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At least 19 records

Incidence and Progression of Chorioretinal Folds During Long-Duration Spaceflight

Importance: The primary contributing factor for development of chorioretinal folds during spaceflight is unknown. Characterizing fold types that develop and tracking their progression may provide insight into the pathophysiology of spaceflight-associated neuro-ocular syndrome and elucidate the risk of fold progression for future exploration-class missions exceeding 12 months in duration. Objective: To determine the incidence and presentation of chorioretinal folds in long-duration International Space Station crew members and objectively quantify the progression of choroidal folds during spaceflight. Design, Setting, and Participants: In this retrospective cohort study, optical coherence tomography scans of the optic nerve head and macula of crew members completing long-duration spaceflight missions were obtained on Earth prior to spaceflight and during flight. A panel of experts examined the scans for the qualitative presence of chorioretinal folds. Peripapillary total retinal thickness was calculated to identify eyes with optic disc edema, and choroidal folds were quantified based on surface roughness within macular and peripapillary regions of interest. Interventions or Exposures: Spaceflight missions ranging 6 to 12 months. Main Outcomes and Measures: Incidence of peripapillary wrinkles, retinal folds, and choroidal folds; peripapillary total retinal thickness; and Bruch membrane surface roughness. Results: A total of 36 crew members were analyzed (mean [SD] age, 46 [6] years; 7 [19%] female). Chorioretinal folds were observed in 12 of 72 eyes (17%; 6 crew members). In eyes with early signs of disc edema, 10 of 42 (24%) had choroidal folds, 4 of 42 (10%) had inner retinal folds, and 2 of 42 (5%) had peripapillary wrinkles. Choroidal folds were observed in all eyes with retinal folds and peripapillary wrinkles. Macular choroidal folds developed in 7 of 12 eyes (4 of 6 crew members) with folds and progressed with mission duration; these folds extended into the fovea in 6 eyes. Circumpapillary choroidal folds developed predominantly superior, nasal, and inferior to the optic nerve head and increased in prevalence and severity with mission duration. Conclusions and Relevance: Choroidal folds were the most common fold type to develop during spaceflight; this differs from reports in idiopathic intracranial hypertension, suggesting differences in the mechanisms underlying fold formation. Quantitative measures demonstrate the development and progression of choroidal folds during weightlessness, and these metrics may help to assess the efficacy of spaceflight-associated neuro-ocular syndrome countermeasures.

Connor R. Ferguson

Improved Method of Design for Folding Inflatable Shells

An improved method of designing complexly shaped inflatable shells to be assembled from gores was conceived for original application to the inflatable outer shell of a developmental habitable spacecraft module having a cylindrical mid-length section with toroidal end caps. The method is also applicable to inflatable shells of various shapes for terrestrial use. The method addresses problems associated with the assembly, folding, transport, and deployment of inflatable shells that may comprise multiple layers and have complex shapes that can include such doubly curved surfaces as toroids and spheres. One particularly difficult problem is that of mathematically defining fold lines on a gore pattern in a double- curvature region. Moreover, because the fold lines in a double-curvature region tend to be curved, there is a practical problem of how to implement the folds. Another problem is that of modifying the basic gore shapes and sizes for the various layers so that when they are folded as part of the integral structure, they do not mechanically interfere with each other at the fold lines. Heretofore, it has been a common practice to design an inflatable shell to be assembled in the deployed configuration, without regard for the need to fold it into compact form. Typically, the result has been that folding has been a difficult, time-consuming process resulting in a An improved method of designing complexly shaped inflatable shells to be assembled from gores was conceived for original application to the inflatable outer shell of a developmental habitable spacecraft module having a cylindrical mid-length section with toroidal end caps. The method is also applicable to inflatable shells of various shapes for terrestrial use. The method addresses problems associated with the assembly, folding, transport, and deployment of inflatable shells that may comprise multiple layers and have complex shapes that can include such doubly curved surfaces as toroids and spheres. One particularly difficult problem is that of mathematically defining fold lines on a gore pattern in a double- curvature region. Moreover, because the fold lines in a double-curvature region tend to be curved, there is a practical problem of how to implement the folds. Another problem is that of modifying the basic gore shapes and sizes for the various layers so that when they are folded as part of the integral structure, they do not mechanically interfere with each other at the fold lines. Heretofore, it has been a common practice to design an inflatable shell to be assembled in the deployed configuration, without regard for the need to fold it into compact form. Typically, the result has been that folding has been a difficult, time-consuming process resulting in a

Johnson, Christopher J.

Deep crustal deformation by sheath folding in the Adirondack Mountains, USA

As described by McLelland and Isachsen, the southern half of the Adirondacks are underlain by major isoclinal (F sub 1) and open-upright (F sub 2) folds whose axes are parallel, trend approximately E-W, and plunge gently about the horizontal. These large structures are themselves folded by open upright folds trending NNE (F sub 3). It is pointed out that elongation lineations in these rocks are parallel to X of the finite strain ellipsoid developed during progressive rotational strain. The parallelism between F sub 1 and F sub 2 fold axes and elongation lineations led to the hypothesis that progressive rotational strain, with a west-directed tectonic transport, rotated earlier F sub 1-folds into parallelism with the evolving elongation lineation. Rotation is accomplished by ductile, passive flow of F sub 1-axes into extremely arcuate, E-W hinges. In order to test these hypotheses a number of large folds were mapped in the eastern Adirondacks. Other evidence supporting the existence of sheath folds in the Adirondacks is the presence, on a map scale, of synforms whose limbs pass through the vertical and into antiforms. This type of outcrop pattern is best explained by intersecting a horizontal plane with the double curvature of sheath folds. It is proposed that sheath folding is a common response of hot, ductile rocks to rotational strain at deep crustal levels. The recognition of sheath folds in the Adirondacks reconciles the E-W orientation of fold axes with an E-W elongation lineation.

Mclelland, J. M.

Exploring the Evolutionary Accident Hypothesis: Are Extant Protein Folds the Fittest or the Luckiest?

Considering the range of functions proteins perform, it is surprising they fold into a relatively small set of structures or "folds" that facilitate such function. One explanation is that only a minority were fit enough to emerge from Darwinian selection during the early evolution of life. Alternatively, perhaps only a fraction of all possible folds were trialed. Understanding proto-catalyst selection will aid understanding of the origins and early evolution of life. To investigate which explanation is correct, we study a protein evolved in vitro to bind ATP by Jack Szostak (Fig. 1). This protein adopts a fold which is absent from nature. We are testing whether this fold would have possessed the capability to evolve that would have been essential to survive natural selection on early Earth. Folds that couldn't improve their fitness and evolve to perform new functions would have been replaced by rivals that could. To determine whether the fold is evolvable, we are attempting to change the function of the protein by rationally redesigning to bind GTP. Two design strategies in the region of the nucleobase have been implemented to provide hydrogen bonding partners for the ligand i) an insertion ii) a MET to ASN mutation. Redesigns are being studied computationally at Ames Research Center including free energy of binding calculations. Binding affinities of promising redesigns are to be validated by experimental collaborators at ForteBio using Super Streptavidin Biosensors. If the fold is found to be non-evolvable, this may suggest that many structures were trialed, but the majority were pruned on the basis of their evolvability. Alternatively, if the fold is demonstrated to be evolvable, it would be difficult to explain its absence from nature without considering the possibility that the fold simply wasn't sampled on early Earth. This would not only further our understanding of the origins of life on Earth but also suggest a common phe-nomenon of proto-catalyst evolution.

Shannon, G.

Evolution and folding of repeat proteins

Repeat proteins are made with tandem copies of similar amino acid stretches that fold into elongated architectures. These proteins constitute excellent model systems to investigate how evolution relates to structure, folding, and function. Here, we propose a scheme to map evolutionary information at the sequence level to a coarse-grained model for repeat-protein folding and use it to investigate the folding of thousands of repeat proteins. We model the energetics by a combination of an inverse Potts-model scheme with an explicit mechanistic model of duplications and deletions of repeats to calculate the evolutionary parameters of the system at the single-residue level. These parameters are used to inform an Ising-like model that allows for the generation of folding curves, apparent domain emergence, and occupation of intermediate states that are highly compatible with experimental data in specific case studies. We analyzed the folding of thousands of natural Ankyrin repeat proteins and found that a multiplicity of folding mechanisms are possible. Fully cooperative all-or-none transitions are obtained for arrays with enough sequence-similar elements and strong interactions between them, while noncooperative element-by-element intermittent folding arose if the elements are dissimilar and the interactions between them are energetically weak. Additionally, we characterized nucleation-propagation and multidomain folding mechanisms. We show that the global stability and cooperativity of the repeating arrays can be predicted from simple sequence scores.

Ezequiel A. Galpern

Folding and translocation of the undecamer of poly-L-leucine across the water-hexane interface. A molecular dynamics study

The undecamer of poly-L-leucine at the water-hexane interface is studied by molecular dynamics simulations. This represents a simple model relevant to folding and insertion of hydrophobic peptides into membranes. The peptide, initially placed in a random coil conformation on the aqueous side of the system, rapidly translocates toward the hexane phase and undergoes interfacial folding into an alpha-helix in the subsequent 36 ns. Folding is nonsequential and highly dynamic. The initially formed helical segment at the N-terminus of the undecamer becomes transiently broken and, subsequently, reforms before the remainder of the peptide folds from the C-terminus. The formation of intramolecular hydrogen bonds during the folding of the peptide is preceded by a dehydration of the participating polar groups, as they become immersed in hexane. Folding proceeds through a short-lived intermediate, a 3(10)-helix, which rapidly interconverts to an alpha-helix. Both helices contribute to the equilibrium ensemble of folded structures. The helical peptide is largely buried in hexane, yet remains adsorbed at the interface. Its preferred orientation is parallel to the interface, although the perpendicular arrangement with the N-terminus immersed in hexane is only slightly less favorable. In contrast, the reversed orientation is highly unfavorable, because it would require dehydration of C-terminus carbonyl groups that do not participate in intramolecular hydrogen bonding. For the same reason, the transfer of the undecamer from the interface to the bulk hexane is also unfavorable. The results suggest that hydrophobic peptides fold in the interfacial region and, simultaneously, translocate into the nonpolar side of the interface. It is further implied that peptide insertion into the membrane is accomplished by rotating from the parallel to the perpendicular orientation, most likely in such a way that the N-terminus penetrates the bilayer.

NASA Discipline Exobiology

Origami-Inspired Folding of Thick, Rigid Panels

To achieve power of 250 kW or greater, a large compression ratio of stowed-to-deployed area is needed. Origami folding patterns were used to inspire the folding of a solar array to achieve synchronous deployment; however, origami models are generally created for near-zero-thickness material. Panel thickness is one of the main challenges of origami-inspired design. Three origami-inspired folding techniques (flasher, square twist, and map fold) were created with rigid panels and hinges. Hinge components are added to the model to enable folding of thick, rigid materials. Origami models are created assuming zero (or near zero) thickness. When a material with finite thickness is used, the panels are required to bend around an increasingly thick fold as they move away from the center of the model. The two approaches for dealing with material thickness are to use membrane hinges to connect the panels, or to add panel hinges, or hinges of the same thickness, at an appropriate width to enable folding.

Trease, Brian P.

Life prediction of expulsion bladders through fatigue test and fold strain analysis.

Consideration of the problem of reducing the probability of mechanical failure of bladder systems used for the expulsion of propellants into liquid rocket engines. It is shown that individual local folds in collapsing bladders can be classified into single and double folds, specifiable by nondimensional geometrical parameters which directly define the maximum strains at these folds. From these maximum strains the number of collapse/inflation cycles to failure can be obtained from low-cycle fatigue data experimentally determined for the bladder material of interest. Cycle life data are presented in terms of true maximum strain for four metals, two plastics, and two elastomers. It is found that double folds give rise to much more severe folding strains than do simple folds.

Chu, H. N.

Observations of Convective and Dynamical Instabilities in Tropopause Folds and their Contribution to Stratosphere-Troposphere Exchange

With aircraft-mounted in-situ and remote sensing instruments for dynamical, thermal. and chemical measurements, we studied two cases of tropopause folding. In both folds we found Kelvin-Helmholtz billows with horizontal wavelength of about 900 m and thickness of about 120 m. In one case the instability was effectively mixing the bottomside of the fold, leading to the transfer of stratospheric air into the troposphere. Also we discovered in both cases small-scale secondary ozone maxima shortly after the aircraft ascended past the topside of the fold that corresponded to regions of convective instability. We interpreted this phenomenon as convectively breaking gravity waves. Therefore, we posit that convectively breaking gravity waves acting on tropopause folds must be added to the list of important irreversible mixing mechanisms leading to stratosphere-troposphere exchange.

Cho, John Y. N.

Molecular Dynamics of Peptide Folding at Aqueous Interfaces

Even though most monomeric peptides are disordered in water they can adopt sequence-dependent, ordered structures, such as a-helices, at aqueous interfaces. This property is relevant to cellular signaling, membrane fusion, and the action of toxins and antibiotics. The mechanism of folding nonpolar peptides at the water-hexane interface was studied in the example of an 11-mer, of poly-L-leucine. Initially placed as a random coil on the water side of the interface, the peptide folded into an a-helix in 36 ns. Simultaneously, the peptide translocated into the hexane side of the interface. Folding was not sequential and involved a 3/10-helix as an intermediate. The folded peptide was either parallel to the interface or had its C-terminus exposed to water. An 11-mer, LQQLLQQLLQL, composed of leucine (L) and glutamine (G), was taken as a model amphiphilic peptide. It rapidly adopted an amphiphilic, disordered structure at the interface. Further folding proceeded through a series of amphiphilic intermediates.

Pohorille, Andrew

Life prediction of expulsion bladders through fatigue test and fold strain analysis

Cycle life data are presented in terms of true maximum strain for four metals, two plastics, and two elastomers. The Coffin-Manson fatigue theory was applied for metals and plastics, and cut-growth fatigue theory for elastomers. The data are based on measurements made at room and elevated temperatures. It was found that double folds give rise to far severer folding strains than do simple folds. It was also found that, except for the elastomers, all the bladder materials develop surface cracks due to double folds after only one cycle. The findings indicate that metals, which are bets for premeation resistance, are worst for fatigue resistance, and vice versa for elastomers. The intermediate plastics were found to be unsatisfactory for both permeation and fatigue resistance for missions of extended duration.

Chu, H. N.

The President's Day cyclone of 18-19 February 1979 - Influence of a tropopause fold on rapid cyclogenesis

The surface and satellite imagery data from the cyclone of February 18-19, 1979 are analyzed. Operational radiosonde data are utilized to study the tropopause fold associated with the polar jet streak. Patterns of vertical motion compatible with the tropopause fold are calculated by the diagnostic ageostrophic circulation equation of Sawyer (1956) and Eliassen (1962); the verification of the calculated patterns is described. The relationship between the stratospheric extrusion and the folded tropopause is determined by examining the potential vorticity and ozone concentrations. The influence of the stratospheric extrusion within the folded tropopause on the development of the cyclone is investigated by analyzing the potential vorticity, static stability, and absolute vorticity from the Eulerian and Lagrangian perspective.

Uccellini, L. W.

The Arctic tropopause fold

Analyses of research-aircraft observations, satellite total-columnar-ozone retrievals, and synoptic upper-air soundings are used to describe the structure of Arctic jetstreams and their associated frontal zones and tropopause folds. These analyses document the presence of major tropopause folding events within the Arctic that occur at the flanks of large-scale (about 2000 km) polar vortices. One example shows a solar vortex and its associated tropopause fold and Arctic front that migrated from the high Canadian Arctic southward into midlatitudes over central North America. Total columnar ozone measurements from the Total Ozone Mapping Spectrometer are shown to identify the location of polar vortices and the mesoscale (about 200 km) ozone gradients at the flanks of these vortices, which coincide with regions of Arctic tropopause folding and associated stratospheric-tropospheric exchange processes.

Shapiro, M. A.

Ten-fold augmentation of endothelial uptake of vascular endothelial growth factor with ultrasound after systemic administration

OBJECTIVES: In this study, the feasibility of delivering and enhancing the uptake of vascular endothelial growth factor (VEGF) into the intact endothelium by using ultrasound (US) facilitation was determined. BACKGROUND: A limitation of tissue-targeted drug delivery is the need for direct arterial cannulation. We postulate a mechanism by which agents injected intravenously may be targeted to a tissue using US and ultrasonic contrast agents. METHODS: We used a rat model to test the ability of US and an ultrasonic contrast agent perflurocarbon exposed sonicated dextrose albumin (PESDA) to increase uptake of VEGF in the myocardium. Continuous wave Doppler US (0.6 W/cm2 at 1 MHz for 15 min) was applied to the chest wall overlying the myocardium during intravenous injection with either VEGF (100 microg/kg) alone or a combination of VEGF and PESDA (0.1%). Control rats had VEGF infused without US or PESDA. The VEGF uptake was measured quantitatively in the heart, lung, liver and kidneys by enzyme-linked immunosorbent assay (ng/g of tissue) and morphologically by fluorescence microscopy. RESULTS: There was an eight-fold increase in VEGF uptake in the heart by US alone (16.86 +/- 1.56 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) and a 13-fold increase with US + PESDA (26.78 +/- 2.88 vs. 2.11 +/- 0.953 ng/g of tissue, p < 0.0001) compared with control rats. Fluorescence microscopy revealed deposition of VEGF in the endothelium of small intramyocardial arterioles. CONCLUSIONS: These results show a marked increase in endothelial VEGF uptake with US and US + PESDA. Thus, US may be used to augment endothelial VEGF uptake 10-fold to 13-fold.

Non-NASA Center

High-Temperature Characterization of Alumina Substrates and Folded Slot Antenna

The characterization of 99.6% polycrystalline alumina substrates and folded slot antennas is presented in this paper. Coplanar Waveguide (CPW) calibration standards where fabricated on 99.6% polycrystalline alumina substrates. Thru-Reflect-Line (TRL) calibrations were performed at temperatures of 25 to 400 C over a frequency range from 0.5 to 50 GHz. The effective dielectric constant of the alumina substrates was determined to be relatively constant at 5.4 from 25 to 200 C and then increased steadily to approximately 6 at 400 C. The loss of the CPW lines increased as temperature and frequency increased as well noting that the increase in loss is even more profound as both the temperature and frequency increased simultaneously. A CPW fed folded slot antenna fabricated on the alumina substrates is also presented. The Return Loss (RL) of a CPW fed folded slot antenna exhibits a self impedance matching technique. The RL of the folded slot antenna at 25 C displays a resonance at 3.5 GHz and is approximately 16 dB in magnitude. At 300 C the resonance shifts down in frequency to approximately 3.3 dB and has roughly the same magnitude. However the loss of the antenna response also increases at this elevated temperature. This work is part of the initial stages of an effort at NASA Glenn research Center to develop wireless sensors for harsh environments. This work can reduce cost, space to house all the hard wired connections, and reduce the weight of the overall units such as aerospace engines and allow for the placement of the wireless sensors in the engine which are not possible with hard wired sensors.

Scardelletti, Maximilian C.

Folded Resonant Horns for Power Ultrasonic Applications

Folded horns have been conceived as alternatives to straight horns used as resonators and strain amplifiers in power ultrasonic systems. Such systems are used for cleaning, welding, soldering, cutting, and drilling in a variety of industries. In addition, several previous NASA Tech Briefs articles have described instrumented drilling, coring, and burrowing machines that utilize combinations of sonic and ultrasonic vibrational actuation. The main advantage of a folded horn, relative to a straight horn of the same resonance frequency, is that the folded horn can be made shorter (that is, its greatest linear dimension measured from the outside can be made smaller). Alternatively, for a given length, the resonance frequency can be reduced. Hence, the folded-horn concept affords an additional degree of design freedom for reducing the length of an ultrasonic power system that includes a horn.

Sherrit, Stewart

A Performance Analysis of Folding Conformal Propeller Blade Designs

NASA’s X-57 Maxwell flight demonstrator has a high-lift system that includes 12 fixed- pitch high-lift propellers located upstream of the wing leading edge for lift augmentation at low speeds. These high-lift propellers are only required at low speeds, and to reduce drag, the propeller blades are folded conformally along the nacelles at other operating conditions. The method of designing the high-lift blades permits several variations of blade cross-section placement along the nacelle surface and a comparative performance analysis was needed to determine if any particular design showed significant benefits. We analyzed the performance of three conformal high-lift propeller designs and compared them to that of a non-conformal baseline propeller to establish both the benefit of stowable blades and the value of each variation. In this study, we first performed a drag analysis of each design in the stowed configuration at the X-57 cruise speed and altitude to determine the drag benefits of each conforming method. Then, among blade designs we compared the thrust, power, and lift for a given input shaft speed to establish any performance losses from the baseline. This analysis shows that the conformal blade designs do not have any appreciable performance losses compared to the baseline blades. Moreover, although the drag in the cruise condition is significantly less than for the non-folding baseline, the drag benefits of each conforming blade approach are similar and the value of each approach largely depends on the ease of integration into the nacelle. This paper presents the results of these studies and discusses the benefits and drawbacks of implementing the conformal blade designs. Specifically, we demonstrate that folding, conformal propeller blades contribute significantly less to cruise drag when compared to windmilling, with an increase relative to a. We also show a less than 1% difference in performance formal, folding propellers and the non-conforming baseline propeller.

Litherland, Brandon L.