Technical Findings, Lessons Learned, and Recommendations Resulting from the Helios Prototype Vehicle Mishap

The Helios Prototype was originally planned to be two separate vehicles, but because of resource limitations only one vehicle was developed to demonstrate two missions. The vehicle consisted of two configurations, one for each mission. One configuration, designated HP01, was designed to operate at extremely high altitudes using batteries and high-efficiency solar cells spread across the upper surface of its 247-foot wingspan. On August 13, 2001, the HP01 configuration reached an altitude of 96,863 feet, a world record for sustained horizontal flight by a winged aircraft. The other configuration, designated HP03, was designed for long-duration flight. The plan was to use the solar cells to power the vehicle's electric motors and subsystems during the day and to use a modified commercial hydrogen-air fuel cell system for use during the night. The aircraft design used wing dihedral, engine power, elevator control surfaces, and a stability augmentation and control system to provide aerodynamic stability and control. At about 30 minutes into the second flight of HP03, the aircraft encountered a disturbance in the way of turbulence and morphed into an unexpected, persistent, high dihedral configuration. As a result of the persistent high dihedral, the aircraft became unstable in a very divergent pitch mode in which the airspeed excursions from the nominal flight speed about doubled every cycle of the oscillation. The aircraft s design airspeed was subsequently exceeded and the resulting high dynamic pressures caused the wing leading edge secondary structure on the outer wing panels to fail and the solar cells and skin on the upper surface of the wing to rip away. As a result, the vehicle lost its ability to maintain lift, fell into the Pacific Ocean within the confines of the U.S. Navy's Pacific Missile Range Facility, and was destroyed. This paper describes the mishap and its causes, and presents the technical recommendations and lessons learned for improving the design, analysis, and testing methods and techniques required for this class of vehicle

The Interaction Properties of the Human Rab GTPase Family – A Comparative Analysis Reveals Determinants of Molecular Binding Selectivity

Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity

Solution Structural Ensembles of Substrate-Free Cytochrome P450_cam

Removal of substrate (+)-camphor from the active site of cytochrome P450_cam (CYP101A1) results in nuclear magnetic resonance-detected perturbations in multiple regions of the enzyme. The ¹H–¹⁵N correlation map of substrate-free diamagnetic Fe­(II) CO-bound CYP101A permits these perturbations to be mapped onto the solution structure of the enzyme. Residual dipolar couplings (RDCs) were measured for ¹⁵N–¹H amide pairs in two independent alignment media for the substrate-free enzyme and used as restraints in solvated molecular dynamics (MD) simulations to generate an ensemble of best-fit structures of the substrate-free enzyme in solution. Nuclear magnetic resonance-detected chemical shift perturbations reflect changes in the electronic environment of the NH pairs, such as hydrogen bonding and ring current shifts, and are observed for residues in the active site as well as in hinge regions between secondary structural features. RDCs provide information about relative orientations of secondary structures, and RDC-restrained MD simulations indicate that portions of a β-rich region adjacent to the active site shift so as to partially occupy the vacancy left by removal of the substrate. The accessible volume of the active site is reduced in the substrate-free enzyme relative to the substrate-bound structure calculated using the same methods. Both symmetric and asymmetric broadening of multiple resonances observed upon substrate removal as well as localized increased errors in RDC fits suggest that an ensemble of enzyme conformations are present in the substrate-free form

Structure activity relationships of anthranilic acid-based compounds on cellular and in vivo mitogen activated protein kinase-5 signaling pathways

status: publishe

Polymorphism and second harmonic generation in a novel diamond-like semiconductor: Li2MnSnS4

© 2015 Elsevier Inc. All rights reserved. High-temperature, solid-state synthesis in the Li2MnSnS4 system led to the discovery of two new polymorphic compounds that were analyzed using single crystal X-ray diffraction. The α-polymorph crystallizes in Pna21 with the lithium cobalt (II) silicate, Li2CoSiO4, structure type, where Z=4, R1=0.0349 and wR2=0.0514 for all data. The β-polymorph possesses the wurtz-kesterite structure type, crystallizing in Pn with Z=2, R1=0.0423, and wR2=0.0901 for all data. Rietveld refinement of synchrotron X-ray powder diffraction was utilized to quantify the phase fractions of the polymorphs in the reaction products. The α/β-Li2MnSnS4 mixture exhibits an absorption edge of ∼2.6-3.0 eV, a wide region of optical transparency in the mid- to far-IR, and moderate SHG activity over the fundamental range of 1.1-2.1 μm. Calculations using density functional theory indicate that the ground state energies and electronic structures for α- and β-Li2MnSnS4, as well as the hypothetical polymorph, γ-Li2MnSnS4 with the wurtz-stannite structure type, are highly similar

A First Look with JWST Aperture Masking Interferometry: Resolving Circumstellar Dust around the Wolf–Rayet Binary WR 137 beyond the Rayleigh Limit

Abstract We present infrared aperture-masking interferometry (AMI) observations of newly formed dust from the colliding winds of the massive binary Wolf–Rayet system WR 137 with JWST using the Near Infrared Imager and Slitless Spectrograph (NIRISS). NIRISS AMI observations of WR 137 and a point-spread function calibrator star, HD 228337, were taken using the F380M and F480M filters in 2022 July and August as part of the Director’s Discretionary Early Release Science program #1349. Interferometric observables (squared visibilities and closure phases) from the WR 137 “interferogram” were extracted and calibrated using three independent software tools: ImPlaneIA, AMICAL, and SAMpip. The analysis of the calibrated observables yielded consistent values except for slightly discrepant closure phases measured by ImPlaneIA. Based on all three sets of calibrated observables, images were reconstructed using three independent software tools: BSMEM, IRBis, and SQUEEZE. All reconstructed image combinations generated consistent images in both F380M and F480M filters. The reconstructed images of WR 137 reveal a bright central core with a ∼300 mas linear filament extending to the northwest. A geometric colliding-wind model with dust production constrained to the orbital plane of the binary system and enhanced as the system approaches periapsis provided a general agreement with the interferometric observables and reconstructed images. Based on a colliding-wind dust condensation analysis, we suggest that dust formation within the orbital plane of WR 137 is induced by enhanced equatorial mass loss from the rapidly rotating O9 companion star, whose axis of rotation is aligned with that of the orbit.</jats:p

Computational Simulations of Interactions of Scorpion Toxins with the Voltage-Gated Potassium Ion Channel

Based on a homology model of the Kv1.3 potassium channel, the recognitions of the six scorpion toxins, viz. agitoxin2, charybdotoxin, kaliotoxin, margatoxin, noxiustoxin, and Pandinus toxin, to the human Kv1.3 potassium channel have been investigated by using an approach of the Brownian dynamics (BD) simulation integrating molecular dynamics (MD) simulation. Reasonable three-dimensional structures of the toxin-channel complexes have been obtained employing BD simulations and triplet contact analyses. All of the available structures of the six scorpion toxins in the Research Collaboratory for Structural Bioinformatics Protein Data Bank determined by NMR were considered during the simulation, which indicated that the conformations of the toxin significantly affect both the molecular recognition and binding energy between the two proteins. BD simulations predicted that all the six scorpion toxins in this study use their β-sheets to bind to the extracellular entryway of the Kv1.3 channel, which is in line with the primary clues from the electrostatic interaction calculations and mutagenesis results. Additionally, the electrostatic interaction energies between the toxins and Kv1.3 channel correlate well with the binding affinities (−logK(d)s), R(2) = 0.603, suggesting that the electrostatic interaction is a dominant component for toxin-channel binding specificity. Most importantly, recognition residues and interaction contacts for the binding were identified. Lys-27 or Lys-28, residues Arg-24 or Arg-25 in the separate six toxins, and residues Tyr-400, Asp-402, His-404, Asp-386, and Gly-380 in each subunit of the Kv1.3 potassium channel, are the key residues for the toxin-channel recognitions. This is in agreement with the mutation results. MD simulations lasting 5 ns for the individual proteins and the toxin-channel complexes in a solvated lipid bilayer environment confirmed that the toxins are flexible and the channel is not flexible in the binding. The consistency between the results of the simulations and the experimental data indicated that our three-dimensional models of the toxin-channel complex are reasonable and can be used as a guide for future biological studies, such as the rational design of the blocking agents of the Kv1.3 channel and mutagenesis in both toxins and the Kv1.3 channel. Moreover, the simulation result demonstrates that the electrostatic interaction energies combined with the distribution frequencies from BD simulations might be used as criteria in ranking the binding configuration of a scorpion toxin to the Kv1.3 channel

Cell Cycle-dependent Phosphorylation and Ubiquitination of a G Protein α Subunit*

A diverse array of external stimuli, including most hormones and neurotransmitters, bind to cell surface receptors that activate G proteins. Mating pheromones in yeast Saccharomyces cerevisiae activate G protein-coupled receptors and initiate events leading to cell cycle arrest in G1 phase. Here, we show that the Gα subunit (Gpa1) is phosphorylated and ubiquitinated in response to changes in the cell cycle. We systematically screened 109 gene deletion strains representing the non-essential yeast kinome and identified a single kinase gene, ELM1, as necessary and sufficient for Gpa1 phosphorylation. Elm1 is expressed in a cell cycle-dependent manner, primarily at S and G2/M. Accordingly, phosphorylation of Gpa1 in G2/M phase leads to polyubiquitination in G1 phase. These findings demonstrate that Gpa1 is dynamically regulated. More broadly, they reveal how G proteins can simultaneously regulate, and become regulated by, progression through the cell cycle