Substitution of Ti3+ and Ti4+ in hibonite (CaAl12O19)

The structures of eight synthetic samples of hibonite, with variable Ti oxidation state and Ti concentration (2.4–15.9 wt% TiO2) that span the range reported for natural hibonite found in meteorites, were determined by Rietveld refinements of neutron powder diffraction data. Ti3+ was found to exclusively occupy the octahedral face-sharing M4 site irrespective of the presence or absence of Ti4+. Ti4+ partitions between the trigonal bipyramidal M2 site and the M4 site. The ratio (Ti4+ on M2):(Ti4+ on M4) appears to be constant for all the samples, with an average of 0.18(2) irrespective of the concentrations of Ti3+ and Ti4+. These substitutional sites were shown to be the most stable configurations for Ti in hibonite from calculations using density functional theory, although the predicted preference of Ti4+ for M4 over M2 is not as strong as is observed. This is attributed to the different Ti contents of the experimental and calculated structures and suggests that the Ti site occupancies might change between these concentrations. Furthermore, it is shown that Ti has a preference to occupy neighboring M4 sites such that Ti-Ti interactions occur with stabilization energies of 83 kJ/mol for Ti3+-Ti3+ and at least 15 kJ/mol for Ti4+-Ti4+. Features in optical spectroscopy and electron spin resonance data from meteoritic and synthetic hibonites that have been used to infer Ti3+/Ti4+ are shown to actually derive from these Ti-Ti interactions. The amount of Ti4+ in hibonite can be determined from the unit-cell parameters if ∑Ti is determined independently. Ti3+/Ti4+ in hibonite may record the oxygen fugacity (fO2) of the early solar nebula, however, the existence of Ti3+-Ti3+ and Ti4+-Ti4+ interactions and the potential for Ti4+-Ti3+ interactions need to be considered when interpreting spectroscopic data in terms of Ti valence state and fO2. Hibonite as a single-mineral oxybarometer must be used with caution due to the potential role of crystal chemistry (including Ti-Ti interactions) to stabilize Ti oxidation states independently of fO2

Pro-active Meeting Assistants: Attention Please!

This paper gives an overview of pro-active meeting assistants, what they are and when they can be useful. We explain how to develop such assistants with respect to requirement definitions and elaborate on a set of Wizard of Oz experiments, aiming to find out in which form a meeting assistant should operate to be accepted by participants and whether the meeting effectiveness and efficiency can be improved by an assistant at all. This paper gives an overview of pro-active meeting assistants, what they are and when they can be useful. We explain how to develop such assistants with respect to requirement definitions and elaborate on a set of Wizard of Oz experiments, aiming to find out in which form a meeting assistant should operate to be accepted by participants and whether the meeting effectiveness and efficiency can be improved by an assistant at all

Categorical Dimensions of Human Odor Descriptor Space Revealed by Non-Negative Matrix Factorization

In contrast to most other sensory modalities, the basic perceptual dimensions of olfaction remain unclear. Here, we use non-negative matrix factorization (NMF) – a dimensionality reduction technique – to uncover structure in a panel of odor profiles, with each odor defined as a point in multi-dimensional descriptor space. The properties of NMF are favorable for the analysis of such lexical and perceptual data, and lead to a high-dimensional account of odor space. We further provide evidence that odor dimensions apply categorically. That is, odor space is not occupied homogenously, but rather in a discrete and intrinsically clustered manner. We discuss the potential implications of these results for the neural coding of odors, as well as for developing classifiers on larger datasets that may be useful for predicting perceptual qualities from chemical structures

Myocardial infarction with unusual presentation of otalgia: a case report

A rare case of a patient with unusual symptoms of earache and sore throat for cardiac ischemia is presented. A diagnosis of non-ST-segment elevation myocardial infarction (NSTEMI) was made based on initial elevation of troponin and an abnormal electrocardiograph (ECG). Percutaneous coronary intervention (PCI) performed with stent placement in the occluded coronary vessel was followed by a decrease in troponin level and complete resolution of the ear and throat pain and patient recovery from cardiac ischemia

Antimalarial 4(1H)-pyridones bind to the Qisite of cytochromebc1

Cytochrome bc1 is a proven drug target in the prevention and treatment of malaria. The rise in drug-resistant strains of Plasmodium falciparum, the organism responsible for malaria, has generated a global effort in designing new classes of drugs. Much of the design/redesign work on overcoming this resistance has been focused on compounds that are presumed to bind the Qo site (one of two potential binding sites within cytochrome bc1) using the known crystal structure of this large membrane-bound macromolecular complex via in silico modeling. Cocrystallization of the cytochrome bc1 complex with the 4(1H)-pyridone class of inhibitors, GSK932121 and GW844520, that have been shown to be potent antimalarial agents in vivo, revealed that these inhibitors do not bind at the Qo site but bind at the Qi site. The discovery that these compounds bind at the Qi site may provide a molecular explanation for the cardiotoxicity and eventual failure of GSK932121 in phase-1 clinical trial and highlight the need for direct experimental observation of a compound bound to a target site before chemical optimization and development for clinical trials. The binding of the 4(1H)-pyridone class of inhibitors to Qi also explains the ability of this class to overcome parasite Qo-based atovaquone resistance and provides critical structural information for future design of new selective compounds with improved safety profiles

Ab-initio Quantum Enhanced Optical Phase Estimation Using Real-time Feedback Control

Optical phase estimation is a vital measurement primitive that is used to perform accurate measurements of various physical quantities like length, velocity and displacements. The precision of such measurements can be largely enhanced by the use of entangled or squeezed states of light as demonstrated in a variety of different optical systems. Most of these accounts however deal with the measurement of a very small shift of an already known phase, which is in stark contrast to ab-initio phase estimation where the initial phase is unknown. Here we report on the realization of a quantum enhanced and fully deterministic phase estimation protocol based on real-time feedback control. Using robust squeezed states of light combined with a real-time Bayesian estimation feedback algorithm, we demonstrate deterministic phase estimation with a precision beyond the quantum shot noise limit. The demonstrated protocol opens up new opportunities for quantum microscopy, quantum metrology and quantum information processing.Comment: 5 figure

Molecular Mechanism of Action of Antimalarial Benzoisothiazolones: Species-Selective Inhibitors of the Plasmodium spp. MEP Pathway enzyme, IspD

The methylerythritol phosphate (MEP) pathway is an essential metabolic pathway found in malaria parasites, but absent in mammals, making it a highly attractive target for the discovery of novel and selective antimalarial therapies. Using high-throughput screening, we have identified 2-phenyl benzo[d]isothiazol-3(2H)-ones as species-selective inhibitors of Plasmodium spp. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD), the third catalytic enzyme of the MEP pathway. 2-Phenyl benzo[d]isothiazol-3(2H)-ones display nanomolar inhibitory activity against P. falciparum and P. vivax IspD and prevent the growth of P. falciparum in culture, with EC50 values below 400 nM. In silico modeling, along with enzymatic, genetic and crystallographic studies, have established a mechanism-of-action involving initial non-covalent recognition of inhibitors at the IspD binding site, followed by disulfide bond formation through attack of an active site cysteine residue on the benzo[d]isothiazol-3(2H)-one core. The species-selective inhibitory activity of these small molecules against Plasmodium spp. IspD and cultured parasites suggests they have potential as lead compounds in the pursuit of novel drugs to treat malaria

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

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