Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells

The death of serum-deprived undifferentiated PC12 cells shows both autophagic and apoptotic features. Since it is still controversial whether the autophagy is instrumental in the cell death or a mere epiphenomenon, we tested the effects of inhibiting the autophagy by a variety of phosphoinositide 3-kinase inhibitors, and provided evidence that the autophagy, or a related trafficking event, is indeed instrumental in the cell death. Furthermore, by comparing the effects of PI3-K inhibition and caspase-inhibition on autophagic and apoptotic cellular events, we showed that in this case the autophagic and apoptotic mechanisms mediate cell death by parallel pathways and do not act in serie

Maximal Entanglement, Collective Coordinates and Tracking the King

Maximal entangled states (MES) provide a basis to two d-dimensional particles Hilbert space, d=prime $\ne 2$. The MES forming this basis are product states in the collective, center of mass and relative, coordinates. These states are associated (underpinned) with lines of finite geometry whose constituent points are associated with product states carrying Mutual Unbiased Bases (MUB) labels. This representation is shown to be convenient for the study of the Mean King Problem and a variant thereof, termed Tracking the King which proves to be a novel quantum communication channel. The main topics, notions used are reviewed in an attempt to have the paper self contained.Comment: 8. arXiv admin note: substantial text overlap with arXiv:1206.3884, arXiv:1206.035

Optimizing P300-speller sequences by RIP-ping groups apart

International audienceSo far P300-speller design has put very little emphasis on the design of optimized flash patterns, a surprising fact given the importance of the sequence of flashes on the selection outcome. Previous work in this domain has consisted in studying consecutive flashes, to prevent the same letter or its neighbors from flashing consecutively. To this effect, the flashing letters form more random groups than the original row-column sequences for the P300 paradigm, but the groups remain fixed across repetitions. This has several important consequences, among which a lack of discrepancy between the scores of the different letters. The new approach proposed in this paper accumulates evidence for individual elements, and optimizes the sequences by relaxing the constraint that letters should belong to fixed groups across repetitions. The method is inspired by the theory of Restricted Isometry Property matrices in Compressed Sensing, and it can be applied to any display grid size, and for any target flash frequency. This leads to P300 sequences which are shown here to perform significantly better than the state of the art, in simulations and online tests

Optimizing P300-speller sequences by RIP-ping groups apart

International audienceSo far P300-speller design has put very little emphasis on the design of optimized flash patterns, a surprising fact given the importance of the sequence of flashes on the selection outcome. Previous work in this domain has consisted in studying consecutive flashes, to prevent the same letter or its neighbors from flashing consecutively. To this effect, the flashing letters form more random groups than the original row-column sequences for the P300 paradigm, but the groups remain fixed across repetitions. This has several important consequences, among which a lack of discrepancy between the scores of the different letters. The new approach proposed in this paper accumulates evidence for individual elements, and optimizes the sequences by relaxing the constraint that letters should belong to fixed groups across repetitions. The method is inspired by the theory of Restricted Isometry Property matrices in Compressed Sensing, and it can be applied to any display grid size, and for any target flash frequency. This leads to P300 sequences which are shown here to perform significantly better than the state of the art, in simulations and online tests

Case studies and analysis of mine shafts incidents in Europe

International audienceEntry to mine workings is normally gained by means of vertical shafts or horizontal or inclined tunnels called adits. Other mining objects such as fan drifts and wheel pits are often associated with mine shafts. Such mining objects may or may not have been filled, wholly or partially, or otherwise sealed to prevent entry when the mine was abandoned. Nowadays mine entries are usually adequately protected on abandonment to prevent accidental ingress. Many earlier mine entries remain open, however, and may pose a threat to human safety. Within the framework of MISSTER (Mine shafts: improving security and new tools for the evaluation of risks), a European RFCS project (Research Fund for Coal and Steel), a selection of representative cases of mine shafts incidents was reviewed. This work was carried out by INERIS (France), GEOCONTROL (Spain), University of Nottingham and Mine Rescue Service Ltd (United Kingdom), Central Mining Institute and KWSA (Poland). The experience accumulated through this work will allow a fuller determination of risk scenarios associated with mine shafts

Buying big into biotech: scale, financing, and the industrial dynamics of UK biotech, 1980--2009

This article explores how the UK's biotech firms have evolved in response to their financial environment. As investors' expectations about the potential of biotech have changed, funding options have opened up and closed down, leading firms to develop new business models and routes of technology development. After a favorable period, new constraints on stock market funding have forced UK biotech firms to compress their life cycles, constraining their ability to generate the late-stage drug candidates sought by large pharmaceutical firms. These changes are analyzed within a neo-Chandlerian framework in the context of a selection environment where rather than firms of varying inefficiencies being selected by an efficient market, we find entrepreneurs submitting themselves to an inefficient investment-selection process at the intersection of industries attempting to achieve their own scale economies. The article highlights the importance of the scale of investment at the firm and industry level, and suggests that decline in the size of the industry can have adverse consequences for investment and firm performance in this setting. Copyright 2013 The Author 2013. Published by Oxford University Press on behalf of Associazione ICC. All rights reserved., Oxford University Press

Commercializing Biomedical Research Through Securitization Techniques

Biomedical innovation has become riskier, more expensive and more difficult to finance with traditional sources such as private and public equity. Here we propose a financial structure in which a large number of biomedical programs at various stages of development are funded by a single entity to substantially reduce the portfolio's risk. The portfolio entity can finance its activities by issuing debt, a critical advantage because a much larger pool of capital is available for investment in debt versus equity. By employing financial engineering techniques such as securitization, it can raise even greater amounts of more-patient capital. In a simulation using historical data for new molecular entities in oncology from 1990 to 2011, we find that megafunds of $5–15 billion may yield average investment returns of 8.9–11.4% for equity holders and 5–8% for 'research-backed obligation' holders, which are lower than typical venture-capital hurdle rates but attractive to pension funds, insurance companies and other large institutional investors

Open access and open source in chemistry

Scientific data are being generated and shared at ever-increasing rates. Two new mechanisms for doing this have developed: open access publishing and open source research. We discuss both, with recent examples, highlighting the differences between the two, and the strengths of both