bluuebunny/crossref_metadata_2025 huggingface dataset:
A new prostate cancer therapeutic approach: Combination of androgen ablation with COX‐2 inhibitor
Authors: Cai Yi , Lee Yi‐Fen , Li Gonghui , Liu Su , Bao Bo‐Ying , Huang Jiaoti , Hsu Cheng‐Lung , Chang Chawnshang
Published: April 2008

Prostate cancer is initially responsive to hormonal therapy, but cancers inevitably progress in an androgen‐independent fashion with virtually all tumors evolving into more aggressive androgen refractory disease. Immunohistological comparisons of cyclooxygenase 2 (COX‐2) expressions in 3 pairs of prostate cancer patients before and after the combined androgen blockade (CAB) therapy show elevated COX‐2 expressions. This observation from clinical specimens is further supported by in vitro laboratory data using human prostate cancer cells in which the antiandrogen hydroxyflutamide (HF) induced COX‐2 expression, and androgen suppressed COX‐2 expression. By applying knockdown and overexpression strategies to modulate AR expression in prostate cancer cells, we confirmed that androgen/AR signal suppressed, and HF induced COX‐2 expression at both protein and mRNA levels. COX‐2 promoter reporter assay indicated that the suppression of COX‐2 by androgen/AR is at the transcriptional level via modulation of NF‐κB signals. Treatment of LNCaP and LAPC4 cells with 1 μM HF in the presence of 1 nM DHT, which mimics the CAB therapy condition, promotes cell growth, and this growth induction can be suppressed via adding the COX‐2 specific inhibitor, NS398. This suggests that HF promoted prostate cancer cell growth is COX‐2 dependent and this HF‐COX‐2 activation pathway can account for one reason of CAB therapy failure. Together, these findings provide a possible explanation how CAB with antiandrogen HF therapy might fail and provide a potential new therapeutic approach to battle prostate cancer via combination of CAB therapy with COX‐2 inhibitor(s). © 2008 Wiley‐Liss, Inc.
In vivo preclinical efficacy of a PDLLA/PGA porous copolymer for dental application
Authors: Tschon Matilde , Fini Milena , Giavaresi Gianluca , Rimondini Lia , Ambrosio Luigi , Giardino Roberto
Published: April 2008

This study aimed to analyze surface morphology and physical–chemical properties of a copolymer of polylactic/polyglycolic acid (Fisiograft, Ghimas SpA, Casalecchio di Reno, Italy) by scanning electron microscopy (SEM), porosimetry, and rheological analysis. Then the material was implanted in vivo to test its efficacy at promoting bone healing and new bone formation in postextraction sockets. Under general anaesthesia, sockets were created in 12 minipigs and then randomly filled with the porous copolymer in SPONGE or GEL form and compared with commercial BioOss (Geistlich Biomaterials) and Biocoral (Inoteb, France). At 15, 30, and 60 days from surgery, the newly formed trabecular bone quality was evaluated by means of histology and histomorphometry. The SEM and rheological analyses performed on GEL showed a surface microporosity and a rheological shear thinning behavior, whereas the SPONGE porosimetric measurements revealed larger pores. At 15 days, the new bone regrowth was observed in all treated sockets but appeared immature, as the trabeculae were very dense and thin. At 30 days, GEL and SPONGE were degraded, and the sockets were filled with bone that, in terms of bone volume fraction, trabecular number, and separation, was not statistically different from normal bone. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Prestresses in bilayered all‐ceramic restorations
Authors: Aboushelib Moustafa N. , Feilzer Albert J. , de Jager Niek , Kleverlaan Cornelis J.
Published: April 2008

Introduction: A general trend in all ceramic systems is to use veneering ceramics of slightly lower thermal expansion coefficients compared with that of the framework resulting in a positive mismatch in thermal expansion coefficient (+ΔTEC). The concept behind this TEC mismatch is to generate compressive stresses in the weaker veneering ceramic and thus enhance the overall strength of the restoration. This technique had excellent results with porcelain fused to metal restorations (PFM). However, there are concerns to apply this concept to all‐ceramic restorations. The aim of this research was to determine the stresses in bilayered all‐ceramic restorations due to the mismatch in TEC. Materials and methods: Two commercial veneering ceramics with a TEC lower than that of zirconia (+ΔTEC); NobelRondo zirconia™ and Lava Ceram™, plus one experimental veneering ceramic with an identical TEC that matches that of zirconia (ΔTEC = 0) were used to veneer zirconia discs. The specimens were loaded in biaxial flexure test setup with the veneer ceramic in tension. The stresses due to load application and TEC mismatch were calculated using fractography, engineering mathematics, and finite element analysis (FEA). Results: In this study, the highest load at failure (64 N) was obtained with the experimental veneer where the thermal mismatch between zirconia and veneering ceramic was minimal. For the two commercial veneer ceramics the magnitude of the thermal mismatch localized at the zirconia veneer interface (42 MPa) exceeded the bond strength between the two materials and resulted in delamination failure during testing (ca. 50 MPa). Significance: For all‐ceramic zirconia veneered restorations it is recommended to minimize the thermal mismatch as much as possible. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
The ethics of advertising, billing, and finances in psychotherapy
Authors: Knapp Samuel , VandeCreek Leon
Published: April 2008

Psychotherapists must deal with practical business matters such as advertising, billing, collecting fees, and other practice management topics. We review the enforceable standards of the American Psychological Association's (2002) Ethics Code that deal with advertising, fees, billing, and related business matters in psychotherapy. Using a principle‐based perspective, we link each of the standards to overarching ethical values and illustrate the concerns with case vignettes. We argue that understanding the moral foundations of ethical standards helps psychotherapists to implement with greater integrity the spirit and the letter of the standards with regard to advertising and business practices. © 2008 Wiley Periodicals, Inc. J Clin Psychol: In Session 64: 1–13, 2008.
Selective gene transfer into neurons via Na,K‐ATPase β1. Targeting gene transfer with monoclonal antibody and adenovirus vector
Authors: Ishii Keiji , Nakamura Kiminori , Kawaguchi Satoshi , Li Rong , Hirai Sachie , Sakuragi Naoya , Wada Takuro , Kato Kazunori , Yamashita Toshihiko , Hamada Hirofumi
Published: March 2008

Background

Neuron‐selective gene transfer is an attractive therapeutic strategy for neurological disorders. However, optimal targets and gene delivery systems remain to be determined.

Methods

Following immunization of mice with PC12 cells, hybridomas were screened by β‐Gal reporter gene assay using FZ33 fiber‐modified adenovirus vectors. Subsequently, the efficacy and specificity of monoclonal antibody (mAb)‐mediated gene transfer via FZ33 and FdZ adenovirus vectors were evaluated by flow cytometry, chemiluminescent β‐Gal reporter gene assay, and immunocytochemistry. Finally, the antigen recognized by the mAb was identified by mass spectrometry and transfection analysis.

Results

A hybridoma clone 6E3 producing monoclonal antibody, mAb6E3, was screened. Flow cytometry, chemiluminescent β‐Gal reporter gene assay, and immunocytochemistry with mAb6E3 and the fiber mutant adenovirus demonstrated efficient gene transfer into the PC12 cells. Treatment of neuron–glia cocultures with mAb6E3 and FdZ adenovirus resulted in neuron‐selective gene transfer. Immunohistochemical images of rat spinal cord tissue showed that mAb6E3 reacts specifically with neurons. Finally, Na,K‐ATPase β1 was identified as the antigen of mAb6E3.

Conclusions

Hybridoma screening using FZ33 fiber‐modified adenovirus vectors serves as an efficient approach to detect antigens in mAb‐targeted gene transfer. Neuronal tropism in the central nervous system through mAb6E3 represents an important initial step towards neuron‐selective gene transfer in the treatment of local neurological disorders, such as spinal cord injury. Copyright © 2008 John Wiley & Sons, Ltd.
Syntheses of (R,S)‐naproxen and its 6‐O‐desmethylated metabolite labelled with 2H
Authors: Fontana E. , Venegoni S.
Published: March 2008

Naproxen, a well‐known non‐steroidal anti‐inflammatory drug, and its 6‐O‐desmethylated metabolite have been labelled with 2H. (R,S)‐Naproxen 7 labelled with 2H was obtained in five steps using the commercially available [2H3]iodomethane 5 as the stable labelled reagent. The demethylation of 7 using 48% HBr in 1‐butyl‐3‐methylimidazolium tetrafluoborate gave the corresponding 2H‐labelled 6‐O‐desmethylated metabolite 8. Copyright © 2008 John Wiley & Sons, Ltd.
Pacific and Indian Ocean climate signals in a tree‐ring record of Java monsoon drought
Authors: D'Arrigo Rosanne , Allan Rob , Wilson Rob , Palmer Jonathan , Sakulich John , Smerdon Jason E. , Bijaksana Satria , Ngkoimani La Ode
Published: March 2008

Extreme climate conditions have dramatic socio‐economic impacts on human populations across the tropics. In Indonesia, severe drought and floods have been associated with El Niño‐Southern Oscillation (ENSO) events that originate in the tropical Indo‐Pacific region. Recently, an Indian Ocean dipole mode (IOD) in sea surface temperature (SST) has been proposed as another potential cause of drought and flood extremes in western Indonesia and elsewhere around the Indian Ocean rim. The nature of such variability and its degree of independence from the ENSO system are topics of recent debate, but understanding is hampered by the scarcity of long instrumental records for the tropics. Here, we describe a tree‐ring reconstruction of the Palmer Drought Severity Index (PDSI) for Java, Indonesia, that preserves a history of ENSO and IOD‐related extremes over the past 217 years. Extreme Javan droughts correspond well to known ENSO and IOD events in recent decades, and most extreme droughts before this recent period can be explained by known ENSO episodes. Coral proxies from regions near or within the two poles of the IOD show good agreement with Javan PDSI extremes over the past ∼150 years. The El Niño of 1877, in conjunction with a positive IOD, was one of the most intense and widespread episodes of the past two centuries, based on instrumental and proxy data from across the tropical Indo‐Pacific and Asian monsoon regions. Although Java droughts typically show the expected association with El Niño‐like conditions and failed Indian monsoons, others (mainly linked to positive IOD conditions) co‐occur with a strengthened Indian monsoon, suggesting linkages between the Indian monsoon, Indonesian drought and Indian Ocean climatic variability. The close associations between the Java PDSI, ENSO and Indian Ocean climate are consistent with the hypothesis that interannual ENSO to decadal ENSO‐like modes interact to generate dipole‐like Indian Ocean variability. Copyright © 2008 Royal Meteorological Society
Polymerization of 2‐(hydroxyethyl)methacrylate by two different initiator/accelerator systems: a Raman spectroscopic monitoring
Authors: Mabilleau G. , Cincu C. , Baslé M. F. , Chappard D.
Published: March 2008

The control of monomer polymerization is important when preparing biocompatible devices. The compound 2‐(hydroxyethyl)methacrylate can be polymerized by redox systems using benzoyl peroxide (BPO) (as accelerator) and a substituted amine (as initiator). However, this system is associated with a highly exothermic polymerization, and end‐products with inflammatory properties are produced. We have used ascorbic acid (AA) to induce BPO fragmentation and have compared the kinetics of the reaction, by Raman microscopy, with that obtained with a substituted amine. The breaking of the C bond (Raman stretching vibration at 1641 cm−1) could be monitored in both cases and reflected the incorporation of new monomer molecules into the chain. The AA‐induced polymerization was slower than with the substituted amine and was accompanied by the appearance of a new band at 1603 cm−1, assigned to the stretching vibrations of COOH species incorporated into the chains. Raman microscopy appears to be a powerful tool in the study of polymeric biomaterial preparation. Copyright © 2008 John Wiley & Sons, Ltd.
Nutritional evaluation of Araucaria angustifolia seed flour as a protein complement for growing rats
Authors: Leite Danielle MC , de Jong Erna V , Noreña Caciano PZ , Brandelli Adriano
Published: March 2008

BACKGROUND: The seeds of Araucaria angustifolia, namely pinhão, are consumed in south and southeast Brazil as flour or baked. There is relatively little information about the chemical composition and nutritional value of the seed and its flour.

RESULTS: Pinhão flour was obtained by drying at constant temperature of 50 °C (PF50) or 80 °C (PF80) in a circulating air drier for 16 h, and evaluated as a feed additive for growing rats. Wistar rats were fed five experimental diets (n = 6 rats per diet) containing different protein sources: casein (diet CAS), casein supplemented with 20% (w/w) flour PF50 or PF80 (diets PF50 and PF80), casein supplemented with 20% pinhão without heat treatment (diet NPF), and a non‐protein group (diet APROT). Values for weight gain, feed ingest, protein efficiency ratio (PER) and net protein ratio (NPR) were similar for diets CAS and PF80. Lowest values for all nutritional parameters were observed for diets complemented with pinhão flour. Trypsin inhibitor activity was detected in PF50 but not in PF80.

CONCLUSION: Pinhão flour heated at 80 °C for 16 h and used as supplementary in diet had the most similar results in all nutritional parameters to casein‐based diets, and can be used as a complementary source, substituting up to 20% of a high biological value protein in food formulations. Copyright © 2008 Society of Chemical Industry
Macromol. Rapid Commun. 7/2008
Authors: Kim Min Sup , Shin Kwang Min , Kim Sun I. , Spinks Geoffrey M. , Kim Seon Jeong
Published: March 2008

Cover: Uniform and continuous polyelectrolyte tubular nanostructures containing linear features of ferritin nanoparticles were directly fabricated using coaxial electrospinning of two immiscible solutions. The TEM images on the cover page indicate the different diameters of the ferritin one dimensional arrays and polymer tubular nanostructures formed by adjusting the concentration of the polymer solution. A schematic illustration is given below each TEM image. Further details can be found in the article by M. S. Kim, K. M. Shin, S. I. Kim, G. M. Spinks, and S. J. Kim* on page 552.
Frequency‐swept HMQC sequences for high‐throughput NMR analysis
Authors: Spitzer Timothy D. , Rutkowske Randy D. , Dorsey George F.
Published: April 2008

We describe here new versions of the DEPT phase‐encoded HMQC experiment that offer robust performance and improved sensitivity. The new sequences rely on frequency‐swept proton and carbon pulses to minimize signal losses from miscalibrated pulses while providing ‘J compensation’ to optimize the signal strength over a range of heteronuclear coupling constants. By including both proton and carbon‐swept pulses, the new sequences also offer an additional signal gain of roughly 10% over well‐calibrated hard‐pulse experiments. The new sequences also demonstrate that one can construct a sequence that incorporates both 90° and 180° frequency‐swept pulses. Although individual pulses in the sequence cause severe phase roll, the phase roll can be eliminated by the proper choice of pulse lengths and sweep directions. Copyright © 2008 John Wiley & Sons, Ltd.
Frequency‐swept HSQC sequences for high‐throughput NMR analysis
Authors: Spitzer Timothy D. , Rutkowske Randy D. , Dorsey George F.
Published: April 2008

This article describes new versions of the DEPT phase‐edited heteronuclear single quantum correlation (HSQC) pulse sequence with sensitivity enhancement. The sequences incorporate frequency‐swept carbon and proton pulses. The new experiments are inherently robust, well‐suited for a high‐throughput setting in which sample‐to‐sample variations may be ignored. The observed signal has the obvious benefit of sensitivity enhancement resulting from the preservation of two magnetization transfer pathways. The two pathways are maintained even in the version of the sequence in which all pulses are frequency‐swept. There is an additional signal gain of roughly 10% that derives from the use of both proton and carbon frequency‐swept pulses. Furthermore, the sequences use J compensation to provide optimal signal over a range of heteronuclear coupling constants. We demonstrate that the new sequences offer good sensitivity and perform well even when the NMR probe is deliberately mistuned. Copyright © 2008 John Wiley & Sons, Ltd.
13C and 15N NMR chemical shifts of 1‐(2′,4′‐dinitrophenyl) and 1‐(2′,4′,6′‐trinitrophenyl) pyrazoles in the solid state and in solution
Authors: Ángeles García M. , Claramunt Rosa M. , Elguero José
Published: March 2008

The 13C and 15N CPMAS NMR spectra of 18 pyrazoles substituted at position 1 by dinitrophenyl and trinitrophenyl (picryl) groups have been recorded. To help in the assignments, some of these compounds were studied in DMSO‐d6 solution. Phenomena such as the conformation of the N‐aryl groups and broadening of splittings due to quadrupolar nuclei are discussed. Copyright © 2008 John Wiley & Sons, Ltd.
Recent Advances in the Study of High‐Temperature Free Radical Acrylic Solution Copolymerization
Authors: Wang Wei , Hutchinson Robin A.
Published: April 2008

Semibatch starved‐feed solution copolymerization is used to produce acrylic resins for coatings formulations. Mechanisms and rate coefficients for polymerization of methacrylates, acrylates, and styrene (ST) under these high‐temperature conditions are reviewed. An extended set of experimental results at 138 °C is used to refine a model describing the solution copolymerization of ST and methacrylates. The data suggest that both changing initiator efficiency and transfer reactions of oxygen‐centered radicals to polymer affect the development of polymer molecular weight. A penultimate model is used to describe the variation in termination rate coefficient with copolymer composition. Significant progress has been made to develop an extended model capable of representing multicomponent high‐temperature acrylic polymerizations.

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What you should know about location modeling
Authors: Daskin Mark S.
Published: March 2008

Facility location models have been applied to problems in the public and private sectors for years. In this article, the author first presents a taxonomy of location problems based on the underlying space in which the problem is embedded. The article illustrates problems from each part of the taxonomy with an emphasis on discrete location problems. Selected recent research in the area is also discussed. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Analysis and optimal design of discrete order picking technologies along a line
Authors: Eisenstein Donald D.
Published: March 2008

Order picking accounts for most of the operating expense of a typical distribution center, and thus is often considered the most critical function of a supply chain. In discrete order picking a single worker walks to pick all the items necessary to fulfill a single customer order. Discrete order picking is common not only because of its simplicity and reliability, but also because of its ability to pick orders quickly upon receipt, and thus is commonly used by e‐commerce operations. There are two primary ways to reduce the cost (walking distance required) of the order picking system. First is through the use of technology—conveyor systems and/or the ability to transmit order information to pickers via mobile units. Second is through the design—where best to locate depots (where workers receive pick lists and deposit completed orders) and how best to lay out the product. We build a stochastic model to compare three configurations of different technology requirements: single‐depot, dual‐depot, and no‐depot. For each configuration we explore the optimal design. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Experimental comparison of four FAIR arterial spin labeling techniques for quantification of mouse cerebral blood flow at 4.7 T
Authors: Kober Frank , Duhamel Guillaume , Cozzone Patrick J.
Published: April 2008

Pulsed arterial spin labeling (ASL) is an attractive and robust method for quantification of rodent cerebral blood flow (CBF) in particular, although there is a need for sensitivity optimization. Look–Locker flow‐sensitive alternating inversion recovery (FAIR) echo planar imaging (EPI) (LLFAIREPI) was expected to be a likely candidate for assessing sensitivity, although it has not yet been applied to rodents. In this study, the performance of two FAIR techniques and two Look–Locker FAIR techniques were compared in mouse brain at 4.7 T. FAIR‐EPI (single inversion time, FAIREPI‐1TI), FAIR‐EPI (eight inversion times, FAIREPI‐8TI), LLFAIREPI and Look–Locker FAIR gradient echo (LLFAIRGE) sequences were implemented with equal spatial resolution and equal FAIR preparation modules. Measurements were carried out sequentially on the brain in 10 healthy mice, and quantitative CBF maps were obtained after different acquisition times up to 23 min. All methods gave similar group variability in CBF. Especially at shorter acquisition times, LLFAIREPI gave lower relative variations in CBF within selected brain regions than the other techniques at the same acquisition time. The Look–Locker techniques, however, overestimated CBF compared with classical FAIR‐EPI, which was attributed to bulk flow in arterioles and T2 effects. The image quality with LLFAIREPI was less reproducible within the group. Both FAIREPI‐1TI and LLFAIREPI appear to be good candidates for serial rapid measurement of CBF, but LLFAIREPI has the additional advantage that apparent T1 can be measured simultaneously with CBF. Copyright © 2008 John Wiley & Sons, Ltd.
Wave computations in irregular layered media using a semidiscrete finite element perturbation method
Authors: Ikeda I. , Tassoulas J. L.
Published: March 2008

A technique that takes into account nonparallel interfaces and lateral inhomogeneities as perturbations with respect to a reference, horizontally layered, laterally homogeneous medium and produces approximations of the perturbed wave motion with little additional computation effort is described. The formulation combines a perturbation method with a semidiscrete finite element technique, providing an approximate treatment of wave propagation in irregular layered media. Consistent transmitting boundaries and other semidiscrete hyperelements as well as Green's functions, already available for regular layered media, can be reformulated within the framework of the method. The method is relevant in problems of foundation dynamics, ground response to seismic waves and site characterization. Example problems are presented toward evaluation of the effectiveness of the method. Copyright © 2008 John Wiley & Sons, Ltd.
Serological proteome analysis to identify systemic candidiasis patients in the intensive care unit: Analytical, diagnostic and prognostic validation of anti‐Candida enolase antibodies on quantitative clinical platforms
Authors: Pitarch Aida , Jiménez Antonio , Nombela César , Gil Concha
Published: April 2008

Systemic candidiasis (SC) is associated with high morbidity and mortality, because it generally affects patients with severe underlying diseases and its diagnosis is difficult and often delayed, resulting in delayed therapy. We used serological proteome analysis to screen serum anti‐Candida IgG antibody‐reactivity profiles in 24 patients under intensive care, 12 of which had confirmed SC (fungal cultures), and in 12 healthy subjects. A total of 15 immunogenic proteins from Candida albicans protoplast lysates were differentially immunorecognized by serum IgG antibodies from SC patients compared to controls. Two‐way hierarchical clustering and principal‐component analyses of these antibody‐reactivity patterns accurately differentiated SC patients from controls. Anti‐Eno1p IgG antibodies were found to be present at high abundance in SC patients and be an important molecular fingerprint in serum for SC diagnosis. Differential anti‐Eno1p IgG antibody reactivity was further validated by a tag capture ELISA and a Western blot assay in 45 SC patients and 118 non‐SC subjects. Both quantitative assays provided comparable analytical, diagnostic and prognostic performances, and verified initial proteomic‐profiling results. If confirmed in prospective cohort studies, these anti‐Eno1p IgG antibodies might be useful for SC diagnosis. However, these, at least as measured by these clinical platforms, appear to have limited prognostic value in SC patients.
Characterization of the Plasticized GAP/PEG and GAP/PCL Block Copolyurethane Binder Matrices and its Propellants
Authors: Sun Min Byoung
Published: March 2008

Though glycidyl azide polymer (GAP) is a well‐known and promising energetic polymer, propellants based on it suffer from poor mechanical and low‐temperature properties. To overcome these problems, plasticized GAP‐based copolymeric binders were prepared and investigated through the incorporation of flexible‐structural polyethylene glycol (PEG) and polycaprolactone (PCL) into a binder recipe under a Desmodur N‐100 polyisocyanate (N‐100)/isophorone diisocyanate (IPDI) (2 : 1, wt. ratio) mixed curative system. The nitrate esters (NEs) or GAP oligomer were used as energetic plasticizers at various ratios to the polymers. The GAP/PCL binders held the plasticizers much more than the GAP/PEG binders did. The glass transition temperatures (Tg) of segmented copolymeric binders were more dependent on the plasticizer level than the PEG or PCL content. The increase in the plasticizer content decreased the mechanical strength and modulus of binders, while the change of strain was modest. Finally, the NE plasticized GAP‐based solid propellants showed enhanced mechanical and thermal properties by the incorporation of PEG or PCL. The properties of GAP/PCL propellants were superior to those of GAP/PEG propellants.
Neurotoxic implications of the agonistic action of CS‐syndrome pyrethroids on the N‐type Cav2.2 calcium channel
Authors: Clark J Marshall , Symington Steven B
Published: March 2008

BACKGROUND: Cismethrin (T‐syndrome) and deltamethrin (CS‐syndrome) pyrethroids have been previously shown to increase membrane depolarization and calcium influx, but only deltamethrin increased Ca2+‐dependent neurotransmitter release from rat brain synaptosomes. Deltamethrin's action was blocked by ω‐conotoxin GVIA, delineating a separate action at N‐type Cav2.2 channels that is consistent with the in vivo release of neurotransmitter. It is hypothesized that other CS‐syndrome pyrethroids will elicit similar actions at presynaptic nerve terminals.

RESULTS: Nine additional pyrethroids were similarly examined, and these data were used in a cluster analysis. CS‐syndrome pyrethroids that possessed α‐cyano groups, cypermethrin, deltamethrin and esfenvalerate, all caused Ca2+ influx and neurotransmitter release and clustered with two other α‐cyano pyrethroids, cyfluthrin and cyhalothrin, that shared these same actions. T‐syndrome pyrethroids, bioallethrin, cismethrin and fenpropathrin, did not share these actions and clustered with two non‐α‐cyano pyrethroids, tefluthin and bifenthrin, which likewise did not elicit these actions. Deltamethrin reduced peak current of heterologously expressed wild‐type Cav2.2, increased peak current of T422E Cav2.2 and was 20‐fold more potent on T422E Cav2.2 than on wild‐type channels, indicating that the permanently phosphorylated form of Cav2.2 is the preferred target.

CONCLUSIONS: Cav2.2 is directly modified by deltamethrin, but the resulting perturbation is dependent upon its phosphorylation state. The present findings may provide a partial explanation for the different toxic syndromes produced by these structurally distinct pyrethroids. Copyright © 2008 Society of Chemical Industry
Resistance of codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), larvae in Michigan to insecticides with different modes of action and the impact on field residual activity
Authors: Mota‐Sanchez David , Wise John C , Poppen Ryan Vander , Gut Larry J , Hollingworth Robert M
Published: March 2008

BACKGROUND: The codling moth is one of the principal pests of apple in the world. Resistance monitoring is crucial to the effective management of resistance in codling moth. Three populations of codling moth in neonate larvae were evaluated for resistance to seven insecticides via diet bioassays, and compared with a susceptible population. In addition, apple plots were treated with labeled field rate doses of four insecticides. Treated fruit were exposed to neonate larvae of two populations from commercial orchards.

RESULTS: Two populations of codling moth expressed two‐ and fivefold resistance to azinphos‐methyl, seven‐ and eightfold resistance to phosmet, six‐ and tenfold resistance to lambda‐cyhalothrin, 14‐ and 16‐fold resistance to methoxyfenozide and sixfold resistance to indoxacarb, but no resistance to acetamiprid and spinosad. The impact of the resistance to azinphos‐methyl, measured as fruit damage, increased as the insecticide residues aged in the field. In contrast, fruit damage in methoxyfenozide‐ and lambda‐cyhalothrin‐treated fruit was observed earlier for resistant codling moth. No differences in efficacy were found for acetamiprid.

CONCLUSIONS: Broad‐spectrum insecticide resistance was detected for codling moth. Resistance to azinphos‐methyl, lambda‐cyhalothrin and methoxyfenozide was associated with reduced residual activity in the field. Broad‐spectrum resistance presents serious problems for management of the codling moth in Michigan. Copyright © 2008 Society of Chemical Industry
HSC on NICE: ‘doing a vital job in difficult circumstances’
Authors: Chaplin Steve
Published: April 2008

Steve Chaplin reviews the recent Health Committee report on the National Institute for Health and Clinical Excellence that was commissioned in response to strong criticism directed at the Institute from patients, clinicians and the pharmaceutical industry. Copyright © 2008 Wiley Interface Ltd
Peptides and pseudopeptides incorporating D‐Phe–Pro–Arg and Arg–Gly–Asp lead sequences as potential antithrombotic agents
Authors: Ilaš Janez , Hudecz Ferenc , Süli‐Vargha Helga , Kikelj Danijel
Published: March 2008

Peptide leads D‐Phe–Pro–Arg for thrombin inhibition and Arg–Gly–Asp for antagonistic activity on fibrinogen receptor were combined in one molecule in order to produce compounds capable of acting both as thrombin inhibitors and as fibrinogen receptor antagonists. Peptide conjugate 7 possessing both leads joined by a tetraglycine linker as well as tripeptides and peptidomimetics with highly overlapped D‐Phe–Pro–Arg and Arg–Gly–Asp pharmacophore groups were prepared. Conjugate 7 was found to possess antagonistic activity on fibrinogen receptor, but was unexpectedly inactive as thrombin inhibitor. Compound 9 comprising of highly integrated D‐Phe–Pro–Arg and Arg–Gly–Asp pharmacophore groups was found to possess a moderate but well balanced thrombin inhibitory and fibrinogen receptor antagonistic activity. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Bioactive peptides derived from the Limulus anti‐lipopolysaccharide factor: structure‐activity relationships and formation of mixed peptide/lipid complexes
Authors: Mora Puig , De La Paz Manuela López , Pérez‐Payá Enrique
Published: March 2008

The design of peptides that would interact and neutralise bacterial endotoxins or LPS could have benefited from the analysis of comparative structure–activity relationships among close‐related analogues. Here, we present a comparative structural characterisation of selected peptides derived from the LALF obtained by single‐amino‐acid replacement, which differ in biological activity. The peptides were characterised in solution using nuclear magnetic resonance, circular dichroism and fluorescence spectroscopies. Membrane mimetic peptide interactions were studied using fluorescence resonance energy transfer with the aid of extrinsic fluorescent probes that allowed the identification of mixed peptide/lipid complexes. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Peptide fragment of the m3 muscarinic acetylcholine receptor activates Gq but not Gi2
Authors: Kubota Makoto , Wakamatsu Kaori
Published: March 2008

Gq, a heterotrimeric guanine nucleotide‐binding protein, plays important roles such as the regulation of calcium mobilization and cell proliferation. This protein is considered as a promising drug target for the treatment of cardiac hypertrophy. Selective activation of Gq would be quite useful for analyzing the role of Gq in signaling pathways. We synthesized m3i3c—a peptide with 16 amino acid residues that corresponds to the junction between the C‐terminus of the third intracellular loop and the sixth transmembrane helix (TM‐VI) of human m3 muscarinic acetylcholine receptor, which couples to Gq but not Gi2. At micromolar concentrations, this peptide was found to activate Gq but not Gi2. This peptide is the first small compound that selectively activates Gq but not Gi2. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.
Herbal and food folk medicines of the Russlanddeutschen living in Künzelsau/Taläcker, South‐Western Germany
Authors: Pieroni Andrea , Gray Charlotte
Published: April 2008

An urban ethnobotanical study was carried out among a community of Russlanddeutschen (Germans from Russia) who in recent years have moved from Russia and Central Asia to Künzelsau, a small town located in Württemberg, in South‐Western Germany. Thirty‐six in‐depth interviews were conducted with the women in this community, and 62 homemade medicinal preparations derived from 46 botanical species were recorded. As well as common medicinal plant uses that are well known in modern evidence‐based German and Western European phytotherapy, we were able to record traces of the community's Russian and Central Asian (Turkic) heritage through the very popular use of sorrel as a depurative or for preventing and treating colds and flu; the use of dill as a digestive; watermelon as a diuretic; birch to relieve rheumatism and arthritis; buckwheat as a tonic; rye‐based fermented beverages as a stimulant and as a depurative, diverse berries to prevent colds and flu; coriander as a digestive, and other medicinal foods. Traces of archaic German preparations were also recorded, which were probably Swabian in origin. Nearly half of the overall quoted items represented folk functional foods. The researchers believe that the findings in this study could stimulate public health policies aimed at improving both the phyto‐pharmacovigilance of lesser‐known herbal drugs, and the health and well‐being of migrants by promoting a better understanding of emic health beliefs and newcomers' healing strategies. Copyright © 2008 John Wiley & Sons, Ltd.
Aqueous extract of rhubarb stabilizes vulnerable atherosclerotic plaques due to depression of inflammation and lipid accumulation
Authors: Liu Yunfang , Yan Fangfang , Liu Yan , Zhang Cheng , Yu Huiming , Zhang Yun , Zhao Yuxia
Published: April 2008

The study evaluated the effect of the traditional Chinese medicine rhubarb on the stability of atherosclerotic plaque. Atherosclerotic lesions were induced in rabbits through balloon injury with a high‐cholesterol diet and then were divided into a control group, a rhubarb group and a simvastatin group. At week 24 recombinant‐p53 adenoviruses were locally delivered to the atherosclerotic plaques. At week 26 plaque rupture was triggered by the intra‐arterial Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathologic, immunohistochemical and gene expression studies were performed. The results showed that the incidence of plaque rupture in the rhubarb group and the simvastatin group was significantly lower than that in the control group (42.86% and 35.71% versus 80.00%, both p < 0.05). Serum TC, LDL‐C (p < 0.05–0.01), IMT (both p < 0.01), PA (both p < 0.01), PB (%) (both p < 0.01) and the mRNA and protein expressions of TLR2, TLR4 and NF‐κB (p < 0.05, 0.01, respectively) in the rhubarb group and the simvastatin group were significantly lower than those in the control group. In contrast, AIIc% (both p < 0.05) in the two treatment groups were significantly higher than those in the control group. These results suggest that rhubarb has antiatherosclerotic and plaque‐stabilizing properties due to antiinflammation and lipid‐lowering effects. Copyright © 2008 John Wiley & Sons, Ltd.
Antiinflammatory activities of flavonoids and a triterpene caffeate isolated fromBauhinia variegata
Authors: Rao Yerra Koteswara , Fang Shih‐Hua , Tzeng Yew‐Min
Published: April 2008

In the continuing search for novel antiinflammatory agents, six flavonoids, namely kaempferol (1), ombuin (2), kaempferol 7,4′‐dimethyl ether 3‐O‐β‐d‐glucopyranoside (3), kaempferol 3‐O‐β‐d‐glucopyranoside (4), isorhamnetin 3‐O‐β‐d‐glucopyranoside (5) and hesperidin (6), together with one triterpene caffeate, 3β‐trans‐(3,4‐dihydroxycinnamoyloxy)olean‐12‐en‐28‐oic acid (7) were isolated from the non‐woody aerial parts ofBauhinia variegata. Compounds 1–7 were evaluated as inhibitors of some macrophage functions involved in the inflammatory process. These seven compounds significantly and dose dependently inhibited lipopolysaccharide (LPS) and interferon (IFN)‐γinduced nitric oxide (NO), and cytokines [tumor necrosis factor (TNF)‐αand interleukin (IL)‐12]. The concentration causing a 50% inhibition (IC50) of NO, TNF‐αand IL‐12 production by compounds 1, 2 and 7 was approximately 30, 50 and 10 µM, respectively, while at 50, 200 and 40 µM compounds 3, 4, and 5, 6 showed 15–30% inhibition, respectively. On the other hand, compounds 3 and 7 showed no inhibitory effect, while compounds 1, 4–6 reduced by around 10–30% the synthesis of NO by macrophages, when inducible NO synthase was already expressed with LPS/IFN‐γfor 24 h. These experimental findings lend pharmacological support to the suggested folkloric uses of the plantB. variegatain the management of inflammatory conditions. Copyright © 2008 John Wiley & Sons, Ltd.
Cardioprotective effects and underlying mechanisms of oxymatrine against Ischemic myocardial injuries of rats
Authors: Hong‐li Sun , Lei Li , Lei Shang , Dan Zhao , De‐li Dong , Guo‐fen Qiao , Yan Liu , Wen‐feng Chu , Bao‐feng Yang
Published: April 2008

Oxymatrine has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that oxymatrine may exert a protective effect on the cardiovascular system. The study was designed to explore the possible role of oxymatrine against myocardial ischemic damage and several related signaling pathways as potential mechanisms. The protective properties of oxymatrine were studied in a rat model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery. The results showed that administration of oxymatrine relieved myocardial injuries during ischemia, and this was achieved by protecting cardiomyocytes from apoptotic death. The beneficial effects of oxymatrine were likely mediated by an inhibition of lipid peroxidation (MDA production) and an increase in endogenous antioxidant activity (SOD), activation of the survival signaling molecule (Bcl‐2), and a reduction of apoptotic mediator (Fas) and intracellular Ca2+ overload. Copyright © 2008 John Wiley & Sons, Ltd.
Improving change tolerance through Capabilities‐based design: an empirical analysis
Authors: Ravichandar Ramya , Arthur James D. , Bohner Shawn A. , Tegarden David P.
Published: April 2008

We introduce a Capabilities‐based approach for constructing large‐scale systems such that they are change‐tolerant. The inherent complexity of software systems increases their susceptibility to change when subjected to the vagaries of user needs, technology advances, market demands, and other change‐inducing factors. Despite the inevitability of change, traditional requirements engineering strives to develop systems based on a fixed solution; a mostly unsuccessful approach as evidenced by the history of system failures. In contrast, we utilize Capabilities—functional abstractions that are neither as amorphous as user needs nor as rigid as system requirements—to architect systems that accommodate change with minimum impact. These entities are designed to exhibit the desirable characteristics of high cohesion, low coupling, and balanced abstraction levels and are generated by a two‐phased process called Capabilities Engineering. Phase I mathematically exploits the structural semantics of a function decomposition graph—a representation of user needs—to formulate change‐tolerant Capabilities. Phase II optimizes these Capabilities to comply with schedule and technology constraints. In this paper, we present the overall framework of this process and detail the algorithm to identify Capabilities. In addition, we empirically evaluate the change tolerance of Capabilities resulting from Phase I. For this we examine the ripple effect of needs change on a real‐world Course Evaluation System based on the original requirements‐based design and the corresponding Capabilities‐based design. Our experimental results indicate, with statistical significance, that the Capabilities‐based design is less impacted by change and thereby improves the change tolerance of the system when subjected to needs volatility. Copyright © 2008 John Wiley & Sons, Ltd.
Morphological, Physicochemical and Textural Properties of Starch Separated from Chinese Water Chestnut
Authors: Lan Wang , Zhihua Yin , Yun Zhang , Bijun Xie , Zhida Sun
Published: April 2008

Chinese water chestnut starch (CWCS) was isolated and its composition, morphological, physicochemical and textural properties investigated. Chinese water chestnut starch granules were round, oval and polyangular in shape, with volumetric mean diameter (D50) 8.46 μm. CWCS had an A‐type crystal pattern and an apparent amylose content of 32.1%. Compared with tapioca and maize starch, CWCS exhibited moderate swelling power and turbidity and high stability against freeze‐thaw treatment. Chinese water chestnut starch showed the highest peak (7957 mPa s), breakdown (4169 mPa s) and final viscosity (4816 mPa s), intermediate setback viscosity (1028 mPa s) and pasting temperature (68.7°C), and lowest enthalpy (10.8 J/g) of gelatinization of the three starches studied. The effect of food additives (NaCl, sucrose and glycerol monostearate) and heating processes (direct heating, steam heating, microwave heating and autoclaving) on the CWCS gel was determined by a texture analyzer. The CWCS gel hardness and gumminess proportionally increased with the concentration of starch gels, ranging from 6% to 16%, but gel springiness and cohesiveness changed indistinctively. CWCS gels with added NaCl gave inconsistent results, but for the most part, they showed similar or increased gel hardness and gumminess as compared with the control. CWCS gels with added glycerol monostearate had lower gel hardness and gumminess than the control. The addition of sucrose (< 15%, w/v) resulted in increased gel hardness and gumminess, but 20% sucrose decreased these features. Both microwave and steam heating on the one hand and autoclaving and directly heating on the other gave rise to similar gel hardness and gumminess, the values of the two groups being significantly different from each other.
An Adaptive Neuro‐Fuzzy Inference System for Modeling Mechanical Properties of Tapioca Starch‐Poly(Lactic Acid) Nanocomposite Foams
Authors: Lee Siew Yoong , Hanna Milford A. , Jones David D.
Published: April 2008

Tapioca starch, poly(lactic acid) and Cloisite 30B nanocomposites foams, with clay contents of 1, 3, 5 and 7% (w/w), were prepared by a melt‐intercalation method. Multiple inputs single output models were developed to predict radial expansion ratio, unit density, bulk compressibility and spring index of the nanocomposite foams. An individual ANFIS model was developed for each mechanical property using clay content, temperature, pressure and torque as input parameters. All models preformed well with R2 values > 0.71. All models had very low root mean squared error values.
Iodine‐binding in Granular Starch: Different Effects of Moisture Content for Corn and Potato Starch
Authors: Saibene Debora , Zobel Henry F. , Thompson Donald B. , Seetharaman Koushik
Published: April 2008

The ability of iodine to complex with glucan polymers has been mainly used to elucidate the structure of dispersed starch molecules. In a previous publication [D. Saibene, K. Seetharaman, Carbohydr. Polym., 2006, 64, 539‐547] we reported the ability of granular corn starches to bind iodine at moisture contents as low as 8%. We presumed that iodine binding in a native granule requires a certain minimal level of mobility of the linear molecules, and that the water content would plasticize the starch, thus increasing the ability to bind iodine by the formation of single helices. The objective of the present study was to investigate iodine complex formation with starch molecules in granular common corn starch (CCS) and potato starch (PS) as a function of water content. CCS and PS granules have approximately similar amylose content (21 and 17% amylose, respectively), but different crystalline structures (A‐ and B‐type, respectively). Variable water contents were achieved using salt solutions at water activities (aw) of 0.33, 0.75 or 0.97, and also using Drierite® (aw less than 0.15). The granular samples were then exposed to iodine vapor before determination of the K/S spectra (the ratio of the absorption and scattering coefficients), and X‐ray diffraction patterns. Based on the K/S spectra, at moisture contents in the range of 12‐20%, CCS binds iodine more effectively than PS. We suggest that the reason may be related to the greater amount of water associated with the crystalline regions of PS. Iodination more strongly diminished the crystallinity of PS granules than it did in CCS granules. This behavior is consistent with a greater involvement of amylose in the crystalline structures of PS than in CCS.
Orofaciodigital syndrome Type IV (Mohr–Majewski): early prenatal diagnosis in siblings
Authors: Rösing B. , Kempe A. , Berg C. , Kahl P. , Knöpfle G. , Gembruch U. , Geipel A.
Published: March 2008

We report the sonographic and autopsy findings in two sibling fetuses with autosomal recessive orofaciodigital syndrome (OFDS) Type IV (Mohr–Majewski) diagnosed at 11–13 weeks' gestation. The first‐trimester anomaly scan showed a markedly increased nuchal translucency (NT) thickness in both fetuses (4.7 mm and 5.1 mm). Both fetuses had multiple anomalies involving the brain, cranium, heart and skeletal system and their karyotypes were normal. The pregnancies were terminated and the autopsies showed findings consistent with Mohr–Majewski syndrome. These cases show the overlap between OFDS Type II (Mohr) and lethal short‐rib–polydactyly syndrome Type II (Majewski) and confirm both the autosomal recessive inheritance of the condition and our ability to diagnose it early in pregnancy using detailed fetal ultrasonography. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.