779 research outputs found

    Energy-Extended CES Aggregate Production: Current Aspects of Their Specification and Econometric Estimation

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    Capital–labour–energy Constant Elasticity of Substitution (CES) production functions and their estimated parameters now form a key part of energy–economy models which inform energy and emissions policy. However, the collation and guidance as to the specification and estimation choices involved with such energy-extended CES functions is disparate. This risks poorly specified and estimated CES functions, with knock-on implications for downstream energy–economic models and climate policy. In response, as a first step, this paper assembles in one place the major considerations involved in the empirical estimation of these CES functions. Discussions of the choices and their implications lead to recommendations for CES empiricists. The extensive bibliography allows those interested to dig deeper into any aspect of the CES parameter estimation process

    Mild Transient Hypercapnia as a Novel Fear Conditioning Stimulus Allowing Re-Exposure during Sleep

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    Introduction:Studies suggest that sleep plays a role in traumatic memories and that treatment of sleep disorders may help alleviate symptoms of posttraumatic stress disorder. Fear-conditioning paradigms in rodents are used to investigate causal mechanisms of fear acquisition and the relationship between sleep and posttraumatic behaviors. We developed a novel conditioning stimulus (CS) that evoked fear and was subsequently used to study re-exposure to the CS during sleep.Methods:Experiment 1 assessed physiological responses to a conditioned stimulus (mild transient hypercapnia, mtHC; 3.0% CO2; n = 17)+footshock for the purpose of establishing a novel CS in male FVB/J mice. Responses to the novel CS were compared to tone+footshock (n = 18) and control groups of tone alone (n = 17) and mild transient hypercapnia alone (n = 10). A second proof of principle experiment re-exposed animals during sleep to mild transient hypercapnia or air (control) to study sleep processes related to the CS.Results:Footshock elicited a response of acute tachycardia (30-40 bpm) and increased plasma epinephrine. When tone predicted footshock it elicited mild hypertension (1-2 mmHg) and a three-fold increase in plasma epinephrine. When mtHC predicted footshock it also induced mild hypertension, but additionally elicited a conditioned bradycardia and a smaller increase in plasma epinephrine. The overall mean 24 hour sleep-wake profile was unaffected immediately after fear conditioning.Discussion:Our study demonstrates the efficacy of mtHC as a conditioning stimulus that is perceptible but innocuous (relative to tone) and applicable during sleep. This novel model will allow future studies to explore sleep-dependent mechanisms underlying maladaptive fear responses, as well as elucidate the moderators of the relationship between fear responses and sleep. © 2013 McDowell et al

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

    Genetic dissection of early endosomal recycling highlights a TORC1-independent role for Rag GTPases

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    Endocytosed cell surface membrane proteins rely on recycling pathways for their return to the plasma membrane. Although endosome-to-plasma membrane recycling is critical for many cellular processes, much of the required machinery is unknown. We discovered that yeast has a recycling route from endosomes to the cell surface that functions efficiently after inactivation of the sec7-1 allele of Sec7, which controls transit through the Golgi. A genetic screen based on an engineered synthetic reporter that exclusively follows this pathway revealed that recycling was subject to metabolic control through the Rag GTPases Gtr1 and Gtr2, which work downstream of the exchange factor Vam6. Gtr1 and Gtr2 control the recycling pathway independently of TORC1 regulation through the Gtr1 interactor Ltv1. We further show that the early-endosome recycling route and its control though the Vam6 > Gtr1/Gtr2 > Ltv1 pathway plays a physiological role in regulating the abundance of amino acid transporters at the cell surface

    A novel nonparametric item response theory approach to measuring socioeconomic position: a comparison using household expenditure data from a Vietnam health survey, 2003

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    BACKGROUND: Measures of household socio-economic position (SEP) are widely used in health research. There exist a number of approaches to their measurement, with Principal Components Analysis (PCA) applied to a basket of household assets being one of the most common. PCA, however, carries a number of assumptions about the distribution of the data which may be untenable, and alternative, non-parametric, approaches may be preferred. Mokken scale analysis is a non-parametric, item response theory approach to scale development which appears never to have been applied to household asset data. A Mokken scale can be used to rank order items (measures of wealth) as well as households. Using data on household asset ownership from a national sample of 4,154 consenting households in the World Health Survey from Vietnam, 2003, we construct two measures of household SEP. Seventeen items asking about assets, and utility and infrastructure use were used. Mokken Scaling and PCA were applied to the data. A single item measure of total household expenditure is used as a point of contrast. RESULTS: An 11 item scale, out of the 17 items, was identified that conformed to the assumptions of a Mokken Scale. All the items in the scale were identified as strong items (Hi > .5). Two PCA measures of SEP were developed as a point of contrast. One PCA measure was developed using all 17 available asset items, the other used the reduced set of 11 items identified in the Mokken scale analaysis. The Mokken Scale measure of SEP and the 17 item PCA measure had a very high correlation (r = .98), and they both correlated moderately with total household expenditure: r = .59 and r = .57 respectively. In contrast the 11 item PCA measure correlated moderately with the Mokken scale (r = .68), and weakly with the total household expenditure (r = .18). CONCLUSION: The Mokken scale measure of household SEP performed at least as well as PCA, and outperformed the PCA measure developed with the 11 items used in the Mokken scale. Unlike PCA, Mokken scaling carries no assumptions about the underlying shape of the distribution of the data, and can be used simultaneous to order household SEP and items. The approach, however, has not been tested with data from other countries and remains an interesting, but under researched approach

    States Of Discontent

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    Latin America’s recent inclusionary turn centers on changing relationships between the popular sectors and the state. Yet the new inclusion unfolds in a region in which most states are weak and prone to severe pathologies, such as corruption, inefficiency, and particularism. The first part of the chapter outlines an argument, developed at more length elsewhere, regarding how “state crises” helped drive the consolidation of three distinct party system trajectories among the eight South American countries where the Left would eventually win power. The second part of the chapter argues that these trajectories differed in three ways that likely conditioned how the concomitant inclusionary Left turn unfolded in each case: the institutionalization of left-wing parties, the occurrence of state transformation via constitutional reform, and the level of state capacity. The discussion helps highlight the central role of the state and its pathologies in both driving alternative paths of political development and in conditioning the politics of inclusion. By putting the emphasis on the state and its pathologies, we can better consider not just the sources of sociopolitical exclusion but also the limits of sociopolitical inclusion

    Oxygen matters: tissue culture oxygen levels affect mitochondrial function and structure as well as responses to HIV viroproteins

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    Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1–11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons
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