bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracheal length changes during zebra finch song and their possible role in upper vocal tract filtering
Authors: Daley Monica , Goller Franz
Published: April 2004

Sounds produced in the avian vocal organ may be modified by filter properties of the upper vocal tract. Possible mechanisms to actively control filter characteristics include movements of the beak, tongue, and larynx and adjustments of tracheal length. We investigated whether length changes of the trachea are a likely mechanism for adjusting upper vocal tract filter properties during song in the zebra finch (Taeniopygia guttata). Tracheal length was monitored at the basal end using sonomicrometry and was recorded together with subsyringeal air sac pressure and acoustic output. Tracheal shortening occurred at the onset of song bouts, and during each motif the tracheal length decreased during expiratory pressure pulses and increased during the short inspirations. A bilateral tracheal syringeal nerve cut confirmed that the initial shortening at the onset of the song bout is an active shortening of the trachea (i.e., mediated by syringeal muscle activity). The modulation of length during the motif was not affected by the denervation and is most likely driven by the pressurization of the interclavicular air sac. The absolute length change during the motif was small (<0.2 mm) and not clearly related to acoustic features of the song. For example, some high‐frequency syllables, which are generated during inspiration, were accompanied by tracheal elongation. Because this elongation shifts tube resonances to lower frequencies, it is inconsistent with an active adjustment of length to enhance high frequency sounds. The small magnitude and inconsistent nature of dynamic tracheal length changes during song make it unlikely that they significantly affect vocal tract filter properties if the trachea is modeled as a rigid tube. © 2004 Wiley Periodicals, Inc. J Neurobiol 59: 319–330, 2004
Reassessing popular participation in Uganda
Authors: Golooba‐Mutebi Frederick
Published: April 2004

The 1980s saw the emergence of popular participation as a mechanism for promoting good governance in developing countries Good governance was seen as crucial to efforts to improve the welfare of poor people in countries where elites had hitherto benefited disproportionately from policies conceived at the top without reference to ordinary citizens at the bottom. Donor pressure helped accelerate the change. In Uganda these developments coincided with the rise to power of a government that sought to democratise the country's politics. A major plank in the democratisation agenda was the establishment of a participatory system of local administration in which ordinary citizens, facilitated by local councils, would participate in public affairs and influence the way government functioned. These aspirations coincided with those of the donor community and enthusiasts of popular participation. This article is an account of the evolution of village councils and popular participation from 1986, when the National Resistance Movement came to power in Uganda, to 1996. It shows that while at the beginning the introduction of local councils seized the public's imagination leading to high levels of participation, with time, public meetings as consultative fora succumbed to atrophy due to participation fatigue and unwarranted assumptions about the feasibility and utility of popular participation as an administrative and policy‐making devise. It calls for political history and the socio‐cultural context to be taken into account in efforts to promote participation. Copyright © 2004 John Wiley & Sons, Ltd.
Loss of Smad4 correlates with loss of the invasion suppressor E‐cadherin in advanced colorectal carcinomas
Authors: Reinacher‐Schick Anke , Baldus Stephan E , Romdhana Bashra , Landsberg Stephanie , Zapatka Marc , Mönig Stefan P , Hölscher Arnulf H , Dienes Hans P , Schmiegel Wolff , Schwarte‐Waldhoff Irmgard
Published: April 2004

Smad4 is a tumour suppressor gene predominantly involved in gastrointestinal carcinogenesis. Loss of Smad4 is considered to be a genetically late step and occurs in up to 30% of metastatic colorectal carcinomas. Smad4, originally characterized as an intracellular transmitter of transforming growth factor‐β (TGF‐β) signals, is a transcriptional co‐modulator capable of integrating cellular responses to multiple signalling cascades. Thus, there are many Smad4 target genes and they are presumably strongly context‐dependent. It was recently shown that re‐expression of Smad4 in Smad4‐deficient SW480 human colon carcinoma cells restored epithelioid morphology and induced P‐cadherin and E‐cadherin transcription. The cadherins are key players in cell–cell adhesion connecting adjacent cells via the cadherin–catenin adhesion complex. Frequent loss of E‐cadherin expression in human cancers has been a long‐standing observation, but the underlying mechanisms are not yet fully understood. To assess the role of Smad4 in E‐cadherin regulation in colorectal carcinogenesis further, the present study has analysed Smad4 and E‐cadherin RNA and protein expression in colorectal carcinoma cell lines and in 51 late‐stage colorectal carcinomas. In primary tumours, loss of Smad4 expression correlated highly significantly with loss of E‐cadherin expression, thus providing further evidence for involvement of the tumour suppressor Smad4 in the control of expression of the tumour and invasion suppressor E‐cadherin. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Endothelial nitric oxide synthase in the control of osteoblastic mineralizing activity and bone integrity
Authors: Afzal Faiza , Polak Julia , Buttery Lee
Published: April 2004

It has been shown previously that osteoblast differentiation and maintenance of bone mass are impaired in endothelial nitric oxide synthase gene knockout mice. The present study shows by analysis of messenger RNA expression that the transcription factor Cbfa‐1/Runx‐2 and the bone matrix protein osteocalcin, which are fundamental to osteoblast differentiation, are significantly reduced in neonatal calvarial osteoblasts from these gene knockout mice. Expression of these genes could be restored to wild‐type levels by exogenous supply of the photoactivatable nitric oxide donor potassium nitrosylpentachlorouthenate, but this was dependent on the timing of its activation and recovery in gene expression was only evident during the latter stages of osteoblast differentiation associated with its mineralizing activity. Calvarial, femoral/pelvic, spinal, and total bone mineral density, together with bone microhardness and expression of osteocalcin in whole femurs, were all reduced significantly in gene knockout mice at 8 weeks of age, but not at 12 weeks, where all of these indices of bone integrity were comparable to wild type. In accordance with these temporal effects, reduced bone mineral density, bone microhardness, and osteocalcin expression could be restored to normal, wild‐type values after 21 days in vivo administration of the nitric oxide donor glyceryl trinitrate to 4‐week‐old endothelial nitric oxide synthase knockout mice, but there was no significant effect in older animals. Taken together, these results further demonstrate the importance of endothelial nitric oxide synthase in the regulation of osteoblast metabolism. In particular, they show that nitric oxide is involved in co‐ordinating specific phases of osteoblast differentiation and bone formation: this could be relevant to its therapeutic actions on bone turnover. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Site‐independent prognostic value of chromosome 9q loss in primary gastrointestinal stromal tumours
Authors: Gunawan Bastian , Schulten Hans‐Jürgen , von Heydebreck Anja , Schmidt Bettina , Enders Christina , Höer Jörg , Langer Claus , Schüler Phillip , Schindler Christian G , Kuhlgatz Jens , Füzesi László
Published: April 2004

Although the significance of tumour site for estimating malignant potential in gastrointestinal stromal tumours (GISTs) has recently been recognized, site‐specific genetic patterns have not to date been defined. This study examined 52 c‐kit‐positive primary GISTs (with a mean follow‐up of 42.3 months in 51 cases) from three different locations (35 gastric, 12 small intestinal, and five colorectal) using comparative genomic hybridization (CGH). In general, tumour site correlated with key prognostic factors, including tumour size, mitotic rate, proliferative activity, and probable malignant potential. Furthermore, several DNA copy number changes showed a site‐dependent pattern. These included losses at 14q (gastric 83%, intestinal 35%; p = 0.001), losses at 22q (gastric 46%, intestinal 82%; p = 0.02), losses at 1p (gastric 23%, intestinal 88%; p = 1 × 10−5), losses at 15q (gastric 14%, intestinal 59%; p = 0.002), losses at 9q (gastric 14%, intestinal 53%; p = 0.006), and gains at 5p (gastric 11%, intestinal 53%; p = 0.002). These data demonstrate strong site‐dependent genetic heterogeneity in GISTs that may form a basis for subclassification. Prognostic evaluation of DNA copy number changes identified losses at 9q as a site‐independent prognostic marker associated with shorter disease‐free survival (p = 0.03) and overall survival (p = 0.002). Furthermore, 9q loss also appeared to carry prognostic value in predicting overall survival for patients with advanced or progressive GISTs (p = 0.003). Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and the downstream effector, MITF‐M
Authors: Kitamura Reiko , Tsukamoto Katsuhiko , Harada Kazutoshi , Shimizu Akira , Shimada Shinji , Kobayashi Takeshi , Imokawa Genji
Published: April 2004

Little is known about the mechanisms involved in the dysfunction of melanocytes in vitiligo epidermis. It is hypothesized that some cytokine/receptor interactions may be affected, resulting in dysfunction and/or loss of melanocytes. This study has compared the expression of endothelin (ET)‐1, the ET‐1 receptor (ETBR), granulocyte macrophage colony stimulating factor (GM‐CSF), stem cell factor (SCF), the SCF receptor (KIT protein), tyrosinase, and S100α between lesional and non‐lesional vitiligo epidermis. Analysis by reverse transcription‐polymerase chain reaction (RT‐PCR) and by western blotting for ET‐1 and SCF unexpectedly demonstrated up‐regulated expression of these cytokines in lesional vitiligo epidermis. Immunohistochemistry with antibodies to melanocyte markers revealed that at the edge of the lesional epidermis, melanocytes remain and express tyrosinase, S100α and ETBR, but not KIT protein or melanocyte‐specific microphthalmia‐associated transcription factor (MITF‐M). Quantitation of the staining revealed a slight or moderate decrease in the number of S100α, tyrosinase, and ETBR‐positive cells at the edge of the lesional epidermis. In contrast, the number of cells expressing KIT protein was markedly decreased at the edge of the lesional epidermis compared with the non‐lesional epidermis. At the centre of the lesional epidermis, there was complete loss of melanocytes expressing KIT protein, S100α, ETBR, and/or tyrosinase. Western blotting revealed down‐regulated expression of c‐kit and MITF‐M proteins at the edge of the lesional epidermis in vitiligo. These findings suggest that reduction in the expression of KIT protein by melanocytes and its downstream effectors, including MITF‐M, may be associated with the dysfunction and/or loss of melanocytes in vitiligo epidermis. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Activation of pro‐MMP‐2 mediated by MT1‐MMP in human salivary gland carcinomas: possible regulation of pro‐MMP‐2 activation by TIMP‐2
Authors: Kayano Kaori , Shimada Taketoshi , Shinomiya Takashi , Nakai Shigeru , Hisa Yasuo , Aoki Takanori , Seiki Motoharu , Okada Yasunori
Published: April 2004

Matrix metalloproteinases (MMPs), a family of extracellular matrix‐degrading enzymes, are considered to play important roles in cancer invasion and metastasis. The present study examined the production levels of eight different MMPs (MMP‐1, 2, 3, 7, 8, 9 and 13, and MT1‐MMP) and two tissue inhibitors of metalloproteinases (TIMP‐1 and 2) in homogenates of human salivary gland carcinomas [mucoepidermoid carcinomas (MECs), adenoid cystic carcinomas (ACCs), and adenocarcinomas (ADEs)] and non‐neoplastic control salivary glands using sandwich enzyme immunoassay systems. The levels of MMP‐1, MMP‐2, MMP‐13, MT1‐MMP, and TIMP‐1 were significantly higher in the carcinoma samples than in the controls (p < 0.05). Gelatin zymography demonstrated that the activation ratio of the MMP‐2 zymogen (pro‐MMP‐2) was significantly higher in the carcinomas than in the controls (p < 0.05). In addition, the activation ratio in MECs was significantly higher than that in ACCs or ADEs (p < 0.01) and also correlated with histological grade and lymph node metastasis in MECs (p < 0.05), whereas the ratio showed no such correlation in ACCs or ADEs. Although the production levels of pro‐MMP‐2 and MT1‐MMP were similar among these carcinoma groups, TIMP‐2 levels were significantly higher in ACCs and ADEs than in MECs (p < 0.01). In carcinoma samples, the pro‐MMP‐2 activation ratio correlated directly with the MT1‐MMP/TIMP‐2 ratio (r = 0.736, n = 23; p < 0.01). Immunohistochemistry and in situ zymography demonstrated localization of MMP‐2, MT1‐MMP, and TIMP‐2 to carcinoma cells, but only in MECs did carcinoma cell nests exhibit gelatinolytic activity, which was inhibited by 1,10‐phenanthroline. These results suggest that enhanced activation of pro‐MMP‐2 mediated by MT1‐MMP is implicated in the invasion and metastasis of MECs and that TIMP‐2 may regulate pro‐MMP‐2 activation in salivary gland carcinomas. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Reversible addition fragmentation chain transfer polymerization of sterically hindered monomers: Toward well‐defined rod/coil architectures
Authors: Szablan Zachary , Toy Andrew Ah , Davis Thomas P. , Hao Xiaojuan , Stenzel Martina H. , Barner‐Kowollik Christopher
Published: April 2004

The sterically hindered monomers dibutyl itaconate (DBI) and dicyclohexyl itaconate (DCHI) were polymerized via reversible addition fragmentation chain transfer (RAFT) free‐radical polymerization. S,S′‐Bis(α,α′‐dimethyl‐α″‐acetic acid) trithiocarbonate, cumyl dithiobenzoate, and cumyl phenyldithioacetate have been used as RAFT agents to mediate a series of polymerizations at 65 °C yielding rod polymers ranging in number average molecular weight from 9000 to 92,000 g mol−1. The progress of the polymerization was followed via online Fourier transform–near infrared spectroscopy. The polydispersity indices of the obtained rod polymers were relatively high at 1.4–1.7. The RAFT polymerizations of the hindered monomers used in the present study displayed both ideal living and hybrid behavior between conventional and living polymerization, depending on the RAFT agent used. DCHI rod polymers generated via the RAFT process were subsequently reinitiated in the presence of styrene to produce a range of BAAB and A‐B rod‐coil block copolymers of molecular weights up to 164,000 g mol−1. The chain extension yields molecular weight distributions that progressively shift to higher molecular weights and are unimodal. Thermogravimetric analysis of the pDCHI‐block‐pStyrene copolymers indicates thermal degradation in two separate steps for the pDCHI and pStyrene blocks. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2432–2443, 2004
Ion‐exchange resins. III. Functionalization–morphology correlations in the synthesis of some macroporous, strong basic anion exchangers and uranium‐sorption properties evaluation
Authors: Dragan Ecaterina Stela , Avram Ecaterina , Axente Damian , Marcu Cristina
Published: April 2004

The synthesis and characterization of a series of macroporous, strong basic anion exchangers (SBAEs), with an average pore radius higher than 50 nm, and the evaluation of their sorption properties for uranyl chlorocomplexes from HCl solutions are reported. Finely divided macroporous styrene–divinylbenzene (S–DVB) copolymers with a narrow distribution of beads sizes, diameters within the range of 90–200 μm, were prepared for this purpose with 2‐ethyl‐1‐hexanol as a porogen, at a high dilution of monomers (D ≥ 0.55 mL/mL). Chloromethyl groups were introduced with (CH2O)n/Me3SiCl as a chloromethylation agent in the presence of a Lewis acid as a catalyst (TiCl4, SnCl4, and FeCl3) in CHCl3 as a reaction medium. SnCl4 and FeCl3 gave comparable chloromethylation degrees in the same reaction conditions. TiCl4 was not efficient as a catalyst in the chloromethylation with this reagent. Diethyl‐2‐hydroxyethylamine was used as a tertiary amine to prepare SBAEs. Structural and morphological characteristics were determined after every functionalization step of the macroporous network. Both the chloromethylation, in the presence of FeCl3 as a catalyst, and the amination reactions determined a significant decrease of the pore volume, in the whole range of the nominal crosslinking degree, comparative with the starting copolymer. The specific surface area and the average pore radius varied in a different way as a function of the nominal crosslinking degree. Thus, the specific surface area increased and the average pore radius decreased after chloromethylation and amination for copolymers with a DVB content lower than 10 wt %. Small decreases of the specific surface area and the average pore radius were observed after chloromethylation and amination reactions for copolymers with a DVB content higher than 10 wt %. SBAEs were also characterized by thermogravimetric analysis and sorption capacity for uranyl chlorocomplexes. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2451–2461, 2004
Synthesis, complex formation, and dilute‐solution associative behavior of linear poly(methacrylic acid)‐graft‐poly(2‐ethyl‐2‐oxazoline)*
Authors: Poe Garrett D. , McCormick Charles L.
Published: April 2004

Poly(methacrylic acid) (PMA) and poly(2‐ethyl‐2‐oxazoline) (PEOZO) are a polyacid/polybase pair capable of forming reversible, pH‐responsive, hydrogen‐bonding complexes stabilized by hydrophobic effects in aqueous media. Linear PMA was modified with long‐chain (number‐average molecular weight: 10,000) PEOZO via statistical coupling reactions in organic media to prepare a series of PMA‐graft‐PEOZO copolymers. Potentiometric titrations revealed that the presence of tethered PEOZO markedly increases the pKa values for PMA‐g‐PEOZO copolymers as compared with simple PMA/PEOZO mixtures at degrees of ionization, α, between 0.0 and 0.1. The dilute‐solution PMA–PEOZO intramolecular association has been probed by monitoring the PEOZO NMR spin–spin (T2) relaxation as a function of pH. Covalently attached PEOZO side chains participate in complexation at higher values of α than untethered PEOZO. Surprisingly, most PEOZO side chains did not take part in hydrogen bonding at low α, and the highest level of PEOZO incorporation induced a decrease in the number of PMA/PEOZO hydrogen bonds. The polymer self‐diffusion as a function of α was measured with dynamic light scattering. At low pH, the copolymers had no charge and they were in a collapsed form. At high pH, the expected conformational expansion of the PMA units was enhanced at moderate levels of PEOZO incorporation. However, the highest PEOZO incorporation induced the onset of intramolecular associations between PEOZO units along the copolymer chains. Low shear rheometry and light scattering measurements were used in conjunction with the T2 NMR measurements to propose a model consistent with the aforementioned behavior. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2520–2533, 2004
Novel, organosoluble, light‐colored fluorinated polyimides based on 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)biphenyl or 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)‐1,1′‐binaphthyl
Authors: Yang Chin‐Ping , Hsiao Sheng‐Huei , Tsai Che‐Yu , Liou Guey‐Sheng
Published: April 2004

Two series of fluorinated polyimides were prepared from 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)biphenyl (2) and 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)‐1,1′‐binaphthyl (4) with various aromatic dianhydrides via a conventional, two‐step procedure that included a ring‐opening polyaddition to give poly(amic acid)s, followed by chemical or thermal cyclodehydration. The inherent viscosities of the polyimides ranged from 0.54 to 0.73 and 0.19 to 0.36 dL/g, respectively. All the fluorinated polyimides were soluble in many polar organic solvents, such as N,N‐dimethylacetamide and N‐methylpyrrolidone, and afforded transparent and light‐colored films via solution‐casting. These polyimides showed glass‐transition temperatures in the ranges of 222–280 and 257–351 °C by DSC, softening temperatures in the range of 264–301 °C by thermomechanical analysis, and a decomposition temperature for 10% weight loss above 520 °C both in nitrogen and air atmospheres. The polyimides had low moisture absorptions of 0.23–0.58%, low dielectric constants of 2.84–3.61 at 10 kHz, and an ultraviolet–visible absorption cutoff wavelength at 351–434 nm. Copolyimides derived from the same dianhydrides with an equimolar mixture of 4,4′‐oxydianiline and diamine 2 or 4 were also prepared and characterized. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2416–2431, 2004
Metal‐induced optical sensing and optical switching in poly(pyridyl phenylene)
Authors: Na Jongho , Kim Young‐Shin , Park Won Ho , Lee Taek Seung
Published: April 2004

The synthesis of a conjugated polymer containing pyridyl units in the polymer backbone was successfully carried out with 2,6‐dibromopyridine and a diboronic acid derivative via the Suzuki coupling reaction. This polymer had a number‐average molecular weight of 4000 and excellent solubility in conventional organic solvents; this suggested the effect of the incorporation of dialkoxy side chains. A metallochromic phenomenon with ferric ions was clearly observed in spin‐coated films and solutions of the polymer. The response of the absorption and the fluorescence changes of the polymer films were rapid and were reproduced more than 15 times. A lightly bound intermolecular interaction between the pyridine ligand and cation was presumed to be responsible for the facile optical switching property of the polymer films. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2444–2450, 2004
Melting behavior in blends of isotactic polypropylene and a liquid crystalline polymer
Authors: Torre J. , Cortázar M. , Gómez M. , Ellis G. , Marco C.
Published: April 2004

The influence of low contents of a liquid crystalline polymer on the crystallization and melting behavior of isotactic polypropylene (iPP) was investigated using electron and optical microscopy, differential scanning calorimetry, and X‐ray diffraction. In pure iPP, the α modification was found, whereas for iPP/Vectra blends at Vectra concentration <5%, both α and β forms were observed. The amount of β phase varied from 0.23 to 0.16. Optical microscopy showed that Vectra was able to nucleate both α and β forms. Non‐isothermal crystallization produces a material with a strong tendency for recrystallization of the α and β forms (αα′ and ββ′ recrystallization) leading to double endotherms for both crystalline forms in DSC thermograms. Melting thermograms after isothermal crystallization at low temperatures showed a similar behavior. At values of Tc > 119 °C for the α form and Tc > 125 °C for the β form, only one melting endotherm was observed because enough perfect crystals, not susceptible to recrystallization, were obtained. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1949–1959, 2004
Effect of photoinitiator on photopolymerization of inorganic–organic hybrid polymers (ORMOCER®)
Authors: Kim Woo‐Soo , Houbertz Ruth , Lee Tae‐Ho , Bae Byeong‐Soo
Published: April 2004

Inorganic–organic hybrid polymers have been developed and tested for evaluation in optical and electrical applications. Although hybrid inorganic–organic polymers can be synthesized by sol–gel chemistry at first, the physical properties of hybrid inorganic–organic polymers are changed during thin film‐making processes, that is, photocuring and thermal curing. To investigate the effect of photoinitiator on the material properties during processing, a model system containing methacrylic groups as organically polymerizable units was selected. The conversion of CC double bond of methacrylic groups depending on some kinds of photoinitiator quantities was characterized by Fourier transform infrared spectroscopy. It was confirmed to correlate the degree of CC double bond conversion with the refractive indices. Thermodynamically, the enthalpy of the photopolymerization of hybrid polymer was investigated by UV–DSC. UV–DSC spectra showed the exothermic nature of photopolymerization of ORMOCER® to be in dependence of photoinitiator quantities. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1979–1986, 2004
Electron spin resonance investigation of molecular motions in oil‐extended styrene–butadiene–styrene block copolymers. I. The temperature dependence of resonance spectra: Glass, narrowing, and inflection temperatures
Authors: Chipara M. , Rowlands C. C. , Galatanu A. N.
Published: April 2004

Spin‐probe research into nanometer‐scale molecular motions occurring in oil‐extended styrene–butadiene–styrene diblock copolymers within the glass‐transition range is reported. Complex resonance spectra are deconvoluted, and their intricate temperature dependence, resulting from the convolution of individual spectra due to nitroxide molecules located in different phases of the block copolymers, is analyzed. It is proved that a Boltzmann sigmoid accurately describes the temperature dependence of outer line separation. The characteristic inflection point of each sigmoid is used to assign an inflection temperature to each phase of the block copolymers. The inflection temperature coincides with the narrowing temperatures, within the experimental error. It is concluded that the inflection temperature is estimated with a higher accuracy than the narrowing temperature and that it allows a more profound analysis of molecular motions. The anomalous dependence of the glass, narrowing, and inflection temperatures for spin probes immobilized within the hard phase on the oil content has been assigned to morphological modifications, on the nanometer scale, induced by oil molecules added to the block copolymers. The experimental data demonstrate the sensitivity of spin‐probe data to modifications of the nanometer‐size architecture of block copolymers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 1960–1971, 2004
Antibody recognition of chiral surfaces. Structural models of antibody complexes with leucine–leucine–tyrosine crystal surfaces
Authors: Geva Merav , Eisenstein Miriam , Addadi Lia
Published: April 2004

Molecular models are built of the recognition domains of two antibodies, which are raised and selected against crystals of (L)leucine‐(L)leucine‐(L)tyrosine. The model of one antibody, which is stereo‐ and enantioselective, reveals astounding chemical and structural complementarity to the recognized crystal surface. The enantioselective binding of this antibody is explained by the significantly fewer chemical interactions arising in the complex, after docking of the antibody to the (D)Leu‐(D)Leu‐(D)Tyr crystal face, relative to its enantiomer, the (L)Leu‐(L)Leu‐(L)Tyr crystal face. The modeling and docking of the second antibody, which is poorly stereoselective and is not enantioselective, indicates that binding is based on electrostatic interactions. The docking models of the antibody–crystal complexes provide a rationale for the experimental results while demonstrating the power of modeling techniques to meet the challenge of describing antibody–antigen interactions in detail. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Magnetically quantized continuum distorted‐wave theory in atomic and molecular collisions
Authors: O'Rourke S. F. C. , McSherry D. M. , Crothers D. S. F.
Published: April 2004

The continuum distorted‐wave eikonal initial‐state (CDW‐EIS) theory of Crothers and McCann (J Phys B 1983, 16, 3229) used to describe ionization in ion–atom collisions is generalized (G) to GCDW‐EIS to incorporate the azimuthal angle dependence of each CDW in the final‐state wave function. This is accomplished by the analytic continuation of hydrogenic‐like wave functions from below to above threshold, using parabolic coordinates and quantum numbers including magnetic quantum numbers, thus providing a more complete set of states. At impact energies lower than 25 keVu−1, the total ionization cross‐section falls off, with decreasing energy, too quickly in comparison with experimental data. The idea behind and motivation for the GCDW‐EIS model is to improve the theory with respect to experiment by including contributions from nonzero magnetic quantum numbers. We also therefore incidentally provide a new derivation of the theory of continuum distorted waves for zero magnetic quantum numbers while simultaneously generalizing it. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Fragmentation patterns of novel dispirocyclopiperazinium dibromides with strong analgesic activity under electrospray ionization tandem mass spectrometry conditions
Authors: Wang Xin , Sha Yaowu , Li Runtao
Published: April 2004

The fragmentation patterns of a series of dispirocyclopiperazinium dibromides with strong analgesic activity are analyzed by positive ion electrospray ionization mass spectrometry in conjunction with tandem mass spectrometry (ESI‐MSn). Instead of the parent molecular ions, the fragment ions [MBr]+ are detected as characteristic double peaks and usually the base peaks. Meanwhile, the fragment ions [M2Br]2+ are unique for this series of diquaternary ammonium dibromides and show high intensity. Besides the common fragmentation patterns around the carbonyl group, elimination of hydrogen bromide from [MBr]+ ions is another important pathway. Following the elimination, an interesting rearrangement takes place in the unsaturated spirocyclopiperazine and transforms it into a dihydropyrrole structure, whose fragmentations are similar to its precursor ion in the succeeding steps. Copyright © 2004 John Wiley & Sons, Ltd.
Polymer‐assisted laser desorption/ionization analysis of small molecular weight compounds
Authors: Woldegiorgis Andreas , Kieseritzky Fredrik von , Dahlstedt Emma , Hellberg Jonas , Brinck Tore , Roeraade Johan
Published: April 2004

The use of non‐polar, small polymers as matrices for the analysis of low molecular weight compounds in polymer‐assisted laser desorption/ionization mass spectrometry (PALDI‐MS) is demonstrated. The matrices evaluated were either based on an oligothiophene or a benzodioxin backbone. Metallocenes, polycyclic hydrocarbons, a fluorosurfactant, and a subset of small organic compounds with various functionalities, served as model analytes. The mechanism of ionization charge transfer is discussed and ionization potentials for the matrices in the study have been estimated using density functional theory (DFT) calculations. Some of the results are possibly contradictory to the generally accepted limiting conditions for gas‐phase charge‐transfer reactions. These results are interpreted in the light of energy pooling. Also a new mass calibration procedure for the low‐mass region in positive ion mode is presented, and some aspects of the ionization/desorption process leading to radical cations are studied. Copyright © 2004 John Wiley & Sons, Ltd.
Structure of Lipid A from Pseudomonas corrugata by electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry
Authors: Corsaro M. M. , Piaz F. Dal , Lanzetta R. , Naldi T. , Parrilli M.
Published: April 2004

The use of the electrospray ionization quadrupole time‐of‐flight tandem mass spectrometry (ESI‐QTOFMS) technique for the structural determination of Lipid A from Pseudomonas corrugata is described. This technique appears to be more sensitive with respect to other commonly used tandem mass spectrometric approaches, and was very valuable in the structural determination of the highly heterogeneous Lipid A fractions. The Lipid A fraction consists mainly of a pentaacyl component in which 3‐hydroxydecanoyl [10:0(3‐OH)] and 3‐hydroxydodecanoyl [12:0(3‐OH)] are linked as primary acyl substituents to the classical bisphosphorylated β‐(1′ → 6)‐linked D‐glucosamine disaccharide. Secondary substitution of N‐acyl fatty acids with dodecanoyl residues [12:0] and/or its 2‐OH derivatives was also observed. Copyright © 2004 John Wiley & Sons, Ltd.
A high‐throughput monoamine oxidase inhibition assay using liquid chromatography with tandem mass spectrometry
Authors: Yan Zhengyin , Caldwell Gary W. , Zhao Boyu , Reitz Allen B.
Published: April 2004

A highly efficient method utilizing liquid chromatography with tandem mass spectrometry (LC/MS/MS) was developed and employed for high‐throughput screening of compounds for monoamine oxidase (MAO) inhibition. The method used kynuramine as a common substrate for both MAO‐A and MAO‐B in incubations, and the 4‐hydroxyquinoline (4‐HQ) resulting from deamination of kynuramine followed by intramolecular condensation was analyzed using LC/MS/MS; formation of 4‐HQ was used as the marker of MAO activity to evaluate the effects of test compounds. Isocratic liquid chromatography was applied to reduce the run time to 2 min. Because of the high specificity and sensitivity of detection of 4‐HQ by LC/MS/MS, this method was able to use MAO enzymes at very low concentrations and to perform short incubations; as a result, consumable cost was minimized, and sample preparations were completely avoided. The inhibition data are highly reproducible, and the IC50 values determined by the method are in good agreement with literature values. The results suggest that this method is very robust and can be used as a generic approach to screen for MAO inhibitors in drug discovery. Copyright © 2004 John Wiley & Sons, Ltd.
Mass spectral fragmentation of 2a,4‐disubstituted 2,2a,3,4‐tetrahydro‐2‐phenoxy‐1H‐azeto[2,1‐d][1,5]benzothiazepin‐1‐ones under electron impact ionization conditions
Authors: Xu Jiaxi , Huang Xu
Published: April 2004

The mass spectrometric fragmentation of 2a,4‐disubstituted 2,2a,3,4‐tetrahydro‐2‐phenoxy‐1H‐azeto[2,1‐d][1,5]benzothiazepin‐1‐ones has been investigated using the aid of mass‐analyzed ion kinetic energy spectrometry. All compounds tend to eliminate a phenoxy, phenol, and phenoxyketene, respectively, from molecular ions. [M+PhO] ions could also form [M+PhOH] ions, which could further lose alkenes. [M+PhOCHCO] ions could further yield 2‐arylbenzothiazole ions and other fragment ions. Copyright © 2004 John Wiley & Sons, Ltd.
Handling drop‐out in longitudinal studies
Authors: Hogan Joseph W. , Roy Jason , Korkontzelou Christina
Published: April 2004

Drop‐out is a prevalent complication in the analysis of data from longitudinal studies, and remains an active area of research for statisticians and other quantitative methodologists. This tutorial is designed to synthesize and illustrate the broad array of techniques that are used to address outcome‐related drop‐out, with emphasis on regression‐based methods. We begin with a review of important assumptions underlying likelihood‐based and semi‐parametric models, followed by an overview of models and methods used to draw inferences from incomplete longitudinal data. The majority of the tutorial is devoted to detailed analysis of two studies with substantial rates of drop‐out, designed to illustrate the use of effective methods that are relatively easy to apply: in the first example, we use both semi‐parametric and fully parametric models to analyse repeated binary responses from a clinical trial of smoking cessation interventions; in the second, pattern mixture models are used to analyse longitudinal CD4 counts from an observational cohort study of HIV‐infected women. In each example, we describe exploratory analyses, model formulation, estimation methodology and interpretation of results. Analyses of incomplete data requires making unverifiable assumptions, and these are discussed in detail within the context of each application. Relevant SAS code is provided. Copyright © 2004 John Wiley & Sons, Ltd.
GEE approaches to marginal regression models for medical diagnostic tests
Authors: Martus Peter , Stroux Andrea , Jünemann Anselm M. , Korth Matthias , Jonas Jost B. , Horn Folkert K. , Ziegler Andreas
Published: April 2004

The evaluation of a new medical diagnostic test may focus on two different scientific questions: (1) The new test may replace an existing one because of lower cost or higher validity. A related question would be the selection of the ‘best’ test(s) from a bundle of new or established measurements. (2) The new test may be used supplementary to other new or established procedures. In a recent publication, Leisenring and co‐workers (Stat Med 1997; 16:1263–1281) developed a general marginal regression model for comparisons of diagnostic tests focussing on question (1), i.e. on the selection of the ‘best’ procedure. They applied the GEE approach of Liang and Zeger (Biometrika 1987; 73:13–22) to adjust for the correlation of data as a nuisance parameter. Using the general framework provided by Leisenring et al., we extend their approach and apply the GEE methodology to question (2), i.e. to the investigation of which of several diagnostic tests should be used supplementary to each other. We analyse data from a longitudinal study concerning pathogenesis, diagnosis and long‐term course of the eye disease glaucoma. We find a dependence of the correlation structure of several diagnostic measurements on the severity of the disease. This result may be useful in clinical applications as regards the selection of subsets of diagnostic measurements in individual diagnostic processes but also in investigations concerning the relationship of the pathogenic process and the rationales of the different diagnostic procedures. Copyright © 2004 John Wiley & Sons, Ltd.
What to add to nothing? Use and avoidance of continuity corrections in meta‐analysis of sparse data
Authors: J. Sweeting Michael , J. Sutton Alexander , C. Lambert Paul
Published: April 2004

Objectives: To compare the performance of different meta‐analysis methods for pooling odds ratios when applied to sparse event data with emphasis on the use of continuity corrections.

Background: Meta‐analysis of side effects from RCTs or risk factors for rare diseases in epidemiological studies frequently requires the synthesis of data with sparse event rates. Combining such data can be problematic when zero events exist in one or both arms of a study as continuity corrections are often needed, but, these can influence results and conclusions.

Methods: A simulation study was undertaken comparing several meta‐analysis methods for combining odds ratios (using various classical and Bayesian methods of estimation) on sparse event data. Where required, the routine use of a constant and two alternative continuity corrections; one based on a function of the reciprocal of the opposite group arm size; and the other an empirical estimate of the pooled effect size from the remaining studies in the meta‐analysis, were also compared. A number of meta‐analysis scenarios were simulated and replicated 1000 times, varying the ratio of the study arm sizes.

Results: Mantel–Haenszel summary estimates using the alternative continuity correction factors gave the least biased results for all group size imbalances. Logistic regression was virtually unbiased for all scenarios and gave good coverage properties. The Peto method provided unbiased results for balanced treatment groups but bias increased with the ratio of the study arm sizes. The Bayesian fixed effect model provided good coverage for all group size imbalances. The two alternative continuity corrections outperformed the constant correction factor in nearly all situations. The inverse variance method performed consistently badly, irrespective of the continuity correction used.

Conclusions: Many routinely used summary methods provide widely ranging estimates when applied to sparse data with high imbalance between the size of the studies' arms. A sensitivity analysis using several methods and continuity correction factors is advocated for routine practice. Copyright 2004 John Wiley & Sons, Ltd.
Decadal variability of circulation in the Arctic Ocean retrieved from climatological data by a variational method
Authors: Nechaev Dmitri , Yaremchuk Max , Ikeda Motoyoshi
Published: April 2004

An inverse 3D finite‐element ocean circulation model has been designed and used to study variability of the Arctic Ocean circulation in the last 4 decades. We obtained stationary model solutions with the temperature and salinity fields close to the ones given by the Environmental Working Group (EWG) [1998] atlas. Transports at the open boundaries, wind forcing and hydrographic fields are treated as unknowns, which are varied to minimize a quadratic cost function subject to model constraints. The inverse problem is solved for 10 gridded hydrographic data sets that were obtained as winter and summer averages of EWG data over each of the 4 decades (1950s to 1980s) and over the whole period of observations (1948–1993) documented in the atlas. The results show that Arctic circulation in the last 4 decades has undergone significant changes, which manifest themselves in (1) 10% reduction of the ventilation rate in the Atlantic sector of the Arctic Ocean; (2) substantial decrease of the advective heat and freshwater import at the lateral boundaries; (3) spinning down of the cyclonic gyre in the northern Greenland sea, which is partly driven by deep convection; and (4) 3400 km3 increase of the net fresh water storage, with 75% taking place in the Atlantic sector of the Arctic Ocean. Most of these changes are similar to the ones observed on seasonal transition from winter to summer climatologies, and indicate that the Arctic Ocean is experiencing a shift toward a warmer state.
Cold‐water coral mounds: Evidence for early Holocene climate change and slope failure
Authors: O'Reilly B. M. , Readman P. W. , Shannon P. M.
Published: April 2004

Cold‐water coral mounds occur in discrete clustered populations over a broad region from the glaciated Norwegian continental margins to the non‐glaciated margins of Iberia and northwest Africa. Here we report on an interesting correlation between the Holocene growth of a mound population west of Ireland and early Holocene paleoclimatic variations in the North Atlantic region, notably the well documented ‘8,200 yr cold event’. An age structure for the population is calculated from growth rate estimates for the coral framework constructor Lophelia pertusa and a previously formulated population growth model. The model growth curve for the Holocene period fits the observed data well, except for a significant deflection in the data trend at about 8,500 calendar years ago. This corresponds to the time that the glacial lakes Agassiz and Ojibway, which were once dammed by a remnant of the Laurentide ice sheet, drained catastrophically into the Labrador Sea and triggered the ‘8,200 yr event’. This cold period may also have played a role in triggering major submarine landslides, such as the Storegga Slide.
The northern hemisphere stratospheric vortex during the 2002–03 winter: Subsidence, chlorine activation and ozone loss observed by the Odin Sub‐Millimetre Radiometer
Authors: Urban J. , Lautié N. , Le Flochmoën E. , Murtagh D. , Ricaud P. , De La Noë J. , Dupuy E. , Drouin A. , El Amraoui L. , Eriksson P. , Frisk U. , Jiménez C. , Kyrölä E. , Llewellyn E. J. , Mégie G. , Nordh L. , Olberg M.
Published: April 2004

We present profile measurements of key constituents relevant to stratospheric chemistry and dynamics such as ozone (O3), nitrous oxide (N2O), and chlorine monoxide (ClO) taken during the 2002–03 northern hemisphere winter by the Odin Sub‐Millimetre Radiometer (SMR), a limb‐sounding satellite sensor launched in February 2001. The observations of the chemically passive tracer N2O show a subsidence of lower stratospheric air masses inside the Arctic vortex in the range of 3–5 km, or 60–100 K in terms of potential temperature, for the period November 2002 to March 2003. Activated chlorine in the form of ClO was observed inside the vortex from the beginning of December until mid‐February. The accumulated chemical ozone loss over this period, derived from the correlation of ozone with N2O, is estimated to be 28 ± 9% on the 50 ppbv level of N2O, i.e., for lower stratospheric air masses subsiding from ∼23 down to 19 km, the lower limit of the Odin/SMR ozone measurement in the 501.8 GHz band.
Energetic particle sounding of the magnetopause: A contribution by Cluster/RAPID
Authors: Zong Q.‐G. , Fritz T. A. , Spence H. , Oksavik K. , Pu Z.‐Y. , Korth A. , Daly P. W.
Published: April 2004

In this paper we present new results using Cluster/Research with Adaptive Particle Imaging Detectors (RAPID) energetic particle observations to remotely sound the high‐latitude magnetopause in three dimensions. We demonstrate that energetic particle flux variations in the vicinity of the magnetopause (inside the magnetosphere) are mainly modulated by the absorbing magnetopause during quiet geomagnetic conditions. Less than two gyro radii from an absorbing boundary a trapped particle distribution becomes nongyrotropic, as particles start to encounter the boundary. Knowing the magnetic field and the particle mass and energy, the direction and distance to the magnetopause can be derived by examining the azimuthal distribution of locally mirroring particles. Combining observations from three nearby spacecraft gives a three‐dimensional, local picture of the magnetopause surface. We exploit anisotropic ion distributions to determine magnetopause distances, orientations, and structures in the interval from 1320 to 1420 UT on 14 January 2001 for the three Cluster spacecraft (Rumba, Samba, and Tango) located on the duskside (at ∼1700 MLT) high‐latitude region. The results clearly illustrate that the magnetopause ion sounding technique as proposed by Williams [1979], Fritz and Fahnenstiel [1982], and Zong et al. [2000] can be used to remotely study the three‐dimensional orientation and location of the magnetopause surface and the gradient variation of the plasma parameters. Intercomparison between energetic particle sounding distance and simultaneous plasma and magnetic field measurements suggests that solar wind plasma can penetrate more than ≈1000 km deeper than the trapping boundary. The fluxes of different ion species are proportional to the distance from the magnetopause, with a correlation coefficient of 0.7 to 0.8. The energetic proton flux gradient as a function of distance from the magnetosphere is about 100 particles cm−2 s−1 sr−1 per kilometer. In contrast, the solar wind plasma density is found to be inversely proportional to the distance. The solar wind plasma appears to be bounded by an exponential with an e‐folding distance of 1000 km.