The structure of propadienone (CH2CCO)

A complete r_o structure has been obtained for propadienone (CH₂CCCO) with the aid of ab initio molecular-orbital calculations. The effect of electron correlation has been investigated using third order Møller-Plesset perturbation theory. The molecule is found to be planar bent (CCC145°) and the calculated structure yields rotational constants which are in good agreemant with experimental values.     

On the boundedness of rough oscillatory singular integrals on Triebel-Lizorkin spaces

We obtain appropriate sharp bounds on Triebel-Lizorkin spaces for rough oscillatory integrals with polynomial phase. By using these bounds and using an extrapolation argument we obtain some new and previously known results for oscillatory integrals under very weak size conditions on the kernel functions.     

Atom-scale ptychographic electron diffractive imaging of boron nitride cones

Ptychographic coherent diffractive imaging (CDI) has been extensively applied using both x rays and electrons. The extension to atomic resolution has been elusive. This Letter demonstrates ptychographic electron diffractive imaging at atomic resolution, permitting identification of structure in a boron nitride helical cone at a resolution of order 1 ?, beyond that of comparative Z-contrast images. A scanning transmission electron microscope is used to create a diverging illumination in a defocused Fresnel CDI geometry, providing a robust strategy leading to a unique solution.     

Empirical analysis of the evolution of a scientific collaboration network

We present an analysis of the temporal evolution of a scientific coauthorship network, the genetic programming network. We find evidence that the network grows according to preferential attachment, with a slightly sublinear rate. We empirically find how a giant component forms and develops, and we characterize the network by several other time-varying quantities: the mean degree, the clustering coefficient, the average path length, and the degree distribution. We find that the first three statistics increase over time in the growing network; the degree distribution tends to stabilize toward an exponentially truncated power-law. We finally suggest an effective network interpretation that takes into account the aging of collaboration relationships.     

MAOS ls for the general synthesis and lead optimization of 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines

General, high-yielding MAOS protocols for the expedient synthesis of functionalized 3,6-disubstituted-[1,2,4]triazolo[4,3-b]pyridazines are described amenable to an iterative analog library synthesis strategy for the lead optimization of an M1 antagonist screening hit. Optimized compounds proved to be highly selective M1 antagonists.     

A study on the interactions of Aurein 2.5 with bacterial membranes

Aurein 2.5 (GLFDIVKKVVGAFGSL-NH₂) is an uncharacterised antimicrobial peptide. At an air/water interface, it exhibited strong surface activity (maximal surface pressure 25 mN m⁻¹) and molecular areas consistent with the adoption of α-helical structure orientated either perpendicular (1.72 nm² molecule⁻¹) or parallel (3.6 nm² molecule⁻¹) to the interface. Aurein 2.5 was strongly antibacterial, exhibiting a minimum inhibitory concentration (MIC) of 30 μM against Bacillus subtilis and Escherichia coli. The peptide induced maximal surface pressure changes of 9 mN m⁻¹ and 5 mN m⁻¹, respectively, in monolayers mimicking membranes of these organisms whilst compression isotherm analysis of these monolayers showed ΔG_Mix > 0, indicating destabilisation by Aurein 2.5. These combined data suggested that toxicity of the peptide to these organisms may involve membrane invasion via the use of oblique orientated α-helical structure. The peptide induced strong, comparable maximal surface changes in monolayers of DOPG (7.5 mN m⁻¹) and DOPE monolayers (6 mN m⁻¹) suggesting that the membrane interactions of Aurein 2.5 were driven by amphiphilicity rather than electrostatic interaction. Based on these data, it was suggested that the differing ability of Aurein 2.5 to insert into membranes of B. subtilis and E. coli was probably related to membrane-based factors such as differences in lipid packing characteristics. The peptide was active against both sessile E. coli and Staphylococcus aureus with an MIC of 125 μM. The broad-spectrum antibacterial activity and non-specific modes of membrane action used by Aurein 2.5 suggested use as an anti-biofilm agent such as in the decontamination of medical devices.     

Rapid parallel synthesis of combinatorial libraries of substituted 3-thio-1,2,4-triazoles and 2-thioimidazoles

Combinatorial libraries of substituted 3-thio-1,2,4-triazoles and 2-thioimidazoles were synthesized in good yield by alkylation of the products via the reaction of isothiocyanates and carboxylic acid hydrazides or beta-aminoketones, respectively. A total of 275 3-thio-1,2,4-triazoles and 283 2-thioimidazoles were synthesized out of the attempted 288 in each case. Most the yields were between 45% and 98%, and all the compounds synthesized were purified to >85% purity. Variations in yields revealed no definitive trends and were mainly attributed to bulky alkylating agents used and the plate well location of the reaction mixtures.     

Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice

Background  

Proteolytic degradation has emerged as a key pathway involved in controlling levels of the Alzheimer's disease (AD)-associated amyloid-β (Aβ) peptide in the brain. The endopeptidase, neprilysin, has been implicated as a major Aβ degrading enzyme in mice and humans. Previous short and intermediate term studies have shown the potential therapeutic application of neprilysin by delivering this enzyme into the brain of APP transgenic mice using gene transfer with viral vectors. However the effects of long-term neprilysin gene transfer on other aspects of Aβ associated pathology have not been explored yet in APP transgenic mice.