Increased emission intensity can compensate for the presence of noise in human click-based echolocation

Echolocating bats adapt their emissions to succeed in noisy environments. In the present study we investigated if echolocating humans can detect a sound-refecting surface in the presence of noise and if intensity of echolocation emissions (i.e. clicks) changes in a systematic pattern. We tested people who were blind and had experience in echolocation, as well as blind and sighted people who had no experience in echolocation prior to the study. We used an echo-detection paradigm where participants listened to binaural recordings of echolocation sounds (i.e. they did not make their own click emissions), and where intensity of emissions and echoes changed adaptively based on participant performance (intensity of echoes was yoked to intensity of emissions). We found that emission intensity had to systematically increase to compensate for weaker echoes relative to background noise. In fact, emission intensity increased so that spectral power of echoes exceeded spectral power of noise by 12 dB in 4-kHz and 5-kHz frequency bands. The efects were the same across all participant groups, suggesting that this efect occurs independently of long-time experience with echolocation. Our fndings demonstrate for the frst time that people can echolocate in the presence of noise and suggest that one potential strategy to deal with noise is to increase emission intensity to maintain signal-to-noise ratio of certain spectral components of the echoes

Domestic Rivalry and Export Performance: Theory and Evidence from International Airline Markets

The much-studied relationship between domestic rivalry and export performance consists of those supporting a national-champion rationale, and those supporting a rivalry rationale. While the empirical literature generally supports the positive effects of domestic rivalry, the national-champion rationale actually rests on firmer theoretical ground. We address this inconsistency by providing a theoretical framework that illustrates three paths via which domestic rivalry translates into enhanced international exports. Furthermore, empirical tests on the world airline industry elicit the existence of one particular path - an enhanced firm performance effect - that connects domestic rivalry with improved international exports

Vav1 Transduces T Cell Receptor Signals to the Activation of Phospholipase C-γ1 via Phosphoinositide 3-Kinase-dependent and -independent Pathways

Vav1 is a signal transducing protein required for T cell receptor (TCR) signals that drive positive and negative selection in the thymus. Furthermore, Vav1-deficient thymocytes show greatly reduced TCR-induced intracellular calcium flux. Using a novel genetic system which allows the study of signaling in highly enriched populations of CD4+CD8+ double positive thymocytes, we have studied the mechanism by which Vav1 regulates TCR-induced calcium flux. We show that in Vav1-deficient double positive thymocytes, phosphorylation, and activation of phospholipase C-γ1 (PLCγ1) is defective. Furthermore, we demonstrate that Vav1 regulates PLCγ1 phosphorylation by at least two distinct pathways. First, in the absence of Vav1 the Tec-family kinases Itk and Tec are no longer activated, most likely as a result of a defect in phosphoinositide 3-kinase (PI3K) activation. Second, Vav1-deficient thymocytes show defective assembly of a signaling complex containing PLCγ1 and the adaptor molecule Src homology 2 domain–containing leukocyte phosphoprotein 76. We show that this latter function is independent of PI3K

Evaluating Baculovirus as a Vector for Human Prostate Cancer Gene Therapy

Gene therapy represents an attractive strategy for the non-invasive treatment of prostate cancer, where current clinical interventions show limited efficacy. Here, we evaluate the use of the insect virus, baculovirus (BV), as a novel vector for human prostate cancer gene therapy. Since prostate tumours represent a heterogeneous environment, a therapeutic approach that achieves long-term regression must be capable of targeting multiple transformed cell populations. Furthermore, discrimination in the targeting of malignant compared to non-malignant cells would have value in minimising side effects. We employed a number of prostate cancer models to analyse the potential for BV to achieve these goals. In vitro, both traditional prostate cell lines as well as primary epithelial or stromal cells derived from patient prostate biopsies, in two- or three-dimensional cultures, were used. We also evaluated BV in vivo in murine prostate cancer xenograft models. BV was capable of preferentially transducing invasive malignant prostate cancer cell lines compared to early stage cancers and non-malignant samples, a restriction that was not a function of nuclear import. Of more clinical relevance, primary patient-derived prostate cancer cells were also efficiently transduced by BV, with robust rates observed in epithelial cells of basal phenotype, which expressed BV-encoded transgenes faster than epithelial cells of a more differentiated, luminal phenotype. Maximum transduction capacity was observed in stromal cells. BV was able to penetrate through three-dimensional structures, including in vitro spheroids and in vivo orthotopic xenografts. BV vectors containing a nitroreductase transgene in a gene-directed enzyme pro-drug therapy approach were capable of efficiently killing malignant prostate targets following administration of the pro-drug, CB1954. Thus, BV is capable of transducing a large proportion of prostate cell types within a heterogeneous 3-D prostate tumour, can facilitate cell death using a pro-drug approach, and shows promise as a vector for the treatment of prostate cancer

Neutrino masses: From fantasy to facts

Theory suggests the existence of neutrino masses, but little more. Facts are coming close to reveal our fantasy: solar and atmospheric neutrino data strongly indicate the need for neutrino conversions, while LSND provides an intriguing hint. The simplest ways to reconcile these data in terms of neutrino oscillations invoke a light sterile neutrino in addition to the three active ones. Out of the four neutrinos, two are maximally-mixed and lie at the LSND scale, while the others are at the solar mass scale. These schemes can be distinguished at neutral-current-sensitive solar & atmospheric neutrino experiments. I discuss the simplest theoretical scenarios, where the lightness of the sterile neutrino, the nearly maximal atmospheric neutrino mixing, and the generation of $\Delta {m^2}_\odot$ & $\Delta {m^2}_{atm}$ all follow naturally from the assumed lepton-number symmetry and its breaking. Although the most likely interpretation of the present data is in terms of neutrino-mass-induced oscillations, one still has room for alternative explanations, such as flavour changing neutrino interactions, with no need for neutrino mass or mixing. Such flavour violating transitions arise in theories with strictly massless neutrinos, and may lead to other sizeable flavour non-conservation effects, such as $\mu \to e + \gamma$, $\mu-e$ conversion in nuclei, unaccompanied by neutrino-less double beta decay.Comment: 33 pages, latex, 16 figures. Invited Talk at Ioannina Conference, Symmetries in Intermediate High Energy Physics and its Applications, Oct. 1998, to be published by Springer Tracts in Modern Physics. Festschrift in Honour of John Vergados' 60th Birthda

Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV

We report the STAR measurement of Phi meson production in Au+Au and p+p collisions at sqrt (s)=200 GeV. Using the event mixing technique, the Phi spectra and yields are obtained at mid-rapidity for five centrality bins in Au+Au collisions and for non-singly-diffractive p+p collisions. It is found that the Phi transverse momentum distributions from Au+Au collisions are better fitted with a single-exponential while the p+p spectrum is better described by a double-exponential distribution. The measured nuclear modification factors indicate that Phi production in central Au+Au collisions is suppressed relative to peripheral collisions when scaled by the number of binary collisions. The systematics of versus centrality and the constant Phi/K- ratio versus beam species, centrality, and collision energy rule out kaon coalescence as the dominant mechanism for Phi production.Comment: 6 pages, 3 figures, submitted to Phys. Rev. Let

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3

Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine

The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, is fueling a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and site-specific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction, involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the photocatalytic diselenide contraction transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21st amino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.Luke J. Dowman, Sameer S. Kulkarni, Juan V. Alegre-Requena, Andrew M. Giltrap, Alexander R. Norman, Ashish Sharma, Liliana C. Gallegos, Angus S.Mackay, Adarshi P. Welegedara, Emma E. Watson, Damian van Raad, Gerhard Niederacher, Susanne Huhmann, Nicholas Proschogo, Karishma Patel, Mark Larance, Christian F. W. Becker, Joel P. Mackay, Girish Lakhwani, Thomas Huber, Robert S. Paton, Richard J. Payn