Abstract
Inter-areal synchronization of neuronal oscillations at frequencies below ~100 Hz is a pervasive feature of neuronal activity and is thought to regulate communication in neuronal circuits. ...In contrast, faster activities and oscillations have been considered to be largely local-circuit-level phenomena without large-scale synchronization between brain regions. We show, using human intracerebral recordings, that 100–400 Hz high-frequency oscillations (HFOs) may be synchronized between widely distributed brain regions. HFO synchronization expresses individual frequency peaks and exhibits reliable connectivity patterns that show stable community structuring. HFO synchronization is also characterized by a laminar profile opposite to that of lower frequencies. Importantly, HFO synchronization is both transiently enhanced and suppressed in separate frequency bands during a response-inhibition task. These findings show that HFO synchronization constitutes a functionally significant form of neuronal spike-timing relationships in brain activity and thus a mesoscopic indication of neuronal communication per se.
When dealing with complex structures with a several number of degrees of freedom (DOFs), it is useful trying to reduce the mesh for computational cost reasons, seeking not affecting the accuracy in ...results. The Finite Element Method can become very costly in calculations and time because of the use of very fine 3D meshes. A possible solution can be the application of the Adaptive Mesh (AM), which allows to concentrate the very fine mesh only in regions where critical conditions are present, in terms of geometrical or loads constrains. By exploiting the Node-Dependent Kinematic approach of the Carrera Unified Formulation and using Lagrange expanding functions, this work presents the application of non-conventional 1D and 2D elements for mesh refinement, offering a new and convenient technique to apply in the framework of AM. The static analysis of some typical study cases is performed and the results are provided in terms of displacements and stresses. The presented elements allow us to combine them in order to obtain a mesh refinement employing much less degrees of freedom with respect to the use of classical 3D finite elements.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
One of the key challenges in developing quantum networks is to generate single photons with high brightness, purity, and long temporal coherence. Semiconductor quantum dots potentially satisfy these ...requirements; however, due to imperfections in the surrounding material, the coherence generally degrades with increasing excitation power yielding a broader emission spectrum. Here we overcome this power-broadening regime and demonstrate an enhanced coherence at exciton saturation where the detected count rates are highest. We detect single-photon count rates of 460 000 counts per second under pulsed laser excitation while maintaining a single-photon purity greater than 99%. Importantly, the enhanced coherence is attained with quantum dots in ultraclean wurtzite InP nanowires, where the surrounding charge traps are filled by exciting above the wurtzite InP nanowire band gap. By raising the excitation intensity, the number of possible charge configurations in the quantum dot environment is reduced, resulting in a narrower emission spectrum. Via Monte Carlo simulations we explain the observed narrowing of the emission spectrum with increasing power. Cooling down the sample to 300 mK, we further enhance the single-photon coherence twofold as compared to operation at 4.5 K, resulting in a homogeneous coherence time, T2, of 1.2 ns, and two-photon interference visibility as high as 83% under strong temporal postselection (~5% without temporal postselection).
The peptidoglycan (PG) cell wall is an essential extracytoplasmic glycopeptide polymer that safeguards bacteria against osmotic lysis and determines cellular morphology. Bacteria use multiprotein ...machineries for the synthesis of the PG cell wall during cell division and elongation that can be targeted by antibiotics such as the β-lactams. Lipid II, the lipid-linked precursor for PG biogenesis, is synthesized in the inner leaflet of the cytoplasmic membrane and then translocated across the bilayer, where it is ultimately polymerized into PG. In Escherichia coli, MurJ, a member of the MOP exporter superfamily, has been recently shown to have lipid II flippase activity that depends on membrane potential. Because of its essentiality, MurJ could potentially be targeted by much needed novel antibiotics. Recent structural information suggests that a central cavity in MurJ alternates between inward- and outward-open conformations to flip lipid II, but how these conformational changes occur are unknown. Here, we utilized structure-guided cysteine cross-linking and proteolysis-coupled gel analysis to probe the conformational changes of MurJ in E. coli cells. We found that paired cysteine substitutions in transmembrane domains 2 and 8 and periplasmic loops of MurJ could be cross-linked with homobifunctional cysteine cross-linkers, indicating that MurJ can adopt both inward- and outward-facing conformations in vivo. Furthermore, we show that dissipating the membrane potential with an ionophore decreases the prevalence of the inward-facing, but not the outward-facing state. Our study provides in vivo evidence that MurJ uses an alternating-access mechanism during the lipid II transport cycle.
Summary
Solid organ transplantation saves and transforms lives. The original type of organ donation from deceased patients was controlled donation after circulatory death, previously referred to as ...non‐heart beating organ donation. The rise of donation after circulatory death in the UK came about through advances in critical care and transplant medicine and support from several key organisations in developing a robust ethical, legal and professional framework. The transplant waiting list reached a historic peak in 2009–2010 of 8000 patients, but fell by 25% to 6000 in 2017–2018. There has also been a steady rise in the number of deceased donors and the number of donations after circulatory death. The contribution of donation after circulatory death to the total number of donations rose steadily between 2000 and 2012 and has remained about 40% since. Although the situation has improved for patients waiting for a transplant, deaths and long waits remain common. Changes to legislative, technical and peri‐mortem procedures may greatly change future practices in donation after circulatory death in the UK.
•Focal lesions can lead to network effects whose neuronal mechanisms are elusive.•We contrast intracranial EEG recorded before and after surgical lesions in humans.•Full-fledged, sleep-like slow ...waves appear in the perilesional area.•Slow waves also percolate through long-range existing patterns of connectivity.•The intrusion of sleep-like activity may underlie the network effect of focal lesions.
Focal cortical lesions are known to result in large-scale functional alterations involving distant areas; however, little is known about the electrophysiological mechanisms underlying these network effects. Here, we addressed this issue by analysing the short and long distance intracranial effects of controlled structural lesions in humans. The changes in Stereo-Electroencephalographic (SEEG) activity after Radiofrequency-Thermocoagulation (RFTC) recorded in 21 epileptic subjects were assessed with respect to baseline resting wakefulness and sleep activity. In addition, Cortico-Cortical Evoked Potentials (CCEPs) recorded before the lesion were employed to interpret these changes with respect to individual long-range connectivity patterns. We found that small structural ablations lead to the generation and large-scale propagation of sleep-like slow waves within the awake brain. These slow waves match those recorded in the same subjects during sleep, are prevalent in perilesional areas, but can percolate up to distances of 60 mm through specific long-range connections, as predicted by CCEPs. Given the known impact of slow waves on information processing and cortical plasticity, demonstrating their intrusion and percolation within the awake brain add key elements to our understanding of network dysfunction after cortical injuries.
Decadal and bi-decadal climate responses to tropical strong volcanic eruptions (SVEs) are inspected in an ensemble simulation covering the last millennium based on the Max Planck Institute—Earth ...system model. An unprecedentedly large collection of pre-industrial SVEs (up to 45) producing a peak annual-average top-of-atmosphere radiative perturbation larger than −1.5 Wm
−2
is investigated by composite analysis. Post-eruption oceanic and atmospheric anomalies coherently describe a fluctuation in the coupled ocean–atmosphere system with an average length of 20–25 years. The study provides a new physically consistent theoretical framework to interpret decadal Northern Hemisphere (NH) regional winter climates variability during the last millennium. The fluctuation particularly involves interactions between the Atlantic meridional overturning circulation and the North Atlantic gyre circulation closely linked to the state of the winter North Atlantic Oscillation. It is characterized by major distinctive details. Among them, the most prominent are: (a) a strong signal amplification in the Arctic region which allows for a sustained strengthened teleconnection between the North Pacific and the North Atlantic during the first post-eruption decade and which entails important implications from oceanic heat transport and from post-eruption sea ice dynamics, and (b) an anomalous surface winter warming emerging over the Scandinavian/Western Russian region around 10–12 years after a major eruption. The simulated long-term climate response to SVEs depends, to some extent, on background conditions. Consequently, ensemble simulations spanning different phases of background multidecadal and longer climate variability are necessary to constrain the range of possible post-eruption decadal evolution of NH regional winter climates.
Shape optimization in unsteady flow problems enables the consideration of dynamic effects on design. The ability to treat unsteady effects is attractive, as it can provide performance gains when ...compared to steady-state design methods for a variety of applications in which time-varying flows are of paramount importance. This is the case, for example, in turbomachinery or rotorcraft design. Given the high computational cost involved in time-accurate design problems, adjoint-based shape optimization is a promising option. However, efficient sensitivity analysis should also be accompanied by a significant decrease in computational cost for the primal flow solution, as well. Reduced-order models, like those based on the harmonic balance concept, in combination with the calculation of gradients via adjoint methods, are proposed for the efficient solution of a certain class of aerodynamics optimization problems. The harmonic balance method is applicable if the flow is characterized by discrete finite dominant flow frequencies that do not need to be integer multiples of a fundamental harmonic. A fully-turbulent harmonic balance discrete adjoint formulation based on a duality-preserving approach is proposed. The method is implemented by leveraging algorithmic differentiation and is applied to two test cases: the constrained shape optimization of both a pitching airfoil and a turbine cascade. A key advantage of the current approach is the accurate computation of gradients as compared to second order finite differences without any approximation in the linearization of the turbulent viscosity. The shape optimization results show significant improvements for the selected time-dependent objective functions, demonstrating that design problems involving almost-periodic unsteady flows can be tackled with manageable computational effort.
•Fully-turbulent discrete adjoint method based on harmonic-balance.•Shape optimization for quasi-periodic unsteady problems.•Application to the constrained shape optimization of problems characterized by a set of discrete frequencies.•Increased significantly the performance of a pitching airfoil and a turbine cascade subject to unsteady inflow conditions.
Most bacteria have a peptidoglycan cell wall that determines their cell shape and helps them resist osmotic lysis. Peptidoglycan synthesis depends on the translocation of the lipid-linked precursor ...lipid II across the cytoplasmic membrane by the MurJ flippase. Structure-function analyses of MurJ from Thermosipho africanus (MurJ
) and Escherichia coli (MurJ
) have revealed that MurJ adopts multiple conformations and utilizes an alternating-access mechanism to flip lipid II. MurJ
activity relies on membrane potential, but the specific counterion has not been identified. Crystal structures of MurJ
revealed a chloride ion bound to the N-lobe of the flippase and a sodium ion in its C-lobe, but the role of these ions in transport is unknown. Here, we investigated the effect of various ions on the function of MurJ
and MurJ
. We found that chloride, and not sodium, ions are necessary for MurJ
function, but neither ion is required for MurJ
function. We also showed that
alleles encoding changes at the crystallographically identified sodium-binding site still complement the loss of native
, although they decreased protein stability and/or function. Based on our data and previous work, we propose that chloride ions are necessary for the conformational change that resets MurJ
after lipid II translocation and suggest that MurJ orthologs may function similarly but differ in their requirements for counterions.
The biosynthetic pathway of the peptidoglycan cell wall is one of the most favorable targets for antibiotic development. Lipid II, the lipid-linked PG precursor, is made in the inner leaflet of the cytoplasmic membrane and then transported by the MurJ flippase so that it can be used to build the peptidoglycan cell wall. MurJ functions using an alternating-access mechanism thought to depend on a yet-to-be-identified counterion. This study fills a gap in our understanding of MurJ's energy-coupling mechanism by showing that chloride ions are required for MurJ in some, but not all, organisms. Based on our data and prior studies, we propose that, while the general transport mechanism of MurJ may be conserved, its specific mechanistic details may differ across bacteria, as is common in transporters. These findings are important to understand MurJ function and its development as an antibiotic target.
Bacterial cell wall synthesis is an essential process in bacteria and one of the best targets for antibiotics. A critical step on this pathway is the export of the lipid-linked cell wall monomer, ...Lipid II, by its transporter MurJ. The mechanism by which MurJ mediates the transbilayer movement of Lipid II is not understood because intermediate states of this process have not been observed. Here we demonstrate a method to capture and detect interactions between MurJ and its substrate Lipid II by photo-cross-linking and subsequent biotin-tagging. We show that this method can be used to covalently capture intermediate transport states of Lipid II on MurJ in living cells. Using this strategy we probed several lethal arginine mutants and found that they retain appreciable substrate-binding ability despite being defective in Lipid II transport. We propose that Lipid II binding to these residues during transport induces a conformational change in MurJ required to proceed through the Lipid II transport cycle. The methods described to detect intermediate transport states of MurJ will be useful for characterizing mechanisms of inhibitors.
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