3,471 research outputs found

    Molecular mimicry, genetic homology, and gene sharing proteomic “molecular fingerprints” using an EBV (Epstein-Barr virus)-derived microarray as a potential diagnostic method in autoimmune disease

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    EBV (Epstein-Barr Virus) and other human DNA viruses are associated with autoimmune syndromes in epidemiologic studies. In this work, immunoglobulin G response to EBV-encoded proteins which share regions with human immune response proteins from the human host including ZEBRA (BZLF-1 encoded protein), BALF-2 recombinase expressed primarily during the viral lytic replication cycle, and EBNA-1 (Epstein-Barr Virus Nuclear Antigen) expressed during the viral latency cycle respectively were characterized using a laser-printed micro-array ( PEPperprint.com ). IgG response to conserved "A/T hooks" in EBV-encoded proteins such as EBNA-1 and the BALF-2 recombinase related to host DNA-binding proteins including RAG-1 recombinase and histones, and EBV-encoded virokines such as the IL-10 homologue BCRF-1 suggest further directions for clinical research. The author suggests that proteomic "molecular fingerprints" of the immune response to viral proteins shared with human immune response genes are potentially useful in early diagnosis and monitoring of autoantibody production and response to therapy in EBV-related autoimmune syndromes

    Emergent hyperuniformity in periodically-driven emulsions

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    We report the emergence of large-scale hyperuniformity in microfluidic emulsions. Upon periodic driving confined emulsions undergo a first-order transition from a reversible to an irreversible dynamics. We evidence that this dynamical transition is accompanied by structural changes at all scales yielding macroscopic yet finite hyperuniform structures. Numerical simulations are performed to single out the very ingredients responsible for the suppression of density fluctuations. We show that as opposed to equilibrium systems the long-range nature of the hydrodynamic interactions are not required for the formation of hyperuniform patterns, thereby suggesting a robust relation between reversibility and hyperuniformity which should hold in a broad class of periodically driven materials.Comment: 5p, 3f, submitte

    Considering the role of cognitive control in expert performance

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    © 2014, Springer Science+Business Media Dordrecht. Dreyfus and Dreyfus’ (1986) influential phenomenological analysis of skill acquisition proposes that expert performance is guided by non-cognitive responses which are fast, effortless and apparently intuitive in nature. Although this model has been criticised (e.g., by Breivik Journal of Philosophy of Sport, 34, 116–134 2007, Journal of the Philosophy of Sport, 40, 85–106 2013; Eriksen 2010; Montero Inquiry:An interdisciplinary Journal of Philosophy, 53, 105–122 2010; Montero and Evans 2011) for over-emphasising the role that intuition plays in facilitating skilled performance, it does recognise that on occasions (e.g., when performance goes awry for some reason) a form of ‘detached deliberative rationality’ may be used by experts to improve their performance. However, Dreyfus and Dreyfus (1986) see no role for calculative problem solving or deliberation (i.e., drawing on rules or mental representations) when performance is going well. In the current paper, we draw on empirical evidence, insights from athletes, and phenomenological description to argue that ‘continuous improvement’ (i.e., the phenomenon whereby certain skilled performers appear to be capable of increasing their proficiency even though they are already experts; Toner and Moran 2014) among experts is mediated by cognitive (or executive) control in three distinct sporting situations (i.e., in training, during pre-performance routines, and while engaged in on-line skill execution). We conclude by arguing that Sutton et al. Journal of the British Society for Phenomenology, 42, 78–103 (2011) ‘applying intelligence to the reflexes’ (AIR) approach may help to elucidate the process by which expert performers achieve continuous improvement through analytical/mindful behaviour during training and competition

    The expressive stance: intentionality, expression, and machine art

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    This paper proposes a new interpretive stance for interpreting artistic works and performances that is relevant to artificial intelligence research but also has broader implications. Termed the expressive stance, this stance makes intelligible a critical distinction between present-day machine art and human art, but allows for the possibility that future machine art could find a place alongside our own. The expressive stance is elaborated as a response to Daniel Dennett's notion of the intentional stance, which is critically examined with respect to his specialized concept of rationality. The paper also shows that temporal scale implicitly serves to select between different modes of explanation in prominent theories of intentionality. It also considers the implications of the phenomenological background for systems that produce art

    Unexpected Effect of Internal Degrees of Freedom on Transverse Phonons in Supercooled Liquids

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    We show experimentally that in a supercooled liquid composed of molecules with internal degrees of freedom the internal modes contribute to the frequency dependent shear viscosity and damping of transverse phonons, which results in an additional broadening of the transverse Brillouin lines. Earlier, only the effect of internal modes on the frequency dependent bulk viscosity and damping of longitudinal phonons was observed and explained theoretically in the limit of weak coupling of internal degrees of freedom to translational motion. A new theory is needed to describe this new effect. We also demonstrate, that the contributions of structural relaxation and internal processes to the width of the Brillouin lines can be separated by measurements under high pressure

    NEXUS/Physics: An interdisciplinary repurposing of physics for biologists

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    In response to increasing calls for the reform of the undergraduate science curriculum for life science majors and pre-medical students (Bio2010, Scientific Foundations for Future Physicians, Vision & Change), an interdisciplinary team has created NEXUS/Physics: a repurposing of an introductory physics curriculum for the life sciences. The curriculum interacts strongly and supportively with introductory biology and chemistry courses taken by life sciences students, with the goal of helping students build general, multi-discipline scientific competencies. In order to do this, our two-semester NEXUS/Physics course sequence is positioned as a second year course so students will have had some exposure to basic concepts in biology and chemistry. NEXUS/Physics stresses interdisciplinary examples and the content differs markedly from traditional introductory physics to facilitate this. It extends the discussion of energy to include interatomic potentials and chemical reactions, the discussion of thermodynamics to include enthalpy and Gibbs free energy, and includes a serious discussion of random vs. coherent motion including diffusion. The development of instructional materials is coordinated with careful education research. Both the new content and the results of the research are described in a series of papers for which this paper serves as an overview and context.Comment: 12 page

    Cognition in Context: Phenomenology, Situated Robotics and the Frame Problem

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    The frame problem is the difficulty of explaining how non-magical systems think and act in ways that are adaptively sensitive to context-dependent relevance. Influenced centrally by Heideggerian phenomenology, Hubert Dreyfus has argued that the frame problem is, in part, a consequence of the assumption (made by mainstream cognitive science and artificial intelligence) that intelligent behaviour is representation-guided behaviour. Dreyfus’ Heideggerian analysis suggests that the frame problem dissolves if we reject representationalism about intelligence and recognize that human agents realize the property of thrownness (the property of being always already embedded in a context). I argue that this positive proposal is incomplete until we understand exactly how the properties in question may be instantiated in machines like us. So, working within a broadly Heideggerian conceptual framework, I pursue the character of a representationshunning thrown machine. As part of this analysis, I suggest that the frame problem is, in truth, a two-headed beast. The intra-context frame problem challenges us to say how a purely mechanistic system may achieve appropriate, flexible and fluid action within a context. The inter-context frame problem challenges us to say how a purely mechanistic system may achieve appropriate, flexible and fluid action in worlds in which adaptation to new contexts is open-ended and in which the number of potential contexts is indeterminate. Drawing on the field of situated robotics, I suggest that the intra-context frame problem may be neutralized by systems of special purpose adaptive couplings, while the inter-context frame problem may be neutralized by systems that exhibit the phenomenon of continuous reciprocal causation. I also defend the view that while continuous reciprocal causation is in conflict with representational explanation, special-purpose adaptive coupling, as well as its associated agential phenomenology, may feature representations. My proposal has been criticized recently by Dreyfus, who accuses me of propagating a cognitivist misreading of Heidegger, one that, because it maintains a role for representation, leads me seriously astray in my handling of the frame problem. I close by responding to Dreyfus’ concerns

    Light scattering spectra of supercooled molecular liquids

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    The light scattering spectra of molecular liquids are derived within a generalized hydrodynamics. The wave vector and scattering angle dependences are given in the most general case and the change of the spectral features from liquid to solidlike is discussed without phenomenological model assumptions for (general) dielectric systems without long-ranged order. Exact microscopic expressions are derived for the frequency-dependent transport kernels, generalized thermodynamic derivatives and the background spectra.Comment: 12 page

    Modulation of p53 activity by IκBα: Evidence suggesting a common phylogeny between NF-κB and p53 transcription factors

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    BACKGROUND: In this work we present evidence that the p53 tumor suppressor protein and NF-κB transcription factors could be related through common descent from a family of ancestral transcription factors regulating cellular proliferation and apoptosis. P53 is a homotetrameric transcription factor known to interact with the ankyrin protein 53BP2 (a fragment of the ASPP2 protein). NF-κB is also regulated by ankyrin proteins, the prototype of which is the IκB family. The DNA binding sequences of the two transcription factors are similar, sharing 8 out of 10 nucleotides. Interactions between the two proteins, both direct and indirect, have been noted previously and the two proteins play central roles in the control of proliferation and apoptosis. RESULTS: Using previously published structure data, we noted a significant degree of structural alignment between p53 and NF-κB p65. We also determined that IκBα and p53 bind in vitro through a specific interaction in part involving the DNA binding region of p53, or a region proximal to it, and the amino terminus of IκBα independently or cooperatively with the ankyrin 3 domain of IκBα In cotransfection experiments, κBα could significantly inhibit the transcriptional activity of p53. Inhibition of p53-mediated transcription was increased by deletion of the ankyrin 2, 4, or 5 domains of IκBα Co-precipitation experiments using the stably transfected ankyrin 5 deletion mutant of κBα and endogenous wild-type p53 further support the hypothesis that p53 and IκBα can physically interact in vivo. CONCLUSION: The aggregate results obtained using bacterially produced IκBα and p53 as well as reticulocyte lysate produced proteins suggest a correlation between in vitro co-precipitation in at least one of the systems and in vivo p53 inhibitory activity. These observations argue for a mechanism involving direct binding of IκBα to p53 in the inhibition of p53 transcriptional activity, analogous to the inhibition of NF-κB by κBα and p53 by 53BP2/ASPP2. These data furthermore suggest a role for ankyrin proteins in the regulation of p53 activity. Taken together, the NFκB and p53 proteins share similarities in structure, DNA binding sites and binding and regulation by ankyrin proteins in support of our hypothesis that the two proteins share common descent from an ancestral transcriptional factor
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