Curved geometry and Graphs

Quantum Graphity is an approach to quantum gravity based on a background independent formulation of condensed matter systems on graphs. We summarize recent results obtained on the notion of emergent geometry from the point of view of a particle hopping on the graph. We discuss the role of connectivity in emergent Lorentzian perturbations in a curved background and the Bose--Hubbard (BH) model defined on graphs with particular symmetries.Comment: are welcome. 4pp, 2 fig. Proceedings of Loops'11 Conference, Madri

Human immunodeficiency virus type-1 (HIV-1) infection increases the sensitivity of macrophages and THP-1 cells to cytotoxicity by cationic liposomes

AbstractCationic liposomes may be valuable for the delivery of anti-sense oligonucleotides, ribozymes, and therapeutic genes into human immunodeficiency virus type 1 (HIV-1)-infected and uninfected cells. We evaluated the toxicity of three cationic liposomal preparations, Lipofectamine, Lipofectin, and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DMRIE) reagent, to HIV-infected and uninfected cells. Monocyte/macrophages were infected with HIV-1BaL and treated with liposomes in medium containing 20% fetal bovine serum (FBS) for 4 h or 24 h at 37°C. Uninfected monocytic THP-1 cells and chronically infected THP-1/HIV-1IIIB cells were treated with phorbol 12-myristate 13-acetate (PMA) and exposed to liposomes in the presence of 10% FBS. Toxicity was evaluated by the Alamar Blue assay and viral p24 production. The toxic effect of cationic liposomes was very limited with uninfected cells, although concentrations of liposomes that were not toxic within a few days of treatment could cause toxicity at later times. In HIV-1Bal-infected macrophages, Lipofectamine (up to 8 μM) and Lipofectin (up to 40 μM) were not toxic after a 4-h treatment, while DMRIE reagent at 40 μM was toxic. While a 4-h treatment of THP-1 /HIV-1 IIIB cells with the cationic liposomes was not toxic, even up to 14 days post-treatment, all three cationic liposomes were toxic to cells at the highest concentration tested after a 24-h treatment. Similar results were obtained with the Alamar Blue assay, Trypan Blue exclusion and a method that enumerates nuclei. Infected cells with relatively high overall viability could be impaired in their ability to produce virions, indicating that virus production appears to be more sensitive to treatment with the cationic liposomes than cell viability. Our results indicate that HIV-infected cells are more susceptible than uninfected cells to killing by cationic liposomes. The molecular basis of this differential effect is unknown; it is proposed that alterations in cellular membranes during virus budding cause enhanced interactions between cationic liposomes and cellular membranes

Human immunodeficiency virus type-1 (HIV-1) infection increases the sensitivity of macrophages and THP-1 cells to cytotoxicity by cationic liposomes

Cationic liposomes may be valuable for the delivery of anti-sense oligonucleotides, ribozymes, and therapeutic genes into human immunodeficiency virus type 1 (HIV-1)-infected and uninfected cells. We evaluated the toxicity of three cationic liposomal preparations, Lipofectamine, Lipofectin, and 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide (DMRIE) reagent, to HIV-infected and uninfected cells. Monocyte/macrophages were infected with HTV-1(BaL) and treated with liposomes in medium containing 20% fetal bovine serum (FBS) for 4 h or 24 h at 37°C. Uninfected monocytic THP-1 cells and chronically infected THP-1/HIV-1(IIIB) cells were treated with phorbol 12-myristate 13-acetate (PMA) and exposed to liposomes in the presence of 10% FBS. Toxicity was evaluated by the Alamar Blue assay and viral p24 production. The toxic effect of cationic liposomes was very limited with uninfected cells, although concentrations of liposomes that were not toxic within a few days of treatment could cause toxicity at later times. In HIV-1(BaL)-infected macrophages, Lipofectamine (up to 8 μM) and Lipofectin (up to 40 μM) were not toxic after a 4-h treatment, while DMRIE reagent at 40 μM was toxic. While a 4-h treatment of THP-1/HIV-1(IIIB) cells with the cationic liposomes was not toxic, even up to 14 days post-treatment, all three cationic liposomes were toxic to cells at the highest concentration tested after a 24-h treatment. Similar results were obtained with the Alamar Blue assay, Trypan Blue exclusion and a method that enumerates nuclei. Infected cells with relatively high overall viability could be impaired in their ability to produce virions, indicating that virus production appears to be more sensitive to treatment with the cationic liposomes than cell viability. Our results indicate that HIV-infected cells are more susceptible than uninfected cells to killing by cationic liposomes. The molecular basis of this differential effect is unknown; it is proposed that alterations in cellular membranes during virus budding cause enhanced interactions between cationic liposomes and cellular membranes

Modeling the functional genomics of autism using human neurons.

Human neural progenitors from a variety of sources present new opportunities to model aspects of human neuropsychiatric disease in vitro. Such in vitro models provide the advantages of a human genetic background combined with rapid and easy manipulation, making them highly useful adjuncts to animal models. Here, we examined whether a human neuronal culture system could be utilized to assess the transcriptional program involved in human neural differentiation and to model some of the molecular features of a neurodevelopmental disorder, such as autism. Primary normal human neuronal progenitors (NHNPs) were differentiated into a post-mitotic neuronal state through addition of specific growth factors and whole-genome gene expression was examined throughout a time course of neuronal differentiation. After 4 weeks of differentiation, a significant number of genes associated with autism spectrum disorders (ASDs) are either induced or repressed. This includes the ASD susceptibility gene neurexin 1, which showed a distinct pattern from neurexin 3 in vitro, and which we validated in vivo in fetal human brain. Using weighted gene co-expression network analysis, we visualized the network structure of transcriptional regulation, demonstrating via this unbiased analysis that a significant number of ASD candidate genes are coordinately regulated during the differentiation process. As NHNPs are genetically tractable and manipulable, they can be used to study both the effects of mutations in multiple ASD candidate genes on neuronal differentiation and gene expression in combination with the effects of potential therapeutic molecules. These data also provide a step towards better understanding of the signaling pathways disrupted in ASD

Cationic liposome-mediated expression of HIV-regulated luciferase and diphtheria toxin a genes in HeLa cells infected with or expressing HIV

HIV-regulated expression of the diphtheria toxin A fragment gene (HIV-DT-A) is a potential gene therapy approach to AIDS. Since cationic liposomes are safe and non-immunogenic for in vivo gene delivery, we examined whether LipofectAMINE or DMRIE reagent could mediate the transfection of HIV-DT-A (pTHA43) or the HIV-regulated luciferase gene (pLUCA43) into HIV-infected or uninfected HeLa cells. pLUCA43 was expressed at a 103-fold higher level in HeLa/LAV cells than in uninfected HeLa cells, while the extent of expression of RSV-regulated luciferase was the same in both cell lines. Co-transfection of HeLa cells with pTHA43 and the proviral HIV clone, HXBΔBgl, resulted in complete inhibition of virus production. In contrast, the delivery of HIV-DT-A to chronically infected HeLa/LAV or HeLa/IIIB cells, or to HeLa CD4+ cells before infection, did not have a specific effect on virus production, since treatment of cells with control plasmids also reduced virus production. This reduction could be ascribed to cytotoxicity of the reagents. The efficiency of transfection, as measured by the percentage of cells expressing β-gal, was ~5%. Thus, cationic liposome mediated transfection was too inefficient to inhibit virus production when the DT-A was delivered by cationic liposomes to chronically- or de novo-infected cells. However, when both the virus and DT-A genes were delivered into the same cells by cationic liposomes, DT-A was very effective at inhibiting virus production. Our results indicate that the successful use of cationic liposomes for gene therapy will require the improvement of their transfection efficiency

Charging and coagulation of dust in protoplanetary plasma environments

Combining a particle-particle, particle-cluster and cluster-cluster agglomeration model with an aggregate charging model, the coagulation and charging of dust particles in various plasma environments relevant for proto-planetary disks have been investigated. The results show that charged aggregates tend to grow by adding small particles and clusters to larger particles and clusters, leading to greater sizes and masses as compared to neutral aggregates, for the same number of monomers in the aggregate. In addition, aggregates coagulating in a Lorentzian plasma (containing a larger fraction of high-energy plasma particles) are more massive and larger than aggregates coagulating in a Maxwellian plasma, for the same plasma densities and characteristic temperature. Comparisons of the grain structure, utilizing the compactness factor, {\phi}{\sigma}, demonstrate that a Lorentzian plasma environment results in fluffier aggregates, with small {\phi}{\sigma}, which exhibit a narrow compactness factor distribution. Neutral aggregates are more compact, with larger {\phi}{\sigma}, and exhibit a larger variation in fluffiness. Measurement of the compactness factor of large populations of aggregates is shown to provide information on the disk parameters that were present during aggregation

Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: The role of CD4, serum and liposome-cell interactions

We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV- 1) by liposomes composed of the cationic lipid N[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA-mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV-1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4-dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4- K562 and Raji cell lines

Extracting the equation of state from a microscopic non-equilibrium model

We study the thermodynamic properties of infinite nuclear matter with the Ultrarelativistic Quantum Molecular Dynamics (URQMD), a semiclassical transport model, running in a box with periodic boundary conditions. It appears that the energy density rises faster than $T^4$ at high temperatures of $T\approx 200-300$~MeV. This indicates an increase in the number of degrees of freedom. Moreover, We have calculated direct photon production in Pb+Pb collisions at 160~GeV/u within this model. The direct photon slope from the microscopic calculation equals that from a hydrodynamical calculation without a phase transition in the equation of state of the photon source.Comment: Proceedings of the XIV International Conference on Particles and Nuclei (PANIC'96), 22-28 May 1996, Williamsburg, Virginia, USA, to be published by World Scientific Publ. Co. (3 pages