Mott insulators without symmetry breaking

We present theoretical models, in one and two space dimensions, that exhibit Mott insulating ground states at fractional occupations without any symmetry breaking. The Hamiltonians of these models are nonlocal in configuration space, but local in phase space.     

Design and evaluation of a real-time activity probe for focal adhesion kinase

Focal adhesion kinase (FAK) has been identified as a potential therapeutic target for the treatment of metastatic cancers. Herein we describe the design, synthesis and optimization of a direct activity sensor for FAK and its application to screening FAK inhibitors. We find that the position of the sensing moiety, a phosphorylation-sensitive sulfonamido-oxine fluorophore, can dramatically influence the performance of peptide sensors for FAK. Real-time fluorescence activity assays using an optimized sensor construct, termed FAKtide-S2, are highly reproducible (Z' = 0.91) and are capable of detecting as little as 1 nM recombinant FAK. Utilizing this robust assay format, we define conditions for the screening of FAK inhibitors and demonstrate the utility of this platform using a set of well-characterized small molecule kinase inhibitors. Additionally, we provide the selectivity profile of FAKtide-S2 among a panel of closely related enzymes, identifying conditions for selectively monitoring FAK activity in the presence of off-target enzymes. In the long term, the chemosensor platform described in this work can be used to identify novel FAK inhibitor scaffolds and potentially assess the efficacy of FAK inhibitors in disease models.     

Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging

Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.     

Copper(II) cyclam-based complexes for radiopharmaceutical applications: synthesis and structural analysis

Two molecular structures of the copper(II) complex, Cu(H(2)TETA), have been determined by X-ray crystallography. The Jahn-Teller distortion differs between the two structures; occurring either along the axis of the pendant acetate arms or across the macrocyclic ring. An analysis of deposited data from over one hundred copper(II) cyclam X-ray structures in the Cambridge Structural Database (CSD) reveals that Jahn-Teller distortion across the ring is highly unusual for such compounds in the solid state. Novel chelators based on the piperazino/side-bridged cyclam have been prepared and copper(II) complexes formed. The single crystal X-ray structures of two copper(II) complexes, with either an ester or acid N-pendant arm, have been determined and in both cases the pendant arm is bound to the metal centre.     

Dual functional, polymeric self-assembled monolayers as a facile platform for construction of patterns of biomolecules

We report a facile approach to the construction of patterns of biomolecules based on polymeric self-assembled monolayers (pSAMs) that possess dual functions: "bio-reactive (post-functionalizable)" and "bio-inert (anti-biofouling)" properties. To prepare pSAMs on Si/SiO2 wafers were synthesized new random copolymers by radical polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA), 3-(trimethoxysilyl)propyl methacrylate (TMSMA), and N-acryloxysuccinimide (NAS), and referred to as poly(TMSMA-r-PEGMA-r-NAS). Poly(TMSMA-r-PEGMA-r-NAS) was designed to play triple roles: "surface-reactive", "bio-reactive", and "bio-inert" ones. The pSAMs of poly(TMSMA-r-PEGMA-r-NAS) were formed on Si/SiO2 wafers with 1 h incubation of the substrates in the polymer solution, which showed approximately a 1 nm-thick film as measured by ellipsometry. After the formation of the pSAMs, the feasibility of the pSAMs as a dual functional surface (bio-inert and bio-reactive properties) was examined. The ability of the pSAMs to block nonspecific adsorption of proteins was evaluated against bovine serum albumin as a model protein. High-resolution N(1s) X-ray photoelectron spectroscopy (XPS) analysis on the protein adsorption revealed that significant reduction up to approximately 97% was observed compared to the unmodified Si/SiO2 wafer. In addition, micropatterns of streptavidin with high signal-to-noise ratios were achieved using microcontact printing (microCP) of NH2-bearing biotin onto the pSAMs of poly(TMSMA-r-PEGMA-r-NAS) on glass slides, which suggests that other biomolecules could also be efficiently immobilized onto the pSAMs with high specificity while minimizing nonspecific adsorption. On the other hand, the surface density of both bio-reactive and anti-biofouling functionality could be tailored by simply changing initial feed ratios of each monomer in the polymer synthesis: different molar ratios of the bio-reactive group (NAS: 33%, 20%, and 10%, respectively) were employed. When micropatterns of streptavidin were constructed, the pSAMs with 33% NAS moiety showed the highest immobilization of the protein. Taken together, the present dual functional, random copolymers may have warrant applications in the field of biosensors and biochips.     

Rapidly reversible hydrophobization: an approach to high first-pass drug extraction

We have investigated a rapidly reversible hydrophobization of therapeutic agents for improving first-pass uptake in locoregional drug therapy. This approach involves the attachment of a hydrophobic moiety to the drug by highly labile chemical linkages that rapidly hydrolyze upon injection. Hydrophobization drastically enhances cell-membrane association of the prodrug and, consequently, drug uptake, while the rapid lability protects nontargeted tissues from exposure to the highly active agent. Using the membrane-impermeable DNA intercalator propidium iodide, and melphalan, we report results from in vitro cellular internalization and toxicity studies. Additionally, we report in vivo results after a single liver arterial bolus injection, demonstrating both tumor targeting and increased survival in a mouse tumor model.     

Finite volume simulation of blood flow through complete bypass models

The presented study introduces the problem of steady blood flow through various idealized bypass models in dependence on several geometrical and flow parameters. The changes in hemodynamics are observed with regard to the occurrence of intimal hyperplasia at the distal anastomosis, which is known to be the main reason for late bypass failure. All numerical simulations were performed using the own developed computational software based on the finite volume method. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Membrane desolvation for the analysis of organic solutions and liquid chromatographic samples with low power helium microwave induced plasma atomic emission detection

A flat sheet membrane desolvator (FSMD) was used to extend the applicability of a 120 W helium microwave induced plasma (He-MIP) to elemental analysis of organic-solvent-based samples and element selective liquid chromatographic detection. With the FSMD on-line, methanol could be nebulized with a sample flow rate of 1.5 ml/min and a carrier gas flow rate of 1.2 l/min without extinguishing the plasma. Under these conditions, applying desolvator countercurrent gas flows in the range 0–8 l/min restored of the original pink color of the pure helium MIP from the bluish-green caused by methanol. Significant reductions in the emission intensities of C₂ species at 436.5, 473.7, 512.9, and 563.6 nm were observed with the application of the FSMD. The intensities of chlorine analyte emission lines at 479.5, 481.0 and 481.9 nm increased with increasing countercurrent gas flow rates and reached a maximum intensity with a flow rate of 5.0 l/min. Detection limits for Cl and Pb were 2.1 and 0.1 ppm using a 1 m focal length monochromator. Other elements and solvent combinations were also examined. Element selective liquid chromatographic detection was preliminarily examined by monitoring 2,6-dichlorobenzene and 5,7-dichlorohydroxyquinoline at the 479.5 nm Cl atomic emission line. Chlorine detection limits in the 3–7 μg range (70–190 ng/s) were obtained.