All-fibre optical system for exciting and detecting the vibration of silicon microresonator sensors

An all-fibre optical system for optical interrogation and detection of the vibrations of a silicon microresonator is reported. Metal-coated silicon microresonators are excited by intensity modulated laser light delivered through an optical fibre, while the vibration of the resonators is detected by an optical fibre interferometer. Measurements have shown that an average optical power of 10 μW is sufficient to maintain the flexural vibration of the resonator. When the resonator is used as a pressure sensor, its resonant frequency changes from 62 kHz to 130 kHz as the pressure varies from -0°6 bar to 1 bar (gauge). A silicon resonator with 700 nm aluminium coating functions as a temperature sensor, showing a frequency shift from 262 kHz to 251 kHz when the temperature changes from 25 °C to 80 °C.     

Discovery of Cell‐Permeable Inhibitors That Target the BRCT Domain of BRCA1 Protein by Using a Small‐Molecule Microarray

BRCTs are phosphoserine‐binding domains found in proteins involved in DNA repair, DNA damage response and cell cycle regulation. BRCA1 is a BRCT domain‐containing, tumor‐suppressing protein expressed in the cells of breast and other human tissues. Mutations in BRCA1 have been found in ca. 50 % of hereditary breast cancers. Cell‐permeable, small‐molecule BRCA1 inhibitors are promising anticancer agents, but are not available currently. Herein, with the assist of microarray‐based platforms, we have discovered the first cell‐permeable protein–protein interaction (PPI) inhibitors against BRCA1. By targeting the (BRCT)₂ domain, we showed compound 15 a and its prodrug 15 b inhibited BRCA1 activities in tumor cells, sensitized these cells to ionizing radiation‐induced apoptosis, and showed synergistic inhibitory effect when used in combination with Olaparib (a small‐molecule inhibitor of poly‐ADP‐ribose polymerase) and Etoposide (a small‐molecule inhibitor of topoisomerase II). Unlike previously reported peptide‐based PPI inhibitors of BRCA1, our compounds are small‐molecule‐like and could be directly administered to tumor cells, thus making them useful for future studies of BRCA1/PARP‐related pathways in DNA damage and repair response, and in cancer therapy.     

Enzymatic profiling system in a small-molecule microarray

[reaction: see text] We have developed a microarray-based strategy for detection of three major classes of hydrolytic enzymes on the basis of their catalytic activities. This enables the sensitive detection of proteins not merely by their bindings but rather by their enzymatic activities. This may provide a valuable tool for screening, identification, and characterization of new enzymes in a high-throughput fashion.     

Multicolor, one- and two-photon imaging of enzymatic activities in live cells with fluorescently Quenched Activity-Based Probes (qABPs)

Fluorescence imaging provides an indispensable way to locate and monitor biological targets within complex and dynamic intracellular environments. Of the various imaging agents currently available, small molecule-based probes provide a powerful tool for live cell imaging, primarily due to their desirable properties, including cell permeability (as a result of their smaller sizes), chemical tractability (e.g., different molecular structures/designs can be installed), and amenability to imaging a wide variety of biological events. With a few exceptions, most existing small molecule probes are however not suitable for in vivo bioimaging experiments in which high-resolution studies of enzyme activity and localization are necessary. In this article, we reported a new class of fluorescently Quenched Activity-Based Probes (qABPs) which are highly modular, and can sensitively image (through multiple enzyme turnovers leading to fluorescence signal amplification) different types of enzyme activities in live mammalian cells with good spatial and temporal resolution. We have also incorporated two-photon dyes into our modular probe design, enabling for the first time activity-based, fluorogenic two-photon imaging of enzyme activities. This, hence, expands the repertoire of 'smart', responsive probes currently available for live cell bioimaging experiments.     

"Click" synthesis of small molecule probes for activity-based fingerprinting of matrix metalloproteases

By using "Click Chemistry", we achieved the facile synthesis of various affinity-based hydroxamate probes that enable generation of activity-based fingerprints of a variety of metalloproteases, including matrix metalloproteases (MMPs), in proteomics experiments.     

Dual Q-switched laser outputs from a single lasing medium using an intracavity MEMS micromirror array

An intracavity array of individually controlled microelectromechanical system scanning micromirrors was used to actively Q-switch a single side-pumped Nd:YAG gain medium. Two equal power independent laser outputs were simultaneously obtained by separate actuation of two adjacent micromirrors with a combined average output power of 125?mW. Pulse durations of 28?ns FWHM at 8.7?kHz repetition frequency and 34?ns FWHM at 7.9?kHz repetition frequency were observed for the two output beams with beam quality factors M² of 1.2 and 1.1 and peak powers of 253?W and 232?W, respectively.     

Microarray-guided discovery of two-photon (2P) small molecule probes for live-cell imaging of cysteinyl cathepsin activities

A microarray immobilized with 105 aldehyde-containing small molecules was screened against mammalian cell lysates over-expressing cathepsin L to identify two potent inhibitors, which were subsequently converted into cell-permeable probes capable of live-cell imaging of endogenous cysteinyl cathepsin activities by two-photon fluorescence microscopy.     

Comparative proteomic profiling of mammalian cell lysates using phosphopeptide microarrays

A library of 176 human phosphotyrosine-containing peptides was used to establish cell lysate binding profiles in a two colour microarray format. The resulting hits led to the pull-down and identification of biomarkers associated with cancer states.     

Alternative fiber-optic backreflectance sensor for measurement of the effective focal lengths of optical elements and distances

An alternative and simple fiber-optic backreflectance sensor method for accurate measurement of either effective focal lengths of optical elements and short distances using a single-mode optical fiber and cw laser is presented. The method is based on the intensity sensing of focused backreflectance laser emission and the spatial location of three specific points: the focal point of the focusing optical element and two object points. The single-mode fiber is a key optical element and serves simultaneously as a point laser source for testing, an object for projecting and a highly sensitive point receiver of the focused backreflectance emission. The experimental and analytical results demonstrate the potential of the method for locating the spatial points and determining the effective focal length with accuracies exceeding 1 μm and 0.5%, respectively, as well as for short distance measurement with submicron accuracy.     

AluminiumkomplexeSchiffscher Basen

Reactions of Aluminium isopropoxide with monofunctional bidentateSchiff bases, such as salicylidene-o-toluidine, salicylidene-p-toluidine, 2-hydroxy-1-naphthylmethylidene-p-toluidine and 2-hydroxy-1-naphthylmethylidene-p-toluidine in different stoichiometric ratios have yielded products of the type Al(OPr ⁱ)₂(SB), Al(OPr ⁱ)(SB)₂, and Al(SB)₃ (whereSB ^– is the anion of the correspondingSchiff base,SBH). Bifunctional tetradentateSchiff bases in 11 and 23 molar ratios [Al(OPr ⁱ)₃:SBH₂] yielded insoluble derivatives of the type Al(OPr ⁱ)SB and Al₂(SB)₃ (whereSB ^– represents the anion of theSchiff baseSBH₂ andSBH₂=bis-salicylaldehyde-o-phenylene-diamine or bis-salicylaldehyde-p-phenylenediamine). The newSchiff base derivatives have been characterized by elemental analyses, infrared spectroscopy and molecular weight determinations.