bluuebunny/crossref_metadata_2025 huggingface dataset:
Limitations of radical thiol‐ene reactions for polymer–polymer conjugation
Authors: Koo Sandy P. S. , Stamenović Milan M. , Prasath R. Arun , Inglis Andrew J. , Du Prez Filip E. , Barner‐Kowollik Christopher , Van Camp Wim , Junker Tanja
Published: March 2010

In this work, we report our findings on the use of radical thiol‐ene chemistry for polymer–polymer conjugation. The manuscript combines the results from the Preparative Macromolecular Chemistry group from the Karlsruhe Institute of Technology (KIT) and the Polymer Chemistry Research group from Ghent University (UGent), which allowed for an investigation over a very broad range of reaction conditions. In particular, thermal and UV initiation methods for the radical thiol‐ene process were compared. In the KIT group, the process was studied as a tool for the synthesis of star polymers by coupling multifunctional thiol core molecules with poly(n‐butyl acrylate) macromonomers (MM), employing thermally decomposing initiators. The product purity and thus reaction efficiency was assessed via electrospray ionization mass spectrometry. Although the reactions with 10 or 5 equivalents of thiol with respect to macromonomer were successful, the coupling reaction with a one‐to‐one ratio of MM to thiol yielded only a fraction of the targeted product, besides a number of side products. A systematic parameter study such as a variation of the concentration and nature of the initiator and the influence of thiol‐to‐ene ratio was carried out. Further experiments with poly(styrene) and poly(isobornyl acrylate) containing a vinylic end group confirmed that thermal thiol‐ene conjugation is far from quantitative in terms of achieving macromolecular star formation. In parallel, the UGent group has been focusing on photo‐initiated thiol‐ene chemistry for the synthesis of functional polymers on one hand and block copolymers consisting of poly(styrene) (PS) and poly(vinyl acetate) (PVAc) on the other hand. Various functionalization reactions showed an overall efficient thiol‐ene process for conjugation reactions of polymers with low molecular weight compounds (∼90% coupling yield). However, while SEC and FT‐IR analysis of the conjugated PS‐PVAc products indicated qualitative evidence for a successful polymer–polymer conjugation, 1H NMR and elemental analysis revealed a low conjugation efficiency of about 23% for a thiol‐to‐ene ratio equal to one. Blank reactions using typical thiol‐ene conditions indicated that bimolecular termination reactions occur as competitive side reactions explaining why a molecular weight increase is observed even though the thiol‐ene reaction was not successful. The extensive study of both research groups indicates that radical thiol‐ene chemistry should not be proposed as a straightforward conjugation tool for polymer–polymer conjugation reactions. Head‐to‐head coupling is a major reaction pathway, which interrupts the propagation cycle of the thiol‐ene process. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1699–1713, 2010
Synthesis of comb polymers via grafting‐onto macromolecules bearing pendant diene groups via the hetero‐Diels‐Alder‐RAFT click concept
Authors: Bousquet Antoine , Barner‐Kowollik Christopher , Stenzel Martina H.
Published: March 2010

Comb polymers were synthesized by the “grafting‐onto” method via a combination of Reversible Addition‐Fragmentation Chain Transfer (RAFT) polymerization and the hetero‐Diels‐Alder (HDA) cycloaddition. The HDA reactive monomer trans, trans‐hexa‐2,4‐dienylacrylate (ttHA) was copolymerized with styrene via the RAFT process. Crosslinking was minimized by decreasing the monomer concentration—whilst keeping monomer to polymer conversions low—resulting in reactive backbones with on average one reactive pendant diene groups for 10 styrene units. The HDA cycloaddition was performed between the diene functions of the copolymer and a poly(n‐butyl acrylate) (PnBA) prepared via RAFT polymerization with pyridin‐2‐yldithioformate, which can act as a dienophile. The coupling reactions were performed within 24 h at 50 °C and the grafting yield varies from 75% to 100%, depending on the number average molecular weight of the PnBA (3500 g mol−1 < Mn < 13,000 g mol−1) grafted chain and the reaction stoichiometry. The molecular weights of the grafted block copolymers range from 19,000 g mol−1 to 58,000 g mol−1 with polydispersities close to 1.25. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1773–1781, 2010
Synthesis and properties of conjugated polymers containing 3,9‐carbazolylene and silylenevinylene moieties in the main chain
Authors: Sasano Tatsuya , Sogawa Hiromitsu , Tamura Kosaku , Shiotsuki Masashi , Masuda Toshio , Sanda Fumio
Published: March 2010

Novel conjugated polymers containing 3,9‐carbazolylene and silylenevinylene moieties were synthesized by the hydrosilylation polymerization of 1,4‐bis(3‐ethynyl‐9‐carbazolyl)benzene (1) with various bis(hydrosilane)s or dihydrosilanes using a rhodium catalyst. Polymers with weight‐average molecular weights ranging from 5400 to 20,000 were obtained in 55–97% yields by the polyaddition with a rhodium catalyst in toluene at 25 °C for 24 h. All the polymers were soluble in CHCl3 and THF, and had predominantly trans‐structures. The polymers exhibited λmax at a longer wavelength region than 1, and emitted fluorescence in 14–50% quantumn yields. The polymers were oxidized and reduced in the region of 0.4–1.6 V, and thermally stable up to 200 °C under air. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1815–1821, 2010
Poly(4,8‐bis(2‐ethylhexyloxy)benzo[1,2‐b:4,5‐b′]dithiophene vinylene): Synthesis, optical and photovoltaic properties
Authors: He Youjun , Zhou Yi , Zhao Guangjin , Min Jie , Guo Xia , Zhang Bo , Zhang Maojie , Zhang Jing , Li Yongfang , Zhang Fengling , Inganäs Olle
Published: March 2010

A new benzodithiophene (BDT)‐based polymer, poly(4,8‐bis(2‐ethylhexyloxy)benzo[1,2‐b:4,5‐b′]dithiophene vinylene) (PBDTV), was synthesized by Pd‐catalyzed Stille‐coupling method. The polymer is soluble in common organic solvents and possesses high thermal stability. PBDTV film shows a broad absorption band covering from 350 nm to 618 nm, strong photoluminescence peaked at 545 nm and high hole mobility of 4.84 × 10−3 cm2/Vs. Photovoltaic properties of PBDTV were studied by fabricating the polymer solar cells based on PBDTV as donor and PC70BM as acceptor. With the weight ratio of PBDTV: PC70BM of 1:4 and the active layer thickness of 65 nm, the power conversion efficiency of the device reached 2.63% with Voc = 0.71 V, Isc = 6.46 mA/cm2, and FF = 0.57 under the illumination of AM1.5, 100 mW/cm2. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1822–1829, 2010
Predicting explosibility properties of chemicals from quantitative structure‐property relationships
Authors: Fayet G. , Rotureau P. , Joubert L. , Adamo C.
Published: March 2010

Quantitative Structure‐Property Relationship (QSPR) type methods have been up to now mainly devoted to biological, toxicological applications but their use to predict physico‐chemical properties is a growing interest. In this context, an original approach associating QSPR methods and quantum chemical calculations for the prediction of chemicals explosibility properties is presented here.

Indeed, the new European regulation of chemicals named REACH implies the new assessment of a tremendous number of substances for their hazardous properties. But, the complete characterization of toxicological, ecotoxicological, and physico‐chemical hazards at experimental level is incompatible with the imposed calendar of REACH. Hence, there is a real need in evaluating capabilities of alternative methods for assessing hazardous properties as a screening process.

This contribution focuses on models that have been established to predict accurately the thermal stability and electric spark sensitivity of a series of potentially explosive nitroaromatic molecules. Descriptors related to their molecular structure (topological, geometrical, electronic, quantum chemical), partially obtained from density functional theory (DFT) calculations, were computed and statistical analyses (multilinear regressions) were performed to link the adequate molecular descriptors with the experimental properties. These first results coupling theoretical calculations and QSPR methods open new perspectives for the prediction of other physico‐chemical properties. © 2010 American Institute of Chemical Engineers Process Saf Prog 2010
Microstructure of N‐face InN grown on Si (111) by plasma‐assisted MBE using a thin GaN–AlN buffer layer
Authors: Dimitrakopulos G. P. , Kehagias Th. , Ajagunna A. , Kioseoglou J. , Kerasiotis I. , Nouet G. , Vajpeyi A. P. , Komninou Ph. , Karakostas Th.
Published: March 2010

The structural properties of 2 µm thick N‐face InN film, grown on Si (111) by plasma source molecular beam epitaxy after the initial deposition of 20 nm AlN and 40 nm GaN, were examined by transmission electron microscopy. The lattice mismatched GaN/AlN and InN/GaN interfaces limited the propagation of threading dislocations (TDs). Dislocation annihilation interactions occurred in the first ∼200 nm of the InN film and reduced the TD density. However, the density of screw and mixed type TDs was four times higher than edge type ones. This was attributed to the observed GaN/InN interfacial roughness, which was introduced by terminating TDs from the GaN/AlN buffer layer. Strain measurements showed that the InN film, as well as both buffer layers, was relaxed.
New twists in LEDs and HFETs based on nitride semiconductors
Authors: Leach J. H. , Ni X. , Lee J. , Özgür Ü. , Matulionis A. , Morkoç H.
Published: March 2010

Despite notable progress in light‐emitting and charge transport devices based on GaN heterostructures containing In, there is still controversy as to the light emission characteristics at high injection levels in InGaN‐based light‐emitting diodes (LEDs) and hot‐carrier scattering in GaN‐based field effect transistors (FETs) with AlGaN or AlInN barriers. For LEDs to be inserted into conventional lighting systems, reasonably high efficiencies would have to be retained at high injection levels to meet intensity requirements which is not yet borne out by many experiments but might be mitigated by use of nonpolar m‐plane varieties according to the most recent data. The efficiency degradation at high injection levels, beyond that which is expected due to heating and current crowding, has been attributed by what is shaping up to be two camps to mainly Auger recombination and carrier spillover. The latter has been attributed to or helped by polarization‐induced fields which is contrary to again recent experiments on LEDs. In terms of the FETs the conventional wisdom of increased carrier concentrations leading to better devices does not seem to hold beyond a certain point. This is due to strong electron LO phonon coupling in this highly ionic material and the resultant hot phonon population. Hot phonon lifetime decreases with increasing carrier concentration up to a point owing to plasmon–phonon interaction. But beyond the concentration at which the plasma frequency and phonon frequency match, the phonon lifetime begins to increase again. Increased phonon lifetimes lead to reduced carrier velocity and inefficient heat transfer, and thus performance degradation ensues. Another intriguing feature is that the aforementioned phenomenon is electric field dependent at least because increased field in FETs means widening of the channel and thus for the same volume density the resonance occurs at higher sheet densities. In this paper the details of carrier recombination in the context of InGaN LEDs both on polar c‐plane and nonpolar m‐plane GaN at high injection levels, and hot‐carrier‐scattering‐related physics in the context of HFETs based on the GaN material family containing In will be elucidated.
23Na and 87Rb relaxation study of the structural phase transitions in the Tutton salts Na2Zn(SO4)2·6H2O and Rb2Zn(SO4)2·6H2O single crystals
Authors: Lim Ae Ran , Lee Ju Ha
Published: March 2010

The NMR spectrum, spin–lattice relaxation times, T1, and the spin–spin relaxation times, T2, for the 23Na and 87Rb nuclei in Tutton salts Na2Zn(SO4)2·6H2O and Rb2Zn(SO4)2·6H2O single crystals were determined by using an FT NMR spectrometer. The NMR spectrum and relaxation times for the 23Na and 87Rb nuclei in two crystals undergo significant changes near TC. These changes close to TC were the only detectable result of the structural transformation; the change is due to the fact that the electric field gradient value becomes 0. Especially, T1 and T2 for 87Rb in the Rb2Zn(SO4)2·6H2O crystals at high temperature have similar values on the order of milliseconds, which is indicative of a liquid‐like system. The motion giving rise to this liquid‐like behavior is probably related to superionic motion at high temperature.
The influence of dipolar interaction on magnetic properties in nanomagnets with different shapes
Authors: Li Ying , Wang TianXing , Li YangXian
Published: March 2010

With the Monte Carlo method, we investigate the magnetic properties of four nanomagnets of different shapes, i.e., the circular‐shaped, the square‐shaped, the elliptical, and the ring‐shaped nanomagnets. A systematic study of the effects of the dipolar interaction on the magnetic configurations is performed in these nanomagnets, and further the coercive field and the remanence as a function of dipolar interaction are analyzed. The results show that the magnetic configuration and thus the magnetization reversal process of nanomagnets are dependent strongly on the strength of dipolar interactions. For the case of small dipolar interaction, the magnetization reversal process is mainly dominated by spin rotation, while the reversal transforms to the vortex nucleation and propagation formations with increasing dipolar interaction. Moreover, if the dipolar interaction is neglected in the calculation of the total energy, no clear difference is found among hysteresis loops of four nanomagnets with same areas, but the inclusion of dipolar interaction can lead to different hysteresis loops for nanomagnets with same areas but different shapes. This indicates that the dipolar interaction is important for accounting for the shape effect of the magnetic properties in nanomagnets.
Feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization mass spectrometry in analyzing anabolic steroids in urine samples
Authors: Ahonen Linda L. , Haapala Markus , Saarela Ville , Franssila Sami , Kotiaho Tapio , Kostiainen Risto
Published: March 2010

We examined the feasibility of capillary liquid chromatography/microchip atmospheric pressure photoionization tandem mass spectrometry (capLC/µAPPI‐MS/MS) for the analysis of anabolic steroids in human urine. The urine samples were pretreated by enzymatic hydrolysis (with β‐glucuronidase from Helix pomatia), and the compounds were liquid‐liquid extracted with diethyl ether. After separation the compounds were vaporized by microchip APPI, photoionized by a 10 eV krypton discharge lamp, and detected by selected reaction monitoring. The capLC/µAPPI‐MS/MS method showed good sensitivity with detection limits at the level of 1.0 ng mL−1, good linearity with correlation coefficients between 0.9954 and 0.9990, and good repeatability with relative standard deviations below 10%. These results demonstrate that microchip APPI combined with capLC/MS/MS provides a new potential method for analyzing non‐polar and neutral compounds in biological samples. Copyright © 2010 John Wiley & Sons, Ltd.
Structural discrimination of isomeric tetrahydrofuran lignan glucosides by tandem mass spectrometry
Authors: Ricci Andreina , Fiorentino Antonio , Piccolella Simona , D'Abrosca Brigida , Pacifico Severina , Monaco Pietro
Published: March 2010

Due to the possible role in human health, the number of analytical studies on lignans aimed at their quali‐ and quantitative analysis in plant extracts, biological fluids and foods is continuously increasing. However, helpful systematic mass spectrometric investigations on these compounds are few and rather limited to specific lignan sub‐classes. To increase the comprehension of the previously outlined picture of the gas‐phase properties of furofuran lignans, we extended the study to tetrahydrofuran lignans and here we reported the collision‐activated dissociation (CAD) fragmentation patterns of the alkali metal cation adducts, [M+Alk]+, and [M–H]− ions of three isomeric tetrahydrofuran lignans, (+)‐8′‐hydroxylariciresinol 4′‐O‐β‐D‐glucopyranoside (1), (+)‐7′‐hydroxylariciresinol 7′‐O‐β‐D‐glucopyranoside (2) and 4‐O‐β‐D‐glucopyranosyloxy‐3,3′‐dimethoxy‐7,9′‐epoxylignan‐5′,8′,9‐triol (3) investigated by electrospray ionization triple quadrupole mass spectrometry (ESI‐TQMS). Hydrogen/deuterium (H/D) solution exchange experiments, allowing the selective H/D exchange of all the acidic hydrogen atoms, proved to be a very effective tool to obtain information on the nature of fragments generated during TQ/CAD processes. The [M+Na]+ CAD mass spectra of the three isomeric tetrahydrofurans revealed four different pathways involving the loss of the glucose moiety, which allowed the assignment of the glycosylation site. In the negative ion mode, the main fragmentation channel of the [M–H]− ions of O‐glucosylated lignans at the phenolic oxygen atoms is represented by the loss of 162 Da. When the sugar is bound to a benzylic OH group the loss of the sugar as a 180 Da unit occurs eventually following the loss of a water molecule involving both the C(9)H2OH chain and the sugar. Copyright © 2010 John Wiley & Sons, Ltd.
Determination of the banned growth promoter moenomycin A in feed stuffs by liquid chromatography coupled to electrospray ion trap mass spectrometry
Authors: Gallo Pasquale , Fabbrocino Serena , Serpe Luigi , Fiori Maurizio , Civitareale Cinzia , Stacchini Paolo
Published: March 2010

Flavomycin complex is an antibiotic banned in the European Union as an additive in feed stuffs. As a consequence, the monitoring programmes for official control within the Community require analysis of feeds for possible illegal use of flavomycin. A method for unambiguous identification and quantification of moenomycin A, the main pharmacologically active component of flamomycin complex, in several feeds by liquid chromatography coupled to electrospray ion trap mass spectrometry (LC/ESI‐MS/MS) is herein described for the first time. The method was developed to be used as a confirmative analytical tool for the network of Italian official control laboratories; both the singly and doubly charged molecular ions were observed as precursor ions, from which four product ions were selected for both quantitative analysis and unambiguous identification of moenomycin A. The method was in‐house validated for feeds in the concentration range 0.50–30.0 µg/g, according to the Regulation 882/2004/EC requirements. Mean recoveries ranging between 83.9–94.2% and relative standard deviations <23% account for method trueness and repeatability, respectively. Moreover, other analytical performance parameters, i.e. method specificity, ruggedness, the linearity of detector response, the limit of quantification (LOQ), the limit of detection (LOD), and measurement uncertainty were evaluated and reported. The ion trap LC/ESI‐MS/MS method is highly selective and reliable; high drug recovery, good reproducibility and an LOQ down to 0.10 µg/g guarantee its applicability for confirmatory purposes in the official control activity in Italy. Copyright © 2010 John Wiley & Sons, Ltd.
Software utilities for the interpretation of mass spectrometric data of glycoconjugates: application to glycosphingolipids of human serum
Authors: Souady Jamal , Dadimov Denis , Kirsch Stephan , Bindila Laura , Peter‐Katalinić Jasna , Vakhrushev Sergey Y.
Published: March 2010

Glycosphingolipids (GSLs) are major components of the outer leaflet of the cell membrane. These lipids are involved in many cell surface events and show disease‐related expression changes. GSLs could thus serve as useful targets for biomarker discovery. The GSL structure is characterized by two entities: a hydrophilic glycan and a hydrophobic ceramide moiety. Both components exhibit numerous structural variations, the combination of which results in a large diversity of GSL structures that can potentially exist. Mass spectrometry (MS) is a powerful tool for high‐throughput analysis of GSL expression analysis and structural elucidation. Yet, the assignment of GSL structures using MS data is tedious and demands highly specialized expertise. SysBioWare, a software platform developed for MS data evaluation in glycomics, was here applied for the MS analysis of human serum GSLs. The program was tuned to provide automated compositional assignment, supporting a variety of glycan and ceramide structures. Upon in silico fragmentation, the masses of predicted ions arising from cleavages in the glycan as well as the ceramide moiety were calculated, thus enabling structural characterization of both entities. Validation of proposed structures was achieved by matching in silico calculated fragment ions with those of experimental MS/MS data. These results indicate that SysBioWare can facilitate data interpretation and, furthermore, help the user to deal with large sets of data by supporting management of MS and non‐MS data. SysBioWare has the potential to be a powerful tool for high‐throughput glycosphingolipidomics in clinical applications. Copyright © 2010 John Wiley & Sons, Ltd.
Kinetics of ethanol decay in mouth‐ and nose‐exhaled breath measured on‐line by selected ion flow tube mass spectrometry following varying doses of alcohol
Authors: Smith David , Pysanenko Andriy , Španěl Patrik
Published: March 2010

A study has been carried out of the decay of ethanol in mouth‐exhaled and nose‐exhaled breath of two healthy volunteers following the ingestion of various doses of alcohol at different dilutions in water. Concurrent analyses of sequential single breath exhalations from the two volunteers were carried out using selected ion flow tube mass spectrometry, SIFT‐MS, on‐line and in real time continuously over some 200 min following each alcohol dose by simply switching sampling between the two volunteers. Thus, the time interval between breath exhalations was only a few minutes, and this results in well‐defined decay curves. Inspection of the mouth‐exhaled and nose‐exhaled breath data shows that mouth contamination of ethanol diminished to insignificant levels after a few minutes. The detailed results of the analyses of nose‐exhaled breath show that the peak levels and the decay rates of breath ethanol are dependent on the ethanol dose and the volume of ethanol/water mixture ingested. From these data, both the efficiency of the first‐pass metabolism of ethanol and the indications of gastric emptying rates at the various doses and ingested volumes have been obtained for the two volunteers. Additionally and simultaneously, acetaldehyde, acetic acid and acetone were measured in each single breath exhalation. Acetaldehyde, the primary product of ethanol metabolism, is seen to track the breath ethanol. Acetic acid, a possible secondary product of this metabolism, was detected in the exhaled breath, but was shown to largely originate in the oral cavity. Breath acetone was seen to increase over the long period of measurement due to the depletion of nutrients. Copyright © 2010 John Wiley & Sons, Ltd.
The dual test: Safeguarding p‐value combination tests for adaptive designs
Authors: Burman Carl‐Fredrik , Lisovskaja Vera
Published: March 2010

Many modern adaptive designs apply an analysis where p‐values from different stages are weighted together to an overall hypothesis test. One merit of this combination approach is that the design can be made very flexible. However, combination tests violate the sufficiency and conditionality principles. As a consequence, combination tests may lead to absurd conclusions, such as ‘proving’ a positive effect while the average effect is negative. We explore the possibility of modifying the test so that such illogical conclusions are no longer possible. The dual test requires both the weighted combination test and a naïve test, ignoring the adaptations, to be statistically significant. The result is that the flexibility and type I error level control of the combination test are preserved, while the naïve test adds a safeguard against unconvincing results. The dual test is, by construction, at least as conservative as the combination test. However, many design changes will not lead to any power loss. A typical situation where the combination approach can be used is two‐stage sample size reestimation (SSR). For this case, we give a complete specification of all sample size modifications for which the two tests are equally powerful. We also study the overall power loss for some suggested SSR rules. Rules based on conditional power generally lead to ignorable power loss while a decision analytic approach exhibits clear discrepancies between the two tests. Copyright © 2010 John Wiley & Sons, Ltd.
Estimation of population attributable fraction (PAF) for disease occurrence in a cohort study design
Authors: Laaksonen M. A. , Härkänen T. , Knekt P. , Virtala E. , Oja H.
Published: March 2010

The population attributable fraction (PAF) is a useful measure for describing the expected change in an outcome if its risk factors are modified. Cohort studies allow researchers to assess the predictive value of the risk factor modification on the incidence of the outcome during a certain follow‐up. Estimation of PAF for both mortality and morbidity in cohort studies with censored survival data has been developed in the recent years. So far, however, censoring due to death in the estimation of PAF for morbidity has been ignored, resulting in estimation of a quantity which is not relevant in practice as some people are likely to die during the follow‐up. The risk factors related to the disease incidence may also be related to mortality, and modification of these risk factors is likely to delay the occurrence of both events. Thus, censoring due to death and the impact of risk factor modification must be considered when estimating PAF for disease incidence. We consider both and introduce two measures of disease burden: PAF for the incidence of disease during lifetime and PAF for the prevalence of disease in the population at a certain time. We demonstrate how consideration of censoring due to death changes the estimated PAF for disease incidence and its confidence interval. This underlines the importance of choosing a correct PAF measure depending on the outcome of interest and the risk factors of interest to obtain accurate and interpretable results. Copyright © 2010 John Wiley & Sons, Ltd.
Toxicity‐evaluation designs for phase I/II cancer immunotherapy trials
Authors: Messer Karen , Natarajan Loki , Ball Edward D. , Lane Thomas A.
Published: March 2010

Objectives: To facilitate more efficient Phase I/II cancer immunotherapy trials by incorporating statistically rigorous safety analysis.

Setting: The standard Phase I oncology trial is designed to find the maximum tolerated dose (MTD) in a setting where serious drug‐related toxicity is expected. However, many newer agents hope to show the efficacy without increasing the background rate of adverse events. Formal statistical designs in this setting are needed.

Results: The Phase I/II toxicity‐evaluation design is suitable when the therapeutic dose is expected to be well below the MTD. In Phase I, the design enrolls multiple cohorts at the target dose, possibly after an initial dose titration stage, and tests a formal safety hypothesis using a standard 3 + 3 enrollment scheme. Phase I serves as an interim safety analysis before proceeding to Phase II efficacy testing. We give an exact upper confidence limit on the toxicity rate at the therapeutic dose using the combined Phase I/II toxicity data, as well as the maximum likelihood estimate of the toxicity rate. We describe an example where the design has been used for a Phase I/II trial of immunotherapy in leukemia.

Conclusions: Phase I/II toxicity‐evaluation designs are simple to execute and may be suitable for some cancer immunotherapy trials. We show how to compute power, expected sample size, and expected number of dose‐limiting toxicities, as well as the maximum likelihood estimator and exact small sample confidence intervals for the toxicity rate at the therapeutic dose. More flexible designs are briefly discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Comparison of state occupation, entry, exit and waiting times in two or more groups based on current status data in a multistate model
Authors: Lan Ling , Datta Somnath
Published: March 2010

We propose mean absolute distance‐based nonparametric bootstrap tests comparing the occupation probabilities, entry, exit and waiting times in a given state in two or more groups in a multistate model. The state occupied is determined at a single inspection time for each individual. Nonparametric monotonic regression and smoothing are used to uniquely define the various marginal estimators for each group which are then compared via a mean absolute distance criterion. A detailed simulation study shows that the proposed tests all have close to nominal size and reasonable power. An illustrative application to a pubertal development data set obtained from the NHANES III (Analytic and Reporting Guidelines: The Third National Health and Nutrition Examination Survey (1988–94). Hyattsville, MD: National Center for Health Statistics, Centers for Disease Control and Prevention, 1997) is also presented. Copyright © 2010 John Wiley & Sons, Ltd.
Modelling multiple sources of dissemination bias in meta‐analysis
Authors: Bowden Jack , Jackson Dan , Thompson Simon G.
Published: March 2010

Asymmetry in the funnel plot for a meta‐analysis suggests the presence of dissemination bias. This may be caused by publication bias through the decisions of journal editors, by selective reporting of research results by authors or by a combination of both. Typically, study results that are statistically significant or have larger estimated effect sizes are more likely to appear in the published literature, hence giving a biased picture of the evidence‐base. Previous statistical approaches for addressing dissemination bias have assumed only a single selection mechanism. Here we consider a more realistic scenario in which multiple dissemination processes, involving both the publishing authors and journals, are operating. In practical applications, the methods can be used to provide sensitivity analyses for the potential effects of multiple dissemination biases operating in meta‐analysis. Copyright © 2010 John Wiley & Sons, Ltd.
A covariate‐adjustment regression model approach to noninferiority margin definition
Authors: Nie Lei , Soon Guoxing
Published: March 2010

To maintain the interpretability of the effect of experimental treatment (EXP) obtained from a noninferiority trial, current statistical approaches often require the constancy assumption. This assumption typically requires that the control treatment effect in the population of the active control trial is the same as its effect presented in the population of the historical trial. To prevent constancy assumption violation, clinical trial sponsors were recommended to make sure that the design of the active control trial is as close to the design of the historical trial as possible. However, these rigorous requirements are rarely fulfilled in practice. The inevitable discrepancies between the historical trial and the active control trial have led to debates on many controversial issues. Without support from a well‐developed quantitative method to determine the impact of the discrepancies on the constancy assumption violation, a correct judgment seems difficult. In this paper, we present a covariate‐adjustment generalized linear regression model approach to achieve two goals: (1) to quantify the impact of population difference between the historical trial and the active control trial on the degree of constancy assumption violation and (2) to redefine the active control treatment effect in the active control trial population if the quantification suggests an unacceptable violation. Through achieving goal (1), we examine whether or not a population difference leads to an unacceptable violation. Through achieving goal (2), we redefine the noninferiority margin if the violation is unacceptable. This approach allows us to correctly determine the effect of EXP in the noninferiority trial population when constancy assumption is violated due to the population difference. We illustrate the covariate‐adjustment approach through a case study. Copyright © 2010 John Wiley & Sons, Ltd.
Cognition and dorsolateral prefrontal cortex volume in corticosteroid‐treated patients given lamotrigine
Authors: Husain Saira , Kuzminski Samuel , Shad Mujeeb U. , Gabrielson Barry , Bret Mary E. , Osuji I. Julian , Brown E. Sherwood
Published: March 2010

In addition to changes in declarative memory and the hippocampus, corticosteroid excess is associated with prefrontal cortex changes. We previously reported that patients receiving exogenous corticosteroid therapy had impaired performance on prefrontal cortex‐related tasks, including working memory and executive functioning tasks. Glutamate release inhibitors attenuate corticosteroid‐effects on the hippocampus in both animal and human models. Twenty‐eight outpatients receiving chronic prednisone therapy for transplant rejection or other medical conditions were randomized to lamotrigine (a glutamate release inhibitor) or placebo for 24 weeks. Dorsolateral prefrontal cortex (DLPFC) volume was manually traced from MRI scans by trained staff members. Cognition was examined using the Stroop Color Word Test (SCWT), Delis‐Kaplan Executive Function System (D‐KEFS) and the Trail Making Test. Groups were compared using analysis of covariance. Consistent with prior findings in corticosteroid‐treated patients, baseline cognitive function was in the low normal range. At baseline, prednisone duration showed a trend towards negative correlation with SCWT and D‐KEFS inhibition switching time error scores, and DLPFC volume showed a trend towards a positive correlation with SCWT scores. No significant between‐group differences in outcomes were observed following lamotrigine therapy. Thus, this study found lamotrigine to not be associated with either positive or negative effects on cognition or DLPFC volume. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of minamata disease status and the perception of unfairness on ill health and inequalities in health amongst residents of Shiranui sea communities
Authors: Ushijima Kayo , Sung Woncheol , Kawakita Minoru , Tanaka Shiro , Mukai Yoshito , Tamura Kenji , Tanaka Mika , Maruyama Sadami
Published: March 2010

Minamata disease (MD) is a neurological disorder caused by eating seafood contaminated with methylmercury, first identified in 1956 in Japan. However, reports of ill health related to MD increased sharply following a ruling by the Supreme Court in 2004. We performed logistic regression analyses to examine the relationship between MD specific socioeconomic status (MD status) and health inequalities amongst residents of Shiranui sea communities. Data were collected by two‐stratified sampling of residents 40–79 years old in 172 postal code areas on the Shiranui sea coast. A questionnaire was distributed to eligible subjects (n = 2100) and collected at a later visit or by mail. Two self‐reported health outcomes were examined: MD‐related physical symptoms (MDRS) and the 12‐item General Health Questionnaire (GHQ‐12). We classified the 1546 respondents according to MD status: Early and Recent (received MD compensation before and after the Supreme Court decision, respectively) and Not Yet (yet to receive compensation). Adjusting for confounding factors, Early and Recent was significantly associated with elevated MDRS and GHQ‐12 compared with Not Yet. After further adjusting for perception of unfairness, the inequality between Early and Recent was reduced. Efforts to improve the population's health in these areas should consider health effects of MD status and perception of unfairness. Copyright ? 2010 John Wiley & Sons, Ltd.
Does subnational region matter? Foreign affiliate performance in the United states and China
Authors: Chan Christine M. , Makino Shige , Isobe Takehiko
Published: March 2010

This study examines the extent to which subnational regions can explain foreign affiliate performance in two host country settings, the United States and China, the world's two largest economies at polar ends of the economic spectrum (i.e., an advanced versus an emerging economy). Our results suggest that the subnational region is significant in explaining foreign affiliate performance, thus confirming its importance as an additional unit of analysis for firm performance. This study also shows that the effects of subnational region are far stronger in China than they are in the United States, thus suggesting that regional differences are more critical in their explanatory power for firm performance in emerging economies than they are in advanced economies. Copyright © 2010 John Wiley & Sons, Ltd.
High Intracellular Iron Oxide Nanoparticle Concentrations Affect Cellular Cytoskeleton and Focal Adhesion Kinase‐Mediated Signaling
Authors: Soenen Stefaan J. H. , Nuytten Nele , De Meyer Simon F. , De Smedt Stefaan C. , De Cuyper Marcel
Published: March 2010

Iron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported. The particles diminish cellular proliferation and affect the actin cytoskeleton and microtubule network architectures as well as focal adhesion formation and maturation. The extent of the effects correlates with the intracellular concentration (= iron mass) of the particles, with the biggest effects for Resovist and MLs at the highest concentration (1000 µg Fe mL−1). Similarly, the expression of focal adhesion kinase (FAK) and the amount of activated kinase (pY397‐FAK) are affected. The data suggest that high levels of perinuclear localized iron oxide nanoparticles diminish the efficiency of protein expression and sterically hinder the mature actin fibers, and could have detrimental effects on cell migration and differentiation.
Building an automated and self‐configurable emulation testbed for grid applications
Authors: Calheiros Rodrigo N. , Buyya Rajkumar , De Rose César A. F.
Published: March 2010

Distributed systems, such as grids, are composed of geographically distributed computing elements that belong to multiple administrative domains and are controlled by multiple entities. It is unlikely that testers are able to acquire repeatedly the same resources, for the same amount of time, and under the same network conditions, which are paramount requirements for enabling reproducible and controlled tests in software under development. An alternative to experiments in real testbeds is the use of emulation tools, which allow the software to run in an environment that behaves like a distributed system. Although advances in virtualization technology allowed the development of efficient emulators, few efforts were put in making operation of such emulators easier. This paper presents the design and the development of the Automated Emulation Framework that allows automatic mapping of virtual machines to hosts, virtual machine deployment, network configuration, and proactive management and reconfiguration of the virtual infrastructure. Copyright © 2010 John Wiley & Sons, Ltd.
Generalizable safety annotations for specification of failure patterns
Authors: Wolforth Ian , Walker Martin , Grunske Lars , Papadopoulos Yiannis
Published: March 2010

Components in programmable systems often exhibit patterns of failure that are independent of function or system context. In this paper, we show that it is possible to capture, and reuse where appropriate, such patterns for the purposes of system safety analysis. We describe a language that enables abstract specification of failure behaviour and define the syntax and semantics of this language. The language extends concepts originally defined in HiP‐HOPS, a technique that enables a largely automated form of compositional system safety analysis. The paper describes how this language can be used to describe component failure patterns and demonstrates how it can be applied using a simple fuel system example. The approach is evaluated on a set of retrospective industrial case studies, where data‐mining and reverse engineering techniques are applied in order to identify hidden patterns in legacy safety analyses. Results show clear potential for practical use of patterns in HiP‐HOPS. We argue that careful specification and reuse of failure patterns in conjunction with a tool that automates Fault Tree and Failure Modes and Effects Analysis can help to simplify complex safety assessments. Copyright © 2010 John Wiley & Sons, Ltd.
Erfahrungen zur Modellierung und Bewertung von Eisenbahnbrücken mit Resonanzrisiko
Authors: Marx Steffen , Geißler Karsten
Published: March 2010

Brücken im Bereich des Hochgeschwindigkeitsverkehrs sind teilweise aufgrund der hohen dynamischen Beanspruchungen mit möglicherweise auftretender Resonanz außerhalb unseres bisherigen Erfahrungsbereiches. Mit dieser Problematik ist bereits im Entwurfsstadium äußerst sensibel umzugehen. Es genügen manchmal nur kleine konstruktive Kniffe, um das dynamische Verhalten zu verbessern.

In folgendem Beitrag werden für diese Bauwerke insbesondere die Fragen der zutreffenden Modellierung der Einwirkungen und des Tragwerkes sowie die Bewertung der Berechnungsergebnisse beispielhaft anhand mehrerer Großbauvorhaben sowie anhand von Bestandsbauwerken angesprochen. Dabei werden nicht nur die Probleme der Tragfähigkeit sondern auch die der Ermüdungssicherheit diskutiert, da sowohl die Schwingbeiwerte als auch die Betriebslastfaktoren bei Resonanz nicht mehr zutreffend sind.

Experiences with modeling and evaluation of railway bridges with risk of resonance. So far no experiences could be accomplished with bridges in the field of high‐speed trains due to high stresses with possible appearances of resonance. This issue has to be treated very sensitive from the design stage on. Little tricks will help to improve the dynamic performance.

This contribution deals with the modeling of the impacts and the structure of the high speed train bridges as well as the evaluation of results of calculations. Problems of ultimate limit strength and fatigue strength are being discussed for some examples because dynamic factors as well as working load factors are no longer correct if resonance is occuring.
Umwickeln mit Butylkautschukbändern – ein innovativer Korrosionsschutz für vollverschlossene Brückenseile
Authors: Saul Reiner , Nützel Oswald
Published: March 2010

Die Oberfläche von neuen vollverschlossenen Brückenseilen und von Seilen im Bestand ist nach dem Regelwerk des BMVBW durch eine ca. 400 μm dicke Beschichtung gegen Korrosion zu schützen. Für die Vorbereitung der Seiloberfläche und die Applikation der Beschichtung im Streichverfahren müssen die Seile auf ganzer Länge mit Gerüsten oder Arbeitswagen zugänglich gemacht werden, was bei bestehenden Brücken zu erheblichen Verkehrsproblemen führen kann.

Die Anforderungen an die Vorbehandlung der Seiloberfläche können erheblich reduziert werden, wenn die Seile mit den vom Korrosionsschutz von Rohrleitungen her bekannten Butylkautschukbändern umwickelt werden. Diese Bänder können mit selbstfahrenden Wickelrobotern aufgebracht werden, womit die Verkehrsbeeinträchtigungen auf ein Minimum reduziert werden.

Es werden generelle Überlegungen zu diesem innovativen und kostengünstigen Korrosionsschutzsystem vorgestellt und über seine erfolgreiche Anwendung bei der Geh‐ und Radwegbrücke über den Rhein Kehl‐Straßburg und bei der Köhlbrandbrücke in Hamburg berichtet.

Wrapping with butylcaoutchouc tapes – an innovative corrosion protection for locked coil ropes of bridges. According to the codes of the German Ministry of Traffic, the surface of new locked coil ropes of bridges – and of existing ropes – has to be protected against corrosion by an about 400 μm thick layer of paint. For the preparation of the rope surface and for the application of the paint layers with a brush, access has to be granted over the entire length of the ropes by fixed or movable scaffoldings. In existing bridges, this may lead to considerable traffic jams.

The requirements for the pretreatment of rope surface may be considerably reduced, if the ropes are wrapped with tapes of butylcaoutchouc which are well‐known from the corrosion protection of pipelines. These tapes can be applied by automotive wrapping robots, so that the impact on the traffic may be reduced to a minimum.

General considerations on this innovative and economic corrosion protection are presented, and its successful application for the pedestrian and bicycle bridge across the Rhine Kehl‐Straßbourg and the road bridge across the Köhlbrand in Hamburg is described.
Der Neubau des Emil‐Schumacher‐Museums in Hagen
Authors: Sobek Werner , Hinz Holger
Published: March 2010

Im Jahre 1999 beschloss die Stadt Hagen, dem Künstler Emil Schumacher – einem Sohn der Stadt – ein eigenes Museum zu bauen. Hierzu wurde ein internationaler Wettbewerb ausgeschrieben, aus dem das Architekturbüro Lindemann Architekten aus Mannheim im Jahre 2000 als Sieger hervorging. Der Entwurf der Architekten sah eine Glashülle mit maximaler Transparenz vor, die den eigentlichen Museumskörper umschloss. Um den Entwurfsgedanken optimal umzusetzen, kam eine von Werner Sobek entwickelte Seilfassade mit ausschließlich vertikal gespannten Seilen zur Ausführung (Bild 1). Nach einer längeren Projektpause konnte das Museum schließlich im August 2009 eingeweiht werden.

The new building of the Emil‐Schumacher‐Museum in Hagen, Germany. In 1999 the City of Hagen decided to build a museum for the painter Emil Schumacher, a son of the city. Lindemann Architects from Mannheim/Germany won the international competition announced on that occasion. The design of the architects envisaged a glass skin offering a maximum of transparency that was to envelop the museum building proper. In order to realise this design, Werner Sobek developed a cablestayed façade with vertical cables only (figure 1). After a prolonged project pause the museum could finally be inaugurated in August 2009.
Fassade der Sparkasse Heinsberg – eine Freiformfläche mit Seilen und punktgehaltenen Gläsern
Authors: Tückmantel Peter
Published: March 2010

Die Realisation von komplexen Geometrien ist eine in der zeitgenössischen Architektur häufig anzutreffende Bauaufgabe. Dieser Aufsatz erläutert eine bisher kaum angewandte Technik, das Erstellen von doppelt‐gekrümmten Flächen mittels eines Seiltragwerkes.

Free‐form cables façades with pointfixed insulating glass unites. In modern architecture the realisation of complex geometrie is one of the most interesting fields. This paper describes an up to now not often used new technique, the construction of double curved envelopes by using a cable‐net structure.