Perceived cannabis use norms and cannabis use among adolescents in the United States.

Due to changes in cannabis policies, concerns about cannabis use (CU) in adolescents have increased. The population of nonwhite groups is growing quickly in the United States. We examined perceived CU norms and their association with CU and CU disorder (CUD) for White, Black, Hispanic, Native-American, Asian-American, Native Hawaiian/Pacific Islander (NH/PI), and mixed-race adolescents. Data were from adolescents (12-17 years) in the 2004-2012 National Surveys on Drug Use and Health (N = 163,837). Substance use and CUD were assessed by computer-assisted, self-interviewing methods. Blacks, Hispanics, Native-Americans, and mixed-race adolescents had greater odds of past-year CU and CUD than Whites. Among past-year cannabis users (CUs), Hispanics and Native-Americans had greater odds of having a CUD than Whites. Asian-Americans had the highest prevalence of perceived parental or close friends' CU disapproval. Native-Americans and mixed-race adolescents had lower odds than Whites of perceiving CU disapproval from parents or close friends. In adjusted analyses, adolescent's disapproval of CU, as well as perceived disapproval by parents or close friends, were associated with a decreased odds of CU in each racial/ethnic group, except for NHs/PIs. Adolescent's disapproval of CU was associated with a decreased odds of CUD among CUs for Whites (personal, parental, and close friends' disapproval), Hispanics (personal, parental, and close friends' disapproval), and mixed-race adolescents (personal, close friends' disapproval). Racial/ethnic differences in adolescent CU prevalence were somewhat consistent with adolescents' reports of CU norm patterns. Longitudinal research on CU health effects should oversample nonwhite adolescents to assure an adequate sample for analysis and reporting.

Conformational kinetics reveals affinities of protein conformational states.

Most biological reactions rely on interplay between binding and changes in both macromolecular structure and dynamics. Practical understanding of this interplay requires detection of critical intermediates and determination of their binding and conformational characteristics. However, many of these species are only transiently present and they have often been overlooked in mechanistic studies of reactions that couple binding to conformational change. We monitored the kinetics of ligand-induced conformational changes in a small protein using six different ligands. We analyzed the kinetic data to simultaneously determine both binding affinities for the conformational states and the rate constants of conformational change. The approach we used is sufficiently robust to determine the affinities of three conformational states and detect even modest differences in the protein's affinities for relatively similar ligands. Ligand binding favors higher-affinity conformational states by increasing forward conformational rate constants and/or decreasing reverse conformational rate constants. The amounts by which forward rate constants increase and reverse rate constants decrease are proportional to the ratio of affinities of the conformational states. We also show that both the affinity ratio and another parameter, which quantifies the changes in conformational rate constants upon ligand binding, are strong determinants of the mechanism (conformational selection and/or induced fit) of molecular recognition. Our results highlight the utility of analyzing the kinetics of conformational changes to determine affinities that cannot be determined from equilibrium experiments. Most importantly, they demonstrate an inextricable link between conformational dynamics and the binding affinities of conformational states.

Suppression of conformational heterogeneity at a protein-protein interface.

Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein-protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.

Electrostatic Energetics of Bacillus subtilis Ribonuclease P Protein Determined by Nuclear Magnetic Resonance-Based Histidine pKa Measurements.

The pKa values of ionizable groups in proteins report the free energy of site-specific proton binding and provide a direct means of studying pH-dependent stability. We measured histidine pKa values (H3, H22, and H105) in the unfolded (U), intermediate (I), and sulfate-bound folded (F) states of RNase P protein, using an efficient and accurate nuclear magnetic resonance-monitored titration approach that utilizes internal reference compounds and a parametric fitting method. The three histidines in the sulfate-bound folded protein have pKa values depressed by 0.21 ± 0.01, 0.49 ± 0.01, and 1.00 ± 0.01 units, respectively, relative to that of the model compound N-acetyl-l-histidine methylamide. In the unliganded and unfolded protein, the pKa values are depressed relative to that of the model compound by 0.73 ± 0.02, 0.45 ± 0.02, and 0.68 ± 0.02 units, respectively. Above pH 5.5, H22 displays a separate resonance, which we have assigned to I, whose apparent pKa value is depressed by 1.03 ± 0.25 units, which is ∼0.5 units more than in either U or F. The depressed pKa values we observe are consistent with repulsive interactions between protonated histidine side chains and the net positive charge of the protein. However, the pKa differences between F and U are small for all three histidines, and they have little ionic strength dependence in F. Taken together, these observations suggest that unfavorable electrostatics alone do not account for the fact that RNase P protein is intrinsically unfolded in the absence of ligand. Multiple factors encoded in the P protein sequence account for its IUP property, which may play an important role in its function.

Interaction design for teaching visually impaired students

This paper reports on the findings for a study on improving interaction design for teaching visually impaired students. The crux of the problem is the ability to draw and understand diagrams. The cognitive issues are often underestimated with insufficient attention being given to the use of metaphors, etc. and "one size fits all solutions" are often the norm. The findings of the original seed funded project have led to design criteria and to an application for a large scale project, to produce generic tools and to enable multi-modal teaching and learning, with connotations for the mentally as well as physically impaired.

Legal myth-making: Medea and the legal representation of the feminine ‘other'

The Law operates by, and through, the creation of ideal benchmarks of conduct that are deemed to be representative of the behavioural norm. It is in this sense that it could be contended that the Law utilises, and relies on, myths in the same way as do other disciplines, notably psycho-analysis. It is possible to go even further and argue that the use of a created narrative mythology is essential to the establishment of a defined legal benchmark of behaviour by which the female defendant is assessed, judged and punished. While mythology expresses and symbolizes cultural and political behaviour, it is the Law that embodies and prescribes punitive sanctions. This element represents a powerful literary strand in classical mythology. This may be seen, for instance, in Antigone’s appeal to the Law as justification for her conduct, as much as in Medea’s challenge to the Law though her desire for vengeance. Despite its image of neutral, objective rationality, the Law, in creating and sustaining the ideals of legally-sanctioned conduct, engages in the same literary processes of imagination, reason and emotion that are central to the creation and re-creation of myth. The (re-)presentation of the Medea myth in literature (especially in theatre) and in art, finds its echo in the theatre of the courtroom where wronged women who have refused to passively accept their place, have instead responded with violence. Consequently, the Medea myth, in its depiction of the (un)feminine, serves as a template for the Law’s judgment of ‘conventional’ feminine conduct in the roles of wife and mother. Medea is an image of deviant femininity, as is Lady Macbeth and the countless other un-feminine literary and mythological women who challenge the power of the dominant culture and its ally, the Law. These women stand opposed to the other dominant theme of both literature and Law: the conformist woman, the passive dupe, who are victims of male oppression – women such as Ariadne of Naxos and Tess of the D’Ubervilles – and who are subsequently consumed by the Law, much as Semele is consumed by the fire of Jupiter’s gaze upon her. All of these women, the former as well as the latter, have their real-life counterparts in the pages of the Law Reports. As Fox puts it, “these women have come to bear the weight of the cultural stereotypes and preconceptions about women who kill.”

Contribution to the knowledge of the genus "Cladonia" in Macaronesia

Sixteen species of the genus Cladonia are reported from Macaronesia from the Canary Islands. Three species are new to canarian flora and, two of them new to Macaronesia. The chemical variation of the taxa is reported. A phytogeographic distribution of the taxa with data on their habitat and ecology are presented.

Questions of 'h' in Northern Ireland: Breathing New Life on the Aspiration Theory

This paper considers existing ideas concerning pronunciation of the letter name for (LNH) in Northern Irish English (NIE). Traditionally, the status of LNH realisation as an ethnic marker has gone unquestioned: Catholics are thought to say [het&Mac186;] while the Protestant norm is assumed to be [etS]. The phonetic difference between these realisations is consistently described as word-initial aspiration versus non-aspiration, with aspiration attributed exclusively to Irish language influence. Here, we show that an explanation based on aspiration alone is phonologically unsatisfying and question whether aspiration is, in fact, an Irish language or ethnically dictated phenomenon. It is further suggested here that the overwhelming stigmatisation of LNH realisation may be responsible for blocking a potential sound change in NIE. While this paper is not intended as a detailed account of ethnolinguistic differences in NI phonology, it engages critically with the over-simplistic and widespread notion that LNH realisation is a result of transfer from the Irish language to the English used by Catholics in Northern Ireland.

The Changing Significance of European Borders

It is necessary to understand how state borders in Europe are changing in order to fully assess the factors which facilitate and encourage cross-border cooperation. This article considers the enduring social significance of borders, the need for a historical understanding of the nature and extent of border change in Europe, and the impact of recent European integration. Change in the structure, functions and meanings of European state borders has been the norm rather than the exception. Although much of this change has been associated with war, violence and coercion, a key contemporary issue facing the architects of European integration is how the ambiguity and contradictory nature border change can be regulated democratically and managed cooperatively.

Desperately Seeking Finance? The Demand for Finance by Women Owned and Led Businesses

The study reported here addresses some issues on gender, entrepreneurship and finance that have been identified as problematic in the literature. For example, much of the research to date is based on the assumption of entrepreneurship as male entrepreneurship; few studies have controlled for structural characteristics that may impact on the relationship between owner gender and a venture's ability to raise finance; and women are less likely than men to seek growth and external financing. Through the conduct of in-depth semi-structured interviews, an attempt has been made to give `voice' to women's intrinsically interesting experiences as the enactment of a situated practice, and not just in comparison with the assumed norm of male entrepreneurial activity. The findings suggest that when variables such as individual and firm characteristics are controlled for, generalizations found in the literature may not be supported. Further, the paper highlights that neither women entrepreneurs nor their businesses are homogeneous in nature and that greater heterogeneity in the study of female entrepreneurship in general, and access to finance in particular, is required.

Time-dependent tight binding

Starting from a Lagrangian mean-field theory, a set of time-dependent tight-binding equations is derived to describe dynamically and self-consistently an interacting system of quantum electrons and classical nuclei. These equations conserve norm, total energy and total momentum. A comparison with other tight-binding models is made. A previous tight-binding result for forces on atoms in the presence of electrical current flow is generalized to the time-dependent domain and is taken beyond the limit of local charge neutrality.

Geometry in preduals of spaces of 2-homogeneous polynomials on Hilbert spaces

Let H be a (real or complex) Hilbert space. Using spectral theory and properties of the Schatten–Von Neumann operators, we prove that every symmetric tensor of unit norm in HoH is an infinite absolute convex combination of points of the form xox with x in the unit sphere of the Hilbert space. We use this to obtain explicit characterizations of the smooth points of the unit ball of HoH .

Decompositions of spaces of measures

Let M be the Banach space of sigma-additive complex-valued measures on an abstract measurable space. We prove that any closed, with respect to absolute continuity norm-closed, linear subspace L of M is complemented and describe the unique complement, projection onto L along which has norm 1. Using this fact we prove a decomposition theorem, which includes the Jordan decomposition theorem, the generalized Radon-Nikodym theorem and the decomposition of measures into decaying and non-decaying components as particular cases. We also prove an analog of the Jessen-Wintner purity theorem for our decompositions.

Disturbance attenuation in linear systems via dynamical compensators: A parametric eigenstructure assignment approach

A simple approach is proposed for disturbance attenuation in multivariable linear systems via dynamical output compensators based on complete parametric eigenstructure assignment. The basic idea is to minimise the H-2 norm of the disturbance-output transfer function using the design freedom provided by eigenstructure assignment. For robustness, the closed-loop system is restricted to be nondefective. Besides the design parameters, the closed-loop eigenvalues are also optimised within desired regions on the left-half complex plane to ensure both closed-loop stability and dynamical performance. With the proposed approach, additional closed-loop specifications can be easily achieved. As a demonstration, robust pole assignment, in the sense that the closed-loop eigenvalues are as insensitive as possible to open-loop system parameter perturbations, is treated. Application of the proposed approach to robust control of a magnetic bearing with a pair of opposing electromagnets and a rigid rotor is discussed.