Robustness of equilibria in the graph model for conflict resolution

A novel approach for assessing the robustness of an equilibrium in conflict resolution is presented.Roughly,an equilibrium is robust if it is resilient,or resistant to deviation.Robustness assessment is based on a new concept called Level of Freedom,which evaluates the relative freedom of a decision maker to escape an equilibrium.Resolutions of a conflict can be affected by changes in decision makers' preferences,which may destabilize an equilibrium,causing the conflict to evolve.Hence,a conflict may become long-term and thereby continue to evolve,even after reaching an equilibrium.The new robustness measure is used to rank equilibria based on robustness,to facilitate distinguishing equilibria that are relatively sustainable.An absolutely robust equilibrium is a special case in which the level of freedom is at an absolute minimum for each individual stability definition.     

Towards an Effective Multi-Stakeholder Consultation Process: Applying the Imagine Method in Context of Abu Dhabi’s Education Policy

This paper is concerned with the many interleaving issues that emerge when engaging multiple stakeholders in decision-making. Whilst recognising the intrinsic value of group work and keeping in mind the numerous issues that obstruct group work (including multiple roles for participants, bias due to domination and distortion emerging from uneven group inputs), we applied the Imagine method to propose a new framework—the ‘Multiple Formation Consultation Framework’ (MFCF)—for organising effective multi-stakeholder consultations along the Policy Sciences Framework. Our proposed framework was applied in the context of education policy in the Emirate of Abu Dhabi, where 24 small group formations were tasked and assessed in a systemic manner. Evidence from the exercise suggests that: (1) when moving participants from heterogeneous to homogenous groups, the working of the groups became more focused and the outcomes gained greater clarity in terms of the thinking of group members. (2) Yet, when groups moved from homogenous formations to heterogeneous, they became more inquisitive and explored broader aspects of the tasks at hand. (3) A repeat of the process over 2-day period where different members of the groups experience both homogenous and heterogeneous formations back and forth (in order to capture the unique value emerging from each composition) have led to more efficient and effective working and outcomes of the groups.     

Non-invasive prenatal measurement of the fetal genome

The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.     

TRPC channel activation by extracellular thioredoxin

Mammalian homologues of Drosophila melanogaster transient receptor potential (TRP) are a large family of multimeric cation channels that act, or putatively act, as sensors of one or more chemical factor. Major research objectives are the identification of endogenous activators and the determination of cellular and tissue functions of these channels. Here we show the activation of TRPC5 (canonical TRP 5) homomultimeric and TRPC5-TRPC1 heteromultimeric channels by extracellular reduced thioredoxin, which acts by breaking a disulphide bridge in the predicted extracellular loop adjacent to the ion-selectivity filter of TRPC5. Thioredoxin is an endogenous redox protein with established intracellular functions, but it is also secreted and its extracellular targets are largely unknown. Particularly high extracellular concentrations of thioredoxin are apparent in rheumatoid arthritis, an inflammatory joint disease that disables millions of people worldwide. We show that TRPC5 and TRPC1 are expressed in secretory fibroblast-like synoviocytes from patients with rheumatoid arthritis, that endogenous TRPC5-TRPC1 channels of the cells are activated by reduced thioredoxin, and that blockade of the channels enhances secretory activity and prevents the suppression of secretion by thioredoxin. The data indicate the presence of a previously unrecognized ion-channel activation mechanism that couples extracellular thioredoxin to cell function.     

Effects of drug-polymer dispersions on solubility and <Emphasis Type="Italic">in vitro</Emphasis> diffusion of artemisinin across a polydimethylsiloxane membrane

Artemisinin(ART) is a sesquiterpene lactone with an endo-peroxide bridge that is thought to be responsible for its antimalarial activity.It has low oral bioavailability because of aqueous insolubility,which leads to local toxicity at the site of aggregation.The present work focused on increasing its solubility and evaluating its permeation across a model membrane to mimic transdermal delivery that bypasses the hepatic metabolism.For this purpose,physical mixtures(PM),solid dispersions(SD) and lyophilized dispersions(LD) with different drug-polymer ratios(1:0.5,1:1,1:2,1:4 and 1:9) were prepared using the hydrophilic polymer polyvinylpyrrolidone(PVP).Drug-polymer dispersions were characterized using X-ray diffraction(XRD) and Fourier transform infrared spectroscopy(FTIR).Solubility was measured in three solvents:de-ionized water,phosphate buffered saline(PBS) and methanol.The toluene-water partition coefficient was evaluated and compared with the literature and calculated logP values.In vitro diffusion of ART was studied across a polydimethylsiloxane membrane from a saturated solution of drug-polymer dispersions.XRD patterns showed a gradual decrease in crystallinity of ART with increasing polymer concentration,while FTIR confirmed no interactions between ART and PVP.Solubility was increased up to 4-,5-and 8-fold for LD in water,PBS and methanol,respectively.The logP for toluene-water was 2.65 ± 0.3,which is in good agreement with literature and calculated logP values.Permeation was enhanced,which is attributed to the decrease in crystallinity and increase in wettability of the drug.The ART flux was significantly higher than that of pure ART(0.12 ± 0.01) with increasing PVP concentration for SD and LD formulations.In conclusion,drug-polymer dispersions with PVP improve the pharmaceutical properties of ART in the order LD>SD>PM.