bluuebunny/crossref_metadata_2025 huggingface dataset:
Two simple and efficient displacement‐based quadrilateral elements for the analysis of composite laminated plates
Authors: Zhang Y. X. , Kim K. S.
Published: October 2004

Two simple 4‐node 20‐DOF and 4‐node 24‐DOF displacement‐based quadrilateral elements named RDKQ‐L20 and RDKQ‐L24 are developed in this paper based on the first‐order shear deformation theory (FSDT) for linear analysis of thin to moderately thick laminates. The deflection and rotation functions of the element sides are obtained from Timoshenko's laminated composite beam functions. Linear displacement interpolation functions of the standard 4‐node quadrilateral isoparametric plane element and displacement functions of a quadrilateral plane element with drilling degrees of freedom are taken as in‐plane displacements of the proposed elements RDKQ‐L20 and RDKQ‐L24, respectively. Due to the application of Timoshenko's laminated composite beam functions, convergence can be ensured theoretically for very thin laminates. The elements are simple in formulation, and shear‐locking free for extremely thin laminates even with full integration. A hybrid‐enhanced procedure is employed to improve the accuracy of stress analysis, especially for transverse shear stresses. Numerical tests show that the new elements are convergent, not sensitive to mesh distortion, accurate and efficient for analysis of thin to moderately thick laminates. Copyright © 2004 John Wiley & Sons, Ltd.
Differential quadrature domain decomposition method for problems on a triangular domain
Authors: Wu Xionghua , Liu Shuting
Published: October 2004

The differential quadrature method (DQM) has been studied for years and it has been shown by many researchers that the DQM is an attractive numerical method with high efficiency and accuracy. The conventional DQM is mostly effective for one‐dimensional and multidimensional problems with geometrically regular domains. But to deal with problems on a triangular domain, we will meet difficulties. In this article we will study how to solve problems on a triangular domain by using DQM combined with the domain decomposition method (DDM). © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Generalized Newton methods for crack problems with nonpenetration condition
Authors: Hintermüller M. , Kovtunenko V. A. , Kunisch K.
Published: October 2004

A class of semismooth Newton methods for unilaterally constrained variational problems modeling cracks under a nonpenetration condition is introduced and investigated. On the continuous level, a penalization technique is applied that allows to argue generalized differentiability of the nonlinear mapping associated to its first‐order optimality characterization. It is shown that the corresponding semismooth Newton method converges locally superlinearly. For the discrete version of the problem, fast local as well as global and monotonous convergence of a discrete semismooth Newton method are proved. A comprehensive report on numerical tests for the two‐dimensional Lamé problem with three collinear cracks under the nonpenetration condition ends the article. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Intravenous 6‐mercaptopurine decreases salvage after relapse in childhood acute lymphoblastic leukemia: A report from the Children's Cancer Group study CCG 1922
Authors: Tolar Jakub , Bostrom Bruce C. , La Mei K. , Sather Harland N.
Published: October 2004

Purpose

To compare outcomes of patients with NCI standard risk acute lymphoblastic leukemia (ALL) who relapsed after being randomized to receive either oral or intravenous 6‐mercaptopurine (6MP) in the Children's Cancer Group study CCG 1922.

Patients and Methods

CCG 1922 accrued patients from March 1993 to August 1995. A total of 1,060 patients were randomly assigned to four treatment groups: oral 6MP plus prednisone (OP), intravenous 6MP plus prednisone (IP), oral 6MP plus dexamethasone (OD), and intravenous 6MP plus dexamethasone (ID). During the 2nd through 4th month of therapy groups OP and OD were treated with 75 mg/m2/day of oral 6MP for 70 days and groups IP and ID with 1,000 mg/m2/week of intravenous 6MP over 10 hr for 11 doses. All patients received a single delayed intensification and all received oral 6MP in maintenance.

Results

Patients randomized to oral 6MP had significantly better 5‐year overall survival (96 ± 1% vs. 92 ± 1%; P = 0.008). There was, however, no statistically significant difference in the event‐free survival (EFS). Of the 179 patients who relapsed, 84 had a second or later event and 68 have died. Forty of the 84 second events were a death. Survival after relapse was significantly greater for patients randomized to oral 6MP during consolidation than those receiving intravenous 6MP (P = 0.002, log rank test) with 4‐year survival post‐relapse of 67 ± 6% vs. 48 ± 6%. The steroid randomization had no influence on outcome. Post‐relapse therapy details are not available and if different between groups may have influenced the outcome.

Conclusion

Treatment with intravenous 6MP during a brief period of total therapy had a significant negative impact on the prognosis in childhood ALL even though oral 6MP was used during maintenance. Pediatr Blood Cancer 2005; 45:5–9. © 2004 Wiley‐Liss, Inc.
Polyurethanes from 4,4′‐diphenylmethane diisocyanate and poly(ethylene glycol)s. II. Crystallographic data, heats of melting and crystallization, thermal stability, crystallinity and density
Authors: Vatalis Argyris S , Stergiou Anagnostis C , Kehayoglou Aristides H , Delides Costas G
Published: October 2004

Wide‐angle X‐ray scattering analysis, heats of melting, crystallization and re‐melting, thermogravimetric analysis and density measurements have been used to study the crystallographic data and degree of crystallinity of linear polyurethanes (PUs) prepared by the polymerization of 4,4′‐diphenylmethane diisocyanate (MDI) with poly(ethylene glycol)s (PEGs) of various number‐average molecular weights (Mns) (106, 200, 400, 1000, 2000 and 4000 g mol−1) in equivalent molar ratios. The crystallinities of polyurethanes PU1000 to PU4000 are shown to be due to the polyoxyethylene segments of the PEGs, while PU400 and PU200 appeared to be amorphous. However, PU106, similarly prepared from diethylene glycol (PEG106), is highly crystalline with a different crystal structure. Thermogravimetric analysis of PU106, PU400 and PU1000 exhibited high thermal stabilities up to 260 °C for these materials under the conditions of measurement (10 °C min−1). The heat of melting for the 100 % crystalline structure of PU106 has been indirectly obtained. Copyright © 2004 Society of Chemical Industry
Direct pyrolysis mass spectrometry analysis of fresh and aged $\hbox{PF}_{6}^{-}$‐doped polythiophenes
Authors: Gozet Tuba , Hacaloglu Jale
Published: October 2004

In this study, pyrolysis mass spectrometry has been applied for the investigation of thermal characteristics of $\hbox{PF}_{6}^{-}$‐doped polythiophene (PTh) films. Thermal degradation of PTh showed behaviour identical with $\hbox{BF}_{4}^{-}$‐doped polythiophene (BF4‐PTh), indicating that the effects of the dopants in question on the thermal characteristics of the PTh are not significant. Besides the oligomer peaks (up to hexamer), peaks indicating decomposition of the thiophene ring have also been detected as in the case of BF4‐PTh. However, the data also indicated that the oxidation of the $\hbox{PF}_{6}^{-}$ dopant was much more effective, yielding mainly POF3, H3PO4 compounds even for the freshly prepared samples. Upon ageing, the yield of these products increased and exposure to air for more than 50 days also caused degradation of the PTh chains. Furthermore, substitution of the thiophene (Th) ring by fluorine has been recorded and was associated with reactions of Th with the reactive oxidation products of the dopant. Analyses of the de‐doped samples showed that although de‐doping was effective to a certain extent, inward diffusion of the counter ion (C4H9)4N+ has also occurred. This diffusion was more efficient than that was observed for BF4‐PTh samples. Copyright © 2004 Society of Chemical Industry
Effect of clay on the properties of poly(styrene‐co‐acrylonitrile)–clay nanocomposites
Authors: Wang Hong‐Wen , Chang Kung‐Chin , Chu Hsuan‐Chih
Published: October 2004

Clay‐dispersed poly(styrene‐co‐acrylonitrile) nanocomposites (PSAN) were synthesized by a free radical polymerization process. The montmorillonite (MMT) was modified by a cationic surfactant hexadecyltrimethylammonium chloride. The structures of PSAN were determined by wide‐angle X‐ray diffraction and FTIR spectroscopy. The dispersion of silicate layers in the polymer matrix was also revealed by transmission electron microscopy (TEM). It was confirmed that the clay was intercalated and exfoliated in the PSAN matrix. The increased thermal stability of PSAN with the addition of clay was observed by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The dielectric properties of PSAN were measured in the frequency range 100 Hz to 1 MHz at 35–70°C. It was found that the dielectric constant from the dipole orientation had been suppressed due to the intercalation of clay. The dielectric loss is strongly related to the residual sodium content of clay, which increases as the sodium content increases by the addition of clay. Copyright © 2004 Society of Chemical Industry
Phase behavior of ternary blends containing dimethylpolycarbonate, tetramethylpolycarbonate and poly[styrene‐co‐(methyl methacrylate)] copolymers (or polystyrene)
Authors: Kim JW , Yoo JE , Kim CK
Published: October 2004

The miscibility and phase behavior of ternary blends containing dimethylpolycarbonate (DMPC), tetramethylpolycarbonate (TMPC) and poly[styrene‐co‐(methyl methacrylate)] copolymer (SMMA) have been explored. Ternary blends containing polystyrene (PS) instead of SMMA were also examined. Blends of DMPC with SMMA copolymers (or PS) did not form miscible blends regardless of methyl methacrylate (MMA) content in copolymers. However, DMPC blends with SMMA (or PS) blends become miscible by adding TMPC. The miscible region of ternary blends is compared with the previously determined miscibility region of binary blends having the same chemical components and compositions. The region where the ternary blends are miscible is much narrower than that of binary blends. Based on lattice fluid theory, the observed phase behavior of ternary blends was analyzed. Even though the term representing the Gibbs free energy change of mixing for certain ternary blends had a negative value, blends were immiscible. It was revealed that a negative value of the Gibbs free energy change of mixing was not a sufficient condition for miscible ternary blends because of the asymmetry in the binary interactions involved in ternary blends. Copyright © 2004 Society of Chemical Industry
Development of amorphous copolyesters based on 1,4‐cyclohexanedimethanol
Authors: Turner S. Richard
Published: October 2004

The modification of poly(ethylene terephthalate) with 1,4‐cyclohexanedimethanol and the modification of poly(1,4‐cyclohexylenedimethylene terephthalate) with ethylene glycol or isophthalic acid retard the crystallization of the copolyester backbone, and over a wide range of comonomer concentrations, very slowly crystallizing, essentially amorphous copolyesters are formed. These amorphous copolyesters possess attractive physical properties such as toughness, low color, and chemical resistance, and since their first commercial introduction in 1977, these copolyesters have become the basis of a large and growing plastics business for Eastman Chemical Co. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5847–5852, 2004
An intimate polycarbonate/poly(methyl methacrylate)/poly(vinyl acetate) ternary blend via coalescence from their common inclusion compound with γ‐cyclodextrin
Authors: Rusa Cristian C. , Uyar Tamer , Rusa Mariana , Hunt Marcus A. , Wang Xingwu , Tonelli Alan E.
Published: October 2004

In this study, we successfully report an intimate ternary blend system of polycarbonate (PC)/poly(methyl methacrylate) (PMMA)/poly(vinyl acetate) (PVAc) obtained by the simultaneous coalescence of the three guest polymers from their common γ‐cyclodextrin (γ‐CD) inclusion compound (IC). The thermal transitions and the homogeneity of the coalesced ternary blend were studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The observation of a single, common glass transition strongly suggests the presence of a homogeneous amorphous phase in the coalesced ternary polymer blend. This was further substantiated by solid‐state 13C NMR observation of the T1ρ(1H)s for each of the blend components. For comparison, ternary blends of PC/PMMA/PVAc were also prepared by traditional coprecipitation and solution casting methods. TGA data showed a thermal stability for the coalesced ternary blend that was improved over the coprecipitated blend, which was phase‐segregated. The presence of possible interactions between the three polymer components was investigated by infrared spectroscopy (FTIR). The analysis indicates that the ternary blend of these polymers achieved by coalescence from their common γ‐CD–IC results in a homogeneous polymer blend, possibly with improved properties, whereas coprecipitation and solution cast methods produced phase separated polymer blends. It was also found that control of the component polymer molar ratios plays a key role in the miscibility of their coalesced ternary blends. Coalescence of two or more normally immiscible polymers from their common CD–ICs appears to be a general method for obtaining well‐mixed, intimate blends. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4182–4194, 2004
Crystallization and structure formation of block copolymers containing a glassy amorphous component
Authors: Takeshita Hiroki , Ishii Naoto , Araki Chie , Miya Masamitsu , Takenaka Katsuhiko , Shiomi Tomoo
Published: October 2004

Formation of higher‐order structure in crystallization from microphase‐separated melts was studied for polystyrene–polyethylene (PS–PE) diblock copolymers and PS–PE–PS triblock copolymers with time‐resolved synchrotron small‐angle X‐ray scattering (SR–SAXS) techniques. The PE block was crystallized at temperatures when the PS block was in the glassy state. In both crystallization and melting processes, only the peak intensity in the SR–SAXS curve changed, however, the peak positions including higher‐order peaks did not change. This means that the microphase‐structure in the crystalline state was completely the same as that in the molten state. These behaviors were observed regardless of any melt microphase structure. Also, once a stable microphase structure was formed in the molten state, the structure was not changed even if crystallization and melting were repeated. Behavior of crystallization from such microphase‐separated melts was also studied. Apparent activation energies of crystallization were high for all block copolymers, compared with that for the PE homopolymer. In particular, the triblock copolymers showed higher apparent activation energies than the diblock copolymers. Both degrees of crystallinity and Avrami indices were greatly suppressed in crystallization from the cylindrical domain. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 4199–4206, 2004
Energy splitting of eg orbitals in Fe‐doped bilayer manganites
Authors: Ma Xiao , Kou Zhiqi , Di Naili , Cheng Zhaohua , Li Qing'An
Published: October 2004

57Fe Mössbauer spectra measurements of Fe‐doped La2–2xSr1+2xMn1.88Fe0.12O7 (x = 0.30, 0.40, and 0.55) compounds were employed to estimate the energy splitting of the Mn3+ ion eg orbital. A large splitting energy ES, about 1.0 eV, was found for each sample. This suggests that there is a strong electron localization effect in these Fe‐doped bilayer manganites. The transport behaviour can be explained on the basis of the effect of ES on the hopping possibility of Mn3+ eg electrons. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dielectric properties of compositionally graded Ba1–xSrxTiO3 thin films described by the transverse‐field Ising model
Authors: Gao Y. H. , Cao H. X. , Jiang Q.
Published: October 2004

This investigation reports on the phase transition and dielectric properties of compositionally graded Ba1–xSrxTiO3 (BST) thin films with x decreasing from 0.20 to 0.10 in successive slabs, based on the transverse‐field Ising model (TIM) within the framework of mean field theory. The random bond model of related parameters is applied to mimic doping. The effect on polarization and dielectric susceptibility arising from a gradient in composition is taken into account. The peaks of dielectric susceptibility versus temperature become comparatively flat by modulating appropriate thickness in each slab in compositionally graded BST thin films, which means that the thickness may weaken the effect of composition gradient. When increasing the number of slabs of thin films, the dielectric susceptibility shows good temperature stability in a wide temperature range, which is useful for reducing the temperature coefficient of dielectric susceptibility without depressors. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Compton profile study of polycrystalline ytterbium
Authors: Ahuja B. L. , Sharma M.
Published: October 2004

In this paper, we present the first experimental Compton profile of ytterbium. Measurement has been made, at an intermediate resolution (0.40 a.u.), using gamma‐ray Compton spectrometry employing a 20 Ci 137Cs source. In the absence of band‐structure calculations, the experimental profile is compared with a free‐electron model‐based profile and renormalised free‐atom (RFA) model. It is seen that the RFA results are comparatively in better agreement with the experiment. Using our Compton profile measurement, we have also derived the cohesive energy of ytterbium. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Continuous flow 2H/1H and 18O/16O analysis of water samples with dual inlet precision
Authors: Gehre M. , Geilmann H. , Richter J. , Werner R. A. , Brand W. A.
Published: October 2004

A method for isotope ratio analysis of water samples is described comprising an on‐line high‐temperature reduction technique in a helium carrier gas. Using a gas‐tight syringe, injection of 0.5 to 1 μL sample is made through a heated septum into a glassy carbon reactor at temperatures in excess of 1300°C. More than 150 injections can be made per day and both isotope ratios of interest, δ2H and δ18O, can be measured with the same setup. The technique has the capability to transfer high‐precision stable isotope ratio analysis of water samples from a specialized to a routine laboratory task compatible with other common techniques (automated injection for GC, LC, etc.). Experiments with an emphasis on the reactor design were made in two different laboratories using two different commercially available high‐temperature elemental analyser (EA) systems.

In the Jena TC/EA unit, sample‐to‐sample memory (single injection) has been reduced to ∼1% and high precision of about 0.1‰ for δ18O and < 1‰ for δ2H has been achieved by a redesign of the glassy carbon reactor and by redirecting the gas flow of the commercial TC/EA unit. With the modified reactor, the contact of water vapour with surfaces other than glassy carbon is avoided completely. The carrier gas is introduced at the bottom of the reactor thereby flushing the outer tube compartment of the tube‐in‐tube assembly before entering the active heart of the reactor.

With the Leipzig high‐temperature reactor (HTP) similar precision was obtained with a minor modification (electropolishing) of the injector metal sleeve. With this system, the temperature dependence of the reaction has been studied between 1100 and 1450°C. Complete yield and constant isotope ratio information has been observed only for temperatures above 1325°C. For temperatures above 1300°C the reactor produces an increasing amount of CO background from reaction of glass carbon with the ceramic tube. This limits the usable temperature to a maximum of 1450°C. Relevant gas permeation through the Al2O3 walls has not been detected up to 1600°C. Copyright © 2004 John Wiley & Sons, Ltd.
Development of a compound‐specific isotope analysis method for acetone via 2,4‐dinitrophenylhydrazine derivatization
Authors: Wen Sheng , Feng Yanli , Wang Xinming , Sheng Guoying , Fu Jiamo , Bi Xinhui
Published: October 2004

A novel method has been developed for compound‐specific isotope analysis for acetone via DNPH (2,4‐dinitrophenylhydrazine) derivatization together with combined gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Acetone reagents were used to assess δ13C fractionation during the DNPH derivatization process. Reduplicate δ13C analyses were designed to evaluate the reproducibility of the derivatization, with an average error (1 standard deviation) of 0.17 ± 0.05‰, and average analytical error of 0.28 ± 0.09‰. The derivatization process introduces no isotopic fractionation for acetone (the average difference between the predicted and analytical δ13C values was 0.09 ± 0.20‰, within the precision limits of the GC/C/IRMS measurements), which permits computation of the δ13C values for the original underivatized acetone through a mass balance equation. Together with further studies of the carbon isotopic effect during the atmospheric acetone‐sampling procedure, it will be possible to use DNPH derivatization for carbon isotope analysis of atmospheric acetone. Copyright © 2004 John Wiley & Sons, Ltd.
TPPP/p25: from unfolded protein to misfolding disease: prediction and experiments
Authors: Orosz F. , Kovács G.G. , Lehotzky A. , Oláh J. , Vincze O. , Ovádi J.
Published: October 2004

Abstract TPPP/p25, the first representative of a new protein family, identified as a brain‐specific unfolded protein induces aberrant microtubule assemblies in vitro, suppresses mitosis in Drosophila embryo and is accumulated in inclusion bodies of human pathological brain tissues. In this paper, we present prediction and additional experimental data that validate TPPP/p25 to be a new member of the “intrinsically unstructured” protein family. The comparison of these characteristics with that of α‐synuclein and tau, involved also in neurodegenerative diseases, suggested that although the primary sequences of these proteins are entirely different, there are similarities in their well‐defined unstructured segments interrupted by “stabilization centres”, phosphorylation and tubulin binding motives. SK‐N‐MC neuroblastoma cells were transfected with pEGFP‐TPPP/p25 construct and a stable clone denoted K4 was selected and used to establish the effect of this unstructured protein on the energy state/metabolism of the cells. Our data by analyzing the mitochondrial membrane polarization by fluorescence microscopy revealed that the high‐energy phosphate production in K4 clone is not damaged by the TPPP/p25 expression. Biochemical analysis with cell homogenates provided quantitative data that the ATP level increased 1.5‐fold and the activities of hexokinase, glucosephosphate isomerase, phosphofructokinase, triosephosphate isomerase and glyceraldehyde‐3‐phosphate dehydrogenase were 1.2 to 2.0‐fold higher in K4 as compared to the control. Our modelling using these data and rate equations of the individual enzymes suggests that the TPPP/p25 expression stimulates glucose metabolism. At pathological conditions TPPP/p25 is localized in inclusion bodies in multiple system atrophy, it tightly co‐localizes with α‐synuclein, partially with tubulin and not with vimentin. The previous and the present studies obtained with immunohistochemistry with pathological human brain tissues rendered it possible to classify among pathological inclusions on the basis of immunolabelling of TPPP/p25, and suggest this protein to be a potential linkage between Parkinson's and Alzheimer's diseases.
Opioid use in the elderly
Authors: Wilder‐Smith Oliver H.G.
Published: October 2004

Pain treatment in the elderly is an important challenge to Western societies due to increasing numbers of old persons, their higher incidence of pain, and their greater susceptibility to adverse effects of pain medication. We provide an overview of the factors liable to influence opioid action in the elderly population.

A major challenge for the physician prescribing opioids in the elderly is their greater risk of medication‐associated problems. Thus, older patients suffer increased vulnerability to adverse drug effects and interactions, higher rates of polypharmacy, and more comorbidity. These problems are compounded by a relative lack of definitive published information. There is clearly a need for more research in this area.

Aging affects opioid pharmacokinetics via altered body composition (distribution volumes) and organ function (liver = metabolism, kidney = excretion). Pharmacodynamics is affected via impaired neurotransmitter/peptide production and changed receptor affinities/populations. Older women may need less morphine analgesia postoperatively, while pain sensitivity tends to increase particularly in older men. However, the net effects of changes in opioid pharmacology with age on clinical opioid analgesia remain unclear, probably due to the significantly greater variability in body function with increasing age.

Practical recommendations for opioid prescription in the elderly include meticulous review of indication for opioid use, not only initially but also at regular intervals thereafter. A policy of careful titration should be followed, with conservative choice of dosage on starting. Dosing intervals may need to be lengthened subsequently. Finally, it should be remembered that old persons do not necessarily need less opioid than younger ones.
Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence
Authors: Lambert M. , Conus P. , Eide P. , Mass R. , Karow A. , Moritz S. , Golks D. , Naber D.
Published: October 2004

Objective

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence.

Methods

The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment.

Results

The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P<0.001), extrapyramidal (P<0.05) and psychic side effects (P<0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P<0.05), were more doubtful about their efficacy (P<0.01) and were less likely to encourage a relative to take such a medication in case of need (P<0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects.

Conclusions

All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.
Expression proteomics identifies biochemical adaptations and defense responses in transgenic plants with perturbed polyamine metabolism
Authors: Franceschetti Marina , Perry Barry , Thompson Benjamin , Hanfrey Colin , Michael Anthony J.
Published: October 2004

Soluble proteins from leaves of transgenic tobacco plants with perturbed polyamine metabolism, caused by S‐adenosylmethionine decarboxylase overexpression, were analysed by comparative proteomics. A group of proteins was found to be increasingly repressed, in parallel with the degree of polyamine perturbation, in each of the three independent transgenic lines. These were identified as isoforms of chloroplast ribonucleoproteins, known to be involved in chloroplast mRNA stability, processing and translation. Another group of eight proteins strongly induced in the most metabolically perturbed line was identified as multiple, uncharacterised isoforms of the defense protein PR‐1, a known marker for systemic acquired resistance.
The iron–sulfur cluster in the l‐serine dehydratase TdcG from Escherichia coli is required for enzyme activity
Authors: Burman Julia D. , Harris Roger L. , Hauton Katherine A. , Lawson David M. , Sawers R.Gary
Published: October 2004

The anaerobically inducible l‐serine dehydratase, TdcG, from Escherichia coli was characterized. Based on UV–visible spectroscopy, iron and labile sulfide analyses, the homodimeric enzyme is proposed to have two oxygen‐labile [4Fe–4S]2+ clusters. Anaerobically isolated dimeric TdcG had a k
cat of 544 s−1 and an apparent K
M for l‐serine of 4.8 mM. l‐threonine did not act as a substrate for the enzyme. Exposure of the active enzyme to air resulted in disappearance of the broad absorption band at 400–420 nm, indicating a loss of the [4Fe–4S]2+ cluster. A concomitant loss of dehydratase activity was demonstrated, indicating that integrity of the [4Fe–4S]2+ cluster is essential for enzyme activity.
Suppression of Sox6 in P19 cells leads to failure of neuronal differentiation by retinoic acid and induces retinoic acid‐dependent apoptosis
Authors: Hamada-Kanazawa Michiko , Ishikawa Kyoko , Ogawa Daisuke , Kanai Miyuki , Kawai Yuichi , Narahara Masanori , Miyake Masaharu
Published: October 2004

The Sox6 gene is a member of the Sox gene family, which encodes transcription factors, and previous studies have suggested that it plays an important role in the development of the central nervous system. Aggregation of embryonic carcinoma P19 cells with retinoic acid (RA) results in the development of neurons, glia, and fibroblast‐like cells. Sox6 mRNA increases rapidly in P19 cells during RA induction and then decreases during differentiation into neuronal cells. To investigate whether Sox6 expression is essential for neuronal differentiation, we established Sox6‐suppressed P19 (P19[anti‐Sox6]) cells by transfection of antisense‐Sox6 cDNA. Most of the P19[anti‐Sox6] cells showed no neurites and were not stained by the anti‐MAP 2 antibody, while the suppression of Sox6 expression nearly totally blocked neuronal differentiation in P19 cells. Further, Sox6 suppression caused RA‐dependent apoptosis by P19[anti‐Sox6] cells: RA‐treated P19[anti‐Sox6] cells showed chromatin condensation, DNA fragmentation, and an increase in caspase‐3‐like activity. Thus, Sox6 is considered essential for neuronal differentiation and may play an important role in the early stages of neuronal differentiation or apoptosis.
Action of solamargine on human lung cancer cells – enhancement of the susceptibility of cancer cells to TNFs
Authors: Liu Li-Feng , Liang Chia-Hua , Shiu Li-Yen , Lin Wei-Ling , Lin Chih-Chao , Kuo Kou-Wha
Published: October 2004

Solamargine (SM), isolated from Solanum incanum herb, displayed a superior cytotoxicity in four human lung cancer cell lines. The half‐inhibitory concentrations (IC50), of the cell viability assay for H441, H520, H661 and H69 cells were 3, 6.7, 7.2 and 5.8 μM, respectively. SM‐induced apoptosis of these cells by PS externalization in a dose‐dependent manner and increased sub‐G1 fraction were observed. Quenching of the expression of tumor necrosis factor receptors (TNFRs) during the progress of human lung carcinogenesis has been previously reported. SM may induce cell apoptosis via modulating the expression of TNFRs and their subsequent TRADD/FADD signal cascades. Subsequently, SM treatment increased the binding activities of TNF‐α and TNF‐β to the lung cancers, and the intrinsic TNFs‐resistant cancer cells became susceptible to TNF‐α and ‐β. In addition, SM caused release of cytochrome c, downregulation of anti‐apoptotic Bcl‐2 and Bcl‐xL, increase of caspase‐3 activity, and DNA fragmentation. Thus, SM could modulate the expressions of TNFRs and Bcl‐2, and might be a potential anticancer agent for TNFs and Bcl‐2 related resistance of human lung cancer cells.
Glycogen synthase kinase‐3β negatively regulates group IIA phospholipase A2 expression in human aortic smooth muscle and HepG2 hepatoma cells
Authors: Menschikowski Mario , Hagelgans Albert , Hempel Ute , Siegert Gabriele
Published: October 2004

The present study shows that the IFN‐γ‐mediated upregulation of secretory phospholipase A2 of group IIA (sPLA2‐IIA) in HASMC and HepG2 cells is synergistically increased after simultaneous inhibition of glycogen synthase kinase‐3β (GSK‐3β) by indirubin‐3′‐monoxime, 5‐iodo or AR‐A014418. The effect of GSK‐3β inhibition was dose‐ and time‐dependent and can be further augmented by its concomitant incubation with Clostridium difficile toxin B, an inhibitor of small Rho proteins, or H‐1152, an inhibitor of Rho‐associated kinase. Using AG‐490 and caffeic acid phenethyl ester (CAPE), it is further demonstrated that the effect of GSK‐3β inhibition on sPLA2‐IIA expression depends on Janus kinase‐2 and NF‐κB‐signaling.
Proteomics‐based identification of proteins interacting with Smad3: SREBP‐2 forms a complex with Smad3 and inhibits its transcriptional activity
Authors: Grimsby Susanne , Jaensson Hanna , Dubrovska Anna , Lomnytska Marta , Hellman Ulf , Souchelnytskyi Serhiy
Published: October 2004

Smad3 is an important component of transforming growth factor‐β (TGFβ) intracellular signalling. To identify novel interacting proteins of Smad3, we performed pull‐down assays with Smad3 constructs fused to glutathione‐S‐transferase. Proteins which formed complexes with these constructs were analyzed by two‐dimensional gel electrophoresis, and were identified by matrix‐assisted laser desorption‐ionization time‐of‐flight mass spectrometry. We identified 14 proteins interacting with the Smad3 construct lacking the N‐terminal Mad homology domain 1 (MH1), and 12 proteins interacting with the construct lacking the C‐terminal MH2 domain. Proteins involved in signalling processes, in metabolism regulation, novel proteins, and components of cytoskeleton form four groups of interacting proteins. Interactions of AGP7, sex‐determining region Y protein, actin β and sterol regulatory element binding protein‐2 (SREBP‐2) proteins with Smad3 constructs were confirmed by immunoblotting with specific antibodies. Interaction of Smad3 with SREBP‐2 was also confirmed by co‐immunoprecipitation of myc‐Smad3 and Flag‐SREBP‐2 upon expression in mammalian cells. We found that SREBP‐2 inhibited the transcriptional activity of Smad3 in luciferase reporter assays.
Second transmembrane domain of human uncoupling protein 2 is essential for its anion channel formation
Authors: Yamaguchi Hiroshi , Jelokhani-Niaraki Masoud , Kodama Hiroaki
Published: October 2004

Uncoupling proteins (UCP) are known to transport anions, such as Cl−, in addition to H+ transport. Although H+ transport by UCP is clearly involved in thermogenesis, the mechanism of its anion transport is not clearly understood. In this study, we examined the anion channel characteristics of the six individual helical transmembrane (TM) domains of the human UCP2. The second TM domain peptide (TM2) forms multi‐state channels by assemblies of conductive oligomers. Furthermore, the TM2 exhibited voltage‐dependent anion channels with properties comparable to those of UCP1 chloride channel. However, the other five TM peptides did not form UCP1‐like channels. Moreover, an analog of TM2 in which two Arg residues were substituted by Ala residues did not form stable channels, implying the significance of Arg residues for anion transport. These results suggest that the anion channel structure of UCP2 protein is oligomeric and the second TM domain is essential for the voltage‐dependence of this anion channel.
High-Throughput Screening at McMaster University: Automation in Academe
Authors: Cechetto Jonathan D. , Elowe Nadine H. , Blanchard Jan E. , Brown Eric D.
Published: October 2004

In December 2001, the McMaster HTS Lab officially opened its doors. Since that time, we have made significant strides in demonstrating that university-based, high-throughput screening (HTS) is a viable proposition for academic scientists seeking to discover novel small molecule probes of biological function. Although the lab has been running screens for just over two years, the process of designing, building and maintaining the lab has been on-going for more than four years. As high-throughput screening technology moves from the industrial sector to the academic and small biotech sectors, strategies for setting up a successful, highly flexible HTS lab on a limited budget becomes very important. In the current communication, we outline some of the considerations in setting up the lab and some of our experiences to date with screening and automation in academe.
Novel Convective Flow Based Approaches for High-Throughput PCR Thermocycling
Authors: Ugaz Victor M. , Krishnan Madhavi
Published: October 2004

A critical need exists for the development of next-generation genomic analysis instrumentation capable of offering significantly higher throughput at a lower cost than current technology. In this paper, we explore the potential of natural convection-based systems to address these issues by providing a thermocycling hardware platform capable of performing rapid polymerase chain reaction (PCR) amplification of DNA. These systems can be arrayed in a multi-well format that is simple to operate, is suitable for integration with high-throughput automated liquid handling systems, and can be easily and inexpensively mass-produced.
The Dispensing Well Plate: A Novel Device for Nanoliter Liquid Handling in Ultra High-Throughput Screening
Authors: Steger Reinhard , Bohl Benjamin , Zengerle Roland , Koltay Peter
Published: October 2004

This article reports on a novel dispensing system for the massive parallel delivery of liquid volumes in the range of 50 nL. Due to the similarity of the device to conventional micro-well plates used for the storage of liquids, the device has been termed “dispensing well plate” (DWP). In contrast to other known micro dispensers, the DWP can consist of up to 1,536 dispensing units in parallel, all of which hold different reagents. The dispensing units can be arranged very closely at the pitch of conventional micro-well plates (2.25 mm or 4.5 mm). Driven by pneumatic actuation, a fixed volume of different liquids can be dispensed simultaneously and contact-free into micro-well plates or onto flat substrates. Because of this, the liquid handling in many chemical, biochemical, and pharmaceutical applications—especially within high-throughput screening (HTS)—can be sped up by a factor of 10 to 100. In our article, the basic operation principle of the device is presented, and experimental evidence of its extraordinary performance is given: a reproducibility of 2% to 5% and a homogeneity within individual droplet arrays of 1% to 2% has been measured, as well as viscosity independent performance for liquids in the range from 1 to 5 mPas. The applicability of the DWP technology within HTS is demonstrated by performing a miniaturized kinase assay at 1 μL assay volume in a 1536-well plate format.
PipeJet: A Simple Disposable Dispenser for the Nano- and Microliter Range
Authors: Streule W. , Lindemann T. , Birkle G. , Zengerle R. , Koltay P.
Published: October 2004

This paper reports on a simple, disposable non-contact dispenser for the nano- and microliter range. In contrast to other known dispensers manufactured by silicon micromachining1-4 the new device simply consists of an elastic polymer tube with a circular cross section. Actuation is done by a piezostack driven piston, squeezing the tube at a defined position near the open end by a significant fraction of the cross section. In contrast to drop-on-demand devices based on an acoustic actuation principle,5 the squeezing of the tube leads to a significant mechanical displacement of the liquid. Our experiments tested a large number of media in the viscosity range from 1 to 27 mPas. Some of our experiments tested up to approximately 2,000 mPas. Frequency characteristics showed an independent dosage volume for water up to a frequency of 15 Hz for tubes with an inner diameter of approximately 200 um. Standard deviation within 1,000 shots resulted in an excellent CV (standard deviation/dosage volume) of less than 2% of the dosage volume. Using tubes with an inner diameter of approximately 1,000 um and a print frequency of 340 Hz, a flow rate of less than or equal to 143 μL/s could be reached. Beyond the possibility to dispense pure liquids, emulsion paints with particles that have a diameter of approximately 40 μm have also been printed successfully.
Salivary Epidermal Growth Factor Concentration in Adults with Reflux Laryngitis
Authors: Eckley Claudia A. , Michelsohn Nelson , Rizzo Luiz Vicente , Tadakoro Carlos Eduardo , Costa Henrique O.
Published: October 2004

OBJECTIVE

The mechanisms involved in the muco‐sal alterations of laryngopharyngeal reflux (LPR) have not been well established. Reports indicate a decrease in the salivary epidermal growth factor (EGF) of patients with reflux esophagitis, but there are no reports of its behavior in LPR. Our objective was to determine the salivary concentration of EGF in adults with LPR.

STUDY DESIGN AND SETTING

Salivary EGF concentration of 26 patients with LPR and 20 healthy controls was determined using a commercially available ELISA kit. Patients with LPR were graded according to endoscopic and laryngoscopic criteria.

RESULTS

Salivary EGF concentration was significantly lower in the LPR group when compared with controls (P = 0.002). No correlation between the severity of laryngeal findings or esophagitis and salivary EGF concentration could be determined.

CONCLUSIONS

The decreased salivary concentration of EGF in adults with LPR suggests that a deficiency in this polypeptide could be associated to the disease.
Incidence of Dehiscence of the Facial Nerve at Surgery for Middle Ear Cholesteatoma
Authors: Lin Jen‐Chih , Ho Kuen‐Yao , Kuo Wen‐Rei , Wang Ling‐Feng , Chai Chee‐Yin , Tsai Shih‐Meng
Published: October 2004

OBJECTIVE

To identify the incidence of dehiscence of the facial nerve in patients undergoing surgery for cholesteatoma and to describe its relevance with iatrogenic facial nerve injury.

STUDY DESIGN AND SETTING

This was a retrospective study including 117 tympanoplasties with or without mastoidectomy performed in 49 men and 66 women.

RESULTS

The presences of FND after exenteration of disease are 33.3% of total surgical procedures, 33% of the initial procedures, and 37.5% of the revision procedures. The locations of facial nerve dehiscence were 87.2% in only the tympanic segment, 7.7% in only the vertical segment, and 5.1% in both the tympanic and vertical segments.

CONCLUSIONS AND SIGNIFICANCE

The incidence of facial nerve dehiscence is high (33.3%) in our study. The surgeon should keep in mind that the location of facial nerve dehiscence with cholesteatoma is comparable with the most common area of iatrogenic facial nerve injury during otologic surgery.
How Do Cartilage and other Material Overlay over a Prosthesis Affect its Vibration Transmission Properties in Ossiculoplasty?
Authors: Morris David P. , Bance Manohar , Van Wijhe Rene G.
Published: October 2004

OBJECTIVE

The prosthesis/eardrum interface is often deliberately modified by cartilage overlay, or by soft tissue in‐growth. We examined the effects of vibration transmission to the footplate of inserting cartilage of varying sizes, and materials of varying rigidities.

STUDY DESIGN AND SETTING

Using fresh human cadaveric temporal bones, stapes vibrations were measured. A partial ossicular reconstruction prosthesis was covered with differing materials and cartilage sizes. Materials used included glass (rigid), cartilage (intermediate), and Merocel® (soft). Cartilage sizes varied in size relative to the prosthesis head.

RESULTS

Rigidity of material had little impact. Cartilage size had an impact, with smaller cartilage covers performing best.

CONCLUSION

Larger cartilage sizes performed worse. This could be a result of increased tension on the eardrum from larger cartilage size. There is little impact stiffness of interposed material stiffness.

SIGNIFICANCE

Cartilage of the size used clinically has little impact on vibration transmission to the footplate. A wide range of materials could clinically be interposed over the prosthesis.
Cyclin D1, p53, MIB1, Intratumoral Microvessel Density, and Human Papillomavirus in Advanced Laryngeal Carcinoma: Association with Nodal Metastasis
Authors: Kumar Rekha V. , Shenoy Ashok M. , Daniel Richard , Shah Keerti V.
Published: October 2004

OBJECTIVE

We sought to study various parameters in laryngeal squamous cell carcinoma (LSCC) that might predict nodal metastasis.

STUDY DESIGN AND SETTING

Sixty‐four LSCCs were examined with respect to their histopathology and, using immunohistochemistry, their proliferative capacity (MIB1), p53 and cyclin D1 status, and intratumoral microvessel density. The presence of human papillomavirus was ascertained by the polymerase chain reaction.

RESULTS

Histopathologically, most tumors had an infiltrating/mixed growth pattern and a diminished inflammatory reaction at the growing margin. In addition, 56% of the tumors were positive for MIB1, with 64% showing p53 overexpression; 70% were positive for cyclin D1; and 59% showed increased tumor microvessel density. Of 42 cases analyzed, 9.5% were positive for human papillomavirus 16.

CONCLUSIONS

Of the parameters studied, a diminished lymphocytic inflammatory response at the periphery (P < 0.05) and cyclin D1 overexpression (P < 0.001) correlated significantly with cervical nodal metastasis at presentation.

SIGNIFICANCE

Cyclin D1 overexpression, easily assessed on biopsy samples, may thus help in optimizing therapy at the outset.
A Simplified Technique for Airway Correction at the Nasal Valve Area
Authors: Friedman Michael , Ibrahim Hani , Lee George , Joseph Ninos J.
Published: October 2004

OBJECTIVE

To describe a simplified system to correct an obstructed nasal airway utilizing the Mitek bone anchor suspension technique (BAST).

STUDY DESIGN

This is a retrospective/prospective study of patients with nasal airway obstruction treated with the BAST. The retrospective study is based on 188 patients who underwent the BAST over the past 5 years and were analyzed to assess complications and subjective results. The prospective group consisted of 52 patients with unilateral or bilateral valve obstruction who were assessed with preoperative and postoperative rhinomanometry and quality of life (QOL) questionnaires.

METHODS

The surgical technique is based on introducing a bone anchor into the orbital rim through a 4‐mm stab incision. The bone anchor system comes with attached sutures that are easily passed to the valve area and secured in position to support and open the valve area. Preoperative and postoperative QOL surveys and rhinometric studies were compared in 52 patients to assess the subjective and objective outcomes of the procedure.

RESULTS

Based on subjective data, over 90% of the patients had significant improvement in their nasal airway. Objectively, cross‐sectional areas at the nasal valve were found to have significantly improved postoperatively (P < 0.046). Complications were rare and limited to localized infection, reaction to sutures, and loss of support.

CONCLUSION

Correction of nasal valve obstruction with this technique provides a simplified alternative in selected patients to improve airflow and decrease nasal resistance. The BAST allows for a simple, highly effective correction of an obstructed airway with minimal complications.