7,546 research outputs found

    Triviality of the ground-state metastate in long-range Ising spin glasses in one dimension

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    We consider the one-dimensional model of a spin glass with independent Gaussian-distributed random interactions, that have mean zero and variance 1/ij2σ1/|i-j|^{2\sigma}, between the spins at sites ii and jj for all iji\neq j. It is known that, for σ>1\sigma>1, there is no phase transition at any non-zero temperature in this model. We prove rigorously that, for σ>3/2\sigma>3/2, any Newman-Stein metastate for the ground states (i.e.\ the frequencies with which distinct ground states are observed in finite size samples in the limit of infinite size, for given disorder) is trivial and unique. In other words, for given disorder and asymptotically at large sizes, the same ground state, or its global spin flip, is obtained (almost) always. The proof consists of two parts: one is a theorem (based on one by Newman and Stein for short-range two-dimensional models), valid for all σ>1\sigma>1, that establishes triviality under a convergence hypothesis on something similar to the energies of domain walls, and the other (based on older results for the one-dimensional model) establishes that the hypothesis is true for σ>3/2\sigma>3/2. In addition, we derive heuristic scaling arguments and rigorous exponent inequalities which tend to support the validity of the hypothesis under broader conditions. The constructions of various metastates are extended to all values σ>1/2\sigma>1/2. Triviality of the metastate in bond-diluted power-law models for σ>1\sigma>1 is proved directly.Comment: 18 pages. v2: subsection on bond-diluted models added, few extra references. 19 pages. v3: published version; a few changes; 20 page

    Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus

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    Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known.Methods: Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively.Results: BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs.Conclusions: Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE. © 2010 Nie et al.; licensee BioMed Central Ltd.published_or_final_versio

    Bursty egocentric network evolution in Skype

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    In this study we analyze the dynamics of the contact list evolution of millions of users of the Skype communication network. We find that egocentric networks evolve heterogeneously in time as events of edge additions and deletions of individuals are grouped in long bursty clusters, which are separated by long inactive periods. We classify users by their link creation dynamics and show that bursty peaks of contact additions are likely to appear shortly after user account creation. We also study possible relations between bursty contact addition activity and other user-initiated actions like free and paid service adoption events. We show that bursts of contact additions are associated with increases in activity and adoption - an observation that can inform the design of targeted marketing tactics.Comment: 7 pages, 6 figures. Social Network Analysis and Mining (2013

    Why social networks are different from other types of networks

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    We argue that social networks differ from most other types of networks, including technological and biological networks, in two important ways. First, they have non-trivial clustering or network transitivity, and second, they show positive correlations, also called assortative mixing, between the degrees of adjacent vertices. Social networks are often divided into groups or communities, and it has recently been suggested that this division could account for the observed clustering. We demonstrate that group structure in networks can also account for degree correlations. We show using a simple model that we should expect assortative mixing in such networks whenever there is variation in the sizes of the groups and that the predicted level of assortative mixing compares well with that observed in real-world networks.Comment: 9 pages, 2 figure

    Networks based on collisions among mobile agents

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    We investigate in detail a recent model of colliding mobile agents [Phys. Rev. Lett.~96, 088702], used as an alternative approach to construct evolving networks of interactions formed by the collisions governed by suitable dynamical rules. The system of mobile agents evolves towards a quasi-stationary state which is, apart small fluctuations, well characterized by the density of the system and the residence time of the agents. The residence time defines a collision rate and by varying the collision rate, the system percolates at a critical value, with the emergence of a giant cluster whose critical exponents are the ones of two-dimensional percolation. Further, the degree and clustering coefficient distributions and the average path length show that the network associated with such a system presents non-trivial features which, depending on the collision rule, enables one not only to recover the main properties of standard networks, such as exponential, random and scale-free networks, but also to obtain other topological structures. Namely, we show a specific example where the obtained structure has topological features which characterize accurately the structure and evolution of social networks in different contexts, ranging from networks of acquaintances to networks of sexual contacts.Comment: 12 pages, 17 figure

    Structure of a large social network

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    We study a social network consisting of over 10410^4 individuals, with a degree distribution exhibiting two power scaling regimes separated by a critical degree kcritk_{\rm crit}, and a power law relation between degree and local clustering. We introduce a growing random model based on a local interaction mechanism that reproduces all of the observed scaling features and their exponents. Our results lend strong support to the idea that several very different networks are simultenously present in the human social network, and these need to be taken into account for successful modeling.Comment: 5 pages, 5 figure

    The major brain cholesterol metabolite 24(s)-hydroxycholesterol is a potent allosteric modulator of N-methyl-d-aspartate receptors

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    N-methyl-d-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABA(A) receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μm. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development

    Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs

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    Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.National Institute for Biomedical Imaging and Bioengineering (U.S.)National Institutes of Health (U.S.)AXA Research Fund (Postdoctoral Fellowship)National Research Foundation of Korea (Postdoctoral Fellowship 2013R1A6A3A03)National Research Foundation of Korea (Grant 2009-0080734
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