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On the Empirical Relevance of the Exchange Rate as a Shock Absorber at the Zero Lower Bound
No full textThe open economy New Keynesian model with flexible exchange rates postulates that the real exchange rate appreciates in response to an asymmetric negative demand shock in a zero lower bound (ZLB) scenario and exacerbates the adverse macroeconomic effects. However, when monetary policy is able to accommodate the adverse effects of the negative demand shock via unconventional measures, the model can generate a real depreciation at the ZLB. This paper examines these counteracting exchange rate channels empirically. We estimate the effect of a negative asymmetric demand shock on the real exchange rate and inflation expectations as well as output and prices by employing state-dependent and sign-restricted local projection methods for the euro area vis-à-vis the United States, Canada, and Japan. We find that the real exchange rate depreciates when interest rates are not at the ZLB but also when they are. Furthermore, our empirical results show that the real exchange rate can absorb considerable variations in output, confirming its shock-absorbing capacity before but also during the ZLB episode. The stabilizing role of the exchange rate is accompanied by a significant expansion of the ECBs balance sheet in the ZLB period, while it remained unaffected in the pre-ZLB period. Overall, our empirical results favor the open economy New Keynesian model with unconventional measures when interest rates are at the ZLB
The Great Moderation: Inventories, Shocks or Monetary Policy?
No full textoai:open.uni-marburg.de:10.17192/es.2024.0210This paper presents a New Keynesian DSGE model with inventory holding firms. The model distinguishes between goods and materials, for both production as well as for inventories. The more detailed treatment of inventory holdings offers new insights into the determinants of business cycles before and during the Great Moderation. Via Bayesian estimation we determine the distributions of the parameters for U.S. data for two subsamples. Our results show that impulse responses change significantly in terms of magnitude and persistence over time. Shocks in the labor market have gained importance since the Great Moderation and they explain the volatility of many variables. We reject the hypothesis of better inventory management and improved monetary policy as explanations for the Great Moderation. Instead, labor supply developments and changes in cost associated with capital play a key role for the reduced fluctuations
The potential of ecoregional range maps for boosting taxonomic coverage in ecology and conservation
No full textExpert range maps (ExpRMs) are frequently used to inform species distributions, but often incomplete or missing for many species, particularly among plants and invertebrates. Many species without ExpRMs also have too few occurrence records for reliable application of species distribution models (SDMs). Here we evaluate the performance of commonly used range surrogates and recommend tools that can help fill this significant knowledge gap across a wide range of understudied taxa. Specifically, we explore an alternative range surrogate (ecoregional range maps; EcoRMs), assess its performance versus traditional approaches for 624 North American butterfly species, and outline its use alone and as part of SDMs. As an alternative range estimate, we use terrestrial ecoregions that represent a regionalization of biogeographical zones and we suggest geographical filters and simplifications that improve their performance. We show that consistently across different spatial scales and both in comparison with ExpRMs and SDMs, EcoRMs have an exceptionally high sensitivity and generally a high mean performance. Particularly for species with fewer than 100 occurrence records, EcoRMs outperform other range surrogates. The congruence of species richness patterns was also similar for all approaches. The use of EcoRMs as substitute for data-poor species without ExpRMs will strongly boost taxonomic coverage of range maps. Additionally, integrating EcoRMs as domains/masks/offsets into SDMs promises significant improvements to model accuracy. For butterflies alone, EcoRMs would thereby provide new range information for 17% and improve basic range information for 43% of all approximately nineteen thousand species. Other technical advantages of generating EcoRMs may also help to overcome issues of the availability, updateability, reproducibility, and circularity of ExpRMs, SDMs and minimum convex hulls (MCVs). In summary, ecoregion-based range maps offer a versatile tool for ecology and conservation of terrestrial taxa and the application of the EcoRM approach may prove similarly useful for freshwater and marine ecoregions.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Impacts of Parental Health Shocks on Children’s Non-Cognitive Skills
No full textWe examine how parental health shocks affect children’s non-cognitive skills.
Based on a German mother-and-child data base, we draw on significant changes in selfreported parental health as an exogenous source of health variation to identify effects on outcomes for children at ages of three and six years. At the age of six, we observe that maternal health shocks in the previous three years have significant negative effects on children’s behavioral outcomes. The most serious of these maternal health shocks decrease the observed non-cognitive skills up to half a standard deviation. Paternal health does not robustly affect non-cognitive outcomes
Proglacial slopes are protected against erosion by trait diverse and dense plant communities associated with specific microbial communities
No full textAbstract:
Soil erosion is a severe threat for ecosystems and anthropogenic infrastructure. Glaciers are retreating rapidly due to global warming and the receding ice leaves unvegetated depositions of sediment, which are prone to mobilisation during precipitation events. Vegetation is known to serve as erosion protection, but how above- and belowground plant traits, vegetation cover and plant diversity on community level are jointly affecting erosion is unclear. Additionally, soil microbial communities may have effects on slope stability by promoting plant growth and function. We measured sediment transport on 30 plots of 2 × 3 m size on proglacial slopes of the Gepatschferner glacier (Kaunertal, Austria) over three years in a natural pristine high alpine environment. Vegetation cover, species abundances and relevant above- and belowground traits were measured for each occurring plant species on community level. Path model analysis revealed that dense and species-rich plant cover characterized by specific plant growth strategies and trait diversity was best suited to decrease erosion. Vegetation properties were also closely linked to the composition of soil microbial communities characterised by next generation amplicon sequencing, which may facilitate soil formation and further enhance the plants’ soil stabilising potential. Our study illustrates that erosion control may benefit from a high vegetation cover, which is facilitated by diverse plant communities with complementary morphological traits. These vegetation properties also affect soil microbiota, but their impact on slope protection in combination with the vegetation remains to be elucidated. Our findings may inform nature-based solutions against erosion such as revegetation of alpine slopes using specific seed mixtures.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Monitoring autochthonous lung tumors induced by somatic CRISPR gene editing in mice using a secreted luciferase
No full textBackground: In vivo gene editing of somatic cells with CRISPR nucleases has facilitated the generation of autochthonous
mouse tumors, which are initiated by genetic alterations relevant to the human disease and progress along
a natural timeline as in patients. However, the long and variable, orthotopic tumor growth in inner organs requires
sophisticated, time-consuming and resource-intensive imaging for longitudinal disease monitoring and impedes the
use of autochthonous tumor models for preclinical studies.
Methods: To facilitate a more widespread use, we have generated a reporter mouse that expresses a Cre-inducible
luciferase from Gaussia princeps (GLuc), which is secreted by cells in an energy-consuming process and can be
measured quantitatively in the blood as a marker for the viable tumor load. In addition, we have developed a flexible,
complementary toolkit to rapidly assemble recombinant adenoviruses (AVs) for delivering Cre recombinase together
with CRISPR nucleases targeting cancer driver genes.
Results: We demonstrate that intratracheal infection of GLuc reporter mice with CRISPR-AVs efficiently induces lung
tumors driven by mutations in the targeted cancer genes and simultaneously activates the GLuc transgene, resulting
in GLuc secretion into the blood by the growing tumor. GLuc blood levels are easily and robustly quantified in
small-volume blood samples with inexpensive equipment, enable tumor detection already several months before
the humane study endpoint and precisely mirror the kinetics of tumor development specified by the inducing gene
combination.
Conclusions: Our study establishes blood-based GLuc monitoring as an inexpensive, rapid, high-throughput and
animal-friendly method to longitudinally monitor autochthonous tumor growth in preclinical studies.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Development and synthesis of potential allosteric modulators of G-protein coupled receptors and potential inhibitors of the eukaryotic initiation factor 4A
No full textDie vorliegende Arbeit ist in drei Teile unterteilt. Der erste Teil bestand in der Synthese von potenziellen allosterischen Liganden, die einen der folgenden G-Protein gekoppelten Rezeptoren (GPCRs) adressieren sollten: Endothelin B- (ETBR), Freie Fettsäure 3-Rezeptor (FFAR3) oder den orphan-Rezeptor GPRC5B. GPCRs bilden mit über 800 Vertretern eine der größten Proteinfamilien. Sie bestehen aus sieben transmembranen Helices und koppeln an verschiedene G-Proteine. Weiterhin werden sie von einer Vielzahl verschiedener endogener Liganden adressiert und sind damit in zahlreiche physiologische Prozesse involviert, wodurch sie in verschiedenen Krankheitsbildern relevant sind. Mehr als 30% aller zugelassenen Arzneistoffe adressieren GPCRs. Die Entwicklung selektiver Liganden ist jedoch herausfordernd, da die orthosterische Bindestelle innerhalb einer Rezeptorfamilie hoch konserviert ist. Die Identifikation und Adressierung von alternativen und weniger konservierten Bindetaschen mithilfe von allosterischen Modulatoren könnte stattdessen hoch selektive Liganden liefern, die weniger unerwünschte Nebenwirkungen hervorrufen. Im Rahmen des GLUE-Projekts (G-Protein coupled receptor ligands for underexplored epitopes) identifizierte die Arbeitsgruppe von Prof. Kolb potenzielle Liganden mithilfe von in silico Docking. Basierend auf den Dockingposen und der synthetischen Zugänglichkeit der Liganden wurden die vielversprechendsten Moleküle für die Synthese ausgewählt. Insgesamt wurden im Zuge dieser Arbeit 110 Verbindungen basierend auf 10 verschiedenen Grundstrukturen synthetisiert, die aus vier Dockingstudien der AG Kolb und einem eigenen de novo-Ansatz hervorgegangen sind. 86 dieser Verbindungen sollten dabei die G-Protein Bindetasche und 7 weitere die Known Site 5 des ETBR adressieren. Außerdem wurden zwei bereits bekannte allosterische Modulatoren mit je einem Derivat synthetisiert. Alle synthetisierten Verbindungen wurden anschließend in der Arbeitsgruppe von Prof. Bünemann in FRET-basierten Assays bei einer initialen Konzentration von 100 µM am ETBR und FFAR3 getestet. Dabei zeigte keine der getesteten Verbindungen eine biologische Aktivität. Die letzten 13 synthetisierten Verbindungen sollten den orphan-Rezeptor GPRC5B adressieren. Die biologische Testung dieser Verbindung steht jedoch noch aus, da bisher kein geeigneter Assay zur Testung etabliert werden konnte.
Der zweite Teil dieser Arbeit bestand in der Entwicklung und Synthese potenzieller Inhibitoren des eukaryotischen Initiationsfaktors 4A (eIF4A). Die RNA-Helikase eIF4A ist an der Translationsinitiation beteiligt. Sie übernimmt die Entwindung von Sekundärstrukturen, die sich innerhalb der 5‘-UTR der mRNA befinden, und ermöglicht so die Protein Biosynthese. In Ermangelung eines eigenen Stoffwechsel-Apparats sind Viren zur Protein Biosynthese auf ihren Wirt angewiesen, was eIF4A zu einem geeigneten Target für potenzielle host-targeting antivirals macht. Basierend auf einem Benzoxazol-Fragment, das von H. Kutzner (AG Schlitzer) entwickelt wurde, war das Ziel dieser Arbeit Arginin-Seitenketten in der Bindetasche mithilfe von polaren Gruppen zu adressieren. Dazu wurden 27 verschiedene Benzoxazol-Derivate mit einem modifizierten Grundgerüst oder einem zusätzlichen polaren Rest synthetisiert. Alle Verbindungen wurden in der Arbeitsgruppe von Prof. Grünweller in einem Thermal Shift Assay untersucht. Die vielversprechendste Verbindung, die eine polare Gruppe aufwies, sollte weiterhin in einem Dual Luciferase Assay untersucht werden, um deren Einfluss auf die Translationseffizienz zu untersuchen. Aufgrund einer bakteriellen Kontamination konnte diese Testung allerdings nicht durchgeführt werden.
Der dritte Teil dieser Arbeit beschäftigte sich mit der Synthese von Piperazin-haltigen Anthranilsäureamiden als potenzielle Anthelminthika gegen Schistosoma mansoni. Im Rahmen dieser Arbeit sollte deren anthelminthische Wirkung gegen Schistosoma mansoni untersucht werden. Schistosomiasis ist eine parasitäre Erkrankung, die von Saugwürmern der Gattung Schistosoma hervorgerufen wird. Die Erkrankung ist in 78 Ländern in tropischen und subtropischen Gebieten endemisch und mindestens 230 Millionen Menschen sind jährlich auf eine präventive Behandlung angewiesen. Zur Behandlung wird hauptsächlich auf Praziquantel zurückgegriffen, sodass neue antischistosomale Wirkstoffe benötigt werden. Die Anthranilsäureamid-Derivate wurden ursprünglich von S. Heinrich (AG Schlitzer) gegen P. falciparum entwickelt. Neben zwei Verbindungen von S. Heinrich wurden vier weitere Derivate entwickelt und synthetisiert. Die Verbindungen wurden in Kooperation mit der Arbeitsgruppe von Prof. Grevelding von Dr. T. Gallinger (AG Schlitzer) bei einer Konzentration von 25 µM gegen S. mansoni getestet. Lediglich die zwei ursprünglichen Verbindungen zeigten dabei eine antischistosomale Aktivität. Allerdings waren sie bei diesen Konzentrationen zytotoxisch, sodass von einer weiteren Entwicklung abgesehen wurde.This work is divided into three different parts. In the first part of this thesis potential allosteric ligands were synthesized to address one of the following G-protein coupled receptors (GPCRs): Endothelin B-, free fatty acid 3-receptor or the orphan receptor GPRC5B. GPCRs represent one of the largest protein families with more than 800 members. Consisting of a seven transmembrane domain they couple to different Gα-proteins on their intracellular side. Furthermore, they are targeted by a variety of different endogenous ligands and therefore are involved in various physiological processes, making them an interesting drug target for several diseases. More than 30 percent of the approved drugs target GPCRs. However, the development of selective ligands is challenging due to their highly conserved orthosteric binding side within a receptor family. Hence, identification as well as targeting alternative and less conserved binding pockets with allosteric modulators could provide selective ligands causing less undesired side effects. As part of the GLUE-project (G-protein coupled receptor ligands for underexplored epitopes) the group of Prof. Kolb identified promising ligands with in silico docking methods. Based on the evaluation of the docking poses and the synthetic accessibility the most promising molecules were selected for synthesis. Overall, 110 compounds were synthesized based on 10 different base structures out of four docking studies performed by the group of Prof. Kolb and an own de novo approach. 86 of these compounds should target the G-protein binding pocket of ETBR, while 7 compounds should address the known site 5 (KS5). Additionally, two already known allosteric modulators and two derivatives were synthesized. All synthesized derivatives were analytically characterized and tested afterwards in the group of Prof. Bünemann. Using FRET-based methods the compounds were tested in a G-protein binding and a receptor sensor assay at an initial concentration of 100 μM on the ETBR and the FFAR3. None of the tested compounds has shown a biological activity in the performed assays. The last 13 compounds were synthesized to address the orphan receptor GPRC5B. Due to the lack of a suitable assay these 13 compounds were not tested for their biological activity so far.
In the second part of this thesis the focus was to design and synthesize potential inhibitors for the eucaryotic initiation factor 4A (eIF4A). The RNA-helicase eIF4A is involved in the initiation process of the translation by unwinding secondary structures within the 5’-UTR of a mRNA and therefore enabling protein synthesis. Due to their lack of an own mechanism for protein synthesis viruses are dependent on the mechanism of their host, making eIF4A a suitable target for potential host-targeting antivirals. Based on a benzoxazole-fragment designed by H. Kutzner (group of Prof. Schlitzer) the aim of this work was to address arginine-residues in the binding pocket by adding polar groups. Therefore 27 different benzoxazole-derivatives with a modified base structure or an additional polar residue were synthesized. All compounds were then tested in the group of Prof. Grünweller in a thermal shift assay. All synthesized compounds had shown a positive thermal shift suggesting the binding to eIF4A. The most promising compound containing a polar residue was selected to be tested in a Dual Luciferase assay to determine the potential of reducing the translation efficiency. Unfortunately, this assay could not be performed due to a bacterial contamination of the selected compound.
In the third part of this work derivatives of a piperazine-containing anthranilic amide originally designed by S. Heinrich (group of Prof. Schlitzer) were synthesized as potential anthelmintics against Schistosoma mansoni. Schistosomiasis is a parasitic disease which is caused by blood flukes of the genus Schistosoma. It is endemic in 78 countries in tropical and subtropical regions and at least 230 million people need preventive treatment annually. The treatment relies mainly on praziquantel, so new antischistosomal drugs are required. The original piperazine-containing compounds designed by S. Heinrich were developed for Plasmodium falciparum and were tested for their antischistosomal potential as part of this work. Besides the synthesis of two compounds from S. Heinrich additional four derivatives were designed and synthesized. The compounds were tested in collaboration with the group of Prof. Grevelding by Dr. T. Gallinger (group of Prof. Schlitzer) against S. mansoni at 25 μM. Only the two original compounds had shown antischistosomal activity but were also cytotoxic at these concentrations, so a further development was not taken into consideration
Policy preferences for inheritance taxation
No full textWe provide a comprehensive empirical study on the factors that drive citizens’ policy preferences regarding inheritance taxation. It builds on a representative survey among more than 1.000 German citizens in 2014 and 2015. Support for inheritance taxation is found to be driven by monetary self-interest and redistributive preferences. It is lower among females and among subjects who overestimate the tax burden. We look beyond the narrow scope of inheritances and account for other forms of transfers in the family, in particular the provision of longterm care. More than 75 percent of our respondents consider it fair that family members who provided long-term care receive higher inheritances in exchange. This fairness preference does not drive policy preferences, but acceptance for inheritance taxation is higher among subjects who expect the typical German family to reward intrafamilial care-giving through a higher inheritance
Time-Varying Network Models for the Temporal Dynamics of Depressive Symptomatology in Patients With Depressive Disorders: Secondary Analysis of Longitudinal Observational Data
No full textBackground: As depression is highly heterogenous, an increasing number of studies investigate person-specific associations
of depressive symptoms in longitudinal data. However, most studies in this area of research conceptualize symptom interrelations
to be static and time invariant, which may lead to important temporal features of the disorder being missed.
Objective: To reveal the dynamic nature of depression, we aimed to use a recently developed technique to investigate whether
and how associations among depressive symptoms change over time.
Methods: Using daily data (mean length 274, SD 82 d) of 20 participants with depression, we modeled idiographic associations
among depressive symptoms, rumination, sleep, and quantity and quality of social contacts as dynamic networks using time-varying
vector autoregressive models.
Results: The resulting models showed marked interindividual and intraindividual differences. For some participants, associations
among variables changed in the span of some weeks, whereas they stayed stable over months for others. Our results further
indicated nonstationarity in all participants.
Conclusions: Idiographic symptom networks can provide insights into the temporal course of mental disorders and open new
avenues of research for the study of the development and stability of psychopathological processes.Gefördert durch den Open-Access-Publikationsfonds der UB Marburg
Monetary Policy Uncertainty and the Response of the Yield Curve to Policy Shocks
No full textThis paper studies the non-linear response of the term structure of interest
rates to monetary policy shocks. We show that uncertainty about monetary
policy changes the way the term structure responds to monetary policy. A
policy tightening leads to a significantly smaller increase in long-term bond
yields if policy uncertainty is high at the time of the shock. We also look at
the decomposition of bond yields into expectations about policy and the term
premium. The weaker response of yields is driven by the fall in term premia,
which fall even more if uncertainty about policy is high. These �ndings are
robust to the measurement of monetary policy uncertainty and the definition
of the monetary policy shock. We argue that short-term uncertainty about
monetary policy tends to make yields of longer maturities relatively more
attractive. As a consequence, investors demand lower term premia. This
intuition is supported by the fact that long-term monetary policy uncertainty
leads to opposite effects with term premia increasing even more after a policy
shock