Support for Same-Sex Marriage at Record High, but Key Segments Remain Opposed

As the Supreme Court prepares to decide a key case involving states' requirements to recognize same-sex marriage, public support for allowing gays and lesbians to marry legally continues its rapid rise: A 57%-majority of Americans now favor allowing same-sex marriage and 39% oppose. As recently as five years ago, more opposed (48%) same-sex marriage than supported it (42%).This is the highest level of support measured for same-sex marriage in nearly 20 years of Pew Research Center polling of the issue. Yet even as support for same-sex marriage has increased among nearly all segments in the public, some groups remain broadly opposed to gay marriage.The Pew Research Center survey, conducted May 12-18 among 2,002 adults, finds that partisans are as divided on this issue as ever: Today, 65% of Democrats and an identical percentage of independents favor gay marriage; only about one third (34%) of Republicans do so. Growing shares of all three groups support same-sex-marriage, yet the differences between Democrats and Republicans are as wide today as they were a decade ago

PocketPicker: analysis of ligand binding-sites with shape descriptors

Background Identification and evaluation of surface binding-pockets and occluded cavities are initial steps in protein structure-based drug design. Characterizing the active site's shape as well as the distribution of surrounding residues plays an important role for a variety of applications such as automated ligand docking or in situ modeling. Comparing the shape similarity of binding site geometries of related proteins provides further insights into the mechanisms of ligand binding. Results We present PocketPicker, an automated grid-based technique for the prediction of protein binding pockets that specifies the shape of a potential binding-site with regard to its buriedness. The method was applied to a representative set of protein-ligand complexes and their corresponding apo-protein structures to evaluate the quality of binding-site predictions. The performance of the pocket detection routine was compared to results achieved with the existing methods CAST, LIGSITE, LIGSITEcs, PASS and SURFNET. Success rates PocketPicker were comparable to those of LIGSITEcs and outperformed the other tools. We introduce a descriptor that translates the arrangement of grid points delineating a detected binding-site into a correlation vector. We show that this shape descriptor is suited for comparative analyses of similar binding-site geometry by examining induced-fit phenomena in aldose reductase. This new method uses information derived from calculations of the buriedness of potential binding-sites. Conclusions The pocket prediction routine of PocketPicker is a useful tool for identification of potential protein binding-pockets. It produces a convenient representation of binding-site shapes including an intuitive description of their accessibility. The shape-descriptor for automated classification of binding-site geometries can be used as an additional tool complementing elaborate manual inspections

PocketGraph : graph representation of binding site volumes

The representation of small molecules as molecular graphs is a common technique in various fields of cheminformatics. This approach employs abstract descriptions of topology and properties for rapid analyses and comparison. Receptor-based methods in contrast mostly depend on more complex representations impeding simplified analysis and limiting the possibilities of property assignment. In this study we demonstrate that ligand-based methods can be applied to receptor-derived binding site analysis. We introduce the new method PocketGraph that translates representations of binding site volumes into linear graphs and enables the application of graph-based methods to the world of protein pockets. The method uses the PocketPicker algorithm for characterization of binding site volumes and employs a Growing Neural Gas procedure to derive graph representations of pocket topologies. Self-organizing map (SOM) projections revealed a limited number of pocket topologies. We argue that there is only a small set of pocket shapes realized in the known ligand-receptor complexes

Negative and positive externalities in intergroup conflict: exposure to the opportunity to help the outgroup reduces the inclination to harm it

Outgroup hate, in the context of intergroup conflict, can be expressed by harming the outgroup, but also by denying it help. Previous work established that this distinction—whether the externality on the outgroup is negative or positive—has an important effect on the likelihood of outgroup hate emerging as a motivation for individual participation in intergroup conflict. The current work uses a within-subject design to examine the behavior of the same individuals in intergroup conflict with negative and positive externalities on the outgroup. Each participant made two choices, one for each type of externality, and the order was counter balanced. The main results are that (1) behavior is fairly consistent across negative and positive externalities, i.e., the tendency to display outgroup hate by harming the outgroup is correlated with the tendency to display outgroup hate by avoiding to help the outgroup; (2) People are reluctant to harm the outgroup after being exposed to the opportunity to help it; (3) Groupness—the degree to which people care about their group and its well-being—is related to outgroup hate only when participants encounter the opportunity to harm the outgroup first (before they encounter the opportunity to help it). In this setting the relationship between groupness and outgroup hate spilled over to the subsequent interaction, where it was possible to help the outgroup. When the opportunity to help the outgroup was encountered first, groupness was not related to outgroup hate

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

Title VII: Legal Protection Against Sexual Harassment

This comment will focus on the three major themes raised by these decisions: (1) whether sexual harassment is or can be gender-based; (2) whether or not the supervisor must be treated as the representative of the employer; and (3) whether recognition of a Title VII cause of action will inundate the courts with unfounded claims of harassment. After exploring the approaches and analyses of the various courts, the comment concludes that sexual harassment can constitute a violation of Title VII\u27s prohibition against sex discrimination; and that whether it does or not is basically a question of fact