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.     

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.     

Relations Between Derived Hochschild Functors via Twisting

Let be a regular ring, and let A, B be essentially finite type -algebras. For any functor F: D(ModA) × ? × D(ModA) → D(ModB) between their derived categories, we define its twist F^!: D(ModA) × ? × D(ModA) → D(ModB) with respect to dualizing complexes, generalizing Grothendieck's construction of f^!. We show that relations between functors are preserved between their twists, and deduce that various relations hold between derived Hochschild (co)-homology and the f^! functor. We also deduce that the set of isomorphism classes of dualizing complexes over a ring (or a scheme) form a group with respect to derived Hochschild cohomology, and that the twisted inverse image functor is a group homomorphism.     

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.     

Double-hybrid functionals for thermochemical kinetics

We propose two new double-hybrid functionals, denoted B2K-PLYP and mPW2K-PLYP, which yield thermochemical performance comparable to existing double-hybrid functionals but offer superior performance for barrier heights of various kinds. We show that the new functionals yield excellent performance for all of the following: (a) main-group thermochemistry; (b) main-group thermochemical kinetics; (c) late transition metal reactions. In addition, B2K-PLYP performs well for weak interactions.     

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.     

Lithium sulfide nanocrystals as cathode materials for advanced batteries

The ever-increasing need for sustainable development requires advanced battery techniques beyond the current generation of lithium ion batteries.Among all candi...     

Pairing-isopairing competition in odd-odd nuclei

We discuss the systematics of 0⁺, v = 0, T = |T_Z| + 1 levels in odd-odd nuclei and conclude about the ground state isospin and seniority of these nuclei. For N = Z nuclei starting from the $\text{1f}{}_{\mathrm{<mtext>7</mtext><mtext>2</mtext>}}$ shell v_g.s = 0 |T_g.s = |T_z + 1. Otherwise v_g.s = 2, T_g.s = |T_z|.