761 research outputs found

    The new keynesian approach to dynamic general equilibrium modeling: models, methods, and macroeconomic policy evaluation

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    This chapter aims to provide a hands-on approach to New Keynesian models and their uses for macroeconomic policy analysis. It starts by reviewing the origins of the New Keynesian approach, the key model ingredients and representative models. Building blocks of current-generation dynamic stochastic general equilibrium (DSGE) models are discussed in detail. These models address the famous Lucas critique by deriving behavioral equations systematically from the optimizing and forward-looking decision-making of households and firms subject to well-defined constraints. State-of-the-art methods for solving and estimating such models are reviewed and presented in examples. The chapter goes beyond the mere presentation of the most popular benchmark model by providing a framework for model comparison along with a database that includes a wide variety of macroeconomic models. Thus, it offers a convenient approach for comparing new models to available benchmarks and for investigating whether particular policy recommendations are robust to model uncertainty. Such robustness analysis is illustrated by evaluating the performance of simple monetary policy rules across a range of recently-estimated models including some with financial market imperfections and by reviewing recent comparative findings regarding the magnitude of government spending multipliers. The chapter concludes with a discussion of important objectives for on-going and future research using the New Keynesian framework

    Effect of Lateral Sliding Calcaneus Osteotomy on Tarsal Tunnel Pressure

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    Background: Lateral sliding calcaneus osteotomies are common procedures to correct hindfoot varus deformities. Shifting the calcaneal tuberosity laterally (lateralization) can lead to tarsal tunnel pressure increase and tibial nerve palsy. The purpose of this cadaveric biomechanical study was to investigate the correlation of lateralization and pressure increase underneath the flexor retinaculum. Methods: The pressure in the tarsal tunnel of 12 Thiel-fixated human cadaveric lower legs was measured in different foot positions and varying degrees of calcaneal lateralization. Results: The mean pressure increased from plantarflexion (PF) to neutral position (NP) and from NP to hindfoot dorsiflexion (DF), and with increasing amounts of lateralization of the calcaneal tuberosity. The mean baseline pressure in PF was 1.5, in NP 2.2, and in DF 6.5 mmHg and increased to 8.1 in PF, 18.4 in NP, and 33.1 mmHg with 12 mm of lateralization. The release of the flexor retinaculum significantly lowered the pressure. Conclusion: Increasing pressures were found in the tarsal tunnel with increasing lateralization of the tuberosity and with both dorsiflexion and plantarflexion of the ankle. Clinical Relevance: A pre-emptive release of the flexor retinaculum for a lateralization of the calcaneal tuberosity of more than 8 mm should be considered, especially if specific patient risk factors are present. No tibial nerve palsy should be expected with 4 mm of lateralization

    Defective Secretion of Islet Hormones in Chromogranin-B Deficient Mice

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    Granins are major constituents of dense-core secretory granules in neuroendocrine cells, but their function is still a matter of debate. Work in cell lines has suggested that the most abundant and ubiquitously expressed granins, chromogranin A and B (CgA and CgB), are involved in granulogenesis and protein sorting. Here we report the generation and characterization of mice lacking chromogranin B (CgB-ko), which were viable and fertile. Unlike neuroendocrine tissues, pancreatic islets of these animals lacked compensatory changes in other granins and were therefore analyzed in detail. Stimulated secretion of insulin, glucagon and somatostatin was reduced in CgB-ko islets, in parallel with somewhat impaired glucose clearance and reduced insulin release, but normal insulin sensitivity in vivo. CgB-ko islets lacked specifically the rapid initial phase of stimulated secretion, had elevated basal insulin release, and stored and released twice as much proinsulin as wildtype (wt) islets. Stimulated release of glucagon and somatostatin was reduced as well. Surprisingly, biogenesis, morphology and function of insulin granules were normal, and no differences were found with regard to β-cell stimulus-secretion coupling. We conclude that CgB is not required for normal insulin granule biogenesis or maintenance in vivo, but is essential for adequate secretion of islet hormones. Consequentially CgB-ko animals display some, but not all, hallmarks of human type-2 diabetes. However, the molecular mechanisms underlying this defect remain to be determined

    Investigating Alkylated Prodigiosenes and Their Cu(II)-Dependent Biological Activity: Interactions with DNA, Antimicrobial and Photoinduced Anticancer Activity

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    Prodigiosenes are a family of red pigments with versatile biological activity. Their tripyrrolic core structure has been modified many times in order to manipulate the spectrum of activity. We have been looking systematically at prodigiosenes substituted at the C ring with alkyl chains of different lengths, in order to assess the relevance of this substituent in a context that has not been investigated before for these derivatives: Cu(II) complexation, DNA binding, self-activated DNA cleavage, photoinduced cytotoxicity and antimicrobial activity. Our results indicate that the hydrophobic substituent has a clear influence on the different aspects of their biological activity. The cytotoxicity study of the Cu(II) complexes of these prodigiosenes shows that they exhibit a strong cytotoxic effect towards the tested tumor cell lines. The Cu(II) complex of a prodigiosene lacking any alkyl chain excelled in its photoinduced anticancer activity, thus demonstrating the potential of prodigiosenes and their metal complexes for an application in photodynamic therapy (PDT). Two derivatives along with their Cu(II) complexes showed also antimicrobial activity against Staphylococcus aureus strains

    Multiple Sclerosis: Improved Detection of Active Cerebral Lesions With 3-Dimensional T1 Black-Blood Magnetic Resonance Imaging Compared With Conventional 3-Dimensional T1 GRE Imaging

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    Objectives: The aim of this study was to assess the diagnostic accuracy of a modified high-resolution whole-brain three-dimensional T1-weighted black-blood sequence (T1-weighted modified volumetric isotropic turbo spin echo acquisition [T1-mVISTA]) in comparison to a standard three-dimensional T1-weighted magnetization-prepared rapid gradient echo (MP-RAGE) sequence for detection of contrast-enhancing cerebral lesions in patients with relapsing-remitting multiple sclerosis (MS).& para;& para;Materials and Methods: After institutional review board approval and informed consent, 22 patients (8 men;aged 31.0 +/- 9.2 years) with relapsing-remitting MS were included in this monocentric prospective cohort study.& para;& para;Contrast-enhanced T1-mVISTA and MP-RAGE, both with 0.8 mm(3) resolution, were performed in all patients. In a substudy of 12 patients, T1-mVISTA was compared with a T1-mVISTA with 1.0 mm(3) resolution (T1-mVISTA_1.0). Reference lesions were 2-defined by an experienced neuroradiologist using all available sequences and served as the criterion standard. T1-mVISTA, T1-mVISTA_1.0, and MP-RAGE sequences were read in random order 4 weeks apart. Image quality, visual contrast enhancement, contrast-to-noise-ratio (CNR), diagnostic confidence, and lesion size were assessed and compared by Wilcoxon and Mann-Whitney U tests.& para;& para;Results: Eleven of 22 patients displayed contrast-enhancing lesions. Visual contrast enhancement, CNR, and diagnostic confidence of contrast-enhancing MS lesions were significantly increased in T1-mVISTA compared with MP-RAGE (P < 0.001). Significantly more contrast-enhancing lesions were detected with T1-mVISTA than with MP-RAGE (71 vs 39, respectively;P < 0.001). With MP-RAGE, 25.6% of lesions were missed in the initial reading, whereas only 4.2% of lesions were missed with T1-mVISTA. Increase of the voxel volume from 0.8 mm to 1.0 mm isotropic in T1-mVISTA_1.0 did not affect the detect-ability of lesions, whereas scan time was decreased from 4:43 to 1:55 minutes.& para;& para;Conclusions: Three-dimensional T1-mVISTA improves the detection rates of contrast-enhancing cerebral MS lesions compared with conventional 3D MP-RAGE sequences by increasing CNR of lesions and might, therefore, be useful in patient management

    A new phenylethanoid triglycoside in Veronica beccabunga L

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    Jensen SR, Opitz S, Gotfredsen CH. A new phenylethanoid triglycoside in Veronica beccabunga L. Biochemical Systematics and Ecology. 2011;39(3):193-197.Besides the expected iridoid glucosides aucubin and catalpol as well as three known esters of the latter, Veronica beccabunga (brooklime) was shown to contain five carboxylated iridoid glucosides, namely gardoside, mussaenosidic acid, 8-epiloganic acid, arborescosidic acid and alpinoside. In addition to these compounds, the plant contained salidroside and a previously unknown caffeoyl phenylethanoid glycoside (CPG) which we have named chionoside J. The structure was elucidated mainly by 1D and 2D NMR spectroscopy to be 2 ''-(beta-glucopyranosyl)-plantamajoside. The distribution of plantamajoside and its derivatives as well as that of carbocyclic iridoids with an 8,9-double bond is briefly discussed, and it is noted that such compounds are mainly confined to the tribe Veroniceae of the Plantaginaceae. (C) 2011 Elsevier Ltd. All rights reserved

    Lipid-DNAs as Solubilizers of mTHPC

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    Hydrophobic drug candidates require innovative formulation agents. We designed and synthesized lipidDNA polymers containing varying numbers of hydrophobic alkyl chains. The hydrophobicity of these amphiphiles is easily tunable by introducing a defined number of alkyl chain-modified nucleotides during standard solid-phase synthesis of DNA using an automated DNA synthesizer. We observed that the resulting self-assembled micelles solubilize the poorly water-soluble drug, meta-tetra-hydroxyphenyl-chlorin (mTHPC) used in photodynamic therapy (PDT) with high loading concentrations and loading capacities. A cell viability study showed that mTHPCloaded micelles exhibit good biocompatibility without irradiation, and high PDT efficacy upon irradiation. LipidDNAs provide a novel class of drug-delivery vehicle, and hybridization of DNA offers a potentially facile route for further functionalization of the drug-delivery system with, for instance, targeting or imaging moieties
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