bluuebunny/crossref_metadata_2025_split huggingface dataset:
Productive Asymmetric Synthesis of All Four Diastereomers of 3‐(trans‐2‐Nitrocyclopropyl)alanine from Glycine with (S)‐ or (R)‐2‐[(N‐Benzylprolyl)amino]benzophenone as a Reusable Chiral Auxiliary
Authors: Larionov Oleg V. , Savel'eva Tatyana F. , Kochetkov Konstantin A. , Ikonnokov Nikolai S. , Kozhushkov Sergei I. , Yufit Dmitrii S. , Howard Judith A. K. , Khrustalev Viktor N. , Belokon Yuri N. , de Meijere Armin 
Published: February 2003

AbstractAll four diastereomers of 3‐(trans‐2‐nitrocyclopropyl)alanine (3) were prepared by asymmetrically induced α‐C alkylation of the glycine moiety in the [(S)‐ or (R)‐Schiff base]NiII complex 7, employing racemic trans‐1‐(iodomethyl)‐2‐nitrocyclopropane (8) as the alkylating agent. A notable difference in solubility between the two diastereomeric products 9a/9b [when (S)‐7 was used as starting material] or 9d/9e [when (R)‐7 was employed] allowed for their separation from the same reaction mixture. All the diastereomers of 3‐(trans‐2‐nitrocyclopropyl)alanine (3) were produced upon brief exposure of the alkylation products 9 to dilute hydrochloric acid, with subsequent purification by ion‐exchange chromatography and crystallization. The absolute configurations of the nickel complexes 9a−e were established by X‐ray crystallographic analyses. In addition, the X‐ray crystal structure of (2S,1′S,2′R)‐3 was determined to confirm the convergence of the configurations of the parent nickel complexes 9 with those of the amino acids 3 derived from them. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Steady spatial asymptotics for the Vlasov–Poisson system
Authors: Schaeffer Jack 
Published: February 2003

AbstractA collisionless plasma is modelled by the Vlasov–Poisson system in three space dimensions. A fixed background of positive charge, which is independent of time and space, is assumed. The situation in which mobile negative ions balance the positive charge as ∣x∣ tends to infinity is considered. Hence, the total positive charge and the total negative charge are infinite. Smooth solutions with appropriate asymptotic behaviour were shown to exist locally in time in a previous work. This paper studies the time behaviour of the net charge and a natural quantity related to energy, and shows that neither is constant in time in general. Also, neither quantity is positive definite. When the background density is a decreasing function of ∣v∣, a positive definite quantity is constructed which remains bounded. A priori bounds are obtained from this. Copyright © 2003 John Wiley & Sons, Ltd.
Potential biases in sampling design and interpretation of intra‐tooth isotope analysis
Authors: Balasse M. 
Published: February 2003

AbstractAn increasing number of studies dealing with environmental and dietary reconstruction involve measurement of intra‐tooth variation of isotope ratios. The sampling procedure typically consists of collecting a sequence of horizontal bands perpendicular to the growth axis of the tooth. The objective is to obtain a temporal sequence of the changes recorded in dental tissues during tooth development. This paper examines some issues associated with this sampling strategy and consequences for interpretation of the data. Time resolution is influenced by the pattern and duration of enamel mineralization, in a way that might, however, depend on the species and the tooth analysed. Although it may be impossible to sample discrete amounts of time, a chronological order seems to be respected, which should be well enough when the objective is to detect changes in isotope ratios with time. Absolute data must be interpreted with caution. Such issues do not affect studies of inter‐individual variability as long as the sampling procedure applied to the compared specimens is consistent. A new sampling strategy is tested on modern goat teeth, involving drilling in an oblique direction. The results obtained from obliquely drilled samples are very similar to those obtained from the horizontal sampling procedure. More work is still needed to determine the value of alternative sampling strategies. Copyright © 2003 John Wiley & Sons, Ltd.
Latitudinal and longitudinal process diversity
Authors: Siebel Nils T , Cook Stephen , Satpathy Manoranjan , Rodrìguez Daniel 
Published: February 2003

AbstractSoftware processes vary across organizations and over time. Managing this process diversity is a delicate balancing act between creative, healthy diversity and chaos. In this paper, we examine a particular aspect of this issue, namely some relationships between diversity in software processes, software evolution and the quality of software products and processes. Our main contribution is to distinguish between two broad kinds of process diversity, which we call latitudinal and longitudinal process diversity. To illustrate the differences between these two, we examine the case of a medium‐sized system (50 000 lines of C++ code) which has undergone major changes during its lifetime of 10 years. The software was originally developed by an individual academic using a research‐oriented process to develop a standalone proof‐of‐concept system. In a current multi‐team project, involving three industrial and three academic partners, the software has been adapted for integration as a subsystem of a near‐market product. We suggest ways in which the observed process diversity seems to be linked to a change in the software's propensity for evolution, and we discuss the impact of this on both product and process quality. Copyright © 2003 John Wiley & Sons, Ltd.
Helpless attributions and depression in adolescents: the roles of anxiety, event valence, and demographics
Authors: Waschbusch Daniel A. , Sellers Denise P. , LeBlanc Monique , Kelley Mary L. 
Published: February 2003

ABSTRACTThe relationship between helpless attributions and depression is well established. This study evaluated whether anxiety, event valence (positive or negative) and demographic variables (gender, age, socioeconomic status or race) influence this relationship. Results showed: (1) adolescents with anxiety and depression who were from lower socioeconomic backgrounds made less helpless attributions for negative events than did adolescents from higher socioeconomic backgrounds, (2) male adolescents with anxiety‐only had helpless attribution styles that were similar to male adolescents with depression, but the same was not true for female adolescents, and (3) African‐American adolescents showed less helpless attributions for negative events than did Caucasian adolescents. Results replicate past research showing that a helpless attribution style is associated with depression in adolescence, but suggest that this pattern may be influenced by demographic factors. Results also suggest that helpless attributions may be related to both anxiety and depression in males.
Viral and Cellular Determinants of Hepatitis C Virus RNA Replication in Cell Culture
Authors: Lohmann Volker , Hoffmann Sandra , Herian Ulrike , Penin Francois , Bartenschlager Ralf 
Published: February 2003

ABSTRACT
Studies on the replication of hepatitis C virus (HCV) have been facilitated by the development of selectable subgenomic replicons replicating in the human hepatoma cell line Huh-7 at a surprisingly high level. Analysis of the replicon population in selected cells revealed the occurrence of cell culture-adaptive mutations that enhance RNA replication substantially. To gain a better understanding of HCV cell culture adaptation, we characterized conserved mutations identified by sequence analysis of 26 independent replicon cell clones for their effect on RNA replication. Mutations enhancing replication were found in nearly every nonstructural (NS) protein, and they could be subdivided into at least two groups by their effect on replication efficiency and cooperativity: (i) mutations in NS3 with a low impact on replication but that enhanced replication cooperatively when combined with highly adaptive mutations and (ii) mutations in NS4B, -5A, and -5B, causing a strong increase in replication but being incompatible with each other. In addition to adaptive mutations, we found that the host cell plays an equally important role for efficient RNA replication. We tested several passages of the same Huh-7 cell line and found up to 100-fold differences in their ability to support replicon amplification. These differences were not due to variations in internal ribosome entry site-dependent translation or RNA degradation. In a search for cellular factor(s) that might be responsible for the different levels of permissiveness of Huh-7 cells, we found that replication efficiency decreased with increasing amounts of transfected replicon RNA, indicating that viral RNA or proteins are cytopathic or that host cell factors in Huh-7 cells limit RNA amplification. In summary, these data show that the efficiency of HCV replication in cell culture is determined both by adaptation of the viral sequence and by the host cell itself.
Diversity of the Human Immunodeficiency Virus Type 1 (HIV-1)
env
Sequence after Vertical Transmission in Mother-Child Pairs Infected with HIV-1 Subtype A
Authors: Verhofstede Chris , Demecheleer Els , De Cabooter Nancy , Gaillard Philippe , Mwanyumba Fabian , Claeys Patricia , Chohan Varsha , Mandaliya Kishorchandra , Temmerman Marleen , Plum Jean 
Published: February 2003

ABSTRACT

Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1,016-bp fragment of the
env
gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.
Genetic Characterization of Rebounding Human Immunodeficiency Virus Type 1 in Plasma during Multiple Interruptions of Highly Active Antiretroviral Therapy
Authors: Dybul Mark , Daucher Marybeth , Jensen Mark A. , Hallahan Claire W. , Chun Tae-Wook , Belson Michael , Hidalgo Bertha , Nickle David C. , Yoder Christian , Metcalf Julia A. , Davey Richard T. , Ehler Linda , Kress-Rock Diane , Nies-Kraske Elizabeth , Liu Shuying , Mullins James I. , Fauci Anthony S. 
Published: February 2003

ABSTRACT

Various strategies of interrupting highly active antiretroviral therapy (HAART) are being investigated for the treatment of human immunodeficiency virus (HIV) infection. Interruptions of greater than 2 weeks frequently result in rebound of plasma HIV RNA. In order to discern changes in the viral population that might occur during cycles of treatment interruption, we evaluated the homology of HIV-1 envelope gene sequences over time in 12 patients who received four to seven cycles of 4 weeks off HAART followed by 8 weeks on HAART by using the heteroduplex tracking assay and novel statistical tools. HIV populations in 9 of 12 patients diverged from those found in the first cycle in at least one subsequent cycle. The substantial genetic changes noted in HIV
env
did not correlate with increased or decreased log changes in levels of plasma HIV RNA (
P
> 0.5). Thus, genetic changes in HIV
env
itself did not contribute in a systematic way to changes in levels of plasma viremia from cycle to cycle of treatment interruption. In addition, the data suggest that there may be multiple compartments contributing to the rebound of plasma viremia and to viral diversity from cycle to cycle of intermittent therapy.
Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells
Authors: Schmidt Susanne M. , Schag Kerstin , Müller Martin R. , Weck Markus M. , Appel Silke , Kanz Lothar , Grünebach Frank , Brossart Peter 
Published: February 2003

AbstractSurvivin, a member of the inhibitor of apoptosis protein family, is expressed in almost all types of malignancies, making this protein a useful tool for the development of broadly applicable vaccination therapies. We used a recently identified HLA-A2 binding peptide and dendritic cells (DCs) from healthy donors to induce survivin-specific cytotoxic T lymphocytes (CTLs) in vitro. These T cells efficiently lysed target cells pulsed with the cognate peptide. Furthermore, survivin-specific CTLs recognized HLA-A2–matched tumor cell lines and primary malignant cells from patients with leukemia in an antigen-specific and HLA-restricted manner as demonstrated with the use of cold target inhibition assays and blocking antibodies. To validate the immunogenicity of survivin we performed the experiments in an autologous setting and used monocyte-derived DCs as targets. Interestingly, we found that DCs up-regulate survivin expression on stimulation with tumor necrosis factor α (TNF-α). However, these mature DCs were not recognized by survivin-specific CTLs, whereas they lysed autologous mature DCs pulsed with the antigenic peptide or transfected with whole tumor RNA purified from a survivin-expressing cell line. To further analyze the possible use of survivin-specific CTLs in cancer therapies, we induced survivin-specific CTLs using peripheral blood mononuclear cells (PBMNCs) and DCs from a patient with chronic lymphocytic leukemia (CLL). The in vitro–generated T cells efficiently recognized autologous malignant CLL cells, whereas they spared autologous-purified nonmalignant B cells or DCs. Our results demonstrate that survivin epitopes are presented on a broad variety of malignancies and can be applied in vaccination therapies.
Human IL-12(p35) gene activation involves selective remodeling of a single nucleosome within a region of the promoter containing critical Sp1-binding sites
Authors: Goriely Stanislas , Demonté Dominique , Nizet Séverine , De Wit Dominique , Willems Fabienne , Goldman Michel , Van Lint Carine 
Published: February 2003

AbstractTo get insight into the regulation of human interleukin-12 (IL-12) synthesis, we determined the chromatin organization of the IL-12(p35) promoter region. First, we determined positioning of nucleosomes within the IL-12(p35) promoter using the indirect end-labeling technique in the THP-1 monocytic cell line. On stimulation with bacterial lipopolysaccharide (LPS) and interferon-γ (IFN-γ), hypersensitivity to digestion with DNase I, micrococcal nuclease, and specific restriction enzymes was detected in the region encompassing nucleotide (nt) –310 to –160, indicating selective inducible chromatin remodeling involving disruption of a single nucleosome (named nuc-2). Using p35 promoter deletion mutants and reporter gene assays, we demonstrated that the –396/–241 region contained critical cis-acting elements. Within this latter region, we characterized physically and functionally 2 Sp1-binding sites, which were acting as key regulatory elements for both basal and LPS/IFN-γ–inducible p35 gene expression: Sp1#1 lies within the remodeled nuc-2 region and Sp1#2 is located in the nucleosome-free region immediately upstream of nuc-2. Finally, we extended the chromatin structure analysis to dendritic cells (DCs) derived from human monocytes and observed the same nucleosomal organization and remodeling as in the THP-1 cell line. Moreover, we found that in DCs, LPS and IFN-γ synergized in the induction of nucleosomal remodeling and that chromatin remodeling at the p35 locus immediately preceded IL-12(p35) mRNA synthesis. Taken together, our results demonstrate that IL-12(p35) gene activation in the course of DC maturation involves selective and rapid remodeling of a single positioned nucleosome within a region of the promoter containing critical Sp1-binding sites.
Generation of Reactive Species by One‐Electron Reduction of Fischer‐Type Carbene Complexes of Group 6 Metals and Their Use for Carbon–Carbon Bond Formation
Authors: Fuchibe Kohei , Iwasawa Nobuharu 
Published: February 2003

AbstractCarbon–carbon bond‐forming reactions mediated by one‐electron reduction of Fischer‐type carbene complexes of Group 6 metals were investigated. In the case of aryl‐ or silylcarbene complexes of tungsten, the anion radical species generated by one‐electron reduction smoothly underwent addition reaction to ethyl acrylate. One‐electron reduction of α,β‐unsaturated carbene complexes afforded biscarbene complexes by dimerization of the corresponding anion radical species at the position γ to the metal center. In contrast, one‐electron reduction of chromium phenyl‐ or alkylcarbene complexes gave, via carbonyl insertion, α‐methoxyacylchromate complexes, which further underwent conjugate addition to various electron‐poor olefins to give the corresponding α‐methoxyketones.
Surviving in an environment of financial indiscipline: a case study from a transition country
Authors: Pejic‐Bach Mirjana 
Published: February 2003

AbstractFinancial indiscipline combined with restricted access to financial markets is a big problem for small businesses in transition countries. In such an environment, small businesses find it hard to collect accounts receivable from their customers, which causes liquidity crises and, in the worst case, bankruptcy. This article describes the development of a system dynamics model to explain the financial indiscipline problem in small businesses. Various policy options are evaluated using this model: (1) retaining profit; (2) borrowing money from the bank; (3) tightening the accounts receivable policy; and (4) delaying payment to suppliers. Tightening the accounts receivable policy in combination with delaying payment to suppliers is found to be the most successful option. However, in most of the transition countries, the legal system is inefficient and such measures would lead to an illiquid economy with a weak small‐business sector. Copyright © 2003 John Wiley & Sons, Ltd.
Stochastic analysis in life office management: applications to large annuity portfolios
Authors: Coppola Mariarosaria , Di Lorenzo Emilia , Sibillo Marilena 
Published: February 2003

AbstractThe paper deals with the riskiness analysis for a large portfolio of life annuities. By means of the limiting distribution of the present value of the portfolio, in the first part of the paper a model for evaluating the investment and the projection risks is presented. In the second part, with regard to the investment risk's effects, the insolvency risk is measured considering the cumulative probability distribution function of the discounted average cost per policy. Copyright © 2003 John Wiley & Sons, Ltd.
SPE/RIA vs LC/MS for measurement of low levels of budesonide in plasma
Authors: Dimova H. , Wang Y. , Pommery S. , Moellmann H. , Hochhaus G. 
Published: February 2003

AbstractA radioimmunoassay is described that measures budesonide in plasma after solid‐phase extraction (SPE/RIA) of the analyte. The performance of the assay was compared with that of a selective LC/MS method. The limit of quantitation of budesonide determined for the LC/MS and SPE/RIA assay was 50 pg/mL and 120 pg/mL, respectively. Based on quality control samples, a higher variability was observed for the SPE/RIA (CV between 4.5 and 23.0%) than for the LC/MS method (CV between 7.5 and 12.5%). Plasma samples obtained from healthy volunteers after administration of budesonide rectal foam were assayed by both methods. In a subset of samples, these results were compared with those measured by direct RIA to evaluate the selectivity of two assays. About two times higher budesonide levels were measured with the direct RIA (lacking the extraction step), presumably because of cross‐reactivity with budesonide metabolites, indicating that the extraction step in SPE/RIA is necessary for selectivity. Both SPE/RIA and LC/MS methods were found to be selective, sensitive and suitable for pharmacokinetic studies. Results obtained from the two methods were compared with a number of statistical methods. Ratios of results obtained for the clinical samples were close to 1 (ratio LC‐MS/ SPE/RIA = 0.98 ± 0.27). Linear regression indicated a slope of 1.17 ± 0.0378. The concordance correlation (r = 0.91) indicated that the agreement between both methods was fair while the Bland–Altman plot indicated that the agreement was less pronounced at higher concentrations (1–3 ng/mL). In summary, the results confirm that the SPE/RIA is an alternative to HPLC/MS and that among the statistical methods tested the concordance correlation analysis was judged to be the most informative test to assess the comparability of two methods. Copyright © 2002 John Wiley & Sons, Ltd.
Quantitative determination of saquinavir from Caco‐2 cell monolayers by HPLC‐UV
Authors: Ucpinar Sibel Demirbas , Stavchansky Salomon 
Published: February 2003

AbstractThe validation and quantitative determination of the protease inhibitor, saquinavir, from confluent Caco‐2 monolayers and from aqueous solution is reported. The high performance liquid chromatographic method consisted of an Ultramex™ 5 C8 reverse‐phase column (250 × 4.6 mm i.d.) and a mobile phase of acetonitrile:water:triethylamine (55:44:1, v/v/v, pH 6.5). Samples were analyzed using an ultraviolet detector at 238 nm, and diltiazem hydrochloride (66 µg/mL) was used as an internal standard. A linear response over a broad concentration range (0.4–8.0 µg/mL, r2 = 0.997) was obtained. The limit of detection and quantitation was set at 0.14 and 0.4 µg/mL, respectively. Over a 4 day period, the intra‐day and inter‐day precision ranged from 1 to 7% with a mean of 4%, and from 1 to 2% with a mean of 1.5%, respectively. Bench–top and storage stability of saquinavir was found to be satisfactory. The permeability of saquinavir through Caco‐2 monolayers was estimated using this assay. Copyright © 2002 John Wiley & Sons, Ltd.