SUMMARY The effects of the synthetic polyanionic interferon inducers maleic acid/divinyl ether copolymer (MA/DVE) and polyinosinic/polycytidylic acid (polyrI/polyrC) were studied in mice challenged intranasally with vesicular stomatitis virus. Young (14-day or 24-day) animals were used. Either local (intranasal) or systemic (intraperitoneal) treatment protected significantly against virus infection. Optimal local protection was given by 40 μg. of polyrI/polyrC instilled 4 hr before virus challenge. Intraperitoneal MA/DVE exerted a more durable effect lasting for at least 10 days, and polyrI/polyrC proved to be active when applied several days after inoculation of virus. PolyrI/polyrC treatment started after virus in the brain had reached maximum concentration retarded progression of the disease, but when delayed until clinical signs of illness occurred, polyrI/polyrC treatment was not effective. The protective activity of MA/DVE and polyrI/polyrC injected intraperitoneally against virus infection at a distant site suggested the mediation by a systemic antivirus state, presumably due to interferon production.
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Using Doppler-free two-photon spectroscopy, we have measured the isotopic shift 20Ne-22Ne for two-photon transitions between the 3s[3/2]2 metastable state and the excited states of the 2p5 4d and 2p5 5s configurations. The results are analyzed using the specific mass shift theory. We show that we can deduce from the expérimental data the expansion of the 1P Russel-Saunders term over the true eigenstates of the atom. We also obtain experimental determinations of the radial integrals J(4d, 2p) and J(5s, 2p). All the experimental results are in good agreement with theoretical predictions of Bauche and Liberman.
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Human CMV (HCMV) is an opportunistic pathogen associated with significant morbidity and mortality among immunocompromised patients (in particular immunosuppressed patients with stem cell or solid organ transplantation, AIDS or cancer). Additionally, congenital HCMV infections are a leading cause of birth defects and infections in children, occurring in 1 to 2% of all live births. Drugs currently available for the treatment of HCMV diseases in the immunocompromised individual include ganciclovir, its oral prodrug valganciclovir, cidofovir, foscavir and fomivirsen. Although these drugs have proved successful in the management of HCMV disease in immunocompromised patients, their use is limited because of toxicity, poor oral bioavailability, modest efficacy and the development of drug resistance. Furthermore, no drug has been licensed for use in the treatment of congenital HCMV. Therefore, there is a need to develop new compounds against HCMV diseases. The search for novel inhibitors of HCMV replication has led to the identification of new molecular targets such as the viral protein kinase UL97, and the viral proteins involved in genome replication or in DNA maturation and egress. Moreover, a new strategy based on the identification of specific cellular targets required for viral replication has been developed. This review focuses on non-nucleoside compounds that inhibit specific viral processes and on cell-based approaches that result in the selective inhibition of virus replication.
Summary Die and mold manufacturing represents a significant area of production technology since it influences the feasibility and economics of producing a very large number of discrete components. Modern die manufacturing includes just about all aspects of manufacturing: part design, geometry handling and transfer, die design, process modeling, prototype production, control of dimensional and surface quality as well as advanced mechanical, electrical, and electrochemical machining methods. This paper, prepared with input from various CIRP colleagues, attempts to review the latest advances and practical applications in the field.
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