bluuebunny/crossref_metadata_2025 huggingface dataset:
Immobilization of oriented protein molecules on poly(ethylene glycol)‐coated Si(111)
Authors: Cha Taewoon , Guo Athena , Jun Yongseok , Pei Duanquing , Zhu Xiao‐Yang
Published: June 2004

A high‐density poly(ethylene glycol) (PEG)‐coated Si(111) surface is used for the immobilization of polyhistidine‐tagged protein molecules. This process features a number of properties that are highly desirable for protein microarray technology: (i) minimal nonspecific protein adsorption; (ii) highly uniform surface functionality; (iii) controlled protein orientation; and (iv) highly specific immobilization reaction without the need of protein purification. The high‐density PEG‐coated silicon surface is obtained from the reaction of a multi‐arm PEG (mPEG) molecule with a chlorine terminated Si(111) surface to give a mPEG film with thickness of 5.2 nm. Four out of the eight arms on each immobilized mPEG molecule are accessible for linking to the chelating iminodiacetic acid (IDA) groups for the binding of Cu2+ions. The resulting Cu2+‐IDA‐mPEG‐Si(111) surface is shown to specifically bind 6x histidine‐tagged protein molecules, including green fluorescent protein (GFP) and sulfotransferase (ST), but otherwise retains its inertness towards nonspecific protein adsorption. We demonstrate a particular advantage of this strategy: the possibility of protein immobilization without the need of prepurification. Surface concentrations of relevant chemical species are quantitatively characterized at each reaction step by X‐ray photoelectron spectroscopy (XPS). This kind of quantitative analysis is essential in tuning surface concentration and chemical environment for optimal sensitivity in probe‐target interaction.
Protein extraction from mature rice leaves for two‐dimensional gel electrophoresis and its application in proteome analysis
Authors: Islam Nazrul , Lonsdale M. , Upadhyaya N. M. , Higgins T. J. , Hirano H. , Akhurst R.
Published: June 2004

Sample preparation is crucial for extraction and higher resolution of proteins by two‐dimensional gel electrophoresis (2‐DE). In this study, we present an efficient protocol to extract proteins from mature rice leaves by minimizing the presence of nonprotein contaminants and by maximizing contact between the sample and extraction buffer. A combination of chemical and physical processes remarkably improved protein extraction for 2‐DE. The efficiency of this protocol was demonstrated by comparison of the rice proteome at two developmental stages.
CP‐MLR/PLS Directed Structure‐Activity Modeling of the HIV‐1 RT Inhibitory Activity of 2,3‐Diaryl‐1,3‐thiazolidin‐4‐ones
Authors: Prabhakar Yenamandra S. , Solomon V. Raja , Rawal Ravindra K. , Gupta Manish K. , Katti S. B.
Published: June 2004

A detailed structure‐activity relationship study of the HIV‐1 Reverse Transcriptase (RT) inhibitory activity of two series of compounds, 2‐(2,6‐dihalo phenyl)‐3‐(substituted pyridin‐2‐yl)‐thiazolidin‐4‐ones and 2‐(2,6‐Dihalophenyl)‐3‐(substituted phenyl)‐thiazolidin‐4‐ones, belonging to 2,3‐diaryl‐thiazolidin‐4‐ones in terms of physicochemical and structural descriptors have been carried out using combinatorial protocol interfaced multiple linear regression (CP‐MLR) and partial least squares (PLS) analysis. The models developed in the study indicate a preference for hydrophobic compounds for better inhibitory activity. Also, a positive regression coefficient of I2,3, an indicator descriptor meant for the joint disposition of substituents of 2,3‐diaryl moieties of thiazolidinones to address their ability in taking a butterfly like conformation, is in agreement with all earlier observations that compounds having the ability to take butterfly like conformation will be showing better inhibitory activity. The identified models suggest that the meta‐positions of 3‐aryl moiety has the ability to accommodate hydrophobic/ steric groups. The replacement of C2″ of 3‐phenyl by nitrogen resulted in 3‐pyridyl variants of these analogues. Even though from geometry point of view, the phenyls and pyridyls span almost the same structural space and steric features, presence of nitrogen in pyridyls gave them a blend of polarity, electronic features and a different hydrophobicity profile when compared to corresponding phenyl analogue. Furthermore the PLS models, developed from those descriptors took part in CP‐MLR models, indicate that most of the descriptors have almost equal influence in accounting for the variation in the activity of these compounds. This suggests that the factors responsible for the variation in the activity have been uniformly distributed across the varying centers of the molecule. The study suggests that thiazolidinones with 3‐(pyridin‐2‐yl) moiety provide scope for further substituent variation to modulate the HIV‐1 RT inhibitory activity.
Status of HTS Data Mining Approaches
Authors: Böcker Alexander , Schneider Gisbert , Teckentrup Andreas
Published: June 2004

High‐throughput screening of large compound collections results in large sets of data. This review gives an overview of the most frequently employed computational techniques for the analysis of such data and the establishment of first QSAR models. Various methods for descriptor selection, classification and data mining are discussed. Recent trends include the application of kernel‐based machine learning methods for the design of focused libraries and compilation of target‐family biased compound collections.
A Re‐evaluation of the Use of Rink, BAL, and PAL Resins and Linkers
Authors: Yraola Francesc , Ventura Rubén , Vendrell Marc , Colombo Aina , Fernàndez Joan‐Carles , de la Figuera Natalia , Fernández‐Forner Dolors , Royo Miriam , Forns Pilar , Albericio Fernando
Published: June 2004

See original QSAR Comb. Sci. 2004, 23, 145–152
Quantitative analysis of D‐24851, a novel anticancer agent, in human plasma and urine by liquid chromatography coupled with tandem mass spectrometry
Authors: Stokvis Ellen , Nan‐Offeringa Lianda G. A. H. , Ouwehand Mariët , Tibben Matthijs M. , Rosing Hilde , Schnaars Yvonne , Grigat Martina , Romeis Peter , Schellens Jan H. M. , Beijnen Jos H.
Published: June 2004

The development of a liquid chromatography/tandem mass spectrometric assay for the quantitative analysis of the novel tubulin inhibitor D‐24851 in human plasma and urine is described. D‐24851 and the deuterated internal standard were extracted from 250 μL of plasma or urine using hexane/ether (1:1, v/v). Subsequently, 10‐μL aliquots of reconstituted extracts were injected onto an Inertsil ODS analytical column (50 × 2.0 mm i.d., 5 μm particle size). An eluent consisting of methanol/5 mM ammonium acetate, 0.004% formic acid in water (80:20, v/v) was pumped at a flow rate of 0.2 mL/min. An API 365 triple quadrupole mass spectrometer was used in the multiple reaction monitoring mode for sensitive detection. For human plasma a dynamic range of 1–1000 ng/mL was validated, and for human urine a range of 0.25–50 ng/mL. Validation was performed according to the most recent FDA guidelines and all results were within requirements. The assay has been successfully applied to support a phase I clinical trial with orally administered D‐24851. Copyright © 2004 John Wiley & Sons, Ltd.
Atmospheric molded poly(methylmethacrylate) microchip emitters for sheathless electrospray
Authors: Muck Alexander , Svatoš Aleš
Published: June 2004

Disposable poly(methylmethacrylate) (PMMA) sheathless electrospray microchip emitters were prepared for the first time using the atmospheric molding fabrication protocol. A sheathless electrospray from uncoated channel outlets, machined to cone‐shaped three‐dimensional tips, is demonstrated utilizing a simple cross design with an on‐chip liquid junction to obviate the need for external unions to voltage electrodes, thus reducing the dead volume effects as well as the complexity of fabrication. The fast replication of microchip emitters was performed by molding prepolymeric methylmethacrylate solutions into silicon‐master/aluminum‐spacer/glass‐plate molds followed by UV‐initiated free radical polymerization. The performance of the new microchip emitters was demonstrated for mass spectral measurements of methionine enkephalin, adrenocorticotropic hormone and insulin peptide/protein mixtures. The samples were infused through capillary connections using hydrodynamic pumping. The polymeric emitters prepared by this flexible fabrication route offer an easy way of operation and high stability, without a need for attachment of external voltage unions or metallizing the emitter tips. The new approach should provide a useful low‐cost tool for widespread coupling of mass spectrometry to chip systems. Copyright © 2004 John Wiley & Sons, Ltd.
Quantification of cyclophosphamide and its metabolites in urine using liquid chromatography/tandem mass spectrometry
Authors: Kasel Dirk , Jetter Alexander , Harlfinger Steffi , Gebhardt Wilhelm , Fuhr Uwe
Published: June 2004

A reliable and easy to use liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantification of urinary concentrations of cyclophosphamide (CP) and its main metabolites excreted in urine, i.e. N‐dechloroethylcyclophosphamide (DCL‐CP), 4‐ketocyclophosphamide (4KetoCP), and carboxyphosphamide (CarboxyCP). Sample preparation consisted of dilution of urine with an aqueous solution of the internal standard D4‐CP and methanol, and centrifugation. LC/MS/MS detection was performed using a triple‐quadrupole mass spectrometer working in selected reaction monitoring mode. All analytes were quantified in a single run within 11.5 min. The limits of detection were 5 ng/mL for CP and 4KetoCP, 1 ng/mL for DCL‐CP, and 30 ng/mL for CarboxyCP. Quantification ranges were adjusted to the expected concentrations in 24‐h urine collections of patients treated with a polychemotherapy regimen (3–175 μg/mL for CP, 0.5–27 μg/mL for 4KetoCP and 0.17–9 μg/mL for CarboxyCP and DCL‐CP, respectively). The method was validated according to international guidelines of the ICH and the FDA. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of desorption/ionization on silicon (DIOS) time‐of‐flight and liquid chromatography/tandem mass spectrometry for assaying enzyme‐inhibition reactions
Authors: Wall Daniel B. , Finch Jeffrey W. , Cohen Steven A.
Published: June 2004

Desorption/ionization on silicon with time‐of‐flight mass spectrometry (DIOS‐TOFMS) was employed for rapid quantification of small molecules and the measurement of critical constants used in enzyme kinetics studies. The approach was used to determine the Michaelis constant (Km) for acetylcholine esterase and the 50% inhibition constant (IC50) for tacrine. The Km was determined from a Lineweaver‐Burk plot to be 98 μM. The IC50 was determined by assaying acetylcholine esterase activity with a range of tacrine concentrations, and measuring the amount of choline produced at a fixed time point by either DIOS‐TOFMS or by liquid chromatography tandem mass spectrometry (LC/MS/MS). DIOS‐TOFMS indicated an IC50 of 32.0 nM while LC/MS/MS gave a value of 31.8 nM. The excellent correlation with the reported IC50 values, ranging from 30.0 to 50.0 nM, and equivalence with the LC/MS/MS results, confirms that the DIOS‐TOFMS method can be used for rapid and specific quantification of enzyme‐inhibition assays. Copyright © 2004 John Wiley & Sons, Ltd.
Generation of C6H by laser vaporization of magnesium with o‐C6H4F2 in argon carrier gas
Authors: Liu Haichuan , Yang Shihe , Balteanu Iulia , Balaj O. Petru , Fox‐Beyer Brigitte S. , Beyer Martin K. , Bondybey Vladimir E.
Published: June 2004

A route to efficient generation of C6H, potentially the benzyne radical cation, is presented. Laser vaporization of Mg+. and supersonic expansion in helium doped with o‐, m‐, or p‐C6H4F2 yields, among other ions, o‐, m‐, p‐C6H4F2Mg+. complexes, but no C6H. Collision‐induced dissociation experiments show that the o‐C6H4F2Mg+. complex can be converted into C6H in a mildly energetic collision, with a center‐of‐mass energy around 1–2 eV. These conditions can also be reached in the ion source when argon is used as a carrier gas. In this way, mass spectra containing the desired m/z 76 peak, i.e. C6H, are obtained. Copyright © 2004 John Wiley & Sons, Ltd.
Time‐of‐flight atom‐probe field ion microscope studies of surface‐related phenomena
Authors: Tsong Tien T.
Published: June 2004

The time‐of‐flight atom‐probe field ion microscope is both a single‐atom detection sensitivity mass‐to‐charge ratio analyser and an ion energy analyser, provided that the instrument resolution is good enough. Its major applications are in material analysis. However, it has been used also for studying surface‐related phenomena such as surface segregation of alloys, mechanisms of ion formation in field desorption, novel ion and cluster ion formation in laser‐stimulated field ion emission, field dissociation of compound ions and its novel isotope effects and analysis of the site‐specific binding energy of surface atoms, etc. Some of these studies are briefly reviewed here. Copyright © 2004 John Wiley & Sons, Ltd.
Atom probe field ion microscopy investigations on the intermetallic Ni49.5Al49.5Re1 alloy
Authors: Deges J. , Fischer R. , Frommeyer G. , Schneider A.
Published: June 2004

The hypoeutectic intermetallic alloy Ni49.5Al49.5Re1 exhibits promising mechanical properties for high‐temperature applications up to 1250°C, therefore atom probe field ion microscopy (APFIM) investigations were performed in the as‐cast state and after various heat treatments (at 1000°C for different times up to 1000 h and at 1300°C for 1000 h). The imaging properties and the effect of various heat treatments on the solubility and precipitation of Re within the NiAl matrix have been investigated. The field ion micrographs of Ni49.5Al49.5Re1 alloy reveal characteristic imaging features of the NiAl–Re system. Single Re atoms dissolved in the NiAl solid solution matrix were observed as bright imaging species. This is due to preferential retention of Re atoms, as well as the high ionization rate caused by adsorption of Ne image gas atoms by Re atoms. The adsorption of Ne image gas atoms is proved by the occurrence of ReNe3+ and ReNe2+ ions detected in the atom probe mass spectra. Rhenium precipitates of different shapes and several tens of nanometres in size were imaged, as well as small clusters of a few atoms. Conglomerations of a few Re atoms have been detected and the site occupancy of Re atoms in the NiAl superlattice was determined by means of APFIM measurements. Copyright © 2004 John Wiley & Sons, Ltd.
Conventional and tomographic atom probe investigations of secondary‐hardening carbides
Authors: Leitner H. , Stiller K. , Andren H‐O. , Danoix F.
Published: June 2004

Secondary‐hardening carbides in high‐speed steels are very important microstructural constituents responsible for the excellent properties of these steels in cutting applications, therefore detailed knowledge about their precipitation reactions and coarsening behaviour is of great interest.

The investigations were carried out on steel grades HS2‐10‐1‐8 and HS6‐5‐2 with nominal chemical compositions (in wt.%) of 1.1C–3.9Cr–1.4W–9.2Mo–1.2V–8Co (HS2‐10‐1‐8) and 0.9C–4.1Cr–6.4W–5Mo–1.8V (HS6‐5‐2). The austenitizing temperatures for HS2‐10‐1‐8 and HS6‐5‐2 were 1190°C and 1210°C, respectively. After quenching, the samples were heated non‐isothermally from room temperature to different final temperatures at 15 K min−1. The resulting precipitates were analysed to determine composition, size and morphology using both a conventional one‐dimensional atom probe and a three‐dimensional tomographic atom probe. The results obtained by both techniques from samples at different heat treatment conditions are compared. Owing to the different evaporation field of the precipitates, an overlap of the ion trajectories from matrix and precipitates can be observed. Methods to correct the analytical results are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Microstructural characterization of Inconel 706 alloy
Authors: Wanderka N. , Naundorf V. , Banhart J. , Mukherji D. , Genovesse D. Del. , Rösler J.
Published: June 2004

Inconel 706 is a wrought Ni–Fe‐based superalloy used for high‐temperature services, e.g. for gas turbine discs. It is age‐hardened by precipitation of coherent γ′ and/or γ″ in the austenitic matrix γ, where γ″ is the main hardening phase. However, the microstructure of Inconel 706 is strongly dependent on the age‐hardening treatment. Direct ageing produces individual γ′ and γ″ precipitates and γ′–γ″ coprecipitates, whereas a three‐step heat treatment with stabilization at 820°C, produces η precipitates mainly at the grain boundaries. Characterization of the composition of precipitate and matrix phases was carried out by three‐dimensional atom probe tomography. The microstructure was investigated by high‐resolution transmission electron microscopy.

After direct ageing the precipitates are generally smaller than after the stabilizing heat treatment. Their average size is ∼10 nm. After the stabilizing heat treatment the γ′–γ″ coprecipitates have sizes between 15 and 20 nm. In addition, much bigger individual γ″ precipitates of size >50 nm were also observed. They are semi‐coherent with the matrix and are oriented parallel to the <001> lattice direction of the γ matrix. Although the γ′ phase is enriched in Ni, Al, Ti and Nb, the γ″ phase contains little Al (<1 at.%) and is enriched in Ti (∼12 at.%) and Nb (∼15 at.%). The results are discussed with respect to the influence that the particular heat treatment has on the morphology and composition of the precipitates and the γ matrix. Copyright © 2004 John Wiley & Sons, Ltd.
Improvement of multilayer analyses with a three‐dimensional atom probe
Authors: Vurpillot Francois , Larson David , Cerezo Alfred
Published: June 2004

Owing to their giant magnetoresistance properties, multilayer thin‐film materials are widely used in information storage technology. However, because this magnetic behaviour is highly sensitive to interface roughness and diffusivity on a subnanometre scale, the structural characterization of these materials with high spatial resolution is of fundamental importance. The three‐dimensional atom probe is one of the instruments that theoretically can provide chemical analyses in three dimensions with the highest spatial resolution. However, because three‐dimensional reconstructions can be subject to strong artefacts due to trajectory aberrations, it is important to combine experimental analyses with theoretical investigations of the evaporation and reconstruction process in order to obtain the most accurate data on interface structure.

In this paper, a simulation model is used in order to compute the ion trajectories close to a field emitter. The model is modified to take into account the unique morphology of the multilayer thin‐film structure. This model gives a sound interpretation of the three‐dimensional atom probe images of multilayer thin films. The three‐dimensional atom probe reconstructions of NiFe/FeCo/Cu multilayer structures are found to be degraded by strong artefacts owing to the difference in evaporation field between the FeCo layer and the Cu layer. By using simulation, these aberration effects are interpreted as errors in the calculation of thez‐dimension within three‐dimensional images. A correction procedure has been developed to improve the reconstruction of multilayer thin films in the three‐dimensional atom probe. Copyright © 2004 John Wiley & Sons, Ltd.
Electronic properties of low‐field‐emitting ultrananocrystalline diamond films
Authors: Frolov V. D. , Pimenov S. M. , Konov V. I. , Polyakov V. I. , Rukovishnikov A. I. , Rossukanyi N. M. , Carlisle J. A. , Gruen D. M.
Published: June 2004

This work reports on electronic properties of nitrogen‐doped, n‐type ultrananocrystalline diamond (UNCD) films grown on p‐type Si substrates from CH4–Ar–N2 gas mixtures using a microwave plasma chemical vapor deposition technique. Films ∼1 µm thick were grown with 5%N2 and 10%N2 in the plasmas. Charge‐based deep‐level transient spectroscopy showed a shallow level of point defects with an activation energy of ∼0.05 eV. The density of these shallow defects was increased with increasing nitrogen content in the plasma. Complex scanning probe microscopy methods were applied to study the film microstructure. Generally it was found that the nitrogen‐doped UNCD films showed a periodic ‘cell‐like’ structure in which the cell with a lateral size of several nanometers was less conducting than the boundary between the cells. The boundary width was found to be 0.5–1 nm. The observed details of the periodic structure can be associated with diamond nanocrystallites (grains) and grain boundaries, respectively. In addition, 2–5 nm high‐conducting inclusions clustered on the film surface were observed. It was noted that the emission field was inversely proportional to the film electroconductivity, and the lowest emission field of F ∼ 10 V µm−1 was detected near the high‐conducting inclusions. Moreover, the surface electron potential at the emission sites was lowered. The reasons why the shallow donor center is predominantly introduced by nitrogen incorporated into the grain boundaries and the possible mechanisms of low‐field electron emission from the nitrogen‐doped UNCD films have been discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Some features of aligned CVD carbon nanotubes for electron field emission
Authors: Bartsch K. , Graff A. , Schöps‐Dörfel V. , Leonhardt A. , Knapp W.
Published: June 2004

Bundles of vertically grown multi‐walled carbon nanotubes were deposited on thin cobalt catalyst layers and heterogeneous WC–Co hard metal surfaces. Two different structures were detected for these layers (tubular and bamboo‐like structures), which are related to the size of the catalyst particles formed and the temperature during the process. Furthermore, free‐standing carbon nanotubes were obtained on WC–Co hard metal surfaces with a reduced Co content. Field emission measurements yielded better results for the bundle‐like carbon nanotube layers. After repeated tests, degradation of the layers was observed. Possible reasons for these effects are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Field emission study of titanium silicide array
Authors: Choi Seong S. , Jung M. Y. , Joo M. S. , Kim D. W. , Park M. J. , Kim S. B. , Jeon H. T.
Published: June 2004

A silicon field emitter array (FEA) was fabricated on n‐type, low‐resistance (5Ω·cm) Si(100) wafer by anisotropic etching (dipping in 40 wt.% KOH solutions). To increase the thermochemical durability of the tip, the long‐term stability and the current density, Ti (30 nm) film was deposited with evaporation and the silicide was formed by annealing at 650°C. The C54–TiSi2 phase of the sample was observed by x‐ray diffraction analysis. The emission characteristics of the titanium silicide FEA were compared with those of an Si FEA under high vacuum conditions of ∼10−7 Torr. The turn‐on voltage of the titanium silicide FEA is ∼1500 V whereas that of the Si FEA is found to be 1950 V. In addition, the emission stability of the titanium silicide FEA proved to be much better than that of the Si FEA. Copyright © 2004 John Wiley & Sons, Ltd.
Phase separation in Cu47Ti33Zr11Ni8Si1
Authors: Miller M. K. , Glade S. C. , Johnson W. L.
Published: June 2004

An atom probe tomography characterization of the microstructure of as‐cast Cu47Ti33Zr11Ni8Si1 that was either injection cast into a copper mold (cooling rate 4 × 103 K s−1) or splat quenched (cooling rate 2 × 106 K s−1) has been performed. In both materials, the bulk metallic glass had phase‐separated into two interconnected amorphous phases. The copper‐enriched regions were depleted in titanium and the copper‐depleted regions were enriched in titanium. There was no difference in the degree of phase separation associated with the cooling rate. Published in 2004 by John Wiley & Sons, Ltd.
Proposed XML‐based three‐dimensional atom probe data standard
Authors: Miller M. K.
Published: June 2004

A platform‐independent extensible markup language (XML) standard to describe all types of three‐dimensional and classical atom probe data is proposed. An associated XML‐based peak assignment or range file format is also described. XML‐based databases of elemental parameters and predefined colors are described. These standard formats should facilitate the exchange and analysis of three‐dimensional atom probe data. Copyright © 2004 John Wiley & Sons, Ltd.
Field emission from thick carbon nanotube film on Si substrate
Authors: Wang Qikun , Zhu Chang‐Chun , Shi Yongsheng
Published: June 2004

A carbon nanotube (CNT) cathode for field emission display was fabricated by coating on Si substrate. The CNTs were obtained from catalytic decomposition of hydrocarbon. A paste mixture for coating was prepared by mixing CNTs, glass frits and organic binder. The paste mixture of well‐dispersed CNTs was coated on Si substrate and subsequently heat treated to fix the CNTs on the substrate and remove the organic binder. With this method we obtained a uniform, flat, thick, conductive CNT film that adhered tightly to the Si substrate. Measurements carried out using a diode structure reveal that the electron field emission of the CNT coating can be turned on with a field as low as 1.0–1.25 V µm−1, and an emission current density of 50 µA cm−2 at 5 V µm−1 can be attained. On increasing the proportion of glass frits, a gradual decrease in emission current is observed. When the sintering time is prolonged, the field emission of the thick CNT film is reduced. Copyright © 2004 John Wiley & Sons, Ltd.
Enhanced field emission of self‐organized laser‐produced Si and Ni micro‐tip arrays with incorporated carbon nanotubes
Authors: Karabutov A. V. , Simakin A. V. , Shafeev G. A.
Published: June 2004

Results are reported on low‐field electron emission from periodic arrays of micro‐tips produced by laser‐assisted evaporation of single‐crystal Si wafers in a vacuum and Ni wafers in liquid. To improve the emission from the micro‐tips, single‐wall carbon nanotubes were incorporated into surface layers of the tips during or after micro‐relief formation. The best samples showed emission at threshold fields as low as 0.3–1 V µm−1 for Si substrate and 1.5–2 V µm−1 for Ni substrate, as measured with the flat screen technique. The emission was stable upon cyclic variation of the electric field. Sufficient improvement of the emission surface uniformity (a number of emission sites per square unit) and lower threshold fields were achieved using carbon nanotube incorporation compared to ‘undoped’ Si and Ni micro‐tips. The experimental data explain the field emission from the tip arrays by a complex geometric field enhancement, including nanotubes and narrow conducting channels in the tip body. The arrays of micro‐tips are promising for a wide range of cold cathode applications. Copyright © 2004 John Wiley & Sons, Ltd.
Field emission current fluctuations from isolated carbon nanotubes
Authors: Tuggle D. W. , Jiao J. , Dong L. F.
Published: June 2004

Field emission current fluctuations from single carbon nanotubes created by a chemical vapor deposition (CVD) process were studied using a field emission microscope equipped with a moveable Faraday cup. The aperture at the entrance to the cup defined the solid angle subtended and allowed conversion of current into angular intensity. A time record of current was constructed by sampling, from which the average current and standard deviation were calculated. Simultaneously, a power spectrum from 1 Hz to 1 kHz was acquired. Normalized comparisons of power spectral densities for nanotube, Schottky and thermal field emitters are presented. The effect of heating the nanotube emitter substrate on the current fluctuation is shown. A limit of ∼0.1 mA sr−1 was observed for angular intensity from carbon nanotubes. Copyright © 2004 John Wiley & Sons, Ltd.
Field electron emission properties from aligned carbon nanotube bundles of different density
Authors: Deng S. Z. , Xu N. S. , Liu J. B. , Chen Jun , Ke Y. L. , She J. C.
Published: June 2004

Details are given of an experimental study of the field emission characteristics of well‐aligned carbon nanotube films. The films were prepared in a catalyst‐assisted process using bias‐enhanced microwave plasma chemical vapour deposition. They consist of bundles of carbon nanotubes, the density of which may be controlled by changing the thickness of the pre‐deposited catalyst film. The transparent anode technique was used to measure the field emission properties of the carbon nanotube films and it was found that films having a low density of bundles have better field emission properties. The findings are explained by the electrostatic screen effect. Copyright © 2004 John Wiley & Sons, Ltd.
Anwendung moderner Beschichtungs‐ technologien – Quo Vadis 2004?. Application of Coatings for Tolling ‐ Quo Vadis 2004?
Authors: Cselle Tibor
Published: June 2004

Jede dritte Patentanmeldung, die sich mit Zerspanungswerkzeugen beschäftigt, stellt einen Hauptanspruch bezüglich Beschichtungen auf. Aber nicht nur deswegen sind Schichten eine der wichtigsten (sogar momentan vielleicht die wichtigste) Antriebskräfte der Weiterentwicklung der Fertigungstechnik. Sie bestimmen die Leistung der Werkzeuge maßgeblich und verbessern diese mit Riesenschritten [1], [12].

Der folgende Beitrag möchte nicht im Sinne der gängigen Reviews den Stand der heutigen Beschichtungstechnik darstellen. Vielmehr werden hier Informationen zu den aktuellsten Fragen, Problemen und Neuigkeiten der Beschichtungspraxis kurz und bündig zusammengefasst. Damit sollte der heute so gestresste Anwender in kurzer Zeit konkrete Antworten auf einige seiner brennenden Fragen erhalten.
Clinical Significance of Serum Carcinoembryonic Antigen, Carbohydrate Antigen 19‐9, and Squamous Cell Carcinoma Antigen Levels in Esophageal Cancer Patients
Authors: Kosugi Shin‐ichi , Nishimaki Tadashi , Kanda Tatsuo , Nakagawa Satoru , Ohashi Manabu , Hatakeyama Katsuyoshi
Published: June 2004

Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19‐9, and squamous cell carcinoma (SCC) antigen levels were assessed to determine if their levels are useful for staging esophageal cancer preoperatively and for predicting patient survival after esophagectomy. Hence their seropositivity was investigated for a correlation with resectability, clinicopathologic parameters of tumor progression, and treatment outcomes in patients with unresectable esophageal cancer (n = 63) and those undergoing esophagectomy for resectable disease (n = 267). Abnormal elevation of serum SCC antigen levels showed a significant correlation with resectability (p < 0.0001), depth of tumor invasion (p < 0.0001), lymph node status (p = 0.0015), TNM stage (p < 0.0001), lymphatic invasion (p = 0.0019), blood vessel invasion (p = 0.0079), and poor survival after esophagectomy (p = 0.0061). A significant relation (p = 0.0145) was found between elevated serum CEA levels and distant metastasis, whereas the seropositivity of CA 19‐9 showed no association with resectability, tumor progression, or patient survival. These results indicate that abnormal elevation of serum SCC antigen is a useful predictor of advanced esophageal cancer associated with poor survival after esophagectomy.
Identification of the Nonrecurrent Laryngeal Nerve during Thyroid Surgery: 20‐Year Experience
Authors: Toniato Antonio , Mazzarotto Renzo , Piotto Andrea , Bernante Paolo , Pagetta Costantino , Pelizzo Maria Rosa
Published: June 2004

The nonrecurrent laryngeal nerve, which is rarely observed during thyroidectomy, is at high risk for damage. During a 20‐year period 6000 thyroidectomies were performed at our institution, and during these operations inferior laryngeal nerves were routinely identified in all the patients with a standard procedure based on the usual anatomic landmarks. A nonrecurrent laryngeal nerve was observed on the right side in 31 cases (0.51%), with no anatomic anomalies found on the left side. The nerve anomaly was diagnosed preoperatively in five patients. A vocal cord deficit, caused by a nerve lesion, was observed in four cases (12.9%). Our results suggest that the best way to avoid morbidity is routine identification of the nerve. This can be done by carefully identifying all the thyroid structures and being suspicious of the presence of the abnormality when the inferior laryngeal nerve is not found in a classic position.
Leisure activities and problem behaviours among Hungarian youth
Authors: Piko Bettina F. , Vazsonyi Alexander T.
Published: June 2004

We examined leisure behaviours and the relationships between leisure and a variety of problem behaviours in a sample of 1422 Hungarian adolescents (age range: 14–19). Findings from multivariate analyses suggest that some aspects of adolescent leisure, such as family or conventional activities, act as protective factors against problem behaviours, while peer‐oriented activities or commercial types of leisure contribute to greater risk for problem behaviours. We also found that the same leisure activities explained problem behaviours for both males and females. The study suggests that the relationships between leisure activities and problem behaviours are highly similar as found among Western youth.
The multifunctional role of fibroblasts during wound healing in Hirudo medicinalis (Annelida, Hirudinea)
Authors: Tettamanti Gianluca , Grimaldi Annalisa , Rinaldi Liliana , Arnaboldi Francesca , Congiu Terenzio , Valvassori Roberto , De Eguileor Magda
Published: June 2004

Summry— Extracellular matrix components play a key role during the angiogenic process for a correct development of blood vessels: fibroblasts are the main cell type involved in the regulation of ECM protein production. In this study we characterize H. medicinalis fibroblasts and demonstrate that they take part to the regulation of angiogenesis that occurs during wound healing process. Massive proliferation and phenotypic modification are two distinctive markers of fibroblast activation. These cells, that are usually responsible for collagen production and function as an energy reservoir, are recruited during wound healing to form a collagen scaffold through a direct mechanic action and through secretion of specific proteoglycans. In addition we show that the activity of fibroblasts is modulated by EGF, a growth factor involved in wound healing in vertebrates. The formation of bundles of collagen fibrils by fibroblasts is fundamental for the development and migration of new blood vessels in lesioned areas during wound repair: administration of lovastatin in explanted leeches affects fibroblasts, damages collagen “scaffold” and indirectly causes the reduction of neo‐capillary formation.
Intracellular phenotype of Mycobacterium avium enters macrophages primarily by a macropinocytosis‐like mechanism and survives in a compartment that differs from that with extracellular phenotype
Authors: Bermudez Luiz E. , Petrofsky Mary , Sangari Felix
Published: June 2004

Mycobacterium avium uptake by human macrophages differs between the phenotypes of bacterium grown in laboratory media (extracellular growth, EG) and bacterium grown within macrophages (intracellular growth, IG). Studies in vivo have confirmed that, when spreading, pathogenic mycobacteria enter macrophages by a complement receptor 3‐independent pathway, in contrast to mycobacteria uptake in vitro. M. avium, grown in macrophages (IG) for 3 or more days, invade fresh macrophages by a macropinocytosis‐like mechanism, in contrast to bacteria grown in media (EG), confirmed by the inhibitory effect of wortmannin, an inhibitor of phosphoinoside‐3‐kinase, on the uptake of IG, but not EG, by macrophages. The IG phenotype was seen in vacuoles with lower pH than those inhabited by the EG phenotype. Incubation of macrophages with bafilomycin A1, an inhibitor of vacuole acidification, decreased the viability of intracellular IG, but not EG, phenotype, suggesting the importance of an acidic environment for the regulation of IG genes. In addition, the percentage of vacuoles that incorporate and retain LAMP‐1 is smaller with EG than with IG bacteria. The formation of M. avium macropinosomes was also shown to be independent of microtubules. These data suggest that uptake of extracellular fluid is part of M. avium IG phenotype uptake by macrophages, and that the IG phenotype inhabits a slightly different vacuole than that of EG.
Residual symptoms of depression: clinical and theoretical implications
Authors: Boulenger Jean-Philippe
Published: June 2004

Residual symptoms of variable intensity often persist following pharmaco/or psychotherapeutic interventions for treatment of major depression (MD). In several studies, such persistent symptoms have been clearly shown to be associated with a higher risk of relapse, chronicity and functional impairment, but their true nature is still controversial. Several authors consider that these symptoms belong to the range of depression proper and thus indicate that the current episode has been inadequately treated, a hypothesis reinforced by their frequent similarity with the symptoms preceding the full-blown picture of MD. However, in the current state of research, their connection with certain personality traits or comorbid disorders—notably anxiety disorders—cannot be completely ruled out. This article reviews the main data from the literature concerning residual symptoms and their treatment, as well as the issues related to their psychopathological meaning. In practice, once the state of a patient has been stabilized in partial remission of the depressive syndrome, the clinician should revise the current therapeutic strategy and seek to find how to return as fully as possible to the previous euthymic state.
Temperament and character inventory (TCI) personality profile in metamphetamine abusers: a controlled study
Authors: Hosák Ladislav , Preiss Marek , Halíř Martin , Čermáková Eva , Csémy Ladislav
Published: June 2004

We applied the temperament and character inventory (TCI) personality questionnaire in 41 inpatients dependent on metamphetamine, and 35 controls. Novelty seeking, harm avoidance and self-transcendence were significantly higher, and persistence, self-directedness and cooperativeness were significantly lower in the patients than in the healthy volunteers. The detected differences may be important for prevention and treatment.
Novel Sm‐like proteins with long C‐terminal tails and associated methyltransferases
Authors: Albrecht Mario , Lengauer Thomas
Published: June 2004

Sm and Sm‐like proteins of the Lsm (like Sm) domain family are generally involved in essential RNA‐processing tasks. While recent research has focused on the function and structure of small family members, little is known about Lsm domain proteins carrying additional domains. Using an integrative bioinformatics approach, we discovered five novel groups of Lsm domain proteins (Lsm12‐16) with long C‐terminal tails and investigated their functions. All of them are evolutionarily conserved in eukaryotes with an N‐terminal Lsm domain to bind nucleic acids followed by as yet uncharacterized C‐terminal domains and sequence motifs. Based on known yeast interaction partners, Lsm12‐16 may play important roles in RNA metabolism. Particularly, Lsm12 is possibly involved in mRNA degradation or tRNA splicing, and Lsm13‐16 in the regulation of the mitotic G2/M phase. Lsm16 proteins have an additional C‐terminal YjeF_N domain of as yet unknown function. The identification of an additional methyltransferase domain at the C‐terminus of one of the Lsm12 proteins also led to the recognition of three new groups of methyltransferases, presumably dependent on S‐adenosyl‐l‐methionine. Further computational analyses revealed that some methyltransferases contain putative RNA‐binding helix–turn–helix domains and zinc fingers.
Folding of Alzheimer's core PHF subunit revealed by monoclonal antibody 423
Authors: Skrabana Rostislav , Kontsek Peter , Mederlyova Anna , Iqbal Khalid , Novak Michal
Published: June 2004

At present, the conformation‐dependent monoclonal antibodies (mAb) provide the only information on folding of tau in the core PHF. Monoclonal antibody MN423 recognizes all and only those Alzheimer's disease (AD) core paired helical filaments (PHFs) subunits, which terminate at Glu391. Using recombinant analogs of the core PHF subunit corresponding to tau residues τ297–391, we found that the C‐terminal pentapeptide 387DHGAE391 represented only one component of the structure recognized by mAb 423. Therefore, deletion mutants of the core subunit were generated to identify assembled parts of this conformational structure. We localized two spatially close components in the region 306–325 (306VQIVYK311 and 321KCGSL325) contributing to formation of the structure identified by mAb 423. Thus, the spatial proximity of three subunit segments 306VQIVYK311, 321KCGSL325 and 387DHGAE391 represents constraints for intramolecular folding of the core PHF subunit. Since PHF represents a compelling drug target in AD, structural knowledge presented could contribute to structure‐based drug design.
Regions of minimal structural variation among members of protein domain superfamilies: application to remote homology detection and modelling using distant relationships
Authors: Chakrabarti Saikat , Sowdhamini R.
Published: June 2004

Structurally conserved regions or structural templates have been identified and examined for features such as amino acid content, solvent accessibility, secondary structures, non‐polar interaction, residue packing and extent of structural deviations in 179 aligned members of superfamilies involving 1208 pairs of protein domains. An analysis of these structural features shows that the retention of secondary structural conservation and similar hydrogen bonding pattern within the templates is 2.5 and 1.8 times higher, respectively, than full‐length alignments suggesting that they form the minimum structural requirement of a superfamily. The identification and availability of structural templates find value in different areas of protein structure prediction and modelling such as in sensitive sequence searches, accurate sequence alignment and three‐dimensional modelling on the basis of distant relationships.
Fluoride curcumin derivatives: new mitochondrial uncoupling agents
Authors: Ligeret Heidi , Barthélémy Sophie , Bouchard Doulakas Géraldine , Carrupt Pierre-Alain , Tillement Jean-Paul , Labidalle Serge , Morin Didier
Published: June 2004

The mitochondrial effects of two fluoride curcumin derivatives were studied. They induced the collapse of mitochondrial membrane potential (Δψ), increased mitochondrial respiration, and decreased O2
− production and promoted Ca2+ release. These effects were reversed by the recoupling agent 6‐Ketocholestanol, but not by cyclosporin A, an inhibitor of the permeability transition pore (PTP), suggesting that these compounds act as uncoupling agents. This idea was reinforced by the analysis of the physico‐chemical properties of the compounds indicating, that they are mainly in the anionic form in the mitochondrial membrane. Moreover, they are able to induce PTP opening by promoting the oxidation of thiol groups and the release of cytochrome c, making these two molecules potential candidates for induction of apoptosis.
Chemically sulfated Escherichia coli K5 polysaccharide derivatives as extracellular HIV‐1 Tat protein antagonists
Authors: Urbinati Chiara , Bugatti Antonella , Oreste Pasqua , Zoppetti Giorgio , Waltenberger Johannes , Mitola Stefania , Ribatti Domenico , Presta Marco , Rusnati Marco
Published: June 2004

The HIV‐1 transactivating factor (Tat) acts as an extracellular cytokine on target cells, including endothelium. Here, we report about the Tat‐antagonist capacity of chemically sulfated derivatives of the Escherichia coli K5 polysaccharide. O‐sulfated K5 with high sulfation degree (K5‐OS(H)) and N,O‐sulfated K5 with high (K5‐N,OS(H)) or low (K5‐N,OS(L)) sulfation degree, but not unmodified K5, N‐sulfated K5, and O‐sulfated K5 with low sulfation degree, bind to Tat preventing its interaction with cell surface heparan sulfate proteoglycans, cell internalization, and consequent HIV‐LTR‐transactivation. Also, K5‐OS(H) and K5‐N,OS(H) prevent the interaction of Tat to the vascular endothelial growth factor receptor‐2 on endothelial cell (EC) surface. Finally, K5‐OS(H) inhibits αvβ3 integrin/Tat interaction and EC adhesion to immobilized Tat. Consequently, K5‐OS(H) and K5‐N,OS(H) inhibit the angiogenic activity of Tat in vivo. In conclusion, K5 derivatives with distinct sulfation patterns bind extracellular Tat and modulate its interaction with cell surface receptors and affect its biological activities. These findings provide the basis for the design of novel extracellular Tat antagonists with possible implications in anti‐AIDS therapies.
Carpal Tunnel Syndrome and Work
Authors: DIAS J. J. , BURKE F. D. , WILDIN C. J. , HERAS-PALOU C. , BRADLEY M. J.
Published: June 2004

The incidence, age at presentation, disability and outcome after surgery were investigated in 327 consecutive women of working age presenting to a hand unit with carpal tunnel syndrome. Two hundred and seventeen were working, 55 of these in repetitive occupations. One hundred and ten were not in employment. All three groups had similar mean ages (around 46 years). On a population basis more women in non-repetitive occupations presented with carpal tunnel syndrome (220/100,000/year) than those in repetitive work (122/100,000/year) or those not working (129/100,000/year), and more were offered surgery (82% versus 67% for those in repetitive work and 58% for those not working). However, symptoms and disability; as assessed with the Michigan Hand Questionnaire and the SF-12, were less severe in working women. This study suggests that working in repetitive or non-repetitive occupations does not cause, aggravate or accelerate carpal tunnel syndrome. Working women may struggle to accommodate their symptoms compared to women who are not in employment causing more to seek help.
Stem cell repair of physeal cartilage
Authors: Ahn Jae I. , Canale S. Terry , Butler Stephanie D. , Hasty Karen A.
Published: June 2004

To evaluate the ability of cultured mesenchymal stem cells (MSC) to repair physeal defects, MSC‐matrix constructs with 5% gelatin (group A), 10% gelatin/Gelfoam (Pharmacia, Peapack, NJ) (group B), and MSC grown in the presence of TGF‐β3 with Gelfoam (group C) were implanted in proximal tibial physeal defects created in 20 immature rabbits. Control groups (untreated partial defect and partial defect treated with Gelfoam) showed bony bar formation with varus deformities of 30° and 28°, respectively. Group A had an average 23° varus deformity with bony bridge formation, and group B had mild varus angulation (average 14°) of the proximal tibia. In group C, there was no significant varus deformity (average 9°), and histologic examination showed that some of the columnation areas interspersed with chondrocytes were irregularly arranged in the matrix. These findings suggest that repair of physeal defects can be enhanced by the implantation of MSC cultured with TGF‐β3. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
On the calculation of electric fields and currents of mesoscale convective systems
Authors: Davydenko S. S. , Mareev E. A. , Marshall T. C. , Stolzenburg M.
Published: June 2004

A layered system of external currents is used to model the electric environment of a mesoscale convective system (MCS). The model takes into account the multilayer structure and appropriate horizontal scales of the MCS charge regions. The detailed model determines the electric field and current inside and in the vicinity of a stationary MCS as well as the net vertical current above the thunderclouds, which is an important measure of its contribution to the global electric circuit. The relatively large horizontal scale of an MCS ensures a more effective coupling to the ionosphere than for an isolated thunderstorm. In the model calculations the MCS‐trailing stratiform region had a net vertical current magnitude of about 25 A versus only 0.4 A for a convective element of the MCS (which is similar to the contribution of an isolated thunderstorm). Additionally, it has been found that an MCS can serve either as an effective generator in the global circuit or as a discharger of it depending on the polarity, magnitude, and thickness of the layers of external current.