bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of first and third year medical students on self-study and reporting processes of problem-based learning
Authors: Musal Berna , Gursel Yucel , Taskiran H Cahit , Ozan Sema , Tuna Arif
Published: September 2004

Background

The objective of this study is to investigate the perceptions of first and third year medical students on self-study and reporting processes of Problem-based Learning (PBL) sessions and their usage of learning resources.

Methods

The questionnaire applied to the students consisted of; questions about students' perceptions on searching and preparing phases of the self-study process, the breadth and depth of discussion during reporting phase and the usage of learning resources.

Results

First-year students spent more time for self-study and more highly rated the depth of discussion compared to third-year students. The searching and preparing phases of the self-study process were considered as statistically important factors strongly influencing the breadth and depth of discussion during the reporting phase. The effect of extensiveness of searching on the depth of discussion was negative among the first-year students, and positive among third-year students.

Conclusions

The relative shortness of third-year students' self-study periods can be related to their mental weariness, decreased motivation or first-year students' slowness in accessing appropriate resources. The third-year students' more frequent use of textbooks may be due to the improvement of their abilities in reaching relevant learning resources. The findings implied that the increase in students' PBL experience paralleled the development of their discussion skills using different learning resources.
Evaluation of the Taguchi methods for the simultaneous assessment of the effects of multiple variables in the tumour microenvironment
Authors: Morsi Hisham , Yong Kwee L , Jewell Andrew P
Published: September 2004

Background

The control of proliferation, differentiation and survival of normal and malignant cells in the tumour microenvironment is under the control of a wide range of different factors, including cell:cell interactions, cytokines, growth factors and hormonal influences. However, the ways in which these factors interact are poorly understood. In order to compare the effects of multiple variables, experimental design becomes complex and difficult to manage. We have therefore evaluated the use of a novel approach to multifactorial experimental design, the Taguchi methods, to approach this problem.

Method

The Taguchi methods are widely used by quality engineering scientists to compare the effects of multiple variables, together with their interactions, with a simple and manageable experimental design. In order to evaluate these methods, we have used a simple and robust system to compare a traditional experimental design with the Taguchi Methods. The effect of G-CSF, GM-CSF, IL3 and M-CSF on daunorubicin mediated cytotoxicity in K562 cells was measured using the MTT assay.

Results

Both methods demonstrated that the same combination of growth factors at the same concentrations minimised daunorubicin cytotoxicity in this assay.

Conclusions

These findings demonstrate that Taguchi methods may be a valuable tool for the investigation of the interactions of multiple variables in the tumour microenvironment.
The big problem of the missing cytology slides
Authors: Gatter Ken M
Published: September 2004

Cytology slides are often unique and irreplaceable. Unlike surgical pathology cases, where additional paraffin sections can be cut, cytology slides often cannot be duplicated because there are only a few direct smears or the diagnostic material is present on a single slide. Cytology slides are often "sent out" to other physicians, laboratories or hospitals, typically so that the pathologist at the institution where the patient will receive treatment can review the slides. Less often, a cytology lab sends out the slides for a second opinion or as part of the discovery process in a lawsuit, where they may or may not be defendants. Rarely, unique and irreplaceable cytology slides are lost. This article presents a hypothetical scenario that is based on reported state appellate court decisions. The article discusses some of the legal issues that will affect the defendant cytologist/cytology lab and the "expert cytologist," and suggests some steps a cytologist/cytology lab can take to minimize the risk of repercussions from a lost unique and irreplaceable cytology slide.
PERSON: A General Model of Interpersonal Perception
Authors: Kenny David A.
Published: September 2004

A general theoretical model of interpersonal perception called PERSON (personality, error, residual, stereotype, opinion, and norm) is developed. This model reparameterizes a weighted-average model (WAM; Kenny, 1991; Kenny, Albright, Malloy, & Kashy, 1994) into six components. Two of those components refer to categorical information and 4 to behavioral information. Based on a formal model, for which parameters are estimatedfrom previous research studies, several implications are developed. The PERSON model can explain the low level of consensus in person perception, the fact that consensus does not increase with greater acquaintance, the strong stability of interpersonal judgment, the overconfidence effect, and the fact that short-term judgments are sometimes as accurate as long-term judgments. The PERSON model generally predicts that acquaintance is not as important in person perception as generally thought.
Comedy between Two Revolutions: Opera Buffa and the Risorgimento, 1831-1848
Authors: Izzo Francesco
Published: September 2004

For more than a century discussions of the relationship between the operatic stage and the socio-political scene of the Risorgimento have relied almost exclusively on serious operas (particularly those of Giuseppe Verdi) and especially on the period after 1848. Roger Parker's recent revision of Verdi's ostensibly exclusive role as "Bard of the Risorgimento" provides an opportunity to reassess the politics of Italian opera during this period, considering also other composers and works. The purpose of this study is to discuss the interaction between opera and the Risorgimento in a group of comic works composed between the revolutions of 1831 and 1848, focusing in particular on the representation and implications of national identity in Luigi Ricci's Il nuovo Figaro(1832) and in two Italian versions of Donizetti's La Fille du rgiment (1840), as well as on the significance of military themes. Furthermore, relevant cases of censorship in these and other comic works are examined. These operas uncover numerous affinities with the political discourse in contemporary serious melodrama, showing that warlike themes, choruses, and other statements of patriotism were not a prerogative of Verdi's operas, nor an exclusive feature of the serious genre. Their authors used conventional buffa procedures, such as modern European settings and encoded allegories of national character, in ways that reveal connections with the tensions and aspirations of the Risorgimento. A better knowledge of this repertory can only improve our understanding of the politics of opera during this crucial period of Italian history.
Embryonic exposure to oestrogen causes eggshell thinning and altered shell gland carbonic anhydrase expression in the domestic hen
Authors: Berg C , Blomqvist A , Holm L , Brandt I , Brunström B , Ridderstråle Y
Published: September 2004

Eggshell thinning among wild birds has been an environmental concern for almost half a century. Although the mechanisms for contaminant-induced eggshell thinning are not fully understood, it is generally conceived to originate from exposure of the laying adult female. Here we show that eggshell thinning in the domestic hen is induced by embryonic exposure to the synthetic oestrogen ethynyloestradiol. Previously we reported that exposure of quail embryos to ethynyloestradiol caused histological changes and disrupted localization of carbonic anhydrase in the shell gland in the adult birds, implying a functional disturbance in the shell gland. The objective of this study was to examine whetherin ovoexposure to ethynyloestradiol can affect eggshell formation and quality in the domestic hen. When examined at 32 weeks of age, hens exposed to ethynyloestradiolin ovo(20 ng/g egg) produced eggs with thinner eggshells and reduced strength (measured as resistance to deformation) compared with the controls. These changes remained 14 weeks later, confirming a persistent lesion. Ethynyloestradiol also caused a decrease in the number of shell gland capillaries and in the frequency of shell gland capillaries with carbonic anhydrase activity. These data suggested that a disrupted carbonic anhydrase expression was involved in the mechanism for the oestrogen-induced eggshell thinning found in this study. The results support our hypothesis that eggshell thinning in avian wildlife can result from a structural and functional malformation in the shell gland, induced by xeno-oestrogen exposure during embryonic development.
Endometrial expression of calbindin (CaBP)-d28k but not CaBP-d9k in primates implies evolutionary changes and functional redundancy of calbindins at implantation
Authors: Luu Kien C , Nie Gui Ying , Hampton Anne , Fu Guo-Qiang , Liu Yi-Xun , Salamonsen Lois A
Published: September 2004

The endometrium is hostile to embryo implantation except during the ‘window of receptivity’. A change in endometrial gene expression is required for the development of receptivity. Calbindin-d9k (CaBP-d9k) and calbindin-d28k (CaBP-d28k) are proteins possessing EF-hand motifs which have high affinity for Ca2+ions. Previously, it has been demonstrated that, in mouse endometrium, the expression of both calbindins is highly regulated during implantation and that both proteins play critical but functionally redundant roles at implantation. This study was the first to determine the expression of these two calbindins in the human and rhesus monkey endometrium. Initial RT-PCR analysis demonstrated that CaBP-d28k but not CaBP-d9k mRNA expression is detectable in the endometrium of both species. Western blot analysis confirmed the presence of immuno-reactive CaBP-d28k protein in the primate endometrium. Furthermore, the endometrial expression pattern of CaBP-d28k mRNA and protein was examined by Northern blot analysis and immunohistochemistry respectively in both species across the menstrual cycle and during early pregnancy. Semi-quantitative statistical analysis of the immunohistochemistry results revealed that, in the human, CaBP-d28k protein expression was maximal in luminal and glandular epithelium during the mid-secretory phase, coinciding with the time when the endometrium is receptive to embryo implantation. Expression in rhesus monkey showed a similar trend. These results suggest that, in the primate endometrium, only CaBP-d28k is expressed and that the specific regulation of this calbindin is potentially important for the establishment of uterine receptivity.
Interrelationships among follicles during the common-growth phase of a follicular wave and capacity of individual follicles for dominance in mares
Authors: Gastal E L , Gastal M O , Beg M A , Ginther O J
Published: September 2004

The changing diameter interrelationships among follicles during the interval from emergence to deviation (common-growth phase) were studied in 59 mares. All follicles of ≥6.0 mm were ablated 10 days after ovulation. The four largest follicles of the postablation wave were ranked D1, D2, D3 and D4 at the expected beginning of deviation (D1 ≥ 20.0 mm), according to descending diameter. The four follicles were also ranked independently, according to order of emergence at 6.0–6.9 mm as E1 (first to emerge), E2, E3 and E4. The follicles emerged during 1.3 ± 0.1 to 3.1 ± 0.1 days, and expected deviation began 6.5 ± 0.1 days after ablation. The frequency of emerging follicles becoming the largest follicle at the beginning of deviation was different (P < 0.0001; chi-square test) among follicles E1 (61%), E2 (25%), E3 (9%) and E4 (5%). There were no differences in growth rates among the four follicles throughout the common-growth phase (overall, 2.8 ± 0.04 mm/day). The differences in diameters between follicles E1 and E2 were similar between 3 days (2.7 ± 0.2 mm) and 6 days (2.9 ± 0.4 mm) after ablation. In controls and after ablation of D1; D1 and D2; or D1, D2 and D3 at the expected beginning of deviation, the largest remaining follicle became dominant in 26 of 34 mares (76%). In 10 of 15 mares (67%), the second-largest follicle became dominant when the largest follicle was ablated 1 or 2 days after the expected beginning of deviation. Results indicated the following: 1) the first follicle to emerge maintained its diameter advantage in most mares and average diameter growth rates were similar among the four follicles throughout the common-growth phase; 2) the hypothesis was supported that the capacity for dominance is similar among the four largest follicles at the beginning of deviation, but dominance by a smaller follicle is blocked when a larger follicle is present; and 3) the second-largest follicle retained the capacity for dominance in most mares for as long as 2 days after the beginning of deviation.
Increase in Ty1 cDNA Recombination in Yeast sir4 Mutant Strains at High Temperature
Authors: Radford Sarah J , Boyle Meredith L , Sheely Catherine J , Graham Joel , Haeusser Daniel P , Zimmerman Leigh , Keeney Jill B
Published: September 2004

Transposition of the Ty1 element of the yeast Saccharomyces cerevisiae is temperature sensitive. We have identified a null allele of the silent information regulator gene SIR4 as a host mutant that allows for transposition at high temperature. We show that the apparent increase in transposition activity in sir4 mutant strains at high temperature is dependent on the RAD52 gene and is thus likely resulting from an increase in Ty1 cDNA recombination, rather than in IN-mediated integration. General cellular recombination is not increased at high temperature, suggesting that the increase in recombination at high temperature in sir4 mutants is specific for Ty1 cDNA. Additionally, this high-temperature Ty1 recombination was found to be dependent on functional Sir2p and Sir3p. We speculate that the increase in recombination seen in sir4 mutants at high temperature may be due to changes in chromatin structure or Ty1 interactions with chromosomal structures resulting in higher recombination rates.
Multivariate Character Process Models for the Analysis of Two or More Correlated Function-Valued Traits
Authors: Jaffrézic Florence , Thompson Robin , Pletcher Scott D
Published: September 2004

Various methods, including random regression, structured antedependence models, and character process models, have been proposed for the genetic analysis of longitudinal data and other function-valued traits. For univariate problems, the character process models have been shown to perform well in comparison to alternative methods. The aim of this article is to present an extension of these models to the simultaneous analysis of two or more correlated function-valued traits. Analytical forms for stationary and nonstationary cross-covariance functions are studied. Comparisons with the other approaches are presented in a simulation study and in an example of a bivariate analysis of genetic covariance in age-specific fecundity and mortality in Drosophila. As in the univariate case, bivariate character process models with an exponential correlation were found to be quite close to first-order structured antedependence models. The simulation study showed that the choice of the most appropriate methodology is highly dependent on the covariance structure of the data. The bivariate character process approach proved to be able to deal with quite complex nonstationary and nonsymmetric cross-correlation structures and was found to be the most appropriate for the real data example of the fruit fly Drosophila melanogaster.
Toward a Theory of Marker-Assisted Gene Pyramiding
Authors: Servin Bertrand , Martin Olivier C , Mézard Marc , Hospital Frédéric
Published: September 2004

We investigate the best way to combine into a single genotype a series of target genes identified in different parents (gene pyramiding). Assuming that individuals can be selected and mated according to their genotype, the best method corresponds to an optimal succession of crosses over several generations (pedigree). For each pedigree, we compute the probability of success from the known recombination fractions between the target loci, as well as the number of individuals (population sizes) that should be genotyped over successive generations until the desired genotype is obtained. We provide an algorithm that generates and compares pedigrees on the basis of the population sizes they require and on their total duration (in number of generations) and finds the best gene-pyramiding scheme. Examples are given for eight target genes and are compared to a reference genotype selection method with random mating. The best gene-pyramiding method combines the eight targets in three generations less than the reference method while requiring fewer genotypings.
Identification of a Locus Under Complex Positive Selection in Drosophila simulans by Haplotype Mapping and Composite-Likelihood Estimation
Authors: Meiklejohn Colin D , Kim Yuseob , Hartl Daniel L , Parsch John
Published: September 2004

The recent action of positive selection is expected to influence patterns of intraspecific DNA sequence variation in chromosomal regions linked to the selected locus. These effects include decreased polymorphism, increased linkage disequilibrium, and an increased frequency of derived variants. These effects are all expected to dissipate with distance from the selected locus due to recombination. Therefore, in regions of high recombination, it should be possible to localize a target of selection to a relatively small interval. Previously described patterns of intraspecific variation in three tandemly arranged, testes-expressed genes (janusA, janusB, and ocnus) in Drosophila simulans included all three of these features. Here we expand the original sample and also survey nucleotide polymorphism at three neighboring loci. On the basis of recombination events between derived and ancestral alleles, we localize the target of selection to a 1.5-kb region surrounding janusB. A composite-likelihood-ratio test based on the spatial distribution and frequency of derived polymorphic variants corroborates this result and provides an estimate of the strength of selection. However, the data are difficult to reconcile with the simplest model of positive selection, whereas a new composite-likelihood method suggests that the data are better described by a model in which the selected allele has not yet gone to fixation.
Linkage Disequilibrium Mapping of Yield and Yield Stability in Modern Spring Barley Cultivars
Authors: Kraakman Arnold T W , Niks Rients E , Van den Berg Petra M M M , Stam Piet , Van Eeuwijk Fred A
Published: September 2004

Associations between markers and complex quantitative traits were investigated in a collection of 146 modern two-row spring barley cultivars, representing the current commercial germ plasm in Europe. Using 236 AFLP markers, associations between markers were found for markers as far apart as 10 cM. Subsequently, for the 146 cultivars the complex traits mean yield, adaptability (Finlay-Wilkinson slope), and stability (deviations from regression) were estimated from the analysis of variety trial data. Regression of those traits on individual marker data disclosed marker-trait associations for mean yield and yield stability. Support for identified associations was obtained from association profiles, i.e., from plots of P-values against chromosome positions. In addition, many of the associated markers were located in regions where earlier QTL were found for yield and yield components. To study the oligogenic genetic base of the traits in more detail, multiple linear regression of the traits on markers was carried out, using stepwise selection. By this procedure, 18–20 markers that accounted for 40–58% of the variation were selected. Our results indicate that association mapping approaches can be a viable alternative to classical QTL approaches based on crosses between inbred lines, especially for complex traits with costly measurements.
Abortive Transposition by a Group II Intron in Yeast Mitochondria
Authors: Dickson Lorna , Connell Stuart , Huang Hon-Ren , Henke R Michael , Liu Lu , Perlman Philip S
Published: September 2004

Group II intron homing in yeast mitochondria is initiated at active target sites by activities of intron-encoded ribonucleoprotein (RNP) particles, but is completed by competing recombination and repair mechanisms. Intron aI1 transposes in haploid cells at low frequency to target sites in mtDNA that resemble the exon 1-exon 2 (E1/E2) homing site. This study investigates a system in which aI1 can transpose in crosses (i.e., in trans). Surprisingly, replacing an inefficient transposition site with an active E1/E2 site supports <1% transposition of aI1. Instead, the ectopic site was mainly converted to the related sequence in donor mtDNA in a process we call “abortive transposition.” Efficient abortive events depend on sequences in both E1 and E2, suggesting that most events result from cleavage of the target site by the intron RNP particles, gapping, and recombinational repair using homologous sequences in donor mtDNA. A donor strain that lacks RT activity carries out little abortive transposition, indicating that cDNA synthesis actually promotes abortive events. We also infer that some intermediates abort by ejecting the intron RNA from the DNA target by forward splicing. These experiments provide new insights to group II intron transposition and homing mechanisms in yeast mitochondria.
An AFLP-Based Interspecific Linkage Map of Sympatric, Hybridizing Colias Butterflies
Authors: Wang Baiqing , Porter Adam H
Published: September 2004

Colias eurytheme and C. philodice are sister species with broad sympatry in North America. They hybridize frequently and likely share a significant portion of their genomes through introgression. Both taxa have been ecologically well characterized and exploited to address a broad spectrum of evolutionary issues. Using AFLP markers, we constructed the first linkage map of Colias butterflies. The map is composed of 452 markers spanning 2541.7 cM distributed over 51 linkage groups (40 major groups and 11 small groups with 2–4 markers). Statistical tests indicate that these AFLP markers tend to cluster over the map, with the coefficient of variation of interval sizes being 1.236 (95% C.I. is 1.234–1.240). This nonrandom marker distribution can account for the nonequivalence between the number of linkage groups and the actual haploid chromosome number (N = 31). This study presents the initial step for further marker-assisted research on Colias butterflies, including QTL and introgression analyses. Further investigation of the genomes will help us understand better the roles of introgression and natural selection in the evolution of hybridizing species and devise more appropriate strategies to control these pests.
Simultaneous Estimation of Haplotype Frequencies and Quantitative Trait Parameters
Authors: Shibata Kyoko , Ito Toshikazu , Kitamura Yutaka , Iwasaki Naoko , Tanaka Hiroshi , Kamatani Naoyuki
Published: September 2004

The analysis of the haplotype-phenotype relationship has become more and more important. We have developed an algorithm, using individual genotypes at linked loci as well as their quantitative phenotypes, to estimate the parameters of the distribution of the phenotypes for subjects with and without a particular haplotype by an expectation-maximization (EM) algorithm. We assumed that the phenotype for a diplotype configuration follows a normal distribution. The algorithm simultaneously calculates the maximum likelihood (L0max) under the null hypothesis (i.e., nonassociation between the haplotype and phenotype), and the maximum likelihood (Lmax) under the alternative hypothesis (i.e., association between the haplotype and phenotype). Then we tested the association between the haplotype and the phenotype using a test statistic, −2 log(L0max/Lmax). The above algorithm along with some extensions for different modes of inheritance was implemented as a computer program, QTLHAPLO. Simulation studies using single-nucleotide polymorphism (SNP) genotypes have clarified that the estimation was very accurate when the linkage disequilibrium between linked loci was rather high. Empirical power using the simulated data was high enough. We applied QTLHAPLO for the analysis of the real data of the genotypes at the calpain 10 gene obtained from diabetic and control subjects in various laboratories.
Co-infection Weakens Selection Against Epistatic Mutations in RNA Viruses
Authors: Froissart Rémy , Wilke Claus O , Montville Rebecca , Remold Susanna K , Chao Lin , Turner Paul E
Published: September 2004

Co-infection may be beneficial in large populations of viruses because it permits sexual exchange between viruses that is useful in combating the mutational load. This advantage of sex should be especially substantial when mutations interact through negative epistasis. In contrast, co-infection may be detrimental because it allows virus complementation, where inferior genotypes profit from superior virus products available within the cell. The RNA bacteriophage φ6 features a genome divided into three segments. Co-infection by multiple φ6 genotypes produces hybrids containing reassorted mixtures of the parental segments. We imposed a mutational load on φ6 populations by mixing the wild-type virus with three single mutants, each harboring a deleterious mutation on a different one of the three virus segments. We then contrasted the speed at which these epistatic mutations were removed from virus populations in the presence and absence of co-infection. If sex is a stronger force, we predicted that the load should be purged faster in the presence of co-infection. In contrast, if complementation is more important we hypothesized that mutations would be eliminated faster in the absence of co-infection. We found that the load was purged faster in the absence of co-infection, which suggests that the disadvantages of complementation can outweigh the benefits of sex, even in the presence of negative epistasis. We discuss our results in light of virus disease management and the evolutionary advantage of haploidy in biological populations.
Dose-Sensitive Autosomal Modifiers Identify Candidate Genes for Tissue Autonomous and Tissue Nonautonomous Regulation by the Drosophila Nuclear Zinc-Finger Protein, Hindsight
Authors: Wilk Ronit , Pickup Amanda T , Hamilton Jill K , Reed Bruce H , Lipshitz Howard D
Published: September 2004

The nuclear zinc-finger protein encoded by the hindsight (hnt) locus regulates several cellular processes in Drosophila epithelia, including the Jun N-terminal kinase (JNK) signaling pathway and actin polymerization. Defects in these molecular pathways may underlie the abnormal cellular interactions, loss of epithelial integrity, and apoptosis that occurs in hnt mutants, in turn causing failure of morphogenetic processes such as germ band retraction and dorsal closure in the embryo. To define the genetic pathways regulated by hnt, 124 deficiencies on the second and third chromosomes and 14 duplications on the second chromosome were assayed for dose-sensitive modification of a temperature-sensitive rough eye phenotype caused by the viable allele, hntpeb; 29 interacting regions were identified. Subsequently, 438 P-element-induced lethal mutations mapping to these regions and 12 candidate genes were tested for genetic interaction, leading to identification of 63 dominant modifier loci. A subset of the identified mutants also dominantly modify hnt308-induced embryonic lethality and thus represent general rather than tissue-specific interactors. General interactors include loci encoding transcription factors, actin-binding proteins, signal transduction proteins, and components of the extracellular matrix. Expression of several interactors was assessed in hnt mutant tissue. Five genes—apontic (apt), Delta (Dl), decapentaplegic (dpp), karst (kst), and puckered (puc)—are regulated tissue autonomously and, thus, may be direct transcriptional targets of HNT. Three of these genes—apt, Dl, and dpp—are also regulated nonautonomously in adjacent non-HNT-expressing tissues. The expression of several additional interactors—viking (vkg), Cg25, and laminin-α (LanA)—is affected only in a nonautonomous manner.
FDA/PI flow cytometry assay of complement‐mediated cytotoxicity of antibodies generated during xenotransplantation
Authors: Díaz Tomas M. , Pértega Sonia , Ortega Dolores , López Eduardo , Centeno Alberto , Mañez Rafael , Doménech Nieves
Published: September 2004

Background

A flow cytometry complement‐mediated cytotoxicity assay (FCCA) using fluorescein diacetate (FDA) and propidium iodide (PI) to measure antibody‐dependent toxicity is useful to determine the success of xenotransplant organs. We evaluated the validity of different mathematical models as a measure of cytotoxicity in FCCA.

Methods

Sera from untreated baboons (n = 7) and from immunosuppressed animals (n = 5) undergoing different xenotransplantation protocols with pig organs were tested by endogenous FCCA and a similar assay also using exogenous complement, and the results were compared with those of a complement‐dependent hemolytic assay to detect anti‐pig antibodies (APHA). The influence of PI/FDA staining and the use of several mathematical models were analyzed.

Results

For both groups of animals, we observed high correlations between the endogenous and exogenous FCCA pathways and between calculations based on PI and FDA staining. Of the four mathematical models tested—the Von Krogh equation, two exponential models, and area under the curve—the Von Krogh equation was the most appropriate in terms of goodness of fit and concordance with APHA.

Conclusions

FDA/PI FCCA is useful to measure endogenous and exogenous complement‐mediated cytotoxicities, and it has advantages related to identification of potential new xenoantibodies. Although all four mathematical models produced acceptable solutions, the Von Krogh equation was the best option. © 2004 Wiley‐Liss, Inc.
Small Cyclic Disulfide Peptides: Synthesis in Preparative Amounts and Characterization by Means of NMR and FT‐IR Spectroscopy
Authors: Kolano Christoph , Gomann Klaus , Sander Wolfram
Published: September 2004

Two cyclic disulfide‐bridged tetrapeptides [cyclo(Boc−Cys−Pro−Aib−Cys−OMe) and cyclo(Boc−Cys−Pro−Phe−Cys−OMe)] were prepared in high yield and purity. The use of double‐walled reaction flasks, which were attached to an external cryostat, gave perfect temperature control of the reaction. The acetamidomethyl and trityl group were used for the protection of the thiol groups of Cys. Disulfide bond formation was obtained by cleavage of the protection groups and subsequent oxidation of the free thiols with iodine under high dilution conditions in one step. The obtained cyclic peptides were checked for purity by analytical HPLC, and identified by NMR spectroscopy and a variety of standard analytical methods (IR, m. p., FAB‐MS, ELA, TLC). Conformational properties of the peptides were derived from one‐ and two‐dimensional NMR experiments. Temperature‐dependent NMR and FT‐IR experiments allowed for the determination of the degree of inter‐ and intramolecular hydrogen bonding of the cyclic tetrapeptides. The results from the temperature‐dependent NMR experiments are in good agreement with the observed dynamics of the peptides in the amide I and II region, which were determined by means of temperature‐dependent FT‐IR spectroscopy using the ATR technique. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Preparation of Chiral 2‐Stannyloxazolidines and First Considerations on the Transacetalisation Reaction Mechanism
Authors: Cintrat Jean‐Christophe , Léat‐Crest Véronique , Parrain Jean‐Luc , Le Grognec Erwan , Beaudet Isabelle , Quintard Jean‐Paul
Published: September 2004

N‐Protected 2‐tributylstannyl‐1,3‐oxazolidines derived from N‐monoprotected chiral β‐amino alcohols were obtained through transacetalisation of (diethoxymethyl)tributylstannane under acidic conditions. In the case of 4‐substituted 2‐tributylstannyl‐1,3‐oxazolidines, the kinetic product of the reaction was shown to be the trans isomer whatever the nature of the protective group, while the thermodynamic product was the cis isomer in the N‐Ts series and the trans isomer in N‐CO2R compounds. Aspects of the transacetalisation reaction are discussed along with those concerning the isomerisation of the products, allowing an interpretation of the obtained results. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
[2+2]‐Cycloaddition of Chlorosulfonyl Isocyanate to (Z)‐Propenyl Ethers Bound to Polystyrene Resins by Alkylsulfonyl Linkers
Authors: Łysek Robert , Grzeszczyk Barbara , Furman Bartłomiej , Chmielewski Marek
Published: September 2004

The 3‐O‐ and 5‐O‐(Z)‐propenyl ethers derived from 1,2‐O‐isopropylidene‐α‐D‐xylo‐ and glucofuranoses, respectively, were attached to the Merrifield, MPPC and NCPSC resins using alkylsulfonyl linkers. The [2+2]‐cycloaddition of chlorosulfonyl isocyanate to the polymer‐bound vinyl ethers followed by the intramolecular alkylation of the β‐lactam nitrogen led to the formation of mixtures of the corresponding diastereomeric oxacephams or clavams with a low stereoselectivity. In the case of Merrifield and MPP resins, the β‐lactams were accompanied by the corresponding oxetanes or oxiranes. Reactions performed using soluble polymer proceeded similarly to those carried out in solution. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Four New Derivatives of Trihomononactic Acids from Streptomyces globisporus
Authors: Řezanka Tomáš , Spížek Jaroslav , Přikrylová Věra , Dembitsky Valery M.
Published: September 2004

New compounds, namely a homolog of nonactic acid (trihomononactic acid), its lactone and dilactones were isolated from a strain of Streptomyces globisporus. Their structures, including the absolute configurations of the hydroxy and methyl groups, were determined by spectroscopic techniques such as UV, IR, MS, 1D and 2D NMR spectroscopy. All compounds were highly active against Gram‐positive bacteria and brine shrimp. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Dithiocarbamates, Thiocarbamic Esters, Dithiocarboimidates, Guanidines, Thioureas, Isothioureas, and Tetraazathiapentalene Derived from 2‐Aminobenzothiazole
Authors: Téllez Fabiola , Cruz Alejandro , López‐Sandoval Horacio , Ramos‐García Iris , Gayosso Martha , Castillo‐Sierra R. Nely , Paz‐Michel Brenda , Nöth Heinrich , Flores‐Parra Angelina , Contreras Rosalinda
Published: September 2004

Reactions between CS2 and the exocyclic amino groups of 2‐aminobenzothiazoles gave series of molecules bearing thiourea, isothiourea, dithiocarbamate, dithiocarboimine, dimethyldithiocarbamate, methyldithiocarbamate, S‐CH3 and O‐alkyl thiocarbamic ester, and guanidine groups. Preferred tautomers and conformers were determined. Most compounds present coordinative bonds between the endocyclic sulfur atom, which behaves as a Lewis acid, and oxygen, nitrogen, and sulfur acting as bases. A new dibenzothiazolyltetraazathiapentalene containing a T‐shaped hypervalent sulfur atom and displaying “single bond‐no bond resonance” is discussed. X‐ray structures of eleven compounds are reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Chiral Poly(aromatic amide ester) Dendrimers Bearing an Amino Acid Derived C3‐Symmetric Core − Synthesis and Properties
Authors: Romagnoli Barbara , van Baal Ingrid , Price David W. , Harwood Laurence M. , Hayes Wayne
Published: September 2004

The effect of hyperbranched macromolecular architectures (dendrimers) upon chirality has received significant attention in recent years in the light of the proposal of amplification of chirality. In particular, several studies have been carried out on the chiroptical properties of dendrimers that contain a chiral core and achiral branches in order to determine if the chirality of the central core can be transmitted to the distal region of the macromolecule. In addition to interest of a pure academic nature, the presence of such chiral conformational order would be extremely useful in the development of asymmetric catalysts. In this paper, a novel class of chiral dendrimers is described − these perfect hyperbranched macromolecules have been prepared by a convergent route by the coupling of a chiral central core based upon tris(2‐aminoethyl)amine and poly(aromatic amide ester) dendritic branches. The chiral properties of these dendrimers have been investigated by detailed optical rotation studies and circular dichroism analysis; the results of these studies are described herein. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Cover Picture: Synthesis of a Novel Enantiopure Spiro‐B‐norestradiol Analogue by Multiple Pd‐Catalyzed Transformations (Eur. J. Org. Chem. 20/2004)
Authors: Tietze Lutz F. , Wiegand J. Matthias , Vock Carsten A.
Published: September 2004

The cover picture shows the unexpected formation of an unusual enantiopure spiro‐B‐norsteroid instead of the corresponding annulated compound by a twofold palladium‐catalyzed transformation of a hydrindane−boronic ester and an ortho‐bromobenzyl chloride. Details are discussed in the article by L. F. Tietze et al. on p. 4107 ff.
Assembly of Glucose Oxidase and Different Polyelectrolytes by Means of Electrostatic Layer‐by‐Layer Adsorption on Thiolated Gold Surface
Authors: Rodríguez Marcela C. , Rivas Gustavo A.
Published: September 2004

A rational strategy for the construction of a bioelectrocatalytic architecture by means of alternate electrostatic adsorption is described. Multilayer films containing glucose oxidase (GOx) and different polyelectrolytes were assembled onto a thiolated‐gold surface and the resulting bioelectrode was used for glucose biosensing. The supramolecular multistructure was prepared by assembling polyethylenimine and Nafion (as anti‐interference barrier), followed by the adsorption of polyethylenimine and DNA (as stabilizing film) and finally by the alternate deposition of polyethylenimine and glucose oxidase (as a biocatalytic layer). The influence of the deposition time and concentration of polyelectrolytes, organization and number of layers on the sensitivity and selectivity of the bioelectrode is discussed. The resulting enzymatic biorecognition layer exhibits very good analytical performance with a fast, sensitive (3.3±0.1)×104 nA M−1 and highly selective (0% interference for 6.0 mg % uric acid and 2.0×10−4 M ascorbic acid) response to glucose, demonstrating that the alternate electrostatic adsorption of conveniently selected polyelectrolytes allow a large improvement in the selectivity and sensitivity of a biosensor.
Ormosil Encapsulated Pyrroloquinoline Quinone‐Modified Electrochemical Sensor for Thiols
Authors: Joshi Kanchan A. , Pandey Prem C. , Chen Wilfred , Mulchandani Ashok
Published: September 2004

An organically modified sol‐gel glass (ORMOSIL) encapsulating pyrroloquinoline quinone (PQQ)‐modified electrode for the rapid, sensitive and simple determination of thiol‐containing compounds such as cysteine and glutathione is reported. The effect of applied potential, nature of thiol compound and pH on the response of the sensor was examined and optimum conditions were determined. The electrochemical responses and detection limits were found to be sensitive to the nature of thiols and pH. The electrochemical responses for cysteine and glutathione at an applied potential of −0.2 V (vs. Ag/AgCl) were found to be linear with detection limits of 18 nM for cysteine and 36 nM for glutathione at pH 3.5, whereas the detection limits at pH 8.5 were 0.5 μM for cysteine and 1 μM for glutathione. The electrode retained 95% of the original response for 7 days when stored at 4 °C. The ORMOSIL‐encapsulated PQQ was also characterized by spectrophotometry. The absorbance measurement using 5,5′‐dithiobis(2‐nitrobenzoic acid) at 412 nm justify the PQQ‐mediated oxidation of glutathione whereas fluorescence measurements (excitation wavelength=380 nm; emission wavelength=480 nm) justify the successful encapsulation of PQQ in ORMOSIL matrix.
Development of Enzyme Biosensor Based on ISFETs for Quantitative Analysis of Serine Proteinases
Authors: Biloivan Olga A. , Dzyadevych Sergiy V. , Boubriak Olga A. , Soldatkin Alexey P. , El'skaya Anna V.
Published: September 2004

A new potentiometric biosensor allowing quantitative determination of the proteinases through their esterase activity has been developed. The biosensor, specific for ester artificial substrates of serine proteinases has been fabricated using a pH‐sensitive field effect transistor (pH‐FET) and an immobilized complex of trypsin and α2‐macroglobulin. It has been shown that created biosensor is able to determine the activity of the soluble trypsin in the range of 0.1–30 U/mL (substrate BAEE). The relative standard deviation for the trypsin determination was approximately 3%. The operation stability of the biosensor was no less than 12 h (40 measurements). The response of the biosensor stored at +4 °C was stable for 30 days.
Modelling of the Potentiometric Response of ENFETs Based on Enzymatic Multilayer Membranes
Authors: Aouni F. , Mlika R. , Martelet C. , Ouada H. Ben , Jaffrezic‐Renault N. , Soldatkin A. P.
Published: September 2004

Based on the modified site‐binding model, the response of urea‐sensitive enzymatic field effect transistors (ENFETs) is fitted. The effect of two types of surface sites (silanol and amine sites) and of additional polymeric permselective membrane on the sensitivity of the biosensor is discussed. It is found that the dependence of the slope of the sensor response versus pUrea, on the buffer concentration and on the diffusion of the urea in the enzymatic membrane can be translated by a parameter α that depends on the membrane composition. Moreover, the enhancement of the sensor sensitivity by deposition of additional permselective membranes can be illustrated by a parameter δ that depends on the association of additional permselective membranes and a buffer; the higher values of parameter δ are obtained with a Nafion membrane associated with a phosphate buffer.
Non‐self‐overlapping structured grid generation on an n‐sided surface
Authors: Wang Charlie C. L. , Tang Kai
Published: September 2004

Most existing meshing algorithms for a 2D or shell figure requires the figure to have exactly four sides. Generating structured grids in the n‐sided parametric region of a trimmed surface thus usually requires to first partition the region into four‐sided sub‐regions. We address the automatic structured grid generation problem in an n‐sided region by fitting a planar Gregory patch so that the partition requirement is naturally avoided. However, self‐overlapping may occur in some portions of the algebraically generated grid; this severely limits its usage in most of engineering and scientific applications where a grid system with no self‐intersecting is strictly required. To solve the problem, we use a functional optimization approach to move grid nodes in the u−v domain of the trimmed surface to eliminate the self‐overlapping. The derivatives of a Gregory patch, which are extremely difficult to compute analytically, are not required in our method. Thus, our optimization algorithm compares favourably at least in terms of speed with some other mesh optimization algorithms, such as the elliptic PDE method. In addition, to overcome the difficulty of guessing a good initial position of every grid node for the conjugate gradient method, a progressive optimization algorithm is incorporated in our optimization. Experiment results are given to illustrate the usefulness and effectiveness of the presented method. Copyright © 2004 John Wiley & Sons, Ltd.
Estimating the demand for health care with panel data: a semiparametric Bayesian approach
Authors: Jochmann Markus , León‐González Roberto
Published: September 2004

This paper is concerned with the problem of estimating the demand for health care with panel data. A random effects model is specified within a semiparametric Bayesian approach using a Dirichlet process prior. This results in a very flexible distribution for both the random effects and the count variable. In particular, the model can be seen as a mixture distribution with a random number of components, and is therefore a natural extension of prevailing latent class models. A full Bayesian analysis using Markov chain Monte Carlo simulation methods is proposed. The methodology is illustrated with an application using data from Germany. Copyright © 2004 John Wiley & Sons, Ltd.
Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice
Authors: Afaq Farrukh , Saleem Mohammad , Krueger Christian G. , Reed Jess D. , Mukhtar Hasan
Published: September 2004

Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single‐target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor‐promoting effects. We first determined the effect of topical application of PFE to CD‐1 mice against 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time‐dependent manner, against TPA‐mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase‐2. We also found that topical application of PFE resulted in inhibition of TPA‐induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF‐κB and IKKα and phosphorylation and degradation of IκBα. We next assessed the effect of skin application of PFE on TPA‐induced skin tumor promotion in 7,12‐dimethylbenz(a)anthracene‐initiated CD‐1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA‐treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE‐treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskin‐tumor‐promoting effects in CD‐1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPA‐induced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in‐depth study to define active agent(s) in PFE capable of affording antitumor‐promoting effect is warranted.