505 research outputs found
The Evolution of Propaganda: Some Aspects of Political Practice
This article examines the evolution of propaganda since the ancient times until the present time as well as the ancient proto-propaganda The authors analyze the transitioning processes from the ancient times to early Christianity from the perspective of state ideology The article also studies the emergence of Protestantism and its role in the development of Capitalism and establishment of the 20th century economic system which the authors call the Keynes-Bernays economic model The newest propagandistic opportunities and the potential for processing big data is also reviewed The article explores the phenomenon of the recent decade social networks as a new instrument of propaganda In this work the authors used the systemic approach as well as the psychological method and the method of comparative historical analysis using modern terminology including the terms newly introduced by the authors which made it possible to improve the methodological foundation of the stud
Non-viral approaches to gene therapy
Several advances in non-viral gene transfer technology have been reported over the past year. Cationic lipids have been successfully used to deliver genes in vivo, providing a clear alternative to recombinant viruses. In addition, investigators have demonstrated that direct application of DNA via injection or particle bombardment can be used for vaccination. Analysis of the mechanisms employed by viruses to invade cells has demonstrated a crucial role for membrane-active proteins or peptides in the entry process. Several non-viral systems that include membrane-active elements are now available
DNA-condensation, redissolution and mesocrystals induced by tetravalent counterions
The distance-resolved effective interaction potential between two parallel
DNA molecules is calculated by computer simulations with explicit tetravalent
counterions and monovalent salt. Adding counterions first yields an attractive
minimum in the potential at short distances which then disappears in favor of a
shallower minimum at larger separations. The resulting phase diagram includes a
DNA-condensation and redissolution transition and a stable mesocrystal with an
intermediate lattice constant for high counterion concentration.Comment: 4 pages, 4 figure
DNA condensation and redissolution: Interaction between overcharged DNA molecules
The effective DNA-DNA interaction force is calculated by computer simulations
with explicit tetravalent counterions and monovalent salt. For overcharged DNA
molecules, the interaction force shows a double-minimum structure. The
positions and depths of these minima are regulated by the counterion density in
the bulk. Using two-dimensional lattice sum and free energy perturbation
theories, the coexisting phases for DNA bundles are calculated. A
DNA-condensation and redissolution transition and a stable mesocrystal with an
intermediate lattice constant for high counterion concentration are obtained.Comment: 26 pages, 10 figure
Solvent and thermal stability, and pH kinetics, of proline-specific dipeptidyl peptidase IV-like enzyme from bovine serum
Proline-specific dipeptidyl peptidase-like (DPP IV; EC 3.4.14.5) activity in bovine serum has attracted little attention despite its ready availability
and the paucity of useful proline-cleaving enzymes. Bovine serum DPP IV-like peptidase is very tolerant of organic solvents, particularly acetonitrile: upon incubation for 1 h at room temperature in 70% acetonitrile, 47% dimethylformamide, 54% DMSO and 33% tetrahydrofuran (v/v
concentrations) followed by dilution into the standard assay mixture, the enzyme retained half of its aqueous activity. As for thermal performance in aqueous buffer, its relative activity increased up to 50 ◦C. Upon thermoinactivation at 71 ◦C, pH 8.0 (samples removed periodically, cooled on ice, then assayed under optimal conditions), residual activities over short times fit a first-order decay with a k-value of 0.071±0.0034 min−1. Over
longer times, residual activities fit to a double exponential decay with k1 and k2 values of 0.218±0.025 min−1 (46±4% of overall decay) and 0.040±0.002 min−1 (54±4% of overall decay), respectively. The enzyme’s solvent and thermal tolerances suggest that it may have potential for use as a biocatalyst in industry. Kinetic analysis with the
fluorogenic substrate Gly-Pro-7-aminomethylcoumarin over a range of pH values indicated two pK values at 6.18±0.07 and at 9.70±0.50. We ascribe the lower value to the active site histidine; the higher may be due to the active site serine or to a free amino group in the substrate
Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder
Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P\u3c1×10−4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p \u3c 5×10−8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD
Solid-phase-assisted synthesis of targeting peptide-PEG-oligo(ethane amino)amides for receptor-mediated gene delivery.
In the forthcoming era of cancer gene therapy, efforts will be devoted to the development of new efficient and non-toxic gene delivery vectors. In this regard, the use of Fmoc/Boc-protected oligo(ethane amino)acids as building blocks for solid-phase-supported assembly represents a novel promising approach towards fully controlled syntheses of effective gene vectors. Here we report on the synthesis of defined polymers containing the following: (i) a plasmid DNA (pDNA) binding domain of eight succinoyl-tetraethylenpentamine (Stp) units and two terminal cysteine residues; (ii) a central polyethylene glycol (PEG) chain (with twenty-four oxyethylene units) for shielding; and (iii) specific peptides for targeting towards cancer cells. Peptides B6 and c(RGDfK), which bind transferrin receptor and αvβ3 integrin, respectively, were chosen because of the high expression of these receptors in many tumoral cells. This study shows the feasibility of designing these kinds of fully controlled vectors and their success for targeted pDNA-based gene transfer
Delivery of drugs, proteins and genes into cells using transferrin as a ligand for receptor-mediated endocytosis
Transferrin, an iron-transporting serum glycoprotein, is efficiently taken up into cells by the process of receptor-mediated endocytosis. Transferrin receptors are found on the surface of most proliferating cells, in elevated numbers on erythroblasts and on many kinds of tumors. The efficient cellular mechanism for uptake of transferrin has been subverted for the delivery of low-molecular-weight drugs, protein toxins, and liposomes by linkage of these agents to transferrin or to anti-transferrin receptor antibodies. Linkage may be via chemical conjugation procedures or by the generation of chimeric fusion proteins. Transferrin conjugated to DNA-binding compounds (e.g. polycations or intercalating agents) has been successfully used for the import of DNA molecules into cells. High-level gene expression is obtained only if endosome-disruptive agents such as influenza hemagglutinin peptides or adenovirus particles are included which release the DNA complex from intracellular vesicles into the cytoplasm
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