Design of Optical-Imaging Probes by Screening of Diverse Substrate Libraries Directly in Disease-Tissue Extracts

Fluorescently quenched probes that are specifically activated in the cancer microenvironment have great potential application for diagnosis, early detection, and surgical guidance. These probes are often designed to target specific enzymes associated with diseases by direct optimization using single purified enzymes. However, this can result in painstaking chemistry efforts to produce a probe with suboptimal performance when applied in vivo. We describe here an alternate, unbiased activity-profiling approach in which whole tissue extracts are used to directly identify optimal peptide sequences for probe design. Screening of tumor extracts with a hybrid combinatorial substrate library (HyCoSuL) identified a combination of natural and non-natural amino-acid residues that was used to generate highly efficient tumor-specific probes. This new strategy simplifies and enhances the process of probe optimization without any a priori knowledge of enzyme targets and has the potential to be applied to diverse disease states using clinical or animal-model tissue samples.     

A Triptycene‐Based Approach to Solubilising Carbon Nanotubes and C60

We describe herein the synthesis of a triptycene‐based surfactant designed with the ability to solubilise single‐walled carbon nanotubes (SWNTs) and C₆₀ in water through non‐covalent interactions. Furthermore, an amphiphilic naphthalene‐based surfactant with the same ability to solubilise SWNTs and C₆₀ has also been prepared. The compounds synthesised were designed with either two ionic or non‐ionic tails to ensure a large number of supramolecular interactions with the solvent, thereby promoting strong solubilisation. The surfactants produced stable suspensions in which the SWNTs are dispersed and the surfactant/SWNT complexes formed are stable for more than one year. UV/Vis/NIR absorption spectroscopy, TEM and AFM were employed to probe the solubilisation properties of the dispersion of surfactants and SWNTs in water.     

Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression

A papillary‐structured collagen fibril membrane is created, mimicking the 3D‐architecture of the human papillary dermis. Primary human keratinocytes cultured to confluency on papillar‐structured films are compared to keratinocytes cultured on flat membranes. Microscopical evaluation reveals the presence of morphologically distinct cells at the base of the papillar structures that are not observed on flat membranes. Gene expression microarrays and RT‐qPCR indicate that these cells are in a more proliferative/migrational state, whereas cells on flat membranes have a more differentiated expression profile. Immunohistochemical stainings confirm these results. In conclusion, specific collagen architecture can direct keratinocyte behavior, and this may be used to further improve skin regeneration.

     

Electrostatic energy calculations by a Finite-difference method: Rapid calculation of charge–solvent interaction energies

Finite-difference Poisson–Boltzmann (FDPB) methods allow a fast and accurate calculations of the reaction field (charge–solvent) energies for molecular systems. Unfortunately, the energy in the FDPB calculations includes the self-energies and the finite-difference approximation to the Coulombic energies as well as the reaction field energy. A second finite-difference calculation, in a uniform dielectric, is therefore necesssary to eliminate these contributions. In this article we describe a rapid and accurate method to calculate the self energy and finite-difference Coulombic energies in a uniform dielectric thus eliminating the need for a second finite-difference calculation. The computational savings for this method range from a factor of 4 for a typical protein to a factor of 10³ for small molecules. © 1992 by John Wiley & Sons, Inc.     

Chemical toxicology searching: a comparative study of online data-bases

A collaborative project to compare and evaluate information resources and searching techniques for the retrieval of chemical toxicology information has been carried out by 14 organizations. The project involved independent searching of test queries, with subsequent extensive evaluation of results and failure analysis. The results relating particularly to online searching are presented and discussed.     

Analysis of the 33-133-133-1final state in photon-photon collisions

The reactione ⁺ e ^- e ⁺ e ^{- 00}e ⁺ e ^- 6 has been analysed using the full data sample taken with the Crystal Ball detector at the DORIS II storage ring at DESY. The ⁰⁰ invariant mass spectrum is dominated by the ', for which we determine the radiative width (') to be (4.5±0.3±0.5)keV. Near 1.9 GeV/c² we observe a second enhancement in the ⁰⁰ mass distribution. Assuming that these events are created by the production and subsequent decay of a wide resonanceX(1900), we have investigated the decay modes, the invariant mass distributions of the ⁰ and ⁰⁰ subsystems and the angular distributions of the final state mesons. We find that the data is best described byJ ^PC=2. For thisJ ^P assignment the resonance parameters are (X) BR(X)=(0.95±0.27±0.20) keV _tot (X)=(221±92±44)MeV, andM(X)=(1881±32±40) MeV/c².Deceased