New upper bounds for the density of translative packings of three-dimensional convex bodies with tetrahedral symmetry

In this paper we determine new upper bounds for the maximal density of translative packings of superballs in three dimensions (unit balls for the $l_3^p$-norm) and of Platonic and Archimedean solids having tetrahedral symmetry. These bounds give strong indications that some of the lattice packings of superballs found in 2009 by Jiao, Stillinger, and Torquato are indeed optimal among all translative packings. We improve Zong's recent upper bound for the maximal density of translative packings of regular tetrahedra from $0.3840\ldots$ to $0.3745\ldots$, getting closer to the best known lower bound of $0.3673\ldots$. We apply the linear programming bound of Cohn and Elkies which originally was designed for the classical problem of packings of round spheres. The proofs of our new upper bounds are computational and rigorous. Our main technical contribution is the use of invariant theory of pseudo-reflection groups in polynomial optimization

The triterpene echinocystic acid and its 3-O-glucoside derivative are revealed as potent and selective glucocorticoid receptor agonists

Glucocorticoids are steroid hormones widely used to control many inflammatory conditions. These effects are primarily attributed to glucocorticoid receptor transrepressional activities but with concomitant receptor transactivation associated with considerable side effects. Accordingly, there is an immediate need for selective glucocorticoid receptor agonists able to dissociate transactivation from transrepression. Triterpenoids have structural similarities with glucocorticoids and exhibit anti-inflammatory and apoptotic activities via mechanisms that are not well-defined. In this study, we examined whether echinocystic acid and its 3-O-glucoside derivative act, at least in part, through the regulation of glucocorticoid receptor and whether they can constitute selective receptor activators. We showed that echinocystic acid and its glucoside induced glucocorticoid receptor nuclear translocation by 75% and 55%. They suppressed the nuclear factor-kappa beta transcriptional activity by 20% and 70%, respectively, whereas they have no glucocorticoid receptor transactivation capability and stimulatory effect on the expression of the phosphoenolopyruvate carboxykinase target gene in HeLa cells. Interestingly, their suppressive effect is diminished in glucocorticoid receptor low level COS-7 cells, verifying the receptor involvement in this process. Induced fit docking calculations predicted favorable binding in the ligand binding domain and structural characteristics which can be considered consistent with the experimental observations. Further, glucocorticoids exert apoptotic activities; we have demonstrated here that the echinocystic acids in combination with the synthetic glucocorticoid, dexamethasone, induce apoptosis. Taken together, our results indicate that echinocystic acids are potent glucocorticoid receptor regulators with selective transrepressional activities (dissociated from transactivation), highlighting the potential of echinocystic acid derivatives as more promising treatments for inflammatory conditions

Antiviral immunity in Drosophila requires systemic RNA interference spread.

Contains fulltext : 80137.pdf (publisher's version ) (Closed access)Multicellular organisms evolved sophisticated defence systems to confer protection against pathogens. An important characteristic of these immune systems is their ability to act both locally at the site of infection and at distal uninfected locations. In insects, such as Drosophila melanogaster, RNA interference (RNAi) mediates antiviral immunity. However, the antiviral RNAi defence in flies seems to be a local, cell-autonomous process, as flies are thought to be unable to generate a systemic RNAi response. Here we show that a recently defined double-stranded RNA (dsRNA) uptake pathway is essential for effective antiviral RNAi immunity in adult flies. Mutant flies defective in this dsRNA uptake pathway were hypersensitive to infection with Drosophila C virus and Sindbis virus. Mortality in dsRNA-uptake-defective flies was accompanied by 100-to 10(5)-fold increases in viral titres and higher levels of viral RNA. Furthermore, inoculating naked dsRNA into flies elicited a sequence-specific antiviral immune response that required an intact dsRNA uptake pathway. These findings suggest that spread of dsRNA to uninfected sites is essential for effective antiviral immunity. Notably, infection with green fluorescent protein (GFP)-tagged Sindbis virus suppressed expression of host-encoded GFP at a distal site. Thus, similar to protein-based immunity in vertebrates, the antiviral RNAi response in flies also relies on the systemic spread of a virus-specific immunity signal

New Upper Bounds for the Density of Translative Packings of Three-Dimensional Convex Bodies with Tetrahedral Symmetry

In this paper we determine new upper bounds for the maximal density of translative packings of superballs in three dimensions (unit balls for the $l^p_3$-norm) and of Platonic and Archimedean solids having tetrahedral symmetry. Thereby, we improve Zong's recent upper bound for the maximal density of translative packings of regular tetrahedra from $0.3840\ldots$ to $0.3745\ldots$, getting closer to the best known lower bound of $0.3673\ldots$ We apply the linear programming bound of Cohn and Elkies which originally was designed for the classical problem of densest packings of round spheres. The proofs of our new upper bounds are computational and rigorous. Our main technical contribution is the use of invariant theory of pseudo-reflection groups in polynomial optimization.Comment: 30 pages, 6 tables, 3 figures, (v3) comments of referees incorporate