Differential and integral W-values for ionization in gaseous water under electron and proton irradiation: consistency of inelastic collision cross sections.

Differential and integral W-values for ionization in gaseous water for electron and proton irradiation have been analyzed from the theoretical point of view for consistency between ionization and total inelastic collision cross sections. For low-energy electrons, which are ubiquitous for all primary radiations, the experimental or compiled cross sections from different sources are sometimes not consistent with one another. A practical, self-consistent procedure is outlined in such cases. The high-energy asymptotic W-values for differential and integral ionization are calculated to be 33.7 and 34.7 eV, respectively, for electron irradiation and 34.6 and 32.5 eV, respectively, for proton irradiation. The computed variations of the W-values with energy are generally in good agreement with experiment. Integral primary W-values due only to the interactions between the incident particle and the water vapor are calculated to be 43.5 and 45.0 eV for electrons and protons, respectively, in the high-energy asymptotic limit.     

Weighted Diallel Analysis Across Environments: Combining Ability and Heterotic Pattern Models

The matrix algebra needed for analysing data from diallel experiments across several environments is provided. Practical considerations for subdividing large incidence matrices and appending constraint matrices are discussed to allow large experiments to be analysed on desk top computers. In particular, a combining ability model and heterotic pattern model have been used to show how heterogeneous variances can be accommodated by weighting. The models provide valuable information on the performance of lines in crosses, the heterotic patterns of the lines, and the heterotic groups to which they belong. The methodology is illustrated by application to a diallel cross conducted among 12 elite white modified opaque-2 maize inbred lines.     

Some Properties of Block Matrices of Models Based on Hierarchical and Crossed Classifications

Proofs of several theorems on some properties of block matrices of linear statistical models based on hierarchical and crossed classifications are given. These properties are useful to deduce the estimator of vector of missing data in the case of any hierarchical classification and cross classification with the interaction of the highest order.     

NMR study of the positions of His-12 and His-119 in the ribonuclease A-uridine vanadate complex.

The binding of uridine vanadate to ribonuclease A has been investigated by one- and two-dimensional 1H NMR. The homonuclear Nuclear Overhauser and exchange spectroscopy spectrum of the uridine vanadate/RNase A complex exhibits cross peaks between both the C5H and C6H protons of uridine vanadate and the H epsilon 1 proton of His-12 of ribonuclease A. These cross peaks suggest that the H epsilon 1 proton of His-12 is in the vicinity of the uracil base of uridine vanadate, as observed in the crystallographic structure of the uridine vanadate/RNase A complex. However, no cross peaks are observed between the C5H and C6H protons of uridine vanadate and the H epsilon 1 proton of His-119 of ribonuclease A, although they were predicted based upon the distances calculated from coordinates of the crystallographic structure of the complex. These results suggest that there is a significant difference between the positioning of the His-119 side chain in the solution and in the crystallographic structures.     

Protons may leak through pure lipid bilayers via a concerted mechanism

Protons are known to permeate pure lipid bilayers at a rate that is anomalous compared to those of other small monovalent cations. The prevailing mechanism via which they cross the membrane is still unclear, and it is unknown how to probe the mechanism directly by experiment. One of the more popular theories assumes the formation of membrane-spanning single-file water wires providing a matrix along which the protons can "hop" over the barrier. However, free energy calculations on such structures (without the presence of an excess proton) suggest that this mechanism alone cannot account for the observed permeation rates. We use the multistate empirical valence bond method to directly study water structures surrounding a (delocalized) excess proton on its way through the membrane. We find that membrane-spanning networks, rather than single-file chains, are formed around the proton. We also find that such structures are considerably stabilized in the presence of the proton, with lifetimes of several hundreds of picoseconds. The observed structures are suggestive of a new, concerted, mechanism and provide some direction for further investigation.     

Temperature dependence of NMR chemical shifts: Tracking and statistical analysis

Isotropic chemical shifts measured by solution nuclear magnetic resonance (NMR) spectroscopy offer extensive insights into protein structure and dynamics. Temperature dependences add a valuable dimension; notably, the temperature dependences of amide proton chemical shifts are valuable probes of hydrogen bonding, temperature‐dependent loss of structure, and exchange between distinct protein conformations. Accordingly, their uses include structural analysis of both folded and disordered proteins, and determination of the effects of mutations, binding, or solution conditions on protein energetics. Fundamentally, these temperature dependences result from changes in the local magnetic environments of nuclei, but correlations with global thermodynamic parameters measured via calorimetric methods have been observed. Although the temperature dependences of amide proton and nitrogen chemical shifts are often well approximated by a linear model, deviations from linearity are also observed and may be interpreted as evidence of fast exchange between distinct conformational states. Here, we describe computational methods, accessible via the Shift‐T web server, including an automated tracking algorithm that propagates initial (single temperature) ¹H? ¹⁵N cross peak assignments to spectra collected over a range of temperatures. Amide proton and nitrogen temperature coefficients (slopes determined by fitting chemical shift vs. temperature data to a linear model) are subsequently calculated. Also included are methods for the detection of systematic, statistically significant deviation from linearity (curvature) in the temperature dependences of amide proton chemical shifts. The use and utility of these methods are illustrated by example, and the Shift‐T web server is freely available at http://meieringlab.uwaterloo.ca/shiftt .     

Monte Carlo transport of swift protons and light ions in water: The influence of excitation cross sections,relativistic effects,and Auger electron emission in w-values

PurposeTo develop a particle transport code to compute w-values and stopping power of swift ions in liquid water and gases of interest for reference dosimetry in hadrontherapy. To analyze the relevance of inelastic and post-collisional processes considered.MethodsThe Monte Carlo code MDM was extended to the case of swift ion impact on liquid water (MDM-Ion). Relativistic corrections in the inelastic cross sections and the post-collisional Auger emission were considered. The effects of introducing different electronic excitation cross sections were also studied.ResultsThe stopping power of swift ions on liquid water, calculated with MDM-Ion, are in excellent agreement with recommended data. The w-values show a strong dependence on the electronic excitation cross sections and on the Auger electron emission. Comparisons with other Monte Carlo codes show the relevance of both the processes considered and of the cross sections employed. W and w-values for swift electron, proton, and carbon ions calculated with the MDM and MDM-Ion codes are in very close agreement with each other and with the 20.8 eV experimental value.ConclusionWe found that w-values in liquid water are independent of ion charge and energy, as assumed in reference dosimetry for hadrontherapy from sparse experimental results for electron and ion impact on gases. Excitation cross sections and Auger emission included in Monte Carlo codes are critical in w-values calculations. The computation of this physical parameter should be used as a benchmark for micro-dosimetry investigations, to assess the reliability of the cross sections employed.     

Premelting thermal fluctuational base pair opening probability of poly(dA).poly(dT) as predicted by the modified self-consistent phonon theory.

We employ a mean field, modified, self-consistent phonon theory to evaluate the single base-pair opening rate and the probability of a base pair in the amino proton exchangeable state for the homopolymer poly(dA).poly(dT) at temperatures below the helix-coil transition region. Our calculated premelting single base-pair opening probabilities are in general agreement with several available experimental estimates from imino proton exchange and formaldehyde-induced DNA melting measurements. These calculated opening probabilities, however, are in disagreement with the prediction of the helix-coil transition theory. Possible reasons for the differences are discussed, especially the possible different definition of a meaningful open state in the premelting region. The premelting open state of the modified self-consistent phonon approximation theory seems to be appropriate to describe a solvent-accessible open configuration that is sufficient to facilitate important chemical reactions such as imino proton exchange and formaldehyde reaction with the bases. This can be compared with the completely unstacked open state of the helix-coil transition theory originally defined in the helix-coil transition region. We propose that the amino proton exchangeable state is different from the open state associated with melting and only involves the breaking of the amino interbase H bond. The agreement between the calculated and experimentally estimated probability of a base pair in the amino proton exchangeable state seems to support this hypothesis.     

Campylobacter spp. detection in the 21st century: A review of the recent achievements in biosensor development

Campylobacter spp. are an important cause of acute bacterial diseases in humans worldwide. Many bacterial species in the Campylobacter genus are considered harmful and may cause several infectious diseases. Currently, there are no commercial biosensors available to detect Campylobacter spp. in food matrices, and little to no testing has been done in research laboratories with actual food matrices. Biosensors potentially provide a powerful means to detect Campylobacter spp. with the advantages of high sensitivity (low limits of detection with a high signal to noise ratio), high specificity (able to selectively detect the target among several similar targets), real time sensing, and in-site monitoring. This review summarizes the latest research in biosensing technologies for detection of Campylobacter spp. based on a variety of transducers and recognition elements. Finally, a comparison is made among all recently reported biosensors for the detection of Campylobacter spp.     

Enhanced surface plasmon resonance with the modified catalytic growth of Au nanoparticles

The catalytic growth of Au nanoparticles (AuNPs) has been employed in several analytical methods for improving the detection sensitivity, or integrated with the enzyme reactions for the quantitative detection of the respective substrates. However, the catalytic growth of Au nanoparticles do not work in some situations, such as surface plasmon resonance (SPR), electrochemistry, where metal matrices were used, because metal matrices used in these techniques, e.g. Au, are susceptible to metal deposition, which increased the background seriously. In this work, a SiO(2) layer was vapor-deposited on the gold film. The inhibition of metal deposition by this SiO(2) layer was investigated by SPR sensor. The results showed that the SiO(2) layer could avoid the deposition of metal on Au film. With the low background achieved by SiO(2)-coated Au films, sensitive detection of DNA hybridization using the catalytic growth of Au nanoparticles enhanced SPR was demonstrated. The work described here maybe helpful for the development of sensitive bioanalytical methods.     

Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI

In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.     

Null matrices and the analysis of species co-occurrences

Patterns in species occurrences on islands have been analyzed by several authors. At issue is the number of non-occurring pairs of species (also known as checkerboards). Previous authors have suggested that if the number of checkerboards differs from what is expected by chance, then island communities might have been structured by competition. Investigators have pursued this problem by first generating random (or null) matrices and then testing a metric derived from the collection of null matrices against the metric calculated from the actual species co-occurrence matrix. The random matrices were constrained by requiring the number of species on each island, and the number of islands on which each species occurred to be equal to their observed values. We show that results from previous studies are generally flawed. We present a fast, efficient algorithm to generate null matrices for any set of fixed row and column sums, and propose a modification of a previously proposed metric as a test statistic. We evaluated the efficacy of our construction method for null creation and our metric using incidence matrices from the avifauna of Vanuatu (formerly New Hebrides). Received: 31 March 1997 / Accepted: 8 April 1998     

基于位置特异性谱和输入加权神经网络的蛋白质亚细胞定位预测

蛋白质必须处于正确的亚细胞位置才能行使其功能。文章利用PSI-BLAST工具搜索蛋白质序列,提取位点特异性谱中的位点特异性得分矩阵作为蛋白质的一类特征,并计算4等分序列的氨基酸含量以及1～7阶二肽含量作为另外两类特征,由这三类特征一共得到蛋白质序列的12个特征向量。通过设计一个简单加权函数对各类特征向量加权处理,作为神经网络预测器的输入,并使用Levenberg-Marquardt算法代替传统的EBP算法来调整网络权值和阈值,大大提高了训练速度。对具有4类亚细胞位置和12类亚细胞位置的两种蛋白质数据集分别进行＂留一法＂测试和5倍交叉验证测试,总体预测精度分别达到88.4%和83.3%。其中,对4类亚细胞位置数据集的预测效果优于普通BP神经网络、隐马尔可夫模型、模糊K邻近等预测方法,对12类亚细胞位置数据集的预测效果优于支持向量机分类方法。最后还对三类特征采取不同加权比例对预测精度的影响进行了讨论,对选择的八种加权比例的预测结果表明,分别给予三类特征合适的权值系数可以进一步提高预测精度。     

Charge delocalization in proton channels, I: the aquaporin channels and proton blockage

The explicit contribution to the free energy barrier and proton conductance from the delocalized nature of the excess proton is examined in aquaporin channels using an accurate all-atom molecular dynamics computer simulation model. In particular, the channel permeation free energy profiles are calculated and compared for both a delocalized (fully Grotthuss shuttling) proton and a classical (nonshuttling) hydronium ion along two aquaporin channels, Aqp1 and GlpF. To elucidate the effects of the bipolar field thought to arise from two alpha-helical macrodipoles on proton blockage, free energy profiles were also calculated for computational mutants of the two channels where the bipolar field was eliminated by artificially discharging the backbone atoms. Comparison of the free energy profiles between the proton and hydronium cases indicates that the magnitude of the free energy barrier and position of the barrier peak for the fully delocalized and shuttling proton are somewhat different from the case of the (localized) classical hydronium. The proton conductance through the two aquaporin channels is also estimated using Poisson-Nernst-Planck theory for both the Grotthuss shuttling excess proton and the classical hydronium cation.     

A semiempirical study of the prototropic tautomerism of hypoxanthine

The total and relative energies, bond order matrices and localized MOs for the eight possible tautomers of hypoxanthine (HYP) have been calculated, with full geometry optimization, using both AM1 and MNDO methods. The AM1 relative energies show that HYP(9,1), HYP(7,1) and HYP (9,10) are the predominant species at room temperature, the two former being in larger concentration that the latter. The calculated IR spectra for these species agree well with the reported spectrum in an isolated matrix, which has been interpreted in terms of the presence of these three tautomeric forms. The MNDO method does not predict the right order, and the more stable tautomer would be HYP(9,10). The calculated structure for the HYP(9,1) species shows that the molecule is essentially planar. The bond distances compare well with those of hypoxanthine hydrochloride and guanine and also correlate well with the calculated bond orders. The proton affinities for the three more stable tautomers have also been calculated. For HYP(9,1) the prefered site of protonation is N7, whereas for HYP(7,1) the protonation occurs rather at N9. These results agree well with¹⁵N and¹³C NMR studies in DMSO.     

A general mixture model approach for mapping quantitative trait loci from diverse cross designs involving multiple inbred lines

Most current statistical methods developed for mapping quantitative trait loci (QTL) based on inbred line designs apply to crosses from two inbred lines. Analysis of QTL in these crosses is restricted by the parental genetic differences between lines. Crosses from multiple inbred lines or multiple families are common in plant and animal breeding programmes, and can be used to increase the efficiency of a QTL mapping study. A general statistical method using mixture model procedures and the EM algorithm is developed for mapping QTL from various cross designs of multiple inbred lines. The general procedure features three cross design matrices, W, that define the contribution of parental lines to a particular cross and a genetic design matrix, D, that specifies the genetic model used in multiple line crosses. By appropriately specifying W matrices, the statistical method can be applied to various cross designs, such as diallel, factorial, cyclic, parallel or arbitrary-pattern cross designs with two or multiple parental lines. Also, with appropriate specification for the D matrix, the method can be used to analyse different kinds of cross populations, such as F2 backcross, four-way cross and mixed crosses (e.g. combining backcross and F2). Simulation studies were conducted to explore the properties of the method, and confirmed its applicability to diverse experimental designs.     

Photoaptamer arrays applied to multiplexed proteomic analysis

Multiplexed photoaptamer-based arrays that allow for the simultaneous measurement of multiple proteins of interest in serum samples are described. Since photoaptamers covalently bind to their target analytes before fluorescent signal detection, the arrays can be vigorously washed to remove background proteins, providing the potential for superior signal-to-noise ratios and lower limits of quantification in biological matrices. Data are presented here for a 17-plex photoaptamer array exhibiting limits of detection below 10 fM for several analytes including interleukin-16, vascular endothelial growth factor, and endostatin and able to measure proteins in 10% serum samples. The assays are simple, scalable, and reproducible. Affinity of the capture reagent is shown to be directly correlated to the limit of detection for the analyte on the array.     

Molecular dynamics analysis of a ribonuclease C-peptide analogue

We have carried out a nanosecond molecular dynamics simulation of an analogue of the ribonuclease C-peptide in water. The overall conformation has an extended region for the first three amino acids connected to an α-helix for residues 4–13, and this basic structure is preserved throughout the simulation, with helical hydrogen bonds present 87% of the time, on average. The final helical hydrogen bond is spontaneously broken and re-formed several times, providing a detailed picture of such winding/unwinding events. The simulation was used to estimate the effects of internal motion on proton nuclear Overhauser effect spectroscopy (NOESY) intensities for several classes of important cross peaks. Within the helical regions, the effects of internal motion vary only a little from one residue to another for backbone–backbone cross peaks, and the relevant correlation functions reach plateau values within about 50 ps. The spectral simulations show, however, that it may be difficult to establish a close quantitative connection between NOESY cross-peak volumes and measures of helical content. © 1993 John Wiley & Sons, Inc.