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At least 1,657 records · Page 92

Characterization of atrial natriuretic peptide degradation by cell-surface peptidase activity on endothelial cells

Atrial natriuretic peptide (ANP) is a fluid-regulating peptide hormone that promotes vasorelaxation, natriuresis, and diuresis. The mechanisms for the release of ANP and for its clearance from the circulation play important roles in modulating its biological effects. Recently, we have reported that the cell surface of an endothelial cell line, CPA47, could degrade 125I-ANP in the presence of EDTA. In this study, we have characterized this degradation of 125I-ANP. The kinetics of ANP degradation by the surface of CPA47 cells were first order, with a Km of 320 +/- 60 nM and Vmax of 35 +/- 14 pmol of ANP degraded/10 min/10(5) cells at pH 7.4. ANP is degraded by the surface of CPA47 cells over a broad pH range from 7.0-8.5. Potato carboxypeptidase inhibitor and bestatin inhibited 125I-ANP degradation, suggesting that this degradative activity on the surface of CPA47 cells has exopeptidase characteristics. The selectivity of CPA47 cell-surface degradation of ANP was demonstrated when 125I-ANP degradation was inhibited in the presence of neuropeptide Y and angiotensin I and II but not bradykinin, bombesin, endothelin-1, or substance P. The C-terminal amino acids phe26 and tyr28 were deduced to be important for ANP interaction with the cell-surface peptidase(s) based on comparison of the IC50 of various ANP analogues and other natriuretic peptides for the inhibition of ANP degradation. These data suggest that a newly characterized divalent cation-independent exopeptidase(s) that selectively recognizes ANP and some other vasoactive peptides exists on the surface of endothelial cells.

NASA Discipline Regulatory Physiology↗

Growing Aligned Carbon Nanotubes for Interconnections in ICs

A process for growing multiwalled carbon nanotubes anchored at specified locations and aligned along specified directions has been invented. Typically, one would grow a number of the nanotubes oriented perpendicularly to a silicon integrated-circuit (IC) substrate, starting from (and anchored on) patterned catalytic spots on the substrate. Such arrays of perpendicular carbon nanotubes could be used as electrical interconnections between levels of multilevel ICs. The process (see Figure 1) begins with the formation of a layer, a few hundred nanometers thick, of a compatible electrically insulating material (e.g., SiO(x) or Si(y)N(z) on the silicon substrate. A patterned film of a suitable electrical conductor (Al, Mo, Cr, Ti, Ta, Pt, Ir, or doped Si), having a thickness between 1 nm and 2 m, is deposited on the insulating layer to form the IC conductor pattern. Next, a catalytic material (usually, Ni, Fe, or Co) is deposited to a thickness between 1 and 30 nm on the spots from which it is desired to grow carbon nanotubes. The carbon nanotubes are grown by plasma-enhanced chemical vapor deposition (PECVD). Unlike the matted and tangled carbon nanotubes grown by thermal CVD, the carbon nanotubes grown by PECVD are perpendicular and freestanding because an electric field perpendicular to the substrate is used in PECVD. Next, the free space between the carbon nanotubes is filled with SiO2 by means of CVD from tetraethylorthosilicate (TEOS), thereby forming an array of carbon nanotubes embedded in SiO2. Chemical mechanical polishing (CMP) is then performed to remove excess SiO2 and form a flat-top surface in which the outer ends of the carbon nanotubes are exposed. Optionally, depending on the application, metal lines to connect selected ends of carbon nanotubes may be deposited on the top surface. The top part of Figure 2 is a scanning electron micrograph (SEM) of carbon nanotubes grown, as described above, on catalytic spots of about 100 nm diameter patterned by electron-beam lithography. These and other nanotubes were found to have lengths ranging from 2 to 10 m and diameters ranging from 30 to 200 nm, the exact values of length depending on growth times and conditions and the exact values of diameter depending on the diameters and thicknesses of the catalyst spots. The bottom part of Figure 2 is an SEM of an embedded array of carbon nanotubes after CMP.

Li, Jun↗

The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport

The phosphoenolpyruvate:carbohydrate phosphotransferase systems are found in bacteria, where they play central roles in sugar uptake and regulation of cellular uptake processes. Little is known about how the membrane-embedded components (EIICs) selectively mediate the passage of carbohydrates across the membrane. Here we report the functional characterization and 2.55-Å resolution structure of a maltose transporter, bcMalT, belonging to the glucose superfamily of EIIC transporters. bcMalT crystallized in an outward-facing occluded conformation, in contrast to the structure of another glucose superfamily EIIC, bcChbC, which crystallized in an inward-facing occluded conformation. The structures differ in the position of a structurally conserved substrate-binding domain that is suggested to play a central role in sugar transport. In addition, molecular dynamics simulations suggest a potential pathway for substrate entry from the periplasm into the bcMalT substrate-binding site. Furthermore, these results provide a mechanistic framework for understanding substrate recognition and translocation for the glucose superfamily EIIC transporters.

59 BASIC BIOLOGICAL SCIENCES↗

Ionic Liquid Functionalizes the Metal Organic Framework for Microwave-Assisted Direct Air Capture of CO 2

Sorbents for direct air capture (DAC) of CO 2 typically employ a chemisorbing material that requires regeneration at elevated temperatures, which is an energy-intensive step. Here, we developed composites of metal organic framework (MOF) with a functional ionic liquid (IL) at 5, 20, and 35 wt % loading, capable of CO 2 chemisorption and regeneration by moisture-swing coupled microwave (MW) irradiation. In dynamic breakthrough measurements, CO 2 from synthetic air (500 ppm of CO 2 ) was selectively absorbed (0.5 mmol/g at 30 °C) and then rapidly released (2–4 min) by dielectric heating at 60 °C. The developed IL/MOF composites demonstrate (1) targeted energy transfer to the IL domains where CO 2 is released due to dielectric heating upon MW irradiation and (2) a fast desorption rate due to large surface area offered by the MOF architecture. Furthermore, this study establishes carbon capture through surface enhancement of a porous substrate with ILs for future DAC processes that can be powered by sustainable energy sources.

36 MATERIALS SCIENCE↗

Skeletal Ni electrode-catalyzed C-O cleavage of diaryl ethers entails direct elimination via benzyne intermediates

Diaryl ethers undergo electrocatalytic hydrogenolysis (ECH) over skeletal Ni cathodes in a mild, aqueous process that achieves direct C-O cleavage without initial benzene ring saturation. Mechanistic studies find that aryl phenyl ethers with a single para or meta functional group (methyl, methoxy, or hydroxy) are selectively cleaved to the substituted benzene and phenol, in contrast to recently reported homogeneous catalytic cleavage processes. Ortho positioning of substituents reverses this C-O bond selectivity, except for the 2-phenoxyphenol case. Together with isotope labeling and co-solvent studies, these results point to two distinct cleavage mechanisms: (a) dual-ring coordination and C-H activation, leading to vicinal elimination to form phenol and a surface-bound aryne intermediate which is then hydrogenated and released as the arene; and (b) surface binding in keto form by the phenolic ring of the hydroxy-substituted substrates, followed by direct displacement of the departing phenol. Notably, acetone inhibits the well-known reduction of phenol to cyclohexanol, affording control of product ring saturation. A byproduct of this work is the discovery that the ECH treatment completely defluorinates substrates bearing aromatic C-F and C-CF 3 groupings.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Structural insights into β-1,3-glucan cleavage by a glycoside hydrolase family

The fundamental and assorted roles of β-1,3-glucans in nature are underpinned on diverse chemistry and molecular structures, demanding sophisticated and intricate enzymatic systems for their processing. Herein, the selectivity and modes of action of a glycoside hydrolase family active on β-1,3-glucans were systematically investigated combining sequence similarity network, phylogeny, X-ray crystallography, enzyme kinetics, mutagenesis and molecular dynamics. This family exhibits a minimalist and versatile (α/β)-barrel scaffold, which can harbor distinguishing exo or endo modes of action, including an ancillary-binding site for the anchoring of triple-helical β-1,3-glucans. The substrate binding occurs via a hydrophobic knuckle complementary to the canonical curved conformation of β-1,3-glucans or through a substrate conformational change imposed by the active-site topology of some fungal enzymes. Together, these findings expand our understanding of the enzymatic arsenal of bacteria and fungi for the breakdown and modification of β-1,3-glucans, which can be exploited for biotechnological applications.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Metal-interconnection-free integration of InGaN/GaN light emitting diodes with AlGaN/GaN high electron mobility transistors

We report a metal-interconnection-free integration scheme for InGaN/GaN light emitting diodes (LEDs) and AlGaN/GaN high electron mobility transistors (HEMTs) by combining selective epi removal (SER) and selective epitaxial growth (SEG) techniques. SER of HEMT epi was carried out first to expose the bottom unintentionally doped GaN buffer and the sidewall GaN channel. A LED structure was regrown in the SER region with the bottom n-type GaN layer (n-electrode of the LED) connected to the HEMTs laterally, enabling monolithic integration of the HEMTs and LEDs (HEMT-LED) without metal-interconnection. In addition to saving substrate real estate, minimal interface resistance between the regrown n-type GaN and the HEMT channel is a significant improvement over metal-interconnection. Furthermore, excellent off-state leakage characteristics of the driving transistor can also be guaranteed in such an integration scheme.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Phonons in complex twisted crystals: Angular momenta, interactions, and topology

We report phonons and their interactions are critically important for a variety of energy-relevant applications ranging from low thermal resistance substrates to thermal barrier coatings. Fundamental insights into the nature of phonons and allowed interactions are governed by the underlying symmetries of the crystal lattice. In this paper, we provide a comprehensive and detailed description of lattice dynamics derived from twist symmetries of chiral and achiral crystals—twist dynamics. Phonon bands naturally carry quantized crystal angular momentum derived from rotational phases, which give insights into the nature of band crossings and avoided crossings, selection rules for phonon interactions, and topological band crossing behaviors. Twist dynamics is demonstrated for a variety of materials covering a range of space groups, symmetry operations, twist axis orientations, and constituent elements. Furthermore, twist symmetry offers insights into peculiar features observed in scattering measurements. In this context, we present inelastic neutron scattering measurements for rutile TiO 2 and explain them using twist dynamics.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Electrical Control of Spin and Valley in Spin-Orbit Coupled Graphene Multilayers

Electrical control of magnetism has been a major technological pursuit of the spintronics community, owing to its far-reaching implications for data storage and transmission. Here, in this study, we propose and analyze a new mechanism for electrical switching of isospin, using chiral-stacked graphene multilayers, such as Bernal bilayer graphene or rhombohedral trilayer graphene, encapsulated by transition metal dichalcogenide (TMD) substrates. Leveraging the proximity-induced spin-orbit coupling from the TMD, we demonstrate electrical switching of correlation-induced spin and/or valley polarization, by reversing a perpendicular displacement field or the chemical potential. We substantiate our proposal with both analytical arguments and self-consistent Hartree-Fock numerics. Finally, we illustrate how the relative alignment of the TMDs, together with the top and bottom gate voltages, can be used to selectively switch distinct isospin flavors, putting forward correlated Van der Waals heterostructures as a promising platform for spintronics and valleytronics.

36 MATERIALS SCIENCE↗

Laser Intensity Profile Effects on the Solidification Microstructure of Ti-6Al-4V and Ti-5553

Traditional machining of Ti-6Al-4V and Ti-5Al-5Mo-5V-3Cr (Ti-5553) is challenging due to high chemical reactivity, adiabatic shear band formation, and material cost. Titanium is attractive because of its high tensile strength, low density, corrosion resistance, and ability to withstand extreme temperatures. Selective Laser Melting (SLM) is capable of manufacturing geometrically complicated parts at a lower expense. Exceptional tolerances can be obtained with properly tuned processing parameters. Alterations on scan parameters permit microstructure and melt pool control. Single track laser melting experiments were performed on Ti-6Al-4V and Ti- 5553 using elliptical intensity profiles. Results show that maintaining constant energy density but increasing power results in a melt pool failing to penetrate the substrate for Ti-5553. Increasing laser energy density increases melt pool width and can increase powder bed denudation. Comparing Ti64 and Ti-5553 microstructures contributes to a better understanding of rapid solidification in titanium.

36 MATERIALS SCIENCE↗

Guide for Atomic Force Microscopy Image Analysis To Discriminate Heteroatoms in Aromatic Molecules [A Guide for AFM Image Analysis To Discriminate Heteroatoms in Aromatic Molecules]

Heteroatoms are essential for functional groups in organic structures and are complementary to hydrocarbon molecules in reactivities and properties. However, it is still a challenge to quickly identify heteroatoms with only non-contact atomic force microscopy (nc-AFM) to resolve chemical structures in complex unknown mixtures. This study aimed to understand the effect of elemental types on the contrast of atomic force microscopy (AFM) images using a few selected model heterocycles, including dibenzothiophene (DBT), acridine (ACR), and carbazole (CBZ). We identified several features that can be used to find common heteroatoms (S and N) and discriminated them from carbon atoms (C) using nc-AFM images alone. The mechanism of the atom and bond contrast was studied with image simulations and was found to be mostly correlated to van der Waals radii, but other factors, such as bonding geometry, electron density, and substrate interaction, need to be considered. As a result, this work will allow for rapid identification of these common heteroatoms in petroleum with AFM.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Gold Aerogel Monoliths with Tunable Ultralow Densities

Herein we report the fabrication of ultralight gold aerogel monoliths with tunable densities and pore structures. Gold nanowires are prepared at the gram scale by substrate-assisted growth with uniform size, ultrathin diameters, high purity, and a high aspect ratio. Freeze-casting of suspensions of these nanowires produces free-standing, monolithic aerogels with tunable densities from 6 to 23 mg/cm 3 , which to the best of our knowledge represents the lowest density monolithic gold material. We also demonstrate that the pore geometries created during freeze-casting can be systematically tuned across multiple length scales by the selection of different solvents and excipients in the feedstock suspension. Here, the mechanical behavior of porous materials depends on relative density and pore architectures.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Harnessing the photonic local density of states in graphene moiré superlattices

In this work we investigate the electromagnetic local density of states (LDOS) near a twisted bilayer graphene (TBG) deposited over a general isotropic substrate. The band structure of the TBG is calculated within a tight-binding framework, and then used to determine the TBG's conductivity. The latter presents a nontrivial dependence upon the angle of twist, which shows up in the LDOS, allowing for a moiré pattern-dependent quantum emission. For some specific twist angles we show that it is possible to either enhance or decrease the LDOS by an order of magnitude at selected frequencies when compared to the monolayer. Furthermore, this impressive variation is explained in terms of the presence/absence of well defined surface plasmon polaritons (SPPs). Altogether our findings demonstrate that TBG is an alternative, versatile material platform for controlling spontaneous emission and enhancing light-matter interactions, and pave the way for further studies and applications of quantum emission in the emerging class of two-dimensional moiré materials.

36 MATERIALS SCIENCE↗

Microwave switching power divider

A pair of parallel, spaced-apart circular ground planes define a microwave cavity with multi-port microwave power distributing switching circuitry formed on opposite sides of a thin circular dielectric substrate disposed between the ground planes. The power distributing circuitry includes a conductive disk located at the center of the substrate and connected to a source of microwave energy. A high speed, low insertion loss switching diode and a dc blocking capacitor are connected in series between the outer end of a transmission line and an output port. A high impedance, microwave blocking dc bias choke is connected between each switching diode and a source of switching current. The switching source forward biases the diodes to couple microwave energy from the conductive disk to selected output ports and, to associated antenna elements connected to the output ports to form a synthesized antenna pattern.

Stockton, R. J.↗

Measuring the Chemical Potential of the Martian Regolith to Generate and Sustain Life

A critical component for identifying chemical biosignatures is the ability to assess in-situ the potential of an aqueous geochemical environment to generate and sustain life. On Mars or other solar bodies, in-situ chemical characterization could provide evidence as to whether the chemical composition of the regolith or evaporites in suspected ancient water bodies have been biologically influenced or possess the chemical parameters within which life may have existed, or may still exist. A variety of analytical techniques have been proposed for use in detecting and identify signatures of past or present life. These techniques fall into two groups; visual observation with instruments such as cameras or optical/atomic-force microscopes; or elemental chemical analysis with such instruments as X-ray fluorescence (XRF) and diffraction (XRD), a-proton backscatter (APX), y-ray, Mossbauer, Raman, IR, UV/VIS spectroscopies, gas chromatography (GC), or mass spectrometry (MS). Direct observation of an identifiable lifeform by the first set of instruments in a single sample is highly unlikely, especially for extinct organisms or on the surface. The later instruments can provide vital data as to the elemental mineralogy and geological history of the planet, but are highly inadequate for understanding the chemistry of the planet in terms of indigenous life or interactions with human explorers. Techniques such as XRD, XRF, and APX, provide elemental composition at high limits of detection. Some of this data can be extrapolated or interpolated to provide chemical parameters such as oxidation state or composition. Gas chromatography (GC) without standards and non-specific detectors, has little chance of identifying a mixture of unknown components. Combined with GC or by itself, mass spectrometry (MS) can provide identification of compounds, but in both cases the sample must be appropriately prepared for accurate and reliable analysis. Life as we know it, and probably identify it as such, requires an aqueous environment. Deciphering die chemical speciation of this aqueous environment is the key to recognizing therein the biosignatures of any extinct or present life forms. Identifying the soluble (ionic and nonionic) components by reacting a currently dormant environment can provide a "picture" of the thermodynamics and chemical components of a possibly bioactive environment. The only devices which can provide such information are electrochemical sensors based on the potentiometric ion selective electrodes (ISEs) and on dynamic techniques such as cyclic voltammetry (CV) and stripping voltammetry (SV). Such an array of devices can provide not only the chemical composition of a water-soluble Martian soil sample, but also several other vital chemical parameters such as pH, conductivity, redox potential, and dissolved gases. To address these issues we have been investigating the possible use of an electrochemically-based ion sensor array as a new integrated approach to quantitative analytical and chemometric electrochemical measurements. The sensor array will consist of specific and semispecific ion selective and amperometric transducers, which can simultaneously and continuously identify and semiquantitatively determine over 50 organic and inorganic analytes in water-based environments. Several individual sensors, based on the same principle, have been flight-tested and have been installed as part of the MECA instrumentation on the Mars 2001 Lander for in-situ analyses. However, the microfabrication, integration and multiplexing of such a large number of these sensors on a single substrate have not been previously attempted.

Kounaves, S. P.↗

Composite Reflective Absorptive IR-Blocking Filters Embedded in Metamaterial Antireflection Coated Silicon

Infrared (IR)-blocking filters are crucial for controlling the radiative loading on cryogenic systems and for optimizing the sensitivity of bolometric detectors in the far-IR. We present a new IR filter approach based on a combination of patterned frequency-selective structures on silicon and a thin (2575 micron thick) absorptive composite based on powdered reststrahlen absorbing materials. For a 300 K blackbody, this combination reflects approximately 50% of the incoming light and blocks greater than.99.8% of the total power with negligible thermal gradients and excellent low-frequency transmission. This allows a reduction in the IR thermal loading to negligible levels in a single cold filter. These composite filters are fabricated on silicon substrates, which provide excellent thermal transport laterally through the filter and ensure that the entire area of the absorptive filter stays near the bath temperature. A metamaterial antireflection coating cut into these substrates reduces in-band reflections to below 1%, and the in-band absorption of the powder mix is below 1% for signal bands below 750 GHz. This type of filter can be directly incorporated into silicon refractive optical elements.

Munson, C. D.↗

Identification of Potent and Selective Inhibitors of Acanthamoeba : Structural Insights into Sterol 14α-Demethylase as a Key Drug Target

Acanthamoeba are free-living pathogenic protozoa that cause blinding keratitis, disseminated infection, and granulomatous amebic encephalitis, which is generally fatal. The development of efficient and safe drugs is a critical unmet need. Acanthamoeba sterol 14α-demethylase (CYP51) is an essential enzyme of the sterol biosynthetic pathway. Repurposing antifungal azoles for amoebic infections has been reported, but their inhibitory effects on Acanthamoeba CYP51 enzymatic activity have not been studied. Here, we report catalytic properties, inhibition, and structural characterization of CYP51 from Acanthamoeba castellanii. The enzyme displays a 100-fold substrate preference for obtusifoliol over lanosterol, supporting the plant-like cycloartenol-based pathway in the pathogen. The strongest inhibition was observed with voriconazole (1 h IC 50 0.45 μM), VT1598 (0.25 μM), and VT1161 (0.20 μM). The crystal structures of A. castellanii CYP51 with bound VT1161 (2.24 Å) and without an inhibitor (1.95 Å), presented here, can be used in the development of azole-based scaffolds to achieve optimal amoebicidal effectiveness.

60 APPLIED LIFE SCIENCES↗

Evaluating the active site-substrate interplay between x-ray crystal structure and molecular dynamics in chorismate mutase

Designing realistic quantum mechanical (QM) models of enzymes is dependent on reliably discerning and modeling residues, solvents, and cofactors important in crafting the active site microenvironment. Interatomic van der Waals contacts have previously demonstrated usefulness toward designing QM-models, but their measured values (and subsequent residue importance rankings) are expected to be influenceable by subtle changes in protein structure. Using chorismate mutase as a case study, this work examines the differences in ligand-residue interatomic contacts between an x-ray crystal structure and structures from a molecular dynamics simulation. Select structures are further analyzed using symmetry adapted perturbation theory to compute ab initio ligand-residue interaction energies. The findings of this study show that ligand-residue interatomic contacts measured for an x-ray crystal structure are not predictive of active site contacts from a sampling of molecular dynamics frames. In addition, the variability in interatomic contacts among structures is not correlated with variability in interaction energies. However, the results spotlight using interaction energies to characterize and rank residue importance in future computational enzymology workflows.

Chemistry↗