972 resultados para Non-optimal Codon
Resumo:
Europe needs to restructure its energy system. The aim to decrease the reliance on fossil fuels to a higher dependence on renewable energy has now been imposed by The European Commission. In order to achieve this goal there is a great interest in Norway to become "The Green Battery of Europe". In the pursuit of this goal a GIS-tool was created to investigate the pump storage potential in Norway. The tool searches for possible connections between existing reservoirs and dams with the criteria selected by the user. The aim of this thesis was to test the tool and see if the results suggested were plausible, develop a cost calculation method for the PSH lines, and make suggestions for further development of the tool. During the process the tool presented many non-feasible pumped storage hydropower (PSH) connections. The area of Telemark was chosen for the more detailed study. The results were discussed and some improvements were suggested for further development of the tool. Also a sensitivity test was done to see which of the parameters set by the user are the most relevant for the PSH connection suggestion. From a range of the most promising PSH plants suggested by the tool, the one between Songavatn and Totak was chosen for a case study, where there already exists a power plant between both reservoirs. A new Pumped Storage Plant was designed with a power production of 1200 MW. There are still many topics open to discussion, such as how to deal with environmental restrictions, or how to deal with inflows and outflows of the reservoirs from the existing power plants. Consequently the GIS-tool can be a very useful tool to establish the best possible connections between existing reservoirs and dams, but it still needs a deep study and the creation of new parameters for the user.
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Un caloducto en bucle cerrado o Loop Heat Pipe (LHP) es un dispositivo de transferencia de calor cuyo principio de operación se basa en la evaporación/condensación de un fluido de trabajo, que es bombeado a través de un circuito cerrado gracias a fuerzas de capilaridad. Gracias a su flexibilidad, su baja masa y su mínimo (incluso nulo) consumo de potencia, su principal aplicación ha sido identificada como parte del subsistema de control térmico de vehículos espaciales. En el presente trabajo se ha desarrollado un LHP capaz de funcionar eficientemente a temperaturas de hasta 125 oC, siguiendo la actual tendencia de los equipos a bordo de satélites de incrementar su temperatura de operación. En la selección del diseño optimo para dicho LHP, la compatibilidad entre materiales y fluido de trabajo se identificó como uno de los puntos clave. Para seleccionar la mejor combinación, se llevó a cabo una exhaustiva revisión del estado del arte, además de un estudio especifico que incluía el desarrollo de un banco de ensayos de compatibilidad. Como conclusión, la combinación seleccionada como la candidata idónea para ser integrada en el LHP capaz de operar hasta 125 oC fue un evaporador de acero inoxidable, líneas de titanio y amoniaco como fluido de trabajo. En esa línea se diseñó y fabricó un prototipo para ensayos y se desarrolló un modelo de simulación con EcosimPro para evaluar sus prestaciones. Se concluyó que el diseño era adecuado para el rango de operación definido. La incompatibilidad entre el fluido de trabajo y los materiales del LHP está ligada a la generación de gases no condensables. Para un estudio más detallado de los efectos de dichos gases en el funcionamiento del LHP se analizó su comportamiento con diferentes cantidades de nitrógeno inyectadas en su cámara de compensación, simulando un gas no condensable formado en el interior del dispositivo. El estudio se basó en el análisis de las temperaturas medidas experimentalmente a distintos niveles de potencia y temperatura de sumidero o fuente fría. Adicionalmente, dichos resultados se compararon con las predicciones obtenidas por medio del modelo en EcosimPro. Las principales conclusiones obtenidas fueron dos. La primera indica que una cantidad de gas no condensable más de dos veces mayor que la cantidad generada al final de la vida de un satélite típico de telecomunicaciones (15 años) tiene efectos casi despreciables en el funcionamiento del LHP. La segunda es que el principal efecto del gas no condensable es una disminución de la conductancia térmica, especialmente a bajas potencias y temperaturas de sumidero. El efecto es más significativo cuanto mayor es la cantidad de gas añadida. Asimismo, durante la campaña de ensayos se observó un fenómeno no esperado para grandes cantidades de gas no condensable. Dicho fenómeno consiste en un comportamiento oscilatorio, detectado tanto en los ensayos como en la simulación. Este efecto es susceptible de una investigación más profunda y los resultados obtenidos pueden constituir la base para dicha tarea. ABSTRACT Loop Heat Pipes (LHPs) are heat transfer devices whose operating principle is based on the evaporation/condensation of a working fluid, and which use capillary pumping forces to ensure the fluid circulation. Thanks to their flexibility, low mass and minimum (even null) power consumption, their main application has been identified as part of the thermal control subsystem in spacecraft. In the present work, an LHP able to operate efficiently up to 125 oC has been developed, which is in line with the current tendency of satellite on-board equipment to increase their operating temperatures. In selecting the optimal LHP design for the elevated temperature application, the compatibility between the materials and working fluid has been identified as one of the main drivers. An extensive literature review and a dedicated trade-off were performed, in order to select the optimal combination of fluids and materials for the LHP. The trade-off included the development of a dedicated compatibility test stand. In conclusion, the combination of stainless steel evaporator, titanium piping and ammonia as working fluid was selected as the best candidate to operate up to 125 oC. An LHP prototype was designed and manufactured and a simulation model in EcosimPro was developed to evaluate its performance. The first conclusion was that the defined LHP was suitable for the defined operational range. Incompatibility between the working fluid and LHP materials is linked to Non Condensable Gas (NCG) generation. Therefore, the behaviour of the LHP developed with different amounts of nitrogen injected in its compensation chamber to simulate NCG generation, was analyzed. The LHP performance was studied by analysis of the test results at different temperatures and power levels. The test results were also compared to simulations in EcosimPro. Two additional conclusions can be drawn: (i) the effects of an amount of more than two times the expected NCG at the end of life of a typical telecommunications satellite (15 years) is almost negligible on the LHP operation, and (ii) the main effect of the NCG is a decrease in the LHP thermal conductance, especially at low temperatures and low power levels. This decrease is more significant with the progressive addition of NCG. An unexpected phenomenon was observed in the LHP operation with large NCG amounts. Namely, an oscillatory behaviour, which was observed both in the tests and the simulation. This effect provides the basis for further studies concerning oscillations in LHPs.
Resumo:
In some countries, such as Spain, it is very common that in the same corridor there are two roads with the same origin and destination but with some differences. The most important contrast is that one is a toll highway which offers a better quality than the parallel road in exchange of a price. The users decide if the price of the toll is worth to pay for the advantages offered. This problem is known as the untolled alternative and it has been largely studied in the academic literature, particularly related to economic efficiency and the optimal welfare toll. However, there is a gap in the literature academic regarding how it affects income distribution to the optimal toll. The main objective of the paper is to fill this gap. In this paper a theoretical model in order to obtain the optimal welfare price in a toll highway that competes for capturing the traffic with a conventional road is developed. This model is done for non-usual users who decide over the expectation of free flow conditions. This model is finally applied to the variables we want to focus on: average value of travel time (VTT) which is strongly related with income, dispersion of this VTT and traffic levels, from free flow to congestion. Derived from the results, we conclude that the higher the average VTT the higher the optimal price, the higher the dispersion of this VTT the lower the optimal price and finally, the more the traffic the higher the optimal toll.
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This paper addresses the problem of optimal constant continuous low-thrust transfer in the context of the restricted two-body problem (R2BP). Using the Pontryagin’s principle, the problem is formulated as a two point boundary value problem (TPBVP) for a Hamiltonian system. Lie transforms obtained through the Deprit method allow us to obtain the canonical mapping of the phase flow as a series in terms of the order of magnitude of the thrust applied. The reachable set of states starting from a given initial condition using optimal control policy is obtained analytically. In addition, a particular optimal transfer can be computed as the solution of a non-linear algebraic equation. Se investiga el uso de series y transformadas de Lie en problemas de optimización de trayectorias de satélites impulsados por motores de bajo empuje
Resumo:
In some countries, such as Spain, it is very common that in the same corridor there are two roads with the same origin and destination but with some differences. The most important contrast is that one is a toll highway which offers a better quality than the parallel road in exchange of a price. The users decide if the price of the toll is worth paying for the advantages offered. This problem is known as the untolled alternative and it has been largely studied in the academic literature, particularly related to economic efficiency and the optimal welfare toll. However, there is a gap in the academic literature regarding how income distribution affects the optimal toll. The main objective of the paper is to fill this gap. In this paper a theoretical model is developed in order to obtain the optimal welfare price in a toll highway that competes with a conventional road for capturing the traffic. This model is done for non-usual users who decide over the expectation of free flow conditions. This model is finally applied to the variables we want to focus on: average value of travel time (VTT) which is strongly related with income, dispersion of this VTT and traffic levels, from free flow to congestion. Derived from the results, we conclude that the higher the average VTT the higher the optimal price, the higher the dispersion of this VTT the lower the optimal price and finally, the more the traffic the higher the optimal toll
Resumo:
Understanding the factors responsible for variations in mutation patterns and selection efficacy along chromosomes is a prerequisite for deciphering genome sequences. Population genetics models predict a positive correlation between the efficacy of selection at a given locus and the local rate of recombination because of Hill–Robertson effects. Codon usage is considered one of the most striking examples that support this prediction at the molecular level. In a wide range of species including Caenorhabditis elegans and Drosophila melanogaster, codon usage is essentially shaped by selection acting for translational efficiency. Codon usage bias correlates positively with recombination rate in Drosophila, apparently supporting the hypothesis that selection on codon usage is improved by recombination. Here we present an exhaustive analysis of codon usage in C. elegans and D. melanogaster complete genomes. We show that in both genomes there is a positive correlation between recombination rate and the frequency of optimal codons. However, we demonstrate that in both species, this effect is due to a mutational bias toward G and C bases in regions of high recombination rate, possibly as a direct consequence of the recombination process. The correlation between codon usage bias and recombination rate in these species appears to be essentially determined by recombination-dependent mutational patterns, rather than selective effects. This result highlights that it is necessary to take into account the mutagenic effect of recombination to understand the evolutionary role and impact of recombination.
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The paper presents the analysis of an important historical building: the Saint James Theater in the city of Corfù (Greece) actually used as the Municipality House. The building, located in the center of the city, is made of carves stones and is characterized by a stocky shape and by the presence of wooden floors. The study deals with the structural identification of such structure through the analysis of its ambient vibrations recorded by means of accelerometers with high accuracy. A full dynamic testing was developed using ambient vibrations to identify the main modal parameters and to make a non-destructive characterization of this building. The results of these dynamic tests are compared with the modal analysis of a complex finite element (FE) simulation of the structure. This analysis may present several problems and uncertainties for this stocky building. Due to the presence of wooden floors, the local modes can be highly excited and, as a consequence, the evaluation of the structural modal parameters presents some difficulties.
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This thesis investigates the design of optimal tax systems in dynamic environments. The first essay characterizes the optimal tax system where wages depend on stochastic shocks and work experience. In addition to redistributive and efficiency motives, the taxation of inexperienced workers depends on a second-best requirement that encourages work experience, a social insurance motive and incentive effects. Calibrations using U.S. data yield higher expected optimal marginal income tax rates for experienced workers for most of the inexperienced workers. They confirm that the average marginal income tax rate increases (decreases) with age when shocks and work experience are substitutes (complements). Finally, more variability in experienced workers' earnings prospects leads to increasing tax rates since income taxation acts as a social insurance mechanism. In the second essay, the properties of an optimal tax system are investigated in a dynamic private information economy where labor market frictions create unemployment that destroys workers' human capital. A two-skill type model is considered where wages and employment are endogenous. I find that the optimal tax system distorts the first-period wages of all workers below their efficient levels which leads to more employment. The standard no-distortion-at-the-top result no longer holds due to the combination of private information and the destruction of human capital. I show this result analytically under the Maximin social welfare function and confirm it numerically for a general social welfare function. I also investigate the use of a training program and job creation subsidies. The final essay analyzes the optimal linear tax system when there is a population of individuals whose perceptions of savings are linked to their disposable income and their family background through family cultural transmission. Aside from the standard equity/efficiency trade-off, taxes account for the endogeneity of perceptions through two channels. First, taxing labor decreases income, which decreases the perception of savings through time. Second, taxation on savings corrects for the misperceptions of workers and thus savings and labor decisions. Numerical simulations confirm that behavioral issues push labor income taxes upward to finance saving subsidies. Government transfers to individuals are also decreased to finance those same subsidies.
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Optimal tax theory in the Mirrlees’ (1971) tradition implicitly relies on the assumption that all agents are single or that couples may be treated as individuals, despite accumulating evidence against this view of household behavior. We consider an economy where agents may either be single or married, in which case choices result from Nash bargaining between spouses. In such an environment, tax schedules must play the double role of: i) defining households’ objective functions through their impact on threat points, and; ii) inducing the desired allocations as optimal choices for households given these objectives. We find that the taxation principle, which asserts that there is no loss in relying on tax schedules is not valid here: there are constrained efficient allocations which cannot be implemented via taxes. More sophisticated mechanisms expand the set of implementable allocations by: i) aligning the households’ and planner’s objectives; ii) manipulating taxable income elasticities, and; iii) freeing the design of singles’ tax schedules from its consequences on households’ objectives.
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Upstream AUGs (uAUGs) and upstream open reading frames (uORFs) are common features of mRNAs that encode regulatory proteins and have been shown to profoundly influence translation of the main ORF. In this study, we employed a series of artificial 5'-untranslated regions (5'-UTRs) containing one or more uAUGs/uORFs to systematically assess translation initiation at the main AUG by leaky scanning and reinitiation mechanisms. Constructs containing either one or two uAUGs in varying contexts but without an in-frame stop codon upstream of the main AUG were used to analyse the leaky scanning mechanism. This analysis largely confirmed the ranking of different AUG contextual sequences that was determined previously by Kozak. In addition, this ranking was the same for both the first and second uAUGs, although the magnitude of initiation efficiency differed. Moreover, similar to10% of ribosomes exhibited leaky scanning at uAUGs in the most favourable context and initiated at a downstream AUG. A second group of constructs containing different numbers of uORFs, each with optimal uAUGs, were used to measure the capacity for reinitiation. We found significant levels of initiation at the main ORF even in constructs containing four uORFs, with nearly 10% of ribosomes capable of reinitiating five times. This study shows that for mRNAs containing multiple uORFs/uAUGs, ribosome reinitiation and leaky scanning are efficient mechanisms for initiation at their main AUGs.
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There are at least two reasons for a symmetric, unimodal, diffuse tailed hyperbolic secant distribution to be interesting in real-life applications. It displays one of the common types of non normality in natural data and is closely related to the logistic and Cauchy distributions that often arise in practice. To test the difference in location between two hyperbolic secant distributions, we develop a simple linear rank test with trigonometric scores. We investigate the small-sample and asymptotic properties of the test statistic and provide tables of the exact null distribution for small sample sizes. We compare the test to the Wilcoxon two-sample test and show that, although the asymptotic powers of the tests are comparable, the present test has certain practical advantages over the Wilcoxon test.
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Different DNA motifs are required for optimal stimulation Of mouse and human immune cells by CpG oligode-oxynucleotides (ODN). These species differences presumably reflect sequence differences in TLR9, the CPG DNA receptor. In this study, we show that this sequence specificity is restricted to phosphorothioate (PS)-modified ODN and is not observed when a natural phosphodiester backbone is used. Thus, human and mouse cells have not evolved to recognize different CpG motifs in natural DNA. Nonoptimal PS-ODN (i.e., mouse CpG motif on human cells and vice versa) gave delayed and less sustained phosphorylation of p38 AWK than optimal motifs. When the CpG dinucleotide was inverted to GC In each ODN some residual activity of the PS-ODN was retained in a species-specific, TLR-9-dependent manner. Thus, TLR9 may he responsible for mediating many published CpG-independent responses to PS-ODN.
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In this paper we propose a range of dynamic data envelopment analysis (DEA) models which allow information on costs of adjustment to be incorporated into the DEA framework. We first specify a basic dynamic DEA model predicated on a number or simplifying assumptions. We then outline a number of extensions to this model to accommodate asymmetric adjustment costs, non-static output quantities, non-static input prices, and non-static costs of adjustment, technological change, quasi-fixed inputs and investment budget constraints. The new dynamic DEA models provide valuable extra information relative to the standard static DEA models-they identify an optimal path of adjustment for the input quantities, and provide a measure of the potential cost savings that result from recognising the costs of adjusting input quantities towards the optimal point. The new models are illustrated using data relating to a chain of 35 retail department stores in Chile. The empirical results illustrate the wealth of information that can be derived from these models, and clearly show that static models overstate potential cost savings when adjustment costs are non-zero.
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Recent studies have demonstrated male mate choice for female ornaments in species without sex-role reversal. Despite these empirical findings, little is known about the adaptive dynamics of female signalling, in particular the evolution of male mating preferences. The evolution of traits that signal mate quality is more complex in females than in males because females usually provide the bulk of resources for the developing offspring. Here, we investigate the evolution of male mating preferences using a mathematical model which: (i) specifically accounts for the fact that females must trade-off resources invested in ornaments with reproduction; and (ii) allows male mating preferences to evolve a non-directional shape. The optimal adaptive strategy for males is to develop stabilizing mating preferences for female display traits to avoid females that either invests too many or too few resources in ornamentation. However, the evolutionary stability of this prediction is dependent upon the level of error made by females when allocating resources to either signal or fecundity.
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Background: Oral itraconazole (ITRA) is used for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis (CF) because of its antifungal activity against Aspergillus species. ITRA has an active hydroxy-metabolite (OH-ITRA) which has similar antifungal activity. ITRA is a highly lipophilic drug which is available in two different oral formulations, a capsule and an oral solution. It is reported that the oral solution has a 60% higher relative bioavailability. The influence of altered gastric physiology associated with CF on the pharmacokinetics (PK) of ITRA and its metabolite has not been previously evaluated. Objectives: 1) To estimate the population (pop) PK parameters for ITRA and its active metabolite OH-ITRA including relative bioavailability of the parent after administration of the parent by both capsule and solution and 2) to assess the performance of the optimal design. Methods: The study was a cross-over design in which 30 patients received the capsule on the first occasion and 3 days later the solution formulation. The design was constrained to have a maximum of 4 blood samples per occasion for estimation of the popPK of both ITRA and OH-ITRA. The sampling times for the population model were optimized previously using POPT v.2.0.[1] POPT is a series of applications that run under MATLAB and provide an evaluation of the information matrix for a nonlinear mixed effects model given a particular design. In addition it can be used to optimize the design based on evaluation of the determinant of the information matrix. The model details for the design were based on prior information obtained from the literature, which suggested that ITRA may have either linear or non-linear elimination. The optimal sampling times were evaluated to provide information for both competing models for the parent and metabolite and for both capsule and solution simultaneously. Blood samples were assayed by validated HPLC.[2] PopPK modelling was performed using FOCE with interaction under NONMEM, version 5 (level 1.1; GloboMax LLC, Hanover, MD, USA). The PK of ITRA and OH‑ITRA was modelled simultaneously using ADVAN 5. Subsequently three methods were assessed for modelling concentrations less than the LOD (limit of detection). These methods (corresponding to methods 5, 6 & 4 from Beal[3], respectively) were (a) where all values less than LOD were assigned to half of LOD, (b) where the closest missing value that is less than LOD was assigned to half the LOD and all previous (if during absorption) or subsequent (if during elimination) missing samples were deleted, and (c) where the contribution of the expectation of each missing concentration to the likelihood is estimated. The LOD was 0.04 mg/L. The final model evaluation was performed via bootstrap with re-sampling and a visual predictive check. The optimal design and the sampling windows of the study were evaluated for execution errors and for agreement between the observed and predicted standard errors. Dosing regimens were simulated for the capsules and the oral solution to assess their ability to achieve ITRA target trough concentration (Cmin,ss of 0.5-2 mg/L) or a combined Cmin,ss for ITRA and OH-ITRA above 1.5mg/L. Results and Discussion: A total of 241 blood samples were collected and analysed, 94% of them were taken within the defined optimal sampling windows, of which 31% where taken within 5 min of the exact optimal times. Forty six per cent of the ITRA values and 28% of the OH-ITRA values were below LOD. The entire profile after administration of the capsule for five patients was below LOD and therefore the data from this occasion was omitted from estimation. A 2-compartment model with 1st order absorption and elimination best described ITRA PK, with 1st order metabolism of the parent to OH-ITRA. For ITRA the clearance (ClItra/F) was 31.5 L/h; apparent volumes of central and peripheral compartments were 56.7 L and 2090 L, respectively. Absorption rate constants for capsule (kacap) and solution (kasol) were 0.0315 h-1 and 0.125 h-1, respectively. Comparative bioavailability of the capsule was 0.82. There was no evidence of nonlinearity in the popPK of ITRA. No screened covariate significantly improved the fit to the data. The results of the parameter estimates from the final model were comparable between the different methods for accounting for missing data, (M4,5,6)[3] and provided similar parameter estimates. The prospective application of an optimal design was found to be successful. Due to the sampling windows, most of the samples could be collected within the daily hospital routine, but still at times that were near optimal for estimating the popPK parameters. The final model was one of the potential competing models considered in the original design. The asymptotic standard errors provided by NONMEM for the final model and empirical values from bootstrap were similar in magnitude to those predicted from the Fisher Information matrix associated with the D-optimal design. Simulations from the final model showed that the current dosing regimen of 200 mg twice daily (bd) would provide a target Cmin,ss (0.5-2 mg/L) for only 35% of patients when administered as the solution and 31% when administered as capsules. The optimal dosing schedule was 500mg bd for both formulations. The target success for this dosing regimen was 87% for the solution with an NNT=4 compared to capsules. This means, for every 4 patients treated with the solution one additional patient will achieve a target success compared to capsule but at an additional cost of AUD $220 per day. The therapeutic target however is still doubtful and potential risks of these dosing schedules need to be assessed on an individual basis. Conclusion: A model was developed which described the popPK of ITRA and its main active metabolite OH-ITRA in adult CF after administration of both capsule and solution. The relative bioavailability of ITRA from the capsule was 82% that of the solution, but considerably more variable. To incorporate missing data, using the simple Beal method 5 (using half LOD for all samples below LOD) provided comparable results to the more complex but theoretically better Beal method 4 (integration method). The optimal sparse design performed well for estimation of model parameters and provided a good fit to the data.