772 research outputs found

    Firm size and productivity from occupational choices

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    We model the distributions of firm sizes and of firms’ total factor productivity (TFP) as outcomes of a market equilibrium from the occupational decisions of individuals with different entrepreneurial skills, of working as employees, employers, or solo entrepreneurs. The model explains empirical regularities such as (i) the positive cross-section correlation between average size of firms and average labor productivity of countries, (ii) the positive association between size and TFP of firms in an economy, and (iii) the power law distribution of firm sizes. Two parameters of the model, one that measures the organizational size diseconomies and other related to the dispersion of the distribution of entrepreneurial skills in the population, appear as main determinants of the differences in firm sizes and in productivity, across economies and among firms within an economy. The results of the paper should be of interest for the design and evaluation of firm-size-dependent policies

    Equatorial ozone characteristics as measured at Natal (5.9 deg S, 35.2 deg W)

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    Ozone density profiles obtained through electrochemical concentration cell (ECC) sonde measurements at Natal were analyzed. Time variations, as expected, are small. Outstanding features of the data are tropospheric densities substantially higher than those measured at other stations, and also a total ozone content that is higher than the averages given by satellite measurements

    Protein interaction perturbation profiling at amino-acid resolution

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    The identification of genomic variants in healthy and diseased individuals continues to rapidly outpace our ability to functionally annotate these variants. Techniques that both systematically assay the functional consequences of nucleotide-resolution variation and can scale to hundreds of genes are urgently required. We designed a sensitive yeast two-hybrid-based 'off switch' for positive selection of interaction-disruptive variants from complex genetic libraries. Combined with massively parallel programmed mutagenesis and a sequencing readout, this method enables systematic profiling of protein-interaction determinants at amino-acid resolution. We defined >1,000 interaction-disrupting amino acid mutations across eight subunits of the BBSome, the major human cilia protein complex associated with the pleiotropic genetic disorder Bardet–Biedl syndrome. These high-resolution interaction-perturbation profiles provide a framework for interpreting patient-derived mutations across the entire protein complex and thus highlight how the impact of disease variation on interactome networks can be systematically assessed

    Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii

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    A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system

    Cumulative regulatory potential of clustered methyl-arginine protein modifications

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    Systematic analysis of human arginine methylation events bifurcates its signaling mechanism, functioning either in isolation akin to canonical PTM regulation or clustered within disordered protein sequence. Hundreds of proteins contain methyl-arginine clusters and are more prone to mutation and more tightly expression-regulated than dispersed methylation targets. Arginine clusters in the highly methylated RNA binding protein SYNCRIP were experimentally shown to function in concert providing a tunable protein interaction interface. Quantitative immuno-precipitation assays defined two distinct cumulative regulatory mechanisms operating across 18 proximal arginine-glycine motifs in SYNCRIP. Functional binding to the methyl-transferase PRMT1 was promoted by continual arginine stretches while interaction with the methyl-binding protein SMN1 was arginine content dependent irrespective of linear position within the unstructured region. This study highlights how highly repetitive di-amino acid motifs in otherwise low structural complexity regions can provide regulatory potential, and with SYNCRIP as an extreme example how PTMs leverage these disordered sequences to drive cellular functions

    Towns with extremely low mortality due to ischemic heart disease in Spain

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    BACKGROUND: The cause of coronary disease inframortality in Spain is unknown. The aim of this study is to identify Spanish towns with very low ischemic heart disease mortality, describe their health and social characteristics, and analyze the relationship with a series of contextual factors. METHODS: We obtained the number of deaths registered for each of 8,122 Spanish towns in the periods 1989-1998 and 1999-2003. Expected deaths, standardized mortality ratio (SMR), smoothed Relative Risk (RR), and Posterior Probability (PP) of RR > 1 were calculated using Bayesian hierarchical models. Inframortality was defined as any town that displayed an RR below the 10th percentile, an SMR of under 1 for both sexes, and a PP of RR > 1 less than or equal to 0.002 for male and 0.005 for female mortality, during the two periods covered. All the remaining towns, except for those with high mortality classified as "tourist towns", were selected as controls. The association among socioeconomic, health, dietary, lifestyle and vascular risk factors was analyzed using sequential mixed logistic regression models, with province as the random-effects variable. RESULTS: We identified 32 towns in which ischemic heart disease mortality was half the national rate and four times lower than the European Union rate, situated in lightly populated provinces spread across the northern half of Spain, and revealed a surprising pattern of geographic aggegation for 23 of the 32 towns. Variables related with inframortality were: a less aged population (OR 0.93, 95% CI 0.89-0.99); a contextual dietary pattern marked by a high fish content (OR 2.13, 95% CI 1.38-3.28) and wine consumption (OR 1.50, 95% CI 1.08-2.07); and a low prevalence of obesity (OR 0.47, 95% CI 0.22-1.01); and, in the case of towns of over 1000 inhabitants, a higher physician-population ratio (OR 3.80, 95% CI 1.17-12.3). CONCLUSIONS: Results indicate that dietary and health care factors have an influence on inframortality. The geographical aggregation suggests that other factors with a spatial pattern, e.g., genetic or environmental might also be implicated. These results will have to be confirmed by studies in situ, with objective measurements at an individual level.This study was funded by research study grant no. PI06/0656 from Spain's Health Research Fund (Fondo de Investigación Sanitaria).S

    Complex-Orbital Order in Fe_3O_4 and Mechanism of the Verwey Transition

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    Electronic state and the Verwey transition in magnetite (Fe_3O_4) are studied using a spinless three-band Hubbard model for 3d electrons on the B sites with the Hartree-Fock approximation and the exact diagonalisation method. Complex-orbital, e.g., 1/sqrt(2)[|zx> + i |yz>], ordered (COO) states having noncollinear orbital moments ~ 0.4 mu_B on the B sites are obtained with the cubic lattice structure of the high-temperature phase. The COO state is a novel form of magnetic ordering within the orbital degree of freedom. It arises from the formation of Hund's second rule states of spinless pseudo-d molecular orbitals in the Fe_4 tetrahedral units of the B sites and ferromagnetic alignment of their fictitious orbital moments. A COO state with longer periodicity is obtained with pseudo-orthorhombic Pmca and Pmc2_1 structures for the low-temperature phase. The state spontaneously lowers the crystal symmetry to the monoclinic and explains experimentally observed rhombohedral cell deformation and Jahn-Teller like distortion. From these findings, we consider that at the Verwey transition temperature, the COO state remaining to be short-range order impeded by dynamical lattice distortion in high temperature is developed into that with long-range order coupled with the monoclinic lattice distortion.Comment: 16 pages, 13 figures, 6 tables, accepted for publication in J. Phys. Soc. Jp

    Identification and quantification of microplastics in wastewater using focal plane array-based reflectance micro-FT-IR imaging

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    Microplastics (<5 mm) have been documented in environmental samples on a global scale. While these pollutants may enter aquatic environments via wastewater treatment facilities, the abundance of microplastics in these matrices has not been investigated. Although efficient methods for the analysis of microplastics in sediment samples and marine organisms have been published, no methods have been developed for detecting these pollutants within organic-rich wastewater samples. In addition, there is no standardized method for analyzing microplastics isolated from environmental samples. In many cases, part of the identification protocol relies on visual selection before analysis, which is open to bias. In order to address this, a new method for the analysis of microplastics in wastewater was developed. A pretreatment step using 30% hydrogen peroxide (H2O2) was employed to remove biogenic material, and focal plane array (FPA)-based reflectance micro-Fourier-transform (FT-IR) imaging was shown to successfully image and identify different microplastic types (polyethylene, polypropylene, nylon-6, polyvinyl chloride, polystyrene). Microplastic-spiked wastewater samples were used to validate the methodology, resulting in a robust protocol which was nonselective and reproducible (the overall success identification rate was 98.33%). The use of FPA-based micro-FT-IR spectroscopy also provides a considerable reduction in analysis time compared with previous methods, since samples that could take several days to be mapped using a single-element detector can now be imaged in less than 9 h (circular filter with a diameter of 47 mm). This method for identifying and quantifying microplastics in wastewater is likely to provide an essential tool for further research into the pathways by which microplastics enter the environment.This work is funded by a NERC (Natural Environment Research Council) CASE studentship (NE/K007521/1) with contribution from industrial partner Fera Science Ltd., United Kingdom. The authors would like to thank Peter Vale, from Severn Trent Water Ltd, for providing access to and additionally Ashley Howkins (Brunel University London) for providing travel and assistance with the sampling of the Severn Trent wastewater treatment plant in Derbyshire, UK. We are grateful to Emma Bradley and Chris Sinclair for providing helpful suggestions for our research
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