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Structure-performance relationships in lignin-based transesterification vitrimers: The role of lignin structural features
Toxoplasma gondii, an Apicomplexan parasite, causes significant morbidity and mortality, including severe disease in immunocompromised hosts and devastating congenital disease, with no effective treatment for the bradyzoite stage. To address this, we used the Tropical Disease Research database, crystallography, molecular modeling, and antisense to identify and characterize a range of potential therapeutic targets for toxoplasmosis. Phosphoglycerate mutase II (PGMII), nucleoside diphosphate kinase (NDK), ribulose phosphate 3-epimerase (RPE), ribose-5-phosphate isomerase (RPI), and ornithine aminotransferase (OAT) were structurally characterized. Crystallography revealed insights into the overall structure, protein oligomeric states and molecular details of active sites important for ligand recognition. Literature and molecular modeling suggested potential inhibitors and druggability. The targets were further studied with vivoPMO to interrupt enzyme synthesis, identifying the targets as potentially important to parasitic replication and, therefore, of therapeutic interest. Targeted vivoPMO resulted in statistically significant perturbation of parasite replication without concomitant host cell toxicity, consistent with a previous CRISPR/Cas9 screen showing PGM, RPE, and RPI contribute to parasite fitness. PGM, RPE, and RPI have the greatest promise for affecting replication in tachyzoites. These targets are shared between other medically important parasites and may have wider therapeutic potential.
The behavior of the axial group speeds of trapped sausage modes plays an important role in determining impulsively generated wave trains, which have often been invoked to account for quasi-periodic signals with quasi-periods of the order of seconds in a considerable number of coronal structures. We conduct a comprehensive eigenmode analysis, both analytically and numerically, on the dispersive properties of sausage modes in pressureless tubes with three families of continuous radial density profiles. We find a rich variety of the dependence on the axial wavenumber k of the axial group speed v{sub gr}. Depending on the density contrast and profile steepness as well as on the detailed profile description, the v{sub gr}--k curves either possess or do not possess cutoff wavenumbers, and they can behave in either a monotonical or non-monotonical manner. With time-dependent simulations, we further show that this rich variety of the group speed characteristics heavily influences the temporal evolution and Morlet spectra of impulsively generated wave trains. In particular, the Morlet spectra can look substantially different from the “crazy tadpoles” found for the much-studied discontinuous density profiles. We conclude that it is necessary to re-examine available high-cadence data to look for the rich set of temporal and spectral features that can be employed to discriminate between the unknown forms of the density distributions transverse to coronal structures.
Yeast tRNA ligase (Trl1) is an essential trifunctional enzyme that catalyzes exon-exon ligation during tRNA biogenesis and the non-conventional splicing of HAC1 mRNA during the unfolded protein response (UPR). The UPR regulates the protein folding capacity of the endoplasmic reticulum (ER). ER stress activates Ire1, an ER-resident kinase/RNase, which excises an intron from HAC1 mRNA followed by exon-exon ligation by Trl1. The spliced product encodes for a potent transcription factor that drives the UPR. Here we report the crystal structure of Trl1 RNA ligase domain from Chaetomium thermophilum at 1.9 Å resolution. Structure-based mutational analyses uncovered kinetic competition between RNA ligation and degradation during HAC1 mRNA splicing. Incompletely processed HAC1 mRNA is degraded by Xrn1 and the Ski/exosome complex. We establish cleaved HAC1 mRNA as endogenous substrate for ribosome-associated quality control. We conclude that mRNA decay and surveillance mechanisms collaborate in achieving fidelity of non-conventional mRNA splicing during the UPR.
Structural design synthesis of recoverable launch vehicle structures
Structural analysis of Injun 5 spacecraft structure
Determination of magnitude of structural over-test received by spacecraft structures when qualified in reverberant rooms
Development of expandable structures concepts for application to structures used in space missions - Part 2
Specimens representative of metal aircraft structural components reinforced with boron filamentary composites were manufactured and tested under cyclic loading, cyclic temperature, or continuously applied loading to evaluate some of the factors that affect structural integrity under cyclic conditions. Bonded, stepped joints were used throughout to provide composite-to-metal transition regions at load introduction points. Honeycomb panels with titanium or aluminum faces reinforced with unidirectional boron composite were fatigue tested at constant amplitude under completely reversed loading. Results indicated that the matrix material was the most fatigue-sensitive part of the design, with debonding initiating in the stepped joints. However, comparisons with equal weight all-metal specimens show a 10 to 50 times improved fatigue life. Fatigue crack propagation and residual strength were studied for several different stiffened panel concepts, and were found to vary considerably depending on the configuration. Composite-reinforced metal specimens were also subjected to creep and thermal cycling tests. Thermal cycling of stepped joint tensile specimens resulted in a ten percent decrease in residual strength after 4000 cycles.
A method of predicting broadband random vibration criteria for components on space vehicles is presented. Large amounts of vibration and acoustic data obtained from flights and static firing tests of space vehicle were formulated into vibroacoustic data banks for structural categories of ring frame, skin stringer, and honeycomb. The vibration spectra with their associated acoustic spectra are normalized to a reference acoustic spectrum. The individual normalized spectra are grouped according to definite structural characteristics and statistically analyzed to form the vibroacoustic data banks described in this report. These data banks represent the reference vibration criteria available for determining the new vehicle vibration criteria.
New design and programming techniques for shuttle software. Based on previous Apollo experience, recommendations are made to apply top-down structured programming techniques to shuttle software. New software verification techniques for large software systems are recommended. HAL, the higher order language selected for the shuttle flight code, is discussed and found to be adequate for implementing these techniques. Recommendations are made to apply the workable combination of top-down, bottom-up methods in the management of shuttle software. Program structuring is discussed relevant to both programming and management techniques.
The use of a structural synthesis computer program to design components for a heavy lift launch vehicle is defined. A loads program was used to determine the vehicle shears, bending moments, and axial loads at two design loading conditions. A comparison was made between results from the structures program and the results of a weight estimating program which used historical data in determining component weights.
The dynamics and stability of large orbiting flexible beams, and platforms and dish type structures oriented along the local horizontal are treated both analytically and numerically. It is assumed that such structures could be gravitationally stabilized by attaching a rigid light-weight dumbbell at the center of mass by a spring loaded hinge which also could provide viscous damping. For the beam, the small amplitude inplane pitch motion, dumbbell librational motion, and the anti-symmetric elastic modes are all coupled. The three dimensional equations of motion for a circular flat plate and shallow spherical shell in orbit with a two-degree-of freedom gimballed dumbbell are also developed and show that only those elastic modes described by a single nodal diameter line are influenced by the dumbbell motion. Stability criteria are developed for all the examples and a sensitivity study of the system response characteristics to the key system parameters is carried out.
A number of missions for the space shuttle were proposed which involve placing large truss platforms on-orbit. These platforms range in size from tens of meters in span for reflector application to several thousand meters for solar power collector application. These proposed sizes and the operational requirements considered are unconventional in comparison to Earthbound structures and little information exists concerning efficient proportions of the structural elements forming the framework of the platforms. Such proportions are of major concern because they have a strong influence on the packaging efficiency and, thus, the transportation effectiveness of the shuttle. The present study is undertaken to: (1) identify efficient ranges of application of deployable and erectable platforms configured for shuttle transport to orbit, and (2) determine sensitivity to key parameters of minimum mass deployable and erectable platform designs.
The feasibility of fabricating beams in space and using them as components of a large, crew assembled structure, was investigated. Two projects were undertaken: (1) design and development of a ground version of an automated beam builder capable of producing triangular cross section aluminum beams; and (2) design and fabrication of lap joints to connect the beams orthogonally and centroidal end caps to connect beams end to end at any desired angle. The first project produced a beam building machine which fabricates aluminum beams suitable for neutral buoyancy evaluation. The second project produced concepts for the lap joint and end cap. However, neither of these joint concepts was suitable for use by a pressure suited crew member in a zero gravity environment. It is concluded that before the beams can be evaluated the joint designs need to be completed and sufficient joints produced to allow assembly of a complex structure.
The Space Transportation System (STS) is used for technology experiments in space. The Space Technology Experiment Platform (STEP) is a Shuttle-borne experiment support facility for use by structures, structural dynamics, and controls technology flight experiments. STEP represents a key element in the commitment to STS utilization. The STEP concept and definition process is discussed, and the results obtained to date on the configuration and function capability are summarized, and preliminary schedule information is presented.
The present study is concerned with a Land Mobile Satellite System (LMSS) which can provide mobile communications for commercial and government applications in nonmetropolitan areas of the continental U.S. and Canada as an augmentation to existing and planned terrestrial systems. The satellite system would provide 'narrow band' telecommunications services, thin-route fixed telephone and data services in the 806-890 MHz band, and continuous emergency beacon monitoring in the 406-406.1 MHz band. It is pointed out that a satellite system operating in concert with terrestrial cellular systems could provide truly ubiquitous mobile communications services in the U.S. and Canada. A single shuttle shuttle launch could place the LMSS spacecraft in geosynchronous orbit over the continental U.S. in 1995 with a 10-year lifetime. Attention is given to the structural concepts, a weight analysis, and a structural analysis.
The development of a thermal and structural model for a hypersonic wing test structure using the NASTRAN finite-element method as its primary analytical tool is described. A detailed analysis was defined to obtain the temperature and thermal stress distribution in the whole wing as well as the five upper and lower root panels. During the development of the models, it was found that the thermal application of NASTRAN and the VIEW program, used for the generation of the radiation exchange coefficients, were definicent. Although for most of these deficiencies solutions could be found, the existence of one particular deficiency in the current thermal model prevented the final computation of the temperature distributions. A SPAR analysis of a single bay of the wing, using data converted from the original NASTRAN model, indicates that local temperature-time distributions can be obtained with good agreement with the test data. The conversion of the NASTRAN thermal model into a SPAR model is recommended to meet the immediate goal of obtaining an accurate thermal stress distribution.