Monetary and fiscal policy aspects of indirect tax changes in a monetary union

In recent years a number of European countries have shifted their tax structure more strongly towards indirect taxes, motivated, inter alia, by the intention to foster competitiveness. Against this background, this paper develops a tractable two-country model of a monetary union, characterised by national fiscal and supranational monetary policy, with price-setting firms and endogenously determined terms of trade. The paper discusses a number of monetary and fiscal policy questions which emerge if one of the countries shifts its tax structure more strongly towards indirect taxes. Qualitatively, it is shown that the long-run effects of such a unilateral policy shift on output and consumption within and between the two countries depend sensitively on whether indirect tax revenues are used to lower direct taxes or to finance additional government expenditures. Moreover, short-run dynamics are shown to depend significantly on the speed at which fiscal adjustments take place, on the choice of the inflation index stabilised by the central bank, and on whether the tax shift is anticipated or not. Quantitatively, the calibrated model version indicates that only if the additional indirect tax revenues are used to finance a cut in direct taxes there is some, though limited scope for non-negligible spillovers between countries. JEL Classification: E61, E63, F42Currency union, fiscal regimes, monetary policy

Monetary and fiscal policy aspects of indirect tax changes in a monetary union

In recent years a number of European countries have shifted their tax structure more strongly towards indirect taxes, motivated, inter alia, by the intention to foster competitiveness. Against this background, this paper develops a tractable two-country model of a monetary union, characterised by national fiscal and supranational monetary policy, with price-setting firms and endogenously determined terms of trade. The paper discusses a number of monetary and fiscal policy questions which emerge if one of the countries shifts its tax structure more strongly towards indirect taxes. Qualitatively, it is shown that the long-run effects of such a unilateral policy shift on output and consumption within and between the two countries depend sensitively on whether indirect tax revenues are used to lower direct taxes or to finance additional government expenditures. Moreover, short-run dynamics are shown to depend significantly on the speed at which fiscal adjustments take place, on the choice of the inflation index stabilised by the central bank, and on whether the tax shift is anticipated or not. Quantitatively, the calibrated model version indicates that only if the additional indirect tax revenues are used to finance a cut in direct taxes there is some, though limited scope for non-negligible spillovers between countries

Light control of RTK activity : from technology development to translational research

Inhibition of receptor tyrosine kinases (RTKs) by small molecule inhibitors and monoclonal antibodies is used to treat cancer. Conversely, activation of RTKs with their ligands, including growth factors and insulin, is used to treat diabetes and neurodegeneration. However, conventional therapies that rely on injection of RTK inhibitors or activators do not provide spatiotemporal control over RTK signaling, which results in diminished efficiency and side effects. Recently, a number of optogenetic and optochemical approaches have been developed that allow RTK inhibition or activation in cells andin vivowith light. Light irradiation can control RTK signaling non-invasively, in a dosed manner, with high spatio-temporal precision, and without the side effects of conventional treatments. Here we provide an update on the current state of the art of optogenetic and optochemical RTK technologies and the prospects of their use in translational studies and therapy.Peer reviewe

Learning from scientific texts: personalizing the text increases transfer performance and task involvement

In an experiment with 65 high-school students, we tested the hypothesis that personalizing learning materials would increase students’ learning performance and motivation to study the learning materials. Students studied either a 915-word standard text on the anatomy and functionality of the human eye or a personalized version of the same text in which 60 definite articles (e.g., “the eye”) were replaced with 60 second-person possessive pronouns (e.g., “your eye”). Afterwards, participants answered comprehension and transfer questions. One week later, the participants were asked to restudy the text and to answer the same questions again with the aim to improve their performance. In the personalized text condition, students showed higher transfer performance, spent more time on restudying the text, and reported being more motivated than students in the standard text condition. However, only duration of restudying (not self-reported motivation) mediated the effect of personalization on transfer performance

Bacterial Phytochrome as a Scaffold for Engineering of Receptor Tyrosine Kinases Controlled with Near-Infrared Light

Optically controlled receptor tyrosine kinases (opto-RTKs) allow regulation of RTK signaling using light. Until recently, the majority of opto-RTKs were activated with blue-green light. Fusing a photosensory core module of Deinococcus radiodurans bacterial phytochrome (DrBphP-PCM) to the kinase domains of neurotrophin receptors resulted in opto-RTKs controlled with light above 650 nm. To expand this engineering approach to RTKs of other families, here we combined the DrBpP-PCM with the cytoplasmic domains of EGFR and FGFR1. The resultant Dr-EGFR and Dr-FGFR1 opto-RTKs are rapidly activated with near-infrared and inactivated with far-red light. The opto-RTKs efficiently trigger ERK1/2, PI3K/Akt, and PLC gamma signaling. Absence of spectral crosstalk between the opto-RTKs and green fluorescent protein-based biosensors enables simultaneous Dr-FGFR1 activation and detection of calcium transients. Action mechanism of the DrBphP-PCM-based opto-RTKs is considered using the available RTK structures. DrBphP-PCM represents a versatile scaffold for engineering of opto-RTKs that are reversibly regulated with far-red and near-infrared light. (C) 2020 Elsevier Ltd. All rights reserved.Peer reviewe

Mechanismen der neuroprotektiven Wirkung von Norrin

Norrin ist ein sekretiertes, aus 133 Aminosäuren-bestehendes Signalprotein, welches durch Bindung an den Fzd4-Rezeptor den klassischen Wnt/β-Catenin-Signalweg aktivieren kann. Neben angiogenen Funktionen konnte auch eine neuroprotektive Wirkung von Norrin auf Nervenzellen der Netzhaut nachgewiesen werden. So wiesen zusätzlich mit Norrin behandelte Retinae nach exzitatorischer Schädigung mit NMDA eine geringere Anzahl apoptotischer Ganglienzellen auf als vergleichbare Kontrollen. In diesem Zusammenhang konnte auch eine erhöhte Expression verschiedener neuroprotektiver Faktoren beobachtet werden, aufgrunddessen ein möglicher Wirkmechanismus von Norrin postuliert wurde. Dabei führt die Norrin-induzierte Aktivierung des Wnt/β-Catenin-Signalwegs in Müllerzellen zu einer vermehrten Sekretion von LIF und über einer Steigerung der Edn2-Expression letztlich zu einer Ausschüttung neurotropher Faktoren. Ziel dieser Arbeit war es, den Mechanismus der Norrin-vermittelten Neuroprotektion anhand von LIF-defizienten Mäusen im akuten Schadensmodell der NMDA-vermittelten exzitatorischen Schädigung retinaler Ganglienzellen genauer zu analysieren. Zusätzlich sollten die Auswirkungen von Norrin auf chronisch degenerierende Ganglienzellen und die damit verbundenen Wirkmechanismen anhand eines Glaukommodells untersucht werden. Hierfür erfolgte die Analyse transgener DBA/2J-Mäuse, welche eine Überexpression von Norrin in den Neuronen der inneren Netzhaut aufweisen. Durch TUNEL-Analysen konnte gezeigt werden, dass der neuroprotektive Effekt von Norrin in Lif⁺/⁻- und Lif⁻/⁻-Mäusen nach Injektion von NMDA und Norrin vollständig unterdrückt ist. Auch war die Expression von Gfap, Edn2 und Fgf2 in diesen Tieren stark vermindert, was auf eine LIF-abhängige Induktion der Faktoren schließen lässt. Gegenüber der vorangegangen Untersuchungen an Albinomäusen konnte jedoch auch in wildtypischen C57Bl/6-Tieren eine verminderte Expression dieser Faktoren beobachtet werden, wobei die ermittelten Fgf2 mRNA-Spiegel hier über denjenigen von Edn2 lagen. Auch hatte die Expression von Gfap keine detektierbare Gliosereaktion der Müllerzellen zur Folge. Die LIF-vermittelte Expression von Edn2 und Fgf2 scheint somit einen zusätzlichen Mechanismus darzustellen, der in den untersuchten C57Bl/6-Mäusen eine untergeordnete Rolle spielt. Über welchen Signalweg LIF die neuroprotektive Wirkung von Norrin in diesen Tieren weitervermittelt, müssen zukünftige Untersuchungen zeigen. Durch Analyse der transgenen Pax6-Norrin-Mäuse konnte gezeigt werden, dass Norrin auch auf chronisch degenerierende Ganglienzellen eine protektive Wirkung ausübt. So wiesen Norrin-überexprimierende DBA/2J-Mäuse im Vergleich zu ihren wildtypischen Geschwistertieren weniger schwer ausgeprägte Vorderkammer-Pathologien, einen niedrigeren Augeninnendruck und eine höhere Anzahl von Axonen im Sehnerv auf. Histologische Färbungen zeigten eine verminderte Anzahl immunreaktiver Makrophagen im Trabekelwerk transgener Tiere, was auf einen immunregulatorischen Einfluss von Norrin hindeutet. Zusätzlich konnte in diesen Tieren eine erhöhte Expression von Igf1 und eine verstärkte Phosphorylierungsrate von AKT beobachtet werden. Im Glaukommodell der DBA/2J-Mäuse scheint Norrin seinen protektiven Effekt auf Ganglienzellen demnach über eine Kombination aus vermindertem intraokulären Druck, schwächer ausgeprägter Immunantwort im Trabekelwerk und Aktivierung des protektiv wirksamen PI3K/AKT-Signalwegs zu vermitteln. Insgesamt konnte durch die Ergebnisse dieser Doktorarbeit gezeigt werden, dass Norrin sowohl auf akut als auch auf chronisch geschädigte retinale Ganglienzellen eine neuroprotektive Wirkung ausübt, wobei unterschiedliche Signalwege genutzt werden

Idiopatyczna czuciowa neuropatia trójdzielna. Opis przypadku

Idiopathic trigeminal sensory neuropathy is a rare clinical condition characterized by sensory disturbances on the face. Its symptoms may be permanent or temporary and a wide variety of diagnostic procedures is usually required to establish the diagnosis. Frequently, it is the first manifestation of a systemic disorder. In the majority of cases causal treatment is not possible, even though patients with trigeminal sensory neuropathy should be carefully monitored by physicians.Idiopatyczna czuciowa neuropatia trójdzielna to rzadka choroba dotycząca zaburzeń czucia w obrębie twarzy. Zjawisko to może mieć charakter przejściowy lub stały, diagnostyka zaś wymaga zazwyczaj wykonania wielu różnych badań. Często neuropatia trójdzielna jest pierwszym objawem choroby układowej. Najczęściej leczenie przyczynowe nie jest możliwe, jednak pacjenci z idiopatyczną neuropatią trójdzielną powinni być pod stałą opieką medyczną

Neurotrophin receptor tyrosine kinases regulated with near-infrared light

Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools.Peer reviewe

Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy

Aims: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). Methods The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA;2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. Results In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. Conclusions: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye