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The ATP-binding cassette transporter TAPL translocates polypeptides from the cytosol into the lysosomal lumen. TAPL can be divided into two functional units: coreTAPL, active in ATP-dependent peptide translocation, and the N-terminal membrane spanning domain, TMD0, responsible for cellular localization and interaction with the lysosomal associated membrane proteins LAMP-1 and LAMP-2. Although the structure and function of ABC transporters were intensively analyzed in the past, the knowledge about accessory membrane embedded domains is limited. Therefore, we expressed the TMD0 of TAPL via a cell-free expression system and confirmed its correct folding by NMR and interaction studies. In cell as well as cell-free expressed TMD0 forms oligomers, which were assigned as dimers by PELDOR spectroscopy and static light scattering. By NMR spectroscopy of uniformly and selectively isotope labeled TMD0 we performed a complete backbone and partial side chain assignment. Accordingly, TMD0 has a four transmembrane helix topology with a short helical segment in a lysosomal loop. The topology of TMD0 was confirmed by paramagnetic relaxation enhancement with paramagnetic stearic acid as well as by nuclear Overhauser effects with c6-DHPC and cross-peaks with water.
Self-organized robots may develop attracting states within the sensorimotor loop, that is within the phase space of neural activity, body and environmental variables. Fixpoints, limit cycles and chaotic attractors correspond in this setting to a non-moving robot, to directed, and to irregular locomotion respectively. Short higher-order control commands may hence be used to kick the system from one self-organized attractor robustly into the basin of attraction of a different attractor, a concept termed here as kick control. The individual sensorimotor states serve in this context as highly compliant motor primitives. We study different implementations of kick control for the case of simulated and real-world wheeled robots, for which the dynamics of the distinct wheels is generated independently by local feedback loops. The feedback loops are mediated by rate-encoding neurons disposing exclusively of propriosensoric inputs in terms of projections of the actual rotational angle of the wheel. The changes of the neural activity are then transmitted into a rotational motion by a simulated transmission rod akin to the transmission rods used for steam locomotives. We find that the self-organized attractor landscape may be morphed both by higher-level control signals, in the spirit of kick control, and by interacting with the environment. Bumping against a wall destroys the limit cycle corresponding to forward motion, with the consequence that the dynamical variables are then attracted in phase space by the limit cycle corresponding to backward moving. The robot, which does not dispose of any distance or contact sensors, hence reverses direction autonomously.
Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus. We show that the dynamics of Q is redox-state-dependent, and that quinol, QH2, moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica. We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.
Strong electron correlations can give rise to extraordinary properties of metals with renormalized Landau quasiparticles. Near a quantum critical point, these quasiparticles can be destroyed and non-Fermi liquid behavior ensues. YbRh2Si2 is a prototypical correlated metal exhibiting the formation of quasiparticle and Kondo lattice coherence, as well as quasiparticle destruction at a field-induced quantum critical point. Here we show how, upon lowering the temperature, Kondo lattice coherence develops at zero field and finally gives way to non-Fermi liquid electronic excitations. By measuring the single-particle excitations through scanning tunneling spectroscopy, we find the Kondo lattice peak displays a non-trivial temperature dependence with a strong increase around 3.3 K. At 0.3 K and with applied magnetic field, the width of this peak is minimized in the quantum critical regime. Our results demonstrate that the lattice Kondo correlations have to be sufficiently developed before quantum criticality can set in.
The detailed biophysical mechanisms through which transcranial magnetic stimulation (TMS) activates cortical circuits are still not fully understood. Here we present a multi-scale computational model to describe and explain the activation of different cell types in motor cortex due to transcranial magnetic stimulation. Our model determines precise electric fields based on an individual head model derived from magnetic resonance imaging and calculates how these electric fields activate morphologically detailed models of different neuron types. We predict detailed neural activation patterns for different coil orientations consistent with experimental findings. Beyond this, our model allows us to predict activation thresholds for individual neurons and precise initiation sites of individual action potentials on the neurons’ complex morphologies. Specifically, our model predicts that cortical layer 3 pyramidal neurons are generally easier to stimulate than layer 5 pyramidal neurons, thereby explaining the lower stimulation thresholds observed for I-waves compared to D-waves. It also predicts differences in the regions of activated cortical layer 5 and layer 3 pyramidal cells depending on coil orientation. Finally, it predicts that under standard stimulation conditions, action potentials are mostly generated at the axon initial segment of corctial pyramidal cells, with a much less important activation site being the part of a layer 5 pyramidal cell axon where it crosses the boundary between grey matter and white matter. In conclusion, our computational model offers a detailed account of the mechanisms through which TMS activates different cortical cell types, paving the way for more targeted application of TMS based on individual brain morphology in clinical and basic research settings.
This paper presents an imaging radar system for structural health monitoring (SHM) of wind turbine blades. The imaging radar system developed here is based on two frequency modulated continuous wave (FMCW) radar sensors with a high output power of 30 dBm. They have been developed for the frequency bands of 24,05 GHz-24,25 GHz and 33.4 GHz-36.0 GHz, respectively. Following the successful proof of damage detection and localization in laboratory conditions, we present here the installation of the sensor system at the tower of a 2 MW wind energy plant at 95 m above ground. The realization of the SHM-system will be introduced including the sensor system, the data acquisition framework and the signal processing procedures. We have achieved an imaging of the rotor blades using inverse synthetic aperture radar techniques under changing environmental and operational condition. On top of that, it was demonstrated that the front wall and back wall radar echo can be extracted from the measured signals demonstrating the full penetration of wind turbine blades during operation.
Far outside the surface of slabs, the exact exchange (EXX) potential vx falls off as −1/z , if z denotes the direction perpendicular to the surface and the slab is localized around z=0 . Similarly, the EXX energy density ex behaves as −n/(2z) , where n is the electron density. Here, an alternative proof of these relations is given, in which the Coulomb singularity in the EXX energy is treated in a particularly careful fashion. This new approach allows the derivation of the next-to-leading order contributions to the asymptotic vx and ex . It turns out that in both cases, the corrections are proportional to 1/z2 in general.
An empirical study of the per capita yield of science Nobel prizes : is the US era coming to an end?
(2018)
We point out that the Nobel prize production of the USA, the UK, Germany and France has been in numbers that are large enough to allow for a reliable analysis of the long-term historical developments. Nobel prizes are often split, such that up to three awardees receive a corresponding fractional prize. The historical trends for the fractional number of Nobelists per population are surprisingly robust, indicating in particular that the maximum Nobel productivity peaked in the 1970s for the USA and around 1900 for both France and Germany. The yearly success rates of these three countries are to date of the order of 0.2–0.3 physics, chemistry and medicine laureates per 100 million inhabitants, with the US value being a factor of 2.4 down from the maximum attained in the 1970s. The UK in contrast managed to retain during most of the last century a rate of 0.9–1.0 science Nobel prizes per year and per 100 million inhabitants. For the USA, one finds that the entire history of science Noble prizes is described on a per capita basis to an astonishing accuracy by a single large productivity boost decaying at a continuously accelerating rate since its peak in 1972.
By the fabrication of periodically arranged nanomagnetic systems it is possible to engineer novel physical properties by realizing artificial lattice geometries that are not accessible via natural crystallization or chemical synthesis. This has been accomplished with great success in two dimensions in the fields of artificial spin ice and magnetic logic devices, to name just two. Although first proposals have been made to advance into three dimensions (3D), established nanofabrication pathways based on electron beam lithography have not been adapted to obtain free-form 3D nanostructures. Here we demonstrate the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures. By employing micro-Hall sensing, we have determined the magnetic stray field generated by our free-form structures in an externally applied magnetic field and we have performed micromagnetic and macro-spin simulations to deduce the spatial magnetization profiles in the structures and analyze their switching behavior. Furthermore we show that the magnetic 3D elements can be combined with other 3D elements of different chemical composition and intrinsic material properties.
Fluctuation spectroscopy measurements of quasi-two-dimensional organic charge-transfer salts (BEDT-TTF) 2 X are reviewed. In the past decade, the method has served as a new approach for studying the low-frequency dynamics of strongly correlated charge carriers in these materials. We review some basic aspects of electronic fluctuations in solids, and give an overview of selected problems where the analysis of 1/f -type fluctuations and the corresponding slow dynamics provide a better understanding of the underlying physics. These examples are related to (1) an inhomogeneous current distribution due to phase separation and/or a percolative transition; (2) slow dynamics due to a glassy freezing either of structural degrees of freedom coupling to the electronic properties or (3) of the electrons themselves, e.g., when residing on a highly-frustrated crystal lattice, where slow and heterogeneous dynamics are key experimental properties for the vitrification process of a supercooled charge-liquid. Another example is (4), the near divergence and critical slowing down of charge carrier fluctuations at the finite-temperature critical endpoint of the Mott metal-insulator transition. Here also indications for a glassy freezing and temporal and spatial correlated dynamics are found. Mapping out the region of ergodicity breaking and understanding the influence of disorder on the temporal and spatial correlated fluctuations will be an important realm of future studies, as well as the fluctuation properties deep in the Mott or charge-ordered insulating states providing a connection to relaxor or ordered ferroelectric states studied by dielectric spectroscopy.