The triazatruxene derivative azatrux binds to the parallel form of the human telomeric G-quadruplex under molecular crowding conditions: Biophysical and molecular modeling studies

The present study has employed a combination of spectroscopic, calorimetric and computational methods to explore the binding of the three side-chained triazatruxene derivative, termed azatrux, to a human telomeric G-quadruplex sequence, under conditions of molecular crowding. The binding of azatrux to the tetramolecular parallel [d(TGGGGT)](4) quadruplex in the presence and absence of crowding conditions, was also characterized. The data indicate that azatrux binds in an end-stacking mode to the parallel G-quadruplex scaffold and highlights the key structural elements involved in the binding. The selectivity of azatrux for the human telomeric G-quadruplex relative to another biologically relevant G-quadruplex (c-Kit87up) and to duplex DNA was also investigated under molecular crowding conditions, showing that azatrux has good selectivity for the human telomeric G-quadruplex over the other investigated DNA structures. (C) 2011 Elsevier Masson SAS. All rights reserved.

A TMA De-Arraying Method for High Throughput Biomarker Discovery in Tissue Research

Background: Tissue MicroArrays (TMAs) represent a potential high-throughput platform for the analysis and discovery of tissue biomarkers. As TMA slides are produced manually and subject to processing and sectioning artefacts, the layout of TMA cores on the final slide and subsequent digital scan (TMA digital slide) is often disturbed making it difficult to associate cores with their original position in the planned TMA map. Additionally, the individual cores can be greatly altered and contain numerous irregularities such as missing cores, grid rotation and stretching. These factors demand the development of a robust method for de-arraying TMAs which identifies each TMA core, and assigns them to their appropriate coordinates on the constructed TMA slide.

Methodology: This study presents a robust TMA de-arraying method consisting of three functional phases: TMA core segmentation, gridding and mapping. The segmentation of TMA cores uses a set of morphological operations to identify each TMA core. Gridding then utilises a Delaunay Triangulation based method to find the row and column indices of each TMA core. Finally, mapping correlates each TMA core from a high resolution TMA whole slide image with its name within a TMAMap.

Conclusion: This study describes a genuine robust TMA de-arraying algorithm for the rapid identification of TMA cores from digital slides. The result of this de-arraying algorithm allows the easy partition of each TMA core for further processing. Based on a test group of 19 TMA slides (3129 cores), 99.84% of cores were segmented successfully, 99.81% of cores were gridded correctly and 99.96% of cores were mapped with their correct names via TMAMaps. The gridding of TMA cores were also extensively tested using a set of 113 pseudo slide (13,536 cores) with a variety of irregular grid layouts including missing cores, rotation and stretching. 100% of the cores were gridded correctly.

Experimental validation of the performance of a microreactor for the high-throughput screening of catalytic coatings

In this paper, the results of computational fluid dynamics simulations of flow, temperature, and concentration distributions used in the design of a microreactor for the high-throughput screening of catalytic coatings (Mies et al., Chem. Eng. J. 2004, 101, 225) are compared with experimental data, and good agreement is obtained in all cases. The experimental results on flow distribution were obtained from laser Doppler anemometry measurements in the range of Reynolds numbers from 6 to 113. The measured flow nonuniformity in the separate reactor compartments was below 2%. The temperature distribution was obtained from thermocouple measurements. The temperature nonuniformity between the reactor compartments was below 3 K at a maximum heat production rate of 1.3 W in ethylene oxidation at 425 degrees C over CuO/Al2O3/Al coatings. With respect to concentration gradients, a deviation from the average rate of reaction of only 2.3% was obtained at realistic process conditions in the ethylene ammoxidation process over identical Co-ZSM-5 coatings in all reactor compartments. The cross talking noise between separate compartments does not exceed 0.1% when the reactor parts have a smooth surface finish. This illustrates the importance of ultraprecision machining of surfaces in microtechnology, when interfaces cannot be avoided.

Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu(4) positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu(4) positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date. (C) 2010 Elsevier Ltd. All rights reserved.

Evaluating the impact of network density, hidden nodes and capture effect for throughput guarantee in multi-hop wireless networks

To optimize the performance of wireless networks, one needs to consider the impact of key factors such as interference from hidden nodes, the capture effect, the network density and network conditions (saturated versus non-saturated). In this research, our goal is to quantify the impact of these factors and to propose effective mechanisms and algorithms for throughput guarantees in multi-hop wireless networks. For this purpose, we have developed a model that takes into account all these key factors, based on which an admission control algorithm and an end-to-end available bandwidth estimation algorithm are proposed. Given the necessary network information and traffic demands as inputs, these algorithms are able to provide predictive control via an iterative approach. Evaluations using analytical comparison with simulations as well as existing research show that the proposed model and algorithms are accurate and effective.