not simply by imposing significant pecuniary sanctions to infringing undertakings. It is also clear that individual sanctions, mostly of an administrative nature, are likely to play an increasingly important role as they focus the minds of those in business who might otherwise be inclined to regard infringing the law as a matter of corporate risk rather than of personal risk. At the EU level, in particular, the adoption of directors’ disqualification promises to deliver more effective compliance and greater overall economic impact.

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In this CEPS Commentary, Daniel Gros turns his attention to the main outstanding problem facing Greece today, namely capital flight. Fearful that the country will leave the euro, depositors are withdrawing cash from their bank accounts – thereby making this event more likely. He outlines a proposal in which outgoing payments from Greek banks in the form of cash or via the TARGET system would be limited to the amount of incoming payments, i.e. revenues from exports or tourism, via an auction system. Greece could remain formally a member of the euro area, but the price for cash withdrawals would encourage depositors to wait and stimulate exports.

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Texas Department of Transportation, Austin

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"Contract FY 81-8/AE-8."