Toward a quantum-mechanical description of metal-assisted phosphoryl transfer in pyrophosphatase

The wealth of kinetic and structural information makes inorganic pyrophosphatases (PPases) a good model system to study the details of enzymatic phosphoryl transfer. The enzyme accelerates metal-complexed phosphoryl transfer 1010-fold: but how? Our structures of the yeast PPase product complex at 1.15 Å and fluoride-inhibited complex at 1.9 Å visualize the active site in three different states: substrate-bound, immediate product bound, and relaxed product bound. These span the steps around chemical catalysis and provide strong evidence that a water molecule (Onu) directly attacks PPi with a pKa vastly lowered by coordination to two metal ions and D117. They also suggest that a low-barrier hydrogen bond (LBHB) forms between D117 and Onu, in part because of steric crowding by W100 and N116. Direct visualization of the double bonds on the phosphates appears possible. The flexible side chains at the top of the active site absorb the motion involved in the reaction, which may help accelerate catalysis. Relaxation of the product allows a new nucleophile to be generated and creates symmetry in the elementary catalytic steps on the enzyme. We are thus moving closer to understanding phosphoryl transfer in PPases at the quantum mechanical level. Ultra-high resolution structures can thus tease out overlapping complexes and so are as relevant to discussion of enzyme mechanism as structures produced by time-resolved crystallography.

On cortical coding of vocal communication sounds in primates

Understanding how the brain processes vocal communication sounds is one of the most challenging problems in neuroscience. Our understanding of how the cortex accomplishes this unique task should greatly facilitate our understanding of cortical mechanisms in general. Perception of species-specific communication sounds is an important aspect of the auditory behavior of many animal species and is crucial for their social interactions, reproductive success, and survival. The principles of neural representations of these behaviorally important sounds in the cerebral cortex have direct implications for the neural mechanisms underlying human speech perception. Our progress in this area has been relatively slow, compared with our understanding of other auditory functions such as echolocation and sound localization. This article discusses previous and current studies in this field, with emphasis on nonhuman primates, and proposes a conceptual platform to further our exploration of this frontier. It is argued that the prerequisite condition for understanding cortical mechanisms underlying communication sound perception and production is an appropriate animal model. Three issues are central to this work: (i) neural encoding of statistical structure of communication sounds, (ii) the role of behavioral relevance in shaping cortical representations, and (iii) sensory–motor interactions between vocal production and perception systems.

Sights for Sounds: The Roles of Illuminated Initials in Italian Music Manuscripts

The scholarship on illuminated initials is substantial, yet there is a significant absence of information when discussing the initials found in music manuscripts specifically. In this paper, I endeavor to supplement the current scholarship by focusing my research on music manuscripts produced in Italy between 1250 and 1500 A.D. in order to provide examples of the relationships between image, music, and text in the context of use. I use mainly iconographic research methods, though a considerable amount of background information is reliant on the research of other authors in the field of medieval philosophy and theology. Through my research I have concluded that the use of illuminated initials in medieval Italian music manuscripts enhances the function of the manuscript by providing another layer of understanding which audience members could use to aid them in their meditation, prayer, and in the performance of the music.

Looking inside for good practice in Deaf bilingual education: a participatory SWOT analysis

Presentation to the Disability Studies Conference, Lancaster University, September 7-9, 2010.

Mechanisms that Trigger a Good Health-Care Response to Intimate Partner Violence in Spain. Combining Realist Evaluation and Qualitative Comparative Analysis Approaches

Background. Health care professionals, especially those working in primary health-care services, can play a key role in preventing and responding to intimate partner violence. However, there are huge variations in the way health care professionals and primary health care teams respond to intimate partner violence. In this study we tested a previously developed programme theory on 15 primary health care center teams located in four different Spanish regions: Murcia, C Valenciana, Castilla-León and Cantabria. The aim was to identify the key combinations of contextual factors and mechanisms that trigger a good primary health care center team response to intimate partner violence. Methods. A multiple case-study design was used. Qualitative and quantitative information was collected from each of the 15 centers (cases). In order to handle the large amount of information without losing familiarity with each case, qualitative comparative analysis was undertaken. Conditions (context and mechanisms) and outcomes, were identified and assessed for each of the 15 cases, and solution formulae were calculated using qualitative comparative analysis software. Results. The emerging programme theory highlighted the importance of the combination of each team’s self-efficacy, perceived preparation and women-centredness in generating a good team response to intimate partner violence. The use of the protocol and accumulated experience in primary health care were the most relevant contextual/intervention conditions to trigger a good response. However in order to achieve this, they must be combined with other conditions, such as an enabling team climate, having a champion social worker and having staff with training in intimate partner violence. Conclusions. Interventions to improve primary health care teams’ response to intimate partner violence should focus on strengthening team’s self-efficacy, perceived preparation and the implementation of a woman-centred approach. The use of the protocol combined with a large working experience in primary health care, and other factors such as training, a good team climate, and having a champion social worker on the team, also played a key role. Measures to sustain such interventions and promote these contextual factors should be encouraged.

Cape of Good Hope and Cape Town Region, South Africa, Nautical Chart, 1822 (Raster Image)

This layer is a georeferenced raster image of the historic, paper map entitled: Survey of the Cape of Good Hope, by Lieut. A.T.E. Vidal of H.M.S. Leven, assisted by Captn. Chas. Lechmere, R.N. Lieut T. Boteler, and Mr. H.A. Gibbons, Admlty. Midn. under the direction of Captn. W.F.W. Owen, 1822. J. & C. Walker sculpt. It was published according to Act of Parliament at the Hydrographical Office of the Admiralty, 4th March 1828. Scale [ca. 1:153,512]. Covers the Cape Peninsula region, including False Bay and Cape Town, South Africa. The image inside the map neatline is georeferenced to the surface of the earth and fit to the 'WGS 1984 UTM 34S' coordinate system. All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, index maps, legends, or other information associated with the principal map. This map shows coastal features such as beacons, rocks, channels, points, coves, islands, bottom soil types, anchorage points, and more. Includes also selected land features such as roads, drainage, land cover, selected buildings, towns, and more. Relief shown by contours; depths by soundings. Includes notes, table of heights, and two views. This layer is part of a selection of digitally scanned and georeferenced historic maps from The Harvard Map Collection as part of the Imaging the Urban Environment project. Maps selected for this project represent major urban areas and cities of the world, at various time periods. These maps typically portray both natural and manmade features at a large scale. The selection represents a range of regions, originators, ground condition dates, scales, and purposes.

The European Citizen's Initiative: next big thing or new false good idea? Egmont Paper No. 59, July 2013

From the Introduction. One innovative element of the Lisbon Treaty was the creation of a European Citizens’ Initiative (ECI). At the time, this was sometimes hailed as a fundamental change in the European institutional system. A few years after the entry into force of the Treaty, however, much less is heard about this “first truly transnational instrument of modern direct democracy”, this “revolution in disguise”, this “very innovative and symbolic” provision. This could seem surprising at first sight. Since the entry into force of the Treaty, the implementation of this provision has been remarkably rapid. Meanwhile, new arguments have risen concerning the lack of democratic legitimacy of the European Union, and the lack of connection between the European institutions and the citizens.