Transmission-Line Class-E Power Amplifier With Extended Maximum Operating Frequency

A novel Class-E power amplifier (PA) topology with transmission-line load network is presented in this brief. When compared with the classic Class-E topology, the new circuit can increase the maximum operating frequency up to 50% higher without trading the other Class-E figures of merit. Neither quarterwave line/massive radio-frequency choke for collector/drain biasing nor additional fundamental-frequency output matching circuit are needed in the proposed PA, thus resulting in a compact design. Closed-form formulations are derived and verified by simulations with practical design limitations carefully taken into consideration and good agreement achieved.

Molecular investigations into vaginal immunization with HIV gp41 antigenic construct H4A in a quick release solid dosage form

A robust vaginal immune response is considered essential for an effective prophylactic vaccine that prevents transmission of HIV and other sexually acquired diseases. Considerable attention has recently focused on the potential of vaginally administered vaccines as a means to induce such local immunity. However, the potential for vaccination at this site remains in doubt as the vaginal mucosa is generally considered to have low immune inductive potential. In the current study, we explored for the first time the use of a quick release, freeze-dried, solid dosage system for practical vaginal administration of a protein antigen. These solid dosage forms overcome the common problem associated with leakage and poor retention of vaginally administered antigen solutions. Mice were immunized vaginally with H4A, an HIV gp41 envelope based recombinant protein, using quick release, freeze-dried solid rods, and the immune responses compared to a control group immunized via subcutaneous H4A injection. Vaginally immunized mice failed to elicit robust immune responses. Our detailed investigations, involving cytokine analysis, the stability of H4A in mouse cervicovaginal lavage, and elucidation of the state of H4A protein in the immediate-release dosage form, revealed that antigen instability in vaginal fluid, the state of the antigen in the dosage form, and the cytokine profile induced are all likely to have contributed to the observed lack of immunogenicity. These are important factors affecting vaginal immunization and provide a rational basis for explaining the typically poor and variable elicitation of immunity at this site, despite the presence of immune responsive cells within the vaginal mucosae. In future mucosal vaccine studies, a more explicit focus on antigen stability in the dosage form and the immune potential of available antigen-responsive cells is recommended. © 2012 Elsevier Ltd. All rights reserved.

Direct Contact as a Moderator of Extended Contact Effects: Cross-Sectional and Longitudinal Impact on Outgroup Attitudes, Behavioral Intentions, and Attitude Certainty

Cross-group friendships (the most effective form of direct contact) and extended contact (i.e., knowing ingroup members who have outgroup friends) constitute two of the most important means of improving outgroup attitudes. Using cross-sectional and longitudinal samples from different intergroup contexts, this research demonstrates that extended contact is most effective when individuals live in segregated neighborhoods having only few, or no, direct friendships with outgroup members. Moreover, by including measures of attitudes and behavioral intentions the authors showed the broader impact of these forms of contact, and, by assessing attitude certainty as one dimension of attitude strength, they tested whether extended contact can lead not only to more positive but also to stronger outgroup orientations. Cross-sectional data showed that direct contact was more strongly related to attitude certainty than was extended contact, but longitudinal data showed both forms of contact affected attitude certainty in the long run.

Extended contact effects as a function of closeness of relationship with ingroup contacts

Using survey data from Catholics and Protestants in Northern Ireland (N = 428), the authors examined the effects of extended contact via different types of ingroup contacts (neighbors, work colleagues, friends, and family members) and tested whether closeness to ingroup contacts moderated the effects of extended contact on outgroup trust. Results demonstrated that extended contact effects varied as a function of the relationship to ingroup contacts, and that extended contact interacted with closeness ratings in predicting outgroup trust. Consistent with hypotheses, extended contacts via more intimate ingroup relationships (i.e., friends and family) were overall more strongly related to outgroup trust than extended contacts via less intimate ingroup relations (i.e., neighbors and work colleagues). Moreover, within each level of intimacy extended contact was related to outgroup trust only at high, and not at low, levels of rated closeness to ingroup contacts. The theoretical contributions, limitations and practical implications of these findings are discussed.

Sustained Release of the CCR5 Inhibitors CMPD167 and Maraviroc from Vaginal Rings in Rhesus Macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for prevention of sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of the entry inhibitors maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously over 28 days from rings in vitro, at rates of 100-2500 µg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady state fluid concentrations were ~106 fold greater than IC50 values for SHIV-162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. Pretreatment of macaques with Depo-Provera® (DP), as commonly used in macaque challenge studies, was shown to significantly modify the bio-distribution of the inhibitors, but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments, and also for ring performance during the human female menstrual cycle. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

An examination of the thermorheological and drug release properties of zinc tetraphenylporphyrin-containing thermoresponsive hydrogels, designed as light activated antimicrobial implants

This study describes the thermorheological, mechanical and drug release properties of novel, light-activated antimicrobial implants. Hydrogels, based on N-isopropylacrylamide (NIPAA) and hydroxyethyl methacryl ate (HEMA) and either devoid of or containing zinc tetraphenylporphyrin, were prepared by free radical polymerisation and characterised using oscillatory rheometry and texture profile analysis. Drug release was studied at both 20 and 37 degrees C. Hydrogels containing NIPAA exhibited a sol-gel temperature (Tin), which increased as the proportion of HEMA increased and was

Mucoadhesive, syringeable drug delivery systems for controlled application of metronidazole to the periodontal pocket: In vitro release kinetics, syringeability, mechanical and mucoadhesive properties

Novel mucoadhesive formulations containing hydroxyethylcellulose (HEC; 3 and 5%, w/w) or Carbopol (3 and 5%, w/w), polycarbophil (PC; 1 and 3%, w/w) and metronidazole (5%, w/w) at pH 6.8 were designed for the treatment of periodontal diseases. Each formulation was characterised in terms of hardness, compressibility, adhesiveness and cohesiveness (using Texture Profile Analysis), drug release, adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode) and, finally, syringeability (using the texture analyser in compression mode). Drug release from all formulations was non-diffusion controlled. Drug release was significantly decreased as the concentration of each polymeric component was increased, due to both the concomitant increased viscosity of the formulations and, additionally, the swelling kinetics of PC following contact with dissolution fluid. Increasing the concentrations of each polymeric component significantly increased formulation hardness, compressibility, adhesiveness, mucoadhesion and syringeability, yet decreased cohesiveness. Increased product hardness, compressibility and syringeability were due to polymeric effects on formulation viscosity. The effects on cohesiveness may be explained both by increased viscosity and also by the increasing semi-solid nature of products containing 5% HEC or Carbopol and PC (1 or 3%). The observations concerning formulation adhesiveness/mucoadhesion illustrate the adhesive nature of each polymeric component. Greatest adhesion was noted in formulations where neutralisation of PC was maximally suppressed. For the most part, increased time of contact between formulation and mucin significantly increased the required force of detachment, due to the greater extent of mucin polymer hydration and interpenetration with the formulations. Significant statistical interactions were observed between the effects of each polymer on drug release and mechanical/mucoadhesive properties. These interactions may be explained by formulatory effects on the extent of swelling of PC. In conclusion, the formulations described offered a wide range of mechanical and drug release characteristics. Formulations containing HEC exhibited superior physical characteristics for improved drug delivery to the periodontal pocket and are now the subject of long-term clinical investigations. (C) 1997 Elsevier Science B.V.

Chlorhexidine release from poly(epsilon-caprolactone) films prepared by solvent evaporation

The effect of selected formulation variables on the release of chlorhexidine from poly(epsilon-caprolactone) films was evaluated in vitro using a complete factorial experimental design. Repeated measures analysis of variance showed chlorhexidine type (diacetate or base), drug load (10, 20 or 30% w/w), chlorhexidine particle size (

CASTING SOLVENT CONTROLLED-RELEASE OF CHLORHEXIDINE FROM ETHYLCELLULOSE FILMS PREPARED BY SOLVENT EVAPORATION

Chlorhexidine release from ethylcellulose films east from solvents of different dichloromethane/ethanol compositions was studied. Release rate was proportional to the square root of time. Increased ethanol content within the casting solvent significantly enhanced release rate. Release rate and cumulative mass released at different time periods (5, 10, 15 and 25 days) were proportional to the solubility parameter of the casting solvent.

Histamine release from human bronchoalveolar lavage mast cells by neurokinin A and bradykinin

Objective and Design: This study examined whether bradykinin and neurokinin A activate human pulmonary mast cells retrieved by bronchoalveolar lavage (BAL).

MODULATORY ACTION OF HELICOBACTER-PYLORI ON HISTAMINE-RELEASE FROM MAST-CELLS AND BASOPHILS IN-VITRO

Helicobacter pylori is important in the aetiology of peptic ulceration. Despite inducing an inflammatory response in the mucosa, the organism persists, suggesting that it has efficient protective mechanisms. Some bacterial and viral products modulate histamine secretion from inflammatory cells. Therefore, this study examined the modulatory effects of H. pylori preparations on histamine release from rat peritoneal mast cells and human basophils. Eleven clinical isolates of H. pylori were prepared in different ways: as whole washed bacteria, washed sonicated bacteria, and formalin-killed bacteria, and as outer-membrane and lipopolysaccharide (LPS) extracts. Histamine release from mast cells or basophils was not elicited by any of these bacterial preparations alone. However, when mixed with various secretory stimulants, the bacterial preparations caused inhibition of histamine release from rat mast cells (calcium ionophore A23187, compound 48/80, concanavalin A, anti-rat IgE) and human basophils (A23187, N-formyl Met-Leu-Phe). The degree of inhibition ranged from 48 % to 97 %. These results indicate that H. pylori exerts an inhibitory effect on cells of the immune system that contributes to its persistence within the gastric mucosa.