Observation of new bands in the N2 Herman infrared system and kinetic study of its formation in a pulsed-discharge apparatus

Four new bands of the unassigned N₂ Herman infrared system (HIR) are observed in a pulsed-discharge apparatus. The upper HIR state is produced by the N₂(A) + N₂(A) energy pooling reaction which is studied by time-resolved spectroscopy; its production rate constant is found to be ?4 × 10^?11 cm³ molecule^?1 s^?1 and its energy $\text{}\text{?}$12eV.     

The azaquinone-methide elimination: comparison study of 1,6- and 1,4-eliminations under physiological conditions

The azaquinone-methide elimination is a powerful and efficient reaction useful for disassembly of spacers in prodrug systems. We and others have used the spacer-technique to develop dendritic and polymeric self-immolative molecular systems that can disassemble through a domino-like mechanism upon a stimulus event. In this report, we study the disassembly of a system that can disintegrate through para- and ortho-azaquinone-methide eliminations. The disassembly was evaluated with molecules that undergo single 1,6- or 1,4-elimination and with molecules that undergo double 1,6- and 1,4-elimination. The 1,6-elimination was slightly faster than the 1,4-elimination under physiological conditions. This study sheds light on the disassembly-behavior of prodrug systems.     

Bacterial membranes as predictors of antimicrobial potency

A wide range of chemical structures having antimicrobial activity have been studied in an effort to treat the increasing emergence of bacteria that are resistant to traditional antibiotics. These agents have varying degrees of toxicity against different bacterial species. We demonstrate, using members of a novel class of antimicrobial agents, the oligomers of acyllysine, that one cause for the difference in species selectivity is the ability to induce the clustering of anionic lipids, resulting in their segregation into domains. This phenomenon occurs only in bacterial membranes composed of both anionic and zwitterionic lipids and not with bacteria whose membrane lipids are largely anionic. As a consequence it can be predicted which bacterial species will be most affected by antimicrobial agents that function principally by this mechanism. This finding allows for the design of new antibiotics with selective toxicity against different groups of bacteria.     

Integrating proteomics with electrochemistry for identifying kinase biomarkers

We present an integrated approach for highly sensitive identification and validation of substrate-specific kinases as cancer biomarkers. Our approach combines phosphoproteomics for high throughput cancer-related biomarker discovery from patient tissues and an impedimetric kinase activity biosensor for sensitive validation. Using non-small-cell lung cancer (NSCLC) as a proof-of-concept study, label-free quantitative phosphoproteomic analysis of a pair of cancerous and its adjacent normal tissues revealed 198 phosphoproteins that are over-phosphorylated in NSCLC. Among the differentially regulated phosphorylation sites, the most significant alteration was in residue S165 in the Hepatoma Derived Growth Factor (HDGF) protein. Hence, HDGF was selected as a model system for the electrochemical studies. Further motif-based analysis of this altered phosphorylation site revealed that extracellular-signal-regulated kinase 1/2 (ERK1/2) are most likely to be the corresponding kinases. For validation of the kinase–substrate pair, densely packed peptide monolayers corresponding to the HDGF phosphorylation site were coupled to a gold electrode. Phosphorylation of the monolayer by ERK2 and dephosphorylation by alkaline phosphatase (AP) were detected by electrochemical impedance spectroscopy (EIS) and surface roughness analysis. Compared to other methods for quantification of kinase concentration, this label-free electrochemical assay offers the advantages of ultra-sensitivity as well as higher specificity for the detection of cancer-related kinase–substrate pair. With implementation of multiple kinase–substrate biomarker pairs, we expect this integrated approach to become a high throughput platform for discovery and validation of phosphorylation-mediated biomarkers.     

Observation of restricted diffusion in the presence of a free diffusion compartment: Single- and double-PFG experiments

Theoretical and experimental studies of restricted diffusion have been conducted for decades using single pulsed field gradient (s-PFG) diffusion experiments. In homogenous samples, the diffusion–diffraction phenomenon arising from a single population of diffusing species has been observed experimentally and predicted theoretically. In this study, we introduce a composite bi-compartmental model which superposes restricted diffusion in microcapillaries with free diffusion in an unconfined compartment, leading to fast and slow diffusing components in the NMR signal decay. Although simplified (no exchange), the superposed diffusion modes in this model may exhibit features seen in more complex porous materials and biological tissues. We find that at low q-values the freely diffusing component masks the restricted diffusion component, and that prolongation of the diffusion time shifts the transition from free to restricted profiles to lower q-values. The effect of increasing the volume fraction of freely diffusing water was also studied; we find that the transition in the signal decay from the free mode to the restricted mode occurs at higher q-values when the volume fraction of the freely diffusing water is increased. These findings were then applied to a phantom consisting of crossing fibers, which demonstrated the same qualitative trends in the signal decay. The angular d-PGSE experiment, which has been recently shown to be able to measure small compartmental dimensions even at low q-values, revealed that microscopic anisotropy is lost at low q-values where the fast diffusing component is prominent. Our findings may be of importance in studying realistic systems which exhibit compartmentation.     

On the Interactive Capacity of Finite-State Protocols

The interactive capacity of a noisy channel is the highest possible rate at which arbitrary interactive protocols can be simulated reliably over the channel. Determining the interactive capacity is notoriously difficult, and the best known lower bounds are far below the associated Shannon capacity, which serves as a trivial (and also generally the best known) upper bound. This paper considers the more restricted setup of simulating finite-state protocols. It is shown that all two-state protocols, as well as rich families of arbitrary finite-state protocols, can be simulated at the Shannon capacity, establishing the interactive capacity for those families of protocols.     

Orientations of circle graphs

Let C(v₁, …,v_n) be a system consisting of a circle C with chords v₁, …,v_n on it having different endpoints. Define a graph G having vertex set V(G) = {v₁, …,v_n} and for which vertices v_i and v_j are adjacent in G if the chords v_i and v_j intersect. Such a graph will be called a circle graph. The chords divide the interior of C into a number of regions. We give a method which associates to each such region an orientation of the edges of G. For a given C(v₁, …,v_n) the number m of different orientations corresponding to it satisfies q + 1 ≤ m ≤ n + q + 1, where q is the number of edges in G. An oriented graph obtained from a diagram C(v₁, …,v_n) as above is called an oriented circle graph (OCG). We show that transitive orientations of permutation graphs are OCGs, and give a characterization of tournaments which are OCGs. When the region is a peripheral one, the orientation of G is acyclic. In this case we define a special orientation of the complement of G, and use this to develop an improved algorithm for finding a maximum independent set in G.     

Muqubilin,a new c24-isoprenoid from a marine sponge

The Red Sea sponge $\text{Prianos}$ sp. contains a cyclic peroxide C₂₄ - nor sesterterpene, Muqubilin ($\text{1}$). The structure of $\text{1}$ was deduced from spectroscopic data and by chemical degradation.