bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete cytogenetic and molecular responses to interferon‐α‐based therapy for chronic myelogenous leukemia are associated with excellent long‐term prognosis
Authors: Kantarjian Hagop M. , O'Brien Susan , Cortes Jorge E. , Shan Jianqin , Giles Francis J. , Rios Mary Beth , Faderl Stefan H. , Wierda William G. , Ferrajoli Alessandra , Verstovsek Srdan , Keating Michael J. , Freireich Emil J. , Talpaz Moshe
Published: February 2003

BACKGROUND

Little is known regarding long‐term prognosis among patients with Philadelphia chromosome (Ph)‐positive chronic myelogenous leukemia (CML) who achieve a complete cytogenetic response (0% Ph‐positive cells) after treatment with interferon‐α.

METHODS

The authors analyzed 512 patients with Ph‐positive, early chronic‐phase CML who were treated with interferon‐based therapies between 1981–1995 for the incidence and durability of complete cytogenetic response, and in relation to long‐term prognosis.

RESULTS

One hundred forty patients (27%) achieved a complete cytogenetic response. Their 10‐year survival rate was 78%. At the time of last follow‐up, 44 patients (31%, 9% of the total) were alive, 21 in first and 23 in second durable complete cytogenetic response (median, 127 months; range, 88–191 months); 39 patients had not received any therapy for a median of 50 months (range, 11–139 months). Analysis by reverse transcriptase‐polymerase chain reaction in 78 patients during complete cytogenetic response showed 46 who had achieved at least 1 complete molecular response. Five of these 78 patients had died by the time of last follow‐up, but only 2 had died of disease‐specific causes. Recurrence rates were significantly lower and cytogenetic response durations were significantly longer among patients who achieved at least one complete molecular response.

CONCLUSIONS

Achieving a complete cytogenetic or molecular response after therapy with interferon‐α appears to be associated with excellent long‐term prognosis. Approximately 10% of patients reportedly can achieve durable complete cytogenetic response, with or without continuation of interferon. This finding emphasizes the potential of long‐term event‐free survival in CML patients outside the context of allogeneic stem cell transplantation, which may be improved with new therapies such as imatinib mesylate. Cancer 2003;97:1033–41. © 2003 American Cancer Society.

DOI 10.1002/cncr.11223
Robust direction‐of‐arrival estimation against array sensor errors using Hopfield neural network
Authors: Yamaoka Tateo , Masada Shiori , Sato Satoshi , Hamada Nozomu
Published: February 2003

When direction‐of‐arrival estimation methods based on eigenvalue expansion such as MUSIC and ESPRIT are applied to an ideal sensor array, high resolution can be attained. However, if there exist array sensor errors due to sensor position errors and degradation of the phase shifters, significant errors may arise in the estimation results. Also, in order to obtain sufficient estimation accuracy, a relatively high signal‐to‐noise ratio is required in the array input. In this paper, the Hopfield neural network is employed for direction‐of‐arrival estimation and a direction‐of‐arrival estimation method that is robust to array errors by virtue of using training signals is proposed. By means of computer simulation, the method is compared with that of MUSIC and its effectiveness is verified. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(6): 19–28, 2003; Pub‐lished online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10062
A neural network model of memory system using hippocampus
Authors: Ito Makoto , Kuroiwa Jousuke , Miyake Shogo
Published: February 2003

When an episodic memory is to be transferred from short‐term memory to long‐term memory, there must be a buffer mechanism that temporarily stores the content of the short‐term memory as a mid‐term memory. It is considered that the hippocampus plays that role. In composing an episodic memory, there must be not only the association of different events without a time factor (spatial pattern), but also the association of different events containing time factors (time sequence pattern). This paper proposes a hippocampus neural network model, based on anatomical and physiological knowledge. The model features the following points. (i) By applying a learning rule where the input history is considered in the hippocampus CA3, which is regarded to have the associative recall function, it is made possible for the model to learn the time sequence pattern. (ii) The orthogonal coding function is provided in the gyrus dentatus, and the decoding function is provided in the hippocampus CA1. It is expected that the memory capacity of the hippocampus will be enlarged by providing the orthogonal coding function. It is shown by a numerical simulation that the mid‐term memory can learn spatial and time sequence patterns, and that associative recall of the memory contents can be realized. This result implies that the proposed hippocampus model can retain episodic memory as a mid‐term memory. The obtained results agree with physiological data, and demonstrate the effectiveness of the proposed model. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(6): 86–97, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.1010
Sequential Metathesis in Oxa‐ and Azanorbornene Derivatives
Authors: Arjona Odón , Csákÿ Aurelio G. , Plumet Joaquín
Published: February 2003

Ring‐opening metathesis (ROM), when applied to the synthesis of bicyclic alkenes, is the basis of ring‐opening‐metathesis polymerisation (ROMP). This polymerisation reaction can be suppressed in the presence of a second open‐chain olefin thus combining the ROM with an intermolecular cross metathesis (CM). In conveniently substituted bicyclic derivatives a third metathetical reaction — ring closing metathesis (RCM) — can be achieved, giving new substituted bicyclic systems. In this account the results of these tandem metathetical reactions performed on oxa‐ and azabicyclic norbornenic derivatives are highlighted. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
A New Crystalline Zwitterionic Product from the Reaction of Bu3P and DMAD
Authors: Aitken R. Alan , Costello Stephen J. , Slawin Alexandra M. Z. , Wilson Neil J.
Published: February 2003

Tributylphosphane reacts with DMAD to give the crystalline adduct 2 which is stabilised by extensive delocalisation and whose formation involves an unusual rearrangement. The isomeric structure 7 for the previously reported adduct with triphenylphosphane is supported by 13C NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Investigations into the Regioselective C‐Deuteration of Acyclic and Exocyclic Enolates
Authors: Eames Jason , Coumbarides Gregory S. , Suggate Michael J. , Weerasooriya Neluka
Published: February 2003

Results are reported on the regioselective C‐deuteration of a series of related acyclic and exocyclic enolates derived from substituted aryl ketones. We comment on factors, such as the presence of additives and the structural nature of the enolate, that influence the observed C‐deuteration and discuss the role of the deuterium donor. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Columbetdione, a New Cyclopentene Derivative from the Fruiting Bodies of Tricholoma columbetta (Basidiomycetes) − Structure and Synthesis
Authors: Vadalà Alessandro , Finzi Paola Vita , Zanoni Giuseppe , Vidari Giovanni
Published: February 2003

A chemical investigation of the fruiting bodies of Tricholoma columbetta (Agaricaceae, Basidiomycetes) led to the isolation of columbetdione, an unprecedented cyclopentene derivative. The structure was determined by spectroscopic methods and molecular modelling and unambiguously confirmed by total synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Straightforward Synthesis of Labeled and Unlabeled Pyrimidine d4Ns via 2′,3′‐Diyne seco Analogues through Olefin Metathesis Reactions
Authors: Gillaizeau Isabelle , Lagoja Irene M. , Nolan Steve P. , Aucagne Vincent , Rozenski Jef , Herdewijn Piet , Agrofoglio Luigi A.
Published: February 2003

The synthesis of dideoxynucleosides (ddNs) or didehydro‐dideoxynucleosides (d4Ns) from nucleosides has been extensively reviewed. While previously described methods are based on the modification of the 2′‐ and/or 3′‐OH group of the intact ribose moiety, the use of a ring‐closing metathesis (RCM) for the formation of the unsaturated cyclic system of nucleosides could be a straightforward approach to the d4Ns. Thus, as part of our drug labeling program, this paper reports a straightforward synthesis of 2′,3′‐didehydro‐2′,3′‐dideoxyuridine (d4U) and [1′,2′,3′,4′,5′‐13C5,6‐13C,1,3‐15N2]d4T using the RCM protocol. This paper discusses the preparation of nucleoside dienes and the activity of ruthenium‐based metathesis catalysts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Determination of the Absolute Configuration of Hydroxyiridals by Chiroptical and NMR Spectroscopic Methods
Authors: Lamshöft Marc , Schmickler Hans , Marner Franz‐Josef
Published: February 2003

Hydroxyiridals − monocyclic triterpenoids − are found abundantly in sword lilies. They feature a homofarnesyl side chain that is hydroxylated at one of the allylic methylene groups, which gives rise to a chiral carbon atom. The absolute configuration of six hydroxyiridals from different sources was determined by the exciton chirality method and by NMR spectroscopy of the diastereoisomeric MTPA and MPA esters. All three measurements gave consistent results, establishing the (R) configuration for all of the hydroxyiridals. The reliability of these methods for the stereochemical analysis of acyclic secondary allylic alcohols was confirmed by applying them to a synthetic model compound of known configuration. In the course of this study, two new iridals − 16,26‐dihydroxyiridal 7 and 18,19‐epoxyiridal 8 − were isolated from extracts of I. versicolor and the iridal fraction of I. missouriensis was analyzed thoroughly. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Eur. J. Org. Chem. 4/2003
Authors: van Axel Castelli Valeria , Dalla Cort Antonella , Mandolini Luigi , Reinhoudt David N. , Schiaffino Luca
Published: February 2003

The cover picture shows the four‐body productive complex involved in the rate‐determining step of the addition of a triethylamine‐activated benzenethiol to a uranyl−salophenactivated 2‐cyclopenten‐1‐one. The background offers a view of the complex rate equation ad hoc developed for the above (two reactant)‐(two catalyst) system involving complexation catalysis and product inhibition. Details are discussed in the article by L. Mansolini, D. N. Reinhoudt et al. on p. 627 ff.
Synthesis of Pyrrole Derivatives through Functionalization of 3,4‐Bis(lithiomethyl)dihydropyrroles
Authors: Barluenga José , Fañanás Francisco J. , Sanz Roberto , Ignacio José M.
Published: February 2003

Bis(2‐lithioallyl)amines 2, substituted at the double bonds, undergo intramolecular carbolithiation of a lithiated double bond in different solvents to afford dilithiated dihydropyrroles 3. Treatment of these dianions with electrophiles allows the preparation of functionalized pyrrole derivatives 5 and 6. Interestingly, treatment of these dianions with carboxylic esters selectively affords either keto or hydroxy compounds (9 or 10), depending on the conditions. Several experiments have been carried out in order to clarify the mechanism of this selective transformation. Finally, dilithiated dihydropyrrole 3a could be transformed in a three‐step procedure into the corresponding 3,4‐bis(bromomethyl) derivative 31, which can easily be converted into bicyclic pyrrole compounds 32−33 by treatment with different nucleophiles. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Determination of Ytterbium Traces by Cathodic Stripping Voltammetry
Authors: Mlakar Marina
Published: February 2003

The method of ytterbium(III) trace concentration in the presence of 2‐thenoyltrifluoroacetone (TTA) and polyethyleneglycol (PEG) in ammonium chloride is described. The adsorption was performed at the HMDE at −1.0 V using linear scan voltammetry and square‐wave voltammetry. The relationship between properties of the SW response of the mixed ligand complex and parameters of a charge transfer were analyzed using theoretical data of SW redox processes.
Influence of the Mixed Adsorption Layer of 1‐Butanol/Toluidine Isomers on the Two Step Electroreduction of Zinc(II) Ions
Authors: Saba J. , Nieszporek J. , Gugala D. , Sienko D. , Szaran J.
Published: February 2003

Studies of mixed adsorption layers with respect to their influence on kinetics of Zn2+ ions reduction indicate dynamics of this process in the presence of inhibitor and accelerating substances. This effect can be seen as a much greater increase of standard constant rates compared with a similar increase without the inhibitor. 1‐Butanol was used as an inhibitor in the studies and p‐toluidine and m‐toluidine as accelerating substances. The adsorption measurements show that in the range of Zn2+ ion reduction potentials in the solutions containing 1‐butanol and the definite isomer of toluidine, toluidine plays a dominant role in establishing equilibrium in the mixed adsorption layer. The obtained values of the true standard constant rates of the transfer of the first electron ks1t and the second electron ks2t indicate that in each of the studied systems the stage of the first electron transfer is more strongly accelerated compared with the stage of the second electron transfer. The linear character of the dependence ks1t and ks2t in the function of the surface excess and in the function of 1‐butanol concentration indicates that active complexes are formed for each case of the mixed adsorption layer.
Potential‐Controlled Chromatography of Short‐Chain Carboxylic Acids
Authors: Knizia M. W. , Vuorilehto K. , Schrader J. , Sell D.
Published: February 2003

A chromatographic column was constructed which could be operated with an electrically conductive stationary phase of graphite particles. This column allowed chromatographic experiments at variable electric potentials of the column material. The chromatographic behavior of selected carboxylic acids was significantly influenced at positive column potentials. An equimolar mixture of three different carboxylic acids were separated at a potential of +600 mV (versus. Ag/AgCl). Surprisingly, the stereoisomers maleic and fumaric acid, which are identical in molecular mass and charge, could also be separated. Further improvements to the chromatographic performance were achieved by applying potential drops and linear potential gradients.
Mediated Electrocatalysis at the Electrodes Covered with [MIII(bpy)3](ClO4)3 (M=Co and Fe) in the Presence of Electroactive Solutes
Authors: Winkler Krzysztof , Plonska Marta E. , Basa Anna , Lach Magdalena , Balch Alan L.
Published: February 2003

Electron transfer processes for selected redox systems (ferrocene0/+, decamethylferrocene0/+, N,N,N′,N′‐tetramethyl‐1,4‐phenylenediamine0/+, 7,7,8,8‐tetracyano‐quinonedimethane0/−/2−, cobaltocene0/+, C600/−, and benzoquinone0/−) at electrodes modified by precipitation of electrochemically inactive [MIII(bpy)3](ClO4)3 (M=Co and Fe, bpy=2,2′‐bipyridine) layers have been investigated by cyclic voltammetry and electrochemical quartz crystal microbalance studies. The mediation of heterogeneous electron transfer is observed for these systems. For an electrode modified with [MIII(bpy)3](ClO4)3, the rate of the electrocatalytic mediation process depends on the formal potential of the redox system. If the formal potential of the redox system is close to the potential of [CoII(bpy)3]2+ oxidation (as is the case with the decamethylferrocene0/+, N,N,N′,N′‐tetramethyl‐1,4‐phenylenediamine0/+ and 7,7,8,8‐tetracyanoquinonedimethane0/− systems), the rate of the electrode reaction is limited by the rate of the chemical reduction of the [CoIII(bpy)3](ClO4)3 solid phase by the reduced form of redox couple. For C60 and benzoquinone, which have more negative formal potentials for reduction, the rate of diffusion of the electroactive reactant to the electrode surface limits the rate of electrode process. The kinetics of mediated electrocatalysis are also affected by the solvent. In the case of the Fe(III)‐based layer, the diffusion of the electroactive reactant in the solution is the rate determining step for the catalytic process at the modified electrode for all studied systems. Electrodes modified with [FeIII(bpy)3](ClO4)3 have been used for the quantitative determination of electroactive compounds. For ferrocene and decamethylferrocene, a linear relationship between the catalytic reduction current and the concentration of reactant in the solution has been observed over the concentration range from 1 to 50 mM.
Enhancement of selectivity and resolution in the enantioseparation of uncharged compounds using mixtures of oppositely charged cyclodextrins in capillary electrophoresis
Authors: Abushoffa Adel M. , Fillet Marianne , Servais Anne‐Catherine , Hubert Philippe , Crommen Jacques
Published: February 2003

The enantiomeric separation of some nonsteroidal anti‐inflammatory drugs (NSAIDs) was investigated in capillary electrophoresis (CE) using dual systems with mixtures of charged cyclodextrin (CD) derivatives. A significant enhancement of selectivity and resolution could be achieved in the enantioseparation of these analytes in their uncharged form by the simultaneous addition of two oppositely charged CD derivatives to the background electrolyte. The combination of the single‐isomer cationic CD, permethyl‐6‐monoamino‐6‐monodeoxy‐β‐CD (PMMAβCD) and the single‐isomer polyanionic CD, heptakis‐6‐sulfato‐β‐cyclodextrin (HSβCD) in a pH 2.5 phosphoric acid‐triethanolamine buffer, was designed and employed for the enantioseparation of profens. The improvement in selectivity and resolution can be attributed to the fact that the two CDs, which lead to independent and enantioselective complexation with the analyte enantiomers, have not only opposite effects on the electrophoretic mobility of these compounds but also opposite affinity patterns towards the enantiomers of these compounds. Binding constants for these enantiomers with each CD were determined using linear regression approach, in order to be able to predict the effect of the concentrations of the two CDs on enantiomeric selectivity and resolution in such dual systems.
Synthesis, analytical characterization and use of octakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐γ‐cyclodextrin, a novel, single‐isomer, chiral resolving agent in low‐pH background electrolytes
Authors: Busby M. Brent , Lim Peniel , Vigh Gyula
Published: February 2003

The third member of the family of single‐isomer, sulfated γ‐cyclodextrins, the sodium salt of octakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐γ‐cyclodextrin has been synthesized, analytically characterized and used for the capillary electrophoretic separation of the enantiomers of nonionic, weak acid and weak base analytes in low‐pH aqueous background electrolytes. Though octakis(2,3‐di‐O‐methyl‐6‐O‐sulfo)‐γ‐cyclodextrin complexes less strongly with many of the analytes tested than the other members of the single‐isomer, 6‐O‐sulfo γ‐cyclodextrin family, such as octa(6‐O‐sulfo)‐γ‐cyclodextrin and octakis(2,3‐di‐O‐acetyl‐6‐O‐sulfo)‐γ‐cyclodextrin, it offers excellent separation selectivities, often complementary to those of both the single‐isomer, 6‐O‐sulfo β‐cyclodextrins and 6‐O‐sulfo γ‐cyclodextrins. Rapid, efficient enantiomer separations were observed for a large number of structurally diverse analytes in acidic aqueous background electrolytes.
Estimation and comparison of ζ‐potentials of silica‐based anion‐exchange type porous particles for capillary electrochromatography from electrophoretic and electroosmotic mobility
Authors: Sánchez Muñoz Orlando L. , Hernández Ever Pérez , Lämmerhofer Michael , Lindner Wolfgang , Kenndler Ernst
Published: February 2003

Mobilities of different chromatographic particles obtained from two electrokinetic methods were determined and compared. The particles were all based on porous silica, between 3 and 15 μm diameter, and were either native, or derivatized. As intermediate of chemical modification 3‐mercaptopropyl‐modified silica particles (TP‐silica) are obtained. These particles were finally transformed into weakly basic anion exchangers with O‐9‐(tert‐butylcarbamoyl)quinine (tBuCQN) as chiral selector. The electrophoretic mobility of the particles was determined from their migration velocity in an electric field using microelectrophoresis. Electrokinetic chromatography with a capillary column packed with the same particles was used to measure the electroosmotic flow generated. All measurements were carried out in background electrolytes of equal ionic strength (10−2 mol/L), at pH varying between 3.5 and 9.5. From these data a rough estimation of the ζ‐potential was made, taking Helmholtz‐Smoluchowski conditions into consideration. With both methods the ζ‐potential of the native silica particles is negative throughout, and its value increases with pH. The weakly basic tBuCQN particles have positive ζ‐potentials at pH lower than about 7.5, but exhibit a negative ζ‐potential above this pH, indicating the dominating effect of residual silanol groups at the silica surface. The ζ‐potential for these anion‐exchange particles ranged between +30 and −40 mV. The ζ‐potentials derived with electrophoresis and electroosmosis agree, showing the adequacy of the approach, although many limitations must be taken into account in the treatment of the electrokinetic phenomena in such porous systems. These restrictions in interpreting mobility and ζ‐potential were discussed.
Sieving mechanisms in polymeric matrices
Authors: Sartori Anna , Barbier Valessa , Viovy Jean‐Louis
Published: February 2003

A critical review of the existing theoretical models and experimental evidences for sieving mechanisms during separation of macromolecules, paying particular attention to capillary electrophoresis applications is presented. Gel models (Ogston and reptation) have been successfully applied to highly entangled polymer solutions, where fast and efficient separations can occur. In order to account for the DNA/polymers collision‐interaction mechanisms during separation in dilute solutions – characterized by a poorer resolution –, approximated analytical models have been developed. An insight in the mechanism regulating the intermediate case of moderately entangled polymer solutions, for low fields and concentrations of small multiples of the overlap concentration c*, is given by the constraint release approach. This model proposes an upper limit of size separation, increasing with matrix concentration and molecular mass. Finally, the coupling between the reptative motion of the analytes and the effect of matrix constraint release very likely plays a fundamental role in the separation mechanism and requires therefore further and deeper investigation, both theoretically and experimentally.
Sample stacking revisited: A personal perspective
Authors: Chien Ring‐Ling
Published: February 2003

One of the major challenges in capillary electrophoresis and other miniaturization separation techniques is to maintain high detection sensitivity in the increasingly smaller dimension. Numerous on‐column sample preconcentrating procedures, based either on electrokinetic focusing or chromatographic effects, have been developed. This review will discuss some practical approaches to sample stacking from a personal perspective. Several recent developments in sample stacking on microfluidic devices are reviewed.
Eigenmobilities in background electrolytes for capillary zone electrophoresis: II. Eigenpeaks in univalent weak electrolytes
Authors: Štědrý Milan , Jaroš Michal , Včeláková Kateřina , Gaš Bohuslav
Published: February 2003

We analyze in detail a mathematical model of capillary zone electrophoresis (CZE) based on the conception of eigenmobilities, which are eigenvalues of the matrix tied to the linearized continuity equations. Our model considers CZE systems, where constituents are weak electrolytes and where pH of the background electrolyte may reach the full range from 0 to 14. Both hydrogen and hydroxide ions are taken into account in relations for conductivity and electroneutrality. An electrophoretic system with N constituents has N eigenmobilities. We reveal that two of the eigenmobilities have a special meaning as they exist due to the presence of hydrogen ions and hydroxide ions (in water solutions). These two eigenmobilities are responsible for the existence of two corresponding system zones (system peaks). We show that the stationary zone (injection zone, water zone, gap, peak, dip) is in many common background electrolytes composed of these two eigenzones which overlap, due to their very low electrophoretic mobility, into one zone. Other eigenmobilities give rise to system zones originating due to a possible existence of double (or multiple) coconstituents in the background electrolyte. The last group of eigenmobilities is connected with the movement of eigenzones accompanying analytes and enabling their indirect UV or conductivity detection. The model allows assessing experimentally available quantities such as effective mobility of the analyte, molar conductivity detection response, transfer ratio, and relative velocity slope and gives a picture about migration of analytes, their electromigration dispersion and signals obtained in detectors. It allows computer simulation of electropherograms and enables optimization of background electrolytes.
Centrifugal Flotation Applied to the Separation of Oil and Fat from Wastewater
Authors: Benker B. , Wollmann A. , Sievers M.
Published: February 2003

New flotation devices such as flotation cyclones and flotation centrifuges have successfully been demonstrated for the beneficiation of coal. In this project a flotation centrifuge developed for that purpose was modified and applied to the treatment of wastewater from a food processing plant containing emulgated oil and fat. The cleaning efficiency of the flotation centrifuge was determined by the COD reduction of the wastewater and depended on its composition and pre‐treatment.
The Biological Path to Reunification
Authors: Martin William
Published: February 2003

The familiar form of the family tree is not applicable to all living organisms. Evolutionary history entails not only the divergence of lineages, but also mergers of distinct unicellular organisms (prokaryotes and protists) to form new cell types
On the Battlefield of Chiapas
Authors: Köhler Ulrich
Published: February 2003

In Mexico, the history of a conflict between ethnic Indians and ethnic Mexicans has survived in the memories of successive generations, having been handed down solely by word of mouth
Personal Gender and the Career
Authors: Krais Beate , Beaufaÿs Sandra
Published: February 2003

Irrespective of their career performance, women in the academic arena are still having to struggle for recognition as “fellow players”
In the Service of the Crown
Authors: Lenz Jürgen , Thies Matthias , Schweizerhof Karl
Published: February 2003

Each year ceramometallic dental restorations worth several hundred million euros are fabricated in Germany. However, during fabrication such restorations can be damaged by thermal stresses. Basic research is supporting the safe production of such porcelain‐fused‐to‐metal systems
The Refuge under the Bark
Authors: Baehr Martin
Published: February 2003

Nearly one quarter of Australia's insect species live under the bark of eucalyptus trees. These fissured trees afford carabids in particular protection from the sun, fire and rapacious enemies. Carabids have adapted extremely well to life under the bark
Nitrogen and the Colour of the Crops
Authors: Heege Hermann J. , Reusch Stefan
Published: February 2003

To each plant its due: An optical sensor on the fertiliser distributor uses leaf colouring to determine the corn's nitrogen requirement. This restricts fertilisation to actual requirements
A set of genes activated in differentiating smooth muscle is also activated in smooth muscle from injured arteries or atherosclerotic lesions
Authors: Jenna Lynn Ray Edward S. Moon , Leach Rebecca L. , Benson Mark R.
Published: February 2003

We stimulated differentiation of purified rat neural crest stem cells (NCSCs) into smooth muscle cells (SMCs) in culture, then subtracted NCSC sequences from SMC sequences to make a cDNA library specific for differentiating smooth muscle cells. Sequence analysis of the library shows that a large subset of clones is strongly associated with smooth muscle biology, confirming the overall success of the differentiation and subtraction procedures. Of this subset of clones, more than half encode proteins that have previously been shown to be upregulated in atherosclerotic or injured vascular smooth muscle as compared to normal vascular smooth muscle. Thus, a set of genes activated in differentiating smooth muscle of the neural crest lineage is also activated in atherosclerotic or injured vascular smooth muscle.
Analysis of Smoothened as a candidate gene for human holoprosencephaly
Authors: Ming Jeffrey E. , Jeng Bennie , deSauvage Frederic J. , Muenke Maximilian
Published: February 2003

Holoprosencephaly (HPE) is the most common structural congenital forebrain malformation in humans and is associated with mental retardation and craniofacial abnormalities. In HPE, the cerebral hemispheres fail to separate into distinct right and left halves. The condition is etiologically heterogeneous, as multiple genes and environmental factors are associated with the condition. Autosomal dominant HPE can be caused by mutations in Sonic Hedgehog (SHH). Smoothened (SMOH; human gene) encodes a transmembrane protein that acts in SHH signal transduction. Because of the critical role of SMOH in the SHH pathway, we performed mutation analysis of this gene in familial and sporadic cases of HPE. Although we identified a number of nucleotide changes in SMOH in affected patients, none of these changes is likely to be pathogenic. Thus, haploinsufficiency for SMOH is unlikely to be a significant cause of human HPE in live‐born infants.
14‐Membered Cyclopeptides from Paliurus ramosissimus and P. hemsleyanus
Authors: Lin Hui‐yi , Chen Chung‐Hsiung , Chen Liu Karin C. S. , Lee Shoei‐Sheng
Published: February 2003

Six 14‐membered cyclopeptide alkaloids, i.e., ramosines A–C, mucronine J, and lotusines A and D, were isolated from the roots of Paliurus ramosissimus, and an additional four, hemsines A–D, from the roots of P. hemsleyanus. Among these, ramosines A–C (1, 5, and 6, resp.) and hemsines A and B (7 and 8, resp.) are new bases of the amphibine‐B type, and hemsines C and D (9 and 10, resp.) are new integerrine‐type alkaloids. Additionally, ramosine C (6) represents the first 14‐membered cyclopeptide alkaloid possessing a substitution (OH) at C(13′). Their structural elucidations were based on spectral analysis and molecular‐modeling studies. Pronounced solvent effects in the 1H‐ and 13C‐NMR spectra of these two types of alkaloids were observed.
On the Reactivity of 1H‐Pyrazino[2,3‐c][1,2,6]thiadiazine 2,2‐Dioxide and Derivatives: Nucleophilic Substitution, Amination, Aldol‐Type Condensation, Oxidation, and Hydrolysis
Authors: Campillo Nuria , Páez Juan Antonio , Goya Pilar
Published: February 2003

The reactivity of the 1H‐pyrazino[2,3‐c][1,2,6]thiadiazine 2,2‐dioxide system, structurally related to pteridine, was studied, and a number of novel derivatives were synthesized. The chemical behaviors of these two related fused polyaza systems were compared.
Reactions of mer(exo)‐ and mer(endo)‐[Co(dien)(dapo)X]2+ Isomers (X=OH, Cl, ONO2, N3)
Authors: Browne Rebecca J. , Buckingham David A. , Clark Charles R. , McKeon Josephine A. , Jackson W. Gregory
Published: February 2003

Properties indirectly determined, or alluded to, in previous publications on the titled isomers have been measured, and the results generally support the earlier conclusions. Thus, the common five‐coordinate intermediate generated in the OH−‐catalyzed hydrolysis of exo‐ and endo‐[Co(dien)(dapo)X]2+ (X=Cl, ONO2) has the same properties as that generated in the rapid spontaneous loss of OH− from exo‐ and endo‐[Co(dien)(dapo)OH]2+ (40±2% endo‐OH, 60±2% exo‐OH) and an unusually large capacity for capturing (R=[CoN3]/[CoOH][]=1.3; exo‐[CoN3]/endo‐[CoN3]=2.1±0.1). Solvent exchange for spontaneous loss of OH− from exo‐[Co(dien)(dapo)OH]2+ has been measured at 0.04 s−1 (k1, 0.50M NaClO4, 25°) from which similar loss from the endo‐OH isomer may be calculated as 0.24 s−1 (k2). The OH−‐catalyzed reactions of exo‐ and endo‐[Co(dien)(dapo)N3]2+ result in both hydrolysis of coordinated via an OH−‐limiting process =153 M−1 s−1; =295 M−1 s−1; KH=1.3±0.1 M−1; 0.50M NaClO4, 25.0°) and direct epimerization between the two reactants =33 M−1 s−1; =110 M−1 s−1; 1.0M NaClO4, 25.0°). Comparisons are made with other rapidly reacting CoIII‐acido systems.
Stereoselective Conversion of Aucubin into Polyfunctionalized Tetrahydro‐1H‐cyclopenta[c]furan Glucosides
Authors: Mouriès Christine , Deguin Brigitte , Koch Michel , Tillequin François
Published: February 2003

Mitsunobu reaction of 2′,3′,4′,6′,10‐penta‐O‐pivaloylaucubin (6) with phthalimide, triphenylphosphine, and diethyl azodicarboxylate gave (6R)‐6‐phthalimido‐perpivaloylbartsioside (10) (Scheme 1). Selective oxidation reactions performed with perpivaloylaucubin (12) yielded (1R)‐ and (1S)‐3(β‐D‐glucopyranosyloxy)‐1H‐cyclopenta[c]furan‐1‐carboxaldehydes 13 and 14 respectively (Scheme 2). Similarly, perpivaloyl‐6‐epiaucubin (9) and 10 afforded the corresponding (1S)‐carboxaldehyde 15 and (1R)‐carboxaldehyde 16, respectively. The protected cyclopentafuran glycosides obtained in this way are versatile synthons, which may prove useful for further chemical diversification.
Oxidative Halogenation of Aromatic Compounds with Metal Halides and Sodium Bismuthate
Authors: Muathen Hussni A.
Published: February 2003

A new mild and efficient method for aromatic halogenation with a wide variety of halides in the presence of sodium bismuthate NaBO3 in AcOH is reported. Metal halides of groups Ia, IIa, IIIa, IVa, Va, and the first row of transition elements are suitable for this method.
Pericyclic Transformations at the Periphery of Chromen‐4‐one (=4H‐1‐Benzopyran‐4‐one): An Unusual Preference for a 1,5‐Shift of Allylic Moieties over the Ene Reaction
Authors: Singh Gurmit , Singh Gurpinder , Ishar Mohan Paul S.
Published: February 2003

Quite unlike the reported facile ene reactions on the periphery of many related heterocyclic systems, similarly disposed moieties on the periphery of the chromen‐4‐one (=4H‐1‐benzopyran‐4‐one) system fail to undergo an ene reaction and display a rather unusual preference for an overall [1,5] shift of the allylic C‐atom. Thus, heating xylene solutions of 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, and 2‐(N‐cinnamylamino)‐substituted (E)‐(oxochromenyl)propenoates 9a–c and 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted (E)‐(oxochromenyl)propenoates 16a–c in a sealed tube at 220–230° leads to a [1,5] shift of the allylic moieties (allyl, crotyl, cinnamyl), which is followed by intramolecular cyclization involving the N‐atom and the ester function, to give the 3‐allyl‐3‐crotyl‐, and 3‐cinnamyl‐substituted‐1‐phenyl‐ or 1‐benzyl‐2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 10a–c and 17a–c. The anticipated carbonyl–ene reaction in the 2‐(N‐allylanilino)‐, 2‐(N‐crotylanilino)‐, 2‐(N‐cinnamylanilino)‐, 2‐[allyl(benzyl)amino]‐, 2‐[benzyl(crotyl)amino]‐, and 2‐[benzyl(cinnamyl)amino]‐substituted 4‐oxochromene‐3‐carboxaldehydes 8a–c and 15a–c is also not observed, and these molecules remain untransformed under identical conditions. No [1,5] shifts of benzyl, phenyl, or methyl groups are observed, even in the absence of allylic moieties, though facile [1,5]‐H shift occurs in 2‐(benzylamino)‐ and 2‐(phenylamino)‐substituted (E)‐(oxochromenyl)propenoates 23a,b, which is followed by a similar intramolecular cyclization leading to the 2H‐[1]benzopyrano[2,3‐b]pyridine‐2,5(1H)‐diones 24a,b.
Enantioselective Entry to the Homalium Alkaloid Hoprominol: Synthesis of an (R,R,R)‐Hoprominol Derivative
Authors: Ensch Corinne , Hesse Manfred
Published: February 2003

The diastereoselective synthesis of the N‐ and O‐protected hoprominol derivative (R,R,R)‐6 is described. The building up of the bicyclic O‐silylated and di(N‐tosylated) asymmetric scaffold 6 succeeded by convergent preparation of the two basic chiral azalactam units 7a and 7b and their subsequent iterative linking by a known method (Scheme 5). Both 4‐alkyl‐hexahydro‐1,5‐diazocin‐2(1H)‐ones 7a and 7b were prepared from the chiral β‐amino acid portions 10a and 10b, respectively, by application of a set of reactions (e.g., N‐alkylation of 10a,b and Sb(OEt)3‐assisted cyclization of the resulting open‐chain intermediates) already known. In comparison with the total syntheses of homaline (1) and homoprine (2), the newness of the described synthesis lies in the asymmetric approach to the difunctionalized fatty acid derivative 10b starting from (−)‐(S)‐malic acid (9) (Schemes 3 and 4). Key step in the preparation of 10b was the diastereoselective amination of the optically pure α,β‐unsaturated δ‐hydroxy homoallylic ester 14 via conjugate intramolecular aza‐Michael cyclization of the acylic δ‐(carbamoyloxy) intermediate 11.
On the Preparation of 2‐Substituted Cephalosporins, Part 2
Authors: Tamás László , Gunda Tamás E. , Batta Gyula , Sztaricskai Ferenc
Published: February 2003

Cephalosporin sulfoxides 1 and 2 containing an enone‐ or dienone‐type moiety at position 2 were treated with 2,3‐dimethylbuta‐1,3‐diene or diethyl azodicarboxylate to synthesize, in DielsAlder reactions, the new cephalosporin derivatives 4 and 5 with a cyclic substituent (Scheme 1). Under the same conditions, ethyl diazoacetate and diazomethane reacted differently: while reactions of 1 and 3 with the former lead to compounds 7–10 corresponding to the 1,3‐dipolar cycloaddition route (Scheme 2), diazomethane produced only enol ethers 12 and 13, respectively (Scheme 3). This difference could be rationalized by assuming two different reaction pathways: an orbital‐symmetry‐controlled concerted cycloaddition and an ionic one.
Solvation Effects in the Grignard Reaction with Carbonyl Compounds
Authors: Sassian Meeri , Tuulmets Ants
Published: February 2003

Ratios of the yields of addition and reduction products for the reactions of butylmagnesium chloride with diisopropyl ketone, methyl 2‐methylpropanoate, and isopropyl 2‐methylpropanoate in toluene were determined at different THF, diethyl ether, and tert‐butyl methyl ether contents in the Grignard reagent. Replacement of the alkoxy group in the ester leads to strikingly different results for very small additions of donors. The results are discussed in terms of the solvation of the species in the reaction mixture.
Radiation heat transfer in three‐dimensional closed space including diffuse and specular surfaces
Authors: Miyanaga Toshiyuki , Nakano Yukio
Published: February 2003

A method of numerical calculation for radiation heat transfer in a three‐dimensional closed space including diffuse and specular surfaces was developed. To enable an analysis of the radiation heat exchange on each surface considering multiple specular reflections and obstacles to radiation in the space, an improved heat ray‐tracing method was presented to calculate view factors accurately. The method was determined to be applicable to complicated problems in test calculations using models with specular surfaces and obstacles. Continuing efforts are being applied to more realistic problems. The example examined in this paper is an infrared emitter with a parabolic specular reflector, which is a conventional electric heating apparatus. The measured result for radiant power distribution agrees well with the calculated one. The practical validity of our method was verified. © 2003 Wiley Periodicals, Inc. Heat Trans Asian Res, 32(2): 108–129, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10074
Dysregulated PTEN‐PKB and negative receptor status in human breast cancer
Authors: Shi Wei , Zhang Xinghe , Pintilie Melania , Ma Nancy , Miller Naomi , Banerjee Diponkar , Tsao Ming‐Sound , Mak Tak , Fyles Anthony , Liu Fei‐Fei
Published: February 2003

Recent studies demonstrate that abnormalities in PTEN may be one of the most frequent genetic events observed in human cancers. PTEN dysfunction leads to tumorigenesis through unopposed survival signals mediated via activated protein kinase B (PKB), which may also be associated with hormone‐independence. We therefore investigated the relationship between PTEN‐PKB and receptor status in human breast cancer. Several molecular variables, including immunohistochemical staining for PTEN, PKB (phosphorylated on ser473), p53 and p21 were evaluated. The p53 gene was sequenced from exons 2–11. Seventy‐eight participants in a randomised breast cancer trial served as the cohort for our study. Twenty‐eight of 77 (36%) patients' tumours demonstrated absent or reduced PTEN expression; 17 of 78 (22%) tumours over‐expressed P‐PKB. A significant inverse relationship was observed between reduced PTEN and increased P‐PKB expression. Reduced PTEN also correlated with reduced ER or PR expression. None of the molecular variables correlated with survival. ER and PR negative tumours, however, experienced a significantly inferior disease‐free survival than other ER/PR status tumours. Immunohistochemical analyses of ER expression in mammary carcinomas arising in PTEN heterozygous knockout mice did not demonstrate a reduction in ER immunoreactivity, in comparison to wild‐type mice. Our data demonstrate that the PTEN–PKB pathway is abnormal in approximately ⅓ of lymph node negative breast cancer. Dysregulated PTEN‐PKB was also associated with reduced ER/PR expression, but this does not appear to be a simple direct causal relationship. These observations support the contention that dysregulation in PTEN‐PKB contributes to disease progression and hormone resistance of human breast cancer. © 2003 Wiley‐Liss, Inc.
Meat, fish and egg intake and risk of breast cancer
Authors: Holmes Michelle D. , Colditz Graham A. , Hunter David J. , Hankinson Susan E. , Rosner Bernard , Speizer Frank E. , Willett Walter C.
Published: February 2003

Intakes of animal protein, meat, and eggs have been associated with breast cancer incidence and mortality in ecological studies, but data from long‐term prospective studies are limited. We therefore examined these relationships in the Nurses' Health Study. We followed 88,647 women for 18 years, with 5 assessments of diet by food frequency questionnaire, cumulatively averaged and updated over time. We calculated the relative risks (RR) and 95% confidence intervals (95% CI) for risk of developing invasive breast cancer, over categories of nutrient and food intake. During follow‐up, 4,107 women developed invasive breast cancer. Compared to the lowest quintile of intake, the RR and 95% CI for the highest quintile of intake were 1.02 (0.92–1.14) for animal protein, 0.93 (0.83–1.05) for red meat and 0.89 (0.79–1.00) for all meat. Results did not differ by menopausal status or family history of breast cancer. We found no evidence that intake of meat or fish during mid‐life and later was associated with risk of breast cancer. © 2003 Wiley‐Liss, Inc.
PTEN/MMAC1 gene mutation is a rare event in soft tissue sarcomas without specific balanced translocations
Authors: Saito Tsuyoshi , Oda Yoshinao , Kawaguchi Ken‐ichi , Takahira Tomonari , Yamamoto Hidetaka , Tamiya Sadafumi , Tanaka Kazuhiro , Matsuda Shuichi , Sakamoto Akio , Iwamoto Yukihide , Tsuneyoshi Masazumi
Published: February 2003

The tumor suppressor gene PTEN/MMAC1 was identified on chromosome 10q23.3, which is homozygously deleted in many human malignancies. The loss of chromosome 10q was also frequently reported in some types of soft tissue sarcomas. Our study was designed to investigate the frequency of PTEN/MMAC1 gene mutation and to evaluate the role of the PTEN/MMAC1 gene in the tumorigenesis of soft tissue sarcomas without specific balanced translocations. We analyzed 51 cases of soft tissue sarcomas without specific balanced translocations for PTEN/MMAC1 mutations by polymerase chain reaction‐single strand conformation polymorphism and direct sequencing. Mutations in the PTEN/MMAC1 gene were found in only 2 cases (3.9%). Both tumors with PTEN/MMAC1 mutation were leiomyosarcomas arising from the retroperitoneum and inferior vena cava, respectively. Two of 3 leiomyosarcomas arising from the intra‐abdominal cavity examined harbored mutations of this tumor suppressor gene. This result suggests that leiomyosarcomas derived from the intra‐abdominal cavity might have different tumorigenesis from those of an extremity or the trunk, from the viewpoint of PTEN/MMAC1 mutation, although PTEN/MMAC1 gene mutations are rare event in these soft tissue sarcomas. © 2003 Wiley‐Liss, Inc.
Antiproliferative effects of the histone deacetylase inhibitor FR901228 on small‐cell lung cancer lines and drug‐resistant sublines
Authors: Tsurutani Junji , Soda Hiroshi , Oka Mikio , Suenaga Mitsuhiro , Doi Seiji , Nakamura Yoichi , Nakatomi Katsumi , Shiozawa Ken , amada Yasuaki Y , Kamihira Shimeru , Kohno Shigeru
Published: February 2003

FR901228 is a novel histone deacetylase (HDAC) inhibitor, and its antiproliferative effects on non‐small cell lung cancer cells have been shown in vitro. However, there have been no reports concerning the effects on small‐cell lung cancer (SCLC). We have recently demonstrated that the HDAC inhibitors trichostatin A and sodium butyrate inhibit expression of the catalytic subunit of telomerase (hTERT) mRNA and telomerase activity in prostate cancer cells. The present study was designed to evaluate the effects of FR901228 on proliferation and telomerase activity in SCLC cells in vitro. FR901228 at 5 to 10 nM increased the fraction of cells in the G2/M and sub‐G1 phases of the cell‐cycle, and inhibited the growth of H69, H526 and H82 cell lines. The expression of hTERT mRNA was inhibited 6 hr after treatment, prior to obvious inhibition of cell growth or cell‐cycle distribution shifts. The inhibition of hTERT mRNA expression and telomerase activity was not a consequence of cell‐growth arrest or apoptosis. Cycloheximide blocked the suppression of hTERT mRNA induced by FR901228, and the inhibition of hTERT mRNA by FR901228 required newly synthesized proteins. FR901228 also effectively inhibited growth of etoposide‐resistant UMCC‐1/VP‐16, irinotecan‐resistant PC‐6/SN2‐5H and cisplatin‐resistant H526/CDDP cells having decreased expression of hTERT mRNA and telomerase activity, as well as their parental cells. This implies that SCLC resistant to these key drugs are not cross‐resistant to FR901228. The present study suggests that FR901228 may be a promising drug for chemotherapy of cancers including SCLC, even for refractory or relapsing tumors after conventional chemotherapy. © 2003 Wiley‐Liss, Inc.