Uniform Diffusion of Cooper Pairing Mediated by Hole Carriers in Topological SbTe/Nb.

Spin-helical Dirac Fermions at a doped topological insulator's boundaries can support Majorana quasiparticles when coupled with -wave superconductors, but in -doped systems, the requisite induced Cooper pairing in topological states is often buried at heterointerfaces or complicated by degenerate coupling with bulk conduction carriers. Rarely probed are -doped topological structures with nondegenerate Dirac and bulk valence bands at the Fermi level, which may foster long-range superconductivity without sacrificing Majorana physics. Using ultrahigh-resolution photoemission, we report proximity pairing with a large decay length in -doped topological SbTe on superconducting Nb.

Automated Grain Boundary Detection for Bright-Field Transmission Electron Microscopy Images via U-Net.

Quantification of microstructures is crucial for understanding processing-structure and structure-property relationships in polycrystalline materials. Delineating grain boundaries in bright-field transmission electron micrographs, however, is challenging due to complex diffraction contrast in images. Conventional edge detection algorithms are inadequate; instead, manual tracing is usually required.

Massive Suppression of Proximity Pairing in Topological (Bi_{1-x}Sb_{x})_{2}Te_{3} Films on Niobium.

Interfacing bulk conducting topological Bi_{2}Se_{3} films with s-wave superconductors initiates strong superconducting order in the nontrivial surface states. However, bulk insulating topological (Bi_{1-x}Sb_{x})_{2}Te_{3} films on bulk Nb instead exhibit a giant attenuation of surface superconductivity, even for films only two layers thick. This massive suppression of proximity pairing is evidenced by ultrahigh-resolution band mappings and by contrasting quantified superconducting gaps with those of heavily n-doped topological Bi_{2}Se_{3}/Nb.

In Situ Strain Tuning of the Dirac Surface States in BiSe Films.

Elastic strain has the potential for a controlled manipulation of the band gap and spin-polarized Dirac states of topological materials, which can lead to pseudomagnetic field effects, helical flat bands, and topological phase transitions. However, practical realization of these exotic phenomena is challenging and yet to be achieved. Here we show that the Dirac surface states of the topological insulator BiSe can be reversibly tuned by an externally applied elastic strain.

Superconducting pairing of topological surface states in bismuth selenide films on niobium.

A topological insulator film coupled to a simple isotropic s-wave superconductor substrate can foster helical pairing of the Dirac fermions associated with the topological surface states. Experimental realization of such a system is exceedingly difficult, however using a novel "flip-chip" technique, we have prepared single-crystalline BiSe films with predetermined thicknesses in terms of quintuple layers (QLs) on top of Nb substrates fresh from in situ cleavage. Our angle-resolved photoemission spectroscopy (ARPES) measurements of the film surface disclose superconducting gaps and coherence peaks of similar magnitude for both the topological surface states and bulk states.

Correlating interfacial octahedral rotations with magnetism in (LaMnO3+δ)N/(SrTiO3)N superlattices.

Lattice distortion due to oxygen octahedral rotations have a significant role in mediating the magnetism in oxides, and recently attracts a lot of interests in the study of complex oxides interface. However, the direct experimental evidence for the interrelation between octahedral rotation and magnetism at interface is scarce. Here we demonstrate that interfacial octahedral rotation are closely linked to the strongly modified ferromagnetism in (LaMnO3+δ)N/(SrTiO3)N superlattices.

Surrogate matrix and surrogate analyte approaches for definitive quantitation of endogenous biomolecules.

Background: Quantitation of biomarkers by LC-MS/MS is complicated by the presence of endogenous analytes. This challenge is most commonly overcome by calibration using an authentic standard spiked into a surrogate matrix devoid of the target analyte. A second approach involves use of a stable-isotope-labeled standard as a surrogate analyte to allow calibration in the actual biological matrix.

Effects of a novel mGlu₂/₃ receptor agonist prodrug, LY2140023 monohydrate, on central monoamine turnover as determined in human and rat cerebrospinal fluid.

Rationale: Accumulating evidence suggests that the primary symptoms of schizophrenia may be associated with altered central glutamate transmission. LY2140023 monohydrate is the methionine prodrug of the selective mGlu(2/3) receptor agonist LY404039 and is currently being assessed for the treatment of schizophrenia.

Objective: The objective of this study was to evaluate the central pharmacological activity of LY2140023 monohydrate in preclinical and clinical studies.

N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a novel metabotropic glutamate 2 potentiator with potential anxiolytic/antidepressant properties: in vivo profiling suggests a link between behavioral and central nervous system neurochemical changes.

The normalization of excessive glutamatergic neurotransmission through the activation of metabotropic glutamate 2 (mGlu2) receptors may have therapeutic potential in a variety of psychiatric disorders, including anxiety/depression and schizophrenia. Here, we characterize the pharmacological properties of N-(4-((2-(trifluoromethyl)-3-hydroxy-4-(isobutyryl)phenoxy)methyl)benzyl)-1-methyl-1H-imidazole-4-carboxamide (THIIC), a structurally novel, potent, and selective allosteric potentiator of human and rat mGlu2 receptors (EC(50) = 23 and 13 nM, respectively). THIIC produced anxiolytic-like efficacy in the rat stress-induced hyperthermia assay and the mouse stress-induced elevation of cerebellar cGMP and marble-burying assays.

Current applications of liquid chromatography/mass spectrometry in pharmaceutical discovery after a decade of innovation.

Current drug discovery involves a highly iterative process pertaining to three core disciplines: biology, chemistry, and drug disposition. For most pharmaceutical companies the path to a drug candidate comprises similar stages: target identification, biological screening, lead generation, lead optimization, and candidate selection. Over the past decade, the overall efficiency of drug discovery has been greatly improved by a single instrumental technique, liquid chromatography/mass spectrometry (LC/MS).

Analysis of glutamine, glutamate, pyroglutamate, and GABA in cerebrospinal fluid using ion pairing HPLC with positive electrospray LC/MS/MS.

A simple and sensitive method for the separation and quantitation of glutamine, glutamate, pyroglutamate, and gamma-aminobutyric acid (GABA) in cerebrospinal fluid (CSF) is presented. The method utilizes ion pairing with heptafluorobutyric acid (HFBA) to achieve HPLC separation with detection by positive ESI LC/MS/MS. The method does not require extraction or derivatization, utilizes a heavy labeled internal standard for each analyte, and allows for rapid throughput with a 5 min run time.

Simultaneous profiling of multiple neurochemical pathways from a single cerebrospinal fluid sample using GC/MS/MS with electron capture detection.

Biogenic amines and amino acids are widely characterized in the pathways representing neurotransmission. Although several analytical methodologies have been used to detect specific target molecules in relevant fluids such as cerebrospinal fluid (CSF), multiple assays must be used to survey the primary pathways involved. This article describes the development of a GC/MS/MS method capable of analyzing up to 43 analytes (representing 20 amino acids and more than seven neurochemical pathways) from a single 50 microl CSF sample.

Electronic reconstruction at SrMnO3-LaMnO3 superlattice interfaces.

We use resonant soft-x-ray scattering (RSXS) to study the electronic reconstruction at the interface between the Mott insulator LaMnO3 and the band insulator SrMnO3. Superlattices of these two insulators were shown previously to have both ferromagnetism and metallic tendencies [Koida, Phys. Rev.

Synthetically lethal interactions involving loss of the yeast ERG24: the sterol C-14 reductase gene.

ERG2 and ERG24 are yeast sterol biosynthetic genes which are targets of morpholine antifungal compounds. ERG2 and ERG24 encode the C-8 sterol isomerase and the C-14 reductase, respectively. ERG2 is regarded as a non-essential gene but the viability of ERG24 depends on genetic background, type of medium, and CaCl(2) concentration.

Dap1/PGRMC1 binds and regulates cytochrome P450 enzymes.

Cytochrome P450 enzymes are heme-dependent monoxygenases that play a central role in human physiology. Despite the numerous physiological processes that P450 enzymes impact, the electron donors P450 oxidoreductase and cytochrome b5 are the only proteins known to interact with and modulate the activity of ER microsomal P450s. Here, we report that Dap1/PGRMC1 is required for ER P450 function in yeast and humans.

Cumulative mutations affecting sterol biosynthesis in the yeast Saccharomyces cerevisiae result in synthetic lethality that is suppressed by alterations in sphingolipid profiles.

UPC2 and ECM22 belong to a Zn(2)-Cys(6) family of fungal transcription factors and have been implicated in the regulation of sterol synthesis in Saccharomyces cerevisiae and Candida albicans. Previous reports suggest that double deletion of these genes in S. cerevisiae is lethal depending on the genetic background of the strain.

Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450.

The biotransformation of prasugrel to R-138727 (2-[1-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid) involves rapid deesterification to R-95913 (2-[2-oxo-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl]-1-cyclopropyl-2-(2-fluorophenyl)ethanone) followed by cytochrome P450 (P450)-mediated formation of R-138727, the metabolite responsible for platelet aggregation. For identification of the P450s responsible for the formation of the active metabolite, the current studies were conducted with R-95913 as the substrate. Incubations required supplementation with reduced glutathione.

Sterol uptake in Candida glabrata: rescue of sterol auxotrophic strains.

Candida glabrata is emerging as a more common and important human pathogen. It is less susceptible to azole antifungals than Candida albicans, thus, posing some unique treatment challenges. Previously undetected C.

Effect of tadalafil on cytochrome P450 3A4-mediated clearance: studies in vitro and in vivo.

Objectives: Tadalafil was examined in vitro and in vivo for its ability to affect human cytochrome P450 (CYP) 3A-mediated metabolism.

Methods: Reversible and mechanism-based inhibition of CYP3A by tadalafil was examined in human liver microsomes. The ability of tadalafil to influence CYP3A activity was also examined in primary cultures of human hepatocytes.

Broken particle-hole symmetry at atomically flat a-axis YBa2Cu3O7-delta interfaces.

We have studied quasiparticle tunneling into atomically flat a-axis films of YBa(2)Cu(3)O(7-delta) and DyBa(2)Cu(3)O(7-delta) through epitaxial CaTiO3 barriers. The junction heterostructures were grown by oxide molecular beam epitaxy and were carefully optimized using in situ monitoring techniques, resulting in unprecedented crystalline perfection of the superconductor-insulator interface. Below T(c), the tunneling conductance shows the evolution of a large unexpected asymmetrical feature near zero-bias.

Genome-wide expression profiling reveals genes associated with amphotericin B and fluconazole resistance in experimentally induced antifungal resistant isolates of Candida albicans.

Objectives: The aim of this study was to identify changes in the gene expression profile of Candida albicans associated with the acquisition of experimentally induced resistance to amphotericin B and fluconazole.

Methods: C. albicans SC5314 was passed in increasing concentrations of amphotericin B to generate isolate SC5314-AR.

An assessment of udp-glucuronosyltransferase induction using primary human hepatocytes.

Uridine diphosphate glucuronosyltransferases (UGTs) catalyze the glucuronidation of a wide range of xenobiotics and endogenous substrates. However, there is a lack of information concerning the response of human UGTs to inducers, and this observation prompted the current investigation. The glucuronidation of estradiol (3- and 17-positions), naphthol, propofol, and morphine (3- and 6-positions) was assessed against a battery of recombinant human UGTs to determine selective glucuronidation reactions for induction studies.