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Alpharetta, GA, United States

Hawkins J.,Pfizer | Kodali S.,Pfizer | Matsuka Y.V.,Pfizer | McNeil L.K.,Pfizer | And 8 more authors.
Clinical and Vaccine Immunology | Year: 2012

Staphylococcus aureus is a Gram-positive pathogen that causes devastating disease and whose pathogenesis is dependent on interactions with host cell factors. Staphylococcal clumping factor A (ClfA) is a highly conserved fibrinogen (Fg)-binding protein and virulence factor that contributes to host tissue adhesion and initiation of infection. ClfA is being investigated as a possible component of a staphylococcal vaccine. We report the development of an Fg-binding assay that is specific for ClfA-mediated binding. Using the assay, we show that despite the presence of anti-ClfA antibodies, human sera from unvaccinated subjects are unable to prevent the binding of S. aureus to an Fg-coated surface. In contrast, antibodies elicited by a recombinant ClfA-containing vaccine were capable of blocking the ClfA-dependent binding of a diverse and clinically relevant collection of staphylococcal strains to Fg. These functional antibodies were also able to displace S. aureus already bound to Fg, suggesting that the ligand-binding activity of ClfA can be effectively neutralized through vaccination. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 99.35K | Year: 1999

Not Available The development of a high-speed corner cube laser beam modulator for free space communication is the subject of this proposal. Free space laser communication is considered to be a viable, cost-effective approach in many applications requiring point-to-point secure communication. In one such application, useful for small satellites constrained by power consumption, a ground CW laser is used and a reflecting corner cube modulator is placed onboard the satellite. For such a system to be accepted, a high-speed modulator operating at 1 MHz or higher rates is needed. Foster-Miller proposes to use a voltage controlled diffractive optical element (DOE) as a high-speed modulator for this application. When fully implemented, the modulator will achieve a megahertz modulation rate, will have a large active aperture of more than 50 mm, and will be wavelength insensitive from the visible to IR range. One of the most important characteristics of the proposed device, which distinguishes it from other designs, is its very short response time consistent with high contrast ratio of better than 100:1, and large aperture. The anticipated drive power requirement of the proposed modulator is less than 10 mW/cm (sup 2). The proposed modulator can be produced using established semiconductor manufacturing technology.

This invention is directed to compounds of Formula (I) having the structure that are useful in the treatment of viral infections in mammals, particularly in humans, mediated, at least in part, by a virus in the Flaviviridae family of viruses.

This invention is directed to novel compounds of formula (I) having the structure (I) wherein U, V, W, Z, R

Pentikis H.S.,SAJE Consulting LLC | Matson M.,PRISM Research Inc. | Atiee G.,ICON Development Solutions | Boehlecke B.,Rho Inc. | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

FV-100 is the prodrug of the highly potent anti-varicella zoster virus bicyclic nucleoside analogue CF-1743. To characterize the pharmacokinetics and safety of oral FV-100, 3 randomized, double-blind, placebo-controlled clinical trials were conducted: (i) a single-ascending-dose study in 32 healthy subjects aged 18 to 55 years (100-, 200-, 400-, and 800-mg doses) with an evaluation of the food effect in the 400-mg group; (ii) a multiple-ascending-dose study in 48 subjects aged 18 to 55 years (100 mg once daily [QD], 200 mg QD, 400 mg QD, 400 mg twice a day, and 800 mg QD for 7 days); and (iii) a 2-part study in subjects aged 65 years and older with a single 400-mg dose in 15 subjects and a 400-mg QD dosing regimen for 7 days in 12 subjects. FV-100 was rapidly and extensively converted to CF-1743, the concentration of which remained above that required to reduce viral activity by 50% for the 24-hour dosing period. Renal excretion of CF-1743 was very low. A high-fat meal reduced exposure to CF-1743; a low-fat meal did not. Pharmacokinetic parameters for the elderly subjects were comparable to those for the younger subjects. FV-100 was well tolerated by all subjects. The pharmacokinetic and safety profiles of FV-100 support its continued investigation for the treatment of herpes zoster and prevention of postherpetic neuralgia with once-daily dosing and without dose modifications for elderly or renally impaired patients. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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