The expanding amyloid family: Structure, stability, function, and pathogenesis
Not Available
Sawaya, Michael R.↗
SEARCH · Engineering Papers
Results for “family stability”
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Robust stability of diamond families of polynomials with complex coefficients
Like the interval model of Kharitonov, the diamond model proves to be an alternative powerful device for taking into account the variation of parameters in prescribed ranges. The robust stability of some kinds of diamond polynomial families with complex coefficients are discussed. By exploiting the geometric characterizations of their value sets, we show that, for the family of polynomials with complex coefficients and both their real and imaginary parts lying in a diamond, the stability of eight specially selected extreme point polynomials is necessary as well as sufficient for the stability of the whole family. For the so-called simplex family of polynomials, four extreme point and four exposed edge polynomials of this family need to be checked for the stability of the entire family. The relations between the stability of various diamonds are also discussed.
Xu, Zhong Ling↗
Familial Alzheimer mutations stabilize synaptotoxic γ-secretase-substrate complexes
Mutations that cause familial Alzheimer’s disease (FAD) are found in amyloid precursor protein (APP) and presenilin, the catalytic component of γ-secretase, that together produce amyloid β-peptide (Aβ). Nevertheless, whether Aβ is the primary disease driver remains controversial. We report here that FAD mutations disrupt initial proteolytic events in the multistep processing of APP substrate C99 by γ-secretase. Cryoelectron microscopy reveals that a substrate mimetic traps γ-secretase during the transition state, and this structure aligns with activated enzyme-substrate complex captured by molecular dynamics simulations. In silico simulations and in cellulo fluorescence microscopy support stabilization of enzyme-substrate complexes by FAD mutations. Neuronal expression of C99 and/or presenilin-1 in Caenorhabditis elegans leads to synaptic loss only with FAD-mutant transgenes. Designed mutations that stabilize the enzyme-substrate complex and block Aβ production likewise led to synaptic loss. Collectively, these findings implicate the stalled process—not the products—of γ-secretase cleavage of substrates in FAD pathogenesis.
59 BASIC BIOLOGICAL SCIENCES↗
Presentation of flight control design and handling quality commonality by separate surface stability augmentation for the family of commuter airplanes
The methodology and results for a flight control design and implementation for common handling qualities by Separate Surface Stability Augmentation (SSSA) for the family of commuter airplanes are contained. The open and closed loop dynamics and the design results of augmenting for common handling qualities are presented. The physical and technology requirements are presented for implementing the SSSA system. The conclusion of this report and recommendations for changes or improvement are discussed.
Hensley, Douglas↗
Directed Gas-Phase Formation of The Propargyl Family of Resonance-Stabilized Radicals in The Reactions of Ground-State Carbon Atoms (C; 3 P j ) with Butene Isomers (C 4 H 8 ): Dimethylpropargyl and Ethylpropargyl
The propargyl radical (C 3 H 3 ) is the simplest resonance-stabilized free radical (RSFR), but how does stepwise methyl substitution in the alkene reactant affect its dynamics of their formation? We report a crossed molecular beam study of the reactions of atomic carbon (C, 3 P j ) with four butene isomers (C 4 H 8 ) under single collision conditions at a collision energy of 28 ± 2 kJ mol −1 . Barrierless addition of atomic carbon to the alkene C=C bond triggers ring opening to triplet substituted allenes—a de facto insertion mechanism—followed by unimolecular decomposition via atomic hydrogen (H), methyl (CH 3 ) or ethyl (C 2 H 5 ) loss, yielding a family of propargyl‑type RSFRs. RRKM calculations reveal that the branching ratios are highly sensitive to the alkene structure. While the methyl loss channel, affording 1‑methylpropargyl, dominates for 2 butenes (80–90%), the predicted hydrogen atom loss channel (≈10%) leading to 1,3 dimethylpropargyl is identified in the experiment by comparison with theoretical energetics. For isobutene, a near‑equal competition is seen, with the reaction producing 3‑methylpropargyl (≈50%) and 1,1‑dimethylpropargyl (≈40%), along with 2‑vinylallyl (≈5%), whose formation is supported by the experimental data. Most notably, the reaction with 1 butene uniquely favors an enthalpically driven hydrogen shift, eventually producing 1 vinylallyl (≈38%), which is assigned based on the excellent agreement between the measured and calculated reaction exothermicity. Rapid entropically favored fragmentation channels yield ≈40% of propargyl type species (propargyl, 1- and 3-ethylpropargyls), slightly outcompeting the allyl type product. Furthermore, these results establish a systematic progression from C 2 H 4 to C 4 H 8 , where the increasing alkyl substitution unlocks new fragmentation channels, providing a versatile gas phase route to alkylated RSFRs—key intermediates in the growth of methylated and ethylated PAHs and aliphatic chains in combustion and cold interstellar environments (molecular clouds).
Alkyls↗
A FAMILY OF HIGH-STABILITY GRANITE STAGES FOR| SYNCHROTRON APPLICATIONS
Engineers at the APS have developed a granite, air-bear- ing stage concept that provides many millimeters of motion range and nanometer-level vibrational stability. This technique was first conceptualized and used on the Velociprobe x-ray microscope [1, 2]. The success of that design spurred adaption of the approach to over 90 devices, including many new instruments at the APS [3] and high performing instruments at other synchrotrons [4]. This paper details the design concept, some performance measurements, and new developments allowing for a six-degree-of-freedom device.
Preissner, C. A.↗
Axisymmetric shapes and stability of isolated charged drops
Axisymmetric equilibrium shapes and stability of isolated charged drops are found by solving simultaneously the Young-Laplace equation for surface shape and the Laplace equation for the electric field. Families of two-, three-, and four-lobed shapes that branch from the trunk family of spheres are treated systematically by means of the Galerkin/finite element method and a tessellation that deforms with the free surface. The results show that at the limit found by Rayleigh in 1882 the spherical family exchanges stability with a family of two-lobed shapes, a transcritically bifurcating family, one arm of which proves to consist of stable shapes. The results are reinforced by those of approximating the stable drop shapes as oblate spheroids. Thus oblate drops carrying charge in excess of the Rayleigh limit ought to be seen in experiments, though none have yet been reported.
Basaran, O. A.↗
Error-correcting codes for fermionic quantum simulation
Utilizing the framework of \mathbb{Z}_2 ℤ 2 lattice gauge theories in the context of Pauli stabilizer codes, we present methodologies for simulating fermions via qubit systems on a two-dimensional square lattice. We investigate the symplectic automorphisms of the Pauli module over the Laurent polynomial ring. This enables us to systematically increase the code distances of stabilizer codes while fixing the rate between encoded logical fermions and physical qubits. We identify a family of stabilizer codes suitable for fermion simulation, achieving code distances of d=2,3,4,5,6,7, allowing correction of any \lfloor \frac{d-1}{2} \rfloor ⌊ d − 1 2 ⌋ -qubit error. In contrast to the traditional code concatenation approach, our method can increase the code distances without decreasing the (fermionic) code rate. In particular, we explicitly show all stabilizers and logical operators for codes with code distances of d=3,4,5. We provide syndromes for all Pauli errors and invent a syndrome-matching algorithm to compute code distances numerically.
Physics↗
Novel Ultrabright and Air-Stable Photocathodes Discovered from Machine Learning and Density Functional Theory Driven Screening
The high brightness, low emittance electron beams achieved in modern X-ray free-electron lasers (XFELs) have enabled powerful X-ray imaging tools, allowing molecular systems to be imaged at picosecond time scales and sub-nanometer length scales. One of the most promising directions for increasing the brightness of XFELs is through the development of novel photocathode materials. Whereas past efforts aimed at discovering photocathode materials have typically employed trial-and-error-based iterative approaches, this work represents the first data-driven screening for high brightness photocathode materials. Through screening over 74 000 semiconducting materials, a vast photocathode dataset is generated, resulting in statistically meaningful insights into the nature of high brightness photocathode materials. This screening results in a diverse list of photocathode materials that exhibit intrinsic emittances that are up to 4x lower than currently used photocathodes. In a second effort, multiobjective screening is employed to identify the family of M 2 O (M = Na, K, Rb) that exhibits photoemission properties that are comparable to the current state-of-the-art photocathode materials, but with superior air stability. This family represents perhaps the first intrinsically bright, visible light photocathode materials that are resistant to reactions with oxygen, allowing for their transport and storage in dry air environments.
36 MATERIALS SCIENCE↗
Metal forming and working of stabilized nanocrystalline Cu-Ta for electrical contacts
The commercialization of nanocrystalline metals and alloys is currently entering a renaissance period. Many of the processing and consolidation challenges that have haunted them are now more fully understood, opening the doors for stabilized nanocrystalline metals to be produced on a bulk scale. While challenges remain, the increased volume at which these materials are being supplied is for the first time allowing for investigations into more traditional methods of metal working, such as extruding, rolling, forming, and forging. Recently, the manufacturing science has been developed to allow nanocrystalline Cu-Ta alloys to progress to this point. This article therefore builds upon the last decade of evolutionary progression within the family of stabilized nanocrystalline Cu-Ta alloys by presenting some of the first findings related to scaled powder synthesis, production of billets, thin sheets, and foils. Here, the mechanical performance and physical properties relevant to forming electrical contacts and pins including, tensile, J-integral fracture toughness, Charpy Impact, bi-axial tension, and conductivity are reported. This introductory investigation into forming such a novel material, provides evidence to these alloys potential at bridging the gap between being a scientific curiosity to that of a real engineering material.
36 MATERIALS SCIENCE↗
Thermodynamics Drives the Stability of the MOF-74 Family in Water
Not Available
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
2019 Community Involvement Report
Sandia National Laboratories is committed to being an informed, compassionate and contributing neighbor in our local communities. This commitment has been demonstrated throughout Sandia's history, and is an enduring part of our future. New Mexico faces many challenges, including one of the highest childhood poverty rates in the United States and one of the lowest educational proficiency rates. Lack of affordable housing and insufficient educational achievement are issues in the Bay Area near our Livermore site. To address the greatest challenges faced in Sandia's communities of Albuquerque, NM, and Livermore, CA, and other remote sites, Sandia's contributions leverage resources in three critical focus areas. In 2019, National Technology and Engineering Solutions of Sandia, contributed $1.4M to our local communities, including $151K in the Livermore area.
99 GENERAL AND MISCELLANEOUS↗
From War to Work: Risks, Challenges, and Evidence-Based Strategies Across the Military Deployment Cycle
This report examines what happens when military service members return from deployment and reenter family life and civilian work. Reintegration is an evolving process shaped by an individual’s military experience and potential combat trauma, family dynamics, and workplace conditions, and it occurs within a broader social context. Reintegration varies widely depending on deployment experiences, the preparedness of families, the stability of home and work environments, and whether a person served on active duty or in the reserves. What emerges consistently across U.S., Israeli, and allied nation studies is the same core insight: Reintegration is deeply individual, often nonlinear, and profoundly influenced by the systems surrounding the returning veteran.
Combat Service Support↗
Cloud Computing Methods for Near Rectilinear Halo Orbit Trajectory Design
Complicated mission design problems require innovative computational solutions. As spacecraft depart from a proposed Gateway in a Near Rectilinear Halo Orbit (NRHO), recontact analysis is required to avoid risk of collision and ensure safe operations. Escape dynamics from NRHOs are governed by multiple gravitational bodies, yielding a trajectory design space that is exhaustively large. This paper summarizes the recontact analysis for departure from the NRHO and describes how the Deep Space Trajectory Explorer (DSTE) trajectory design software incorporates high performance cloud computing to compute and visualize the orbit design space. Recent focus on exploration missions to cislunar space has kindled accelerated interest in multibody orbit solutions. Trajectory analysis in the presence of multiple gravity fields is complex, and innovative computational tools are needed to simplify complicated design spaces, to generate large quantities of data quickly, and to visualize the output for user accessibility. The Gateway mission is a prime example. The Gateway1 is proposed as a human outpost in deep space. The current baseline orbit for the Gateway is a Near Rectilinear Halo Orbit (NRHO) near the Moon.2 The NRHO exists in a regime that experiences the gravitational effects of the Earth and the Moon simultaneously, complicating orbit analysis. The mission design process benefits greatly from updated computational tools for multibody missions like the Gateway. As an example, consider the problem of assessing the risk of collision in an NRHO. As a staging location to missions to the lunar surface and beyond the Earth-Moon system, the Gateway will experience spacecraft and other objects regularly arriving and departing. Departing objects potentially include spent logistics modules, visiting crew vehicles, debris objects, wastewater particles, and cubesats. Each departure is governed by the dynamics of the Gateway orbit and the surrounding dynamical environment. Over time, any unmaintained object in such an orbit eventually departs due to the small instabilities associated with the NRHOs. A separation maneuver speeds the departure from the NRHO, but the effects of the maneuver on the spacecraft behavior depend on the location, magnitude, and direction of the burn. Escape dynamics from the NRHO with regard to these maneuver options open up an enormous potential trajectory design space where subtle changes in input can produce dramatically large changes in the results. Any departing object must avoid recontacting the Gateway as it leaves the lunar vicinity, and a recontact analysis thus involves a significant number of computations and extensive output data. To explore the dynamics of this extensive design space, the Deep Space Trajectory Explorer3 (DSTE) trajectory design software incorporates new High Performance Computing (HPC) services and novel interactive visualizations. This paper details the HPC and cloud infrastructure techniques that are implemented in the DSTE, applying the new capabilities to analysis of recontact risk with the Gateway in NRHO. NEAR RECTILINEAR HALO ORBITS The Gateway is planned to fly in a lunar NRHO as its baseline orbit. The NRHO families of orbits are subsets of the larger halo families, which originate from planar orbits near the L1 and L2 libration points; the Earth-Moon L2 halo family appears in Figure 1. Each halo orbit is perfectly periodic in the Circular Restricted 3-Body Problem (CR3BP) and becomes a quasi-periodic orbit in a higher fidelity ephemeris force model. The NRHOs are defined as those members of the halo family with bounded stability properties;2 they pass near the Moon at perilune and are nearly polar. Families exist with apolunes located both above the lunar north pole and above the lunar south pole; the Gateway is planned to reside in a southern L2 NRHO in a 9:2 resonance with the lunar synodic period. The 9:2 NRHO is characterized by a period of about 6.5 days, a perilune radius of about 3,500 km, and an apolune radius of about 71,000 km; it is strongly affected by the gravity of both the Earth and the Moon simultaneously. This NRHO offers extended communications with assets on the south pole of the Moon,4 as well as low-cost orbit maintenance and attitude control,5 favorable eclipse avoidance properties,6 and inexpensive transfers from Earth and to other destinations.5,7 The NRHO portion of the southern L2 halo family is highlighted in black in Figure 1, and the 9:2 NRHO appears in blue.
Phillips, Sean M.↗
L2-stability of distributed feedback systems: Singular perturbation
A continuous time, single input-single output, linear, time-invariant, distributed feedback system F sup epsilon, containing a small delay of length epsilon in the loop, is considered. Conditions are given under which L2-stability and L2-instability of this feedback system can be deduced from those of the reduced model obtained by neglecting the delay. The two system models associated with F sup epsilon are the low-frequency model F and the high frequency model F. The condition for neglecting the small delay is the L2-stability of the family of high-frequency models, where epsilon or = 0 is sufficiently small. A lemma and a theorem are given. The lemma gives sharp Nyquist-type conditions for the L2-stability and L2-instability of the family of high frequency models for sufficiently small epsilon or = 0, while the Theorem gives explicit conditions under which the small delay may or may not be neglected.
Barman, J. F.↗
A widespread family of molecular chaperones promotes the intracellular stability of type VIIb secretion system– exported toxins
To survive in highly competitive environments, bacteria use specialized secretion systems to deliver antibacterial toxins into neighboring cells, thereby inhibiting their growth. In many Gram-positive bacteria, the export of such toxins requires a membrane-bound molecular apparatus known as the type VIIb secretion system (T7SSb). Recently, it was shown that toxin recruitment to the T7SSb requires a physical interaction between a toxin and two or more so-called targeting factors, which harbor key residues required for T7SS-dependent protein export. However, in addition to these targeting factors, some toxins additionally require a protein belonging to the DUF4176 protein family. Here, by examining two toxin–DUF4176 protein pairs, we demonstrate that DUF4176 constitutes a family of toxin-specific molecular chaperones. In addition to being required for toxin stability in producing cells, we find that DUF4176 proteins facilitate toxin export by specifically interacting with a previously uncharacterized intrinsically disordered region found in many T7SS toxins. Using X-ray crystallography, we determine structures of several DUF4176 chaperones in their unbound state, and of a DUF4176 chaperone in complex with the binding site of its cognate toxin. These structures reveal that this binding site consists of a disordered amphipathic α-helix that requires interaction with its cognate chaperone for proper folding. Overall, we have identified a family of secretion system associated molecular chaperones found throughout T7SSb-containing Gram-positive bacteria.
Gkragkopoulou, Polyniki↗
A two parameter survey of periodic orbits in the restricted problem of three bodies
Within the context of the restricted problem of three bodies the effects caused by varying the mass ratio of the primaries and the eccentricity of their orbits, upon periodic orbits of the infinitesimal mass which are numerical continuations of circular orbits in the ordinary problem of two bodies are shown. A recursive power series technique is used to numerically integrate the equations of motion as well as the first variational equations in order to generate a two parameter family of perodic orbits and identify the linear stability characteristics. Seven such families are investigated with equally spaced mass ratios from 0.0 to 1.0 and eccentricities of the orbits of the primaries in a range 0.0 to 0.6. Stable orbits are associated with large distances of the infinitesimal mass from the perturbing primary, nearly circular motion of the primaries, and small mass ratios of the primaries. Unstable orbits for the infinitesimal mass are associated with small distances from the perturbing primary, highly elliptic orbits of the primaries and large mass ratios.
Shelus, P. J.↗
A Lanthanum‐Filled Carbon–Boron Clathrate
Abstract We report a carbon‐boron clathrate with composition 2 La@B 6 C 6 (LaB 3 C 3 ). Like recently reported SrB 3 C 3 , [1] single‐crystal X‐ray diffraction and computational modelling indicate that the isostructural La member crystallizes in the cubic bipartite sodalite structure (Type‐VII clathrate) with La atoms encapsulated within truncated octahedral cages composed of alternating carbon and boron atoms. The covalent nature of the B−C bonding results in a hard, incompressible framework, and owing to the balanced electron count, La 3+ [B 3 C 3 ] 3− exhibits markedly improved pressure stability and is a semiconductor with an indirect band gap predicted near 1.3 eV. A variety of different guest atoms may potentially be substituted within Type‐VII clathrate cages, presenting opportunities for a large family of boron‐stabilized, carbon‐based clathrates with ranging physical properties.
Strobel, Timothy A.↗