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121.
M Maliepaard NJ de Mol M Tomasz D Gargiulo LH Janssen JP van Duynhoven EJ van Velzen W Verboom DN Reinhoudt 《Canadian Metallurgical Quarterly》1997,36(30):9211-9220
Reductive activation of racemic 1,10-bis(acetoxy)-7-methoxymitosene WV15 in the presence of DNA, followed by enzymatic digestion and HPLC analysis, revealed the formation of various DNA adducts. Reduction is a necessary event for adduct formation to occur. This reductive activation was performed under hypoxic conditions in various ways: (1) chemically, using a 2-fold excess of sodium dithionite (Na2S2O4), (2) enzymatically using NADH-cytochrome c reductase, (3) electrochemically on a mercury pool working electrode, and (4) catalytically, using a H2/PtO2 system. Five different mitosene-DNA adducts were detected. These adducts were also present when poly(dG-dC) was used instead of DNA, but were absent with poly(dA-dT). All were shown to be adducts of guanine. Reduction of 1, 10-dihydroxymitosene WV14 in the presence of DNA did not result in detectable adduct formation, demonstrating the importance of good leaving groups for efficient adduct formation by these mitosenes. Finally, two of the adducts were isolated and their structures elucidated, using mass spectrometry, 1H NMR and circular dichroism (CD). The structures were assigned as the diastereoisomers N2-(1"-n-hydroxymitosen-10"-yl), 2'-deoxyguanosine (n = alpha or beta). These type of adducts, in which the mitosene C-10 is covalently bonded to the N-2 of a guanosylic group, are different from the well-known mitomycin C 2'-deoxyguanosine monoadducts, that is linked via the mitomycin C C-1 position, demonstrating that the order of reactivity of the C-1 and C-10 in these mitosenes is reversed, as compared to mitomycin C. The 7-methoxy substituent of WV15 is a likely factor causing this switch. Evidence is presented that the 7-substituent of mitosenes also influences their DNA alkylation site. Adducts 4 and 5 represent the first isolated and structurally characterized covalent adducts of DNA and a synthetic mitosene. 相似文献
122.
123.
DN Burshtyn AS Lam M Weston N Gupta PA Warmerdam EO Long 《Canadian Metallurgical Quarterly》1999,162(2):897-902
The heart has been recognized as a major target of thyroid hormone action. Our study investigates both the regulation of cardiac-specific genes and contractile behavior of the heart in the presence of a mutant thyroid hormone receptor beta1 (T3Rbeta1-delta337T) derived from the S kindred. The mutant receptor was originally identified in a patient with generalized resistance to thyroid hormone. Cardiac expression of the mutant receptor was achieved by a transgenic approach in mice. As the genes for myosin heavy chains (MHC alpha and MHC beta) and the cardiac sarcoplasmic reticulum Ca2+ adenosine triphosphatase (SERCA2) are known to be regulated by T3, their cardiac expression was analyzed. The messenger RNA levels for MHC alpha and SERCA2 were markedly down-regulated, MHC beta messenger RNA was up-regulated. Although T3 levels were normal in these animals, this pattern of cardiac gene expression mimics a hypothyroid phenotype. Cardiac muscle contraction was significantly prolonged in papillary muscles from transgenic mice. The electrocardiogram of transgenic mice showed a substantial prolongation of the QRS interval. Changes in cardiac gene expression, cardiac muscle contractility, and electrocardiogram are compatible with a hypothyroid cardiac phenotype despite normal T3 levels, indicating a dominant negative effect of the T3Rbeta mutant. 相似文献
124.
I Gramaglia DN Mauri KT Miner CF Ware M Croft 《Canadian Metallurgical Quarterly》1999,162(3):1333-1338
Lymphotoxin (LT) is a cytokine that orchestrates lymphoid neogenesis and formation of germinal center reactions. LT exists as a membrane heterotrimer of alpha and beta subunits and is secreted as a homotrimer, LTalpha3. Using LTbetaR.Fc, expression of LTalphabeta on CD4 T cell subsets was investigated in a TCR transgenic model. LTalphabeta was evident 24-72 h after activation of naive T cells with specific Ag, and declined thereafter. Early expression was independent of IFN-gamma and IL-12, however, IL-12 prolonged expression. LTalphabeta was reinduced within 2-4 h after Ag restimulation, but declined by 24 h regardless of IL-12 or IFN-gamma priming. Exposure of naive T cells to IL-4 did not affect early LTalphabeta expression at 24 h, but resulted in subsequent down-regulation. IL-4-differentiated Th2 effectors did not re-express LTalphabeta, and LTalphabeta was transiently found on Th1 clones but not Th2 clones. LTalpha3 and TNF were immunoprecipitated from supernatants and lysates of IL-12 primed cells but not IL-4 primed cells. These studies demonstrate that LTalphabeta is expressed by activated naive CD4 cells, unpolarized IL-2-secreting effectors, and Th1 effectors. In contrast, loss of surface LTalphabeta and a lack of LTalpha3 and TNF secretion is associated with prior exposure to IL-4 and a Th2 phenotype. 相似文献
125.
When plane-polarized light impinges on a solution of optically active molecules, the polarization of the light that emerges is rotated. This simple phenomenon arises from the interaction of light with matter and is well understood, in principle, van't Hoff's rule of optical superposition correlates the molar rotation with the individual contributions to optical activity of isolated centers of asymmetry. This straightforward empirical additivity rule is rarely used for structure elucidation nowadays because of its limitations in the assessment of conformationally restricted or interacting chiral centers. However, additivity can be used successfully to assign the configuration of complex natural products such as hennoxazole A if appropriate synthetic partial structures are available. Therefore, van't Hoff's principle is a powerful stereochemical complement to natural products' total synthesis. The quest for reliable quantitative methods to calculate the angle of rotation a priori has been underway for a long time. Both classical and quantum methods for calculating molar rotation have been developed. Of particular practical importance for determining the absolute structure of molecules by calculation is the manner in which interactions between multiple chiral centers in a single molecule are included, leading to additive or non-additive optical rotation angles. This problem is addressed here using semi-empirical electronic structure models and the Rosenfeld equation. 相似文献
126.
Biswas G Manders EJ Ramirez J Mahadevan N Abdelwahed S 《Habitation (Elmsford, N.Y.)》2004,10(1):21-37
This article describes methods for online model-based diagnosis of subsystems of the advanced life support system (ALS). The diagnosis methodology is tailored to detect, isolate, and identify faults in components of the system quickly so that fault-adaptive control techniques can be applied to maintain system operation without interruption. We describe the components of our hybrid modeling scheme and the diagnosis methodology, and then demonstrate the effectiveness of this methodology by building a detailed model of the reverse osmosis (RO) system of the water recovery system (WRS) of the ALS. This model is validated with real data collected from an experimental testbed at NASA JSC. A number of diagnosis experiments run on simulated faulty data are presented and the results are discussed. 相似文献
127.
This article presents the design and implementation of a controller scheme for efficient resource management in Advanced Life Support Systems. In the proposed approach, a switching hybrid system model is used to represent the dynamics of the system components and their interactions. The operational specifications for the controller are represented by utility functions, and the corresponding resource management problem is formulated as a safety control problem. The controller is designed as a limited-horizon online supervisory controller that performs a limited forward search on the state-space of the system at each time step, and uses the utility functions to decide on the best action. The feasibility and accuracy of the online algorithm can be assessed at design time. We demonstrate the effectiveness of the scheme by running a set of experiments on the Reverse Osmosis (RO) subsystem of the Water Recovery System (WRS). 相似文献
128.
Low‐Noise Multispectral Photodetectors Made from All Solution‐Processed Inorganic Semiconductors 下载免费PDF全文
Jesse R. Manders Tzung‐Han Lai Yanbin An Weikai Xu Jaewoong Lee Do Young Kim Gijs Bosman Franky So 《Advanced functional materials》2014,24(45):7205-7210
Infrared, visible, and multispectral photodetectors are important components for sensing, security and electronics applications. Current fabrication of these devices is based on inorganic materials grown by epitaxial techniques which are not compatible with low‐cost large‐scale processing. Here, air‐stable multispectral solution‐processed inorganic double heterostructure photodetectors, using PbS quantum dots (QDs) as the photoactive layer, colloidal ZnO nanoparticles as the electron transport/hole blocking layer (ETL/HBL), and solution‐derived NiO as the hole transport/electron blocking layer (HTL/EBL) are reported. The resulting device has low dark current density of 20 nA cm‐2 with a noise equivalent power (NEP) on the order of tens of picowatts across the detection spectra and a specific detectivity (D*) value of 1.2 × 1012 cm Hz1/2 W‐1. These parameters are comparable to commercially available Si, Ge, and InGaAs photodetectors. The devices have a linear dynamic range (LDR) over 65 dB and a bandwidth over 35 kHz, which are sufficient for imaging applications. Finally, these solution‐processed inorganic devices have a long storage lifetime in air, even without encapsulation. 相似文献
129.
Jesse R. Manders Sai‐Wing Tsang Michael J. Hartel Tzung‐Han Lai Song Chen Chad M. Amb John R. Reynolds Franky So 《Advanced functional materials》2013,23(23):2993-3001
The detailed characterization of solution‐derived nickel (II) oxide (NiO) hole‐transporting layer (HTL) films and their application in high efficiency organic photovoltaic (OPV) cells is reported. The NiO precursor solution is examined in situ to determine the chemical species present. Coordination complexes of monoethanolamine (MEA) with Ni in ethanol thermally decompose to form non‐stoichiometric NiO. Specifically, the [Ni(MEA)2(OAc)]+ ion is found to be the most prevalent species in the precursor solution. The defect‐induced Ni3+ ion, which is present in non‐stoichiometric NiO and signifies the p‐type conduction of NiO, as well as the dipolar nickel oxyhydroxide (NiOOH) species are confirmed using X‐ray photoelectron spectroscopy. Bulk heterojunction (BHJ) solar cells with a polymer/fullerene photoactive layer blend composed of poly‐dithienogermole‐thienopyrrolodione (pDTG‐TPD) and [6,6]‐phenyl‐C71‐butyric acid methyl ester (PC71BM) are fabricated using these solution‐processed NiO films. The resulting devices show an average power conversion efficiency (PCE) of 7.8%, which is a 15% improvement over devices utilizing a poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL. The enhancement is due to the optical resonance in the solar cell and the hydrophobicity of NiO, which promotes a more homogeneous donor/acceptor morphology in the active layer at the NiO/BHJ interface. Finally, devices incorporating NiO as a HTL are more stable in air than devices using PEDOT:PSS. 相似文献
130.