bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel process for the preparation of thick porous silicon layers with very high porosity
Authors: Feyh A. , Laermer F. , Kronmüller S. , Mokwa W.
Published: May 2005

A novel process for the preparation of thick porous silicon layers having very high porosities is proposed. Starting with thick layers of intermediate porosity the porosity is further increased in an additional step. This is done by means of controlled partial oxidation of the silicon skeleton followed by selective removal of the oxide film in an HF vapor phase etching process. Due to this, porosities beyond 90% are accessible since any further liquid phase contact is avoided and therefore no additional drying steps are necessary. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electron beam irradiation of porous silicon for application in micromachining and sensing
Authors: Borini S. , Rocchia M. , Rossi A. M. , Boarino L. , Amato G.
Published: May 2005

We have studied the effect of the electron beam (EB) irradiation on porous silicon (PS), in order to find new possibilities for the local modification of the material at the submicrometer scale. The interaction between the accelerated electrons and PS has been investigated by means of two main techniques: infrared spectroscopy and profilometric measurements. All the results show that a strong increase of reactivity is induced on PS surface under exposure to the EB, due to the hydrogen desorption provoked by the incident electrons. We demonstrate that this phenomenon can be exploited for both the lateral structuring and the local functionalization of PS, at the submicrometer scale, depending on the different treatments applied to the samples after the EB bombardment. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Temperature dependence of thermally‐carbonized porous silicon humidity sensor
Authors: Björkqvist M. , Paski J. , Salonen J. , Lehto V.‐P.
Published: May 2005

Thermal carbonization of porous silicon (PS) at 820 °C under acetylene atmosphere is an appropriate method for humidity sensing purposes. It produces stable and hydrophilic surface still maintaining originally large specific surface area of PS. We report the temperature dependence of various electrical param‐ eters measured for the thermally‐carbonized PS humidity sensor. Capacitance of the sensor in dry air (6 RH%) is almost constant at various temperatures, whereas in higher relative humidity values, the temperature dependence becomes evident. The resistance variation of the sensor is less dependent on RH as the temperature increases. While the capacitance showed linear behavior as a function of temperature, the resistance had a clear non‐linear temperature dependence. In order to get information about the effects of frequency on capacitance values, we measured a phase angle and admittance of the sensor as a function of frequency at three different temperatures in low and high humidity. According to these results, it is preferable to operate this sensor construction using low frequency (<1 kHz). (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Properties of cubic GaN films obtained by nitridation of porous GaAs(001)
Authors: Kidalov V. V. , Sukach G. A. , Revenko A. S. , Bayda A. D.
Published: May 2005

With the help of nitridation of porous GaAs(001) in nitrogen plasma thin films of cubic‐GaN were obtained. The conclusion was made that the quality of the GaN films is dependent on the degree of porosity of the GaAs substrate. XPS spectra were used to investigate the chemical composition of porous GaAs substrates, obtained by electrochemical etching. Porous GaAs substrate at first was annealed in a H2 flow at a temperature of 550 °C (with the aim of removing oxygen from the surface of the porous GaAs). Then, the porous GaAs substrate was annealed in atomic nitrogen at a temperature of 400 °C, and then annealed in vacuum at 600 °C. From XPS measurement we determined that the annealing in atomic nitrogen leads to the formation of GaN films. X‐ray diffraction measurements show that cubic GaN on porous GaAs substrate has no tensile strain. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Pictorial markings and labels for safe transport and handling of packaged goods
Authors: Singh S. Paul , Singh Jagjit
Published: May 2005

This paper presents the various sources of pictorial markings and warning labels that can be used on packaged goods. Lack of appropriate warnings or markings can result in severe hazards that can affect the safety of individuals and the work environment. The paper shows examples of good and poor applications of warnings and also discusses the various standards that assist in developing appropriate package markings for your goods. New markings recently being developed will also be discussed. Copyright © 2005 John Wiley & Sons, Ltd.
Discrimination of diastereoisomers by electron ionization mass spectrometry in the 1,3‐dioxane series
Authors: Loutelier‐Bourhis C. , Balog M. , Grosu I. , Ramondenc Y. , Plé G. , Lange C. M.
Published: May 2005

Important differences in the electron ionization (EI) mass spectra of cis,cis and trans,trans isomers of some 2(r)‐R‐2,4(R),6(S)‐trimethyl‐1,3‐dioxanes are recorded and the significant preference for the fragmentation with the cleavage of the axial substituents at C(2) position is revealed. The fragmentation pattern is elucidated by high‐resolution mass measurements, metastable ion spectra and linked‐scan mass spectrometry. Copyright © 2005 John Wiley & Sons, Ltd.
Serum protein profiling by miniaturized solid‐phase extraction and matrix‐assisted laser desorption/ionization mass spectrometry
Authors: Callesen Anne K. , Mohammed Shabaz , Bunkenborg Jakob , Kruse Torben A. , Cold Søren , Mogensen Ole , Christensen Rene dePont , Vach Werner , Jørgensen Per E. , Jensen Ole N.
Published: May 2005

Serum profiling by matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) holds promise as a clinical tool for early diagnosis of cancer and other human diseases. Sample preparation is key to achieving reproducible and well‐resolved signals in MALDI‐MS; a prerequisite for translation of MALDI‐MS based diagnostic methods to clinical applications. We have investigated a number of MALDI matrices and several miniaturized solid‐phase extraction (SPE) methods for serum protein concentration and desalting with the aim of generating reproducible, high‐quality protein profiles by MALDI‐MS. We developed a simple protocol for serum profiling that combines a matrix mixture of 2,5‐dihydroxybenzoic acid and α‐cyano‐4‐hydroxycinnamic acid with miniaturized SPE and MALDI‐MS. Functionalized membrane discs with hydrophobic, ion‐exchange or chelating properties allowed reproducible MALDI mass spectra (m/z 1000–12 000) to be obtained from serum. In a proof‐of‐principle application, SPE with chelating material and MALDI‐MS identified protein peaks in serum that had been previously reported for distinguishing a person diagnosed with breast cancer from a control. These preliminary results indicate that this simple SPE/MALDI‐MS method for serum profiling provides a versatile and scalable platform for clinical proteomics. Copyright © 2005 John Wiley & Sons, Ltd.
Diagnostic protein discovery using liquid chromatography/mass spectrometry for proteolytic peptide targeting
Authors: Koomen John M. , Zhao Haitao , Li Donghui , Nasser Waleed , Hawke David H. , Abbruzzese James L. , Baggerly Keith A. , Kobayashi Ryuji
Published: May 2005

A peptide targeting method has been developed for diagnostic protein discovery, which combines proteolytic digestion of fractionated plasma proteins and liquid chromatography coupled to electrospray time‐of‐flight mass spectrometry (LC/ESI‐TOFMS) profiling. Proteolysis prior to profiling overcomes molecular weight limitations and compensates for the poor sensitivity of matrix‐assisted laser desorption/ionization (MALDI) protein profiling. LC/MS increases the peak capacity compared to crude fractionation techniques or single sample MALDI analysis. Differentially expressed peptides are targeted in the mass chromatograms using bioinformatic techniques and subsequently sequenced with MALDI tandem MS. In a model study comparing pancreatic cancer patients to controls, 74% of the peptide targets were successfully sequenced. This profiling method was superior to previous experiments using single sample MALDI analysis for protein profiling or proteolytic peptide profiling, because more potential protein markers were identified. Copyright © 2005 John Wiley & Sons, Ltd.
Use of a five‐channel multiplexed electrospray quadrupole time‐of‐flight hybrid mass spectrometer for metabolite identification
Authors: Leclercq Laurent , Delatour Claude , Hoes Ilse , Brunelle Françoise , Labrique Xavier , Castro‐Perez José
Published: May 2005

Metabolism data provided with reduced cycle time has become of increasing importance for the early evaluation of DMPK properties of drugs in discovery. In this regard, quadrupole time‐of‐flight hybrid mass spectrometers (Q‐TOF) can provide very reliable metabolite identification via accurate mass measurement of ions and the consequent access to the elemental composition of the metabolite. However, due to their cost, they are often used for drug metabolism studies on later stage drug candidates or to address challenging metabolism questions. A new prototype, consisting of a five‐channel multiplexed electrospray ionization (ESI) source on a Q‐TOF with one channel used for lock‐mass compound infusion, was evaluated for metabolite identification. The goal was to increase the sample throughput of a single ESI‐MS system by a factor of 4, while maintaining efficient metabolite separation in high‐performance liquid chromatography (HPLC) as well as adequate sensitivity and mass accuracy, and ultimately improve the speed and quality of metabolism studies supporting drug discovery. The analytical performance of the system was assessed by evaluating the sensitivity and mass accuracy (using real in vitro and in vivo samples), inter‐channel differences in retention times, MS/UV response, and cross‐talk among channels. The sensitivity using the multiplexed ESI source was on average 2‐fold lower than with single ESI, correlating well with previous literature data. The mass accuracy was comparable to that obtained using single ESI in both MS and MS/MS modes, making the metabolite identification process using the multiplexed ESI source as reliable as with single ESI. Compound‐dependent differences in ionization efficiencies were observed among channels, and were minimized by analyzing related samples on the same channel. Finally, the level of cross‐talk among channels was acceptable (around 0.3%) and comparable to levels previously published for quantitative applications using multiplexed ESI. The paper also focuses on the advantages and disadvantages of this new approach compared to other approaches in the literature in the field of metabolite identification. Copyright © 2005 John Wiley & Sons, Ltd.
Electrospray ionization mass spectrometry as a tool for determination of drug binding sites to human serum albumin by noncovalent interaction
Authors: Benkestock Kurt , Edlund Per‐Olof , Roeraade Johan
Published: May 2005

Most proteins in blood plasma bind ligands. Human serum albumin (HSA) is the main transport protein with a very high capacity for binding of endogenous and exogenous compounds in plasma. Many pharmacokinetic properties of a drug depend on the level of binding to plasma proteins. This work reports studies of noncovalent interactions by means of nanoelectrospray ionization mass spectrometry (nanoESI‐MS) for determination of the specific binding of selected drug candidates to HSA. Warfarin, iopanoic acid and digitoxin were chosen as site‐specific probes that bind to the main sites of HSA. Two drug candidates and two known binders to HSA were analyzed using a competitive approach. The drugs were incubated with the target protein followed by addition of site‐specific probes, one at a time. The drug candidates showed predominant affinity to site I (warfarin site). Naproxen and glyburide showed affinity to both sites I and II. The advantages of nanoESI‐MS for these studies are the sensitivity, the absence of labeled molecules and the short method development time. Copyright © 2005 John Wiley & Sons, Ltd.
Quantification of the plant‐derived hallucinogen Salvinorin A in conventional and non‐conventional biological fluids by gas chromatography/mass spectrometry after Salvia divinorum smoking
Authors: Pichini Simona , Abanades Sergio , Farré Magí , Pellegrini Manuela , Marchei Emilia , Pacifici Roberta , Torre Rafael de la , Zuccaro Piergiorgio
Published: May 2005

A gas chromatography method with mass spectrometric detection is described for the determination of Salvinorin A, the main active ingredient of the hallucinogenic mint Salvia divinorum. The method was validated in plasma, urine, saliva and sweat using 17‐α‐methyltestosterone as internal standard. The analytes were extracted from biological matrices with chloroform/isopropanol (9:1, v/v). Chromatography was performed on a 5% phenyl methyl silicone capillary column and analytes were determined in the selected ion monitoring mode. The method was validated over the concentration range 0.015–5 μg/mL plasma, urine and saliva and 0.01–5 μg/patch in the case of sweat. Mean recoveries ranged between 77.1 and 92.7% for Salvinorin A in different biological matrices, with precision and accuracy always better than 15%. The method was applied to the analysis of urine, saliva and sweat from two consumers after smoking 75 mg plant leaves to verify the presence of the active ingredient of S. divinorum in human biological fluids as a biomarker of plant consumption. Salvinorin A was detected in urine (2.4 and 10.9 ng/mL) and saliva (11.1 and 25.0 ng/mL), but not in sweat patches from consumers. Copyright © 2005 John Wiley & Sons, Ltd.
Elucidation of the molecular structure of lipid A isolated from both a rough mutant and a wild strain of Aeromonas salmonicida lipopolysaccharides using electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry
Authors: El‐Aneed Anas , Banoub Joseph
Published: May 2005

The chemical structure of lipid A, isolated by mild acid hydrolysis from a rough mutant and a wild strain of Aeromonas salmonicida lipopolysaccharide, was investigated using electrospray ionization quadrupole time‐of‐flight (QqToF) hybrid tandem mass spectrometry and showed a great degree of microheterogeneity. The chemical structure of the main constituent of this heterogeneous mixture was identified as a β‐D‐(1 → 6) linked D‐glucosamine disaccharide substituted by two phosphate groups, one being bound to the non‐reducing end at position O‐4′ and the other to the position O‐1 of the reducing end of the D‐glucosamine disaccharide. The location of the fatty acids linked to the disaccharide backbone was established by identifying diagnostic ions in the conventional QqToF‐MS scan. Low‐energy collision tandem mass spectrometry analysis of the selected precursor diagnostic ions confirmed, unambiguously, their proposed molecular structures. We have established that myristyloxylauric (C14:0(3‐O(12:0))) acid residues were both N‐2′ and O‐3′ linked to the non‐reducing end of the D‐GlcN residue, and that two 3‐hydroxymyristic (C14:0(3‐OH)) acid chains acylated the remaining positions of the reducing end. The MS and MS/MS data obtained allowed us to determine the complex molecular structure of lipid A. The QqToF‐MS/MS instrument has shown excellent superiority over a conventional quadrupole‐hexapole‐quadrupole tandem instrument which failed to fragment the selected precursor ion. Copyright © 2005 John Wiley & Sons, Ltd.
Liquid chromatography/electrospray mass spectrometric analysis of metabolites from an inhibitory RNA duplex
Authors: Beverly Michael , Hartsough Kim , Machemer Lynn
Published: May 2005

Liquid chromatography/mass spectrometry (LC/MS) was used as a method for analyzing the metabolites of a model short interfering RNA (siRNA) duplex. The model siRNA duplex incorporated oligonucleotide stabilizing and protecting chemistries as these have been shown to increase the half‐life of oligonucleotides. Two complementary 23 nucleotide single strands were joined to form the duplex. The intact duplex was analyzed using ion‐pair reversed‐phase chromatography coupled to electrospray ionization mass spectrometry (ESI‐MS). The method used a hexafluoroisopropanol/triethylamine ion‐pairing buffer with a methanol gradient to separate single‐stranded oligonucleotide components from the duplex. This buffer system with ESI also preserved the duplex in the gas phase for analysis by a triple quadrupole mass spectrometer. Using this methodology, in vitro and in vivo metabolites from urine and rabbit ocular vitreous humor were determined and a pattern of duplex siRNA degradation was established. The masses of the metabolites were determined by ESI‐MS and used with the known sequence of the siRNA duplex to identify the metabolites. Over the time course of the metabolism experiments it was shown that the breakdown products of the siRNA are consistent with the nuclease protection given by chemical modifications and that the duplex structure adds additional stability compared to the single strands alone. This study demonstrates that the ability of LC/MS to analyze duplex oligonucleotides has unique benefits for the study of siRNA metabolism. Copyright © 2005 John Wiley & Sons, Ltd.
Fast analysis of low molecular mass compounds present in snake venom: identification of ten new pyroglutamate‐containing peptides
Authors: Wermelinger Luciana Serrão , Dutra Denis L. S. , Oliveira‐Carvalho Ana L. , Soares Márcia Regina , Bloch Carlos , Zingali Russolina B.
Published: May 2005

Characterization of the peptide content in snake venoms can be an important tool for the investigation of new pharmacological lead compounds. For this purpose, single‐step analysis of crude venoms has recently been demonstrated using mass spectrometry (MS) techniques. Reproducible profiles of ions in MS and MS/MS spectra may also be used to compare venoms from different species. In this work matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) was used to obtain mass patterns of the major peptides (<8 kDa) found in pooled venoms from the genera Bothrops and Crotalus. Venoms from five different Bothrops species (B. jararaca, B. insularis, B. alternatus, B. jararacussu, and B. neuwiedi) and three Crotalus species (C. viridis, C. adamanteus and C. durissus terrificus) were analyzed. In agreement with other reports, venoms from Bothrops species contained a variety of peptides in the range m/z 1000–1500, and in some samples larger components (m/z 7000–8000) were detected. In the Crotalus species venoms were rich in peptides ranging from m/z 1000–1500 and 4000–5500. MS/MS experiments on the low molecular mass peptides (m/z 1000–1500) confirmed the presence of ten new bradykinin‐potentiating peptides among venoms from genera Bothrops and Crotalus. In order to determine whether additional peptides could be identified after partial purification, B. jararaca venom was subjected to size‐exclusion chromatography on Sephacryl S‐200, and two distinct low molecular mass pools were analyzed further by MALDI‐TOFMS. No additional peptides were detected from the pool with masses below 2000 Da but a substantial improvement with better resolution was observed for the pool with masses above 7000 Da, indicating that complex samples such as crude snake venoms can be analyzed for low molecular mass peptides using a single‐step procedure. Copyright © 2005 John Wiley & Sons, Ltd.
The synthesis of internal standards for the quantitative determination of sphingolipids by tandem mass spectrometry
Authors: Mills Kevin , Eaton Simon , Ledger Victoria , Young Elisabeth , Winchester Bryan
Published: May 2005

Novel internal standards have been synthesised for the quantitative determination by tandem mass spectrometry (MS/MS) of the sphingolipids that accumulate in lysosomal storage diseases. The [d4]C16‐ and [d47]C24‐isoforms of galactosylceramide (CMH), lactosylceramide (CDH), globotriaosylceramide (CTH), cerebroside sulphate, sphingomyelin and GM1‐, GM2‐ and GM3‐gangliosides were synthesised by the reaction of their lyso‐forms with the acid chlorides of hexadecanoic 5,5,6,6‐d4 acid ([d4]‐palmitic acid) and tetracosanoic‐d47 acid ([d47]‐lignoceric acid), respectively. The acid chlorides were formed using oxalyl chloride. The structures of the internal standards were confirmed by MS/MS. The fragmentation pattern of each novel compound was similar to that of the corresponding natural form of the sphingolipid, making it a good internal standard for the quantitative determination of the natural sphingolipid by ESI‐MS/MS. Characteristic product ions were identified for each compound. Copyright © 2005 John Wiley & Sons, Ltd.
Sulfonamide bond cleavage in benzenesulfonamides and rearrangement of the resulting p‐aminophenylsulfonyl cations: application to a 2‐pyrimidinyloxybenzylaminobenzenesulfonamide herbicide
Authors: Wang Hao‐Yang , Zhang Xiang , Guo Yin‐Long , Dong Xi‐Cheng , Tang Qing‐Hong , Lu Long
Published: May 2005

The gas‐phase fragmentation/rearrangement reactions of compound 1, [2‐(4,6‐dimethoxypyrimidin‐2‐yloxy)‐benzyl]‐[4‐(piperidine‐1‐sulfonyl)phenyl]amine, have been examined by Fourier transform ion cyclotron resonance mass spectrometry (FTICR‐MS). The analyses reveal that under sustained off‐resonance irradiation collision‐induced dissociation (SORI‐CID) conditions in the FTICR cell, protonated 1 undergoes two competitive pathways initiated by different protonation positions. The first pathway is initiated by protonation on the amino group and yields only one fragment ion due to loss of the entire benzenesulfonamide moiety. In the second pathway, protonation of the sulfonamide group leads to cleavage of a sulfonamide bond with loss of the neutral piperidine, followed by loss of SO via a sulfonyl cation rearrangement. An intramolecular SNAr mechanism is proposed to rationalize the rearrangement of the p‐aminophenylsulfonyl cation and the resulting SO loss. To test the generality of this process, SORI‐CID spectra of protonated sulfamethoxazole and of the p‐aminophenylsulfonyl cation (SBN) were obtained. For the SBN ion, SORI‐CID experiments as well as density functional theory (B3LYP) calculations show that rearrangement, assigned as a SNAr reaction of the sulfonyl cation group, can account for the observed SO loss process. Candidate transition state structures were optimized at the B3LYP/6‐31+G (d, p) level of theory using the Gaussian98 molecular modeling package. The computational results show that the barrier for SO loss from SBN is much lower than that for SO2 loss, which satisfactorily rationalizes the SORI‐CID experimental results for SBN. Moreover, it is proposed that a fragment ion at m/z 196 in the MS/MS spectrum of protonated 1 is formed via the ion resulting from SO loss via a second intramolecular SNAr mechanism. Copyright © 2005 John Wiley & Sons, Ltd.
A monolithic PNGase F enzyme microreactor enabling glycan mass mapping of glycoproteins by mass spectrometry
Authors: Palm Anders K. , Novotny Milos V.
Published: May 2005

We demonstrate a simple and rapid single‐step method to fabricate an enzyme microreactor incorporating the N‐glycosidase PNGase F (peptide‐N‐glycosidase F) into a porous polymer‐based monolith. The monolith is contained in a capillary format, while the enzyme reactor is ready to use within 1 h of preparation. The monomers making up the monolith, including N‐acryloxysuccinimide for covalent immobilization of the enzyme, are mixed with PNGase F and introduced into the column by capillary force for polymerization/immobilization. Glycoproteins (ribonuclease B, asialofetuin, α1‐acid glycoprotein, and ovalbumin) perfused through the PNGase F reactor were shown to be effectively deglycosylated on a time‐scale of seconds/low minutes using low nanogram to microgram per microliter concentration (corresponding to a total sample consumption of 0.1–20 μg of a glycoprotein). The reactor enzyme activity was shown to be reproducible for at least 8 weeks when used and stored at room temperature. Evaluation was performed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry. Copyright © 2005 John Wiley & Sons, Ltd.
Advantages of atmospheric pressure photoionization mass spectrometry in support of drug discovery
Authors: Cai Yanxuan , Kingery David , McConnell Oliver , Bach Alvin C.
Published: May 2005

The performance of the atmospheric pressure photoionization (APPI) technique was evaluated against five sets of standards and drug‐like compounds and compared to atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). The APPI technique was first used to analyze a set of 86 drug standards with diverse structures and polarities with a 100% detection rate. More detailed studies were then performed for another three sets of both drug standards and proprietary drug candidates. All 60 test compounds in these three sets were detected by APPI with an overall higher ionization efficiency than either APCI or ESI. Most of the non‐polar compounds in these three sets were not ionized by APCI or ESI. Analysis of a final set of 201 Wyeth proprietary drug candidates by APPI, APCI and ESI provided an additional comparison of the ionization techniques. The detection rates in positive ion mode were 94% for APPI, 84% for APCI, and 84% for ESI. Combining positive and negative ion mode detection, APPI detected 98% of the compounds, while APCI and ESI detected 91%, respectively. This analysis shows that APPI is a valuable tool for day‐to‐day usage in a pharmaceutical company setting because it is able to successfully ionize more compounds, with greater structural diversity, than the other two ionization techniques. Consequently, APPI could be considered a more universal ionization method, and therefore has great potential in high‐throughput drug discovery especially for open access liquid chromatography/mass spectrometry (LC/MS) applications. Copyright © 2005 John Wiley & Sons, Ltd.
Combinatorial criteria for uniqueness of Gibbs measures
Authors: Weitz Dror
Published: May 2005

We generalize previously known conditions for uniqueness of the Gibbs measure in statistical physics models by presenting conditions of any finite size for models on any underlying graph. We give two dual conditions, one requiring that the total influenceona site is small, and the other that the total influenceofa site is small. Our proofs are combinatorial in nature and use tools from the analysis of discrete Markov chains, in particular the path coupling method. The implications of our conditions for the mixing time of natural Markov chains associated with the models are discussed as well. We also present some examples of models for which the conditions hold. © 2005 Wiley Periodicals, Inc. Random Struct. Alg., 2005
On the asymptotic behavior of some algorithms
Authors: Robert Philippe
Published: May 2005

A simple approach is presented to study the asymptotic behavior of some algorithms with an underlying tree structure. It is shown that some asymptotic oscillating behaviors can be precisely analyzed without resorting to complex analysis techniques as it is usually done in this context. A new explicit representation of periodic functions involved is obtained at the same time. © 2005 Wiley Periodicals, Inc. Random Struct. Alg., 2005
The impact of choice of reference charts and equations on the assessment of fetal biometry
Authors: Salomon L. J. , Bernard J. P. , Duyme M. , Buvat I. , Ville Y.
Published: May 2005

Objectives

The assessment of fetal biometry is usually based on the comparison of measured values with predicted values derived from reference charts or equations in a normal population. This study was undertaken to assess the impact of the choice of reference charts and to develop a Z‐score‐based tool that could help sonographers to choose the reference charts that best fit their practice.

Methods

Fetal biparietal diameter, head circumference, abdominal circumference and femur diaphysis length measurements were made at 20–24 and 30–34 weeks' gestation by four experienced sonographers. All measurements were transformed into Z‐scores calculated according to three prediction equations (Snijders and Nicolaides, 1994; Chitty et al., 1994 and Kurmanavicius et al., 1999). Distributions of Z‐scores were compared to the expected standard normal distribution based on mean, SD and Kolmogorov–Smirnov test. Simulations were made to assess sensitivity (Se), specificity (Sp) and Youden's index (Se + Sp − 1) of each reference equation, reflecting their ability to identify fetuses with abnormal biometry in our population. The reference that best fitted our practice was determined based on these results.

Results

The Z‐scores of all biometric parameters were significantly different (P < 0.001) when using any of the three reference equations, and none of the Z‐score distributions could be considered similar to the standard normal distribution. The number of measurements that would be considered as abnormal according to these references ranged from 2.6% to 23.6%. Se and Sp ranged from 39.59% to 67.12% and 90.14% to 99.69%, respectively.

Conclusion

Assessment of fetal biometry is largely dependent on the choice of reference charts. We suggest that the choice of reference charts for fetal biometry could be controlled using Z‐scores in each institution and that this could be the first step towards any quality assessment policy. The method we describe for the choice of the most appropriate fetal biometry reference chart might be used for all size charts. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Outcome of 60 neonates who had ARED flow prenatally compared with a matched control group of appropriate‐for‐gestational age preterm neonates
Authors: Hartung J. , Kalache K. D. , Heyna C. , Heling K.‐S. , Kuhlig M. , Wauer R. , Bollmann R. , Chaoui R.
Published: May 2005

Objective

To describe the course and outcome of fetuses with absent or reversed end‐diastolic (ARED) flow in the umbilical artery (UA) and to examine the influence of prematurity according to gestational age at delivery.

Methods

Sixty pregnancies complicated by ARED flow in the UA were monitored by repeat Doppler measurements of arterial and venous vessels, non‐stress tests (cardiotocogram (CTG)) and maternal investigations, and were delivered between 24 and 34 weeks. Fetal outcome was investigated and compared to a control group of appropriate‐for‐gestational age (AGA) preterm neonates, matched for gestational age. Mortality, birth weight, Apgar scores, postnatal cord arterial pH and need for ventilation were all recorded, as were cases of respiratory distress syndrome, bronchopulmonary dysplasia, persistent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage, periventricular leukomalacia, abnormal neurological findings and those requiring surgical intervention. Additionally, the group of fetuses with ARED flow was divided into three subgroups of different degrees of prematurity (delivery between 24 + 0 and 28 + 6 weeks, delivery between 29 + 0 and 31 + 6 weeks, and delivery after 32 weeks) and compared according to the above parameters.

Results

Pre‐ or postnatal death occurred in 16 cases. Comparing the 44 (61%) that were born alive with the AGA neonates, significant differences were found in birth weight (P < 0.001), arterial pH value (P < 0.001), bronchopulmonary dysplasia (P = 0.002) and intestinal complications (P < 0.01). Prematurity‐related complications were: need for ventilation (P = 0.001), respiratory distress syndrome (P < 0.0001), periventricular leukomalacia (P = 0.002) and pathological neurological testing (P = 0.005).

Conclusions

Neonates displaying ARED flow before birth are growth restricted, acidemic at delivery and are at high risk of developing bronchopulmonary dysplasia and intestinal complications. While perinatal mortality seems to be related to abnormal fetal Doppler velocimetry, age at delivery has a significant impact on short‐term morbidity. After 32 weeks, morbidity is low and delivery should be considered. It could be speculated from our data that prolongation of pregnancy with Doppler velocimetry monitoring could help to reduce morbidity, although prolongation remains limited in most cases. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Three‐dimensional ultrasound for the assessment of breast lesions
Authors: Watermann D. O. , Földi M. , Hanjalic‐Beck A. , Hasenburg A. , Lüghausen A. , Prömpeler H. , Gitsch G. , Stickeler E.
Published: May 2005

Objective

To evaluate the diagnostic accuracy of three‐dimensional (3D) ultrasound in comparison with conventional two‐dimensional (2D) ultrasound in the characterization of breast lesions.

Methods

The digitally stored 2D ultrasound images and the corresponding 3D scans of 100 breast lesions (57 malignant, 43 benign) that had been morphologically classified as solid tumors, were independently analyzed by six investigators. Ten 2D and 13 3D ultrasound characteristics were determined. Lesion characterization was classified on a four‐point scale and a logistic regression model was used to analyze the data. A receiver–operating characteristics curve (ROC) analysis was performed to determine the diagnostic performance of 2D and 3D ultrasound, respectively.

Results

Ultrasound criteria showed major differences between 2D and 3D ultrasound. Logistic regression revealed the retraction phenomenon in the coronal plane of the 3D ultrasound scan to be a significant and independent factor for lesion characterization. The characteristics determined on the conventional planes of 3D ultrasound differed from those determined on the 2D ultrasound images. The diagnostic accuracy of 2D and 3D ultrasound in the ROC analysis was almost identical (area under the curve 0.846 and 0.851, respectively).

Conclusions

Ultrasound features on 3D ultrasound differ significantly from those on 2D ultrasound. However, the diagnostic accuracy of both methods is almost identical. 3D ultrasound as an adjunct to conventional 2D ultrasound should be evaluated in larger trials to determine its clinical value in breast imaging. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal sonographic findings in Peters‐plus syndrome
Authors: Boog G. , Le Vaillant C. , Joubert M.
Published: May 2005

Peters syndrome is a congenital disease resulting from deficient cleavage of the anterior chamber of the eye. Peters‐plus syndrome (PpS) is characterized by the typical ocular anomalies of Peters syndrome in association with impaired growth, mental retardation and other malformations. We report the first prenatal description of PpS in the 20‐week fetus of a consanguineous couple. Ultrasound examination revealed microphthalmia and hyperechogenicity of the anterior part of the eye with a central defect, micrognathia and long philtrum, short limbs with broad extremities and unilateral multicystic kidney. The pregnancy was terminated on parental request. Autopsy, including careful ocular examination, established the diagnosis of PpS. PpS has an autosomal‐recessive mode of inheritance. The ocular anomaly has been linked with mutations in genes PAX6, PITX2, PITX3 and CYP1B1, but the causal factor of PpS remains unknown. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Prenatal findings in epidermolysis bullosa with pyloric atresia in a family not known to be at risk
Authors: De Jenlis Sicot B. , Deruelle P. , Kacet N. , Vaillant C. , Subtil D.
Published: May 2005

Epidermolysis bullosa with pyloric atresia (EB‐PA) is a rare autosomal recessive genetic disease with a poor prognosis. We report a case of EB‐PA in a non‐consanguineous couple with a non‐contributory family history. The primigravid woman was referred to us because of polyhydramnios associated with fetal gastric dilatation at 33 weeks of gestation. Maternal serum alpha‐fetoprotein (AFP) had been elevated at 15 weeks' gestation (3.08 multiples of the median), and ultrasound examination showed polyhydramnios with echogenic amniotic fluid, gastric dilatation, and no other associated malformation. The fetal karyotype was normal female (46,XX). Acetylcholinesterase (ACHe) and AFP levels in the amniotic fluid were normal. Labor occurred spontaneously at 35 weeks' gestation. Clinical examination of the newborn showed large areas of cutaneous blisters and erosions, as well as pyloric atresia. Immunofluorescence analysis of skin samples confirmed EB‐PA. Molecular analysis showed a new mutation of the integrin β‐4 gene: heterozygote missense deletions (3807delC/310delC, respectively, exons 31 and 5). The child died from severe sepsis at the age of 13 days. Our observation emphasizes the difficulty of interpreting prenatal ultrasound findings when there is no suggestive context. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Qualitative venous Doppler flow waveform analysis in preterm intrauterine growth‐restricted fetuses with ARED flow in the umbilical artery—correlation with short‐term outcome
Authors: Schwarze A. , Gembruch U. , Krapp M. , Katalinic A. , Germer U. , Axt‐Fliedner R.
Published: May 2005

Objective

The aim of this retrospective study was to examine the significance of severe Doppler waveform abnormalities in the ductus venosus (DV) and the umbilical vein (UV) for the prediction of adverse outcomes in very preterm growth‐restricted fetuses with absent or reversed end‐diastolic flow in the umbilical artery (UA) at 24–34 weeks of gestation.

Methods

Seventy‐four fetuses with intrauterine growth restriction (IUGR) and absent or reversed end‐diastolic (ARED) flow in the UA at 24–34 weeks of gestation, which were delivered before 34 weeks' gestation, were examined. Absent or reversed flow during atrial contraction (a‐wave) in the DV and pulsatile flow in the UV were examined to predict severe perinatal outcomes (stillbirth, neonatal death, perinatal death, acidemia, 5 min Apgar < 7, intraventricular hemorrhage and elevated nucleated red blood cell counts at delivery).

Results

Twelve (16.2%) perinatal deaths, of which eight were stillbirths (10.8%), and two (2.7%) neonatal deaths occurred among 74 fetuses. Logistic regression analysis confirmed that abnormal DV Doppler waveforms (R2 = 0.57, P < 0.001) together with gestational age at delivery (R2 = 0.57, P < 0.001) showed the strongest association with perinatal death, whereas only gestational age was significantly related to neonatal death (R2 = 0.67, P < 0.05). Abnormal DV Doppler waveforms (R2 = 0.86, P < 0.001) and gestational age (R2 = 0.49, P < 0.05) were strongly associated with adverse outcome (including stillbirth, perinatal death or neonatal death). Abnormal venous Doppler flow patterns performed better in the prediction of fetal or perinatal demise than did ARED flow or brain sparing.

Conclusion

Abnormal venous Doppler waveforms in preterm IUGR fetuses with ARED flow are strongly related to adverse fetal and perinatal outcomes before 32 weeks of gestation. The possible benefit of prolonging these pregnancies can only be evaluated in a prospective randomized study. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Screening for Down syndrome based on maternal age or fetal nuchal translucency: a randomized controlled trial in 39 572 pregnancies
Authors: Saltvedt S. , Almström H. , Kublickas M. , Valentin L. , Bottinga R. , Bui T.‐H. , Cederholm M. , Conner P. , Dannberg B. , Malcus P. , Marsk A. , Grunewald C.
Published: May 2005

Objectives

Nuchal translucency (NT) screening increases antenatal detection of Down syndrome (DS) compared to maternal age‐based screening. We wanted to determine if a change in policy for prenatal diagnosis would result in fewer babies born with DS.

Methods

A total of 39 572 pregnant women were randomized to a scan at 12–14 gestational weeks including NT screening for DS (12‐week group) or to a scan at 15–20 weeks with screening for DS based on maternal age (18‐week group). Fetal karyotyping was offered if risk according to NT was ≥ 1:250 in the 12‐week group and if maternal age was ≥ 35 years in the 18‐week group. Both policies included the offer of karyotyping in cases of fetal anomaly detected at any scan during pregnancy or when there was a history of fetal chromosomal anomaly. The number of babies born with DS and the number of invasive tests for fetal karyotyping were compared.

Results

Ten babies with DS were born alive with the 12‐week policy vs. 16 with the 18‐week policy (P = 0.25). More fetuses with DS were spontaneously lost or terminated in the 12‐week group (45/19 796) than in the 18‐week group (27/19 776; P = 0.04). All women except one with an antenatal diagnosis of DS at < 22 weeks terminated the pregnancy. For each case of DS detected at < 22 weeks in a living fetus there were 16 invasive tests in the 12‐week group vs. 89 in the 18‐week group. NT screening detected 71% of cases of DS for a 3.5% test‐positive rate whereas maternal age had the potential of detecting 58% for a test‐positive rate of 18%.

Conclusions

The number of newborns with DS differed less than expected between pregnancies that had been screened at 12–14 weeks' gestation by NT compared with those screened at 15–20 weeks by maternal age. One explanation could be that NT screening—because it is performed early in pregnancy—results in the detection and termination of many pregnancies with a fetus with DS that would have resulted in miscarriage without intervention, and also by many cases of DS being detected because of a fetal anomaly seen on an 18‐week scan. The major advantage of the 12‐week scan policy is that many fewer invasive tests for fetal karyotyping are needed per antenatally detected case of DS. Copyright © 2005 ISUOG. Published by John Wiley & Sons, Ltd.
Improvement in detection limits by using helium ions for particle‐induced x‐ray emission
Authors: Beck Lucile
Published: May 2005

PIXE analysis is usually carried out by using protons as the incident projectiles. Protons generally present the advantages of large penetration depth and high ionization power. However, the use of heavier ions can be useful in a specific context. Deuterons or helium‐4 ions produce negligible nuclear bremsstrahlung for matrix elements whose Z/A is close to 0.5 and the secondary electron bremsstrahlung is shifted to lower x‐ray energies. Thanks to the reduction of these backgrounds, better limits of detection are expected. In this study, helium‐induced x‐ray emission (HIXE) analysis was applied to various thick specimens. We observed that the detection of light trace elements in medium‐Z matrices can be improved by selecting an appropriate energy for the helium ion beam. For calcite, brass or casting iron, the signal‐to‐background ratios for Mg, Si, P, S, etc. are enhanced by using helium ions instead of protons. Moreover, as the intensity of the major element peaks (Ca, Cu or Fe) is low, the use of x‐ray absorbers for limiting the counting rate is less necessary. As a result, the detection limits of the low elements in these matrices are reduced by a factor of two. Copyright © 2005 John Wiley & Sons, Ltd.
Improvement of matrix solutions of generalized nonlinear wave equation
Authors: Gudkov V.V.
Published: May 2005

Four classes of nonlinear wave equations are joined in one generalized nonlinear wave equation. A theorem is proved that the whole series of matrix functions satisfy the generalized wave equation. A justification of rotational properties of matrix solutions is given and a mathematical model of the ring vortex around the acute edge is proposed using of matrix solutions.
On the simultaneous effects of gas rarefaction, wall porosity, and inertia in microchannel flows
Authors: Stevanovic N.D. , Djordjevic V.D.
Published: May 2005

The superposition of two effects that cause the flow to slip over the walls of a microchannel: Gas rarefaction and wall porosity, is treated in the paper. At that, in order to account for moderately high values of the Reynolds number, observed in some experiments, the effect of inertia is included into the analysis as a second order effect. The approach is fully analytic and consists in the development of a simple perturbation scheme in which the Knudsen number plays the role of a unique small parameter. The obtained results are in qualitative agreement with experiments, and may be usefully applied for the design of aerostatic bearings in which a porous material is used as the flow restrictor.
Refinement is complete for implementations
Authors: Huth Michael
Published: May 2005

Modal transition systems specify sets of implementations, their refining labelled transition systems, through Larsen & Thomsen’s co-inductive notion of refinement. We demonstrate that refinement precisely captures the identification of a modal transition system with its set of implementations: refinement is reverse containment of sets of implementations. This result extends to models that combine state and event observables and is drawn from a
SFP
-domain whose elements are equivalence classes of modal transition systems under refinement [HJS04], and abstraction-based finite-model properties proved in this paper. As a corollary, validity checking is model checking for Hennessy-Milner formulas that characterize modal transition systems with bounded computation paths. We finally sketch how techniques developed in this paper can be used to detect inconsistencies between multiple modal transition systems and, if consistent, to verify properties of all common implementations.
A genome‐wide analysis of sumoylation‐related biological processes and functions in human nucleus
Authors: Zhou Fengfeng , Xue Yu , Lu Hualei , Chen Guoliang , Yao Xuebiao
Published: May 2005

Protein sumoylation is an important reversible post‐translational modification of proteins in the nucleus, and it orchestrates a variety of the cellular processes. Genome‐wide analysis of functional abundance and distribution of Small Ubiquitin‐related MOdifier (SUMO) substrates may shed a light on how sumoylation is involved in nuclear biological processes and functions. Two interesting questions about sumoylation have emerged: (1) how many SUMO substrates exist in mammalian proteomes, such as human and mouse, (2) and what are their functions and how are they involved in a variety of biological processes? To address these two questions,we present an in silico genome‐scale analysis for SUMO substrates in human. Based on the pattern recognition and phylogenetic conservation, we retrieved a list of 2683 potential SUMO substrates conserved in both human and mouse. Then, by functional enrichment analysis, we surveyed the over‐represented GO terms and functional domains of them against the whole human proteome. Besides the consistence between our analyses and in vivo or in vitro work, the in silico predicted candidates also point to several potential roles of sumoylation, e.g., perception of sound. These potential SUMO substrates in human are of great value for further in vivo or in vitro experimental analysis.
Direct interaction between the reductase domain of endothelial nitric oxide synthase and the ryanodine receptor
Authors: Martínez-Moreno Mónica , Álvarez-Barrientos Alberto , Roncal Fernando , Albar Juan Pablo , Gavilanes Francisco , Lamas Santiago , Rodríguez-Crespo Ignacio
Published: May 2005

We have performed the recombinant expression and purification of the reductase domain of endothelial nitric oxide synthase (eNOS) and used it as a bait in search for interacting proteins present in endothelial cells. Using mass spectrometry of the bound proteins run in a PAGE–SDS gel, we were able to identify the ryanodine receptor (RyR) as a novel eNOS‐binding partner. This interaction was confirmed through immunoprecipitation of both RyR and eNOS from endothelial cells and cardiac myocytes. Immunofluorescence data indicated that a subpopulation of eNOS associates with RyR in perinuclear regions of the cell, where eNOS might be responsible for the known nitrosylation of RyR.