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No abstract is provided for this article.
No abstract is provided for this article.
sponsorship: Financial support from the National Natural Science Foundation of China (NSFC Grants 30873133, 30772629, 30371686, and 81102320), Key Project of NSFC for International Cooperation (Grant 30910103908), Research Fund for the Doctoral Program of Higher Education of China (Grant 070422083), Independent Innovation Foundation of Shandong University (IIFSDU, Grant 2010GN044), Shangdong Postdoctoral Innovation Science Research Special Program (Grant 201002023), and China Postdoctoral Science Foundation Funded Project (Grant 20100481282) is gratefully acknowledged. (National Natural Science Foundation of China (NSFC)|30873133, National Natural Science Foundation of China (NSFC)|30772629, National Natural Science Foundation of China (NSFC)|30371686, National Natural Science Foundation of China (NSFC)|81102320, NSFC for International Cooperation|30910103908, Research Fund for the Doctoral Program of Higher Education of China|070422083, Independent Innovation Foundation of Shandong University (IIFSDU)|2010GN044, Shangdong Postdoctoral Innovation Science Research Special Program|201002023, China Postdoctoral Science Foundation|20100481282)
CycloSal-d4TMP and two different bis(benzyl) phosphate triesters of the antivirally active nucleoside analog d4T were studied with regard to their chemical hydrolysis behavior at pH 7.3, in CEM/0 cell extracts, and their anti-HIV activity. In contrast to triesters 2-4, bis-(o-AB)-d4TMP 1 was found to be chemically exquisitely stable. All compounds led to the formation of d4TMP in cell extracts and all triesters achieved the TK-bypass.
The phosphonylmethoxyalkyl derivative (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) was evaluated for its in vivo efficacy in several model infections for herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) and thymidine kinase-deficient (TK-) HSV-1 in mice. In hairless mice infected intracutaneously with HSV-1 or HSV-2, HPMPC completely suppressed all manifestations of the disease (skin lesions, paralysis of the hind legs, and mortality) if it was administered topically at a concentration of as low as 0.1, 0.3, or 1%. Similarly, HPMPC completely suppressed TK- HSV-1 infection in athymic nude mice if it was administered topically at 0.1 or 0.3% or intraperitoneally at 100 or 250 mg/kg/day. HPMPC was also effective against intraperitoneal HSV infection if it was given orally at a dose of 50 mg/kg/day or higher. In mice inoculated intracerebrally with HSV-2, intraperitoneal HPMPC treatment achieved a significant and dose-dependent protection at doses ranging from 5 to 400 mg/kg/day. The protective effect of HPMPC (at 200 mg/kg/day) was accompanied by a complete inhibition of virus multiplication in the brain. In all models of infections studied, the efficacy of HPMPC proved to be superior to that of acyclovir. The most remarkable feature of HPMPC was that a single administration of the compound, even as late as 4 days after infection, conferred significant protection against HSV-1 or HSV-2 infection. Topical or systemic HPMPC treatment is efficacious in murine models of HSV-1, HSV-2, and TK- HSV infections.
No abstract is provided for this article.
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This paper describes ongoing research and development of a Holonic Machine Controller. The characteristics of this new prototype controller will be more flexible and open in comparison with present NC technology. PC based software has been developed on a Windows 16-bit platform that embeds the full functionality of the Machine Control Unit (MCU) of a five axis milling machine. The input to the MCU should be a feature based part description. The new controller is intended to autonomously generate machining NC sequences that are stepwise downloaded and executed by the original NC controller, using the LSV-2 communication protocol. The protocol is conceived as a device-driver. A device-driver can process NIOs (Non-Interruptable Operations) for machining, process gauging, etc. Holonic behaviour will be supported by advanced planning, execution, and monitoring (PEM) actions.
A series of 23 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives that were highly potent inhibitors of wild-type human immunodeficiency virus type 1 strain IIIB (HIV-1/IIIB) replication in CEM cells were evaluated against a panel of HIV-1 mutant strains containing the replacement of leucine by isoleucine at position 100 (100-Leu-->Ile), 103-Lys-->Asn, 106-Val-->Ala, 138-Glu-->Lys, 181-Tyr-->Cys, 181-Tyr-->Ile, or 188-Tyr-->His in their reverse transcriptase (RT). A different structure-antiviral activity relationship was found, depending on the nature of the mutated amino acid in the HIV-1 RT. The results show that 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylphenylthio)uracil, and 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylphenylthio)-2-thiouracil remain active against the majority of viruses containing single mutations which confer resistance to nonnucleoside RT inhibitors.
