The substrate binding domains of human SIAH E3 ubiquitin ligases are now crystal clear
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Hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyltransferase (HCT) is an essential acyltransferase that mediates flux through plant phenylpropanoid metabolism by catalyzing a reaction between p-coumaroyl-CoA and shikimate, yet it also exhibits broad substrate permissiveness in vitro. How do enzymes like HCT avoid functional derailment by cellular metabolites that qualify as non-native substrates? Here, we combine X-ray crystallography and molecular dynamics to reveal distinct dynamic modes of HCT under native and non-native catalysis. We find that essential electrostatic and hydrogen-bonding interactions between the ligand and active site residues, permitted by active site plasticity, are elicited more effectively by shikimate than by other non-native substrates. This work provides a structural basis for how dynamic conformational states of HCT favor native over non-native catalysis by reducing the number of futile encounters between the enzyme and shikimate.
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A physical explanation of the lateral guiding mechanism in channeled-substrate-planar (CSP) lasers based on the amount of wavefront tilt of the transverse field outside the channel region is presented. Because of this inherent wavefront tilt, all CSP lasers will have a very slight asymmetry in their transverse far-field pattern. The nature of the guiding mechanism does not require light absorption by the substrate. Design curves showing the complex lateral effective index step as a function of n-clad thickness with the active layer as a parameter are also presented. Depending on the specific layer compositions and thicknesses, the CSP guiding mechanism can provide a positive lateral index step for substrates with mole fractions of AlAs ranging from 0 to higher than 0.2.
Systems and apparatus are provided for power electronics substrates adapted for direct substrate cooling. A power electronics substrate comprises a first surface configured to have electrical circuitry disposed thereon, a second surface, and a plurality of physical features on the second surface. The physical features are configured to promote a turbulent boundary layer in a coolant impinged upon the second surface.
Methods of aluminizing the surface of a metal substrate. The methods of the present invention do not require establishment of a vacuum or a reducing atmosphere, as is typically necessary. Accordingly, aluminization can occur in the presence of oxygen, which greatly simplifies and reduces processing costs by allowing deposition of the aluminum coating to be performed, for example, in air. Embodiments of the present invention can be characterized by applying a slurry that includes a binder and powder granules containing aluminum to the metal substrate surface. Then, in a combined step, a portion of the aluminum is diffused into the substrate and a portion of the aluminum is oxidized by heating the slurry to a temperature greater than the melting point of the aluminum in an oxygen-containing atmosphere.
Coincident site lattice-matched wurtzite (0001) In{sub 0.31}Ga{sub 0.69}N, emitting in the important green wavelength region, is demonstrated by molecular beam epitaxy on a cubic (111) MgAl{sub 2}O{sub 4} spinel substrate. The coincident site lattice matching condition involves a 30 deg. rotation between the lattice of the InGaN epitaxial layer and the lattice of the spinel. This work describes an alternative approach towards realizing more compositionally homogenous InGaN films with low dislocation density emitting in the ''green gap'' of low efficiency currently observed for semiconductor light emitting diodes (LEDs). This approach could lead to higher efficiency green LEDs presently of great interest for solid-state lighting applications.
Highlights: •Inhibitors against MDR HIV-1 protease were designed, synthesized and evaluated. •Lead peptide (6a) showed potent inhibition (IC{sub 50}: 4.4 nM) of MDR HIV-1 protease. •(6a) Showed favorable binding isotherms against NL4-3 and MDR proteases. •(6a) Induced perturbations in the {sup 15}N-HSQC spectrum of MDR HIV-1 protease. •Molecular modeling suggested that (6a) may induce total flap closure inMDR protease. -- Abstract: Multidrug-resistant (MDR) clinical isolate-769, human immunodeficiency virus type-1 (HIV-1) protease (PDB ID: (1TW7)), was shown to exhibit wide-open flaps and an expanded active site cavity, causing loss of contacts with protease inhibitors. In the current study, the expanded active site cavity of MDR769 HIV-1 protease was screened with a series of peptide-inhibitors that were designed to mimic the natural substrate cleavage site, capsid/p2. Scanning Ala/Phe chemical mutagenesis approach was incorporated into the design of the peptide series to mimic the substrate co-evolution. Among the peptides synthesized and evaluated, a lead peptide (6a) with potent activity (IC{sub 50}: 4.4 nM) was identified against the MDR769 HIV-1 protease. Isothermal titration calorimetry data showed favorable binding profile for 6aagainst both wild type and MDR769 HIV-1 protease variants. Nuclear magnetic resonance spectrum of {sup 15}N-labeled MDR769 HIV-1 protease in complex with 6a showed some major perturbations in chemical shift, supporting the peptide induced conformational changes in protease. Modeling analysis revealed multiple contacts between 6a and MDR769 HIV-1 protease. The lead peptide-inhibitor, 6a, with high potency and good binding profile can be used as the basis for developing potent small molecule inhibitors against MDR variants of HIV.
While nanowires and nanosheets (NSs) grown on lattice-mismatched substrates have a number of promising technological applications such as solar cells, generation of misfit dislocations (MFDs) at their interfaces is a major concern for the efficiency of these devices. Here, combined molecular-dynamics and quantum-mechanical simulations are used to study MFDs at the interface between a GaAs NS and a Si substrate. Simulation results show the existence of a critical NS thickness, below which NSs are grown free of MFDs. The calculated critical thickness value is consistent with available experimental observations. Charge transfer at the MFD core is found to modify the electronic band profile at the GaAs/Si interface significantly. These effects should have profound impacts on the efficiency of lattice-mismatched NS devices.
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A controllable and smooth potassium hydroxide-based wet etching technique was developed for the AlGaN system. High selectivity between AlN and Al{sub x}Ga{sub 1−x}N (up to 12×) was found to be critical in achieving effective substrate thinning or removal for AlGaN-based deep ultraviolet light emitting diodes, thus increasing light extraction efficiency. The mechanism of high selectivity of AlGaN as a function of Al composition can be explained as related to the formation and dissolution of oxide/hydroxide on top of N-polar surface. Cross-sectional transmission electron microscopic analysis served as ultimate proof that these hillocks were not related to underlying threading dislocations.
Antiphase-domain (APD) free GaP films were grown on Si(100) substrates prepared by annealing under dilute AsH{sub 3} in situ in an MOCVD reactor. LEED and AES surface analysis of Si(100) surfaces prepared by this treatment show that AsH{sub 3} etching quickly removes O and C contaminants at a relatively low temperature (690–740 °C), and creates a single-domain “A-type” As/Si surface reconstruction. The resulting GaP epilayers grown at the same temperature are APD-free, and could thereby serve as templates for direct growth of III-V semiconductors on Si. This single chamber process has a low thermal budget, and can enable heteroepitaxial integration of III-Vs and Si at an industrial scale.
In this work, the electrical performance of strain-balanced quantum well tunnel junctions with varying designs is presented. Strain-balanced quantum well tunnel junctions comprising compressively strained InAlAs wells and tensile-strained InAlAs barriers were grown on InP substrates using solid-source molecular beam epitaxy. The use of InAlAs enables InP-based tunnel junction devices to be produced using wide bandgap layers, enabling high electrical performance with low absorption. The impact of well and barrier thickness on the electrical performance was investigated, in addition to the impact of Si and Be doping concentration. Finally, the impact of an InGaAs quantum well at the junction interface is presented, enabling a peak tunnel current density of 47.6 A/cm{sup 2} to be realized.
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Active matter exploits motion to induce changes in shape and conformation via external input. Here, in this paper, we establish theoretically that viscous liquid droplets containing magnetic nanoparticles with frozen-in magnetic moments, sitting on a solid substrate and surrounded by an ambient gas phase, can deform and migrate under the influence of a magnetic torque. The effect arises because the collective rotation of the magnetic nanoparticles at the liquid–gas interface tilts the droplet away from a symmetric configuration, breaks the reflection symmetry with respect to the centre axis, and leads to a left–right asymmetry of the contact angles. A sufficiently strong magnetic torque leads the contact angles to overcome hysteresis effects leading the droplet to migrate. We develop a general framework to explain how symmetry-breaking affects droplet migration. Thus previous results of droplet spreading and migration can be recovered as special cases. Such droplets can be employed as agents in active surfaces and can move against gravity, chemical and thermal gradients, providing a mechanism that could be utilized by both industry and medicine.