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At least 847 records · Page 47

Targeting Mycobacterium tuberculosis Persistence through Inhibition of the Trehalose Catalytic Shift

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is the leading cause of death worldwide by infectious disease. Treatment of Mtb infection requires a six-month course of multiple antibiotics, an extremely challenging regimen necessitated by Mtb’s ability to form drug-tolerant persister cells. Mtb persister formation is dependent on the trehalose catalytic shift, a stress-responsive metabolic remodeling mechanism in which the disaccharide trehalose is liberated from cell surface glycolipids and repurposed as an internal carbon source to meet energy and redox demands. Here, using a biofilm-persister model, metabolomics, and cryo-electron microscopy (EM), we found that azidodeoxy- and aminodeoxy-d-trehalose analogues block the Mtb trehalose catalytic shift through inhibition of trehalose synthase TreS (Rv0126), which catalyzes the isomerization of trehalose to maltose. Out of a focused eight-member compound panel constructed by chemoenzymatic synthesis, the natural product 2-trehalosamine exhibited the highest potency and significantly potentiated first- and second-line TB drugs in broth culture and macrophage infection assays. We also report the first structure of TreS bound to a substrate analogue inhibitor, obtained via cryo-EM, which revealed conformational changes likely essential for catalysis and inhibitor binding that can potentially be exploited for future therapeutic development. Our results demonstrate that inhibition of the trehalose catalytic shift is a viable strategy to target Mtb persisters and advance trehalose analogues as tools and potential adjunctive therapeutics for investigating and targeting mycobacterial persistence.

60 APPLIED LIFE SCIENCES↗

A magnetic analog of pressure–strain interaction

We study the evolution equation for magnetic energy density for a non-relativistic magnetized plasma in the (Lagrangian) reference frame comoving with the electron bulk velocity. Analyzing the terms that arise due to the ideal electric field, namely, perpendicular electron compression and magnetic field line bending, we recast them to reveal a quantity with a functional form analogous to the often-studied pressure–strain interaction term that describes one piece of internal energy density evolution of the species in a plasma, except with the species pressure tensor replaced by the magnetic stress tensor. We dub it the “magnetic stress–strain interaction.” We discuss decompositions of the magnetic stress–strain interaction analogous to those used for pressure–strain interaction. These analogies facilitate the interpretation of the evolution of the various forms of energy in magnetized plasmas and should be useful for a wide array of applications, including magnetic reconnection, turbulence, collisionless shocks, and wave–particle interactions. We display and analyze all the terms that can change magnetic energy density in the Lagrangian reference frame of the electrons using a particle-in-cell simulation of magnetic reconnection.

Barbhuiya, M. Hasan (ORCID:0000000163301650)↗

PPO foam - Liquid hydrogen insulation

An extensive fabrication and test program is described which has demonstrated the integrity of PPO (polyphenylene oxide) foam as an internal insulation. PPO is shown to be capable of withstanding multiple reuses on such cryogenic-fueled launch vehicles as the Space Shuttle. The major advantages of this internal insulation is the absence of a pressure load on the insulation, reduced handling damage, and minimization of cyclic thermal stresses by a 'warm' bond line.

Yates, G. B.↗

Stress-intensity factors for cracks emanating from the loaded fastener hole

Using a series approach and the Muskhelishvili formulation in the two-dimensional theory of elasticity, stress-intensity factors K are derived for problems in which cracks emanate radially from the boundary of an arbitrarily loaded internal circular hole in an infinite plate. Numerical values are obtained for K(I) and K(II) for radial cracks from a hole containing a loose-fitted pin or rivet that is pulled perpendicular to the crack direction in the plane of the plate. The method is a general one for determining K for a set of symmetrically emanating radial cracks for a variety of concentrated or distributed tractions on the circular hole.

Shivakumar, V.↗

Two-dimensiosnal electron beam charging model for polymer films

A two dimensional model was developed to describe the charging of thin polymer films exposed to a uniform mon-energetic electron beam. The study was motivated by observed anomalous behavior of geosynchronous satellites which was attributed to electrical discharges associated with the differential charging of satellite surfaces of magnetospheric electrons. Electric fields both internal and external to the irradiated specimen were calculated at steady state in order to identify regions of high electrical stress. Particular emphasis was placed on evaluating the charging characteristics near the material's edge. The model was used to identify and quantify the effects of some of the experimental parameters notably: beam energy; beam angle of incidence; beam current density; material thickness; and material width. Simulations of the following situations were also conducted: positive or negative precharging over part of the surface; a central gap in the material; and a discontinuity in the material's thickness.

Reeves, R. D.↗

Antarctica - Lessons for a Mars exploration program

The history of exploration and the international system of control of Antarctica has often been cited as a paradigm for the exploration of space. The small isolated research stations have been used to model the psychological stresses of future space missions. In addition, the programmatic structure of the U.S. Antarctic Research Program provides several possible analogs to future Mars Programs presently under discussion. These are: (1) Continued presence; (2) Civilian, military and private sector involvement; (3) Scientific activities; (4) Risk assessment and logistical support; (5) Accessibility for non-specialists; (6) Political and strategic motivations; (7) International cooperation/competition. Survival in Antarctica is contingent on advanced technology and the active transport of supplies. The scientific exploration of this remote and barren expanse without, of course, the aid and guidance of indigenous people certainly provides one of the closest analogs available to future science activities on the Martian surface.

Mckay, C. P.↗

Analysis of results from wind tunnel tests of inlets for an advanced turboprop nacelle installation

Inlets for tractor installations of advanced turboprop propulsion systems were tested in three phases, covering a period from November, 1982 to January, 1984. Nacelle inlet configuration types included single scoop, twin scoop, and annular arrangements. Tests were performed with and without boundary layer diverters and several different diverter heights were tested for the single scoop inlet. This same inlet was also tested at two different axial positions. Test Mach numbers ranged from Mach 0.20 to 0.80. Types of data taken were: (1) internal and external pressures, including inlet throat recoveries; (2) balance forces, including thrust-minus-drag; and (3) propellar blade stresses.

Hancock, J. P.↗

Computational prediction of isolated performance of an axisymmetric nozzle at Mach number 0.90

An improved ability to predict external propulsive performance was incorporated into the three-dimensional Navier-Stokes code PAB3D. The improvements are the ability to account for skin friction and external pressure forces. Performance parameters for two axisymmetric supersonic cruise nozzle configurations were calculated to test the improved methodology. Internal and external flow-field regions were computed using a two-equation kappa-epsilon turbulent viscous-stress model. The computed thrust-minus-drag ratios were within 1 percent of the absolute level of experimental data and the trends of data were predicted accurately. The predicted trend of integrated nozzle pressure drag matched the trend of the integrated experimental pressure drag over a range of nozzle pressure ratios, but absolute drag levels were not accurately predicted.

Carlson, John R.↗

Nonlinear Response of Thin Cylindrical Shells with Longitudinal Cracks and Subjected to Internal Pressure and Axial compression Loads

The results of an analytical study of the nonlinear response of a thin unstiffened aluminum cylindrical shell with a longitudinal crack are presented. The shell is analyzed with a nonlinear shell analysis code that maintains the shell in a nonlinear equilibrium state while the crack is grown. The analysis accurately accounts for global and local structural response phenomena. Results are presented for internal pressure, axial compression, and combined internal pressure and axial compression loads. The effects of varying crack length on the nonlinear response of the shell subjected to internal pressure are described. The effects of varying crack length on the prebuckling, buckling and postbuckling responses of the shell subjected to axial compression, and subjected to combined internal pressure and axial compression are also described. The results indicate that the nonlinear interaction between the in-plane stress resultants and the out-of-plane displacements near a crack can significantly affect the structural response of the shell. The results also indicate that crack growth instabilities and shell buckling instabilities can both affect the response of the shell as the crack length is increased.

Starnes, James H.↗

Skin, Stringer, and Fastener Loads in Buckled Fuselage Panels

The results of a numerical study to assess the effect of skin buckling on the internal load distribution in a stiffened fuselage panel, with and without longitudinal cracks, are presented. In addition, the impact of changes in the internal loads on the fatigue life and residual strength of a fuselage panel is assessed. A generic narrow-body fuselage panel is considered. The entire panel is modeled using shell elements and considerable detail is included to represent the geometric-nonlinear response of the buckled skin, cross section deformation of the stiffening components, and details of the skin-string attachment with discrete fasteners. Results are presented for a fixed internal pressure and various combinations of axial tension or compression loads. Results illustrating the effect of skin buckling on the stress distribution in the skin and stringer, and fastener loads are presented. Results are presented for the pristine structure, and for cases where damage is introduced in the form of a longitudinal crack adjacent to the stringer, or failed fastener elements. The results indicate that axial compression loads and skin buckling can have a significant effect on the circumferential stress in the skin, and fastener loads, which will influence damage initiation, and a comparable effect on stress intensity factors for cases with cracks. The effects on stress intensity factors will influence damage propagation rates and the residual strength of the panel.

Young, Richard D.↗

Burst Testing of Triaxial Braided Composite Tubes

Applications using triaxial braided composites are limited by the materials transverse strength which is determined by the delamination capacity of unconstrained, free-edge tows. However, structural applications such as cylindrical tubes can be designed to minimize free edge effects and thus the strength with and without edge stresses is relevant to the design process. The transverse strength of triaxial braided composites without edge effects was determined by internally pressurizing tubes. In the absence of edge effects, the axial and transverse strength were comparable. In addition, notched specimens, which minimize the effect of unconstrained tow ends, were tested in a variety of geometries. Although the commonly tested notch geometries exhibited similar axial and transverse net section failure strength, significant dependence on notch configuration was observed. In the absence of unconstrained tows, failure ensues as a result of bias tow rotation, splitting, and fracture at cross-over regions.

Triaxial Braided Composites↗

Experimental Comparison of Piezoelectric and Magnetostrictive Shunt Dampers

A novel mechanism called the vibration ring is being developed to enable energy conversion elements to be incorporated into the driveline of a helicopter or other rotating machines. Unwanted vibration is transduced into electrical energy, which provides a damping effect on the driveline. The generated electrical energy may also be used to power other devices (e.g., health monitoring sensors). PZT (piezoceramic) and PMN-30PT (single crystal) stacks, as well as a Tb_0.3 Dy_0.7 Fe_1.92 (Terfenol-D) rod with a bias magnet array and a pickup coil, were tested as alternative energy conversion elements to use within the vibration ring. They were tuned for broadband damping using shunt resistors, and dynamic compression testing was conducted in a high-speed load frame. Energy conversion was experimentally optimized at 750Hz by tuning the applied bias stress and resistance values. Dynamic testing was conducted up to 1000Hz to determine the effective compressive modulus, shunt loss factor, internal loss factor, and total loss factor. Some of the trends of modulus and internal loss factor versus frequency were unexplained. The single crystal device exhibited the greatest shunt loss factor whereas the Terfenol-D device had the highest internal and total loss factors. Simulations revealed that internal losses in the Terfenol-D device were elevated by eddy current effects, and an improved magnetic circuit could enhance its shunt damping capabilities. Alternatively, the Terfenol-D device may be simplified to utilize only the eddy current dissipation mechanism (no pickup coil or shunt) to create broadband damping.

energy conversion↗

Experimental Comparison of Piezoelectric and Magnetostrictive Shunt Dampers

A novel mechanism called the vibration ring is being developed to enable energy conversion elements to be incorporated into the driveline of a helicopter or other rotating machines. Unwanted vibration is transduced into electrical energy, which provides a damping effect on the driveline. The generated electrical energy may also be used to power other devices (e.g., health monitoring sensors). PZT (piezoceramic) and PMN-30%PT (single crystal) stacks, as well as a Tb_0.3 Dy_0.7 Fe_1.92 (Terfenol-D) rod with a bias magnet array and a pickup coil, were tested as alternative energy conversion elements to use within the vibration ring. They were tuned for broadband damping using shunt resistors, and dynamic compression testing was conducted in a high-speed load frame. Energy conversion was experimentally optimized at 750Hz by tuning the applied bias stress and resistance values. Dynamic testing was conducted up to 1000Hz to determine the effective compressive modulus, shunt loss factor, internal loss factor, and total loss factor. Some of the trends of modulus and internal loss factor versus frequency were unexplained. The single crystal device exhibited the greatest shunt loss factor whereas the Terfenol-D device had the highest internal and total loss factors. Simulations revealed that internal losses in the Terfenol-D device were elevated by eddy current effects, and an improved magnetic circuit could enhance its shunt damping capabilities. Alternatively, the Terfenol-D device may be simplified to utilize only the eddy current dissipation mechanism (no pickup coil or shunt) to create broadband damping.

piezoelectric↗

Space Shuttle Main Engine structural analysis and data reduction/evaluation. Volume 6: Primary nozzle diffuser analysis

The primary nozzle diffuser routes fuel from the main fuel valve on the Space Shuttle Main Engine (SSME) to the nozzle coolant inlet mainfold, main combustion chamber coolant inlet mainfold, chamber coolant valve, and the augmented spark igniters. The diffuser also includes the fuel system purge check valve connection. A static stress analysis was performed on the diffuser because no detailed analysis was done on this part in the past. Structural concerns were in the area of the welds because approximately 10 percent are in areas inaccessible by X-ray testing devices. Flow dynamics and thermodynamics were not included in the analysis load case. Constant internal pressure at maximum SSME power was used instead. A three-dimensional, finite element method was generated using ANSYS version 4.3A on the Lockheed VAX 11/785 computer to perform the stress computations. IDEAS Supertab on a Sun 3/60 computer was used to create the finite element model. Rocketdyne drawing number RS009156 was used for the model interpretation. The flight diffuser is denoted as -101. A description of the model, boundary conditions/load case, material properties, structural analysis/results, and a summary are included for documentation.

Foley, Michael J.↗

A fully associative, nonisothermal, nonlinear kinematic, unified viscoplastic model for titanium alloys

Specific forms for both the Gibb's and complementary dissipation potentials are chosen such that a complete (i.e., fully associative) potential base multiaxial, nonisothermal unified viscoplastic model is obtained. This model possesses one tensorial internal state variable (that is, associated with dislocation substructure) and an evolutionary law that has nonlinear kinematic hardening and both thermal and strain induced recovery mechanisms. A unique aspect of the present model is the inclusion of nonlinear hardening through the use of a compliance operator, derived from the Gibb's potential, in the evolution law for the back stress. This nonlinear tensorial operator is significant in that it allows both the flow and evolutionary laws to be fully associative (and therefore easily integrated), greatly influences the multiaxial response under non-proportional loading paths, and in the case of nonisothermal histories, introduces an instantaneous thermal softening mechanism proportional to the rate of change in temperature. In addition to this nonlinear compliance operator, a new consistent, potential preserving, internal strain unloading criterion has been introduced to prevent abnormalities in the predicted stress-strain curves, which are present with nonlinear hardening formulations, during unloading and reversed loading of the external variables. The specific model proposed is characterized for a representative titanium alloy commonly used as the matrix material in SiC fiber reinforced composites, i.e., TIMETAL 21S. Verification of the proposed model is shown using 'specialized' non-standard isothermal and thermomechanical deformation tests.

Arnold, S. M.↗

In-service Oxidation and IASCC in High Fluence Baffle-Former Bolts Retrieved from a Westinghouse PWR

Baffle-former bolts (BFBs) are subjected to significant mechanical stress and neutron irradiation from the reactor core during the plant operation. Over the long operation period, these conditions lead to potential degradation and reduced load-carrying capacity of the bolts, and life extension of existing pressurized water reactors (PWRs) would only cause more damage to the bolt material. To this end, the Light Water Reactor Sustainability (LWRS) Program Materials Research Pathway (MRP) successfully harvested two high fluence BFBs from a Westinghouse two-loop downflow type PWR in 2016. In the same year, the two BFBs were received at the Westinghouse Churchill facility for inspection and specimen fabrication. The fabrication was completed in 2017 with specimens shipped to Oak Ridge National Laboratory (ORNL) for further testing. The objective of this project is to provide information that is integral to evaluating end of life microstructure and properties as a benchmark of international models developed for predicting radiation-induced swelling, segregation, precipitation, mechanical property degradation, and with the latest findings, susceptibility to irradiation-assisted stress corrosion cracking (IASCC).

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Spacelab - Ten years of international cooperation

The history, current status, and future plans of the Spacelab program are reviewed, with a focus on the cooperative relationship between ESA and NASA. The initial decision to undertake the program and the three agreements signed to begin its implementation are examined, and the division of responsibilities and financial contributions is discussed insofar as it affected the management structure. Consideration is given to the major facilities, the 50-mission operational cycle, communications, the currently scheduled activities (through 1985), the prospective later uses, and the ten dedicated discipline laboratories. The importance of continuous mutual support during the planning and development phases is stressed. The program so far is considered a success, in terms of the goals set by the participants and in terms of the resolution of the problems inherent in international technological endeavors.

Bignier, M.↗