bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple congenital anomalies associated with in utero exposure of phenytoin: Possible hypoxic ischemic mechanism?
Authors: Lyon Helen M. , Holmes Lewis B. , Huang Taosheng
Published: December 2003

BACKGROUND

The characteristics of the phenotype of the malformed phenytoin‐exposed infant can help to clarify the mechanism of the drug's teratogenesis. One postulated mechanism is vascular disruption.

CASE

An infant who was exposed to phenytoin as monotherapy throughout pregnancy was born with the following abnormalities: midface hypoplasia, digit hypoplasia with syndactyly in the hands and feet, meningomyelocele, talipes equinovarus, and a long skin pedicle on the back. The mother was also exposed to cigarette smoking and alcohol during the pregnancy.

CONCLUSIONS

The malformations of the hands and feet, and the talipes deformity are potential effects of vascular disruption, a postulated fetal effect of both phenytoin and cigarette smoking. The mechanism of the teratogenicity of phenytoin may have included episodes of bradyarrhythmia in the fetus; however, no such episodes were documented. Birth Defects Research (Part A) 67:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Puerto Rican primary physicians' knowledge about folic acid supplementation for the prevention of neural tube defects
Authors: Miranda Ana , Dávila Torres René R. , Gorrín Peralta José J. , Montes De Longo Idalina
Published: December 2003

BACKGROUND

We conducted a study of a group of primary physicians in Puerto Rico to evaluate their knowledge about folic acid supplementation to prevent neural tube defects.

METHOD

The study design was transverse‐correlational. A total of 66 primary physicians in two hospitals (public and private) participated in the study. The sample was nonrandom and opportunistic, and only those physicians present in the hospitals at the moment of distribution of the questionnaires participated. A self‐administered and anonymous questionnaire was used. Descriptive statistics and cross‐tabular analysis were used to describe the results of this study. Inferential statistics were also used, including Chi square and t‐tests to establish the associations/differences between physician knowledge and the independent variables.

RESULTS

Of the participants, 87.9% demonstrated an inadequate knowledge about folic acid supplementation for the prevention of neural tube defects as part of preconception care and only 12.1% demonstrated adequate knowledge. Older physicians had greater knowledge about folic acid. Also, women demonstrated greater knowledge about folic acid than did men. Most of the physicians who always recommend supplementation to their patients demonstrated a greater knowledge about folic acid, and all participants with adequate knowledge came from the public hospital.

CONCLUSIONS

Despite a concerted effort by the Health Department of Puerto Rico to provide education in the importance of folic acid supplementation to reduce the incidence of neural tube defects, primary physicians in two Puerto Rican hospitals generally have not availed themselves of this training and showed a lack of knowledge on this important clinical issue. Birth Defects Research (Part A) 67:000–000, 2003. © 2003 Wiley‐Liss, Inc.
Otto von Guericke und die Kosmologie im 17.?Jahrhundert
Authors: Knobloch Eberhard
Published: December 2003

Otto von Guericke's scientific method was based on reason and experimental science. His cosmology was embedded in theology and can be interpreted as a refutation of Descartes's worldview. He used Nicolaus Cusanus's theory of quantities in order to characterize the space. The notion of space has to be distinguished from that of world or heaven. Forces play a crucial role in this respect described by Kircher in his ‘Celestial journey’. Guericke read this work very diligently. In spite of some obvious similarities between Guericke's and Newton's scientific aims and methods there are crucial differences between the scientific convictions and results of these scholars.
In Situ Investigations of Structure–Activity Relationships in Heteropolyoxomolybdates as Partial Oxidation Catalysts
Authors: Wienold Julia , Timpe Olaf , Ressler Thorsten
Published: December 2003

The structural evolution of Keggin‐type heteropolyoxomolybdates (HPOM) during thermal treatment in propene and in propene and oxygen in the temperature range from 300 to 773 K was investigated by in situ X‐ray diffraction (XRD) and in situ X‐ray absorption spectroscopy (XAS) combined with mass spectrometry. During treatment in propene or hydrogen and at reaction temperatures above 673 K, the initially triclinic H3[PMo12O40]⋅13 H2O is transformed quantitatively into a cubic HPOM (Pn$\bar 3$m, a=11.853 Å) exhibiting a long‐range structure similar to that of the corresponding cesium salts. The treatment described constitutes the first readily available preparation route for a cubic HPOM without alkali metal ions in the structure. For both H3[PMo12O40] and Cs2H[PMo12O40] migration of molybdenum from the Keggin ion onto interstitial sites is proposed to occur in propene or hydrogen at temperatures above about 573 K to give thermally stable, partially reduced lacunary Keggin ions. During activation in propene and oxygen the onset of catalytic activity of H3[PMo12O40] and Cs2H[PMo12O40] at about 573 K correlates with partial reduction of Mo and characteristic changes in the local structure of the Keggin ion. The structural changes observed indicate that, similar to the treatment of the HPOM in propene, migration of molybdenum from the Keggin ions onto interstitial sites and formation of lacunary Keggin ions take place. Moreover, the formation of these partially reduced lacunary Keggin ions appears to be a prerequisite for the material to become an active heterogeneous catalyst. Evidently, the undistorted Keggin ion in the as‐prepared HPOM has to be regarded as a precursor of the active catalyst.
Assembled Dendritic Titanium Catalysts for Enantioselective Hetero‐Diels–Alder Reaction of Aldehydes with Danishefsky's Diene
Authors: Ji Baoming , Yuan Yu , Ding Kuiling , Meng Jiben
Published: December 2003

A new type of dendritic 2‐amino‐2′‐hydroxy‐1,1′‐binaphthyl (NOBIN)‐derived Schiff‐base ligands have been synthesized and applied to the titanium‐catalyzed hetero‐Diels–Alder reaction of Danishefsky's diene with aldehydes. These reactions afforded the corresponding 2‐substituted 2,3‐dihydro‐4H‐pyran‐4‐ones in quantitative yields and with excellent enantioselectivities (up to 97.2 % ee). The disposition of the dendritic wedges and the dendron size in the ligands were found to have significant impact on the enantioselectivity of the reaction. The recovered dendritic catalyst could be reused without further addition of the Ti source or a carboxylic acid additive for at least three cycles, retaining similar activity and enantioselectivity. The high stability of this type of assembled dendritic titanium catalyst may be attributed to the stabilization effect of large‐sized dendron units in the catalyst molecule. The other important phenomenon observed with this catalyst system is that a higher degree of asymmetric amplification has been achieved by attachment of the dendron unit to the chiral ligand, which represents a new advantage of dendrimer catalysts for asymmetric reactions using chiral ligands of lower optical purity.
Palladium‐Catalyzed Highly Regio‐ and Stereoselective Addition of Organoboronic Acids to Allenes in the Presence of AcOH
Authors: Ma Shengming , Jiao Ning , Ye Longwu
Published: December 2003

The Pd0‐catalyzed regio‐ and stereoselective addition of organoboronic acids to allenes leads to stereodefined tri‐ or tetrasubstituted alkenes. Furthermore, this method shows high substitutent‐loading capability and tolerance of various substitutents. A hydropalladation–Suzuki coupling mechanism, which may account for the regio‐ and stereoselectivity, is proposed.
Cover Picture: Structural Basis for Vapoluminescent Organoplatinum Materials Derived from Noncovalent Interactions as Recognition Components (Chem. Eur. J. 24/2003)
Authors: Lu Wei , Chan Michael C. W. , Zhu Nianyong , Che Chi‐Ming , He Zhike , Wong Kwok‐Yin
Published: December 2003

The cover picture shows the crystal packing of the organometallic inclusion complex [(tBu2bpy)Pt(CCpyridyl‐4)2]⋅CH2Cl2 (tBu2bpy=4,4′‐bis‐tert‐butyl‐2,2′‐bipyridine), illustrating infinite “chains” of (CH2Cl2)∞ molecules encapsulated in hydrophobic channels together with the weak noncovalent interactions. These interactions include CH⋅⋅⋅π(CC), CH⋅⋅⋅N(py), Cl⋅⋅⋅Cl, and CH⋅⋅⋅FC interactions, and have been identified in the crystal lattices of this platinum(II) bis(functionalized acetylide) system. These structural features apparently orchestrate the switch‐on vapoluminescent behavior and selectivity of this microporous solid towards VOCs (volatile organic compounds). Further details are given by C. M. Che et al. on p. 6155 ff.
Neuronal and astrocyte expression of nicotinic receptor subunit β4 in the adult mouse brain
Authors: Gahring Lorise C. , Persiyanov Karina , Rogers Scott W.
Published: December 2003

Neuronal nicotinic acetylcholine receptor (nAChR) expression and function are customized in different brain regions through assembling receptors from closely related but genetically distinct subunits. Immunohistochemical analysis of one of these subunits, nAChRβ4, in the mouse brain suggests an extensive and potentially diverse role for this subunit in both excitatory and inhibitory neurotransmission. Prominent immunostaining included: 1) the medial habenula, efferents composing the fasciculus retroflexus, and the interpeduncular nucleus; 2) nuclei and ascending tracts of the auditory system inclusive of the medial geniculate; 3) the sensory cortex barrel field and cell bodies of the ventral thalamic nucleus; 4) olfactory‐associated structures and the piriform cortex; and 5) sensory and motor trigeminal nuclei. In the hippocampus, nAChRβ4 staining was limited to dendrites and soma of a subset of glutamic acid dehydrogenase‐positive neurons. In C57BL/6 mice, but to a lesser extent in C3H/J, CBA/J, or CF1 mice, a subpopulation of astrocytes in the hippocampal CA1 region prominently expressed nAChRβ4 (and nAChRα4). Collectively, these results suggest that the unique functional and pharmacological properties exerted by nAChRβ4 on nAChR function could modify and specialize the development of strain‐specific sensory and hippocampal‐related characteristics of nicotine sensitivity including the development of tolerance. J. Comp. Neurol. 468:322–333, 2004. © 2003 Wiley‐Liss, Inc.
Anatomical evidence for transsynaptic influences of estrogen on brain‐derived neurotrophic factor expression
Authors: Blurton‐Jones M. , Kuan P.N. , Tuszynski M.H.
Published: December 2003

Several studies have demonstrated that estrogen modulates brain‐derived neurotrophic factor (BDNF) mRNA and protein within the adult hippocampus and cortex. However, mechanisms underlying this regulation are unknown. Although an estrogen response element (ERE)‐like sequence has been identified within the BDNF gene, such a classical mechanism of estrogen‐induced transcriptional activation requires the colocalized expression of estrogen receptors within cells that produce BDNF. Developmental studies have demonstrated such a relationship, but to date no studies have examined colocalization of estrogen receptors and BDNF within the adult brain. By utilizing double‐label immunohistochemistry for BDNF, estrogen receptor‐α (ER‐α), and estrogen receptor‐β (ER‐β), we found only sparse colocalization between ER‐α and BDNF in the hypothalamus, amygdala, prelimbic cortex, and ventral hippocampus. Furthermore, ER‐β and BDNF do not colocalize in any brain region. Given the recent finding that cortical ER‐β is almost exclusively localized to parvalbumin‐immunoreactive GABAergic neurons, we performed BDNF/parvalbumin double labeling and discovered that axons from cortical ER‐β‐expressing inhibitory neurons terminate on BDNF‐immunoreactive pyramidal cells. Collectively, these findings support a potential transsynaptic relationship between estrogen state and cortical BDNF: By directly modulating GABAergic interneurons, estrogen may indirectly influence the activity and expression of BDNF‐producing cortical neurons. J. Comp. Neurol. 468:347–360, 2004. © 2003 Wiley‐Liss, Inc.
A note on enrichment functions for modelling crack nucleation
Authors: Bellec J. , Dolbow J. E.
Published: December 2003

For particular discretizations and crack configurations, the enhanced approximations of the eXtended finite‐element method (X‐FEM) cannot accurately represent the discontinuities in the near‐tip displacement fields. In this note, we focus on the particular case where the extent of the crack approaches the support size of the nodal shape functions. Under these circumstances, the asymptotic ‘branch’ functions for each tip may extend beyond the length of the crack, resulting in a non‐conforming approximation. We explain the limitations of the standard approximation for arbitrary discontinuities, and propose a set of adjustments to remedy the deficiencies. We also provide numerical results that demonstrate the advantages of the modified approximation. Copyright © 2003 John Wiley & Sons, Ltd.
Cognitive color
Authors: Derefeldt Gunilla , Swartling Tiina , Berggrund Ulf , Bodrogi Peter
Published: December 2003

This report surveys cognitive aspects of color in terms of behavioral, neuropsychological, and neurophysiological data. Color is usually defined as a color stimulus or as perceived color. In this article, a definition of the concept of cognitive color is formulated. To elucidate this concept, those visual tasks are described where it is relevant: in color categorization, color coding, color naming, the Stroop effect, spatial organization of colored visual objects, visual search, and color memory. © 2003 Wiley Periodicals, Inc. Col Res Appl, 29, 7–19, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10209
Color measurements for pearlescent coatings
Authors: Nadal Maria E. , Early Edward A.
Published: December 2003

This article describes recent developments at the National Institution of Standards and Technology in the colorimetric characterization of pearlescent coatings. The goal of this research is to develop a measurement protocol for the accurate color characterization of these coatings using an understanding of their scattering mechanism as a guide. A large ensemble of bi‐directional reflectance measurements on a series of pearl interference pigmented coatings show general trends in the color variations with illumination and viewing angles. These measurements were used to define a set of geometries (illumination angles of 15°, 45°, and 65° and aspecular angles of 15°, 35°, 45°, 70°, and 85°) to characterize the angle dependent color travel observed in these coatings. © 2003 Wiley Periodicals, Inc. Col Res Appl, 29, 38–42, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10210
A comparison of task pools for dynamic load balancing of irregular algorithms
Authors: Korch Matthias , Rauber Thomas
Published: December 2003

Since a static work distribution does not allow for satisfactory speed‐ups of parallel irregular algorithms, there is a need for a dynamic distribution of work and data that can be adapted to the runtime behavior of the algorithm. Task pools are data structures which can distribute tasks dynamically to different processors where each task specifies computations to be performed and provides the data for these computations. This paper discusses the characteristics of task‐based algorithms and describes the implementation of selected types of task pools for shared‐memory multiprocessors. Several task pools have been implemented in C with POSIX threads and in Java. The task pools differ in the data structures to store the tasks, the mechanism to achieve load balance, and the memory manager used to store the tasks. Runtime experiments have been performed on three different shared‐memory systems using a synthetic algorithm, the hierarchical radiosity method, and a volume rendering algorithm. Copyright © 2004 John Wiley & Sons, Ltd.
Performance and scalability of MPI on PC clusters
Authors: Luecke Glenn R. , Kraeva Marina , Yuan Jing , Spanoyannis Silvia
Published: December 2003

The purpose of this paper is to compare the communication performance and scalability of MPI communication routines on a Windows Cluster, a Linux Cluster, a Cray T3E‐600, and an SGI Origin 2000. All tests in this paper were run using various numbers of processors and two message sizes. In spite of the fact that the Cray T3E‐600 is about 7 years old, it performed best of all machines for most of the tests. The Linux Cluster with the Myrinet interconnect and Myricom's MPI performed and scaled quite well and, in most cases, performed better than the Origin 2000, and in some cases better than the T3E. The Windows Cluster using the Giganet Full Interconnect and MPI/Pro's MPI performed and scaled poorly for small messages compared with all of the other machines. Copyright © 2004 John Wiley & Sons, Ltd.
Kinetics of Oxidation of Azide by [Ethylenebis(biguanide)]silver(III) in Aqueous Acidic Media
Authors: Bandyopadhyay Prabir , Dhar Basab Bijayi , Bhattacharyya Jhimli , Mukhopadhyay Subrata
Published: December 2003

In aqueous acidic media sodium azide and the orange‐yellow title complex react quantitatively generating N2 gas along with a colourless solution of Ag+ ion and the ligand, ethylenebis(biguanide). The parent complex, [Ag(H2L)]3+, and one of its conjugate bases, [Ag(HL)]2+, participate in the reaction with N3− as the kinetically reactive reductant. Ag+ has no catalytic effect. At 25.0 °C, I = 1.0 M (NaNO3), rate constants for the reactions [Ag(H2L)]3+ + N3− and that for [Ag(HL)]2+ + N3− are (12.3±0.5) and (3.8±0.6) M−1·s−1, respectively. The high rate constants along with the very low equilibrium constant (10−15 M−1) calculated for the first reaction strongly suggest inner‐sphere redox mechanism. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The First Stable Monomeric Triaminostannane of Composition [(Me3Si)3CSn(NHtBu)3] Containing Three Substituted NH Groups
Authors: Janssen Jörg , Schmidt Hans‐Georg , Noltemeyer Mathias , Roesky Herbert W.
Published: December 2003

Triaminostannanes of secondary amines have been known since 1977 and are widely used in tin organic chemistry. However, the corresponding nitrogen substituted stannanes of primary amines are not cited in the literature. Herein we report on the ammonolysis reaction of [(Me3Si)3CSnCl3] with tBuNH2 in the presence of a strong base and the X‐ray structural analysis of [(Me3Si)3CSn(NHtBu)3], the first monomeric triaminostannane containing protons at the nitrogen atoms. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
The Isoelectronic Replacement of E = P+ and Si in the Trinuclear Organotin−Oxo Clusters [Ph2E(OSntBu2)2O·tBu2Sn(OH)2]
Authors: Beckmann Jens , Dakternieks Dainis , Duthie Andrew , Jurkschat Klaus , Mehring Michael , Mitchell Cassandra , Schürmann Markus
Published: December 2003

The trinuclear organotin−oxo cluster [Ph2P(OSntBu2)2O· tBu2Sn(OH)2][O3SCF3] (6), was prepared in good yield by the consecutive reaction of (tBu2SnO)3 with F3CSO3H and Ph2PO2H, and adopts a common tricyclic ESn3O3X2 structural motif with E = P; X = OH, similar to those found in the recently reported species [M(OSntBu2)2O·tBu2Sn(OH)2] [M = Ph2Si (1), Me2Si (2), CO (3), MesB (4)] and [Ph2Si(OSntBu2)2O·tBu2SnF2] (5) where E = Si, C, B and X = OH, F. Compound 6 was characterized by multinuclear NMR spectroscopy, IR spectroscopy, electrospray mass spectrometry and single‐crystal X‐ray diffraction analysis. A natural population analysis (NPA) performed on the B3LYP/LANL2DZ level of theory for the molecular structures of the isoelectronic species [Ph2Si(OSntBu2)2O·tBu2Sn(OH)2] (1) and [Ph2P(OSntBu2)2O·tBu2Sn(OH)2]+ (6a) suggests that the positive charge of the latter is partially delocalised over the phenyl rings. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Analysis of Coordination and Organometallic Compounds Using Photoionisation Mass Spectrometric Techniques
Authors: Dorcier Antoine , Dyson Paul J. , McIndoe J. Scott
Published: December 2003

A range of coordination and organometallic compounds have been analysed by quadrupole ion‐trap mass spectrometry using various photoionisation methods. Atmospheric‐pressure photo ionisation (APPI), which combines atmospheric‐pressure chemical ionisation (APCI) with a photolysis lamp, was compared with the new technique photo‐assisted electrospray ionisation (PAESI). Additionally, the atmospheric‐pressure matrix‐assisted laser desorption ionisation (AP‐MALDI) was also evaluated and compared to MALDI quadrupole ion‐trap time‐of‐flight (MALDI‐QIT‐TOF) mass spectrometry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Non‐Oxo Vanadium(IV) Complexes of Aminebis(phenolate) [O,N,O] Donor Ligands and Solution Studies of Isostructural VIV and MnIV Complexes (Eur. J. Inorg. Chem. 24/2003)
Authors: Paine Tapan K. , Weyhermüller Thomas , Bill Eckhard , Bothe Eberhard , Chaudhuri Phalguni
Published: December 2003

The cover picture shows the multiple characterization methods used to unravel the electronic and geometrical structures of the unit MAIIIMBII, in which three oximato groups (=N−O)− are present as bridging ligands. Variable‐temperature magnetic susceptibility and EPR measurements provide a consistent answer to the question of electronic ground states for different heterometallic combinations. Mößbauer spectroscopy helps to differentiate between the species CoIII(l.s.)FeII(l.s.) and FeII(h.s.)CoIII(l.s.). Details on the preparation and characterization of the species FeIIIMII and related heterometallic compounds are presented in the article by P. Chaudhuri et al. on p. 4299 ff.
Rational Design of Cesium‐Selective Ionophores: Dihydrocalix[4]arene Crown‐6 Ethers
Authors: Sachleben Richard A. , Bryan Jeffrey C. , Engle Nancy L. , Haverlock Tamara J. , Hay Benjamin P. , Urvoas Agathe , Moyer Bruce A.
Published: December 2003

Molecular mechanics calculations performed on calix[4]arene crown‐6 ethers predict that the 1,3‐dihydro derivatives will exhibit greater complementarity for potassium and cesium ions than the parent 1,3‐bis(alkyloxy) calixcrowns. The X‐ray crystal structures of 1,3‐alt‐bis(octyloxy)calix[4]arene benzocrown‐6 ether, dihydrocalix[4]arene benzocrown‐6 ether, and the cesium nitrate complex of dihydrocalix[4]arene benzocrown‐6 ether were determined. The structure of the cesium complex corresponds closely to the structure predicted by molecular mechanics. The dihydrocalix[4]arene crown‐6 ethers exhibit enhanced cesium selectivity in the extraction of alkali‐metal salts. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Ring Contraction of 3,6‐Dihydro‐2H‐thiopyrans to Thiolanes by an Iodo‐Oxyacylation Reaction
Authors: Lucassen Andre C. B. , Zwanenburg Binne
Published: December 2003

Reaction of functionalized 3,6‐dihydro‐2H‐thiopyrans with N‐iodosuccinimide in the presence of carboxylic acids results in the stereospecific formation of poly‐functionalised thiolanes in good yield. The formation of these thiolanes is believed to proceed through either a nucleophilic or an electrophilic pathway leading to 4,5‐cis‐substituted derivatives. The use of unsymmetrical 2,2‐substituted 3,6‐dihydro‐2H‐thiopyrans gave mixtures of isomers that could be separated in several cases. From a 3‐substituted thiopyran a 2,2,3,4,5‐pentasubstituted thiolane was obtained. Attempts to use alcohols as external nucleophiles were unsuccessful with NIS, NBS, and N‐bromoacetamide. Iodo‐azidination with in situ generated IN3 was also unsuccessful. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Threefold Bridged p‐tert‐Butylcalix[9]arene Triphosphate
Authors: Gloede Jörg , Ozegowski Sigrid , Costisella Burkhard , Gutsche C. David
Published: December 2003

p‐tert‐Butylcalix[9]arene 1 reacts with phosphorus pentachloride and then with water to give the p‐tert‐butylcalix[9]arene triphosphate 5, representing the first bridged calix[9]arene derivative to be described in the literature. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
An Efficient Method for the Large‐Scale Preparation of 3‐O‐Acetyl‐11‐oxo‐β‐boswellic Acid and Other Boswellic Acids
Authors: Jauch Johann , Bergmann Jochen
Published: December 2003

3‐O‐Acetyl‐11‐oxo‐β‐boswellic acid (AKBA), found in incense, is a potent inhibitor of 5‐lipoxygenase, p38 and p42 MAP kinase and topoisomerases. Starting from crude extracts from incense, procedures are presented for the efficient large‐scale synthesis of AKBA and other boswellic acids (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Preparation of Multiply Protected Alkylhydrazine Derivatives by Mitsunobu and PTC Approaches
Authors: Brosse Nicolas , Pinto Maria‐Fatima , Jamart‐Grégoire Brigitte
Published: December 2003

Alkylation reactions of hydrazine derivatives by Mitsunobu or PTC approaches are described. It has been shown that aminophthalimide derivatives are better acidic partners than their aminoimidodicarbonate (NBoc2) analogues, the presence of the phthaloyl group increasing the acidity of the sole proton and concomitantly reducing steric hindrance. Moreover, N‐aminophthalimide derivatives can be efficiently converted into the corresponding N‐amino‐imidodicarbonates by a three‐stage, one‐flask procedure under very mild conditions. These procedures can also be efficiently used for the preparation of orthogonally Nα,Nβ‐diprotected α‐hydrazino esters. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Stereoselective Synthesis of C‐ and N‐Ketosides by Lewis Acid‐Catalyzed C‐ and N‐Glycosidation of Alkynyl, Phenyl, and Methyl Ketoses
Authors: Gómez Ana M. , Uriel Clara , Jarosz Slawomir , Valverde Serafín , López J. Cristóbal
Published: December 2003

C‐Ketosides can be prepared conveniently, in a stereoselective manner, from alkynyl, phenyl and methyl glucopyranose hemiketals by reaction with carbon nucleophiles in the presence of Lewis acids. The reaction of the hemiketals with trimethylsilyl azide provides an efficient route to the corresponding N‐ketopyranosides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Deslipping of Ester Rotaxanes: A Cooperative Interplay of Hydrogen Bonding with Rotational Barriers
Authors: Linnartz Petra , Bitter Stephan , Schalley Christoph A.
Published: December 2003

A series of rotaxanes has been synthesized which contain two ester groups in their axles. All rotaxanes bear the same tetralactam wheel. The kinetics of the de‐slipping reaction of these rotaxanes were monitored in tetrachloroethane (TCE) and dimethyl sulfoxide (DMSO) resulting in the observation of a significant solvent effect. In TCE, two isomeric rotaxanes that differ merely with respect to the orientation of the ester groups show a remarkable difference in their deslipping behavior. When the ester carbonyl group is directly attached to the axle center piece, the rotaxane decomposes with a half life of ca. 10 h at 100 °C. The reverse orientation with the carbonyl group attached to the stopper blocks deslipping almost completely and a lower limit for the half life at 100 °C of 25,000 h was obtained. These results can be interpreted by inferring a cooperative action of hydrogen bonding between wheel and axle and differences in rotational barriers. Molecular modeling and AM1 calculations support this interpretation. The implications of these results for the determination of steric size and the optimization of molecular machines are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Elucidation of the Solution Conformations of Loloatin C by NMR Spectroscopy and Molecular Simulation
Authors: Chen Heru , Haynes Richard K. , Scherkenbeck Jürgen , Sze Kong H. , Zhu Guang
Published: December 2003

NMR experiments combined with molecular simulation with X‐PLOR have been employed to determine the solution conformation of the cyclic decapeptide loloatin C in three different solutions. In DMSO, the molecule possesses a hydrophobic aromatic “wall” consisting of Trp6 and Phe7, and a type I β‐turn structure involving Val1, Trp10, Asp9 and Asn8 with a hydrophobic head at Val1/Trp10 and a hydrophilic tail at Asp9 and Asn8; another type II′ β‐turn was also located between Leu3, Tyr4, Pro5, and Trp6. In 70/30 [D3]TFE/H2O, however, loloatin C possesses a dumbbell structure with all the hydrophobic side chains projecting upward on one side, forming a hydrophobic surface, and the hydrophilic side chains projecting to the other side, together with most of carbonyl oxygen atoms, thereby forming a hydrophilic surface. However, in 30:70 [D3]TFE/H2O, loloatin C possesses an inverse γ‐turn incorporating Tyr4, Pro5, and Trp6, a hydrophobic zone involving the side chains of Leu3, Trp6, Trp10, and Phe7 and a hydrophilic tail involving the hydrophilic side chains of Orn2, Asn8, and Asp9. The amphiphilicity of the dumbbell structure in 70/30 [D3]TFE/H2O is of interest in relation to the antibiotic activity of loloatin C. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis of Cyclic Hexapeptides Based on the Antibiotic Cyclic Decapeptide Loloatin C by an in situ Indirect Cyclization Method
Authors: Chen Heru , Haynes Richard K. , Scherkenbeck Jürgen
Published: December 2003

Three cyclic hexapeptide units based on the parent loloatin C scaffold have been identified by a ‘sliding window’ method as part of an expeditious SAR search for the basis of the antibiotic activity of the loloatins. Modified Fmoc‐based solid‐phase synthesis was used to prepare cyclic(L‐valyl‐Lornithyl‐D‐phenylalanyl‐L‐asparaginyl‐L‐aspartyl‐L‐tryptophanyl) and cyclic(L‐valyl‐L‐ornithyl‐L‐leucyl‐L‐tryptophanyl‐D‐phenylalanyl‐L‐asparaginyl) in overall yields of 42%−47%. A new solution method combined with an in situ indirect cyclization was specifically developed to prepare cyclic(L‐ornithyl‐L‐leucyl‐D‐tyrosyl‐L‐prolyl‐L‐tryptophanylD‐phenylalanyl), involving cyclization of the linear peptide through the amino group in leucine, liberated selectively from the Fmoc‐protected amine in situ, with the activated p‐nitrophenyl ester of ornithine. The method was also effectively used for cyclization of the linear precursors of the first two cyclic hexapeptides. NOE analyses coupled with peptide backbone modelling were used to establish conformations of the target compounds. All have helix‐like structures with γ‐turns. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Synthesis and Water Solubility of Novel Fullerene Bisadduct Derivatives
Authors: Bosi Susanna , Feruglio Luigi , Milic Dragana , Prato Maurizio
Published: December 2003

The synthesis of four classes of bisadduct derivatives of C60 is reported. The solubility of the new compounds in aqueous solvents is enhanced and is among the highest ever reported for fullerene derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Novel D‐Secoestrone Isoquinuclidines by an Unpredicted Iminium Ion‐Induced 1,5‐Hydride Shift
Authors: Wölfling János , Frank Éva , Schneider Gyula , Tietze Lutz F.
Published: December 2003

Unique 9,13‐bridged D‐secoestrone alkaloids have been synthesized and structurally characterized. Treatment of 3‐methoxy‐16,17‐secoestra‐1,3,5(10)‐trien‐17‐al (6a) with aniline (7) or substituted aniline derivatives 8−28 in the presence of different Lewis and Brønsted acids produces the bridged azaestrone derivatives 51−67 and the alkenes 68−73 in high yields in a domino‐type process. The imines 29−50 are proposed as intermediates, undergoing 1,5‐hydride shifts via the iminium ion salts 75 to give the cations 77, which, depending on the substitution pattern on the aniline moiety, either afford the bridged compounds through a nucleophilic addition of the formed secondary amine to the benzylic carbocation or give the alkenes through the abstraction of a proton at C‐8. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Chalcogeno Morita−Baylis−Hillman Reaction of 2‐(Methylchalcogeno)phenyl Vinyl Ketones with Aldehydes, Ketones, and α‐Dicarbonyl Compounds
Authors: Kinoshita Hironori , Kinoshita Sayaka , Munechika Yukari , Iwamura Tatsunori , Watanabe Shin‐ichi , Kataoka Tadashi
Published: December 2003

Reactions of 2‐(methylchalcogeno)phenyl vinyl ketones 1 and 4 with aldehydes 5 were conducted in the presence of BF3·Et2O. The reaction was quenched by addition of Et3N and gave the Morita−Baylis−Hillman adducts 6−7 in good yields. When the reaction mixture of 1 with 5a was worked up with saturated aqueous NaHCO3, the sulfonium salt 8a was obtained together with 6. Ketones 10, α‐diketones, and α‐oxo esters 13, which hardly react in the traditional Morita−Baylis−Hillman reaction, similarly reacted with 2‐(methylchalcogeno)phenyl vinyl ketones 1 and 4 to give the Morita−Baylis−Hillman adducts 11−12 and 14−15. Selenochromanones 9 and 16 were obtained together with 7 and 15 from reactions of seleno derivative 4, with 5 and 13 as by‐products. The formation mechanism for the sulfonium salt syn‐trans‐8a is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Organic Chemistry of Vitamin D Analogues (Deltanoids)
Authors: Posner Gary H. , Kahraman Mehmet
Published: December 2003

An increasing number of synthetic vitamin D analogues (deltanoids) are now being used as sensitive molecular biology probes and also as new drug candidates and new drugs for treatment of various human diseases. The design and stereocontrolled synthesis of such new deltanoids are guided by considering catabolism inhibition and by using large steroidal chirons and small steroid‐derived chirons. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Synthesis and Water Solubility of Novel Fullerene Bisadduct Derivatives (Eur. J. Org. Chem. 24/2003)
Authors: Bosi Susanna , Feruglio Luigi , Milic Dragana , Prato Maurizio
Published: December 2003

The cover picture shows water‐soluble fullerene derivatives floating in the Trieste bay, Italy, with the magnificent Miramare Castle, built between 1856 and 1860 by Maximilian of Habsburg, in the background. Details of the synthesis and water solubility of novel fullerene bisadduct derivatives are discussed in the article by M. Prato et al. on p. 4741 ff.
Carbon nanotubes as separation carrier in capillary electrophoresis
Authors: Wang Zonghua , Luo Guoan , Chen Jianfang , Xiao Sufang , Wang Yiming
Published: December 2003

The utility and versatility of carboxylic single‐walled carbon nanotubes (c‐SWNT) in capillary electrophoresis (CE) is demonstrated, using as model solutes homologues and structural isomers. In the case of homologues of caffeine and theobromine, distinct changes in the electrophoretic parameters occur at a critical concentration of c‐SWNT in the run buffer. It is suggested that the c‐SWNT of a definite concentration could form a network in the run buffer as a pseudostationary phase on the basis of the unique tubule structure, providing a different separation from sodium dodecyl sulfate (SDS) micelles. In the case of structural isomers of catechol and hydroquinone, differing from the homologues, it is mainly attributable to the functional groups on the c‐SWNT that have an effect on the electrophoretic behaviors by forming intermolecular hydrogen bonding with analytes. Furthermore, aggregated c‐SWNT serve as anticonvective media and minimize solute diffusion contributing to zone broadening. The presence of charged c‐SWNT suppressed the electrodiffusion and decreased the adsorption between capillary wall and solutes, which led to better peak shapes of isomers.
A novel thermogelling matrix for microchannel DNA sequencing based on poly‐N‐alkoxyalkylacrylamide copolymers
Authors: Kan Cheuk‐Wai , Doherty Erin A. S. , Barron Annelise E.
Published: December 2003

We have developed a novel class of thermogelling polymer networks based on poly‐N‐alkoxyalkylacrylamides, and demonstrated their use as DNA sequencing matrices for high‐throughput microchannel electrophoresis in capillary arrays. Polymers and copolymers of N‐ethoxyethylacrylamide (NEEA) and N‐methoxyethylacrylamide (NMEA) were synthesized by aqueous‐phase free‐radical polymerization and characterized by tandem gel permeation chromatography‐multi‐angle laser light scattering. These copolymer matrices exhibit “re‐entrant”‐type volume phase transitions, forming entangled networks with high shear viscosity at low (< 20°C) and high (> 35°C) temperatures, and undergoing a “coil‐to‐globular”, lower critical solution temperature (LCST)‐like phase transition over an intermediate temperature range (20–35°C). Hence, matrix viscosity is relatively low at room temperature (25°C), and increases rapidly above 35°C. The material properties and phase behavior of these thermogelling polymer networks were studied by steady‐shear rheometry. These matrices are easily loaded into capillary arrays at room temperature while existing as viscous fluids, but thermogel above 35°C to form transparent hydrogels via a thermo‐associative phase transition. The extent of the intermediate viscosity drop and the final viscosity increase depends on the composition of the copolymers. DNA sequencing by capillary array electrophoresis with four‐color laser‐induced fluorescence (LIF) detection shows that these thermogelling networks provide enhanced resolution of both small and large DNA sequencing fragments and longer sequencing read lengths, in comparison to appropriate control (closely related, nonthermogelling) polymer networks. In particular, a copolymer comprised of 90% w/w NMEA and 10% w/w NEEA, with a molecular mass of ∼ 2 MDa, delivers around 600 bases at 98.5% base‐calling accuracy in 100 min of electrophoresis.
Modulation of plasma lipid levels affects benzo[a]pyrene‐induced DNA damage in tissues of two hyperlipidemic mouse models
Authors: Curfs Daniëlle M.J. , Beckers Linda , Godschalk Roger W.L. , Gijbels Marion J.J. , van Schooten Frederik J.
Published: December 2003

The role of plasma lipids in the uptake, transportation, and distribution of lipophilic carcinogens like benzo[a]pyrene (B[a]P) remains unclear. Therefore, we studied the effects of dietary‐modulated plasma lipids on B[a]P‐induced DNA damage in several organs of two hyperlipidemic mouse models. Male apolipoprotein E (ApoE)*3‐Leiden (n = 22) and ApoE knockout (ApoE‐KO) mice (n = 20) were fed a high‐fat cholesterol (HFC) diet or low‐fat cholesterol (LFC; standard mouse chow) diet for 3 weeks, after which the animals were exposed to a single oral dose of 5 mg/kg bw B[a]P or vehicle and killed 4 days later. Plasma lipids were determined and DNA adducts were measured in aorta, heart, lung, liver, brain, and stomach. Total cholesterol and low‐density lipoprotein (LDL) cholesterol were increased in all animals on a HFC diet, whereas a decrease of triglycerides was seen only in the ApoE‐KO mice. In ApoE‐KO mice on a normal diet, DNA‐adduct levels were highest in aorta (10.8 ± 1.4 adducts/108 nucleotides), followed by brain (7.8 ± 1.3), lung (3.3 ± 0.7), heart (3.1 ± 0.6), liver (1.5 ± 0.2) and stomach (1.2 ± 0.2). In the ApoE*3‐Leiden mice, adduct levels were equally high in aorta, heart, and lung (4.6 ± 0.7, 5.0 ± 0.5 and 4.6 ± 0.4, respectively), followed by stomach (2.7 ± 0.4), brain (2.3 ± 0.2), and liver (1.7 ± 0.2). In the ApoE‐KO mice, the HFC diet intervention resulted in lower adduct levels in lung (2.1 ± 0.2), heart (1.9 ± 0.2), and brain (2.9 ± 0.5), as compared with the LFC group. In contrast, a nonsignificant increase of adducts was found in aorta (13.1 ± 1.5). A similar but nonsignificant trend was observed in the ApoE*3‐Leiden mice. Multiple regression analysis showed that in aorta, DNA adducts were inversely related to plasma triglycerides (P = 0.004) and were also modulated by the ApoE genotype (P < 0.001). The results of the present study support further investigation into the role of dietary modulation of plasma lipids, ApoE, and polycyclic aromatic hydrocarbon exposure on the formation of DNA adducts in chronic degenerative diseases. Environ. Mol. Mutagen. 42:243–249, 2003. © 2003 Wiley‐Liss, Inc.
Barium chromate is cytotoxic and genotoxic to human lung cells
Authors: Wise Sandra S. , Schuler Julie H.C. , Katsifis Spiros P. , Wise John Pierce
Published: December 2003

Hexavalent chromium (Cr(VI)) compounds are widely accepted as human lung carcinogens. However, there have been few investigations of the genotoxicity of Cr(VI) in human lung cells. Moreover, our knowledge of the effects of Cr(VI) in human lung cells is further limited because the available data generally focus on the effects of only lead chromate (PbCrO4) and sodium chromate (Na2CrO4). To fully understand these carcinogenic compounds, the genotoxic effects to its target cells need to be evaluated for additional Cr(VI) salts. Accordingly, we investigated the cytotoxicity and clastogenicity of barium chromate (BC) in a human lung cell culture model (WTHBF‐6 cells). We found that BC induced concentration‐dependent cytotoxicity in WTHBF‐6 cells, with relative survival of 88%, 74%, 67%, 12%, 3%, and 0.1% after exposure to 0.01, 0.05, 0.1, 0.5, 1, and 5 μg/cm2 BC, respectively. Similarly, the amount of chromosomal damage also increased with concentration after a 24‐h exposure. Specifically, 0.01, 0.05, 0.1, and 0.5 μg/cm2 BaCrO4 damaged 5%, 9%, 22%, and 49% of metaphase cells, with the total damage reaching 5, 10, 28, and 65 aberrations per 100 metaphases, respectively. Concentrations of 1 and 5 μg/cm2 BC induced a profound cell cycle delay, and no metaphases were observed. The spectrum of damage included chromatid and chromosome‐type lesions consistent with mechanistic events associated with the activation of oncogenes and inactivation of tumor suppressor genes. Overall the data indicate that BC is cytotoxic and genotoxic to human lung cells. Environ. Mol. Mutagen. 42:274–278, 2003. © 2003 Wiley‐Liss, Inc.
Life under the “Cold Skin”
Authors: Spindler Michael , Gradinger Rolf
Published: December 2003

The Arctic sea ice is the habitat of an astonishing abundance of plant and animal life. These biocenoses have a momentous impact on the polar ecosystem
Cluster analysis of fMRI data using dendrogram sharpening
Authors: Stanberry Larissa , Nandy Rajesh , Cordes Dietmar
Published: December 2003

The major disadvantage of hierarchical clustering in fMRI data analysis is that an appropriate clustering threshold needs to be specified. Upon grouping data into a hierarchical tree, clusters are identified either by specifying their number or by choosing an appropriate inconsistency coefficient. Since the number of clusters present in the data is not known beforehand, even a slight variation of the inconsistency coefficient can significantly affect the results. To address these limitations, the dendrogram sharpening method, combined with a hierarchical clustering algorithm, is used in this work to identify modality regions, which are, in essence, areas of activation in the human brain during an fMRI experiment. The objective of the algorithm is to remove data from the low‐density regions in order to obtain a clearer representation of the data structure. Once cluster cores are identified, the classification algorithm is run on voxels, set aside during sharpening, attempting to reassign them to the detected groups. When applied to a paced motor paradigm, task‐related activations in the motor cortex are detected. In order to evaluate the performance of the algorithm, the obtained clusters are compared to standard activation maps where the expected hemodynamic response function is specified as a regressor. The obtained patterns of both methods have a high concordance (correlation coefficient = 0.91). Furthermore, the dependence of the clustering results on the sharpening parameters is investigated and recommendations on the appropriate choice of these variables are offered. Hum. Brain Mapping 20:201–219, 2003. © 2003 Wiley‐Liss, Inc.
An empirical comparison of EQ‐5D and SF‐6D in liver transplant patients
Authors: Longworth Louise , Bryan Stirling
Published: December 2003

There remains disagreement about the preferred utility‐based measure of health‐related quality of life for use in constructing quality‐adjusted life years (QALYs). The recent development of a new measure, the SF‐6D, has highlighted this issue. The SF‐6D and EuroQol EQ‐5D measure health‐related utilities on a scale where 0 represents death and 1 represents full health, and both have utility scores generated from random samples of the general UK population. This study explored whether, in a large sample of liver transplant patients, the two instruments provide similar results. The empirical data highlight important variation in the results generated from the use of the two instruments. The data are consistent with a view that the SF‐6D does not describe health states at the lower end of the utility scale but is more sensitive than EQ‐5D in detecting small changes towards the top of the scale. Copyright © 2003 John Wiley & Sons, Ltd.
Classical versus relational approaches to understanding controls on a contract with independent GPs in South Africa
Authors: Palmer Natasha , Mills Anne
Published: December 2003

Contracts have played a central role in public sector reforms in developed countries over the last decade, and research increasingly highlights their varied nature. In low and middle income countries the use of contracts is encouraged but little attention has been paid to features of the setting that may influence their operation. A qualitative case study was used to examine different dimensions of a contract with private GPs in South Africa. Features of the contract are compared with the notions of classical and relational contracts. Formal aspects of the contract such as design, monitoring and resort to sanctions were found to offer little control over its outcome. The relational rather than classical model of contracting offered a more meaningful framework of analysis, with social and institutional factors found to play an important role. In particular, the individual nature of GP practices highlighted the role played by individual motivation where a contract exercised little formal control. Due to the similarity of factors likely to be present, results are argued to be relevant in many other LMIC settings, and policy‐makers considering contracts for clinical services are advised to consider the possibility of experiencing a similar outcome. Copyright © 2003 John Wiley & Sons, Ltd.
An experiment on simplifying conjoint analysis designs for measuring preferences
Authors: Maddala Tara , Phillips Kathryn A. , Reed Johnson F.
Published: December 2003

In conjoint analysis (CA) studies, choosing between scenarios with multiple health attributes may be demanding for respondents. This study examined whether simplifying the choice task in CA designs, by using a design with more overlap of attribute levels, provides advantages over standard minimal‐overlap methods. Two experimental conditions, minimal and increased‐overlap discrete choice CA designs, were administered to 353 respondents as part of a larger HIV testing preference survey. In the minimal‐overlap survey, all six attribute levels were allowed to vary. In the increased‐overlap survey, an average of two attribute levels were the same between each set of scenarios. We hypothesized that the increased‐overlap design would reduce cognitive burden, while minimally impacting statistical efficiency. We did not find any significant improvement in consistency, willingness to trade, perceived difficulty, fatigue, or efficiency, although several results were in the expected direction. However, evidence suggested that there were differences in stated preferences. The results increase our understanding of how respondents answer CA questions and how to improve future surveys. Copyright © 2003 John Wiley & Sons, Ltd.