Angular dependence of core hole screening in LiCoO2: A DFT+U calculation of the oxygen and cobalt K-edge x-ray absorption spectra

Angular dependent core-hole screening effects have been found in the cobalt K-edge x-ray absorption spectrum of LiCoO2, using high-resolution data and parameter-free GGA+U calculations. The Co 1s core-hole on the absorber causes strong local attraction. The core-hole screening on the nearest neighbours cobalt induces a 2 eV shift in the density of states with respect to the on-site 1s-3d transitions, as detected in the Co K pre-edge spectrum. Our DFT+U calculations reveal that the off-site screening is different in the out-of-plane direction, where a 3 eV shift is visible in both calculations and experiment. The detailed analysis of the inclusion of the core-hole potential and the Hubbard parameter U shows that the core-hole is essential for the off-site screening, while U improves the description of the angular dependent screening effects. In the case of oxygen K-edge, both the core-hole potential and the Hubbard parameter improve the relative positions of the spectral features

Computer Aided Detection of Anemia-like Pallor

Paleness or pallor is a manifestation of blood loss or low hemoglobin concentrations in the human blood that can be caused by pathologies such as anemia. This work presents the first automated screening system that utilizes pallor site images, segments, and extracts color and intensity-based features for multi-class classification of patients with high pallor due to anemia-like pathologies, normal patients and patients with other abnormalities. This work analyzes the pallor sites of conjunctiva and tongue for anemia screening purposes. First, for the eye pallor site images, the sclera and conjunctiva regions are automatically segmented for regions of interest. Similarly, for the tongue pallor site images, the inner and outer tongue regions are segmented. Then, color-plane based feature extraction is performed followed by machine learning algorithms for feature reduction and image level classification for anemia. In this work, a suite of classification algorithms image-level classifications for normal (class 0), pallor (class 1) and other abnormalities (class 2). The proposed method achieves 86% accuracy, 85% precision and 67% recall in eye pallor site images and 98.2% accuracy and precision with 100% recall in tongue pallor site images for classification of images with pallor. The proposed pallor screening system can be further fine-tuned to detect the severity of anemia-like pathologies using controlled set of local images that can then be used for future benchmarking purposes.Comment: 4 pages,2 figures, 2 table

Fuzzy virtual ligands for virtual screening

A new method to bridge the gap between ligand and receptor-based methods in virtual screening (VS) is presented. We introduce a structure-derived virtual ligand (VL) model as an extension to a previously published pseudo-ligand technique [1]: LIQUID [2] fuzzy pharmacophore virtual screening is combined with grid-based protein binding site predictions of PocketPicker [3]. This approach might help reduce bias introduced by manual selection of binding site residues and introduces pocket shape information to the VL. It allows for a combination of several protein structure models into a single "fuzzy" VL representation, which can be used to scan screening compound collections for ligand structures with a similar potential pharmacophore. PocketPicker employs an elaborate grid-based scanning procedure to determine buried cavities and depressions on the protein's surface. Potential binding sites are represented by clusters of grid probes characterizing the shape and accessibility of a cavity. A rule-based system is then applied to project reverse pharmacophore types onto the grid probes of a selected pocket. The pocket pharmacophore types are assigned depending on the properties and geometry of the protein residues surrounding the pocket with regard to their relative position towards the grid probes. LIQUID is used to cluster representative pocket probes by their pharmacophore types describing a fuzzy VL model. The VL is encoded in a correlation vector, which can then be compared to a database of pre-calculated ligand models. A retrospective screening using the fuzzy VL and several protein structures was evaluated by ten fold cross-validation with ROC-AUC and BEDROC metrics, obtaining a significant enrichment of actives. Future work will be devoted to prospective screening using a novel protein target of Helicobacter pylori and compounds from commercial providers

Computational screening of magnetocaloric alloys

An exciting development over the past few decades has been the use of high-throughput computational screening as a means of identifying promising candidate materials for a variety of structural or functional properties. Experimentally, it is often found that the highest-performing materials contain substantial atomic site disorder. These are frequently overlooked in high-throughput computational searches however, due to difficulties in dealing with materials that do not possess simple, well-defined crystallographic unit cells. Here we demonstrate that the screening of magnetocaloric materials with the help of the density functional theory-based magnetic deformation proxy can be extended to systems with atomic site disorder. This is accomplished by thermodynamic averaging of the magnetic deformation for ordered supercells across a solid solution. We show that the highly non-monotonic magnetocaloric properties of the disordered solid solutions Mn(Co$_{1-x}$Fe$_x$)Ge and (Mn$_{1-x}$Ni$_x$)CoGe are successfully captured using this method.Comment: Main text: 8 pages, 6 figures. Supplemental Material: 2 pages, 2 figure

A combined computational-experimental approach to define the structural origin of antibody recognition of sialyl-Tn, a tumor-associated carbohydrate antigen.

Anti-carbohydrate monoclonal antibodies (mAbs) hold great promise as cancer therapeutics and diagnostics. However, their specificity can be mixed, and detailed characterization is problematic, because antibody-glycan complexes are challenging to crystallize. Here, we developed a generalizable approach employing high-throughput techniques for characterizing the structure and specificity of such mAbs, and applied it to the mAb TKH2 developed against the tumor-associated carbohydrate antigen sialyl-Tn (STn). The mAb specificity was defined by apparent KD values determined by quantitative glycan microarray screening. Key residues in the antibody combining site were identified by site-directed mutagenesis, and the glycan-antigen contact surface was defined using saturation transfer difference NMR (STD-NMR). These features were then employed as metrics for selecting the optimal 3D-model of the antibody-glycan complex, out of thousands plausible options generated by automated docking and molecular dynamics simulation. STn-specificity was further validated by computationally screening of the selected antibody 3D-model against the human sialyl-Tn-glycome. This computational-experimental approach would allow rational design of potent antibodies targeting carbohydrates

Choice, morality and vulnerability : young women's discourses of cervical screening : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Psychology (endorsement in Health Psychology) at Massey University, Albany, New Zealand

Cervical screening is a health surveillance tool used to prevent cervical cancer. In New Zealand, research into cervical screening has largely focused on barriers to participation. This type of research implicitly assumes that cervical screening is a desirable health behaviour for women to engage in, and does not explore how social and political factors are implicated in cervical screening behaviour. This research sought to explore women’s understandings and experiences of cervical screening. Ten women aged 20 to 30 were interviewed, their responses recorded and transcribed, and an interpretive analysis conducted. From the analysis, three broad webs of discourse surrounding cervical screening – choice, morality and vulnerability – were identified and discussed. Each web of discourse was used to construct cervical screening in different ways. For choice, participants constructed cervical screening as an autonomous choice, routine, or an obligation. Morality was drawn upon for its role in cervical screening around ideas of individual and social responsibility, and sexual activity. Finally, vulnerability was explored through the fear of getting cervical cancer, the vulnerability experienced as part of screening, and the protection it was seen to offer. Choice, morality and vulnerability worked together to limit the available ways of experiencing and acting in relation to cervical screening, constructing compliance as the only option for women. Those who do not comply are positioned as problematic, irresponsible and immoral by women, their friends and families, and health professionals. This research highlighted the ways in which discourses produce realities which create and maintain power imbalances which govern and control women’s bodies. Rather than viewing cervical screening as a desirable yet morally neutral act which all women ought to participate in, it is a site where women may choose to comply or resist dominant discourses which exert power over women’s bodies

Electronic structure of the MO oxides (M=Mg, Ca, Ti, V) in the GW approximation

The quasiparticle band structures of nonmagnetic monoxides, MO (M=Mg, Ca, Ti, and V), are calculated by the GW approximation. The band gap and the width of occupied oxygen 2p states in insulating MgO and CaO agree with experimental observation. In metallic TiO and VO, conduction bands originated from metal 3d states become narrower. Then the partial densities of transition metal e_g and t_2g states show an enhanced dip between the two. The effects of static screening and dynamical correlation are discussed in detail in comparison with the results of the Hartree-Fock approximation and the static Coulomb hole plus screened exchange approximation. The d-d Coulomb interaction is shown to be very much reduced by on-site and off-site d-electron screening in TiO and VO. The dielectric function and the energy loss spectrum are also presented and discussed in detail.Comment: 10 pages, 5 figure

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Evaluation of a novel virtual screening strategy using receptor decoy binding sites

Virtual screening is used in biomedical research to predict the binding affinity of a large set of small organic molecules to protein receptor targets. This report shows the development and evaluation of a novel yet straightforward attempt to improve this ranking in receptor-based molecular docking using a receptor-decoy strategy. This strategy includes defining a decoy binding site on the receptor and adjusting the ranking of the true binding-site virtual screen based on the decoy-site screen. The results show that by docking against a receptor-decoy site with Autodock Vina, improved Receiver Operator Characteristic Enrichment (ROCE) was achieved for 5 out of fifteen receptor targets investigated, when up to 15 % of a decoy site rank list was considered. No improved enrichment was seen for 7 targets, while for 3 targets the ROCE was reduced. The extent to which this strategy can effectively improve ligand prediction is dependent on the target receptor investigated