Spin State Selective Excitation of Single Quantum Transitions Using Multiple Quantum Spectroscopy- an Aid to Analyse Complex Proton NMR spectra of Oriented Molecules

NMR spectra of molecules oriented in liquid-crystalline matrix provide information on the structure and orientation of the molecules. Thermotropic liquid crystals used as an orienting media result in the spectra of spins that are generally strongly coupled. The number of allowed transitions increases rapidly with the increase in the number of interacting spins. Furthermore, the number of single quantum transitions required for analysis is highly redundant. In the present study, we have demonstrated that it is possible to separate the subspectra of a homonuclear dipolar coupled spin system on the basis of the spin states of the coupled heteronuclei by multiple quantum (MQ)−single quantum (SQ) correlation experiments. This significantly reduces the number of redundant transitions, thereby simplifying the analysis of the complex spectrum. The methodology has been demonstrated on the doubly 13C labeled acetonitrile aligned in the liquid-crystal matrix and has been applied to analyze the complex spectrum of an oriented six spin system.

Prioritization of candidate cancer genes-an aid to oncogenomic studies

The development of techniques for oncogenomic analyses such as array comparative genomic hybridization, messenger RNA expression arrays and mutational screens have come to the fore in modern cancer research. Studies utilizing these techniques are able to highlight panels of genes that are altered in cancer. However, these candidate cancer genes must then be scrutinized to reveal whether they contribute to oncogenesis or are coincidental and non-causative. We present a computational method for the prioritization of candidate (i) proto-oncogenes and (ii) tumour suppressor genes from oncogenomic experiments. We constructed computational classifiers using different combinations of sequence and functional data including sequence conservation, protein domains and interactions, and regulatory data. We found that these classifiers are able to distinguish between known cancer genes and other human genes. Furthermore, the classifiers also discriminate candidate cancer genes from a recent mutational screen from other human genes. We provide a web-based facility through which cancer biologists may access our results and we propose computational cancer gene classification as a useful method of prioritizing candidate cancer genes identified in oncogenomic studies.

Missionary survey as an aid to intelligent co-operation in foreign missions, by Roland Allen, and Thomas Cochrane.

http://www.archive.org/details/missionarysurvey13360gut

Development of a decision aid to inform patients' and families' renal replacement therapy selection decisions.

BACKGROUND: Few educational resources have been developed to inform patients' renal replacement therapy (RRT) selection decisions. Patients progressing toward end stage renal disease (ESRD) must decide among multiple treatment options with varying characteristics. Complex information about treatments must be adequately conveyed to patients with different educational backgrounds and informational needs. Decisions about treatment options also require family input, as families often participate in patients' treatment and support patients' decisions. We describe the development, design, and preliminary evaluation of an informational, evidence-based, and patient-and family-centered decision aid for patients with ESRD and varying levels of health literacy, health numeracy, and cognitive function. METHODS: We designed a decision aid comprising a complementary video and informational handbook. We based our development process on data previously obtained from qualitative focus groups and systematic literature reviews. We simultaneously developed the video and handbook in "stages." For the video, stages included (1) directed interviews with culturally appropriate patients and families and preliminary script development, (2) video production, and (3) screening the video with patients and their families. For the handbook, stages comprised (1) preliminary content design, (2) a mixed-methods pilot study among diverse patients to assess comprehension of handbook material, and (3) screening the handbook with patients and their families. RESULTS: The video and handbook both addressed potential benefits and trade-offs of treatment selections. The 50-minute video consisted of demographically diverse patients and their families describing their positive and negative experiences with selecting a treatment option. The video also incorporated health professionals' testimonials regarding various considerations that might influence patients' and families' treatment selections. The handbook was comprised of written words, pictures of patients and health care providers, and diagrams describing the findings and quality of scientific studies comparing treatments. The handbook text was written at a 4th to 6th grade reading level. Pilot study results demonstrated that a majority of patients could understand information presented in the handbook. Patient and families screening the nearly completed video and handbook reviewed the materials favorably. CONCLUSIONS: This rigorously designed decision aid may help patients and families make informed decisions about their treatment options for RRT that are well aligned with their values.

Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?

Prediction of tandem mass spectrometric (MS/MS) fragmentation for non-peptidic molecules based on structure is of immense interest to the mass spectrometrist. If a reliable approach to MS/MS prediction could be achieved its impact within the pharmaceutical industry could be immense. Many publications have stressed that the fragmentation of a molecular ion or protonated molecule is a complex process that depends on many parameters, making prediction difficult. Commercial prediction software relies on a collection of general heuristic rules of fragmentation, which involve cleaving every bond in the structure to produce a list of 'expected' masses which can be compared with the experimental data. These approaches do not take into account the thermodynamic or molecular orbital effects that impact on the molecule at the point of protonation which could influence the potential sites of bond cleavage based on the structural motif. A series of compounds have been studied by examining the experimentally derived high-resolution MS/MS data and comparing it with the in silico modelling of the neutral and protonated structures. The effect that protonation at specific sites can have on the bond lengths has also been determined. We have calculated the thermodynamically most stable protonated species and have observed how that information can help predict the cleavage site for that ion. The data have shown that this use of in silico techniques could be a possible way to predict MS/MS spectra. Copyright (C) 2009 John Wiley & Sons, Ltd.