bluuebunny/crossref_metadata_2025 huggingface dataset:
Substructure versus Whole‐molecule Approaches for Calculating Log P
Authors: Mannhold Raimund , Petrauskas Alanas
Published: June 2003

The validity of log P calculations is checked for the substructure methods CLOGP, KOWWIN, and AB/logP and the whole‐molecule method SciLogP via experimental log P for 174 molecules, comprising 90 simple organics and 84 more complex drugs. Averaged absolute residual sums (AARS) give the following ranking for the entire set: CLOGP>KOWWIN≈AB/logP>SciLogP. Separate analysis of simple organics yields: CLOGP>KOWWIN>AB/logP>SciLogP. For the drugs we find: CLOGP≈KOWWIN≈AB/LogP>SciLogP. In a second step, we compared the validity of the calculation programs focussing on structural factors with a critical impact on log P such as resonance and H‐bonding interactions. AARS values show that CLOGP and KOWWIN scored slightly better than AB/LogP and SciLogP; this agrees with the good performance of CLOGP and KOWWIN when dealing with simple compounds. AB/LogP averaged correction factors obtained from both simple and complex compounds, so it produced a slightly lower accuracy. α‐Effects, representing strong interactions between conjugated π‐electrons within polar functional groups, were identified from compounds lacking “isolating carbons”, which break α‐effects. All compounds in this data set are difficult to deal with for the substructure methods, but should be easy to deal with for the whole‐molecule approach. In practice, however, SciLogP performed worse than the substructure methods. The best performance was shown by CLOGP, followed by KOWWIN and AB/LogP. Taken together, all substructure methods produced better results than the whole‐molecule method. The possible explanation may be that substructure methods automatically account for unknown effects by splitting compounds into fragments and/or conducting class‐specific analyses. Whole‐molecule approaches cannot account for unknown effects, as long as they neglect class‐specific analyses. Among the substructure approaches, our results correlate with the methodology of algorithm development. CLOGP and KOWWIN were developed in a long iterative process, using simple organics for increment derivation and complex drugs for algorithm refinement. AB/LogP was developed in a fast two‐step procedure that did not discriminate between simple and complex compounds. So it produced slightly lower accuracy for simple organics, but not lower accuracy for the complex drugs.
Quantitative Electronic Structure‐Activity Relations: The Influence of Basis Set Selection on Prediction Quality
Authors: Lahsen Joaquín , Schmidhammer Helmut , Spetea Mariana , Rode Bernd M.
Published: June 2003

Quantitative electronic structure‐activity relations (QESAR) based on ab initio calculated atomic charge data have been investigated with respect to basis set influence on quality and predictability. A series of 11 nonpeptide δ‐opioid receptor ligands has been utilized to study the basis set effect, and to determine the active center of these compounds. The geometries were fully optimized using the semiempirical method AM1. Net atomic charges obtained from ab initio MO calculations were used as electronic predictors. Multivariate adaptive regression splines were applied to the data matrix for the construction of QESAR models, whose predictability was rated by PRESS. The best model yielded a PRESS value of 0.08 and it was obtained using the atomic charges derived from the basis set 6‐311G. This model contains the C(9), C(12), C(14), and O(19) atoms as predictors. The 3‐21G basis set supplies an almost equivalent model and can be seen as an economic alternative, therefore, for large compounds.
Flow injection of the lock mass standard for accurate mass measurement in electrospray ionization time‐of‐flight mass spectrometry coupled with liquid chromatography
Authors: Charles Laurence
Published: June 2003

A method of flow injection of the lock mass for accurate mass measurement using electrospray ionization time‐of‐flight mass spectrometry is described. The reference compound is introduced in the chromatographic effluent via a six‐port valve placed post‐column, prior to the split connector. Flow injection is performed in such a way that the reference elution peak is superimposed in the total ion current and partially overlaps that of the investigated analyte, allowing independent ionization of the two compounds and thus accurate mass measurement with no ion suppression effects. Different lock mass molecules can be injected in a single analytical run to target various analytes. The performance of this methodology is demonstrated in both isocratic and gradient liquid chromatography modes. The molecular ion of the flow‐injected lock mass could also be used as a reference for mass measurement of the in‐source fragments of the analytes. Good mass accuracy, within 4 mDa of the theoretical values, was obtained. Copyright © 2003 John Wiley & Sons, Ltd.
Product ion spectral simplification using time‐delayed fragment ion capture with tandem linear ion traps
Authors: Hager James W.
Published: June 2003

A new technique to generate product ion spectra as the internal energy of a collisionally activated precursor ion evolves is described. The precursor ion is activated by acceleration into a mass‐selective linear ion trap under conditions whereby some of the fragment ions formed are unstable within the trap. After a time delay the stability parameters of the ion trap are changed to allow capture of fragments that that were previously unstable. The result is a product ion spectrum that originates from precursor ions with a modified internal energy distribution. It is possible to follow the evolution of the precursor internal energy distribution for many milliseconds after admittance of the precursor ions into the linear ion trap. Time‐delayed fragmentation product ion spectra typically display reduced sequential fragmentation products leading to spectra that are more easily interpreted. Several important experimental parameters important to time‐delayed fragmentation have been identified and are discussed. The technique has applications for both small precursor ions and multiply charged peptides. Copyright © 2003 John Wiley & Sons, Ltd.
Structural analysis of oligosaccharides by a combination of electrospray mass spectrometry and bromine isotope tagging of reducing‐end sugars with 2‐amino‐5‐bromopyridine
Authors: Li Min , Kinzer Jeffery A.
Published: June 2003

Model reducing‐end oligosaccharides were successfully labeled by a brominated aromatic amine reagent, 2‐amino‐5‐bromopyridine (ABP), through reductive amination. Using either a combination of liquid chromatography/electrospray ionization mass spectrometry (LC/ESI‐MS) with in‐source fragmentation or liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI‐MS/MS), sequence information corresponding to the model oligosaccharides was revealed with little ambiguity via the diagnostic unique twin peaks arising from the bromine isotopes, for both the molecular ions of the derivatized oligosaccharides and their fragments. No fragment ions arising from loss of the bromine atom were observed. Copyright © 2003 John Wiley & Sons, Ltd.
Parallel high‐throughput accurate mass measurement using a nine‐channel multiplexed electrospray liquid chromatography ultraviolet time‐of‐flight mass spectrometry system
Authors: Fang Liling , Demee Michael , Cournoyer Jason , Sierra Teresa , Young Connie , Yan Bing
Published: June 2003

A nine‐channel multiplexed electrospray (MUX) liquid chromatography ultraviolet time‐of‐flight mass spectrometry (LC/UV/TOFMS) system has been used to simultaneously measure accurate masses of eluting components from eight parallel gradient LC columns. Accuracies better than 5 and 10 ppm were achieved for 50 and 80% of samples, respectively, from a single batch analysis of ten plates (960 samples) of a Fmoc‐Asp(OtBu)‐OH and reserpine mixture. Combinatorial library compounds were analyzed using this parallel high‐throughput system in both positive and negative modes to rigorously verify expected products and identify side products. A mass accuracy of 10 ppm root mean square (RMS) is routinely obtained for combinatorial library samples from this high‐throughput accurate mass LC/MS system followed by automated data processing. This mass accuracy is critical in revealing combinatorial synthesis problems that would be missed by unit mass measurement. Copyright © 2003 John Wiley & Sons, Ltd.
Congener‐specific analysis of hexabromocyclododecane by high‐performance liquid chromatography/electrospray tandem mass spectrometry
Authors: Budakowski Wesley , Tomy Gregg
Published: June 2003

A congener‐specific method based on high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES‐MS/MS) in the negative ion mode was developed for the analysis of hexabromocyclododecane (HBCDD). On a C18 analytical column, with a methanol/water mobile phase, the α‐isomer was completely resolved from the β‐ and γ‐isomers while the β‐ and γ‐isomers were sufficiently resolved at half their peak heights. The ES spray voltage strongly influenced the intensity of the ion signal. For MS, a source temperature of 500°C and a collision energy of 50 eV were found to be optimum for the [M–H]− to Br− transition. Run‐to‐run and day‐to‐day (n = 3) variability was minimal, with relative standard deviations of 2.6–4.1 and 2.4–4.4%, respectively. The limit of detection was 4–6 pg on‐column. When applied to tissue samples from Lake Winnipeg fish both α‐ and γ‐isomers of HBCDD were found in low‐ng/g (lipid corrected) concentrations. Copyright © 2003 John Wiley & Sons, Ltd.
Probing the mechanisms of the self ion‐molecule reactions of dopamine in an ion trap mass spectrometer
Authors: Wu Hui‐Fen , Chen Chien‐Hung , Lu Li‐Chi
Published: June 2003

Our previous work was the first to report [M+CH]+ and [M+C2H3]+ ions in the self ion‐molecule reactions (SIMR) of two aza‐crown ethers in an ion trap mass spectrometer (ITMS). In this study, the CH and C2H3 addition ions were also found in the SIMR of dopamine. The SIMR of dopamine lead to the formation of the protonated molecules ([M+H]+), of adduct ions ([M+F]+, where F represents fragment ions), and of [M+CH]+, [M+C2H3]+ and [2M+H]+ ions. Based on the combination of the results of isolation experiments and semi‐empirical calculations, the reactive site for the formation of the [M+H]+ and [M+CH]+ ions of dopamine is proposed to be the amino group. Copyright © 2003 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometry of AZT H‐phosphonates conjugated with steroids
Authors: Xiao Qiang , Ju Yong , Yang Xinping , Zhao Yu‐Fen
Published: June 2003

AZT H‐phosphonates conjugated with steroids were synthesized and determined by positive and negative ion electrospray ionization mass spectrometry (ESI‐MS) in conjunction with tandem mass spectrometry (MS/MS). The fragmentation pathways were investigated in detail. There are very different characteristic fragment ions in the positive and negative ion MS/MS spectra. The azide group of compounds 6a and 6b underwent either elimination of HN3 or rearrangement to an amine in both positive and negative ion mass spectrometry. Copyright © 2003 John Wiley & Sons, Ltd.
Cone voltage induced in‐source dissociation of glucuronides in electrospray and implications in biological analyses
Authors: Yan Zhengyin , Caldwell Gary W. , Jones William J. , Masucci John A.
Published: June 2003

Glucuronidation is a common mechanism in drug metabolism. In‐source dissociation of glucuronides in electrospray generates fragment ions identical to those of the precursor ions of the original drugs. The effect of experimental parameters on the process was investigated in the present study using both commercially available compounds and glucuronides generated from microsomal glucuronidation incubations. It was found that cone voltage was the most critical parameter contributing to in‐source fragmentation of both O‐ and N‐glucuronides, whereas both the desolvation temperature and the source temperature had little effect. Additionally, the extent of in‐source dissociation varied for different glucuronides and could be minimized by lowering cone voltage. As demonstrated in real examples, minimizing in‐source dissociation can lead to higher sensitivity in detecting glucuronides in biological samples. In addition, product ions resulting from in‐source dissociation of glucuronides potentially interfere with accurate determinations of corresponding drug levels if chromatographic separation is not adequate. For cases in which chromatographic separation of glucuronides from the original drugs is not readily achieved or high‐throughput analyses are desired, interference caused by in‐source dissociation can usually be eliminated simply by using lower cone voltage. This approach has been proven to be effective in the analysis of more than 100 glucuronides generated from in vitro microsomal incubations. Copyright © 2003 John Wiley & Sons, Ltd.
Exact mass measurement of product ions for the structural confirmation and identification of unknown compounds using a quadrupole time‐of‐flight spectrometer: a simplified approach using combined tandem mass spectrometric functions
Authors: Clauwaert Karine , Casteele Sofie Vande , Sinnaeve Bart , Deforce Dieter , Lambert Willy , Van Peteghem Carlos , Van Bocxlaer Jan
Published: June 2003

This article describes a simple method to perform lock mass corrected accurate mass measurements in tandem mass spectrometry (MS/MS) with a quadrupole time‐of‐flight (Q‐TOF) mass spectrometer. The experimental approach consists of using the protonated molecule of a known compound, which is measured in a MS/MS function using low collision energy (no fragmentation), as mass calibrator. The unknown compound is acquired in MS/MS mode albeit using high collision energy. After the acquisition, the two MS/MS spectra of unknown and mass calibrator are combined, and the fragments of the unknown are lock mass corrected by using the protonated molecule of the mass calibrator. To prove this concept, 10 compounds were analyzed using this approach, the fragments interpreted and, where possible, related to structural data available in the literature. All the unequivocally assigned fragments were accurately mass measured with mass errors within appropriate limits, i.e. for m/z values <200 with a mass tolerance of 3 mDa while for m/z > 200 the mass tolerance is expressed as 10 ppm. Copyright © 2003 John Wiley & Sons, Ltd.
Charge state separation for protein applications using a quadrupole time‐of‐flight mass spectrometer
Authors: Chernushevich I. V. , Fell L. M. , Bloomfield N. , Metalnikov P. S. , Loboda A. V.
Published: June 2003

A novel method for separating ions according to their charge state using a quadrupole time‐of‐flight mass spectrometer is presented. The benefits of charge state separation are particularly apparent in protein identification applications at low femtomole concentration levels, where in conventional TOF MS spectra peptide ions are often lost in a sea of chemical noise. When doubly and triply charged tryptic peptide ions need to be filtered from singly charged background ions, the latter are suppressed by two to three orders of magnitude, while from 10–50% of multiply charged ions remain. The suppression of chemical noise reduces the need for chromatography and can make this experimental approach the electrospray equivalent of conventional MALDI peptide maps. If unambiguous identification cannot be achieved, MS/MS experiments are performed on the precursor ions identified through charge separation, while the previously described Q2‐trapping duty cycle enhancement is tuned for approximately 1.4 of the precursor m/z to enhance intensities of ions with m/z values above that of the precursor. The resulting product ion spectra contain few fragments of impurities and provide quick and unambiguous identification through database search. The multiple charge separation technique requires minimal tuning and may become a useful tool for analysis of complex mixtures. Copyright © 2003 John Wiley & Sons, Ltd.
Mass spectral determination of skeletal/cardiac actin isoform ratios in cardiac muscle
Authors: Bergen H. Robert , Ajtai Katalin , Burghardt Thomas P. , Nepomuceno Angelito I. , Muddiman David C.
Published: June 2003

Skeletal and cardiac muscle contains actin isoforms that vary by two juxtaposed amino acids and two amino acid substitutions (Met299Leu and Ser358Thr). This close sequence homology does not allow cardiac and skeletal actin isoforms to be resolved in traditional SDS‐PAGE analysis as the molecular weights (Δmass = 32 Da) are not significantly different and the pIs are identical (5.2). Although cardiac actin is the predominant form in cardiac muscle, there appears to be a specific skeletal/cardiac actin ratio in a normal heart that may vary in a compromised or diseased heart. In an effort to ascertain the validity of this hypothesis we developed a mass spectrometric technique to measure the ratio of skeletal to cardiac actin. The technique involves purification of muscle actin and subsequent liquid chromatography coupled with electrospray ionization Fourier transform ion cylcotron resonance (LC/FTICR‐MS) mass spectrometry. A 7 Tesla FTICR mass spectrometer was utilized to compare skeletal/cardiac actin isoform ratios. Additionally, a new dual electrospray ionization source was employed to determine accurate masses of the α‐skeletal and α‐cardiac actins. Copyright © 2003 John Wiley & Sons, Ltd.
High‐temperature elemental analysis and pyrolysis techniques for stable isotope analysis
Authors: Gehre Matthias , Strauch Gerhard
Published: June 2003

A universal method for pyrolysis and elemental analysis, suitable for the online determination of deuterium, carbon, nitrogen and oxygen isotopes for organic and inorganic substances, is presented. The samples are pyrolytically decomposed in a high‐temperature pyrolysis (HTP) system, at a temperature exceeding 1400°C, in the presence of reactive carbon. The method is suitable for the analysis of stable isotope ratios from hydrogen, carbon, nitrogen and oxygen. The instrumentation and experimental procedure are simple and cost‐effective. The reproducibility of the delta values for D/H is better than 3‰, and for 18O, 13C (organic) and 15N (inorganic) it is ∼0.2‰. The HTP system is suitable for solid and liquid samples and can use an autosampler for the samples. Results are presented for the isotopic composition of international reference materials and selected laboratory reference materials, which demonstrate the precision and accuracy of the method. Possible problems in the measurement of nitrates and their solutions are particularly discussed. The analyses of oxygen isotopes in selected geological samples (carbonates, silicate, biotite) are demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.
Solid‐state glycation of β‐lactoglobulin monitored by electrospray ionisation mass spectrometry and gel electrophoresis techniques
Authors: Fenaille François , Morgan François , Parisod Véronique , Tabet Jean‐Claude , Guy Philippe A.
Published: June 2003

Glycation of β‐lactoglobulin (β‐Lg) with either lactose or galactose in a solid‐state medium was monitored using gel electrophoresis techniques and liquid chromatography coupled to electrospray ionisation mass spectrometry (LC/ESI‐MS). The kinetics of glycation monitored by SDS polyacrylamide gel electrophoresis showed a molecular weight increase over time of the β‐Lg bands for both sugars, but no significant amounts of aggregated proteins were observed. The isoelectric point of the protein, observed by isoelectric focusing gel electrophoresis, was dramatically affected by galactosylation. LC/MS measurements of β‐Lg variants A and B, over the whole glycation reaction time, showed a larger extent of glycation with galactose (from 4 up to 22 adducts) as compared with lactose (from 0 up to 14 adducts), and confirmed that early Maillard reaction products were the main species observed. Based on the relative abundances obtained from the deconvoluted mass spectra after a 8 h 15 min incubation time at 60°C, the mean values of lactose and galactose molecules bound to the protein species were calculated to be 10.4 and 17.9, and 10.5 and 18.6, for variants A and B, respectively. Furthermore, the charge state distribution data obtained by ESI‐MS was studied using different methanol percentages, and indicated that adduct formation with lactose, but more significantly galactose, tends to improve the stability properties of the native protein towards denaturation. Copyright © 2003 John Wiley & Sons, Ltd.
An efficient chemical method for dephosphorylation of phosphopeptides
Authors: Kuyama Hiroki , Toda Chikako , Watanabe Makoto , Tanaka Koichi , Nishimura Osamu
Published: June 2003

Phosphate moieties found on serine, threonine or tyrosine residues in peptides, e.g., in proteolytic digests of proteins, were cleaved using hydrofluoric acid or hydrogen fluoride–pyridine without side reactions. Copyright © 2003 John Wiley & Sons, Ltd.
A simple method for oxygen‐18 determination of milligram quantities of water using NaHCO3 reagent
Authors: Ijiri Akira , Tsunogai Urumu , Gamo Toshitaka
Published: June 2003

This paper presents a modified H2OCO2 equilibration method for stable oxygen isotopic composition (δ18O) analysis of water. This method enables rapid and simple δ18O analysis of milligram quantities of water, by employing solid reagent NaHCO3 as the CO2 source, a small (0.6 mL) glass vial for the equilibration chamber, and an isotope‐monitoring gas chromatography/mass spectrometry (irm‐GC/MS) system for $\delta ^{18} {\rm O}_{{\rm CO}_{\rm 2} }$ analysis. This method has several advantages, including simple handling for the H2OCO2 equilibration (without purging and/or evacuation treatments), rapid and easy δ18O analysis of equilibrated CO2, and highly sensitive and highly precise δ18O analysis of H2O, using samples as small as 10 mg and with a precision of less than ±0.12‰. The time needed to attain oxygen isotopic equilibration between CO2 and water is also comparable (17 h for 10 mg H2O and 10 h for 100 mg H2O) to other previous methods using CO2 gas for the CO2 source. The extent of δ18O variation of sample water from its initial δ18O value due to isotope exchange with added NaHCO3 is also discussed. It is concluded that the correction needed is negligible (less than 0.1‰) as long as the oxygen atom ratio (${\rm O}_{{\rm NaHCO}_{\rm 3} } {\rm /O}_{{\rm H}_{\rm 2} {\rm O}}$) is less than 3.3 ± 10−3 and provided the $\delta ^{18} {\rm O}_{{\rm H}_{\rm 2} {\rm O}}$ determination is made by comparing δ18O of CO2 equilibrated with sample water and that equilibrated with standard water of a moderately close δ18O value, less than 30‰ difference. Copyright © 2003 John Wiley & Sons, Ltd.
Membrane fusion mediated by herpesvirus glycoproteins: the paradigm of varicella‐zoster virus
Authors: Cole Nancy L. , Grose Charles
Published: June 2003

Varicella‐zoster virus (VZV) is well known for its propensity to cause polykaryons (syncytia) in the vesicles within infected skin. Similarly in cultured cells, VZV induces extensive syncytial formation by virus‐mediated cell‐to‐cell fusion. Statistical analyses of fusion parameters demonstrated three‐way interactive effects among all three tested variables (incubation temperature, cell type and virus strain). For example, fusion was greatly enhanced at 33°C vs 37°C; also fusion was pronounced in epidermal cells but negligible in fibroblast cells. As with all herpesviruses, VZV gH was a major fusogen. VZV cell fusion was inhibited by antibody to gH, but surprisingly was enhanced by antibody to gE. Other evidence implicating a role for VZV gE in the fusion process was provided by two mutant viruses, in which gE cell surface expression was enhanced. Under transfection conditions, VZV fusion formation occurred after expression of the gH/gL complex; in contrast, pseudorabies virus requires expression of gH, gL and gB, while the herpes simplex virus (HSV) types 1 and 2 require the quartet of gH, gL, gB and gD. VZV has no gD gene and no apparent gD functional homologue. On the other hand, VZV gE exerts a greater effect than HSV gE on membrane fusion. Taken together, the data in this review suggest that VZV has evolved viral glycoprotein machinery more geared toward cell‐to‐cell fusion (fusion‐from‐within) than toward virus‐to‐cell fusion (entry/fusion‐from‐without), as a means for syncytium formation within the human epidermis. Copyright © 2003 John Wiley & Sons, Ltd.
Cell‐mediated cytotoxicity in recovery from poxvirus infections
Authors: Müllbacher Arno
Published: June 2003

The availability of mutant and gene targeted knockout mice with defects in components of cellular cytotoxicity mediated by either the Fas or the exocytosis pathway permitted an analysis of their role in recovery from poxvirus infections. Ectromelia (EV), a natural mouse pathogen causing mousepox, the closely related orthopoxviruses cow pox (CPV) and vaccinia virus (VV), each encode serpins that inhibit Fas mediated apoptosis and lysis of target cells. Nevertheless, distinct differences were seen when the three viruses were inoculated into perforin‐;deficient mice: highly resistant C57Bl/6 mice became susceptible to low doses of EV; resistance to CPV increased whereas there was no effect on VV infections. Absence of the cytolytic granule associated granzymes (gzm) A and B rendered C57Bl/6 mice increasingly more susceptible to EV infections. Lack of both gzms rendered them as susceptible as perforin deficient mice, despite the presence of functionally active perforin. Elevated EV titres in liver and spleen of gzmA×B deficient mice, early after infection and before cytotoxic T cells were detectable, strongly suggests that these two gzms exert an antiviral effect by a mechanism distinct from effector molecules of NK and cytotoxic T cells. Copyright © 2003 John Wiley & Sons, Ltd.
Transgenic mouse models of hepatitis B virus‐associated hepatocellular carcinoma
Authors: Singh Mahavir , Kumar Vijay
Published: June 2003

The multi‐factorial and multi‐step nature of cancer development makes analysis difficult in cell culture and non‐genetic animal models. Recent progress in technology has allowed the development of several transgenic animal models addressing various aspects of liver diseases caused by hepatitis B virus in human patients. The experimental data from these studies in vivo highlight the importance of HBV gene products that alone or in conjunction with other host cellular protein(s) can deregulate the cell cycle control checkpoints in the hepatocytes of transgenic mice leading to the development of hepatocellular carcinoma. Moreover, these models are extremely useful in analysing and ascertaining the stages of malignant transformation linked to multiple genetic and non‐genetic events of cancer development and in developing novel strategies of intervention. Copyright © 2003 John Wiley & Sons, Ltd.
Polynomial time approximation schemes for dense instances of minimum constraint satisfaction
Authors: Bazgan Cristina , Fernandez de la Vega W. , Karpinski Marek
Published: June 2003

It is known that large fragments of the class of dense Minimum Constraint Satisfaction (MIN‐CSP) problems do not have polynomial time approximation schemes (PTASs) contrary to their Maximum Constraint Satisfaction analogs. In this paper we prove, somewhat surprisingly, that the minimum satisfaction of dense instances ofkSAT‐formulas, and linear equations mod 2, Ek‐LIN2, do have PTASs for anyk.The MIN‐Ek‐LIN2 problems are equivalent to thek‐ary versions of the Nearest Codeword problem, the problem which is known to be exceedingly hard to approximate on general instances. The method of solution of the above problems depends on the development of a new density sampling technique fork‐uniform hypergraphs which could be of independent interest. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 23: 73–91, 2003
Three theorems regarding testing graph properties
Authors: Goldreich Oded , Trevisan Luca
Published: June 2003

Property testing is a relaxation of decision problems in which it is required to distinguish YES‐instances (i.e., objects having a predetermined property) from instances that are far from any YES‐instance. We presents three theorems regarding testing graph properties in the adjacency matrix representation. More specifically, these theorems relate to the project of characterizing graph properties according to the complexity of testing them (in the adjacency matrix representation). The first theorem is that there exist monotone graph properties in 𝒩𝒫 for which testing is very hard (i.e., requires to examine a constant fraction of the entries in the matrix). The second theorem is that every graph property that can be tested making a number of queries that is independent of the size of the graph can be so tested by uniformly selecting a set of vertices and accepting iff the induced subgraph has some fixed graph property (which is not necessarily the same as the one being tested). The third theorem refers to the framework of graph partition problems, and is a characterization of the subclass of properties that can be tested using a one‐sided error tester making a number of queries that is independent of the size of the graph. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 23: 23–57, 2003
Deterministic approximation of the cover time
Authors: Feige Uriel , Rabinovich Yuri
Published: June 2003

The cover time is the expected time it takes a random walk to cover all vertices of a graph. Despite the fact that it can be approximated with arbitrary precision by a simple polynomial time Monte‐Carlo algorithm which simulates the random walk, it is not known whether the cover time of a graph can be computed in deterministic polynomial time. In the present paper we establish a deterministic polynomial time algorithm that, for any graph and any starting vertex, approximates the cover time within polylogarithmic factors. More generally, our algorithm approximates the cover time for arbitrary reversible Markov chains. The new aspect of our algorithm is that the starting vertex of the random walk may be arbitrary and is given as part of the input, whereas previous deterministic approximation algorithms for the cover time assume that the walk starts at the worst possible vertex. In passing, we show that the starting vertex can make a difference of up to a multiplicative factor of$\Theta(n^{3/2}/\sqrt{\log\, n})$in the cover time of ann‐vertex graph. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 23: 1–22, 2003
Rate of convergence of crossover operators
Authors: Ollivier Yann
Published: June 2003

We study the convergence of mating operators on {0, 1}n. In particular, we answer questions of Rabani, Rabinovich, and Sinclair (1998) by giving tight estimates on the divergence between the finite‐ and infinite‐population processes, thus solving positively the problem of the simulability of such quadratic dynamical systems. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 23: 58–72, 2003
Space complexity of random formulae in resolution
Authors: Ben‐Sasson Eli , Galesi Nicola
Published: June 2003

We study the space complexity of refuting unsatisfiable randomk‐CNFs in the Resolution proof system. We prove that for Δ ≥ 1 and any ϵ > 0, with high probability a randomk‐CNF overnvariables and Δnclauses requires resolution clause space of Ω(n/Δ1+ϵ). For constant Δ, this gives us linear, optimal, lower bounds on the clause space. One consequence of this lower bound is the first lower bound for size of treelike resolution refutations of random 3‐CNFs with clause density Δ ≫n. This bound is nearly tight. Specifically, we show that with high probability, a random 3‐CNF with Δnclauses requires treelike refutation size of exp(Ω(n/Δ1+ϵ)), for any ϵ > 0. Our space lower bound is the consequence of three main contributions: (1) We introduce a 2‐player Matching Game on bipartite graphsGto prove that there are no perfect matchings inG. (2) We reduce lower bounds for the clause space of a formulaFin Resolution to lower bounds for the complexity of the game played on the bipartite graphG(F) associated withF. (3) We prove that the complexity of the game is large wheneverGis an expander graph. Finally, a simple probabilistic analysis shows that for a random formulaF, with high probabilityG(F) is an expander. We also extend our result to the case ofG‐PHP, a generalization of the Pigeonhole principle based on bipartite graphsG. © 2003 Wiley Periodicals, Inc. Random Struct. Alg., 23: 92–109, 2003
Calculated bulk vacancy formation energy (Ev) for a Schottky defect in Al single crystals
Authors: Terblans J. J.
Published: June 2003

In this paper the bulk vacancy formation energies (Ev) of Al single crystals (with different surface orientations (111), (100) and (110)) were calculated with the embedded atom method using the empirical many‐body potential of Sutton and Chen. These calculations indicate that there is a significant difference in the bulk vacancy formation energy underneath different surface orientations. The crystal with the (111) surface had the highest bulk vacancy formation energy and the crystal with the (110) surface had the lowest bulk vacancy formation energy. Copyright © 2003 John Wiley & Sons, Ltd.
Quantitative SIMS analysis of SiC
Authors: Kudriavtsev Yu. , Villegas A. , Godines A. , Asomoza R. , Usov I.
Published: June 2003

We performed a systematic study of ion‐implanted 6H‐SiC standards to find the optimal regimes for SIMS analysis. Relative sensitivity factors (RSFs) were acquired for operating conditions typical of practical SIMS applications. The experimental SiC RSFs were compared with those found for silicon:1 the matrix effect was insignificant in most cases. It was found that the SiO− cluster ion cannot represent correctly the real oxygen distribution in SiC. The physics of the effect is discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Mechanism of electroless deposition of Ni–W–P alloys by adding surfactants
Authors: Hamid Z. Abdel
Published: June 2003

This paper describes an electroless deposition method for the formation of a thin metallic film containing mainly nickel with significant amounts of tungsten (up to 25%) and phosphorus (5–10%). The film was deposited from an aqueous electrolyte that contained sodium tungstate as a source of tungsten, nickel sulphate as a source of nickel and hypophosphite as the reducing agent and a source of phosphorus. The surfactants were p‐hexyloxy‐p‐sodium sulphonate azobenzene (HSA) with the formula H13C6OC6H4N2 C6H4SO3Na and p‐hexylbenzyltriethanol ammonium chloride (HBC) with the formula H13C6H4CH2N+ (C2H4OH)3Cl−, added as stabilizers.

In this study the process parameters of typical solutions, such as temperature, pH and concentration of tungstate salt and the concentration of different surfactants, were presented and discussed. Adsorption of the surfactants on a metal surface was dependent, among other things, on the structure of their hydrophobic and hydrophilic portions. The effect of adsorption of these surfactants on a metal surface was examined above and below the critical micelle concentration (CMC). The deposition process involves several reactions that occur simultaneously and are described in detail in this work. The mechanism for interaction of the surfactants with the steel surface was proposed through the isotherm for adsorption from aqueous solution. Furthermore, the surface properties of the surfactants were measured, particularly the CMC, the surface tension reduction and the maximum surface excess Γmax.

The tungsten percentage in the deposit layer was strongly influenced by the plating conditions and the critical concentration of each surfactant. The results were discussed according to the surface properties of the additive. The thin film of Ni–W–P achieved high crystal refinement and high hardness, it was smooth and uniform and it exhibited superior corrosion resistance. Copyright © 2003 John Wiley & Sons, Ltd.
Study of the degradation of plasma‐oxidized polystyrene by time‐ and angle‐resolved x‐ray photoelectron spectroscopy
Authors: Tremblay M.‐C. , Paynter R. W.
Published: June 2003

Angle‐resolved x‐ray photoelectron spectroscopy (ARXPS) measurements were made, in repeated sequences employing Al and Mg x‐ray sources alternately, on a polystyrene sample that had been exposed to an oxygen plasma. It was observed that oxygen was lost from the sample over a period of 5 h and 40 min. The ARXPS data sets were corrected for the time displacement between consecutive measurements at different photoemission angles and fitted with three simple models in order to extract oxygen concentration–depth profiles, consistent with the data, as a function of time. The oxygen depth profiles were found to evolve in a consistent manner, indicating both a loss of average oxygen content and thickness in the ‘oxidized polymer layer’. Copyright © 2003 John Wiley & Sons, Ltd.
Ultrathin SiO2 on Si IV. Intensity measurement in XPS and deduced thickness linearity
Authors: Seah M. P. , Spencer S. J.
Published: June 2003

The procedures for measuring the intensities and for subsequent calculation of the thickness of thermal SiO2 layers on Si in the range 0.3–8 nm have been evaluated to determine the best measurement protocols. This work is based on earlier work where the measurements for (100) and (111) Si surfaces indicate the need to work at a reference geometry. In the spectra, the Si 2p peaks may be separated clearly into the substrate Si and the overlayer SiO2 but it is recommended here that, for accuracies better than 1%, the interface oxides are also analysed. The analysis here is for thermal oxides. Oxides grown by other routes may require a modification of this analysis. It is shown that, in evaluating the data to determine the layer thickness, the failure to remove x‐ray satellites or the use of a straight‐line background will both lead to unacceptable errors that may exceed 5%. On the other hand, if a Shirley background is used consistently for both the peak area analysis and for evaluation of the ratio of intensities for bulk SiO2 and Si, Ro, the results should be linear over the above range to within ±0.025 nm. This excellent result includes the non‐linearities arising from elastic scattering effects and the data reduction method. Equations are provided, together with a value of Ro for Mg and Al x‐rays, to calculate the oxide thicknesses with the above linearity. In order to determine the oxide thickness accurately, the relevant inelastic mean free paths also must be known. Theoretical evaluations are only accurate to 17.4% and so better values need to be obtained by calibration. This paper provides the infrastructure to do this. Crown Copyright © 2003 Published by John Wiley & Sons, Ltd.
Uranium association with corroding carbon steel surfaces
Authors: Eng C. W. , Halada G. P. , Francis A. J. , Dodge C. J. , Gillow J. B.
Published: June 2003

We investigated the association of uranium with clean and corroded surfaces of 1010 carbon steel. Studying steel contaminated by uranium species will have an important effect on the development of methods used to clean radioactively contaminated metal waste. X‐ray photoelectron spectroscopy, synchrotron infrared microspectroscopy and laboratory‐based Fourier transform infrared analysis of steel surfaces exposed to uranyl nitrate showed the presence of crystallized hydrated uranyl oxides, uranyl hydroxides, iron oxyhydroxides and iron oxides. In general, heavily corroded areas physically shield the uranium species, which tended to associate spatially with hydroxyl groups and lepidocrocite. Lightly corroded areas contained uranium species with stronger axial U–O bonding. Infrared spectroscopy, Rutherford backscattering spectroscopy and energy‐dispersive spectroscopy mapping analysis revealed that the uranium species are well distributed within the upper micron of the thick corrosion layer and associated more with areas of high hydroxide content. Parameters such as the concentration of uranyl nitrate solution used to expose the carbon steel coupons, the method of contamination (dipped or sprayed with dilute uranyl nitrate solution) and the degree of corrosion (accelerated corrosion before and/or after contamination) played significant roles in the distribution and nature of the uranyl hydroxide/iron oxyhydroxide corrosion products found on the surface of all coupons. These factors must be considered in the development and optimization of decontamination processes for metal waste. Copyright © 2003 John Wiley & Sons, Ltd.
In situ SERS study of the adsorption of inhibitors of carbon dioxide corrosion
Authors: Durnie William H. , De Marco Roland , Jefferson Alan , Kinsella Brian J.
Published: June 2003

A specially designed electrochemical cell incorporating a rotating disc electrode has been used for in situ surface‐enhanced Raman spectroscopy (SERS) studies of the adsorption of inhibitors of carbon dioxide corrosion onto silver‐coated mild steel electrodes. It is shown that SERS‐active inhibitors comprising aromatic moieties may be detected using the SERS technique. Furthermore, the efficacy of adsorption of corrosion inhibitors employed in the present study is optimal near the open cell or corrosion potential, demonstrating that electrode polarization induces electrostatic forces of repulsion that retard the adsorption of the inhibitor to the corroding steel surface. Copyright © 2003 John Wiley & Sons, Ltd.
Evaluation of the sputtering rate variation in SIMS ultra‐shallow depth profiling using multiple short‐period delta layers
Authors: Homma Y. , Takenaka H. , Toujou F. , Takano A. , Hayashi S. , Shimizu R.
Published: June 2003

We have developed multiple short‐period delta layers as a reference material for SIMS ultra‐shallow depth profiling. Boron nitride delta layers and silicon spacer layers were sputter‐deposited alternately, with a silicon spacer thickness of 1–5 nm. These delta‐doped layers were used to measure the sputtering rate change in the initial stage of oxygen ion bombardment. A significant variation of sputtering rate was observed in the initial 3 nm or less. The sputtering rate in the initial 3 nm was estimated to be about four times larger than the steady‐state value for 1000 eV oxygen ions. Copyright © 2003 John Wiley & Sons, Ltd.
Some statistical methods for investigating the date of birth as a disease indicator
Authors: Le Chap T. , Liu Ping , Lindgren Bruce R. , Daly Kathleen A. , Scott Giebink G.
Published: June 2003

Some methods of temporal statistics are presented and proposed for investigating the date of birth as a disease predictor. A subject's birthday is proposed to be used as a continuous variable with a circular distribution, a special type of interval scale without a true zero point. Three types of endpoints are then considered: a dichotomous endpoint; a continuous endpoint; and time‐to‐event. A study of otitis media is used for illustration. We found, for example, that children born in late winter to early spring tend to have higher cord blood pneumococcal antibody concentration and lower risk of disease as compared to those born in summer to early fall perhaps due largely to exposure to indoor pollution by pregnant mothers. Copyright © 2003 John Wiley & Sons, Ltd.
Age‐specific back‐projection of HIV diagnosis data
Authors: Becker Niels G. , Lewis James J. C. , Li Zhengfeng , McDonald Ann
Published: June 2003

A method for reconstructing the HIV infection curve from data on both HIV and AIDS diagnoses is enhanced by using age as a covariate and by using the diagnosis data to estimate parameters that were previously assumed known. Maximum likelihood estimation is used for parameters of the induction distribution. Each of the set of parameters that specify the baseline rate of infection over time and the set of parameters giving the relative susceptibility over age are estimated by maximizing the likelihood subject to a smoothness requirement. We find that estimating the extra parameters is feasible, producing estimates with good precision. Including age as a covariate gives 90 per cent confidence intervals for the HIV incidence curve that are about 20 per cent narrower than those obtained when age data are not used. Copyright © 2003 John Wiley & Sons, Ltd.
Analysis of pregnancy and other factors on detection of human papilloma virus (HPV) infection using weighted estimating equations for follow‐up data
Authors: Ziegler Andreas , Kastner Christian , Chang‐Claude Jenny
Published: June 2003

Generalized estimating equations have been well established to draw inference for the marginal mean from follow‐up data. Many studies suffer from missing data that may result in biased parameter estimates if the data are not missing completely at random. Robins and co‐workers proposed using weighted estimating equations (WEE) in estimating the mean structure if drop‐out occurs missing at random. We illustrate the differences between the WEE and the commonly applied available case analysis in a simulation study. We apply the WEE and reanalyse data of a longitudinal study of pregnancy and human papilloma virus (HPV) infection. We estimate the response probabilities and demonstrate that the data are not missing completely at random. Upon use of the WEE, we are able to show that pregnant women have an increased odds for an HPV infection compared with non‐pregnant women after delivery (p=0.027). We conclude that the WEE are useful for dealing with monotone missing data due to drop‐outs in follow‐up data. Copyright © 2003 John Wiley & Sons, Ltd.
An overview of the variables selection methods for the minimum sum of absolute errors regression
Authors: André Carmen D. S. , Narula Subhash C. , Elian Silvia N. , Tavares Rodrigo A.
Published: June 2003

The minimum sum of absolute errors regression is a robust alternative to the least squares regression whenever the errors follow a distribution for which the sample median is a more efficient estimator of location parameter than the sample mean, the errors follow a long tailed distribution, there are outliers in the values of the response variable in the data or the absolute error loss function is more appropriate than the quadratic loss function. Often an initial model may contain a large number of variables. However, in many situations, it is neither necessary nor important to include all the variables in the model. The methods for variable selection for the minimum sum of absolute errors regression are not as well documented and known as for the least squares regression. Our objective is to present an overview of the procedures to fit models with fewer variables and some criteria for selecting a model. Copyright © 2003 John Wiley & Sons, Ltd.
Joint models for efficient estimation in proportional hazards regression models
Authors: Slasor Peter , Laird Nan
Published: June 2003

In survival studies, information lost through censoring can be partially recaptured through repeated measures data which are predictive of survival. In addition, such data may be useful in removing bias in survival estimates, due to censoring which depends upon the repeated measures. Here we investigate joint models for survival T and repeated measurements , given a vector of covariates . Mixture models indexed as f(T∣) f(∣T,) are well suited for assessing covariate effects on survival time. Our objective is efficiency gains, using non‐parametric models for in order to avoid introducing bias by misspecification of the distribution for . We model (T∣) as a piecewise exponential distribution with proportional hazards covariate effect. The component (∣T,) has a multinomial model. The joint likelihood for survival and longitudinal data is maximized, using the EM algorithm. The estimate of covariate effect is compared to the estimate based on the standard proportional hazards model and an alternative joint model based estimate. We demonstrate modest gains in efficiency when using the joint piecewise exponential joint model. In a simulation, the estimated efficiency gain over the standard proportional hazards model is 6.4 per cent. In clinical trial data, the estimated efficiency gain over the standard proportional hazards model is 10.2 per cent. Copyright © 2003 John Wiley & Sons, Ltd.