National economic policy simulations with global interdependencies : a sensitivity analysis for Germany

"Policy simulations for national economies with econometric models in general are done using a stand alone national model with exogenous export values and import prices. In a globalised world such an exercise is critical, since the policy in question may change the export prices and the import volumes of the particular country and induce via international trade a change of the economic activities of the global economy and a feed back to the export values and import prices of the particular country. The paper at hand presents a sensitivity analysis for Germany comparing the impacts of a shock on investment in a stand alone simulation using the multisector model INFORGE with the results, which occur, if the same model is linked to the global multicountry/multisector model GINFORS endogenising Germany's export values and import prices. The results are striking: The effect on real GDP is 50% higher in the global simulation than in the stand alone case. Because of the specialisation in trade the differences on the sector level are even stronger." (Author's abstract, IAB-Doku) ((en))Wirtschaftspolitik, Globalisierung - Auswirkungen, Export, Preisniveau, Importquote, Exportquote, Welthandel, Ökonometrie - Modell, Bruttoinlandsprodukt, volkswirtschaftliche Gesamtrechnung, Außenhandelspolitik, Außenhandelsentwicklung

National economic policy simulations with global interdependencies: a sensitivity analysis for Germany

"Policy simulations for national economies with econometric models in general are done using a stand alone national model with exogenous export values and import prices. In a globalised world such an exercise is critical, since the policy in question may change the export prices and the import volumes of the particular country and induce via international trade a change of the economic activities of the global economy and a feed back to the export values and import prices of the particular country. The paper at hand presents a sensitivity analysis for Germany comparing the impacts of a shock on investment in a stand alone simulation using the multisector model INFORGE with the results, which occur, if the same model is linked to the global multicountry/multisector model GINFORS endogenising Germany's export values and import prices. The results are striking: The effect on real GDP is 50Prozent higher in the global simulation than in the stand alone case. Because of the specialisation in trade the differences on the sector level are even stronger." (author's abstract)Nationale wirtschaftspolitische Simulationen mit Hilfe ökonometrischer Modelle bedienen sich im allgemeinen eines autonomen nationalen Modells mit exogenen Exportwerten und Importpreisen. In einer globalen Welt ist eine solche Praxis kritisch, weil die zu untersuchende Politik die Exportpreise und die Importvolumina des betreffenden Landes verändern und weiter über den internationalen Handel eine Veränderung der wirtschaftlichen Aktivitäten der globalen Ökonomie auslösen kann. Dies wiederum hat Rückwirkungen auf die Exportwerte und die Importpreise des betreffenden Landes. Der Beitrag präsentiert die Ergebnisse einer Sensitivitätsanalyse für Deutschland und vergleicht die Auswirkungen eines Investitionsschocks in einer autonomen Simulation mit Hilfe des Mehrsektorenmodells INFORGE mit den Ergebnissen, die man erhält, wenn das gleiche Modell mit dem globalen Mehrländer-/Mehrsektorenmodell GINFORS verlinkt und so die deutschen Exportwerte und Importpreise endogenisiert. Die Ergebnisse sind bemerkenswert: Die Auswirkung auf das reale BIP (Bruttoinlandsprodukt) ist in der globalen Simulation um 50 Prozent höher als in der autonom nationalen. Wegen der Spezialisierung des Handels sind die Unterschiede auf diesem Sektor sogar noch stärker. (IAB

Predicting the Response to Intravenous Immunoglobulins in an Animal Model of Chronic Neuritis

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a disabling autoimmune disorder of the peripheral nervous system (PNS). Intravenous immunoglobulins (IVIg) are effective in CIDP, but the treatment response varies greatly between individual patients. Understanding this interindividual variability and predicting the response to IVIg constitute major clinical challenges in CIDP. We previously established intercellular adhesion molecule (ICAM)-1 deficient non-obese diabetic (NOD) mice as a novel animal model of CIDP. Here, we demonstrate that similar to human CIDP patients, ICAM-1 deficient NOD mice respond to IVIg treatment by clinical and histological measures. Nerve magnetic resonance imaging and histology demonstrated that IVIg ameliorates abnormalities preferentially in distal parts of the sciatic nerve branches. The IVIg treatment response also featured great heterogeneity allowing us to identify IVIg responders and non- responders. An increased production of interleukin (IL)-17 positively predicted IVIg treatment responses. In human sural nerve biopsy sections, high numbers of IL-17 producing cells were associated with younger age and shorter disease duration. Thus, our novel animal model can be utilized to identify prognostic markers of treatment responses in chronic inflammatory neuropathies and we identify IL-17 production as one potential such prognostic marker

Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling

Background: The lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are pleiotropic signaling molecules with a broad range of physiological functions. Targeting the S1P1 receptor on lymphocytes with the immunomodulatory drug fingolimod has proven effective in the treatment of multiple sclerosis. An emerging body of experimental evidence points to additional direct effects on cells of the central and peripheral nervous system. Furthermore, fingolimod has been reported to reduce LPA synthesis via inhibition of the lysophospholipase autotaxin. Here we investigated whether modulation of particular signaling aspects of S1P as well as LPA by fingolimod might propagate peripheral nerve regeneration in vivo and independent of its anti-inflammatory potency. Methods: Sciatic nerve crush was performed in wildtype C57BL/6, in immunodeficient Rag1−/− and Foxn1−/− mice. Analyses were based on walking track analysis and electrophysiology, histology, and cAMP formation. Quantification of different LPA species was performed by liquid chromatography coupled to tandem mass spectrometry. Furthermore, functional consequences of autotaxin inhibition by the specific inhibitor PF-8380 and the impact of fingolimod on early cytokine release in the injured sciatic nerve were investigated. Results: Clinical and electrophysiological measures indicated an improvement of nerve regeneration under fingolimod treatment that is partly independent of its anti-inflammatory properties. Fingolimod treatment correlated with a significant elevation of axonal cAMP, a crucial factor for axonal outgrowth. Additionally, fingolimod significantly reduced LPA levels in the injured nerve. PF-8380 treatment correlated with improved myelin thickness. Sciatic nerve cytokine levels were not found to be significantly altered by fingolimod treatment. Conclusions: Our findings provide in vivo evidence for direct effects of fingolimod on cells of the peripheral nervous system that may propagate nerve regeneration via a dual mode of action, differentially affecting axonal outgrowth and myelination by modulating relevant aspects of S1P and LPA signaling

Quinpramine Ameliorates Rat Experimental Autoimmune Neuritis and Redistributes MHC Class II Molecules

Activation of inflammatory cells is central to the pathogenesis of autoimmune demyelinating diseases of the peripheral nervous system. The novel chimeric compound quinpramine—generated from imipramine and quinacrine—redistributes cholesterol rich membrane domains to intracellular compartments. We studied the immunological and clinical effects of quinpramine in myelin homogenate induced Lewis rat experimental autoimmune neuritis (EAN), a model system for acute human inflammatory neuropathies, such as the Guillain-Barré syndrome. EAN animals develop paresis of all limbs due to autoimmune inflammation of peripheral nerves. Quinpramine treatment ameliorated clinical disease severity of EAN and infiltration of macrophages into peripheral nerves. It reduced expression of MHC class II molecules on antigen presenting cells and antigen specific T cell proliferation both in vitro and in vivo. Quinpramine exerted its anti-proliferatory effect on antigen presenting cells, but not on responder T cells. Our data suggest that quinpramine represents a candidate pharmaceutical for inflammatory neuropathies

Mutational Analysis of the SOX9 Gene in Campomelic Dysplasia and Autosomal Sex Reversal: Lack of Genotype/Phenotype Correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformation

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations