Pharmacokinetics of UC781-loaded intravaginal ring segments in rabbits: a comparison of polymer matrices

UC781 is a potent and poorly water-soluble nonnucleoside reverse transcriptase inhibitor being investi- gated as a potential microbicide for preventing sexual transmission of HIV-1. This study was designed to evaluate the in vivo release and pharmacokinetics of UC781 delivered from matrix-type intravaginal ring segments in rabbits. Three polymer matrices (polyurethane, ethylene vinyl acetate copolymer, and silicone elastomer) and two drug loadings (5 and 15 mg/segment) were evaluated in at least one of two independent studies for up to 28 days in vivo. Inter-study comparison of in vivo release, vaginal tissue, and plasma concentrations for similar formulations demonstrated good reproducibility of the animal model. Mean estimates for a 28-day in vivo release ranged from 0.35 to 3.17 mg UC781 per segment. Mean proximal vaginal tissue levels (adjacent to the IVR segment) were 8– 410 ng/g and did not change significantly with time for most formulations. Distal vaginal tissue levels of UC781 were 6- to 49-fold lower than proximal tissue levels. Mean UC781 plasma levels were low for all formulations, at 0.09–0.58 ng/mL. All formulations resulted in similar UC781 concentrations in vaginal tissue and plasma, except the low loading polyurethane group which provided significantly lower levels. Loading dependent release and pharmacokinetics were only clearly observed for the polyurethane matrix. Based on these results, intravaginal ring segments loaded with UC781 led to vaginal tissue concen- trations ranging from below to approximately two orders of magnitude higher than UC781’s EC50 under in vitro conditions (2.8 ng/mL), with little influence by polymer matrix or UC781 loading. Moreover, these findings support the use of rabbit vaginal pharmacokinetic studies in preclinical testing of microbicide intravaginal rings.

Alternating ring-opening metathesis copolymerization of bicyclo[2.2.1]hept-2-ene and cyclopentene

Almost alternating copolymers of bicyclo[2.2.1]hept-2-ene and cyclopentene have been formed by ring-opening metathesis polymerization using a RuCl3-phenol catalyst system; this highly novel result is attributed to differential steric influences exerted by a hydrogen-bonded solvent cage which encloses the catalyst site.

Conflict, Transformation, and Former Loyalist Paramilitary Prisoners in Northern Ireland

Following the 1998 Belfast Agreement in Northern Ireland, levels of paramilitary violence have declined substantially. Among loyalists, the Ulster Volunteer Force (UVF) and associated Red Hand Commando (RHC) have formally renounced violence, and dissolved their 'military structures', and perhaps the most reticent of all of the major paramilitary groupings, the Ulster Defence Association (UDA), has taken on board the central tenets of conflict transformation, and 'stood down' all of its 'active service units' in the Ulster Freedom Fighters (UFF). Thus, paramilitary violence now is mainly confined to the activities of 'dissident' republican groups, notably the Real and Continuity IRAs, although low-level sectarian violence remains a problem. Such dramatic societal and political change has resulted in a focus on the roles of formal party political leadership as agents of social change. This gaze, however, tends to obscure other important events such as the efforts, structures and approaches taken at the grassroots level to uphold and sustain conflict transformation and to maintain a reduction in violence. This article provides analysis of the role played by former loyalist paramilitary combatants in conflict transformation, and draws on material obtained through significant access to those former paramilitaries engaged in processes of societal shifts. In both personal and structural terms there is evidence of former combatants working to diminish the political tensions that remain as a result of the long-term inter-communal hostility developed across decades of violence and conflict.

Re-imagining DDR Ex-combatants, leadership and moral agency in conflict transformation

Drawing upon criminological studies in the field of prisoner rehabilitation, this essay explores the relevance of the Demobilisation, Disarmament and Reintegration (DDR) framework to the process of conflict transformation in Northern Ireland. In a similar fashion to the critique of 'passivity' offered by, for example, the 'strengths based' or 'good lives' approach to prisoner resettlement and reintegration more generally, the authors contend that the Northern Ireland peace process offers conspicuous examples of former prisoners and combatants as agents and indeed leaders in the process of conflict transformation. They draw out three broad styles of leadership which have emerged amongst ex-combatants over the course of the Northern Ireland transition from conflict-political, military and communal. They suggest that cumulatively such leadership speaks to the potential of ex-prisoners and ex-combatants as moral agents in conflict transformation around which peacemaking can be constructed rather than as obstacles which must be 'managed' out of existence.

Resistance, transition and exclusion: Politically motivated ex-prisoners and conflict transformation in Northern Ireland

The landscape of political imprisonment in Northern Ireland was changed due to the general release and reintegration of politically motivated prisoners as part of the Belfast Agreement. This article reflects upon the post-prison experiences of former prisoners and their families, and in particular how the move from a resistant to a transitional framework has facilitated a greater openness and willingness amongs ex-prisoners to acknowledge the personal and familial problems related to incarceration. We also explore the ways in which ex-prisoners have attempted to deal with the continued social, political and civic exclusion which arises as a result of their conflict-related 'criminal' convictions. In the final section of the article, the authors further develop the move from a resistant to a transitional characterization of incarceration and its consequences.

Double cyclometalation via carbon-silicon bond cleavage by palladium(II) acetate. X-ray structure of a cationic 1,4-dipalladated benzene ring and selective synthesis of heterobimetallic 1,4-phenylene-bridged platinum(II)-palladium(II) complexes

The disilylated compound 1,4-bis(trimethylsilyl)-2,3,5,6-tetrakis((dimethylamino)methyl)benzene, (Me(3)Si)(2)C2N4, 4, can be electrophilically palladated selectively at the C-Si bonds to afford the neutral 1,4-bis(palladium) complex [(AcOPd)(2)(C2N4)], from which the dicationic [(LPd)(2)(C2N4)](2+) (L = MeCN) organometallic species are accessible. The monosilylated species (Me(3)Si)(H)C2N4, 5, can be used for the preparation of the dicationic heterodinuclear platinum(II)-palladium(II) species [(LPd)(LPt)(C2N4)](2+) (L = MeCN) via a sequence of transmetalation of the organolithium derivative of 5 with [PtCl2(SEt(2))(2)], followed by a C-Si bond palladation reaction.

Transformation of vaterite into calcite in the absence and the presence of copper(II) species. Thermal analysis, IR and EPR study

The transformation of vaterite into calcite may be performed by heating in the presence and the absence of oxygen. Vaterite remains thermally stable until a calcination temperature of 450°C. It transforms progressively to calcite up to 500°C giving two exothermic peaks: 1) at 481°C due to the transformation of vaterite surface which is in contact with a small amount of calcite phase already formed with the time on the solid surface from the humidity atmosphere; 2) at 491°C due to the transformation of pure vaterite bulk. The calcite phase remains stable until 700°C. Above this temperature the formation of CaO is observed.

Frequency selective surface using nested split ring slot elements as a lens with mechanically reconfigurable beam steering capability

The design is described of a double layer frequency selective surface which can produce a differential phase shift of 180 ° as the wave propagates through it at normal incidence. The hand of an applied circularly polarized signal is reversed due to the 180° phase shift, and it is demonstrated that the exit circularly polarized output signal can be phase advanced or phase retarded by 180 ° upon rotation of the elements comprising the structure. This feature allows the surface to act as a spatial phase shifter. In this paper the beam steering capabilities of a 10 × 10 array of such elements are demonstrated. Here the individual elements comprising the array are rotated relative to each other in order to generate a progressive phase shift. At normal incidence the 3 dB Axial Ratio Bandwidth for LHCP to RHCP conversion is 5.3% and the insertion loss was found to be -2.3 dB, with minimum axial ratio of 0.05 dB. This array is shown to be able to steer a beam from -40 ° to +40 ° while holding axial ratio at the pointing angle to below 4 dB. The measured radiation patterns match the theoretical calculation and full-wave simulation results. © 2010 IEEE.