Rhodopsin and the Others: A Historical Perspective on Structural Studies of G Protein-Coupled Receptors

The role of rhodopsin as a structural prototype for the study of the whole superfamily of G protein-coupled receptors (GPCRs) is reviewed in an historical perspective. Discovered at the end of the nineteenth century, fully sequenced since the early 1980s, and with direct three-dimensional information available since the 1990s, rhodopsin has served as a platform to gather indirect information on the structure of the other superfamily members. Recent breakthroughs have elicited the solution of the structures of additional receptors, namely the beta 1- and beta 2-adrenergic receptors and the A(2A) adenosine receptor, now providing an opportunity to gauge the accuracy of homology modeling and molecular docking techniques and to perfect the computational protocol. Notably, in coordination with the solution of the structure of the A(2A) adenosine receptor, the first "critical assessment of GPCR structural modeling and docking" has been organized, the results of which highlighted that the construction of accurate models, although challenging, is certainly achievable. The docking of the ligands and the scoring of the poses clearly emerged as the most difficult components. A further goal in the field is certainly to derive the structure of receptors in their signaling state, possibly in complex with agonists. These advances, coupled with the introduction of more sophisticated modeling algorithms and the increase in computer power, raise the expectation for a substantial boost of the robustness and accuracy of computer-aided drug discovery techniques in the coming years.

The use of lytic bacteriophages in the prevention and eradication of biofilms of Proteus mirabilis and Escherichia coli.

Antibiotics have been the cornerstone of the clinical management of bacterial infections since their discovery in the early part of the last century. Eight decades later, their widespread, often indiscriminate use, has resulted in an overall reduction in their effectiveness, with reports of multidrug-resistant bacteria now commonplace. Increasing reliance on indwelling medical devices, which are inherently susceptible to biofilm-mediated infections, has contributed to unacceptably high rates of nosocomial infections, placing a strain on healthcare budgets. This study investigates the use of lytic bacteriophages in the treatment and prevention of biofilms of bacterial species commonly associated with infections of indwelling urological devices and catheter-associated urinary tract infections. The use of lytic bacteriophages against established biofilms of Proteus mirabilis and Escherichia coli is described, whereby biofilm populations have been reduced successfully by three to four log cycles (99.9-99.99% removal). The prevention of biofilm formation on Foley catheter biomaterials following impregnation of hydrogel-coated catheter sections with a lytic bacteriophage has also been investigated. This has revealed an approximate 90% reduction in both P. mirabilis and E. coli biofilm formation on bacteriophage-treated catheters when compared with untreated controls.

Nineteenth and twentieth century sea-level changes in Tasmania and New Zealand

Positive deviations from linear sea-level trends represent important climate signals if they are persistent and geographically widespread. This paper documents rapid sea-level rise reconstructed from sedimentary records obtained from salt marshes in the Southwest Pacific region (Tasmania and New Zealand). A new late Holocene relative sea-level record from eastern Tasmania was dated by AMS(14)C (conventional, high precision and bomb-spike), Cs-137, Pb-210, stable Pb isotopic ratios, trace metals, pollen and charcoal analyses. Palaeosea-level positions were determined by foraminiferal analyses. Relative sea level in Tasmania was within half a metre of present sea level for much of the last 6000 yr. Between 1900 and 1950 relative sea level rose at an average rate of 4.2 +/- 0.1 mm/yr. During the latter half of the 20th century the reconstructed rate of relative sea-level rise was 0.7 +/- 0.6 mm/yr. Our study is consistent with a similar pattern of relative sea-level change recently reconstructed for southern New Zealand. The change in the rate of sea-level rise in the SW Pacific during the early 20th century was larger than in the North Atlantic and could suggest that northern hemisphere land-based ice was the most significant melt source for global sea-level rise. (C) 2011 Elsevier B.V. All rights reserved.

Imported and translated landscapes: Buenos Aires nineteenth-century waterfront parks

The study of urban and landscape history has recently questioned the peripheral condition of certain areas and re-examined them as valuable parts of an international network . In such a framework cities are not only recipients of foreign influences but active agents in their own urban transformations. Meanwhile, the regeneration of urban waterfronts appears increasingly in the spotlight globally , but the re-use of the waterfront as public space began more than a century ago.

Buenos Aires is an example of a ‘peripheral’ city, in which waterfront parks at the end of the nineteenth century were the product of international influences combined with local conditions, needs and expertise. Buenos Aires developed a continuous increase and diversity of leisure waterfront space, making it different from most European or ‘central’ cities. This paper will analyse the process of translation of landscape design on Buenos Aires’ waterfront while outlining the significance of waterfront parks to the city and its growing urban population.

Opening the Frontier: The Gubbio-Perugia Frontier in the Course of History.

The frontier between Gubbio (ancient Umbria) and Perugia (ancient Etruria), in the northeast part of the modern region of Umbria, was founded in the late sixth century BC. The frontier endured in different forms, most notably in the late antique and medieval periods, as well as fleetingly in 1944, and is fossilized today in the local government boundaries. Archaeological, documentary and
philological evidence are brought together to investigate different scales of time that vary from millennia to single days in the representation of a frontier that captured a watershed of geological origins. The foundation of the frontier appears to have been a product of the active agency of the Etruscans, who projected new settlements across the Tiber in the course of the sixth century BC,
protected at the outer limit of their territory by the naturally defended farmstead of Col di Marzo. The immediate environs of the ancient abbey of Montelabate have been studied intensively by targeted, systematic and geophysical survey in conjunction with excavation, work that is still in progress. An overview of the development of the frontier is presented here, employing the data currently available.

Rapid changes in the level of Kluane Lake in Yukon Territory over the last millennium

The level of Kluane Lake, the largest lake in Yukon Territory, was lower than at present during most of the Holocene. The lake rose rapidly in the late seventeenth century to a level 12 m above present, drowning forest and stranding driftwood on a conspicuous high-stand beach, remnants of which are preserved at the south end of the lake. Kluane Lake fell back to near its present level by the end of the eighteenth century and has fluctuated within a range of about 3 m over the last 50 yr. The primary control on historic fluctuations in lake level is the discharge of Slims River, the largest source of water to the lake. We use tree ring and radiocarbon ages, stratigraphy and sub-bottom acoustic data to evaluate two explanations for the dramatic changes in the level of Kluane Lake. Our data support the hypothesis of Hugh Bostock, who suggested in 1969 that the maximum Little Ice Age advance of Kaskawulsh Glacier deposited large amounts of sediment in the Slims River valley and established the present course of Slims River into Kluane Lake. Bostock argued that these events caused the lake to rise and eventually overflow to the north. The overflowing waters incised the Duke River fan at the north end of Kluane Lake and lowered the lake to its present level. This study highlights the potentially dramatic impacts of climate change on regional hydrology during the Little Ice Age in glacierised mountains. © 2006 University of Washington.

A Comparison of Programming Models for Multiprocessors with Explicitly Managed Memory Hierarchies

On multiprocessors with explicitly managed memory hierarchies (EMM), software has the responsibility of moving data in and out of fast local memories. This task can be complex and error-prone even for expert programmers. Before we can allow compilers to handle the complexity for us, we must identify the abstractions that are general enough to allow us to write applications with reasonable effort, yet speci?c enough to exploit the vast on-chip memory bandwidth of EMM multi-processors. To this end, we compare two programming models against hand-tuned codes on the STI Cell, paying attention to programmability and performance. The ?rst programming model, Sequoia, abstracts the memory hierarchy as private address spaces, each corresponding to a parallel task. The second, Cellgen, is a new framework which provides OpenMP-like semantics and the abstraction of a shared address spaces divided into private and shared data. We compare three applications programmed using these models against their hand-optimized counterparts in terms of abstractions, programming complexity, and performance.

A.J. Raffles and Arsène Lupin in Literature, Theatre, and Film: On The Transnational Adaptations of Popular Fiction (1905-1930)

As a consequence of the accelerating technological development and the impact of cultural globalisation, the transnational aspects of the process of adaptation have become increasingly crucial in recent years. To go back to the very beginnings of the twentieth century and research the historical connections between popular literature, theatre, and film can shed greater light on the origins of these phenomena. By focusing on two case studies from turn-of-the-century crime fiction, this paper examines the extent to which practices of serialisation, translation, and adaptation of literary works contributed to the formation of a transnational market for popular culture. Ernest W. Hornung’s A. J. Raffles and Maurice Leblanc’s Arsène Lupin were the heroes of two crime series that were immediately translated, imitated, and adapted into countless theatrical plays and films all over the world. Given the resemblance between the two characters, the two franchises frequently ended by overlapping. Their ability to move from a medium to another as well as from a country to another was the result of the logic of ‘recycling, remaking, retelling’ (Brian Naremore) that guides not only the process of adaptation but also the creation of any work of popular culture.

Identity and Geopolitics in Hergé's Adventures of Tintin

This is a study of identity and geopolitics in Hergé's Adventures of Tintin, a series of adventure comics created from 1929 to 1976. The Tintin comics became increasingly popular throughout the mid-twentieth century, and their creator, Hergé, is still a subject of intrigue in the press and popular publications. Recent work in popular geopolitics has pioneered the use of comics as a new type of source material in critical geography. Hergé's approach to the comics format combines an iconic protagonist with detailed and textured environments that draw upon some of the geopolitical discourses of the twentieth century. Three forms of geopolitical meaning are identified within the Tintin comics: discourses of colonialism, European pre-eminence and anti-Americanism. These overlapping trends amount to different facets of one single discourse, which places European ideologies at the centre of its world-view. This is highlighted by focusing on three geographical spaces of the Tintin series, and by contextualising the life and selected works of Hergé. © 2009 Taylor & Francis.

Imported landscapes:Buenos Aires nineteenth century waterfront parks

The study of urban and landscape history has recently questioned the peripheral condition of certain areas and re-examined them as valuable parts of an international network . Meanwhile, the regeneration of urban waterfronts appears increasingly in the spotlight globally , while the re-use of the waterfront as public space actually began more than a century ago.
Buenos Aires is an example of a peripheral city, where waterfront parks at the end of the nineteenth century were the product of international influences combined with local conditions, needs and expertise. This paper will analyse the process of translation of landscape design on Buenos Aires’ waterfront while outlining the significance of waterfront parks for civilising the growing urban population.

An anthropometric history of the World, 1810-1980: did migration and globalization influence country trends?

We find that regional height levels around the world were fairly uniform throughout most of the 19th century, with two exceptions: above-average levels in Anglo-Saxon settlement regions and below-average levels in Southeast Asia. After 1880, substantial diver- gences began to differentiate other regions -- making the world population taller, but more unequal. During the late 19th century and 20th century, heights between world regions devi- ated significantly, when incomes also became very unequal. Interestingly, during the “breaking point period” between the two regimes, heights declined significantly in the cattle-rich New World countries, whereas they started to increase in Old Europe. We discuss in this study whether immigration was a core factor to influence the height decline in the “Anthropometric Decline of the Cowboy and Gaucho Empires”.