1,647 research outputs found

    Quantum Holographic Encoding in a Two-dimensional Electron Gas

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    The advent of bottom-up atomic manipulation heralded a new horizon for attainable information density, as it allowed a bit of information to be represented by a single atom. The discrete spacing between atoms in condensed matter has thus set a rigid limit on the maximum possible information density. While modern technologies are still far from this scale, all theoretical downscaling of devices terminates at this spatial limit. Here, however, we break this barrier with electronic quantum encoding scaled to subatomic densities. We use atomic manipulation to first construct open nanostructures--"molecular holograms"--which in turn concentrate information into a medium free of lattice constraints: the quantum states of a two-dimensional degenerate Fermi gas of electrons. The information embedded in the holograms is transcoded at even smaller length scales into an atomically uniform area of a copper surface, where it is densely projected into both two spatial degrees of freedom and a third holographic dimension mapped to energy. In analogy to optical volume holography, this requires precise amplitude and phase engineering of electron wavefunctions to assemble pages of information volumetrically. This data is read out by mapping the energy-resolved electron density of states with a scanning tunnelling microscope. As the projection and readout are both extremely near-field, and because we use native quantum states rather than an external beam, we are not limited by lensing or collimation and can create electronically projected objects with features as small as ~0.3 nm. These techniques reach unprecedented densities exceeding 20 bits/nm2 and place tens of bits into a single fermionic state.Comment: Published online 25 January 2009 in Nature Nanotechnology; 12 page manuscript (including 4 figures) + 2 page supplement (including 1 figure); supplementary movie available at http://mota.stanford.ed

    Macrophage Subset Sensitivity to Endotoxin Tolerisation by Porphyromonas gingivalis

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    Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14hi and CD14lo M1- and M2-like MΦs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and vitamin D3, respectively. MΦ subsets were pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity

    Evidenz und Tradition am Beispiel der Phytopharmaka

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    Summary Herbal medicinal products - Evidence and tradition from a historical perspective Background: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, proof of tradition, has so far been dealt with in different ways and fails to meet the criteria of good practice. Method: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry. Results and discussion: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice. Conclusion: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied

    Signatures of arithmetic simplicity in metabolic network architecture

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    Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that several of the properties predicted by the artificial chemistry model hold for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity

    Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

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    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins

    Abundant Fas expression by gastrointestinal stromal tumours may serve as a therapeutic target for MegaFasL

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    Although the tyrosine kinase inhibitor imatinib has been shown to be an active agent in patients with gastrointestinal stromal tumours (GIST), complete remissions are almost never seen and most patients finally experience disease progression during their course of treatment. An alternative therapeutic option is to target death receptors such as Fas. We showed that a panel of imatinib-sensitive (GIST882) and imatinib-resistant (GIST48, GIST430 and GIST430K-) cell lines expressed Fas. MegaFasL, a recently developed hexameric form of soluble Fas ligand (FasL), appeared to be an active apoptosis-inducing agent in these cell lines. Moreover, MegaFasL potentiated the apoptotic effects of imatinib. Immunohistochemical evaluations, in 45 primary GISTs, underscored the relevance of the Fas pathway: Fas was expressed in all GISTs and was expressed strongly in 93%, whereas FasL was expressed at moderate and strong levels in 35 and 53% of GISTs, respectively. Fas and FasL expression were positively correlated in these primary GISTs, but there was no association between Fas or FasL expression and primary site, histological subtype, tumour size, mitotic index, risk classification, and KIT mutation status. The abundant immunohistochemical Fas and FasL expression were corroborated by western blot analysis. In conclusion, our data implicate Fas as a potential therapeutic target in GIST

    Nuclearity of rapidly decreasing ultradifferentiable functions and time-frequency analysis

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    [EN] We use techniques from time-frequency analysis to show that the space S(omega )of rapidly decreasing omega-ultradifferentiable functions is nuclear for every weight function omega(t) = o(t) as t tends to infinity. Moreover, we prove that, for a sequence (M-p)(p) satisfying the classical condition (M1) of Komatsu, the space of Beurling type S-(M)p when defined with L-2 norms is nuclear exactly when condition (M2)' of Komatsu holds.We thank the reviewer very much for the careful reading of our manuscript and the comments to improve the paper. The first three authors were partially supported by the Project FFABR 2017 (MIUR), and by the Projects FIR 2018 and FAR 2018 (University of Ferrara). The first and third authors are members of the Gruppo Nazionale per l'Analisi Matematica, la Probabilita e le loro Applicazioni (GNAMPA) of the Istituto Nazionale di Alta Matematica (INdAM). The research of the second author was partially supported by the project MTM2016-76647-P and the grant BEST/2019/172 from Generalitat Valenciana. The fourth author is supported by FWF-project J 3948-N35.Boiti, C.; Jornet Casanova, D.; Oliaro, A.; Schindl, G. (2021). Nuclearity of rapidly decreasing ultradifferentiable functions and time-frequency analysis. Collectanea mathematica. 72(2):423-442. https://doi.org/10.1007/s13348-020-00296-0S423442722Asensio, V., Jornet, D.: Global pseudodifferential operators of infinite order in classes of ultradifferentiable functions. Rev. R. Acad. Cienc. Exactas Fís. Nat. Ser. A Mat. RACSAM 113(4), 3477–3512 (2019)Aubry, J.-M.: Ultrarapidly decreasing ultradifferentiable functions, Wigner distributions and density matrices. J. London Math. Soc. 2(78), 392–406 (2008)Björck, G.: Linear partial differential operators and generalized distributions. Ark. Mat. 6(21), 351–407 (1966)Boiti, C., Jornet, D., Oliaro, A.: Regularity of partial differential operators in ultradifferentiable spaces and Wigner type transforms. J. Math. Anal. Appl. 446, 920–944 (2017)Boiti, C., Jornet, D., Oliaro, A.: The Gabor wave front set in spaces of ultradifferentiable functions. Monatsh. Math. 188(2), 199–246 (2019)Boiti, C., Jornet, D., Oliaro, A.: About the nuclearity of S(Mp)\cal{S}_{(M_{p})} and Sω\cal{S}_{\omega }. In: Boggiatto, P., et al. (eds.) Advances in Microlocal and Time-Frequency Analysis. Applied and Numerical Harmonic Analysis, pp. 121–129. Birkhäuser, Cham (2020)Boiti, C., Jornet, D., Oliaro, A.: Real Paley-Wiener theorems in spaces of ultradifferentiable functions. J. Funct. Anal. 278(4), 108348 (2020)Bonet, J., Meise, R., Melikhov, S.N.: A comparison of two different ways to define classes of ultradifferentiable functions. Bull. Belg. Math. Soc. Simon Stevin 14(3), 425–444 (2007)Braun, R.W., Meise, R., Taylor, B.A.: Ultradifferentiable functions and Fourier analysis. Result. Math. 17, 206–237 (1990)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators on non-quasianalytic classes of Beurling type. Studia Math. 167(2), 99–131 (2005)Fernández, C., Galbis, A., Jornet, D.: Pseudodifferential operators of Beurling type and the wave front set. J. Math. Anal. Appl. 340(2), 1153–1170 (2008)Franken, U.: Weight functions for classes of ultradifferentiable functions. Results Math. 25, 50–53 (1994)Gröchenig, K.: Foundations of Time-Frequency Analysis. Birkhäuser, Boston (2001)Gröchenig, K., Leinert, M.: Wiener’s Lemma for twisted convolution and Gabor frames. J. Am. Math. Soc. 17(1), 1–18 (2004)Gröchenig, K., Zimmermann, G.: Spaces of Test Functions via the STFT. J. Funct. Spaces Appl. 2(1), 25–53 (2004)Heinrich, T., Meise, R.: A support theorem for quasianalytic functionals. Math. Nachr. 280(4), 364–387 (2007)Hörmander, L.: Notions of Convexity. Progress in Mathematics, vol. 127. Birkhäuser, Boston (1994)Janssen, A.J.E.M.: Duality and Biorthogonality for Weyl-Heisenberg Frames. J. Fourier Anal. Appl. 1(4), 403–436 (1995)Komatsu, H.: Ultradistributions I. Structure theorems and a characterization. J. Fac. Sci. Univ. Tokyo Sect IA Math. 20, 25–105 (1973)Langenbruch, M.: Hermite functions and weighted spaces of generalized functions. Manuscripta Math. 119(3), 269–285 (2006)Meise, R., Vogt, D.: Introduction to Functional Analysis. Clarendon Press, Oxford (1997)Petzsche, H.J.: Die nuklearität der ultradistributionsräume und der satz vom kern I. Manuscripta Math. 24, 133–171 (1978)Pietsch, A.: Nuclear Locally Convex Spaces. Springer, Berlin (1972)Pilipović, S., Prangoski, B., Vindas, J.: On quasianalytic classes of Gelfand-Shilov type. Parametrix and convolution. J. Math. Pures Appl. 116, 174–210 (2018)Rodino, L.: Linear Partial Differential Operators in Gevrey Spaces. World Scientific Publishing Co. Inc, River Edge, NJ (1993)Rodino, L., Wahlberg, P.: The Gabor wave front set. Monatsh. Math. 173, 625–655 (2014)Schmets, J., Valdivia, M.: Analytic extension of ultradifferentiable Whitney jets. Collect. Math. 50(1), 73–94 (1999

    Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

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    BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function

    Evidence of means–end behavior in Asian elephants (Elephas maximus)

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    The present study explores to what extent Asian elephants show “means–end” behavior. We used captive Asian elephants (N = 2) to conduct four variations of the Piagetian “support” problem, which involves a goal object that is out of reach, but rests on a support within reach. In the first condition, elephants were simultaneously presented with two identical trays serving as the “support”, with the bait on one tray and the other tray left empty. In the next two conditions, the bait was placed on one tray, while additional bait was placed beside the other tray. In the last condition, both trays contained bait, but one of the trays had a small gap which prevented the elephants from reaching the reward. Subjects were required to choose and pull either tray with their trunk and to obtain the bait (i.e. goal). Results showed that one elephant performed all of the support problems significantly above chance after several sessions, suggesting that the elephant was capable of understanding that pulling the tray was the “means” for achieving the “end” of obtaining the bait. This study showed that elephants show means–end behavior when subjected to a Piagetian “support” task, and indicates that such goal-directed behavior occurs in species other than primates
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