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At least 271 records · Page 15

Lipid interactions and angle of approach to the HIV-1 viral membrane of broadly neutralizing antibody 10E8: Insights for vaccine and therapeutic design

Among broadly neutralizing antibodies to HIV, 10E8 exhibits greater neutralizing breadth than most. Consequently, this antibody is the focus of prophylactic/therapeutic development. The 10E8 epitope has been identified as the conserved membrane proximal external region (MPER) of gp41 subunit of the envelope (Env) viral glycoprotein and is a major vaccine target. However, the MPER is proximal to the viral membrane and may be laterally inserted into the membrane in the Env prefusion form. Nevertheless, 10E8 has not been reported to have significant lipid-binding reactivity. Here we report x-ray structures of lipid complexes with 10E8 and a scaffolded MPER construct and mutagenesis studies that provide evidence that the 10E8 epitope is composed of both MPER and lipid. 10E8 engages lipids through a specific lipid head group interaction site and a basic and polar surface on the light chain. In the model that we constructed, the MPER would then be essentially perpendicular to the virion membrane during 10E8 neutralization of HIV-1. As the viral membrane likely also plays a role in selecting for the germline antibody as well as size and residue composition of MPER antibody complementarity determining regions, the identification of lipid interaction sites and the MPER orientation with regard to the viral membrane surface during 10E8 engagement can be of great utility for immunogen and therapeutic design.

59 BASIC BIOLOGICAL SCIENCES↗

Results of the plasma analyzer experiment on Pioneers 10 and 11

The plasma-analyzer experiments on Pioneers 10 and 11 have determined that the characteristics of the solar-wind interaction with the Jovian magnetosphere are basically similar to those observed for the solar-wind interaction of earth and differ mainly in terms of the scale size of the interaction. The Jovian magnetosheath flow field and the calculated normals to the Jovian magnetosphere indicate that the Jovian magnetosphere is extremely thick and blunt in shape. The size of the Jovian magnetosphere in the sunward (dayside) direction can change by as much as a factor of two in response to relatively minor changes in solar-wind dynamic pressure. The outer dayside Jovian magnetosphere is inflated with a high-beta thermal plasma.

Intriligator, D. S.↗

A flexible flight display research system using a ground-based interactive graphics terminal

Requirements and research areas for the air transportation system of the 1980 to 1990's were reviewed briefly to establish the need for a flexible flight display generation research tool. Specific display capabilities required by aeronautical researchers are listed and a conceptual system for providing these capabilities is described. The conceptual system uses a ground-based interactive graphics terminal driven by real-time radar and telemetry data to generate dynamic, experimental flight displays. These displays are scan converted to television format, processed, and transmitted to the cockpits of evaluation aircraft. The attendant advantages of a Flight Display Research System (FDRS) designed to employ this concept are presented. The detailed implementation of an FDRS is described. The basic characteristics of the interactive graphics terminal and supporting display electronic subsystems are presented and the resulting system capability is summarized. Finally, the system status and utilization are reviewed.

Hatfield, J. J.↗

Solar Array Module Plasma Interaction Experiment (SAMPIE): Technical requirements document

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is a NASA shuttle space flight experiment scheduled for launch in early 1994. The SAMPIE experiment will investigate plasma interactions of high voltage space power systems in low earth orbit. Solar cell modules, representing several technologies, will be biased to high voltages to characterize both arcing and plasma current collection. Other solar modules, specially modified in accordance with current theories of arcing and breakdown, will demonstrate the possibility of arc suppression. Finally, several test modules will be included to study the basic nature of these interactions. The science and technology goals for the project are defined in the Technical Requirements Document (TRD) which is presented here.

Hillard, G. Barry↗

The Solar Array Module Plasma Interactions Experiment (SAMPIE) - A Shuttle-based plasma interactions experiment

The Solar Array Module Plasma Interactions Experiment (SAMPIE), an approved Shuttle space flight experiment with a tentative launch date in July 1993, is intended to investigate plasma interactions of high-voltage space power systems. Solar cell modules, representing several technologies, will be biased to high voltages to characterize both arcing (negative potential) and current collection (positive potential). Other solar modules, specially modified in accordance with current theories of arcing and breakdown, will demonstrate the possibility of arc suppression. Finally, several additional test specimens will be included to study the basic nature of these interactions. The authors describe the rationale for the space flight experiment, the measurements to be made, the significance of the expected results, and the current design status of the flight hardware.

Wald, Lawrence W.↗

The strainrange conversion principle for treating cumulative fatigue damage in the creep range

A formula is derived for combining effects of successive hysteresis loops in the creep range of materials when one loop has excess tensile creep, while the other contains excess compressive creep. The resultant effect resembles single loops involving balanced tensile and compressive creep. The attempt to use the Interaction Damage Rule as a tool in combining loops of non-equal size and complex strainrange content has led to important new concepts useful in future studies of creep-fatigue. It turns out that the Interaction Damage Rule is basically an expression of how a set of hysteresis loops involving only single generic strains can combine to produce the same micromechanistic damage as the loop containing the combined strainranges which it analyzes. Making use of the underlying concept of Strainrange Partitioning that only the strainrange content of a hysteresis loop governs fatigue life, not order of introducing strainranges, a rational derivation of the Interaction Damage Rule is provided, showing also how it can effectively be used to synthesize independent loops and determine both damaging and healing effects.

Manson, S. S.↗

The SAMPIE flight experimental final technical requirements document

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is a shuttle based flight experiment scheduled for launch in early 1994. SAMPIE will investigate plasma interactions of high voltage space power systems in low earth orbit. Solar cell modules, representing several technologies, will be biased through a series of high voltages to characterize both arcing and plasma current collection. Other solar modules, specially modified in accordance with current theories of arcing and breakdown, will demonstrate the possibility of arc suppression. Finally, several test modules will be included to study the basic nature of these interactions. The science and technology goals for the project are defined in the Technical Requirements Document (TRD) which is presented here in its final form. The experiment is being developed at NASA LeRC in Cleveland, Ohio, and is sponsored by the NASA Office of Aeronautics and Space Technology (OAST).

Hillard, G. Barry↗

The Solar Array Module Plasma Interactions Experiment (SAMPIE): Science and technology objectives

The Solar Array Module Plasma Interactions Experiment (SAMPIE) is an approved NASA Space Shuttle space flight experiment to be launched in Jul. 1993. The SAMPIE experiment is designed to investigate the interaction of high voltage space power systems with ionospheric plasma. To study the behavior of solar cells, a number of cell coupons, representing technologies of current interest, will be biased to high voltages to characterize both negative potential arcing and positive potential current collection. Additionally, various theories of arc suppression will be tested by including several specially modified cell coupons. Finally, SAMPIE will include experiments to study the basic nature of these interactions. The rationale for a space flight experiment, the measurements to be made, the significance of the expected results, and the current design status of the flight hardware are described.

Hillard, G. Barry↗

Rocket Science 101 Interactive Educational Program

To better educate the public on the basic design of NASA s current mission rockets, Rocket Science 101 software has been developed as an interactive program designed to retain a user s attention and to teach about basic rocket parts. This program also has helped to expand NASA's presence on the Web regarding educating the public about the Agency s goals and accomplishments. The software was designed using Macromedia s Flash 8. It allows the user to select which type of rocket they want to learn about, interact with the basic parts, assemble the parts to create the whole rocket, and then review the basic flight profile of the rocket they have built.

Armstrong, Dennis↗

Interplay of electronic, magnetic, and structural properties of GdB 6 from first principles

Gadolinium hexaboride (GdB 6 ) is a well-known field emitter material that has been investigated for more than three decades. We perform a systematical density-functional theory study of GdB 6 by using the generalized-gradient approximation and considering the electron interaction parameter U. The basic structural and electronic properties are carefully revised, as well as a strong U-value dependence in determining the antiferromagnetic (AFM) magnetic structures of Gd 4f electronic states. We found a small U(0 ~ 3 eV) showing the most consistent experimental ground-state properties, which gives rise to a magnetic structure with a ground state of C-AFM and a second stable E-AFM. Moreover, we find the distortion modes of boron octahedron play an important role in the interaction between spin and lattice structures in this system. Furthermore, these results will deepen our understanding of the boron-based correlated rare earth compounds.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Metabolism and Evolution of a Biofuel-Producing Microbial Coculture

Specialized features of individual microbial species can be combined in coculture to produce useful fuels and chemicals. Cocultures can also be used to address how microbes cooperate in nature through metabolic interactions but with a level of experimental control that is not possible in natural systems. However, the challenge of maintaining stable microbial relationships and the limited assays available for studying single strains in consortia has impeded progress in characterizing and implementing synthetic communities. In this project, my lab developed a stable and highly reproducible H 2 biofuel-producing coculture between fermentative Escherichia coli and phototrophic Rhodopseudomonas palustris . In this coculture each species provides or 'cross-feeds' a nutrient that the other requires for growth. My lab used this coculture along with mathematical modeling to uncover basic principles governing mutualistic interactions between microbes, including (i) the potential for cross-fed nutrients to alternatively act as toxins depending on the level to which they are produced, (ii) how mutualistic cross-feeding can establish and persist in nutrient-deprived environments where the highest biofuel yields were observed, and (iii) the potential for competition between mutualistic partners for a cross-fed nutrient when that nutrient holds value for both species involved. In using ethanol-producing Zymomonas mobilis in place of E. coli in the coculture, my lab also discovered that Z. mobilis can use N 2 gas as a nitrogen source, with potential cost-savings for the industrial production of cellulosic ethanol.

59 BASIC BIOLOGICAL SCIENCES↗

Large-scale interaction of the solar wind with comets Halley and Giacobini-Zinner

In-situ measurements of comets Halley and Giacobini-Zinner have confirmed the accepted basic physics of comet/solar wind interaction. The solar wind magnetic field is captured by the comet through the mechanism of field-line loading by cometary ions and the field lines drape around the cometary ionosphere. With this basic model in hand, the large-scale structure of the plasma tail as revealed by submissions to the Large Scale Phenomena Network of the International Halley Watch is reviewed. The turn-on and turn-off of plasma activity seem consistent with theory. Some 16 obvious disconnection events (DEs) have been recorded. Preliminary results showed agreement with the sector-boundary model; a detailed analysis of all DEs will be required in order to make a definitive statement. A study of plasma activity around the time of the VEGA encounters provides strong support for the sector-boundary model and illustrates once again the power of simultaneous remote and in-situ measurements.

Brandt, John C.↗

Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions

The cyclic AMP response element (CRE) binding protein (CREB) is a transcription factor that contains a 280-residue N-terminal transactivation domain and a basic leucine zipper that mediates interaction with DNA. The transactivation domain comprises three subdomains, the glutamine-rich domains Q1 and Q2 and the kinase inducible activation domain (KID). NMR chemical shifts show that the isolated subdomains are intrinsically disordered but have a propensity to populate local elements of secondary structure. The Q1 and Q2 domains exhibit a propensity for formation of short β-hairpin motifs that function as binding sites for glutamine-rich sequences. These motifs mediate intramolecular interactions between the CREB Q1 and Q2 domains as well as intermolecular interactions with the glutamine-rich Q1 domain of the TATA-box binding protein associated factor 4 (TAF4) subunit of transcription factor IID (TFIID). Using small-angle X-ray scattering, NMR, and single-molecule Förster resonance energy transfer, we show that the Q1, Q2, and KID regions remain dynamically disordered in a full-length CREB transactivation domain (CREB TAD ) construct. The CREB TAD polypeptide chain is largely extended although some compaction is evident in the KID and Q2 domains. Paramagnetic relaxation enhancement reveals transient long-range contacts both within and between the Q1 and Q2 domains while the intervening KID domain is largely devoid of intramolecular interactions. Phosphorylation results in expansion of the KID domain, presumably making it more accessible for binding the CBP/p300 transcriptional coactivators. In conclusion, our study reveals the complex nature of the interactions within the intrinsically disordered transactivation domain of CREB and provides molecular-level insights into dynamic and transient interactions mediated by the glutamine-rich domains.

59 BASIC BIOLOGICAL SCIENCES↗

Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles

A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials. - Highlights: • Cell penetrable human scFvs (transbodies) to Ebolavirus (EBOV) VP40 were produced. • The transbodies inhibited egress of EBOV-like particles (VLPs) from human hepatocytes. • They interacted with VP40 CTD basic residues important for plasma membrane binding. • And hence interfere with viral matrix assembly and viral progeny budding. • This is the first report on human antibodies that target intracellular EBOV VP40.

60 APPLIED LIFE SCIENCES↗

Nonlinear effects in manybody van der Waals interactions

Van der Waals interactions are ubiquitous and they play an important role for the stability of materials. Current understanding of this type of coupling is based on linear response theory, while optical nonlinearities are rarely considered in this context. Many materials, however, exhibit strong optical nonlinear response, which prompts further evaluation of dispersive forces beyond linear response. Here we present a approach that takes into account linear and nonlinear properties of all dipolar nanoparticles in a given system. This method is based on a Hamiltonian for nonlinear dipoles, which we apply in different systems uncovering a complex interplay of distance, anisotropy, polarizabilities, and hyperpolarizabilities in the vdW energy. This investigation broadens our basic understanding of dispersive interactions, especially in the context of nonlinear materials. Published by the American Physical Society 2024

Le, Dai-Nam (ORCID:0000000307568742)↗

Molecular Simulation-Based Structural Prediction of Protein Complexes in Mass Spectrometry: The Human Insulin Dimer

Protein electrospray ionization (ESI) mass spectrometry (MS)-based techniques are widely used to provide insight into structural proteomics under the assumption that non-covalent protein complexes being transferred into the gas phase preserve basically the same intermolecular interactions as in solution. Here we investigate the applicability of this assumption by extending our previous structural prediction protocol for single proteins in ESI-MS to protein complexes. We apply our protocol to the human insulin dimer (hIns2) as a test case. Our calculations reproduce the main charge and the collision cross section (CCS) measured in ESI-MS experiments. Molecular dynamics simulations for 0.075 ms show that the complex maximizes intermolecular non-bonded interactions relative to the structure in water, without affecting the cross section. The overall gas-phase structure of hIns2 does exhibit differences with the one in aqueous solution, not inferable from a comparison with calculated CCS. Hence, care should be exerted when interpreting ESI-MS proteomics data based solely on NMR and/or X-ray structural information.

59 BASIC BIOLOGICAL SCIENCES↗

Is the Chemisorbed CO 2 in Ionic Liquid Electrolytes Active for Electrochemical Utilization? A Case Study on Carboxylate and Carbamate Speciation

This study examines the activity of chemisorbed CO 2 species in the microenvironment formed by bifunctional ionic liquids (ILs) in the reactive capture and conversion (RCC) of CO 2 to CO on silver. Comparative electroanalytical measurements with imidazolium based ILs were performed to probe the impact of electrostatic interactions, anion and cation basicity, and hydrogen bonding on RCC. Particularly, ILs with 1-ethyl-3-methylimidazolium ([EMIM]+) and 1-ethyl-2,3-dimethylimidazolium ([EMMIM]+) cations and aprotic heterocyclic anions of 2-cyanopyrrolide ([2-CNpyr]) and 1,2,4-triazolide ([124-Triz]) were examined for RCC. It was found that anion–CO 2 carbamate complexes facilitate RCC at significantly lower overpotentials compared to cation–CO 2 carboxylate complexes. Additionally, [EMIM]+ was found to better stabilize anion–CO 2 complexes at the interface than [EMMIM]+. Furthermore, it was found that 2-CNpyrH that naturally forms during CO 2 absorption competes for electrode surface adsorption with the anion–CO 2 carbamate complex, thereby reducing the electrochemical activity of the anion–CO 2 complex. These results highlight the importance of IL structure in tuning the interfacial interactions and suggest that ILs with anion-dominated CO 2 chemisorption enhances CO 2 utilization in RCC applications.

Coskun, Oguz Kagan [Case Western Reserve Univ., Cl↗

Final Report - Few-Body Studies Using Electromagnetic Interactions

The work discussed here is an extension of work previously funded by U.S. Department of Energy Grant DE-FG02-97ER41025. Measurements of charged pion photoproduction from deuterium using the Laser Electron Gamma Source (LEGS) at the Brookhaven National Laboratory previously made by us, as members of the LEGS Collaboration, resulted in the most interesting result of two decades of work. By measuring the production of a charged pion (π + ) in coincidence with an emitted photon we observed structures in the residual two-nucleon system. These indicated the existence of rare, long-lived states not explicable by standard nuclear theory; they suggested a set of configurations not explicable in terms of a nucleon-nucleon pair. The existence of such “exotic” structures has formed the foundation for most of the work that has ensued. Several measurements at various laboratories have supported, but not proved, the existence of these exotic states. The rarity of these states made their existence undetectable in most previous measurements. Only by observing characteristic signatures of such states (i.e., decay photons), by using very specific kinematics which isolate certain reaction products, or by measuring polarization-dependent observables. During the period of this grant we pursued and made progress on the development of experiments to be performed at the High Intensity Gamma Source (HIGS) of the Tri Universities Nuclear Laboratory (TUNL). Our understanding of photon- and electron-induced nuclear reactions depends on understanding of the basic electron and photon interaction. Recently, the issue of two-photon contributions has arisen in the context of deeply inelastic electron scattering. One way to address this is to measure asymmetries in the Bethe-Heitler ee process. We also made progress in developing the detectors required to measure these asymmetries at HIGS. During the last several years the apparent discrepancy between the size of the proton as measured using electrons and that as measured using muons has received a great deal of attention. Working with colleagues at the Jefferson Laboratory (JLAB) we showed that the apparent discrepancy was almost surely the result of mistakes in the statistical analysis of electron scattering data, that there is almost surely no discrepancy.

43 PARTICLE ACCELERATORS↗