Identification of the ribosome binding sites of translation initiation factor IF3 by multidimensional heteronuclear NMR spectroscopy

Titrations of Escherichia coli translation initiation factor IF3, isotopically labeled with 15N, with 30S ribosomal subunits were followed by NMR by recording two-dimensional (15N,1H)-HSQC spectra. In the titrations, intensity changes are observed for cross peaks belonging to amides of individual amino acids. At low concentrations of ribosomal subunits, only resonances belonging to amino acids of the C-domain of IF3 are affected, whereas all those attributed to the N-domain are still visible. Upon addition of a larger amount of 30S subunits cross peaks belonging to residues of the N-terminal domain of the protein are also selectively affected. Our results demonstrate that the two domains of IF3 are functionally independent, each interacting with a different affinity with the ribosomal subunits, thus allowing the identification of the individual residues of the two domains involved in this interaction. Overall, the C-domain interacts with the 30S subunits primarily through some of its loops and a-helices and the residues involved in ribosome binding are distributed rather symmetrically over a fairly large surface of the domain, while the N-domain interacts mainly via a small number of residues distributed asymmetrically in this domain. The spatial organization of the active sites of IF3, emerging through the comparison of the present data with the previous chemical modification and mutagenesis data, is discussed in light of the ribosomal localization of IF3 and of the mechanism of action of this factor

Laser-heated capillary discharge plasma waveguides for electron acceleration to 8 GeV

A plasma channel created by the combination of a capillary discharge and inverse Bremsstrahlung laser heating enabled the generation of electron bunches with energy up to 7.8 GeV in a laser-driven plasma accelerator. The capillary discharge created an initial plasma channel and was used to tune the plasma temperature, which optimized laser heating. Although optimized colder initial plasma temperatures reduced the ionization degree, subsequent ionization from the heater pulse created a fully ionized plasma on-axis. The heater pulse duration was chosen to be longer than the hydrodynamic timescale of ≈ 1 ns, such that later temporal slices were more efficiently guided by the channel created by the front of the pulse. Simulations are presented which show that this thermal self-guiding of the heater pulse enabled channel formation over 20 cm. The post-heated channel had lower on-axis density and increased focusing strength compared to relying on the discharge alone, which allowed for guiding of relativistically intense laser pulses with a peak power of 0.85 PW and wakefield acceleration over 15 diffraction lengths. Electrons were injected into the wake in multiple buckets and times, leading to several electron bunches with different peak energies. To create single electron bunches with low energy spread, experiments using localized ionization injection inside a capillary discharge waveguide were performed. A single injected bunch with energy 1.6 GeV, charge 38 pC, divergence 1 mrad, and relative energy spread below 2% full-width half-maximum was produced in a 3.3 cm-long capillary discharge waveguide. This development shows promise for mitigation of energy spread and future high efficiency staged acceleration experiments

Plasma Equilibrium inside Various Cross-Section Capillary Discharges

Plasma properties inside a hydrogen-filled capillary discharge waveguide were modeled with dissipative magnetohydrodynamic simulations to enable analysis of capillaries of circular and square cross-sections implying that square capillaries can be used to guide circularly-symmetric laser beams. When the quasistationary stage of the discharge is reached, the plasma and temperature in the vicinity of the capillary axis has almost the same profile for both the circular and square capillaries. The effect of cross-section on the electron beam focusing properties were studied using the simulation-derived magnetic field map. Particle tracking simulations showed only slight effects on the electron beam symmetry in the horizontal and diagonal directions for square capillary.Comment: 6 pages, 10 figure

Laser beam coupling with capillary discharge plasma for laser wakefield acceleration applications

One of the most robust methods, demonstrated up to date, of accelerating electron beams by laser-plasma sources is the utilization of plasma channels generated by the capillary discharges. These channels, i.e., plasma columns with a minimum density along the laser pulse propagation axis, may optically guide short laser pulses, thereby increasing the acceleration length, leading to a more efficient electron acceleration. Although the spatial structure of the installation is simple in principle, there may be some important effects caused by the open ends of the capillary, by the supplying channels etc., which require a detailed 3D modeling of the processes taking place in order to get a detailed understanding and improve the operation. However, the discharge plasma, being one of the most crucial components of the laser-plasma accelerator, is not simulated with the accuracy and resolution required to advance this promising technology. In the present work, such simulations are performed using the code MARPLE. First, the process of the capillary filling with a cold hydrogen before the discharge is fired, through the side supply channels is simulated. The main goal of this simulation is to get a spatial distribution of the filling gas in the region near the open ends of the capillary. A realistic geometry is used for this and the next stage simulations, including the insulators, the supplying channels as well as the electrodes. Second, the simulation of the capillary discharge is performed with the goal to obtain a time-dependent spatial distribution of the electron density near the open ends of the capillary as well as inside the capillary. Finally, to evaluate effectiveness of the beam coupling with the channeling plasma wave guide and electron acceleration, modeling of laser-plasma interaction was performed with the code INF&RNOComment: 11 pages, 9 figure

On production and asymmetric focusing of flat electron beams using rectangular capillary discharge plasmas

A method for the asymmetric focusing of electron bunches, based on the active plasma lensing technique is proposed. This method takes advantage of the strong inhomogeneous magnetic field generated inside the capillary discharge plasma to focus the ultrarelativistic electrons. The plasma and magnetic field parameters inside the capillary discharge are described theoretically and modeled with dissipative magnetohydrodynamic computer simulations enabling analysis of the capillaries of rectangle cross-sections. Large aspect ratio rectangular capillaries might be used to transport electron beams with high emittance asymmetries, as well as assist in forming spatially flat electron bunches for final focusing before the interaction point.Comment: 16 pages, 7 figures, 1 tabl

Group velocity and pulse lengthening of mismatched laser pulses in plasma channels

Analytic solutions are presented to the non-paraxial wave equation describing an ultra-short, low-power, laser pulse propagating in aplasma channel. Expressions for the laser pulse centroid motion and laser group velocity are derived, valid for matched and mismatchedpropagation in a parabolic plasma channel, as well as in vacuum, for an arbitrary Laguerre-Gaussian laser mode. The group velocity of amismatched laser pulse, for which the laser spot size is strongly oscillating, is found to be independent of propagation distance andsignificantly less than that of a matched pulse. Laser pulse lengthening of a mismatched pulse owing to laser mode slippage isexamined and found to dominate over that due to dispersive pulse spreading for sufficiently long pulses. Analytic results are shown tobe in excellent agreement with numerical solutions of the full Maxwell equations coupled to the plasma response. Implications for plasmachannel diagnostics are discussed

Genetic Markers in Long-Term Survivors of Glioblastoma Multiforme

Scope: Genistein from foods or supplements is metabolized by the gut microbiota and the human body, thereby releasingmany different metabolites into systemic circulation. The order of their appearance in plasma and the possible influence of food format are still unknown. This study compared the nutrikinetic profiles of genistein metabolites. Methods and results: In a randomized cross-over trial, 12 healthy young volunteers were administered a single dose of 30mggenistein provided as a genistein tablet, a genistein tablet in low fat milk, and soy milk containing genistein glycosides. A high mass resolution LC-LTQ-Orbitrap FTMS platform detected and quantified in human plasma: free genistein, seven of its phase-II metabolites and 15 gut-derived metabolites. Interestingly, a novel metabolite, genistein-4- glucuronide-7-sulfate (G-4 G7S) was identified. Nutrikinetic analysis using population-based modeling revealed the order of appearance of five genistein phase II metabolites in plasma: (1) genistein-4,7-diglucuronide, (2) genistein-7-sulfate, (3) genistein-4--sulfate-7-glucuronide, (4) genistein-4-glucuronide, and (5) genistein-7-glucuronide, independent of the food matrix. Conclusion: The conjugated genistein metabolites appear in a distinct order in human plasma. The specific early appearance of G-4 ,7-diG suggests a multistep formation process for the mono and hetero genistein conjugates, involving one or two deglucuronidation steps

Can verbal instruction enhance the recall of an everyday task and promote error-monitoring in people with dementia of the Alzheimer-type?

People with dementia of the Alzheimer-type (DAT) have difficulties with performing everyday tasks and error awareness is poor. Here we investigated whether recall of actions and error monitoring in everyday task performance improved when they instructed another person on how to make tea. In this situation, both visual and motor cues are present, and attention sustained by the requirement to keep instructing. The data were drawn from a longitudinal study recording performance in four participants with DAT, filmed regularly for five years in their own homes, completing three tea-making conditions: performed-recall (they made tea themselves); instructed-recall (they instructed the experimenter on how to make tea); and verbal-recall (they described how to make tea). Accomplishment scores (percentage of task they correctly recalled), errors and error-monitoring were coded. Task accomplishment was comparable in the performed-recall and instructed-recall conditions, but both were significantly better than task accomplishment in the verbal-recall condition. Third person instruction did not improve error-monitoring. This study has implications for everyday task rehabilitation for people with DAT