bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast improvements for scrolling‐color LCoS
Authors: Shimizu J. A. , Janssen P. , Yakovenko S. , Anderson D.
Published: January 2005

Abstract— A scrolling‐color LCoS (liquid‐crystal‐on‐silicon) display must exhibit both fast speed and high contrast. These requirements drive design choices for the liquid crystal and optics of the image kernel. The input director was aligned to the incoming polarization and a compensated 45TN0 effect was choosen. Contrast demands place tight requirements on interfacial reflections. A wire‐grid PBS can achieve high contrast and can simplify the system construction. With attention to the above, we report a sequential contrast of 800:1 at the viewing screen. With a 90TN0 effect, the contrast can be increased even further, but with some penalty in light efficiency. With this effect, sequential contrast of 2000:1 was measured.
Enhanced PL and VUV absorption of BaZr(BO3)2:Eu3+ by Al3+ incorporation
Authors: Tian Lianhua , Mho Sun‐il , Yu Byung‐Yong , Pyun Chong‐Hong
Published: January 2005

Abstract— The photoluminescence (PL) and vacuum‐ultraviolet excitation (VUV) properties of BaZr(BO3)2 doped with the Eu3+ activator ion were studied as a new red phosphor for PDP applications. The excitation spectrum shows strong absorption in the VUV region with an absorption band edge at 200 nm. The charge‐transfer excitation band of Eu3+ was enhanced by co‐doping with an Al3+ ion into the BaZr(BO3)2 lattices. The PL spectrum shows the strongest emission at 615 nm, corresponding to the electric dipole 5D0 → 7F2 transition of Eu3+ in BaZr(BO3)2, which results in good red‐color purity.
The effects of barge shocks on soybean basis levels in Arkansas: A study of market integration
Authors: McKenzie Andrew M.
Published: January 2005

The response of Arkansas Delta and Gulf soybean basis levels to barge rate shocks is investigated. Results suggest basis levels react negatively to an increase in the barge rate, implying the burden of higher transportation costs are at least in part transmitted to the farm level. Internal Arkansas Delta markets are highly integrated with the Gulf export market. For example, Gulf soybean shocks, which reflect unexpected increases in soybean export demand, are simultaneously transmitted to internal markets, and result in correspondingly higher Arkansas Delta basis levels. Domestic market disturbances such as crush margin and financial storage cost shocks are found to immediately affect barge rates and to subsequently impact both Gulf and internal basis levels. [EconLit citations: F150.] © 2005 Wiley Periodicals, Inc. Agribusiness 21: 37–52, 2005.
Developing marketing strategies for green grocers: An application of SERVQUAL
Authors: Eastwood David B. , Brooker John R. , Smith James D.
Published: January 2005

Successful food retailing depends to a significant degree on providing a positive shopping environment for consumers. The SERVQUAL format is one way of gathering information about shoppers' ideal and actual ratings of an outlet's characteristics. Three modifications of the conventional application of the questionnaire are described. Implementation of the methodology is shown to be an effective tool for a retailer to identify strengths and weaknesses with respect to patrons' evaluations of outlet characteristics. Six green grocers were selected to reflect the diversity of outlets in a state, and the survey was conducted in the spring of 2000. Results indicate consumer ratings vary by feature group for ideal, actual, and actual minus ideal subgroup scores. The information can be used to generate better store‐specific strategies to meet consumer expectations. [EconLit citations: C42, Q13.] © 2005 Wiley Periodicals, Inc. Agribusiness 21: 81–96, 2005.
Conservation, markets, and fisheries policy: The North Atlantic bluefin tuna and the Japanese sashimi market
Authors: Martínez‐Garmendia Josué , Anderson James L.
Published: January 2005

This paper empirically illustrates the importance of market considerations for conservation with the U.S. bluefin tuna fishery. It measures the actual gains of a systemic approach to fisheries conservation where market, fishing technology, and fish population information are integrated in the regulatory process. In particular, we investigate the potential for increased rent extraction from the U.S. North Atlantic bluefin tuna fishery. We investigate how much the Japanese sashimi market would reward the U.S. fishery for improvements in quality, and whether the expected rise in revenues would be cost‐effective. The optimal results indicate moving away from gears such as purse‐seines and long‐lines in favor of harpoons and rod‐and‐reels, and concentrating the catch towards the end of the season. The analyses further indicate that it is more profitable to harvest fewer tuna but of greater size and quality than to focus on a great number of fish captures. This allows for a lower mortality and therefore a greater level of conservation of the resource. [EconLit citations: F180, Q220.] © 2005 Wiley Periodicals, Inc. Agribusiness 21: 17–36, 2005.
Overcoming informal trade barriers among Japanese intermediaries: An attitudinal assessment
Authors: Gehrt Kenneth C. , Lotz Sherry , Shim Soyeon , Sakano Tomoaki , Onzo Naoto
Published: January 2005

Access to foreign markets is increasingly critical to the U.S. as global competition increases. Past efforts by the U.S. to penetrate the Japanese market have often focused on overcoming formal trade barriers including tariffs, quotas, and product standards. Although this form of intervention has enjoyed success, limited effort has been devoted to analyzing informal trade barriers. This study examines informal trade barriers in terms of the attitudes of Japanese distributors toward U.S. products. The study focuses on a product‐market for which Japan is the leading single‐country importer for the U.S.: fruit. Recent inroads into the Japanese market by other countries have eroded the position of the U.S. This erosion will continue unless U.S. exporters can develop appropriate strategies based on sound market intelligence. © 2005 Wiley Periodicals, Inc. Agribusiness 21: 53–63, 2005.
A family based study of catechol‐O‐methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD)
Authors: Turic D. , Williams H. , Langley K. , Owen M. , Thapar A. , O'Donovan M.C.
Published: January 2005

Neurobiological studies have suggested that altered dopaminergic function may contribute to the etiology of attention deficit hyperactivity disorder (ADHD). The gene encoding catechol‐O‐methyltransferase (COMT) is an attractive candidate for ADHD susceptibility as it plays a major role in the degradation of dopamine. Moreover, a functional Val158Met polymorphism in COMT that alters the activity of the encoded protein has been strongly implicated in frontal lobe function, with the high activity Valine allele being associated with poorer performance, and ADHD is thought to involve fronto‐striatal pathways. We have examined this functional variant for association with ADHD in a family based association sample comprising 279 probands and their parents. We have also examined two other markers in the COMT gene (rs737865, rs165599) which, together with the Val/Met variant, have recently been shown to be associated with altered COMT expression rather than enzyme activity. No evidence for association was observed with any single marker or haplotype in a sample of 279 affected children and their parents. © 2004 Wiley‐Liss, Inc.
Meta‐analysis of the association of a functional serotonin transporter promoter polymorphism with alcohol dependence
Authors: Feinn Richard , Nellissery Maggie , Kranzler Henry R.
Published: January 2005

The neurotransmitter serotonin (5‐HT) has been shown to regulate alcohol consumption in both animals and humans. Since activity of the 5‐HT transporter protein (5‐HTT) regulates 5‐HT levels, the gene encoding this protein may contribute to the risk of alcohol dependence (AD). Studies of the association to AD of a functional insertion‐deletion polymorphism in the 5‐HTT‐linked promoter region (5‐HTTLPR) have yielded inconsistent results. We conducted a meta‐analysis of data from 17 published studies (including 3,489 alcoholics and 2,325 controls) investigating the association between 5‐HTTLPR alleles and AD. The frequency of the short (S) allele at 5‐HTTLPR was significantly associated with AD [odds ratio (OR) = 1.18, 95% CI = 1.03–1.33). Moreover, a greater association with the S allele was seen among individuals with AD complicated by either a co‐morbid psychiatric condition or an early‐onset or more severe AD subtype [OR = 1.34 (95% CI = 1.11–1.63)]. Allelic variation at 5‐HTTLPR contributes to risk for AD, with the greatest effect observed among individuals with a co‐occurring clinical feature. © 2004 Wiley‐Liss, Inc.
Family history influences age of onset in bipolar I disorder in females but not in males
Authors: Grigoroiu‐Serbanescu Maria , Nöthen Markus M. , Ohlraun Stephanie , Propping Peter , Maier Wolfgang , Wickramaratne Priya , Georgescu Marie‐Jana , Prelipceanu Dan , Grimberg Mihaela , Sima Dorina , Rietschel Marcella
Published: January 2005

Age of onset (AO) has been proposed as a promising criterion by which to select homogeneous subgroups for the genetic analysis of bipolar disorder. This is the first study to investigate the effect of the interaction between gender and family history (FH)‐type on AO in bipolar disorder. In accordance with the literature, no difference in AO was observed between females and males in our sample of 264 Romanian bipolar I probands. Cox regression, however, showed a strong influence of FH‐type on AO (P = 0.006). This was due to a significant variation in AO according to the type of FH in females (P = 0.002) but not in males (P = 0.64). Female bipolar disorder patients with a negative FH (FH−) had a later AO than females with either a FH of bipolar and/or schizoaffective disorder (P = 0.001) or a FH of recurrent unipolar major depression only (P = 0.04). Females with FH− had a later AO than males with FH− (P = 0.03). No sex difference was observed for AO in the group with a FH of recurrent unipolar depression. In the group with a FH of bipolar and/or schizoaffective disorder, females had an earlier AO than males (P = 0.01). A trend for support was observed in an independent sample of 217 German bipolar I patients for an influence of FH‐type on AO in females (P = 0.09) but not in males (P = 0.15). Female bipolar disorder patients with FH− had a later AO than females with either a FH of bipolar and/or schizoaffective disorder (P = 0.04) or a FH of recurrent unipolar major depression only (P = 0.05). Females with FH− had a later AO than males with FH− (P = 0.05). Other comparisons were statistically not significant, which may be due to limited sample size. Our findings emphasize that the interaction between gender and FH‐type is a source of heterogeneity for AO in bipolar disorder. © 2004 Wiley‐Liss, Inc.
Site‐specific cytosine methylation in S‐COMT promoter in 31 brain regions with implications for studies involving schizophrenia
Authors: Murphy Brenda C. , O'Reilly Richard L. , Singh Shiva M.
Published: January 2005

The catechol‐o‐methyltransferase (COMT) gene on chromosome 22q11 has been considered a strong candidate gene for schizophrenia (SZ) susceptibility. A functional Val/Met polymorphism in exon 4, with potential to affect COMT activity has been implicated in SZ, but the results remain inconclusive. We hypothesized that the association of COMT gene with SZ is not strictly a genetic alteration but could involve DNA methylation, as an epigenetic alteration. Thus, we chose to examine the cytosine DNA methylation profile of the human COMT promoter regions, which partially overlaps with the MB‐COMT coding region and covers a total of 56 cytosines. Our analysis of 31 brain regions and 51 individual blood samples suggests that the cytosine methylation in his region is restricted to the CpG dinucleotides only. Also, the methylation pattern is nearly identical in the brain and blood with few exceptions. One cytosine (#27) is partially methylated in 5 brain regions and another cytosine (#23) is partially methylated in 81 of 82 samples studied. The exception being the blood DNA from a single SZ patient with prominent extreme negative symptoms, which was completely methylated. Interestingly, there was no difference in methylation at these sites in the blood DNA from three pairs of monozygotic twins discordant for SZ. The results support the use of blood DNA in methylation studies and rule out S‐COMT promoter methylation as a common cause of SZ. The unique observation of a completely methylated cytosine 23 in one patient with SZ may have the potential to affect COMT mRNA transcription and gene activity, but remains to be evaluated. © 2004 Wiley‐Liss, Inc.
The metabolism of methylarsine oxide and sulfide
Authors: Cullen William R , McBride Barry C , Manji Hasseini , Pickett A Wendy , Reglinski John
Published: January 2005

Methylarsine oxide and sulfide are more toxic to Candida humicola than arsenite; the sulfide is rapidly metabolized to trimethylarsine (Me3As) and methylarsine (MeAsH2) and the oxide to dimethylarsinic acid [Me2AsO(OH)]. Cell‐free extracts of C. humicola also convert the oxide to Me2AsO(OH). The glutathione (RSH) derivative Me2AsSR is metabolized by C. humicola to Me3As and Me2AsH, but some other Me2AsSR′ compounds are unaffected. Studies involving the interaction of the arsenic(III) compounds with natural ecosystems and other micro‐organisms such as Scopulariopsis brevicaulis, Straptococcus sanguis, Escherichia coli, and Veillonella alcalescens are described.
Diagnostic value of sonography in patients with suspected carpal tunnel syndrome: A prospective study
Authors: Ziswiler Hans‐Rudolf , Reichenbach Stephan , Vögelin Esther , Bachmann Lucas M. , Villiger Peter M. , Jüni Peter
Published: January 2005

Objective

To determine the diagnostic value of sonography in patients with suspected carpal tunnel syndrome (CTS).

Methods

We conducted a prospective study of 110 wrists in 74 consecutive patients with suspected CTS who had been referred to a tertiary care center. We determined the largest cross‐sectional area of the median nerve at the carpal tunnel. Because of the lack of a universally accepted reference standard, we first examined the association of sonography with nerve conduction. Then, we compared sonography with a reference standard based on the combination of nerve conduction studies and signs and symptoms. Sonography and reference standard tests were performed independently and interpreted under blinded conditions. Based on a fitted receiver operating characteristic curve, we estimated likelihood ratios (LRs) and posttest probabilities for different cutoffs.

Results

There was a high concordance between sonography and nerve conduction. Based on the combined reference standard, a cutoff of 10 mm2 resulted in approximately equal sensitivity and specificity, but only moderate LRs. A cutoff of <8 mm2 had satisfactory power to rule out CTS: the fitted‐negative LR was 0.13. Conversely, a cutoff of ≥12 mm2 had excellent power to rule in CTS, with a fitted‐positive LR of 19.9. For nerves ≥12 mm2 and a pretest probability of 70% expected in patients with suspected CTS in tertiary care, we found a posttest probability of CTS of 98%.

Conclusion

Depending on setting and purpose, different cutoff values for the largest cross‐sectional area may be used to accurately rule in or rule out CTS. Using sonography as a first‐line test may cost‐effectively reduce the number of nerve conduction studies in patients with suspected CTS. A large‐scale, randomized controlled trial is required to determine the effects of sonography on clinical outcomes, the number of nerve conduction studies performed, and the total cost.
Increase in activated CD8+ T lymphocytes expressing perforin and granzyme B correlates with disease activity in patients with systemic lupus erythematosus
Authors: Blanco Patrick , Pitard Vincent , Viallard Jean‐François , Taupin Jean‐Luc , Pellegrin Jean‐Luc , Moreau Jean‐François
Published: January 2005

Objective

Cytotoxic T lymphocyte–mediated killing using granzyme B has recently been proposed to be a preferential and selective source of autoantigens in systemic autoimmune diseases, including systemic lupus erythematosus (SLE), while other reports have indicated that cytolytic activity in SLE patients was decreased. The aim of this study was to examine the phenotypic and functional status of the CD8+ T cells in SLE patients.

Methods

Phenotype analysis of CD8+ T cells was carried out using flow cytometry. The cytotoxic potential of CD8+ T cells and its consequences were examined in redirected‐killing experiments. SLE patients with quiescent disease (n = 41) were compared with SLE patients with active disease (n = 20), normal individuals (n = 36), and control patients with vasculitis (n = 14). Cytotoxic CD8+ T cell differentiation was examined by coculture with differentiated dendritic cells (DCs) in the presence of SLE patient sera.

Results

Patients with disease flares were characterized by higher proportions of perforin‐ and/or granzyme B–positive lymphocytes with a differentiated effector phenotype (CCR7− and CD45RA+). The frequency of these cells in peripheral blood correlated with clinical disease activity as assessed by the SLE Disease Activity Index. These cells generated high amounts of soluble nucleosomes as well as granzyme B–dependent unique autoantigen fragments. Finally, the activation of DCs with serum from a patient with active lupus induced granzyme B expression in CD8+ T lymphocytes.

Conclusion

DCs generated in the presence of sera from SLE patients with active disease could promote the differentiation of CD8+ effector T lymphocytes that are fully functional and able to generate SLE autoantigens. Our data disclose a new and pivotal role of activated CD8+ T lymphocytes in SLE pathogenesis.
Überprüfung und Bewertung der seismischen Bemessungsgrößen nach DIN 19700 am Beispiel der Thüringer Talsperren
Authors: Schwarz Jochen , Biewald Wolfgang , Deubner Helmut
Published: January 2005

Durch die DIN 19700 werden Talsperren u. ä. Wasserbauwerke hinsichtlich ihrer Bedeutung, ihres Stauvolumens und Höhe (bzw. Stauhöhe) in unterschiedliche Klassen eingeteilt, verbunden mit unterschiedlichen Anforderungen an die Auslegung und Nachweisführung. Da die Talsperren in seismisch unterschiedlich aktiven Erdbebengebieten liegen, sind die Nachweisanforderungen in Abhängigkeit von der Gefährdung (Erdbebenzonen mit bestimmten Intensitätsintervallen) zu staffeln.

Es wird untersucht, welche Anforderungen aus der Einführung DIN 19700 abzuleiten sind und wie auf Ebene der Bundesländer die praktische Umsetzung erfolgen kann. In diesem Zusammenhang wird die Thüringer Technische Anleitung Stauanlagen gesondert gewürdigt, die gegenüber der DIN veränderte Festlegungen beinhaltet.

Im folgenden werden Grundzüge einer vereinheitlichten Vorgehensweise für den Freistaat Thüringen entwickelt und die notwendigen Bearbeitungsphasen erläutert. Sie sind so gestaltet, daß Synergieeffekte erreicht werden können und eine Übertragbarkeit auf die anderen Bundesländer gewährleistet ist.
Bemessung und Überwachung einer geokunststoffbewehrten Tragschicht auf HSP‐Pfählen
Authors: Bussert Florian , Meyer Norbert , de Lange Andre P. , van der Stoel Almer E. C.
Published: January 2005

Zur kreuzungsfreien Querung einer 2spurigen Nahverkehrstraße und einer Autobahn mußte im Anschluß an eine neu errichtete Vierfeldbrücke ein Dammbauwerk errichtet werden. Der bis zu 8,50 m hohe Damm wurde mit einer Böschungsneigung von 1:2 erstellt, um eine möglichst geringe Baubreite aufzuweisen.

Trotz sehr geringer Untergrundsteifigkeiten sollte eine kurzfristige Inbetriebnahme bei langfristig möglichst geringen Unterhaltungskosten gewährleistet werden. In enger Zusammenarbeit zwischen der bauausführenden Behörde, dem geotechnischen Ingenieurbüro CRUX Engineering BV und der bauausführenden Firma Voorbij Funderingstechniek BV wurde ein flexibles Gründungssystem entworfen, das lokal an die Tragfähigkeit des Untergrundes angepaßt werden kann, Setzungsdifferenzen bauwerksverträglich überbrückt und das benachbarte Naherholungsgebiet minimal beeinträchtigt. Zur Abtragung der Dammlasten in die tragfähigen Sandschichten wurde eine Kombination aus Voton HSP‐Pfählen (Hochgeschwindigkeitspfählen) und einem darüberliegenden lastverteilenden geokunststoffbewehrten Erdkörper gewählt. Diese innovative Kombination ermöglicht bei größter Wirtschaftlichkeit eine optimale Abtragung der Lasten in den tragfähigen Baugrund. Ein geotechnisches Meßprogramm wurde installiert um nachzuweisen, daß die auftretenden Belastungen der Bauglieder die zulässigen nicht überschreiten.
Räumliche Ausbreitung von Feinstbindemittelsuspensionen im Lockergestein
Authors: Kuk Matthias , Schlötzer Carsten
Published: January 2005

Bei der Injektion von Feinstbindemittelsuspensionen kommt es als Folge von Tiefenfiltrationsmechanismen zu einer Anreicherung der Bindemittelpartikel in der Nähe der Injektionsquelle sowie reduzierten Bindemittelgehalten in den Randzonen der Injektionskörper. Hierdurch kommt es zu einer Verringerung der prognostizierten Injektionsreichweiten. Gleichzeitig ergeben sich in den Randzonen der Injektionskörper erhöhte Durchlässigkeiten und reduzierte Festigkeiten. Mit Hilfe einer Serie von großmaßstäblichen Injektionsversuchen wurden die Auswirkungen von Tiefenfiltrationsmechanismen auf die Ausbreitung von Feinstbindemittelsuspensionen in Lockergesteinen untersucht und Hinweise für die Ausführung von Injektionsmaßnahmen mit Feinstbindemittelsuspensionen gegeben.
Aus Sand erbaut – Saugspannungen infolge Teil sättigung ermöglichen scheinbar Unmögliches
Authors: Grabe Jürgen , Schwarz Heli‐Natalie
Published: January 2005

Aus teilgesättigtem Sand lassen sich erstaunliche Figuren und Bauwerke erstellen. “Curver” formen Kunstobjekte aus Sand, die dann in Ausstellungen unter freiem Himmel präsentiert werden. Es kann gezeigt werden, daß Saugspannungen aus Zwickelwasserfilmen in den Porenräumen die physikalische Ursache für die erstaunliche Zugfestigkeit von teilgesättigtem Sand sind.
CTRL‐Tunnelbauwerke – TBM‐Vortriebe beendet
Authors: Brux Gunther
Published: January 2005

Großbritanniens erste Eisenbahn‐Hochgeschwindigkeitsstrecke, Channel Tunnel Rail Link (CTRL), wird den Kanaltunnel mit der City von London verbinden. Der erste Bauabschnitt (74 km) mit dem im Sprengvortrieb aufgefahrenen North Downs Tunnel wurde Ende 2003 in Betrieb genommen; mit der Fertigstellung des zweiten 39 km langen Bauabschnitts mit 60% Tunnelanteil rechnet man erst im Jahr 2007.
The recalcitrance of overconfidence and its contribution to decision aid neglect
Authors: Sieck Winston R. , Arkes Hal R.
Published: January 2005

Three experiments tested the hypothesis that people's overconfidence in the quality of their intuitive judgment strategies contributes to their reluctance to use helpful actuarial judgment aids. Participants engaged in a judgment task that required them to use five cues to decide whether a prospective juror favored physician‐assisted suicide. Participants had the opportunity to examine the judgments of a statistical equation that correctly classified 77% of the prospective jurors. In all experiments, participants infrequently examined the equation, performed worse than the equation, and were highly overconfident. In Experiments 1 and 2, outcome feedback and calibration feedback failed to reduce overconfidence. In Experiment 3, enhanced calibration feedback reduced overconfidence and increased reliance on the equation, thus leading to improved judgment performance. Copyright © 2005 John Wiley & Sons, Ltd.
Synthesis and Application of Fluorescent Ras Proteins for Live‐Cell Imaging
Authors: Reents Reinhard , Wagner Melanie , Schlummer Stefanie , Kuhlmann Jürgen , Waldmann Herbert
Published: January 2005

Semisynthetic Ras proteins are efficient probes for cell‐biology experiments. With a Bodipy FL fluorophore introduced at an appropriate site on the Ras peptide by solid‐phase synthesis, the resulting Ras chimera is processed by the cellular machinery and the intracellular localization of the protein can then be visualized by means of confocal laser fluorescence microscopy at relatively low concentrations. The absence of a large N‐terminal protein tag overcomes possible interferences in the interaction with cellular partner proteins. The fluorescence emission from Bodipy FL is continuous and disappears only after irreversible bleaching. These characteristics make Ras proteins with nonprotein fluorophores suitable for biophysical analysis. The easy accessibility of the lipopeptide moiety by chemical synthesis opens up numerous options for further biological investigations.
Electronic Communication through π‐Conjugated Wires in Covalently Linked Porphyrin/C60 Ensembles
Authors: de la Torre Gema , Giacalone Francesco , Segura José L. , Martín Nazario , Guldi Dirk M.
Published: January 2005

Novel photo‐ and electroactive triads, in which π‐conjugated p‐phenylenevinylene oligomers (oPPVs) of different length are connected to a photoexcited‐state electron donor (i.e., zinc tetraphenylporphyrin) and an electron acceptor (i.e., C60), were designed, synthesized, and tested as electron‐transfer model systems. A detailed physicochemical investigation, concentrating mainly on long‐range charge separation and charge recombination and kinetics, revealed small attenuation factors β of 0.03±0.005 Å−1. Energy matching between the HOMO levels of C60 and oPPVs emerged as a key parameter for supporting molecular‐wire‐like behavior: It favors rapid and efficient electron or hole injection into the oPPV wires. Large electronic coupling values were determined as a result of paraconjugation in the oPPV moieties.
Pharmacokinetic data of propranolol enantiomers in a comparative human study with (S)‐ and (R,S)‐propranolol
Authors: Lindner W. , Rath M. , Stoschitzky K. , Semmelrock H. J.
Published: January 2005

The pharmacokinetics of (S)‐propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)‐propranolol. The results of this study indicate that the bioavailability of (S)‐propranolol, as expressed by the mean area uner the concentration‐time curve (AUC) and maximum serum concentration, is lower after 40mg of the optically pure drug than after the racemic drug.
The stereochemical resolution of enantiomeric free and derivatized amino acids using and hplc chiral stationary phase based on immobilized α‐chymotrypsin: Ciral separation due to solue structure or enzyme activity
Authors: Jadaud Philippe , Thelohan Sylvie , Schonbaum Gregory R. , Wainer Irving W.
Published: January 2005

The stereochemical separation of free and derivatized amino acids on active α‐chymotrypsin bonded to silica is governed by two mechanisms based on the structure of the solutes or on the enzymatic activity of the enzyme. Te deactivation of the hydrolytically active site of the enzyme demonstrated that a significant portion of the retention on this support is due to hydrophobic interactions at other sites. These sites appear to be stereoselective for the ester derivatives of amino acids but not for the other studied solutes.
The absolute configuration of benproperinium dihydrogen phosphate, an antitussive drug
Authors: Schjelderup Lise , Aasen Arne JØRgen
Published: January 2005

The (+)‐ and (−)‐enantiomers of benproperinium dihydrogen phosphate, an antitussive drug, have been assigned the R‐ and S‐configurations, respectively, by syntheses of both enantiomers using (S)‐2‐hydroxypropanoic acid (L‐lactic acid) as chiral synthon. The key intermediate, (S)‐2‐metyl‐2‐[‐2‐(phenylmethyl)phenoxy]ethyl p‐toluenesulfonate, was subjected to an SN2‐type reaction with piperidine furnishing (+)‐(R)‐benproperinium dihydrogen phosphate. (−)‐(S)‐Benproperinium dihydrogen phosphate was obtained by submitting the same tosylate to two consecutive SN2‐type reactions with Br− and piperidine, respectively, acting as nucleophiles.
Stereoselective sulfation of terbutaline by the rat liver cytosol: evaluation of experimental approaches
Authors: Walle U. Kristina , Walle Thomas
Published: January 2005

Little is known about the stereochemistry of sulfation of chiral phenolic drugs. In this study we examined several in vitro approaches to this question, using (+)‐, (−)‐, or (±)‐terbutaline as the substrate and the rat liver cytosol as the phenolsulfotransferase enzyme source. The cosubstrate PAPS was either generated by the cytosol from inorganic sulfate and ATP or added to the cytosol. The intact sulfate conjugates formed were determined by HPLC. Using the PAPS generating system, which is best suited for the production of relatively large quantities of sulfate conjugates, with the individual enantiomers as substrates, (+)‐terbutaline was conjugated to a much greater extent than (−)‐terbutaline; the (+)/(−)‐enantiomer ratio was 7.3 ± 0.3 (mean ± SE). When (±)‐terbutaline was the substrate and chiral derivatization was employed to separate the sulfate enantiomers formed, a similar (+)/(−)‐enantiomer ratio of 7.9 ± 0.2 was obtained. With PAP35S added to the cytosol, an approach best suited for kinetic studies, the substrate concentration dependence of sulfation could be determined. The Km app for this reaction was identical for (+)‐ and (−)‐terbutaline. However, the Vmax app was 8.1 ± 0.4 times greater for (+)‐terbutaline. This study for the first time shows enantioselectivity in sulfation of a chiral phenolic drug. The experimental approaches used should be valuable for human studies of stereoselectiven sulfation of terbutaline and other chiral drugs.
Direct separation of albendazole sulfoxide enantiomers by liquid chromatography on a chiral column deriving from (S)‐N‐(3,5‐dinitrobenzoyl)tyrosine: application to enantiomeric assays on plasma samples
Authors: Lienne M. , Caude M. , Rosset R. , Tambuté A. , Delatour P.
Published: January 2005

The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)‐N‐(3,5‐dinitrobenzoyl)tyrosine‐O‐(2‐propen‐1‐yl) methyl ester on a γ‐mercaptopropylsilanized silica gel. A comparison with the resolution achieved on commercially available Pirkle‐type CSPs obtained from N‐(3,5‐dinitrobenzoyl) derivatives of (R)‐phenyglycine or (S)‐phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane–dioxane–ethanol ternary mixture affords an almost baseline resolution (Rs = 1.25); however, in this case, albendazole sulfone (SO2ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane–ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane–ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO2ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.
Stereochemistry of tissue distribution of racemic propranolol in the dog
Authors: Walle U. Kristina , Thibodeaux Harold , Privitera Philip J. , Walle Thomas
Published: January 2005

Only limited information is available on the stereochemistry of the in vivo distribution of β‐receptor‐blocking drugs. In this study we determined the levels of the propranolol enantiomers in plasma, cerebrospinal fluid (CSF) and central nervous system (CNS), and peripheral tissues in the dog following an intravenous dose of a deuterium‐labeled pseudoracemate. The appearance of the propranolol enantiomers in the CSF was rapid and nonstereoselective, with maximum concentrations reached at 15 min after dosing. The levels of the enantiomers in both CSF and plasma then declined in a parallel biphasic fashion, with a terminal t1/2 of about 125 min. Except for an early high CSF/plasma concentration ratio of 0.35, the CSF propranolol levels corresponded to the unbound concentration in plasma, CSF/plasma 0.20. All areas of the brain showed a similar uptake of propranolol, with a tissue concentration exceeding that in plasma about 10‐fold during the terminal phase of elimination. The uptake of propranolol by peripheral tissues varied widely, ranging from a 50‐fold accumulation by the lungs compared to plasma to no accumulation by adipose tissue. However, as for the CSF, there was no evidence of stereoselective uptake of propranolol by any CNS or peripheral tissue except for the liver. A significantly higher level of (+)‐ vs. (–)‐propranolol in liver tissue presumably was a reflection of stereoselective hepatic metabolism of (–)‐propranolol by this tissue. The slight stereoselectivity in plasma binding of propranolol known to exist in the dog had no significant influence on tissue or CSF distribution.
The determination of (−)‐(S)‐ and (+)‐(R)‐ ifosfamide in plasma using enantioselective gas chromatography: A validated assay for pharmacokinetic and clinical studies
Authors: Young Connie L. , Frank Hartmut , Stewart Cynthia R. , Wainer Irving W.
Published: January 2005

An enantioselective gas chromatographic method has been developed and validated for the determination of the plasma concentration of the enantiomers of the anticancer drug ifosfamide (IFF). In this approach, the IFF enantiomers are separated from the plasma matrix by solid phase extraction, chromatographically resolved by gas chromatography on a chiral stationary phase, and detected by mass selective detection using selective ion monitoring. The assay has been validated for routine clinical and pharmacokinetic use and has a limit of detection in plasma of 250 ng/ml of each isomer.
Chiral stationary phase high‐performance liquid chromatographic resolution and absolute configuration of enantiomeric benzo[a]pyrene diol‐epoxides and tetrols
Authors: Weems Henri B. , Yang Shen K.
Published: January 2005

Enantiomers of diastereomeric benzo[a]pyrene (BP) diol‐epoxides, r‐7,t‐8‐dihydroxy‐t‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 7,8‐diol‐anti‐9,10‐epoxide), r‐‐‐‐7,t‐8‐dihydroxy‐c‐9,10‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 7,8‐diol‐syn‐9,10‐epoxide), r‐9,t‐10‐dihydroxy‐t‐7,8‐epoxy‐7,8,9,10‐tetrahydro‐BP (BP 9,10‐diol‐antiy7,8‐epoxide), and several 7,8,9,10‐tetrahydroxy‐7,8,9,10‐tetrahydrobenzo[a]pyrenes (BP tetrols) were resolved by high‐performance liquid chromatography (HPLC) using columns packed with either (R)‐N‐(3,5‐dinitrobenzoyl)phenylglycine[(R)‐DNBPG] or (S)‐N‐(3,5‐dinitrobenzoyl)leucine [(S)‐DNBL], which is either ionically or covalently bonded to γ‐aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet‐visible absorption and circular dichroism spectral analyses. Resolved enantiomers of BP diol‐epoxides were each hydrolyzed in acidic solution to a pair of diastereomeric tetrols which were separated by reversed‐phase HPLC. Absolute stereochemistries of enantiomeric diol‐epoxides were deduced by the absolute configuration of their hydrolysis products.
Interactions of chiral molecules with an (r)‐n‐(3,5‐dinitrobenzoyl) phenylglycine HPLC stationary phase
Authors: Berthod Alain , Jin Heng Liang , Stalcup Apryll M. , Armstrong Daniel W.
Published: January 2005

Forty different chiral molecules were studied by liquid chromatography with a Pirkle‐type, (R)‐N‐(3,5‐dinitrobenzoyl) phenylglycine (DNBPG), chiral stationary phase column. The dramatic effect of a small molecular change on chiral recognition was demonstrated using DL‐amino acid derivatives. The inductive effect on chiral recognition was also studied using trifluoro‐, trichloro‐, dichloro‐, monochloroacetyl, and acetyl derivatives of four different chiral amines. The study of the enantiomer separation of 11 different crown ethers of 2,2′‐binaphthyldiyl showed that the rigidity of the chiral center can be an additional parameter in chiral recognition for the DNBPG phase but not for a β‐cyclodextrin bonded chiral phase. It is apparent from this study that steric effects, inductive effects, and molecular rigidity play important roles in chiral recognition with DNBPG chiral stationary phases.
Resolution of derivatized acids and amines on JTB‐X: A new urea bonded chiral stationary phase
Authors: Kakodkar Sunil V. , Zief Morris
Published: January 2005

A new urea‐bonded chiral stationary phase has been developed in our laboratory. This bonded phase has been shown to resolve N‐terminal substituted amino acids and the carboxyl derivatized anti‐inflammatory drugs. Typical α‐value for dinitrobenzoyl phenylglycine was 1.7. Values for derivatized ibuprofen, naproxen, and fenoprofen were 2, 1.84, and 1.6, respectively. Further application of these studies to biologically active compounds such as peptides and drugs is in progress.
Enantioselective hydrolysis of oxazepam 3‐acetate by esterases in human and rat liver microsomes and rat brain s9 fraction
Authors: Yang Shen K. , Liu Kan , Guengerich F. Peter
Published: January 2005

Rates of hydrolysis of racemic and enantiomeric oxazepam 3‐acetates (OXA) by esterases in human and rat liver microsomes and rat brain S9 fraction were compared. When rac‐OXA was the substrate, esterases in human and rat liver microsomes were highly enantioselective toward (R)‐OXA. In contrast, esterases in rat brain S9 fraction were highly enantioselective toward (S)‐OXA. Hydrolysis rates of rac‐OXA were highly dependent on the amount of esterases used. At 0.05 mg protein equivalent of esterases and 150 nmol of rac‐OXA per ml of incubation mixture, the (R)‐OXA was hydrolyzed 3.6‐fold and 18.5‐fold faster than (S)‐OXA by rat and human liver microsomes, respectively. The specific activities (nmol of OXA hydrolyzed/mg microsomal protein/min) of liver microsomes in the hydrolysis of enantiomerically pure (R)‐OXA were approximately 120 (rat) and 1,980 (human), and in the hydrolysis of enantiomerically pure (S)‐OXA were 4 (rat) and 7 (human), respectively. In the incubation of rac‐OXA with rat brain S9 fraction, (S)‐OXA was hydrolyzed ∼6‐fold faster than (R)‐OXA. Results also indicated an enantiomeric interaction in the hydrolysis of rac‐OXA by esterases in rat and human liver microsomes; the presence of (R)‐OXA stimulated the hydrolysis of (S)‐OXA, whereas the presence of (S)‐OXA inhibited the hydrolysis of (R)‐OXA. In rat brain S9 fraction, the presence of (R)‐OXA inhibited the hydrolysis of (S)‐OXA, whereas the presence of (S)‐OXA appeared to have stimulated the hydrolysis of (R)‐OXA.
Investigation of the chiral recognition by “Brush‐Type” phases in liquid chromatography using crystal structure analyses of diastereomeric 1:1 complexes of a π‐donor and a π‐acceptor derivative of leucine
Authors: Däppen R. , Rihs Grety , Mayer Carl W.
Published: January 2005

(R,S)‐N‐Acetyl‐leucine‐2‐naphthylamide can be resolved into its enantiomers on a (S)‐DNBLeucine chiral stationary phase. The mechanism of this separation was investigated using as model complexes the 1:1 S,S‐ and the 1:1 R,S‐cocrystals of the above naphthylamide and N‐3,5‐dinitrobenzoylleucinemethylamide, a soluble analogue of the stationary phase. The observed enantiomeric elution order can be rationalized from their X‐ray data.
Enantiomeric resolution of DNS‐amino acids by ligand exchange chromatography: Comparison of different chiral amino acid amides as additives to the mobile phase
Authors: Girelli A. M. , Sinibaldi M.
Published: January 2005

A study developing enantiomeric separations by metal chelate additives to the mobile phase in reversed‐phase liquid chromatography is reported. In particular the use of Cu(II) complexes of L‐prolinamide (L‐ProNH2) and L‐valinamide (L‐ValNH2) is examined and discussed. Interestingly, for a series of DNS‐amino acids these selectors show higher enantioselectivity than that obtained with the corresponding nonderivatized amino acid–Cu(II) complexes.
A vivid model illustrating chiral recognition induced by achiral structures
Authors: Davankov Vadim A. , Meyer Veronika R. , Rais Maya
Published: January 2005

If diastereomeric complexes are adsorbed on a surface or if they include a molecule of solvent, two points of attractive interaction between the chiral species of the complex can be sufficient for mutual chiral recognition of these species. In special cases even one single point of interaction is sufficient. This extension of the three‐point contact rule of Dalgliesh, first observed in chiral ligand‐exchange chromatogrphy, can be demonstrated by using hands.
Studies on the stereoselective effects of a novel 5‐HT2 receptor antagonist on contractile responses of rat aorta
Authors: Mikkelsen Erich O. , Nielsen Tove J. , Nyborg Niels C. B.
Published: January 2005

The effect of the enantiomers of a novel 5‐HT2 receptor antagonist, (±)‐(1R,3S)‐1‐[2‐[4‐[3‐(p‐fluorophenyl)‐1‐indanyl]‐piperazinyl]ethyl]–2‐imidazolidinone, was studied on serotonin (5‐HT), noradrenaline (NA), potassium (K+), and calcium (Ca2+)‐induced contractions in isolated rat thoracic aorta. The enantiomers shifted the 5‐HT, NA, K+, and Ca2+ concentration–response curves to the right in a concentration‐dependent manner and depressed the maximal contractile responses. The (+)‐enantiomer was a far more potent inhibitor of 5‐HT‐induced contractions than the (−)‐enantiomer. The (+)‐enantiomer and phentolamine, both at 10−6 M, had equal inhibitory effects on NA‐evoked contractions. The (+)‐enantiomer was again more potent in inhibiting NA‐induced contractions than the (−)‐enantiomer. Both enantiomers had an equieffective inhibitory effect on K+ and Ca2+‐induced contractions. The results show that the 5‐HT and α‐adrenoceptor antagonism of the two enantiomers is stereoselective, the (+)‐enantiomer being more potent than the (−)‐enantiomer. In contrast the enantiomers had equal, nonstereoselective inhibitory effects on K+ and Ca2+‐evoked contractions.
High‐Performance liquid chromatographic resolution of oxamniquine enantiomers: Application to in vitro metabolism studies
Authors: Noctor Terence A. G. , Fell Anthony F. , Kaye Barry
Published: January 2005

A method is described for the HPLC analysis of oxamniquine enantiomers in liver fraction incubates, using a second‐generation α1‐acid glycoprotein‐based column (Chiral‐AGP). Oxamniquine is extracted from the incubation media by liquid–liquid extraction, using diethyl ether. The dried residue is redissolved in eluent, filtered, then injected directly onto the analytical column. The extraction method affords recoveries of oxamniquine of approximately 93%, at concentrations up to 525 μg/ml, with an average relative standard deviation of 5.9%. The limit of detection of the method (to give an SNR = 2 at 246 nm) is 0.3 ng on‐column for the first eluting, laevorotatory enantiomer and 2.3 ng for the dextrorotatory isomer. The method allowed study of the depletion of oxamniquine enantiomers in liver postimicrosomal incubates. In the rat, a turnover of 21.9% was observed, with no apparent enantioselectivity. Similar observations were made for a mouse liver subcellular fraction incubation. The absence of enantioselectivity in this biotransformation may be attributable to the low substrate specificity of the oxidase or dehydrogenase enzymes involved.
Enantiomers of 11‐hydroxy‐10‐methylaporphine having opposing pharmacological effects at 5‐HT1A receptors
Authors: Cannon Joseph G. , Moe Scott T. , Long John Paul
Published: January 2005

The two enantiomers of the title compound have been prepared by different synthetic routes. Both bind strongly to 5‐HT1A receptors from rat forebrain membrane tissue. However, in a guinea pig ileum preparation, the (R)‐enantiomer exhibits properties consistent with its being an agonist, whereas the (S)‐enantiomer shows no agonist effect, but it blocks the actions of the (R)‐enantiomer and of 8‐hydroxy‐2‐di‐n‐propylaminotetralin (8‐OH‐DPAT), a 5‐HT1A agonist. These data are presented as a rare example of enantiomers which demonstrate opposite pharmacological effects at the same receptor.
Direct measurement of enantiomeric ratios of enzymatic resolution by chiral high‐performance liquid chromatography
Authors: Wu Shih‐Hsiung , Lai Su‐Yuan , Lin Shu‐Ling , Chu Fei‐Ya , Wang Kung‐Tsung
Published: January 2005

(R)‐ and (S)‐Methyl 2‐(phenoxy)propionate and their acids could be separated simultaneously by a Chiralcel OD or OK column, while (R)‐ and (S)‐methyl 2‐(4‐chlorophenoxy)propionate and their acids were separated concurrently only by an OK column. This is a novel and facile way to measure the enantiomeric excesses of the remaining substrate and product in the reaction of enzymatic resolution; enantiomeric ratios could then be calculated.
In vitro hydrolysis of RR,SS‐threo‐methylphenidate by blood esterases—differential and enantioselective interspecies variability
Authors: Srinivas N. R. , Hubbard J. W. , McKay G. , Hawes E. M. , Midha K. K.
Published: January 2005

Enantioselective in vitro hydrolysis of methylphenidate (MPH) by the blood esterases of seven mammalian species is reported. The species included rats, rabbits, dogs, cattle, horses, monkeys, and humans. In vitro incubations up to 8 h were carried out in plasma, red blood cells, and whole blood of the various species. Enantioselective differences were evident among the different species on comparison of the data obtained from the three biological fluids. The esterases present in plasma appeared to show greater activity in the hydrolysis of MPH in all species where comparison with the other two biofluids was possible. Only in the case of humans did esterases present in plasma and red blood cells demonstrate opposite enantioselectivity in the hydrolysis of MPH. Thus after 8 h incubation, the RR‐MPH/SS‐MPH ratios in plasma and red blood cells were 0.31 and 1.16, respectively.
Separating enantiomers by HPLC on silica dynamically coated with a chiral stationary phase of permethylated β‐cyclodextrin
Authors: Pawlowska Maria
Published: January 2005

The paper demonstrates that the technique of solvent generated liquid‐‐solid chromatography can be used to create normal phase systems for chiral separations. The chiral adsorption layer was generated by pumping a binary hexane:ethanol eluent containing a small fraction of permethylated β‐cyclodextrin through a column packed with microparticulate silica. This technique leads to columns with good time stability and reproducibility. The possibility of generating normal phase systems with permethylated β‐cyclodextrin as chiral component via the mobile phase broadens the range of phase system which can be used to separate enantiomers by HPLC.
A method for the quantitative enantioselective HPLC analysis of ethambutol and its stereoisomers
Authors: Blessington B. , Beiraghi A.
Published: January 2005

A rapid, quantitative, enantioselective HPLC method, using N,N′‐dibenzylethylenediamine as internal standard, for the analysis of the three stereoisomers of the antituberculosis drug ethambutol and 2‐aminobutan‐1‐ol is described. The derivatisation and chromatographic procedures and their reproducibility, durability, and sensitivity are discussed. Application to assays of raw material, tablet content, and synthetic reactions are illustrated. The method involves perbenzoylation, in pyridine, followed by direct HPLC on a “Pirkle covalent bonded column” containing a 3,5‐dinitrobenzoyl‐D‐phenylglycine as chiral stationary phase (CSP) using hexane/IPA as mobile phase and detection at 230 nm.