Magnetic Relaxation And Intrinsic Pinning In A Single Crystal Of Bi2sr2cacu2ox

Magnetic-relaxation experiments were performed on Bi2Sr2CaCu2Ox single crystals with the direction of the field parallel to the ab plane. Based on the relaxation data, we have obtained relationships between the activation energy U and the current density j by an approach we developed previously. We found that the activation energy has a logarithmic dependence on j in a wide regime of driving force. It has been reported that CuO2 planes in high-Tc superconductors can act as strong intrinsic pinning centers and that the relation U∼U0ln(jc/j) may describe such a pinning mechanism. Our experimental results have shown good agreement with such a physical model of intrinsic flux pinning. © 1993 The American Physical Society.4795414541

Preparation of YBCO Films on CeO 2 -Buffered (001) YSZ Substrates by a Non-Fluorine MOD Method

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66369/1/j.1551-2916.2004.01669.x.pd

Title Page: Going beyond common drug metabolizing enzymes: Case studies of biotransformation involving aldehyde oxidase, gamma-glutamyl transpeptidase, cathepsin B, flavin-containing monooxygenase, and ADP-ribosyltransferase Running Title Page: Non-P450 d

adenine dinucleotide and its reduced form, NADP+/H, nicotinamide adenine dinucleotide phosphate and its reduced form, NMN, nicotinamide mononucleotide; PAB, para-aminobenzyl; Val-Cit, valine-citrulline. DMD #70169 3 Abstract The significant roles that cytochrome P450 (P450) and UDP-glucuronosyl transferase (UGT) enzymes play in drug discovery cannot be ignored, and these enzyme systems are commonly examined during drug optimization using liver microsomes or hepatocytes. At the same time, other drug metabolizing enzymes have a role in the metabolism of drugs and can lead to challenges in drug optimization that could be mitigated if the contributions of these enzymes were better understood. This paper presents examples (mostly from Genentech) of five different non-P450 and non-UGT enzymes that contribute to the metabolic clearance or bioactivation of drugs and drug candidates. Aldehyde oxidase mediates a unique amide hydrolysis of GDC-0834, leading to high clearance of the drug. Likewise, the rodent-specific ribose conjugation by ADP-ribosyltransferase leads to high clearance of an interleukin-2-inducible T-cell kinase inhibitor. Metabolic reactions by flavin-containing monooxygenases (FMO) are easily mistaken for P450-mediated metabolism such as oxidative defluorination of 4-fluoro-N-methylaniline by FMO. Gamma-glutamyl transpeptidase is involved in the initial hydrolysis of glutathione metabolites, leading to formation of proximate toxins and nephrotoxicity, as is observed with cisplatin in the clinic, or renal toxicity, as is observed with efavirenz in rodents. Finally, cathepsin B is a lysosomal enzyme that is highly expressed in human tumors and has been targeted to release potent cytotoxins, as in the case of brentuximab vedotin. These examples of non-P450-and non-UGT-mediated metabolism show that a more complete understanding of drug metabolizing enzymes allows for better insight into the fate of drugs and improved design strategies of molecules in drug discovery. DMD #70169

The development of Y Ba2Cu3Ox thin films using a fluorine-free sol–gel approach for coated conductors

Despite great success in the TFA methods of depositing Y Ba2Cu3Ox (YBCO) thin films for coated conductors, critical issues involved in removing BaCO3 have not entirely been settled. There could be other possible ways of dealing with carbon that remains in the film. We have recently developed a fluorine-free sol–gel synthesis with several important advantages including precursor solution stability, improved film density, and elimination of HF during processing. With this approach, high-quality YBCO films have been developed on single crystal substrates with the transport Jc s up to 106 A cm−2. In this study, the precursor solution stoichiometry was altered and its effects on superconducting properties were studied. The fluorine-free sol–gel-derived films on the LaAlO3 (LAO) substrate exhibited epitaxial growth with excellent in- and out-of-plane texture. Experimental details are reported on the sol–gel synthesis chemistry and XRD and TEM characterization of the YBCO thin films. Also discussed is the underlying formation mechanism of the YBCO phase during the synthesis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48992/2/sust4_12_011.pd

Preclinical discovery of apixaban, a direct and orally bioavailable factor Xa inhibitor

Apixaban (BMS-562247; 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide), a direct inhibitor of activated factor X (FXa), is in development for the prevention and treatment of various thromboembolic diseases. With an inhibitory constant of 0.08 nM for human FXa, apixaban has greater than 30,000-fold selectivity for FXa over other human coagulation proteases. It produces a rapid onset of inhibition of FXa with association rate constant of 20 μM−1/s approximately and inhibits free as well as prothrombinase- and clot-bound FXa activity in vitro. Apixaban also inhibits FXa from rabbits, rats and dogs, an activity which parallels its antithrombotic potency in these species. Although apixaban has no direct effects on platelet aggregation, it indirectly inhibits this process by reducing thrombin generation. Pre-clinical studies of apixaban in animal models have demonstrated dose-dependent antithrombotic efficacy at doses that preserved hemostasis. Apixaban improves pre-clinical antithrombotic activity, without excessive increases in bleeding times, when added on top of aspirin or aspirin plus clopidogrel at their clinically relevant doses. Apixaban has good bioavailability, low clearance and a small volume of distribution in animals and humans, and a low potential for drug–drug interactions. Elimination pathways for apixaban include renal excretion, metabolism and biliary/intestinal excretion. Although a sulfate conjugate of Ο-demethyl apixaban (O-demethyl apixaban sulfate) has been identified as the major circulating metabolite of apixaban in humans, it is inactive against human FXa. Together, these non-clinical findings have established the favorable pharmacological profile of apixaban, and support the potential use of apixaban in the clinic for the prevention and treatment of various thromboembolic diseases

Enhanced irreversibility by crystal defects in the Bi-Sr-Ca-Cu-O system

We measured magnetic irreversibility, H*(T), in liquid-quenched Bi-Sr-Ca-Cu-O samples with various microstructures at high applied field (up to 7 T). We found that H*(T) is considerably increased in the Bi{sub 2}Sr{sub 2}Ca{sub 3}Cu{sub 4}O{sub x} (2234) sample with a large amount of crystal defects, including severe lattice distortion and calcium and copper rich precipitates. We argue that the lattice distortion may affect the degree of anisotropy and the Josephson coupling between the Cu-O layers, which in turn enhance the irreversibility in the Bi-Sr-Ca-Cu-O system. A critical current density, J{sub c}, of 8 {times} 10{sup 4} A/cm{sup 2} at 8 kG and 40 K was obtained in the 2234 sample with many defects, while the J{sub c} dropped significantly at the same temperature and field in the near stoichiometry Bi{sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub x} (2223) sample with a uniform microstructure

Uniform deposition of ultrathin polymer films on the surfaces of Al2O3Al2O3 nanoparticles by a plasma treatment

Surface modification of nanoparticles will present great challenges due to their extremely small dimensions, high surface areas, and high surface energies. In this research, we demonstrate the uniform deposition of ultrathin polymer films of 2 nm on the surfaces of alumina nanoparticles. The deposited film can also be tailored to multilayers. Time-of-flight secondary ion mass spectroscopy was used to confirm the pyrrole thin film on the nanoparticle surfaces. Using such a nanocoating, it is possible to alter the intrinsic properties of materials that cannot be achieved by conventional methods and materials. © 2001 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70221/2/APPLAB-78-9-1243-1.pd

Melt-texturing of carbon containing YBa{sub 2}Cu{sub 3}O{sub 7-x}: Influence of processing parameters on microstructure and flux-pinning behavior

A detailed study of the flux-pinning behavior of sintered and melt-textured YBa{sub 2}Cu{sub 3}O{sub 7-x} has been carried out by means of microstructural investigations (optical microscopy, SEM, TEM, EDS, DTA, and XRD) and magnetization measurements. It was found that both microstructure and magnetization behavior strongly depend on the starting material, the production method, and the maximum processing temperature. In our experiments, the critical current density, J{sub c}, increased with increasing processing temperature between 920{degrees}C and 1050{degrees}C (25 - 130 emu/cm{sup 3}), but those samples processed at temperatures just above the peritectic transformation point (1020 OC and 1030 OC) exhibited a decreased J{sub c}. The carbon content of the starting powder and the powder`s melting behavior seem to play an important role in the development of microstructure and flux-pinning behavior during melt-texturing. A comparison of our data with previously published results shows that an optimized melt-texturing process can result in materials with critical current densities comparable to those of samples produced by Quench-Melt Growth