237 research outputs found

    Benefit incidence analysis in developing countries

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    As interesting and difficult as it is to allocate tax burdens to individuals, the profession knows even less about allocating benefits. The authors survey the literature on benefit incidence since DeWulf's (1975) review, focusing on the methodology and results of benefit incidence analysis in developing countries. Research in this area faces all the general-equilibrium difficulties faced by tax incidence analysis as well as the difficult task of measuring benefits from publicly provided goods and services. Despite the inherent pitfalls of this methodology, the authors believe that benefit incidence analysis can provide an important perspective on the budget by combining data on household use with data on project costs. In particular, benefit incidence analyses can help illuminate the distributional impacts of proposed reallocations of government resources among projects. The value of such research is especially high considering the scarcity of recent research in this area. The authors review the existing methodology, survey the available results, and point out areas in which further research might have large payoffs. They also make specific methodological suggestions that might help ensure that future research is as useful for policymakers as possible. For example: Aggregate results based on the zero-government counterfactual rely on strong assumptions about fixed relative prices and incomes, government efficiency, and the relationship between marginal and total benefits. And those studies are often not designed to identify which types of public services benefit the poor. Researchers should focus more on providing benefit incidence studies on specific government functions or programs that can help policymakers reach conclusions about proposed reallocations of resources among government programs. Benefit incidence should be assigned to households based on household survey information on usage rather than on ad hoc assumptions that assign benefits based on income or the number of members in the household. Improved annual cost measures for services need to be developed, particulary for capital inputs. Researchers should group households by deciles and whenever possible should consider other groupings based on household income adjusted for household composition, age, location, and other relevant socioeconomic variables. Careful attention to life-cycle benefits, benefit shifting, rent-seeking, out-of-pocket costs, displacement of private sector efforts, average versus marginal incidence, and several other issues can significantly increase the value of benefit incidence analysis to policymakers.Economic Theory&Research,Environmental Economics&Policies,Poverty Assessment,Health Economics&Finance,Banks&Banking Reform

    Metabolomic and 13C-metabolic flux analysis of a xylose-consuming Saccharomyces cerevisiae strain expressing xylose isomerase

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    Over the past two decades, significant progress has been made in the engineering of xylose-consuming Saccharomyces cerevisiae strains for production of lignocellulosic biofuels. However, the ethanol productivities achieved on xylose are still significantly lower than those observed on glucose for reasons that are not well understood. We have undertaken an analysis of central carbon metabolite pool sizes and metabolic fluxes on glucose and on xylose under aerobic and anaerobic conditions in a strain capable of rapid xylose assimilation via xylose isomerase in order to investigate factors that may limit the rate of xylose fermentation. We find that during xylose utilization the flux through the non-oxidative Pentose Phosphate Pathway (PPP) is high but the flux through the oxidative PPP is low, highlighting an advantage of the strain employed in this study. Furthermore, xylose fails to elicit the full carbon catabolite repression response that is characteristic of glucose fermentation in S. cerevisiae. We present indirect evidence that the incomplete activation of the fermentation program on xylose results in a bottleneck in lower glycolysis, leading to inefficient re-oxidation of NADH produced in glycolysis.Shell Oil CompanyNational Institute of General Medical Sciences (U.S.) Biotechnology Training Progra

    Cyclohexene Photo-oxidation over Vanadia Catalyst Analyzed by Time Resolved ATR-FT-IR Spectroscopy

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    Vanadia was incorporated in the 3-dimensional mesoporous material TUD-1 with a loading of 2percent w/w vanadia. The performance in the selective photo-oxidation of liquid cyclohexene was investigated using ATR-FT-IR spectroscopy. Under continuous illumination at 458 nm a significant amount of product, i.e. cyclohexenone, was identified. This demonstrates for the first time that hydroxylated vanadia centers in mesoporous materials can be activated by visible light to induce oxidation reactions. Using the rapid scan method, a strong perturbation of the vanadyl environment could be observed in the selective oxidation process induced by a 458 nm laser pulse of 480 ms duration. This is proposed to be caused by interaction of the catalytic centre with a cyclohexenyl hydroperoxide intermediate. The restoration of the vanadyl environment could be kinetically correlated to the rate of formation of cyclohexenone, and is explained by molecular rearrangement and dissociation of the peroxide to ketone and water. The ketone diffuses away from the active center and ATR infrared probing zone, resulting in a decreasing ketone signal on the tens of seconds time scale after initiation of the photoreaction. This study demonstrates the high potential of time resolved ATR FT-IR spectroscopy for mechanistic studies of liquid phase reactions by monitoring not only intermediates and products, but by correlating the temporal behavior of these species to molecular changes of the vanadyl catalytic site

    Huntington’s Disease iPSC-Derived Brain Microvascular Endothelial Cells Reveal WNT-Mediated Angiogenic and Blood-Brain Barrier Deficits

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    Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls. We demonstrate that HD iBMECs have intrinsic abnormalities in angiogenesis and barrier properties, as well as in signaling pathways governing these processes. Thus, our findings provide an iPSC-derived BBB model for a neurodegenerative disease and demonstrate autonomous neurovascular deficits that may underlie HD pathology with implications for therapeutics and drug delivery.American Heart Association (12PRE10410000)American Heart Association (CIRMTG2-01152)National Institutes of Health (U.S.) (NIHNS089076

    Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

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    Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.National Science Foundation (U.S.) (Grant T32GM007287

    An analysis of waves underlying grid cell firing in the medial enthorinal cortex

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    Layer II stellate cells in the medial enthorinal cortex (MEC) express hyperpolarisation-activated cyclic-nucleotide-gated (HCN) channels that allow for rebound spiking via an I_h current in response to hyperpolarising synaptic input. A computational modelling study by Hasselmo [2013 Neuronal rebound spiking, resonance frequency and theta cycle skipping may contribute to grid cell firing in medial entorhinal cortex. Phil. Trans. R. Soc. B 369: 20120523] showed that an inhibitory network of such cells can support periodic travelling waves with a period that is controlled by the dynamics of the I_h current. Hasselmo has suggested that these waves can underlie the generation of grid cells, and that the known difference in I_h resonance frequency along the dorsal to ventral axis can explain the observed size and spacing between grid cell firing fields. Here we develop a biophysical spiking model within a framework that allows for analytical tractability. We combine the simplicity of integrate-and-fire neurons with a piecewise linear caricature of the gating dynamics for HCN channels to develop a spiking neural field model of MEC. Using techniques primarily drawn from the field of nonsmooth dynamical systems we show how to construct periodic travelling waves, and in particular the dispersion curve that determines how wave speed varies as a function of period. This exhibits a wide range of long wavelength solutions, reinforcing the idea that rebound spiking is a candidate mechanism for generating grid cell firing patterns. Importantly we develop a wave stability analysis to show how the maximum allowed period is controlled by the dynamical properties of the I_h current. Our theoretical work is validated by numerical simulations of the spiking model in both one and two dimensions
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