bluuebunny/crossref_metadata_2025 huggingface dataset:
Über die Bromierung von 5‐Benzylidenpyrrolin‐2‐onen
Authors: Stachel Hans‐Dietrich , Poschenrieder Hermann
Published: October 2006

Es wird die Herstellung und Stereochemie einer Reihe von ein‐ und mehrfach bromierten 5‐Benzylidenpyrrolin‐2‐onen und ‐pyrrolidin‐2‐onen beschrieben. Einige der neuen Verbindungen sind Strukturverwandte von marinen Antibiotika.
Synthesen mit Nitrilen, 71. Mitt. Zur Synthese von 4‐Hydroxynicotinsäure aus Butadiendicarbonitrilen
Authors: Mittelbach Marti , Kastner Gabriele , Junek Hans
Published: October 2006

Kondensation von 1,1‐Dicyan‐2‐ethoxypropen‐1 (1) und Dimethylformamid‐dimethylacetal führt zu den Butadiendicarbonitrilen 2. Durch Reaktion von 2 mit Halogenwasserstoffen bzw. Ammoniak entstehen 4‐Alkoxy‐2‐halo‐(bzw. 2‐amino)pyridin‐3‐carbonitrile 3 bzw. 5. Katalytische Reduktion von 3 ergibt 4‐Alkoxypyridin‐3‐carbonitrile 8, welche durch Hydrolyse mit konz. Salzsäure 4‐Hydroxynicotinsäure (9) liefern.
Über ein neues Amantadinanalogon
Authors: Buchbauer Gerhard , Stefanich Maria , Haslinger Ernst , Robien Wolfgang
Published: October 2006

Ausgehend vom adamantanähnlichen 2‐Hydroxy‐8‐methyltricyclo[7.3.1.02,7]tridecan‐13‐on (1) wurde das neue amantadinanaloge Amin 4 synthetisiert. 4 besitzt eine schwache antivirale, aber keine antibakterielle oder antifungale Aktivität.
Konformere 3‐Oxa‐7‐azabicyclo[3.3.1]nonanone und ihre Reduktionsprodukte
Authors: Haller Rolf , Ashauer Ulrike
Published: October 2006

Die Konformation substituierter, isomerer 3‐Oxa‐7‐azabicyclo[3.3.1]nonanone‐ (9) wird anhand von 13C‐NMR‐Spektren diskutiert. Die Reaktion mit Natriumborhydrid ergibt je nach Konformation des Ketons und Polarität der Reaktionslösung einen bzw. zwei epimere Alkohole. Die Konfiguration der Alkohole wird durch 13C‐NMR‐ und Massenspektren bestimmt.
Penetration von 8‐Methoxypsoralen in die Saugblasenflüssigkeit bei Ratten
Authors: Schäfer‐Korting Monika
Published: October 2006

Die Konz. von 8‐Methoxypsoralen (8‐MOP) in Blut und Saugblasenflüssigkeit (SBF) sowie in ausgewählten Organen wurden nach i.v. Injektion von 6,7 mg/kg an Ratten untersucht. Die Blutspiegel können mittels eines 2‐Kompartiment‐Modells beschrieben werden, der Verlauf der SBF‐Spiegel mittels einer Bateman‐Funktion. Es besteht eine enge Korrelation zwischen den Konz. in der SBF und den errechneten Mengen im peripheren Kompartiment (r = 0,94). 8‐MOP liegt in Plasma und SBF zu 85 bzw. 60% albumingebunden vor und verteilt sich homogen zwischen Plasma und Erythrozyten. In der terminalen Phase übersteigen die ungebundenen Konz. in der SBF diejenigen im Plasma. Auch der Konzentrationsverlauf in Haut und Muskulatur unterscheidet sich vom Blutspiegelverlauf; diese Organe sind Teil des peripheren Kompartiments. Die Ergebnisse zeigen, daß die Messung von 8‐MOP‐Konz. in der SBF eine geeignete Methode zur Bestimmung dieser Substanz an ihrem Wirkort ist. Bei Extrapolation der Ergebnisse auf die orale Gabe an Patienten ergeben sich keine Hinweise auf Unterschiede im Konzentrationsverlauf von 8‐MOP in Plasma und Haut.
Zur Reaktion von Phthalaldehyd mit Anthranilsäureestern
Authors: Görlitzer Klaus , Buß Dietrich
Published: October 2006

In Abhängigkeit vom verwendeten Lösungsmittel wurden bei der Titelreaktion die (1+1)‐Addukte 3, die (2+1)‐Produkte 5 und die (2+2)‐Spirane 7 erhalten. Phthalaldehyd reagiert mit 4‐Aminobenzoesäureestern zu den Amidinen 19. Die Strukturen werden durch chemische und spektroskopische Methoden bewiesen.
Chromatographische Artefakte bei Arzneistoffen der 3,5‐Pyrazolidindion‐Gruppe, 2. Mitt. „Post‐Photoeffekt”︁ bei bestrahlten Kieselgel‐Fertigplatten
Authors: Takács Mihály , Kertész Piroska , Wiener Erzsébet , Reisch Johannes
Published: October 2006

Bestimmte Kieselgel Dünnschichten gewinnen beim Bestrahlen mit UV‐oder intensivem Sonnen‐Licht oxydierende Eigenschaften. Werden auf derartigen DC‐Platten z.B. Arzneistoffe der 3,5‐Pyrazolidindion(3,5‐PD)‐Gruppe (Phenylbutazon, Oxyphenbutazon, Kebuzon usw.) chromatographiert, erleiden diese teilweise, einige sogar völlige Zersetzung. Die bestrahlten Fertigplatten bewahren ihre Reaktionsfähigkeit tagelang; selbst dann, wenn sie vor dem Auftragen der Substanzen vakuumbehandelt oder mit Methanol gewaschen werden.

Auf den unter Lichteinfluß oxydierend gewordenen DC‐Platten wandelt sich Phenylbutazon in 4‐Hydroxyphenylbutazon um. Mutmaßlich erleiden auch die anderen 3,5‐PD‐Verbindungen – soweit sie einen freien C‐4‐Wasserstoff besitzen‐eine C‐4‐Oxidation.
Potentielle Radiopharmaka zur Nebennierenszintigraphie, 2. Mitt. Zur Radioiodmarkierung von p‐Hydroxyphenylderivaten des Digitoxigenins, Dihydrodigitoxigenins und Scillarenins
Authors: Röder Erhard , Lütz Johannes
Published: October 2006

Als potentielle Radiopharmaka zur szintigraphischen Darstellung der Nebennieren wurden p‐Hydroxyphenylderivate der Aglyka Digitoxigenin (1), Dihydrodigitoxigenin (2) und Scillarenin (3) hergestellt und radioiodiert.

Die Genine werden durch Oxidation zur jeweiligen Ketostufe dehydriert und regioselektiv mit 2‐(4‐Lithiumphenoxy‐tetrahydropyran (18) zu den Verbindungen 7–9 umgesetzt. Diese werden unter milden Bedingungen durch Abspaltung der Schutzgruppe in die Verbindungen 34p‐Hydroxyphenyl)‐3‐hydroxy‐digitoxigenin (10), 3‐(p‐Hydroxyphenyl)‐3‐hydroxy‐dihydrodigitoxigenin (11) und 3‐(p‐Hydroxyphenyl)‐3‐hydroxy‐scillarenin (12) überführt. Der Einbau des p‐Hydroxyphenylrestes macht die Geninderivate einer schnellen Radioiodmarkierung zugänglich. Mit trägerfreiem Na131I konnte eine Aktivität von 10 bis 41 mCi iodmarkierten Produkts/mg Ausgangsmaterial erreicht werden.
Vinyloge Amidiniumsalze durch Einwirkung von Methyliodid auf sekundäre β‐Ketoenamine
Authors: Böhme Horst , Tränka Manfred
Published: October 2006

Von Anilin oder Benzylamin abgeleitete sekundäre β‐Ketoenamine 1 reagieren beim Erhitzen mit überschüssigem Methyliodid zu N,N′‐Diphenyl‐ bzw. N,N'‐Dibenzyl‐4‐amino‐3‐penten‐2‐iminiumiodiden 2a bzw. 2b.
Untersuchungen an 1,4‐Naphthochinonen, 10. Mitt. Reaktionen von Methylethern des 1,5‐Dihydroxynaphthalins mit Singulettsauerstoff
Authors: Wurm Gotthard , Geres Uwe
Published: October 2006

Während 1,5‐Dihydroxynaphthalin bei der farbstoffsensibilisierten Photooxidation unter Cycloaddition von 1O2 regiospezifisch Juglon (3) in hoher Ausbeute liefert, entstehen unter gleichen Reaktionsbedingungen aus dem Monomethylether 1 die Verbindungen 2, 3 und 4 und aus dem Dimethylether 5 die Verbindungen 2, 6 und 7. Die Etherspaltungen sind nicht das Ergebnis von 1O2‐Reaktionen im Sinne einer Cycloaddition, sondern Elektronentransferoxidationen über Radikalionenpaare mit O2·− als Anionen.
Kondensation von Indeno[2,1‐c]‐1,2‐dithiolen zu Diindeno‐[2,1‐b: 1′,2′‐e]thiopyran‐Derivaten
Authors: Hartke Klaus , Hoederath Wolfgang , Krampitz Dieter
Published: October 2006

Indeno[2,1‐c]‐1,2‐dithiole1„dimerisieren”︁ unter Säurekatalyse und Verlust von zwei Schwefelatomen zu Diindeno‐thiopyranen2I/2II. Eine analoge Reaktion ist vom 3‐Methyl‐5‐phenyl‐1,2‐dithiolylium‐perchlorat (3) bekannt, das mit Pyridin die beiden isomeren Thiopyrane4I/IIliefert. Kondensation von 1‐Acyl‐2‐indanonen13mit Acetanhydrid/Perchlorsäure ergibt die zu2I/2IIstrukturanalogen Sauerstoffverbindungen14und15.
Untersuchungen über die Reaktion von N‐Isopropyl‐N′‐phenylcarbodiimid mit Benzoylchlorid, Oxalsäuredichlorid und Quadratsäuredichlorid
Authors: Grüunefeld Johann , Zinner Gerwalt
Published: October 2006

Die Struktur der Additionsprodukte aus N‐Isopropyl‐N‐phenylcarbodiimid (1) und Benzoylchlorid bzw. Quadratsäuredichlorid wird durch spektroskopische Vergleiche mit Referenzsubstanzen bestimmt.
Additionsreaktionen von β‐Ketosulfoxiden und Bis(phenylsulfinyl)methan an Isocyanate
Authors: Messinger Paul , Kunick Conrad
Published: October 2006

Die Natriumsalze der β‐Ketosulfoxide 1 reagieren mit Isocyanaten 2 zu α‐Acyl‐α‐sulfinyl‐acetamiden 4, analog entsteht aus Bis(phenylsulfinyl)methan (11) und Phenylisocyanat (2a) 2,2‐Bis‐(phenylsulfinyl)‐N‐phenyl‐acetamid (12). 4a wird zu Benzoylacetanilid (9) und Benzolsulfinsäure (10) hydrolysiert.
Antivirale Wirkstoffe, 27. Mitt. Die Aminomethinylierung von 5‐Oxo‐2‐pyrazolin‐3‐carbonsäurederivaten
Authors: Kreutzberger Alfred , Kolter Karl
Published: October 2006

Aus der mit s‐Triazin (1) durchgeführten Aminomethinylierung der 5‐Oxo‐2‐pyrazolin‐3‐carbonsäurederivate 2a,b gehen die 4‐Aminomethylen‐5‐oxo‐2‐pyrazolin‐3‐carbonsäurederivat 4a,b und die C‐Rubazonsäuren 5a,b hervor. Bei 4a deuten die spektroskopischen Daten auf das Vorliegen der Z‐Form (Abb. 1), für 5a auf das der Z‐s‐cis‐(OH)‐Form (Abb. 2) hin. Die Strukturtypen 4 und 5 weisen Vertreter mit antiviraler, entzündungshemmender, temperatursenkender und antimykotischer Wirkung auf.
Zur Stereochemie der 3‐Oxo‐5‐phenyl‐1‐cyclopentancarbonsäuren, 9. Mitt. Synthese kernfluorierter stereomerer 3‐Oxo‐5‐phenyl‐1‐cyclopentancarbonsäuren
Authors: Beck Martin , Jaunich Siegfried , Frahm August W.
Published: October 2006

Es wird die stereoselektive Synthese der kernfluorierten cis‐ und trans‐5‐Phenyl‐3‐oxo‐cyclopentan‐carbonsäuren 5a‐d/6a‐d durch kombinierte Michael‐ und Dieckmannreaktion aus Ethantricarbonsäuretrimethylester und den fluorierten Zimtsäuremethylestern 1a‐d beschrieben. Der saure bzw. basische Abbau der 5‐Phenyl‐3‐oxo‐cyclopentan‐1.1.t‐4‐tricarbonsäure‐trimethylester 2a‐d führt über die 5‐Phenyl‐c‐1‐methoxycarbonyl‐3‐oxo‐cyclopentan‐t‐1‐carbonsäuren 3a‐d und die 5‐Phenyl‐3‐oxo‐cyclopentan‐1.1‐dicarbonsäuren 4a‐d. Zum Strukturbeweis werden 5a‐d zu 7a‐d, 6a‐d zu 8a‐d, sowie 3a‐d und 4a‐d zu 9a‐d mit Diazomethan verestert.
Basisch substituierte Pyrrolidin‐2,5‐dione, 2. Mitt. Konfiguration der Enantiomere
Authors: Knabe Joachim , Konrad Horst
Published: October 2006

Aus den ORD‐ und CD‐Spektren der in Ethanol rechtsdrehenden Enantiomere der Pyrrolidindione 1a‐1c ergibt sich, daß sie gleiche Konfiguration besitzen. Der chemische Abbau von (+)1c führt zu R(+)‐3‐Ethyl‐1‐methyl‐3‐phenylpyrrolidin‐2,5‐dion [R(+)‐1i]. Hieraus läßt sich für (+)1a ‐ (+)1c R‐Konfiguration ableiten. (+)3a und (+)3b, durch katalytische Hydrierung von (+)1a und (+)1b gewonnen, besitzen ebenfalls R‐Konfiguration. Die ORD‐ und CD‐Spektren der 3‐(2‐Thienyl)pyrrolidindione (+)2a und (+)2b zeigen, daß beide Verbindungen gleich konfiguriert sind.
Umsetzung von 1,2‐Dihydro‐3‐indazolon mit ω‐Dialkylaminoalkylhalogeniden und α,ω‐Dihalogenalkanen
Authors: Oelschläger Herbert , Matthiesen Uwe , Shaik Mohammed Al
Published: October 2006

Während das K‐Salz des 1,2‐Dihydro‐3‐indazolons in trockenem Dioxan mit ω‐Dialkylaminoalkylhalogeniden zu den analgetisch wirkenden basischen Lactimethern reagiert, entstehen bei der Umsetzung mit α, ω‐Dihalogenpropanen zwei basische Verbindungen, die als 3,4‐Dihydro‐2H‐(1,3)oxazino[2,2‐b]indazol (1) und 2,3‐Dihydro‐1H‐pyrazolo[1,2‐a]indazol‐9‐on (2) identifiziert wurden. 2 läßt sich mit LiAlH4 zu 2,3‐Dihydro‐1H, 9H‐pyrazolo [1, 2‐a] indazol (5) reduzieren.
P‐Glycoprotein Effects of Cyclic Urea HIV Protease Inhibitor DMP 323 in Competitional Absorption Studies
Authors: Richter Martin , Gyémánt Nóra , Molnár Joséf , Hilgeroth Andreas
Published: October 2006

Cyclic ureas form a perspective class of non‐peptidic HIV‐1 protease inhibitors with major bioavailability problems. Low absorption rates of DMP 323 as one of the first representatives led to investigations whether transport efflux pump P‐glycoprotein (P‐gp) within the intestine may be partly responsible for the low absorption rates. DMP 323 proved to be a P‐gp substrate in competition studies with P‐gp inhibitor ritonavir and H17 as a representative of another class of non‐peptidic HIV‐1 protease inhibitors. Intestinal DMP 323 absorption was mainly increased under co‐application of both ritonavir and H17. DMP 323 used as a membrane efflux pump inhibitor itself showed little affinities to P‐gp compared to H17 as strong P‐gp inhibitor. So P‐gp proved to play a decisive role in the low intestinal absorption of the cyclic urea representative DMP 323.
Clinician reviewers in birth defects surveillance programs: Survey of the National Birth Defects Prevention Network
Authors: Lin Angela E. , Forrester Mathias B. , Cunniff Christopher , Higgins Cathleen A. , Anderka Marlene
Published: October 2006

BACKGROUND: Some birth defects surveillance programs utilize a clinician reviewer (“Clinician”) to assist the multidisciplinary staff in the process of case review, coding and classification. The untested assumption is that expertise in the evaluation of individuals with birth defects and genetic syndromes in clinical practice, usually clinical genetics, is useful in reviewing medical records. METHODS: We conducted an exploratory survey of the 50 functioning birth defects surveillance programs that participated in the National Birth Defects Prevention Network in 2004. The survey was mailed electronically to program coordinators and included 10 questions with check‐off option replies. Open‐ended comments were also solicited. RESULTS: Responses were received from 31 of 50 (62%) programs, 21 (68%) which used a Clinician. In addition to the 9 centers that identified themselves as participants in the National Birth Defects Prevention Study (NBDPS), there were 12 non‐NBDPS programs using a Clinician, 2 of whom were not clinical geneticists (1 nurse genetic counselor and 1 primary pediatrician). A total of 86% (18/21) of Clinicians were employed part‐time or as consultants; 1 was full‐time, and 2 were volunteers. In addition to the core activities of classifying defects and reviewing cases to determine if a syndrome was present, over one‐half of the Clinicians participated in education of birth defects surveillance programs staff, research, and program development. Most (86%; 18/21) Clinicians had been trained informally for their roles. Only 1 had received a formal performance review. CONCLUSIONS: Aside from the 9 centers in the NBDPS in which the position of Clinician is funded by the Centers for Disease Control and Prevention (CDC), about one‐half of the remaining respondent birth defects surveillance programs used a Clinician. Future research is needed to determine why a birth defects surveillance program hires or refrains from using a Clinician, and whether a Clinician accomplishes the desired goals. This survey reveals a lack of formal training for the Clinicians in their roles in the surveillance programs, and a lack of quality monitors, which might be addressed in the future. Birth Defects Research (Part A), 2006. © 2006 Wiley‐Liss, Inc.
The Water‐Exchange Mechanism of the [UO2(OH2)5]2+ Ion Revisited: The Importance of a Proper Treatment of Electron Correlation
Authors: Rotzinger François P.
Published: October 2006

The water‐exchange mechanism of [UO2(OH2)5]2+ has been reinvestigated by using ab initio molecular orbital (MO) methods. The geometries and the vibrational frequencies were computed with CAS‐SCF(12/11)‐SCRF and CAS‐SCF(12/11)‐PCM methods, which take into account static electron correlation (using the complete active space self‐consistent field (CAS‐SCF) technique, based on an active space of 12 electrons in 11 orbitals) and hydration (using the self‐consistent reaction field (SCRF) and polarizable continuum model (PCM) techniques). The total energies were computed with multiconfiguration quasi‐degenerate second‐order perturbation theory, the MCQDPT2(12/11)‐PCM method, which treats static and dynamic electron correlation as well as hydration. The adequacies of other currently used quantum chemical methods, MP2, CCSD(T), B3 LYP, and BLYP, are discussed. For the associative and dissociative pathways, thermodynamic activation parameters (ΔH≠, ΔS≠, and ΔG≠) were computed. For the associative mechanism, the calculated ΔH≠ and ΔG≠ values agree with experiment, whereas for the dissociative mechanism, they are higher by ≈20 kJ mol−1. The dissociative mechanism is preferred for substitution reactions of uranyl(VI) complexes with ligands that are stronger electron donors than water. The question of whether a concerted (Ia or Id) or a stepwise (A or D) mechanism operates is discussed on the basis of the computed lifetime of the respective intermediate, and the duration of the vibration with which the intermediate is transformed into the product.
Theoretical Investigation of the Second‐Order Nonlinear Optical Properties of Helical Pyridine–Pyrimidine Oligomers
Authors: Botek Edith , Castet Frédéric , Champagne Benoît
Published: October 2006

The structure and second‐order nonlinear optical properties of a series of helical pyridine–pyrimidine oligomers recently synthesized by Barboiu and Lehn have been investigated theoretically by combining molecular mechanics and quantum chemistry approaches. In the absence of substituents, the hyper‐Rayleigh scattering response (βHRS) and the projection of the first hyperpolarizability on the dipole moment (β∥) exhibit periodic variations with chain length, but these nonlinear optical responses remain small. The first hyperpolarizabilities can, however, be enhanced by adding substituents. The greatest enhancement is obtained by substituting the pyrimidine groups by donor groups. Moreover, regular distributions of the donor groups around the helices enable the design of supramolecular structures exhibiting dipolar, octupolar or Λ‐shaped nonlinear optical characters, evident from the values of the depolarization ratios in hyper‐Rayleigh scattering. Therefore this theoretical investigation demonstrates the potential of helical structures for the organization of chromophores in such a way that they exhibit large and specific second‐order nonlinear optical responses.
Combined AFM and Two‐Focus SFCS Study of Raft‐Exhibiting Model Membranes
Authors: Chiantia Salvatore , Ries Jonas , Kahya Nicoletta , Schwille Petra
Published: October 2006

Dioleoylphosphatidylcholine/sphingomyelin/cholesterol (DOPC/SM/cholesterol) model membranes exhibit liquid–liquid phase separation and therefore provide a physical model for the putative liquid‐ordered domains present in cells. Here we present a combination of atomic force microscopy (AFM) imaging, force measurements, confocal fluorescence imaging and two‐focus scanning fluorescence correlation spectroscopy (two‐focus SFCS) to obtain structural and dynamical information about this model membrane system. Partition coefficients and diffusion coefficients in the different phases were measured with two‐focus SFCS for numerous fluorescent lipid analogues and proteins, while being directly related to the lateral organization of the membrane and its mechanical properties probed by AFM. Moreover we show how the combination of these different approaches is effective in reducing artifacts resulting from the use of a single technique.
Nucleus image properties assessed by video image analysis in mouse hepatocytes under a short lysis for extended chromatin fiber formation
Authors: Vidal Benedicto C. , Moraes Alberto S. , Mello Maria Luiza S.
Published: October 2006

Background:

How much DNA remains in mouse hepatocyte nuclei after extended chromatin fiber (ECF) formation or whether this content varies within the nuclear population is not known. This information could be relevant to understanding chromatin extensibility as related to chromatin organization, possibly associated with variable nuclear activities in hepatocytes.

Methods:

A protocol for ECF formation under the gravity action, image analysis of Feulgen‐stained unfixed mouse hepatocyte remnants, and DAPI fluorescence were used.

Results:

Areas, shape, Feulgen‐DNA amounts, and chromatin texture were affected in unfixed, lysed nuclei. The Feulgen‐DNA values in nuclear remnants represented ∼37% of the content in fixed, nonlysed nuclei in terms of median values; the coefficient of variation of Feulgen‐DNA values in the nuclear remnants was much higher than those in controls. Enhancement in DAPI fluorescence was evident in chromocenters of the fixed nuclei and in remnants and some ECF granules of the unfixed, lysed nuclei.

Conclusions:

The DNA content of the nuclear remnants was much more variable than that assumed from known variability in hepatocyte ploidy degrees. The variable constraint to chromatin extrusion from hepatocyte nuclei is hypothesized to depend on variable chromatin organization with possible involvement of nuclear matrix association, transcriptional activities, and AT‐rich DNA‐containing heterochromatin. © 2006 International Society for Analytical Cytology
Cell behaviors associated with somite segmentation and rotation in Xenopus laevis
Authors: Afonin Bonnie , Ho Minh , Gustin Jean K. , Meloty‐Kapella Caroline , Domingo Carmen R.
Published: October 2006

During vertebrate development the formation of somites is a critical step, as these structures will give rise to the vertebrae, muscle, and dermis. In Xenopus laevis, somitogenesis consists of the partitioning of the presomitic mesoderm into somites, which undergo a 90‐degree rotation to become aligned parallel to the notochord. Using a membrane‐targeted green fluorescent protein to visualize cell outlines, we examined the individual cell shape changes occurring during somitogenesis. We show that this process is the result of specific, coordinated cell behaviors beginning with the mediolateral elongation of cells in the anterior presomitic mesoderm and then the subsequent bending of these elongated cells to become oriented parallel with the notochord. By labeling a clonal population of paraxial mesoderm cells, we show that cells bend around their dorsoventral axis. Moreover, this cell bending correlates with an increase in the number of filopodial protrusions, which appear to be posteriorly directed toward the newly formed segmental boundary. By examining the formation of somites at various positions along the anteroposterior axis, we show that the general sequence of cell behaviors is the same; however, somite rotation in anterior somites is slower than in posterior somites. Lastly, this coordinated set of cell behaviors occurs in a dorsal‐to‐ventral progression within each somite such that cells in the dorsal aspect of the somite become aligned along the anteroposterior axis before cells in other regions of the same somite. Together, our data further define how these cell behaviors are temporally and spatially coordinated during somite segmentation and rotation. Developmental Dynamics 235:3268–3279, 2006. © 2006 Wiley‐Liss, Inc.
Improvement of search performance in genetic algorithms with fitness prediction
Authors: Tanaka Masaharu , Mizoguchi Masanobu , Takami Isao
Published: October 2006

When genetic algorithm (GA) is applied to actual engineering problems, for example, optimization of design parameters, the searching time is usually huge because the fitness is calculated by repetitive simulation or analysis, which requires a large amount of calculation time. In order to shorten the searching time, a method called fitness prediction GA has been proposed. It reduces the calculation time by predicting fitness instead of actually calculating it, and eventually shortens the searching time. In this paper, we propose a new method, Dual Population GA (DPGA), which employs both real and virtual populations. Real populations have actual fitness value, and virtual ones have predicted ones. DPGA can prevent the decline of performance caused by prediction errors, which may occur in fitness prediction GA, by appropriately migrating virtual populations into real ones and accelerating evolution. A fitness predictor based on a neural network is also proposed in this paper. Through computer simulations, DPGA is demonstrated to improve the searching performance of fitness prediction GA. © 2006 Wiley Periodicals, Inc. Electr Eng Jpn, 158(1): 60–68, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20205
Cross‐priming with an epicutaneously introduced soluble protein antigen generates Tc1 cells
Authors: Wang Li‐Fang , Hsu Chih‐Jung , Miaw Shi‐Chuen , Chiu Hsien‐Ching , Liu Ching‐Yi , Yu Hsin‐Su
Published: October 2006

Epicutaneous sensitization with a protein antigen was demonstrated to induce a predominant type 2 CD4 T cell response with high IgE production in mice. On the other hand, its CD8 T cell responses have not been addressed probably partly because of the generally accepted concept that cross‐priming of soluble protein is an inefficient process. Here, we used an established patch‐applied murine model to demonstrate that cross‐priming with an epicutaneously introduced soluble protein antigen, though inefficient, generated mainly Tc1 cells, but not Tc2 cells. In the presence of an irritant or hapten, the efficiency of this cross‐priming process could be enhanced and more Tc1 cells were generated. CpG oligonucleotides also promote the generation of Tc1 cells. In contrast, lipopolysaccharide and poly (inosinic‐cytidylic) acid [poly (I:C)] have no effect. Together, these results provide supportive evidence of the epicutaneous sensitization of human cutaneous lymphocyte‐associated antigen‐positive CD8 T cells found in the peripheral blood or tissues of patients. The surprising observation of the type 1 character of the generated CD8 T cells will also help us to better understand the complicated pathogenesis of atopic and cutaneous inflammatory diseases.
In vitro generated human memory‐like T cells are CD95 type II cells and resistant towards CD95‐mediated apoptosis
Authors: Fas Stefanie C. , Baumann Sven , Krueger Andreas , Frey Christian R. , Schulze‐Bergkamen Henning , Brenner Dirk , Stumpf Christine , Kappes Kathrin , Krammer Peter H.
Published: October 2006

An adaptive immune response implies expansion of activated T cells and subsequent elimination to maintain homeostasis in a process called activation‐induced cell death. Some cells, however, differentiate into memory cells and ensure a strong secondary immune response. To analyze the apoptosis phenotype of memory T cells on a cellular and molecular level, we have established an in vitro model of T cell activation and generation of cells phenotypically and functionally similar to memory cells. These long‐term cultured T cells show a CD95‐resistant phenotype, although they are still sensitive towards TCR/CD3‐mediated apoptosis. Biochemical analysis revealed that these cells shift from CD95 type I (direct signaling from the receptor) during the effector phase to CD95 type II cells (dependent on the mitochondrial amplification loop). Moreover, their mitochondria are protected, probably due to high expression levels of Bcl‐xL and Bcl‐2. Thus, our data suggest a mechanism how memory T cells acquire resistance towards bystander cell death via the CD95 system.
An important role of Tyk2 in APC function of dendritic cells for priming CD8+ T cells producing IFN‐γ
Authors: Aizu Keiji , Li Wei , Yajima Toshiki , Arai Toshiyuki , Shimoda Kazuya , Nimura Yuji , Yoshikai Yasunobu
Published: October 2006

Tyrosine kinase 2 (Tyk2) contributes to the signals triggered by IL‐12 for IFN‐γ production by NK cells and T cells. We found in this study that Tyk2‐deficient (–/–) mice showed increased susceptibility at the early stage after an i.p. infection with Listeria monocytogenes, accompanied by impaired IFN‐γ production. The numbers of both MHC class Ib (H2‐M3)‐ or MHC class Ia (Kb)‐restricted CD8+ T cells producing IFN‐γ and exhibiting cytotoxicity were significantly decreased in Tyk2–/– mice after infection with L. monocytogenes. Using an adoptive transfer system of OT‐I cells expressing OVA257–264/Kb‐specific TCR into Tyk2–/– mice followed by challenge with recombinant L. monocytogenes expressing OVA, we found that the defective Tyk2 signaling in the host environment was at least partially responsible for the impaired CD8+ T cytotoxic‐1 (Tc1) cell responses in Tyk2–/– mice following the infection. Adoptive transfer with MHC class Ib‐ or MHC class Ia‐binding peptide‐pulsed BM‐derived DC from Tyk2–/– mice induced lower levels of the Ag‐specific CD8+ Tc1 cells producing IFN‐γ. These results suggest that Tyk2 signaling is also important for DC function in the induction of MHC class Ia‐ and class Ib‐restricted CD8+ Tc1 cells following L. monocytogenes infection.
CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactions by blocking influx of effector T cells into inflamed tissue
Authors: Ring Sabine , Schäfer Stephan C. , Mahnke Karsten , Lehr Hans‐Anton , Enk Alexander H.
Published: October 2006

CD4+CD25+ regulatory T cells (Treg) exert suppressive functions on effector T cells in vitro and in vivo. However, the exact cellular events that mediate this inhibitory action remain largely unclear. To elucidate these events, we used intravital microscopy in a model of contact hypersensitivity (CHS) and visualized the leukocyte‐endothelium interaction at the site of antigen challenge in awake C57BL/6 mice. Injection of Treg i.v. into sensitized mice at the time of local hapten challenge significantly inhibited rolling and adhesion of endogenous leukocytes to the endothelium. A similar inhibition of leukocyte recruitment could be recorded after injection of Treg‐derived tissue culture supernatant. Thus, these data indicate that soluble factors may account for the suppressive effects. Accordingly we found that IL‐10, but not TGF‐β, was produced by Treg upon stimulation and that addition of anti‐IL‐10 antibodies abrogated the suppressive effects of Treg and tissue culture supernatant in CHS reactions. Moreover, CD4+CD25+ T cells isolated from IL‐10–/– mice were not able to suppress the immune response induced by hapten treatment in C57BL/6 mice. In conclusion, our data suggest that cytokine‐dependent rather than cell‐cell contact‐dependent mechanisms play a pivotal role in the suppression of CHS reactions by Treg in vivo.
The conserved histidine 166 residue of the human neonatal Fc receptor heavy chain is critical for the pH‐dependent binding to albumin
Authors: Andersen Jan Terje , Dee Qian Julie , Sandlie Inger
Published: October 2006

The MHC class I‐related neonatal Fc receptor (FcRn) serves in the homeostatic regulation of IgG and albumin by increasing their half‐lives. FcRn may bind IgG and albumin simultaneously, and in a pH‐dependent manner, with ligand binding at pH 6.0–6.5 and release at pH 7.0–7.4. The FcRn‐IgG interaction has been extensively characterized at the amino acid level and shown to depend on conserved histidine residues in the IgG‐Fc part that interact with negatively charged residues in the α‐2 domain of FcRn. The recently discovered FcRn‐albumin interaction remains to be elucidated. Guided by the pH dependence of the FcRn‐albumin interaction, we compared the sequence of the FcRn α‐2 domain from eleven different species, and identified histidine residues that were conserved in all (H166) or seven (H161) of these. Both residues are located directly opposite to the IgG interaction site in the folded molecule. We did in vitro mutagenesis (H161A or H166A) in combination with interaction studies (ELISA and surface plasmon resonance) with recombinant, soluble, purified receptors and IgG and albumin to investigate the role of the two histidine residues. Our results show clear evidence that the conserved H166 is a key player in the FcRn‐albumin interaction.
Simvastatin inhibits the MHC class II pathway of antigen presentation by impairing Ras superfamily GTPases
Authors: Ghittoni Raffaella , Napolitani Giorgio , Benati Daniela , Uliveri Cristina , Patrussi Laura , Laghi Pasini Franco , Lanzavecchia Antonio , Baldari Cosima T.
Published: October 2006

Statins are widely used hypocholesterolemic drugs that inhibit 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase, a rate‐limiting enzyme of the mevalonate pathway whose biosynthetic endproduct is cholesterol. As a result of this activity, statins may perturb the composition of cell membranes, resulting in lipid raft disruption. Furthermore, by inhibiting protein prenylation, a process also dependent on mevalonate, statins block membrane targeting and activity of small GTPases. Antigen uptake, processing and presentation involve the interplay of Rab and Rho family GTPases. Furthermore, lipid rafts have been implicated both in antigen internalization by the BCR and in MHC class II clustering at the immunological synapse. Here we have addressed the effects of simvastatin on antigen processing and presentation by human B cells and dendritic cells. The results show that simvastatin potently suppresses tetanus toxoid processing and presentation to CD4+ T cells by HLA‐DR by inhibiting protein antigen uptake through both receptor‐mediated endocytosis and macropinocytosis. This effect can be largely accounted for by defective prenylation of Rho and Rab GTPases in the absence of any measurable perturbation of lipid rafts. In addition, simvastatin was found to preferentially affect the invariant chain‐dependent MHC class II pathway, thereby identifying this route of antigen processing and presentation as a selective target of statins.
Dimeric Complexes of Lanthanide(III) Hexafluoroacetylacetonates with4‐Cyanopyridine N‐Oxide: Synthesis, Crystal Structure, Magnetic and Photoluminescent Properties
Authors: Eliseeva Svetlana V. , Ryazanov Mikhail , Gumy Frédéric , Troyanov Sergey I. , Lepnev Leonid S. , Bünzli Jean‐Claude G. , Kuzmina Natalia P.
Published: October 2006

A series of new mixed‐ligand lanthanide complexes [Ln(hfa)3(4‐cpyNO)]2 (Ln = SmIII–HoIII and TmIII; hfa– = hexafluoroacetylacetonate; 4‐cpyNO = 4‐cyanopyridine N‐oxide) have been synthesised by treating the corresponding lanthanide hexafluoroacetylacetonates with 4‐cpyNO (molar ratio 1:1) in chloroform. Single‐crystal X‐ray analysis revealed that [Tb(hfa)3(4‐cpyNO)]2 and [Ho(hfa)3(4‐cpyNO)]2 are isostructural and are comprised of two types of symmetrically independent dimetallic molecules. Within a dimer, the eightfold‐coordinated metal atoms are bridged by two 4‐cpyNO ligands through the oxygen atoms of the N‐oxide groups. The magnetic susceptibility data for the GdIII and TbIII complexes indicate the presence of weak antiferromagnetic interactions within the dimetallic Ln2O2 units. The thermal stability of the [Ln(hfa)3(4‐cpyNO)]2 adducts was studied by thermogravimetric analysis and their volatility estimated from sublimation experiments under reduced pressure. The photoluminescent properties were measured for solid samples upon excitation at 330–360 nm. The mixed‐ligand complexes of SmIII, EuIII, TbIII, DyIII and TmIII exhibit metal‐centred luminescence in the entire visible spectral range with characteristic pink, red, green, yellow and blue emission, respectively. The introduction of ancillary 4‐cpyNO molecules into the coordination sphere of the lanthanide(III) ions was found to significantly affect their luminescence quantum yields. [Eu(hfa)3(4‐cpyNO)]2 thin films on quartz substrates were obtained by the vacuum evaporation technique and their photoluminescent properties were found to be enhanced when compared with those of the bulk samples. This suggests that these dimers could be good candidates for the fabrication of emitting layers for light‐emitting diodes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
4‐Substituted‐Phenyl(bisoxazoline)‐Rhodium Complexes: Efficiency in the Catalytic Asymmetric Reductive Aldol Reaction
Authors: Shiomi Takushi , Ito Jun‐ichi , Yamamoto Yoshihiko , Nishiyama Hisao
Published: October 2006

Electronic effects of the substituents on the phenyl ring of the phenyl(bisoxazoline) ligand skeleton of rhodium catalysts was examined in the asymmetric reductive aldol reactions of acrylates and aldehydes. The electron‐withdrawing NO2 group of Rh(4‐NO2‐Phebox‐R)(OAc)2 showed an increase in the enantioselectivity of the products in the reductive reaction of methyl acrylate but not in the reactions of tert‐butyl‐ and trimethylsilyl acrylates. Theoretical calculations of the corresponding model rhodium‐Phebox complexes indicate that the remote electron‐withdrawing substituent slightly shortens the Rh–Cphebox bond. Also, the Rh–C bonds of Rh(4‐NO2‐Phebox‐iPr)(OAc)2 and the corresponding Rh(4‐H‐Phebox‐iPr)(OAc)2 were compared on the basis of X‐ray analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
Transaction tax and market quality of the Taiwan stock index futures
Authors: Chou Robin K. , Wang George H. K.
Published: October 2006

On May 1, 2000, the Taiwan government reduced the tax levied on futures transactions on the Taiwan Futures Exchange from 5 to 2.5 basis points. This event provides a unique opportunity to test empirically the impact of a tax rate reduction on trading volume, bid‐ask spreads, and price volatility. Intraday and daily time series data from May 1, 1999, through April 30, 2001, are tested in a three‐equation structural model. Findings show that transaction taxes have a negative impact on trading volume and bid‐ask spreads, as trading volume increased and bid‐ask spreads decreased in the period following the reduction in the transaction tax. This study's analysis is not consistent with the argument that the imposition of a transaction tax may reduce price volatility because there are no significant changes in price volatility after the tax reduction. Further, it was found that although the reduction in the transaction tax did reduce tax revenues, the proportional decrease in tax revenues is less than the 50% reduction in the tax rate. Finally, tax revenues in the second and third year after the tax reduction increased, as compared to the year before the tax reduction. © 2006 Wiley Periodicals, Inc. Jrl Fut Mark 26:1195–1216, 2006
The attitudes to ageing questionnaire (AAQ): development and psychometric properties
Authors: Laidlaw K. , Power M. J. , Schmidt S.
Published: October 2006

Objective

This paper describes the development of the Attitudes to Ageing Questionnaire (AAQ) which is a self‐report measure with which older people themselves can express their attitudes to the process of ageing.

Method

The development of the AAQ followed a coherent, logical and empirical process taking full account of relevant gerontological knowledge and modern and classical psychometric analytical methods. Pilot testing with 1,356 participants from 15 centres worldwide refined the scale and provided the basis for a field test. A total of 5,566 participants from 20 centres worldwide contributed to the further development of this new scale with the derivation involving both classical and modern psychometric methods.

Results

The result is a 24‐item cross‐cultural attitudes to ageing questionnaire consisting of a three‐factor model encompassing psychological growth, psychosocial loss, and physical change. The three‐factor model suggests a way of conceptualizing and measuring successful ageing in individuals.

Conclusions

The AAQ provides researchers, clinicians and policy makers with a unique scale to measure the impact of successful ageing interventions. It also provides a vehicle for the measurement of how individuals age across cultures and under different economic, political and social circumstances. Copyright © 2006 John Wiley & Sons, Ltd.
Scaling model of a rainfall intensity‐duration‐frequency relationship
Authors: Bougadis John , Adamowski Kaz
Published: October 2006

Intensity‐duration‐frequency (IDF) relationships are currently constructed based on an at‐site frequency analysis of rainfall data separately for different durations. These relationships are not accurate and reliable since they depend on many assumptions such as distribution selection for each duration; they require a large number of parameters, and are not time‐independent.

In this study, scaling properties of extreme rainfall are examined to establish scaling behaviour of statistical non‐central moments over different durations. A scale invariance concept is explored for disaggregation (or downscaling) of rainfall intensity from low to high resolution and is applied to the derivation of scaling IDF curves. These curves are developed for gauged sites based on scaling of the generalized extreme value (GEV) and Gumbel probability distributions.

Numerical analysis was performed on annual maximum rainfall series for the province of Ontario, for storm durations of 5, 10, 15, and 30 min (the typical time of concentration for small urban catchments) and 1, 2, 6, 12, and 24 h (the typical time of concentration for larger rural watersheds).

Results show that rainfall does follow a simple scaling process. Estimates found from the scaling procedure are comparable to estimates obtained from traditional techniques; however, the scaled approach was more efficient and gives more accurate estimates compared with the observed rainfall total at all stations. Copyright © 2006 John Wiley & Sons, Ltd.
Male characteristics on female mud snails caused by antifouling bottom paints
Authors: Smith Blakeman S.
Published: October 2006

This study continues an investigation of ananatomical abnormality, named ‘imposex’, which consists of a superimposition of male characteristics on to a functionally normal female reproductive anatomy of the dioecious snail Nassarius obsoletus Say. Imposex is prevalent in natural populations living near yacht basins and rarely found distant from them. In the current study caged snails were transferred between a yacht basin and a distant ‘clean’ locality where the natural population of snails was normal. Imposex was induced in some normal snails kept at the marina and suppressed, but not lost in abnormal snails kept at the clean locality. A similar positive result was obtained in the laboratory by exposing normal snails to organotincontaining antifouling paints and abnormal snails to clean sea water. Results were negative in parallel tests of various marina‐associated materials which did not contain organotin. The laboratory studies have thus identified a causative factor of the anatomical abnormalities common near yacht basins in the natural environment. They also provide a rare, if not unique, example of a chemical agent which causes the appearance of superfluous anatomical features in an animal.
The inhibitory effect of serum from diethyldithiocarbamate treated rats on bovine adrenal dopamine‐β‐hydroxylase activity
Authors: Jarvis J. A. E. , Magos L. , Jacobs R.
Published: October 2006

The activity of serum dopamine‐β‐hydroxylase does not depend solely on the presence of exogenous inhibitors: its activity also depends on the rate of release into plasma and is influenced by sympathetic activity or pathological conditions. This fluctuation may disguise the effect of an exogenous inhibitor on the enzyme. It has been shown in the present work that boiling of serum obtained from sodium diethyldithiocarbamate treated rats did not eliminate the dopamine‐β‐hydroxylase inhibitory effect on a bovine adrenal dopamine‐β‐hydroxylase preparation. Thus it is possible to measure the dopamine‐β‐hydroxylase inhibitory effect of an exogenous inhibitor of this type without interference from the enzyme present in serum. Serum taken from rats treated with sodium diethyldithiocarbamate depressed in a time and dose dependent way the activity of bovine adrenal dopamine‐β‐hydroxylase preparation.
Absorption of the toxins of lantana camara L. from the digestive system of sheep
Authors: Pass Michael A. , McSweeney Christopher S. , Reynoldson James A.
Published: October 2006

When lantana was given into different regions of the alimentary tract, absorption sufficient to cause intoxication occurred from the stomachs, small intestine and large intestine, but absorption from the small intestine was quantitatively the most important. However, it was shown that the passage of ingesta into the small intestine decreased markedly a few hours after the toxin was given and it is suggested that absorption from all areas of the gastrointestinal tract is important for the progression of the disease. When bile was diverted away from the small intestine, animals were still intoxicated by lantana. This indicates that bile is not important for absorption of lantana toxins. Other experiments indicated that the lantana toxins are transported to the liver mainly in the portal blood.
The role of nitroaromatic compounds in the direct‐acting mutagenicity of diesel particle extracts
Authors: Pederson T. C. , Siak J‐S.
Published: October 2006

The Salmonella mutation assay has been adapted to a number of experimental procedures used to characterize the chemical components and molecular mechanisms involved in the direct‐acting mutagenicity of diesel particle extracts. The mutagens were found to be unreactive towards purified DNA. Mutagenic activity was decreased in nitroreductase‐deficient bacteria and increased in the absence of oxygen, suggesting that bacterial enzymes activate the mutagens. The extract was fractionated by thin layer chromatography using both normal and reverse phase silica gel plates. On normal silica plates, a separation was made between unsubstituted PAH, nitro‐PAH and the more polar aromatic compounds. About a third of the mutagenic activity in the particle extract was recovered in fractions containing monosubstituted nitro‐PAH compounds. The absorption spectra and reverse phase chromatographic properties indicate 1‐nitropyrene is a predominant component but not the only mutagen in these fractions. The remaining activity was in the more polar fractions, and mutagenicity assays using anaerobic conditions and nitroreductase‐deficient bacteria suggest they contain other nitro‐substituted compounds.
Pulmonary function testing of animals chronically exposed to diluted diesel exhaust
Authors: Gross Kenneth B.
Published: October 2006

The purpose of this work was to assess the potential effect that chronic inhalation of diesel exhaust may have on lung mechanics and lung volume. Noninvasive pulmonary function tests that produced data on lung air flows and volumes have been conducted repeatedly on 25 male Fischer‐344 rats exposed to diesel exhaust at a particulate concentration of 1500 μg m−3, 20 h per day, 51/2 days per week, for 612 days. The same tests were conducted on 25 clean air control animals. When the data were normalized, the majority of tests did not reveal any significant deviation from the norm for the first year of exposure. In the second year, the functional residual capacity and its component volumes – expiratory reserve and residual volume, maximum expiratory flow at 40% of vital capacity, maximum expiratory flow at 20% of vital capacity and the forced expiratory volume in 0.1 s – were significantly greater in the diesel exposed animals. The data are inconsistent with known clinically significant adverse health effects. Although the lung volume changes in the diesel exposed animals could be indicative of emphysema or other forms of chronic obstructive lung disease, this interpretation is contradicted by the air flow data which suggest simultaneous lowering of the resistance of the smaller airways. The observations are not consistent with documented clinical lung disease in man.
Changes in thyroid hormones following liver intoxication with carbon tetrachloride
Authors: Mourelle Marisabel , Rubalcava Boanerges
Published: October 2006

The metabolism of thyroid hormones was studied after carbon tetrachloride (CCl4) liver damage. Thyroxine (T4) and triiodothyronine (T3) levels fell and reached a nadir in the first 24 hours after CCl4 administration. Thyroxine binding globulins (TBG) and thyroid stimulating hormone (TSH) also decreased, reaching their lower values in the same period. Blood and liver T4 turnover measured in CCl4 treated rats were faster than in control animals. Therefore, at least three phenomena appear to be involved after CCI4 intoxication in rats: (1) increased utilization and turnover of thyroxine by the regenerating liver; (2) diminished thyroid hormone secretion by the thyroid gland, and (3) reduced concentration of serum iodothyronine carrier proteins. The results support the concept that the liver participates in the metabolic regulation of T3 and T4 which, in turn, control hepatocellular growth.