Synthesis of the antifungal beta-1,3-glucan synthase inhibitor CANCIDAS (caspofungin acetate) from pneumocandin B0

A novel three-step synthesis of the highly functionalized antifungal agent CANCIDAS (caspofungin acetate, 2) is described, starting from the natural product pneumocandin B0 (1). The highlights of the synthesis include a stereoselective formation of a phenylthioaminal, a remarkable chemoselective, high-yielding, one-step borane reduction of a primary amide, and a stereoselective substitution of the phenylthioaminal with ethylenediamine producing 2 in a 45% overall yield.     

Determination of membrane domain size by fluorescence resonance energy transfer: effects of domain polydispersity and packing

Fluorescence resonance energy transfer (FRET) is sensitive to lateral heterogeneity in multicomponent membranes. Recently, we developed a model that enables the extraction of domain size from time-resolved FRET data, and here we examine the effects of domain polydispersity and spatial ordering on the accuracy of domain size determination. The model is applied to Monte Carlo calculations of membranes containing polydisperse domains, either randomly or hexagonally packed for three probe-partitioning schemes and three domain surface coverages. Statistical analysis of the model fitting results supports the conclusion that time-resolved FRET is a robust and precise technique for determining the size of small membrane domains (相似文献   

Multifunctional layer-by-layer coating of digitally encoded microparticles

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick "multiplexing" assays. By making use of encoded microparticles, such assays allow simultaneous determination of the presence of several analytes in a biological sample. The microparticles under investigation in this study are encoded by writing a digital dot or bar code in their central plane. This study evaluates to what extent a "multifunctional" coating can be applied around the digitally encoded microparticles by the layer-by-layer (LbL) technology. We show that a LbL coating containing CrO2 nanoparticles allows (a) an optimal (optical) readout of the dot and bar codes, (b) a perfect orientation of the microparticles, necessary to be able to read the code, and (c) an optimal coupling of capture probes to the surface of the microparticles.     

A novel method to fabricate patterned bilayer lipid membranes

We introduce a new method for forming tethered bilayer lipid membranes on surfaces patterned using a photocleavable self-assembled monolayer (SAM). A SAM terminated with a hydrophobic fluorocarbon residue was bound to a gold surface through a link containing a photocleavable ortho-nitrobenzyl moiety. Hydrophilic regions were produced by irradiation with soft UV (365 nm) through a photomask. The patterned surface was characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Tethered bilayer lipid membranes with well-defined bilayer and monolayer regions were then formed by exposure to egg PC vesicles. The membranes had resistance and capacitance values of 0.52 MOmega.cm2 and 0.83 microF.cm-2, respectively.     

Shear wave speed recovery using moving interference patterns obtained in sonoelastography experiments

Two new experiments were created to characterize the elasticity of soft tissue using sonoelastography. In both experiments the spectral variance image displayed on a GE LOGIC 700 ultrasound machine shows a moving interference pattern that travels at a very small fraction of the shear wave speed. The goal of this paper is to devise and test algorithms to calculate the speed of the moving interference pattern using the arrival times of these same patterns. A geometric optics expansion is used to obtain Eikonal equations relating the moving interference pattern arrival times to the moving interference pattern speed and then to the shear wave speed. A cross-correlation procedure is employed to find the arrival times; and an inverse Eikonal solver called the level curve method computes the speed of the interference pattern. The algorithm is tested on data from a phantom experiment performed at the University of Rochester Center for Biomedical Ultrasound.     

Domain Analysis and Motif Matcher (DAMM): A Program to Predict Selectivity Determinants in Monosiga brevicollis PDZ Domains Using Human PDZ Data

Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational software suite, Domain Analysis and Motif Matcher (DAMM), that analyzes peptide-binding cleft sequence identity as compared with human PDZ domains and that can be used in combination with literature searches of known human PDZ-interacting sequences to predict target specificity in choanoflagellate PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 μM affinity, a value commonly considered the threshold for cellular PDZ–peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contribute to investigations into choanoflagellate signaling and how it informs metazoan evolution.     

Analysis of external latch-up protection test structure design using numerical simulation

With each new CMOS technology the latch-up sensitivity and effects of prevention strategies change. Products built in these technologies must adhere to stringent guidelines for latch-up ‘Hardness’, and for this reason characterisation of new technologies is needed through the use of test structures. This paper shows a numerical simulation approach which can determine the relative effectiveness of guard-rings in ESD protection device test structures. In this work, time taken to characterise latch-up protection test structures and to chose a protection strategy is greatly reduced by using numerical simulations to design the test structures. The results presented are for variations to the guard-rings for two technologies. Included in these are the typical simulation times and resources required. The technique outlined has the joint advantages of providing accurately representative simulations of the technology and test structure layout in a practical time frame.     

An Ordered Nanoporous Monolith from an Elastomeric Crosslinked Block Copolymer Precursor

Summary: An ordered nanoporous monolith was prepared from a poly(isoprene‐b‐dimethylsiloxane) (PI‐PDMS) hexagonally packed cylinder precursor. The PDMS cylinders were macroscopically aligned, the PI was crosslinked with dicumyl peroxide, and the PDMS was removed using tetrabutylammonium fluoride. The stability of the pores depended on the modulus of the matrix. At high crosslink density the pores were stable, but they collapsed at a low crosslink density. The nanoporous materials could be swollen in toluene.

A scanning electron micrograph of the end‐on view of crosslinked degraded poly(isoprene‐b‐dimethylsiloxane).     

Evaluation of recombinant strains of Zymomonas mobilis for ethanol production from glucose/xylose media

The fermentation characteristics of two recombinant strains of Zymomonas mobilis, viz. CP4 (pZB5) and ZM4 (pZB5), capable of converting both glucose and xylose to ethanol, have been characterized in batch and continuous culture studies. The strain ZM4 (pZB5) was found to be capable of converting a mixture of 65 g/L glucose and 65 g/L xylose to 62 g/L ethanol in 48h with a yield of 0.46 g/g. Higher sugar concentrations resulted in incompletexylose utilization (80h) presumably owing to ethanol inhibition of xylose assimilation or metabolism. The fermentation results with ZM4 (pZB5) show a significant improvement over results published previously for recombinant yeasts and other bacteria capable of glucose and xylose utilization.     

Rate constants and Arrhenius parameters for the reactions of Cl atoms with the halogenated ethers: CF3CH2OCHF2, CF3CHClOCHF2, and CF3CH2OCClF2

Rate constants have been determined for the reactions of Cl atoms with the halogenated ethers CF₃CH₂OCHF₂, CF₃CHClOCHF₂, and CF₃CH₂OCClF₂ using a relative‐rate technique. Chlorine atoms were generated by continuous photolysis of Cl₂ in a mixture containing the ether and CD₄. Changes in the concentrations of these two species were measured via changes in their infrared absorption spectra observed with a Fourier transform infrared (FTIR) spectrometer. Relative‐rate constants were converted to absolute values using the previously measured rate constants for the reaction, Cl + CD₄ → DCl + CD₃. Experiments were carried out at 295, 323, and 363 K, yielding the following Arrhenius expressions for the rate constants within this range of temperature:Cl + CF₃CH₂OCHF₂: k = (5.1₅ ± 0.7) × 10⁻¹² exp(−1830 ± 410 K/T) cm³ molecule⁻¹ s⁻¹ Cl + CF₃CHClOCHF₂: k = (1.6 ± 0.2) × 10⁻¹¹ exp(−2450 ± 250 K/T) cm³ molecule⁻¹ s⁻¹ Cl + CF₃CH₂OCClF₂: k = (9.6 ± 0.4) × 10⁻¹² exp(−2390 ± 190 K/T) cm³ molecule⁻¹ s⁻¹ The results are compared with those obtained previously for the reactions of Cl atoms with other halogenated methyl ethyl ethers. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 165–172, 2001