Oxygen vacancy segregation and space-charge effects in grain boundaries of dry and hydrated BaZrO3

A space-charge model is applied to describe the equilibrium effects of segregation of double-donor oxygen vacancies to grain boundaries in dry and wet acceptor-doped samples of the perovskite oxide BaZrO3. The grain boundary core vacancy concentrations and electrostatic potential barriers resulting from different vacancy segregation energies are evaluated. Density-functional calculations on vacancy segregation to the mirror-symmetric \Sigma 3 (112) [-110] tilt grain boundary are also presented. Our results indicate that oxygen vacancy segregation can be responsible for the low grain boundary proton conductivity in BaZrO3 reported in the literature

Automatic Filtering and Substantiation of Drug Safety Signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Effects of anoxia and sulfide on concentrations of total and methyl mercury in sediment and water in two Hg-polluted lakes

Between May and December 1996, monthly samples of surface sediment (0-1 cm), settling matter, and water were taken at a shallow site and a deep site in each of two consecutive Hg-polluted riverine lakes. In the upper lake, the sediment was polluted also with cellulose fiber. Both hypolimnia turned anoxic, but sulfide was detected only in the upper lake. When sulfide appeared, hypolimnetic methyl mercury (MeHg) increased and reached 47 pM (9.4 ng.L-1), whereas MeHg in the sediment below decreased. The increase in hypolimnetic inorganic Hg (IHg = total Hg - MeHg), which reached a peak of 40 pM (8.0 ng.L-1), was slower, possibly because mobilized IHg was methylated. In the lower lake, hypolimnetic MeHg and IHg increased less dramatically during summer stratification, reaching only 5 and 24 pM (1.0 and 4.8 ng.L-1), respectively. There was no detectable concomitant decrease in sediment MeHg. In both lakes, MeHg appeared to increase simultaneously with total Fe and Mn in the hypolimnion, as did IHg in the lower lake. Our observations suggest that the presence of hydrous ferric and manganese oxides decreased the mobility of Hg in both lakes but increased MeHg production in the upper lake

Electrically commanded surfaces for namatic liquid crystal displays

Electrically commanded surfaces (ECS) is a liquid crystal display concept whereby the switching of the alignment layer, which is driven by an electric field applied across the layer, is further transferred to the bulk liquid crystal material via elastic forces. This work presents the electro-optic response of a sandwich cell with alignment layer made of siloxane-based ferroelectric liquid crystal polymer, representing the ECS. The bulk liquid crystal material of choice was an in-house nematic mixture comprising fluorinated liquid crystalline compounds with negative dielectric anisotropy (<0). We report a distinct linear electro-optic response, arising from the field-induced in-plane switching of the nematic which in turn is mediated by the ECS

Controllable alignment of nematics by nanostructured polymeric layers

A method for a continuous control of the pretilt angle of the easy axis in the range 0-90\ub0 degrees and of the anchoring strength by using nanostructured polymers as alignment layers is described. The nanostructured polymers are blends of two different side-chain polymers each of them promoting planar and homeotropic alignment, respectively. A model to interpret the alignment of a nematic liquid crystal induced by such polymer layers is proposed. We show that in this case the anisotropic part of the surface tension can be approximated by a simple extension of the Rapini-Papoular expression. The predicted trend of the pretilt of the easy axis versus the concentration of the side-chain polymer promoting the planar alignment, for instance, is in good agreement with the experimental data. We also show that the effective anchoring strength of the system depends on the concentration of the side-chain polymer promoting planar alignment, and exhibits a minimum for a well-defined value of this quantity. The results obtained in this work seems to be of importance for liquid crystal displays technology since the control of the pretilt and the anchoring strength strongly affect the performance of liquid crystal displays

Drug-induced acute myocardial infarction: identifying 'prime suspects' from electronic healthcare records-based surveillance system.

BACKGROUND: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings. OBJECTIVE: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. METHODS: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. RESULTS: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects'): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. LIMITATIONS: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. CONCLUSION: A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association, but also public health relevance, novelty, and biological plausibility. Although this strategy needs to be further evaluated using other healthcare data sources, the list of 'prime suspects' makes a good starting point for further clinical, laboratory, and epidemiologic investigation