Carrier-envelope offset stable, coherently combined ytterbium-doped fiber CPA delivering 1 kW of average power

We present a carrier-envelope offset (CEO) stable ytterbium-doped fiber chirped-pulse amplification system employing the technology of coherent beam combining and delivering more than 1 kW of average power at a pulse repetition rate of 80 MHz. The CEO stability of the system is 220 mrad rms, characterized out-of-loop with an f -to-2f interferometer in a frequency offset range of 10 Hz to 20 MHz. The high-power amplification system boosts the average power of the CEO stable oscillator by five orders of magnitude while increasing the phase noise by only 100 mrad. No evidence of CEO noise deterioration due to coherent beam combining is found. Low-frequency CEO fluctuations at the chirped-pulse amplifier are suppressed by a “slow loop” feedback. To the best of our knowledge, this is the first demonstration of a coherently combined laser system delivering an outstanding average power and high CEO stability at the same time. © 2020 Optical Society of Americ

Helix compactness and stability: Electron structure calculations of conformer dependent thermodynamic functions

Structure, stability, cooperativity and molecular packing of two major backbone forms: 310-helix and β-strand are investigated. Long models HCO-(Xxx)n-NH2 Xxx = Gly and (l-)Ala, n ⩽ 34, are studied at two levels of theory including the effect of dispersion forces. Structure and folding preferences are established, the length modulated cooperativity and side-chain determined fold compactness is quantified. By monitoring ΔG°β→α rather than the electronic energy, ΔEβ→α, it appears that Ala is a much better helix forming residue than Gly. The achiral Gly forms a more compact 310-helix than any chiral amino acid residue probed here for l-Ala

Functional Rotation of the Transporter AcrB: Insights into Drug Extrusion from Simulations

The tripartite complex AcrAB-TolC is the major efflux system in Escherichia coli. It extrudes a wide spectrum of noxious compounds out of the bacterium, including many antibiotics. Its active part, the homotrimeric transporter AcrB, is responsible for the selective binding of substrates and energy transduction. Based on available crystal structures and biochemical data, the transport of substrates by AcrB has been proposed to take place via a functional rotation, in which each monomer assumes a particular conformation. However, there is no molecular-level description of the conformational changes associated with the rotation and their connection to drug extrusion. To obtain insights thereon, we have performed extensive targeted molecular dynamics simulations mimicking the functional rotation of AcrB containing doxorubicin, one of the two substrates that were co-crystallized so far. The simulations, including almost half a million atoms, have been used to test several hypotheses concerning the structure-dynamics-function relationship of this transporter. Our results indicate that, upon induction of conformational changes, the substrate detaches from the binding pocket and approaches the gate to the central funnel. Furthermore, we provide strong evidence for the proposed peristaltic transport involving a zipper-like closure of the binding pocket, responsible for the displacement of the drug. A concerted opening of the channel between the binding pocket and the gate further favors the displacement of the drug. This microscopically well-funded information allows one to identify the role of specific amino acids during the transitions and to shed light on the functioning of AcrB

A candidate ion-retaining state in the inward-facing conformation of sodium/galactose symporter: Clues from atomistic simulations

The recent Vibrio parahaemolyticus sodium/galactose (vSGLT) symporter crystal structure captures the protein in an inward-facing substrate-bound conformation, with the sodium ion placed, by structural alignment, in a site equivalent to the Na2 site of the leucine transporter (LeuT). A recent study, based on molecular dynamics simulations, showed that the sodium ion spontaneously leaves its initial position diffusing outside vSGLT, toward the intracellular space. This suggested that the crystal structure corresponds to an ion-releasing state of the transporter. Here, using metadynamics, we identified a more stable Na+ binding site corresponding to a putative ion-retaining state of the transporter. In addition, our simulations, consistently with mutagenesis studies, highlight the importance of D189 that, without being one of the NA(+)-coordinating residues, regulates its binding/release

Properties of the Liquid-Vapor Interface of Acetone-Water Mixtures. A Computer Simulation and ITIM Analysis Study

Molecular dynamics simulations of the liquid-vapor interface of acetone-water mixtures of different compositions, covering the entire composition range have been performed on the canonical (N, V, T) ensemble at 298 K, using a model combination that excellently describes the mixing properties of these compounds. The properties of the intrinsic liquid surfaces have been analyzed in terms of the Identification of the Truly Interfacial Molecules (ITIM) method. Thus, the composition, width, roughness, and separation of the subsurface molecular layers, as well as self-association, orientation, and dynamics of exchange with the bulk phase of the surface molecules have been analyzed in detail. Our results show that acetone molecules are strongly adsorbed at the liquid surface, and this adsorption extends to several molecular layers. Like molecules in the surface layer are found to form relatively large lateral self-associates. The effect of the vicinity of the vapor phase on a number of properties of the liquid phase vanishes beyond the first molecular layer, with the second subsurface layer already part of the bulk liquid phase in these respects. The orientational preferences of the surface molecules are governed primarily by the dipole-dipole interaction of the neighboring acetone molecules, and hydrogen bonding interaction of the neighboring acetone-water pairs. (Figure Presented). © 2015 American Chemical Society

Nanomolar oxytocin synergizes with weak electrical afferent stimulation to activate the locomotor CPG of the rat spinal cord in vitro.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM-1 \u3bcM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits

Generation of three-cycle multi-millijoule laser pulses at 318 W average power

The generation of three-cycle multi-millijoule pulses at 318 W power is reported by compressing pulses of a Yb-fiber chirped pulse amplifier in a 6 m long stretched flexible hollow fiber. This technique brings high-power lasers to the few-cycle regime