bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue distribution of the novel DPP‐4 inhibitor BI 1356 is dominated by saturable binding to its target in rats
Authors: Fuchs Holger , Binder Rudolf , Greischel Andreas
Published: June 2009

BI 1356 (INN: linagliptin) is an inhibitor of dipeptidyl peptidase‐4 (DPP‐4). This study investigated whether saturable binding of BI 1356 to its target DPP‐4 occurs in tissues and whether drug accumulation occurs at these sites in vivo. In order to test these hypotheses, the tissue distribution of BI 1356 was determined in wild‐type and DPP‐4 deficient rats at different dose levels by means of whole body autoradiography and measurement of tissue radioactivity concentrations after single i.v. dosing of [14C]‐radio labeled BI 1356. The accumulation behavior of drug‐related radioactivity in tissues was further explored in an oral repeat dose study. Tissue levels of [14C]BI 1356 related radioactivity were markedly lower in all investigated tissues of the DPP‐4 deficient rats and the difference of the dose‐dependent increase of radioactivity tissue levels between both rat strains indicates that tissue distribution at low doses of BI 1356 is dominated by binding of BI 1356 to DPP‐4 in tissues. As the binding to DPP‐4 is strong but reversible, the tissue binding results in a long terminal half‐life in several tissues including plasma. The binding capacity to DPP‐4 is, however, limited. In the rat, saturation of DPP‐4 binding is suggested at an intravenous dose above 0.01–0.1 mg/kg [14C]BI 1356. As the DPP‐4 binding capacity is saturated already at low doses, accumulation of BI 1356 in tissues is unlikely, despite the long persistence of low amounts in the body. Copyright © 2009 John Wiley & Sons, Ltd.
Artemisinin–a possible CYP2B6 probe substrate?
Authors: Asimus Sara , Ashton Michael
Published: June 2009

Aim. To comparein vitrometabolism rates for artemisinin and the CYP2B6 substrates, bupropion, propofol and efavirenz in human liver microsomes.

Methods. Rate constants of artemisinin, bupropion, propofol and efavirenz metabolism by human liver microsomes from a panel of 12 donors, with different levels of CYP2B6 activity, were estimated in WinNonlin. Correlations between the metabolic rate constant for artemisinin and the other CYP2B6 substrates were examined.

Results. Artemisinin and propofol depletion data in human liver microsomes were described by first order kinetic models. For bupropion and efavirenz, metabolite formation data were incorporated in the model. Rate constants varied considerably for all substrates. There was a high degree of correlation of rate constants between substrates (r⩾0.87,p<0.001).

Conclusions. The rate ofin vitrometabolism of artemisinin was correlated significantly to that of bupropion, propofol and efavirenz, suggesting artemisinin to be a potential alternative marker to assess CYP2B6 activity. Further studies characterizing the metabolic fate of artemisinin are needed in order to evaluate its utility as anin vitroandin vivoCYP2B6 probe substrate, since CYP2B6 might not be the only CYP isoform involved in the depletion of artemisinin. Copyright © 2009 John Wiley & Sons, Ltd.
Evaluation of the effect of intravenous volume expanders upon the volume of distribution of gentamicin in septic neonates
Authors: Sherwin Catherine M. T. , Kostan Esther , Broadbent Roland S. , Medlicott Natalie J. , Reith David M.
Published: June 2009

Sepsis has been reported to increase the volume of distribution of gentamicin in neonates. To determine whether this was caused by the use of intravenous volume expanders a retrospective nested case–control study was performed comparing confirmed septic neonates with non‐septic controls. Data were collected on intravenous administration of 0.45% saline/10% dextrose, 0.45% saline/5% dextrose, 0.9% normal saline, red blood cells, platelets, immunoglobulin (Intragam P) and albumin. A population pharmacokinetic analysis was performed using NONMEM for 116 neonates (29 confirmed septic) from which 363 gentamicin serum concentrations were available. The final covariate model was CL=0.097×(current weight/2)1.3×(postnatal age/7)0.29 and V=1.07×(current weight/2)0.8+(confirmed sepsis)×0.13. The gentamicin volume of distribution was not significantly influenced by the cumulative intravenous volume expanders. The principal covariates that affected the gentamicin volume of distribution were current body weight and confirmed sepsis. Copyright © 2009 John Wiley & Sons, Ltd.
Changes in synaptic efficacy and seizure susceptibility in rat brain slices following extremely low‐frequency electromagnetic field exposure
Authors: Varró Petra , Szemerszky Renáta , Bárdos György , Világi Ildikó
Published: July 2009

The effects of electromagnetic fields (EMFs) on living organisms are recently a focus of scientific interest, as they may influence everyday life in several ways. Although the neural effects of EMFs have been subject to a considerable number of investigations, the results are difficult to compare since dissimilar exposure protocols have been applied on different preparations or animals. In the present series of experiments, whole rats or excised rat brain slices were exposed to a reference level‐intensity (250–500 µT, 50 Hz) EMF in order to examine the effects on the synaptic efficacy in the central nervous system. Electrophysiological investigation was carried out ex vivo, on neocortical and hippocampal slices; basic synaptic functions, short‐ and long‐term plasticity and seizure susceptibility were tested. The most pronounced effect was a decrease in basic synaptic activity in slices treated directly ex vivo observed as a diminution in amplitude of evoked potentials. On the other hand, following whole‐body exposure an enhanced short‐ and long‐term synaptic facilitation in hippocampal slices and increased seizure susceptibility in neocortical slices was also observed. However, these effects seem to be transient. We can conclude that ELF‐EMF exposure exerts significant effects on synaptic activity, but the overall changes may strongly depend on the synaptic structure and neuronal network of the affected region together with the specific spatial parameters and constancy of EMF. Bioelectromagnetics 30:631–640, 2009. © 2009 Wiley‐Liss, Inc.
Tragfähigkeit von randnahen Kopfbolzen bei der Versagensart seitlicher Betonausbruch
Authors: Hofmann Jan , Eligehausen Rolf
Published: June 2009

Kopfbolzen, die sehr nahe am Bauteilrand verankert werden, können infolge seitlichen Betonausbruchs versagen. Bei dieser Versagensart kommt es zu einem Abplatzen des Betons auf der Seitenfläche des Bauteils. Die Berechnung der Tragfähigkeit erfolgt dabei mit dem CC‐Verfahren.

Numerische und experimentelle Untersuchungen zeigen, dass der bisherige Berechnungsansatz konservative Ergebnisse liefert. Um den Einfluss einzelner Parameter auf die Tragfähigkeit zu bestimmen, wurden Versuche verschiedener Autoren ausgewertet und ergänzende numerische Untersuchungen durchgeführt. Diese zeigen, dass

– der kritische Randabstand von 3.c1 auf 2.c1 reduziert werden kann.

– der Einfluss des Randabstandes geringer als bisher angenommen ist.

– der Einfluss der Betondruckfestigkeit unterschätzt wird.

– der Einfluss direkt nebeneinander liegender Kopfbolzen nicht berücksichtigt wird. Um wirtschaftlichere Ergebnisse für die Tragfähigkeit von randnahen Kopfbolzen zu erhalten wird ein modifizierter Berechnungsansatz aufgezeigt, der die Versuchsergebnisse und numerischen Berechnungen gut abbildet. Dieser Ansatz findet Eingang in die neue europäische Bemessungsnorm 'Design of Fasteners for Use in Concrete' und ermöglicht damit eine genauere Berechnung von Kopfbolzenverankerungen nahe am Bauteilrand für die Versagensart Blow Out.

Load Bearing Capacity of Headed Studs in Case of Blow Out Failure Mode

Headed studs placed near to the edge of a concrete member can fail because of blow out. In case of this failure mode the concrete spalls at the lateral surface of the concrete member. The failure load can be calculated by the Concrete capacity method (CCmethod).

Numerical and experimental investigation show that the CC‐method leads to conservative results. To determine the influence parameters on the load bearing capacity the tests of different authors are evaluated and advanced numerical simulations are carried out. The evaluation shows that

– the critical edge can be reduced to two times the edge distance.

– the influence of the edge distance is smaller than assumed.

– the influence of the concrete compressive strength is underestimated.

– the influence of headed stud placed sided by side is not considered. To get more economic results relating the load capacity of headed studs at the edge a modification of the CC‐Method is proposed. This modified CC‐method corresponds quite well with the test results as well as with the results of the numerical simulations. The proposed design equation will be included in the European design guide 'Design of Fasteners for Use in Concrete'.
Rissbildung und Zugtragverhalten von mit Fasern verstärktem Stahlbeton am Beispiel ultrahochfesten Betons
Authors: Leutbecher Torsten , Fehling Ekkehard
Published: June 2009

Wegen des Problems möglicher Inhomogenitäten der Faserverteilung/‐ orientierung ist der Einsatz von Fasern als alleinige Bewehrung im konstruktiven Ingenieurbau auf wenige Anwendungsgebiete beschränkt (z. B. Aufnahme von Zwangbeanspruchungen). Unter Zugbeanspruchung lässt sich zudem mit den in der Praxis für normalfeste Betone gebräuchlichen Fasergehalten nach der Erstrissbildung kaum ein verfestigendes Verhalten erzielen. Kombiniert man jedoch Stabstahlbewehrung und Faserbewehrung zu einem stahlfaserverstärkten Stahlbeton, so addieren sich die Vorteile beider Verbundwerkstoffe gleichermaßen. Besonders bei erhöhten Anforderungen an die Rissbreite (Größenordnung: unter 0, 1 mm) kann durch gemischte Bewehrung aus Stabstahl und Fasern eine wesentliche Verbesserung gegenüber Stahlbeton erzielt werden. Im Teil 1 dieses Beitrags wurden die für das Verständnis der unterschiedlichen Wirkungsweisen der beiden Bewehrungselemente “Stabstahl” und “Fasern” erforderlichen mechanischen Zusammenhänge dargestellt. Im Teil 2 erfolgt eine Überprüfung der abgeleiteten Beziehungen anhand experimenteller Untersuchungen an gemischt bewehrten Zugelementen aus ultrahochfestem Beton (UHPC). Für UHPC erreicht die Thematik besondere Aktualität, da aus Gründen der Duktilität der Einsatz von Fasen bei diesen Betonen die Regel ist. Der Nachweis der Begrenzung der Rissbreite bei kombinierter Bewehrung wird zudem an zwei Rechenbeispielen veranschaulicht.

Crack Formation and Tensile Behaviour of Concrete Members Reinforced with Rebars and Fibres exemplified by Ultra‐High‐Performance Concrete. Part 2: Experimental Investigations and Examples of Application

Due to the problem of possible inhomogeneities of fibre distribution/orientation the use of fibres as sole reinforcement is limited in engineering practice to few applications (e. g. coverage of stresses due to constraints). In addition, it is hardly possible to obtain strain hardening after first crack formation with fibre contents commonly used for normal strength concretes. However, if steel fibre reinforcement is used in combination with bar reinforcement, the advantages of both components are additive in the composite material. Especially for enhanced requirements concerning the crack width (order of magnitude: 0.1 mm), with combined reinforcement of rebars and fibres an essential improvement compared to reinforced concrete can be achieved. In part 1 of this contribution the mechanical relationships required for the understanding of the different behaviours of the two reinforcing elements “rebars” and “fibres” have been presented. In part 2 the derived relationships are validated on the basis of experimental investigations on tensile members with combined reinforcement made of ultra‐high‐performance concrete (UHPC). For UHPC the topic is of special interest, because fibres are added to these concretes generally to improve ductility. The crack width control with combined reinforcement is furthermore illustrated by means of two examples.
Verstärkung einer denkmalgeschützten Tonnenschale mit Textilbeton
Authors: Schladitz Frank , Lorenz Enrico , Jesse Frank , Curbach Manfred
Published: June 2009

Bei dem Umbau der Ingenieurschule Zwickau in ein Finanzamt wurde eine über 100 Jahre alte Stahlbetondachkonstruktion mit Textilbeton verstärkt. Im Vergleich mit anderen Verstärkungsmöglichkeiten konnte nur eine Textilbetonverstärkung den Anforderungen des Denkmal‐ und Brandschutzes, des Architekten sowie des Bauherrn gerecht werden und die statischen Forderung erfüllen. Die Textilbetonschicht, aus Feinbeton und textiler Bewehrung, wurde mit Gesamtdicken von nur 1,0 bis 1,5 cm aufgetragen.
Modelling Tree Roots in Mixed Forest Stands by Inhomogeneous Marked Gibbs Point Processes
Authors: Eckel Stefanie , Fleischer Frank , Grabarnik Pavel , Kazda Marian , Särkkä Aila , Schmidt Volker
Published: July 2009

The aim of the paper is to apply point processes to root data modelling. We propose a new approach to parametric inference when the data are inhomogeneous replicated marked point patterns. We generalize Geyer's saturation point process to a model, which combines inhomogeneity, marks and interaction between the marked points. Furthermore, the inhomogeneity influences the definition of the neighbourhood of points. Using the maximum pseudolikelihood method, this model is then fitted to root data from mixed stands of Norway spruce (Picea abies(L.)Karst.) and European beech (Fagus sylvatica L.) to quantify the degree of root aggregation in such mixed stands. According to the analysis there is no evidence that the two root systems are not independent.
Development of predictive quantitative retention–activity relationship models of alkaloids by mixed micellar liquid chromatography
Authors: Chen Yu , Wu Li‐ping , Chen Cong , Ye Li‐ming
Published: July 2009

The mixed micellar liquid chromatography is a mode that uses mixed micellar system of Brij35/SDS (85 : 15) as a mobile phase under adequate experimental conditions, can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged. In this article, the applications of biopartitioning micellar chromatography, using mixed micellar system to describe and estimate bioactivities of alkaloids, has been focused. The BMCBrij35/SDS‐QRAR models of half‐life time, volume of distribution, plasma clearance and area under concentration–time curve were obtained using Brij35‐SDS retention data. The aim is to take a look at the capability of the mixed micellar liquid chromatography model to describe and/or estimate the bioactivity of alkaloids. Copyright © 2009 John Wiley & Sons, Ltd.
Enhanced interferon‐β production by CHO cells through elevated osmolality and reduced culture temperature
Authors: Han Young Kue , Koo Tai Young , Lee Gyun Min
Published: July 2009

For efficient production of native interferon‐β (IFN‐β) in recombinant CHO cell culture, the IFN‐β molecular aggregation that occurs during culture needs to be minimized. To do so, we investigated the effect of hyperosmolality and hypothermia on IFN‐β production and molecular aggregation in rCHO cell culture. Both hyperosmolality (470 mOsm/kg) and hypothermia (32°C) increased specific native INF‐β productivity qIFN‐β. Furthermore, they decreased the IFN‐β molecular aggregation, although severe IFN‐β molecular aggregation could not be avoided in the later phase of culture. To overcome growth suppression at hyperosmolality and hypothermia, cells were cultivated in a biphasic mode. Cells were first cultivated at 310 mOsm/kg and 37°C for 2 days to rapidly obtain a reasonably high cell concentration. The temperature and osmolality were then shifted to 32°C and 470 mOsm/kg, respectively, to achieve high qIFN‐β and reduced IFN‐β molecular aggregation. Due to the enhanced qIFN‐β and delayed molecular aggregation, the highest native IFN‐β concentration achieved on day 6 was 18.03 ± 0.61 mg/L, which was 5.30–fold higher than that in a control batch culture (310 mOsm/kg and 37°C). Taken together, a combination of hyperosmolality and hypothermia in a biphasic culture is a useful strategy for improved native IFN‐β production from rCHO cells. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Precisely Programmed and Robust 2D Streptavidin Nanoarrays by Using Periodical Nanometer‐Scale Wells Embedded in DNA Origami Assembly
Authors: Kuzuya Akinori , Kimura Mayumi , Numajiri Kentaro , Koshi Naohiro , Ohnishi Toshiyuki , Okada Fuminori , Komiyama Makoto
Published: June 2009

A new punched DNA origami assembly with periodic nanometer‐scale wells has been successfully designed and constructed. Through the attachment of two biotins at the two edges of each well, just one streptavidin (SA) tetramer (d=5 nm) was size‐selectively captured in each 6.8×12×2.0 nm well; this allowed formation of a 28 nm‐period SA nanoarray of individual molecules. The position of SA capture can be fully controlled by placement of biotins in the nanoarray well. Moreover, construction of a 2D nanoarray of individual SA tetramers through selective positioning of SA tetramers in any desired wells in a complex of such punched origami motifs is also possible. The stability of the SA captured by this fixation strategy (DNA wells and two biotin linkers) was directly compared on the same molecule with the stability of SA captured with other possible strategies that do not employ wells or two linkers. In this way, the robustness of this means of fixation was clearly established.
Effect of Important Precipitation Process Parameters on the Redispersion Process and the Micromechanical Properties of Precipitated Silica
Authors: Schilde C. , Gothsch T. , Quarch K. , Kind M. , Kwade A.
Published: July 2009

In the past, the importance of the industrial mass production of high‐quality products and specialty chemicals by precipitation increased rapidly. In the industry, usually larger aggregates are produced and in order to produce colloidal systems with the desired properties, a more or less intense dispersion of the precipitated particles is necessary. The micromechanical properties such as the maximum indentation force, the plastic and elastic deformation energy, and the strength can give information on the product and the efficiency of the dispersion process. Generally, the temperature, as one of the most important parameters of the semi‐batch precipitation process of silica, was varied in order to change the structure, the primary particle size, the aggregate size, and the primary particle interactions in the aggregates. Dispersion of the precipitated silica in a stirred media mill and a dissolver show that the higher the precipitation temperature, the higher is the product fineness and, thus, the smaller is the strength of the aggregates. The reason for this effect is the increase of the primary particle size and the decrease of the solid bonds with increasing precipitation temperature. Because of higher stress intensities, the product fineness in a stirred media mill is considerably higher than in the dissolver. In principal, the maximum achievable product fineness and the energy efficiency of the dispersion process increase with decreasing particle strength and maximum indentation force. Besides the maximum indentation force, the maximum achievable product fineness and the energy efficiency of the dispersion process increase with increasing quotient of plastic and elastic deformation energy.
Ionic Liquids in Oxygen Compression
Authors: Predel T. , Schlücker E.
Published: July 2009

Ionic liquids are still a relatively new and very promising class of substances which have received increased research attention in recent years. Due to their unique physical and chemical properties these compounds are ideal for use in industrial applications and also offer a variety of very interesting possibilities in process technology, with a high potential of increasing performance and reducing investment and operating costs [1]. Ionic liquids are remarkable for their high chemical inertness and good lubricity. Therefore, one very promising application is the lubricated compression of oxygen as an alternative to the dry compression technique that has to be used because of the extremely high reactivity of pure oxygen with organic lubricating media. A screening of the relevant parameters including thermal stability, flammability, chemical inertness to pure oxygen, corrosiveness, tribological behavior and oxygen solubility was performed. Based on the results obtained, the most suitable ionic liquid was identified and used in a screw compressor setup that achieves a final pressure of 30 bar with a delivery volume of up to 200 Nm3/h.
The Controlled Formation and Cleavage of an Intramolecular d8–d8 Pt–Pt Interaction in a Dinuclear Cycloplatinated Molecular “Pivot‐Hinge”
Authors: Koo Chi‐Kin , Wong Ka‐Leung , Lau Kai‐Cheung , Wong Wai‐Yeung , Lam Michael Hon‐Wah
Published: June 2009

The bis(diphenylphosphino)methane (dppm)‐bridged dinuclear cycloplatinated complex {[Pt(L)]2(μ‐dppm)}2+ (Pt2⋅dppm; HL: 2‐phenyl‐6‐(1H‐pyrazol‐3‐yl)‐pyridine) demonstrates interesting reversible “pivot‐hinge”‐like intramolecular motions in response to the protonation/deprotonation of L. In its protonated “closed” configuration, the two platinum(II) centers are held in position by intramolecular d8–d8 Pt–Pt interaction. In its deprotonated “open” configuration, such Pt–Pt interaction is cleaved. To further understand the mechanism behind this hingelike motion, an analogous dinuclear cycloplatinated complex, {[Pt(L)]2(μ‐dchpm)}2+ (Pt2⋅dchpm) with bis(dicyclohexylphosphino)methane (dchpm) as the bridging ligand, was synthesized. From its protonation/deprotonation responses, it was revealed that aromatic π–π interactions between the phenyl moieties of the μ‐dppm and the deprotonated pyrazolyl rings of L was essential to the reversible cleavage of the intramolecular Pt–Pt interaction in Pt2⋅dppm. In the case of Pt2⋅dchpm, spectroscopic and spectrofluorometric titrations as well as X‐ray crystallography indicated that the distance between the two platinum(II) centers shrank upon deprotonation, thus causing a redshift in its room‐temperature triplet metal–metal‐to‐ligand charge‐transfer emission from 614 to 625 nm. Ab initio calculations revealed the presence of intramolecular hydrogen bonding between the deprotonated and negatively charged 1‐pyrazolyl‐N moiety and the methylene CH and phenyl C–H of the μ‐dppm. The “open” configuration of the deprotonated Pt2⋅dppm was estimated to be 19 kcal mol−1 more stable than its alternative “closed” configuration. On the other hand, the open configuration of the deprotonated Pt2⋅dchpm was 6 kcal mol−1 less stable than its alternative closed configuration.
A Study of the Influence of Ionic Liquids Properties on the Kemp Elimination Reaction
Authors: D'Anna Francesca , La Marca Sandra , Lo Meo Paolo , Noto Renato
Published: June 2009

The morpholino‐induced elimination of 5‐nitrobenzisoxazole into the relevant 2‐cyano‐4‐nitrophenolate has been used as a sample reaction in order to investigate molecular properties of some room temperature ionic liquids. The kinetic study was carried out at 298 K by means of spectrophotometric measurements. Ionic liquids, which differ in both their cation and anion properties, were used as solvent systems. In particular, aliphatic (pyrrolidinium, piperidinium, and ammonium) and aromatic (imidazolium and pyridinium) ionic liquids were used. For aromatic cations, imidazolium ions having different hydrogen‐bond donor ability or a different alkyl‐chain length were taken into account. The anions chosen ([BF4−], [PF6−], [SbF6−], and [NTf2−]; where NTf2=bis(trifluoromethansulfonyl)imide) showed different shape, size, and coordination ability. Solvent parameters of all ionic liquids used were determined by using spectroscopic probes, such as 4‐nitroaniline, N,N‐diethyl‐4‐nitroaniline, Nile Red, and Reichardt’s dye. Finally, in order to obtain information on the structural organization of the solvent systems, resonance light‐scattering measurements were carried out. The collected data provide evidence that ionic liquids are solvent media which exhibit peculiar features, whose effects can be rationalized only considering all parameters affecting their three‐dimensional structure.
Lanthanide(III) Complexes with Two Hexapeptides Incorporating Unnatural Chelating Amino Acids: Secondary Structure and Stability
Authors: Cisnetti Federico , Gateau Christelle , Lebrun Colette , Delangle Pascale
Published: June 2009

Unnatural metal‐chelating amino acids bearing aminodiacetate side‐chains have been introduced into two hexapeptides to obtain efficient lanthanide‐binding peptides. The synthesis of the enantiopure Fmoc‐Adan(tBu)2‐OH synthons is described with overall yields of 32 and 50 % forn=2 andn=3 side‐chain carbon atoms, respectively. The two peptides AcWAdanPGAdanGNH2(Pn) were synthesized from the protected synthons by standard solid‐phase peptide synthesis. Studies of the lanthanide complexes of the two peptidesPnby luminescence titrations, mass spectrometry, circular dichroism, and solution NMR spectroscopy demonstrate that the Adanchain length has a dramatic effect on the complexation properties. Indeed, the flexible compoundP3forms a mononuclear complex of moderate stability (β11=109.9), which tends to transform into a binuclear species in the presence of excess of the metal ion. Interestingly, the more compact peptideP2provides stable Ln3+complexes with the exclusive formation of the mononuclear LnP2adduct. The stability constant of TbP2is two orders of magnitude higher (β11=1012.1) than that measured forP3. The 800 MHz NMR spectrum of the La3+complex ofP2evidences a well‐defined type II β‐turn as well as a hydrophobic Trp(indole)–Pro interaction. These interactions exemplify the non‐innocent character of the peptide spacer in the complex LaP2as well as the role of a peptide secondary structure in the stabilization of metal complexes.
A Straightforward Total Synthesis of (−)‐Chaetominine
Authors: Malgesini Beatrice , Forte Barbara , Borghi Daniela , Quartieri Francesca , Gennari Cesare , Papeo Gianluca
Published: June 2009

A total synthesis of the tripeptide alkaloid (−)‐chaetominine (1) was achieved in 9.3 % overall yield starting from commercially available D‐tryptophan methyl ester, based on a short and straightforward (nine steps) sequence. The early stage introduction (first step) of the quinazolinone moiety and the late stage introduction (penultimate step) of the hydroxy group allowed a synthetic strategy devoid of protective groups. The key step of the process is the a–c tricyclic ring construction via an unprecedented NCS‐mediated N‐acyl cyclization on an indole ring to give tetrahydro‐1H‐pyrido[2,3‐b]indole 11. In the penultimate step, oxidation of the tetracyclic intermediate 14 with oxaziridine 15 gave only one of the four possible diastereoisomers, the cis‐diastereoisomer 16 resulting from the attack of the oxaziridine to the double bond face opposite to the c–d ring substituents. In the last step, the complete stereocontrol of the Et3SiH/TFA reduction of compound 16, probably involving a N‐acyliminium ion, can be attributed to ring constrain, which forces the b–c ring junction in the more stable cis‐orientation. (−)‐Chaetominine (1) showed a negligible inhibitory activity on several cancer cell lines.
Feinstäube und Umweltzonen#
Authors: Zellner R. , Kuhlbusch T. A. J. , Diegmann V. , Herrmann H. , Kasper M. , Schmidt K.‐G. , Dott W. , Bruch J.
Published: June 2009

Umweltzonen zum Schutz der Bevölkerung vor den gesundheitsschädigenden Auswirkungen der Feinstaubbelastung sind zum Alltagsbild vieler deutscher Großstädte geworden. Nach gut einem Jahr ihrer Einrichtung werden sie von den Befürwortern gelobt und von den Gegnern nach wie vor abgelehnt. Eine Gruppe von Experten aus dem Arbeitsausschuss „Feinstäube”︁ von ProcessNet, KRdL und GDCh hat sich kürzlich mit den Grundlagen der Feinstaubbelastung und ihrer Wirkung befasst und die Sinnhaftigkeit von Umweltzonen unter wissenschaftlichen Aspekten überprüft. Danach sind Umweltzonen durchaus sinnvoll. Die verwendete Metrik eines rein massenbezogenen Grenzwertes ist aus zahlreichen epidemiologischen Untersuchungen wirkungsseitig abgeleitet, jedoch nicht toxikologisch begründet. Der Expertenkreis befürwortet deshalb wirkungsbezogene Forschungen, in denen die Relevanz anderer Partikelmetriken, wie die chemische Zusammensetzung, Größe und Oberfläche, für die menschliche Gesundheit geklärt wird.
MS Binding Assays—with MALDI toward High Throughput
Authors: Höfner Georg , Merkel Dietrich , Wanner Klaus Theodor
Published: June 2009

A novel type of MS binding assay, a substitute for radioligand binding, in which the quantification of the MS marker is performed by MALDI‐MS–MS (FlashQuant) has been established. Because conventional MS binding assays can only be carried out by LC–ESI‐MS–MS, the use of the FlashQuant system substantially increases the throughput capacity of this method. The study was performed for mGAT1 as a model system. First, a method was developed to quantify NO 711 as a marker for mGAT1 in a range from 208 pMto 16.7 nMusing [2H10]NO 711 as an internal standard. On this basis, MS binding assays for mGAT1 could be implemented. Affinity constants determined in both saturation and competition experiments were in excellent agreement with those obtained in MS binding assays based on LC–ESI‐MS–MS quantification. As the MALDI‐MS system takes only a few seconds for quantification per sample, and the whole assay procedure is executed in a 96‐well format, this technique is amenable to high‐throughput screening.
Oxygen‐Ion Transport in a Dual‐Phase Scandia–Yttria‐Stabilized Zirconia Solid Electrolyte: A Molecular Dynamics Simulation
Authors: Chang Kai‐Shiun , Tung Kuo‐Lun
Published: June 2009

A molecular dynamics (MD) simulation is adopted to investigate oxygen‐ion diffusion mechanisms in dual‐phase (cubic/monoclinic phase) zirconia‐based solid electrolytes. XRD analysis is performed to validate the phase structure composition after an MD duration of 500 ps. The radial distribution function of the ion pairs is used to analyze the microstructure and mobility of the oxygen ions inside the electrolyte. The mean‐squared displacement, displacement distribution, and moving path of oxygen ions indicate that ion mobility increases with Sc2O3 content. Furthermore, the mobility of oxygen ions is relatively lower in the dual‐phase solid‐electrolyte models than in the pure cubic models. This is due to their intrinsically unfavorable configuration for ion penetration. Comparison of the diffusion coefficient and ionic conductivity of the oxygen ions in various phase compositions shows an obvious effect of phase composition complexity in the systems with high Sc2O3 concentration. The introduction of the dual‐phase composition concept for the MD simulation of oxygen‐ion conduction behavior is a promising approach to obtaining a more realistic understanding of ion transport in a solid electrolyte.
Pharmacological efficacy and safety profile of taranabant in preclinical species
Authors: Fong T.M. , Shearman L.P. , Stribling D.S. , Shu J. , Lao J. , Huang C.R.‐R. , Xiao J.C. , Shen C.‐P. , Tyszkiewicz J. , Strack A.M. , DeMaula C. , Hubert M.‐F. , Galijatovic‐Idrizbegovic A. , Owen R. , Huber A.C. , Lanning C.L.
Published: July 2009

Taranabant is a highly selective and potent cannabinoid CB1receptor inverse agonist. We compared the pharmacological properties of taranabant with another inverse agonist, rimonabant, and determined the preclinical safety margins of taranabant. In vitro studies demonstrated that taranabant is ∼10‐fold more potent than rimonabant at the CB1receptor, and taranabant is more selective based on off‐target in vitro screening. In vivo efficacy studies demonstrated that taranabant is ∼10‐fold more potent than rimonabant in diet‐induced obese rats. In repeat‐dose toxicological studies, taranabant did not cause mortality in rodents and monkeys at exposure margins ≤6478 and 1922 times the estimated human exposure at 0.5 mg/day−1. Taranabant did not produce CNS signs, including seizures, when administered to monkeys for 1 year at 10 mg/kg−1day−1(highest dose tested chronically), corresponding to an exposure margin of 974 times. In contrast to primates, taranabant produced brief handling‐induced seizure‐like activity in rodents, species predisposed to handling‐induced seizures. Throughout the entire preclinical program, taranabant did not cause histopathological changes in the peripheral or central nervous system. In summary, the highly selective nature of taranabant is consistent with its generally favorable preclinical safety profile. Drug Dev Res 2009. © 2009 Wiley‐Liss, Inc.
Processing of urea‐formaldehyde‐based particleboard from hazelnut shell and improvement of its fire and water resistance
Authors: Gürü M. , Aruntaş Y. , Tüzün F. N. , Bilici İ.
Published: July 2009

The purpose of this study was to manufacture urea‐formaldehyde‐based particleboard from hazelnut shell and eliminate its disadvantages such as flammability, water absorption, swelling thickness by using fly ash and phenol‐formaldehyde. Synthesized urea‐formaldehyde and grained hazelnut shells were blended at different ratios ranging from 0.8 to 3.2 hazelnut shell/urea‐formaldehyde and dried at 70°C in an oven until constant weight was reached. In addition, other parameters affecting polymer composite particleboard from hazelnut shell and urea‐formaldehyde were investigated to be the amount of fly ash, amount of phenol formaldehyde and the effects of these parameters on bending stress, limit oxygen index, water absorption capacity and swelling in the thickness. The optimization results showed that the maximum bending strength was 4.1N/mm2, at urea‐formaldehyde ratio of 1.0, reaction temperature of 70°C, reaction time of 25 min, hazelnut shell/urea‐formaldehyde resin of 2.4 and mean particle size of 0.1 mm. Although the limited oxygen index and smoke density of composite particleboard without fly ash has 22.3 and 1.62, with fly ash of 16% (w/w) according to the filler has 38.2 and 1.47, respectively. Water absorption and increase in the swelling thickness exponentially decreased with increasing phenol formaldehyde. Copyright © 2009 John Wiley & Sons, Ltd.
Cyclic αvβ6‐targeting peptide selected from biopanning with clinical potential for head and neck squamous cell carcinoma
Authors: Hsiao Jenn‐Ren , Chang Yao , Chen Yuh‐Ling , Hsieh Su‐Huei , Hsu Keng‐Fu , Wang Chun‐Fu , Tsai Sen‐Tien , Jin Ying‐Tai
Published: July 2009

Background.

A cyclic peptide‐displaying phage library was used for biopanning on oral squamous cell carcinoma (OSCC) cells to identify cancer‐targeting peptides. This study was designed to characterize the receptor specificity of a candidate phage clone/peptide (phage/peptide‐29) and to explore the clinical potential of this peptide.

Methods.

Immunofluorescent confocal microscopy, phage binding assay, and immunohistochemical studies were used to demonstrate the receptor specificity of phage/peptide‐29. The effect of peptide‐29 on the proliferation of OSCC cells was studied using 3‐dimensional (3D) cell cultures.

Results.

Phage/peptide‐29 preferentially binds integrin αvβ6 rather than other αv‐associated integrins. Peptide‐29 significantly inhibits the proliferation of OSCC cells in 3D cell cultures. On human pathological sections, phage‐29 targets oral cancer cells in a αvβ6‐dependent manner. Besides, we showed that integrin αvβ6 is universally (94.7%, 36/38) expressed in all major kinds of head and neck squamous cell carcinomas (HNSCC).

Conclusions.

Peptide‐29 selected from biopanning may have clinical potential for HNSCC. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Evaluation of salt sources and loads in the upland areas of the Murray–Darling Basin, Australia
Authors: White Ian , Macdonald Ben C. T. , Somerville Peter D. , Wasson Robert
Published: July 2009

Estimates of catchment salt balances throughout the Murray‐Darling Basin (MDB) suggest mobilization of salt stores and generally increasing stream salinities. It is widely assumed these salts are rainfall‐deposited cyclic salts of marine‐aerosol origin, concentrated by evapotranspiration, stored in groundwaters and mobilized by clearing of native vegetation. In this paper, the assumptions about the sources of salts, in upland catchments in the south‐eastern region of the MDB are re‐evaluated. The estimation of dissolved salts is re‐examined using electrical conductivity (EC), the assessment of stream salt loads from sporadic EC measurements and the sources of salts in upland catchments. It is concluded that, although evapotranspiration plays a significant role in the concentrations of salts in the lower MDB, mineral weathering is a major contributor to stream salt loads in upland rivers of the MDB that supply over 80% of surface runoff to the Murray River. Copyright © 2009 John Wiley & Sons, Ltd.
Transient storage and downstream solute transport in nested stream reaches affected by beaver dams
Authors: Jin Li , Siegel Donald I. , Lautz Laura K. , Otz Martin H.
Published: July 2009

Transient storage constitutes a key element in the hydrologic cycle of watersheds. Both in‐channel slow moving water (dead zones) and hyporheic zones can contribute to transient storage, which retains water and solutes, increases residence time and influences solute transport in streams. Beaver dams and other in‐stream obstructions throughout low‐order streams attenuate streamflow and provide dead zone storage in pools. In this article, we report the results of four tracer tests in nested stream reaches in Cherry Creek (Wyoming, USA) covering ∼2·5 km of stream length to explore how the degree of beaver dam obstructions and their impoundments influence water transient storage and downstream solute transport in low‐order streams in the Rocky Mountain region of the American West. Travel‐time parameters for the tracer tests increased linearly with beaver dam number (N) and pond size (V). Linear regression of the travel time to the peak concentration (Tp), the leading (Tl) and tailing edge (Tt) of the dye cloud and the duration of the dye cloud (Td) versus N and V were all significant (R2 = 0·99). Slopes of the linear regressions of Tt versus N and V, were three times larger than those for Tl, suggesting that longer residence times may be caused, in part, by transient storage in the stream system. One‐dimensional transport with inflow and storage (OTIS) modelled cross‐sectional area of transient storage zone (As) and dispersion coefficients (D) increased linearly with N and V and reach length. Two transient storage metrics, Fmean and $F_{\rm {med}}^{200}$, also showed a general increase with N and V, although the relationship was not as strong. This suggests that in‐channel dead zones associated with beaver dams provide opportunities for generating transient water storage. The linear relationship between dispersion coefficient and reach length suggests the dispersion process might be analogous to the hydrodynamic dispersion in groundwater settings. Copyright © 2009 John Wiley & Sons, Ltd.
The predictive value of different infant attachment measures for socioemotional development at age 5 years
Authors: Smeekens Sanny , Riksen‐Walraven J. Marianne , Van Bakel Hedwig J.A.
Published: July 2009

The predictive value of different infant attachment measures was examined in a community‐based sample of 111 healthy children (59 boys, 52 girls). Two procedures to assess infant attachment, the Attachment Q‐Set (applied on a relatively short observation period) and a shortened version of the Strange Situation Procedure (SSSP), were applied to the children at age 15 months and related to a comprehensive set of indicators of the children's socioemotional development at age 5 years. Three attachment measures were used as predictors: AQS security, SSSP security, and SSSP attachment disorganization. AQS security and SSSP security jointly predicted the security of the children's attachment representation at age 5. Apart from that, SSSP attachment disorganization was a better predictor of the children's later socioemotional development than were the other two early attachment measures. First, attachment disorganization was the only attachment measure to predict the children's later ego‐resiliency, school adjustment, and dissociation. Second, as for the socioemotional measures at age 5 that also were related to AQS or SSSP security (i.e., peer social competence and externalizing problems), the attachment security measures did not explain any extra variance beyond what was explained by attachment disorganization.
Cognitive‐behavioral therapy of delusions: mental imagery within a goal‐directed framework
Authors: Serruya Gail , Grant Paul
Published: July 2009

Central to psychotic disorders, delusions are associated with disability and often respond inadequately to pharmacotherapy. Cognitive‐behavioral treatments have been developed over the last 20 years that successfully address delusions. However, meta‐analyses suggest only a modest improvement in psychotic symptoms. Because delusions share considerable overlap with anxiety, adapting principles and techniques that have demonstrated efficacy in the treatment of anxiety disorders might improve the impact of cognitive‐behavioral treatment of delusions. We report a case illustrating a cognitive‐behavioral approach to delusions with an emphasis on mental imagery techniques. A 25‐year‐old male diagnosed with paranoid schizophrenia whose clinical presentation was dominated by paranoid delusions received 6 months of treatment. At the end of the follow‐up period, the patient's delusions were minimal and his negative symptoms had significantly improved. Mental imagery may be an important treatment tool for delusions. © 2009 Wiley Periodicals, Inc. J Clin Psychol: In Session 65:1–12, 2009.
Organisational channel discrepancies between CVBs and meeting planners in the USA
Authors: Kim Dae‐Young , Lehto Xinran Y. , Kline Sheryl F.
Published: July 2009

The purpose of the study is to compare the perception of advertising and communication channels between convention and visitor bureaus (CVBs) and meeting planners in the USA. By employing 245 of CVBs and 226 meeting planners through an online survey method, the results of the study reveal clear channel discrepancies between CVBs and meeting planners in terms of preference, attitude and usage of communication and advertising channels. In addition, the study identifies different linkages between advertising channels and advertising effects in the two different groups. Implications for industry practitioners as well as suggestions for future study are discussed. Copyright © John Wiley & Sons, Ltd.
Influence of age and gender on dose and effectiveness of botulinum toxin for laryngeal dystonia
Authors: Vasconcelos Silvio , Bırkent Hakan , Sardesaı Maya G. , Meratı Albert L. , Hıllel Allen D.
Published: July 2009

Objectives/Hypothesis:

To evaluate the influence of age and gender on the required dose and resulting efficacy of botulinum toxin injection for adductor laryngeal dystonia.

Design:

Retrospective chart review.

Methods:

All patients treated with botulinum toxin for laryngeal dystonia at the University of Washington Medical Center between 1991 and 2008 were identified from a large clinical database. Only patients undergoing thyroarytenoid muscle injection for adductor laryngeal dystonia were included in this study. Each patient's gender, age at treatment, stable dose of botulinum toxin, and patient‐reported duration of beneficial effect was recorded.

Results:

A total of 155 patients (50 males, 105 females) were identified, with average ages of 50.6 years for men and 54.4 years for women. The mean treatment doses of botulinum toxin were 1.85 ± 0.84 U for males and 2.15 ± 1.40 U for females. The associated mean durations of beneficial effect were 12.8 ± 7.7 weeks for males and 13.9 ± 7.3 weeks for females. Neither the difference in dose nor in duration was found to be statistically significant (P = .395 and P = .511, respectively). When analyzed by age, the mean doses of botulinum toxin were 1.87 ± 1.00 U for patients younger than 50 years and 2.20 ± 1.41 U for the older group. The associated mean durations of beneficial effect were 13.7 ± 7.4 weeks for the younger group and 13.5 ± 7.4 weeks for the older group. Again, neither difference was found to be statistically significant (P = .113 and P = .730, respectively).

Conclusions:

Dosage and duration of beneficial effect of botulinum toxin in treatment of adductor laryngeal dystonia do not appear to vary with age or gender. Laryngoscope, 2009
Liver‐derived extracellular matrix as a biologic scaffold for acute vocal fold repair in a canine model
Authors: Gilbert Thomas W. , Agrawal Vineet , Gilbert Mark R. , Povirk Katherine M. , Badylak Stephen F. , Rosen Clark A.
Published: July 2009

Objectives/Hypothesis:

The objective of the study was to evaluate a naturally derived liver extracellular matrix (L‐ECM) scaffold for repair of an acute injury to the vocal fold lamina propria in a canine model.

Methods:

The vocal fold lamina propria was removed bilaterally in four dogs. One vocal fold in each dog was repaired with a porcine L‐ECM scaffold, which was chosen because it contains hepatocyte growth factor, an antifibrotic growth factor that aids the healing of vocal folds. The other vocal fold was left untreated. At 3 months after surgery, morphologic and histologic analysis was performed to assess the vocal fold shape, collagen density, collagen composition, elastic fiber content, and glycosaminoglycan content.

Results:

The L‐ECM–treated vocal fold showed increased collagen density in the superficial aspect of the vocal fold (P < .05). The L‐ECM–treated vocal fold also showed an increased collagen III/I ratio as compared to the nontreated group (P < .05). However, the elastic fiber content was found to be increased in both groups, and the glycosaminoglycan content was decreased in both groups as compared to the normal vocal fold (P < .05) with no differences detected between groups.

Conclusions:

The L‐ECM scaffold did not restore the biochemical composition or histologic appearance of the injured vocal fold as compared to normal. However, the increased ratio of collagen III/I and elastic fiber content suggests that L‐ECM leads to formation of connective tissue that may be more pliable as compared to no treatment. Additional investigation, including functional assessment, is warranted. Laryngoscope, 2009
Culture of nasal epithelial cells using chitosan‐based membranes
Authors: Huang Tsung‐Wei , Young Yi‐Ho , Cheng Po‐Wen , Chan Yen‐Hui , Young Tai‐Horng
Published: July 2009

Objectives/Hypothesis:

The aim of this study was to evaluate whether chitosan‐based membranes can be used as scaffolds for growth and differentiation of nasal epithelial cells (NECs). Our final goal was to establish a novel methodology for enhancing the regeneration of the respiratory system.

Study Design:

Prospective study.

Methods:

Human NECs were cultured on three various substrates, e.g., chitosan membranes, collagen, and chitosan‐collagen membranes. Morphology of NECs was examined via light and electron microscopy, the area of ciliated cells was measured by confocal microscopy, and ciliary beat frequency was also evaluated. Expression of mucin genes was investigated with reverse‐transcription polymerase chain reaction.

Results:

NECs were found to be successfully adhesive with collagen and chitosan‐collagen membranes at day 3 after seeding, but not with chitosan membranes. The cilia area on collagen were 6.1% ± 1.2%, 8.4% ± 1.4%, and 12.5% ± 1.9% at days 7, 14, and 21 after confluence, respectively, compared with 5.1% ± 0.9%, 8.6% ± 1.6%, and 12.3% ± 2.1% in chitosan‐collagen membranes, exhibited nonsignificant difference (P > .05). There were no significant differences in ciliary beat frequency between each group. The expression levels of mucin genes, namely, MUC5AC, MUC5B, and MUC2, in NECs on both collagen and chitosan‐collagen membranes did not differ significantly (P > .05).

Conclusions:

A small amount collagen mixed with chitosan substrate may improve the biocompatibility and promote the mucociliary differentiation in NECs. It appears that chitosan‐collagen membrane is a promising scaffold for culture of the nasal epithelium, which sets the stage for studying tissue regeneration in the respiratory system. Laryngoscope, 2009