258 research outputs found
Modeling and Analysis of Power Processing Systems
The feasibility of formulating a methodology for the modeling and analysis of aerospace electrical power processing systems is investigated. It is shown that a digital computer may be used in an interactive mode for the design, modeling, analysis, and comparison of power processing systems
Multi-kilowatt modularized spacecraft power processing system development
A review of existing information pertaining to spacecraft power processing systems and equipment was accomplished with a view towards applicability to the modularization of multi-kilowatt power processors. Power requirements for future spacecraft were determined from the NASA mission model-shuttle systems payload data study which provided the limits for modular power equipment capabilities. Three power processing systems were compared to evaluation criteria to select the system best suited for modularity. The shunt regulated direct energy transfer system was selected by this analysis for a conceptual design effort which produced equipment specifications, schematics, envelope drawings, and power module configurations
Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1
Screening of a carefully selected library of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic nucleotide-binding domain (CNB) of the cAMP sensor, EPAC1. Two of these hits (I942 and I178) were selected for their robust and reproducible inhibitory effects within the primary screening assay. Follow-up characterisation by ligand observed nuclear magnetic resonance (NMR) revealed direct interaction of I942 and I178 with EPAC1 and EPAC2-CNBs in vitro. Moreover, in vitro guanine nucleotide exchange factor (GEF) assays revealed that I942 and, to a lesser extent, I178 had partial agonist properties towards EPAC1, leading to activation of EPAC1, in the absence of cAMP, and inhibition of GEF activity in the presence of cAMP. In contrast, there was very little agonist action of I942 towards EPAC2 or protein kinase A (PKA). To our knowledge, this is the first observation of non-cyclic-nucleotide small molecules with agonist properties towards EPAC1. Furthermore, the isoform selective agonist nature of these compounds highlights the potential for the development of small molecule tools that selectively up-regulate EPAC1 activity
Structural and electrical transport properties of superconducting Au{0.7}In{0.3} films: A random array of superconductor-normal metal-superconductor (SNS) Josephson junctions
The structural and superconducting properties of Au{0.7}In{0.3} films, grown
by interdiffusion of alternating Au and In layers, have been studied. The films
were found to consist of a uniform solid solution of Au{0.9}In{0.1}, with
excess In precipitated in the form of In-rich grains of various Au-In phases
(with distinct atomic compositions), including intermetallic compounds. As the
temperature was lowered, these individual grains became superconducting at a
particular transition temperature (Tc), determined primarily by the atomic
composition of the grain, before a fully superconducting state of zero
resistance was established. From the observed onset Tc, it was inferred that up
to three different superconducting phases could have formed in these
Au{0.7}In{0.3} films, all of which were embedded in a uniform Au{0.9}In{0.1}
matrix. Among these phases, the Tc of a particular one, 0.8 K, is higher than
any previously reported for the Au-In system. The electrical transport
properties were studied down to low temperatures. The transport results were
found to be well correlated with those of the structural studies. The present
work suggests that Au{0.7}In{0.3} can be modeled as a random array of
superconductor-normal metal-superconductor (SNS) Josephson junctions. The
effect of disorder and the nature of the superconducting transition in these
Au{0.7}In{0.3} films are discussed.Comment: 8 text pages, 10 figures in one separate PDF file, submitted to PR
Strong spin-orbit interaction and -factor renormalization of hole spins in Ge/Si nanowire quantum dots
The spin-orbit interaction lies at the heart of quantum computation with spin
qubits, research on topologically non-trivial states, and various applications
in spintronics. Hole spins in Ge/Si core/shell nanowires experience a
spin-orbit interaction that has been predicted to be both strong and
electrically tunable, making them a particularly promising platform for
research in these fields. We experimentally determine the strength of
spin-orbit interaction of hole spins confined to a double quantum dot in a
Ge/Si nanowire by measuring spin-mixing transitions inside a regime of
spin-blockaded transport. We find a remarkably short spin-orbit length of
65 nm, comparable to the quantum dot length and the interdot distance. We
additionally observe a large orbital effect of the applied magnetic field on
the hole states, resulting in a large magnetic field dependence of the
spin-mixing transition energies. Strikingly, together with these orbital
effects, the strong spin-orbit interaction causes a significant enhancement of
the -factor with magnetic field.The large spin-orbit interaction strength
demonstrated is consistent with the predicted direct Rashba spin-orbit
interaction in this material system and is expected to enable ultrafast Rabi
oscillations of spin qubits and efficient qubit-qubit interactions, as well as
provide a platform suitable for studying Majorana zero modes
Slope Stability Analysis of a Saturated Riparian Buffer: A Case Study
A relatively new solution to reduce nitrate export from agricultural drainage is to use existing riparian buffer zones along the field edge as media to provide storage volume by distributing drainage water to saturate the soil, commonly referred to as a “saturated riparian buffer” (SRB). Though previous research has proven the effectiveness of SRBs to reduce nitrate export, uncertainties about long-term impacts prevent widespread adoption of the practice. One significant uncertainty is the stability of the streambank after saturation, raising concerns about slope instability and erosion. Current design standards use conservative guidelines for minimum buffer width and maximum bank height to prevent bank failure from occurring, thereby limiting site eligibility for installation of SRBs. This study investigated the impact of SRB design parameters on the stability of the streambank at a site in Hamilton County, Iowa. Installation of the SRB did not substantially decrease the factor of safety against failure. Additionally, our model shows that a moderate reduction in buffer width decreases the factor of safety but does not lead to slope failure.This proceeding is published as Dickey, L. C., A. R. McEachran, C. Rutherford, M. A. Perez, C. R. Rehmann, T. Isenhart, D. Jaynes, and T. Groh. "Slope Stability Analysis of a Saturated Riparian Buffer: A Case Study." In Geo-Congress 2020, pp. 267-274. Reston, VA: American Society of Civil Engineers, 2020. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted
The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation
Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al
Identification of A Novel Class of Benzofuran Oxoacetic Acid-Derived Ligands that Selectively Activate Cellular EPAC1
Cyclic AMP promotes EPAC1 and EPAC2 activation through direct binding to a specific cyclic nucleotide-binding domain (CNBD) within each protein, leading to activation of Rap GTPases, which control multiple cell responses, including cell proliferation, adhesion, morphology, exocytosis, and gene expression. As a result, it has become apparent that directed activation of EPAC1 and EPAC2 with synthetic agonists may also be useful for the future treatment of diabetes and cardiovascular diseases. To identify new EPAC agonists we have developed a fluorescent-based, ultra-high-throughput screening (uHTS) assay that measures the displacement of binding of the fluorescent cAMP analogue, 8-NBD-cAMP to the EPAC1 CNBD. Triage of the output of an approximately 350,000 compound screens using this assay identified a benzofuran oxaloacetic acid EPAC1 binder (SY000) that displayed moderate potency using orthogonal assays (competition binding and microscale thermophoresis). We next generated a limited library of 91 analogues of SY000 and identified SY009, with modifications to the benzofuran ring associated with a 10-fold increase in potency towards EPAC1 over SY000 in binding assays. In vitro EPAC1 activity assays confirmed the agonist potential of these molecules in comparison with the known EPAC1 non-cyclic nucleotide (NCN) partial agonist, I942. Rap1 GTPase activation assays further demonstrated that SY009 selectively activates EPAC1 over EPAC2 in cells. SY009 therefore represents a novel class of NCN EPAC1 activators that selectively activate EPAC1 in cellulae
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