Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.

Dangerous Exits: The Abuse of Women in Rural America

Decade after decade, violence against women has gained more attention from scholars, policy makers, and the general public. Social scientists in particular have contributed significant empirical and theoretical understandings to this issue. Strikingly, scant attention has focused on the victimization of women who want to leave their hostile partners. This groundbreaking work challenges the perception that rural communities are safe havens from the brutality of urban living. Identifying hidden crimes of economic blackmail and psychological mistreatment, and the complex relationship between patriarchy and abuse, Walter S. DeKeseredy and Martin D. Schwartz propose concrete and effective solutions, giving voice to women who have often suffered in silence.

Violence Against Women: Myths, Facts, Controversies

In Violence Against Women, award-winning author Walter S. DeKeseredy offers a passionate but well-documented sociological overview of a sobering problem. He starts by outlining the scope of the challenge and debunks current attempts to label intimate violence as gender neutral. He then lays bare the structural practices that sustain this violence, leading to a discussion of long- and short-term policies to address the issue. DeKeseredy includes an examination of male complicity and demonstrates how boys and men can change their roles. Throughout, he responds to myths that dismiss threats to women's health and safety and provides an impassioned call to action for women, men, and policymakers.

Detecting common dynamics in transitory components

This paper considers VECMs for variables exhibiting cointegration and common features in the transitory components. While the presence of cointegration between the permanent components of series reduces the rank of the long-run multiplier matrix, a common feature among the transitory components leads to a rank reduction in the matrix summarizing short-run dynamics. The common feature also implies that there exists linear combinations of the first-differenced variables in a cointegrated VAR that are white noise and traditional tests focus on testing for this characteristic. An alternative, however, is to test the rank of the short-run dynamics matrix directly. Consequently, we use the literature on testing the rank of a matrix to produce some alternative test statistics. We also show that these are identical to one of the traditional tests. The performance of the different methods is illustrated in a Monte Carlo analysis which is then used to re-examine an existing empirical study. Finally, this approach is applied to provide a check for the presence of common dynamics in DSGE models.

Semi-parametric forecasting of realized volatility

Forecasts generated by time series models traditionally place greater weight on more recent observations. This paper develops an alternative semi-parametric method for forecasting that does not rely on this convention and applies it to the problem of forecasting asset return volatility. In this approach, a forecast is a weighted average of historical volatility, with the greatest weight given to periods that exhibit similar market conditions to the time at which the forecast is being formed. Weighting is determined by comparing short-term trends in volatility across time (as a measure of market conditions) by means of a multivariate kernel scheme. It is found that the semi-parametric method produces forecasts that are significantly more accurate than a number of competing approaches at both short and long forecast horizons.

An exploration of affine group laws for elliptic curves

Several forms of elliptic curves are suggested for an efficient implementation of Elliptic Curve Cryptography. However, a complete description of the group law has not appeared in the literature for most popular forms. This paper presents group law in affine coordinates for three forms of elliptic curves. With the existence of the proposed affine group laws, stating the projective group law for each form becomes trivial. This work also describes an automated framework for studying elliptic curve group law, which is applied internally when preparing this work.

Kaleidoscopes and contradictions : the legitimacy of social media for public relations

If the current discourses of progress are to be believed, the new or social media promise a kaleidoscope of opportunity for connecting and informing citizens. This is by allegedly revitalizing the fading legitimacy and practice of institutions and providing an agent for social interaction. However, as social media adoption has increased, it has revealed a wealth of contradictions both of its own making and reproduction of past action. This has created a crisis for traditional media as well as for public relations. For example, social media such as WikiLeaks have bypassed official channels about government information. In other cases, social media such as Facebook and Twitter informed BBC coverage of the Rio Olympics. Although old media are unlikely to go away, social media have had an impact with several large familybased media companies collapsing or being reintegrated into the new paradigm. To use Walter Lippman’s analogy of the phantom public, the social media contradictorily serve to both disparate the phantom in part and reinforce it...

Queen's Parks in Queensland

Queen's Park in Maryborough is one of many public gardens established in the nineteenth century in Queensland: in Brisbane, Ipswich, Toowoomba, Warwick, Rockhampton, Mackay, Townsville, Cairns and Cooktown. They were created primarily as places of horticultural experimentation, as well as for recreational purposes. They formed a local area network, with the Brisbane Botanic Garden and the Government Botanist, Walter Hill, at the centre – at least in the 1870s. From here, the links extended to other botanic gardens in Australia, and beyond Australia to the British colonial network managed through the Royal Botanic Gardens (RBG), Kew. It was an informal network, supplying a knowledge of basic economic botany that founded many tropical agricultural industries and also provided much-needed recreational, educational and inspirational opportunities for colonial newcomers and residents. The story of these parks, from the time when they were first set aside as public reserves by the government surveyors to the present day, is central to the history of urban planning in regional centres. This article provides a statewide overview together with a more in-depth examination of Maryborough's own historic Queen's Park.

Nangkha Nangdrik in the land of the Thunder Dragon : psychology, religion and the potential of mediation in the Kingdom of Bhutan

This article will consider the role that Alternative Dispute Resolution (‘Dham Kha Chen Ki Khendum’ or ‘Nangkha Nangdrik’) currently plays in resolving legal conflict in Bhutan. With a Constitution that has committed to the pursuit of Gross National Happiness, non-adversarial dispute resolution processes that promote continuing relationships and goodwill assume greater importance. One difficulty for Bhutan is that alternative dispute resolution procedures such as mediation (Dhum Drik) are being referred to in enactments of the Bhutanese National Council and National Assembly (bicameral parliament), without a shared understanding as to the characteristics and functionality of these procedures. This article will focus particularly on the current practice of mediation in Bhutan and investigate whether particular models of mediation are more suited to the Bhutanese context, given the particularities of Bhutanese culture, the search for gross national happiness, psychological understandings of happiness and the omnipresent influence of Mahayana Buddhism.

Routledge handbook of critical criminology

The Routledge Handbook of Critical Criminology is a collection of original essays specifically designed to offer students, faculty, policy makers, and others an in-depth overview of the most up-to-date empirical, theoretical, and political contributions made by critical criminologists around the world. Special attention is devoted to new theoretical directions in the field, such as cultural criminology, masculinities studies, and feminist criminologies. Its diverse essays not only cover the history of critical criminology and cutting edge theories, but also the variety of research methods used by leading scholars in the field and the rich data generated by their rigorous empirical work. In addition, some of the chapters suggest innovative and realistic short- and long-term policy proposals that are typically ignored by mainstream criminology. These progressive strategies address some of the most pressing social problems facing contemporary society today, and that generate much pain and suffering for socially and economically disenfranchised people. The Handbook explores up-to-date empirical, theoretical, and political contributions, and is specifically designed to be a comprehensive resource for undergraduate and post-graduate students, researchers, and policy makers.