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991.
Six-mercaptopurine in the free form and complexed with Pt, Pd, or Bi metals was used at various dosage levels to treat L1210 leukemia in mice. Anticarcinogenic activity was shown by six-mercaptopurine and the Pd and Bi complexes, inactivity by the Pt complex, and toxicity by the highest dosage level of six-mercaptopurine. 相似文献
992.
993.
Dr. Koen Steert Dr. Maya Berg Prof. Dr. Jeremy C. Mottram Dr. Gareth D. Westrop Prof. Dr. Graham H. Coombs Prof. Dr. Paul Cos Prof. Dr. Louis Maes Dr. Jurgen Joossens Prof. Dr. Pieter Van der Veken Prof. Dr. Achiel Haemers Prof. Dr. Koen Augustyns 《ChemMedChem》2010,5(10):1734-1748
Cysteine proteases of the papain superfamily are present in nearly all eukaryotes and also play pivotal roles in the biology of parasites. Inhibition of cysteine proteases is emerging as an important strategy to combat parasitic diseases such as sleeping sickness, Chagas disease, and leishmaniasis. Inspired by the in vivo antiparasitic activity of the vinylsulfone‐based cysteine protease inhibitors, a series of α‐ketoheterocycles were developed as reversible inhibitors of a recombinant L. mexicana cysteine protease, CPB2.8. Three isoxazoles and especially one oxadiazole compound are potent reversible inhibitors of CPB2.8; however, in vitro whole‐organism screening against a panel of protozoan parasites did not fully correlate with the observed inhibition of the cysteine protease. 相似文献
994.
Thatchawan Thanasupawat Aleksandra Glogowska Christopher Pascoe Sai Nivedita Krishnan Maliha Munir Farhana Begum Jason Beiko Jerry Krcek Marc R. Del Bigio Marshall Pitz Yaoqing Shen Victor Spicer Kevin M. Coombs John Wilkins Sabine Hombach-Klonisch Thomas Klonisch 《International journal of molecular sciences》2021,22(17)
Malignant gliomas derive from brain glial cells and represent >75% of primary brain tumors. This includes anaplastic astrocytoma (grade III; AS), the most common and fatal glioblastoma multiforme (grade IV; GBM), and oligodendroglioma (ODG). We have generated patient-derived AS, GBM, and ODG cell models to study disease mechanisms and test patient-centered therapeutic strategies. We have used an aptamer-based high-throughput SOMAscan® 1.3K assay to determine the proteomic profiles of 1307 different analytes. SOMAscan® proteomes of AS and GBM self-organized into closely adjacent proteomes which were clearly distinct from ODG proteomes. GBM self-organized into four proteomic clusters of which SOMAscan® cluster 4 proteome predicted a highly inter-connected proteomic network. Several up- and down-regulated proteins relevant to glioma were successfully validated in GBM cell isolates across different SOMAscan® clusters and in corresponding GBM tissues. Slow off-rate modified aptamer proteomics is an attractive analytical tool for rapid proteomic stratification of different malignant gliomas and identified cluster-specific SOMAscan® signatures and functionalities in patient GBM cells. 相似文献
995.
William M. Coombs Roger S. Crouch 《Computer Methods in Applied Mechanics and Engineering》2011,200(9-12):1021-1037
Analytical backward Euler stress integration is presented for a volumetrically non-associated pressure-sensitive yield criterion based on a modified Reuleaux triangle. This advances previous work on associated Reuleaux plasticity using energy-mapped stress space. The analytical solution is 2–4 times faster than a standard numerical backward Euler algorithm. The merit in transforming to (and operating in) this space is that the stress return is truly the closest point on the surface to the elastic trial state. The paper includes a tension cut-off (formed by a second cone) and describes the steps necessary to allow the model’s incorporation within a finite deformation framework. Finite-element results show a 59% runtime saving for a modified Reuleaux model over a Willam–Warnke cone giving comparable accuracy in a thick-walled cylinder expansion problem. The consistent tangent provides asymptotically quadratic convergence in the Newton–Raphson scheme under both (i) small strain, infinitesimal deformation and (ii) large strain, finite deformation finite-element simulations. It is shown that the introduction of non-associated flow changes the plastic deformation field and reduces the heave predicted in a plane strain rigid strip-footing problem. The proposed model offers a significant improvement over the Drucker–Prager and Mohr–Coulomb formulations by better reproducing the material dependence on the Lode angle and intermediate principal stress, at little extra computational effort. 相似文献
996.
Amaya Albalat Sebastian G. Gornik William Mullen Alan Crozier Robert J. A. Atkinson Graham H. Coombs Douglas M. Neil 《International Journal of Food Science & Technology》2011,46(7):1413-1421
The quality deterioration of Norway lobster (Nephrops norvegicus) tail meat was monitored during ice storage. The K‐value started at 0.7% and reached a value of 39.7% on day 14. Muscle pH followed a sigmoidal pattern that reached a plateau on day 6. Bacterial load and trimethylamine (TMA) increased only after a lag phase to reach considerable levels by day 14 (5.3 log cfu and 10.2 mg (100 g)?1, respectively). These analytical data were compared with sensory data. Principal component analysis (PCA) indicated that laboratory measures were correlated positively with the smell strength of cooked product (increasingly strong) and negatively with the smell character of raw and cooked product (sour‐ammoniacal in raw and neutral in cooked products), flavour and aftertaste (both increasingly bland–bitter). The effects of icing delays on the quality of tail meat were also evaluated. Changes in K‐values, microbial load, muscle pH and TMA indicated that the delay to icing should be no more than 4 h (at 16 °C) to ensure that quality is not compromised during subsequent post‐harvest storage. 相似文献
997.
A series of acyclic and cyclic 1-alkoxy- and 1-arylsulfonyloxy-substituted TpMo(CO)(2)(η(3)-allyl) complexes was synthesized and characterized, and exchange of the oxygenated substituent was investigated under a variety of reaction conditions. 1-Alkoxy-substituted η(3)-allyl and η(3)-butenyl complexes participated in direct, uncatalyzed exchange of the alkoxy substituent with benzylamine, but required a Lewis acid for exchange with alcohols. The 1-alkoxy-substituted η(3)-cyclohexenyl complex was unreactive towards exchange under all conditions investigated. The corresponding acyclic arylsulfonyloxy-substituted complexes underwent direct, uncatalyzed exchange with both benzylamine and alcohols, while the arylsulfonyloxy-substituted cyclohexenyl compounds participated in direct substitution with benzylamine, but not alcohols. High enantiopurity acyclic and cyclic alkoxy- and arylsulfonyloxy-substituted complexes provided exchange products with predominant, but incomplete, losses in enantiomeric excess in all cases examined. Mechanisms accounting for the observed reactivity trends and for the losses in enantiomeric excess are discussed. Reaction of alkoxy-substituted complexes through an associative mechanism and of arylsulfonyloxy-substituted compounds through a dissociative mechanism is suggested. 相似文献
998.
Underwater vibratory sources simultaneously present acoustic and hydrodynamic disturbances. Because vibratory dipole sources are poor sonic projectors, most researchers have assumed that such sources are of greatest relevance to the lateral line system. Both hydroacoustic principles and empirical studies have shown that dipole sources are also a potent stimulus to the inner ear. Responses to vibratory sources in mottled sculpin (Cottus bairdi) were assessed using unconditioned orienting, differential and nondifferential conditioning. Orienting responses are dominated by lateral line inputs and eliminated by lateral line inactivation. Simple conditioning depends on inputs from other systems and was not affected by lateral line inactivation. Differential conditioning alters behavioral control, and sculpin could be conditioned to ignore substrate-borne vibrations and respond only to hydroacoustic stimulation of the ear. The lateral line and inner ear of mottled sculpin do not necessarily exhibit range fractionation, as both systems operate over a similar distance (within 1.5 body lengths) and respond to many of the same sources. Vibratory dipole sources generate compound stimuli that simultaneously activate multiple octavolateralis systems, and sculpin make use of the channels differentially under different behavioral tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
999.
RW Sidwell JH Huffman KW Bailey MH Wong A Nimrod A Panet 《Canadian Metallurgical Quarterly》1996,40(11):2626-2631
The oxygen free-radical scavenger recombinant human manganese superoxide dismutase (MnSOD) was studied for its effects on influenza virus infections in mice when used alone and in combination with ribavirin. Mice challenged with influenza A/NWS/33 (H1N1) virus were treated parenterally in doses of 25, 50, and 100 mg/kg of body weight per day every 8 h for 5 days beginning at 48 h post-virus exposure. An increase in mean day to death, lessened decline in arterial oxygen saturation, and reduced lung consolidation and lung virus titers occurred in the treated animals. To determine the influence of viral challenge, experiments were run in which mice were infected with a 100 or 75% lethal dose of virus and were treated intravenously once daily for 5 days beginning 96 h after virus exposure. Weak inhibition of the mortality rate was seen in mice receiving the high viral challenge, whereas significant inhibition occurred in the animals infected with the lower viral challenge, indicating that MnSOD effects are virus dose dependent. To determine if treatment with small-particle aerosol would render an antiviral effect, infected mice were treated by this route for 1 h daily for 5 days beginning 72 h after virus exposure. A dose-responsive disease inhibition was seen. An infection induced by influenza B/Hong Kong/5/72 virus in mice was mildly inhibited by intravenous MnSOD treatment as seen by increased mean day to death, lessened arterial oxygen saturation decline, and lowered lung consolidation. MnSOD was well tolerated in all experiments. A combination of MnSOD and ribavirin, each administered with small-particle aerosol, resulted in a generally mild improvement of the disease induced by the influenza A virus compared with use of either material alone. 相似文献
1000.
AL Edinger JL Mankowski BJ Doranz BJ Margulies B Lee J Rucker M Sharron TL Hoffman JF Berson MC Zink VM Hirsch JE Clements RW Doms 《Canadian Metallurgical Quarterly》1997,94(26):14742-14747
Brain capillary endothelial cells (BCECs) are targets of CD4-independent infection by HIV-1 and simian immunodeficiency virus (SIV) strains in vitro and in vivo. Infection of BCECs may provide a portal of entry for the virus into the central nervous system and could disrupt blood-brain barrier function, contributing to the development of AIDS dementia. We found that rhesus macaque BCECs express chemokine receptors involved in HIV and SIV entry including CCR5, CCR3, CXCR4, and STRL33, but not CCR2b, GPR1, or GPR15. Infection of BCECs by the neurovirulent strain SIV/17E-Fr was completely inhibited by aminooxypentane regulation upon activation, normal T cell expression and secretion in the presence or absence of ligands, but not by eotaxin or antibodies to CD4. We found that the envelope (env) proteins from SIV/17E-Fr and several additional SIV strains mediated cell-cell fusion and virus infection with CD4-negative, CCR5-positive cells. In contrast, fusion with cells expressing the coreceptors STRL33, GPR1, and GPR15 was CD4-dependent. These results show that CCR5 can serve as a primary receptor for SIV in BCECs and suggest a possible CD4-independent mechanism for blood-brain barrier disruption and viral entry into the central nervous system. 相似文献