Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory

Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessible volume, but average water thermodynamic properties were not distinctive from other interfacial regions. Interfacial water molecules are frequently stabilized by enthalpy and destabilized entropy with respect to bulk, but counter-examples occasionally occur. Overall detailed inspection of the local coordinating environment appears necessary to gauge the thermodynamic stability of water in protein structures

Assessing the authority of political office-holders: the leadership capital index

This article argues that the extent to which political office-holders can effectively attain and wield authority is a function of the stock of ‘leadership capital.’ Drawing on the concept of political capital, we define leadership capital as aggregate authority composed of three dimensions: skills; relations; and reputation of a leader. Leadership capital ebbs and flows over time within a trajectory of acquisition, expenditure and inevitable depreciation. We present a Leadership Capital Index (LCI) that systematically maps out the three broad areas combining concrete measures with interpretive aspects. This can be used as a tool for systematically tracking and comparing the political fortunes of leaders in a way that is both more nuanced and robust than exclusive reliance on the latest approval ratings. We offer an illustrative case study of Tony Blair demonstrating the LCI. We conclude by discerning several promising paths for future development of the LCI

Let\u27s Talk About How We Talk: Communication Agreements in the Library Workplace

Purpose: This chapter introduces a new tool, termed the Communication Agreement, for enhancing communication in the library workplace. The chapter defines the communication agreement, provides discussion questions for forming a communication agreement, provides examples of how communication agreements are beneficial to a diverse library workforce, and provides strategies to informally assess communication agreements’ effectiveness. Practical implications: Communication problems in diverse library workplaces can lead to, or exacerbate, conflict between employees. Generational, cross-cultural, gender, and other differences can lead to misunderstandings and conflict between employees. The communication agreement provides library managers with a tool to bridge differences in communication styles between employees, enable employees to engage in more effective communication, assist employees in developing better understandings and respect for colleagues of different backgrounds, and raise employees’ emotional intelligences. Originality/Value: Numerous resources and publications provide generalized approaches to communicating with others in a heterogeneous workplace or team, but the communication agreement provides a new approach for developing effective communication between people in a diverse library workplace. Limitations: The chapter lays out informal assessment strategies for the communication agreement, but formal assessment methods and metrics still need to be developed

DIAGNOSTIC AND PREVENTIVE SERVICES IN A NATIONAL INCREMENTAL DENTAL PLAN FOR CHILDREN

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65579/1/j.1752-7325.1977.tb02874.x.pd

The Rise of the Resilient Local Authority?

The term resilience is increasingly being utilised within the study of public policy to depict how individuals, communities and organisations can adapt, cope, and ‘bounce back’ when faced with external shocks such as climate change, economic recession and cuts in public expenditure. In focussing on the local dimensions of the resilience debate, this article argues that the term can provide useful insights into how the challenges facing local authorities in the UK can be reformulated and reinterpreted. The article also distinguishes between resilience as ‘recovery’ and resilience as ‘transformation’, with the latter's focus on ‘bouncing forward’ from external shocks seen as offering a more radical framework within which the opportunities for local innovation and creativity can be assessed and explained. While also acknowledging some of the weaknesses of the resilience debate, the dangers of conceptual ‘stretching’, and the extent of local vulnerabilities, the article highlights a range of examples where local authorities – and crucially, local communities – have enhanced their adaptive capacity, within existing powers and responsibilities. From this viewpoint, some of the barriers to the development of resilient local government are not insurmountable, and can be overcome by ‘digging deep’ to draw upon existing resources and capabilities, promoting a strategic approach to risk, exhibiting greater ambition and imagination, and creating space for local communities to develop their own resilience

Caring Leadership: A Heideggerian Perspective

This paper develops the idea of caring leadership based on Heidegger’s philosophy of care. From this perspective, caring leadership is grounded in the practices of ‘leaping-in’ and ‘leaping-ahead’ as modes of intervention in the affairs of the world and the efforts of others. This involves gauging and taking responsibility for the ramifications of intervention, balancing the urge for certainty of outcome and visibility of contribution with the desire to encourage and enable others. Our analysis suggests several twists to contemporary leadership debates. We argue that the popular models of transactional and transformational leadership are to be critiqued not for their over-reliance, but rather, their under-reliance on agency. This is a different kind of agency to that of heroic or charismatic models. It involves tolerance of complexity and ambivalence; a rich sense of temporal trajectory; concern for one’s presence in the world; and crucially, the ability to resist the soothing normativity of ‘best practice’. From this position, we argue that the problem with the growing scholarly interest in an ethic of care is that it provides too tempting a recipe to follow. In a Heideggerian view, caring leadership has little to do with compassion, kindness or niceness; it involves and requires a fundamental organization and leadership of self

Gravity Probe B: Final Results of a Space Experiment to Test General Relativity

Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of General Relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6,601.8+/- 18.3 mas/yr and a frame-dragging drift rate of -37.2 +/- 7.2 mas/yr, to be compared with the GR predictions of -6,606.1 mas/yr and -39.2 mas/yr, respectively (`mas' is milliarc-second; 1mas = 4.848 x 10-9 rad)

Studying strategies and types of players:Experiments, logics and cognitive models

How do people reason about their opponent in turn-taking games? Often, people do not make the decisions that game theory would prescribe. We present a logic that can play a key role in understanding how people make their decisions, by delineating all plausible reasoning strategies in a systematic manner. This in turn makes it possible to construct a corresponding set of computational models in a cognitive architecture. These models can be run and fitted to the participants’ data in terms of decisions, response times, and answers to questions. We validate these claims on the basis of an earlier game-theoretic experiment about the turn-taking game “Marble Drop with Surprising Opponent”, in which the opponent often starts with a seemingly irrational move. We explore two ways of segregating the participants into reasonable “player types”. The first way is based on latent class analysis, which divides the players into three classes according to their first decisions in the game: Random players, Learners, and Expected players, who make decisions consistent with forward induction. The second way is based on participants’ answers to a question about their opponent, classified according to levels of theory of mind: zero-order, first-order and second-order. It turns out that increasing levels of decisions and theory of mind both correspond to increasing success as measured by monetary awards and increasing decision times. Next, we use the logical language to express different kinds of strategies that people apply when reasoning about their opponent and making decisions in turn-taking games, as well as the ‘reasoning types’ reflected in their behavior. Then, we translate the logical formulas into computational cognitive models in the PRIMs architecture. Finally, we run two of the resulting models, corresponding to the strategy of only being interested in one’s own payoff and to the myopic strategy, in which one can only look ahead to a limited number of nodes. It turns out that the participant data fit to the own-payoff strategy, not the myopic one. The article closes the circle from experiments via logic and cognitive modelling back to predictions about new experiments

Drosophila Sperm Swim Backwards in the Female Reproductive Tract and Are Activated via TRPP2 Ion Channels

Sperm have but one purpose, to fertilize an egg. In various species including Drosophila melanogaster female sperm storage is a necessary step in the reproductive process. Amo is a homolog of the human transient receptor potential channel TRPP2 (also known as PKD2), which is mutated in autosomal dominant polycystic kidney disease. In flies Amo is required for sperm storage. Drosophila males with Amo mutations produce motile sperm that are transferred to the uterus but they do not reach the female storage organs. Therefore Amo appears to be a mediator of directed sperm motility in the female reproductive tract but the underlying mechanism is unknown.Amo exhibits a unique expression pattern during spermatogenesis. In spermatocytes, Amo is restricted to the endoplasmic reticulum (ER) whereas in mature sperm, Amo clusters at the distal tip of the sperm tail. Here we show that flagellar localization of Amo is required for sperm storage. This raised the question of how Amo at the rear end of sperm regulates forward movement into the storage organs. In order to address this question, we used in vivo imaging of dual labelled sperm to demonstrate that Drosophila sperm navigate backwards in the female reproductive tract. In addition, we show that sperm exhibit hyperactivation upon transfer to the uterus. Amo mutant sperm remain capable of reverse motility but fail to display hyperactivation and directed movement, suggesting that these functions are required for sperm storage in flies.Amo is part of a signalling complex at the leading edge of the sperm tail that modulates flagellar beating and that guides a backwards path into the storage organs. Our data support an evolutionarily conserved role for TRPP2 channels in cilia

FitEM2EM—Tools for Low Resolution Study of Macromolecular Assembly and Dynamics

Studies of the structure and dynamics of macromolecular assemblies often involve comparison of low resolution models obtained using different techniques such as electron microscopy or atomic force microscopy. We present new computational tools for comparing (matching) and docking of low resolution structures, based on shape complementarity. The matched or docked objects are represented by three dimensional grids where the value of each grid point depends on its position with regard to the interior, surface or exterior of the object. The grids are correlated using fast Fourier transformations producing either matches of related objects or docking models depending on the details of the grid representations. The procedures incorporate thickening and smoothing of the surfaces of the objects which effectively compensates for differences in the resolution of the matched/docked objects, circumventing the need for resolution modification. The presented matching tool FitEM2EMin successfully fitted electron microscopy structures obtained at different resolutions, different conformers of the same structure and partial structures, ranking correct matches at the top in every case. The differences between the grid representations of the matched objects can be used to study conformation differences or to characterize the size and shape of substructures. The presented low-to-low docking tool FitEM2EMout ranked the expected models at the top