Pharmacokinetics of a CCR5 inhibitor in rhesus macaques following vaginal, rectal and oral application

Objectives: This study measured and compared the pharmacokinetics of CMPD167, a small molecule antiretro- viral CCR5 inhibitor with potential as an HIV microbicide, following vaginal, rectal and oral administration in rhe- sus macaques.
Methods: A vaginal hydroxyethylcellulose (HEC) gel, a rectal HEC gel, a silicone elastomer matrix-type vaginal ring and an oral solution, each containing CMPD167, were prepared and administered to rhesus macaques pretreated with Depo-Provera. CMPD167 concentrations in vaginal fluid, vaginal tissue (ring only), rectal fluid and blood plasma were quantified by HPLC–mass spectrometry.
Results: CMPD167 concentrations measured in rectal fluid, vaginal fluid and blood plasma were highly depend- ent on both the route of administration and the formulation type. Although rectal and vaginal fluid concentra- tions were highest when CMPD167 was administered locally (via either gel or ring), lower concentrations of the drug were also measured in these compartments following administration at the remote mucosal site or orally. CMPD167 levels in the vaginal and rectal fluid following oral administration were relatively low compared with local administration.
Conclusions: The study provides clear evidence for vaginal – rectal and rectal – vaginal drug transfer pathways and suggests that oral pre-exposure prophylaxis with CMPD167 may be less efficacious at preventing sexual trans- mission of HIV-1 than topically applied products.

BER evaluation of a low complexity transmit diversity scheme and its application to MIMO-BICM

In this paper, we first provide a theoretical validation for a low-complexity transmit diversity algorithm which employs only one RF chain and a low-complexity switch for transmission. Our theoretical analysis is compared to the simulation results and proved to be accurate. We then apply the transmit diversity scheme to multiple-input and multiple-output (MIMO) systems with bit-interleaved coded modulation (BICM). © 2012 IEEE.

Structuring reductive media containing protic ionic liquids and their application to the formation of metallic nanoparticles

Herein, we present a facile method for the formation of monodispersed metal nanoparticles (NPs) at room temperature from M^(III)Cl₃ (with M = Au, Ru, Mn, Fe or V) in different media based on N,N-dimethylformamide (DMF) or water solutions containing a protic ionic liquid (PIL), namely the octylammonium formate (denoted OAF) or the bis(2-ethyl-hexyl)ammonium formate (denoted BEHAF). These two PILs present different structures and redox-active structuring properties that influence their interactions with selected molecular compounds (DMF or water), as well as the shape and the size of formed metal NPs in these solutions. Herein, the physical properties, such as the thermal, transport and micellar properties, of investigated PIL solutions were firstly investigated in order to understand the relation between PILs structure and their properties in solutions with DMF or water. The formation of metal NPs in these solutions was then characterized by using UV–vis spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and dynamic light scattering (DLS) measurements. From our investigations, it appears that the PILs structure and their aggregation pathways in selected solvents affect strongly the formation, growths, the shape and the size of metal NPs. In fact by using this approach, the shape-/size-controlled metal NPs can be generated under mild condition. This approach suggests also a wealth of potential for these designer nanomaterials within the biomedical, materials, and catalysis communities by using designer and safer media based on PILs.

Rational Partial Choice Functions and Their Application to Belief Revision.

Necessary and sufficient conditions for choice functions to be rational have been intensively studied in the past. However, in these attempts, a choice function is completely specified. That is, given any subset of options, called an issue, the best option over that issue is always known, whilst in real-world scenarios, it is very often that only a few choices are known instead of all. In this paper, we study partial choice functions and investigate necessary and sufficient rationality conditions for situations where only a few choices are known. We prove that our necessary and sufficient condition for partial choice functions boils down to the necessary and sufficient conditions for complete choice functions proposed in the literature. Choice functions have been instrumental in belief revision theory. That is, in most approaches to belief revision, the problem studied can simply be described as the choice of possible worlds compatible with the input information, given an agent’s prior belief state. The main effort has been to devise strategies in order to infer the agents revised belief state. Our study considers the converse problem: given a collection of input information items and their corresponding revision results (as provided by an agent), does there exist a rational revision operation used by the agent and a consistent belief state that may explain the observed results?

A Reliability Assessment Approach for the Urban Energy System and Its Application in Energy Hub Planning

With the increasing utilization of combined heat and power plants (CHP), electrical, gas, and thermal systems are becoming tightly integrated in the urban energy system (UES). However, the three systems are usually planned and operated separately, ignoring their interactions and coordination. To address this issue, the coupling point of different systems in the UES is described by the energy hub model. With this model, an integrated load curtailment method is proposed for the UES. Then a Monte Carlo simulation based approach is developed to assess the reliability of coordinated energy supply systems. Based on this approach, a reliability-optimal energy hub planning method is proposed to accommodate higher renewable energy penetration. Numerical studies indicate that the proposed approach is able to quantify the UES reliability with different structures. Also, optimal energy hub planning scheme can be determined to ensure the reliability of the UES with high renewable penetration.

Measuring non-use value of environmental goods using the contingent valuation method:problems of information and cognition and the application of cognitive questionnaire design methods

Much interest now focuses on the use of the contingent valuation method (CVM) to assess non-use value of environmental goods. The paper reviews recent literature and highlights particular problems of information provision and respondent knowledge, comprehension and cognition. These must be dealt with by economists in designing CVM surveys for eliciting non-use values. Cognitive questionnaire design methods are presented which invoke concepts from psychology and tools from cognitive survey design (focus groups and verbal reports) to reduce a complex environmnetal good into a meaningful commodity that can be valued by respondents in a contingent market. This process is illustrated with examples from the authors' own research valuing alternative afforestation programmes. -Authors

Novel monoclonal antibody and peptide binders for Mycobacterium avium subsp. paratuberculosis and their application for magnetic separation

The generation of novel Mycobacterium avium subsp. paratuberculosis (MAP)-specific monoclonal antibodies and phage-display derived peptide binders, along with their application for the magnetic separation (MS) of MAP cells, is described. Our aim was to achieve even greater MAP capture capability than is possible with peptide-mediated magnetic separation (PMS) using a 50:50 mix of biotinylated-aMp3 and biotinylated-aMptD peptide-coated beads. Gamma-irradiated whole MAP cells and ethanol extracted antigens (EEA) from these cells were used to elicit an immune response and as phage-display biopanning targets. A range of novel binders was obtained and coated onto paramagnetic beads, both individually and in various combinations, for MS evaluation. IS900 PCR was employed after MS to provide quick results. Capture sensitivity was assessed using a range of MAP concentrations after which the most promising beads were tested for their specificity for MAP, by performing MS followed by culture using 10 other Mycobacterium species. Magnetic beads coated with the biotinylated EEA402 peptide demonstrated a greater level of MAP capture than the current PMS method, even when low numbers of MAP (<10 cfu/ml) were present; however these beads also captured a range of other mycobacteria and so lacked capture specificity. Magnetic beads coated with monoclonal antibodies 6G11 and 15D10 (used as a 50:50 mix or as dually coated beads) also demonstrated improved MAP capture relative to the current PMS method, but with little cross-reactivity to other Mycobacterium spp. Therefore, two new MS protocols are suggested, the application of which would be dependent upon the required endpoint. Biotinylated EEA402-coated beads could potentially be used with a MAP-specific PCR to ensure detection specificity, while beads coated with 6G11 and 15D10 monoclonal antibodies could be used with culture or the phage amplification assay.

Conversations with the Future: Creativity, Aesthetics and Industry Application in Anthropological Practice

This article presents a series of conversations with anthropologists working in collaborative, interdisciplinary settings and projects. It examines the changing role and place of anthropology on the island of Ireland, particular for early career anthropologists. With anthropologists now working in settings as diverse as business schools, health, music, documentary making and industry (to name but a few), early career researchers are now dealing with new challenges. In this piece, we map out a number of these debates and show how a multiplicity of anthropologies and practices are emerging on the island.