The metabolites NADP and NADPH are the targets of the circadian protein Nocturnin (Curled)
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Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among V H 3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of V H 3-30 antibodies and reveals that 3I14 represents a novel structural solution within the V H 3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.
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We report the first structures of bacterial HAQs bound to their target DHODH and provide insights into mechanism of inhibition.
A laser ion source coupled with a radio frequency quadrupole linac accelerator is being proposed as a suitable system for the production of a low energy, high-current stable lithium beam. In order to maximize the lithium yield, plasmas generated by laser ablation of different materials based on lithium (Li, LiOH, and LiNbO3) have been characterized by using a Faraday cup and an electrostatic ion analyzer in the time of flight configuration. A wide range of laser power density has been investigated (109–1012 W/cm2) using two Nd:YAG lasers operating at different wavelengths (1064 nm and 532 nm), pulse durations (6 ns and 17 ns), and maximum energies (1400 mJ and 210 mJ). This paper outlines the pros and cons of the investigated materials by studying how the ion energy, yields, and charge state distributions are modified when the laser power density is changed. Considerable attention has been paid to the higher charge states of oxygen, which may occur with the same mass-to-charge ratio of Li3+. The analysis has evidenced that LiNbO3 represents a valid target since it allows minimizing the O6+/7Li3+ ratio down to 2.5% by using a laser power density of 1.8 × 1010 W/cm2. For such a condition, a Li3+ current of 1.4 mA/cm2 has been measured.
The de novo design of polar protein–protein interactions is challenging because of the thermodynamic cost of stripping water away from the polar groups. Here, we describe a general approach for designing proteins which complement exposed polar backbone groups at the edge of beta sheets with geometrically matched beta strands. We used this approach to computationally design small proteins that bind to an exposed beta sheet on the human transferrin receptor (hTfR), which shuttles interacting proteins across the blood–brain barrier (BBB), opening up avenues for drug delivery into the brain. We describe a design which binds hTfR with a 20 nM K d , is hyperstable, and crosses an in vitro microfluidic organ-on-a-chip model of the human BBB. Our design approach provides a general strategy for creating binders to protein targets with exposed surface beta edge strands.
Here, the unpolarized semi-inclusive deep-inelastic scattering (SIDIS) differential cross sections in 3 He(e,e'π ± )X have been measured for the first time in Jefferson Lab experiment E06-010 with a 5.9 GeV e – beam on a 3 He gas target. The experiment focuses on the valence quark region, covering a kinematic range 0.12 < x bj < 0.45,1 < Q 2 < 4(GeV/c) 2 ,0.45 < z h < 0.65, and 0.05 < P t < 0.55GeV/c. The extracted SIDIS differential cross sections of π± production are compared with existing phenomenological models while the 3 He nucleus approximated as two protons and one neutron in a plane-wave picture, in multidimensional bins. Within the experimental uncertainties, the azimuthal modulations of the cross sections are found to be consistent with zero.
Optimization of electron coupling into small solid angles is of extreme importance to applications, such as Fast Ignition, that require maximum electron energy deposition within a small volume. To optimize this coupling, we use the ultra-high-contrast Trident laser, which remains below intensity of 10 11 W/cm 2 until < 0.1 ns before the main pulse, while still attaining high-energy, 75 J, and peak intensity of 5 x 10 19 W/cm 2 . Using a cone-wire target, we find that the coupling into the 40 μm diameter wire is increased by a factor of 2.7x over the low-contrast Titan laser at similar peak intensity. Full-scale simulations are used to model the laser interaction and quantitatively reproduce the experimental results. These show that increase in coupling is due to both a closer interaction, as well as the reduction of laser filamentation and self-focusing.
Five different types of transgenic ( GAUT4 , miRNA, MYB4, COMT and FPGS ) Panicum virgatum L. (switchgrass) were grown in a field in Knoxville, Tenn., USA over two consecutive years between 2011 and 2015 in separate experiments. Clonal replicates were established (year-one) and produced much greater biomass during the second year. After each growing season the above ground biomass was analyzed for cell wall sugars and for recalcitrance to enzymatic digestibility, and biofuel using a separate hydrolysis and fermentation (SHF) screen. Here, each transgenic event and control had more glucan, xylan and less ethanol (g/g basis) from the second year of growth relative to the first year plants. There was no correlation between plant carbohydrate content and biofuel production. In each of cell wall-targeted transgenics, GAUT4 , MYB4, COMT and FPGS , the second year of growth resulted in increased carbohydrate abundance (up to 12%) and reduced recalcitrance through higher ethanol yields (up to 21%) over the non-transgenic control plants.
An alternate conformation is found for the major antibody target on hepatitis C virus to aid in rational vaccine design.
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In 2014/2015 at the Omega laser facility, several experiments took place to calibrate the National Ignition Facility (NIF) X-ray spectrometer (NXS), which is used for high-resolution time-resolved spectroscopic experiments at NIF. The spectrometer allows experimentalists to measure the X-ray energy emitted from high-energy targets, which is used to understand key data such as mixing of materials in highly compressed fuel. The purpose of the experiments at Omega was to obtain information on the instrument performance and to deliver an absolute photometric calibration of the NXS before it was deployed at NIF. The X-ray emission sources fabricated for instrument calibration were 1-mm fused silica spheres with precisely known alloy composition coatings of Si/Ag/Mo, Ti/Cr/Ag, Cr/Ni/Zn, and Zn/Zr, which have emission in the 2- to 18-keV range. Critical to the spectrometer calibration is a known atomic composition of elements with low uncertainty for each calibration sphere. This study discusses the setup, fabrication, and precision metrology of these spheres as well as some interesting findings on the ternary magnetron-sputtered alloy structure.
This grant involved three objectives for producing high specific activity radionuclides using reactor and accelerator technologies that would find use in medical, industrial and research applications. There was a strong emphasis in all projects to develop and train staff and students in all aspects of targetry, reactor and accelerator production, separation of radionuclides from enriched target material, and evaluating the specific activity of the product radionuclides. An additional objective was training of students (undergraduate, graduate, postdoctoral) in all aspects of radiochemistry.
Angular distribution of thick target bremsstrahlung produced by electron bombardment of Be, Sn and Au surfaces
Closed-loop control of discrete time systems with uncertainty, discussing minimax reachability of target sets and tubes
Obtain physical and astrometric observations of: (1) spacecraft targets to support mission operations; (2) known asteroids with unusual orbits to help determine their origin; and (3) newly discovered minor planets (including both asteroids and comets) that represent a particular opportunity to add significant new knowledge of the Solar System.
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