bluuebunny/crossref_metadata_2025 huggingface dataset:
A MODEL FOR THE OPTIMAL ASSET-LIABILITY MANAGEMENT FOR INSURANCE COMPANIES
Authors: SBARAGLIA S. , PAPI M. , BRIANI M. , BERNASCHI M. , GOZZI F.
Published: May 2003

This paper is devoted to the formulation of a model for the optimal asset-liability management for insurance companies. We focus on a typical guaranteed investment contract, by which the holder has the right to receive after T years a return that cannot be lower than a minimum predefined rate rg. We take account of the rules that usually are imposed to insurance companies in the management of this funds as reserves and solvency margin. We formulate the problem as a stochastic optimization problem in a discrete time setting comparing this approach with the so-called hedging approach. The utility function to maximize depends on various parameters including specific goals of the company management.

Some preliminary numerical results are reported to ease the comparison between the two approaches.
A FAMILY OF MODELS EXPLAINING THE LEVEL-SLOPE-CURVATURE EFFECT
Authors: FORZANI LILIANA , TOLMASKY CARLOS
Published: May 2003

One of the most widely used methods to build yield curve models is to use principal components analysis on the correlation matrix of the innovations. R. Litterman and J. Scheinkman found that three factors are enough to explain most of the moves in the case of the US treasury curve. These factors are level, steepness and curvature. Working in the context of commodity futures, G. Cortazar and E. Schwartz found that the spectral structure of the correlation matrices is strikingly similar to those found by R. Litterman and J. Scheinkman. We observe that in both cases the correlation between two different contracts maturing at times t and s is roughly of the form ρ|t-s|, for a certain (fixed) 0 ≤ ρ ≤ 1. Assuming this correlation structure we prove that the observed factors are perturbations of cosine waves and we extend the analysis to multiple curves.
AN ADAPTIVE METHOD FOR EVALUATING MULTIDIMENSIONAL CONTINGENT CLAIMS: PART I
Authors: DAHL LARS O.
Published: May 2003

The paper presents an adaptive method for the evaluation of multidimensional integrals over the unit cube. The measure used to partition the domain is suited for integrands which are monotonic in each dimension individually, and is therefore suitable for problems stemming from finance where this is often the case. We use a QMC method for each sub-problem resulting from the partitioning of the domain. The article is part one of a work on this topic, and presents the method together with various local variance reduction techniques. The material is presented with an alignment to option pricing problems. In the companion paper we present an option pricing problem and simulation results on different setups of this. We compare the convergence properties of the adaptive method with the convergence properties of the QMC method used directly on the problem. We find that the adaptive method in many configurations outperform the conventional QMC method, and we develop criteria on the problem for when the adaptive method can be expected to outperform the conventional.
Postinfarction Treatment With an Adenoviral Vector Expressing Hepatocyte Growth Factor Relieves Chronic Left Ventricular Remodeling and Dysfunction in Mice
Authors: Li Yiwen , Takemura Genzou , Kosai Ken-ichiro , Yuge Kentaro , Nagano Satoshi , Esaki Masayasu , Goto Kazuko , Takahashi Tomoyuki , Hayakawa Kenji , Koda Masahiko , Kawase Yukinori , Maruyama Rumi , Okada Hideshi , Minatoguchi Shinya , Mizuguchi Hiroyuki , Fujiwara Takako , Fujiwara Hisayoshi
Published: May 2003

Background—

Hepatocyte growth factor (HGF) is implicated in tissue regeneration, angiogenesis, and antiapoptosis. However, its chronic effects are undetermined on postinfarction left ventricular (LV) remodeling and heart failure.

Methods and Results—

In mice, on day 3 after myocardial infarction (MI), adenovirus encoding human HGF (Ad.CAG-HGF) was injected into the hindlimb muscles (n=13). As a control (n=15), LacZ gene was used. A persistent increase in plasma human HGF was confirmed in the treated mice: 1.0±0.2 ng/mL 4 weeks later. At 4 weeks after MI, the HGF-treated mice showed improved LV remodeling and dysfunction compared with controls, as indicated by the smaller LV cavity and heart/body weight ratio, greater % fractional shortening and LV ±dP/dt, and lower LV end-diastolic pressure. The cardiomyocytes near MI, including the papillary muscles and trabeculae, were greatly hypertrophied in the treated mice. The old infarct size was similar between the groups, but the infarct wall was thicker in the treated mice, where the density of noncardiomyocyte cells, including vessels, was greater. Fibrosis of the ventricular wall was significantly reduced in them. Examination of 10-day-old MI revealed no proliferation or apoptosis but showed augmented expression of c-Met/HGF receptor in cardiomyocytes near MI, whereas a greater proliferating activity and smaller apoptotic rate of granulation tissue cells in the HGF-treated hearts was observed compared with controls.

Conclusions—

Postinfarction HGF gene therapy improved LV remodeling and dysfunction through hypertrophy of cardiomyocytes, infarct wall thickening, preservation of vessels, and antifibrosis. These findings imply a novel therapeutic approach against postinfarction heart failure.
Variants of Toll-Like Receptor 4 Modify the Efficacy of Statin Therapy and the Risk of Cardiovascular Events
Authors: Boekholdt S. Matthijs , Agema Willem R.P. , Peters Ron J.G. , Zwinderman Aeilko H. , van der Wall Ernst E. , Reitsma Pieter H. , Kastelein John J.P. , Jukema J. Wouter
Published: May 2003

Background—

Atherosclerosis is increasingly considered to be a chronic inflammatory process. We examined whether genetic variants of the toll-like receptor 4 (TLR4), which are correlated with impaired innate immunity and with progression of carotid atherosclerosis, are also associated with coronary atherosclerosis and predict the risk of cardiovascular events.

Methods and Results—

Two polymorphisms of the TLR4 gene (Asp299Gly and Thr399Ile) were determined in 655 men with angiographically documented coronary atherosclerosis. All patients participated in a prospective cholesterol-lowering trial evaluating the effect on coronary artery disease and were randomly assigned to either pravastatin or placebo for 2 years. There were no significant differences between genetically defined subgroups with respect to baseline risk factors, treatment, or in-trial changes of lipid, lipoprotein, or angiographic measurements. Genotype was not associated with progression of atherosclerosis. In the pravastatin group, 299Gly carriers had a lower risk of cardiovascular events during follow-up than noncarriers (2.0% versus 11.5%,
P
=0.045). Among noncarriers, pravastatin reduced the risk of cardiovascular events from 18.1% to 11.5% (
P
=0.03), whereas among 299Gly carriers this risk was strikingly reduced from 29.6% to 2.0% (
P
=0.0002,
P
=0.025 for interaction).

Conclusions—

Among symptomatic men with documented coronary artery disease, the TLR4 Asp299Gly polymorphism was associated with the risk of cardiovascular events. This variant also modified the efficacy of pravastatin in preventing cardiovascular events, such that carriers of the variant allele had significantly more benefit from pravastatin treatment.
Longitudinal Myocardial Function Assessed by Tissue Velocity, Strain, and Strain Rate Tissue Doppler Echocardiography in Patients With AL (Primary) Cardiac Amyloidosis
Authors: Koyama Jun , Ray-Sequin Patricia A. , Falk Rodney H.
Published: May 2003

Background—

AL amyloidosis with heart failure is associated with decreased longitudinal myocardial contraction measured by pulsed tissue Doppler imaging. We sought to clarify whether new modalities of myocardial strain Doppler (change in length per unit length) or strain rate (the temporal derivative of strain) were more sensitive than tissue Doppler and could detect early regional myocardial dysfunction before the onset of congestive heart failure (CHF) in patients with AL (primary) amyloidosis.

Methods and Results—

Ninety-seven biopsy-proven patients with AL amyloidosis were divided into 3 groups. Group 1 patients had no cardiac involvement (n=36), group 2 had heart involvement but no CHF (n=32), and group 3 had heart involvement and CHF (n=29). All patients underwent tissue velocity (TV) imaging, strain, and strain rate imaging (SR) at the basal, mid, and apical ventricle in 2 apical views. With the use of TV, differences in systolic function were only apparent between group 3 (basal mean value, 3.0±1.1 cm/s) and groups 1 and 2 (5.0±1.3 and 4.6±1.2 cm/s, respectively). In contrast, basal peak systolic SR (l/s) showed significant differences among all 3 groups (−2.0±0.4, −1.55±0.6, and −0.76±0.3 for groups 1 to 3, respectively.
P
<0.01). Basal strain also demonstrated statistically significant differences among the groups (−19±4%, −15±4.5%, and −8.0±5%;
P
<0.01).

Conclusions—

Cardiac amyloidosis is characterized by an early impairment in systolic function at a time when fractional shortening remains normal. This abnormality precedes the onset of CHF and can be detected by strain and SR but is not apparent by TV imaging.
JUAN DE SALCEDO JOINS THE NATIVE FORM OF WARFARE
Authors: Rodriguez Felice Noelle
Published: May 2003

From the beginning of the sixteenth century the Spanish in the Philippines documented their triumph over the native population, but failed to appreciate the way in which the latter understood the conduct of war. This essay focuses on the conflict between local and Spanish forces in 1570 which historians usually interpret as a Spanish victory. A closer reading of the sources, however, reveals the complexities of the local situation. By discussing indigenous forms of warfare the essay places the Spanish 'triumph' in the context of the indigenous rules underlying pangangayao, the native game of warfare. Les documents rédigés dès le début du XVIe siècle par les Espagnols font état de leur « triomphe » sur les populations locales. Ils ne font en revanche aucune mention, faute peut être d'en avoir une compréhension suffisante, de la manière dont la guerre était alors conçue par les autochtones. Cet article traite tout particulièrement du con it de 1570 entre les indigènes et les Espagnols que les historiens lisent généralement comme une victoire ibérique. Mais une lecture minutieuse des sources nous révèle la complexité de la situation. On s'efforce donc ici de s'intéresser à la perception locale du conflit et de replacer le « triomphe espagnol » dans la perspective du pangangayao, l'art autochtone de la guerre.
Late-onset X-linked sideroblastic anemia following hemodialysis
Authors: Furuyama Kazumichi , Harigae Hideo , Kinoshita Chiharu , Shimada Toshihiko , Miyaoka Kazuko , Kanda Chiaki , Maruyama Yoshifumi , Shibahara Shigeki , Sassa Shigeru
Published: May 2003

X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 years while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.
Application of the Wigner-Ville distribution to identification of a cracked rotor
Authors: Zou J , Chen J , Niu J C , Geng Z M
Published: May 2003

The dynamic equation of transient response in a cracked rotor is modelled, and is based on the simple hinge crack model. The numerical simulation solutions of the uncracked rotor and the cracked rotor are obtained from the model. Using the Wigner-Ville distribution, the time-frequency features of the cracked rotor and the uncracked rotor are compared, and a new algorithm using the Wigner-Ville distribution to identify the cracked rotor is proposed. By simulation research, the sensitivity of the Wigner-Ville distribution to the stiffness variation is investigated, and the influence of the unbalance and the inhabiting angle on the time-frequency feature is discussed. The Wigner-Ville time-frequency feature is unique, and can be used as the criterion for identification of a cracked rotor in engineering practices.
Multimodal tuning of a vibrating ring using laser ablation
Authors: Gallacher B J , Hedley J , Burdess J S , Harris A J , McNie M E
Published: May 2003

This paper investigates laser ablation as a mechanism for fine tuning the flexural modes of vibration of a slightly imperfect suspended ring. A theoretical analysis of the effect of ablation on the natural frequencies of both in-plane and out-of-plane flexural modes is developed. Contributions made to the frequency shift from the reduced mechanical stiffness and reduced mass, as a result of ablation, are included. A specific cyclic symmetric relationship between the modes of vibration and the ablation configuration permitting multimodal tuning is developed. This relationship is expanded for the particular case of flexural modes of order 2 and 3, which are commonly used in vibrating ring gyroscope designs. For vibrating ring gyroscopes, tuning between certain flexural modes of vibration greatly increases the sensitivity of the device to applied rates of rotation. Therefore, a fine-tuning mechanism is highly desirable.

An experimental examination of multimodal tuning using laser ablation is performed. In-plane modes of order 2 and out-of-plane modes of order 3 are investigated. Stiffness reduction as a possible method for modifying the natural frequencies of the out-of-plane modes of vibration is explored.
An uncapped RNA suggests a model for Caenorhabditis elegans polycistronic pre-mRNA processing
Authors: LIU YINGMIAO , KUERSTEN SCOTT , HUANG TAO , LARSEN ALISON , MACMORRIS MARGARET , BLUMENTHAL THOMAS
Published: May 2003

Polycistronic pre-mRNAs from Caenohabditis elegans operons are processed by internal cleavage and polyadenylation to create 3’ ends of mature mRNAs. This is accompanied by trans-splicing with SL2 ∼100 nucleotides downstream of the 3’ end formation sites to create the 5’ ends of downstream mRNAs. SL2 trans-splicing depends on a U-rich element (Ur), located ∼70 nucleotides upstream of the trans-splice site in the intercistronic region (ICR), as well as a functional 3′ end formation signal. Here we report the existence of a novel gene-length RNA, the Ur-RNA, starting just upstream of the Ur element. The expression of Ur-RNA is dependent on 3′ end formation as well as on the presence of the Ur element, but does not require a trans-splice site. The Ur-RNA is not capped, and alteration of the location of the Ur element in either the 5′ or 3′ direction alters the location of the 5′ end of the Ur-RNA. We propose that a 5’ to 3’ exonuclease degrades the precursor RNA following cleavage at the poly(A) site, stopping when it reaches the Ur element, presumably attributable to a bound protein. Part of the function of this protein can be performed by the MS2 coat protein. Recruitment of coat protein to the ICR in the absence of the Ur element results in accumulation of an RNA equivalent to Ur-RNA, and restores trans-splicing. Only SL1, however, is used. Therefore, coat protein is sufficient for blocking the exonuclease and thereby allowing formation of a substrate for trans-splicing, but it lacks the ability to recruit the SL2 snRNP. Our results also demonstrate that MS2 coat protein can be used as an in vivo block to an exonuclease, which should have utility in mRNA stability studies.
Recognition of the 5′ leader of pre-tRNA substrates by the active site of ribonuclease P
Authors: ZAHLER NATHAN H. , CHRISTIAN ERIC L. , HARRIS MICHAEL E.
Published: May 2003

The bacterial tRNA processing enzyme ribonuclease P (RNase P) is a ribonucleoprotein composed of a ∼400 nucleotide RNA and a smaller protein subunit. It has been established that RNase P RNA contacts the mature tRNA portion of pre-tRNA substrates, whereas RNase P protein interacts with the 5′ leader sequence. However, specific interactions with substrate nucleotides flanking the cleavage site have not previously been defined. Here we provide evidence for an interaction between a conserved adenosine, A248 in the Escherichia coli ribozyme, and N(-1), the substrate nucleotide immediately 5′ of the cleavage site. Specifically, mutations at A248 result in miscleavage of substrates containing a 2′ deoxy modification at N(-1). Compensatory mutations at N(-1) restore correct cleavage in both the RNA-alone and holoenzyme reactions, and also rescue defects in binding thermodynamics caused by A248 mutation. Analysis of pre-tRNA leader sequences in Bacteria and Archaea reveals a conserved preference for U at N(-1), suggesting that an interaction between A248 and N(-1) is common among RNase P enzymes. These results provide the first direct evidence for RNase P RNA interactions with the substrate cleavage site, and show that RNA and protein cooperate in leader sequence recognition.
A novel unanticipated type of pseudouridine synthase with homologs in bacteria, archaea, and eukarya
Authors: KAYA YUSUF , OFENGAND JAMES
Published: May 2003

Putative pseudouridine synthase genes are members of a class consisting of four subgroups that possess characteristic amino acid sequence motifs. These genes have been found in all organisms sequenced to date. In Escherichia coli, 10 such genes have been identified, and the 10 synthase gene products have been shown to function in making all of the pseudouridines found in tRNA and ribosomal RNA except for tRNAGlu pseudouridine13. In this work, a protein able to make this pseudouridine was purified by standard biochemical procedures. Amino-terminal sequencing of the isolated protein identified the synthase as YgbO. Deletion of the ygbO gene caused the loss of tRNAGlu pseudouridine13 and plasmid-borne restoration of the structural gene restored pseudouridine13. Reaction of the overexpressed gene product, renamed TruD, with a tRNAGlu transcript made in vitro also yielded only pseudouridine13. A search of the database detected 58 homologs of TruD spanning all three phylogenetic domains, including ancient organisms. Thus, we have identified a new wide-spread class of pseudouridine synthase with no sequence homology to the previously known four subgroups. The only completely conserved sequence motif in all 59 organisms that contained aspartate was GXKD, in motif II. This aspartate was essential for in vitro activity.
Cognitive style, working memory and learning behaviour and attainment in school subjects
Authors: Riding Richard J. , Grimley Michael , Dahraei Hassan , Banner Gloria
Published: May 2003

Background: Both working memory capacity and cognitive style have independently been found to affect performance on school‐type tasks, but their effects in interaction have not been considered.

Aims: The aims of this study were to consider the relationship between working memory, cognitive style and gender on (a) overall learning behaviour, and (b) performance on a range of school subjects.

Sample: The sample comprised 206 13‐year‐old secondary comprehensive school Year 8 pupils, being all pupils in that year who completed the principal assessments.

Method: The pupils did an assessment of working memory efficiency — the Information Processing Index (Riding, 2000a). They also completed the Cognitive Styles Analysis (Riding, 1991) to determine their positions on the two fundamental cognitive styles, which were indicated by two ratios: the Wholist‐Analytic ratio and the Verbal‐Imagery ratio. Overall learning behaviour was rated by the pupils' tutors. In addition, attainment in each of 10 subjects was rated by their subject teachers.

Results: For overall learning behaviour, there was an interaction between working memory capacity and cognitive style. With the Wholist‐Analytic style dimension, memory made a marked difference for Analytics but had little effect for Wholists, and with the Verbal‐Imagery dimension Verbalisers were affected but not Imagers. With the school subjects, these differed in terms of their sensitivity to gender, memory and style.

Conclusion: The results were discussed in terms of differences between the styles in terms of information‐processing demands. Practical ways of improving learning performance were also considered.
Self‐perceived competence, learning conceptions and preferred learning situations in the domain of communication
Authors: Bakx Anouke W.E.A. , Vermetten Yvonne J. M. , Van der Sanden Johan M.M.
Published: May 2003

Background: An important purpose of education in the field of social work is the development of social‐communicative competence and students' individual learning theories (ILTs) concerning this domain.

Aims: Our first aim was to develop diagnostic instruments for ILT assessment and to understand the relationships between ILT variables. Our second purpose was to study the differences in ILT variables between students of three study years.

Samples: A total of 396 full‐time social work students participated in this study: 176 first‐year, 147 second‐year and 73 fourth‐year students (92% women and 8% men).

Method: Based on a theoretical framework, three questionnaires have been constructed, covering three ILT variables: self‐perceived competence, learning conceptions and preferred learning situations. For scale construction, principal component analyses and reliability analyses were conducted. ANOVAs and post hoc comparisons of means were used to investigate cross‐sectional differences regarding ILT variables. Pearson correlations and regression analyses were performed to gain more insight into the relationships between ILT variables.

Results: Five aspects of self‐perceived competence, four learning conceptions and five preferred learning situations were found. Learning conceptions and self‐perceived competencies were found to be predictors of students' preferred learning situations. Many differences were found between the three groups of students, especially between the first‐year students and the others.

Conclusions: When studying the acquisition of social‐communicative competence, it is important to take students' individual learning theories into account. Increased insight into the role ILTs play can be of help in improving social work education.
Using the Mann‐Whitney test on informetric data
Authors: Huber John C. , Wagner‐Döbler Roland
Published: May 2003

The fields of informetrics and scientometrics have suffered from the lack of a powerful test to detect the differences between two samples. We show that the Mann‐Whitney test is a good test on the publication productivity of journals and of authors. Its main limitation is a lack of power on small samples that have small differences. This is not the fault of the test, but rather reflects the fact that small, similar samples have little to distinguish between them.
Efficient single‐pass index construction for text databases
Authors: Heinz Steffen , Zobel Justin
Published: May 2003

Efficient construction of inverted indexes is essential to provision of search over large collections of text data. In this article, we review the principal approaches to inversion, analyze their theoretical cost, and present experimental results. We identify the drawbacks of existing inversion approaches and propose a single‐pass inversion method that, in contrast to previous approaches, does not require the complete vocabulary of the indexed collection in main memory, can operate within limited resources, and does not sacrifice speed with high temporary storage requirements. We show that the performance of the single‐pass approach can be improved by constructing inverted files in segments, reducing the cost of disk accesses during inversion of large volumes of data.
Lysosomal amino acid transporter LYAAT‐1 in the rat central nervous system: An in situ hybridization and immunohistochemical study
Authors: Agulhon Cendra , Rostaing Philippe , Ravassard Philippe , Sagné Corinne , Triller Antoine , Giros Bruno
Published: May 2003

A first mammalian lysosomal transporter (LYAAT‐1) was recently identified and functionally characterized. Preliminary immunocytochemical data revealed that LYAAT‐1 localizes to lysosomes in some neurons. In order to determine whether it is expressed in specific neuron populations and other cell types, and to confirm whether it is localized at the membrane of lysosomes, we used in situ hybridization and immunohistochemistry methods in adult rat central nervous system (CNS). We found that LYAAT‐1 is expressed in most areas of the CNS, specifically in neurons, but also in choroid plexus and ependymal epithelium cells. LYAAT‐1‐IR (immunoreactivity) levels varied among different neuroanatomical structures but were present in neurons independently of the neurotransmitter used (glutamate, GABA, acetylcholine, noradrenaline, serotonin, or glycine). Light and confocal microscopy demonstrated that LYAAT‐1 and the lysosomal marker cathepsin D colocalized throughout the brain and electron microscopy showed that LYAAT‐1‐IR was associated with lysosomal membranes. In addition, LYAAT‐1‐IR was also found associated with other membranes belonging to the Golgi apparatus and lateral saccules and less frequently with multivesicular bodies, endoplasmic reticulum, and occasionally with the plasma membrane. The localization of LYAAT‐1 at the lysosomal membrane is consistent with the view that it mediates amino acid efflux from lysosomes. Furthermore, its cell expression pattern suggests that it may contribute to specialized cellular function in the rat CNS such as neuronal metabolism, neurotransmission, and control of brain amino acid homeostasis. J. Comp. Neurol. 462:71–89, 2003. © 2003 Wiley‐Liss, Inc.
Bioorganic Chemistry of Ceramide
Authors: Brodesser Susanne , Sawatzki Peter , Kolter Thomas
Published: May 2003

Ceramide is the hydrophobic membrane anchor of glycosphingolipids, a vital component of the human skin, and a novel signaling substance. We give an overview of ceramide analogues that have been prepared to address biochemical questions related to the various functions of this lipid. We also discuss possible therapeutic applications. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
4‐(Trifluoromethyl)quinoline Derivatives
Authors: Lefebvre Olivier , Marull Marc , Schlosser Manfred
Published: May 2003

Under carefully controlled conditions, ethyl 4,4,4‐trifluoroacetoacetate (ethyl 4,4,4‐trifluoro‐3‐oxobutanoate) can be condensed with anilines and subsequently cyclized to give 4‐trifluoromethyl‐2‐quinolinones 1 although only in poor yield. Heating these products with phosphoryl tribromide affords 2‐bromo‐4‐(trifluoromethyl)quinolines 2 which can be converted into 4‐(trifluoromethyl)quinolines 3 by reduction, 4‐trifluoromethyl‐2‐quinolinecarboxylic acids 4 by permutational halogen/metal exchange followed by carboxylation, and 2‐bromo‐4‐trifluoromethyl‐3‐quinolinecarboxylic acids 5 by consecutive treatment with lithium diisopropylamide and dry ice. Debromination of acids 5 makes 4‐trifluoromethyl‐3‐quinolinecarboxylic acids 6 available. As at any time 2‐trifluoromethyl‐4‐quinolinones 9 may form instead of the expected isomers 1, the structures have to be assigned on the basis of unequivocal NMR spectral criteria. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Synthesis of Fluorinated Cycloalkyl N‐Phenylcarbamates and Their Microbial Defluorination/Oxygenation by Beauveria bassiana
Authors: Haufe Günter , Pietz Sylke , Wölker Dörthe , Fröhlich Roland
Published: May 2003

Earlier investigations showed that cycloalkyl N‐phenylcarbamates were hydroxylated by the fungus Beauveria bassiana predominantly in the 4‐position relative to the electron‐rich substituent. In cases involving fluorinated methylene groups potentially capable of hydroxylation, however, defluorination and formation of a ketone was observed. The formation of the ketone can be explained by primary hydroxylation to form an unstable geminal fluorohydrin, which is subsequently dehydrofluorinated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Syntheses of Enantiomerically Pure Cyclopent‐2‐ene‐1‐carboxylic Acid and (Cyclopent‐2‐enyl)acetic Acid by Enantioselective Palladium‐Catalyzed Allylic Alkylations − Synthesis of Enantiomerically Pure (−)‐Chaulmoogric Acid
Authors: Seemann Matthias , Schöller Markus , Kudis Steffen , Helmchen Günter
Published: May 2003

Asymmetric Pd‐catalyzed allylic alkylations of dimethyl malonate and diethyl 2‐acetoxymalonate with 3‐chlorocyclopentene, using phosphanyloxazolines 1 and ent‐1 as chiral ligands, gave products (−)‐2 and (+)‐3b with 95 and 99.5% ee, respectively. Oxidative degradation of (+)‐3b furnished (+)‐(R)‐cyclopent‐2‐ene‐1‐carboxylic acid [(+)‐4] with > 99% ee. Alkylation product (−)‐2 was transformed into enantiomerically pure (−)‐(R)‐(cyclopent‐2‐enyl)acetic acid [(−)‐5] by three simple steps. Availability of (−)‐5 enabled the first synthesis of enantiomerically pure (−)‐chaulmoogric acid [(−)‐9] in three steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: (Aryl)(phosphanyl)Carbene: Ground‐ and Excited‐State Reactions (Eur. J. Org. Chem. 11/2003)
Authors: Despagnet‐Ayoub Emmanuelle , Gornitzka Heinz , Bourissou Didier , Bertrand Guy
Published: May 2003

The cover picture shows ground‐state as well as excited‐state reactions for a stable (aryl)(phosphanyl)carbene. Cyclopropanation and carbene coupling reactions demonstrate the ambiphilic character of the ground state while the 1,2‐migration reaction only occurred under irradiation and thus involves an excited state of the stable carbene. Details are discussed in the article by D. Bourissou and G. Bertrand et al. on p. 2039 ff. Thanks are due to Mr. Chistian Pradel for his help in generating this cover illustration.
Potential of Müller glia to become neurogenic retinal progenitor cells
Authors: Fischer Andy J. , Reh Thomas A.
Published: May 2003

The possibility of neural regeneration has gained credence with the identification of neural stem cells seeded within different regions of the adult central nervous system (CNS). Recently, this possibility has received an additional boost from reports that glia, the support cells of the CNS, might provide a source of neural regeneration. We review some of our findings that Müller glia in the chicken retina are a source of proliferating progenitors that can generate neurons. These Müller cells are fully differentiated glial cells that serve functions ascribed to this cell type. In response to damage or exogenous growth factors, Müller glia dedifferentiate, proliferate, express combinations of transcription factors normally expressed by embryonic retinal progenitors, and produce new neurons and glia. In light of these data, the potential of Müller glia as a source of neural regeneration in the retina of nonavian species, namely humans, seems an avenue of investigation that warrants serious consideration. GLIA 43:70–76, 2003. © 2003 Wiley‐Liss, Inc.
Elusive radial glial cells: Historical and evolutionary perspective
Authors: Rakic Pasko
Published: May 2003

Since the discovery of radial glial cells in the human fetal forebrain, this specialized cellular population has been identified in most regions of the vertebrate brain during restricted developmental periods. However, their size, longevity, and significance for guiding migrating neurons have increased with the evolutionary expansion of the mammalian neocortex, reaching a peak in the gyrencephalic human forebrain. The phenotypic distinction of radial glial cells from the more specialized neuronal progenitors in the proliferative zones and from the migrating neurons in the intermediate zone of the primate fetal forebrain, based initially on morphological criteria, has been supported by their ultrastructural, molecular, and physiological characteristics. In addition, modern in vivo and in vitro approaches revealed that these specialized embryonic cells can also generate neuronal cell lines, which either immediately, or after several divisions, migrate along radial shaft processes of the mother cells that span the expanding and convoluted cerebral wall. The multiple functions of radial glial cells and their species‐specific adaptations indicate a pivotal role in evolution, development, and pathology of the cerebral neocortex. GLIA 43:19–32, 2003. © 2003 Wiley‐Liss, Inc.
Verhalten laserschockverfestigter und festgewalzter Randschichten der Ti‐Legierung Ti‐6Al‐4V bei schwingender Beanspruchung unter erhöhten Temperaturen
Authors: Altenberger I. , Nalla R.K. , Noster U. , Liu G. , Scholtes B.
Published: May 2003

Es ist seit langem bekannt, dass mechanische Oberflächenbehandlungen wie etwa Festwalzen, Kugelstrahlen oder Laserschockoberflächenbehandlungen, um nur einige zu nennen, das Ermüdungsverhalten hochbeanspruchter metallischer Bauteile entscheidend verbessern können. Insbesondere Festwalzen und Laserschockoberflächenbehandlungen haben sich als besonders wirksam herausgestellt, da sie tiefe Druckeigenspannungs‐ und Verfestigungsprofile sowie eine vergleichsweise glatte Oberflächentopographie erzeugen. Tatsächlich wird z. B. das Festwalzen bereits serienmässig zur Erhöhung der Schwingfestigkeit von Stählen, wie etwa beim Festwalzen von Kurbelwellen, eingesetzt. Obwohl die meisten Arbeiten zum Festwalzen sich mit Stählen beschäftigen, wurde dieses Verfahren in jüngerer Zeit auch auf eine Reihe von Titanwerkstoffen erfolgreich angewendet.

Die vorliegenden Untersuchungen beschäftigen sich mit dem Einfluss von Festwalzbehandlungen auf das Niedrig‐ und Hochlastwechselermüdungsverhalten der wichtigsten kommerziellen Titanlegierung Ti‐6Al‐4V, wobei besonderes Augenmerk auf die thermische und mechanische Stabilität randnaher Eigenspannungszustände und Mikrostrukturen gerichtet wurde. Zusätzlich werden erste Ergebnisse zum Eigenspannungszustand und zur Schwingfestigkeit lasergeschockter Ti‐6Al‐4V‐Proben präsentiert und mit Resultaten festgewalzter Zustände verglichen. Ausserdem wird untersucht, ob die Oberflächenbehandlungen auch bei erhöhten Temperaturen (bis 450 °C) ihre Wirksamkeit zur Verbesserung der Schwingfestigkeit behalten. Basierend auf Wechselverformungs‐ und Lebensdaueruntersuchungen, in Kombination mit Röntgendiffraktometrie und In‐situ‐Transmissionselektronenmikroskopie, lässt sich feststellen, dass Laserschockoberflächenbehandlungen und insbesondere Festwalzen die Rissbildung und Ausbreitung in hochtemperaturschwingbeanspruchtem Ti‐6Al‐4V trotz eines fast völligen Druckeigenspannungsabbaus wirkungsvoll hemmt. Daraus lässt sich ableiten, dass zusätzlich zu Eigenspannungen vor allem randnahe Mikrostrukturen, welche im Falle von mechanisch randschichtverfestigtem Ti‐6Al‐4V durch sehr hohe Versetzungsdichten und Nanokristallite gekennzeichnet ist, einen wesentlichen Einfluss bei der Lebensdauererhöhung durch Randschichtverfestigung haben.
Stabilität antielektrostatischer Beschichtungen auf der Basis von Polyethylendioxithiophenen
Authors: Kolesov I. S. , Münstedt H.
Published: May 2003

Die antielektrostatische Ausrüstung von Bauteilen aus Polymerwerkstoffen ist von großem anwendungstechnischem Interesse. Für den technischen Kunststoff Polyamid 6 und den Hochtemperaturthermoplasten Polyethersulfon wurde gezeigt, dass durch die Beschichtung mit Polyethylendioxithiophen eine für antielektrostatische Anwendungen ausreichende Leitfähigkeit zu erreichen ist. Aufgrund von chemischen Alterungsvorgängen des leitfähigen Polymers nimmt der Oberflächenwiderstand der beschichteten Prüfkörper jedoch zu. Für verschiedene Temperaturen, Schichtdicken und Rezepturen wurde die zeitliche Veränderung des elektrischen Widerstandes gemessen. Die Alterung zeigt in einer für technische Zwecke ausreichenden Näherung ein Arrhenius‐Verhalten. Somit werden Abschätzungen von Widerstandsänderungen unter verschiedenen Anwendungsbedingungen möglich.
Klebflächenvorbehandlung von Aluminiumoberflächen mit Haftvermittler
Authors: Anagreh N. , Dorn L.
Published: May 2003

Der Einfluss dreistufiger Vorbehandlung Entfetten, Strahlen und Primer und zweistufiger Vorbehandlung Entfetten und Strahlen auf das Klebverhalten von Aluminiumlegierung AlMg4,5Mn0,5 wurde ermittelt. Die Untersuchungen wurden mit zwei kaltaushärtenden Zweikomponenten‐Epoxidklebstoffen, einem warmaushärtenden Einkompnenten‐Epoxidklebstoff und einem kaltaushärtenden Zweikomponenten‐Polyurethanklebstoff durchgeführt. Die dreistufige Vorbehandlung wies bei Epoxidklebstoffen höhere Klebfestigkeitswerte auf als bei zweistufiger, beim PU‐Klebstoff unterscheiden sich dagegen die ermittelten Klebfestigkeitswerten kaum voneinander. Das Weglassen des Arbeitsschritts Entfetten nach dem Korundstrahlen, der zur Beseitigung von Strahlmittelrückständen führt, bewirkt bei PU‐, EP 2‐ und EP 3‐Klebstoff eine merkliche Reduzierung der Klebfestigkeiten gegenüber entfetteten Proben. Die Primervorbehandlung führt wegen erhöhter Viskosität zur Überdeckung der topographischen Strukturen von gestrahlten Aluminiumoberflächen, was eine starke Abnahme der Oberflächenrauheiten bewirkt. Es trat auch eine starke Veränderung der chemischen Zusammensetzung gegenüber nur entfetteten bzw. gestrahlten Oberflächen ein.
Reasons for Melting of Chemical Elements and some Consequences
Authors: Hoffmann H.‐J.
Published: May 2003

When studying the causes for melting, solid chemical elements are considered to be the simplest systems. Data of the melting enthalpy, ΔHm, and entropy, ΔSm, taken from the literature are investigated as well as the molar specific heat capacities immediately below and above the melting temperature, Tm. In many cases, the molar specific heat capacity at constant volume exceeds the classical limit for the lattice vibrations CV = 3R above the Debye temperature. This excess specific heat is due to electronic transitions of bonding electrons and of the electrons near the Fermi‐edge to states with higher energy. The wave functions of the electrons in these higher states are different from those of the original lower states causing the core ions to be attracted to different new positions. In addition, the vibrations may modify the local potential of the electrons and thus their wave‐functions with similar results. Melting occurs if sufficient core ions relax to new positions within the lifetime of the excited states and if their order and arrangement is changing according to the random time series of the different occupied electronic states with their respective wave‐functions. This mechanism can also be applied to explain diffusion, thermal expansion and the glass transition temperature.
Electrochemical behavior of vanadium in EDTA
Authors: Ameer Magda A. M.
Published: May 2003

The use of chelating agents as cleaning chemicals to remove metal deposits is gaining interest. In this study the Electrochemical behavior of vanadium in EDTA, EA and EAC solutions was studied using AC impedance technique at different immersion time. The results indicate that the values of Rct for EA solution are higher than that for EDTA and EAC. This may be due to the presence of ascorbic acid as reducing agent. The presence of surface film is confirmed by capacitance measurements. It is shown that the capacitance is time‐dependent. Generally, the capacitance decreases with immersion time and this can be discussed on the basis that the concentration of vanadium ions at the interface increases with immersion time.
C‐reactive protein (CRP) as tumor marker in pediatric and adolescent patients with Hodgkin disease
Authors: Wieland Annemarie , Kerbl Reinhold , Berghold Andrea , Schwinger Wolfgang , Mann Georg , Urban Christian
Published: May 2003

Background

C‐reactive protein (CRP) is an acute phase protein produced in the liver. An elevated CRP is a nonspecific marker of inflammation. Additionally, it also appears to be a prognostic marker in several malignancies. Elevated CRP levels in adult patients with Hodgkin disease (HD) were reported previously. However, levels of CRP have not been evaluated in pediatric and adolescent HD patients.

Procedure

We analyzed CRP serum levels in 95 consecutive pediatric and adolescent patients with Hodgkin disease. CRP levels were correlated with stage, absence or presence of B symptoms, and prognosis.

Results

At the time of diagnosis increased serum CRP levels were found in 64 % (61/95) of the patients with a median of 21 mg/L (range: <5–211). Serum C‐reactive protein levels correlated with stage and were higher in patients with B symptoms. Higher CRP levels were associated with an increased risk of relapse.

Conclusion

In addition to soluble interleukin 2 receptor (sIL‐2R) levels, CRP holds promise as a diagnostic and prognostic index and follow‐up monitor in pediatric and adolescent patients with Hodgkin disease, and merits further investigation. Med Pediatr Oncol 2003;41:21–25. © 2003 Wiley‐Liss, Inc.
FISH analyses for alterations in chromosomes 1, 2, 3, and 11 define high‐risk groups in neuroblastoma
Authors: Spitz Ruediger , Hero Barbara , Ernestus Karen , Berthold Frank
Published: May 2003

Background

The prognostic chromosomal markers 1p loss and MYCN amplification (MNA) are only present in a subgroup of approximately 30% of neuroblastomas. To further characterize high and low risk subsets we investigated alterations in chromosome arms 3p and 11q, additional changes in 1p and MYCN as well as the somy‐status of chromosome 1 in the same sample.

Procedure

Fluorescence in situ hybridization (FISH) was used as an alternative technique to PCR/LOH‐ or comparative genomic hybridization (CGH) analyses. Alterations in chromosomes 3p and 11q were investigated in 182 unselected tumors, 1p loss and MNA in 174 and 179 of these, respectively. The somy‐status of chromosome 1 was determined in 165 tumors as it highly correlates with the tumor ploidy.

Results

Alterations in the four chromosomal regions were found in the following frequencies: 3p26: 19%, 11q23: 29%, 1p36: 29%, MNA: 19%. Fifty‐two percent of all cases displayed structural aberrations in at least one chromosomal region, 83% in stage 4 and 30% in stages 1–3, 4s. All aberrations were thus correlated with stage 4 disease but were also present in a substantial subset of localized and 4s tumors. Trisomy of chromosome 1 was found in 38% of the tumors, disomy or tetrasomy in 62%. Patients with alterations in any of the four chromosomes and di/tetrasomy 1 showed a significantly increased age at diagnosis. Loss in 1p and MNA were closely associated with each other, as well as 3p and 11q aberrations but not the groups 1p/MNA versus 3p/11q. Only a small portion of trisomic tumors showed aberrations in at least one of the four chromosomal regions (14%) in contrast to the majority of the di/tetrasomic cases (74%). As already known the MYCN status discriminated between good and poor outcome in localized and metastatic stage 4 tumors. In addition alterations in 1p or 11q, deletion in 3p and di/tetrasomy 1 were associated with an unfavorable prognosis in MYCN single copy tumors of stages 1–3, 4s. Multivariate analysis revealed 11q alterations and MNA as the most important chromosomal prognostic factors in all stages.

Conclusion

FISH analyses for chromosomal alterations in 3p and 11q as well as in 1p and MYCN allows to define different groups with an increased risk for disease progression. Med Pediatr Oncol 2003;41:30–35. © 2003 Wiley‐Liss, Inc.
New modified substrates for discriminating between human DNA polymerases α and ϵ
Authors: Jasko Maxim V. , Semizarov Dmitry G. , Victorova Lyubov S. , Mozzherin Dmitry Ju. , Krayevsky Alexander A. , Kukhanova Marina K.
Published: May 2003

Two 2′‐deoxynucleoside 5′‐α‐methylenephosphonyl‐β,γ‐diphosphates were synthesized. They were incorporated into the DNA chain by DNA polymerase α from human placenta. Meanwhile, they were not recognized by DNA polymerases ϵ and β of the same origin as well as by reverse transcriptases from human immunodeficiency virus and avian myeloblastosis virus.
MALDI‐MS for C‐terminal sequence determination of peptides and proteins degraded by carboxypeptidase Y and P
Authors: Thiede Bernd , Wittmann-Liebold Brigitte , Bienert Michael , Krause Eberhard
Published: May 2003

Matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) has been used for C‐terminal amino acid sequence determination of peptides and proteins. The usefulness of MALDI‐MS was demonstrated by analyzing peptide mixtures (C‐terminal peptide ladder) which were generated by enzymatic digestion of substance P, glucagon, angiotensinogen, insulin B chain and myoglobin with the exopeptidases carboxypeptidase Y and P. The results clearly show that up to 11 amino acid residues can be determined in the pmol range by analyzing the molecular masses of the truncated peptides. For proteins it is possible to investigate enzymatic or chemical digests in the same manner.
Differential penetration of fatty acyl‐coenzyme A and fatty acylcarnitines into phospholipid monolayers
Authors: Asun Requero M. , González Martín , Goñi Félix M. , Alonso Alicia , Fidelio Gerardo
Published: May 2003

The ability of fatty acyl‐CoA's and fatty acylcarnitines to penetrate phospholipid monolayers was comparatively studied, in view of the important role of both kinds of derivatives in fatty acid transport across mitochondrial membranes. The interaction occurs predominantly through hydrophobic forces. Acylcarnitines penetrate phospholipid monolayers more strongly than acyl‐CoAs; in addition the former show a positive cooperativity when they bind to the interface. These properties would facilitate membrane transfer of fatty acylcarnitines over that of their CoA homologues.
Molecular cloning of an orphan transporter A new member of the neurotransmitter transporter family
Authors: Smith Kelli E. , Fried Steven G. , Durkin Margaret M. , Gustafson Eric L. , Borden Laurence A. , Branchek Theresa A. , Weinshank Richard L.
Published: May 2003

A complementary DNA clone predicted to encode a novel transporter was isolated from rat brain and the localization of its mRNA was examined. The cDNA, designated rB21a, predicts a protein with 12 putative transmembrane domains that exhibits significant sequence homology with neurotransmitter transporters. Expression studies have not yet identified the endogenous substrate for this transporter, but the presence of rB21a mRNA within the leptomeninges of the brain suggests the transporter may regulate CSF levels of its substrate. The cloning of rB21a provides the means to determine its physiological functions and the potential to design novel, transporter‐based therapeutic agents for neurological and psychiatric disorders.
The prothymosin α gene is specifically expressed in ectodermal and mesodermal regions during early postimplantation mouse embryogenesis
Authors: del Amo Francisco Franco , Freire Manuel
Published: May 2003

Prothymosin α (ProTα) is a highly acidic nuclear protein, once believed to have an extracellular immunoregulatory role but more recently implicated in cell proliferation and/or differentiation. Several recent studies have revealed that ProTα mRNA is present during embryogenesis. However, these studies did not investigate the spatial distribution of ProTα mRNA in the embryo. Here we present a detailed study of the spatial distribution of ProTα mRNA during the early stages of postimplantation development (6.5–12.5 dpc) of the mouse. Three findings are of particular interest. First, ProTα mRNA levels increase during the early postimplantation stages (6.5–8.5 dpc) of mouse embryogenesis. Second, ProTα mRNA is not uniformly distributed in the mouse embryo, but is present in a spatially specific manner. Third, we have observed that the mouse ProTα gene is expressed almost exclusively in ectodermal and mesoderm‐derived structures, and not in cells which give rise to the definitive endoderm.