Testing Interval Forecasts: A GMM‐Based Approach

This paper proposes a new evaluation framework for interval forecasts. Our model‐free test can be used to evaluate interval forecasts and high‐density regions, potentially discontinuous and/or asymmetric. Using a simple J‐statistic, based on the moments defined by the orthonormal polynomials associated with the binomial distribution, this new approach presents many advantages. First, its implementation is extremely easy. Second, it allows for a separate test for unconditional coverage, independence and conditional coverage hypotheses. Third, Monte Carlo simulations show that for realistic sample sizes our GMM test has good small‐sample properties. These results are corroborated by an empirical application on SP500 and Nikkei stock market indexes. It confirms that using this GMM test leads to major consequences for the ex post evaluation of interval forecasts produced by linear versus nonlinear models. Copyright © 2011 John Wiley & Sons, Ltd.     

Dynamics of Drosophila embryonic patterning network perturbed in space and time using microfluidics

Biochemical networks are perturbed both by fluctuations in environmental conditions and genetic variation. These perturbations must be compensated for, especially when they occur during embryonic pattern formation. Complex chemical reaction networks displaying spatiotemporal dynamics have been controlled and understood by perturbing their environment in space and time. Here, we apply this approach using microfluidics to investigate the robust network in Drosophila melanogaster that compensates for variation in the Bicoid morphogen gradient. We show that the compensation system can counteract the effects of extremely unnatural environmental conditions--a temperature step--in which the anterior and posterior halves of the embryo are developing at different temperatures and thus at different rates. Embryonic patterning was normal under this condition, suggesting that a simple reciprocal gradient system is not the mechanism of compensation. Time-specific reversals of the temperature step narrowed down the critical period for compensation to between 65 and 100 min after onset of embryonic development. The microfluidic technology used here may prove useful to future studies, as it allows spatial and temporal regulation of embryonic development.     

Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells

A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8-30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs.     

The genome sequence of the rice blast fungus Magnaporthe grisea

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.     

Human spleen inhibitor of leukaemic cell growth

Resumen En este trabajo se describe la purificación de un inhibidor de la síntesis de ARN que afecta secundariamente la síntesis de ADN, y actividad mitótica. El factor ha sido aislado de ocho bazos humanos, comprendiendo dos de enfermos con leucemia mielocítica crónica (LMC) sanas, en los cuales se efectuó la esplenectomía por ruptura traumática del bazo El inhibidor esplénico posee fuerte citotoxicidad sobre células en cultivo provenientes de enfermos con LMC. Estas células tienen el cromosoma de Philadelphia. El inhibidor esplénico tiene un peso molecular de alrededor de 1,000 y es probablaemente un péptido o glicopéptido.     

Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling

B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries. The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism.     

Quantum teleportation over 143 kilometres using active feed-forward

The quantum internet is predicted to be the next-generation information processing platform, promising secure communication and an exponential speed-up in distributed computation. The distribution of single qubits over large distances via quantum teleportation is a key ingredient for realizing such a global platform. By using quantum teleportation, unknown quantum states can be transferred over arbitrary distances to a party whose location is unknown. Since the first experimental demonstrations of quantum teleportation of independent external qubits, an internal qubit and squeezed states, researchers have progressively extended the communication distance. Usually this occurs without active feed-forward of the classical Bell-state measurement result, which is an essential ingredient in future applications such as communication between quantum computers. The benchmark for a global quantum internet is quantum teleportation of independent qubits over a free-space link whose attenuation corresponds to the path between a satellite and a ground station. Here we report such an experiment, using active feed-forward in real time. The experiment uses two free-space optical links, quantum and classical, over 143?kilometres between the two Canary Islands of La Palma and Tenerife. To achieve this, we combine advanced techniques involving a frequency-uncorrelated polarization-entangled photon pair source, ultra-low-noise single-photon detectors and entanglement-assisted clock synchronization. The average teleported state fidelity is well beyond the classical limit of two-thirds. Furthermore, we confirm the quality of the quantum teleportation procedure without feed-forward by complete quantum process tomography. Our experiment verifies the maturity and applicability of such technologies in real-world scenarios, in particular for future satellite-based quantum teleportation.     

Insights on Social Responsibility of NGOS

Systemic Practice and Action Research - The social responsibility of nongovernmental organizations starts from the values this sector defends. Despite the social vocation, a question arises as to...