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91.
Current Understanding of Structure–Processing–Property Relationships in BaTiO3–Bi(M)O3 Dielectrics
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Michaela A. Beuerlein Nitish Kumar Tedi‐Marie Usher Harlan James Brown‐Shaklee Natthaphon Raengthon Ian M. Reaney David P. Cann Jacob L. Jones Geoff L. Brennecka 《Journal of the American Ceramic Society》2016,99(9):2849-2870
As part of a continued push for high permittivity dielectrics suitable for use at elevated operating temperatures and/or large electric fields, modifications of BaTiO3 with Bi(M)O3, where M represents a net‐trivalent B‐site occupied by one or more species, have received a great deal of recent attention. Materials in this composition family exhibit weakly coupled relaxor behavior that is not only remarkably stable at high temperatures and under large electric fields, but is also quite similar across various identities of M. Moderate levels of Bi content (as much as 50 mol%) appear to be crucial to the stability of the dielectric response. In addition, the presence of significant Bi reduces the processing temperatures required for densification and increases the required oxygen content in processing atmospheres relative to traditional X7R‐type BaTiO3‐based dielectrics. Although detailed understanding of the structure–processing–property relationships in this class of materials is still in its infancy, this article reviews the current state of understanding of the mechanisms underlying the high and stable values of both relative permittivity and resistivity that are characteristic of BaTiO3‐Bi(M)O3 dielectrics as well as the processing challenges and opportunities associated with these materials. 相似文献
92.
The Change of X‐ray Diffraction Peak Width During in situ Conventional Sintering of Nanoscale Powders
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Jean‐Marie Lebrun Shikhar K. Jha Kiran S. Naik Kevin C. Seymour Waltraud M. Kriven Rishi Raj 《Journal of the American Ceramic Society》2016,99(3):765-768
Diffraction peaks of nanoscale particles of 3 mol% yttria‐stabilized zirconia become sharper as the powder sinters. The reduction in the peak width is correlated with the increase in density. The sharpening of the peak agrees reasonably well with the remaining free surface area as the sample sinters. Therefore, high curvature of the free surface of the pores is assumed to lead to peak broadening (the grain boundaries that grow at the expense of the free surfaces of the pores do not have this curvature). The change in the grain size during sintering does not make a significant contribution to peak width. 相似文献
93.
Rafaela Gladysz Prof. Dr. Anne‐Marie Lambeir Dr. Jurgen Joossens Prof. Dr. Koen Augustyns Prof. Dr. Pieter Van der Veken 《ChemMedChem》2016,11(5):467-476
Substrate activity screening (SAS) was presented a decade ago by Ellman and co‐workers as a straightforward methodology for the identification of fragment‐sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment‐sized hits into potent inhibitors. 相似文献
94.
Structure–Activity Relationships of JMV4463, a Vectorized Cathepsin D Inhibitor with Antiproliferative Properties: The Unique Role of the AMPA‐Based Vector
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Dr. Lubomir L. Vezenkov Clément A. Sanchez Dr. Virginie Bellet Dr. Vincent Martin Dr. Marie Maynadier Dr. Nadir Bettache Prof. Vincent Lisowski Prof. Jean Martinez Dr. Marcel Garcia Dr. Muriel Amblard Dr. Jean‐François Hernandez 《ChemMedChem》2016,11(3):302-308
Cathepsin D (CathD) is overexpressed and secreted by several solid tumors and stimulates their growth, the mechanism of which is still not understood. In this context, the pepstatin bioconjugate JMV4463 [Ac‐arg‐O2Oc‐(Val)3‐Sta‐Ala‐Sta‐(AMPA)4‐NH2; O2Oc=8‐amino‐3,6‐dioxaoctanoyl, Sta=statine, AMPA=ortho‐aminomethylphenylacetyl], containing a new kind of cell‐penetrating vector, was previously shown to exhibit potent antiproliferative effects in vitro and to delay the onset of tumors in vivo. In this study, we performed a structure–activity relationship analysis to evaluate the significance of the inhibitor and vector moieties of JMV4463. By modifying both statine residues of pepstatin we found that the antiproliferative activity is correlated with CathD inhibition, supporting a major role of the catalytic activity of intracellular CathD in cancer cell proliferation. Replacing the vector composed of four AMPA units with other vectors was found to abolish cytotoxicity, although all of the conjugates enabled pepstatin transport into cells. In addition, the AMPA4 vector must be localized at the C terminus of the bioconjugate. The unexpected importance of the vector structure and position for cytotoxic action suggests that AMPA4 enables pepstatin to inhibit the proteolysis of critical CathD substrates involved in cell proliferation via a unique mechanism of action. 相似文献
95.
Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
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Dr. Gordon J. Florence Andrew L. Fraser Dr. Eoin R. Gould Elizabeth F. King Stefanie K. Menzies Dr. Joanne C. Morris Marie I. Thomson Dr. Lindsay B. Tulloch Marija K. Zacharova Prof. Dr. Terry K. Smith 《ChemMedChem》2016,11(14):1503-1506
Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment. 相似文献
96.
Dr. Tessa Lühmann Valerie Spieler Dr. Vera Werner Dr. Marie‐Gabrielle Ludwig Dr. Juliane Fiebig Prof. Dr. Thomas D. Mueller Prof. Dr. Dr. Lorenz Meinel 《Chembiochem : a European journal of chemical biology》2016,17(22):2123-2128
Driving macrophage (M?) polarization into the M2 phenotype provides potential against inflammatory diseases. Interleukin‐4 (IL‐4) promotes polarization into the M2‐M? phenotype, but its systemic use is constrained by dose‐limiting toxicity. Consequently, we developed IL‐4‐decorated surfaces aiming at sustained and localized activity. IL‐4 muteins were generated by genetic code expansion; Lys42 was replaced by unnatural amino acids (uAAs). Both muteins showed cell‐stimulation ability and binding affinity to IL4Rα similar to those of wt‐IL‐4. Copper‐catalyzed (CuAAC) and copper‐free strain‐promoted (SPAAC) 1,3‐dipolar azide–alkyne cycloadditions were used to site‐selectively anchor IL‐4 to agarose surfaces. These surfaces had sustained IL‐4 activity, as demonstrated by TF‐1 cell proliferation and M2, but not M1, polarization of M‐CSF‐generated human M?. The approach provides a blueprint for the engineering of cytokine‐activated surfaces profiled for sustained and spatially controlled activity. 相似文献
97.
Dr. Marie Monestier Peggy Charbonnier Dr. Christelle Gateau Dr. Martine Cuillel Faustine Robert Colette Lebrun Dr. Elisabeth Mintz Prof. Olivier Renaudet Dr. Pascale Delangle 《Chembiochem : a European journal of chemical biology》2016,17(7):590-594
Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes. 相似文献
98.
99.
This paper introduces a new methodology to measure the elastic constants of transversely isotropic rocks from a single uniaxial compression test. We first give the mathematical proof that a uniaxial compression test provides only four independent strain equations. As a result, the exact determination of all five independent elastic constants from only one test is not possible. An approximate determination of the Young's moduli and the Poisson's ratios is however practical and efficient when adding the Saint–Venant relation as the fifth equation. Explicit formulae are then developed to calculate both secant and tangent definitions of the five elastic constants from a minimum of four strain measurements. The results of this new methodology applied on three granitic samples demonstrate a significant stress-induced nonlinear behavior, where the tangent moduli increase by a factor of three to four when the rock is loaded up to 20 MPa. The static elastic constants obtained from the uniaxial compression test are also found to be significantly smaller than the dynamic ones obtained from the ultrasonic measurements. 相似文献
100.
Rakhi Sood Mona Marie Obadia Bhanu Prakash Mudraboyina Biao Zhang Anatoli Serghei Julien Bernard Eric Drockenmuller 《Polymer》2014
Nitroxide-mediated radical polymerization of a tailor-made acrylate carrying a 1,2,3-triazole group with an undecanoyl spacer affords a well-defined (Mn = 7860 g mol−1 and D = 1.39) neutral polyacrylate precursor. A series of 1,2,3-triazolium-based poly(ionic liquid)s (TPILs) is then obtained by straightforward quaternization of the 1,2,3-triazole groups with methyl iodide and subsequent anion metathesis reactions. Among the prepared materials, TPIL with bis(trifluoromethane)sulfonimide anion exhibits low glass transition temperature (Tg = −40 °C), high thermal stability (Td10 = 325 °C) and anhydrous ionic conductivity of 4 × 10−6 S cm−1 at 30 °C, as measured by differential scanning calorimetry, thermogravimetric analysis and broadband dielectric spectroscopy, respectively. 相似文献