GaN/NbN epitaxial semiconductor/superconductor heterostructures.

Epitaxy is a process by which a thin layer of one crystal is deposited in an ordered fashion onto a substrate crystal. The direct epitaxial growth of semiconductor heterostructures on top of crystalline superconductors has proved challenging. Here, however, we report the successful use of molecular beam epitaxy to grow and integrate niobium nitride (NbN)-based superconductors with the wide-bandgap family of semiconductors-silicon carbide, gallium nitride (GaN) and aluminium gallium nitride (AlGaN). We apply molecular beam epitaxy to grow an AlGaN/GaN quantum-well heterostructure directly on top of an ultrathin crystalline NbN superconductor. The resulting high-mobility, two-dimensional electron gas in the semiconductor exhibits quantum oscillations, and thus enables a semiconductor transistor-an electronic gain element-to be grown and fabricated directly on a crystalline superconductor. Using the epitaxial superconductor as the source load of the transistor, we observe in the transistor output characteristics a negative differential resistance-a feature often used in amplifiers and oscillators. Our demonstration of the direct epitaxial growth of high-quality semiconductor heterostructures and devices on crystalline nitride superconductors opens up the possibility of combining the macroscopic quantum effects of superconductors with the electronic, photonic and piezoelectric properties of the group III/nitride semiconductor family.

Dynamic Mode Suppression and Frequency Tuning in S-Band GaN/YIG Magnetoelastic HBARs.

This work presents the detailed characterization and analysis of recently reported magnetoelastic high-overtone bulk acoustic resonators (ME-HBARs), which are multimode RF-acoustic (phononic) resonators operating in the S -band. These unique devices are fabricated by microtransfer printing (MTP) piezoelectric GaN transducers onto a ferrimagnetic yttrium iron garnet (YIG) substrate. The YIG substrate also supports spin waves (magnons) when biased with an external magnetic field. The resulting phonon-magnon hybridization can be used to suppress or tune the acoustic modes of the ME-HBAR. The experiment spans 66 distinct acoustic resonance modes from 2.4 to 3 GHz, each of which can be suppressed or tuned as much as ±6 MHz, with a bias magnetic field ≤ 0.21 T. The experimental ME-HBAR data show good agreement with analytical modeling of the magnetoelastic hybridization in YIG. Such ME-HBARs can be used as dynamically tunable or switchable resonators, oscillators, comb filters, or frequency selective limiters in RF signal processing subcomponents. By integrating incompatible materials (YIG, epitaxial GaN) and disparate functionalities (spin waves, acoustic waves) into one hybrid multidomain system, this work also demonstrates the power and broad scope of the MTP technique.

Random local temporal structure of category fluency responses.

The Category Fluency Test (CFT) provides a sensitive measurement of cognitive capabilities in humans related to retrieval from semantic memory. In particular, it is widely used to assess progress of cognitive impairment in patients with dementia. Previous research shows that, in the first approximation, the intensity of tested individuals' responses within a standard 60-s test period decays exponentially with time, with faster decay rates for more cognitively impaired patients. Such decay rate can then be viewed as a global (macro) diagnostic parameter of each test. In the present paper we focus on the statistical properties of the properly de-trended time intervals between consecutive responses (inter-call times) in the Category Fluency Test. In a sense, those properties reflect the local (micro) structure of the response generation process. We find that a good approximation for the distribution of the de-trended inter-call times is provided by the Weibull Distribution, a probability distribution that appears naturally in this context as a distribution of a minimum of independent random quantities and is the standard tool in industrial reliability theory. This insight leads us to a new interpretation of the concept of "navigating a semantic space" via patient responses.

Phase Identification and Ordered Vacancy Imaging in Epitaxial Metallic Ta2N Thin Films.

Epitaxial transition metal nitrides (TMNs) are an emerging class of crystalline thin film metals that can be heteroepitaxially integrated with common group III-nitride semiconductors such as GaN and AlN. Within a binary family of TMN compounds (i.e., TaxNy), several phases typically exist, many with similar crystal structures that are difficult to distinguish by conventional X-ray diffraction or other bulk characterization means. In this work, we demonstrate the combined power of high-resolution transmission and aberration-corrected scanning transmission electron microscopy for definitive phase identification of tantalum nitrides with different N-sublattice ordering. Analysis of molecular beam epitaxy-grown γ-Ta2N films on SiC substrates shows that the films are γ phase, threading dislocation-free, and Ta-deficient. The lack of Ta manifests as ordered Ta vacancy planar defects oriented in the plane perpendicular to the [0001] growth direction and accounts for the substoichiometry. Optimization of the growth parameters should reduce the Ta vacancy concentration, and alternatively, exploitation of the attractive nature of the Ta vacancies may enable novel planar structures. These findings serve as an important first step in applying this epitaxial TMN material for new electronic and superconducting device structures.

Passive High Power RF Comb Filters Using Epitaxial GaN/NbN/SiC HBARs.

This report presents the first demonstration of passive RF comb filters made using epitaxial GaN/NbN/SiC high overtone bulk acoustic resonators (epi-HBARs). The two-port device is fabricated on electronic-grade GaN, electrically transduced, and acoustically coupled. The multi-mode epi-HBAR comb filter demonstrated here has 158 sharp filter passbands periodically distributed between 1 and 4 GHz (L-S-bands) with a free spectral range (FSR) of 17 MHz. The individual passbands of the epi-HBAR comb filter demonstrate transmission bandwidths (BWs) up to 800 kHz, f × Q values of up to 7×1014 Hz, and an average [Formula: see text] figure of merit of 41.2 at room temperature. The GaN/NbN/SiC epi-HBAR comb filter is capable of operating at high RF power levels, with linear and distortion-free performance seen up to at least 1 W of continuous wave (CW) power and up to at least 10 W of pulsed power. The compact epi-HBAR comb filters can be co-fabricated with GaN-based electronics and could potentially replace larger, off-chip or discrete-component comb filters. They can be used for spectrum sensing and as signal processing elements for remote sensing and pulsed radar.

An all-epitaxial nitride heterostructure with concurrent quantum Hall effect and superconductivity.

Creating seamless heterostructures that exhibit the quantum Hall effect and superconductivity is highly desirable for future electronics based on topological quantum computing. However, the two topologically robust electronic phases are typically incompatible owing to conflicting magnetic field requirements. Combined advances in the epitaxial growth of a nitride superconductor with a high critical temperature and a subsequent nitride semiconductor heterostructure of metal polarity enable the observation of clean integer quantum Hall effect in the polarization-induced two-dimensional (2D) electron gas of the high-electron mobility transistor. Through individual magnetotransport measurements of the spatially separated GaN 2D electron gas and superconducting NbN layers, we find a small window of magnetic fields and temperatures in which the epitaxial layers retain their respective quantum Hall and superconducting properties. Its analysis indicates that in epitaxial nitride superconductor/semiconductor heterostructures, this window can be significantly expanded, creating an industrially viable platform for robust quantum devices that exploit topologically protected transport.

Epitaxial bulk acoustic wave resonators as highly coherent multi-phonon sources for quantum acoustodynamics.

Solid-state quantum acoustodynamic (QAD) systems provide a compact platform for quantum information storage and processing by coupling acoustic phonon sources with superconducting or spin qubits. The multi-mode composite high-overtone bulk acoustic wave resonator (HBAR) is a popular phonon source well suited for QAD. However, scattering from defects, grain boundaries, and interfacial/surface roughness in the composite transducer severely limits the phonon relaxation time in sputter-deposited devices. Here, we grow an epitaxial-HBAR, consisting of a metallic NbN bottom electrode and a piezoelectric GaN film on a SiC substrate. The acoustic impedance-matched epi-HBAR has a power injection efficiency >99% from transducer to phonon cavity. The smooth interfaces and low defect density reduce phonon losses, yielding (f × Q) and phonon lifetimes up to 1.36 × 1017 Hz and 500 µs respectively. The GaN/NbN/SiC epi-HBAR is an electrically actuated, multi-mode phonon source that can be directly interfaced with NbN-based superconducting qubits or SiC-based spin qubits.

Band Alignment of ScxAl1-xN/GaN Heterojunctions.

ScAlN is an emergent ultrawide-band-gap material with both a high piezoresponse and demonstrated ferroelectric polarization switching. Recent demonstration of epitaxial growth of ScAlN on GaN has unlocked prospects for new high-power transistors and nonvolatile memory technologies fabricated from these materials. An understanding of the band alignments between ScAlN and GaN is crucial in order to control the electronic and optical properties of engineered devices. To date, there have been no experimental studies of the band offsets between ScAlN and GaN. This work presents optical characterization of the band gap of molecular beam epitaxy grown ScxAl1-xN using spectroscopic ellipsometry and measurements of the band offsets of ScxAl1-xN with GaN using X-ray photoemission spectroscopy, along with a comparison to first-principles calculations. The band gap is shown to continuously decrease as a function of increasing ScN alloy fraction with a negative bowing parameter. Furthermore, a crossover from straddling (type-I) to staggered (type-II) band offsets is demonstrated as Sc composition increases beyond approximately x = 0.11. These results show that the ScAlN/GaN valence band alignment can be tuned by changing the Sc alloy fraction, which can help guide the design of heterostructures in future ScAlN/GaN-based devices.

Near-UV electroluminescence in unipolar-doped, bipolar-tunneling GaN/AlN heterostructures.

Cross-gap light emission is reported in n-type unipolar GaN/AlN double-barrier heterostructure diodes at room temperature. Three different designs were grown on semi-insulating bulk GaN substrates using molecular beam epitaxy (MBE). All samples displayed a single electroluminescent spectral peak at 360 nm with full-width at half-maximum (FWHM) values no greater than 16 nm and an external quantum efficiency (EQE) of ≈0.0074% at 18.8 mA. In contrast to traditional GaN light emitters, p-type doping and p-contacts are completely avoided, and instead, holes are created in the GaN on the emitter side of the tunneling structure by direct interband (that is, Zener) tunneling from the valence band to the conduction band on the collector side. The Zener tunneling is enhanced by the high electric fields (~5 × 106 V cm-1) created by the notably large polarization-induced sheet charge at the interfaces between the AlN and GaN.

Plasma-assisted Molecular Beam Epitaxy of N-polar InAlN-barrier High-electron-mobility Transistors.

Plasma-assisted molecular beam epitaxy is well suited for the epitaxial growth of III-nitride thin films and heterostructures with smooth, abrupt interfaces required for high-quality high-electron-mobility transistors (HEMTs). A procedure is presented for the growth of N-polar InAlN HEMTs, including wafer preparation and growth of buffer layers, the InAlN barrier layer, AlN and GaN interlayers and the GaN channel. Critical issues at each step of the process are identified, such as avoiding Ga accumulation in the GaN buffer, the role of temperature on InAlN compositional homogeneity, and the use of Ga flux during the AlN interlayer and the interrupt prior to GaN channel growth. Compositionally homogeneous N-polar InAlN thin films are demonstrated with surface root-mean-squared roughness as low as 0.19 nm and InAlN-based HEMT structures are reported having mobility as high as 1,750 cm2/V∙sec for devices with a sheet charge density of 1.7 x 1013 cm-2.

The role of two novel regulatory sites in the activation of the cGMP-dependent protein kinase from Plasmodium falciparum.

The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) uniquely contains three cGMP binding sites, but also has a 'degenerate' fourth site. The role of each cGMP-binding site in PfPKG activation remains unknown. We have analysed the effect of mutation of each cGMP-binding site (individually and in combination) on PfPKG activation in vitro. The most striking result was that mutation of cGMP site 3 resulted in a 10-49-fold increase in the K (a((cGMP))) value and a 45-55% decrease in maximal activity compared with wild-type. Mutations involving only cGMP-binding sites 1 and 2 had less effect on both the K (a((cGMP))) values and the maximal activities. These results suggest that, although all three cGMP-binding sites are involved in PfPKG activation, cGMP-binding site 3 has the greatest influence on activation. A mutation in the fourth, degenerate cGMP-binding site decreased PfPKG maximal activity by 40%, but did not change the K (a((cGMP))) value for the PfPKG mutant, suggesting that this site does not bind cGMP, but is required for full activation of PfPKG. The distinct activation properties of PfPKG from mammalian isoforms may be exploitable in the design of a parasite-specific inhibitor and development of a novel anti-malarial drug.

The relationship of physico-chemical properties and structure to the differential antiplasmodial activity of the cinchona alkaloids.

BACKGROUND: The 8-amino and 9-hydroxy substituents of antimalarial cinchona alkaloids have the erythro orientation while their inactive 9-epimers are threo. From the X-ray structures a 90 degrees difference in torsion angle between the N1-H1 and C9-O12 bonds in the two series is believed to be important. In order to kill the malaria parasite, alkaloids must cross the erythrocyte and parasite membranes to accumulate in the acid digestive vacuole where they prevent detoxication of haematin produced during haemoglobin breakdown. METHODS: Ionization constants, octanol/water distribution and haematin interaction are examined for eight alkaloids to explain the influence of small structural differences on activity. RESULTS: Erythro isomers have a high distribution ratio of 55:1 from plasma to the erythrocyte membrane, while for the more basic threo epimers this is only 4.5:1. This gives an increased transfer rate of the erythro drugs into the erythrocyte and thence into the parasite vacuole where their favourable conformation allows interaction with haematin, inhibiting its dimerization strongly (90 +/- 7%) and thereby killing the parasite. The threo compounds not only enter more slowly but are then severely restricted from binding to haematin by the gauche alignment of their N1-H1 and C9-O12 bonds. Confirmatory molecular models allowed measurement of angles and bond lengths and computation of the electronic spectrum of a quinine-haematin complex. CONCLUSION: Differences in the antiplasmodial activity of the erythro and threo cinchona alkaloids may therefore be attributed to the cumulative effects of lipid/aqueous distribution ratio and drug-haematin interaction. Possible insights into the mechanism of chloroquine-resistance are discussed.

Whole genome scan detects an allelic variant of fad2 associated with increased oleic acid levels in maize.

We used whole genome scan association mapping to identify loci with major effect on oleic acid content in maize kernels. Single nucleotide polymorphism haplotypes at 8,590 loci were tested for association with oleic acid content in 553 maize inbreds. A single locus with major effect on oleic acid was mapped between 380 and 384 cM in the IBM2 neighbors genetic map on chromosome 4 and confirmed in a biparental population. A fatty acid desaturase, fad2, identified approximately 2 kb from the associated genetic marker, is the most likely candidate gene responsible for the differences in the phenotype. The fad2 alleles with high- and low-oleic acid content were sequenced and allelic differences in fad2 RNA level in developing embryos was investigated. We propose that a non-conservative amino acid polymorphism near the active site of fad2 contributes to the effect on oleic acid content. This is the first report of the use of a high resolution whole genome scan association mapping where a putative gene responsible for a quantitative trait was identified in plants.

Serum amyloid A protein binds to outer membrane protein A of gram-negative bacteria.

Serum amyloid A (SAA) is the major acute phase protein in man and most mammals. We observed SAA binding to a surprisingly large number of Gram-negative bacteria, including Escherichia coli, Salmonella typhimurium, Shigella flexneri, Klebsiella pneumoniae, Vibrio cholerae, and Pseudomonas aeruginosa. The binding was found to be high affinity and rapid. Importantly, this binding was not inhibited by high density lipoprotein with which SAA is normally complexed in serum. Binding was also observed when bacteria were offered serum containing SAA. Ligand blots following SDS-PAGE or two-dimensional gels revealed two major ligands of 29 and 35 kDa that bound SAA when probing with radiolabeled SAA or SAA and monoclonal anti-SAA. Following fractionation the ligand was found in the outer membrane fraction of E. coli and was identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry to be outer membrane protein A (OmpA). OmpA-deficient E. coli did not bind SAA, and following purification of OmpA the protein retained binding activity. The ligands on other bacteria were likely to be homologues of OmpA because wild type, but not OprF-deficient, P. aeruginosa bound SAA.

Identification and characterization of endoplasmic reticulum-associated degradation proteins differentially affected by endoplasmic reticulum stress.

The disposal of misfolded proteins from the lumen of the endoplasmic reticulum (ER) is one of the quality control mechanisms present in the protein secretory pathway. Through ER-associated degradation, misfolded substrates are targeted to the cytosol where they are degraded by the proteasome. We have identified four maize (Zea mays) Der1-like genes (Zm Derlins) that encode homologs of Der1p, a yeast (Saccharomyces cerevisiae) protein implicated in ER-associated degradation. Zm Derlins are capable of functionally complementing a yeast Der1 deletion mutant. Such complementation indicates that the Der1p function is conserved among species. Zm Derlin genes are expressed at low levels throughout the plant, but appear prevalent in tissues with high activity of secretory protein accumulation, including developing endosperm cells. Expression of three of the four Zm Derlin genes increases during ER stress, with Zm Derlin1-1 showing the strongest induction. Subcellular fractionation experiments localized Zm Derlin proteins to the membrane fraction of microsomes. In maize endosperm, Zm Derlin proteins were found primarily associated with ER-derived protein bodies regardless of the presence of an ER stress response.

TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate specificity restricted to fatty acid and phospholipid hydroperoxides, is localized to the endoplasmic reticulum.

Until recently, it had been thought that trypanosomes lack glutathione peroxidase activity. Here we report the subcellular localization and biochemical properties of a second glutathione-dependent peroxidase from Trypanosoma cruzi (TcGPXII). TcGPXII is a single-copy gene which encodes a 16 kDa protein that appears to be specifically dependent on glutathione as the source of reducing equivalents. Recombinant TcGPXII was purified and shown to have peroxidase activity towards a narrow substrate range, restricted to hydroperoxides of fatty acids and phospholipids. Analysis of the pathway revealed that TcGPXII activity could be readily saturated by glutathione and that the peroxidase functioned by a Ping Pong mechanism. Enzyme reduction was shown to be the rate-limiting step in this pathway. Using immunofluorescence, TcGPXII was shown to co-localize with a homologue of immunoglobulin heavy-chain binding protein (BiP), a protein restricted to the endoplasmic reticulum and Golgi. As the smooth endoplasmic reticulum is the site of phospholipid and fatty acid biosynthesis, this suggests that TcGPXII may play a specific role in the T. cruzi oxidative defence system by protecting newly synthesized lipids from peroxidation.

A Full-Coordinate Model of the Polymerase Domain of HIV-I Reverse Transcriptase and its Interaction With a Nucleic Acid Substrate.

Abstract We present a full-coordinate model of residues 1-319 of the polymerase domain of HIV-I reverse transcriptase. This model was constructed from the x-ray crystallographic structure of Jacobo-Molina et al. (Jacobo-Molina et al., P.N.A.S. USA 90, 6320-6324 (1993)) which is currently available to the degree of C- coordinates. The backbone and side-chain atoms were constructed using the MAXSPROUT suite of programs (L. Holm and C. Sander, Mol. Biol. 218, 183-194 (1991)) and refined through molecular modeling. A seven base pair A-form dsDNA was positioned in the nucleic acid binding cleft to represent the template-primer complex. The orientation of the template-primer complex in the nucleic acid binding cleft was guided by the positions of phosphorus atoms in the crystal structure. Two magnesium ions were placed in the active site in order to better understand the polymerization mechanism. The positions of metal ions in a number of structures guided the placement of ions in this study (L.S. Beese and T.A. Steitz, EMBO. J10, 25-33 (1991); T.A. Steitz and J.A. Steitz, P.N.A.S. USA 90, 6498-6502 (1993); D.L. Sloan et al., J. Biol. Chem. 250, 8913-8920 (1975); R.F. Setlik et al., J. Biomol. Str. Dyn. 10, 945-972 (1993)). The geometry of the active site allowed metal ions to be bound to Asp 110 and Asp 186 of the catalytic triad. However, due to spacial constraints, Asp 185 was found unable to bind to a metal ion. Due to its proximity to the attacking 3'OH group of the 3' terminal residue of the primer strand, it is proposed that this residue acts as a general base which abstracts a proton from the attacking group. Based on the locations of these metal ions with respect to the attacking group of the 3' end of the primer strand and to an incoming dTTP placed in the active site, we propose roles for the magnesium ions and discuss a mechanism through which chain elongation occurs. Also reported are the interactions between the polymerase domain and the template-primer complex observed in our model. These interactions are discussed in view of their possible roles in positioning the nucleic acid complex in the binding cleft and in regard to other structural and functional roles. The importance of these residues as observed in our model is compared to results from multiple sequence alignments and various mutational studies on HIV-I reverse transcriptase.

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites.

Homologues of human macrophage migration inhibitory factor from a parasitic nematode. Gene cloning, protein activity, and crystal structure.

Cytokines are the molecular messengers of the vertebrate immune system, coordinating the local and systemic immune responses to infective organisms. We report here functional and structural data on cytokine-like proteins from a eukaryotic pathogen. Two homologues of the human cytokine macrophage migration inhibitory factor (MIF) have been isolated from the parasitic nematode Brugia malayi. Both molecules (Bm-MIF-1 and Bm-MIF-2) show parallel functions to human MIF. They are chemotactic for human monocytes and activate them to produce IL-8, TNF-alpha, and endogenous MIF. The human and nematode MIF homologues share a tautomerase enzyme activity, which is in each case abolished by the mutation of the N-terminal proline residue. The crystal structure of Bm-MIF-2 at 1.8-A resolution has been determined, revealing a trimeric assembly with an inner pore created by beta-stranded sheets from each subunit. Both biological activity and crystal structure reveal remarkable conservation between a human cytokine and its parasite counterpart despite the considerable phylogenetic divide among these organisms. The strength of the similarity implies that MIF-mediated pathways play an important role in nematode immune evasion strategies.