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DOE OSTI2016

Anchorless forms of prion protein – Impact of truncation on structure destabilization and prion protein conversion

Prion diseases are a group of fatal neurodegenerative diseases caused by scrapie form of prion protein, PrP{sup Sc}. Prion protein (PrP) is bound to the cell via glycophosphatidylinositol (GPI) anchor. The role of GPI anchor in PrP{sup Sc} replication and propagation remains unclear. It has been shown that anchorless and truncated PrP accelerate the formation and propagation of prions in vivo and further increases the risk for transmission of prion diseases among species. To explain the role of anchorless forms of PrP in the development of prion diseases, we have prepared five C-terminal PrP truncated variants, determined their thermodynamic properties and analyzed the kinetics of conversion into amyloid fibrils. According to our results thermodynamic and kinetic properties are affected both by pH and truncation. We have shown that the shortest variant was the most destabilized and converted faster than other variants in acidic pH. Other variants converted with longer lag time of fibrillization than WT despite comparable or even decreased stability in acidic pH. Our results indicate that even the change in length for 1 amino acid residue can have a profound effect on in vitro conversion. - Highlights: • Truncation effects prion protein stability and fibrillization properties. • Protein destabilization and fibrillization properties are affected by pH and truncation. • Important intramolecular interactions between loop β{sub 2}−α{sub 2} and C-terminus of helix α{sub 3}.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2022

Destabilization of binary mixing layer in supercritical conditions

Compressible mixing layer instabilities are of importance to a wide range of environmental and industrial applications. Past studies have focused on either ideal-gas or real-fluid thermodynamic regimes of single-species mixing layers. However, mixing layers of binary mixtures at supercritical conditions, commonly encountered in fuel injection systems, introduce additional complexities due to the added compositional degree-of-freedom. Moreover, the effect of strong variations in thermodynamic response functions across the Widom line on the binary mixing layer stability remains poorly understood. Thus, the objective of this study is to examine the coupling between the hydrodynamic instability and the real-fluid thermodynamics across the Widom line and its effects on the overall binary mixing layer dynamics. To this end, we develop a linear stability analysis of the full binary-species compressible transport equations coupled with the PC-SAFT equation of state. Analysis shows the existence of a novel instability mechanism that arises from juxtapositioning of the Widom-line transition and the hydrodynamic inflection point. This novel thermodynamically induced instability mechanism has the net effect of destabilizing the binary mixing layer at lowering supercritical conditions towards the critical pressure point. This is in contrast to previous stability analyses of supercritical single-species mixing layers, where increasing pressure destabilizes the flow due to its effect on reducing the density stratification. The discovered thermodynamically induced instability mechanism of binary mixing flows highlights the need for an extension of classical instability criteria to incorporate the effect of strong variations in the thermodynamic response functions across the Widom line on mixing layer instability.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2022

Sulfur Geochemistry Destabilizes Population Oscillations of Wild Rice ( Zizania palustris )

Abstract Elevated inputs of sulfate to freshwater systems can increase sulfide concentrations in anoxic soils and subsequently destabilize aquatic plant populations, but the interactions between sulfate, other geochemical cycles, and interannual plant population cycles are poorly understood. Increased sulfate loading increases mineralization of nitrogen from litter, but the sulfide produced during this process can limit nitrogen uptake by plants. In some cases, iron may mitigate sulfide's impacts on plants by precipitating iron sulfide. We examined the interannual effects of sulfate loading on mesocosm populations of wild rice, an emergent aquatic plant that undergoes population oscillations and is sensitive to sulfide. Using experimental mesocosms with self‐perpetuating populations, we investigated how population dynamics respond to manipulations of surface water sulfate (10 mg L −1 or 300 mg L −1 ), sediment iron (4.3 mg g −1 or 10.9 mg g −1 dry weight), and shoot litter (present or removed). Populations exposed to constant 10 mg L −1 sulfate concentrations had stable biomass oscillations of approximately 3‐year periods, consistent with previous studies that demonstrated litter‐driven oscillations in nitrogen availability. Populations exposed to 300 mg L −1 sulfate concentrations produced fewer and smaller seeds and declined to extinction in 6 years or less. We did not find a strong effect of iron loading or litter removal on wild rice biomass or seed production. Our observations show the potential of elevated surface water sulfate to rapidly destabilize wild rice populations under varying iron and organic carbon concentrations.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Ion-driven destabilization of a toroidal electron plasma—A 3D3V PIC simulation

Ion-driven destabilization of a toroidal electron plasma in a small aspect ratio axisymmetric toroidal device is reported for A r + ions of different initial density values using a high fidelity 3D3V PIC solver. Stability of a recently discovered quiescent quasi-steady state (QQS) of a toroidal electron plasma obtained from “seed” solution as a result of entropy extremization at zero inertia is addressed in the presence of a small ion population. An initial value (f0) of the ion fraction (f = n i / n e) and the corresponding secondary electrons are “preloaded” into the system after the electron plasma attains a QQS state. This procedure is regarded as a proxy to the conventional production of ions in the experimental devices via impact ionization. The resulting electron plasma exhibits destabilized “center of charge motion” (m = 1) along with higher order harmonics with dominant power in the second harmonic. Gradual loss of ions (and also electrons) is observed resulting in time varying f values. Beyond a certain value of f0 (≥ 0.005), growth in wall probe current is observed, which saturates at later simulation time due to the loss of particles. In conclusion, trajectories of ion particles indicate ion trapping in the potential well, which is qualitatively similar to the ion resonance instability in pure electron plasmas.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2023

Cardiac troponin T N-domain variant destabilizes the actin interface resulting in disturbed myofilament function

Missense variant Ile79Asn in human cardiac troponin T (cTnT-I79N) has been associated with hypertrophic cardiomyopathy and sudden cardiac arrest in juveniles. cTnT-I79N is located in the cTnT N-terminal (TnT1) loop region and is known for its pathological and prognostic relevance. A recent structural study revealed that I79 is part of a hydrophobic interface between the TnT1 loop and actin, which stabilizes the relaxed (OFF) state of the cardiac thin filament. Given the importance of understanding the role of TnT1 loop region in Ca 2+ regulation of the cardiac thin filament along with the underlying mechanisms of cTnT-I79N-linked pathogenesis, we investigated the effects of cTnT-I79N on cardiac myofilament function. Transgenic I79N (Tg-I79N) muscle bundles displayed increased myofilament Ca 2+ sensitivity, smaller myofilament lattice spacing, and slower crossbridge kinetics. These findings can be attributed to destabilization of the cardiac thin filament’s relaxed state resulting in an increased number of crossbridges during Ca 2+ activation. Additionally, in the low Ca 2+ -relaxed state (pCa8), we showed that more myosin heads are in the disordered-relaxed state (DRX) that are more likely to interact with actin in cTnT-I79N muscle bundles. Dysregulation of the myosin super-relaxed state (SRX) and the SRX/DRX equilibrium in cTnT-I79N muscle bundles likely result in increased mobility of myosin heads at pCa8, enhanced actomyosin interactions as evidenced by increased active force at low Ca 2+ , and increased sinusoidal stiffness. These findings point to a mechanism whereby cTnT-I79N weakens the interaction of the TnT1 loop with the actin filament, which in turn destabilizes the relaxed state of the cardiac thin filament.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Flow-shear destabilization of multiscale electron turbulence

The impact of sheared ${\mathbf{E} \hskip -1pt \times \hskip -1pt \mathbf{B}}$ flow on multiscale turbulence is studied with nonlinear gyrokinetic simulations. Simulations are based on DIII-D-like, high-confinement mode (H-mode) pedestal parameters in the regime of low ion temperature gradient drive, where there is a broad spectrum of electron temperature gradient (ETG)-driven turbulence. It is found that ${\mathbf{E} \hskip -1pt \times \hskip -1pt \mathbf{B}}$ shear can have a significant effect on ETG-driven electron transport, with an unexpected transition from a turbulence stabilization regime at moderate to large shearing rates $γ_E$ to a novel turbulence destabilization regime at low levels of $γ_E$. In the turbulence stabilization regime, the electron energy flux decreases monotonically with $γ_E$, even when $γ_E$ is small compared to electron mode growth rates. The stabilizing effect comes dominantly from the electron, not ion, gyrokinetic equation. In the novel destabilization regime, reduction of zonal energy results from the interaction of $γ_E$-modulated nonlinear drive in the zonal ion gyrokinetic equation, increasing the electron transport over a broad range of shearing rates. Finally, neither of these effects has been observed in previous electron-scale simulations.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2025

Shafranov-shift destabilization of ballooning-type micro-instabilities

Contrary to common wisdom, we argue that the Shafranov shift is destabilizing for the ambient ballooning-type instabilities, which account for most of the transport flux in tokamak core plasmas. Higher Shafranov shift indeed reduces the magnetic drift frequency ω d , i.e. improves the bad curvature mildly, around the outboard midplane. However, this improvement is limited to a very narrow spatial region while ω d is increased over the remaining poloidal space. The eigenfunction averaged $\langle$ω d $\rangle$ is effectively enhanced due to the finite mode width of the eigenfunction and is thus destabilizing to the ballooning-type mode, as demonstrated by gyrokinetic simulations with the CGYRO code using local Miller equilibrium geometry. The predicted nonlinear flux also increases with Shafranov shift, consistent with linear simulations. The reduced transport model TGLF can capture the physics reasonably well.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2017

The ongoing destabilization of the mosul dam as observed by synthetic aperture radar interferometry

We present a detailed survey here on the ongoing destabilization process of the Mosul dam. The dam is located on the Tigris river and is the biggest hydraulic structure in Iraq. From a geological point of view the dam foundation is unstable due to the underlying geology that is formed by alternate and variable strata of highly soluble materials such as gypsum, anhydrite, marl and limestone. We present the first comprehensive multi-sensor cumulative deformation map for the dam generated from space-based synthetic aperture radar (SAR) measurements from the Italian constellation COSMO-SkyMed and the European Sentinel-1a satellite. We compared 2014-2016 data to an historic dataset spanning 2004-2010 acquired with the Envisat ASAR sensor. We found that deformation was rapid during 2004-2010, slowed down in 2012-2014, and restarted in August 2014 when grouting operations stopped due to the temporary capture of the dam by the self proclaimed Islamic State in Iraq and Syria (ISIS). We took advantage of the availability of data from multiple SAR satellites to infer the deformation at the dam in great spatial and temporal detail and shed new light on the processes of the ongoing destabilization. This study highlights how new constellations of SAR sensors together with the availability of historical datasets are leading to important advances in deformation monitoring of small scale geologic and manmade features.

58 GEOSCIENCES↗

DOE OSTI2025

Destabilizing a Social Network Model via Intrinsic Feedback Vulnerabilities

Social influence plays a significant role in shaping individual sentiments and actions, particularly in a world of ubiquitous digital interconnection. The rapid development of generative artificial intelligence (AI) has given rise to well-founded concerns regarding the potential implementation of radicalization techniques in social media. Motivated by these developments, we present a case study investigating the effects of small but intentional perturbations on a simple social network. We employ Taylor's classic model of social influence and tools from robust control theory (most notably the Dynamical Structure Function (DSF)), to identify perturbations that qualitatively alter the system's behavior while remaining as unobtrusive as possible. We examine two such scenarios: perturbations to an existing link and perturbations that introduce a new link to the network. In each case, we identify destabilizing perturbations of minimal norm and simulate their effects. Remarkably, we find that small but targeted alterations to network structure may lead to the radicalization of all agents, exhibiting the potential for large-scale shifts in collective behavior to be triggered by comparatively minuscule adjustments in social influence. Given that this method of identifying perturbations that are innocuous yet destabilizing applies to any suitable dynamical system, our findings emphasize a need for similar analyses to be carried out on real systems (e.g., real social networks), to identify the places where such dynamics may already exist.

Rogers, Lane [ORNL]↗

NASA NTRS1985

Destabilization of yttria-stabilized zirconia induced by molten sodium vanadate-sodium sulfate melts

The extent of surface destabilization of ZrO2 - 8 wt percent Y2O3 ceramic disks was determined after exposure to molten salt mixtures of sodium sulfate containing up to 15 mole percent sodium metavanadate (NaVO3) at 1173 K. The ceramic surface was observed to transform from the cubic/tetragonal to monoclinic phase, concurrent with chemical changes in the molten salt layer in contact with the ceramic. Significant attack rates were observed in both pure sulfate and metavanadate sulfate melts. The rate of attack was found to be quite sensitive to the mole fraction of vanadate in the molten salt solution and the partial pressure of sulfur trioxide in equilibrium with the salt melt. The observed parabolic rate of attack is interpreted to be caused by a reaction controlled by diffusion in the salt that penetrates into the porous layer formed by the destabilization. The parabolic rate constant in mixed sodium metavanadate - sodium sulfate melts was found to be proportional to the SO3 partial pressure and the square of the metavanadate concentration. In-situ Raman spectroscopic measurements allowed simultaneous observations of the ceramic phases and salt chemistry during the attack process.

Nagelberg, A. S.↗

NASA NTRS2000

Fingertip contact suppresses the destabilizing influence of leg muscle vibration

Touch of the hand with a stationary surface at nonmechanically supportive force levels (<1 N) greatly attenuates postural sway during quiet stance. We predicted such haptic contact would also suppress the postural destabilization caused by vibrating the right peroneus brevis and longus muscles of subjects standing heel-to-toe with eyes closed. In experiment 1, ten subjects were tested under four conditions: no-vibration, no-touch; no-vibration, touch; vibration, no-touch; and vibration, touch. A hand-held physiotherapy vibrator (120 Hz) was applied approximately 5 cm above the malleolous to stimulate the peroneus longus and brevis tendons. Touch conditions involved contact of the right index finger with a laterally positioned surface (<1 N of force) at waist height. Vibration in the absence of finger contact greatly increased the mean sway amplitude of the center of pressure and of the head relative to the no-vibration, no-touch control condition (P < 0.001). The touch, no-vibration and touch-vibration conditions were not significantly different (P > 0.05) from each other and both had significantly less mean sway amplitude of head and of center of pressure than the other conditions (P < 0.01). In experiment 2, eight subjects stood heel-to-toe under touch and no-touch conditions involving 40-s duration trials of peroneus tendon vibration at different duty cycles: 1-, 2-, 3-, and 4-s ON and OFF periods. The vibrator was attached to the subject's leg and remotely activated. In the no-touch conditions, subjects showed periodic postural disruptions contingent on the duty cycle and mirror image rebounds with the offset of vibration. In the touch conditions, subjects were much less disrupted and showed compensations occurring within 500 ms of vibration onset and mirror image rebounds with vibration offset. Subjects were able to suppress almost completely the destabilizing influence of the vibration in the 3- and 4-s duty cycle trials. These experiments show that haptic contact of the hand with a stable surface can suppress abnormal proprioceptive and motor signals in leg muscles.

NASA Discipline Neuroscience↗

NASA NTRS2008

Flight Results of the NF-15B Intelligent Flight Control System (IFCS) Aircraft with Adaptation to a Longitudinally Destabilized Plant

Adaptive flight control systems have the potential to be resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. The goal for the adaptive system is to provide an increase in survivability in the event that these extreme changes occur. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane. The adaptive element was incorporated into a dynamic inversion controller with explicit reference model-following. As a test the system was subjected to an abrupt change in plant stability simulating a destabilizing failure. Flight evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to stabilize the vehicle and reestablish good onboard reference model-following. Flight evaluation with the simulated destabilizing failure and adaptation engaged showed improvement in the vehicle stability margins. The convergent properties of this initial system warrant additional improvement since continued maneuvering caused continued adaptation change. Compared to the non-adaptive system the adaptive system provided better closed-loop behavior with improved matching of the onboard reference model. A detailed discussion of the flight results is presented.

Bosworth, John T.↗

DOE OSTI2021

Additive Destabilization of Porous Magnesium Borohydride Framework with Core--Shell Structure

Design of interfaces with thermodynamic and kinetic specificity is of great importance for hydrogen storage from both an applied and fundamental perspective. Here, in order to destabilize the metal hydride and protect the dehydrogenated products from oxidizing, a unique core-shell structure of porous Mg(BH4)2-based framework with a thin layer (no more than 5 nm) of MgCl2 additives on the surface, has been proposed and synthesized via a wet-chemical method. The local structure and electronic state of the present complex system are systematically investigated to understand the correlation between the distribution of additives and dehydrogenation property of Mg(BH4)2. A significant improvement is achieved for hydrogen desorption with chlorides: initial hydrogen release from MgCl2 decorated ..gamma..-phase Mg(BH4)2 particles commences at 100 °C and reaches a maximum of 9.4 wt% at 385 °C. Besides the decreased decomposition temperature, an activation barrier of about 76.4 kJ mol-1 lower than that of Mg(BH4)2 without MgCl2 is obtained. Moreover, MgCl2 decoration can also prevent the whole decomposed system (both Mg- and B- elements) from oxidizing, which is a necessary condition to reversibility.

74 ATOMIC AND MOLECULAR PHYSICS↗

NASA NTRS1993

The Swelling and Destabilization of a Coronal Mass Ejection (abstract)

We will present and discuss data for a bugle that was particularly well observed. Apparently the swelling of the bugle and its destabilization were caused by the newly emerging flux and its interaction with the pre-existing active regions and coronal structures.

bugle destabilization coronal mass ejection swelli↗

DOE OSTI2015

Kinetic Destabilization of Metal–Metal Single Bonds: Isolation of a Pentacoordinate Manganese(0) Monoradical

Abstract The 17e − monoradical [Mn(CO) 5 ] is widely recognized as an unstable organometallic transient and is known to dimerize rapidly with the formation of a MnMn single bond. As a result of this instability, isolable analogues of [Mn(CO) 5 ] have remained elusive. Herein, we show that two sterically encumbering isocyanide ligands can destabilize the MnMn bond leading to the formation of the isolable, manganese(0) monoradical [Mn(CO) 3 (CNAr Dipp2 ) 2 ] (Ar Dipp2 =2,6‐(2,6‐( i Pr) 2 C 6 H 3 ) 2 C 6 H 3 ). The persistence of [Mn(CO) 3 (CNAr Dipp2 ) 2 ] has allowed for new insights into nitrosoarene spin‐trapping studies of [Mn(CO) 5 ].

Agnew, Douglas W.↗

DOE OSTI2018

Dilution destabilizes engineered ligand-coated nanoparticles in aqueous suspensions

It is normally accurate that a diluted colloidal suspension is more stable over time than a concentrated one because dilution reduces collision rates of the particles and therefore delays the formation of aggregates. However, this generalization does not apply for some engineered ligand-coated nanoparticles (NPs). We observed the opposite relationship between stability and concentration of NPs. We tested 4 different types of NPs: CdSe-11-mercaptoundecanoic acid, CdTe-polyelectrolytes, Ag-citrate, and Ag-polyvinylpyrrolidone. The results reflected that dilution alone induced aggregation and subsequent sedimentation of the NPs that were originally monodispersed at very high concentrations. Increased dilution caused NPs to progressively become unstable in the suspensions. The extent of the dilution impact on the stability of NPs is different for different types of NPs. We hypothesize that the unavoidable decrease in free ligand concentration in the aqueous phase following dilution causes detachment of ligands from the suspended NP cores. The ligands attached to NP core surfaces must generally approach exchange equilibrium with free ligands in the aqueous phase; thus, ligand detachment and destabilization are expected consequences of dilution. More studies are necessary to test this hypothesis. Because the stability of NPs determines their physicochemical and kinetic behavior including toxicity, dilution-induced instability needs to be understood to realistically predict the behavior of engineered ligand-coated NPs in aqueous systems.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2023

Experimentally simulated sea level rise destabilizes carbon-mineral associations in temperate tidal marsh soil

How sea level rise (SLR) alters carbon (C) dynamics in tidal salt marsh soils is unresolved. Changes in hydrodynamics could influence organo-mineral associations, influencing dissolved organic carbon (DOC) fluxes. As SLR increases the duration of inundation, we hypothesize that lateral DOC export will increase due to reductive dissolution of C-bearing iron (Fe) oxides, destabilizing soil C stocks and influencing greenhouse gas emissions. To test this, soil cores (0–8 cm depth) were collected from the high marsh of a temperate salt marsh that currently experiences changes in water level and soil redox oscillation due to spring-neap tides. Mesocosms experimentally simulated SLR by continuously inundating high marsh soils and were compared to mesocosms with Control conditions, where the water level oscillated on a spring-neap cycle. Porewater DOC, lateral DOC, and porewater reduced Fe (Fe 2+ ) concentrations were significantly higher in SLR treatments (1.7 ± 0.5 mM, 0.63 ± 0.14 mM, and 0.15 ± 0.11 mM, respectively) than Control treatments (1.2 ± 0.35 mM, 0.56 ± 0.15 mM, and 0.08 ± 01 mM, respectively Solid phase analysis with Fe extended X-ray absorption fine-structure spectroscopy further revealed that SLR led to > 3 times less Fe oxide-C coprecipitates than Control conditions In addition, the overall global warming potential (GWP) decreased under SLR due to suppressed CO 2 emissions. Our data suggest that SLR may increase lateral C export of current C stocks by dissolving C-bearing Fe oxides but decrease the overall GWP from emissions of soil trace gases. Finally, these findings have implications for understanding the fate of SOC dynamics under future SLR scenarios.

dissolved organic carbon↗

DOE OSTI2018

Introduction of an extra tryptophan fluorophore by cataract-associating mutations destabilizes βB2-crystallin and promotes aggregation

Highlights: • S31W and R145W introduce an extra fluorophore in βB2-crystallin. • S31W and R145W destabilize βB2-crystallin and promote thermal aggregation. • S31W accelerates but R145W retards UV-induced aggregation of βB2-crystallin. • The number of Trp fluorophores in β/γ-crystallin is evolutionarily optimized. β/γ-Crystallins are predominant structural proteins in vertebrate lens with unique properties of extremely high solubility, long-term stability and resistance to UV damage. Four conserved Trp residues in β/γ-crystallins account for UV absorbance and thereafter fluorescence quenching to avoid photodamage. Herein we found that βB2-crystallin Trp fluorescence was greatly enhanced by the introduction of an extra unquenched Trp fluorophore by cataract-associated mutations S31W and R145W. Both mutations impaired oligomerization, decreased stability and promote thermal aggregation, while S31W was more deleterious. S31W accelerated βB2-crystallin aggregation under UV damaging conditions, whereas R145W delayed. These observations suggested that the introduction of an extra Trp fluorophore had complicated effects on βB2-crystallin stability and aggregation against various stresses. Our findings highlight that the number of Trp fluorophores in β/γ-crystallin is evolutionarily optimized to exquisitely perform their structural roles in the lens.

60 APPLIED LIFE SCIENCES↗