Collective exchange processes reveal an active site proton cage in bacteriorhodopsin

Proton translocation across membranes is vital to all kingdoms of life. Mechanistically, it relies on characteristic proton flows and modifications of hydrogen bonding patterns, termed protonation dynamics, which can be directly observed by fast magic angle spinning (MAS) NMR. Here, we demonstrate that reversible proton displacement in the active site of bacteriorhodopsin already takes place in its equilibrated dark-state, providing new information on the underlying hydrogen exchange processes. In particular, MAS NMR reveals proton exchange at D85 and the retinal Schiff base, suggesting a tautomeric equilibrium and thus partial ionization of D85. We provide evidence for a proton cage and detect a preformed proton path between D85 and the proton shuttle R82. The protons at D96 and D85 exchange with water, in line with ab initio molecular dynamics simulations. We propose that retinal isomerization makes the observed proton exchange processes irreversible and delivers a proton towards the extracellular release site

Error Resilient Quantum Amplitude Estimation from Parallel Quantum Phase Estimation

We show how phase and amplitude estimation algorithms can be parallelized. This can reduce the gate depth of the quantum circuits to that of a single Grover operator with a small overhead. Further, we show that for quantum amplitude estimation, the parallelization can lead to vast improvements in resilience against quantum errors. The resilience is not caused by the lower gate depth, but by the structure of the algorithm. Even in cases with errors that make it impossible to read out the exact or approximate solutions from conventional amplitude estimation, our parallel approach provided the correct solution with high probability. The results on error resilience hold for the standard version and for low depth versions of quantum amplitude estimation. Methods presented are subject of a patent application [Quantum computing device: Patent application EP 21207022.1]

The effect of alcohol on cervical and ocular vestibular evoked myogenic potentials in healthy volunteers

OBJECTIVE: We investigated the effect of alcohol on the cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs). As alcohol produces gaze-evoked nystagmus (GEN), we also tested the effect of nystagmus independent of alcohol by recording oVEMPs during optokinetic stimulation (OKS). METHODS: The effect of alcohol was tested in 14 subjects over multiple rounds of alcohol consumption up to a maximum breath alcohol concentration (BrAC) of 1.5‰ (mean 0.97‰). The effect of OKS was tested in 11 subjects at 5, 10 and 15deg/sec. RESULTS: oVEMP amplitude decreased from baseline to the highest BrAC level by 27% (range 5-50%, P<0.001), but there was no significant effect on oVEMP latency or cVEMP amplitude or latency. There was a significant negative effect of OKS on oVEMP amplitude (16%, P=0.006). CONCLUSIONS: We found a selective effect of alcohol on oVEMP amplitude, but no effect on the cVEMP. Vertical nystagmus elicited by OKS reduced oVEMP amplitude. SIGNIFICANCE: Alcohol selectively affects oVEMP amplitude. Despite the effects of alcohol and nystagmus, both reflexes were reliably recorded in all subjects and conditions. An absent response in a patient affected by alcohol or nystagmus indicates a vestibular deficit

Quantum amplitude estimation with error mitigation for time-evolving probabilistic networks

We present a method to model a discretized time evolution of probabilistic networks on gate-based quantum computers. We consider networks of nodes, where each node can be in one of two states: good or failed. In each time step, probabilities are assigned for each node to fail (switch from good to failed) or to recover (switch from failed to good). Furthermore, probabilities are assigned for failing nodes to trigger the failure of other, good nodes. Our method can evaluate arbitrary network topologies for any number of time steps. We can therefore model events such as cascaded failure and avalanche effects which are inherent to financial networks, payment and supply chain networks, power grids, telecommunication networks and others. Using quantum amplitude estimation techniques, we are able to estimate the probability of any configuration for any set of nodes over time. This allows us, for example, to determine the probability of the first node to be in the good state after the last time step, without the necessity to track intermediate states. We present the results of a low-depth quantum amplitude estimation on a simulator with a realistic noise model. We also present the results for running this example on the AQT quantum computer system PINE. Finally, we introduce an error model that allows us to improve the results from the simulator and from the experiments on the PINE system

'Brain Circulation' – Diaspora als treibende Kraft bei der Entwicklung der Herkunftsländer:Seminar "Brain Drain und Brain Gain. Migration und Entwicklung"

Seit Beginn des 21. Jahrhunderts hat die Diskussion über den Zusammenhang von Migration und Entwicklung eine neue Richtung bekommen. Wurde die Emigration von Hochqualifizierten aus Entwicklungsländern bislang zumeist als ein abgeschlossener Prozess gesehen, der für die Abgabeländer in einem Humankapitalverlust (brain drain) und für die Aufnahmeländer (meistenteils Industrieländer) in einem Humankapitalgewinn (brain gain) resultiert, so wird Elitenmigration heute mehr und mehr als ein zirkulärer Prozess der Hin- und Her- bzw. Weiterwanderung angesehen (brain circulation), von dem nicht nur Industrieländer, sondern potentiell auch Entwicklungsländer profitieren können. Alle hier veröffentlichten Arbeiten des Politikwissenschaftsseminars "Brain Drain und Brain Gain. Migration und Entwicklung" unter Leitung von Prof. Thränhardt und Dr. Uwe Hunger aus dem Sommersemester 2005 stellen originäre und eigenständige Forschungsarbeiten dar und tragen durch ihre sorgfältige Recherche dazu bei, weitere neue, wichtige Erkenntnisse für diese immer noch junge Forschungsrichtung zusammenzutragen. Die eigenständigen Arbeiten der Studierenden behandeln ein Thema, das sich in der Forschung gerade durchzusetzen beginnt und Lösungsansätze für die Probleme einer globalisierten und zusammenwachsenden Welt öffnet

Ethanol consumption impairs vestibulo-ocular reflex function measured by the video head impulse test and dynamic visual acuity

Ethanol affects many parts of the nervous system, from the periphery to higher cognitive functions. Due to the established effects of ethanol on vestibular and oculomotor function, we wished to examine its effect on two new tests of the vestibulo-ocular reflex (VOR): the video head impulse test (vHIT) and dynamic visual acuity (DVA). We tested eight healthy subjects with no history of vestibular disease after consumption of standardized drinks of 40% ethanol. We used a repeated measures design to track vestibular function over multiple rounds of ethanol consumption up to a maximum breath alcohol concentration (BrAC) of 1.38‰. All tests were normal at baseline. VOR gain measured by vHIT decreased 25% by the highest BrAC level tested in each subject. Catch-up saccades were negligible at baseline and increased in number and size with increasing ethanol consumption (from 0.13° to 1.43° cumulative amplitude per trial). DVA scores increased by 86% indicating a deterioration of acuity, while static visual acuity (SVA) remained unchanged. Ethanol consumption systematically impaired the VOR evoked by high-acceleration head impulses and led to a functional loss of visual acuity during head movement.NHMR

No downregulation of immune function during breeding in two year-round breeding bird species in an equatorial East African environment

Some equatorial environments exhibit substantial within-location variation in environmental conditions throughout the year and yet have year-round breeding birds. This implies that breeding in such systems are potentially unrelated to the variable environmental conditions. By breeding not being influenced by environmental conditions, we become sure that any differences in immune function between breeding and non-breeding birds do not result from environmental variation, therefore allowing for exclusion of the confounding effect of variation in environmental conditions. This create a unique opportunity to test if immune function is down-regulated during reproduction compared to non-breeding periods. We compared the immune function of sympatric male and female chick-feeding and non-breeding red-capped Calandrella cinerea and rufous-naped larks Mirafra africana in equatorial East Africa. These closely-related species occupy different niches and have different breeding strategies in the same grassland habitat. Red-capped larks prefer areas with short grass or almost bare ground, and breed during low rainfall periods. Rufous-naped larks prefer areas of tall grass and scattered shrubs and breed during high rainfall. We measured the following immune indices: nitric oxide, haptoglobin, agglutination and lysis, and measured total monthly rain, monthly average minimum (T-min) and maximum (T-max) temperatures. Contrary to our predictions, we found no down-regulation of immune function during breeding; breeding birds had higher nitric oxide than non-breeding ones in both species, while the other three immune indices did not differ between breeding phases. Red-capped larks had higher nitric oxide concentrations than Rufous-naped larks, which in turn had higher haptoglobin levels than red-capped larks. T-max was higher during breeding than during non-breeding for red-capped larks only, suggesting potential confounding effect of T-max on the comparison of immune function between breeding and non-breeding birds for this species. Overall, we conclude that in the two year-round breeding equatorial larks, immune function is not down-regulated during breeding

Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals

Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools

Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals