Organic molecular beam deposition of oligophenyls on Au111: A study by X-ray absorption spectroscopy.

Near-edge X-ray absorption fine structure (NEXAFS) spectroscopy has been applied to reveal the molecular arrangement of ultrathin oligophenyl films [p-quaterphenyl (4P) and p-hexaphenyl (6P)] on Au(111). In the half-monolayer films the molecules lie flat on the surface but still have a considerable inter-ring twist of 30 degrees -40 degrees , similar to the gas-phase conformation. In the saturated monolayer film the second half of the molecules is side-tilted by an angle of less than 66 degrees with respect to the surface. This arrangement is already similar to that in bulk net planes of thicker films parallel to the surface, that is, the 4P(211) and 6P(21-3) planes, respectively.     

Intra-operative optical diagnostics with vibrational spectroscopy

Established methods for characterization of tissue and diagnostics, for example histochemistry, magnetic resonance imaging (MRI), X-ray tomography, or positron emission tomography (PET), are mostly not suitable for intra-operative use. However, there is a clear need for an intra-operative diagnostics especially to identify the borderline between normal and tumor tissue. Currently, vibrational spectroscopy techniques (both Raman and infrared) complement the standard methods for tissue diagnostics. Vibrational spectroscopy has the potential for intra-operative use, because it can provide a biochemically based profile of tissue in real time and without requiring additional contrast agents, which may perturb the tissue under investigation. In addition, no electric potential needs to be applied, and the measurements are not affected by electromagnetic fields. Currently, promising approaches include Raman fiber techniques and nonlinear Raman spectroscopy. Infrared spectroscopy is also being used to examine freshly resected tissue ex vivo in the operating theater. The immense volume of information contained in Raman and infrared spectra requires multivariate analysis to extract relevant information to distinguish different types of tissue. The promise and limitations of vibrational spectroscopy methods as intra-operative tools are surveyed in this review.     

Synthesis of a difunctional orthogonal coupler for the preparation of carbohydrate-functionalized sP(EO-stat-PO) hydrogels

The synthesis and characterization of a new difunctional coupler (4) based on trimethylolpropane (TMP) are described. The coupler is used to connect biologically active N-acetylglucosamine (GlcNAc) on amino-reactive microtiter plates and on star-shaped poly[(ethylene oxide)-stat-(propylene oxide)] hydrogel layers in microtiter plates. The biological activity of immobilized carbohydrates is determined using an enzyme-linked lectin assay.     

Classification of malignant gliomas by infrared spectroscopic imaging and linear discriminant analysis

Infrared (IR) spectroscopy provides a sensitive molecular fingerprint for tissue without external markers. Supervised classification models can be trained to identify the tissue type based on the spectroscopic fingerprint. Infrared imaging spectrometers equipped with multi-channel detectors combine the spectral and spatial information. Tissue areas of 4 x 4 mm(2) can be analyzed within a few minutes in the macroscopic imaging mode. An approach is described to apply this methodology to human astrocytic gliomas, which are graded according to their malignancy from one to four. Multiple IR images of three tissue sections from one patient with a malignant glioma are acquired and assigned to the six classes normal brain tissue, astrocytoma grade II, astrocytoma grade III, glioblastoma multiforme grade IV, hemorrhage, and other tissue by a linear discriminant analysis model which was trained by data from a single-channel detector. Before the model is applied here, the spectra are shown to be virtually identical. The first specimen contained approximately 95% malignant glioma regions, that means astrocytoma grade III or glioblastoma. The smaller percentage of 12-34% malignant glioma in the second specimen is consistent with its location at the tumor periphery. The detection of less than 0.2% malignant glioma in the third specimen points to a location outside the tumor. The results were correlated with the cellularity of the tissue which was obtained from the histopathologic gold standard. Potential applications of IR spectroscopic imaging as a rapid tool to complement established diagnostic methods are discussed.     

Fast and efficient in silico 3D screening: toward maximum computational efficiency of pharmacophore-based and shape-based approaches

In continuation of our recent studies on the quality of conformational models generated with CATALYST and OMEGA we present a large-scale survey focusing on the impact of conformational model quality and several screening parameters on pharmacophore-based and shape-based virtual high throughput screening (vHTS). Therefore, we collected known active compounds of CDK2, p38 MAPK, PPAR-gamma, and factor Xa and built a set of druglike decoys using ilib:diverse. Subsequently, we generated 3D structures using CORINA and also calculated conformational models for all compounds using CAESAR, CATALYST FAST, and OMEGA. A widespread set of 103 structure-based pharmacophore models was developed with LigandScout for virtual screening with CATALYST. The performance of both database search modes (FAST and BEST flexible database search) as well as the fit value calculation procedures (FAST and BEST fit) available in CATALYST were analyzed in terms of their ability to discriminate between active and inactive compounds and in terms of efficiency. Moreover, these results are put in direct comparison to the performance of the shape-based virtual screening platform ROCS. Our results prove that high enrichment rates are not necessarily in conflict with efficient vHTS settings: In most of the experiments, we obtained the highest yield of actives in the hit list when parameter sets for the fastest search algorithm were used.