QSAR models using a large diverse set of estrogens

Endocrine disruptors (EDs) have a variety of adverse effects in humans and animals. About 58,000 chemicals, most having little safety data, must be tested in a group of tiered assays. As assays will take years, it is important to develop rapid methods to help in priority setting. For application to large data sets, we have developed an integrated system that contains sequential four phases to predict the ability of chemicals to bind to the estrogen receptor (ER), a prevalent mechanism for estrogenic EDs. Here we report the results of evaluating two types of QSAR models for inclusion in phase III to quantitatively predict chemical binding to the ER. Our data set for the relative binding affinities (RBAs) to the ER consists of 130 chemicals covering a wide range of structural diversity and a 6 orders of magnitude spread of RBAs. CoMFA and HQSAR models were constructed and compared for performance. The CoMFA model had a r2 = 0.91 and a q2LOO = 0.66. HQSAR showed reduced performance compared to CoMFA with r2 = 0.76 and q2LOO = 0.59. A number of parameters were examined to improve the CoMFA model. Of these, a phenol indicator increased the q2LOO to 0.71. When up to 50% of the chemicals were left out in the leave-N-out cross-validation, the q2 remained significant. Finally, the models were tested by using two test sets; the q2pred for these were 0.71 and 0.62, a significant result which demonstrates the utility of the CoMFA model for predicting the RBAs of chemicals not included in the training set. If used in conjunction with phases I and II, which reduced the size of the data set dramatically by eliminating most inactive chemicals, the current CoMFA model (phase III) can be used to predict the RBA of chemicals with sufficient accuracy and to provide quantitative information for priority setting.     

换热器的效能与熵产分析

本文给出了以进口冷热流体温度、热容量流比和传热单元数表示的顺流、逆流及两边混合的叉流换热器熵产数的分析表达式，研究了这三类换热器熵产数随热容量流比及传热单元数变化的规律，给出了由于不平衡流动和传热面积有限产生的熵产数的表达式。分析表明，在进、出口温度均匀条件下换热器效能与熵产数之间存在一一对应的关系，效能与熵产数一样，所表征的是换热器热力学第二定律的完善程度。     

Matrix-assisted laser desorption/ionization directed nano-electrospray ionization tandem mass spectrometric analysis for protein identification

In those cases where the information obtained by peptide mass fingerprinting or matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) is not sufficient for unambiguous protein identification, nano-electrospray ionization (nano-ESI) and/or electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis must be performed. The sensitivity of nano-ESI/MS, however, is lower than that of MALDI-MS, especially at very low analyte concentrations and/or in the presence of contaminants, such as salt and detergents. Moreover, to perform ESI-MS/MS, the peptide masses of the precursor ions must be known. The approach described in this paper, MALDI-directed nano-ESI-MS/MS, makes use of information obtained from the more sensitive MALDI-MS experiments in order to direct subsequent nano-ESI-MS/MS experiments. Peptide molecular ions found in the MALDI-MS analysis are then selected, as their (+2) precursor ions, for nano-ESI-MS/MS sequencing, even though these ions cannot be detected in the ESI-MS spectra. This method, originally proposed by Tempst et al. (Anal. Chem. 2000, 72: 777-790), has been extended to provide better sensitivity and shorter analysis times; also, a comparison with liquid chromatography/tandem mass spectrometry (LC/MS/MS) has been performed. These experiments, performed using quadrupole time-of-flight instruments equipped with commercially available nano-ESI sources, have allowed the unambiguous identification of in-gel digested proteins at levels below their ESI-MS detection limits, even in the presence of salts and detergents.     

Diffractive lens fabricated with binary features less than 60 nm

We designed, fabricated, and characterized a binary diffractive lens with features less than 60 nm. The lens was designed for operation in the red portion of the spectrum. Experimental measurements of lens performance agree with predictions generated by rigorous models of diffraction.     

Imaging cytoplasmic cAMP in mouse brainstem neurons

Background  

cAMP is an ubiquitous second messenger mediating various neuronal functions, often as a consequence of increased intracellular Ca²⁺ levels. While imaging of calcium is commonly used in neuroscience applications, probing for cAMP levels has not yet been performed in living vertebrate neuronal tissue before.     

Stable isotopic studies of earthworm feeding ecology in tropical ecosystems of Puerto Rico

Feeding strategies of earthworms and their influence on soil processes are often inferred from morphological, behavioral and physiological traits. We used (13)C and (15)N natural abundance in earthworms, soils and plants to explore patterns of resource utilization by different species of earthworms in three tropical ecosystems in Puerto Rico. In a high altitude dwarf forest, native earthworms Trigaster longissimus and Estherella sp. showed less (15)N enrichment ((15)N = 3-6 per thousand) than exotic Pontoscolex corethrurus ((15)N =7-9 per thousand) indicating different food sources or stronger isotopic discrimination by the latter. Conversely, in a lower altitude tabonuco forest, Estherella sp. and P. corethrurus overlapped completely in (15)N enrichment ((15)N = 6-9 per thousand), suggesting the potential for interspecific competition for N resources. A tabonuco forest converted to pasture contained only P. corethrurus which were less enriched in (15)N than those in the forest sites, but more highly enriched in (13)C suggesting assimilation of C from the predominant C(4) grass. These results support the utility of stable isotopes to delineate resource partitioning and potential competitive interactions among earthworm species. Copyright 1999 John Wiley & Sons, Ltd.     

How important are dispersion interactions to the strength of aromatic stacking interactions in solution?

In this study, the contributions of London dispersion forces to the strength of aromatic stacking interactions in solution were experimentally assessed using a small molecule model system. A series of molecular torsion balances were designed to measure an intramolecular stacking interaction via a conformational equilibrium. To probe the importance of the dispersion term, the size and polarizability of one of the aromatic surfaces were systematically increased (benzene, naphthalene, phenanthrene, biphenyl, diphenylethene, and diphenylacetylene). After correcting for solvophobic, linker, and electrostatic substituent effects, the variations due to polarizability were found to be an order of magnitude smaller in solution than in comparison to analogous computational studies in vacuo. These results suggest that in solution the dispersion term is a small component of the aromatic stacking interaction in contrast to their dominant role in vacuo.