bluuebunny/crossref_metadata_2025 huggingface dataset:
Bulk properties of dendronized polymers with tailored end‐groups emanating from the same backbone
Authors: Nyström Andreas M. , Furó István , Malmström Eva , Hult Anders
Published: August 2005

Dendronized polymers with a methacrylate backbone bearing pendant aliphatic polyester dendrons based on 2,2‐bis(methylol)propionic acid have been investigated by rheological measurements, differential scanning calorimetry (DSC), size exclusion chromatography (SEC), and 1H NMR self‐diffusion techniques. The change in material properties due to the attachment of larger dendrons and/or different end‐groups to a backbone of the same length is investigated. Dendronized polymers of the second to fourth generation with hydroxyl, acetonide, or hexadecyl end‐group functionalities have been studied. DSC revealed that the glass transition temperature of the amorphous polymers increases with increasing size of the dendrons, and that the ability for the hexadecyl functional polymers to crystallize decreases with increasing size of dendrons. 1H NMR self‐diffusion and longitudinal relaxation data are consistent with an elongated rod‐like model of the polymers in solution. Larger dendrons lead to a larger rod diameter that approximately double when increasing the generation of dendronized polymer from two to four. Rheological measurements demonstrated that the complex viscosity at low frequency increased with dendron size. Independently of the functionality, the second and third generation samples initially showed a Newtonian plateau, followed by a shear thinning region at higher frequencies. The fourth generation samples only showed shear thinning over the whole frequency region. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4496–4504, 2005
Synthesis and characterization of poly(imide‐urethane) based on novel chain‐extender containing both imide and sulphone functions
Authors: Qin XiuMin , Yang XiaoHui , Wang XinLing , Wang MingJun
Published: August 2005

Several new glycols containing both imide and sulfone groups, sulfonyl bisimide glycol (SBIG), were prepared from primary aromatic diamine, trimellitic anhydride and excess low molecular glycols. Then these SBIGs were used as chain extender to prepare a series of thermoplastic poly(imide‐urethane) (PIU), which introduced imide rings into the backbones. Compared to conventional linear polyurethane (PU), these PIUs exhibited better thermal stabilities because of the presence of the sulfone and built‐in imide groups. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4469–4477, 2005
Synthesis, structure, and characterization of nematic liquid‐crystalline thermosets based on bisacrylates
Authors: Hu Jian‐She , Zhang Bao‐Yan , Yao Dan‐Shu , Xiao Wen‐Qiang , Dong Yan‐Li
Published: August 2005

Four bisacrylate mesogenic monomers and the corresponding liquid‐crystalline thermosets were synthesized. The chemical structures of the intermediate compounds and monomers obtained were confirmed by elemental analyses, Fourier transform infrared, and 1H NMR and 13C NMR spectra. The mesomorphic properties and thermal stability were investigated with differential scanning calorimetry, thermogravimetric analysis, polarized optical microscopy, and X‐ray diffraction measurements. The influence of the curing temperatures and time on the phase behavior and thermal stability of the thermosets was discussed. All the monomers and thermosets exhibited a nematic schlieren texture. However, the monomers only showed the melting transition, and the thermosets displayed the glass transition. The experimental results demonstrated that the monomer structures strongly affected the phase behavior and the curing reaction rate, and the glass‐transition temperatures and thermal stability of the thermosets increased with the curing temperature and time. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4478–4485, 2005
Polymerization of substituted acetylenes by various rhodium catalysts: Comparison of catalyst activity and effect of additives
Authors: Nakazato Atsushi , Saeed Irfan , Katsumata Toru , Shiotsuki Masashi , Masuda Toshio , Zednik Jiri , Vohlidal Jiri
Published: August 2005

This research deals with comparison of the activity of various Rh catalysts in the polymerization of monosubstituted acetylenes and the effect of various amines used in conjunction with [Rh(nbd)Cl]2 in the polymerization of phenylacetylene. A zwitterionic Rh complex, Rh+(nbd)[(η6‐C6H5)B−(C6H5)3] (3), was able to polymerize phenylacetylene (5a), t‐butylacetylene (5b), N‐propargylhexanamide (5c) and n‐hexyl propiolate (5d), and displayed higher activity than the other catalysts examined, that is [Rh(nbd)Cl]2 (1), [Rh(cod)(O‐o‐cresol)]2 (2), and Rh‐vinyl complex (4). Monomers 5a and 5c polymerized virtually quantitatively or in fair yields with all these catalysts, while monomer 5b was polymerizable only with catalyts 3 and 4. Monomer 5d did not polymerize in high yields with these Rh complexes. The catalytic activity tended to decrease in the order of 3 > 4 > 2 > 1. Although polymerization of 5a did not proceed at all in toluene with [Rh(nbd)Cl]2 alone, it smoothly polymerized in the presence of various amines as cocatalysts. The polymerization rate as well as the molecular weight of polymer depended on the basicity and steric bulkiness of amines. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4530–4536, 2005
Assessment of acute and chronic pain symptoms in children with cystic fibrosis
Authors: Koh Jeffrey L. , Harrison Dale , Palermo Tonya M. , Turner Helen , McGraw Terrence
Published: August 2005

Pain is important to assess and treat in children with cystic fibrosis (CF), because pain symptoms may limit children's ability to participate in their CF‐related care and may reduce their overall well‐being and quality of life. The aims of this study were to: 1) assess acute and chronic pain symptoms as reported by children with CF, and 2) examine the relationship between pain symptoms and disease severity as measured by percentage of forced expired volume in 1 sec (FEV1%). Forty‐six children completed a self‐report questionnaire assessing characteristics of chronic disease‐related pain (frequency, intensity, duration, associated emotional upset, and location of pain). Children also rated their pain intensity associated with common CF‐related procedures. The primary locations of pain reported were the abdominal/pelvic region, chest, and head/neck. Forty‐six percent of the sample described pain occurring at least once per week. Most children reported their pain intensity as mild and of short duration. However, a small subgroup of children reported longer‐lasting and moderately intense pain. Children with chest pain were found to be particularly at risk for experiencing more functional limitations and a significantly lower FEV1% compared to children without chest pain. The majority of children reported that nonpharmacological therapies (e.g., medication, rest, or distracting activities) provided some pain relief. Disease‐related pain is common for children and adolescents with CF, suggesting that pain assessment should be a routine part of their clinical care. Further research is clearly needed to better understand the sources of pain and how best to provide relief. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.
Structure and stability of a model three‐helix‐bundle protein on tailored surfaces
Authors: Knotts Thomas A. , Rathore Nitin , de Pablo Juan J.
Published: August 2005

The interaction of protein molecules with surfaces is important in numerous applications. Theoretical work on protein adsorption has been limited. In particular, it is difficult to obtain quantitative predictions about the structure and stability of proteins on surfaces. In this study, density‐of‐states‐based simulations were performed on a Gō‐like model of a three‐helix‐bundle fragment from protein A (PDB ID: 1bdd). Both mechanical and thermal stability were investigated on neutral and attractive surfaces and compared to that in the absence of a surface. It was found that attaching the peptide to any type of surface decreases its melting temperature by as much as 9 K, depending upon orientation. Calorimetric cooperativity, as measured by van't Hoff to calorimetric enthalpy ratios, similarly decreased. It was also found that the mechanical strength of the peptide attached to surfaces is degraded to varying extents, depending upon the surface type and protein orientation. A comparison of mechanical and thermal stability showed that the two are not synonymous, but occur through different pathways, and that system configurations that are more thermally stable are not always so mechanically. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Temperature‐dependent structural and functional features of a hyperthermostable enzyme using elastic neutron scattering
Authors: Koutsopoulos Sotirios , van der Oost John , Norde Willem
Published: August 2005

The dynamic behavior of an endoglucanase from the hyperthermophilic microorganism Pyrococcus furiosus was investigated using elastic neutron scattering. The temperature dependence of the atomic motions was correlated with conformational and functional characteristics of the enzyme. The onset of biological function at temperatures higher than approximately 25°C (the hyperthermostable enzyme is essentially inactive at room temperature) was associated with a dynamical transition in the anharmonic motions domain. This transition from the nonactive to the enzymatically active conformation involved structurally similar conformational substates in the energy landscape. From the mean‐square displacement of the protein atoms, the molecular flexibility and the effective force constants were calculated at different temperature zones. The results showed that the activity increases at higher temperatures where the intramolecular bonds are weakened and the overall rigidity of the protein is decreased. Further temperature increase resulted in significantly increased atomic fluctuations featuring heat denaturation of the protein. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Proton transfer in a Thr200His mutant of human carbonic anhydrase II
Authors: Bhatt Deepa , Tu Chingkuang , Fisher S. Zoë , Hernandez Prada Jose A. , McKenna Robert , Silverman David N.
Published: August 2005

Human carbonic anhydrase II (HCA II) has a histidine at position 64 (His64) that donates a proton to the zinc‐bound hydroxide in catalysis of the dehydration of bicarbonate. To examine the effect of the histidine location on proton shuttling, His64 was replaced with Ala and Thr200 replaced with histidine (H64A‐T200H HCAII), effectively relocating the proton shuttle residue ∼ 2 Å closer to the zinc‐bound hydroxide compared to wild type HCA II. The crystal structure of H64A‐T200H HCA II at 1.8 Å resolution shows the side chain of His200 directly hydrogen‐bonded with the zinc‐bound solvent. Different proton transfer processes were observed at pH 6 and at pH 8 during the catalytic hydration‐dehydration cycle, measured by mass spectrometry as the depletion of 18O from C18O2 by H64A‐T200H HCA II. The process at pH 6.0 is attributed to proton transfer between the side chain of His200 and the zinc‐bound hydroxide, in analogy with proton transfer involving His64 in wild‐type HCA II. At pH 8.0 it is attributed to proton transfer between bicarbonate and the zinc‐bound hydroxide, as supported by the dependence of the rate of proton transfer on bicarbonate concentration and on solvent hydrogen isotope effects. This study establishes that a histidine directly hydrogen‐bonded to the zinc‐bound hydroxide, can adopt the correct distance geometry to support proton transfer. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Impedance spectroscopy on organic bulk‐heterojunction solar cells
Authors: Glatthaar M. , Mingirulli N. , Zimmermann B. , Ziegler T. , Kern R. , Niggemann M. , Hinsch A. , Gombert A.
Published: August 2005

We measured the electrical impedance spectra of organic bulk‐heterojunction solar cells based on an absorber blend of poly(3‐hexylthiophene) and [6,6]‐phenyl C61‐butyric acid methyl ester. Comparing the spectra of the non‐treated device and after two consecutive treatments with applied forward bias voltage at 110 °C, we observed a region in the semiconductor with a low conductivity, which was expanding after the treatments. We concluded that this region is a depletion region at the aluminium contact. This was confirmed by the bias dependence of the impedance spectra. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Leveraging the Advantages Offered by Microfluidics to Enhance the Drug Discovery Process
Authors: Wong Hawkes Stephanie Y. F. , Chapela Maria J. V. , Montembault Mickael
Published: August 2005

Why is GlaxoSmithKline (GSK) interested in Microsystems Technology (MST) and how can MST be utilised in organic synthesis and biological screening for lead optimisation? The highly competitive world of the drug market forces pharmaceutical companies to undertake expensive searches for safe and effective leads. Although industrialisation and high‐throughput implementation of traditionally scaled technology has served to increase the individual productivity of the medicinal chemist in the pharmaceutical industry, this is still insufficient to identify the best lead. Microfluidics and MST are regarded as two of the more promising new disruptive techniques for carrying out ultra‐high‐throughput chemical synthesis. The utilisation of microchannels in organic synthesis has a wide range of advantages, for example, lower reaction times than for macroscale synthesis , the use of minute amounts of reagents and solvents, reduction of costs and avoidance of storage. The ultimate aim is to create a microreactor environment capable of performing in a fast serial mode, where the synthesis, purification and screening of small quantities of thousands of compounds a day are handled with ease, thereby reducing the cycle time per synthesis‐assay run. The tiny amounts of compounds produced in the microchannels are compatible with modern miniaturised screening techniques that require less than a nano‐mole of test compound. Close integration of the chemistry generator with the assay also eliminates storage and supply‐chain issues. Larger amounts of compounds can be obtained by numbering up (paralleling) the microreactors.
Electrochemical Combinatorial Organic Syntheses Using Microflow Systems
Authors: Suga Seiji , Okajima Masayuki , Fujiwara Kazuyuki , Yoshida Jun‐ichi
Published: August 2005

The “cation flow” method, in which highly reactive carbocations are generated in the absence of nucleophiles by low temperature electrolysis and are allowed to react with carbon nucleophiles in the microflow system to achieve direct electrooxidative CC bond formation, has been developed. As an extension of the cation flow method, an electrochemical paired microflow system that involves concurrent anodic generation of carbocations and cathodic generation of carbon nucleophiles followed by their reactions to achieve straightforward CC bond formation has also been developed.
Continuous‐Flow Chemical Processing in Three‐Dimensional Microchannel Network for On‐Chip Integration of Multiple Reactions in a Combinatorial Mode
Authors: Kikutani Yoshikuni , Ueno Masaharu , Hisamoto Hideaki , Tokeshi Manabu , Kitamori Takehiko
Published: August 2005

Chemical syntheses using microchemical chips have been intensively investigated in recent years, but they have still not fully reached the stage of practical use. Combinatorial synthesis has been expected to be one of their useful applications. Benefits of using microchips, such as reduction in quantity of reagents and wastes, are thought to be suited for combinatorial syntheses, where numerous variations of products have to be synthesized each in small amounts. There are two modes of combinatorial syntheses using microchemical chips. One is sequential synthesis, in which reactant solutions are introduced sequentially in various combinations to a reaction microchannel. The other is parallel synthesis, where the number of reaction channels is the same as the number of final products, and starting materials are distributed to all the reaction channels in different combinations. Sequential synthesis has been considered as the more favorable way, because, especially when libraries of starting materials are large, numerous microchannels and complicated pipings for distribution of reagents to the channels are required for the parallel mode. Therefore, research on parallel microcombinatorial syntheses has been done only rarely, whereas there have been many reports of sequential microcombinatorial syntheses. Against this trend, our research group has taken an alternative path and tried to integrate both parallel reaction microchannels onto a glass microchip and channels for distributing reactant solutions to each reaction channel in a combinatorial mode. Microchips fabricated by laminating multiple layers of glass substrates have been used to construct three‐dimensional microchannel networks necessary for mixing reagent flows in different combinations. We utilized low Reynolds number multi‐phase laminar flow and developed micro‐unit operations (MUOs). By combining MUOs in the multi‐phase continuous laminar flows, microchemical systems were constructed. We called this micro‐integration methodology “continuous‐flow chemical processing (CFCP)”, and by using it, a sequence of various operations in chemical syntheses could be integrated on a microchemical chip. Not just simple mixing of two reagents, which was most commonly done in microreactors, but also multi‐step processes including other chemical operations, such as extraction and separation, could be carried out via CFCP. In the first part of this short review article, we explain CFCP with an example. Then, a microchemical chip with a three‐dimensional microchannel network for a parallel reaction system is introduced. Finally, we present a case in which CFCP was realized in a three‐dimensional microchannel network.
The Application of Microreactors in Combinatorial Chemistry
Authors: Watts Paul
Published: August 2005

The miniaturisation of chemical reactors offers many fundamental and practical advantages of relevance to the pharmaceutical and fine chemicals industries, which are constantly searching for controllable, information‐rich, high‐throughput and environmentally friendly methods of producing products with a high degree of chemical selectivity. This review explores how miniaturisation may revolutionise chemical synthesis, highlighting in particular the commercial and environmental benefits of this new technology in combinatorial synthesis.
Synthesis of a Library of Ciprofloxacin Analogues By Means of Sequential Organic Synthesis in Microreactors
Authors: Schwalbe Thomas , Kadzimirsz Daniel , Jas Gerhard
Published: August 2005

The realm of combinatorial chemistry is strongly based on the concept of parallel chemistry and its ease of automation. Although this batch‐type approach in general may be considered a success story, some limitations remain rarely addressable by conventional approaches. Particularly, scaling‐up problems such as the re‐synthesis of multigram amounts of active compounds as well as the synthesis of building blocks and scaffolds in large amounts may prove to be problematic. Our expertise in continuous chemistry prompted us to develop a microreaction system for sequential organic synthesis that should overcome these limitations. In the present contribution we describe this system as well as its application to the first library approach towards fluoro‐quinolone antibiotics such as Ciprofloxacin solely using microreaction technology. A known one‐pot batch procedure for the synthesis of this compound class was split in its individual reaction steps, which were successfully adapted to a continuous conduct. After some optimisation studies the overall sequence was suitable for chemical diversification. Particularly it was shown, that the first step of the synthesis – the acylation reaction of a β‐dimethylamino acrylate with trifluoro‐benzoic acid chloride – was accessible to synthesis of high quantities without any difficulties to yield a primary building block suitable for subsequent library synthesis. In a first diversification step, the Michael addition of a set of primary amines was followed by nucleophilic ring closure providing the difluoro‐quinolone system, which was subjected to a second diversification step by means of a nucleophilic aromatic substitution reaction. Thus, a number of Ciprofloxacin analogues could be synthesised in good overall yield and purity. Isolated yields ranged from 71 to 85% in the first diversification step and from 59 to 99% in the second step.
A Novel Method for High‐Throughput Reduction of Compounds through Automated Sequential Injection into a Continuous‐Flow Microfluidic Reactor
Authors: Jones Richard , Gödörházy Lajos , Szalay Dániel , Gerencsér János , Dormán György , Ürge László , Darvas Ferenc
Published: August 2005

A high‐throughput system for heterogeneous hydrogenation through the integration of a microfluidic reactor into an automated injector‐fraction collector robot is described. The reduction of a small nitro compound library is used to demonstrate the high‐throughput capability of the system and the results are compared to those of a batch reactor.
Determination of agrochemical compounds in soya plants by imaging matrix‐assisted laser desorption/ionisation mass spectrometry
Authors: Mullen Alexander K. , Clench Malcolm R. , Crosland Susan , Sharples Kate R.
Published: August 2005

Detection and imaging of the herbicide mesotrione (2‐(4‐mesyl‐2‐nitrobenzoyl)cyclohexane‐1,3‐dione) and the fungicide azoxystrobin (methyl (E)‐2‐{2‐[6‐(2‐cyanophenoxy)pyrimidin‐4‐yloxy]phenyl}‐3‐methoxyacrylate), on the surface of the soya leaf, and the detection and imaging of azoxystrobin inside the stem of the soya plant, have been achieved using matrix‐assisted laser desorption/ionisation quadrupole time‐of‐flight mass spectrometry. In leaf analysis experiments, the two pesticides were deposited onto the surface of individual soya leaves on growing plants. The soya leaves were removed and prepared for direct and indirect (following blotting onto matrix‐coated cellulose membranes) imaging analysis at different periods after initial pesticide application. In stem analysis experiments, azoxystrobin was added to the nutrient solution of a soya plant growing in a hydroponics system. The plant was left for 48 h, and then horizontal and vertical stem sections were prepared for direct imaging analysis. The images obtained demonstrate the applicability of MALDI imaging to the detection and imaging of small organic compounds in plant tissue and further extend the analytical repertoire of the versatile MALDI technique. Copyright © 2005 John Wiley & Sons, Ltd.
Enhancement of matrix‐assisted laser desorption/ionization photodissociation tandem time‐of‐flight mass spectra; spectral reduction and cleanup of isotopomeric contamination
Authors: Moon Jeong Hee , Yoon So Hee , Kim Myung Soo
Published: August 2005

Weak signal intensity and poor precursor ion selection are the major difficulties in tandem time‐of‐flight (TOF) mass spectrometry of ions generated by matrix‐assisted laser desorption/ionization (MALDI). Even though the latter can be overcome in photodissociation (PD) tandem TOF mass spectrometry via ion pulse‐PD laser pulse synchronization, clean monoisotopic selection of precursor ions of highm/zcan often be difficult for various reasons. A considerable enhancement of post‐source decay (PSD) and PD tandem mass spectra has been achieved in this work via single‐ion detection and post‐acquisition reduction of the spectra. Also, an algorithm has been developed to clean up isotopomeric contamination when the resolution for precursor ion selection is less than adequate. A high‐quality tandem TOF mass spectrum which results from PD of virtually monoisotopic precursor ions has been obtained. Copyright © 2005 John Wiley & Sons, Ltd.
Characterization of adducts formed between human serum albumin and the butadiene metabolite epoxybutanediol
Authors: Lindh Christian H. , Kristiansson Monica H. , Berg‐Andersson Ulrika A. , Cohen Arieh S.
Published: August 2005

1,3‐Butadiene (BD) has been classified as a potential human carcinogen. It occurs in the environment as well as in industrial settings. In humans, BD is readily metabolized to reactive epoxides (e.g. 1,2‐epoxy‐3,4‐butanediol). In this study, conjugates between human serum albumin (HSA) and EBD were synthesized (molar ratios of 1:600, 1:1 and 1:0.1; HSA/EBD) under physiological conditions. The 1:600 conjugate and a blank HSA sample were digested with trypsin to obtain specific peptides that were fractionated by preparative liquid chromatography (LC). The fractions were analyzed using nanoelectrospray quadrupole time‐of‐flight mass spectrometry (nanoES‐QqTOFMS). Adducted HSA tryptic peptides were identified and the adducted amino acid residues were identified by sequence analysis based on tandem mass spectrometry (MS/MS). A total of 26 2,3,4‐trihydroxybutyl (THB) adducts were identified on 23 tryptic peptides in the HSA/EBD conjugate. The adducted amino acids were the N‐terminal aspartic acid residue, six glutamic acid residues, five histidine residues and 14 lysine residues. Results from the nanoES‐QqTOFMS experiments were used to set up a more sensitive liquid chromatographic/mass spectrometric (LC/MS) analysis using selected reaction monitoring. Eight of the adducted peptides could be detected in tryptic digests of the 1:0.1 HSA/EBD conjugate. Copyright © 2005 John Wiley & Sons, Ltd.
Examining the collision‐induced decomposition spectra of ammoniated triglycerides as a function of fatty acid chain length and degree of unsaturation. I. The OXO/YOY series
Authors: Li Xingwen , Evans Jason J.
Published: August 2005

A series of positionally pure triglycerides (TAGs) of the form OXO and YOY, where O is the oleate moiety and X and Y are large arrays of different fatty acid moieties, was synthesized and analyzed by reversed‐phase high‐performance liquid chromatography/tandem mass spectrometry. The intensities of the collision‐induced decomposition (CID) products of ammoniated TAGs (ammonium ion adducts) were examined as a function of chain length, degree of unsaturation, double‐bond position, and cis/trans configuration of X and Y. The major CID products, the diglyceride fragment ions and the MH+ ion, were plotted as functions of chain length for the saturated and mono‐unsaturated series of X and Y. Different trends for each of these series were observed. Trends in the abundances of these fragment ions were also characterized as a function of degree of unsaturation in the TAGs. In general, the fractional abundances of the MH+ ions vary linearly with degree of unsaturation. However, the presence of double bonds positioned close to the carbonyl carbon of the fatty acid chain promotes the formation of the diglyceride fragment ion corresponding to loss of that fatty acid. Mechanisms of the formation and decomposition of ammoniated TAGs are proposed that fit the trends observed in the data. Extensions of this work are described, and a vision of a derived library of CID spectra is discussed as a platform for comprehensive analysis of complex TAG mixtures. Copyright © 2005 John Wiley & Sons, Ltd.
Use of monoatomic and polyatomic projectiles for the characterisation of polylactic acid by static secondary ion mass spectrometry
Authors: Boschmans Bart , Van Royen Pieter , Van Vaeck Luc
Published: August 2005

The application of polyatomic primary ions is a strongly developing branch of static secondary ion mass spectrometry (S‐SIMS), since these projectiles allow a significant increase in the secondary ion yields to be achieved. However, the different limitations and possibilities of certain polyatomic primary ions for use on specific functional classes of samples are still not completely known. This paper compares the use of monoatomic and polyatomic primary ions in S‐SIMS for thin layers of polylactic acid (PLA), obtained by spin‐coating solutions on silicon wafers. Bombardment with Ga+, Xe+ and SF primary ions allowed the contribution of the projectile mass and number of atoms in the gain in ion yield and molecular specificity (relative importance of high m/z and low m/z signals) to be assessed. Samples obtained by spin‐coating solutions with increasing concentration showed that optimal layer thickness depended on the primary ion used. In comparison with the use of Ga+ projectiles, the yield of structural ions increased by a factor of about 1.5 to 2 and by about 7 to 12 when Xe+ and SF primary ion bombardment were applied, respectively. A detailed fragmentation pattern was elaborated to interpret ion signal intensity changes for different projectiles in terms of energy deposition and collective processes in the subsurface, and the internal energy of radical and even‐electron precursor ions. Copyright © 2005 John Wiley & Sons, Ltd.
Nitrogen balance and δ15N: why you're not what you eat during nutritional stress
Authors: Fuller Benjamin T. , Fuller James L. , Sage Nancy E. , Harris David A. , O'Connell Tamsin C. , Hedges Robert E. M.
Published: August 2005

While past experiments on animals, birds, fish, and insects have shown changes in stable isotope ratios due to nutritional stress, there has been little research on this topic in humans. To address this issue, a small pilot study was conducted. Hair samples from eight pregnant women who experienced nutritional stress associated with the nausea and vomiting of morning sickness (hyperemesis gravidarum) were measured for carbon (δ13C) and nitrogen (δ15N) stable isotope ratios. The δ13C results showed no change during morning sickness or pregnancy when compared with pre‐pregnancy values. In contrast, the δ15N values generally increased during periods of weight loss and/or restricted weight gain associated with morning sickness. With weight gain and recovery from nutritional stress, the hair δ15N values displayed a decreasing trend over the course of gestation towards birth. This study illustrates how δ15N values are not only affected by diet, but also by the nitrogen balance of an individual. Potential applications of this research include the development of diagnostic techniques for tracking eating disorders, disease states, and nitrogen balance in archaeological, medical, and forensic cases. Copyright © 2005 John Wiley & Sons, Ltd.
Electronic substituent effects in the electron impact mass spectrometry of 2‐(arylazo)‐4‐phenylphenols
Authors: Pérez‐Caballero Guadalupe , Jiménez‐Cruz Federico , Matamoros Pablo Hernández , García José Guadalupe , Cortés‐Guzmán Fernando , Miranda René
Published: August 2005

A mass spectrometric study of a set of six novel 2‐(arylazo)‐4‐phenylphenols 1–6 was performed. The electron impact spectra were acquired and analyzed for five of the compounds in order to establish a fragmentation pattern. The suggested pathways were investigated and confirmed by means of tandem mass spectrometry (MS/MS) experiments together with high‐resolution accurate mass data. However, the sixth molecule, a sodium sulfonate salt, was studied using fast atom bombardment (FAB) ionization in positive and negative modes. In addition, some electronic substituent effects were investigated by analyzing Hammett‐McLafferty linear free energy correlations for some peaks derived from the corresponding molecular ions. Also, the role of the OH · · · N hydrogen bond present in the target compounds was analyzed. The roles of these Hbonds were consistent with the corresponding acidity constant values obtained experimentally as well as by theoretical quantum chemistry calculations using HF/6‐31 + G(d,p) and B3LYP/6‐31G(d,p). Some spectrometric data were correlated with topological properties derived from the atoms‐in‐molecules (AIM) theory. Copyright © 2005 John Wiley & Sons, Ltd.
Electrospray tandem mass spectrometry of new porphyrin amino acid conjugates
Authors: Serra V. Vaz , Domingues M. R. M. , Faustino M. A. F. , Domingues P. , Tomé J. P. C. , Neves M. G. P. M. S. , Tomé A. C. , Cavaleiro J. A. S. , Ferrer‐Correia A. J.
Published: August 2005

Porphyrin amino acid conjugates with one or two porphyrin units were analyzed by electrospray ionization tandem mass spectrometry (ESI‐MS/MS). The ESI‐MS spectra of all the porphyrins studied, obtained in positive ion mode, show the presence of the corresponding protonated molecule [M+H]+; ESI‐MS spectra of diporphyrinyl compounds also show the doubly charged ions [M+2H]2+. The fragmentations of these ions induced by collision with argon were studied (ESI‐MS/MS). ESI‐MS/MS gives detailed structural information about the amino acids associated with the porphyrin. Cleavage of the bonds in the vicinity of the porphyrin moiety and those involving the side chain of amino acid residues gives structural information about this type of association. A fragmentation common to all derivatives corresponds to the cleavage of the phenylCO bond. The expected cleavage of the amide bond, that links the porphyrin to the amino acid moiety, is a minor fragmentation, which in some cases is even absent. The MS/MS spectra of the monoporphyrinyl derivatives show product ions characteristic of the amino acid linked to the porphyrin; the fragmentation also indicates when the amino acids has a terminal carboxylic group or a terminal ester group. The fragmentations of the diporphyrinyl compounds occur mainly by the cleavage of the spacer, leading, in the case of the doubly charged ions, to predominantly mono‐charged ions, indicating a preferential location of the two protons in separated porphyrinic units. Copyright © 2005 John Wiley & Sons, Ltd.
A liquid chromatography/tandem mass spectrometry method for the simultaneous quantification of isoniazid and ethambutol in human plasma
Authors: Chen Xiaoyan , Song Bo , Jiang Hongjian , Yu Kate , Zhong Dafang
Published: August 2005

Isoniazid and ethambutol are commonly used in various combination treatments for tuberculosis, and for this reason a rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for simultaneous quantification of these two drugs in human plasma. After a simple protein precipitation using methanol, the analytes and the internal standard metformin were chromatographed on a C18 column and detected by MS/MS. An atmospheric pressure chemical ionization interface was chosen to reduce ion suppression from sample matrix components and provide high sensitivity. The LC retention times for isoniazid and ethambutol were 2.46 and 2.27 min, respectively. The method was linear in the concentration range of 10.0–5000 ng/mL for each analyte using 100 µL plasma. The intra‐ and inter‐day precisions, expressed as the relative standard deviation (RSD), were less than 5.7 and 6.4%, determined from QC samples for isoniazid and ethambutol, and the accuracies were within ±2.1% and ±4.5% in terms of relative error, respectively. The method was successfully employed in a pharmacokinetic study after oral administration of a multicomponent formulation containing 150 mg isoniazid, 500 mg ethambutol, 150 mg rifampicin and 250 mg pyrazinamide. Copyright © 2005 John Wiley & Sons, Ltd.
‘All‐in‐One’ analysis for metabolite identification using liquid chromatography/hybrid quadrupole time‐of‐flight mass spectrometry with collision energy switching
Authors: Wrona Mark , Mauriala Timo , Bateman Kevin P. , Mortishire‐Smith Russell J. , O'Connor Desmond
Published: August 2005

The removal of bottlenecks in discovery stage metabolite identification studies is an ongoing challenge for the pharmaceutical industry. We describe the use of an ‘All‐in‐One’ approach to metabolite characterization that leverages the fast scanning and high mass accuracy of hybrid quadrupole time‐of‐flight mass spectrometry (QqToFMS) instruments. Full‐scan MS and MS/MS data is acquired using collision energy switching without the preselection, either manually or in a data‐dependent manner, of precursor ions. The acquisition of ‘clean’ MS/MS data is assisted by the use of ultrahigh‐performance chromatography. Data acquired using this method can then be mined post‐acquisition in a number of ways. These include using narrow window extracted ion chromatograms (nwXICs) for expected biotransformations, XICs for the product ions of the parent compound and/or expected modification of these product ions, and neutral loss chromatograms. This approach has the potential to be truly comprehensive for the determination of in vitro biotransformations in a drug discovery environment. Copyright © 2005 John Wiley & Sons, Ltd.
Identification of heat‐induced degradation products from purified betanin, phyllocactin and hylocerenin by high‐performance liquid chromatography/electrospray ionization mass spectrometry
Authors: Herbach Kirsten M. , Stintzing Florian C. , Carle Reinhold
Published: August 2005

Betanin, phyllocactin (malonylbetanin) and hylocerenin (3‐hydroxy‐3‐methylglutarylbetanin) were isolated from purple pitaya (Hylocereus polyrhizus [Weber] Britton & Rose) juice, and their degradation products generated by heating at 85°C were subsequently monitored by high‐performance liquid chromatography/electrospray ionization tandem mass spectrometry. Thermal degradation of phyllocactin and hylocerenin in purified solution excluding the alleged protective effects by the juice matrix is reported for the first time. Betanin was predominantly degraded by hydrolytic cleavage, while decarboxylation and dehydrogenation were of minor relevance. In contrast, hylocerenin showed a strong tendency to decarboxylation and dehydrogenation, hydrolytic cleavage of the aldimine bond occurring secondarily. Phyllocactin degradation was most complex because of additional decarboxylation of the malonic acid moiety as well as generation and subsequent degradation of betanin due to phyllocactin demalonylation. Upon prolonged heating, all betacyanins under observation formed degradation products characterized by an additional double bond at C2C3. Hydrolytic cleavage of the aldimine bond of phyllocactin and hylocerenin yielded previously unknown acylated cyclo‐dopa derivatives traceable by positive ionization, while application of ESI(–) facilitated the detection of a glycosylated aminopropanal derivative and dopamine, which have never been described before as betanin degradation products. Copyright © 2005 John Wiley & Sons, Ltd.
Epac1 regulates integrity of endothelial cell junctions through VE‐cadherin
Authors: Kooistra Matthijs R.H. , Corada Monica , Dejana Elisabetta , Bos Johannes L.
Published: August 2005

We have previously shown that Rap1 as well as its guanine nucleotide exchange factor Epac1 increases cell–cell junction formation. Here, we show that activation of Epac1 with the exchange protein directly activated by cAMP (Epac)‐specific cAMP analog 8CPT‐2′O‐Me‐cAMP (007) resulted in a tightening of the junctions and a decrease in the permeability of the endothelial cell monolayer. In addition, 007 treatment resulted in the breakdown of actin stress fibers and the formation of cortical actin. These effects were completely inhibited by siRNA against Epac1. In VE‐cadherin knock‐out cells Epac1 did not affect cell permeability, whereas in cells re‐expressing VE‐cadherin this effect was restored. Finally, the effect of Epac activation on the actin cytoskeleton was independent of junction formation. From these results we conclude that in human umbilical vein endothelial cells Epac1 controls VE‐cadherin‐mediated cell junction formation and induces reorganization of the actin cytoskeleton.
Gene induction by desiccation stress in human cell cultures
Authors: Huang Zebo , Tunnacliffe Alan
Published: August 2005

One strategy for investigating desiccation tolerance is to use mammalian cells, which are sensitive to desiccation, as a model for testing putative adaptive mechanisms. However, how mammalian cells themselves respond to desiccation is poorly characterised. Although MAPK signal transduction pathways are activated by desiccation of human cells, hypertonicity‐responsive genes AR, BGT1 and SMIT are not significantly induced, although they are proposed to be regulated by physiological changes which should occur during drying. To determine whether a response to desiccation occurs at the transcriptional level in human cells, we performed genome‐wide microarray analysis. Twenty upregulated genes, including early stress response and transcription factor genes, were identified, most of which, e.g., EGR1, EGR3, SNAI1, RASD1 and GADD45B, were also induced by hypertonicity, indicating common regulatory mechanisms. Our data suggest that human cells can initiate a complex desiccation stress response distinct from, but overlapping with, that to hypertonic stress.
Vitellogenin regulates hormonal dynamics in the worker caste of a eusocial insect
Authors: Guidugli Karina R. , Nascimento Adriana M. , Amdam Gro V. , Barchuk Angel R. , Omholt Stig , Simões Zilá L.P. , Hartfelder Klaus
Published: August 2005

Functionally sterile honey bee workers synthesize the yolk protein vitellogenin while performing nest tasks. The subsequent shift to foraging is linked to a reduced vitellogenin and an increased juvenile hormone (JH) titer. JH is a principal controller of vitellogenin expression and behavioral development. Yet, we show here that silencing of vitellogenin expression causes a significant increase in JH titer and its putative receptor. Mathematically, the increase corresponds to a dynamic dose–response. This role of vitellogenin in the tuning of the endocrine system is uncommon and may elucidate how an ancestral pathway of fertility regulation has been remodeled into a novel circuit controlling social behavior.
A role for K268 in V2R folding
Authors: Gouill Christian Le , Darden Thomas , Madziva Michael T. , Birnbaumer Mariel
Published: August 2005

The V2 vasopressin receptor, a member of the rhodopsin subfamily of GPCRs, mediates arginine vasopressin control of water reabsorption in the kidney by activating Gs. Requirement of the third intracellular loop of the V2R for Gsactivation was identified by introducing V2R segments into the Gq coupled V1aR [Liu, J. and Wess, J. (1996) J. Biol. Chem. 271, 8772–8778]; the same approach recognized glutamate 231 and glutamine 225 at the amino terminus of loop 3i as being needed for signal transduction. Site‐directed mutagenesis of the V2R confirmed their observations. Recently, we found that a positively charged amino acid at codon 268 is essential for V2R expression, although a double‐mutant bearing lysine at position 231 and glutamic acid at position 268 was expressed at higher levels than the wild type V2R and displayed unchanged ligand‐binding affinity. Ligand‐induced internalization and phosphorylation of the double‐mutant receptor was indistinguishable from that observed with the wild type protein but signaling activity was greatly diminished. The data suggested these two amino acids might interact with each other and might play a role in promoting GDP/GTP exchange.
Control of p53 nuclear accumulation in stressed cells
Authors: Inoue Tomomi , Wu Liqing , Stuart Jeremy , Maki Carl G.
Published: August 2005

Wild‐type p53 accumulates in the nucleus following stress. Current models suggest this nuclear accumulation involves phosphorylation at p53 N‐terminal sites, and inhibition of murine double minute (MDM)2‐dependent nuclear export. We monitored the effects of stress on MDM2‐dependent nuclear export of wild‐type p53 and a mutant lacking N‐terminal phosphorylation sites. Etoposide and ionizing radiation inhibited nuclear export of wild‐type p53 and the phosphor‐mutant to comparable extents, indicating nuclear export inhibition does not require N‐terminal phosphorylation. Cytoplasmic p53 accumulated in the nucleus of transfected cells treated with the nuclear export‐inhibitor leptomycin B (LMB). Interestingly, LMB caused less p53 nuclear accumulation than stress treatment, suggesting stress‐induced nuclear accumulation of p53 does not result solely from inhibited nuclear export.
Episodic gullying and paleomonsoon cycles on the Chinese Loess Plateau
Authors: Porter Stephen C. , An Zhisheng
Published: August 2005

Buried gullies exposed in road excavations along the margin of a loess tableland on the Loess Plateau of central China lie within a thick loess-paleosol succession that spans ≥780,000 years. Constraining ages for gully cutting and filling are provided by dates of loess and soil units cut by and capping the paleogullies. An episode of gully cutting begins at the onset of an interglaciation and ceases as the gullies begin to fill with colluvium and airborne dust during the transition to full-glacial conditions. The episodic cutting and filling of gullies implies a basic astronomical (orbital) control of gully evolution involving cyclic changes in dominant summer and winter monsoon climates, surface hydrology, and vegetation cover.
hiv/aids in rural india: context and health care needs
Authors: pallikadavath saseendran , garda laila , apte hemant , freedman jane , william stones r.
Published: August 2005

primary research on hiv/aids in india has predominantly focused on known risk groups such as sex workers, sti clinic attendees and long-distance truck drivers, and has largely been undertaken in urban areas. there is evidence of hiv spreading to rural areas but very little is known about the context of the infection or about issues relating to health and social impact on people living with hiv/aids. in-depth interviews with nineteen men and women infected with hiv who live in rural areas were used to collect experiences of testing and treatment, the social impacts of living with hiv and differential impacts on women and men. eight focus group discussions with groups drawn from the general population in the four villages were used to provide an analysis of community level views about hiv/aids. while men reported contracting hiv from sex workers in the cities, women considered their husbands to be the source of their infection. correct knowledge about hiv transmission co-existed with misconceptions. men and women tested for hiv reported inadequate counselling and sought treatment from traditional healers as well as professionals. owing to the general pattern of husbands being the first to contract hiv women faced a substantial burden, with few resources remaining for their own or their children’s care after meeting the needs of sick husbands. stigma and social isolation following widowhood were common, with an enforced return to the natal home. implications for potential educational and service interventions are discussed within the context of gender and social relations.
childhood iq of parents related to characteristics of their offspring: linking the scottish mental survey 1932 to the midspan family study
Authors: hart c. l. , deary i. j. , davey smith g. , upton m. n. , whalley l. j. , starr j. m. , hole d. j. , wilson v. , watt g. c. m.
Published: August 2005

the objective of the study was to investigate the relationship between childhood iq of parents and characteristics of their adult offspring. it was a prospective family cohort study linked to a mental ability survey of the parents and set in renfrew and paisley in scotland. participants were 1921-born men and women who took part in the scottish mental survey in 1932 and the renfrew/paisley study in the 1970s, and whose offspring took part in the midspan family study in 1996. there were 286 offspring from 179 families. parental iq was related to some, but not all characteristics of offspring. greater parental iq was associated with taller offspring. parental iq was inversely related to number of cigarettes smoked by offspring. higher parental iq was associated with better education, offspring social class and offspring deprivation category. there were no significant relationships between parental iq and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. structural equation modelling showed parental iq associated with offspring education directly and mediated via parental social class. offspring education was associated with offspring smoking and social class. the smoking finding may have implications for targeting of health education.