Imiglucerase in the treatment of Gaucher disease: a history and perspective

The scientific and therapeutic development of imiglucerase (Cerezyme®) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ultra-orphan disorder: Gaucher disease

Evaporation induced flow inside circular wells

Flow field and height averaged radial velocity inside a droplet evaporating in an open circular well were calculated for different modes of liquid evaporation.Comment: 5 page, 3 figures, submitted to European Physical Journal

The Irish Coral Task Force and Atlantic Coral Ecosystem Study: Report on Two Deep-Water Coral Conservation Stakeholder Workshops Held in Galway in 2000 and 2002

Increasing public and media awareness of the unique nature of European deep-water corals has put the focus firmly on the need for sustainable management of European offshore living resources. The well documented destruction of deep-water corals off Norway and potentially along the entire European margin combined with extremely slow coral habitat recovery rates, has created a sense of urgency to move towards implementation of the appropriate management measures to ensure the long-term survival of this spectacular and important habitat. In the process, deep-water coral conservation has become in many ways a paradigm for a shift away from traditional sectoral driven resource management approaches, towards an inclusive integrated ecosystem approach to the management of European offshore resources. The EU Fifth Framework Programme, in an effort to increase the socio-economic impact of its R&D projects strongly encouraged the formation of scientist-stakeholder partnerships and development of a suitable research-product delivery mechanism. The major (€2.1 million) European Union funded research project: the Atlantic Coral Ecosystem Study successfully responded to these new challenges in a number of innovative ways. In particular, the establishment of an ACES project-stakeholder partnership through consultative workshops, provided a means for stakeholders to prioritise the scientific research and created a forum for rapid dissemination of scientific results. Complementary initiatives arising from these meetings, such as the formation of the ad hoc Irish Coral Task Force, provided a mechanism whereby scientific findings could be translated into policy advice for the appropriate national authorities. This report serves as a record of the consultative process undertaken during two stakeholder workshops held in Galway on 23rd June 2000 and 24th June 2002. Section A contains conclusions and summary records of the two meetings. Section B contains a series of papers presented at the workshops to provide detailed information on: cold-water coral research and conservation initiatives; fishing related issues; oil and gas related issues and conservation legislation and legal issues. The 2000 meeting was sponsored by the Atlantic Coral Ecosystem Study, while the 2002 meeting was sponsored by the Marine Institute (Ireland), as part of its support for the Irish Coral Task Force and ACES. Between the first and the second meeting, the need for scientific advice to support the designation of Special Areas of Conservation to protect corals under the EU Habitats Directive became a clear priority. Finally, it is obvious that much work remains to be done to achieve effective protection of deep-water corals and similarly threatened 'hot spots' of marine biodiversity along the European shelf and slope. It is also clear, however, that successful implementation of conservation measures will require on-going dialogue with stakeholders, and their participation in the decision making process.Funder: Marine Institut

Oscillating Fracture in Rubber

We have found an oscillating instability of fast-running cracks in thin rubber sheets. A well-defined transition from straight to oscillating cracks occurs as the amount of biaxial strain increases. Measurements of the amplitude and wavelength of the oscillation near the onset of this instability indicate that the instability is a Hopf bifurcation

Ground-state properties of rutile: electron-correlation effects

Electron-correlation effects on cohesive energy, lattice constant and bulk compressibility of rutile are calculated using an ab-initio scheme. A competition between the two groups of partially covalent Ti-O bonds is the reason that the correlation energy does not change linearly with deviations from the equilibrium geometry, but is dominated by quadratic terms instead. As a consequence, the Hartree-Fock lattice constants are close to the experimental ones, while the compressibility is strongly renormalized by electronic correlations.Comment: 1 figure to appear in Phys. Rev.

Floating stones off El Hierro, Canary Islands: xenoliths of pre-island sedimentary origin in the early products of the October 2011 eruption

The eruption that started off the south coast of El Hierro, Canary Islands, in October 2011 has emitted intriguing eruption products found floating in the sea. These specimens appeared as floating volcanic "bombs" that have in the meantime been termed "restingolites" (after the close-by village of La Restinga) and exhibit cores of white and porous pumice-like material. Currently the nature and origin of these "floating stones" is vigorously debated among researchers, with important implications for the interpretation of the hazard potential of the ongoing eruption. The "restingolites" have been proposed to be either (i) juvenile high-silica magma (e.g. rhyolite), (ii) remelted magmatic material (trachyte), (iii) altered volcanic rock, or (iv) reheated hyaloclastites or zeolite from the submarine slopes of El Hierro. Here, we provide evidence that supports yet a different conclusion. We have collected and analysed the structure and composition of samples and compared the results to previous work on similar rocks found in the archipelago. Based on their high silica content, the lack of igneous trace element signatures, and the presence of remnant quartz crystals, jasper fragments and carbonate relicts, we conclude that "restingolites" are in fact xenoliths from pre-island sedimentary rocks that were picked up and heated by the ascending magma causing them to partially melt and vesiculate. They hence represent messengers from depth that help us to understand the interaction between ascending magma and crustal lithologies in the Canary Islands as well as in similar Atlantic islands that rest on sediment/covered ocean crust (e.g. Cape Verdes, Azores). The occurrence of these "restingolites" does therefore not indicate the presence of an explosive high-silica magma that is involved in the ongoing eruption

Inhibition of IRE1 alpha RNase activity reduces NLRP3 inflammasome assembly and processing of pro-IL1 beta

The inflammasome is a multiprotein complex assembled in response to Pathogen Associated Molecular Patterns (PAMPs) and Danger Associated Molecular Patterns (DAMPS). Inflammasome activation occurs through a two-step mechanism, with the first signal facilitating priming of inflammasome components while the second signal triggers complex assembly. Once assembled, the inflammasome recruits and activates pro-caspase-1, which in turn processes pro-interleukin (IL)-18 and pro-IL-1 beta into their bio-active forms. Owing to its key role in the regulation of innate immune responses, the inflammasome has emerged as a therapeutic target for the treatment of inflammatory conditions. In this study we demonstrate that IRE1 alpha, a key component of the Unfolded Protein Response, contributes to assembly of the NLRP3 inflammasome. Blockade of IRE1 alpha RNase signaling lowered NLRP3 inflammasome assembly, caspase-1 activation and pro-IL-1 beta processing. These results underscore both the importance and potential therapeutic relevance of targeting IRE1 alpha signaling in conditions of excessive inflammasome formation